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Classifications

Harrison's Part

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Discussions and Knowledge Gaps

2

Immune checkpoint inhibitor-induced bullous pemphigoid is a clinically important and increasingly recognized trigger, but is named only in the `environmental` description rather than curated with its own evidence.

CURATION TODO OPEN bp_checkpoint_inhibitor_trigger_uncurated

The gliptin/DPP-4-inhibitor arm is now evidenced (PMID:39091267) under `environmental`. The checkpoint-inhibitor arm still lacks a quotable source in this entry: the closest candidate found during curation, PMID:41747673 (a real-life comparative study of gliptin- and checkpoint-inhibitor-induced versus idiopathic BP), is indexed in PubMed without an abstract, so no excerpt satisfies the evidence SOP. Resolving this needs a paper with retrievable text reporting the checkpoint-inhibitor risk association.

Bullous pemphigoid is consistently associated with neurological disease (dementia, Parkinson disease, stroke). Is this association causal in either direction, and is it explained by shared BP180/BP230 (dystonin) expression in the central nervous system?

OPEN QUESTION OPEN bp_neurological_association_direction

BP180 (collagen XVII) and BP230 (dystonin) have neural isoforms expressed in the central nervous system, giving a plausible route by which neurodegeneration could expose cross-reactive epitopes and break tolerance. The association is robust epidemiologically, but the cited cohort cannot establish direction, and its per-condition results are not internally uniform - Alzheimer disease was actually more common in controls, discordant with several other reports. The association is recorded here as an open question rather than as a curated causal edge in the pathograph.

Proposed experiments

Temporal sequencing of neurological diagnosis relative to BP onset

bp_neuro_temporal_sequence

Longitudinal population cohort determining whether neurological diagnoses precede or follow first BP diagnosis, with time-to-event analysis in both directions.

Decision criterion

Consistent precedence of neurological diagnosis over BP onset would favour neurodegeneration-driven epitope exposure over a shared-susceptibility or reverse-causation model.

Supporting outcome

Neurological disease precedes BP onset at a rate exceeding the reverse ordering.

Refuting outcome

No consistent temporal ordering, or BP predominantly precedes neurological diagnosis.

Anti-BP180/BP230 serology in neurodegenerative disease without skin disease

bp_neuro_crossreactive_serology

Serological screening for anti-BP180 NC16A and anti-BP230 reactivity in dementia, Parkinson disease and stroke cohorts with no cutaneous disease, against age-matched neurologically healthy controls.

Decision criterion

Elevated subclinical autoantibody reactivity in neurodegenerative cohorts would support CNS epitope exposure as the tolerance-breaking event.

Supporting outcome

Significantly higher anti-BP180/BP230 reactivity in neurodegenerative cohorts than controls.

Refuting outcome

Equivalent reactivity across neurodegenerative and control groups.

Show evidence (2 references)

PMID:30663128 SUPPORT Human Clinical

"Our cohort of bullous pemphigoid and neurological disorders demonstrates a significant association between bullous pemphigoid and neurological disorders, including dementia, Parkinson's disease and stroke."

Case-control study of 183 BP patients and 348 matched controls finds a significant association with dementia, Parkinson disease and stroke.

PMID:30663128 SUPPORT Human Clinical

"These included dementia (P < 0.0001), Parkinson`s disease (P = 0.0434), stroke (P = 0.0015) and other neurological disorders but not Alzheimer's diseases, which was more common among patients in the control group."

Records the per-condition detail including the negative finding for Alzheimer disease, which was more common in controls in this cohort - a discordance with other reports worth preserving rather than smoothing over.

⚙

Pathophysiology

4

Anti-Hemidesmosomal Autoantibody Formation

Loss of tolerance to hemidesmosomal structural proteins generates autoantibodies against BP180 (collagen XVII) and BP230 (dystonin), the proteins that anchor basal keratinocytes to the underlying dermis. The immunodominant epitope lies in the extracellular juxtamembranous NC16A domain of BP180.

B cell CL:0000236

COL17A1 hgnc:2194 DST hgnc:1090

Downstream

Complement Activation and Inflammatory Cell Recruitment Autoantibody binding at the dermal-epidermal junction initiates classical complement activation and mast cell degranulation.

Show evidence (2 references)

PMID:39979318 SUPPORT Human Clinical

"The disease arises from autoantibodies targeting hemidesmosomal proteins BP180 and BP230, which are crucial for dermal-epidermal adhesion."

The Nature Reviews Disease Primers overview identifies BP180 and BP230 autoantibodies as the initiating lesion.

PMID:41127641 SUPPORT Human Clinical

"a microarray of overlapping peptides spanning the NC16A domain of BP180 and the C-terminus of BP230 autoantigens was screened with sera of 13 patients with bullous pemphigoid and 2 control sera."

Confirms NC16A of BP180 and the BP230 C-terminus as the autoantibody-reactive regions interrogated in patient sera.

Complement Activation and Inflammatory Cell Recruitment

Autoantibody deposition at the basement membrane zone activates the classical complement pathway and degranulates mast cells, recruiting neutrophils and eosinophils to the dermal-epidermal junction.

mast cell CL:0000097 neutrophil CL:0000775 eosinophil CL:0000771

complement activation GO:0006956 ↑ INCREASED mast cell mediated immunity GO:0002448 ↑ INCREASED

Downstream

Proteolytic Degradation of the Dermal-Epidermal Junction Recruited granulocytes release proteinases and granule proteins at the basement membrane zone.

Show evidence (2 references)

PMID:29545809 SUPPORT Model Organism

"Mast cells and mast cell-derived mediators including inflammatory cytokines and proteases are increased in lesional skin and blister fluids of BP."

Documents mast cell mediator enrichment in human BP lesional skin and blister fluid.

PMID:40488683 SUPPORT Model Organism

"STAT6-deficient mice exhibited reduced subepidermal blister formation and eosinophil infiltration in 2 BP mouse models."

Reduced eosinophil infiltration accompanies reduced blistering in two BP mouse models, supporting eosinophil recruitment as a required step.

Proteolytic Degradation of the Dermal-Epidermal Junction

Neutrophil proteinases together with the eosinophil granule proteins eosinophil-derived neurotoxin (EDN) and eosinophil cationic protein (ECP) degrade BP180 and impair keratinocyte adhesion at the basement membrane zone.

keratinocyte CL:0000312

neutrophil degranulation GO:0043312 ↑ INCREASED

Downstream

Subepidermal Blister Formation Loss of hemidesmosomal anchoring separates the epidermis from the dermis, forming the blister cavity.

Show evidence (1 reference)

PMID:40488683 SUPPORT Human Clinical

"Eosinophil-derived neurotoxin and eosinophil cationic protein were substantially elevated and localized within bullous areas of skin samples from patients with BP."

Localizes the effector granule proteins to blistering skin in human BP biopsies.

Subepidermal Blister Formation

Separation occurs within the lamina lucida, superficial to the lamina densa, producing tense bullae with an intact epidermal roof. Because the cleavage plane spares the dermis, lesions heal without scarring - in contrast to the intraepidermal, desmoglein-mediated acantholytic split of pemphigus vulgaris.

Downstream

Tense Bullae The subepidermal cleavage plane yields clinically tense, fluid-filled blisters.

Show evidence (1 reference)

PMID:40488683 SUPPORT Model Organism

"Eosinophil-derived neurotoxin and eosinophil cationic protein play a critical role in subepidermal blister formation in BP."

Names subepidermal blister formation as the endpoint of the eosinophil granule protein mechanism.

✶

Histopathology

1

Subepidermal Blister with Eosinophil-Rich Infiltrate

Histology shows a subepidermal split with an inflammatory infiltrate rich in eosinophils. The cleavage plane lies above the lamina densa, which is why lesions re-epithelialize without scarring.

Show evidence (2 references)

PMID:39979318 SUPPORT Human Clinical

"Bullous pemphigoid is a chronic, subepidermal autoimmune blistering disease characterized by tense blisters on erythematous or normal skin"

Establishes the subepidermal level of the split that defines the histological picture.

PMID:40488683 SUPPORT Human Clinical

"Eosinophil-derived neurotoxin and eosinophil cationic protein were substantially elevated and localized within bullous areas of skin samples from patients with BP."

Localizes eosinophil granule proteins to the blistering areas of BP skin biopsies, the tissue correlate of the eosinophil-rich infiltrate.

⬡

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.

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Phenotypes

6

Blood 1

Increased Eosinophil Count Increased total eosinophil count HP:0001880

Peripheral and tissue eosinophilia accompany BP and are mechanistically linked to blister formation. Frequency band omitted pending a quantitative source.

Show evidence (1 reference)

PMID:40488683 SUPPORT Human Clinical

"Eosinophil-derived neurotoxin and eosinophil cationic protein were substantially elevated and localized within bullous areas of skin samples from patients with BP."

Documents eosinophil granule protein elevation in BP patient skin, the tissue correlate of the eosinophilic infiltrate.

Head and Neck 1

Mucosal Involvement OCCASIONAL Erosion of oral mucosa HP:0031446

Mucosal disease occurs in a minority of BP patients, most often oral. This is a key clinical discriminator from pemphigus vulgaris, where mucosal erosions are typically the presenting and near-universal feature. The cited 10-20% range maps to OCCASIONAL (29-5%) at its lower end and slightly exceeds it at the upper end; OCCASIONAL is retained as the closest single band.

Show evidence (1 reference)

PMID:29545809 SUPPORT Human Clinical

"About 10–20% of patients show mucosal involvement, with the oral mucosa being the most common mucosal site"

Quantifies mucosal involvement at 10-20% with oral mucosa the commonest site, supporting the OCCASIONAL band.

Immune 1

Eczematous Lesions (Non-Bullous Prodrome) OCCASIONAL Eczematoid dermatitis HP:0000964

The eczematous component of the same non-bullous prodrome. Curated as a distinct phenotype from the urticarial component because the two are named separately in the source and are separately recognizable clinically.

Show evidence (1 reference)

PMID:42206441 SUPPORT Human Clinical

"Up to 20% of patients with diagnosed BP present with only mild pruritus, excoriations, eczematous, papular, and urticarial lesions, without blistering"

Names eczematous lesions among the non-bullous presenting features, quantified at up to 20%.

Integument 2

Tense Bullae Abnormal blistering of the skin HP:0008066

Tense, fluid-filled subepidermal blisters arising on erythematous or normal skin, classically on flexural surfaces, trunk and proximal limbs. Frequency band omitted: the cited primer establishes tense blisters as the defining morphology but reports no occurrence rate.

Show evidence (1 reference)

PMID:39979318 SUPPORT Human Clinical

"Bullous pemphigoid is a chronic, subepidermal autoimmune blistering disease characterized by tense blisters on erythematous or normal skin that predominantly affects the older population."

The Nature Reviews Disease Primers definition identifies tense blistering as the cardinal manifestation.

Pruritus VERY_FREQUENT HP:0000989

Severity: SEVERE

Severe itch, frequently preceding blistering by weeks to months as a non-bullous prodrome. Band supported by "almost all patients", which maps to VERY_FREQUENT (80-100%) per the frequency-evidence guidelines.

Show evidence (1 reference)

PMID:29545809 SUPPORT Human Clinical

"In almost all patients, severe pruritus is present."

States that severe pruritus is present in almost all patients with BP, supporting both the phenotype and the VERY_FREQUENT band.

Other 1

Urticarial Lesions (Non-Bullous Prodrome) OCCASIONAL Urticarial plaque HP:0030351

Part of the non-bullous prodromal phase, in which pruritus, excoriations and eczematous, papular and urticarial lesions occur without blistering, often for weeks to months before bullae appear. "Up to 20%" of diagnosed BP patients present this way, which maps to OCCASIONAL (5-29%).

Show evidence (1 reference)

PMID:42206441 SUPPORT Human Clinical

"Up to 20% of patients with diagnosed BP present with only mild pruritus, excoriations, eczematous, papular, and urticarial lesions, without blistering"

Quantifies the non-bullous presentation at up to 20% and names urticarial lesions among its features, supporting the OCCASIONAL band.

🧬

Genetic Associations

1

HLA-DQB1*03:01 Susceptibility (HLA-DQB1*03:01 is the most consistently replicated HLA class II susceptibility allele in bullous pemphigoid, associated with both idiopathic and gliptin-associated disease.)

Gene: HLA-DQB1 hgnc:4944 relationship_type: SUSCEPTIBILITY

Show evidence (1 reference)

PMID:39091267 SUPPORT Human Clinical

"A significant association between HLA-DQB1*03:01 allele and IBP and GABP patients was found."

Finds HLA-DQB1*03:01 significantly associated with both idiopathic and gliptin-associated BP in an Italian cohort.

💊

Medical Actions

4

Systemic Corticosteroids

Action: Pharmacotherapy NCIT:C15986

Agent: corticosteroid CHEBI:50858

Corticosteroids remain the mainstay of treatment, aiming to reduce symptoms and prevent new blister formation.

Show evidence (1 reference)

PMID:39979318 SUPPORT Human Clinical

"Treatment aims to reduce symptoms and prevent new blister formation, using corticosteroids, immunosuppressive agents and biologics such as rituximab and omalizumab."

The primer identifies corticosteroids as the core of current BP management.

Doxycycline

Action: Pharmacotherapy NCIT:C15986

Agent: doxycycline CHEBI:50845

Doxycycline as an initial treatment strategy is non-inferior to oral prednisolone for short-term blister control and significantly safer over the long term, making it an important steroid-sparing option in a frail elderly population.

Show evidence (2 references)

PMID:28279484 SUPPORT Human Clinical

"Starting patients on doxycycline is non-inferior to standard treatment with oral prednisolone for short-term blister control in bullous pemphigoid and significantly safer in the long-term."

The BLISTER randomised non-inferiority trial establishes doxycycline as a viable first-line strategy.

PMID:28279484 SUPPORT Human Clinical

"For those starting doxycycline, 83 (74%) of 112 patients had three or fewer blisters at 6 weeks compared with 92 (91%) of 101 patients on prednisolone, an adjusted difference of 18·6% (90% CI 11·1-26·1) favouring prednisolone"

Records the efficacy trade-off underlying the non-inferiority conclusion - prednisolone achieved better 6-week blister control - so the doxycycline recommendation is not read as equivalent efficacy.

Rituximab

Action: Pharmacotherapy NCIT:C15986

Agent: rituximab NCIT:C1702

Anti-CD20 B cell depletion, used as a biologic option in refractory disease.

Mechanism Target:

INHIBITS Anti-Hemidesmosomal Autoantibody Formation — B cell depletion reduces production of pathogenic anti-BP180/BP230 autoantibodies.

Show evidence (1 reference)

PMID:39979318 SUPPORT Human Clinical

"using corticosteroids, immunosuppressive agents and biologics such as rituximab and omalizumab"

Partial. The primer establishes rituximab as an accepted BP biologic, but does not itself state the anti-CD20 mechanism; the B-cell-depletion link to autoantibody production is inferred from the drug class.

Show evidence (1 reference)

PMID:39979318 SUPPORT Human Clinical

"using corticosteroids, immunosuppressive agents and biologics such as rituximab and omalizumab"

The primer names rituximab among the biologics used in BP.

Omalizumab

Action: Pharmacotherapy NCIT:C15986

Agent: omalizumab NCIT:C29299

Anti-IgE monoclonal antibody, reflecting the pathogenic contribution of IgE autoantibodies and downstream mast cell activation.

Mechanism Target:

INHIBITS Complement Activation and Inflammatory Cell Recruitment — IgE neutralization dampens mast cell degranulation and downstream granulocyte recruitment.

Show evidence (2 references)

PMID:29545809 SUPPORT Human Clinical

"Mast cells and mast cell-derived mediators including inflammatory cytokines and proteases are increased in lesional skin and blister fluids of BP."

Partial. Human observation in BP lesional skin and blister fluid, establishing the mast cell contribution that anti-IgE therapy is intended to interrupt, but does not itself test omalizumab; the same review notes the pathogenic role of mast cells has been questioned.

PMID:29545809 SUPPORT Model Organism

"BP animal model evidence also implicates mast cells in the pathogenesis of BP."

Partial. The passive-transfer mouse model implicates mast cells causally, which the human lesional-tissue observation alone cannot establish, but it does not test omalizumab and is model-organism evidence for a human mechanism.

Show evidence (1 reference)

PMID:39979318 SUPPORT Human Clinical

"using corticosteroids, immunosuppressive agents and biologics such as rituximab and omalizumab"

The primer names omalizumab among the biologics used in BP.

🌍

Environmental Factors

1

Drug and Ultraviolet Radiation Triggers

No proven cause is established for bullous pemphigoid, but several trigger factors are recognized: medications (notably gliptins/DPP-4 inhibitors used in type 2 diabetes, and immune checkpoint inhibitors), ultraviolet radiation, and other skin disorders such as psoriasis and lichen planus.

Show evidence (2 references)

PMID:42206441 SUPPORT Human Clinical

"a number of different trigger factors have been described, such as medications, ultraviolet (UV) radiation"

Names medications and UV radiation among recognized BP trigger factors.

PMID:39091267 SUPPORT Human Clinical

"Treatment with gliptins, used for type 2 diabetes, was reported as associated with BP onset."

Documents the gliptin (DPP-4 inhibitor) association with BP onset, the best-characterized drug trigger.

🔬

Diagnosis

2

Direct Immunofluorescence of Perilesional Skin

Direct immunofluorescence on a perilesional skin biopsy is the diagnostic reference standard, demonstrating linear deposition of IgG and/or C3 along the epidermal basement membrane zone. It distinguishes bullous pemphigoid from the intercellular (net-like) pattern of pemphigus vulgaris.

direct immunofluorescence of perilesional skin NCIT:C18020

Results: Linear IgG and/or C3 deposition along the dermal-epidermal basement membrane zone.

Show evidence (1 reference)

PMID:39979318 SUPPORT Human Clinical

"Diagnosis involves clinical presentation, histopathology, direct immunofluorescence and serological tests."

The primer names direct immunofluorescence as a core component of the diagnostic workup.

BP180 NC16A Serology

Serological detection of circulating autoantibodies against the NC16A domain of BP180, routinely by ELISA. Titres correlate with disease activity and the assay underpins non-invasive diagnosis and monitoring.

BP180 NC16A ELISA NCIT:C18020

Results: Circulating anti-BP180 NC16A IgG autoantibodies.

Show evidence (2 references)

PMID:41127641 SUPPORT Human Clinical

"Reactivity strongly correlated with commercial BP180 NC16A ELISA (r = 0.72, P < .0001)."

Establishes the commercial BP180 NC16A ELISA as the reference serological assay against which a new peptide assay was benchmarked.

PMID:39979318 SUPPORT Human Clinical

"Diagnosis involves clinical presentation, histopathology, direct immunofluorescence and serological tests."

The primer names serological testing as a core component of the diagnostic workup.

📊

Prevalence

2

Worldwide

Annual Incidence 0.26–4.28 per 100,000 1–9 per 100,000

Reported annual incidence spans 2.6-42.8 cases per million depending on the population studied, i.e. 0.26-4.28 per 100,000. The range straddles two Orphanet bands; the class is taken from the canonical range rule used elsewhere in this KB (_band_from_rate applied to the midpoint, 2.27 per 100,000), which keeps it consistent with rate_high and with the Sweden record below. The width reflects genuine geographic and ascertainment variation. Incidence is rising with population ageing.

Show evidence (2 references)

PMID:42206441 SUPPORT Human Clinical

"incidence of BP varies between 2.6 and 42.8 cases per million, depending on the population studied"

Gives the reported worldwide annual incidence range, normalized here to 0.26-4.28 per 100,000.

PMID:39979318 SUPPORT Human Clinical

"The incidence of bullous pemphigoid is increasing, attributed to an ageing population and improved diagnostic recognition."

Establishes the rising direction of the incidence trend and its drivers.

Sweden

Annual Incidence 7.1 per 100,000 1–9 per 100,000

71.0 cases per million = 7.1 per 100,000, described as one of the highest rates in Europe and well above the general 2.6-42.8 per million range recorded above. Curated as a separate record rather than folded into the worldwide range, which would misrepresent both.

Show evidence (1 reference)

PMID:42206441 SUPPORT Human Clinical

"with an incidence rate of 71.0 cases per million in Sweden, considered one of the highest rates in Europe"

Gives the Swedish national annual incidence, normalized here to 7.1 per 100,000.

⚖️

Clinical Burden

High

Bullous pemphigoid carries substantially increased mortality relative to the age-, sex- and residence-matched general population, reflecting both disease severity and the comorbidity burden of an elderly population. Long-term management is complicated by the toxicity of systemic corticosteroids in frail older patients.

Show evidence (2 references)

PMID:42206441 SUPPORT Human Clinical

"BP patients had a significantly higher all-cause mortality (HR 2.15, 95% CI 2.06-2.24) than controls, with 1- and 10-year mortality rates of 21.2% and 80.2%, respectively."

Nationwide Swedish cohort quantifies the mortality excess (HR 2.15) and absolute 1- and 10-year mortality.

PMID:39979318 SUPPORT Human Clinical

"Despite therapeutic advancements, challenges persist in long-term management, especially in older patients with comorbidities."

The primer identifies long-term management in comorbid older patients as the persisting clinical challenge.

{ }

Source YAML

click to show

name: Bullous Pemphigoid
creation_date: '2026-07-26T19:00:00Z'
description: >-
  Bullous pemphigoid is the most common autoimmune subepidermal blistering
  disease, predominantly affecting older adults. IgG (and IgE) autoantibodies
  target the hemidesmosomal antigens BP180 (collagen XVII, COL17A1) and BP230
  (dystonin, DST), which mediate dermal-epidermal adhesion; the immunodominant
  epitope lies in the juxtamembranous extracellular NC16A domain of BP180.
  Autoantibody binding activates the classical complement pathway and triggers
  mast cell degranulation, recruiting neutrophils and eosinophils whose released
  granule proteins and proteinases cleave BP180 and other
  hemidesmosome-associated proteins, separating the dermal-epidermal junction
  and producing tense subepidermal bullae. Because the split lies above the
  lamina densa, lesions characteristically heal without scarring - the
  histological and clinical counterpoint to the intraepidermal, desmoglein-driven
  split of pemphigus vulgaris. Disease is frequently preceded by a non-bullous
  prodrome of intense pruritus and urticarial plaques and is strongly associated
  with neurological comorbidity.
category: Complex
parents:
- Dermatological Disease
- Autoimmune Disease
disease_term:
  preferred_term: bullous pemphigoid
  term:
    id: MONDO:0019082
    label: bullous pemphigoid
prevalence:
- population: Worldwide
  measure_type: ANNUAL_INCIDENCE
  prevalence_class: BAND_1_9_PER_100000
  rate_low: 0.26
  rate_high: 4.28
  notes: >-
    Reported annual incidence spans 2.6-42.8 cases per million depending on the
    population studied, i.e. 0.26-4.28 per 100,000. The range straddles two
    Orphanet bands; the class is taken from the canonical range rule used
    elsewhere in this KB (_band_from_rate applied to the midpoint, 2.27 per
    100,000), which keeps it consistent with rate_high and with the Sweden
    record below. The width reflects genuine geographic and ascertainment
    variation. Incidence is rising with population ageing.
  evidence:
  - reference: PMID:42206441
    reference_title: 'Increased Mortality in Patients with Bullous Pemphigoid: A Nationwide Population-based Cohort Study of 5,738 Patients in Sweden.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "incidence of BP varies between 2.6 and 42.8 cases per million, depending on the population studied"
    explanation: Gives the reported worldwide annual incidence range, normalized here to 0.26-4.28 per 100,000.
  - reference: PMID:39979318
    reference_title: Bullous pemphigoid.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The incidence of bullous pemphigoid is increasing, attributed to an ageing population and improved diagnostic recognition."
    explanation: Establishes the rising direction of the incidence trend and its drivers.
- population: Sweden
  measure_type: ANNUAL_INCIDENCE
  prevalence_class: BAND_1_9_PER_100000
  rate_per_100000: 7.1
  notes: >-
    71.0 cases per million = 7.1 per 100,000, described as one of the highest
    rates in Europe and well above the general 2.6-42.8 per million range
    recorded above. Curated as a separate record rather than folded into the
    worldwide range, which would misrepresent both.
  evidence:
  - reference: PMID:42206441
    reference_title: 'Increased Mortality in Patients with Bullous Pemphigoid: A Nationwide Population-based Cohort Study of 5,738 Patients in Sweden.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "with an incidence rate of 71.0 cases per million in Sweden, considered one of the highest rates in Europe"
    explanation: Gives the Swedish national annual incidence, normalized here to 7.1 per 100,000.
pathophysiology:
- name: Anti-Hemidesmosomal Autoantibody Formation
  description: >
    Loss of tolerance to hemidesmosomal structural proteins generates
    autoantibodies against BP180 (collagen XVII) and BP230 (dystonin), the
    proteins that anchor basal keratinocytes to the underlying dermis. The
    immunodominant epitope lies in the extracellular juxtamembranous NC16A
    domain of BP180.
  biological_scale: MOLECULAR
  cell_types:
  - preferred_term: B cell
    term:
      id: CL:0000236
      label: B cell
  genes:
  - preferred_term: COL17A1
    term:
      id: hgnc:2194
      label: COL17A1
  - preferred_term: DST
    term:
      id: hgnc:1090
      label: DST
  downstream:
  - target: Complement Activation and Inflammatory Cell Recruitment
    description: Autoantibody binding at the dermal-epidermal junction initiates classical complement activation and mast cell degranulation.
    causal_link_type: DIRECT
    evidence:
    - reference: PMID:29545809
      reference_title: 'The Autoimmune Skin Disease Bullous Pemphigoid: The Role of Mast Cells in Autoantibody-Induced Tissue Injury.'
      supports: SUPPORT
      evidence_source: MODEL_ORGANISM
      snippet: "key cellular and molecular events leading to the BP disease phenotype are identified, including binding of pathogenic IgG to its target, complement activation of the classical pathway, mast cell degranulation, and infiltration and activation of neutrophils."
      explanation: Passive-transfer mouse models place complement activation and mast cell degranulation immediately downstream of pathogenic IgG binding.
  evidence:
  - reference: PMID:39979318
    reference_title: Bullous pemphigoid.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The disease arises from autoantibodies targeting hemidesmosomal proteins BP180 and BP230, which are crucial for dermal-epidermal adhesion."
    explanation: The Nature Reviews Disease Primers overview identifies BP180 and BP230 autoantibodies as the initiating lesion.
  - reference: PMID:41127641
    reference_title: Peptide Epitopes of NC16A BP180 in the Diagnostics of Bullous Pemphigoid.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "a microarray of overlapping peptides spanning the NC16A domain of BP180 and the C-terminus of BP230 autoantigens was screened with sera of 13 patients with bullous pemphigoid and 2 control sera."
    explanation: Confirms NC16A of BP180 and the BP230 C-terminus as the autoantibody-reactive regions interrogated in patient sera.
- name: Complement Activation and Inflammatory Cell Recruitment
  description: >
    Autoantibody deposition at the basement membrane zone activates the
    classical complement pathway and degranulates mast cells, recruiting
    neutrophils and eosinophils to the dermal-epidermal junction.
  biological_scale: CELLULAR
  cell_types:
  - preferred_term: mast cell
    term:
      id: CL:0000097
      label: mast cell
  - preferred_term: neutrophil
    term:
      id: CL:0000775
      label: neutrophil
  - preferred_term: eosinophil
    term:
      id: CL:0000771
      label: eosinophil
  biological_processes:
  - preferred_term: complement activation
    term:
      id: GO:0006956
      label: complement activation
    modifier: INCREASED
  - preferred_term: mast cell mediated immunity
    term:
      id: GO:0002448
      label: mast cell mediated immunity
    modifier: INCREASED
  downstream:
  - target: Proteolytic Degradation of the Dermal-Epidermal Junction
    description: Recruited granulocytes release proteinases and granule proteins at the basement membrane zone.
    causal_link_type: DIRECT
    evidence:
    - reference: PMID:29545809
      reference_title: 'The Autoimmune Skin Disease Bullous Pemphigoid: The Role of Mast Cells in Autoantibody-Induced Tissue Injury.'
      supports: SUPPORT
      evidence_source: MODEL_ORGANISM
      snippet: "Proteinases released by infiltrating neutrophils cleave BP180 and other hemidesmosome-associated proteins, causing DEJ separation."
      explanation: Directly links granulocyte recruitment to proteolytic cleavage of the hemidesmosomal complex.
  evidence:
  - reference: PMID:29545809
    reference_title: 'The Autoimmune Skin Disease Bullous Pemphigoid: The Role of Mast Cells in Autoantibody-Induced Tissue Injury.'
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "Mast cells and mast cell-derived mediators including inflammatory cytokines and proteases are increased in lesional skin and blister fluids of BP."
    explanation: Documents mast cell mediator enrichment in human BP lesional skin and blister fluid.
  - reference: PMID:40488683
    reference_title: Eosinophil-derived neurotoxin and eosinophil cationic protein are key molecules for blister formation in bullous pemphigoid.
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "STAT6-deficient mice exhibited reduced subepidermal blister formation and eosinophil infiltration in 2 BP mouse models."
    explanation: Reduced eosinophil infiltration accompanies reduced blistering in two BP mouse models, supporting eosinophil recruitment as a required step.
- name: Proteolytic Degradation of the Dermal-Epidermal Junction
  conforms_to: "dermal_epidermal_junction_adhesion_failure#Loss of Adhesive Integrity at a Defined Cleavage Plane"
  description: >
    Neutrophil proteinases together with the eosinophil granule proteins
    eosinophil-derived neurotoxin (EDN) and eosinophil cationic protein (ECP)
    degrade BP180 and impair keratinocyte adhesion at the basement membrane
    zone.
  biological_scale: TISSUE
  cell_types:
  - preferred_term: keratinocyte
    term:
      id: CL:0000312
      label: keratinocyte
  biological_processes:
  - preferred_term: neutrophil degranulation
    term:
      id: GO:0043312
      label: neutrophil degranulation
    modifier: INCREASED
  downstream:
  - target: Subepidermal Blister Formation
    description: Loss of hemidesmosomal anchoring separates the epidermis from the dermis, forming the blister cavity.
    causal_link_type: DIRECT
    evidence:
    - reference: PMID:40488683
      reference_title: Eosinophil-derived neurotoxin and eosinophil cationic protein are key molecules for blister formation in bullous pemphigoid.
      supports: SUPPORT
      evidence_source: IN_VITRO
      snippet: "Importantly, these proteins significantly impaired keratinocyte adhesion in vitro."
      explanation: Eosinophil granule proteins directly impair keratinocyte adhesion, the proximate cause of dermal-epidermal separation.
  evidence:
  - reference: PMID:40488683
    reference_title: Eosinophil-derived neurotoxin and eosinophil cationic protein are key molecules for blister formation in bullous pemphigoid.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Eosinophil-derived neurotoxin and eosinophil cationic protein were substantially elevated and localized within bullous areas of skin samples from patients with BP."
    explanation: Localizes the effector granule proteins to blistering skin in human BP biopsies.
- name: Subepidermal Blister Formation
  conforms_to: "dermal_epidermal_junction_adhesion_failure#Mechanically Induced Dermal-Epidermal Separation and Blistering"
  description: >
    Separation occurs within the lamina lucida, superficial to the lamina densa,
    producing tense bullae with an intact epidermal roof. Because the cleavage
    plane spares the dermis, lesions heal without scarring - in contrast to the
    intraepidermal, desmoglein-mediated acantholytic split of pemphigus
    vulgaris.
  biological_scale: TISSUE
  downstream:
  - target: Tense Bullae
    description: The subepidermal cleavage plane yields clinically tense, fluid-filled blisters.
    causal_link_type: DIRECT
    evidence:
    - reference: PMID:39979318
      reference_title: Bullous pemphigoid.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "Bullous pemphigoid is a chronic, subepidermal autoimmune blistering disease characterized by tense blisters on erythematous or normal skin that predominantly affects the older population."
      explanation: Ties the subepidermal cleavage plane to the characteristic tense blister morphology.
  evidence:
  - reference: PMID:40488683
    reference_title: Eosinophil-derived neurotoxin and eosinophil cationic protein are key molecules for blister formation in bullous pemphigoid.
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "Eosinophil-derived neurotoxin and eosinophil cationic protein play a critical role in subepidermal blister formation in BP."
    explanation: Names subepidermal blister formation as the endpoint of the eosinophil granule protein mechanism.
phenotypes:
- name: Tense Bullae
  category: Dermatological
  diagnostic: true
  notes: >-
    Tense, fluid-filled subepidermal blisters arising on erythematous or normal
    skin, classically on flexural surfaces, trunk and proximal limbs. Frequency
    band omitted: the cited primer establishes tense blisters as the defining
    morphology but reports no occurrence rate.
  phenotype_term:
    preferred_term: Abnormal blistering of the skin
    term:
      id: HP:0008066
      label: Abnormal blistering of the skin
  evidence:
  - reference: PMID:39979318
    reference_title: Bullous pemphigoid.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Bullous pemphigoid is a chronic, subepidermal autoimmune blistering disease characterized by tense blisters on erythematous or normal skin that predominantly affects the older population."
    explanation: The Nature Reviews Disease Primers definition identifies tense blistering as the cardinal manifestation.
- name: Pruritus
  category: Dermatological
  frequency: VERY_FREQUENT
  notes: >-
    Severe itch, frequently preceding blistering by weeks to months as a
    non-bullous prodrome. Band supported by "almost all patients", which maps to
    VERY_FREQUENT (80-100%) per the frequency-evidence guidelines.
  phenotype_term:
    preferred_term: Pruritus
    term:
      id: HP:0000989
      label: Pruritus
    severity: SEVERE
  evidence:
  - reference: PMID:29545809
    reference_title: 'The Autoimmune Skin Disease Bullous Pemphigoid: The Role of Mast Cells in Autoantibody-Induced Tissue Injury.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "In almost all patients, severe pruritus is present."
    explanation: States that severe pruritus is present in almost all patients with BP, supporting both the phenotype and the VERY_FREQUENT band.
- name: Mucosal Involvement
  category: Oral
  frequency: OCCASIONAL
  notes: >-
    Mucosal disease occurs in a minority of BP patients, most often oral. This
    is a key clinical discriminator from pemphigus vulgaris, where mucosal
    erosions are typically the presenting and near-universal feature. The cited
    10-20% range maps to OCCASIONAL (29-5%) at its lower end and slightly
    exceeds it at the upper end; OCCASIONAL is retained as the closest single
    band.
  phenotype_term:
    preferred_term: Erosion of oral mucosa
    term:
      id: HP:0031446
      label: Erosion of oral mucosa
  evidence:
  - reference: PMID:29545809
    reference_title: 'The Autoimmune Skin Disease Bullous Pemphigoid: The Role of Mast Cells in Autoantibody-Induced Tissue Injury.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "About 10–20% of patients show mucosal involvement, with the oral mucosa being the most common mucosal site"
    explanation: Quantifies mucosal involvement at 10-20% with oral mucosa the commonest site, supporting the OCCASIONAL band.
- name: Urticarial Lesions (Non-Bullous Prodrome)
  category: Dermatological
  frequency: OCCASIONAL
  notes: >-
    Part of the non-bullous prodromal phase, in which pruritus, excoriations and
    eczematous, papular and urticarial lesions occur without blistering, often
    for weeks to months before bullae appear. "Up to 20%" of diagnosed BP
    patients present this way, which maps to OCCASIONAL (5-29%).
  phenotype_term:
    preferred_term: Urticarial plaque
    term:
      id: HP:0030351
      label: Urticarial plaque
  evidence:
  - reference: PMID:42206441
    reference_title: 'Increased Mortality in Patients with Bullous Pemphigoid: A Nationwide Population-based Cohort Study of 5,738 Patients in Sweden.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Up to 20% of patients with diagnosed BP present with only mild pruritus, excoriations, eczematous, papular, and urticarial lesions, without blistering"
    explanation: Quantifies the non-bullous presentation at up to 20% and names urticarial lesions among its features, supporting the OCCASIONAL band.
- name: Eczematous Lesions (Non-Bullous Prodrome)
  category: Dermatological
  frequency: OCCASIONAL
  notes: >-
    The eczematous component of the same non-bullous prodrome. Curated as a
    distinct phenotype from the urticarial component because the two are named
    separately in the source and are separately recognizable clinically.
  phenotype_term:
    preferred_term: Eczematoid dermatitis
    term:
      id: HP:0000964
      label: Eczematoid dermatitis
  evidence:
  - reference: PMID:42206441
    reference_title: 'Increased Mortality in Patients with Bullous Pemphigoid: A Nationwide Population-based Cohort Study of 5,738 Patients in Sweden.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Up to 20% of patients with diagnosed BP present with only mild pruritus, excoriations, eczematous, papular, and urticarial lesions, without blistering"
    explanation: Names eczematous lesions among the non-bullous presenting features, quantified at up to 20%.
- name: Increased Eosinophil Count
  category: Laboratory
  notes: >-
    Peripheral and tissue eosinophilia accompany BP and are mechanistically
    linked to blister formation. Frequency band omitted pending a quantitative
    source.
  phenotype_term:
    preferred_term: Increased total eosinophil count
    term:
      id: HP:0001880
      label: Increased total eosinophil count
  evidence:
  - reference: PMID:40488683
    reference_title: Eosinophil-derived neurotoxin and eosinophil cationic protein are key molecules for blister formation in bullous pemphigoid.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Eosinophil-derived neurotoxin and eosinophil cationic protein were substantially elevated and localized within bullous areas of skin samples from patients with BP."
    explanation: Documents eosinophil granule protein elevation in BP patient skin, the tissue correlate of the eosinophilic infiltrate.
diagnosis:
- name: Direct Immunofluorescence of Perilesional Skin
  description: >-
    Direct immunofluorescence on a perilesional skin biopsy is the diagnostic
    reference standard, demonstrating linear deposition of IgG and/or C3 along
    the epidermal basement membrane zone. It distinguishes bullous pemphigoid
    from the intercellular (net-like) pattern of pemphigus vulgaris.
  diagnosis_term:
    preferred_term: direct immunofluorescence of perilesional skin
    term:
      id: NCIT:C18020
      label: Diagnostic Procedure
    qualifiers:
    - predicate:
        preferred_term: diagnostic procedure
        term:
          id: NCIT:C18020
          label: Diagnostic Procedure
      value:
        preferred_term: direct immunofluorescence
        term:
          id: NCIT:C17370
          label: Fluorescent Antibody Procedure
  results: Linear IgG and/or C3 deposition along the dermal-epidermal basement membrane zone.
  evidence:
  - reference: PMID:39979318
    reference_title: Bullous pemphigoid.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Diagnosis involves clinical presentation, histopathology, direct immunofluorescence and serological tests."
    explanation: The primer names direct immunofluorescence as a core component of the diagnostic workup.
- name: BP180 NC16A Serology
  description: >-
    Serological detection of circulating autoantibodies against the NC16A domain
    of BP180, routinely by ELISA. Titres correlate with disease activity and the
    assay underpins non-invasive diagnosis and monitoring.
  diagnosis_term:
    preferred_term: BP180 NC16A ELISA
    term:
      id: NCIT:C18020
      label: Diagnostic Procedure
    qualifiers:
    - predicate:
        preferred_term: diagnostic procedure
        term:
          id: NCIT:C18020
          label: Diagnostic Procedure
      value:
        preferred_term: ELISA
        term:
          id: NCIT:C16553
          label: ELISA
  results: Circulating anti-BP180 NC16A IgG autoantibodies.
  evidence:
  - reference: PMID:41127641
    reference_title: Peptide Epitopes of NC16A BP180 in the Diagnostics of Bullous Pemphigoid.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Reactivity strongly correlated with commercial BP180 NC16A ELISA (r = 0.72, P < .0001)."
    explanation: Establishes the commercial BP180 NC16A ELISA as the reference serological assay against which a new peptide assay was benchmarked.
  - reference: PMID:39979318
    reference_title: Bullous pemphigoid.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Diagnosis involves clinical presentation, histopathology, direct immunofluorescence and serological tests."
    explanation: The primer names serological testing as a core component of the diagnostic workup.
histopathology:
- name: Subepidermal Blister with Eosinophil-Rich Infiltrate
  description: >-
    Histology shows a subepidermal split with an inflammatory infiltrate rich in
    eosinophils. The cleavage plane lies above the lamina densa, which is why
    lesions re-epithelialize without scarring.
  diagnostic: true
  evidence:
  - reference: PMID:39979318
    reference_title: Bullous pemphigoid.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Bullous pemphigoid is a chronic, subepidermal autoimmune blistering disease characterized by tense blisters on erythematous or normal skin"
    explanation: Establishes the subepidermal level of the split that defines the histological picture.
  - reference: PMID:40488683
    reference_title: Eosinophil-derived neurotoxin and eosinophil cationic protein are key molecules for blister formation in bullous pemphigoid.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Eosinophil-derived neurotoxin and eosinophil cationic protein were substantially elevated and localized within bullous areas of skin samples from patients with BP."
    explanation: Localizes eosinophil granule proteins to the blistering areas of BP skin biopsies, the tissue correlate of the eosinophil-rich infiltrate.
genetic:
- name: HLA-DQB1*03:01 Susceptibility
  gene_term:
    preferred_term: HLA-DQB1
    term:
      id: hgnc:4944
      label: HLA-DQB1
  relationship_type: SUSCEPTIBILITY
  association: >-
    HLA-DQB1*03:01 is the most consistently replicated HLA class II
    susceptibility allele in bullous pemphigoid, associated with both idiopathic
    and gliptin-associated disease.
  notes: >-
    Susceptibility genetics only. The hemidesmosomal genes COL17A1 (BP180) and
    DST (BP230) are deliberately NOT listed here: in bullous pemphigoid they are
    autoantibody targets, not inherited disease genes, and are curated on the
    pathophysiology node instead. Germline COL17A1/DST variants cause
    epidermolysis bullosa, a mechanistically distinct disease.
  evidence:
  - reference: PMID:39091267
    reference_title: "HLA alleles associated to susceptibility to gliptin-associated bullous pemphigoid in Italian patients."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "A significant association between HLA-DQB1*03:01 allele and IBP and GABP patients was found."
    explanation: Finds HLA-DQB1*03:01 significantly associated with both idiopathic and gliptin-associated BP in an Italian cohort.
environmental:
- name: Drug and Ultraviolet Radiation Triggers
  description: >-
    No proven cause is established for bullous pemphigoid, but several trigger
    factors are recognized: medications (notably gliptins/DPP-4 inhibitors used
    in type 2 diabetes, and immune checkpoint inhibitors), ultraviolet
    radiation, and other skin disorders such as psoriasis and lichen planus.
  evidence:
  - reference: PMID:42206441
    reference_title: 'Increased Mortality in Patients with Bullous Pemphigoid: A Nationwide Population-based Cohort Study of 5,738 Patients in Sweden.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "a number of different trigger factors have been described, such as medications, ultraviolet (UV) radiation"
    explanation: Names medications and UV radiation among recognized BP trigger factors.
  - reference: PMID:39091267
    reference_title: "HLA alleles associated to susceptibility to gliptin-associated bullous pemphigoid in Italian patients."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Treatment with gliptins, used for type 2 diabetes, was reported as associated with BP onset."
    explanation: Documents the gliptin (DPP-4 inhibitor) association with BP onset, the best-characterized drug trigger.
clinical_burden:
  burden_level: HIGH
  rationale: >-
    Bullous pemphigoid carries substantially increased mortality relative to the
    age-, sex- and residence-matched general population, reflecting both disease
    severity and the comorbidity burden of an elderly population. Long-term
    management is complicated by the toxicity of systemic corticosteroids in
    frail older patients.
  evidence:
  - reference: PMID:42206441
    reference_title: 'Increased Mortality in Patients with Bullous Pemphigoid: A Nationwide Population-based Cohort Study of 5,738 Patients in Sweden.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "BP patients had a significantly higher all-cause mortality (HR 2.15, 95% CI 2.06-2.24) than controls, with 1- and 10-year mortality rates of 21.2% and 80.2%, respectively."
    explanation: Nationwide Swedish cohort quantifies the mortality excess (HR 2.15) and absolute 1- and 10-year mortality.
  - reference: PMID:39979318
    reference_title: Bullous pemphigoid.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Despite therapeutic advancements, challenges persist in long-term management, especially in older patients with comorbidities."
    explanation: The primer identifies long-term management in comorbid older patients as the persisting clinical challenge.
discussions:
- discussion_id: bp_checkpoint_inhibitor_trigger_uncurated
  kind: CURATION_TODO
  status: OPEN
  prompt: >-
    Immune checkpoint inhibitor-induced bullous pemphigoid is a clinically
    important and increasingly recognized trigger, but is named only in the
    `environmental` description rather than curated with its own evidence.
  rationale: >-
    The gliptin/DPP-4-inhibitor arm is now evidenced (PMID:39091267) under
    `environmental`. The checkpoint-inhibitor arm still lacks a quotable source
    in this entry: the closest candidate found during curation, PMID:41747673
    (a real-life comparative study of gliptin- and checkpoint-inhibitor-induced
    versus idiopathic BP), is indexed in PubMed without an abstract, so no
    excerpt satisfies the evidence SOP. Resolving this needs a paper with
    retrievable text reporting the checkpoint-inhibitor risk association.
- discussion_id: bp_neurological_association_direction
  kind: OPEN_QUESTION
  status: OPEN
  prompt: >-
    Bullous pemphigoid is consistently associated with neurological disease
    (dementia, Parkinson disease, stroke). Is this association causal in either
    direction, and is it explained by shared BP180/BP230 (dystonin) expression
    in the central nervous system?
  rationale: >-
    BP180 (collagen XVII) and BP230 (dystonin) have neural isoforms expressed in
    the central nervous system, giving a plausible route by which neurodegeneration
    could expose cross-reactive epitopes and break tolerance. The association is
    robust epidemiologically, but the cited cohort cannot establish direction, and
    its per-condition results are not internally uniform - Alzheimer disease was
    actually more common in controls, discordant with several other reports. The
    association is recorded here as an open question rather than as a curated
    causal edge in the pathograph.
  proposed_experiments:
  - experiment_id: bp_neuro_temporal_sequence
    name: Temporal sequencing of neurological diagnosis relative to BP onset
    description: >-
      Longitudinal population cohort determining whether neurological diagnoses
      precede or follow first BP diagnosis, with time-to-event analysis in both
      directions.
    decision_criterion: >-
      Consistent precedence of neurological diagnosis over BP onset would favour
      neurodegeneration-driven epitope exposure over a shared-susceptibility or
      reverse-causation model.
    supporting_outcome:
    - Neurological disease precedes BP onset at a rate exceeding the reverse ordering.
    refuting_outcome:
    - No consistent temporal ordering, or BP predominantly precedes neurological diagnosis.
  - experiment_id: bp_neuro_crossreactive_serology
    name: Anti-BP180/BP230 serology in neurodegenerative disease without skin disease
    description: >-
      Serological screening for anti-BP180 NC16A and anti-BP230 reactivity in
      dementia, Parkinson disease and stroke cohorts with no cutaneous disease,
      against age-matched neurologically healthy controls.
    decision_criterion: >-
      Elevated subclinical autoantibody reactivity in neurodegenerative cohorts
      would support CNS epitope exposure as the tolerance-breaking event.
    supporting_outcome:
    - Significantly higher anti-BP180/BP230 reactivity in neurodegenerative cohorts than controls.
    refuting_outcome:
    - Equivalent reactivity across neurodegenerative and control groups.
  evidence:
  - reference: PMID:30663128
    reference_title: Neurological disorders are associated with bullous pemphigoid.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Our cohort of bullous pemphigoid and neurological disorders demonstrates a significant association between bullous pemphigoid and neurological disorders, including dementia, Parkinson's disease and stroke."
    explanation: Case-control study of 183 BP patients and 348 matched controls finds a significant association with dementia, Parkinson disease and stroke.
  - reference: PMID:30663128
    reference_title: Neurological disorders are associated with bullous pemphigoid.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "These included dementia (P < 0.0001), Parkinson`s disease (P = 0.0434), stroke (P = 0.0015) and other neurological disorders but not Alzheimer's diseases, which was more common among patients in the control group."
    explanation: >-
      Records the per-condition detail including the negative finding for
      Alzheimer disease, which was more common in controls in this cohort -
      a discordance with other reports worth preserving rather than smoothing over.
treatments:
- name: Systemic Corticosteroids
  description: >-
    Corticosteroids remain the mainstay of treatment, aiming to reduce symptoms
    and prevent new blister formation.
  therapeutic_modality: SMALL_MOLECULE
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: corticosteroid
      term:
        id: CHEBI:50858
        label: corticosteroid
  evidence:
  - reference: PMID:39979318
    reference_title: Bullous pemphigoid.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Treatment aims to reduce symptoms and prevent new blister formation, using corticosteroids, immunosuppressive agents and biologics such as rituximab and omalizumab."
    explanation: The primer identifies corticosteroids as the core of current BP management.
- name: Doxycycline
  description: >-
    Doxycycline as an initial treatment strategy is non-inferior to oral
    prednisolone for short-term blister control and significantly safer over the
    long term, making it an important steroid-sparing option in a frail elderly
    population.
  therapeutic_modality: SMALL_MOLECULE
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: doxycycline
      term:
        id: CHEBI:50845
        label: doxycycline
  evidence:
  - reference: PMID:28279484
    reference_title: 'Doxycycline versus prednisolone as an initial treatment strategy for bullous pemphigoid: a pragmatic, non-inferiority, randomised controlled trial.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Starting patients on doxycycline is non-inferior to standard treatment with oral prednisolone for short-term blister control in bullous pemphigoid and significantly safer in the long-term."
    explanation: The BLISTER randomised non-inferiority trial establishes doxycycline as a viable first-line strategy.
  - reference: PMID:28279484
    reference_title: 'Doxycycline versus prednisolone as an initial treatment strategy for bullous pemphigoid: a pragmatic, non-inferiority, randomised controlled trial.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "For those starting doxycycline, 83 (74%) of 112 patients had three or fewer blisters at 6 weeks compared with 92 (91%) of 101 patients on prednisolone, an adjusted difference of 18·6% (90% CI 11·1-26·1) favouring prednisolone"
    explanation: >-
      Records the efficacy trade-off underlying the non-inferiority conclusion -
      prednisolone achieved better 6-week blister control - so the doxycycline
      recommendation is not read as equivalent efficacy.
- name: Rituximab
  description: Anti-CD20 B cell depletion, used as a biologic option in refractory disease.
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: rituximab
      term:
        id: NCIT:C1702
        label: Rituximab
  therapeutic_modality: MONOCLONAL_ANTIBODY
  target_mechanisms:
  - target: Anti-Hemidesmosomal Autoantibody Formation
    treatment_effect: INHIBITS
    description: B cell depletion reduces production of pathogenic anti-BP180/BP230 autoantibodies.
    evidence:
    - reference: PMID:39979318
      reference_title: Bullous pemphigoid.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "using corticosteroids, immunosuppressive agents and biologics such as rituximab and omalizumab"
      explanation: >-
        Partial. The primer establishes rituximab as an accepted BP biologic, but
        does not itself state the anti-CD20 mechanism; the B-cell-depletion link
        to autoantibody production is inferred from the drug class.
  evidence:
  - reference: PMID:39979318
    reference_title: Bullous pemphigoid.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "using corticosteroids, immunosuppressive agents and biologics such as rituximab and omalizumab"
    explanation: The primer names rituximab among the biologics used in BP.
- name: Omalizumab
  description: >-
    Anti-IgE monoclonal antibody, reflecting the pathogenic contribution of IgE
    autoantibodies and downstream mast cell activation.
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: omalizumab
      term:
        id: NCIT:C29299
        label: Omalizumab
  therapeutic_modality: MONOCLONAL_ANTIBODY
  target_mechanisms:
  - target: Complement Activation and Inflammatory Cell Recruitment
    treatment_effect: INHIBITS
    description: IgE neutralization dampens mast cell degranulation and downstream granulocyte recruitment.
    evidence:
    - reference: PMID:29545809
      reference_title: 'The Autoimmune Skin Disease Bullous Pemphigoid: The Role of Mast Cells in Autoantibody-Induced Tissue Injury.'
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "Mast cells and mast cell-derived mediators including inflammatory cytokines and proteases are increased in lesional skin and blister fluids of BP."
      explanation: >-
        Partial. Human observation in BP lesional skin and blister fluid,
        establishing the mast cell contribution that anti-IgE therapy is
        intended to interrupt, but does not itself test omalizumab; the same
        review notes the pathogenic role of mast cells has been questioned.
    - reference: PMID:29545809
      reference_title: 'The Autoimmune Skin Disease Bullous Pemphigoid: The Role of Mast Cells in Autoantibody-Induced Tissue Injury.'
      supports: SUPPORT
      evidence_source: MODEL_ORGANISM
      snippet: "BP animal model evidence also implicates mast cells in the pathogenesis of BP."
      explanation: >-
        Partial. The passive-transfer mouse model implicates mast cells causally,
        which the human lesional-tissue observation alone cannot establish, but
        it does not test omalizumab and is model-organism evidence for a human
        mechanism.
  evidence:
  - reference: PMID:39979318
    reference_title: Bullous pemphigoid.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "using corticosteroids, immunosuppressive agents and biologics such as rituximab and omalizumab"
    explanation: The primer names omalizumab among the biologics used in BP.
classifications:
  harrisons_chapter:
  - classification_value: DERMATOLOGY
  - classification_value: IMMUNE_RHEUMATOLOGIC

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References & Deep Research

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Asta Literature Retrieval: Pathophysiology and clinical mechanisms of Bullous Pemphigoid. Core disease mechanisms, molecular and cellular pathwa...

Asta Scientific Corpus Retrieval 19 citations 2026-07-31T21:07:05.520333

Asta Literature Retrieval: Pathophysiology and clinical mechanisms of Bullous Pemphigoid. Core disease mechanisms, molecular and cellular pathwa...

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Snippets retrieved: 20

Relevant Papers

[1] Pruritogens in pemphigoid diseases: Possible therapeutic targets for a burdensome symptom

Authors: S. Hiroyasu, J. Barit, Aoi Hiroyasu, D. Tsuruta
Year: 2022
Venue: The Journal of Dermatology
URL: https://www.semanticscholar.org/paper/439345d0ec9a68d501e7f33442df621509b7f3d0
DOI: 10.1111/1346-8138.16652
PMID: 36477831
PMCID: 10108135
Citations: 2
Summary: The present understanding of pruritus specific to pemphigoid diseases, especially the pruritogens that induce it, and the therapeutic options that have been explored so far are summarized.
Evidence snippets:
Snippet 1 (score: 0.536) > Pruritus is a hallmark feature in pemphigoid diseases, where it can be severe and greatly impact the quality of life of affected patients. Despite being a key symptom, the exact pathophysiological mechanisms involved in pruritus in pemphigoid are yet to be fully elucidated and effective therapies addressing them are limited. This review summarizes the present understanding of pruritus specific to pemphigoid diseases, especially the pruritogens that induce it, and the therapeutic options that have been explored so far. The majority of the available evidence is on bullous pemphigoid and epidermolysis bullosa acquisita. Histamine derived from basophils correlates with pruritus severity, with omalizumab demonstrating promising efficacy in pruritus for bullous pemphigoid. IL‐4/−13 contribute to itch in bullous pemphigoid with dupilumab being evaluated in clinical trials. Other pruritogens of interest include substance P, tryptase, and thymic stromal lymphopoetin, with therapies targeting them requiring further investigation. Scratching behaviors contribute directly to blister formation through various mechanisms, such as pathological autoantibody recruitment, T helper cell type 1 polarization, and exposure of intracellular autoantigens. Treatments addressing these pathways may contribute to decreasing disease severity. Additional studies are needed to fully characterize how pruritus is regulated in pemphigoid diseases, to help pave the way to develop novel and effective therapeutics that will not only address pruritic symptoms but also decrease disease severity.

[2] A Scoping Review of the Role of Metalloproteinases in the Pathogenesis of Autoimmune Pemphigus and Pemphigoid

Authors: N. Cirillo, S. Prime
Year: 2021
Venue: Biomolecules
URL: https://www.semanticscholar.org/paper/6969c4ad3fe0903815379325160d3881f6c93683
DOI: 10.3390/biom11101506
PMID: 34680139
PMCID: 8533820
Citations: 29
Summary: The results demonstrated that ADAM10 and MMP-9 activity is necessary for blister formation in experimental models of pemphigus vulgaris (PV) and BP, respectively.
Evidence snippets:
Snippet 1 (score: 0.514) > Pemphigus and pemphigoid are members of a heterogeneous group of chronic, potentially fatal autoimmune diseases associated with blistering of the skin and mucosae. Once considered part of the same disease spectrum, these bullous dermatoses were first classified as distinct entities by Lever in 1953 [1]. Histologically, pemphigus presents as an intraepithelial split (acantholysis) whereas in pemphigoid, the blisters develop at the dermo-epidermal junction resulting in a subepithelial split. > The two major pemphigus variants, pemphigus vulgaris and pemphigus foliaceus, account for 90-95% of diagnoses [2,3]. Pemphigus diseases are characterized by flaccid blisters and erosions and are treated with high dose corticosteroids and immunosuppressants. By contrast, pemphigoid presents with tense blisters and erosions, a negative Nikolsky sign and, commonly, is controlled using topical steroids although in more severe cases, systemic steroids are an option [2]. > The development of molecular techniques has facilitated the further classification of these blistering diseases. The pemphigoid group is now known to include at least eight disorders for which the molecular target antigens have been identified [4], although controversy exists regarding the pathogenic mechanisms of blistering [5]. In pemphigus, distinct autoantibody profiles and, in particular, the presence/absence and type of antibodies to cadherins determines the acantholytic signaling pathways [6,7] and possibly the clinical phenotype [8,9]. Despite advances in understanding the pathophysiology of these disorders, however, the mainstay of treatment is the use of corticosteroids and immune suppressants and, significantly, no mechanism-based treatments have been successfully translated to patient care. > Pemphigus and pemphigoid result from a deficit in cellular adhesion.

[3] Review on Bullous Pemphigoid: Fixed Drug Eruption or Autoimmune Disorder

Authors: Adarsh Keshari, K. Jain, Roshan Pandey, Ayush Mishra, Sarita Jangra et al.
Year: 2024
Venue: Journal of Pharmaceutical Technology, Research and Management
URL: https://www.semanticscholar.org/paper/e1dea81c672a1cb5aee440e0961d510a9d9f0890
DOI: 10.15415/jptrm.2024.122002
Summary: Bullous pemphigoid is a distinct autoimmune disease with unique immunopathological mechanisms compared to fixed drug eruption, and understanding its pathogenesis, drug interactions, and diagnostic methods enhances accurate diagnosis and management of both spontaneous and drug-induced bullous pemphigoid.
Evidence snippets:
Snippet 1 (score: 0.509) > Background: Bullous pemphigoid is a blistering disease of autoimmune nature predominantly affecting the geriatric population. It is characterized by blister formation at the subepidermal level, due to autoantibodies at the dermo-epidermal junction targeting proteins BP180XV11 and BP230. Mainly an autoimmune condition, diagnosis and treatment get complicated as it overlaps with drug-induced hypersensitivity reactions, including fixed drug eruption. Unlike Bullous Pemphigoid, it is a condition of localized hypersensitivity mediated by T cells. > Purpose: The review tries to establish Bullous Pemphigoid as an autoimmune condition separate from fixed drug eruption. It is centered on the causative role of medications, which include diuretics, antibiotics, and dipeptidyl peptidase-4 inhibitors, in drug-induced bullous pemphigoid. Besides, it examines genetic, immunological, and environmental etiologies of the disease and delineates clinical and diagnostic characteristics of Bullous Pemphigoid and fixed drug eruptions. > Method: A systematic analysis of current literature was performed, focusing on the pathophysiology, immunological mechanisms, and histopathological differences between Bullous Pemphigoid and fixed drug eruptions. The review also examines the role of medications, genetic predispositions such as specific human leukocyte antigen haplotypes, and the diagnostic utility of histopathological and immunological methods like direct immunofluorescence. > Results: Autoantibodies against BP180 and BP230 in bullous pemphigoid initiate inflammatory cascades, causing subepidermal blistering and eosinophilic infiltration. Fixed drug eruption involves basal cell necrosis and localized lymphocytic infiltration. Drugs like dipeptidyl peptidase-4 inhibitors exacerbate bullous pemphigoid through immune modulation and oxidative stress. Genetic susceptibility plays a significant role, and immunological tests such as direct immunofluorescence help distinguish the two conditions. > Conclusion: Bullous pemphigoid is a distinct autoimmune disease with unique

[4] Role of Regulatory Immune Cells and Molecules in Autoimmune Bullous Dermatoses

Authors: T. Cao, S. Shao, H. Fang, Bing Li, Gang Wang
Year: 2019
Venue: Frontiers in Immunology
URL: https://www.semanticscholar.org/paper/c8b752685c67600e6005dd7262f2c71d7cebe877
DOI: 10.3389/fimmu.2019.01746
PMID: 31428090
PMCID: 6688483
Citations: 17
Summary: The role of regulatory immune cells and molecules in the pathogenesis of pemphigus vulgaris and bullous pemPHigoid, the two most representative forms of AIBD, are highlighted, and issues that should be addressed in future investigations are indicated.
Evidence snippets:
Snippet 1 (score: 0.500) > In contrast, pemphigoid diseases are characterized by autoantibodies that directly attack structural proteins within the dermal-epidermal junction, leading to urticarial lesions, and tense blisters on the skin (8). This group includes bullous pemphigoid (BP), linear IgA bullous dermatosis, dermatitis herpetiformis, mucous membrane pemphigoids, herpes gestationis, and epidermolysis bullosa acquisita (7). > Recent studies have shown several regulatory immune cells and molecules to be involved in the progression of AIBD. In this review, we aim to elucidate the different mechanisms and roles of regulatory immune cells and molecules in AIBD by summarizing and discussing the findings of various clinical and experimental studies, and outline some of the challenges that lie ahead.

[5] Editorial: Autoimmune blistering diseases: advances in the understanding of pathogenesis and new therapeutic horizons

Authors: G. Gasparini, K. Amber, E. Cozzani, Aurora Parodi
Year: 2023
Venue: Frontiers in Medicine
URL: https://www.semanticscholar.org/paper/115e121ccba4f8dca8a2feb68b98a3d416aee829
DOI: 10.3389/fmed.2023.1243878
PMID: 37502359
PMCID: 10369339
Summary: This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY).
Evidence snippets:
Snippet 1 (score: 0.491) > Developing in vitro and animal models of AIBDs is a one the fundamental approaches for investigating pathogenic mechanisms and also for initial testing of new drugs. Radine et al. evaluated in electron microscopy the ultrastructural desmosomal morphology in the human skin organ culture (HSOC) model injected with either anti-desmoglein (DSG) 1/3 single-chain variable fragment (scFv, termed Px4-3). The authors demonstrated that the HSOC pemphigus model is an attractive tool to unravel novel therapeutic targets (Radine et al.). > Currently, several clinical trials are ongoing for the two most common AIBDs, namely pemphigus and bullous pemphigoid (BP). On the other hand, for rarer AIBDs, such as epidermolysis bullosa acquisita, mucous membrane pemphigoid or paraneoplastic pemphigus, specifically designed interventional clinical trials are scant. This phenomenon is reflected also in the research trends on AIBDs. Huang et al. analyzed with a bibliometric study the trending topics in the field of pemphigoid diseases and highlighted that most publications focus on molecular mechanisms and disease management, but 70% of the studies focus on BP while only a minority investigated other AIBDs belonging to the pemphigoid group. > New drugs targeting various pathways are currently being studied for the treatment of BP. The main targeted pathways are: type 2 immune response (both innate and adaptive; e.g., IL4/IL13, IL5, and eosinophils), immunoglobulins production and catabolism [B cells, circulating IgEs, and neonatal Fc receptor (FcRn)], complement cascade and IL-17 axis. > Zeng and Murrell thoroughly describe in their review article, how type II immunity, in particular eosinophils, are at the core of BP pathogenesis, and how other pathways, including IL-17/23 axis and complement, converge on this mechanism, making it a promising therapeutic target in BP. Nonetheless, not all studied targeted therapies for eosinophils gave satisfactory results.

[6] Researching trends in pemphigoid diseases: A bibliometric study of the top 100 most cited publications

Authors: Shih-Cheng Huang, Tsu-Man Chiu, Chien-Ying Lee, Hui-Chin Chang, Wen-Jun Wu et al.
Year: 2023
Venue: Frontiers in Medicine
URL: https://www.semanticscholar.org/paper/4af460839fcaf5dd1cbbe9f3b52a70f36211c4fa
DOI: 10.3389/fmed.2022.1088083
PMID: 36698818
PMCID: 9868262
Citations: 6
Summary: This comprehensive bibliographic study of pemphigoid diseases provided an overview of current research focuses in the field, and topics such as disease management, molecular mechanism of pathogenesis, and drug-inducing pemphygoid diseases were highly mentioned in the most-cited studies.
Evidence snippets:
Snippet 1 (score: 0.471) > Background In the field of autoimmune and inflammatory disorders, different approaches were applied to provide information regarding disease activity, comorbidities, epidemiological reports and risk factors. However, no previous studies had thoroughly analyzed the research trend in the field, and the bibliometric analysis focusing on pemphigoid diseases was available. The objective of the current study was to evaluate the current research trend in the field. Methods A search has been conducted for the Web of Science database based on various subcategories of pemphigoid diseases. Detailed information including articles’ publication types, Author information, citation, and publication information was attained for further analysis. Results Within the 6,995 studies, the top 100 most-cited articles were extracted for analysis. Among the top 100 studies, 70% of the studies focused on bullous pemphigoid. More than 60% of the top 100 studies were studies with original data. Furthermore, 30% of the studies were guidelines and narrative reviews. For the issues primarily focused on, most of the high-impact studies described the molecular mechanism of pemphigoid diseases (26%), managements (19%), risk factors of pemphigoid diseases (17%). Additionally, some other studies provided general review or discussed about the issue of epidemiology, diagnosis/definition, comorbidities and clinical characteristics of pemphigoid diseases. Conclusion This comprehensive bibliographic study of pemphigoid diseases provided an overview of current research focuses in the field. Topics such as disease management, molecular mechanism of pathogenesis, and drug-inducing pemphigoid diseases were highly mentioned in the most-cited studies. For researchers and clinicians, the researching trend and study focus in the top-100 cited studies could serve as a potential reference for future investigation and patient management.

[7] The pathological function of neutrophils in pemphigoid diseases

Authors: Daisuke Matsumoto, Beni Amatya, Daisuke Tsuruta, S. Hiroyasu
Year: 2024
Venue: Dermatologica Sinica
URL: https://www.semanticscholar.org/paper/79539c6a9740572c4073936d7ddfbb8b6f998494
DOI: 10.4103/ds.ds-d-24-00027
Citations: 1
Summary: The present review provides a comprehensive summary and critical evaluation of the current understanding regarding the role of neutrophils in PDs and discusses the potential of targeting neutrophil-associated pathways as a novel therapeutic approach for the diseases.
Evidence snippets:
Snippet 1 (score: 0.458) > Pemphigoid diseases (PDs) are a group of autoimmune blistering diseases, including bullous pemphigoid, epidermolysis bullosa acquisita, mucous membrane pemphigoid, linear immunoglobulin A disease, and other rare variants. These diseases are characterized by the presence of autoantibodies that target proteins at the dermal-epidermal junction, resulting in the formation of tense blisters and erosions on the skin and/or mucosa. The current therapeutic approaches, such as systemic corticosteroid, are associated with significant adverse effects, highlighting that safer and more effective treatment options are an urgent clinical need. To address this unmet need, a comprehensive understanding of the detailed mechanisms underlying PDs is essential. Based on their histopathological infiltration in pemphigoid lesions, neutrophils have long been implicated as major contributors to the initiation and progression of the diseases. Numerous in vivo and in vitro studies have investigated the role of neutrophils in the pemphigoid pathology, revealing various pathological mechanisms induced by these cells, including the release of neutrophil elastase and matrix metalloproteinase-9, as well as the formation of neutrophil extracellular traps. The present review provides a comprehensive summary and critical evaluation of the current understanding regarding the role of neutrophils in PDs. In addition, it discusses the potential of targeting neutrophil-associated pathways as a novel therapeutic approach for the diseases.

[8] Pathophysiology of Bullous Pemphigoid: Role of Type 2 Inflammation and Emerging Treatment Strategies (Narrative Review)

Authors: V. Werth, D. Murrell, P. Joly, Renata Heck, Jamie M. Orengo et al.
Year: 2024
Venue: Advances in Therapy
URL: https://www.semanticscholar.org/paper/5eeb52d8f8bf82cce9767679886c0779b09d573e
DOI: 10.1007/s12325-024-02992-w
PMID: 39425892
PMCID: 11550233
Citations: 12
Summary: This review presents what is known about BP pathophysiology, including the role of type 2 inflammation, and discusses how findings from studies of biologics targeting type 2 immune mediators have helped to clarify the biological mechanisms driving BP pathophysiology.
Evidence snippets:
Snippet 1 (score: 0.447) > Bullous pemphigoid (BP) is an autoimmune blistering disease that most often affects elderly individuals and has a significant negative impact on quality of life. The disease is characterized primarily by autoantibodies to hemidesmosomal proteins BP180 and/or BP230, and an inflammatory reaction with notable features of type 2 inflammation, including elevated serum IgE, increased numbers of eosinophils in lesions and peripheral blood, and elevated expression of type 2 cytokines and chemokines in skin lesions. In this review, we present what is known about BP pathophysiology, including the role of type 2 inflammation, and discuss how findings from studies of biologics targeting type 2 immune mediators have helped to clarify the biological mechanisms driving BP pathophysiology. Future studies of these targeted therapies and others in development will help to further elucidate the mechanisms underlying BP pathophysiology and potentially provide better treatment options for patients.

[9] Prognostic factors for mortality in bullous pemphigoid: A systematic review and meta-analysis

Authors: Xianxia Chen, Yaqiang Zhang, Zhicheng Luo, Yujuan Wu, Taoxiang Niu et al.
Year: 2022
Venue: PLoS ONE
URL: https://www.semanticscholar.org/paper/1ab716082d41a510faf6031d1dfd8c741b3afd07
DOI: 10.1371/journal.pone.0264705
PMID: 35427358
PMCID: 9012347
Citations: 13
Influential citations: 1
Summary: Positive bullous pemphigoid 180 antibody, dementia, stroke, heart disease and diabetes mellitus were the prognostic factors for mortality in bullouspemphIGoid.
Evidence snippets:
Snippet 1 (score: 0.445) > In the recent two years, the effect of statins as a new indicator has emerged and had been considered to reduce the mortality of patients with bullous pemphigoid [11]. The specific mechanism may be immunomodulatory by reduction of the metabolites of the L-mevalonate pathway and up-regulation of the immune response through inhibition of 3-hydroxy-3-methylglutaryl CoA reductase [39]. Attention should be paid to the possible protective role of statins for the clinical prevention and treatment of patients with bullous pemphigoid. Hospitalisation days have been considered to be associated with increased mortality in patients with bullous pemphigoid. Monshi [10] believed that longer hospitalization days reflected the degree of disease, the complications in the disease course, and the occurrence of adverse events during treatment. However, there had been no uniform standard for the length of hospitalization, and this index can be easily affected by many factors, such as medical conditions and treatment levels.

[10] A Case Report on Idiopathic Severe Bullous Pemphigoid

Authors: F. Mohammadi, S. Zoha, Mohammed Baleeqhuddin, S. Ali, A. Faizan
Year: 2020
Venue: Journal of Drug Delivery and Therapeutics
URL: https://www.semanticscholar.org/paper/aaf23b1a887294962eea662c3ac2397e88fd41c5
DOI: 10.22270/jddt.v10i4-s.4311
Citations: 1
Summary: The treatment for bullous pemphigoid is systemic corticosteroids, topical steroids in combination with nicotinamide plus tetracycline, minocycline or doxycycline have shown success in multiple cases.
Evidence snippets:
Snippet 1 (score: 0.442) > Bullous Pemphigoid (BP) is an autoimmune disorder which exploits the immune system and affecting sub-epidermal region of skin causing mild itching to infection and blistering of sub-epidermal region. Bullous Pemphigoid is a rare dermatological disorder which can be seen in all age groups but mainly affecting elderly patients. 1 iology:-Many cases of bullous pemphigoid are due to autoantibodies against proteins arranged at the dermal-epidermal junction. Drug-induced bullous pemphigoid occurs up to 3 months after medication initiation and is usually noted during a younger to older subset of patients. Drugs which trigger this reaction are diuretics such as furosemide and spironolactone, NSAIDs, amoxicillin, PD-1/PD-L1 inhibitors, gliptins, and TNF-alpha inhibitors. 2 Pathophysiology:-There are 2 main components to the pathophysiology of BP: immunologic and inflammatory. The immunologic elements comprise autoantibodies against 2 parts of the basal keratinocyte hemidesmosomal proteins BP antigen 230 (BPAG1) and BP antigen 180 (BPAG2 or type XVII collagen) 3 These antigens play an essential part in the adhesion complexes that promote epithelial-stromal adhesion. When autoantibodies bind to their target antigen, the inflammatory component follows which then activates complement and mast cells. This causes neutrophils and eosinophils to release a variety of inflammatory cells resulting in the release of proteolytic enzymes that damage the dermal-epidermal junction 4 Clinical Presentation: -In the prodromal phase, patients may experience moderateto-severe pruritus alone or associated with urticarial, papular lesions. 5 This later evolves to bullae in weeks to months and are typically present in the axillae, on the flexor surface of the forearms, medial thighs, trunk, and abdomen. Approximately 20% of patients will have neither bullae nor erosions at time of presentation 6 . > Constitutional symptoms are uncommon, except in widespread, severe disease.

[11] Coexistence of mucous membrane pemphigoid and vitiligo

Authors: Sanath Aithal, Satyaki Ganguly, S. Kuruvila
Year: 2014
Venue: Indian Dermatology Online Journal
URL: https://www.semanticscholar.org/paper/26aef582489e608b542541748f9755d040252df4
DOI: 10.4103/2229-5178.142511
PMID: 25396136
PMCID: 4228648
Citations: 2
Summary: A very rare coexistence of MMP and vitiligo is reported from India, the first such report from India.
Evidence snippets:
Snippet 1 (score: 0.425) > MMP is described as a heterogeneous group of chronic, infl ammatory, mucous membrane-dominated, subepithelial blistering diseases that manifest a varying constellation of oral, ocular, skin, genital, nasopharyngeal, esophageal, and laryngeal lesions. Life-threatening airway obstruction and sight-threatening ocular scarring can occur in this condition, also known as cicatricial pemphigoid, benign MMP and incorrectly as ocular pemphigoid. [1] Various basement membrane zone components have been identifi ed as targets of autoantibodies in MMP. These include bullous pemphigoid antigen 1 (BPAg1, 230 kDa), bullous pemphigoid antigen 2 (BPAg2, 180kDa), laminin 5, laminin 6, α 6 -integrin subunit, β 4 -integrin subunit, collagen VII, and other proteins of unknown identity and/or function. Considerable variability exists in the clinical presentation of MMP. [2] arring is common at non-oral sites of involvement, contributing to disease-related morbidity. [2] A multidisciplinary approach is essential in the management of MMP. Early recognition of this disorder and treatment may reduce disease-related complications. The choice of agents for treatment of MMP is based upon the sites of involvement, clinical severity, and disease progression. > Cicatricial pemphigoid (MMP) has been rarely reported in Indian literature. [3] Nayar et al. found there is an association with autoimmune diseases, both organ and non-organ-specifi c in a group of 34 patients with cicatricial pemphigoid suggesting a possible genetic basis for the association. [4] toimmune mechanisms with an underlying genetic predisposition are the most likely causes of vitiligo, although neurohumoral and autocytotoxic hypotheses are alternative theories or contributing mechanisms. Vitiligo is associated with a number of disorders also considered to be autoimmune.

[12] Analysis of the therapeutic effect of comprehensive nursing combined with digital droplet PCR technology on bullous dermatoid diseases

Authors: Conghui Chen
Year: 2025
Venue: Molecular & Cellular Biomechanics
URL: https://www.semanticscholar.org/paper/5f527759dd205eee4ef131dfad11c0c9f5587f97
DOI: 10.62617/mcb1291
Summary: Bullous skin disease is an autoimmune disorder characterized by blistering of the skin or mucous membranes that can seriously affect quality of life and health. Similar to studies at the biomolecular (Protein-Protein Interactions Mechanics), cellular (including Cell Membrane Elasticity, Cell Adhesion Mechanics, Cytoskeleton Mechanics, Mechanical Stimuli Response, Cellular Deformation Mechanisms, Intracellular Force Transmission), and tissue levels, the goal of this study is to facilitate more...
Evidence snippets:
Snippet 1 (score: 0.421) > All cases of bullous dermatosis are diagnosed through methods such as Wood's lamp examination, direct microscopic examination of disease material, and fungal culture [23]. From the perspective of Cell Mechanics and Molecular Mechanics, when counting the incidence, pathogen type, onset season, age, gender, site of onset, types, and detection methods in detail, we can potentially gain insights into how these factors interact with Cellular Deformation Mechanisms and Protein-Protein Interactions Mechanies within the context of bullous skin diseases. This in-depth analysis helps to explore the pathogenesis and characteristics of bullous skin diseases. > Figure 1 illustrates a model for the treatment of dermatological diseases. In terms of Nucleic Acid Mechanics and Protein-Nucleic Acid Interactions Mechanies, this model aims to determine effective diagnosis and treatment methods. By considering Biomolecular Force Spectroscopy, it can screen out rapid and accurate diagnostic methods suitable for bullous skin diseases in the region. These methods may be related to the study of how mechanical forces at the biomolecular level affect the detection and understanding of the disease. Applying these methods to clinical treatment can improve diagnosis and treatment efficiency. Moreover, in the process, it also promotes biomolecular research. This research could potentially uncover more about the role of Molecular Motor Mechanics and Cytoskeleton Mechanics in the pathophysiology of bullous skin diseases, as well as how Mechanical Stimuli Response within the cells might be involved in the disease process and its diagnosis and treatment. Additionally, understanding the Cell Membrane Elasticity and Cell Adhesion Mechanics in the context of bullous skin diseases can contribute to developing more targeted diagnostic and treatment strategies. > A total of 60 patients participated in this study, including 32 males and 28 females; The age range ranged from 25 to 70 years old, with an average age of 48.5 years, and the participation period was during the 12 months from January 2022 to December 2022. Patients are recruited from XYZ Hospital, a tertiary care center specializing in dermatology. All patients included in the study had a diagnosis of herpetiform dermatoses, specifically pemphigus vulgaris and pemphigus foliaceus, based on clinical findings and laboratory findings.

[13] A Multicenter Analysis of Patients with Bullous Pemphigoid: Clinical Characteristics and Insights into Drug-Associated Disease

Authors: A. Małolepsza, Aleksandra Kośny, K. Juczyńska, J. Czerwińska, Magdalena Jałowska et al.
Year: 2026
Venue: International Journal of Molecular Sciences
URL: https://www.semanticscholar.org/paper/5f61e343822b9955eacc5b2502fd0e59d0892be5
DOI: 10.3390/ijms27125587
PMID: 42353304
PMCID: 13299889
Summary: The clinical complexity of BP is highlighted and the importance of medication review and direct immunofluorescence in diagnostic evaluation is highlighted, as well as the importance of medication review and direct immunofluorescence in diagnostic evaluation.
Evidence snippets:
Snippet 1 (score: 0.418) > Based on routine clinical practice, this category may have included tetracyclines, particularly doxycycline, which are used as an evidence-based treatment option in selected patients with bullous pemphigoid. However, because the original retrospective data collection form did not systematically capture specific therapies within the "other" category, this assumption could not be reliably confirmed [13]. Furthermore, treatment-related data were descriptive and did not include standardized information on treatment sequence, treatment response, and relapse rates. In our cohort, patients with more comorbidities tended to receive fewer treatment modalities, suggesting that multimorbidity may limit rather than intensify therapeutic options. This is clinically plausible, as frailty, cardiovascular and metabolic comorbidities, and the risk of adverse events may reduce the feasibility of systemic treatment escalation. Thus, comorbidity burden should be considered an important factor shaping real-world therapeutic decision-making in BP. > In recent years, increasing attention has been given to drugs capable of inducing bullous pemphigoid, raising the question of how such a wide range of structurally diverse molecules can trigger the development of a single disease entity. The pathophysiology is characterized by autoantibodies directed against basement membrane proteins BP180 and BP230, but the underlying mechanisms remain incompletely understood. Some authors even distinguish two distinct entities: drug-associated BP and drug-triggered BP [29]. In the latter, the clinical course closely resembles that of classical BP, with recurrent exacerbations and remissions persisting despite withdrawal of the suspected triggering agent. > Recently, particular emphasis has been placed on the role of dipeptidyl peptidase-4 inhibitors and immune checkpoint inhibitors in the development of drug-associated bullous pemphigoid. In the context of DPP-4 inhibitors, some studies suggest a distinct clinical phenotype with less inflammatory skin manifestations, whereas others have not confirmed these differences [14,[30][31][32][33][34]]. These differences have been observed in studies conducted in Japan and China, whereas European studies do not emphasize this distinction.

[14] Blister Fluid Induces MMP-9-Associated M2-Type Macrophages in Bullous Pemphigoid

Authors: M. Riani, C. Muller, C. Bour, P. Bernard, F. Antonicelli et al.
Year: 2019
Venue: Frontiers in Immunology
URL: https://www.semanticscholar.org/paper/df6625983c6e076b7543bca3bf24d92ed5a9dd9d
DOI: 10.3389/fimmu.2019.01858
PMID: 31440247
PMCID: 6692716
Citations: 15
Influential citations: 3
Summary: The influence of serum and blister fluid from patients with BP on the polarization status of macrophages with regards to the metalloproteinase-9 (MMP-9) expression strongly support the presence of M2-phenotype macrophage phenotype with pro-inflammatory properties susceptible to favor blister formation in BP.
Evidence snippets:
Snippet 1 (score: 0.416) > Bullous pemphigoid (BP) is the most common skin autoimmune subepidermal blistering disease (1,2). The disease typically presents in the elderly with a generalized pruriginous, erythematous and bullous eruption. Biologically, BP is characterized by the binding of autoantibodies directed against two components of the hemidesmosome, BP230 and BP180 that generates an inflammatory response critical for blister formation. A pathophysiological mechanism of blister formation was established, which typically involved a variety of cellular types including eosinophils, neutrophils, lymphocytes, mast cells, and macrophages (3,4). Mast cell activation upon immune complex binding play a major role in neutrophils recruitment, while macrophages were supposed to rather amplify the neutrophil infiltration in a mast cell-dependent fashion (5,6). However, the role of macrophage polarization has not been taken into consideration in the pathophysiological BP process, and especially regarding the production of MMP-9, a metalloproteinase widely involved in blister formation (7). > Macrophages display a remarkable plasticity and can change their physiology in response to environmental factors with at one extremity the inflammatory or classically activated macrophage M1 phenotype and at the other, the anti-inflammatory or alternatively activated macrophage M2 phenotype (8). The M1 phenotype is classically induced by microbial products or proinflammatory cytokines such as IFN-γ and TNFα, whereas molecules such as IL-4, IL-13, M-CSF, immune complexes, IL-10, and glucocorticoids favor the orientation toward the M2type macrophage phenotype.

[15] Bullous Pemphigoid and Other Pemphigoid Dermatoses

Authors: Valeryia Pratasava, V. Sahni, Aishwarya Suresh, Simo Huang, Abhi C. Are et al.
Year: 2021
Venue: Medicina
URL: https://www.semanticscholar.org/paper/b95124eac88691c8a63e2d1db3972ab0ef713201
DOI: 10.3390/medicina57101061
PMID: 34684098
PMCID: 8539012
Citations: 32
Influential citations: 2
Summary: Clinicians that encounter the pemphigoid disorders may benefit from an overview of their clinical presentation, diagnostic work-up, and therapeutic management, with an emphasis on the most frequently encountered pemPhigoid disease, bullous pemPHigoid.
Evidence snippets:
Snippet 1 (score: 0.413) > The pemphigoid family of dermatoses is characterized by autoimmune subepidermal blistering. The classic paradigm for pemphigoid, and the most common member, is bullous pemphigoid. Its variable clinical presentation, with or without frank bullae, is linked by significant pruritus afflicting the elderly. Mucous membrane pemphigoid is an umbrella term for a group of subepidermal blistering dermatoses that favor the mucosal membranes and can scar. Epidermolysis bullosa acquisita is a chronic blistering disorder characterized by skin fragility, sensitivity to trauma, and its treatment-refractory nature. Clinicians that encounter these pemphigoid disorders may benefit from an overview of their clinical presentation, diagnostic work-up, and therapeutic management, with an emphasis on the most frequently encountered pemphigoid disease, bullous pemphigoid.

[16] Heat Shock Protein 90 (Hsp90) and Hsp70 as Potential Therapeutic Targets in Autoimmune Skin Diseases

Authors: S. Tukaj, K. Sitko
Year: 2022
Venue: Biomolecules
URL: https://www.semanticscholar.org/paper/95a3cb15dc2a25a86387bace586e3821ced8cb81
DOI: 10.3390/biom12081153
PMID: 36009046
PMCID: 9405624
Citations: 45
Influential citations: 1
Summary: Preclinical data on the involvement of Hsp90 and Hsp70 in modulating the immune response is presented, specifically in the context of the treatment of selected autoimmune skin diseases with emphasis on autoimmune bullous skin diseases and psoriasis.
Evidence snippets:
Snippet 1 (score: 0.413) > Autoimmune bullous diseases (AIBDs) belong to a relatively rare and potentially life-threatening organ-specific group of inflammatory skin diseases characterized by the presence of autoantibodies against various structural proteins of the skin present in desmosomes (e.g., pemphigus vulgaris-PV) and hemidesmosomes (e.g., bullous pemphigoid-BP and epidermolysis bullosa acquisita-EBA), or against epidermal/tissue transglutaminases present in Duhring disease (also known as dermatitis herpetiformis-DH). Despite understanding of the pathophysiology of AIBDs, in which both innate and adaptive mechanisms of the immune response are undoubtedly involved, treatment for this group of diseases remains a challenge, due to frequent relapses after the discontinuation of therapy, numerous side effects associated with using, e.g., corticosteroids, or due to the lack of a fully effective drug [67][68][69].

[17] BULLOUS PEMPHIGOID A RARE AUTOIMMUNE DISEASE: A CASE REPORT

Authors: S. Biradar, S. Dhanavidya, P. Kavya, T. Keerthi, N. Sunanda et al.
Year: 2019
Venue: International Journal of Medicine and Medical Research
URL: https://www.semanticscholar.org/paper/efce45b04f023311dcaefd694b1a6f40159a7bed
DOI: 10.11603/ijmmr.2413-6077.2018.2.9248
Citations: 3
Summary: In the present case study, the use of Prednisolone has proven its efficacy in the extensive disease state of BP and improved the patient’s quality of life.
Evidence snippets:
Snippet 1 (score: 0.411) > Bullous pemphigoid is a rare autoimmune blistering disease; it typically affects the elderly and is followed by significant morbidity and mortality [7]. The clinical symptoms of the disease are development of oral lesions in about one-third of the patients; lesions may occur on the trunk, extremities, and intertriginous areas. In most of the cases, no clear precipitating factors are identified; some precipitating factors are exposure to ultraviolet light, radiation therapy and exposed to certain drugs like furosemide, penicillin, sulfasalazine, and captopril [7]. The disease is characterized by the formation of IgG auto antibodies targeting dystonin (bullous pemphigoid antigen 1 (BPAG1), and /or type XVII collagen also called bullous pemphigoid antigen 2 (BPAG2), which is a component of hemides mosomes [2]. In the present case fluid-filled lesions were seen initially over the trunk and gradually progressed involving lower and upper extremities. > The recommended treatment for BP is as follows [8]: > Initial therapy. Initial therapy is determined by the extent and rate of progression of the lesions. The priority is to control lesions usually in a slowly progressive form of the disease; initial treatment includes intralesional injections of corticosteroids or topical applications of corticosteroids. > Maintenance therapy. Once most lesions are healed, the dose and type of medication are gradually reduced to limit the risk of side effects. Understanding the rate of dose reduction is determined by clinical response and overall disease activity. It is important to monitor this balance and limit use of unnecessary medication as many fatalities are related to complications associated with the therapy. > The available treatments work via different mechanisms. Some aim to suppress the inflammatory process e.g. corticosteroids, antibiotics, anti-inflammatory mediators. Immune modulating treatments include intravenous immunoglobulins. Intravenous immunoglobulin has been widely tried as an immunomodulatory agent in various auto-antibody mediated blistering diseases. Systemic corticosteroids are most commonly used: dexamethasone and prednisolone.

[18] Upadacitinib for the management of bullous pemphigoid coexisting with psoriasis vulgaris: a case report and literature review

Authors: Fang Su, Tai Wang, Qunshi Qin, Zhi Xie
Year: 2024
Venue: Journal of Dermatological Treatment
URL: https://www.semanticscholar.org/paper/7da301fc8c62b90a0f42d61eac32645825001789
DOI: 10.1080/09546634.2024.2302394
PMID: 38263708
Citations: 18
Summary: Based on clinical observations, upadacitinib appears to be a promising and well-tolerated therapeutic option for patients with concurrent BP and psoriasis, offering valuable insights for developing appropriate treatment strategies in clinical practice.
Evidence snippets:
Snippet 1 (score: 0.403) > Bullous pemphigoid (Bp) is an autoimmune blistering skin disease, characterized by severe pruritus and the formation of blisters beneath the epidermis. Its pathogenesis involves an imbalance in th1/th2 subsets, with a predominance of th2 cytokines (1). psoriasis is an immune-mediated chronic, recurrent, inflammatory, and systemic disease, influenced by both genetic and environmental factors. the typical clinical manifestation includes localized or widespread scaly erythema or plaques, wherein dysfunctional helper t cells (th1, th17, etc.) play a crucial role in its pathogenesis (2). Both bullous pemphigoid and psoriasis are immune-related dermatological conditions that have garnered increasing attention in recent years. the precise mechanisms underlying their pathogenesis remain unclear; however, it is speculated that they may involve immune mechanisms, inflammatory cells, cytokines among others. Given the conflicting treatment approaches for Bp and psoriasis management strategies available currently, there exists significant importance in identifying effective therapeutic interventions. > the JaK/stat signaling pathway is a widely expressed signal transduction pathway involved in various biological processes, including cell proliferation, apoptosis, and immune regulation. It plays a crucial role in the development of inflammatory diseases (3,4), autoimmune disorders, and malignant tumors by activating JaKs and stats. Due to its potent regulatory effect, small molecule targeted drugs known as JaK inhibitors (JaKi) have emerged as a promising research focus for the treatment of immune-related skin diseases. JaKi can efficiently hinder JaK activation and obstruct the stat pathway by attaching to the adenosine triphosphate (atp) binding site on proteins, thus accomplishing therapeutic objectives (5). Notably, first-generation JaK inhibitors such as baricitinib or tofacitinib have shown efficacy in treating mucosal pemphigoid (6,7), while different targets alone or in combination inhibition by JaK inhibitors has demonstrated significant therapeutic effects in psoriasis (8).
Snippet 2 (score: 0.402) > Abstract Both bullous pemphigoid (BP) and psoriasis are common immune-related dermatological conditions in clinical practice, but the co-occurrence of these two diseases is rare. Currently, there is no consensus on the long-term safe and effective treatment for patients with both BP and psoriasis. JAK inhibitors are emerging as targeted therapeutic drugs that act by inhibiting Janus kinase activity, regulating the JAK/STAT pathway, blocking the transduction pathway of key proinflammatory cytokines, and influencing T-cell differentiation. These cytokines upstream of the JAK/STAT pathway play a pivotal role in the pathogenesis of numerous inflammatory and autoimmune disorders. Upadacitinib, a second-generation JAK inhibitor with high selectivity, demonstrates promising potential. This case report aims to provide a description of the successful treatment of bullous pemphigoid (BP) and psoriasis vulgaris by using upadacitinib, highlighting significant clinical outcomes. Additionally, we aim to analyze the underlying mechanism of upadacitinib in treating these two comorbidities by reviewing relevant literature from both domestic and international sources. Based on our clinical observations, upadacitinib appears to be a promising and well-tolerated therapeutic option for patients with concurrent BP and psoriasis, offering valuable insights for developing appropriate treatment strategies in clinical practice.

[19] Advances in Pemphigus and Pemphigoid: A Report of the International Meeting of the Pemphigus and Pemphigoid Foundation in Thessaloniki, Greece

Authors: Meropi Karakioulaki, Patrick Dunn, D. Murrell, Aimee S. Payne, Enno Schmidt et al.
Year: 2024
Venue: JID Innovations
URL: https://www.semanticscholar.org/paper/fe389e1a6cc07426f4a9357f3a2095cee6d5bb9b
DOI: 10.1016/j.xjidi.2024.100339
PMID: 39877685
PMCID: 11773198
Citations: 3
Summary: and
Evidence snippets:
Snippet 1 (score: 0.403) > The recent international meeting of the Pemphigus and Pemphigoid Foundation in Thessaloniki, Greece, marked a significant step forward in the understanding and management of these complex autoimmune diseases. > One of the primary areas of progress highlighted was the deepening understanding of molecular pathways involved in the pathogenesis of pemphigus and pemphigoid. This expanding knowledge offers new insights into how these diseases develop and, more importantly, opens up potential avenues for targeted therapies that could more precisely address disease mechanisms. > Nonetheless, the meeting also underscored ongoing unmet needs in treatment approaches, particularly the goal of achieving early control and sustained remission with reduced or no dependence on steroids. Developing therapies that minimize steroid use remains critical for patient QOL and safety because long-term steroid exposure can lead to serious side effects. The need for such therapies emphasizes the importance of innovative drug development and continued research into disease-modifying agents. > Looking to the future, participants identified several challenges that must be addressed to advance care further. Improving clinical trial design to better evaluate treatment outcomes and achieving consensus with regulatory agencies on metrics for success will be crucial for moving promising therapies forward. In addition, further characterization of disease pathogenesis, with a focus on individualized genetic and molecular profiles, is essential to enable more personalized, effective treatment plans for patients. > The meeting concluded with a collective expression of gratitude to all organizers and participants and a commitment to ongoing collaboration. Regular meetings such as this one will be vital for sustaining progress and fostering the innovations needed to transform patient care in pemphigus and pemphigoid.

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Relevant Papers

[1] Pruritogens in pemphigoid diseases: Possible therapeutic targets for a burdensome symptom

[2] A Scoping Review of the Role of Metalloproteinases in the Pathogenesis of Autoimmune Pemphigus and Pemphigoid

[3] Review on Bullous Pemphigoid: Fixed Drug Eruption or Autoimmune Disorder

[4] Role of Regulatory Immune Cells and Molecules in Autoimmune Bullous Dermatoses

[5] Editorial: Autoimmune blistering diseases: advances in the understanding of pathogenesis and new therapeutic horizons

[6] Researching trends in pemphigoid diseases: A bibliometric study of the top 100 most cited publications

[7] The pathological function of neutrophils in pemphigoid diseases

[8] Pathophysiology of Bullous Pemphigoid: Role of Type 2 Inflammation and Emerging Treatment Strategies (Narrative Review)

[9] Prognostic factors for mortality in bullous pemphigoid: A systematic review and meta-analysis

[10] A Case Report on Idiopathic Severe Bullous Pemphigoid

[11] Coexistence of mucous membrane pemphigoid and vitiligo

[12] Analysis of the therapeutic effect of comprehensive nursing combined with digital droplet PCR technology on bullous dermatoid diseases

[13] A Multicenter Analysis of Patients with Bullous Pemphigoid: Clinical Characteristics and Insights into Drug-Associated Disease

[14] Blister Fluid Induces MMP-9-Associated M2-Type Macrophages in Bullous Pemphigoid

[15] Bullous Pemphigoid and Other Pemphigoid Dermatoses

[16] Heat Shock Protein 90 (Hsp90) and Hsp70 as Potential Therapeutic Targets in Autoimmune Skin Diseases

[17] BULLOUS PEMPHIGOID A RARE AUTOIMMUNE DISEASE: A CASE REPORT

[18] Upadacitinib for the management of bullous pemphigoid coexisting with psoriasis vulgaris: a case report and literature review

[19] Advances in Pemphigus and Pemphigoid: A Report of the International Meeting of the Pemphigus and Pemphigoid Foundation in Thessaloniki, Greece

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