Erysipelas - dismech

🏷

Classifications

Harrison's Part

⚙

Pathophysiology

5

Predisposing Lymphatic Impairment

Subclinical or overt lymphatic impairment and leg edema lower local clearance capacity in the skin and make the limb susceptible to a first or recurrent erysipelas episode.

lymphatic vessel UBERON:0001473

Downstream

Streptococcal Dermal Infection Leg edema and impaired lymphatic drainage act as an independent local susceptibility factor that favors dermal infection after a barrier break admits streptococci.

Show evidence (1 reference)

PMID:40542699 SUPPORT Human Clinical

"Subclinical lymphedema on the unaffected leg was found in 82% of patients, with a similar prevalence in all genders and age groups, and in patients with or without erysipelas risk factors."

Lymphoscintigraphy shows frequent subclinical lymphatic dysfunction even in the clinically unaffected limb of people with erysipelas.

Cutaneous Barrier Portal of Entry

Traumatic wounds, toe-web intertrigo, excoriated dermatoses, and plantar scaling lesions breach the skin and create portals through which streptococci can reach the superficial dermis.

keratinocyte CL:0000312

skin UBERON:0002097

Downstream

Streptococcal Dermal Infection A compromised skin barrier enables beta-hemolytic streptococci to enter and establish infection in superficial dermis and dermal lymphatics.

Show evidence (1 reference)

PMID:16484815 SUPPORT Human Clinical

"disruption of the cutaneous barrier (i.e. traumatic wound, toe-web intertrigo, excoriated leg dermatosis or plantar squamous lesions) and leg edema were independently associated with erysipelas of the leg, with respective odds ratios of 13.6 (95% confidence interval: 6.0-31) and 7.0 (1.3-38)."

Demonstrates skin-barrier disruption as a strong, independent risk factor for leg erysipelas.

Streptococcal Dermal Infection

Beta-hemolytic streptococci proliferate in the superficial dermis and dermal lymphatics after barrier entry.

dermis UBERON:0002067 lymphatic vessel UBERON:0001473

Downstream

Acute Dermal Inflammatory Response Streptococcal infection in superficial dermis and dermal lymphatics produces the sharply demarcated inflammatory erythema and early constitutional symptoms of acute erysipelas.

Post-Erysipelas Lymphatic Damage Erysipelas episodes can worsen lymphatic drainage and feed a recurrence-prone edema-infection cycle.

Show evidence (1 reference)

PMID:26734653 SUPPORT Human Clinical

"Serology or blood or tissue culture confirmed beta-hemolytic streptococcal (BHS) etiology in 72% (146 of 203) of cases."

Confirms beta-hemolytic streptococcal etiology for most clinically diagnosed cellulitis cases, the diagnostic neighborhood that includes erysipelas.

Acute Dermal Inflammatory Response

The acute host response to streptococcal growth in the superficial dermis produces bright, well-demarcated erythema and early systemic symptoms such as fever and chills.

neutrophil CL:0000775

inflammatory response GO:0006954

dermis UBERON:0002067

Downstream

Erythema Upper-dermal inflammation produces the bright red, shiny erythema used to diagnose erysipelas clinically.

Fever Systemic inflammatory signaling during acute erysipelas commonly manifests with fever among the early constitutional symptoms.

Chills The same early constitutional inflammatory response can present with chills or shivers around erythema onset.

Pain Local dermal inflammation can make the erythematous lesion painful or tender in acute erysipelas.

Post-Erysipelas Lymphatic Damage

Erysipelas episodes can leave or amplify chronic lymphatic impairment, predisposing to recurrent infections and chronic swelling.

lymphatic vessel UBERON:0001473

Downstream

Predisposing Lymphatic Impairment Repeated erysipelas episodes increase the prevalence of subclinical lymphedema, feeding the lymphatic susceptibility that permits subsequent episodes.

Lymphedema Erysipelas-associated lymphatic damage can persist as chronic lymphedema and, in severe cases, elephantiasis.

Lymphangitis Erysipelas involving superficial dermal lymphatics can be complicated by clinically recognized lymphangitis.

Show evidence (1 reference)

PMID:18069381 SUPPORT Human Clinical

"Complications, such as abscess formation, lymphangitis, venous insufficiency, osteitis, arthritis, septic tendonitis and elephantiasis were found in 25%."

Documents lymphatic and chronic swelling complications in a 10-year erysipelas cohort.

⬡

Pathograph

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

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Phenotypes

6

Cardiovascular 1

Erythema HP:0010783

Show evidence (1 reference)

PMID:41562377 SUPPORT Human Clinical

"erysipelas presents clinically as acute, warm, more or less painful, bright red erythema with a shiny surface, relatively well-defined borders"

The erythematous plaque morphology is a clinical discriminator of erysipelas.

Metabolism 2

Fever HP:0001945

Show evidence (1 reference)

PMID:41562377 SUPPORT Human Clinical

"Of the patients with erysipelas, 92.1% (70 of 76) reported that they had experienced constitutional symptoms in the form of fever, chills, shivers, and feeling fatigued or ill at or before detection of the erythema"

Fever is one of the early constitutional symptoms reported by the erysipelas cohort.

Lymphedema HP:0001004

Show evidence (2 references)

PMID:40542699 SUPPORT Human Clinical

"Subclinical lymphedema on the unaffected leg was found in 82% of patients, with a similar prevalence in all genders and age groups, and in patients with or without erysipelas risk factors."

Lymphoscintigraphy showed a high burden of otherwise subclinical leg lymphedema in people with erysipelas.

PMID:40542699 SUPPORT Human Clinical

"Moreover, the prevalence of subclinical lymphedema increased proportionally with the number of erysipelas episodes: among those with a single episode, 74% exhibited subclinical lymphedema, whereas among those with 3 or more episodes, the prevalence was 100%."

Episode-count association connects recurrent erysipelas to a greater prevalence of leg lymphedema.

Constitutional 2

Chills HP:0025143

Show evidence (1 reference)

PMID:41562377 SUPPORT Human Clinical

"Of the patients with erysipelas, 92.1% (70 of 76) reported that they had experienced constitutional symptoms in the form of fever, chills, shivers, and feeling fatigued or ill at or before detection of the erythema"

Chills are one of the early constitutional symptoms reported by the erysipelas cohort.

Pain HP:0012531

Show evidence (1 reference)

PMID:41562377 SUPPORT Human Clinical

"Pain was reported in 47 patients with erysipelas (59.5%), the other 34 patients (43%) had denied having pain."

Pain was captured as a local symptom in the erysipelas cohort.

Other 1

Lymphangitis

Coarse binding: no hpo term

Ontology gap: `uv run runoak -i ols:hp search lymphangitis` on 2026-09-27 returned lymphangioma and lymphangiectasis terms, but no lymphatic-vessel inflammation term. No term request has been filed yet.

Show evidence (1 reference)

PMID:18069381 SUPPORT Human Clinical

"Complications, such as abscess formation, lymphangitis, venous insufficiency, osteitis, arthritis, septic tendonitis and elephantiasis were found in 25%."

Lymphangitis was one of the complications observed in a 10-year erysipelas cohort.

💊

Medical Actions

4

Penicillin G therapy

Action: Pharmacotherapy NCIT:C15986

Agent: benzylpenicillin CHEBI:18208

Platform: Small molecule

Benzylpenicillin is a narrow-spectrum beta-lactam used for acute streptococcal erysipelas.

Mechanism Target:

INHIBITS Streptococcal Dermal Infection — Penicillin G inhibits the beta-hemolytic streptococci driving the acute dermal infection.

Show evidence (2 references)

PMID:15822466 SUPPORT Human Clinical

"Erysipelas can be controlled with antibiotics; treatment is essentially based on penicillin G 4 mega units intramuscularly every day (60.58%) for mean duration of 10.13 days."

Large erysipelas series supporting intramuscular penicillin G as a common erysipelas antibiotic regimen in that cohort.

PMID:41562377 SUPPORT Human Clinical

"Of the 60 patients treated with penicillin, 59 patients (98.3%) responded within 2 days, revealing fine wrinkling of the skin, followed by fading of redness and then reduction of the erythematous area accompanied by an improvement of still existing constitutional symptoms."

A retrospective erysipelas cohort documents rapid clinical response in nearly all patients treated with penicillin.

Penicillin V recurrence prophylaxis

Action: Pharmacotherapy NCIT:C15986

Agent: phenoxymethylpenicillin CHEBI:27446

Platform: Small molecule

Oral phenoxymethylpenicillin can be used as low-dose prophylaxis to reduce recurrent leg cellulitis/erysipelas episodes while prophylaxis continues.

Mechanism Target:

INHIBITS Streptococcal Dermal Infection — Suppressive oral penicillin reduces recurrence of streptococcal lower-limb cellulitis/erysipelas during prophylaxis.

Show evidence (2 references)

PMID:23635049 SUPPORT Human Clinical

"During the prophylaxis phase, 30 of 136 participants in the penicillin group (22%) had a recurrence, as compared with 51 of 138 participants in the placebo group (37%) (hazard ratio, 0.55; 95% confidence interval [CI], 0.35 to 0.86; P=0.01), yielding a number needed to treat to prevent one..."

Randomized trial evidence that penicillin V prophylaxis reduces recurrence in the overlapping recurrent leg cellulitis/erysipelas syndrome.

PMID:28631307 SUPPORT Human Clinical

"In terms of recurrence, incidence, and time to next episode, antibiotic is probably an effective preventive treatment for recurrent cellulitis of the lower limbs in those under prophylactic treatment, compared with placebo or no treatment (moderate-certainty evidence)."

Cochrane review evidence supports antibiotic prophylaxis for recurrent lower-limb cellulitis/erysipelas while treatment continues.

Toe-web intertrigo and wound care

Action: Supportive Care NCIT:C15747

Platform: Other

Detecting and treating toe-web intertrigo, fungal foot disease, and traumatic wounds reduces the portal-of-entry substrate for leg erysipelas.

Mechanism Target:

INHIBITS Cutaneous Barrier Portal of Entry — Treating interdigital and traumatic skin lesions closes portals through which streptococci enter the dermis.

Show evidence (1 reference)

PMID:16484815 SUPPORT Human Clinical

"Detecting and treating toe-web intertrigo and traumatic wounds should be considered in the prevention of erysipelas of the leg."

The case-control study conclusion directly supports portal-of-entry management to prevent leg erysipelas.

Compression therapy for lymphedema prevention

Action: Compression Therapy NCIT:C157735

Platform: Behavioral / lifestyle

Bilateral leg compression can be used after erysipelas to counter lymphedema and reduce the lymphatic susceptibility to recurrence.

Mechanism Target:

INHIBITS Predisposing Lymphatic Impairment — Compression therapy reduces leg lymphedema, limiting the lymphatic drainage impairment that predisposes to recurrent erysipelas.

Show evidence (1 reference)

PMID:40542699 SUPPORT Human Clinical

"Thus, our clinical recommendation suggests bilateral leg compression therapy in erysipelas patients to prevent recurrence and lymphedema exacerbation."

Lymphoscintigraphy findings led the investigators to recommend bilateral leg compression for recurrence prevention and lymphedema control.

🌍

Environmental Factors

3

Skin barrier disruption

Wounds, toe-web intertrigo, excoriated dermatoses, and plantar scaling lesions predispose to leg erysipelas by opening portals of entry in skin.

Show evidence (1 reference)

PMID:16484815 SUPPORT Human Clinical

"disruption of the cutaneous barrier (i.e. traumatic wound, toe-web intertrigo, excoriated leg dermatosis or plantar squamous lesions) and leg edema were independently associated with erysipelas of the leg, with respective odds ratios of 13.6 (95% confidence interval: 6.0-31) and 7.0 (1.3-38)."

Quantifies skin barrier disruption as an upstream erysipelas risk factor.

Mechanism Target:

PREDISPOSES Cutaneous Barrier Portal of Entry — Mechanical or inflammatory barrier defects increase susceptibility to streptococcal dermal entry.

Toe-web intertrigo and tinea pedis

Toe-web intertrigo and tinea pedis disrupt the foot skin barrier and supply portals of entry for streptococci that cause lower-limb erysipelas.

Show evidence (2 references)

PMID:16484815 SUPPORT Human Clinical

"disruption of the cutaneous barrier (i.e. traumatic wound, toe-web intertrigo, excoriated leg dermatosis or plantar squamous lesions) and leg edema were independently associated with erysipelas of the leg, with respective odds ratios of 13.6 (95% confidence interval: 6.0-31) and 7.0 (1.3-38)."

Toe-web intertrigo is part of the independently associated skin-barrier disruption risk factor in this leg erysipelas case-control study.

PMID:29427797 SUPPORT Human Clinical

"tinea pedis (AOR 3.05, 95% CI 1.45-6.42, p 0.003)"

Population-based case-control data identify tinea pedis as an independent risk factor for severe lower-limb cellulitis.

Mechanism Target:

PREDISPOSES Cutaneous Barrier Portal of Entry — Interdigital fungal disease and maceration open cutaneous entry sites for beta-hemolytic streptococci.

Leg edema and lymphatic impairment

Leg edema and lymphedema increase susceptibility to leg erysipelas.

Show evidence (1 reference)

PMID:16484815 SUPPORT Human Clinical

"disruption of the cutaneous barrier (i.e. traumatic wound, toe-web intertrigo, excoriated leg dermatosis or plantar squamous lesions) and leg edema were independently associated with erysipelas of the leg, with respective odds ratios of 13.6 (95% confidence interval: 6.0-31) and 7.0 (1.3-38)."

Case-control data identify leg edema as an independent local risk factor for leg erysipelas.

Mechanism Target:

PREDISPOSES Predisposing Lymphatic Impairment — Edematous and lymphatically impaired tissue has diminished local fluid clearance and is prone to recurrent streptococcal infection.

🔬

Diagnosis

2

Clinical erysipelas recognition

Erysipelas is recognized clinically by its acute warm, painful, bright-red erythematous plaque with a shiny surface, relatively well-defined borders, and early fever or chills that help distinguish it from cellulitis.

clinical diagnosis NCIT:C18020

Results: Characteristic sharply demarcated erythema with constitutional symptoms supports erysipelas rather than uncomplicated cellulitis.

Show evidence (2 references)

PMID:41562377 SUPPORT Human Clinical

"Constitutional symptoms like chills and fever may help in diagnosis."

The retrospective comparison tested fever and chills as clinical cues that help differentiate erysipelas from uncomplicated cellulitis.

PMID:41562377 SUPPORT Human Clinical

"erysipelas presents clinically as acute, warm, more or less painful, bright red erythema with a shiny surface, relatively well-defined borders"

The quoted morphology describes the core clinical lesion used to recognize erysipelas.

Streptococcal serology

Paired acute and convalescent antistreptolysin O and anti-DNase B titers can support beta-hemolytic streptococcal etiology when cultures are negative.

Diagnostic Serology Testing NCIT:C217458

Results: Rising or persistently elevated ASO or anti-DNase B titers provide evidence of beta-hemolytic streptococcal skin infection.

Show evidence (1 reference)

PMID:26734653 SUPPORT Human Clinical

"Acute and convalescent sera were available in 200 cases. Positive BHS serology was found in 71% of cases; 60% of cases were positive for ASO, and 30% of cases were positive for ADB (Figure 2B)."

Prospective cellulitis and erysipelas-adjacent data show that paired streptococcal serology often identifies beta-hemolytic streptococcal etiology.

📈

Progression

1

Recurrent erysipelas

Episodes often recur, especially in limbs with edema or lymphatic impairment, maintaining an edema-infection cycle.

Show evidence (1 reference)

PMID:18069381 SUPPORT Human Clinical

"The recurrent cases occurred in 67.3% cases with lower limb localisation in 69.44% cases."

A 10-year retrospective erysipelas cohort documents frequent recurrent lower-limb disease.

🦠

Infectious Agent

2

Streptococcus pyogenes

Group A Streptococcus is one of the principal beta-hemolytic streptococci isolated from erysipelas lesions and blood cultures.

Streptococcus pyogenes NCBITaxon:1314

Show evidence (1 reference)

PMID:26424182 SUPPORT Human Clinical

"Wound cultures were taken in 343 episodes and 56 grew group A streptococci (GAS), 53 grew group G streptococci (GGS), 11 grew group C streptococci (GCS), and 153 grew Staphylococcus aureus."

Large erysipelas cohort identifying group A streptococci among the streptococcal isolates cultured from erysipelas episodes.

Streptococcus dysgalactiae subsp. equisimilis

Group C and group G streptococci, represented by Streptococcus dysgalactiae subsp. equisimilis, are frequent beta-hemolytic streptococcal agents in erysipelas.

Streptococcus dysgalactiae subsp. equisimilis NCBITaxon:119602

Show evidence (1 reference)

PMID:26424182 SUPPORT Human Clinical

"The GGS isolates as well as the three GCS isolates were determined to be Streptococcus dysgalactiae using MALDI-TOF MS."

Large erysipelas cohort identifying Streptococcus dysgalactiae among the group G and group C streptococci recovered from positive blood cultures.

{ }

Source YAML

click to show

name: Erysipelas
creation_date: "2026-09-26T06:42:40Z"
category: Infectious Disease
description: >-
  Erysipelas is an acute bacterial infection of the superficial dermis and
  dermal lymphatics caused predominantly by beta-hemolytic streptococci. Skin
  barrier disruption and edema or lymphatic impairment predispose to dermal
  streptococcal inoculation, local streptococcal spread, and
  recurrence driven by persistent or infection-damaged lymphatic drainage.
synonyms:
- St. Anthony's fire
disease_term:
  preferred_term: erysipelas
  term:
    id: MONDO:0001266
    label: erysipelas
parents:
- Bacterial Infection
classifications:
  harrisons_chapter:
  - classification_value: INFECTIOUS_DISEASES
    evidence:
    - reference: PMID:40542699
      reference_title: Prevalence of Pre-Existing Subclinical Leg Lymphedema in Patients with Erysipelas.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Erysipelas is a common bacterial infection of the skin and subcutaneous
        tissue.
      explanation: >-
        A clinical erysipelas imaging study frames the disorder as a bacterial
        skin infection, supporting its Harrison's infectious-disease
        classification.
infectious_agent:
- name: Streptococcus pyogenes
  description: >-
    Group A Streptococcus is one of the principal beta-hemolytic streptococci
    isolated from erysipelas lesions and blood cultures.
  infectious_agent_term:
    preferred_term: Streptococcus pyogenes
    term:
      id: NCBITaxon:1314
      label: Streptococcus pyogenes
  evidence:
  - reference: PMID:26424182
    reference_title: "Erysipelas, a large retrospective study of aetiology and clinical presentation."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Wound cultures were taken in 343 episodes and 56 grew group A
      streptococci (GAS), 53 grew group G streptococci (GGS), 11 grew group C
      streptococci (GCS), and 153 grew Staphylococcus aureus.
    explanation: >-
      Large erysipelas cohort identifying group A streptococci among the
      streptococcal isolates cultured from erysipelas episodes.
- name: Streptococcus dysgalactiae subsp. equisimilis
  description: >-
    Group C and group G streptococci, represented by Streptococcus
    dysgalactiae subsp. equisimilis, are frequent beta-hemolytic streptococcal
    agents in erysipelas.
  infectious_agent_term:
    preferred_term: Streptococcus dysgalactiae subsp. equisimilis
    term:
      id: NCBITaxon:119602
      label: Streptococcus dysgalactiae subsp. equisimilis
  evidence:
  - reference: PMID:26424182
    reference_title: "Erysipelas, a large retrospective study of aetiology and clinical presentation."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The GGS isolates as well as the three GCS isolates were determined to be
      Streptococcus dysgalactiae using MALDI-TOF MS.
    explanation: >-
      Large erysipelas cohort identifying Streptococcus dysgalactiae among the
      group G and group C streptococci recovered from positive blood cultures.
pathophysiology:
- name: Predisposing Lymphatic Impairment
  description: >-
    Subclinical or overt lymphatic impairment and leg edema lower local
    clearance capacity in the skin and make the limb susceptible to a first or
    recurrent erysipelas episode.
  locations:
  - preferred_term: lymphatic vessel
    term:
      id: UBERON:0001473
      label: lymphatic vessel
  downstream:
  - target: Streptococcal Dermal Infection
    description: >-
      Leg edema and impaired lymphatic drainage act as an independent local
      susceptibility factor that favors dermal infection after a barrier break
      admits streptococci.
    evidence:
    - reference: PMID:16484815
      reference_title: "Risk factors for erysipelas of the leg in Tunisia: a multicenter case-control study."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        disruption of the cutaneous barrier (i.e. traumatic wound, toe-web
        intertrigo, excoriated leg dermatosis or plantar squamous lesions) and
        leg edema were independently associated with erysipelas of the leg,
        with respective odds ratios of 13.6 (95% confidence interval: 6.0-31)
        and 7.0 (1.3-38).
      explanation: >-
        Case-control data support edema and skin-barrier disruption as
        independent, upstream risk factors for leg erysipelas.
  evidence:
  - reference: PMID:40542699
    reference_title: Prevalence of Pre-Existing Subclinical Leg Lymphedema in Patients with Erysipelas.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Subclinical lymphedema on the unaffected leg was found in 82% of
      patients, with a similar prevalence in all genders and age groups, and in
      patients with or without erysipelas risk factors.
    explanation: >-
      Lymphoscintigraphy shows frequent subclinical lymphatic dysfunction even
      in the clinically unaffected limb of people with erysipelas.
- name: Cutaneous Barrier Portal of Entry
  description: >-
    Traumatic wounds, toe-web intertrigo, excoriated dermatoses, and plantar
    scaling lesions breach the skin and create portals through which
    streptococci can reach the superficial dermis.
  locations:
  - preferred_term: skin
    term:
      id: UBERON:0002097
      label: skin of body
  cell_types:
  - preferred_term: keratinocyte
    term:
      id: CL:0000312
      label: keratinocyte
  downstream:
  - target: Streptococcal Dermal Infection
    description: >-
      A compromised skin barrier enables beta-hemolytic streptococci to enter
      and establish infection in superficial dermis and dermal lymphatics.
    evidence:
    - reference: PMID:15822466
      reference_title: "[Erysipelas. Retrospective study of 647 patients]."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Erysipelas predominately involved in the lower limbs (91.2%).
        Antecedents of erysipelas were found in 26.12 %. Portal of entry was
        found in 76.66% represented essentially by toe-web intertrigo.
      explanation: >-
        Large erysipelas series linking lower-limb disease to portals of entry,
        most often toe-web intertrigo.
  evidence:
  - reference: PMID:16484815
    reference_title: "Risk factors for erysipelas of the leg in Tunisia: a multicenter case-control study."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      disruption of the cutaneous barrier (i.e. traumatic wound, toe-web
      intertrigo, excoriated leg dermatosis or plantar squamous lesions) and
      leg edema were independently associated with erysipelas of the leg, with
      respective odds ratios of 13.6 (95% confidence interval: 6.0-31) and 7.0
      (1.3-38).
    explanation: >-
      Demonstrates skin-barrier disruption as a strong, independent risk factor
      for leg erysipelas.
- name: Streptococcal Dermal Infection
  description: >-
    Beta-hemolytic streptococci proliferate in the superficial dermis and
    dermal lymphatics after barrier entry.
  locations:
  - preferred_term: dermis
    term:
      id: UBERON:0002067
      label: dermis
  - preferred_term: lymphatic vessel
    term:
      id: UBERON:0001473
      label: lymphatic vessel
  downstream:
  - target: Acute Dermal Inflammatory Response
    description: >-
      Streptococcal infection in superficial dermis and dermal lymphatics
      produces the sharply demarcated inflammatory erythema and early
      constitutional symptoms of acute erysipelas.
    evidence:
    - reference: PMID:26424182
      reference_title: "Erysipelas, a large retrospective study of aetiology and clinical presentation."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        The clinical picture is characterized by an inflammatory reaction of
        the upper dermis with a sharp demarcation of the erythema.
      explanation: >-
        The cohort review places erysipelas' characteristic erythema at the
        inflammatory upper-dermal response downstream of infection.
  - target: Post-Erysipelas Lymphatic Damage
    description: >-
      Erysipelas episodes can worsen lymphatic drainage and feed a
      recurrence-prone edema-infection cycle.
    evidence:
    - reference: PMID:40542699
      reference_title: Prevalence of Pre-Existing Subclinical Leg Lymphedema in Patients with Erysipelas.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Moreover, the prevalence of subclinical lymphedema increased
        proportionally with the number of erysipelas episodes: among those with
        a single episode, 74% exhibited subclinical lymphedema, whereas among
        those with 3 or more episodes, the prevalence was 100%.
      explanation: >-
        Episode-count association supports the recurrent erysipelas and
        lymphatic dysfunction amplification cycle.
  evidence:
  - reference: PMID:26734653
    reference_title: "Etiology of Cellulitis and Clinical Prediction of Streptococcal Disease: A Prospective Study."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Serology or blood or tissue culture confirmed beta-hemolytic
      streptococcal (BHS) etiology in 72% (146 of 203) of cases.
    explanation: >-
      Confirms beta-hemolytic streptococcal etiology for most clinically
      diagnosed cellulitis cases, the diagnostic neighborhood that includes
      erysipelas.
- name: Acute Dermal Inflammatory Response
  description: >-
    The acute host response to streptococcal growth in the superficial dermis
    produces bright, well-demarcated erythema and early systemic symptoms such
    as fever and chills.
  locations:
  - preferred_term: dermis
    term:
      id: UBERON:0002067
      label: dermis
  cell_types:
  - preferred_term: neutrophil
    term:
      id: CL:0000775
      label: neutrophil
  biological_processes:
  - preferred_term: inflammatory response
    term:
      id: GO:0006954
      label: inflammatory response
  downstream:
  - target: Erythema
    description: >-
      Upper-dermal inflammation produces the bright red, shiny erythema used to
      diagnose erysipelas clinically.
    evidence:
    - reference: PMID:41562377
      reference_title: Constitutional symptoms and response to Penicillin G in erysipelas and cellulitis - a monocentric, retrospective, explorative study.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        erysipelas presents clinically as acute, warm, more or less painful,
        bright red erythema with a shiny surface, relatively well-defined
        borders
      explanation: >-
        The retrospective comparison describes the visible erythematous lesion
        that follows acute dermal infection.
  - target: Fever
    description: >-
      Systemic inflammatory signaling during acute erysipelas commonly
      manifests with fever among the early constitutional symptoms.
    evidence:
    - reference: PMID:41562377
      reference_title: Constitutional symptoms and response to Penicillin G in erysipelas and cellulitis - a monocentric, retrospective, explorative study.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Of the patients with erysipelas, 92.1% (70 of 76) reported that they
        had experienced constitutional symptoms in the form of fever, chills,
        shivers, and feeling fatigued or ill at or before detection of the
        erythema
      explanation: >-
        The study documents fever within the early constitutional symptom
        complex that accompanies erysipelas onset.
  - target: Chills
    description: >-
      The same early constitutional inflammatory response can present with
      chills or shivers around erythema onset.
    evidence:
    - reference: PMID:41562377
      reference_title: Constitutional symptoms and response to Penicillin G in erysipelas and cellulitis - a monocentric, retrospective, explorative study.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Of the patients with erysipelas, 92.1% (70 of 76) reported that they
        had experienced constitutional symptoms in the form of fever, chills,
        shivers, and feeling fatigued or ill at or before detection of the
        erythema
      explanation: >-
        Chills were one component of the constitutional syndrome present at or
        before the skin lesion in nearly all erysipelas cases in this cohort.
  - target: Pain
    description: >-
      Local dermal inflammation can make the erythematous lesion painful or
      tender in acute erysipelas.
    evidence:
    - reference: PMID:41562377
      reference_title: Constitutional symptoms and response to Penicillin G in erysipelas and cellulitis - a monocentric, retrospective, explorative study.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Pain was reported in 47 patients with erysipelas (59.5%), the other 34
        patients (43%) had denied having pain.
      explanation: >-
        The cohort documents pain in the infected erythematous site of more than
        half of the erysipelas cases.
- name: Post-Erysipelas Lymphatic Damage
  description: >-
    Erysipelas episodes can leave or amplify chronic lymphatic impairment,
    predisposing to recurrent infections and chronic swelling.
  locations:
  - preferred_term: lymphatic vessel
    term:
      id: UBERON:0001473
      label: lymphatic vessel
  downstream:
  - target: Predisposing Lymphatic Impairment
    description: >-
      Repeated erysipelas episodes increase the prevalence of subclinical
      lymphedema, feeding the lymphatic susceptibility that permits subsequent
      episodes.
    evidence:
    - reference: PMID:40542699
      reference_title: Prevalence of Pre-Existing Subclinical Leg Lymphedema in Patients with Erysipelas.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Moreover, the prevalence of subclinical lymphedema increased
        proportionally with the number of erysipelas episodes: among those with
        a single episode, 74% exhibited subclinical lymphedema, whereas among
        those with 3 or more episodes, the prevalence was 100%.
      explanation: >-
        Episode-count association supports cumulative lymphatic impairment as a
        link from one erysipelas episode to greater susceptibility to the next.
  - target: Lymphedema
    description: >-
      Erysipelas-associated lymphatic damage can persist as chronic lymphedema
      and, in severe cases, elephantiasis.
    evidence:
    - reference: PMID:18069381
      reference_title: "[Erysipelas--course of disease, recurrence, complications; a 10 years retrospective study]."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Complications, such as abscess formation, lymphangitis, venous
        insufficiency, osteitis, arthritis, septic tendonitis and elephantiasis
        were found in 25%.
      explanation: >-
        The 10-year erysipelas cohort lists elephantiasis among complications,
        supporting severe chronic lymphedema as a downstream manifestation.
  - target: Lymphangitis
    description: >-
      Erysipelas involving superficial dermal lymphatics can be complicated by
      clinically recognized lymphangitis.
    evidence:
    - reference: PMID:18069381
      reference_title: "[Erysipelas--course of disease, recurrence, complications; a 10 years retrospective study]."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Complications, such as abscess formation, lymphangitis, venous
        insufficiency, osteitis, arthritis, septic tendonitis and elephantiasis
        were found in 25%.
      explanation: >-
        The 10-year erysipelas cohort lists lymphangitis among complications of
        erysipelas.
  evidence:
  - reference: PMID:18069381
    reference_title: "[Erysipelas--course of disease, recurrence, complications; a 10 years retrospective study]."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Complications, such as abscess formation, lymphangitis, venous
      insufficiency, osteitis, arthritis, septic tendonitis and elephantiasis
      were found in 25%.
    explanation: >-
      Documents lymphatic and chronic swelling complications in a 10-year
      erysipelas cohort.
progression:
- phase: Recurrent erysipelas
  notes: >-
    Episodes often recur, especially in limbs with edema or lymphatic
    impairment, maintaining an edema-infection cycle.
  evidence:
  - reference: PMID:18069381
    reference_title: "[Erysipelas--course of disease, recurrence, complications; a 10 years retrospective study]."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The recurrent cases occurred in 67.3% cases with lower limb localisation
      in 69.44% cases.
    explanation: >-
      A 10-year retrospective erysipelas cohort documents frequent recurrent
      lower-limb disease.
phenotypes:
- name: Erythema
  category: Dermatologic
  description: >-
    Acute erysipelas causes a bright red, shiny, well-demarcated erythematous
    lesion over infected superficial dermis.
  phenotype_term:
    preferred_term: Erythema
    term:
      id: HP:0010783
      label: Erythema
  diagnostic: true
  evidence:
  - reference: PMID:41562377
    reference_title: Constitutional symptoms and response to Penicillin G in erysipelas and cellulitis - a monocentric, retrospective, explorative study.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      erysipelas presents clinically as acute, warm, more or less painful,
      bright red erythema with a shiny surface, relatively well-defined borders
    explanation: >-
      The erythematous plaque morphology is a clinical discriminator of
      erysipelas.
- name: Fever
  category: Constitutional
  description: >-
    Fever can accompany erysipelas at or before erythema onset as part of its
    early constitutional symptom complex.
  phenotype_term:
    preferred_term: Fever
    term:
      id: HP:0001945
      label: Fever
  evidence:
  - reference: PMID:41562377
    reference_title: Constitutional symptoms and response to Penicillin G in erysipelas and cellulitis - a monocentric, retrospective, explorative study.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Of the patients with erysipelas, 92.1% (70 of 76) reported that they had
      experienced constitutional symptoms in the form of fever, chills, shivers,
      and feeling fatigued or ill at or before detection of the erythema
    explanation: >-
      Fever is one of the early constitutional symptoms reported by the
      erysipelas cohort.
- name: Chills
  category: Constitutional
  description: >-
    Chills or shivers can occur early in acute erysipelas before or alongside
    the visible erythematous lesion.
  phenotype_term:
    preferred_term: Chills
    term:
      id: HP:0025143
      label: Chills
  evidence:
  - reference: PMID:41562377
    reference_title: Constitutional symptoms and response to Penicillin G in erysipelas and cellulitis - a monocentric, retrospective, explorative study.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Of the patients with erysipelas, 92.1% (70 of 76) reported that they had
      experienced constitutional symptoms in the form of fever, chills, shivers,
      and feeling fatigued or ill at or before detection of the erythema
    explanation: >-
      Chills are one of the early constitutional symptoms reported by the
      erysipelas cohort.
- name: Pain
  category: Constitutional
  description: >-
    Many patients report pain at the acutely inflamed erysipelas lesion.
  phenotype_term:
    preferred_term: Pain
    term:
      id: HP:0012531
      label: Pain
  evidence:
  - reference: PMID:41562377
    reference_title: Constitutional symptoms and response to Penicillin G in erysipelas and cellulitis - a monocentric, retrospective, explorative study.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Pain was reported in 47 patients with erysipelas (59.5%), the other 34
      patients (43%) had denied having pain.
    explanation: >-
      Pain was captured as a local symptom in the erysipelas cohort.
- name: Lymphedema
  category: Lymphatic
  description: >-
    Subclinical or overt lymphedema is common in erysipelas and becomes nearly
    universal in the imaged cohort after three or more erysipelas episodes.
  phenotype_term:
    preferred_term: Lymphedema
    term:
      id: HP:0001004
      label: Lymphedema
  evidence:
  - reference: PMID:40542699
    reference_title: Prevalence of Pre-Existing Subclinical Leg Lymphedema in Patients with Erysipelas.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Subclinical lymphedema on the unaffected leg was found in 82% of patients,
      with a similar prevalence in all genders and age groups, and in patients
      with or without erysipelas risk factors.
    explanation: >-
      Lymphoscintigraphy showed a high burden of otherwise subclinical leg
      lymphedema in people with erysipelas.
  - reference: PMID:40542699
    reference_title: Prevalence of Pre-Existing Subclinical Leg Lymphedema in Patients with Erysipelas.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Moreover, the prevalence of subclinical lymphedema increased
      proportionally with the number of erysipelas episodes: among those with a
      single episode, 74% exhibited subclinical lymphedema, whereas among those
      with 3 or more episodes, the prevalence was 100%.
    explanation: >-
      Episode-count association connects recurrent erysipelas to a greater
      prevalence of leg lymphedema.
- name: Lymphangitis
  category: Lymphatic
  description: >-
    Lymphangitis is a reported complication of erysipelas in long-term hospital
    cohorts.
  phenotype_term:
    preferred_term: Lymphangitis
    coarse_binding_basis: NO_HPO_TERM
    term_gap: >-
      `uv run runoak -i ols:hp search lymphangitis` on 2026-09-27 returned
      lymphangioma and lymphangiectasis terms, but no lymphatic-vessel
      inflammation term. No term request has been filed yet.
  evidence:
  - reference: PMID:18069381
    reference_title: "[Erysipelas--course of disease, recurrence, complications; a 10 years retrospective study]."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Complications, such as abscess formation, lymphangitis, venous
      insufficiency, osteitis, arthritis, septic tendonitis and elephantiasis
      were found in 25%.
    explanation: >-
      Lymphangitis was one of the complications observed in a 10-year erysipelas
      cohort.
environmental:
- name: Skin barrier disruption
  presence: PRESENT
  description: >-
    Wounds, toe-web intertrigo, excoriated dermatoses, and plantar scaling
    lesions predispose to leg erysipelas by opening portals of entry in skin.
  influences_mechanisms:
  - target: Cutaneous Barrier Portal of Entry
    environmental_effect: PREDISPOSES
    description: >-
      Mechanical or inflammatory barrier defects increase susceptibility to
      streptococcal dermal entry.
  evidence:
  - reference: PMID:16484815
    reference_title: "Risk factors for erysipelas of the leg in Tunisia: a multicenter case-control study."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      disruption of the cutaneous barrier (i.e. traumatic wound, toe-web
      intertrigo, excoriated leg dermatosis or plantar squamous lesions) and
      leg edema were independently associated with erysipelas of the leg, with
      respective odds ratios of 13.6 (95% confidence interval: 6.0-31) and 7.0
      (1.3-38).
    explanation: >-
      Quantifies skin barrier disruption as an upstream erysipelas risk factor.
- name: Toe-web intertrigo and tinea pedis
  presence: PRESENT
  description: >-
    Toe-web intertrigo and tinea pedis disrupt the foot skin barrier and supply
    portals of entry for streptococci that cause lower-limb erysipelas.
  influences_mechanisms:
  - target: Cutaneous Barrier Portal of Entry
    environmental_effect: PREDISPOSES
    description: >-
      Interdigital fungal disease and maceration open cutaneous entry sites for
      beta-hemolytic streptococci.
  evidence:
  - reference: PMID:16484815
    reference_title: "Risk factors for erysipelas of the leg in Tunisia: a multicenter case-control study."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      disruption of the cutaneous barrier (i.e. traumatic wound, toe-web
      intertrigo, excoriated leg dermatosis or plantar squamous lesions) and
      leg edema were independently associated with erysipelas of the leg, with
      respective odds ratios of 13.6 (95% confidence interval: 6.0-31) and 7.0
      (1.3-38).
    explanation: >-
      Toe-web intertrigo is part of the independently associated skin-barrier
      disruption risk factor in this leg erysipelas case-control study.
  - reference: PMID:29427797
    reference_title: "Severe lower limb cellulitis: defining the epidemiology and risk factors for primary episodes in a population-based case-control study."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      tinea pedis (AOR 3.05, 95% CI 1.45-6.42, p 0.003)
    explanation: >-
      Population-based case-control data identify tinea pedis as an independent
      risk factor for severe lower-limb cellulitis.
- name: Leg edema and lymphatic impairment
  presence: PRESENT
  description: >-
    Leg edema and lymphedema increase susceptibility to leg erysipelas.
  influences_mechanisms:
  - target: Predisposing Lymphatic Impairment
    environmental_effect: PREDISPOSES
    description: >-
      Edematous and lymphatically impaired tissue has diminished local fluid
      clearance and is prone to recurrent streptococcal infection.
  evidence:
  - reference: PMID:16484815
    reference_title: "Risk factors for erysipelas of the leg in Tunisia: a multicenter case-control study."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      disruption of the cutaneous barrier (i.e. traumatic wound, toe-web
      intertrigo, excoriated leg dermatosis or plantar squamous lesions) and
      leg edema were independently associated with erysipelas of the leg, with
      respective odds ratios of 13.6 (95% confidence interval: 6.0-31) and 7.0
      (1.3-38).
    explanation: >-
      Case-control data identify leg edema as an independent local risk factor
      for leg erysipelas.
diagnosis:
- name: Clinical erysipelas recognition
  description: >-
    Erysipelas is recognized clinically by its acute warm, painful, bright-red
    erythematous plaque with a shiny surface, relatively well-defined borders,
    and early fever or chills that help distinguish it from cellulitis.
  diagnosis_term:
    preferred_term: clinical diagnosis
    term:
      id: NCIT:C18020
      label: Diagnostic Procedure
  results: >-
    Characteristic sharply demarcated erythema with constitutional symptoms
    supports erysipelas rather than uncomplicated cellulitis.
  evidence:
  - reference: PMID:41562377
    reference_title: Constitutional symptoms and response to Penicillin G in erysipelas and cellulitis - a monocentric, retrospective, explorative study.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Constitutional symptoms like chills and fever may help in diagnosis.
    explanation: >-
      The retrospective comparison tested fever and chills as clinical cues that
      help differentiate erysipelas from uncomplicated cellulitis.
  - reference: PMID:41562377
    reference_title: Constitutional symptoms and response to Penicillin G in erysipelas and cellulitis - a monocentric, retrospective, explorative study.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      erysipelas presents clinically as acute, warm, more or less painful,
      bright red erythema with a shiny surface, relatively well-defined borders
    explanation: >-
      The quoted morphology describes the core clinical lesion used to recognize
      erysipelas.
- name: Streptococcal serology
  description: >-
    Paired acute and convalescent antistreptolysin O and anti-DNase B titers can
    support beta-hemolytic streptococcal etiology when cultures are negative.
  diagnosis_term:
    preferred_term: Diagnostic Serology Testing
    term:
      id: NCIT:C217458
      label: Diagnostic Serology Testing
  results: >-
    Rising or persistently elevated ASO or anti-DNase B titers provide evidence
    of beta-hemolytic streptococcal skin infection.
  evidence:
  - reference: PMID:26734653
    reference_title: "Etiology of Cellulitis and Clinical Prediction of Streptococcal Disease: A Prospective Study."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Acute and convalescent sera were available in 200 cases. Positive BHS
      serology was found in 71% of cases; 60% of cases were positive for ASO,
      and 30% of cases were positive for ADB (Figure 2B).
    explanation: >-
      Prospective cellulitis and erysipelas-adjacent data show that paired
      streptococcal serology often identifies beta-hemolytic streptococcal
      etiology.
treatments:
- name: Penicillin G therapy
  description: >-
    Benzylpenicillin is a narrow-spectrum beta-lactam used for acute
    streptococcal erysipelas.
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: benzylpenicillin
      term:
        id: CHEBI:18208
        label: benzylpenicillin
  therapeutic_modality: SMALL_MOLECULE
  target_mechanisms:
  - target: Streptococcal Dermal Infection
    treatment_effect: INHIBITS
    description: >-
      Penicillin G inhibits the beta-hemolytic streptococci driving the acute
      dermal infection.
  evidence:
  - reference: PMID:15822466
    reference_title: "[Erysipelas. Retrospective study of 647 patients]."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Erysipelas can be controlled with antibiotics; treatment is essentially
      based on penicillin G 4 mega units intramuscularly every day (60.58%) for
      mean duration of 10.13 days.
    explanation: >-
      Large erysipelas series supporting intramuscular penicillin G as a common
      erysipelas antibiotic regimen in that cohort.
  - reference: PMID:41562377
    reference_title: Constitutional symptoms and response to Penicillin G in erysipelas and cellulitis - a monocentric, retrospective, explorative study.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Of the 60 patients treated with penicillin, 59 patients (98.3%) responded
      within 2 days, revealing fine wrinkling of the skin, followed by fading of
      redness and then reduction of the erythematous area accompanied by an
      improvement of still existing constitutional symptoms.
    explanation: >-
      A retrospective erysipelas cohort documents rapid clinical response in
      nearly all patients treated with penicillin.
- name: Penicillin V recurrence prophylaxis
  description: >-
    Oral phenoxymethylpenicillin can be used as low-dose prophylaxis to reduce
    recurrent leg cellulitis/erysipelas episodes while prophylaxis continues.
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: phenoxymethylpenicillin
      term:
        id: CHEBI:27446
        label: phenoxymethylpenicillin
  therapeutic_modality: SMALL_MOLECULE
  target_mechanisms:
  - target: Streptococcal Dermal Infection
    treatment_effect: INHIBITS
    description: >-
      Suppressive oral penicillin reduces recurrence of streptococcal lower-limb
      cellulitis/erysipelas during prophylaxis.
  evidence:
  - reference: PMID:23635049
    reference_title: Penicillin to prevent recurrent leg cellulitis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      During the prophylaxis phase, 30 of 136 participants in the penicillin
      group (22%) had a recurrence, as compared with 51 of 138 participants in
      the placebo group (37%) (hazard ratio, 0.55; 95% confidence interval
      [CI], 0.35 to 0.86; P=0.01), yielding a number needed to treat to prevent
      one recurrent cellulitis episode of 5 (95% CI, 4 to 9).
    explanation: >-
      Randomized trial evidence that penicillin V prophylaxis reduces
      recurrence in the overlapping recurrent leg cellulitis/erysipelas
      syndrome.
  - reference: PMID:28631307
    reference_title: Interventions for the prevention of recurrent erysipelas and cellulitis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      In terms of recurrence, incidence, and time to next episode, antibiotic is
      probably an effective preventive treatment for recurrent cellulitis of the
      lower limbs in those under prophylactic treatment, compared with placebo
      or no treatment (moderate-certainty evidence).
    explanation: >-
      Cochrane review evidence supports antibiotic prophylaxis for recurrent
      lower-limb cellulitis/erysipelas while treatment continues.
- name: Toe-web intertrigo and wound care
  description: >-
    Detecting and treating toe-web intertrigo, fungal foot disease, and
    traumatic wounds reduces the portal-of-entry substrate for leg erysipelas.
  treatment_term:
    preferred_term: Supportive Care
    term:
      id: NCIT:C15747
      label: Supportive Care
  therapeutic_modality: OTHER
  target_mechanisms:
  - target: Cutaneous Barrier Portal of Entry
    treatment_effect: INHIBITS
    description: >-
      Treating interdigital and traumatic skin lesions closes portals through
      which streptococci enter the dermis.
  evidence:
  - reference: PMID:16484815
    reference_title: "Risk factors for erysipelas of the leg in Tunisia: a multicenter case-control study."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Detecting and treating toe-web intertrigo and traumatic wounds should be
      considered in the prevention of erysipelas of the leg.
    explanation: >-
      The case-control study conclusion directly supports portal-of-entry
      management to prevent leg erysipelas.
- name: Compression therapy for lymphedema prevention
  description: >-
    Bilateral leg compression can be used after erysipelas to counter
    lymphedema and reduce the lymphatic susceptibility to recurrence.
  treatment_term:
    preferred_term: Compression Therapy
    term:
      id: NCIT:C157735
      label: Compression Therapy
  therapeutic_modality: BEHAVIORAL
  target_mechanisms:
  - target: Predisposing Lymphatic Impairment
    treatment_effect: INHIBITS
    description: >-
      Compression therapy reduces leg lymphedema, limiting the lymphatic
      drainage impairment that predisposes to recurrent erysipelas.
  evidence:
  - reference: PMID:40542699
    reference_title: Prevalence of Pre-Existing Subclinical Leg Lymphedema in Patients with Erysipelas.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Thus, our clinical recommendation suggests bilateral leg compression
      therapy in erysipelas patients to prevent recurrence and lymphedema
      exacerbation.
    explanation: >-
      Lymphoscintigraphy findings led the investigators to recommend bilateral
      leg compression for recurrence prevention and lymphedema control.
notes: >-
  MONDO:0001266 refers to streptococcal erysipelas, not erysipeloid or swine
  erysipelas caused by Erysipelothrix rhusiopathiae. The OpenScientist report
  surfaced several Erysipelothrix papers, but those were deliberately excluded
  from this human streptococcal skin-infection entry.

📚

References & Deep Research

Deep Research

1

Deep research results are used as seeds for research; they do not undergo the same validation as the main records and may contain errors. How we use deep research.

Evaluations and curation notes (1)

Create: Erysipelas · 2026-09-26T07:27:10Z · View source

Created a new MONDO:0001266 Erysipelas entry from an OpenScientist deep-research report, after manual MONDO identity preflight confirmed the report targeted streptococcal erysipelas rather than Erysipelothrix erysipeloid or swine erysipelas. Curated beta-hemolytic streptococcal agents, skin-barrier and lymphatic susceptibility mechanisms, fever/chills phenotypes, penicillin G/V treatment records, and cache-verified PMID evidence.

OpenScientist ▸

Key Findings

openscientist-autonomous 38 citations 2026-09-26T00:12:16.505244

Key Findings

Finding 1 — β-hemolytic streptococci are the predominant cause

Erysipelas is overwhelmingly a streptococcal infection. In a large retrospective cohort of 1,142 erysipelas episodes (981 patients), wound cultures grew group A streptococci (GAS, n=56), group G streptococci (GGS, n=53), group C streptococci (GCS, n=11), and Staphylococcus aureus (n=153); blood cultures (obtained in 49% of episodes) were positive in 50, most commonly GGS (n=21) followed by GAS (n=13) (PMID: 26424182). Because superficial cultures frequently recover skin-colonizing S. aureus that is not the true pathogen, serologic and prospective data are decisive. In a prospective cellulitis study (n=216), β-hemolytic streptococcal etiology was confirmed serologically or by culture in 72% (146/203) of cases, rising to 85% when probable cases were included; in lower-extremity infection, GCS/GGS were actually more common than GAS (36 vs 22) (PMID: 26734653).

"Wound cultures were taken in 343 episodes and 56 grew group A streptococci (GAS), 53 grew group G streptococci (GGS), 11 grew group C streptococci (GCS), and 153 grew Staphylococcus aureus." (PMID: 26424182)

"Serology or blood or tissue culture confirmed β-hemolytic streptococcal (BHS) etiology in 72% (146 of 203) of cases." (PMID: 26734653)

The relevant pathogens (NCBITaxon suggestions): Streptococcus pyogenes (NCBITaxon:1314), Streptococcus dysgalactiae subsp. equisimilis (NCBITaxon:119602). Group C/G streptococci carry virulence factors closely paralleling GAS — M protein, streptolysin O, streptolysin S, streptokinase, hyaluronidase, and C5a peptidase (PMID: 20607346).

Finding 2 — Skin barrier disruption and leg edema/lymphedema are the dominant risk factors

The two strongest, most reproducible risk factors are a breach in the skin barrier and leg edema. In a Tunisian multicenter case-control study (114 cases, 208 matched controls), multivariate analysis showed that disruption of the cutaneous barrier (traumatic wound, toe-web intertrigo, excoriated dermatosis, plantar squamous lesions) carried an odds ratio of 13.6 (95% CI 6.0–31) and leg edema an OR of 7.0 (95% CI 1.3–38); notably there was no association with diabetes, alcoholism, or smoking (PMID: 16484815). A large population-based case-control study of severe lower-leg cellulitis (29,062 case-control pairs) independently confirmed tinea pedis (AOR 3.05, 95% CI 1.45–6.42), varicose veins (AOR 2.95), lymphoedema (AOR 2.65), and obesity (AOR 2.05); incidence reached 204.8/100,000 by 2013, rising 4.7%/year (PMID: 29427797).

"disruption of the cutaneous barrier ... and leg edema were independently associated with erysipelas of the leg, with respective odds ratios of 13.6 (95% confidence interval: 6.0-31) and 7.0 (1.3-38)" (PMID: 16484815)

"varicose veins (AOR 2.95, 95% CI 2.50-3.48, p < 0.001), lymphoedema (AOR 2.65, 95% CI 1.71-4.10, p < 0.001), tinea pedis (AOR 3.05, 95% CI 1.45-6.42, p 0.003)" (PMID: 29427797)

The clinical corollary is that toe-web intertrigo is a high-attributable-risk, modifiable portal of entry, and secondary prevention targeting it has long been advocated (PMID: 11319357).

Finding 3 — Prophylactic low-dose penicillin V reduces recurrence

Recurrence prevention is evidence-based. In the PATCH I double-blind RCT (n=274, patients with ≥2 prior episodes), penicillin V 250 mg twice daily for 12 months reduced recurrence during prophylaxis to 22% (30/136) vs 37% (51/138) on placebo — HR 0.55 (95% CI 0.35–0.86, P=0.01), number-needed-to-treat ≈5 (PMID: 23635049). The protective effect waned after stopping the drug. PATCH II (n=123, mostly patients with a single prior episode) showed a concordant but non-significant 47% risk reduction (HR 0.53, 95% CI 0.26–1.07, P=0.08) (PMID: 21910701). A pooled economic analysis (n=397) found a 29% reduction in recurrences (IRR 0.71, 95% CI 0.53–0.90, P=0.02) and cost-effectiveness (PMID: 24551029).

"30 of 136 participants in the penicillin group (22%) had a recurrence, as compared with 51 of 138 participants in the placebo group (37%) (hazard ratio, 0.55; ... P=0.01)" (PMID: 23635049)

Finding 4 — Rapid penicillin response; narrow-spectrum guideline adherence improves outcomes

Erysipelas responds rapidly to penicillin: in a retrospective study, 98.3% of erysipelas patients responded within 2 days to Penicillin G, and constitutional symptoms (chills/fever) preceded or coincided with erythema in 91.4% of erysipelas vs only 36.2% of cellulitis patients — supporting clinical differentiation (PMID: 41562377). In prospective facial cellulitis (n=65), β-hemolytic streptococcal etiology was probable/confirmed in 75% and penicillin(-class) monotherapy cured 68% (PMID: 28768452). In a cohort of 630 erysipelas/cellulitis cases, adherence to narrow-spectrum guidelines was associated with fewer poor outcomes (6.3% vs 12.7%, p=0.007); bacteremia (AOR 5.21) and peripheral arterial disease (AOR 4.80) predicted poor outcome (PMID: 30685804).

"Of patients with erysipelas, 98.3% responded within 2 days to penicillin" (PMID: 41562377)

"A poor outcome was recorded in 54 (8.5%) patients, less frequently in case of adherence to guidelines: 26/410 (6.3%) vs 28/220 (12.7%), p = 0.007" (PMID: 30685804)

Finding 5 — Erysipelas and lymphedema form a self-reinforcing vicious cycle

Lymphatic dysfunction is both cause and consequence. Lymphoscintigraphy of 106 post-erysipelas patients found subclinical lymphedema in the clinically unaffected leg in 82%, rising from 74% after a single episode to 100% after ≥3 episodes — implicating pre-existing lymphatic impairment as a primary trigger and demonstrating cumulative damage (PMID: 40542699). A prospective cohort of 428 patients identified obesity, diabetes mellitus, venous insufficiency, lymphedema, and prior surgery as independent risk factors for recurrence (Cox model, all p<0.05) (PMID: 33413190). A retrospective-prospective cohort (n=313) found recurrent erysipelas significantly associated with obesity (p<0.0001), chronic edema/lymphedema, peripheral arterial disease, fungal foot infection, and tonsillectomy (p=0.000001) (PMID: 30976336).

"Subclinical lymphedema on the unaffected leg was found in 82% of patients" (PMID: 40542699)

Finding 6 — Epidemiology: adult/elderly, female-predominant, leg-predominant, seasonal

Hospital cohorts converge: 428 patients (mean age 58.6 y, 51% women; hypertension 51.6%, diabetes 41.6%, venous insufficiency 36.2%, obesity 12.1%, lymphedema 4.2%; seasonal) (PMID: 20147345); a Tunisian series of 647 patients (mean age 44.7 y, M:F ≈1.55, lower limbs 91.2%, portal of entry 76.7% mainly toe-web intertrigo, prior erysipelas 26.1%, good outcome 87.8% on IM penicillin G ×10 days) (PMID: 15822466); and a 10-year study (n=319, median age 63 y, 65% female, summer-predominant, lower limb 59.2%, recurrence 67.3%, complications 25% including abscess, lymphangitis, and elephantiasis) (PMID: 18069381).

"Erysipelas predominately involved in the lower limbs (91.2%). Antecedents of erysipelas were found in 26.12 %. Portal of entry was found in 76.66% represented essentially by toe-web intertrigo." (PMID: 15822466)

"Complications, such as abscess formation, lymphangitis, venous insufficiency, osteitis, arthritis, septic tendonitis and elephantiasis were found in 25%." (PMID: 18069381)

Finding 7 — Streptococcal erysipelas is distinct from Erysipelothrix disease

Erysipeloid (Baker-Rosenbach disease) is an occupational human skin infection caused by traumatic penetration of Erysipelothrix rhusiopathiae, presenting as a violaceous, well-demarcated erythematous edema usually on the hand/fingers, often self-limited and penicillin-responsive; it can rarely cause endocarditis (aortic valve predilection) (PMID: 19663854). In animals, E. rhusiopathiae causes swine erysipelas, with domestic pigs the principal host; 30–50% of healthy/convalescent pigs carry the organism in tonsils/lymphoid tissue, and wild boar are a potential reservoir (PMID: 42687202). It is a zoonosis affecting farmers, butchers, fishers, and veterinarians (PMID: 20171435).

"Erysipeloid is an occupational infection of the skin caused by traumatic penetration of Erysipelothrix rhusiopathiae. The disease is characterized clinically by an erythematous oedema, with well-defined and raised borders, usually localized to the back of one hand and/or fingers." (PMID: 19663854)

Finding 8 — Cochrane meta-analysis supports antibiotic prophylaxis

A 2017 Cochrane systematic review (6 RCTs, 573 evaluable participants, mean age 50–70) concluded that antibiotic prophylaxis (mainly penicillin/erythromycin) reduces recurrence risk while on treatment, with the protective effect diminishing after prophylaxis is stopped — consistent with PATCH I/II (PMID: 28631307).

"We included six trials, with a total of 573 evaluable participants, who were aged on average between 50 and 70." (PMID: 28631307)

Section-by-Section Report

1. Disease Information

Overview. Erysipelas is an acute, non-necrotizing bacterial infection of the upper dermis and superficial dermal lymphatics, classically presenting as a fiery-red, raised, well-demarcated, indurated plaque with an advancing border, warmth, tenderness, and abrupt systemic symptoms (high fever, chills). The sharp elevation and clear demarcation distinguish it from cellulitis, which involves deeper dermis and subcutaneous fat with less distinct borders. It is a clinical diagnosis made at the disease level (case series, cohorts), not from molecular/EHR variant data.

Key identifiers: - MONDO: MONDO:0001266 - ICD-10: A46 (Erysipelas); ICD-11: 1B70.0 - MeSH: Erysipelas (D004886) - SNOMED CT: 33438006 (Erysipelas) - OMIM / Orphanet: Not applicable — erysipelas is an acquired infectious disease with no Mendelian OMIM entry and is not a rare disease with an Orphanet number.

Synonyms / alternative names: St. Anthony's fire (historical), "ignis sacer," "the rose" (regional). Note that "erysipelas" in a veterinary/occupational context refers to Erysipelothrix disease (see Section 14), which must not be conflated with this streptococcal entity.

Source type: Aggregated disease-level evidence (cohorts, case-control studies, RCTs, systematic reviews); no patient-level EHR dataset was supplied for this investigation.

2. Etiology

Causal factors. Erysipelas is an infectious disease caused predominantly by β-hemolytic streptococci — S. pyogenes (GAS) and groups C/G (S. dysgalactiae); S. aureus is a less common contributor and often a colonizer (Finding 1). There is no genetic causal factor and no Mendelian inheritance.

Risk factors (environmental / host):

Risk factor	Effect size	Source
Cutaneous barrier disruption (wound, toe-web intertrigo, dermatosis)	OR 13.6 (6.0–31)	PMID: 16484815
Leg edema	OR 7.0 (1.3–38)	PMID: 16484815
Tinea pedis	AOR 3.05 (1.45–6.42)	PMID: 29427797
Varicose veins	AOR 2.95 (2.50–3.48)	PMID: 29427797
Lymphoedema	AOR 2.65 (1.71–4.10)	PMID: 29427797
Obesity	AOR 2.05	PMID: 29427797
Diabetes, venous insufficiency, prior surgery	Recurrence RFs (p<0.05)	PMID: 33413190

Genetic risk factors: None established. The Tunisian case-control study found no association with diabetes, alcoholism, or smoking after multivariate adjustment (PMID: 16484815), underlining the environmental/host-mechanical rather than genetic basis.

Protective factors: Treatment of the portal of entry (antifungal therapy for tinea pedis), edema/lymphedema control (compression, elevation), weight reduction, and — for recurrence — antibiotic prophylaxis (Findings 3, 8). No genetic protective alleles are described.

Gene–environment interactions: Not applicable in the classical sense; the disease is driven by pathogen–host barrier–lymphatic interactions rather than genotype-by-environment effects.

3. Phenotypes

Phenotype	Type	HPO suggestion	Frequency / notes
Sharply demarcated erythematous plaque	Clinical sign	HP:0000988 (Skin rash) / HP:0011121 (Abnormal skin morphology)	Defining feature
Fever	Symptom	HP:0001945 (Fever)	~91% report chills/fever at/before onset (PMID: 41562377)
Chills	Symptom	HP:0025143 (Chills)	Common, precedes rash
Local warmth / edema	Clinical sign	HP:0000969 (Edema)	Common
Regional lymphangitis / lymphadenopathy	Clinical sign	HP:0002716 (Lymphadenopathy)	Component of complications (PMID: 18069381)
Leukocytosis / elevated CRP	Lab abnormality	HP:0001974 (Leukocytosis)	Inflammatory response, higher in recurrent cases (PMID: 19694769)
"Milian's ear sign" (auricle involvement in facial erysipelas)	Clinical sign	—	Localizing sign (PMID: 32241881)

Characteristics: Adult/elderly onset; acute onset (hours to 1–2 days); severity mild-to-severe (bullous, hemorrhagic, or abscess-forming variants); course episodic/recurrent. Quality-of-life impact: recurrent episodes and resulting chronic lymphedema/elephantiasis impose substantial disability, repeated hospitalization, and reduced mobility. Disease-specific QoL instruments were not identified in the reviewed literature.

4. Genetic / Molecular Information

Not applicable. Erysipelas has no causal genes, no pathogenic germline/somatic variants, no modifier genes, no disease-associated epigenetic signature, and no chromosomal abnormalities. It is an acquired infectious disease. (The molecular determinants of virulence reside in the bacterial genome — e.g., streptolysin O/S, M protein, streptokinase, hyaluronidase, C5a peptidase — PMID: 20607346; PMID: 20385762 — not the human host.)

5. Environmental Information

Environmental / occupational: breaks in skin from trauma, animal bites/stings (insect bites are a recognized portal → erysipelas PMID: 16679881), and use of depigmenting agents (in some populations PMID: 21695874).
Lifestyle: obesity is a strong, reproducible factor (Findings 2, 5). Smoking/alcohol were not independently associated (PMID: 16484815).
Infectious agents (NCBITaxon): Streptococcus pyogenes (NCBITaxon:1314); S. dysgalactiae subsp. equisimilis (groups C/G, NCBITaxon:119602); occasionally Staphylococcus aureus (NCBITaxon:1280). Interdigital dermatophytes (Trichophyton spp.) act as facilitators by breaching the barrier.

6. Mechanism / Pathophysiology

Ordered causal chain:

Predisposing lymphatic impairment (pre-existing subclinical lymphedema, venous insufficiency, obesity) reduces local immune clearance in the dermis — demonstrated by 82% subclinical lymphedema in the unaffected leg (PMID: 40542699).
A breach in the cutaneous barrier (toe-web tinea, wound, dermatosis) provides a portal of entry → leads to streptococcal inoculation of the dermis (PMID: 16484815; PMID: 15822466).
β-hemolytic streptococci proliferate in the superficial dermis and spread along dermal lymphatics → results in the characteristic sharply demarcated, raised, advancing plaque (PMID: 26424182; PMID: 26734653).
Streptococcal virulence factors (streptolysin O/S, M protein, streptokinase, hyaluronidase, C5a peptidase) promote tissue spread and impair neutrophil recruitment → drives local injury and dissemination (inferred for human erysipelas from GAS biology and animal models: PMID: 20607346; PMID: 28947648; PMID: 11801184).
The innate immune / inflammatory response (neutrophil influx, cytokine release) produces erythema, warmth, edema, and systemic fever/chills and leukocytosis/↑CRP → causes the clinical syndrome (PMID: 41562377; PMID: 19694769).
Inflammatory injury to lymphatic vessels further impairs lymphatic drainage → worsens edema. [BRANCH → vicious cycle] This cumulative lymphatic damage increases susceptibility to the next episode, and repeated episodes drive chronic lymphedema → elephantiasis nostras verrucosa (subclinical lymphedema rises to 100% after ≥3 episodes: PMID: 40542699; complications incl. elephantiasis in 25%: PMID: 18069381).
[BRANCH → systemic] In a minority, bacteremia (blood cultures positive in ~6.9% overall) leads to invasive complications — abscess, necrotizing fasciitis, rarely myocarditis (PMID: 23498835) — associated with poor outcome (PMID: 30685804).

Lymphatic impairment ─┐
      ├─► Barrier breach ─► Strep dermal invasion ─► Lymphatic spread
Skin breach ──────────┘                                                    │
                                                           ▼
     ┌──────────────────  Inflammation (fever, chills, erythema)  ◄────────┤
     │                                                                     ▼
     │                                            Lymphatic vessel injury
     │                                                     │
     └──────────  VICIOUS CYCLE  ◄── worsening edema ◄─────┘
        │
        └─► chronic lymphedema ─► elephantiasis (~25%)

Molecular pathways / cellular processes: innate inflammatory signaling (NF-κB–driven cytokine production), neutrophil chemotaxis and phagocytosis. GO suggestions: GO:0006954 (inflammatory response), GO:0006935 (chemotaxis), GO:0050900 (leukocyte migration), GO:0001945 (lymph vessel development, relevant to damage/repair).
Immune involvement: acute innate response; no autoimmunity or immunodeficiency required, though HIV can predispose to severe disease/necrotizing fasciitis (PMID: 21695874).
Cell types (CL): neutrophil (CL:0000775), keratinocyte (CL:0000312), dermal lymphatic endothelial cell (CL:0002138), macrophage (CL:0000235).

7. Anatomical Structures Affected

Primary organ: skin (UBERON:0002097), specifically the superficial dermis (UBERON:0002067) and dermal lymphatic vessels (UBERON:0001473 lymphatic vessel).
Body systems: integumentary and lymphatic/lymphoid system (UBERON:0002465 lymphoid system).
Localization: lower limb / leg (UBERON:0000978 leg) in ~90% of cases (PMID: 15822466); face (UBERON:0000033 head) is the classic second site (Milian's ear sign, PMID: 32241881).
Lateralization: typically unilateral; bilateral leg erysipelas is rare and should prompt reconsideration of the diagnosis (pseudocellulitis/stasis dermatitis, PMID: 36800152).
Tissue/cell level: epithelial (epidermis/keratinocytes) and lymphatic endothelium; secondary organ involvement — abscess, osteitis, arthritis, septic tendonitis, rarely myocarditis (Finding 6; PMID: 23498835).

8. Temporal Development

Onset: adult/elderly predominance (mean age 44–63 y across series); acute onset over hours, often with prodromal chills/fever preceding the rash (PMID: 41562377).
Progression: rapid local spread over 1–3 days; self-limited with treatment (≈98% respond to penicillin within 2 days, PMID: 41562377), but strongly recurrent/episodic (recurrence 26–67% across cohorts; PMID: 15822466, PMID: 18069381).
Patterns: treatment-induced remission is the norm; the critical intervention window is early narrow-spectrum antibiotics plus portal-of-entry and edema management to interrupt the vicious cycle. Seasonal (summer) clustering is reported (PMID: 18069381; PMID: 20147345).

9. Inheritance and Population

Epidemiology: population-based incidence of severe lower-leg cellulitis reached 204.8/100,000 (2013), rising 4.7%/year (PMID: 29427797).
Inheritance: none — not a genetic disease (no AD/AR/X-linked/mitochondrial pattern; no penetrance/expressivity/anticipation/founder/consanguinity/carrier-frequency parameters apply).
Demographics: adult/elderly; female predominance in most hospital series (51–65% women); leg-predominant (~90%); comorbidities hypertension (~52%), diabetes (~42%), venous insufficiency (~36%), obesity (~12%), lymphedema (~4%) (PMID: 20147345; PMID: 15822466; PMID: 18069381).
Geographic: cosmopolitan; toe-web intertrigo as portal of entry is prominent in warm-climate series (Tunisia, Togo).

10. Diagnostics

Clinical diagnosis based on the characteristic sharply demarcated, raised, fiery-red plaque with acute fever/chills; constitutional symptoms preceding erythema favor erysipelas over cellulitis (PMID: 41562377).
Laboratory: leukocytosis, elevated CRP (LOINC 1988-5), often higher in recurrent cases (PMID: 19694769). Blood cultures positive in only ~6.9% and generally low-yield (PMID: 30685804); serology (anti-streptolysin O, anti-DNase B) increases etiologic confirmation (PMID: 26734653).
Imaging: ultrasound/MRI to exclude abscess or necrotizing fasciitis in atypical/severe presentations (PMID: 28865532).
Differential diagnosis (critical): stasis dermatitis and other "pseudocellulitis" are frequently misdiagnosed as cellulitis/erysipelas — bilateral presentation, chronicity, and lack of fever favor pseudocellulitis; misdiagnosis drives ~$195–515M/yr in avoidable US spending and unnecessary antibiotics (PMID: 27806170; PMID: 36800152). Also exclude DVT, contact dermatitis, and necrotizing fasciitis.
Genetic/omics testing: not applicable.

11. Outcome / Prognosis

Favorable with prompt therapy: good outcome in 87.8% (PMID: 15822466); poor outcome in ~8.5%, reduced by guideline adherence (PMID: 30685804).
Complications (~25%): abscess, lymphangitis, osteitis, arthritis, septic tendonitis, chronic venous insufficiency, and elephantiasis nostras verrucosa; rare systemic sequelae include myocarditis and necrotizing fasciitis (PMID: 18069381; PMID: 23498835; PMID: 21695874).
Prognostic factors for poor outcome: bacteremia (AOR 5.21), peripheral arterial disease (AOR 4.80) (PMID: 30685804); obesity, diabetes, lymphedema for recurrence (Finding 5).
Mortality is low for uncomplicated disease; deaths cluster in necrotizing fasciitis and immunocompromised patients (PMID: 21695874).

12. Treatment

First-line pharmacotherapy: penicillin (penicillin G IV/IM, or oral penicillin V / amoxicillin) — narrow-spectrum, rapidly effective (Finding 4). NCIT: C692 (Penicillin), C61785 (Penicillin V). Duration typically 10 days (PMID: 15822466).
Penicillin-allergic: macrolides (erythromycin/roxithromycin), clindamycin, or pristinamycin; a network meta-analysis found no significant cure-rate differences among first/second-line agents for cellulitis, with pristinamycin showing the highest cure rates for erysipelas (at some cost in rash) (PMID: 39240378).
Adjunctive/emerging: omadacycline and iclaprim have activity in skin/soft-tissue infection including erysipelas (90% clinical success at end of treatment for omadacycline) (PMID: 42413095; PMID: 35928265).
Supportive: limb elevation, edema/compression management, analgesia, and treatment of the portal of entry (topical antifungals for tinea pedis).
Recurrence prophylaxis: low-dose penicillin V 250 mg BID (Findings 3, 8). NCIT: C15329 (Antibiotic Therapy).
Pharmacogenomics: not applicable.

13. Prevention

Primary: foot hygiene, prompt treatment of tinea pedis and interdigital intertrigo, wound care, weight management, and edema/venous-insufficiency control (compression) — targeting the highest-attributable, modifiable risk factors (PMID: 11319357; PMID: 16484815; PMID: 29427797).
Secondary/tertiary: interrupting the erysipelas–lymphedema cycle through lymphedema therapy and, after ≥2 episodes, antibiotic prophylaxis with effect confirmed by RCTs and Cochrane review (Findings 3, 8). Protection wanes once prophylaxis stops, so long-term strategy must combine antibiotics with durable risk-factor modification.
Immunization: no licensed vaccine; GAS vaccine development is ongoing but not erysipelas-specific.

14. Other Species / Natural Disease

Important distinction (Finding 7): Streptococcal erysipelas (this entry) is a human disease. The name "erysipelas" is also applied to Erysipelothrix rhusiopathiae disease: - Swine erysipelas — a veterinary disease of domestic pigs (Sus scrofa domesticus, NCBITaxon:9825); 30–50% of healthy/convalescent pigs are tonsillar carriers; wild boar (Sus scrofa) are a reservoir (45.5% tonsil culture-positive) (PMID: 42687202). - Human erysipeloid (Baker-Rosenbach disease) — a zoonotic occupational skin infection of farmers, butchers, fishers, and veterinarians, with rare systemic forms (endocarditis with aortic-valve predilection; paravertebral abscess/spondylitis) (PMID: 19663854; PMID: 20171435; PMID: 30542523; PMID: 22526696).

For streptococcal erysipelas itself, there is no significant naturally occurring companion-animal counterpart; GAS/GCS/GGS are human-adapted (GCS/GGS also colonize animals, but streptococcal erysipelas as a clinical entity is essentially human).

15. Model Organisms

Human streptococcal erysipelas is not modeled as a discrete named disease, but murine skin-infection models of S. pyogenes recapitulate key mechanistic steps: dermonecrotic/subcutaneous mouse models demonstrate the roles of streptolysin S and platelet-activating-factor acetylhydrolase Sse in inhibiting neutrophil recruitment and enabling systemic spread (PMID: 28947648; PMID: 11801184; PMID: 20385762). These are pathogen-focused models (studying bacterial virulence and innate immune evasion) rather than models of the host lymphedema cycle. Resource: MGI for mouse strains; no dedicated erysipelas model database exists. Limitation: mouse dermonecrosis models capture bacterial invasion/immune evasion but not the chronic lymphatic-damage/recurrence dynamics central to human erysipelas.

Mechanistic Model / Interpretation

Erysipelas is best understood as a two-hit, self-amplifying disease. The first hit is a susceptible host terrain — impaired lymphatic drainage (often subclinical), venous insufficiency, and obesity — that locally weakens immune surveillance. The second hit is a portal of entry (usually toe-web tinea) admitting β-hemolytic streptococci to the dermis. The organism's virulence arsenal drives rapid lymphatic spread and a brisk innate inflammatory response producing the pathognomonic plaque and systemic toxicity. Critically, that same inflammation injures lymphatics, so each episode leaves the host more vulnerable — the empirical signature being subclinical lymphedema in 74% of single-episode patients rising to 100% after ≥3 episodes. This explains why erysipelas is simultaneously highly treatable (near-universal rapid penicillin response) and highly recurrent, and why durable prevention requires attacking both hits (antifungal/portal care + edema management) alongside antibiotic prophylaxis whose benefit is real but reverses on discontinuation.

Axis	Upstream driver	Downstream consequence
Host terrain	Lymphedema, venous insufficiency, obesity	Reduced dermal immune clearance
Portal	Tinea pedis, wounds, dermatoses	Streptococcal inoculation
Pathogen	SLO/SLS, M protein, spreading factors	Lymphatic spread, neutrophil evasion
Response	Innate inflammation	Plaque + fever + lymphatic injury → cycle

Evidence Base

PMID	Contribution	Type
26424182	Bacteriologic spectrum (n=1142); GGS common in blood	Human, retrospective
26734653	72–85% BHS etiology; GCS/GGS > GAS in legs	Human, prospective
16484815	Barrier breach OR 13.6, edema OR 7.0	Human, case-control
29427797	Tinea pedis, varicose veins, lymphoedema, obesity; incidence 204.8/100k	Human, population case-control
23635049	PATCH I: penicillin HR 0.55	Human RCT
21910701	PATCH II: HR 0.53 (NS)	Human RCT
24551029	Pooled IRR 0.71; cost-effective	Human, economic analysis
28631307	Cochrane: prophylaxis reduces recurrence on-treatment	Systematic review
41562377	98.3% penicillin response ≤2 days	Human, retrospective
30685804	Guideline adherence improves outcomes	Human, cohort
28768452	75% BHS, penicillin cure in facial disease	Human, prospective
40542699	82%→100% subclinical lymphedema	Human, imaging
33413190	Recurrence risk factors	Human, prospective cohort
30976336	Comorbidities in recurrence	Human, cohort
20147345	Age/sex/comorbidity epidemiology (n=428)	Human, cohort
15822466	Leg 91%, toe-web portal 77% (n=647)	Human, retrospective
18069381	Recurrence 67%, complications 25%	Human, retrospective
19663854	Erysipeloid definition	Review
42687202	Pig reservoir for Erysipelothrix	Veterinary
39240378	Antibiotic network meta-analysis	Systematic review
27806170	Misdiagnosis cost/harm	Human, cross-sectional

Consistency: All etiologic sources converge on β-hemolytic streptococcal predominance; all risk-factor studies converge on barrier breach + edema/lymphedema + obesity; both RCTs and the Cochrane review agree on prophylaxis benefit with post-treatment waning. No reviewed study contradicted the core model.

Limitations and Knowledge Gaps

Etiologic uncertainty at the bedside: blood/wound cultures are low-yield (bacteremia ~6.9%); much etiologic attribution is serologic or presumptive, and S. aureus isolates may be colonizers rather than pathogens.
Erysipelas vs cellulitis overlap: many studies pool the two entities; findings are partly extrapolated across the boundary.
No molecular/host-genetic layer: because erysipelas is non-genetic, entire template sections (causal genes, variants, inheritance, pharmacogenomics) are not applicable — a structural mismatch with a genetics-oriented template, not a gap in the literature.
Prophylaxis durability: benefit reverses off-treatment; optimal duration and the role of combined risk-factor modification are not fully defined.
QoL data specific to erysipelas are sparse; no validated disease-specific instrument was identified.
Model systems capture bacterial virulence but not the chronic lymphedema/recurrence cycle.

Proposed Follow-up Experiments / Actions

Prospective interventional trial combining tinea pedis eradication + compression lymphedema therapy vs standard care to quantify reduction in first and recurrent episodes (targets the highest-attributable, modifiable factors).
Biomarker study correlating baseline lymphoscintigraphy and CRP kinetics with recurrence, to risk-stratify candidates for prophylaxis.
Comparative-effectiveness / duration study of penicillin prophylaxis (e.g., 12 vs 24 months, continuous vs intermittent) with off-treatment follow-up to address waning.
Curation action: ensure the knowledge base cleanly separates MONDO:0001266 (streptococcal erysipelas) from Erysipelothrix erysipeloid/swine erysipelas to prevent conflation.
Diagnostic stewardship: deploy/validate clinical decision tools to reduce pseudocellulitis misdiagnosis and unnecessary antibiotic use.

Report compiled from 5 discovery iterations, 8 confirmed findings, and 44 reviewed papers. Evidence is predominantly human clinical (cohort, case-control, RCT, systematic review), supplemented by murine pathogen-virulence models and veterinary/zoonotic sources for the nosological distinction.

Artifacts

Reference Validation

Checked with linkml-reference-validator 0.3.0rc2.

Outcome	Count
References checked	38
Resolved	38
Unresolved (possible confabulation)	0
Unverifiable	0
Quoted claims checked	12
Quoted claims found in source	12
Quoted claims not found in source	0
References weighed for topical relevance	38
On topic	11
Off topic	3

References that may not be about this subject

These identifiers resolve, so they are not fabrications, but the records they resolve to share almost none of this report's vocabulary. That is a clue and not a verdict - a paper can be relevant in ways its title and abstract do not spell out - so read them before deciding:

PMID:11801184 (5 mentions) - Mouse skin passage of a Streptococcus pyogenes Tn917 mutant of sagA/pel restores virulence, beta-hemolysis and sagA/pel expression without altering the position or sequence of the transposon.
shared terms: streptococcal
PMID:27806170 (4 mentions) - Costs and Consequences Associated With Misdiagnosed Lower Extremity Cellulitis.
shared terms: antibiotic, cellulitis
PMID:30542523 (3 mentions) - Aortic valve endocarditis with Erysipelothrix rhusiopathiae: A rare zoonosis.
shared terms: human

Weighed against this report's own most characteristic terms: erysipelas, disease, lymphedema, recurrence, edema, streptococcal, penicillin, obesity, clinical, portal, episode, human, prophylaxis, tinea, antibiotic, cohort, lymphatic, cellulitis, fever, pedis.

All extracted references resolved successfully. Resolving is not the same as being relevant, though - see the references listed above as possibly off topic.

Term Validation

Checked with linkml-term-validator 0.4.5, through the ols: adapter.

Outcome	Count
Terms checked	26
Resolved	26
Unresolved (possible confabulation)	0
Obsolete	0
Unverifiable	0
Terms whose name was checked	9
Terms named correctly	6
Terms named as a different term	0
Terms whose name is worth a second look	3

Terms whose name is worth a second look

The report's name for these is recognisably related to the term's own name without being one of them. A loose paraphrase reads the same way as a citation of the wrong sibling term - and so does a related synonym, which the ontology records precisely because it names something adjacent rather than the same thing - so these are listed rather than judged:

MONDO:0001266 (4 mentions) - the report calls it "streptococcal erysipelas"; MONDO calls it erysipelas
NCBITaxon:119602 (2 mentions) - the report calls it "equisimilis"; NCBITaxon calls it Streptococcus dysgalactiae subsp. equisimilis, and lists "Streptococcus equisimilis" among its other names
HP:0001974 (1 mention) - the report calls it "Leukocytosis"; HP calls it Increased total leukocyte count, and lists "Leukocytosis" among its other names

Every term resolved, and every label the report gave matched.

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Key Findings

Finding 1 — β-hemolytic streptococci are the predominant cause

Finding 2 — Skin barrier disruption and leg edema/lymphedema are the dominant risk factors

Finding 3 — Prophylactic low-dose penicillin V reduces recurrence

Finding 4 — Rapid penicillin response; narrow-spectrum guideline adherence improves outcomes

Finding 5 — Erysipelas and lymphedema form a self-reinforcing vicious cycle

Finding 6 — Epidemiology: adult/elderly, female-predominant, leg-predominant, seasonal

Finding 7 — Streptococcal erysipelas is distinct from Erysipelothrix disease

Finding 8 — Cochrane meta-analysis supports antibiotic prophylaxis

Section-by-Section Report

1. Disease Information

2. Etiology

3. Phenotypes

4. Genetic / Molecular Information

5. Environmental Information

6. Mechanism / Pathophysiology

7. Anatomical Structures Affected

8. Temporal Development

9. Inheritance and Population

10. Diagnostics

11. Outcome / Prognosis

12. Treatment

13. Prevention

14. Other Species / Natural Disease

15. Model Organisms

Mechanistic Model / Interpretation

Evidence Base

Limitations and Knowledge Gaps

Proposed Follow-up Experiments / Actions

Artifacts

Reference Validation

References that may not be about this subject

Term Validation

Terms whose name is worth a second look