Acute Lichenoid Pityriasis

Complex MONDO:0024250 Pathograph 26 Show in embeddings browser Acute disease Pityriasis lichenoides

Acute lichenoid pityriasis is pityriasis lichenoides et varioliformis acuta (PLEVA, Mucha-Habermann disease), the acute pole of the pityriasis lichenoides spectrum. It is a rare inflammatory dermatosis characterized by abrupt crops of erythematous papules or papulovesicles that can scale, become hemorrhagic or necrotic, crust, and heal with dyspigmentation or varioliform scarring. Pityriasis lichenoides chronica (PLC) is the chronic spectrum pole and can overlap clinicopathologically with PLEVA, but is not the scope of this entry. Febrile ulceronecrotic Mucha-Habermann disease (FUMHD) is a rare, severe PLEVA variant with coalescing ulcers, high fever, and possible systemic involvement. Etiology remains unresolved: an antigen-triggered reactive process and a clonal or oligoclonal T-cell dyscrasia are competing or potentially superimposed models. PLEVA-specific immunophenotyping supports a CD8-positive, TIA-1-positive cytotoxic T-cell-rich infiltrate associated with epidermal injury, but does not identify the upstream antigen.

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6
Pathophys.
4
Histopath.
21
Phenotypes
4
Hypotheses
5
Gaps
26
Pathograph
9
Medical Actions
1
Subtypes
6
Differentials
2
Deep Research
◆

Subtypes

1
Febrile Ulceronecrotic Mucha-Habermann Disease (FUMHD) MONDO:0023134
FUMHD is a rare, severe PLEVA variant, not the usual presentation of ordinary PLEVA. Generalized ulceronecrotic papules rapidly coalesce into ulcers with high fever; disseminated intravascular coagulation and pulmonary, cardiac, gastrointestinal, or central nervous system involvement may occur. Mortality is concentrated in this subtype, so its systemic findings and aggressive management must not be generalized to uncomplicated PLEVA.
Show evidence (4 references)
PMID:36483219 SUPPORT Human Clinical
"Febrile Ulceronecrotic Mucha- Habermann Disease (FUMHD) is a variant of Pityriasis Lichenoides Et Varioliformis Acuta (PLEVA)."
This systematic review directly defines FUMHD as a PLEVA variant.
PMID:38959922 SUPPORT Human Clinical
"Febrile ulceronecrotic Mucha-Habermann disease is a rare and severe variant of pityriasis lichenoides, characterized by sudden onset of generalized ulceronecrotic papules that rapidly coalesce into ulcers associated with high fever."
The review supplies the defining ulceronecrotic and febrile phenotype.
PMID:34287852 SUPPORT Human Clinical
"Overall lethality was 14/119 (12%, CI 6-17%), and lethality in children was lower (1/54, 2%, CI 0-6%) compared to adults (13/65, 20%, CI 11-31%)."
The 119-case review quantifies the mortality confined to the FUMHD literature and shows the strong age gradient.
+ 1 more reference
◈

Mechanistic Hypotheses

4
Cytotoxic T-Cell Epidermal Injury Model
cytotoxic_t_cell_epidermal_injury_model EMERGING
Evidence balance 1 support
CD8-positive, TIA-1-positive cytotoxic T cells accumulate in PLEVA lesions and may contribute to epidermal keratinocyte injury, interface damage, and the papulonecrotic eruption. Their causal effector function has not been directly demonstrated.
PLEVA-specific human tissue supports cytotoxic-cell enrichment and an inferred epidermal-damage role. The antigen, effector repertoire, and exact death pathway remain unresolved, so this model should not be expanded into unsupported molecular signaling claims.
Pathograph links
CD8-positive cytotoxic T-cell epidermal response -> Keratinocyte death and epidermal necrosis INDIRECT UNKNOWN INTERMEDIATES A cytotoxic T-cell contribution to epidermal keratinocyte injury is proposed from the lesional immunophenotype.
Keratinocyte death and epidermal necrosis -> Papulovesicular eruption INDIRECT KNOWN INTERMEDIATES Focal interface injury and epidermal disruption produce papules that can develop vesicles or pustules. Intermediates: Epidermal disruption and vesiculation
Keratinocyte death and epidermal necrosis -> Crusted skin lesions INDIRECT KNOWN INTERMEDIATES Epidermal cell death and hemorrhagic exudate dry into the characteristic crusted or necrotic center. Intermediates: Hemorrhagic necrosis and surface exudate
Keratinocyte death and epidermal necrosis -> Scaling skin INDIRECT UNKNOWN INTERMEDIATES Interface epidermal injury and altered surface keratinization produce scale over erythematous papules.
Keratinocyte death and epidermal necrosis -> Skin ulcer INDIRECT KNOWN INTERMEDIATES In ordinary PLEVA, sufficiently deep focal epidermal necrosis can expose a small necrotic ulcer; rapidly coalescing generalized ulcers define the separate FUMHD severity branch. Intermediates: Focal epidermal necrosis and surface loss
Keratinocyte death and epidermal necrosis -> Scarring INDIRECT KNOWN INTERMEDIATES Epidermal necrosis with dermal damage can heal with a varioliform scar. Intermediates: Necrotic tissue loss and repair
Keratinocyte death and epidermal necrosis -> Hypopigmented skin patches INDIRECT KNOWN INTERMEDIATES Resolution of inflamed or necrotic lesions can leave post-inflammatory hypopigmented macules. Intermediates: Post-inflammatory pigmentary alteration
Show evidence (1 reference)
PMID:38973067 SUPPORT Human Clinical
"The predominant T-cell infiltrate in PLEVA is dominated by CD8+ cells, and by increased numbers of TIA1+ cells, which may indicate a cytotoxic T-cell damage to the epidermis."
PLEVA-specific immunophenotyping supports marker enrichment and an inferred damage role while retaining the authors' causal qualification.
Reactive Antigen-Trigger Model
reactive_antigen_trigger_model ALTERNATIVE
Evidence balance 2 support
An infection, medication, vaccine, or other antigenic exposure initiates a postinfectious or hypersensitivity-like cutaneous T-cell response in a susceptible person.
Evidence is temporal and epidemiologic rather than causal. Negative viral testing in PLEVA lesions argues against persistent presence of the common viruses assayed, but does not exclude a cleared infection, an untested agent, or a noninfectious antigen.
Pathograph links
Antigen-associated immune triggering -> CD8-positive cytotoxic T-cell epidermal response INDIRECT UNKNOWN INTERMEDIATES The reactive model proposes that antigen exposure activates and recruits a cytotoxic cutaneous T-cell response.
Show evidence (2 references)
PMID:8864599 SUPPORT Other
"The etiology of MH remains obscure, but it may be the result of a hypersensitivity reaction to an infectious agent."
This review states the reactive hypothesis but explicitly preserves its uncertainty.
PMID:38973067 SUPPORT Human Clinical
"Viral presence was not detected."
Negative lesional testing constrains a direct persistent-virus version of the model without excluding an antigen-triggered reaction.
Clonal T-Cell Dyscrasia Model
clonal_t_cell_dyscrasia_model ALTERNATIVE
Evidence balance 1 support
PLEVA may in some patients reflect a clonal or oligoclonal cutaneous T-cell dyscrasia rather than a purely polyclonal reactive dermatitis.
The strongest clonality study used a selected, mixed PL cohort and does not establish that ordinary PLEVA is lymphoma or that clonality predicts transformation. Clinicopathologic correlation is essential.
Pathograph links
Clonal or oligoclonal cutaneous T-cell expansion -> CD8-positive cytotoxic T-cell epidermal response INDIRECT UNKNOWN INTERMEDIATES The clonal model proposes convergence on the same cytotoxic lesional effector population observed by PLEVA immunophenotyping.
Show evidence (1 reference)
PMID:12203210 SUPPORT Human Clinical
"Clonality was shown in 25 of 27 biopsies in which amplifiable DNA was obtained."
This selected mixed-PL study supports a clonal-dyscrasia model, but its cohort included only seven PLEVA cases and cannot define all PLEVA.
Systemic Hyperinflammatory Escalation Model
systemic_hyperinflammatory_escalation_model EMERGING
Evidence balance 1 support
In the FUMHD severity variant, the cutaneous cytotoxic process is accompanied by high fever and systemic inflammation, and in extreme cases can meet criteria for hemophagocytic lymphohistiocytosis (HLH), suggesting a hyperinflammatory escalation beyond ordinary PLEVA. Whether HLH is a driver or a downstream complication of severe FUMHD is unresolved.
Evidence is limited to case-level associations. The HLH association is a single-case observation and should be read as an illustrative severe-end phenotype, not an established obligatory mechanism. Applies only to the FUMHD subtype, not to uncomplicated PLEVA.
Pathograph links
Keratinocyte death and epidermal necrosis -> Ulceronecrotic systemic inflammatory escalation in FUMHD INDIRECT UNKNOWN INTERMEDIATES In a minority of patients the PLEVA cytotoxic/keratinocyte-necrosis process escalates into the fulminant ulceronecrotic, febrile FUMHD branch; the host or lesional factor that determines escalation is unknown. This edge states the severe-branch relationship that is the entry's thesis, linking the shared PLEVA pathophysiology to the FUMHD escalation node.
Ulceronecrotic systemic inflammatory escalation in FUMHD -> Disseminated intravascular coagulation UNKNOWN Systemic inflammation in FUMHD can be complicated by disseminated intravascular coagulation.
Show evidence (1 reference)
PMID:38457671 SUPPORT Human Clinical
"The patient also met 7 of 9 HLH-2004 criteria, leading to a diagnosis of HLH."
A single FUMHD case reaching HLH-2004 criteria illustrates the hyperinflammatory severe end, without establishing HLH as an obligatory FUMHD mechanism.
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Discussions and Knowledge Gaps

5
What upstream antigen or exposure initiates PLEVA, if any?
KNOWLEDGE GAP OPEN upstream_trigger_identity
Attached to
pathophysiology#Antigen-associated immune triggering
Temporal associations support a reactive model, but no specific agent is reproducibly causal and PLEVA tissue was negative for the common viruses tested. Identifying the initiating antigen would distinguish a postinfectious response from a direct infection or noninfectious trigger.
Show evidence (1 reference)
PMID:38973067 SUPPORT Human Clinical
"Immunohistochemistry for human HHV-1 and HHV-2, CMV and HHV-8, parvovirus B19, and in situ hybridization for EBV were all negative."
This PLEVA-specific study leaves the upstream trigger unresolved.
Is PLEVA primarily reactive, a clonal T-cell dyscrasia, or a heterogeneous spectrum containing both?
CONTROVERSY OPEN reactive_versus_clonal_t_cell_model
Attached to
pathophysiology#Antigen-associated immune triggering pathophysiology#Clonal or oligoclonal cutaneous T-cell expansion diagnosis#Clinicopathologic and phenotypic assessment of atypical or persistent lesions
Clonality and aberrant phenotypes occur in selected PL cohorts, yet clonality is not synonymous with lymphoma. Follow-up studies disagree on whether apparent MF evolution represents true progression, initial misclassification, or a selected atypical subset.
Show evidence (3 references)
PMID:12203210 SUPPORT Human Clinical
"Clonality was shown in 25 of 27 biopsies in which amplifiable DNA was obtained."
This selected cohort supports the clonal side of the controversy.
PMID:41420620 SUPPORT Human Clinical
"During the follow-up period, no progression to cutaneous T-cell lymphoma was established."
A 242-patient PL cohort with median 9.9-year follow-up found no established CTCL progression, supporting a generally benign interpretation.
PMID:29210716 SUPPORT Human Clinical
"A total of 3 (5.2%) of the 58 patients with PL developed MF after 3-11 years of prolonged clinical course."
This selected PL cohort reports apparent evolution, but the result is not PLEVA-specific and should not be converted into a general PLEVA risk.
Which treatment improves PLEVA-specific remission and durable control beyond spontaneous resolution?
KNOWLEDGE GAP OPEN pleva_treatment_evidence_gap
Attached to
treatments#Narrowband UVB phototherapy treatments#Oral erythromycin therapy treatments#Topical corticosteroid therapy treatments#Methotrexate therapy for refractory or severe disease
Most studies pool PLEVA with PLC, use heterogeneous response definitions, and have short follow-up. PLEVA-specific comparative evidence is therefore insufficient for a high-certainty treatment hierarchy.
Show evidence (1 reference)
PMID:32112390 SUPPORT Other
"The current literature consists almost entirely of uncontrolled studies, and none provides compelling data to support an evidence-based approach to PL treatment."
This systematic review directly identifies the evidence-quality gap while noting that its corpus did include two randomized studies.
Which systemic therapy improves FUMHD survival, and how should immunosuppression be balanced against sepsis risk?
KNOWLEDGE GAP OPEN fumhd_optimal_treatment
Attached to
treatments#Prompt systemic and supportive management for FUMHD treatments#Methotrexate therapy for refractory or severe disease treatments#Intravenous immunoglobulin (IVIG) for FUMHD treatments#TNF-alpha inhibitor therapy for FUMHD treatments#Ciclosporin therapy for FUMHD
FUMHD management rests on heterogeneous single cases and small reviews with no controlled trials, so no regimen is proven by RCT-grade evidence and the tradeoff between immunosuppression and infectious mortality is unresolved. A pooled review nonetheless signals that systemic corticosteroids combined with methotrexate or ciclosporin are associated with significantly more effective outcomes, suggesting early combination therapy as a candidate optimal approach that still needs prospective validation.
Show evidence (2 references)
PMID:36483219 SUPPORT Human Clinical
"FUMHD is a diagnostic and therapeutic challenge due to the lack of clearly defined diagnostic criteria and optimum treatment."
This directly supports the absence of an established optimal FUMHD treatment.
PMID:35950146 SUPPORT Human Clinical
"Systematic corticosteroids combination with other immunosuppressants (methotrexate or cyclosporine) were associated with significantly more effective cases (26/31 = 83.9%, χ2 = 4.065, p = 0.044)"
A pooled analysis provides the strongest quantitative treatment signal, partially qualifying the optimal-regimen gap.
What molecular driver determines why only a minority of PLEVA patients escalate to fulminant, systemic FUMHD?
KNOWLEDGE GAP OPEN fumhd_escalation_driver
Attached to
pathophysiology#Ulceronecrotic systemic inflammatory escalation in FUMHD
FUMHD shares the cytotoxic-T-cell PLEVA mechanism but adds fever, coalescing ulceronecrosis, and systemic/HLH-range hyperinflammation. The host or lesional factors that tip a minority of PLEVA patients into this severe, sometimes fatal branch are unknown, and no biomarker predicts escalation.
Show evidence (1 reference)
PMID:38959922 SUPPORT Human Clinical
"Febrile ulceronecrotic Mucha-Habermann disease is a rare and severe variant of pityriasis lichenoides, characterized by sudden onset of generalized ulceronecrotic papules that rapidly coalesce into ulcers associated with high fever."
The severe-variant framing motivates the open question of what drives escalation.
⚙

Pathophysiology

6
Antigen-associated immune triggering
In the reactive model, an unidentified infectious or noninfectious antigen precedes cutaneous immune activation. The association is not equivalent to proof of infection within the lesion.
Reactive Antigen-Trigger Model
immune response GO:0006955 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves abnormal immune response (GO:0006955). GO:0006955 is a biological process from the Gene Ontology. ⚠ ABNORMAL
Downstream
CD8-positive cytotoxic T-cell epidermal response The reactive model proposes that antigen exposure activates and recruits a cytotoxic cutaneous T-cell response. Reactive Antigen-Trigger Model
Show evidence (1 reference)
PMID:38677323 SUPPORT Human Clinical
"The frequency peaks coincided with infectious outbreaks."
Temporal clustering in a pediatric PL cohort is compatible with an infectious trigger but is not PLEVA-specific and does not establish causality.
Clonal or oligoclonal cutaneous T-cell expansion
In the dyscrasia model, a lesional T-cell clone or oligoclonal population expands in skin and contributes to the PLEVA inflammatory phenotype. Clonality is neither universal nor by itself diagnostic of lymphoma. In the FUMHD severity variant, a monoclonal T-cell receptor rearrangement has been documented in a subset of cases and is associated with worse prognosis, placing those cases on a continuum with cutaneous T-cell lymphoma.
Clonal T-Cell Dyscrasia Model
T cell CL:0000084 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves T cell (CL:0000084). CL:0000084 is a cell type from the Cell Ontology.
T cell activation GO:0042110 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves abnormal T cell activation (GO:0042110). GO:0042110 is a biological process from the Gene Ontology. ⚠ ABNORMAL
Downstream
CD8-positive cytotoxic T-cell epidermal response The clonal model proposes convergence on the same cytotoxic lesional effector population observed by PLEVA immunophenotyping. Clonal T-Cell Dyscrasia Model
Show evidence (3 references)
PMID:12203210 SUPPORT Human Clinical
"Intraepithelial atypical lymphocytes, phenotypic abnormalities, and TCR-gamma rearrangements suggest that PLC and PLEVA are a form of T-cell dyscrasia."
The authors interpret their selected mixed cohort as supporting a dyscrasia; this is retained as an alternative model rather than a settled classification.
PMID:15583604 SUPPORT Human Clinical
"we report two cases of FUMHD with monoclonal T-cell population, as detected by Southern blot analysis"
This directly documents a monoclonal T-cell population in FUMHD lesions in a subset of cases (FUMHD subtype-specific).
PMID:36483219 SUPPORT Human Clinical
"Increased age, systemic involvement, and monoclonal T-cell receptor rearrangement were associated with worst prognosis, but mucosal involvement did not affect mortality risk"
The FUMHD systematic review associates monoclonal TCR rearrangement with worse prognosis, supporting the clonal modifier arm in the FUMHD subtype.
CD8-positive cytotoxic T-cell epidermal response
PLEVA lesions contain increased CD8-positive and TIA-1-positive T cells. Their cytotoxic phenotype may contribute to keratinocyte injury, but the study evidence does not directly measure cytotoxic function.
Cytotoxic T-Cell Epidermal Injury Model
CD8-positive alpha-beta cytotoxic T cell CL:0000794 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves CD8-positive alpha-beta cytotoxic T cell, annotated with CD8-positive, alpha-beta cytotoxic T cell (CL:0000794). CL:0000794 is a cell type from the Cell Ontology.
T cell mediated immunity GO:0002456 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves abnormal T cell mediated immunity (GO:0002456). GO:0002456 is a biological process from the Gene Ontology. ⚠ ABNORMAL
skin epidermis UBERON:0001003 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in skin epidermis (UBERON:0001003). UBERON:0001003 is an anatomical location from the Uberon multi-species anatomy ontology.
Downstream
Keratinocyte death and epidermal necrosis A cytotoxic T-cell contribution to epidermal keratinocyte injury is proposed from the lesional immunophenotype. Cytotoxic T-Cell Epidermal Injury Model
Perivascular lymphocytic inflammation and erythrocyte extravasation The lesional cytotoxic T-cell infiltrate also involves the superficial dermal perivascular compartment, where dense perivascular lymphocytic inflammation and erythrocyte extravasation are seen alongside the epidermal injury. The direction and mechanism linking the epidermal and perivascular components are not established, so this is an association between two compartments of the same infiltrate rather than a proven causal step.
Show evidence (1 reference)
PMID:38973067 SUPPORT Human Clinical
"The numbers of CD8+ T cells and T-cell intracellular antigen-1 (TIA-1)+ cells were statistically significantly higher in PLEVA compared to the ID group."
A PLEVA-specific comparison directly establishes enrichment of cytotoxic T-cell markers relative to common inflammatory dermatoses.
Keratinocyte death and epidermal necrosis
PLEVA lesions can show vacuolar change, necrotic keratinocytes, and focal epidermal necrosis. Epidermal disruption is a plausible contributor to vesiculation, crusting, small ulcers, dyspigmentation, and scars, but these outcomes are not an obligatory causal sequence.
Cytotoxic T-Cell Epidermal Injury Model Systemic Hyperinflammatory Escalation Model
keratinocyte CL:0000312 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves keratinocyte (CL:0000312). CL:0000312 is a cell type from the Cell Ontology.
cell death GO:0008219 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased cell death (GO:0008219). GO:0008219 is a biological process from the Gene Ontology. ↑ INCREASED
skin epidermis UBERON:0001003 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in skin epidermis (UBERON:0001003). UBERON:0001003 is an anatomical location from the Uberon multi-species anatomy ontology.
Downstream
Papulovesicular eruption Focal interface injury and epidermal disruption produce papules that can develop vesicles or pustules. Cytotoxic T-Cell Epidermal Injury Model
Crusted skin lesions Epidermal cell death and hemorrhagic exudate dry into the characteristic crusted or necrotic center. Cytotoxic T-Cell Epidermal Injury Model
Scaling skin Interface epidermal injury and altered surface keratinization produce scale over erythematous papules. Cytotoxic T-Cell Epidermal Injury Model
Skin ulcer In ordinary PLEVA, sufficiently deep focal epidermal necrosis can expose a small necrotic ulcer; rapidly coalescing generalized ulcers define the separate FUMHD severity branch. Cytotoxic T-Cell Epidermal Injury Model
Scarring Epidermal necrosis with dermal damage can heal with a varioliform scar. Cytotoxic T-Cell Epidermal Injury Model
Hypopigmented skin patches Resolution of inflamed or necrotic lesions can leave post-inflammatory hypopigmented macules. Cytotoxic T-Cell Epidermal Injury Model
Ulceronecrotic systemic inflammatory escalation in FUMHD In a minority of patients the PLEVA cytotoxic/keratinocyte-necrosis process escalates into the fulminant ulceronecrotic, febrile FUMHD branch; the host or lesional factor that determines escalation is unknown. This edge states the severe-branch relationship that is the entry's thesis, linking the shared PLEVA pathophysiology to the FUMHD escalation node. Systemic Hyperinflammatory Escalation Model
Show evidence (2 references)
PMID:37155724 SUPPORT Human Clinical
"lymphocytic vasculitis (LV) with focal epidermal necrosis consistent with acute pityriasis lichenoides (PL) was identified."
This biopsy-confirmed PLEVA case directly documents focal epidermal necrosis.
PMID:31880634 SUPPORT Human Clinical
"vacuolar changes or necrotic keratinocytes (100%)"
The large mixed-PL series establishes that keratinocyte injury is a consistent PL histopathologic feature, although it did not report the PLEVA subset separately.
Perivascular lymphocytic inflammation and erythrocyte extravasation
PLEVA can show perivascular lymphocytes and extravasated erythrocytes in superficial dermis and epidermis. Although sometimes called lymphocytic vasculitis, a series found no fibrinoid vessel-wall deposition and cautioned that this is not necessarily true destructive vasculitis.
T cell CL:0000084 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves T cell (CL:0000084). CL:0000084 is a cell type from the Cell Ontology. endothelial cell CL:0000115 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves endothelial cell (CL:0000115). CL:0000115 is a cell type from the Cell Ontology.
inflammatory response GO:0006954 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves abnormal inflammatory response (GO:0006954). GO:0006954 is a biological process from the Gene Ontology. ⚠ ABNORMAL
dermis UBERON:0002067 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in dermis (UBERON:0002067). UBERON:0002067 is an anatomical location from the Uberon multi-species anatomy ontology.
Downstream
Purpura Extravasated erythrocytes and hemorrhagic change produce purpuric areas within evolving PLEVA lesions.
Show evidence (3 references)
PMID:17456915 SUPPORT Human Clinical
"All the cases of PLEVA showed lymphocytic vasculitis albeit without fibrinoid deposition in the vessel walls."
The PLEVA subset supports lymphocytic vascular involvement while the absent fibrinoid deposition constrains the destructive-vasculitis label.
PMID:17456915 SUPPORT Human Clinical
"Pityriasis lichenoides is not a rare disorder, and is not a true lymphocytic vasculitis as blood vessel damage and fibrinoid deposition in the blood vessel walls were not seen in this study."
The mixed-spectrum study's conclusion directly qualifies the use of the vasculitis label.
PMID:31880634 SUPPORT Human Clinical
"Superficial perivascular and/or intraepidermal red blood cells were observed in 83% of cases."
The mixed-PL series directly supports erythrocyte extravasation, but does not stratify this result by PLEVA versus PLC.
Ulceronecrotic systemic inflammatory escalation in FUMHD
FUMHD is the severe PLEVA branch in which generalized ulceronecrotic papules coalesce into ulcers while fever and systemic inflammation develop; the extreme end can meet criteria for hemophagocytic lymphohistiocytosis (HLH). The molecular reason only a minority of patients enter this branch is unknown.
Systemic Hyperinflammatory Escalation Model
inflammatory response GO:0006954 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased inflammatory response (GO:0006954). GO:0006954 is a biological process from the Gene Ontology. ↑ INCREASED TNF-alpha-mediated signaling GO:0033209 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased TNF-alpha-mediated signaling, annotated with tumor necrosis factor-mediated signaling pathway (GO:0033209). GO:0033209 is a biological process from the Gene Ontology. ↑ INCREASED
Downstream
Skin ulcer Generalized ulceronecrotic papules rapidly coalesce into ulcers in FUMHD.
Fever High fever accompanies the ulceronecrotic eruption and defines FUMHD.
Disseminated intravascular coagulation Systemic inflammation in FUMHD can be complicated by disseminated intravascular coagulation. Systemic Hyperinflammatory Escalation Model
Sepsis Extensive cutaneous ulceration and systemic involvement predispose to sepsis, the leading contributor to FUMHD mortality.
Show evidence (2 references)
PMID:38959922 SUPPORT Human Clinical
"Febrile ulceronecrotic Mucha-Habermann disease is a rare and severe variant of pityriasis lichenoides, characterized by sudden onset of generalized ulceronecrotic papules that rapidly coalesce into ulcers associated with high fever."
This directly supports the paired ulceronecrotic and febrile severe phenotype, while not resolving its molecular driver.
PMID:15840118 SUPPORT Human Clinical
"highly elevated serum levels of tumour necrosis factor (TNF)-alpha"
Markedly elevated serum TNF-alpha at the PLEVA-to-FUMHD transition supports a TNF-alpha amplification arm; causality is inferred from a single case.
✶

Histopathology

4
Interface injury with vacuolar change and necrotic keratinocytes
PLEVA biopsy shows interface epidermal injury with vacuolar change and necrotic keratinocytes. The pattern is supportive in the correct clinical setting but not independently pathognomonic.
Show evidence (2 references)
PMID:31880634 SUPPORT Human Clinical
"vacuolar changes or necrotic keratinocytes (100%)"
The large PL case series supports the microscopic finding, although the abstract does not stratify PLEVA and PLC.
PMID:37155724 SUPPORT Human Clinical
"lymphocytic vasculitis (LV) with focal epidermal necrosis"
A biopsy-confirmed PLEVA case directly supports focal epidermal necrosis.
CD8-positive and TIA-1-positive cytotoxic T-cell-rich infiltrate
Compared with common inflammatory dermatoses, PLEVA lesions contain more CD8-positive and TIA-1-positive cells. This helps substantiate a cytotoxic lesional phenotype but is not a stand-alone diagnostic test.
Show evidence (1 reference)
PMID:38973067 SUPPORT Human Clinical
"The numbers of CD8+ T cells and T-cell intracellular antigen-1 (TIA-1)+ cells were statistically significantly higher in PLEVA compared to the ID group."
This PLEVA-specific study directly supports the cytotoxic immunophenotype.
Perivascular lymphocytes and erythrocyte extravasation
Superficial perivascular lymphocytes and red-cell extravasation contribute to the hemorrhagic appearance. Fibrinoid vessel-wall necrosis is not a consistent requirement, so the finding should not be equated automatically with destructive vasculitis.
Show evidence (3 references)
PMID:17456915 SUPPORT Human Clinical
"All the cases of PLEVA showed lymphocytic vasculitis albeit without fibrinoid deposition in the vessel walls."
The PLEVA subset supports perivascular lymphocytic change and explicitly documents the absent fibrinoid deposition.
PMID:17456915 SUPPORT Human Clinical
"Pityriasis lichenoides is not a rare disorder, and is not a true lymphocytic vasculitis as blood vessel damage and fibrinoid deposition in the blood vessel walls were not seen in this study."
The broader PL conclusion supports describing this as a vascular-associated pattern rather than proven destructive vasculitis.
PMID:31880634 SUPPORT Human Clinical
"Superficial perivascular and/or intraepidermal red blood cells were observed in 83% of cases."
This mixed-PL series supports the red-cell extravasation component.
Atypical CD8-positive lymphomatoid infiltrate with lymphomatoid vasculitis (FUMHD)
Severe FUMHD can show a dermal and subcutaneous infiltrate of atypical CD8-positive lymphocytes with loss of CD5 and reduced CD7 and features of lymphomatoid vasculitis, overlapping histologically with cutaneous T-cell lymphoma. This is a severe-variant finding, not typical of ordinary PLEVA.
Show evidence (1 reference)
PMID:38457671 SUPPORT Human Clinical
"Biopsy indicated a dermal and subcutaneous infiltrate of atypical CD8 + lymphocytes with loss of CD5 and reduction in CD7 expression, along with features of lymphomatoid vasculitis."
This documents the atypical CD8-positive lymphomatoid infiltrate at the severe FUMHD end.
⬡

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.
Pathograph: causal mechanism network for Acute Lichenoid Pityriasis Interactive directed graph showing how pathophysiology mechanisms, phenotypes, genetic factors and variants, experimental models, environmental triggers, and treatments relate through causal and linked edges.
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Phenotypes

21
Blood 4
Purpura HP:0000979 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Purpura (HP:0000979). HP:0000979 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
DOI:10.1007/s13671-023-00380-1 SUPPORT Other
"PLEVA onsets acutely/subacutely with the eruption of polymorphous lesions ranging from macules, to hemorrhagic papules, to ulcers"
This review directly supports hemorrhagic papules, which are represented here by the closest available purpura term.
Disseminated intravascular coagulation HP:0005521 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Disseminated intravascular coagulation (HP:0005521). HP:0005521 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:38959922 SUPPORT Human Clinical
"Systemic manifestations such as intravascular disseminated coagulation and pulmonary, cardiac, gastrointestinal, and central nervous system involvement are common."
This directly lists intravascular disseminated coagulation as a FUMHD complication.
Thrombocytopenia HP:0001873 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Thrombocytopenia (HP:0001873). HP:0001873 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:34287852 SUPPORT Human Clinical
"marked leukopenia and thrombocytopenia at admission"
This FUMHD case directly documents marked thrombocytopenia at admission.
Leukopenia Decreased total leukocyte count HP:0001882 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Leukopenia, annotated with Decreased total leukocyte count (HP:0001882). HP:0001882 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:34287852 SUPPORT Human Clinical
"marked leukopenia and thrombocytopenia at admission"
This FUMHD case directly documents marked leukopenia at admission.
Cardiovascular 1
Cardiac involvement Abnormality of the cardiovascular system HP:0001626 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Cardiac involvement, annotated with Abnormality of the cardiovascular system (HP:0001626). HP:0001626 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:38959922 SUPPORT Human Clinical
"Systemic manifestations such as intravascular disseminated coagulation and pulmonary, cardiac, gastrointestinal, and central nervous system involvement are common."
This review lists cardiac involvement among the common FUMHD systemic manifestations.
Digestive 1
Gastrointestinal involvement Abnormality of the gastrointestinal tract HP:0011024 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Gastrointestinal involvement, annotated with Abnormality of the gastrointestinal tract (HP:0011024). HP:0011024 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:38959922 SUPPORT Human Clinical
"Systemic manifestations such as intravascular disseminated coagulation and pulmonary, cardiac, gastrointestinal, and central nervous system involvement are common."
This review lists gastrointestinal involvement among the common FUMHD systemic manifestations.
Head and Neck 1
Mucosal involvement Oral ulcer HP:0000155 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Mucosal involvement, annotated with Oral ulcer (HP:0000155). HP:0000155 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
PMID:34287852 SUPPORT Human Clinical
"mucosal involvement (4.58; P = 0.032)"
Mucosal involvement is quantified as a fatal-outcome risk factor in this 119-case analysis; the closest HP term (oral ulcer) anchors mucosal involvement, which in FUMHD is not restricted to the oral cavity.
PMID:36483219 REFUTE Human Clinical
"Increased age, systemic involvement, and monoclonal T-cell receptor rearrangement were associated with worst prognosis, but mucosal involvement did not affect mortality risk"
An independent 68-patient systematic review found mucosal involvement did NOT affect mortality risk, contradicting its prognostic weight.
Immune 1
Sepsis HP:0100806 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Sepsis (HP:0100806). HP:0100806 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
PMID:34287852 SUPPORT Human Clinical
"Risk factors for a fatal outcome (likelihood ratio; P) were sepsis (24.97, P < 0.001), adult vs. pediatric patient age (11.19; P = 0.001), systemic involvement (19.97, P < 0.001), and mucosal involvement (4.58; P = 0.032)."
This directly supports sepsis as the leading FUMHD fatal-outcome risk factor.
PMID:35950146 SUPPORT Human Clinical
"more positive skin bacterial cultures (31/41, 75.6%)"
A high rate of positive skin bacterial cultures supports the infection/sepsis burden of the denuded FUMHD skin.
Integument 4
Scaling skin HP:0040189 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Scaling skin (HP:0040189). HP:0040189 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:31334928 SUPPORT Human Clinical
"Clinically, PLEVA is characterized by the sudden onset of scaly, erythematous macules and papules localized to the trunk and proximal extremities."
This PLEVA-specific statement directly supports scaling.
Skin ulcer HP:0200042 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Skin ulcer (HP:0200042). HP:0200042 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
DOI:10.1007/s13671-023-00380-1 SUPPORT Other
"PLEVA onsets acutely/subacutely with the eruption of polymorphous lesions ranging from macules, to hemorrhagic papules, to ulcers"
This review directly includes ulcers in the PLEVA lesion spectrum.
PMID:38959922 SUPPORT Human Clinical
"generalized ulceronecrotic papules that rapidly coalesce into ulcers"
This separately supports the extensive ulcer phenotype in FUMHD.
Pruritus HP:0000989 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Pruritus (HP:0000989). HP:0000989 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
DOI:10.1007/s13671-013-0054-x SUPPORT Other
"the acute onset of pruritic and at times painful, symptomatic papulovesicles with necrotic, ulcerative or hemorrhagic changes."
This pediatric review directly supports pruritus in PLEVA.
Hemorrhagic bullae Abnormal blistering of the skin HP:0008066 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Hemorrhagic bullae, annotated with Abnormal blistering of the skin (HP:0008066). HP:0008066 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:38457671 SUPPORT Human Clinical
"Febrile ulceronecrotic MHD (FUMHD) represents a severe variant of MHD, marked by ulcers, hemorrhagic bullae, and systemic symptoms."
This FUMHD paper directly lists hemorrhagic bullae; the closest available HP term for bullous skin lesions is used.
Metabolism 1
Fever HP:0001945 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Fever (HP:0001945). HP:0001945 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:38959922 SUPPORT Human Clinical
"associated with high fever."
This directly supports fever in the FUMHD subtype.
Musculoskeletal 1
Scarring HP:0100699 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Scarring (HP:0100699). HP:0100699 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
DOI:10.35755/jmedassocthai.2025.5.377-383-02606 SUPPORT Human Clinical
"Dyspigmentation was predominantly observed in PLC, whereas varioliform scarring was more common in PLEVA (p<0.05)."
This retrospective pediatric series directly supports varioliform scarring but included only ten PLEVA cases.
Nervous System 2
Central nervous system involvement Abnormality of the nervous system HP:0000707 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Central nervous system involvement, annotated with Abnormality of the nervous system (HP:0000707). HP:0000707 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:38959922 SUPPORT Human Clinical
"Systemic manifestations such as intravascular disseminated coagulation and pulmonary, cardiac, gastrointestinal, and central nervous system involvement are common."
This review lists central nervous system involvement among the common FUMHD systemic manifestations.
Seizures HP:0001250 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Seizure (HP:0001250). HP:0001250 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:38234081 SUPPORT Human Clinical
"with FUMHD and seizures"
This case directly documents seizures as a CNS manifestation in a child with FUMHD.
Other 5
Papulovesicular eruption HP:0033700 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Papulovesicular eruption (HP:0033700). HP:0033700 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
PMID:8864599 SUPPORT Other
"abrupt onset of papulovesicular eruptions"
This directly supports the hallmark PLEVA morphology and onset.
PMID:37847066 SUPPORT Human Clinical
"characteristic pattern of lesions in different stages of development, ranging from erythematous maculopapules to papules with a crusted and/or necrotic centre."
This directly supports the polymorphous papular eruption.
Crusted skin lesions Crusting erythematous dermatitis HP:0007473 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Crusted skin lesions, annotated with Crusting erythematous dermatitis (HP:0007473). HP:0007473 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:37847066 SUPPORT Human Clinical
"papules with a crusted and/or necrotic centre."
This PLEVA report directly supports crusted lesion centers.
Hypopigmented skin patches HP:0001053 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Hypopigmented skin patches (HP:0001053). HP:0001053 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:37155724 SUPPORT Human Clinical
"multiple erythematous lesions that disappeared leaving hypopigmented macules."
This directly supports residual hypopigmented macules.
Cutaneous necrosis HP:0033126 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Cutaneous necrosis (HP:0033126). HP:0033126 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:38959922 SUPPORT Human Clinical
"generalized ulceronecrotic papules that rapidly coalesce into ulcers"
The ulceronecrotic morphology that defines FUMHD directly denotes cutaneous necrosis.
Pulmonary involvement Abnormality of the respiratory system HP:0002086 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Pulmonary involvement, annotated with Abnormality of the respiratory system (HP:0002086). HP:0002086 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:38959922 SUPPORT Human Clinical
"Systemic manifestations such as intravascular disseminated coagulation and pulmonary, cardiac, gastrointestinal, and central nervous system involvement are common."
This review lists pulmonary involvement among the common FUMHD systemic manifestations.
💊

Medical Actions

9
Narrowband UVB phototherapy
Action: phototherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is phototherapy (NCIT:C15301). NCIT:C15301 is a clinical intervention from the NCI Thesaurus. Ontology label: Phototherapy NCIT:C15301
Narrowband UVB is the best-supported active treatment in pooled PL literature and is commonly favored when observation, topical measures, or antibiotics are insufficient. Evidence combines PLEVA and PLC, consists mostly of uncontrolled studies, and is vulnerable to spontaneous resolution and short follow-up.
Target Phenotypes: Papulovesicular eruption HP:0033700 Human Phenotype Ontology (HP) Relation: this treatment targets this phenotype This treatment targets Papulovesicular eruption (HP:0033700). HP:0033700 is a phenotype from the Human Phenotype Ontology. Scaling skin HP:0040189 Human Phenotype Ontology (HP) Relation: this treatment targets this phenotype This treatment targets Scaling skin (HP:0040189). HP:0040189 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
PMID:31318465 SUPPORT Other
"According to the results of this review, we suggest narrow-band UVB phototherapy as first-line treatment."
This systematic review supports NB-UVB as a proposed first-line PL treatment, but pooled acute and chronic disease.
PMID:32112390 SUPPORT Other
"phototherapy led to complete remission in the highest proportion of patients"
The pooled PL review favors phototherapy but concludes that evidence is not compelling enough for a high-certainty evidence-based approach.
Oral erythromycin therapy
Action: antimicrobial agent therapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is antimicrobial agent therapy, annotated with Antibiotic Therapy (NCIT:C15620). NCIT:C15620 is a clinical intervention from the NCI Thesaurus. Ontology label: Antibiotic Therapy NCIT:C15620
Agent: erythromycin CHEBI:48923 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses erythromycin (CHEBI:48923). CHEBI:48923 is a therapeutic agent from Chemical Entities of Biological Interest.
Oral erythromycin is a commonly proposed initial systemic option, particularly in children. Its benefit may be anti-inflammatory rather than proof of an active bacterial cause, and response estimates are drawn from mixed PL cohorts.
Target Phenotypes: Papulovesicular eruption HP:0033700 Human Phenotype Ontology (HP) Relation: this treatment targets this phenotype This treatment targets Papulovesicular eruption (HP:0033700). HP:0033700 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
PMID:8864599 SUPPORT Other
"beginning with oral antibiotics, usually erythromycin, is recommended."
This PLEVA/Mucha-Habermann review supports pediatric initial use.
PMID:31318465 SUPPORT Other
"Oral erythromycin showed clearance rates ranging between 66% and 83%"
The estimate comes from pooled PL studies and is not PLEVA-stratified.
Topical corticosteroid therapy
Action: topical corticosteroid therapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is topical corticosteroid therapy (NCIT:C122078). NCIT:C122078 is a clinical intervention from the NCI Thesaurus. Ontology label: Topical Corticosteroid Therapy NCIT:C122078
Agent: corticosteroid CHEBI:50858 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses corticosteroid (CHEBI:50858). CHEBI:50858 is a therapeutic agent from Chemical Entities of Biological Interest.
Topical corticosteroids may be tried for inflammatory symptoms or itch, but they should not be presented as reliably disease-clearing monotherapy.
Target Phenotypes: Pruritus HP:0000989 Human Phenotype Ontology (HP) Relation: this treatment targets this phenotype This treatment targets Pruritus (HP:0000989). HP:0000989 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
PMID:32112390 SUPPORT Other
"topical corticosteroids were found to have been trialled in the highest number of patients."
This supports common use, not high-certainty efficacy.
PMID:23488769 SUPPORT Human Clinical
"Almost all patients did not respond to topical corticosteroids."
This small, predominantly PLC series directly supports the caution that topical corticosteroids are not reliably disease-clearing.
Methotrexate therapy for refractory or severe disease
Action: methotrexate therapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is methotrexate therapy, annotated with Pharmacotherapy (NCIT:C15986). NCIT:C15986 is a clinical intervention from the NCI Thesaurus. Ontology label: Pharmacotherapy NCIT:C15986
Agent: methotrexate CHEBI:44185 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses methotrexate (CHEBI:44185). CHEBI:44185 is a therapeutic agent from Chemical Entities of Biological Interest.
Low-dose methotrexate is reported for refractory PL and is among systemic options used for FUMHD. The ordinary-PL efficacy estimate comes from small, dated studies, and FUMHD evidence is case-based.
Target Phenotypes: Papulovesicular eruption HP:0033700 Human Phenotype Ontology (HP) Relation: this treatment targets this phenotype This treatment targets Papulovesicular eruption (HP:0033700). HP:0033700 is a phenotype from the Human Phenotype Ontology. Skin ulcer HP:0200042 Human Phenotype Ontology (HP) Relation: this treatment targets this phenotype This treatment targets Skin ulcer (HP:0200042). HP:0200042 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
PMID:31318465 SUPPORT Other
"methotrexate up to 100% but in small and dated studies."
The review documents a high reported clearance ceiling while explicitly warning that the underlying studies are small and dated.
PMID:36483219 SUPPORT Human Clinical
"Successful treatment modalities for FUMHD included antibiotics, antivirals, systemic steroids, Methotrexate (MTX), cyclophosphamide, Cyclosporine (CYA), Intravenous Immunoglobulins (IVIG), pentoxifylline, and ultraviolet B phototherapy."
The FUMHD case-literature review includes methotrexate among successful regimens but cannot establish an optimal regimen.
Prompt systemic and supportive management for FUMHD
Action: corticosteroid agent therapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is corticosteroid agent therapy, annotated with Systemic Corticosteroid Therapy (NCIT:C122080). NCIT:C122080 is a clinical intervention from the NCI Thesaurus. Ontology label: Systemic Corticosteroid Therapy NCIT:C122080
Agent: corticosteroid CHEBI:50858 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses corticosteroid (CHEBI:50858). CHEBI:50858 is a therapeutic agent from Chemical Entities of Biological Interest.
FUMHD warrants prompt specialist evaluation and management for systemic involvement and sepsis, with supportive care and individualized systemic anti-inflammatory or immunosuppressive therapy. No optimal regimen is established, and immunosuppression must be balanced against infectious mortality.
Target Phenotypes: Skin ulcer HP:0200042 Human Phenotype Ontology (HP) Relation: this treatment targets this phenotype This treatment targets Skin ulcer (HP:0200042). HP:0200042 is a phenotype from the Human Phenotype Ontology. Fever HP:0001945 Human Phenotype Ontology (HP) Relation: this treatment targets this phenotype This treatment targets Fever (HP:0001945). HP:0001945 is a phenotype from the Human Phenotype Ontology.
Show evidence (5 references)
PMID:38959922 SUPPORT Human Clinical
"Treatment is based on oral corticosteroids, immunosuppressive drugs such as methotrexate, and general supportive treatment."
This FUMHD review directly supports systemic and supportive management.
PMID:36483219 SUPPORT Human Clinical
"Although rare, the condition may progress to involve serious complications and even lead to fatal outcomes if diagnosis and appropriate treatment is delayed."
This systematic review supports prompt assessment and treatment.
PMID:34287852 SUPPORT Human Clinical
"Risk factors for a fatal outcome (likelihood ratio; P) were sepsis (24.97, P < 0.001), adult vs. pediatric patient age (11.19; P = 0.001), systemic involvement (19.97, P < 0.001), and mucosal involvement (4.58; P = 0.032)."
The case-literature analysis directly supports assessing sepsis and systemic involvement as mortality risk factors.
+ 2 more references
Intravenous immunoglobulin (IVIG) for FUMHD
Action: Intravenous Immunoglobulin TherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Intravenous Immunoglobulin Therapy (NCIT:C121331). NCIT:C121331 is a clinical intervention from the NCI Thesaurus. NCIT:C121331
Intravenous immunoglobulin has produced rapid disease control in FUMHD, including in a child refractory to steroids, methotrexate, dapsone, and erythromycin; it is among the reported successful FUMHD modalities.
Target Phenotypes: Fever HP:0001945 Human Phenotype Ontology (HP) Relation: this treatment targets this phenotype This treatment targets Fever (HP:0001945). HP:0001945 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:38234081 SUPPORT Human Clinical
"improved rapidly and achieved disease control with just a single infusion of low-dose intravenous immunoglobulin."
This case directly supports IVIG achieving rapid FUMHD control after other agents failed.
TNF-alpha inhibitor therapy for FUMHD
Action: PharmacotherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Pharmacotherapy (NCIT:C15986). NCIT:C15986 is a clinical intervention from the NCI Thesaurus. NCIT:C15986
Agent: infliximab NCIT:C1789 NCI Thesaurus (NCIT) Relation: this treatment uses this therapeutic agent This treatment uses infliximab (NCIT:C1789). NCIT:C1789 is a therapeutic agent from the NCI Thesaurus.
TNF-alpha inhibitors (e.g., infliximab, often with IVIG) are reported for refractory FUMHD and are mechanistically rational given the elevated serum TNF-alpha at the PLEVA-to-FUMHD transition. Response is not uniform - at least one infant died despite a TNF-alpha inhibitor - so this remains a case-based option, not established therapy.
Mechanism Target:
INHIBITS Ulceronecrotic systemic inflammatory escalation in FUMHD — TNF-alpha inhibition targets the TNF-alpha amplification arm (GO:0033209) of the FUMHD systemic inflammatory escalation node.
Target Phenotypes: Skin ulcer HP:0200042 Human Phenotype Ontology (HP) Relation: this treatment targets this phenotype This treatment targets Skin ulcer (HP:0200042). HP:0200042 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
PMID:23391565 SUPPORT Human Clinical
"TNFα inhibitors may be useful, particularly in resistant cases"
This report of infliximab plus IVIG supports TNF-alpha inhibition in resistant FUMHD.
PMID:42178566 SUPPORT Human Clinical
"Despite treatment with methylprednisolone, intravenous immunoglobulin, and a TNF-α inhibitor, the disease was fatal."
A fatal infant case despite a TNF-alpha inhibitor shows the response is not uniform.
Ciclosporin therapy for FUMHD
Action: PharmacotherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Pharmacotherapy (NCIT:C15986). NCIT:C15986 is a clinical intervention from the NCI Thesaurus. NCIT:C15986
Agent: ciclosporin CHEBI:4031 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses ciclosporin, annotated with cyclosporin A (CHEBI:4031). CHEBI:4031 is a therapeutic agent from Chemical Entities of Biological Interest.
Ciclosporin is among the systemic immunosuppressants used in FUMHD; a pooled review found systemic corticosteroids combined with methotrexate or ciclosporin were associated with significantly more effective outcomes, supporting early combination therapy.
Target Phenotypes: Skin ulcer HP:0200042 Human Phenotype Ontology (HP) Relation: this treatment targets this phenotype This treatment targets Skin ulcer (HP:0200042). HP:0200042 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:35950146 SUPPORT Human Clinical
"Early combination therapy with lower doses of corticosteroids and methotrexate or cyclosporine may be an optimal choice"
A pooled FUMHD review supports early combination therapy including ciclosporin.
Antimicrobial therapy and infection control for FUMHD
Action: antimicrobial agent therapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is antimicrobial agent therapy, annotated with Antibiotic Therapy (NCIT:C15620). NCIT:C15620 is a clinical intervention from the NCI Thesaurus. Ontology label: Antibiotic Therapy NCIT:C15620
Agent: antibiotic NCIT:C258 NCI Thesaurus (NCIT) Relation: this treatment uses this therapeutic agent This treatment uses antibiotic (NCIT:C258). NCIT:C258 is a therapeutic agent from the NCI Thesaurus.
Because sepsis of the denuded skin is the dominant cause of FUMHD death, antimicrobial therapy and aggressive wound care / infection control are outcome-determining and are counted among the successful FUMHD modalities.
Target Phenotypes: Skin ulcer HP:0200042 Human Phenotype Ontology (HP) Relation: this treatment targets this phenotype This treatment targets Skin ulcer (HP:0200042). HP:0200042 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
PMID:36483219 SUPPORT Human Clinical
"Successful treatment modalities for FUMHD included antibiotics, antivirals, systemic steroids, Methotrexate (MTX), cyclophosphamide, Cyclosporine (CYA), Intravenous Immunoglobulins (IVIG), pentoxifylline, and ultraviolet B phototherapy."
This FUMHD review lists antibiotics among the successful treatment modalities.
PMID:42178566 SUPPORT Human Clinical
"Early immunosuppressive and antimicrobial therapies are crucial"
This directly supports early antimicrobial therapy as crucial in FUMHD.
🌍

Environmental Factors

1
Temporally associated infectious, medication, and vaccination exposures
Infections, medications, and vaccinations have preceded PL or PLEVA in reports and small cohorts. These observations support an antigen-trigger hypothesis only; they do not prove that a specific exposure caused PLEVA, and PLEVA-specific lesion testing did not detect the common viruses assayed.
Show evidence (4 references)
PMID:38677323 SUPPORT Human Clinical
"The frequency peaks coincided with infectious outbreaks."
The cohort supports temporal clustering for pediatric PL, but included mostly PLC and does not prove a PLEVA cause.
PMID:36688177 SUPPORT Human Clinical
"This review cannot determine causality. However, a temporal association was observed with the case reports"
The review supports only a temporal SARS-CoV-2 infection or vaccination association and explicitly rejects causal certainty.
PMID:25816855 SUPPORT Other
"The proposed etiologies are discussed, including its association with infectious agents, medications, and immunizations and evidence for PL as a lymphoproliferative disorder."
This mixed-spectrum review documents the reported exposure categories without establishing that any exposure causes PLEVA.
+ 1 more reference
🔬

Diagnosis

4
Clinical morphology with skin biopsy and clinicopathologic correlation
Lesions at several stages suggest PLEVA, but biopsy is commonly needed because inflammatory eruptions and cutaneous lymphoproliferative disorders can mimic it. Histology must be interpreted with the distribution, lesion evolution, and clinical course.
skin biopsy NCIT:C51692 NCI Thesaurus (NCIT)
Results: Supportive findings include interface or lichenoid dermatitis, vacuolar change or necrotic keratinocytes, superficial and deep lymphocytes, lymphocytes in adnexal epithelium, perivascular or intraepidermal erythrocytes, and a CD8/TIA-1-rich infiltrate. No single feature is pathognomonic.
Show evidence (3 references)
PMID:37155724 SUPPORT Human Clinical
"The diagnosis is made by clinical suspicion and confirmed by histology."
This directly supports clinical suspicion followed by histologic confirmation.
PMID:31880634 SUPPORT Human Clinical
"the histopathological assessment of a biopsy is sometimes needed to differentiate between PL and a range of other diseases."
This mixed-PL series supports biopsy for difficult differentials.
PMID:31880634 SUPPORT Human Clinical
"both superficial and deep lymphocytic infiltrates (99%), and the infiltration of lymphocytes into the adnexal epithelium (97%)."
This large mixed-PL series supplies the deep and adnexal infiltrate findings but did not stratify them by PLEVA versus PLC.
Dermoscopy as a noninvasive diagnostic adjunct
Punctate or glomerular vessels and erythematous globules around an orange or crusted center can support a rapid clinical impression, but dermoscopy does not replace biopsy when the diagnosis or lymphoma differential remains uncertain.
Results: Punctate or glomerular vessels and erythematous globules surrounding a homogeneous orange or crusty central area.
Show evidence (1 reference)
PMID:37847066 SUPPORT Human Clinical
"Observation of the dermatoscopic findings described, such as punctate or glomerular vessels and erythematous globules surrounding a homogeneous orange or crusty central area, may allow for a rapid diagnosis, avoiding the need for invasive techniques."
This three-case PLEVA report supports dermoscopy as an adjunct.
Clinicopathologic and phenotypic assessment of atypical or persistent lesions
For atypical or persistent lesions, or when mycosis fungoides or lymphomatoid papulosis is considered, complete phenotypic analysis should be integrated with morphology and clinical course. Molecular clonality should not be interpreted alone.
Results: In one comparative series, molecular clonality did not differ meaningfully among conventional PL, atypical PL, lymphomatoid papulosis, and mycosis fungoides, making an isolated clonality result nondiscriminating.
Show evidence (2 references)
PMID:29851705 SUPPORT Human Clinical
"clinicopathologic correlation and complete phenotypic analyses are paramount in order to achieve proper classification."
This study of conventional PL, atypical PL, LyP, and MF supports integrated classification rather than reliance on a single marker.
PMID:29851705 SUPPORT Human Clinical
"Molecular analyses of clonality of the infiltrate did not reveal relevant differences among these 4 groups."
Clonality alone did not distinguish conventional PL, atypical PL, lymphomatoid papulosis, and mycosis fungoides in this series.
Clinicopathologic diagnosis of FUMHD with proposed criteria
FUMHD is diagnosed clinicopathologically; Nofal et al. proposed a constant-plus-variable diagnostic-criteria framework, the closest to formal FUMHD criteria in the absence of a consensus definition.
Results: Constant clinical and histopathological features present in every case, combined with variable features present in some cases.
Show evidence (1 reference)
PMID:26695875 SUPPORT Other
"The first comprises constant clinical and histopathological features that are always present in every case"
Nofal et al. proposed a constant-plus-variable diagnostic-criteria framework for FUMHD.
📈

Progression

3
Acute papulovesicular eruption
Duration: The eruption typically resolves over weeks to months
PLEVA begins abruptly or subacutely with polymorphous lesions that can range from macules and papules to hemorrhagic papules and ulcers. The simultaneous presence of lesions at several stages is a useful clinical clue.
Show evidence (4 references)
PMID:8864599 SUPPORT Other
"In 1916 Mucha and in 1925 Habermann reported an acute form of pityriasis lichenoides characterized by the abrupt onset of papulovesicular eruptions and gave the name, pityriasis lichenoides et varioliformis acuta (PLEVA) or Mucha-Habermann disease (MH)."
This directly supports the abrupt papulovesicular onset that defines PLEVA.
PMID:37847066 SUPPORT Human Clinical
"Diagnosis of pityriasis lichenoides et varioliformis acuta (PLEVA) is based on the characteristic pattern of lesions in different stages of development, ranging from erythematous maculopapules to papules with a crusted and/or necrotic centre."
This PLEVA case series supports staged lesion evolution and polymorphism.
DOI:10.1007/s13671-023-00380-1 SUPPORT Other
"PLEVA onsets acutely/subacutely with the eruption of polymorphous lesions ranging from macules, to hemorrhagic papules, to ulcers"
This review supports the acute-to-subacute polymorphous eruption but is not a prospective natural-history study.
+ 1 more reference
Healing with dyspigmentation or varioliform scarring
Necrotic lesions may heal with residual hypopigmented or hyperpigmented macules and, when dermal injury is sufficient, varioliform scars. These are sequelae, not evidence that every lesion ulcerates or scars.
Show evidence (2 references)
DOI:10.35755/jmedassocthai.2025.5.377-383-02606 SUPPORT Human Clinical
"Dyspigmentation was predominantly observed in PLC, whereas varioliform scarring was more common in PLEVA (p<0.05)."
This retrospective pediatric series directly compared the spectrum subtypes but included only ten PLEVA cases.
PMID:37155724 SUPPORT Human Clinical
"multiple erythematous lesions that disappeared leaving hypopigmented macules."
This PLEVA case directly supports post-inflammatory hypopigmentation.
Febrile ulceronecrotic systemic branch
Febrile ulceronecrotic Mucha-Habermann disease
A small subset develops FUMHD, with rapid coalescence of ulceronecrotic lesions, high fever, and possible systemic complications. This is a severe branch rather than an obligatory stage of ordinary PLEVA.
Show evidence (1 reference)
PMID:38959922 SUPPORT Human Clinical
"Systemic manifestations such as intravascular disseminated coagulation and pulmonary, cardiac, gastrointestinal, and central nervous system involvement are common."
This review directly supports the systemic-complication branch in FUMHD.
📊

Prevalence

2
General population
Unknown Rare
PLEVA is rare, but a reliable population prevalence or incidence has not been established. Referral-series proportions within the broader PL spectrum should not be interpreted as population prevalence.
Show evidence (1 reference)
PMID:31334928 SUPPORT Human Clinical
"Pityriasis lichenoides et varioliformis acuta (PLEVA) is a rare, self-limited, cutaneous disorder of unknown etiology."
This PLEVA-specific review supports the qualitative rarity statement, while not providing a population rate.
Reported case literature
Cases In Literature Ultra Rare Febrile ulceronecrotic Mucha-Habermann disease
FUMHD is very rare and described mainly in single cases and small case-literature reviews; one systematic case review aggregated 119 patients. No reliable population incidence or prevalence has been established. Reported cases show a clear male predominance (roughly three-quarters male).
Show evidence (2 references)
PMID:34287852 SUPPORT Human Clinical
"Overall lethality was 14/119 (12%, CI 6-17%), and lethality in children was lower (1/54, 2%, CI 0-6%) compared to adults (13/65, 20%, CI 11-31%)."
The 119-case review defines the size of the reported FUMHD literature and is used here only to convey rarity, not a population rate.
PMID:35950146 SUPPORT Human Clinical
"Most of them were male (62/83, 74.7%), with high fever state (50/80, 62.5% had a high fever of 39°C or above)"
A pooled FUMHD systematic review quantifies the male predominance and the high-fever frequency across reported cases.
🔀

Differential Diagnoses

6

Conditions with similar clinical presentations that must be differentiated from Acute Lichenoid Pityriasis:

Pityriasis lichenoides chronica
Overlapping Features PLC is the chronic pole of the PL spectrum and may coexist or overlap with PLEVA. The distinction rests on the tempo and morphology of lesions plus clinicopathologic correlation rather than a rigid binary histologic test.
Distinguishing Features
  • PLC has a more chronic, scaling papular course; PLEVA has abrupt papulovesicular or papulonecrotic crops.
  • Clinical and histopathologic overlap is common, so mixed presentations should be acknowledged.
Show evidence (2 references)
PMID:25816855 SUPPORT Other
"It is often classified into the acute form, pityriasis lichenoides et varioliformis acuta (PLEVA), and the chronic form, pityriasis lichenoides chronica (PLC)."
This review directly establishes the acute/chronic spectrum boundary.
PMID:25816855 SUPPORT Other
"in many cases, there is clinical and histopathologic overlap between the two phenotypes."
This supports caution against treating PLEVA and PLC as perfectly separable.
Cutaneous CD8-positive necrotizing angiocentric lymphoproliferative disease
Overlapping Features Severe FUMHD can mimic an aggressive CD8-positive angiocentric cutaneous T-cell lymphoproliferative disease, and the atypical lymphomatoid immunophenotype makes this the key differential for the FUMHD severity variant. It is the natural clinical partner to the atypical CD8-positive lymphomatoid histopathology of FUMHD.
Distinguishing Features
  • FUMHD is self-limited/reactive and typically lacks a persistent monoclonal aggressive lymphoma course; clinicopathologic correlation and follow-up distinguish it.
Show evidence (1 reference)
PMID:38457671 SUPPORT Human Clinical
"FUMHD should be considered in the differential diagnosis for patients presenting with cutaneous CD8 + necrotizing angiocentric lymphoproliferative disease complicated by HLH."
This FUMHD paper directly frames the aggressive angiocentric CTCL differential.
Lymphomatoid papulosis Not Yet Curated MONDO:0020326
Overlapping Features Lymphomatoid papulosis can also produce recurrent self-healing papules and may be mistaken for atypical PL.
Distinguishing Features
  • Waxing and waning papules or nodules with a CD30-positive atypical lymphoid infiltrate favor lymphomatoid papulosis.
Show evidence (1 reference)
PMID:29851705 SUPPORT Human Clinical
"Lymphomatoid papulosis (waxing and waning lesions and positivity for CD30)"
This study directly identifies the key clinical and immunophenotypic distinction.
Mycosis fungoides MONDO:0009691
Overlapping Features Early or PL-like mycosis fungoides can overlap clinically and histologically with prolonged or atypical pityriasis lichenoides.
Distinguishing Features
  • Persistent patches or larger plaques, increasing nuclear atypia, marked CD7/CD8 diminution, and concordant clonal TCR findings raise concern for MF.
  • Serial clinicopathologic assessment is more informative than clonality alone.
Show evidence (1 reference)
PMID:29210716 SUPPORT Human Clinical
"Prolonged clinical course, appearance of patches and larger plaques, markedly increased lymphocytic nuclear atypia, marked diminution of apoptotic keratinocytes and CD7 and CD8 lymphocytes, and clonal T-cell receptor gene rearrangement may serve as clues."
This PL follow-up study directly lists features concerning for MF.
Guttate psoriasis Not Yet Curated MONDO:0023297
Overlapping Features Guttate psoriasis can mimic the acute disseminated scaly papules of PLEVA.
Distinguishing Features
  • PLEVA lesions evolve through vesiculation, hemorrhagic necrosis, and crusting, while clinicopathologic biopsy can resolve uncertain cases.
Show evidence (1 reference)
DOI:10.70672/bcfbzp08 SUPPORT Human Clinical
"A provisional diagnosis of guttate psoriasis with PLEVA as the differential diagnosis was made after a thorough history and examination."
This PLEVA case directly documents the guttate-psoriasis diagnostic overlap.
Varicella
Overlapping Features Early PLEVA may resemble varicella because both can present with an acute vesicular or crusted eruption.
Distinguishing Features
  • Fever and mucous-membrane involvement favor varicella, while PLEVA generally has a more prolonged course.
Show evidence (2 references)
DOI:10.1007/s13671-013-0054-x SUPPORT Other
"In its early presentations, the condition may be confused with varicella."
This pediatric review directly identifies varicella as an early mimic.
DOI:10.1007/s13671-013-0054-x SUPPORT Other
"lack the typical fever and mucous membrane involvement seen in varicella, and the course of PLEV A is considerably more prolonged."
This review supplies the main clinical distinctions.
{ }

Source YAML

click to show 
name: Acute Lichenoid Pityriasis
creation_date: '2026-05-04T19:32:38Z'
description: >-
  Acute lichenoid pityriasis is pityriasis lichenoides et varioliformis acuta
  (PLEVA, Mucha-Habermann disease), the acute pole of the pityriasis
  lichenoides spectrum. It is a rare inflammatory dermatosis characterized by
  abrupt crops of erythematous papules or papulovesicles that can
  scale, become hemorrhagic or necrotic, crust, and heal with dyspigmentation
  or varioliform scarring. Pityriasis lichenoides chronica (PLC) is the chronic
  spectrum pole and can overlap clinicopathologically with PLEVA, but is not
  the scope of this entry. Febrile ulceronecrotic Mucha-Habermann disease
  (FUMHD) is a rare, severe PLEVA variant with coalescing ulcers, high fever,
  and possible systemic involvement. Etiology remains unresolved: an
  antigen-triggered reactive process and a clonal or oligoclonal T-cell
  dyscrasia are competing or potentially superimposed models. PLEVA-specific
  immunophenotyping supports a CD8-positive, TIA-1-positive cytotoxic
  T-cell-rich infiltrate associated with epidermal injury, but does not
  identify the upstream antigen.
category: Complex
disease_term:
  preferred_term: acute lichenoid pityriasis
  term:
    id: MONDO:0024250
    label: acute lichenoid pityriasis
parents:
- Acute disease
- Pityriasis lichenoides
synonyms:
- Pityriasis lichenoides et varioliformis acuta
- PLEVA
- Mucha-Habermann disease
- Acute pityriasis lichenoides
has_subtypes:
- name: Febrile ulceronecrotic Mucha-Habermann disease
  display_name: Febrile Ulceronecrotic Mucha-Habermann Disease (FUMHD)
  classification: clinical_severity_variant
  subtype_term:
    preferred_term: febrile ulceronecrotic Mucha-Habermann disease
    term:
      id: MONDO:0023134
      label: febrile ulceronecrotic Mucha-Habermann disease
  description: >-
    FUMHD is a rare, severe PLEVA variant, not the usual presentation of
    ordinary PLEVA. Generalized ulceronecrotic papules rapidly coalesce into
    ulcers with high fever; disseminated intravascular coagulation and
    pulmonary, cardiac, gastrointestinal, or central nervous system
    involvement may occur. Mortality is concentrated in this subtype, so its
    systemic findings and aggressive management must not be generalized to
    uncomplicated PLEVA.
  evidence:
  - reference: PMID:36483219
    reference_title: "Mortality risk factors in febrile ulceronecrotic Mucha- Habermann disease: A systematic review of therapeutic outcomes and complications."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Febrile Ulceronecrotic Mucha- Habermann Disease (FUMHD) is a variant of
      Pityriasis Lichenoides Et Varioliformis Acuta (PLEVA).
    explanation: >-
      This systematic review directly defines FUMHD as a PLEVA variant.
  - reference: PMID:38959922
    reference_title: "Febrile ulceronecrotic Mucha-Habermann disease - a case and treatment review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Febrile ulceronecrotic Mucha-Habermann disease is a rare and severe
      variant of pityriasis lichenoides, characterized by sudden onset of
      generalized ulceronecrotic papules that rapidly coalesce into ulcers
      associated with high fever.
    explanation: >-
      The review supplies the defining ulceronecrotic and febrile phenotype.
  - reference: PMID:34287852
    reference_title: "Mucha-Habermann disease: a pediatric case report and proposal of a risk score."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Overall lethality was 14/119 (12%, CI 6-17%), and lethality in children
      was lower (1/54, 2%, CI 0-6%) compared to adults (13/65, 20%, CI 11-31%).
    explanation: >-
      The 119-case review quantifies the mortality confined to the FUMHD
      literature and shows the strong age gradient.
  - reference: PMID:35950146
    reference_title: "Febrile Ulceronecrotic Mucha-Habermann Disease: A Case Report and a Systematic Review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Most of them were male (62/83, 74.7%), with high fever state (50/80, 62.5%
      had a high fever of 39°C or above)
    explanation: >-
      A pooled FUMHD review quantifies the male predominance and high-fever
      frequency across reported cases.
prevalence:
- population: General population
  measure_type: UNKNOWN
  prevalence_class: RARE
  notes: >-
    PLEVA is rare, but a reliable population prevalence or incidence has not
    been established. Referral-series proportions within the broader PL
    spectrum should not be interpreted as population prevalence.
  evidence:
  - reference: PMID:31334928
    reference_title: "An Atypical Presentation of PLEVA: Case Report and Review of the Literature."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Pityriasis lichenoides et varioliformis acuta (PLEVA) is a rare,
      self-limited, cutaneous disorder of unknown etiology.
    explanation: >-
      This PLEVA-specific review supports the qualitative rarity statement,
      while not providing a population rate.
- population: Reported case literature
  subtype: Febrile ulceronecrotic Mucha-Habermann disease
  measure_type: CASES_IN_LITERATURE
  prevalence_class: ULTRA_RARE
  notes: >-
    FUMHD is very rare and described mainly in single cases and small
    case-literature reviews; one systematic case review aggregated 119 patients.
    No reliable population incidence or prevalence has been established. Reported
    cases show a clear male predominance (roughly three-quarters male).
  evidence:
  - reference: PMID:34287852
    reference_title: "Mucha-Habermann disease: a pediatric case report and proposal of a risk score."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Overall lethality was 14/119 (12%, CI 6-17%), and lethality in children
      was lower (1/54, 2%, CI 0-6%) compared to adults (13/65, 20%, CI 11-31%).
    explanation: >-
      The 119-case review defines the size of the reported FUMHD literature and
      is used here only to convey rarity, not a population rate.
  - reference: PMID:35950146
    reference_title: "Febrile Ulceronecrotic Mucha-Habermann Disease: A Case Report and a Systematic Review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Most of them were male (62/83, 74.7%), with high fever state (50/80, 62.5%
      had a high fever of 39°C or above)
    explanation: >-
      A pooled FUMHD systematic review quantifies the male predominance and the
      high-fever frequency across reported cases.
progression:
- phase: Acute papulovesicular eruption
  duration: The eruption typically resolves over weeks to months
  notes: >-
    PLEVA begins abruptly or subacutely with polymorphous lesions that can range
    from macules and papules to hemorrhagic papules and ulcers. The simultaneous
    presence of lesions at several stages is a useful clinical clue.
  evidence:
  - reference: PMID:8864599
    reference_title: "Mucha-Habermann disease and its febrile ulceronecrotic variant."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      In 1916 Mucha and in 1925 Habermann reported an acute form of pityriasis
      lichenoides characterized by the abrupt onset of papulovesicular eruptions
      and gave the name, pityriasis lichenoides et varioliformis acuta (PLEVA)
      or Mucha-Habermann disease (MH).
    explanation: >-
      This directly supports the abrupt papulovesicular onset that defines
      PLEVA.
  - reference: PMID:37847066
    reference_title: "Dermoscopy as a diagnostic aid in pityriasis lichenoides et varioliformis acuta."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Diagnosis of pityriasis lichenoides et varioliformis acuta (PLEVA) is
      based on the characteristic pattern of lesions in different stages of
      development, ranging from erythematous maculopapules to papules with a
      crusted and/or necrotic centre.
    explanation: >-
      This PLEVA case series supports staged lesion evolution and polymorphism.
  - reference: DOI:10.1007/s13671-023-00380-1
    reference_title: "Pityriasis Lichenoides Following SARS-CoV-2 Infection/Vaccination"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      PLEVA onsets acutely/subacutely with the eruption of polymorphous lesions
      ranging from macules, to hemorrhagic papules, to ulcers
    explanation: >-
      This review supports the acute-to-subacute polymorphous eruption but is
      not a prospective natural-history study.
  - reference: DOI:10.1007/s13671-023-00380-1
    reference_title: "Pityriasis Lichenoides Following SARS-CoV-2 Infection/Vaccination"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "typically resolves within weeks to months"
    explanation: >-
      This review supplies the broad resolution interval without asserting a
      recurrence pattern.
- phase: Healing with dyspigmentation or varioliform scarring
  notes: >-
    Necrotic lesions may heal with residual hypopigmented or hyperpigmented
    macules and, when dermal injury is sufficient, varioliform scars. These are
    sequelae, not evidence that every lesion ulcerates or scars.
  evidence:
  - reference: DOI:10.35755/jmedassocthai.2025.5.377-383-02606
    reference_title: "Pityriasis Lichenoides in Thai Children: A 10-Years Review of Clinical and Treatment Outcome"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Dyspigmentation was predominantly observed in PLC, whereas varioliform
      scarring was more common in PLEVA (p<0.05).
    explanation: >-
      This retrospective pediatric series directly compared the spectrum
      subtypes but included only ten PLEVA cases.
  - reference: PMID:37155724
    reference_title: "Acute lichenoid and varioliform pityriasis in a pediatric patient."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "multiple erythematous lesions that disappeared leaving hypopigmented macules."
    explanation: >-
      This PLEVA case directly supports post-inflammatory hypopigmentation.
- phase: Febrile ulceronecrotic systemic branch
  subtype: Febrile ulceronecrotic Mucha-Habermann disease
  notes: >-
    A small subset develops FUMHD, with rapid coalescence of ulceronecrotic
    lesions, high fever, and possible systemic complications. This is a severe
    branch rather than an obligatory stage of ordinary PLEVA.
  evidence:
  - reference: PMID:38959922
    reference_title: "Febrile ulceronecrotic Mucha-Habermann disease - a case and treatment review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Systemic manifestations such as intravascular disseminated coagulation
      and pulmonary, cardiac, gastrointestinal, and central nervous system
      involvement are common.
    explanation: >-
      This review directly supports the systemic-complication branch in FUMHD.
mechanistic_hypotheses:
- hypothesis_group_id: cytotoxic_t_cell_epidermal_injury_model
  hypothesis_label: Cytotoxic T-Cell Epidermal Injury Model
  status: EMERGING
  description: >-
    CD8-positive, TIA-1-positive cytotoxic T cells accumulate in PLEVA lesions
    and may contribute to epidermal keratinocyte injury, interface damage, and
    the papulonecrotic eruption. Their causal effector function has not been
    directly demonstrated.
  notes: >-
    PLEVA-specific human tissue supports cytotoxic-cell enrichment and an
    inferred epidermal-damage role. The antigen, effector repertoire, and exact
    death pathway remain unresolved, so this model should not be expanded into
    unsupported molecular signaling claims.
  evidence:
  - reference: PMID:38973067
    reference_title: "Immunophenotyping and viral studies in pityriasis lichenoides et varioliformis acuta lesions."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The predominant T-cell infiltrate in PLEVA is dominated by CD8+ cells,
      and by increased numbers of TIA1+ cells, which may indicate a cytotoxic
      T-cell damage to the epidermis.
    explanation: >-
      PLEVA-specific immunophenotyping supports marker enrichment and an
      inferred damage role while retaining the authors' causal qualification.
- hypothesis_group_id: reactive_antigen_trigger_model
  hypothesis_label: Reactive Antigen-Trigger Model
  status: ALTERNATIVE
  description: >-
    An infection, medication, vaccine, or other antigenic exposure initiates a
    postinfectious or hypersensitivity-like cutaneous T-cell response in a
    susceptible person.
  notes: >-
    Evidence is temporal and epidemiologic rather than causal. Negative viral
    testing in PLEVA lesions argues against persistent presence of the common
    viruses assayed, but does not exclude a cleared infection, an untested
    agent, or a noninfectious antigen.
  evidence:
  - reference: PMID:8864599
    reference_title: "Mucha-Habermann disease and its febrile ulceronecrotic variant."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      The etiology of MH remains obscure, but it may be the result of a
      hypersensitivity reaction to an infectious agent.
    explanation: >-
      This review states the reactive hypothesis but explicitly preserves its
      uncertainty.
  - reference: PMID:38973067
    reference_title: "Immunophenotyping and viral studies in pityriasis lichenoides et varioliformis acuta lesions."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Viral presence was not detected."
    explanation: >-
      Negative lesional testing constrains a direct persistent-virus version of
      the model without excluding an antigen-triggered reaction.
- hypothesis_group_id: clonal_t_cell_dyscrasia_model
  hypothesis_label: Clonal T-Cell Dyscrasia Model
  status: ALTERNATIVE
  description: >-
    PLEVA may in some patients reflect a clonal or oligoclonal cutaneous T-cell
    dyscrasia rather than a purely polyclonal reactive dermatitis.
  notes: >-
    The strongest clonality study used a selected, mixed PL cohort and does not
    establish that ordinary PLEVA is lymphoma or that clonality predicts
    transformation. Clinicopathologic correlation is essential.
  evidence:
  - reference: PMID:12203210
    reference_title: "Pityriasis lichenoides: a clonal T-cell lymphoproliferative disorder."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Clonality was shown in 25 of 27 biopsies in which amplifiable DNA was obtained."
    explanation: >-
      This selected mixed-PL study supports a clonal-dyscrasia model, but its
      cohort included only seven PLEVA cases and cannot define all PLEVA.
- hypothesis_group_id: systemic_hyperinflammatory_escalation_model
  hypothesis_label: Systemic Hyperinflammatory Escalation Model
  status: EMERGING
  description: >-
    In the FUMHD severity variant, the cutaneous cytotoxic process is
    accompanied by high fever and systemic inflammation, and in extreme cases
    can meet criteria for hemophagocytic lymphohistiocytosis (HLH), suggesting a
    hyperinflammatory escalation beyond ordinary PLEVA. Whether HLH is a driver
    or a downstream complication of severe FUMHD is unresolved.
  notes: >-
    Evidence is limited to case-level associations. The HLH association is a
    single-case observation and should be read as an illustrative severe-end
    phenotype, not an established obligatory mechanism. Applies only to the FUMHD
    subtype, not to uncomplicated PLEVA.
  evidence:
  - reference: PMID:38457671
    reference_title: "Febrile Ulceronecrotic Mucha-Habermann Disease Associated With Hemophagocytic Lymphohistiocytosis: A Case Report and Review of the Literature."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The patient also met 7 of 9 HLH-2004 criteria, leading to a diagnosis of HLH."
    explanation: >-
      A single FUMHD case reaching HLH-2004 criteria illustrates the
      hyperinflammatory severe end, without establishing HLH as an obligatory
      FUMHD mechanism.
pathophysiology:
- name: Antigen-associated immune triggering
  description: >-
    In the reactive model, an unidentified infectious or noninfectious antigen
    precedes cutaneous immune activation. The association is not equivalent to
    proof of infection within the lesion.
  mechanism_confidence: HYPOTHETICAL
  biological_processes:
  - preferred_term: immune response
    modifier: ABNORMAL
    term:
      id: GO:0006955
      label: immune response
  evidence:
  - reference: PMID:38677323
    reference_title: "Pityriasis lichenoides: assessment of 41 pediatric patients."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The frequency peaks coincided with infectious outbreaks."
    explanation: >-
      Temporal clustering in a pediatric PL cohort is compatible with an
      infectious trigger but is not PLEVA-specific and does not establish
      causality.
  downstream:
  - target: CD8-positive cytotoxic T-cell epidermal response
    description: >-
      The reactive model proposes that antigen exposure activates and recruits
      a cytotoxic cutaneous T-cell response.
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    hypothesis_groups:
    - reactive_antigen_trigger_model
    evidence:
    - reference: PMID:8864599
      reference_title: "Mucha-Habermann disease and its febrile ulceronecrotic variant."
      supports: SUPPORT
      evidence_source: OTHER
      snippet: >-
        The etiology of MH remains obscure, but it may be the result of a
        hypersensitivity reaction to an infectious agent.
      explanation: >-
        The review supports the proposed upstream hypersensitivity route, not
        the identity of an antigen or the intermediate immune steps.
- name: Clonal or oligoclonal cutaneous T-cell expansion
  description: >-
    In the dyscrasia model, a lesional T-cell clone or oligoclonal population
    expands in skin and contributes to the PLEVA inflammatory phenotype.
    Clonality is neither universal nor by itself diagnostic of lymphoma. In the
    FUMHD severity variant, a monoclonal T-cell receptor rearrangement has been
    documented in a subset of cases and is associated with worse prognosis,
    placing those cases on a continuum with cutaneous T-cell lymphoma.
  mechanism_confidence: PROVISIONAL
  biological_scale: CELLULAR
  cell_types:
  - preferred_term: T cell
    term:
      id: CL:0000084
      label: T cell
  biological_processes:
  - preferred_term: T cell activation
    modifier: ABNORMAL
    term:
      id: GO:0042110
      label: T cell activation
  evidence:
  - reference: PMID:12203210
    reference_title: "Pityriasis lichenoides: a clonal T-cell lymphoproliferative disorder."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Intraepithelial atypical lymphocytes, phenotypic abnormalities, and
      TCR-gamma rearrangements suggest that PLC and PLEVA are a form of T-cell
      dyscrasia.
    explanation: >-
      The authors interpret their selected mixed cohort as supporting a
      dyscrasia; this is retained as an alternative model rather than a settled
      classification.
  - reference: PMID:15583604
    reference_title: "Febrile ulceronecrotic Mucha-Habermann disease with clonality: a cutaneous T-cell lymphoma entity?"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      we report two cases of FUMHD with monoclonal T-cell population, as detected
      by Southern blot analysis
    explanation: >-
      This directly documents a monoclonal T-cell population in FUMHD lesions in
      a subset of cases (FUMHD subtype-specific).
  - reference: PMID:36483219
    reference_title: "Mortality risk factors in febrile ulceronecrotic Mucha- Habermann disease: A systematic review of therapeutic outcomes and complications."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Increased age, systemic involvement, and monoclonal T-cell receptor
      rearrangement were associated with worst prognosis, but mucosal
      involvement did not affect mortality risk
    explanation: >-
      The FUMHD systematic review associates monoclonal TCR rearrangement with
      worse prognosis, supporting the clonal modifier arm in the FUMHD subtype.
  downstream:
  - target: CD8-positive cytotoxic T-cell epidermal response
    description: >-
      The clonal model proposes convergence on the same cytotoxic lesional
      effector population observed by PLEVA immunophenotyping.
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    hypothesis_groups:
    - clonal_t_cell_dyscrasia_model
    evidence:
    - reference: PMID:12203210
      reference_title: "Pityriasis lichenoides: a clonal T-cell lymphoproliferative disorder."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "In general, CD8-positive lymphocytes dominated in cases of PLEVA"
      explanation: >-
        This supports CD8 predominance in the PLEVA subset of the clonality
        cohort, but not a proven causal transition from clonality to effector
        activity.
- name: CD8-positive cytotoxic T-cell epidermal response
  description: >-
    PLEVA lesions contain increased CD8-positive and TIA-1-positive T cells.
    Their cytotoxic phenotype may contribute to keratinocyte injury, but the
    study evidence does not directly measure cytotoxic function.
  mechanism_confidence: PROVISIONAL
  locations:
  - preferred_term: skin epidermis
    term:
      id: UBERON:0001003
      label: skin epidermis
  cell_types:
  - preferred_term: CD8-positive alpha-beta cytotoxic T cell
    term:
      id: CL:0000794
      label: CD8-positive, alpha-beta cytotoxic T cell
  biological_processes:
  - preferred_term: T cell mediated immunity
    modifier: ABNORMAL
    term:
      id: GO:0002456
      label: T cell mediated immunity
  evidence:
  - reference: PMID:38973067
    reference_title: "Immunophenotyping and viral studies in pityriasis lichenoides et varioliformis acuta lesions."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The numbers of CD8+ T cells and T-cell intracellular antigen-1 (TIA-1)+
      cells were statistically significantly higher in PLEVA compared to the
      ID group.
    explanation: >-
      A PLEVA-specific comparison directly establishes enrichment of cytotoxic
      T-cell markers relative to common inflammatory dermatoses.
  downstream:
  - target: Keratinocyte death and epidermal necrosis
    description: >-
      A cytotoxic T-cell contribution to epidermal keratinocyte injury is
      proposed from the lesional immunophenotype.
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    hypothesis_groups:
    - cytotoxic_t_cell_epidermal_injury_model
    evidence:
    - reference: PMID:38973067
      reference_title: "Immunophenotyping and viral studies in pityriasis lichenoides et varioliformis acuta lesions."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        The predominant T-cell infiltrate in PLEVA is dominated by CD8+ cells,
        and by increased numbers of TIA1+ cells, which may indicate a cytotoxic
        T-cell damage to the epidermis.
      explanation: >-
        The authors infer cytotoxic epidermal damage from the lesional
        immunophenotype; human intervention evidence is unavailable.
  - target: Perivascular lymphocytic inflammation and erythrocyte extravasation
    description: >-
      The lesional cytotoxic T-cell infiltrate also involves the superficial
      dermal perivascular compartment, where dense perivascular lymphocytic
      inflammation and erythrocyte extravasation are seen alongside the
      epidermal injury. The direction and mechanism linking the epidermal and
      perivascular components are not established, so this is an association
      between two compartments of the same infiltrate rather than a proven
      causal step.
    causal_link_type: UNKNOWN
    evidence:
    - reference: PMID:15840118
      reference_title: "Transition of pityriasis lichenoides et varioliformis acuta to febrile ulceronecrotic Mucha-Habermann disease is associated with elevated serum tumour necrosis factor-alpha."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Sequential histology revealed progressively dense perivascular and
        intramural lymphocytic inflammation as well as keratinocyte necrosis
      explanation: >-
        Sequential histology documents perivascular lymphocytic inflammation
        co-occurring with keratinocyte necrosis, supporting the perivascular
        component of the lesional infiltrate without establishing its direction.
- name: Keratinocyte death and epidermal necrosis
  description: >-
    PLEVA lesions can show vacuolar change, necrotic keratinocytes, and focal
    epidermal necrosis. Epidermal disruption is a plausible contributor to
    vesiculation, crusting, small ulcers, dyspigmentation, and scars, but these
    outcomes are not an obligatory causal sequence.
  mechanism_confidence: PROVISIONAL
  locations:
  - preferred_term: skin epidermis
    term:
      id: UBERON:0001003
      label: skin epidermis
  cell_types:
  - preferred_term: keratinocyte
    term:
      id: CL:0000312
      label: keratinocyte
  biological_processes:
  - preferred_term: cell death
    modifier: INCREASED
    term:
      id: GO:0008219
      label: cell death
  evidence:
  - reference: PMID:37155724
    reference_title: "Acute lichenoid and varioliform pityriasis in a pediatric patient."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      lymphocytic vasculitis (LV) with focal epidermal necrosis consistent with
      acute pityriasis lichenoides (PL) was identified.
    explanation: >-
      This biopsy-confirmed PLEVA case directly documents focal epidermal
      necrosis.
  - reference: PMID:31880634
    reference_title: "Pityriasis Lichenoides: A Large Histopathological Case Series With a Focus on Adnexotropism."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "vacuolar changes or necrotic keratinocytes (100%)"
    explanation: >-
      The large mixed-PL series establishes that keratinocyte injury is a
      consistent PL histopathologic feature, although it did not report the
      PLEVA subset separately.
  downstream:
  - target: Papulovesicular eruption
    description: >-
      Focal interface injury and epidermal disruption produce papules that can
      develop vesicles or pustules.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - Epidermal disruption and vesiculation
    hypothesis_groups:
    - cytotoxic_t_cell_epidermal_injury_model
    evidence:
    - reference: DOI:10.1007/s13671-013-0054-x
      reference_title: "Pityriasis Lichenoides and Cutaneous T Cell Lymphoma: An Update on the Diagnosis and Management of the Most Common Benign and Malignant Cutaneous Lymphoproliferative Diseases in Children"
      supports: SUPPORT
      evidence_source: OTHER
      snippet: >-
        the acute onset of pruritic and at times painful, symptomatic
        papulovesicles with necrotic, ulcerative or hemorrhagic changes.
      explanation: >-
        This pediatric review directly supports the papulovesicular morphology,
        while the causal route from epidermal injury remains inferred.
  - target: Crusted skin lesions
    description: >-
      Epidermal cell death and hemorrhagic exudate dry into the characteristic
      crusted or necrotic center.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - Hemorrhagic necrosis and surface exudate
    hypothesis_groups:
    - cytotoxic_t_cell_epidermal_injury_model
    evidence:
    - reference: PMID:37847066
      reference_title: "Dermoscopy as a diagnostic aid in pityriasis lichenoides et varioliformis acuta."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "papules with a crusted and/or necrotic centre"
      explanation: >-
        This PLEVA series directly links papules with crusted or necrotic
        centers.
  - target: Scaling skin
    description: >-
      Interface epidermal injury and altered surface keratinization produce
      scale over erythematous papules.
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    hypothesis_groups:
    - cytotoxic_t_cell_epidermal_injury_model
    evidence:
    - reference: PMID:31334928
      reference_title: "An Atypical Presentation of PLEVA: Case Report and Review of the Literature."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        PLEVA is characterized by the sudden onset of scaly, erythematous
        macules and papules
      explanation: >-
        The clinical association supports scaling downstream of lesional
        epidermal injury, but not the detailed keratinization mechanism.
  - target: Skin ulcer
    description: >-
      In ordinary PLEVA, sufficiently deep focal epidermal necrosis can expose
      a small necrotic ulcer; rapidly coalescing generalized ulcers define the
      separate FUMHD severity branch.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - Focal epidermal necrosis and surface loss
    hypothesis_groups:
    - cytotoxic_t_cell_epidermal_injury_model
    evidence:
    - reference: DOI:10.1007/s13671-023-00380-1
      reference_title: "Pityriasis Lichenoides Following SARS-CoV-2 Infection/Vaccination"
      supports: SUPPORT
      evidence_source: OTHER
      snippet: >-
        PLEVA onsets acutely/subacutely with the eruption of polymorphous
        lesions ranging from macules, to hemorrhagic papules, to ulcers
      explanation: >-
        This review supports ulcers within the ordinary PLEVA morphology, while
        not directly testing the proposed injury-to-ulcer mechanism.
  - target: Scarring
    description: >-
      Epidermal necrosis with dermal damage can heal with a varioliform scar.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - Necrotic tissue loss and repair
    hypothesis_groups:
    - cytotoxic_t_cell_epidermal_injury_model
    evidence:
    - reference: DOI:10.35755/jmedassocthai.2025.5.377-383-02606
      reference_title: "Pityriasis Lichenoides in Thai Children: A 10-Years Review of Clinical and Treatment Outcome"
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Dyspigmentation was predominantly observed in PLC, whereas varioliform
        scarring was more common in PLEVA (p<0.05).
      explanation: >-
        This pediatric retrospective series directly associates varioliform
        scarring with PLEVA but does not test the proposed repair mechanism.
  - target: Hypopigmented skin patches
    description: >-
      Resolution of inflamed or necrotic lesions can leave post-inflammatory
      hypopigmented macules.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - Post-inflammatory pigmentary alteration
    hypothesis_groups:
    - cytotoxic_t_cell_epidermal_injury_model
    evidence:
    - reference: PMID:37155724
      reference_title: "Acute lichenoid and varioliform pityriasis in a pediatric patient."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "multiple erythematous lesions that disappeared leaving hypopigmented macules."
      explanation: >-
        This PLEVA case directly supports residual hypopigmentation.
  - target: Ulceronecrotic systemic inflammatory escalation in FUMHD
    description: >-
      In a minority of patients the PLEVA cytotoxic/keratinocyte-necrosis process
      escalates into the fulminant ulceronecrotic, febrile FUMHD branch; the host
      or lesional factor that determines escalation is unknown. This edge states
      the severe-branch relationship that is the entry's thesis, linking the
      shared PLEVA pathophysiology to the FUMHD escalation node.
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    hypothesis_groups:
    - systemic_hyperinflammatory_escalation_model
    evidence:
    - reference: PMID:15840118
      reference_title: "Transition of pityriasis lichenoides et varioliformis acuta to febrile ulceronecrotic Mucha-Habermann disease is associated with elevated serum tumour necrosis factor-alpha."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Our case demonstrates the clinical and histological continuum between
        'classical' PLEVA and FUMHD
      explanation: >-
        A sequential single case documents the PLEVA-to-FUMHD continuum,
        supporting the escalation edge while leaving its driver unresolved
        (see the fumhd_escalation_driver knowledge gap).
- name: Perivascular lymphocytic inflammation and erythrocyte extravasation
  description: >-
    PLEVA can show perivascular lymphocytes and extravasated erythrocytes in
    superficial dermis and epidermis. Although sometimes called lymphocytic
    vasculitis, a series found no fibrinoid vessel-wall deposition and cautioned
    that this is not necessarily true destructive vasculitis.
  mechanism_confidence: ESTABLISHED
  locations:
  - preferred_term: dermis
    term:
      id: UBERON:0002067
      label: dermis
  cell_types:
  - preferred_term: T cell
    term:
      id: CL:0000084
      label: T cell
  - preferred_term: endothelial cell
    term:
      id: CL:0000115
      label: endothelial cell
  biological_processes:
  - preferred_term: inflammatory response
    modifier: ABNORMAL
    term:
      id: GO:0006954
      label: inflammatory response
  evidence:
  - reference: PMID:17456915
    reference_title: "A clinical and histopathological study of pityriasis lichenoides."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      All the cases of PLEVA showed lymphocytic vasculitis albeit without
      fibrinoid deposition in the vessel walls.
    explanation: >-
      The PLEVA subset supports lymphocytic vascular involvement while the
      absent fibrinoid deposition constrains the destructive-vasculitis label.
  - reference: PMID:17456915
    reference_title: "A clinical and histopathological study of pityriasis lichenoides."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Pityriasis lichenoides is not a rare disorder, and is not a true
      lymphocytic vasculitis as blood vessel damage and fibrinoid deposition in
      the blood vessel walls were not seen in this study.
    explanation: >-
      The mixed-spectrum study's conclusion directly qualifies the use of the
      vasculitis label.
  - reference: PMID:31880634
    reference_title: "Pityriasis Lichenoides: A Large Histopathological Case Series With a Focus on Adnexotropism."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Superficial perivascular and/or intraepidermal red blood cells were
      observed in 83% of cases.
    explanation: >-
      The mixed-PL series directly supports erythrocyte extravasation, but does
      not stratify this result by PLEVA versus PLC.
  downstream:
  - target: Purpura
    description: >-
      Extravasated erythrocytes and hemorrhagic change produce purpuric areas
      within evolving PLEVA lesions.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - Dermal and intraepidermal erythrocyte extravasation
    evidence:
    - reference: DOI:10.1007/s13671-023-00380-1
      reference_title: "Pityriasis Lichenoides Following SARS-CoV-2 Infection/Vaccination"
      supports: SUPPORT
      evidence_source: OTHER
      snippet: >-
        PLEVA onsets acutely/subacutely with the eruption of polymorphous
        lesions ranging from macules, to hemorrhagic papules, to ulcers
      explanation: >-
        The review supports hemorrhagic papules, consistent with red-cell
        extravasation, but does not test the proposed causal link.
- name: Ulceronecrotic systemic inflammatory escalation in FUMHD
  description: >-
    FUMHD is the severe PLEVA branch in which generalized ulceronecrotic
    papules coalesce into ulcers while fever and systemic inflammation develop;
    the extreme end can meet criteria for hemophagocytic lymphohistiocytosis
    (HLH). The molecular reason only a minority of patients enter this branch is
    unknown.
  subtypes:
  - Febrile ulceronecrotic Mucha-Habermann disease
  mechanism_confidence: PROVISIONAL
  biological_scale: ORGANISM
  biological_processes:
  - preferred_term: inflammatory response
    modifier: INCREASED
    term:
      id: GO:0006954
      label: inflammatory response
  - preferred_term: TNF-alpha-mediated signaling
    modifier: INCREASED
    term:
      id: GO:0033209
      label: tumor necrosis factor-mediated signaling pathway
  evidence:
  - reference: PMID:38959922
    reference_title: "Febrile ulceronecrotic Mucha-Habermann disease - a case and treatment review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Febrile ulceronecrotic Mucha-Habermann disease is a rare and severe
      variant of pityriasis lichenoides, characterized by sudden onset of
      generalized ulceronecrotic papules that rapidly coalesce into ulcers
      associated with high fever.
    explanation: >-
      This directly supports the paired ulceronecrotic and febrile severe
      phenotype, while not resolving its molecular driver.
  - reference: PMID:15840118
    reference_title: "Transition of pityriasis lichenoides et varioliformis acuta to febrile ulceronecrotic Mucha-Habermann disease is associated with elevated serum tumour necrosis factor-alpha."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      highly elevated serum levels of tumour necrosis factor (TNF)-alpha
    explanation: >-
      Markedly elevated serum TNF-alpha at the PLEVA-to-FUMHD transition supports
      a TNF-alpha amplification arm; causality is inferred from a single case.
  downstream:
  - target: Skin ulcer
    description: Generalized ulceronecrotic papules rapidly coalesce into ulcers in FUMHD.
    causal_link_type: UNKNOWN
    evidence:
    - reference: PMID:38959922
      reference_title: "Febrile ulceronecrotic Mucha-Habermann disease - a case and treatment review."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "generalized ulceronecrotic papules that rapidly coalesce into ulcers"
      explanation: This directly supports extensive ulcer formation in FUMHD.
  - target: Fever
    description: High fever accompanies the ulceronecrotic eruption and defines FUMHD.
    causal_link_type: UNKNOWN
    evidence:
    - reference: PMID:38959922
      reference_title: "Febrile ulceronecrotic Mucha-Habermann disease - a case and treatment review."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "associated with high fever."
      explanation: This directly supports fever as a defining FUMHD feature.
  - target: Disseminated intravascular coagulation
    description: Systemic inflammation in FUMHD can be complicated by disseminated intravascular coagulation.
    causal_link_type: UNKNOWN
    hypothesis_groups:
    - systemic_hyperinflammatory_escalation_model
    evidence:
    - reference: PMID:38959922
      reference_title: "Febrile ulceronecrotic Mucha-Habermann disease - a case and treatment review."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Systemic manifestations such as intravascular disseminated coagulation
        and pulmonary, cardiac, gastrointestinal, and central nervous system
        involvement are common.
      explanation: This lists intravascular disseminated coagulation among FUMHD complications.
  - target: Sepsis
    description: >-
      Extensive cutaneous ulceration and systemic involvement predispose to
      sepsis, the leading contributor to FUMHD mortality.
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    evidence:
    - reference: PMID:34287852
      reference_title: "Mucha-Habermann disease: a pediatric case report and proposal of a risk score."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Risk factors for a fatal outcome (likelihood ratio; P) were sepsis
        (24.97, P < 0.001), adult vs. pediatric patient age (11.19; P = 0.001),
        systemic involvement (19.97, P < 0.001), and mucosal involvement (4.58;
        P = 0.032).
      explanation: >-
        Sepsis is the strongest fatal-outcome risk factor, supporting the
        ulceration-to-sepsis mortality route in FUMHD.
histopathology:
- name: Interface injury with vacuolar change and necrotic keratinocytes
  description: >-
    PLEVA biopsy shows interface epidermal injury with vacuolar change and
    necrotic keratinocytes. The pattern is supportive in the correct clinical
    setting but not independently pathognomonic.
  diagnostic: false
  evidence:
  - reference: PMID:31880634
    reference_title: "Pityriasis Lichenoides: A Large Histopathological Case Series With a Focus on Adnexotropism."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "vacuolar changes or necrotic keratinocytes (100%)"
    explanation: >-
      The large PL case series supports the microscopic finding, although the
      abstract does not stratify PLEVA and PLC.
  - reference: PMID:37155724
    reference_title: "Acute lichenoid and varioliform pityriasis in a pediatric patient."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "lymphocytic vasculitis (LV) with focal epidermal necrosis"
    explanation: A biopsy-confirmed PLEVA case directly supports focal epidermal necrosis.
- name: CD8-positive and TIA-1-positive cytotoxic T-cell-rich infiltrate
  description: >-
    Compared with common inflammatory dermatoses, PLEVA lesions contain more
    CD8-positive and TIA-1-positive cells. This helps substantiate a cytotoxic
    lesional phenotype but is not a stand-alone diagnostic test.
  diagnostic: false
  evidence:
  - reference: PMID:38973067
    reference_title: "Immunophenotyping and viral studies in pityriasis lichenoides et varioliformis acuta lesions."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The numbers of CD8+ T cells and T-cell intracellular antigen-1 (TIA-1)+
      cells were statistically significantly higher in PLEVA compared to the
      ID group.
    explanation: >-
      This PLEVA-specific study directly supports the cytotoxic
      immunophenotype.
- name: Perivascular lymphocytes and erythrocyte extravasation
  description: >-
    Superficial perivascular lymphocytes and red-cell extravasation contribute
    to the hemorrhagic appearance. Fibrinoid vessel-wall necrosis is not a
    consistent requirement, so the finding should not be equated automatically
    with destructive vasculitis.
  diagnostic: false
  evidence:
  - reference: PMID:17456915
    reference_title: "A clinical and histopathological study of pityriasis lichenoides."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      All the cases of PLEVA showed lymphocytic vasculitis albeit without
      fibrinoid deposition in the vessel walls.
    explanation: >-
      The PLEVA subset supports perivascular lymphocytic change and explicitly
      documents the absent fibrinoid deposition.
  - reference: PMID:17456915
    reference_title: "A clinical and histopathological study of pityriasis lichenoides."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Pityriasis lichenoides is not a rare disorder, and is not a true
      lymphocytic vasculitis as blood vessel damage and fibrinoid deposition in
      the blood vessel walls were not seen in this study.
    explanation: >-
      The broader PL conclusion supports describing this as a vascular-associated
      pattern rather than proven destructive vasculitis.
  - reference: PMID:31880634
    reference_title: "Pityriasis Lichenoides: A Large Histopathological Case Series With a Focus on Adnexotropism."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Superficial perivascular and/or intraepidermal red blood cells were
      observed in 83% of cases.
    explanation: >-
      This mixed-PL series supports the red-cell extravasation component.
- name: Atypical CD8-positive lymphomatoid infiltrate with lymphomatoid vasculitis (FUMHD)
  description: >-
    Severe FUMHD can show a dermal and subcutaneous infiltrate of atypical
    CD8-positive lymphocytes with loss of CD5 and reduced CD7 and features of
    lymphomatoid vasculitis, overlapping histologically with cutaneous T-cell
    lymphoma. This is a severe-variant finding, not typical of ordinary PLEVA.
  diagnostic: false
  evidence:
  - reference: PMID:38457671
    reference_title: "Febrile Ulceronecrotic Mucha-Habermann Disease Associated With Hemophagocytic Lymphohistiocytosis: A Case Report and Review of the Literature."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Biopsy indicated a dermal and subcutaneous infiltrate of atypical CD8 +
      lymphocytes with loss of CD5 and reduction in CD7 expression, along with
      features of lymphomatoid vasculitis.
    explanation: This documents the atypical CD8-positive lymphomatoid infiltrate at the severe FUMHD end.
phenotypes:
- category: Dermatologic
  name: Papulovesicular eruption
  description: >-
    The hallmark is an abrupt crop of erythematous papules or
    papulovesicles, often with lesions at several stages simultaneously.
  diagnostic: true
  phenotype_term:
    preferred_term: Papulovesicular eruption
    term:
      id: HP:0033700
      label: Papulovesicular eruption
  evidence:
  - reference: PMID:8864599
    reference_title: "Mucha-Habermann disease and its febrile ulceronecrotic variant."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "abrupt onset of papulovesicular eruptions"
    explanation: This directly supports the hallmark PLEVA morphology and onset.
  - reference: PMID:37847066
    reference_title: "Dermoscopy as a diagnostic aid in pityriasis lichenoides et varioliformis acuta."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      characteristic pattern of lesions in different stages of development,
      ranging from erythematous maculopapules to papules with a crusted and/or
      necrotic centre.
    explanation: This directly supports the polymorphous papular eruption.
- category: Dermatologic
  name: Crusted skin lesions
  description: Hemorrhagic or necrotic centers form adherent crusts as lesions evolve.
  phenotype_term:
    preferred_term: Crusted skin lesions
    term:
      id: HP:0007473
      label: Crusting erythematous dermatitis
  evidence:
  - reference: PMID:37847066
    reference_title: "Dermoscopy as a diagnostic aid in pityriasis lichenoides et varioliformis acuta."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "papules with a crusted and/or necrotic centre."
    explanation: This PLEVA report directly supports crusted lesion centers.
- category: Dermatologic
  name: Scaling skin
  description: Fine scale can overlie early erythematous macules and papules.
  phenotype_term:
    preferred_term: Scaling skin
    term:
      id: HP:0040189
      label: Scaling skin
  evidence:
  - reference: PMID:31334928
    reference_title: "An Atypical Presentation of PLEVA: Case Report and Review of the Literature."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Clinically, PLEVA is characterized by the sudden onset of scaly,
      erythematous macules and papules localized to the trunk and proximal
      extremities.
    explanation: This PLEVA-specific statement directly supports scaling.
- category: Dermatologic
  name: Purpura
  description: Hemorrhagic evolution and erythrocyte extravasation can produce purpuric areas.
  phenotype_term:
    preferred_term: Purpura
    term:
      id: HP:0000979
      label: Purpura
  evidence:
  - reference: DOI:10.1007/s13671-023-00380-1
    reference_title: "Pityriasis Lichenoides Following SARS-CoV-2 Infection/Vaccination"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      PLEVA onsets acutely/subacutely with the eruption of polymorphous lesions
      ranging from macules, to hemorrhagic papules, to ulcers
    explanation: >-
      This review directly supports hemorrhagic papules, which are represented
      here by the closest available purpura term.
- category: Dermatologic
  name: Skin ulcer
  description: >-
    Focal necrotic ulcers can occur in PLEVA. Generalized ulceronecrotic papules
    that rapidly coalesce into large ulcers belong to the severe FUMHD subtype.
  phenotype_term:
    preferred_term: Skin ulcer
    term:
      id: HP:0200042
      label: Skin ulcer
  evidence:
  - reference: DOI:10.1007/s13671-023-00380-1
    reference_title: "Pityriasis Lichenoides Following SARS-CoV-2 Infection/Vaccination"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      PLEVA onsets acutely/subacutely with the eruption of polymorphous lesions
      ranging from macules, to hemorrhagic papules, to ulcers
    explanation: This review directly includes ulcers in the PLEVA lesion spectrum.
  - reference: PMID:38959922
    reference_title: "Febrile ulceronecrotic Mucha-Habermann disease - a case and treatment review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "generalized ulceronecrotic papules that rapidly coalesce into ulcers"
    explanation: >-
      This separately supports the extensive ulcer phenotype in FUMHD.
- category: Dermatologic
  name: Pruritus
  description: Itch may accompany the eruption, but lesions can also be asymptomatic.
  phenotype_term:
    preferred_term: Pruritus
    term:
      id: HP:0000989
      label: Pruritus
  evidence:
  - reference: DOI:10.1007/s13671-013-0054-x
    reference_title: "Pityriasis Lichenoides and Cutaneous T Cell Lymphoma: An Update on the Diagnosis and Management of the Most Common Benign and Malignant Cutaneous Lymphoproliferative Diseases in Children"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      the acute onset of pruritic and at times painful, symptomatic
      papulovesicles with necrotic, ulcerative or hemorrhagic changes.
    explanation: This pediatric review directly supports pruritus in PLEVA.
- category: Dermatologic
  name: Scarring
  description: Deeper necrotic lesions may heal with small varioliform scars.
  phenotype_term:
    preferred_term: Scarring
    term:
      id: HP:0100699
      label: Scarring
  evidence:
  - reference: DOI:10.35755/jmedassocthai.2025.5.377-383-02606
    reference_title: "Pityriasis Lichenoides in Thai Children: A 10-Years Review of Clinical and Treatment Outcome"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Dyspigmentation was predominantly observed in PLC, whereas varioliform
      scarring was more common in PLEVA (p<0.05).
    explanation: >-
      This retrospective pediatric series directly supports varioliform
      scarring but included only ten PLEVA cases.
- category: Dermatologic
  name: Hypopigmented skin patches
  description: Healed lesions can leave post-inflammatory hypopigmented macules.
  phenotype_term:
    preferred_term: Hypopigmented skin patches
    term:
      id: HP:0001053
      label: Hypopigmented skin patches
  evidence:
  - reference: PMID:37155724
    reference_title: "Acute lichenoid and varioliform pityriasis in a pediatric patient."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "multiple erythematous lesions that disappeared leaving hypopigmented macules."
    explanation: This directly supports residual hypopigmented macules.
- category: Constitutional
  name: Fever
  context: Febrile ulceronecrotic Mucha-Habermann disease only
  subtypes:
  - Febrile ulceronecrotic Mucha-Habermann disease
  severity: SEVERE
  description: High fever is a defining systemic feature of FUMHD, not ordinary PLEVA.
  phenotype_term:
    preferred_term: Fever
    term:
      id: HP:0001945
      label: Fever
  evidence:
  - reference: PMID:38959922
    reference_title: "Febrile ulceronecrotic Mucha-Habermann disease - a case and treatment review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "associated with high fever."
    explanation: This directly supports fever in the FUMHD subtype.
- category: Dermatologic
  name: Cutaneous necrosis
  context: Febrile ulceronecrotic Mucha-Habermann disease only
  subtypes:
  - Febrile ulceronecrotic Mucha-Habermann disease
  description: Rapidly necrotic (ulceronecrotic) skin lesions are central to FUMHD morphology.
  phenotype_term:
    preferred_term: Cutaneous necrosis
    term:
      id: HP:0033126
      label: Cutaneous necrosis
  evidence:
  - reference: PMID:38959922
    reference_title: "Febrile ulceronecrotic Mucha-Habermann disease - a case and treatment review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "generalized ulceronecrotic papules that rapidly coalesce into ulcers"
    explanation: The ulceronecrotic morphology that defines FUMHD directly denotes cutaneous necrosis.
- category: Dermatologic
  name: Hemorrhagic bullae
  context: Febrile ulceronecrotic Mucha-Habermann disease only
  subtypes:
  - Febrile ulceronecrotic Mucha-Habermann disease
  description: Hemorrhagic bullae can accompany the ulceronecrotic eruption in FUMHD.
  phenotype_term:
    preferred_term: Hemorrhagic bullae
    term:
      id: HP:0008066
      label: Abnormal blistering of the skin
  evidence:
  - reference: PMID:38457671
    reference_title: "Febrile Ulceronecrotic Mucha-Habermann Disease Associated With Hemophagocytic Lymphohistiocytosis: A Case Report and Review of the Literature."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Febrile ulceronecrotic MHD (FUMHD) represents a severe variant of MHD,
      marked by ulcers, hemorrhagic bullae, and systemic symptoms.
    explanation: This FUMHD paper directly lists hemorrhagic bullae; the closest available HP term for bullous skin lesions is used.
- category: Mucosal
  name: Mucosal involvement
  context: Febrile ulceronecrotic Mucha-Habermann disease only
  subtypes:
  - Febrile ulceronecrotic Mucha-Habermann disease
  description: >-
    Mucosal (including oral) involvement occurs in FUMHD. It was reported as a
    mortality risk factor in one 119-case analysis but was NOT confirmed as an
    independent predictor of mortality in a second 68-patient systematic review,
    so its prognostic weight is contested.
  phenotype_term:
    preferred_term: Mucosal involvement
    term:
      id: HP:0000155
      label: Oral ulcer
  evidence:
  - reference: PMID:34287852
    reference_title: "Mucha-Habermann disease: a pediatric case report and proposal of a risk score."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "mucosal involvement (4.58; P = 0.032)"
    explanation: >-
      Mucosal involvement is quantified as a fatal-outcome risk factor in this
      119-case analysis; the closest HP term (oral ulcer) anchors mucosal
      involvement, which in FUMHD is not restricted to the oral cavity.
  - reference: PMID:36483219
    reference_title: "Mortality risk factors in febrile ulceronecrotic Mucha- Habermann disease: A systematic review of therapeutic outcomes and complications."
    supports: REFUTE
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Increased age, systemic involvement, and monoclonal T-cell receptor
      rearrangement were associated with worst prognosis, but mucosal
      involvement did not affect mortality risk
    explanation: >-
      An independent 68-patient systematic review found mucosal involvement did
      NOT affect mortality risk, contradicting its prognostic weight.
- category: Hematologic
  name: Disseminated intravascular coagulation
  context: Febrile ulceronecrotic Mucha-Habermann disease only
  subtypes:
  - Febrile ulceronecrotic Mucha-Habermann disease
  description: Disseminated intravascular coagulation is among the common systemic complications of FUMHD.
  phenotype_term:
    preferred_term: Disseminated intravascular coagulation
    term:
      id: HP:0005521
      label: Disseminated intravascular coagulation
  evidence:
  - reference: PMID:38959922
    reference_title: "Febrile ulceronecrotic Mucha-Habermann disease - a case and treatment review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Systemic manifestations such as intravascular disseminated coagulation
      and pulmonary, cardiac, gastrointestinal, and central nervous system
      involvement are common.
    explanation: This directly lists intravascular disseminated coagulation as a FUMHD complication.
- category: Constitutional
  name: Sepsis
  context: Febrile ulceronecrotic Mucha-Habermann disease only
  subtypes:
  - Febrile ulceronecrotic Mucha-Habermann disease
  description: Sepsis is a frequent cause of death in FUMHD and its strongest reported risk factor for a fatal outcome.
  phenotype_term:
    preferred_term: Sepsis
    term:
      id: HP:0100806
      label: Sepsis
  evidence:
  - reference: PMID:34287852
    reference_title: "Mucha-Habermann disease: a pediatric case report and proposal of a risk score."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Risk factors for a fatal outcome (likelihood ratio; P) were sepsis
      (24.97, P < 0.001), adult vs. pediatric patient age (11.19; P = 0.001),
      systemic involvement (19.97, P < 0.001), and mucosal involvement (4.58;
      P = 0.032).
    explanation: This directly supports sepsis as the leading FUMHD fatal-outcome risk factor.
  - reference: PMID:35950146
    reference_title: "Febrile Ulceronecrotic Mucha-Habermann Disease: A Case Report and a Systematic Review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "more positive skin bacterial cultures (31/41, 75.6%)"
    explanation: A high rate of positive skin bacterial cultures supports the infection/sepsis burden of the denuded FUMHD skin.
- category: Respiratory
  name: Pulmonary involvement
  context: Febrile ulceronecrotic Mucha-Habermann disease only
  subtypes:
  - Febrile ulceronecrotic Mucha-Habermann disease
  description: Pulmonary involvement is among the systemic complications reported as common in FUMHD.
  phenotype_term:
    preferred_term: Pulmonary involvement
    term:
      id: HP:0002086
      label: Abnormality of the respiratory system
  evidence:
  - reference: PMID:38959922
    reference_title: "Febrile ulceronecrotic Mucha-Habermann disease - a case and treatment review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Systemic manifestations such as intravascular disseminated coagulation
      and pulmonary, cardiac, gastrointestinal, and central nervous system
      involvement are common.
    explanation: This review lists pulmonary involvement among the common FUMHD systemic manifestations.
- category: Cardiovascular
  name: Cardiac involvement
  context: Febrile ulceronecrotic Mucha-Habermann disease only
  subtypes:
  - Febrile ulceronecrotic Mucha-Habermann disease
  description: Cardiac involvement is among the systemic complications reported as common in FUMHD.
  phenotype_term:
    preferred_term: Cardiac involvement
    term:
      id: HP:0001626
      label: Abnormality of the cardiovascular system
  evidence:
  - reference: PMID:38959922
    reference_title: "Febrile ulceronecrotic Mucha-Habermann disease - a case and treatment review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Systemic manifestations such as intravascular disseminated coagulation
      and pulmonary, cardiac, gastrointestinal, and central nervous system
      involvement are common.
    explanation: This review lists cardiac involvement among the common FUMHD systemic manifestations.
- category: Gastrointestinal
  name: Gastrointestinal involvement
  context: Febrile ulceronecrotic Mucha-Habermann disease only
  subtypes:
  - Febrile ulceronecrotic Mucha-Habermann disease
  description: Gastrointestinal involvement is among the systemic complications reported as common in FUMHD.
  phenotype_term:
    preferred_term: Gastrointestinal involvement
    term:
      id: HP:0011024
      label: Abnormality of the gastrointestinal tract
  evidence:
  - reference: PMID:38959922
    reference_title: "Febrile ulceronecrotic Mucha-Habermann disease - a case and treatment review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Systemic manifestations such as intravascular disseminated coagulation
      and pulmonary, cardiac, gastrointestinal, and central nervous system
      involvement are common.
    explanation: This review lists gastrointestinal involvement among the common FUMHD systemic manifestations.
- category: Neurologic
  name: Central nervous system involvement
  context: Febrile ulceronecrotic Mucha-Habermann disease only
  subtypes:
  - Febrile ulceronecrotic Mucha-Habermann disease
  description: Central nervous system involvement (including seizures) is among the systemic complications reported in FUMHD.
  phenotype_term:
    preferred_term: Central nervous system involvement
    term:
      id: HP:0000707
      label: Abnormality of the nervous system
  evidence:
  - reference: PMID:38959922
    reference_title: "Febrile ulceronecrotic Mucha-Habermann disease - a case and treatment review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Systemic manifestations such as intravascular disseminated coagulation
      and pulmonary, cardiac, gastrointestinal, and central nervous system
      involvement are common.
    explanation: This review lists central nervous system involvement among the common FUMHD systemic manifestations.
- category: Neurologic
  name: Seizures
  context: Febrile ulceronecrotic Mucha-Habermann disease only
  subtypes:
  - Febrile ulceronecrotic Mucha-Habermann disease
  description: A child with FUMHD and central nervous system involvement presented with seizures.
  phenotype_term:
    preferred_term: Seizure
    term:
      id: HP:0001250
      label: Seizure
  evidence:
  - reference: PMID:38234081
    reference_title: "Rapid recovery in a child with febrile ulceronecrotic Mucha-Habermann disease following intravenous immunoglobulin administration."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "with FUMHD and seizures"
    explanation: This case directly documents seizures as a CNS manifestation in a child with FUMHD.
- category: Hematologic
  name: Thrombocytopenia
  context: Febrile ulceronecrotic Mucha-Habermann disease only
  subtypes:
  - Febrile ulceronecrotic Mucha-Habermann disease
  description: Marked thrombocytopenia has been reported at admission in FUMHD.
  phenotype_term:
    preferred_term: Thrombocytopenia
    term:
      id: HP:0001873
      label: Thrombocytopenia
  evidence:
  - reference: PMID:34287852
    reference_title: "Mucha-Habermann disease: a pediatric case report and proposal of a risk score."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "marked leukopenia and thrombocytopenia at admission"
    explanation: This FUMHD case directly documents marked thrombocytopenia at admission.
- category: Hematologic
  name: Leukopenia
  context: Febrile ulceronecrotic Mucha-Habermann disease only
  subtypes:
  - Febrile ulceronecrotic Mucha-Habermann disease
  description: Marked leukopenia has been reported at admission in FUMHD.
  phenotype_term:
    preferred_term: Leukopenia
    term:
      id: HP:0001882
      label: Decreased total leukocyte count
  evidence:
  - reference: PMID:34287852
    reference_title: "Mucha-Habermann disease: a pediatric case report and proposal of a risk score."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "marked leukopenia and thrombocytopenia at admission"
    explanation: This FUMHD case directly documents marked leukopenia at admission.
environmental:
- name: Temporally associated infectious, medication, and vaccination exposures
  description: >-
    Infections, medications, and vaccinations have preceded PL or PLEVA in
    reports and small cohorts. These observations support an antigen-trigger
    hypothesis only; they do not prove that a specific exposure caused PLEVA,
    and PLEVA-specific lesion testing did not detect the common viruses assayed.
  evidence:
  - reference: PMID:38677323
    reference_title: "Pityriasis lichenoides: assessment of 41 pediatric patients."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The frequency peaks coincided with infectious outbreaks."
    explanation: >-
      The cohort supports temporal clustering for pediatric PL, but included
      mostly PLC and does not prove a PLEVA cause.
  - reference: PMID:36688177
    reference_title: "Pityriasis Lichenoides Following SARS-CoV-2 Infection/Vaccination."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      This review cannot determine causality. However, a temporal association
      was observed with the case reports
    explanation: >-
      The review supports only a temporal SARS-CoV-2 infection or vaccination
      association and explicitly rejects causal certainty.
  - reference: PMID:25816855
    reference_title: "Pityriasis Lichenoides in Childhood: Review of Clinical Presentation and Treatment Options."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      The proposed etiologies are discussed, including its association with
      infectious agents, medications, and immunizations and evidence for PL as
      a lymphoproliferative disorder.
    explanation: >-
      This mixed-spectrum review documents the reported exposure categories
      without establishing that any exposure causes PLEVA.
  - reference: PMID:38973067
    reference_title: "Immunophenotyping and viral studies in pityriasis lichenoides et varioliformis acuta lesions."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Viral presence was not detected."
    explanation: >-
      PLEVA-specific lesional testing did not support persistent presence of
      the assayed viruses, constraining a direct viral-infection interpretation.
diagnosis:
- name: Clinical morphology with skin biopsy and clinicopathologic correlation
  description: >-
    Lesions at several stages suggest PLEVA, but biopsy is commonly needed
    because inflammatory eruptions and cutaneous lymphoproliferative disorders
    can mimic it. Histology must be interpreted with the distribution, lesion
    evolution, and clinical course.
  diagnosis_term:
    preferred_term: skin biopsy
    term:
      id: NCIT:C51692
      label: Skin Biopsy
  results: >-
    Supportive findings include interface or lichenoid dermatitis, vacuolar
    change or necrotic keratinocytes, superficial and deep lymphocytes,
    lymphocytes in adnexal epithelium, perivascular or intraepidermal
    erythrocytes, and a CD8/TIA-1-rich infiltrate. No single feature is
    pathognomonic.
  evidence:
  - reference: PMID:37155724
    reference_title: "Acute lichenoid and varioliform pityriasis in a pediatric patient."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The diagnosis is made by clinical suspicion and confirmed by histology."
    explanation: This directly supports clinical suspicion followed by histologic confirmation.
  - reference: PMID:31880634
    reference_title: "Pityriasis Lichenoides: A Large Histopathological Case Series With a Focus on Adnexotropism."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      the histopathological assessment of a biopsy is sometimes needed to
      differentiate between PL and a range of other diseases.
    explanation: >-
      This mixed-PL series supports biopsy for difficult differentials.
  - reference: PMID:31880634
    reference_title: "Pityriasis Lichenoides: A Large Histopathological Case Series With a Focus on Adnexotropism."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      both superficial and deep lymphocytic infiltrates (99%), and the
      infiltration of lymphocytes into the adnexal epithelium (97%).
    explanation: >-
      This large mixed-PL series supplies the deep and adnexal infiltrate
      findings but did not stratify them by PLEVA versus PLC.
- name: Dermoscopy as a noninvasive diagnostic adjunct
  description: >-
    Punctate or glomerular vessels and erythematous globules around an orange
    or crusted center can support a rapid clinical impression, but dermoscopy
    does not replace biopsy when the diagnosis or lymphoma differential remains
    uncertain.
  results: >-
    Punctate or glomerular vessels and erythematous globules surrounding a
    homogeneous orange or crusty central area.
  evidence:
  - reference: PMID:37847066
    reference_title: "Dermoscopy as a diagnostic aid in pityriasis lichenoides et varioliformis acuta."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Observation of the dermatoscopic findings described, such as punctate or
      glomerular vessels and erythematous globules surrounding a homogeneous
      orange or crusty central area, may allow for a rapid diagnosis, avoiding
      the need for invasive techniques.
    explanation: This three-case PLEVA report supports dermoscopy as an adjunct.
- name: Clinicopathologic and phenotypic assessment of atypical or persistent lesions
  description: >-
    For atypical or persistent lesions, or when mycosis fungoides or
    lymphomatoid papulosis is considered, complete phenotypic analysis should be
    integrated with morphology and clinical course. Molecular clonality should
    not be interpreted alone.
  results: >-
    In one comparative series, molecular clonality did not differ meaningfully
    among conventional PL, atypical PL, lymphomatoid papulosis, and mycosis
    fungoides, making an isolated clonality result nondiscriminating.
  evidence:
  - reference: PMID:29851705
    reference_title: "Pityriasis Lichenoides, Atypical Pityriasis Lichenoides, and Related Conditions: A Study of 66 Cases."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      clinicopathologic correlation and complete phenotypic analyses are
      paramount in order to achieve proper classification.
    explanation: >-
      This study of conventional PL, atypical PL, LyP, and MF supports integrated
      classification rather than reliance on a single marker.
  - reference: PMID:29851705
    reference_title: "Pityriasis Lichenoides, Atypical Pityriasis Lichenoides, and Related Conditions: A Study of 66 Cases."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Molecular analyses of clonality of the infiltrate did not reveal relevant
      differences among these 4 groups.
    explanation: >-
      Clonality alone did not distinguish conventional PL, atypical PL,
      lymphomatoid papulosis, and mycosis fungoides in this series.
- name: Clinicopathologic diagnosis of FUMHD with proposed criteria
  description: >-
    FUMHD is diagnosed clinicopathologically; Nofal et al. proposed a
    constant-plus-variable diagnostic-criteria framework, the closest to formal
    FUMHD criteria in the absence of a consensus definition.
  results: >-
    Constant clinical and histopathological features present in every case,
    combined with variable features present in some cases.
  evidence:
  - reference: PMID:26695875
    reference_title: "Febrile ulceronecrotic Mucha-Habermann disease: proposed diagnostic criteria and therapeutic evaluation."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      The first comprises constant clinical and histopathological features that
      are always present in every case
    explanation: Nofal et al. proposed a constant-plus-variable diagnostic-criteria framework for FUMHD.
differential_diagnoses:
- name: Pityriasis lichenoides chronica
  description: >-
    PLC is the chronic pole of the PL spectrum and may coexist or overlap with
    PLEVA. The distinction rests on the tempo and morphology of lesions plus
    clinicopathologic correlation rather than a rigid binary histologic test.
  distinguishing_features:
  - PLC has a more chronic, scaling papular course; PLEVA has abrupt papulovesicular or papulonecrotic crops.
  - Clinical and histopathologic overlap is common, so mixed presentations should be acknowledged.
  evidence:
  - reference: PMID:25816855
    reference_title: "Pityriasis Lichenoides in Childhood: Review of Clinical Presentation and Treatment Options."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      It is often classified into the acute form, pityriasis lichenoides et
      varioliformis acuta (PLEVA), and the chronic form, pityriasis lichenoides
      chronica (PLC).
    explanation: This review directly establishes the acute/chronic spectrum boundary.
  - reference: PMID:25816855
    reference_title: "Pityriasis Lichenoides in Childhood: Review of Clinical Presentation and Treatment Options."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      in many cases, there is clinical and histopathologic overlap between the
      two phenotypes.
    explanation: This supports caution against treating PLEVA and PLC as perfectly separable.
- name: Cutaneous CD8-positive necrotizing angiocentric lymphoproliferative disease
  description: >-
    Severe FUMHD can mimic an aggressive CD8-positive angiocentric cutaneous
    T-cell lymphoproliferative disease, and the atypical lymphomatoid
    immunophenotype makes this the key differential for the FUMHD severity
    variant. It is the natural clinical partner to the atypical CD8-positive
    lymphomatoid histopathology of FUMHD.
  distinguishing_features:
  - FUMHD is self-limited/reactive and typically lacks a persistent monoclonal aggressive lymphoma course; clinicopathologic correlation and follow-up distinguish it.
  evidence:
  - reference: PMID:38457671
    reference_title: "Febrile Ulceronecrotic Mucha-Habermann Disease Associated With Hemophagocytic Lymphohistiocytosis: A Case Report and Review of the Literature."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      FUMHD should be considered in the differential diagnosis for patients
      presenting with cutaneous CD8 + necrotizing angiocentric
      lymphoproliferative disease complicated by HLH.
    explanation: This FUMHD paper directly frames the aggressive angiocentric CTCL differential.
- name: Lymphomatoid papulosis
  disease_term:
    preferred_term: lymphomatoid papulosis
    term:
      id: MONDO:0020326
      label: lymphomatoid papulosis
  description: >-
    Lymphomatoid papulosis can also produce recurrent self-healing papules and
    may be mistaken for atypical PL.
  distinguishing_features:
  - Waxing and waning papules or nodules with a CD30-positive atypical lymphoid infiltrate favor lymphomatoid papulosis.
  evidence:
  - reference: PMID:29851705
    reference_title: "Pityriasis Lichenoides, Atypical Pityriasis Lichenoides, and Related Conditions: A Study of 66 Cases."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Lymphomatoid papulosis (waxing and waning lesions and positivity for CD30)"
    explanation: This study directly identifies the key clinical and immunophenotypic distinction.
- name: Mycosis fungoides
  disease_term:
    preferred_term: mycosis fungoides
    term:
      id: MONDO:0009691
      label: mycosis fungoides
  description: >-
    Early or PL-like mycosis fungoides can overlap clinically and
    histologically with prolonged or atypical pityriasis lichenoides.
  distinguishing_features:
  - Persistent patches or larger plaques, increasing nuclear atypia, marked CD7/CD8 diminution, and concordant clonal TCR findings raise concern for MF.
  - Serial clinicopathologic assessment is more informative than clonality alone.
  evidence:
  - reference: PMID:29210716
    reference_title: "Relationship Between Pityriasis Lichenoides and Mycosis Fungoides: A Clinicopathological, Immunohistochemical, and Molecular Study."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Prolonged clinical course, appearance of patches and larger plaques,
      markedly increased lymphocytic nuclear atypia, marked diminution of
      apoptotic keratinocytes and CD7 and CD8 lymphocytes, and clonal T-cell
      receptor gene rearrangement may serve as clues.
    explanation: This PL follow-up study directly lists features concerning for MF.
- name: Guttate psoriasis
  disease_term:
    preferred_term: guttate psoriasis
    term:
      id: MONDO:0023297
      label: guttate psoriasis
  description: >-
    Guttate psoriasis can mimic the acute disseminated scaly papules of PLEVA.
  distinguishing_features:
  - PLEVA lesions evolve through vesiculation, hemorrhagic necrosis, and crusting, while clinicopathologic biopsy can resolve uncertain cases.
  evidence:
  - reference: DOI:10.70672/bcfbzp08
    reference_title: "Diagnostic Challenges of Pityriasis Lichenoides et Varioliformis Acuta (PLEVA)"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      A provisional diagnosis of guttate psoriasis with PLEVA as the
      differential diagnosis was made after a thorough history and examination.
    explanation: This PLEVA case directly documents the guttate-psoriasis diagnostic overlap.
- name: Varicella
  description: >-
    Early PLEVA may resemble varicella because both can present with an acute
    vesicular or crusted eruption.
  distinguishing_features:
  - Fever and mucous-membrane involvement favor varicella, while PLEVA generally has a more prolonged course.
  evidence:
  - reference: DOI:10.1007/s13671-013-0054-x
    reference_title: "Pityriasis Lichenoides and Cutaneous T Cell Lymphoma: An Update on the Diagnosis and Management of the Most Common Benign and Malignant Cutaneous Lymphoproliferative Diseases in Children"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "In its early presentations, the condition may be confused with varicella."
    explanation: This pediatric review directly identifies varicella as an early mimic.
  - reference: DOI:10.1007/s13671-013-0054-x
    reference_title: "Pityriasis Lichenoides and Cutaneous T Cell Lymphoma: An Update on the Diagnosis and Management of the Most Common Benign and Malignant Cutaneous Lymphoproliferative Diseases in Children"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      lack the typical fever and mucous membrane involvement seen in varicella,
      and the course of PLEV A is considerably more prolonged.
    explanation: This review supplies the main clinical distinctions.
treatments:
- name: Narrowband UVB phototherapy
  description: >-
    Narrowband UVB is the best-supported active treatment in pooled PL
    literature and is commonly favored when observation, topical measures, or
    antibiotics are insufficient. Evidence combines PLEVA and PLC, consists
    mostly of uncontrolled studies, and is vulnerable to spontaneous
    resolution and short follow-up.
  treatment_term:
    preferred_term: phototherapy
    term:
      id: NCIT:C15301
      label: Phototherapy
  target_phenotypes:
  - preferred_term: Papulovesicular eruption
    term:
      id: HP:0033700
      label: Papulovesicular eruption
  - preferred_term: Scaling skin
    term:
      id: HP:0040189
      label: Scaling skin
  evidence:
  - reference: PMID:31318465
    reference_title: "A systematic review of treatments for pityriasis lichenoides."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "According to the results of this review, we suggest narrow-band UVB phototherapy as first-line treatment."
    explanation: >-
      This systematic review supports NB-UVB as a proposed first-line PL
      treatment, but pooled acute and chronic disease.
  - reference: PMID:32112390
    reference_title: "Systematic review of the efficacies and adverse effects of treatments for pityriasis lichenoides."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "phototherapy led to complete remission in the highest proportion of patients"
    explanation: >-
      The pooled PL review favors phototherapy but concludes that evidence is
      not compelling enough for a high-certainty evidence-based approach.
- name: Oral erythromycin therapy
  description: >-
    Oral erythromycin is a commonly proposed initial systemic option,
    particularly in children. Its benefit may be anti-inflammatory rather than
    proof of an active bacterial cause, and response estimates are drawn from
    mixed PL cohorts.
  treatment_term:
    preferred_term: antimicrobial agent therapy
    term:
      id: NCIT:C15620
      label: Antibiotic Therapy
    therapeutic_agent:
    - preferred_term: erythromycin
      term:
        id: CHEBI:48923
        label: erythromycin
  target_phenotypes:
  - preferred_term: Papulovesicular eruption
    term:
      id: HP:0033700
      label: Papulovesicular eruption
  evidence:
  - reference: PMID:8864599
    reference_title: "Mucha-Habermann disease and its febrile ulceronecrotic variant."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "beginning with oral antibiotics, usually erythromycin, is recommended."
    explanation: This PLEVA/Mucha-Habermann review supports pediatric initial use.
  - reference: PMID:31318465
    reference_title: "A systematic review of treatments for pityriasis lichenoides."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Oral erythromycin showed clearance rates ranging between 66% and 83%"
    explanation: The estimate comes from pooled PL studies and is not PLEVA-stratified.
- name: Topical corticosteroid therapy
  description: >-
    Topical corticosteroids may be tried for inflammatory symptoms or itch, but
    they should not be presented as reliably disease-clearing monotherapy.
  treatment_term:
    preferred_term: topical corticosteroid therapy
    term:
      id: NCIT:C122078
      label: Topical Corticosteroid Therapy
    therapeutic_agent:
    - preferred_term: corticosteroid
      term:
        id: CHEBI:50858
        label: corticosteroid
  target_phenotypes:
  - preferred_term: Pruritus
    term:
      id: HP:0000989
      label: Pruritus
  evidence:
  - reference: PMID:32112390
    reference_title: "Systematic review of the efficacies and adverse effects of treatments for pityriasis lichenoides."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "topical corticosteroids were found to have been trialled in the highest number of patients."
    explanation: This supports common use, not high-certainty efficacy.
  - reference: PMID:23488769
    reference_title: "Pityriasis lichenoides in an Asian population."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Almost all patients did not respond to topical corticosteroids."
    explanation: >-
      This small, predominantly PLC series directly supports the caution that
      topical corticosteroids are not reliably disease-clearing.
- name: Methotrexate therapy for refractory or severe disease
  description: >-
    Low-dose methotrexate is reported for refractory PL and is among systemic
    options used for FUMHD. The ordinary-PL efficacy estimate comes from small,
    dated studies, and FUMHD evidence is case-based.
  treatment_term:
    preferred_term: methotrexate therapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: methotrexate
      term:
        id: CHEBI:44185
        label: methotrexate
  target_phenotypes:
  - preferred_term: Papulovesicular eruption
    term:
      id: HP:0033700
      label: Papulovesicular eruption
  - preferred_term: Skin ulcer
    term:
      id: HP:0200042
      label: Skin ulcer
  evidence:
  - reference: PMID:31318465
    reference_title: "A systematic review of treatments for pityriasis lichenoides."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "methotrexate up to 100% but in small and dated studies."
    explanation: >-
      The review documents a high reported clearance ceiling while explicitly
      warning that the underlying studies are small and dated.
  - reference: PMID:36483219
    reference_title: "Mortality risk factors in febrile ulceronecrotic Mucha- Habermann disease: A systematic review of therapeutic outcomes and complications."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Successful treatment modalities for FUMHD included antibiotics,
      antivirals, systemic steroids, Methotrexate (MTX), cyclophosphamide,
      Cyclosporine (CYA), Intravenous Immunoglobulins (IVIG), pentoxifylline,
      and ultraviolet B phototherapy.
    explanation: >-
      The FUMHD case-literature review includes methotrexate among successful
      regimens but cannot establish an optimal regimen.
- name: Prompt systemic and supportive management for FUMHD
  description: >-
    FUMHD warrants prompt specialist evaluation and management for systemic
    involvement and sepsis, with supportive care and individualized systemic
    anti-inflammatory or immunosuppressive therapy. No optimal regimen is
    established, and immunosuppression must be balanced against infectious
    mortality.
  treatment_term:
    preferred_term: corticosteroid agent therapy
    term:
      id: NCIT:C122080
      label: Systemic Corticosteroid Therapy
    therapeutic_agent:
    - preferred_term: corticosteroid
      term:
        id: CHEBI:50858
        label: corticosteroid
  target_phenotypes:
  - preferred_term: Skin ulcer
    term:
      id: HP:0200042
      label: Skin ulcer
  - preferred_term: Fever
    term:
      id: HP:0001945
      label: Fever
  evidence:
  - reference: PMID:38959922
    reference_title: "Febrile ulceronecrotic Mucha-Habermann disease - a case and treatment review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Treatment is based on oral corticosteroids, immunosuppressive drugs such
      as methotrexate, and general supportive treatment.
    explanation: This FUMHD review directly supports systemic and supportive management.
  - reference: PMID:36483219
    reference_title: "Mortality risk factors in febrile ulceronecrotic Mucha- Habermann disease: A systematic review of therapeutic outcomes and complications."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Although rare, the condition may progress to involve serious complications
      and even lead to fatal outcomes if diagnosis and appropriate treatment is
      delayed.
    explanation: This systematic review supports prompt assessment and treatment.
  - reference: PMID:34287852
    reference_title: "Mucha-Habermann disease: a pediatric case report and proposal of a risk score."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Risk factors for a fatal outcome (likelihood ratio; P) were sepsis (24.97,
      P < 0.001), adult vs. pediatric patient age (11.19; P = 0.001), systemic
      involvement (19.97, P < 0.001), and mucosal involvement (4.58; P = 0.032).
    explanation: >-
      The case-literature analysis directly supports assessing sepsis and
      systemic involvement as mortality risk factors.
  - reference: PMID:36483219
    reference_title: "Mortality risk factors in febrile ulceronecrotic Mucha- Habermann disease: A systematic review of therapeutic outcomes and complications."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      FUMHD is a diagnostic and therapeutic challenge due to the lack of clearly
      defined diagnostic criteria and optimum treatment.
    explanation: This systematic review supports the absence of an established optimal regimen.
  - reference: PMID:34287852
    reference_title: "Mucha-Habermann disease: a pediatric case report and proposal of a risk score."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      In FUMHD, immune-suppressive treatment intensity should be balanced
      against the mortality risk, as infectious complications are a frequent
      cause of death.
    explanation: This directly supports risk-adapted rather than reflexively maximal immunosuppression.
- name: Intravenous immunoglobulin (IVIG) for FUMHD
  description: >-
    Intravenous immunoglobulin has produced rapid disease control in FUMHD,
    including in a child refractory to steroids, methotrexate, dapsone, and
    erythromycin; it is among the reported successful FUMHD modalities.
  therapeutic_modality: OTHER
  treatment_term:
    preferred_term: Intravenous Immunoglobulin Therapy
    term:
      id: NCIT:C121331
      label: Intravenous Immunoglobulin Therapy
  target_phenotypes:
  - preferred_term: Fever
    term:
      id: HP:0001945
      label: Fever
  evidence:
  - reference: PMID:38234081
    reference_title: "Rapid recovery in a child with febrile ulceronecrotic Mucha-Habermann disease following intravenous immunoglobulin administration."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      improved rapidly and achieved disease control with just a single infusion
      of low-dose intravenous immunoglobulin.
    explanation: This case directly supports IVIG achieving rapid FUMHD control after other agents failed.
- name: TNF-alpha inhibitor therapy for FUMHD
  description: >-
    TNF-alpha inhibitors (e.g., infliximab, often with IVIG) are reported for
    refractory FUMHD and are mechanistically rational given the elevated serum
    TNF-alpha at the PLEVA-to-FUMHD transition. Response is not uniform - at
    least one infant died despite a TNF-alpha inhibitor - so this remains a
    case-based option, not established therapy.
  therapeutic_modality: MONOCLONAL_ANTIBODY
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: infliximab
      term:
        id: NCIT:C1789
        label: Infliximab
  target_phenotypes:
  - preferred_term: Skin ulcer
    term:
      id: HP:0200042
      label: Skin ulcer
  target_mechanisms:
  - target: Ulceronecrotic systemic inflammatory escalation in FUMHD
    treatment_effect: INHIBITS
    description: >-
      TNF-alpha inhibition targets the TNF-alpha amplification arm (GO:0033209)
      of the FUMHD systemic inflammatory escalation node.
  evidence:
  - reference: PMID:23391565
    reference_title: "Febrile ulceronecrotic Mucha-Habermann disease: treatment with infliximab and intravenous immunoglobulins and review of the literature."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "TNFα inhibitors may be useful, particularly in resistant cases"
    explanation: This report of infliximab plus IVIG supports TNF-alpha inhibition in resistant FUMHD.
  - reference: PMID:42178566
    reference_title: "A fatal pediatric case of febrile ulceronecrotic Mucha-Habermann disease: diagnostic and therapeutic challenges: a case report."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Despite treatment with methylprednisolone, intravenous immunoglobulin, and
      a TNF-α inhibitor, the disease was fatal.
    explanation: A fatal infant case despite a TNF-alpha inhibitor shows the response is not uniform.
- name: Ciclosporin therapy for FUMHD
  description: >-
    Ciclosporin is among the systemic immunosuppressants used in FUMHD; a pooled
    review found systemic corticosteroids combined with methotrexate or
    ciclosporin were associated with significantly more effective outcomes,
    supporting early combination therapy.
  therapeutic_modality: SMALL_MOLECULE
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: ciclosporin
      term:
        id: CHEBI:4031
        label: cyclosporin A
  target_phenotypes:
  - preferred_term: Skin ulcer
    term:
      id: HP:0200042
      label: Skin ulcer
  evidence:
  - reference: PMID:35950146
    reference_title: "Febrile Ulceronecrotic Mucha-Habermann Disease: A Case Report and a Systematic Review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Early combination therapy with lower doses of corticosteroids and
      methotrexate or cyclosporine may be an optimal choice
    explanation: A pooled FUMHD review supports early combination therapy including ciclosporin.
- name: Antimicrobial therapy and infection control for FUMHD
  description: >-
    Because sepsis of the denuded skin is the dominant cause of FUMHD death,
    antimicrobial therapy and aggressive wound care / infection control are
    outcome-determining and are counted among the successful FUMHD modalities.
  therapeutic_modality: SMALL_MOLECULE
  treatment_term:
    preferred_term: antimicrobial agent therapy
    term:
      id: NCIT:C15620
      label: Antibiotic Therapy
    therapeutic_agent:
    - preferred_term: antibiotic
      term:
        id: NCIT:C258
        label: Antibiotic
  target_phenotypes:
  - preferred_term: Skin ulcer
    term:
      id: HP:0200042
      label: Skin ulcer
  evidence:
  - reference: PMID:36483219
    reference_title: "Mortality risk factors in febrile ulceronecrotic Mucha- Habermann disease: A systematic review of therapeutic outcomes and complications."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Successful treatment modalities for FUMHD included antibiotics,
      antivirals, systemic steroids, Methotrexate (MTX), cyclophosphamide,
      Cyclosporine (CYA), Intravenous Immunoglobulins (IVIG), pentoxifylline,
      and ultraviolet B phototherapy.
    explanation: This FUMHD review lists antibiotics among the successful treatment modalities.
  - reference: PMID:42178566
    reference_title: "A fatal pediatric case of febrile ulceronecrotic Mucha-Habermann disease: diagnostic and therapeutic challenges: a case report."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Early immunosuppressive and antimicrobial therapies are crucial"
    explanation: This directly supports early antimicrobial therapy as crucial in FUMHD.
discussions:
- discussion_id: upstream_trigger_identity
  prompt: What upstream antigen or exposure initiates PLEVA, if any?
  kind: KNOWLEDGE_GAP
  status: OPEN
  attaches_to:
  - pathophysiology#Antigen-associated immune triggering
  rationale: >-
    Temporal associations support a reactive model, but no specific agent is
    reproducibly causal and PLEVA tissue was negative for the common viruses
    tested. Identifying the initiating antigen would distinguish a postinfectious
    response from a direct infection or noninfectious trigger.
  evidence:
  - reference: PMID:38973067
    reference_title: "Immunophenotyping and viral studies in pityriasis lichenoides et varioliformis acuta lesions."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Immunohistochemistry for human HHV-1 and HHV-2, CMV and HHV-8,
      parvovirus B19, and in situ hybridization for EBV were all negative.
    explanation: This PLEVA-specific study leaves the upstream trigger unresolved.
- discussion_id: reactive_versus_clonal_t_cell_model
  prompt: Is PLEVA primarily reactive, a clonal T-cell dyscrasia, or a heterogeneous spectrum containing both?
  kind: CONTROVERSY
  status: OPEN
  attaches_to:
  - pathophysiology#Antigen-associated immune triggering
  - pathophysiology#Clonal or oligoclonal cutaneous T-cell expansion
  - diagnosis#Clinicopathologic and phenotypic assessment of atypical or persistent lesions
  rationale: >-
    Clonality and aberrant phenotypes occur in selected PL cohorts, yet
    clonality is not synonymous with lymphoma. Follow-up studies disagree on
    whether apparent MF evolution represents true progression, initial
    misclassification, or a selected atypical subset.
  evidence:
  - reference: PMID:12203210
    reference_title: "Pityriasis lichenoides: a clonal T-cell lymphoproliferative disorder."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Clonality was shown in 25 of 27 biopsies in which amplifiable DNA was obtained."
    explanation: This selected cohort supports the clonal side of the controversy.
  - reference: PMID:41420620
    reference_title: "Pityriasis lichenoides: a university department long-term follow-up study."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "During the follow-up period, no progression to cutaneous T-cell lymphoma was established."
    explanation: >-
      A 242-patient PL cohort with median 9.9-year follow-up found no
      established CTCL progression, supporting a generally benign interpretation.
  - reference: PMID:29210716
    reference_title: "Relationship Between Pityriasis Lichenoides and Mycosis Fungoides: A Clinicopathological, Immunohistochemical, and Molecular Study."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "A total of 3 (5.2%) of the 58 patients with PL developed MF after 3-11 years of prolonged clinical course."
    explanation: >-
      This selected PL cohort reports apparent evolution, but the result is not
      PLEVA-specific and should not be converted into a general PLEVA risk.
- discussion_id: pleva_treatment_evidence_gap
  prompt: Which treatment improves PLEVA-specific remission and durable control beyond spontaneous resolution?
  kind: KNOWLEDGE_GAP
  status: OPEN
  attaches_to:
  - treatments#Narrowband UVB phototherapy
  - treatments#Oral erythromycin therapy
  - treatments#Topical corticosteroid therapy
  - treatments#Methotrexate therapy for refractory or severe disease
  rationale: >-
    Most studies pool PLEVA with PLC, use heterogeneous response definitions,
    and have short follow-up. PLEVA-specific comparative evidence is therefore
    insufficient for a high-certainty treatment hierarchy.
  evidence:
  - reference: PMID:32112390
    reference_title: "Systematic review of the efficacies and adverse effects of treatments for pityriasis lichenoides."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      The current literature consists almost entirely of uncontrolled studies,
      and none provides compelling data to support an evidence-based approach
      to PL treatment.
    explanation: >-
      This systematic review directly identifies the evidence-quality gap while
      noting that its corpus did include two randomized studies.
- discussion_id: fumhd_optimal_treatment
  prompt: Which systemic therapy improves FUMHD survival, and how should immunosuppression be balanced against sepsis risk?
  kind: KNOWLEDGE_GAP
  status: OPEN
  attaches_to:
  - treatments#Prompt systemic and supportive management for FUMHD
  - treatments#Methotrexate therapy for refractory or severe disease
  - treatments#Intravenous immunoglobulin (IVIG) for FUMHD
  - treatments#TNF-alpha inhibitor therapy for FUMHD
  - treatments#Ciclosporin therapy for FUMHD
  rationale: >-
    FUMHD management rests on heterogeneous single cases and small reviews with
    no controlled trials, so no regimen is proven by RCT-grade evidence and the
    tradeoff between immunosuppression and infectious mortality is unresolved. A
    pooled review nonetheless signals that systemic corticosteroids combined with
    methotrexate or ciclosporin are associated with significantly more effective
    outcomes, suggesting early combination therapy as a candidate optimal
    approach that still needs prospective validation.
  evidence:
  - reference: PMID:36483219
    reference_title: "Mortality risk factors in febrile ulceronecrotic Mucha- Habermann disease: A systematic review of therapeutic outcomes and complications."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      FUMHD is a diagnostic and therapeutic challenge due to the lack of clearly
      defined diagnostic criteria and optimum treatment.
    explanation: This directly supports the absence of an established optimal FUMHD treatment.
  - reference: PMID:35950146
    reference_title: "Febrile Ulceronecrotic Mucha-Habermann Disease: A Case Report and a Systematic Review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Systematic corticosteroids combination with other immunosuppressants
      (methotrexate or cyclosporine) were associated with significantly more
      effective cases (26/31 = 83.9%, χ2 = 4.065, p = 0.044)
    explanation: >-
      A pooled analysis provides the strongest quantitative treatment signal,
      partially qualifying the optimal-regimen gap.
- discussion_id: fumhd_escalation_driver
  prompt: What molecular driver determines why only a minority of PLEVA patients escalate to fulminant, systemic FUMHD?
  kind: KNOWLEDGE_GAP
  status: OPEN
  attaches_to:
  - pathophysiology#Ulceronecrotic systemic inflammatory escalation in FUMHD
  rationale: >-
    FUMHD shares the cytotoxic-T-cell PLEVA mechanism but adds fever, coalescing
    ulceronecrosis, and systemic/HLH-range hyperinflammation. The host or
    lesional factors that tip a minority of PLEVA patients into this severe,
    sometimes fatal branch are unknown, and no biomarker predicts escalation.
  evidence:
  - reference: PMID:38959922
    reference_title: "Febrile ulceronecrotic Mucha-Habermann disease - a case and treatment review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Febrile ulceronecrotic Mucha-Habermann disease is a rare and severe
      variant of pityriasis lichenoides, characterized by sudden onset of
      generalized ulceronecrotic papules that rapidly coalesce into ulcers
      associated with high fever.
    explanation: The severe-variant framing motivates the open question of what drives escalation.
📚

References & Deep Research

Deep Research

2
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Acute Lichenoid Pityriasis (PLEVA) — Comprehensive Disease Characteristics Report
Edison Scientific Literature 39 citations 2026-05-04T16:01:54.708920

Acute Lichenoid Pityriasis (PLEVA) — Comprehensive Disease Characteristics Report

Target disease

Acute lichenoid pityriasis is most consistently used in the clinical literature as a synonym for pityriasis lichenoides et varioliformis acuta (PLEVA), the acute pole of the pityriasis lichenoides (PL) spectrum; some sources also refer to PLEVA as Mucha–Habermann disease, and the most severe ulceronecrotic systemic variant as febrile ulceronecrotic Mucha–Habermann disease (FUMHD). (jung2020systematicreviewof pages 1-2, ma2024diagnosticchallengesof pages 1-3, fatturi2024pityriasislichenoidesassessment pages 1-2)

Domain Key points (with numbers) Evidence type (review/series/case report) Citation IDs Publication year URL/DOI
Definitions / synonyms Acute lichenoid pityriasis corresponds to pityriasis lichenoides et varioliformis acuta (PLEVA); also called Mucha-Habermann disease in some sources. It is the acute pole of the pityriasis lichenoides spectrum; severe ulceronecrotic variant = febrile ulceronecrotic Mucha-Habermann disease (FUMHD). Review; case report (jung2020systematicreviewof pages 1-2, ma2024diagnosticchallengesof pages 1-3, fatturi2024pityriasislichenoidesassessment pages 1-2) 2020, 2024 https://doi.org/10.1111/bjd.18977 ; https://doi.org/10.70672/bcfbzp08 ; https://doi.org/10.1016/j.jped.2024.03.011
Epidemiology stats Rare disease; one review cites incidence around 0.05% with slight male predominance and onset in late childhood/young adulthood. Pediatric review noted slight male predominance 56%. Pediatric Brazilian series: 41 patients total, 5/41 PLEVA (12.2%), 32/41 PLC (78.0%). Thai pediatric series: 43 patients, 10/43 PLEVA (23.3%), male:female 1.3:1, common onset age 4–7 years. A 2013 pediatric review summarized series with PLEVA frequencies ranging 25% to 57.3% among PL cohorts. Review; retrospective pediatric series (jung2020systematicreviewof pages 1-2, ma2024diagnosticchallengesof pages 1-3, fatturi2024pityriasislichenoidesassessment pages 1-2, rujimethapass2025pityriasislichenoidesin pages 5-6, boos2013pityriasislichenoidesand pages 1-2) 2020, 2024, 2025, 2013 https://doi.org/10.1111/bjd.18977 ; https://doi.org/10.70672/bcfbzp08 ; https://doi.org/10.1016/j.jped.2024.03.011 ; https://doi.org/10.35755/jmedassocthai.2025.5.377-383-02606 ; https://doi.org/10.1007/s13671-013-0054-x
Key clinical features and course Acute eruption of erythematous papules/papulovesicles that may become hemorrhagic/necrotic and heal with varioliform scarring. Lesions often involve trunk and extremities; pruritus common; lesions resolve over weeks but recur in crops. Thai series: PLEVA disease duration 1–20 months, mean about 4 ± 2 months; diagnosis lag about 1.5 months in PLEVA vs 3 months in PLC. Systemic symptoms (e.g., fever, hepatomegaly) were more common in PLEVA; varioliform scars were seen only in PLEVA. Severe FUMHD may include mucosal lesions, high fever, sepsis, cardiomyopathy, pulmonary involvement. Review; retrospective series; case report (ma2024diagnosticchallengesof pages 1-3, rujimethapass2025pityriasislichenoidesin pages 5-6, boos2013pityriasislichenoidesand pages 1-2, marinhernandez2023acutelichenoidand pages 1-2) 2024, 2025, 2013, 2023 https://doi.org/10.70672/bcfbzp08 ; https://doi.org/10.35755/jmedassocthai.2025.5.377-383-02606 ; https://doi.org/10.1007/s13671-013-0054-x ; https://doi.org/10.24875/bmhim.22000043
Histopathology / diagnostics / differentials Diagnosis is clinicopathologic and usually confirmed by skin biopsy. Reported findings: parakeratosis, spongiosis, lichenoid/interface dermatitis, dyskeratotic keratinocytes, erythrocyte extravasation, focal epidermotropism, epidermal necrosis, hemorrhagic crusting/ulceration; one pediatric case showed lymphocytic vasculitis with focal epidermal necrosis. DIF may be negative for IgG/IgA/IgM/C3. Important differentials: guttate psoriasis, varicella, pityriasis rosea, secondary syphilis, and occasionally mycosis fungoides. Review; case report; diagnostic image/table extraction (ma2024diagnosticchallengesof pages 1-3, ma2024diagnosticchallengesof pages 3-9, boos2013pityriasislichenoidesand pages 1-2, marinhernandez2023acutelichenoidand pages 1-2, ma2024diagnosticchallengesof media c2c2a990) 2024, 2013, 2023 https://doi.org/10.70672/bcfbzp08 ; https://doi.org/10.1007/s13671-013-0054-x ; https://doi.org/10.24875/bmhim.22000043
Triggers / etiology hypotheses Etiopathogenesis remains uncertain. Main hypotheses: T-cell dyscrasia / lymphoproliferative process, immune-complex hypersensitivity, or inflammatory reaction to antigenic stimuli. Reported infectious associations include EBV, HIV, VZV, HSV-2, Toxoplasma gondii, group A streptococcus, parvovirus B19, HHV-8. Reported exposure triggers include drugs (e.g., antidepressants, statins, anti-TNF agents), subcutaneous immunoglobulin, and vaccines (including MMR; case reports after COVID-19 vaccination also reported in the literature). Pediatric review cited preceding URI in 33% and drug/vaccination exposure in 20%. Review; case report; pediatric review (ma2024diagnosticchallengesof pages 1-3, boos2013pityriasislichenoidesand pages 1-2) 2024, 2013 https://doi.org/10.70672/bcfbzp08 ; https://doi.org/10.1007/s13671-013-0054-x
Treatments and reported response / remission rates No standardized guideline-supported regimen. Systematic review of 27 studies (502 participants) found phototherapy had the highest proportion of complete remissions; NB-UVB often recommended first-line. Pediatric Brazilian series: overall remission 71.9% (23 patients); remission with antibiotics 56.6% (17 patients) and with phototherapy 80% (4 patients). Thai series: erythromycin used in 95.3%, prednisolone 9.3%, methotrexate 9.3%; one FUMHD patient responded to methylprednisolone plus methotrexate. Review/case sources list oral erythromycin ± topical corticosteroids and low-dose methotrexate as common second-line options; refractory disease/FUMHD has been treated with methotrexate, acitretin, dapsone, cyclosporine, and other immunomodulators. One case resolved after 2 months of oral plus topical corticosteroids. Systematic review; retrospective pediatric series; case report (jung2020systematicreviewof pages 1-2, fatturi2024pityriasislichenoidesassessment pages 1-2, rujimethapass2025pityriasislichenoidesin pages 5-6, ma2024diagnosticchallengesof pages 3-9, ma2024diagnosticchallengesof pages 1-3) 2020, 2024, 2025 https://doi.org/10.1111/bjd.18977 ; https://doi.org/10.1016/j.jped.2024.03.011 ; https://doi.org/10.35755/jmedassocthai.2025.5.377-383-02606 ; https://doi.org/10.70672/bcfbzp08
Prognosis / CTCL progression signals Usually benign and self-limited/relapsing, but persistent monitoring is advised. Long-term PL-to-MF progression appears uncommon but documented: one study found 3/58 (5.2%) developed mycosis fungoides after 3–11 years; another pediatric cohort reported 1/43 (2.3%) later diagnosed with MF. In non-MF-associated PL, 85% (35/41) reported lasting complete remissions in one series. Signals concerning for CTCL evolution include prolonged clinical course, appearance of patches/larger plaques, increased lymphocytic atypia, reduced apoptotic keratinocytes, reduced CD7+/CD8+ cells, and clonal TCR rearrangement. Molecular clinicopathologic study; pediatric series; review (rujimethapass2025pityriasislichenoidesin pages 5-6, rujimethapass2025pityriasislichenoidesin pages 6-7) 2025 https://doi.org/10.35755/jmedassocthai.2025.5.377-383-02606
Immunopathogenesis / clonality signals Data are mixed and not disease-defining. A pediatric review summarized one study reporting monoclonal TCR rearrangement in 57% of PLEVA vs 8% of PLC, while another found only 1/23 positive, underscoring uncertainty. Overall interpretation in reviews: clonality can occur in PLEVA/PL and does not by itself establish lymphoma; clinicopathologic correlation remains essential. Review summarizing molecular studies (boos2013pityriasislichenoidesand pages 1-2) 2013 https://doi.org/10.1007/s13671-013-0054-x

Table: This table compacts the main disease-characteristics evidence for acute lichenoid pityriasis (PLEVA), including epidemiology, phenotype, diagnosis, triggers, treatment outcomes, and prognosis. It is useful as a quick-reference scaffold for a disease knowledge base entry with source-linked claims.

1. Disease information

Overview / definition (current understanding)

PLEVA is an uncommon inflammatory papulosquamous dermatosis characterized clinically by crops of erythematous papules/papulovesicles that may become necrotic/hemorrhagic and can heal with varioliform scarring, with recurrences over time. (ma2024diagnosticchallengesof pages 1-3, jung2020systematicreviewof pages 1-2, marinhernandez2023acutelichenoidand pages 1-2)

Key identifiers (OMIM/Orphanet/ICD/MeSH/MONDO)

Within the retrieved primary and review sources in this run, ICD-10/ICD-11, MeSH, OMIM, Orphanet, and MONDO identifiers were not explicitly provided, so they cannot be safely asserted from the evidence base assembled here. (ma2024diagnosticchallengesof pages 1-3, jung2020systematicreviewof pages 1-2)

Common synonyms / alternative names

  • Pityriasis lichenoides et varioliformis acuta (PLEVA) (marinhernandez2023acutelichenoidand pages 1-2, jung2020systematicreviewof pages 1-2)
  • Mucha–Habermann disease (jung2020systematicreviewof pages 1-2, ma2024diagnosticchallengesof pages 1-3)
  • Febrile ulceronecrotic Mucha–Habermann disease (FUMHD) (severe variant) (ma2024diagnosticchallengesof pages 1-3, fatturi2024pityriasislichenoidesassessment pages 1-2)

Evidence provenance

Evidence is primarily derived from aggregated disease-level resources (systematic reviews and cohort/case series) and supplemented by individual case reports. (jung2020systematicreviewof pages 1-2, marinhernandez2023acutelichenoidand pages 1-2, fatturi2024pityriasislichenoidesassessment pages 1-2)

2. Etiology

Disease causal factors (mechanistic hypotheses)

Etiopathogenesis remains uncertain. Frequently cited hypotheses include: 1) T-cell dyscrasia / lymphoproliferative process (i.e., antigen-driven clonal/oligoclonal T-cell expansion in skin), and 2) immune-complex hypersensitivity reaction to infectious/drug antigens. (ma2024diagnosticchallengesof pages 1-3, boos2013pityriasislichenoidesand pages 1-2, fatturi2024pityriasislichenoidesassessment pages 1-2)

Risk factors / triggers (2023–2024 emphasis)

Evidence supports PLEVA/PL being triggered (not proven caused) by infections, drugs, or vaccines in some patients.

In a 2024 pediatric series (n=41), triggers were documented in 11/41 (26.8%) patients, including fever (3), COVID-19 infection (2), and single cases of sun exposure, HIV, parotitis, tonsillitis, cold weather, and COVID-19 vaccination. (fatturi2024pityriasislichenoidesassessment pages 2-4)

A 2024 diagnostic-focused report lists reported infectious triggers (e.g., EBV, HIV, varicella-zoster virus, HSV-2, Toxoplasma gondii, group A streptococcus) and notes drug and vaccine triggers in the literature (including anti-TNF and vaccination). (ma2024diagnosticchallengesof pages 1-3)

A pediatric review summarizes that a preceding upper respiratory infection was reported in 33% and drug/vaccination exposure in 20% in one summarized series. (boos2013pityriasislichenoidesand pages 1-2)

Protective factors

No validated genetic or environmental protective factors were identified in the retrieved evidence. (jung2020systematicreviewof pages 1-2, fatturi2024pityriasislichenoidesassessment pages 1-2)

Gene–environment interactions

No specific gene–environment interaction findings were available in the retrieved full text, although one systematic review explicitly calls for future work on “understanding the interplay between genetic predisposition and environmental factors.” (everettUnknownyear…forpityriasisa pages 61-64)

3. Phenotypes

Core clinical phenotypes (with suggested HPO terms)

Key phenotypes include: * Crops of erythematous papules/papulovesicles, sometimes necrotic/hemorrhagic (suggested HPO: Papule [HP:0200031], Vesicle [HP:0100796], Skin ulcer [HP:0001053]) (ma2024diagnosticchallengesof pages 1-3, marinhernandez2023acutelichenoidand pages 1-2) * Crusting/necrosis and potential ulceration (HPO: Skin necrosis [HP:0001032], Crusting [HP:0030799]) (ma2024diagnosticchallengesof pages 1-3) * Pruritus (HPO: Pruritus [HP:0000989]) (rujimethapass2025pityriasislichenoidesin pages 5-6, boos2013pityriasislichenoidesand pages 1-2) * Varioliform scarring (HPO: Abnormal scar [HP:0100699]) (rujimethapass2025pityriasislichenoidesin pages 5-6, marinhernandez2023acutelichenoidand pages 1-2) * Post-inflammatory dyspigmentation (HPO: Hypopigmentation of the skin [HP:0001042]) (marinhernandez2023acutelichenoidand pages 1-2, rujimethapass2025pityriasislichenoidesin pages 5-6)

Age of onset

Onset often occurs in childhood/young adulthood; pediatric cohorts show onset peaks around preschool/early school ages. (jung2020systematicreviewof pages 1-2, rujimethapass2025pityriasislichenoidesin pages 5-6, fatturi2024pityriasislichenoidesassessment pages 1-2)

Severity and progression/course

PLEVA is typically acute/subacute and may recur in crops; a Thai pediatric cohort reported PLEVA duration range 1–20 months with mean ~4±2 months. (rujimethapass2025pityriasislichenoidesin pages 5-6)

Severe FUMHD can present with mucosal involvement, high fever, and systemic complications (e.g., sepsis, cardiomyopathy, pulmonary involvement). (ma2024diagnosticchallengesof pages 1-3)

Frequency among affected individuals

In pediatric PL cohorts, PLEVA frequency varies widely by setting and referral patterns; for example, in a 2024 pediatric Brazilian cohort PLEVA was 5/41 (12.2%). (fatturi2024pityriasislichenoidesassessment pages 1-2)

Quality of life impact

Formal HRQoL instruments were not reported in retrieved primary sources; however, a 2024 diagnostic report notes misdiagnosis can lead to substantial emotional/psychological stress (qualitative impact). (ma2024diagnosticchallengesof pages 1-3)

4. Genetic/molecular information

Causal genes / pathogenic variants

No causal genes or pathogenic germline variants were identified in the retrieved literature; PLEVA is generally treated as a complex inflammatory dermatosis rather than a monogenic disorder in these sources. (jung2020systematicreviewof pages 1-2, fatturi2024pityriasislichenoidesassessment pages 1-2)

Molecular findings (limited)

Immunophenotyping can show T-cell–predominant infiltrates. A 2023 pediatric case reported lesional IHC including CD3+, CD4+++, CD8+, CD7+++, and CD20−. (marinhernandez2023acutelichenoidand pages 1-2)

T-cell receptor clonality is variably detected and is not diagnostic of lymphoma by itself; a pediatric review summarized one study with monoclonal TCR rearrangement in 57% of PLEVA vs 8% of PLC, while another series found only 1/23 positive, emphasizing heterogeneity and uncertain clinical significance. (boos2013pityriasislichenoidesand pages 1-2)

5. Environmental information

Environmental contributors are mainly reported as triggering exposures (infections, drugs, vaccines) rather than chronic toxic or occupational exposures. (ma2024diagnosticchallengesof pages 1-3, fatturi2024pityriasislichenoidesassessment pages 2-4)

6. Mechanism / pathophysiology

Proposed causal chain (current consensus framing)

A common mechanistic framing is: antigenic stimulus (infectious agent, drug, vaccine) → cutaneous immune activation with T-cell–predominant interface/lichenoid dermatitis → keratinocyte injury/necrosis and vascular/inflammatory changes → papulonecrotic lesions with crusting → post-inflammatory dyspigmentation or varioliform scarring. (ma2024diagnosticchallengesof pages 1-3, marinhernandez2023acutelichenoidand pages 1-2, boos2013pityriasislichenoidesand pages 1-2)

Cellular processes and pathways (ontology suggestions)

Because the retrieved sources do not provide pathway-specific transcriptomic/proteomic findings, ontology terms are suggested at a high level based on clinicopathology: * GO biological processes: T cell activation, inflammatory response, keratinocyte apoptotic process, leukocyte migration (supported conceptually by interface/lichenoid pattern and T-cell infiltrates) (ma2024diagnosticchallengesof pages 1-3, marinhernandez2023acutelichenoidand pages 1-2) * Cell types (Cell Ontology): T cell (CL:0000084); plausible involvement of CD4-positive, alpha-beta T cell (CL:0000624) and CD8-positive, alpha-beta T cell (CL:0000625) consistent with reported IHC (marinhernandez2023acutelichenoidand pages 1-2)

Immune system involvement

PLEVA lesions show interface/lichenoid dermatitis with epidermotropism in some cases, and PLEVA may represent a benign clonal or oligoclonal T-cell–driven process in a subset. (ma2024diagnosticchallengesof pages 3-9, boos2013pityriasislichenoidesand pages 1-2)

7. Anatomical structures affected

Organ and tissue level

Primary involvement is the skin (UBERON: skin [UBERON:0002097]), with lesions commonly on trunk and extremities. (marinhernandez2023acutelichenoidand pages 1-2, ma2024diagnosticchallengesof pages 1-3)

Severe FUMHD can involve mucosa and systemic organs (cardiopulmonary involvement described). (ma2024diagnosticchallengesof pages 1-3)

Subcellular level

Not resolved in retrieved evidence.

8. Temporal development

  • Onset pattern: acute/subacute crops of papules; individual lesions may resolve within weeks but new lesions recur (ma2024diagnosticchallengesof pages 1-3, marinhernandez2023acutelichenoidand pages 1-2)
  • Course: variable, often self-limited but may persist months; pediatric cohort mean duration for PLEVA ~4 months (rujimethapass2025pityriasislichenoidesin pages 5-6)
  • Severe course: FUMHD can be rapidly progressive with systemic complications (ma2024diagnosticchallengesof pages 1-3)

9. Inheritance and population

PLEVA is not presented as a Mendelian disorder in the retrieved sources; inheritance pattern and penetrance are not established. (jung2020systematicreviewof pages 1-2)

Epidemiology statistics (available)

  • A systematic review cites incidence approximately 0.05% and notes slight male predominance and typical onset in late childhood/young adulthood. (jung2020systematicreviewof pages 1-2)
  • A 2023 pediatric report estimated incidence as ~1/2000 inhabitants (noted as an estimate in that report). (marinhernandez2023acutelichenoidand pages 1-2)

Because these numbers come from different sources with different contexts, they should be treated as approximate. (jung2020systematicreviewof pages 1-2, marinhernandez2023acutelichenoidand pages 1-2)

10. Diagnostics

Clinical evaluation

PLEVA can mimic multiple papulovesicular/papulosquamous eruptions. Diagnostic work-up typically relies on clinical morphology and distribution plus biopsy confirmation. (ma2024diagnosticchallengesof pages 1-3, jung2020systematicreviewof pages 1-2)

Histopathology

Commonly described findings include lichenoid/interface dermatitis, parakeratosis, spongiosis, erythrocyte extravasation, epidermal necrosis, subepidermal blistering, and sometimes focal epidermotropism; one pediatric case highlighted lymphocytic vasculitis with focal epidermal necrosis. (ma2024diagnosticchallengesof pages 1-3, ma2024diagnosticchallengesof pages 3-9, marinhernandez2023acutelichenoidand pages 1-2)

Direct immunofluorescence may be negative for immune deposits at the dermal–epidermal junction (IgG/IgA/IgM/C3 negative in a reported case). (ma2024diagnosticchallengesof pages 1-3)

Differential diagnosis

A differential table extracted from a 2024 diagnostic paper highlights confusion with guttate psoriasis, varicella, pityriasis rosea, and secondary syphilis. (ma2024diagnosticchallengesof media c2c2a990)

Histopathology figures supporting interface dermatitis and focal epidermotropism are available from the same report. (ma2024diagnosticchallengesof media 72391849, ma2024diagnosticchallengesof media 01b2711c)

Omics/genetic testing

Routine genetic testing is not described for PLEVA in the retrieved sources. (jung2020systematicreviewof pages 1-2)

11. Outcome / prognosis

General prognosis

PLEVA is generally benign/self-limited but can be relapsing. (jung2020systematicreviewof pages 1-2, rujimethapass2025pityriasislichenoidesin pages 5-6)

Risk of progression to cutaneous T-cell lymphoma (CTCL)

Progression risk is debated; in a Thai pediatric cohort, 1/43 (2.3%) was later diagnosed as mycosis fungoides on repeat biopsy. (rujimethapass2025pityriasislichenoidesin pages 5-6)

Clinical concern for MF/CTCL is heightened when clinical morphology changes or the course is prolonged; a 2023 pediatric case illustrates diagnostic overlap when an initial biopsy was read as suggestive of mycosis fungoides but was later revised to PLEVA with lymphocytic vasculitis. (marinhernandez2023acutelichenoidand pages 1-2)

12. Treatment

Evidence quality (expert appraisal)

A 2020 systematic review (British Journal of Dermatology) notes: “The current literature consists almost entirely of uncontrolled studies, and none provides compelling data to support an evidence-based approach to PL treatment.” (May 2020). (jung2020systematicreviewof pages 1-2)

First-line and second-line approaches (real-world implementations)

Across reviews and recent summaries, narrow-band UVB (NB-UVB) phototherapy is commonly recommended as first-line, with oral erythromycin or low-dose methotrexate (± topical corticosteroids) used as second-line options. (ma2024diagnosticchallengesof pages 3-9, feschuk2023pityriasislichenoidesfollowing pages 1-3)

Quantitative treatment outcomes

Phototherapy (systematic review evidence): In a 2020 systematic review, complete response rates were reported as 75.0% (102/136) for NB-UVB and 69% (25/36) for PUVA, with relapse after phototherapy in 25.7% (66/257). (jung2020systematicreviewof pages 2-4)

Pediatric real-world outcomes (2024 series): In a 2024 pediatric cohort, overall remission was 71.9%; among antibiotic-treated patients remission was 56.6% (17/30); among phototherapy-treated patients remission was 80% (4/5). (fatturi2024pityriasislichenoidesassessment pages 1-2)

Pediatric phototherapy-focused evidence: A pediatric phototherapy literature review reported initial clearance rates of 89.6% for BB-UVB (with 23.1% recurrence), 73% for NB-UVB (with no recurrence), and 83% for PUVA (with 60% recurrence), with generally mild erythema as the main side effect. (maranda2016phototherapyforpityriasis pages 1-2)

Systemic therapy for severe disease (FUMHD)

FUMHD may require systemic immunosuppression; methotrexate is repeatedly cited as important in refractory PLEVA/FUMHD. (ma2024diagnosticchallengesof pages 3-9, rujimethapass2025pityriasislichenoidesin pages 5-6)

MAXO (Medical Action Ontology) suggestions

  • Phototherapy (e.g., NB-UVB phototherapy) (jung2020systematicreviewof pages 2-4, maranda2016phototherapyforpityriasis pages 1-2)
  • Systemic antibiotic therapy (macrolides/tetracyclines) (fatturi2024pityriasislichenoidesassessment pages 2-4, fatturi2024pityriasislichenoidesassessment pages 1-2)
  • Topical corticosteroid therapy (supportive symptom control) (ma2024diagnosticchallengesof pages 3-9)
  • Systemic immunosuppressive therapy (methotrexate; severe/refractory cases) (ma2024diagnosticchallengesof pages 3-9, rujimethapass2025pityriasislichenoidesin pages 5-6)

Clinical trials

A ClinicalTrials.gov search in this run returned no relevant interventional trials for PLEVA; retrieved NCT records were unrelated false positives. (clinical trial search output not relevant to PLEVA; no citeable PLEVA trial context IDs available)

13. Prevention

No evidence-based primary prevention strategies were identified in retrieved sources; because triggers are inconsistent and causality is unproven, prevention is limited to pragmatic measures (avoidance of suspected individual triggers when reproducibly associated) and close follow-up for severe/systemic features suggestive of FUMHD. (ma2024diagnosticchallengesof pages 1-3, ma2024diagnosticchallengesof pages 3-9)

14. Other species / natural disease

No evidence was found in the retrieved sources for naturally occurring PLEVA in other species or zoonotic considerations. (maranda2016phototherapyforpityriasis pages 1-2, ma2024diagnosticchallengesof pages 3-9)

15. Model organisms

No explicit model organism systems or animal models for PLEVA were described in the retrieved, PLEVA-focused texts in this run. (maranda2016phototherapyforpityriasis pages 1-2, ma2024diagnosticchallengesof pages 3-9)

Recent developments and latest research highlights (prioritize 2023–2024)

1) SARS-CoV-2 infection/vaccination temporal association literature (2023): A 2023 review of 14 cases reported that 9/14 (64.3%) followed vaccination and 4/14 (28.6%) followed infection; 12/14 (85.7%) had marked improvement or complete resolution at follow-up, and the authors state “Naranjo’s ADRPS suggests SARS-CoV-2 may be a ‘probable’ cause of PL,” while emphasizing uncertainty and possible coincidence. (Jan 2023; https://doi.org/10.1007/s13671-023-00380-1). (feschuk2023pityriasislichenoidesfollowing pages 3-4)

2) Pityriasis eruptions after COVID-19 vaccination (systematic review, 2023): A systematic review identified 94 patients with pityriasis/pityriasis-like eruptions after vaccination; PLEVA accounted for 7.4% of reported cases; biopsy was performed in 41/94. (Aug 2023; https://doi.org/10.4081/dr.2023.9742). (duzett2023pityriasisfollowingcovid19 pages 2-3)

3) Large pediatric series with quantified remission predictors (2024): A 2024 pediatric cohort reported documented triggers in 26.8% and remission rates by therapy (antibiotics vs phototherapy), and found remission odds were higher with onset after age 5 (OR 13.33). (Sep 2024; https://doi.org/10.1016/j.jped.2024.03.011). (fatturi2024pityriasislichenoidesassessment pages 2-4, fatturi2024pityriasislichenoidesassessment pages 1-2)

4) Diagnostic pitfalls and histopathology emphasis (2024): A 2024 diagnostic report underscores clinical overlap with guttate psoriasis/varicella/pityriasis rosea/secondary syphilis and provides histopathology examples (subepidermal blistering, interface dermatitis, focal epidermotropism) to support biopsy confirmation. (Nov 2024; https://doi.org/10.70672/bcfbzp08). (ma2024diagnosticchallengesof media c2c2a990, ma2024diagnosticchallengesof media 72391849, ma2024diagnosticchallengesof media 01b2711c)

References

  1. (jung2020systematicreviewof pages 1-2): F. Jung, C. Sibbald, M. Bohdanowicz, J. Ingram, V. Piguet, V. Piguet, and V. Piguet. Systematic review of the efficacies and adverse effects of treatments for pityriasis lichenoides. British Journal of Dermatology, 183:1026-1032, May 2020. URL: https://doi.org/10.1111/bjd.18977, doi:10.1111/bjd.18977. This article has 30 citations and is from a highest quality peer-reviewed journal.

  2. (ma2024diagnosticchallengesof pages 1-3): Abd Rahman MA, Jamani NA, Abdul Halim S, and Zainun N. Diagnostic challenges of pityriasis lichenoides et varioliformis acuta (pleva). Asian Journal of Medicine & Health Sciences, 7:279-287, Nov 2024. URL: https://doi.org/10.70672/bcfbzp08, doi:10.70672/bcfbzp08. This article has 0 citations.

  3. (fatturi2024pityriasislichenoidesassessment pages 1-2): Aluhine L. Fatturi, Mariana A.P. Morgan, Jandrei R. Markus, Lucero Noguera-Morel, and Vânia O. Carvalho. Pityriasis lichenoides: assessment of 41 pediatric patients. Jornal de Pediatria, 100:527-532, Sep 2024. URL: https://doi.org/10.1016/j.jped.2024.03.011, doi:10.1016/j.jped.2024.03.011. This article has 9 citations and is from a peer-reviewed journal.

  4. (rujimethapass2025pityriasislichenoidesin pages 5-6): MD¹ Nootchanard Rujimethapass, MD¹ Wanida Limpongsanurak, and MD¹ Srisupalak Singalavanija. Pityriasis lichenoides in thai children: a 10-years review of clinical and treatment outcome. Journal of the Medical Association of Thailand, 108:377-383, May 2025. URL: https://doi.org/10.35755/jmedassocthai.2025.5.377-383-02606, doi:10.35755/jmedassocthai.2025.5.377-383-02606. This article has 1 citations.

  5. (boos2013pityriasislichenoidesand pages 1-2): Markus D. Boos, Sara S. Samimi, Alain H. Rook, Albert C. Yan, and Ellen J. Kim. Pityriasis lichenoides and cutaneous t cell lymphoma: an update on the diagnosis and management of the most common benign and malignant cutaneous lymphoproliferative diseases in children. Current Dermatology Reports, 2:203-211, Aug 2013. URL: https://doi.org/10.1007/s13671-013-0054-x, doi:10.1007/s13671-013-0054-x. This article has 6 citations.

  6. (marinhernandez2023acutelichenoidand pages 1-2): Eduardo Marín-Hernández, Laura N. Escobar-García, Martha G. Contreras, Alfredo Valero-Gómez, and Georgina A. Siordia-Reyes. Acute lichenoid and varioliform pityriasis in a pediatric patient. Boletín Médico del Hospital Infantil de México, Jun 2023. URL: https://doi.org/10.24875/bmhim.22000043, doi:10.24875/bmhim.22000043. This article has 5 citations.

  7. (ma2024diagnosticchallengesof pages 3-9): Abd Rahman MA, Jamani NA, Abdul Halim S, and Zainun N. Diagnostic challenges of pityriasis lichenoides et varioliformis acuta (pleva). Asian Journal of Medicine & Health Sciences, 7:279-287, Nov 2024. URL: https://doi.org/10.70672/bcfbzp08, doi:10.70672/bcfbzp08. This article has 0 citations.

  8. (ma2024diagnosticchallengesof media c2c2a990): Abd Rahman MA, Jamani NA, Abdul Halim S, and Zainun N. Diagnostic challenges of pityriasis lichenoides et varioliformis acuta (pleva). Asian Journal of Medicine & Health Sciences, 7:279-287, Nov 2024. URL: https://doi.org/10.70672/bcfbzp08, doi:10.70672/bcfbzp08. This article has 0 citations.

  9. (rujimethapass2025pityriasislichenoidesin pages 6-7): MD¹ Nootchanard Rujimethapass, MD¹ Wanida Limpongsanurak, and MD¹ Srisupalak Singalavanija. Pityriasis lichenoides in thai children: a 10-years review of clinical and treatment outcome. Journal of the Medical Association of Thailand, 108:377-383, May 2025. URL: https://doi.org/10.35755/jmedassocthai.2025.5.377-383-02606, doi:10.35755/jmedassocthai.2025.5.377-383-02606. This article has 1 citations.

  10. (fatturi2024pityriasislichenoidesassessment pages 2-4): Aluhine L. Fatturi, Mariana A.P. Morgan, Jandrei R. Markus, Lucero Noguera-Morel, and Vânia O. Carvalho. Pityriasis lichenoides: assessment of 41 pediatric patients. Jornal de Pediatria, 100:527-532, Sep 2024. URL: https://doi.org/10.1016/j.jped.2024.03.011, doi:10.1016/j.jped.2024.03.011. This article has 9 citations and is from a peer-reviewed journal.

  11. (everettUnknownyear…forpityriasisa pages 61-64): L Everett. … for pityriasis lichenoides chronica, pityriasis lichenoides et varioliformis acuta, and febrile ulceronecrotic mucha–habermann disease: a systematic review. Unknown journal, Unknown year.

  12. (ma2024diagnosticchallengesof media 72391849): Abd Rahman MA, Jamani NA, Abdul Halim S, and Zainun N. Diagnostic challenges of pityriasis lichenoides et varioliformis acuta (pleva). Asian Journal of Medicine & Health Sciences, 7:279-287, Nov 2024. URL: https://doi.org/10.70672/bcfbzp08, doi:10.70672/bcfbzp08. This article has 0 citations.

  13. (ma2024diagnosticchallengesof media 01b2711c): Abd Rahman MA, Jamani NA, Abdul Halim S, and Zainun N. Diagnostic challenges of pityriasis lichenoides et varioliformis acuta (pleva). Asian Journal of Medicine & Health Sciences, 7:279-287, Nov 2024. URL: https://doi.org/10.70672/bcfbzp08, doi:10.70672/bcfbzp08. This article has 0 citations.

  14. (feschuk2023pityriasislichenoidesfollowing pages 1-3): Aileen M. Feschuk, Maxwell Green, Nadia Kashetsky, and Howard I. Maibach. Pityriasis lichenoides following sars-cov-2 infection/vaccination. Current Dermatology Reports, 12:27-32, Jan 2023. URL: https://doi.org/10.1007/s13671-023-00380-1, doi:10.1007/s13671-023-00380-1. This article has 7 citations.

  15. (jung2020systematicreviewof pages 2-4): F. Jung, C. Sibbald, M. Bohdanowicz, J. Ingram, V. Piguet, V. Piguet, and V. Piguet. Systematic review of the efficacies and adverse effects of treatments for pityriasis lichenoides. British Journal of Dermatology, 183:1026-1032, May 2020. URL: https://doi.org/10.1111/bjd.18977, doi:10.1111/bjd.18977. This article has 30 citations and is from a highest quality peer-reviewed journal.

  16. (maranda2016phototherapyforpityriasis pages 1-2): Eric Laurent Maranda, Megan Smith, Austin H. Nguyen, Vivek N. Patel, Lawrence A. Schachner, and Jimenez J. Joaquin. Phototherapy for pityriasis lichenoides in the pediatric population: a review of the published literature. American Journal of Clinical Dermatology, 17:583-591, Aug 2016. URL: https://doi.org/10.1007/s40257-016-0216-2, doi:10.1007/s40257-016-0216-2. This article has 27 citations and is from a peer-reviewed journal.

  17. (feschuk2023pityriasislichenoidesfollowing pages 3-4): Aileen M. Feschuk, Maxwell Green, Nadia Kashetsky, and Howard I. Maibach. Pityriasis lichenoides following sars-cov-2 infection/vaccination. Current Dermatology Reports, 12:27-32, Jan 2023. URL: https://doi.org/10.1007/s13671-023-00380-1, doi:10.1007/s13671-023-00380-1. This article has 7 citations.

  18. (duzett2023pityriasisfollowingcovid19 pages 2-3): Laura Duzett, Guadalupe Mercado, Vasiliki Tasouli-Drakou, Alicia Kane, and Alison Tam. Pityriasis following covid-19 vaccinations: a systematic review. Dermatology Reports, Aug 2023. URL: https://doi.org/10.4081/dr.2023.9742, doi:10.4081/dr.2023.9742. This article has 2 citations.

OpenScientist ▸
1. Disease Information
openscientist-autonomous 41 citations 2026-05-05T00:43:15.812091

1. Disease Information

Overview

Pityriasis Lichenoides et Varioliformis Acuta (PLEVA) is a rare inflammatory skin disorder first described by Mucha in 1916 and Habermann in 1925 (PMID: 8864599). The disease is characterized by the abrupt onset of recurrent crops of erythematous papulovesicular lesions that undergo necrosis and crusting, predominantly affecting the trunk and proximal extremities. PLEVA represents the acute end of the pityriasis lichenoides (PL) spectrum, which also encompasses pityriasis lichenoides chronica (PLC) and the severe febrile ulceronecrotic Mucha-Habermann disease (FUMHD).

Key Identifiers

Identifier Code/ID
MONDO MONDO:0024250 (Pityriasis lichenoides et varioliformis acuta)
ICD-10 L41.0 (Pityriasis lichenoides et varioliformis acuta)
ICD-11 EA92.0 (Pityriasis lichenoides et varioliformis acuta)
MeSH D017514 (Pityriasis Lichenoides)
OMIM Not assigned (no Mendelian inheritance established)
Orphanet ORPHA:33111 (Pityriasis lichenoides)
SNOMED CT 238696003 (Pityriasis lichenoides et varioliformis acuta)

Synonyms and Alternative Names

  • Pityriasis lichenoides et varioliformis acuta (PLEVA)
  • Mucha-Habermann disease (MHD)
  • Acute parapsoriasis
  • Acute guttate parapsoriasis
  • Parapsoriasis varioliformis
  • Parapsoriasis acuta
  • Pityriasis lichenoides acuta

The severe variant is known as: - Febrile ulceronecrotic Mucha-Habermann disease (FUMHD) - Degos disease (referring to the 1966 description by Degos of the febrile ulceronecrotic variant)

Information Sources

The information in this report is derived from aggregated disease-level resources including systematic reviews, retrospective cohort studies, case series, and individual case reports published in peer-reviewed literature. No large-scale electronic health record (EHR) studies or population registries specific to PLEVA exist.

2. Etiology

Disease Causal Factors

The etiology of PLEVA remains unknown. It is generally considered a T-cell-mediated inflammatory dermatosis rather than a true neoplastic process, although debate persists regarding its relationship to cutaneous T-cell lymphoproliferative disorders (PMID: 12203210). The leading etiologic hypothesis is that PLEVA represents a hypersensitivity reaction to an infectious agent, as suggested by Mucha-Habermann disease reviews: "The etiology of MH remains obscure, but it may be the result of a hypersensitivity reaction to an infectious agent" (PMID: 8864599).

Risk Factors

Infectious Triggers

Multiple infectious agents have been temporally associated with PLEVA onset: - Streptococcal infections: A case of PLC manifesting ten days after streptococcal pharyngitis has been documented (PMID: 39365630) - Varicella (chickenpox): FUMHD following suspected hemorrhagic chickenpox has been reported in a 20-month-old boy (PMID: 25627543) - SARS-CoV-2 infection/vaccination: A systematic review identified 14 cases of PL following COVID-19 infection or vaccination, with one case recurring after vaccination suggesting a possible association (PMID: 36688177) - Various COVID-19 vaccines (BNT162b2 Pfizer-BioNTech, Oxford-AstraZeneca, Sinopharm) have been temporally associated with PLEVA onset or flare-up (PMID: 35841285; PMID: 35617206; PMID: 34751995; PMID: 34617317; PMID: 35716105) - Other viruses: HIV, EBV, CMV, parvovirus B19, adenovirus, and VZV have been implicated in individual case reports - Toxoplasma gondii has been reported as a possible trigger

Demographic Risk Factors

  • Age: PLEVA primarily affects children and young adults. Pediatric onset average is 6.5 years (PMID: 25816855)
  • Sex: Male predominance in children (M:F ratio 1.7:1), but female predominance in adults (M:F ratio 0.6:1) (PMID: 41420620)

Genetic Risk Factors

  • No causal genetic variants have been identified for PLEVA
  • No GWAS studies have been conducted
  • No susceptibility loci have been mapped
  • PLEVA is not classified among the autoinflammatory keratinization diseases (AiKDs), unlike keratosis lichenoides chronica which involves NLRP1 mutations (PMID: 38103162)

Protective Factors

No specific genetic or environmental protective factors have been identified for PLEVA. This represents a significant knowledge gap.

Gene-Environment Interactions

No gene-environment interactions have been characterized for PLEVA, consistent with the absence of identified causal genes.

3. Phenotypes

Primary Cutaneous Phenotypes

1. Papulovesicular Eruption (Hallmark)

  • HPO: HP:0200037 (Vesiculobullous skin lesion), HP:0200034 (Papule)
  • Type: Physical manifestation / clinical sign
  • Onset: Acute; mean age 6.5 years in children (PMID: 25816855)
  • Severity: Mild to moderate; severe in FUMHD variant
  • Progression: Episodic, with recurrent crops; self-limited
  • Frequency: Present in virtually 100% of patients
  • Description: Sudden onset of erythematous macules and papules that develop central vesiculation, necrosis, and hemorrhagic crusting. Individual lesions evolve through stages from erythematous papule to crusted/necrotic papule to healing with dyspigmentation
  • QoL impact: Cosmetic concern; post-inflammatory pigmentary changes particularly distressing in darker-skinned individuals

2. Scaling and Crusting

  • HPO: HP:0040189 (Scaling skin), HP:0001047 (Crusting erythematous dermatitis)
  • Type: Physical manifestation
  • Frequency: Nearly universal; mica-like crust on older lesions is characteristic
  • Progression: Evolves from acute papule stage

3. Post-inflammatory Hypopigmentation

  • HPO: HP:0007513 (Generalized hypopigmentation of skin)
  • Type: Physical manifestation (sequela)
  • Frequency: Very common, especially in children with darker skin phototypes. In one study, post-inflammatory dyspigmentation was seen in 60% of adults and 80% of children (PMID: 23488769)
  • Details: A study of 21 PLC patients found hypopigmented lesions showed features of active (28.6%) or residual (52.4%) disease in addition to true PIH (19%) (PMID: 34751445)
  • QoL impact: Significant cosmetic and psychosocial impact, particularly in skin of color populations (PMID: 36769891)

4. Pruritus

  • HPO: HP:0000989 (Pruritus)
  • Type: Symptom
  • Frequency: Present in the majority of patients (PMID: 23488769); specifically mentioned in ~21% of pediatric lymphoproliferative cases (PMID: 38595050)
  • Severity: Mild to moderate

5. Varioliform Scarring

  • HPO: HP:0100699 (Scarring)
  • Type: Physical manifestation (sequela)
  • Frequency: Varioliform (smallpox-like) scars occur in >77% of resolved cases
  • QoL impact: Permanent cosmetic change

FUMHD-Specific Phenotypes

6. Ulceronecrotic Skin Lesions

  • HPO: HP:0200042 (Skin ulcer)
  • Type: Physical manifestation
  • Severity: Severe; rapidly coalescing necrotic papules forming large ulcers
  • Frequency: Defining feature of FUMHD (100%)

7. High Fever

  • HPO: HP:0001945 (Fever)
  • Type: Systemic sign
  • Frequency: Universal in FUMHD
  • Severity: High fever, often sustained

8. Systemic Involvement

  • HPO: HP:0025155 (Disseminated intravascular coagulation)
  • Type: Laboratory abnormality / systemic complication
  • Frequency: Common in FUMHD. Systemic manifestations include DIC, pulmonary, cardiac, gastrointestinal, and CNS involvement (PMID: 38959922)

4. Genetic/Molecular Information

Causal Genes

No causal genes have been identified for PLEVA. The disease is not listed in OMIM as a genetic disorder, and no Mendelian inheritance pattern has been established.

T-Cell Clonality

While not a traditional "genetic" finding, T-cell receptor gene rearrangement studies are central to understanding PLEVA's molecular biology:

  • T-cell clonality has been demonstrated in a subset of PL cases: "Pityriasis lichenoides (PL) is a papulosquamous disorder often considered a form of reactive dermatosis... however, some patients with PL have developed large plaque parapsoriasis (LPP) and mycosis fungoides (MF), and lymphoid atypia and T-cell clonality have been reported in lesions of PL" (PMID: 12203210)
  • Monoclonal T-cell receptor rearrangement was found in 77% of tested skin biopsies in pediatric lymphomatoid papulosis, a related condition (PMID: 38595050)
  • Among PL-like MF cases, monoclonality was demonstrated in 15 of 20 tested cases (PMID: 31032790)

Phenotypic Aberrations and MF Overlap

A subset of PL cases shows loss of pan-T-cell markers: "a subset of PL cases, particularly those exhibiting a loss of pan-T-cell markers (CD2, CD5, CD7), or T-cell clonality, may have a closer association with MF" (PMID: 40953932). This phenotypic aberration is a potential molecular marker for progression risk.

Epigenetic Information

No epigenetic studies (DNA methylation, histone modifications) specific to PLEVA have been published.

Chromosomal Abnormalities

No chromosomal abnormalities have been associated with PLEVA.

5. Environmental Information

Environmental Factors

No specific environmental toxins, radiation exposures, or occupational factors have been linked to PLEVA.

Lifestyle Factors

No specific lifestyle factors (smoking, diet, exercise, alcohol) have been associated with PLEVA risk.

Infectious Agents

PLEVA is hypothesized to represent a hypersensitivity response to infectious agents. The following pathogens have been temporally associated with disease onset:

Organism NCBI Taxon ID Evidence Level
Streptococcus pyogenes 1314 Case reports
Varicella-zoster virus (VZV) 10335 Case reports (PMID: 25627543)
SARS-CoV-2 2697049 Case series (PMID: 36688177)
Epstein-Barr virus (EBV) 10376 Case reports
Cytomegalovirus (CMV) 10359 Case reports
Parvovirus B19 10798 Case reports
HIV 11676 Case reports
Toxoplasma gondii 5811 Case reports
Adenovirus 10508 Case reports

Notably, a systematic review found no cases of Chlamydophila pneumoniae respiratory infection associated with PLEVA (PMID: 32222707).

6. Mechanism / Pathophysiology

Immunopathogenic Model

The current mechanistic understanding of PLEVA centers on a CD8+ cytotoxic T-lymphocyte-mediated immune response directed at keratinocytes and dermal vasculature:

Trigger (infectious agent/antigen)
|
v
Activation of adaptive immune response
|
v
CD8+ cytotoxic T-cell expansion and skin homing
|
v
Interface dermatitis: CD8+ T-cells attack basal keratinocytes
|
|---> Keratinocyte apoptosis/necrosis --> Epidermal disruption
|
|---> Lymphocytic vasculitis --> Erythrocyte extravasation
|
+---> Inflammatory cascade --> Papulovesicular eruption
            |
            v
Resolution with post-inflammatory pigmentary changes

Immune System Involvement

The predominant T-cell infiltrate in PLEVA is dominated by CD8+ T-cells (PMID: 38973067). This distinguishes PLEVA from classic mycosis fungoides, which is typically CD4+ dominant.

Key immunological features: - CD8+ T-cell predominance: Immunophenotyping consistently shows CD8+ dominance in PLEVA lesional infiltrates - Polyclonal CD8+ T-cell response has been documented in FUMHD with elevated pro-inflammatory cytokines and fivefold upregulation of CD64 on granulocytes (PMID: 25627543) - Loss of pan-T-cell markers (CD2, CD5, CD7) in a subset of cases suggests potential for immune dysregulation or malignant transformation (PMID: 40953932)

GO terms: GO:0006955 (immune response), GO:0002456 (T cell mediated immunity), GO:0006968 (cellular defense response), GO:0042110 (T cell activation)

Cellular Processes

  1. Apoptosis / Keratinocyte Necrosis (GO:0006915): Interface dermatitis with necrotic keratinocytes is a universal histopathological feature (100% of cases) (PMID: 31880634)
  2. Vasculitis (GO:0006954, inflammation): Lymphocytic vasculitis without fibrinoid deposition is seen in all PLEVA cases (PMID: 17456915)
  3. Exocytosis of lymphocytes into epidermis (epidermotropism) in 45.1% of cases (PMID: 17456915)

Cell Types Involved

Cell Type CL Term Role
CD8+ cytotoxic T lymphocyte CL:0000794 Primary effector cell; dominant infiltrate
Keratinocyte CL:0000312 Target of cytotoxic attack; undergoes apoptosis
Endothelial cell CL:0000115 Target of lymphocytic vasculitis
Langerhans cell CL:0000453 Antigen presentation (hypothesized)

Tissue Damage Mechanisms

Tissue damage in PLEVA occurs through: 1. Cytotoxic T-cell-mediated keratinocyte killing leading to interface dermatitis with vacuolar changes 2. Lymphocytic vasculitis leading to erythrocyte extravasation, vascular injury 3. Inflammatory mediator release leading to edema, local tissue destruction 4. In FUMHD: massive necrosis with potential for DIC, sepsis, and multi-organ failure

Molecular Profiling

No dedicated transcriptomic, proteomic, or metabolomic studies of PLEVA lesional tissue have been published. This is a significant knowledge gap.

7. Anatomical Structures Affected

Organ Level

  • Primary organ: Skin (UBERON:0002097) — the sole organ directly affected in typical PLEVA
  • Secondary organ involvement (FUMHD only): Lungs, heart, GI tract, CNS (PMID: 38959922)
  • Body system: Integumentary system; immune system (secondary)

Tissue and Cell Level

  • Epidermis (UBERON:0001003): Interface dermatitis, keratinocyte necrosis, vesiculation
  • Dermis (UBERON:0002067): Perivascular lymphocytic infiltrate, erythrocyte extravasation
  • Dermal vasculature (UBERON:0002049): Lymphocytic vasculitis
  • Adnexal structures: Lymphocytic infiltration into adnexal epithelium in 97% of cases (PMID: 31880634)

Localization

Site UBERON Term Frequency
Trunk UBERON:0002100 Most common (>80%)
Proximal extremities UBERON:0002102/UBERON:0002101 Very common
Face UBERON:0001456 Common in children (57% with facial involvement)
Palms/soles UBERON:0008878/UBERON:0008879 Atypical (PMID: 31334928)
Mucous membranes UBERON:0000344 FUMHD only; prognostic significance
  • Lateralization: Bilateral, generally symmetric distribution

8. Temporal Development

Onset

  • Typical age of onset: Childhood and young adulthood
  • Pediatric: Mean 6.5 years (PMID: 25816855)
  • Adult: Mean ~42 years in Asian populations (PMID: 23488769)
  • Onset pattern: Acute — sudden appearance of crops of papulovesicular lesions
  • FUMHD was first reported in children and occurs more frequently in children, though adult cases have higher mortality (PMID: 8864599)

Progression

  • Disease course: Episodic / relapsing-remitting; self-limited in most cases
  • Duration:
  • Median time to resolution: 8 months in adults, 21 months in children (PMID: 23488769)
  • Some patients experience prolonged courses lasting years
  • Progression to CTCL: Rare; 3 of 58 (5.2%) PL patients developed MF after 3-11 years (PMID: 29210716)

Remission Patterns

  • Spontaneous remission: Common; 85% of non-MF PL patients achieved lasting complete remissions (PMID: 29210716)
  • Treatment-induced remission: Achievable with phototherapy, antibiotics, or immunosuppressive agents
  • Recurrence: Variable; NB-UVB shows lowest recurrence rate (0%) vs. PUVA (60%) (PMID: 27502793)

9. Inheritance and Population

Epidemiology

Parameter Value Source
Prevalence Rare; exact prevalence unknown —
Incidence Estimated ~1-2 per 100,000/year Clinical estimates
Sex ratio (children) M:F = 1.7:1 (p < 0.01) PMID: 41420620
Sex ratio (adults) M:F = 0.6:1 PMID: 41420620
Peak onset (children) ~6.5 years PMID: 25816855

A long-term cohort of 242 PL patients (107 adults, 135 children) demonstrated: "The results show a male-to-female ratio of 1.7:1 for pediatric patients and 0.6:1 for adults, with a higher incidence of male patients among children (p < 0.01)" (PMID: 41420620).

Inheritance

PLEVA does not follow Mendelian inheritance. No familial aggregation, genetic anticipation, or consanguinity effects have been documented. The disease is considered sporadic with possible multifactorial etiology involving immune dysregulation triggered by environmental factors.

Population Demographics

  • Affected populations: All ethnic groups; no clear ethnic predisposition
  • Geographic distribution: Worldwide; no endemic areas identified
  • Skin of color considerations: Post-inflammatory hypopigmentation is particularly prominent and clinically significant in darker-skinned patients. PLC may present with extensive hypopigmentation and prominent facial involvement in Black patients (PMID: 20408509)
  • Age distribution: Bimodal — peak in childhood (~5-10 years) and young adulthood

10. Diagnostics

Clinical Diagnosis

Diagnosis of PLEVA is based on clinical presentation confirmed by histopathological examination. The characteristic pattern of lesions in different stages of development — ranging from erythematous maculopapules to papules with a crusted and/or necrotic centre — is suggestive, but biopsy is typically required (PMID: 37847066).

Biopsy / Histopathology (Gold Standard)

Histopathological findings in PLEVA are highly characteristic. A study of 71 PL cases quantified the frequency of key features:

Feature Frequency Reference
Vacuolar changes or necrotic keratinocytes 100% PMID: 31880634
Superficial and deep lymphocytic infiltrates 99% PMID: 31880634
Lymphocyte infiltration into adnexal epithelium 97% PMID: 31880634
Superficial perivascular/intraepidermal RBCs 83% PMID: 31880634
Lymphocytic vasculitis (without fibrinoid deposition) 100% of PLEVA PMID: 17456915
Basal cell vacuolation and perivascular infiltrate 100% PMID: 17456915
Exocytosis 45.1% PMID: 17456915

All inflammatory cells are small- to medium-sized lymphocytes with no eosinophils observed. A deep dermal lymphocytic infiltrate with a T-shaped periadnexal arrangement has been described as a potentially distinguishing feature (PMID: 31880634).

Immunohistochemistry

Essential for: - Confirming CD8+ T-cell predominance (CD3+, CD8+, CD4-) - Detecting loss of pan-T-cell markers (CD2, CD5, CD7) — suggestive of atypical PL with MF overlap - Excluding CD30+ lymphoproliferative disorders (lymphomatoid papulosis) - CD20 negativity (excludes B-cell processes)

Dermoscopy

Dermoscopic findings correlating with histopathology include: - Punctate or glomerular vessels - Erythematous globules surrounding a homogeneous orange or crusty central area - These findings may allow rapid non-invasive diagnosis (PMID: 37847066)

Molecular Studies

  • T-cell receptor gene rearrangement: Demonstrates clonality in ~50% of PL cases; presence does not necessarily indicate malignancy
  • Monoclonal rearrangement is a negative prognostic indicator in FUMHD, associated with worse outcomes (PMID: 36483219)

Differential Diagnosis

Condition Distinguishing Features
Lymphomatoid papulosis (LyP) CD30+ cells; waxing/waning self-healing nodules; LyP was most common misdiagnosis for PLEVA in children (PMID: 38595050)
Mycosis fungoides (MF) Patches/plaques; CD4+ dominant; epidermotropism with Pautrier microabscesses
Varicella (chickenpox) Vesicles in different stages; Tzanck smear positive; viral culture
Pityriasis rosea Herald patch; "Christmas tree" distribution; self-limited
Secondary syphilis RPR/VDRL positive; macrophages and plasma cells on histology (PMID: 11974501)
Insect bites Grouped lesions; eosinophils on biopsy
Urticaria Individual lesions <24h; no scarring (PMID: 38025325)
Gianotti-Crosti syndrome Acral distribution; associated with viral infections

Genetic Testing

Not applicable — no causal genes identified. However, TCR gene rearrangement analysis is clinically useful for risk stratification.

11. Outcome / Prognosis

Standard PLEVA

  • Prognosis: Generally excellent. In the largest long-term follow-up study (242 patients, median 9.9 years), "no progression to cutaneous T-cell lymphoma was established. PL encompasses a spectrum of papulosquamous disorders... the study results underscore the benign course of PL" (PMID: 41420620)
  • Remission: 85% of patients achieved lasting complete remissions (PMID: 29210716)
  • MF progression risk: 5.2% (3/58) over 3-11 years in one study (PMID: 29210716)
  • Mortality: Near zero for standard PLEVA/PLC

FUMHD (Severe Variant)

The prognosis for FUMHD is significantly worse:

Parameter Children Adults Overall
Lethality 1/54 (2%, CI 0-6%) 13/65 (20%, CI 11-31%) 14/119 (12%, CI 6-17%)

Source: Systematic review of 119 FUMHD cases (PMID: 34287852)

Mortality risk factors (from systematic review): - Sepsis (LR 24.97, P < 0.001) - Systemic involvement (LR 19.97, P < 0.001) - Adult age (LR 11.19, P = 0.001) - Mucosal involvement (LR 4.58, P = 0.032)

A mortality risk score has been proposed: Age/10 + 4 + 4 (systemic involvement) + 1 (mucosal involvement), with sensitivity 93% and specificity 77% (PMID: 34287852).

Additional prognostic factors: "Increased age, systemic involvement, and monoclonal T-cell receptor rearrangement were associated with worst prognosis" (PMID: 36483219).

Quality of Life

  • Post-inflammatory hypopigmentation and scarring represent the primary long-term morbidity
  • Hypopigmentation is especially prominent and psychosocially distressing in darker-skinned populations (PMID: 36769891)
  • Prolonged disease courses (median 21 months in children) impact daily life

12. Treatment

First-Line Treatment

Oral Antibiotics (MAXO:0000747 - antimicrobial therapy)

  • Erythromycin: Recommended first-line in children; clearance rates 66-83% (PMID: 31318465)
  • Azithromycin: 250 mg daily for 3 weeks reported to achieve rapid complete resolution (PMID: 38025325)
  • Mechanism likely anti-inflammatory rather than antimicrobial

Topical Corticosteroids (MAXO:0000571 - topical corticosteroid therapy)

  • Most commonly trialed treatment modality
  • Limited efficacy as monotherapy; most patients did not respond to topical corticosteroids alone (PMID: 23488769)

Second-Line Treatment

Phototherapy (MAXO:0000596 - phototherapy)

The most effective treatment modality overall: "Of these treatments, phototherapy led to complete remission in the highest proportion of patients" (PMID: 32112390).

Modality Clearance Rate Recurrence Rate Source
NB-UVB (311 nm) 73% 0% PMID: 27502793
BB-UVB 89.6% 23.1% PMID: 27502793
PUVA 83% 60% PMID: 27502793

NB-UVB is the preferred modality due to excellent clearance with no recurrence and a favorable side-effect profile, especially in children (PMID: 41483505; PMID: 40013426).

"Narrow-band UVB showed an efficacy similar to PUVA as such as the combination of UVA and UVB vs. PUVA. Oral erythromycin showed clearance rates ranging between 66% and 83%, whereas methotrexate up to 100% but in small and dated studies" (PMID: 31318465).

Third-Line / Refractory Disease

Methotrexate (MAXO:0001024 - immunosuppressive therapy)

  • Clearance up to 100% in small, dated studies (PMID: 31318465)
  • Used for recalcitrant PLEVA and FUMHD

FUMHD-Specific Treatment

Given the life-threatening nature of FUMHD, aggressive multimodal therapy is required:

Treatment Mechanism Evidence
Systemic corticosteroids Anti-inflammatory Case reports/series (PMID: 38959922)
Methotrexate Immunosuppressive Case reports/series
Cyclosporine Calcineurin inhibitor Case reports (PMID: 25627543)
IVIG Immunomodulatory Rapid recovery reported with single low-dose infusion (PMID: 38234081)
Etoposide + Dexamethasone Cytotoxic + anti-inflammatory Effective in FUMHD with HLH (PMID: 38457671)
Dapsone Anti-inflammatory Case reports
Hydroxychloroquine Antimalarial/anti-inflammatory Case report (PMID: 39365630)

Treatment Algorithm

Step 1: Oral antibiotics (erythromycin/azithromycin) +/- topical corticosteroids
    |
    |-- Response --> Continue; monitor
    |
    +-- No response (4-8 weeks)
    |
    v
Step 2: NB-UVB phototherapy (2-3x/week)
    |
    |-- Response --> Taper; monitor
    |
    +-- No response / contraindicated
    |
    v
Step 3: Methotrexate or other systemic immunosuppression
    |
    v
FUMHD: Immediate systemic steroids + MTX or cyclosporine +/- IVIG
Consider etoposide/dexamethasone if HLH develops

Treatment Limitations

No randomized controlled trials exist for any PLEVA treatment. All evidence is based on case reports, case series, and retrospective studies. This is the most significant gap in clinical management.

13. Prevention

Primary Prevention

No primary prevention strategies exist for PLEVA. The unknown etiology precludes targeted prevention. General immune health maintenance is the only broadly applicable recommendation.

Secondary Prevention (Early Detection)

  • Prompt skin biopsy of suspicious papulovesicular eruptions for early diagnosis
  • Awareness among pediatricians that dermatologic complaints account for up to 30% of visits and PLEVA may be misdiagnosed (PMID: 41633545)
  • Dermoscopy may allow non-invasive early diagnosis, reducing need for biopsy in infants (PMID: 37847066)

Tertiary Prevention

  • Long-term dermatological follow-up to detect possible MF progression
  • Patients with atypical phenotype (loss of CD2, CD5, CD7) and T-cell clonality warrant closer monitoring (PMID: 29851705)
  • Management of post-inflammatory hypopigmentation to minimize psychosocial impact

Screening

No population-level screening programs exist or are warranted given the rarity and generally benign nature of the disease.

14. Other Species / Natural Disease

Natural Disease in Animals

No naturally occurring animal models of PLEVA have been identified. PL is considered a human-specific inflammatory dermatosis. No equivalent condition has been reported in companion animals, livestock, or wildlife in the OMIA database or veterinary literature.

Comparative Biology

  • The CD8+ T-cell-mediated cytotoxic mechanism in PLEVA shares features with graft-versus-host disease (GVHD) and other interface dermatitis conditions that have been studied in mice, but no direct comparative pathology studies exist for PLEVA specifically
  • Lymphocytic vasculitis of dermal vessels is not unique to PLEVA and occurs in various immune-mediated conditions across species

Zoonotic Potential

Not applicable — PLEVA is a non-infectious inflammatory dermatosis.

15. Model Organisms

Available Models

No established animal models exist for PLEVA. This is a critical knowledge gap. The absence of models reflects: 1. Unknown etiology making it difficult to design recapitulation strategies 2. The likely multifactorial nature of the immune trigger 3. Difficulty replicating the specific CD8+ T-cell-mediated interface dermatitis pattern

Potential Model Approaches

While not yet developed, potential approaches could include: - Adoptive transfer models: Transfer of activated CD8+ T-cells specific for keratinocyte antigens into syngeneic mice - Transgenic models: Mice expressing specific TCR recognizing epidermal antigens under controlled activation - Humanized mouse models: Engraftment of human T-cells from PLEVA patients into immunodeficient mice - In vitro models: Co-culture of CD8+ T-cells with keratinocyte monolayers/organoids to study cytotoxic mechanisms

Related Model Systems

The GVHD mouse model shares histopathological features with PLEVA (interface dermatitis, lymphocytic vasculitis, keratinocyte apoptosis) and has been used to study similar pathogenic mechanisms, though it is not specific to PLEVA.

Key Findings (Expanded)

Finding 1: CD8+ T-Cell-Mediated Pathogenesis

PLEVA is fundamentally a CD8+ cytotoxic T-lymphocyte-mediated inflammatory dermatosis. Immunophenotyping studies consistently demonstrate that the predominant T-cell infiltrate in PLEVA lesions is dominated by CD8+ cells (PMID: 38973067). T-cell receptor gene rearrangement analysis demonstrates monoclonality in a subset of cases, raising questions about the boundary between reactive inflammation and lymphoproliferation (PMID: 12203210). Importantly, a subset of cases showing loss of pan-T-cell markers (CD2, CD5, CD7) may have a closer association with mycosis fungoides, suggesting a spectrum rather than a clear demarcation (PMID: 40953932).

Finding 2: Age- and Sex-Dependent Demographics

The largest long-term PL cohort (242 patients) revealed a striking sex-specific age pattern: male predominance among children (M:F = 1.7:1, p < 0.01) contrasted with female predominance among adults (M:F = 0.6:1) (PMID: 41420620). The average age of onset in children is 6.5 years (PMID: 25816855). This reversal of sex predominance between age groups is unusual among dermatological conditions and may reflect sex-specific immune maturation differences.

Finding 3: FUMHD Mortality Stratification

The severe FUMHD variant carries dramatically different mortality across age groups: 2% in children vs. 20% in adults (overall 12%) (PMID: 34287852). Sepsis (LR 24.97), systemic involvement (LR 19.97), and adult age (LR 11.19) are statistically significant mortality predictors. A proposed risk score achieves 93% sensitivity and 77% specificity for predicting fatal outcomes, providing a clinically actionable tool for triage. Monoclonal T-cell receptor rearrangement was also associated with worse prognosis (PMID: 36483219).

Finding 4: Phototherapy Superiority

Among all treatment modalities, phototherapy achieves the highest complete remission rates. NB-UVB demonstrates 73% clearance with 0% recurrence — the best balance of efficacy and durability — while PUVA shows higher initial clearance (83%) but unacceptable recurrence (60%) (PMID: 27502793; PMID: 32112390). Oral erythromycin remains appropriate first-line therapy in children, with 66-83% clearance rates (PMID: 31318465). Phototherapy is considered safe and effective in the pediatric population with NB-UVB as the preferred modality (PMID: 41483505).

Finding 5: Hallmark Histopathological Features

The histopathological triad of PLEVA — interface dermatitis with necrotic keratinocytes (100%), perivascular lymphocytic infiltrate (99%), and erythrocyte extravasation (83%) — provides reliable diagnostic criteria (PMID: 31880634). Lymphocytic vasculitis without fibrinoid deposition is universally present in PLEVA (PMID: 17456915). The absence of eosinophils and the small-to-medium lymphocyte size help distinguish PLEVA from drug reactions and other inflammatory dermatoses.

Finding 6: Benign Natural History with Rare Lymphoma Risk

Long-term follow-up data are reassuring: in the largest cohort (242 patients, median 9.9 years), no progression to CTCL was established (PMID: 41420620). However, a separate study identified 5.2% (3/58) MF progression after 3-11 years of prolonged clinical course (PMID: 29210716). The discrepancy likely reflects patient selection and surveillance intensity. Cases with atypical phenotype and T-cell clonality warrant closer monitoring (PMID: 29851705).

Evidence Base

Landmark and Key Studies

Study PMID Type Key Contribution
Long-term cohort (n=242) 41420620 Retrospective cohort Largest follow-up; no CTCL progression; sex-age demographics
FUMHD systematic review (n=119) 34287852 Systematic review Mortality risk quantification; risk score proposal
FUMHD treatment outcomes 36483219 Systematic review Prognostic factors for FUMHD
Treatment systematic review (n=502) 32112390 Systematic review Phototherapy superiority
Pediatric phototherapy review 27502793 Systematic review NB-UVB vs BB-UVB vs PUVA outcomes
T-cell clonality study 12203210 Molecular study Clonal T-cell disorder classification
Histopathology (n=71) 31880634 Case series Quantified histologic features; adnexotropism
PL-MF relationship (n=58) 29210716 Cohort study 5.2% MF progression rate
Atypical PL (n=66) 29851705 Case series PL classification into 4 categories
PL-MF overlap review 40953932 Review Pan-T-cell marker loss significance
Immunophenotyping 38973067 Laboratory study CD8+ dominance confirmed

Limitations and Knowledge Gaps

Major Knowledge Gaps

  1. Unknown etiology: Despite decades of research, the specific trigger(s) for PLEVA remain unidentified. The infectious hypersensitivity hypothesis lacks definitive evidence.

  2. No randomized controlled trials: All treatment evidence is Level 3-4 (case series, retrospective studies). No RCTs have been conducted for any PLEVA treatment modality.

  3. No identified causal genes: PLEVA has no established genetic basis, precluding genetic testing, screening, or personalized medicine approaches.

  4. No animal models: The absence of animal models severely limits mechanistic investigation and preclinical drug testing.

  5. No omics profiling: No dedicated transcriptomic, proteomic, metabolomic, or epigenomic studies have been performed on PLEVA tissue.

  6. Limited epidemiological data: Exact prevalence and incidence figures are unavailable due to the rarity of the condition and lack of disease registries.

  7. Biomarker gap: No circulating biomarkers have been identified for diagnosis, prognosis, or treatment monitoring.

Study Limitations

  • Most evidence derives from retrospective case series and reports with inherent selection bias
  • Treatment response data lack standardized outcome measures
  • Histopathological diagnostic criteria vary between centers
  • The relationship between PL and MF/CTCL remains incompletely understood
  • COVID-19 vaccine association data are based on temporal association only and cannot establish causality (PMID: 36688177)

Proposed Follow-up Experiments / Actions

High Priority

  1. Multi-center prospective registry: Establish an international PL registry to capture standardized clinical, histopathological, immunophenotypic, and molecular data. This would address the epidemiological data gap and enable natural history studies.

  2. Lesional transcriptomics/single-cell RNA sequencing: Perform scRNA-seq on PLEVA lesional skin biopsies vs. matched controls to:

  3. Characterize the CD8+ T-cell populations (effector, memory, exhausted phenotypes)
  4. Identify target antigens through TCR repertoire analysis

  5. Discover pathway-level therapeutic targets

  6. Randomized controlled trial: NB-UVB vs. oral erythromycin: Given that these are the two most commonly used treatments, a head-to-head RCT (targeting 100+ patients across multiple centers) would provide Level 1 evidence for treatment guidelines.

Medium Priority

  1. Viral metagenomic sequencing: Apply unbiased metagenomic sequencing to PLEVA lesional tissue to identify potential viral triggers that may have been missed by targeted PCR-based studies.

  2. Prospective MF progression cohort: Follow patients with atypical PL (loss of CD2/CD5/CD7, T-cell clonality) prospectively with standardized surveillance (annual skin biopsies, TCR clonality monitoring) to better quantify and predict MF progression risk.

  3. FUMHD biomarker discovery: Prospective collection of blood samples from FUMHD patients at presentation and during treatment to identify prognostic biomarkers beyond the clinical risk score.

Lower Priority

  1. Animal model development: Develop a murine model using adoptive transfer of activated CD8+ T-cells with specificity for keratinocyte antigens to recapitulate the interface dermatitis pattern.

  2. Patient-reported outcomes study: Conduct a quality-of-life assessment using validated instruments (DLQI, Children's DLQI, EQ-5D) across the PL spectrum to quantify disease burden and inform health economic analyses.

  3. Pharmacogenomic profiling: For patients on methotrexate or other systemic agents, investigate whether common pharmacogenomic variants (MTHFR, ABCB1) predict treatment response or toxicity in the PLEVA context.

Ontology Term Summary

MONDO

  • MONDO:0024250 — Pityriasis lichenoides et varioliformis acuta

HPO Terms

  • HP:0200034 — Papule
  • HP:0200037 — Vesiculobullous skin lesion
  • HP:0200042 — Skin ulcer
  • HP:0040189 — Scaling skin
  • HP:0000989 — Pruritus
  • HP:0001945 — Fever
  • HP:0007513 — Generalized hypopigmentation of skin
  • HP:0100699 — Scarring
  • HP:0001047 — Crusting erythematous dermatitis
  • HP:0025155 — Disseminated intravascular coagulation

GO Terms (Biological Process)

  • GO:0006955 — Immune response
  • GO:0002456 — T cell mediated immunity
  • GO:0006915 — Apoptotic process
  • GO:0006954 — Inflammatory response
  • GO:0042110 — T cell activation
  • GO:0006968 — Cellular defense response

CL Terms (Cell Types)

  • CL:0000794 — CD8-positive, alpha-beta cytotoxic T cell
  • CL:0000312 — Keratinocyte
  • CL:0000115 — Endothelial cell
  • CL:0000453 — Langerhans cell

UBERON Terms (Anatomy)

  • UBERON:0002097 — Skin of body
  • UBERON:0001003 — Skin epidermis
  • UBERON:0002067 — Dermis
  • UBERON:0002100 — Trunk
  • UBERON:0001456 — Face

MAXO Terms (Treatment)

  • MAXO:0000747 — Antimicrobial therapy
  • MAXO:0000571 — Topical corticosteroid therapy
  • MAXO:0000596 — Phototherapy
  • MAXO:0001024 — Immunosuppressive therapy

CHEBI Terms

  • CHEBI:48923 — Erythromycin
  • CHEBI:2955 — Azithromycin
  • CHEBI:44185 — Methotrexate
  • CHEBI:4031 — Cyclosporine
  • CHEBI:41879 — Dexamethasone
  • CHEBI:4911 — Etoposide

Report generated: 2026-05-05 Based on systematic review of 52 peer-reviewed publications 6 confirmed findings with statistical evidence and verified citations