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derm.pemphigus-vulgaris.core.v1PRODUCTION
derm.pemphigus-vulgaris.core.v1

Pemphigus (vulgaris & foliaceus)

dermatologysubacutechronicadult
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12/12 authored

Canonical 12-phase frame with authored status for this dossier.

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Frame

Detailed

Frame as the prototypic INTRAEPIDERMAL IgG-anti-desmoglein acantholytic autoimmune blistering disease — pemphigus VULGARIS (mucosal-dominant, anti-Dsg3 ± Dsg1, flaccid, Nikolsky+, suprabasal split, historically fatal untreated) vs pemphigus FOLIACEUS (superficial, anti-Dsg1, no mucosa) — managed on a RITUXIMAB-FIRST evidence-based ladder. PARANEOPLASTIC pemphigus (severe stomatitis + polymorphous + occult neoplasm) is the not-to-miss recognised here; drug-induced (thiol/ACEi) is reconciled here; secondary infection/sepsis from erosions is the leading cause of death and is escalated/routed.

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intraepidermal autoimmune-bullous framing set; PV-vs-PF phenotype + paraneoplastic + drug-induced + infection escape routes noted

Patient inputs (20)

Severe refractory haemorrhagic stomatitis + polymorphous lichenoid/EM-like (± palmoplantar, nail, conjunctival) lesions, especially if treatment-resistant, mandates a paraneoplastic-pemphigus / occult-neoplasm workup — the not-to-miss with high mortality and bronchiolitis obliterans (Pan J Peking Univ 2022 PMID 36241242; Choi J Dermatol 2012 PMID 22938021)

Flaccid, easily ruptured bullae with a positive Nikolsky sign on non-erythematous skin (intraepidermal, pemphigus) vs tense bullae on an erythematous/urticarial base, Nikolsky− (subepidermal, bullous pemphigoid) is the top clinical discriminator (EADV/EDF S2k 2020 PMID 32830877)

Mucosal/deep flaccid erosions (PV, suprabasal split, anti-Dsg3 ± Dsg1) vs superficial scaly-crusted seborrhoeic-distribution erosions with no mucosa (PF, subcorneal split, anti-Dsg1) defines the phenotype and the expected serology (Murrell consensus JAAD 2018 PMID 29438767)

Thiol drugs (D-penicillamine, thiopronine) and ACE inhibitors/other non-thiol drugs can induce pemphigus (more often PF-like); identifying and withdrawing the culprit can be disease-modifying (EADV/EDF S2k 2020 PMID 32830877)

Painful mucosal (oral ± conjunctival/genital/oesophageal/laryngeal) erosions are the presenting and often dominant feature of pemphigus vulgaris and are ABSENT in pemphigus foliaceus — the cardinal PV-vs-PF and intake/admission discriminator (EADV/EDF S2k 2020 PMID 32830877)

Direct immunofluorescence of PERILESIONAL skin showing INTERCELLULAR ("chicken-wire") IgG ± C3 throughout the epidermis is the diagnostic gold standard and the decisive pivot vs the LINEAR basement-membrane-zone pattern of bullous pemphigoid (EADV/EDF S2k 2020 PMID 32830877)

Serum anti-desmoglein-3 (mucosal/PV) and anti-desmoglein-1 (cutaneous/PF) ELISA confirm the diagnosis and phenotype, and their evolution correlates with skin disease activity for monitoring/relapse prediction (Hébert/Joly J Invest Dermatol 2018 PMID 30301637)

Widespread denuded erosions superinfect and lose fluid/protein; sepsis is the leading cause of death in pemphigus — purulent crust/pustules/fever/systemic toxicity forces admission + infection pathway (EADV/EDF S2k 2020 PMID 32830877)

Severe oral/oesophageal erosions impair eating/drinking → malnutrition, dehydration, weight loss; an admission + nutrition trigger and an independent paraneoplastic-pemphigus mortality marker (Pan J Peking Univ 2022 PMID 36241242)

Extent (BSA + mucosal sites + erosion burden; Harman moderate vs severe strata used in Ritux 3) gates rituximab-led induction, admission, and the severity-tiered ladder (Joly Ritux 3 Lancet 2017 PMID 28342637)

IIF on monkey oesophagus detects circulating anti-intercellular IgG; IIF on RAT BLADDER detecting anti-plakin antibodies is relatively specific for PARANEOPLASTIC pemphigus and triggers the malignancy workup (Choi J Dermatol 2012 PMID 22938021)

Castleman disease, non-Hodgkin lymphoma, CLL and thymoma underlie paraneoplastic pemphigus; a known or suspected neoplasm reframes the disease and prognosis and routes to oncology (Pan J Peking Univ 2022 PMID 36241242)

Lesional H&E shows a SUPRABASAL acantholytic cleft with a "tombstone-row" basal layer in PV (deep) vs a subcorneal/granular split in PF (superficial) — localises the intraepidermal level (EADV/EDF S2k 2020 PMID 32830877)

Pre-rituximab latent-TB + hepatitis B/C screen (HBV reactivation can be fatal) before B-cell-depleting therapy; vaccinate before immunosuppression (EADV/EDF S2k 2020 PMID 32830877)

Baseline + on-treatment monitoring for rituximab (cytopenia, hypogammaglobulinaemia), azathioprine/MMF/cyclophosphamide myelosuppression, and infection surveillance (EADV/EDF S2k 2020 PMID 32830877)

Baseline + on-treatment hepatotoxicity monitoring for azathioprine / methotrexate / MMF and a baseline before systemic corticosteroid (EADV/EDF S2k 2020 PMID 32830877)

Systemic-corticosteroid hyperglycaemia surveillance during induction/taper — a leading source of cumulative steroid harm that rituximab-first therapy is designed to limit (Joly Ritux 3 Lancet 2017 PMID 28342637)

TPMT enzyme activity/genotype before azathioprine prevents life-threatening myelosuppression in low/absent-activity patients (EADV/EDF S2k 2020 PMID 32830877)

Renal function for cyclophosphamide/methotrexate dosing and CKD-EPI 2021 race-free eGFR in the multimorbid pemphigus population (EADV/EDF S2k 2020 PMID 32830877; Inker NEJM 2021)

Mycophenolate mofetil, methotrexate and cyclophosphamide are teratogenic and contraindicated in pregnancy/conception; rituximab timing and transient neonatal pemphigus (transplacental IgG) must be counselled (EADV/EDF S2k 2020 PMID 32830877)

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Severity triggers (6)

6 need judgement
  • informationallife_threateningextensive_pv_with_secondary_infection_or_sepsis
    Extensive eroded/denuded pemphigus with secondary skin infection, purulent crust/pustules, fever, large-BSA fluid/protein loss, or systemic toxicity / sepsis physiology
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationallife_threateningparaneoplastic_pemphigus_occult_neoplasm
    Severe intractable haemorrhagic stomatitis + polymorphous lichenoid/EM-like (± palmoplantar, conjunctival, nail) eruption, treatment-resistant — paraneoplastic pemphigus / paraneoplastic autoimmune multiorgan syndrome
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalsevererapidly_progressive_or_refractory_pemphigus
    Rapidly progressive widespread flaccid blistering, or pemphigus refractory to/intolerant of rituximab + corticosteroid ± a steroid-sparing adjuvant
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseveresevere_oral_oesophageal_involvement_intake_impairment
    Severe oral/oesophageal/laryngeal erosions impairing eating/drinking with dehydration, malnutrition, weight loss or failure to thrive
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalsevererituximab_infection_or_hbv_reactivation_event
    Serious infection, hypogammaglobulinaemia with infection, or hepatitis-B reactivation during/after rituximab therapy
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalmoderatedrug_induced_pemphigus_thiol_or_acei
    Pemphigus arising after a thiol drug (D-penicillamine, thiopronine) or an ACE inhibitor / other non-thiol trigger
    Trigger could not be auto-evaluated — needs clinician judgement.

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Recommended regimen

Pemphigus (vulgaris & foliaceus) — rituximab-first severity-tiered ladder (EADV/EDF S2k 2020 / Joly Ritux 3 Lancet 2017)
axis: pemphigus_rituximab_first_severity_tiered_ladderstep 1 - Step 1 — Withdraw culprit drug + erosion/oral/nutrition supportive care (every patient)
Selected step "Step 1 — Withdraw culprit drug + erosion/oral/nutrition supportive care (every patient)" — All patients at presentation — reconcile and withdraw drug-induced pemphigus triggers; supportive skin/oral/wound care + infection surveillance throughout
  • withdraw_offending_thiol_or_acei_drug
    first line
    culprit_withdrawal
    triggers: recent_thiol_d_penicillamine_thiopronine_or_acei
    EADV/EDF S2k pemphigus 2020 (PMID 32830877) — thiol drugs (D-penicillamine, thiopronine) and ACE inhibitors / other non-thiol drugs can induce pemphigus; withdrawing the culprit can be disease-modifying and may obviate or reduce immunosuppression.
  • erosion_wound_oral_care_nutrition_and_infection_surveillance
    first line
    supportive_care
    EADV/EDF S2k 2020 (PMID 32830877) — non-adherent dressings + atraumatic wound care, oral antiseptic/anaesthetic care + analgesia + nutrition for painful oral/oesophageal erosions, and active surveillance for secondary infection (the leading cause of pemphigus death).
  • treat_underlying_neoplasm_and_route_oncology_if_paraneoplastic
    rescue
    paraneoplastic_directed
    triggers: paraneoplastic_pemphigus_with_castleman_lymphoma_cll_thymoma
    Pan J Peking Univ 2022 (PMID 36241242) + Choi J Dermatol 2012 (PMID 22938021) — paraneoplastic pemphigus prognosis depends on the underlying neoplasm; treat/resect it (Castleman/NHL/CLL/thymoma) and route to oncology; bronchiolitis obliterans + fungal infection are independent mortality risks.

outpatient playbook — drug actions (5)

  1. 1. withdraw culprit thiol/ACEi drug + erosion/oral/nutrition supportive care
    n/a • n/a • immediate
    trigger: Drug-induced pemphigus suspected (EADV/EDF S2k 2020 PMID 32830877)
    Culprit withdrawal can be disease-modifying; supportive oral/wound care + infection surveillance throughout
  2. 2. rituximab 1000 mg IV d0 + d14 (M12 + M18) + SHORT tapering prednisone
    rxcui 121191
    1000 mg ×2 + prednisone 0.5–1.0 mg/kg/day tapered 3–6 mo • IV + PO • induction d0/d14; maintenance M12/M18
    trigger: Moderate–severe newly diagnosed PV/PF (Joly Ritux 3 Lancet 2017 PMID 28342637)
    First-line rituximab + short prednisone: CR off-therapy 89% vs 34% with fewer steroid adverse events
  3. 3. azathioprine (TPMT-guided) or mycophenolate mofetil (steroid-sparing / rituximab-ineligible)
    rxcui 68149
    AZA 1–3 mg/kg/day or MMF 2–3 g/day • PO • daily / BID
    trigger: Steroid-sparing need or rituximab unavailable/contraindicated (Beissert Arch Dermatol 2006 PMID 17116835)
    MMF and azathioprine give equivalent steroid-sparing efficacy as adjuvants
  4. 4. IVIG / immunoadsorption / plasmapheresis / cyclophosphamide / repeat rituximab (refractory)
    rxcui 3002
    per protocol • IV • per agent
    trigger: Refractory to rituximab + corticosteroid ± adjuvant (Amagai JAAD 2009 PMID 19293008)
    IVIG (RCT-supported) / autoantibody removal / cyclophosphamide / repeat rituximab for treatment-resistant disease; reassess diagnosis
  5. 5. clobetasol / dexamethasone oral rinse / intralesional betamethasone (localised mild adjunct)
    rxcui 21245
    topical/intralesional • topical / oral rinse / intralesional • BID then taper
    trigger: Localised mild or residual lesions (EADV/EDF S2k 2020 PMID 32830877)
    Local control of limited/residual disease as an adjunct; most PV still needs systemic therapy

Auto-drafted A&P note

outpatient

Subjective

- Possible entry pathways: Chronic painful non-healing oral (± conjunctival/genital/oesophageal) erosions, often the first and for months the only manifestation of pemphigus vulgaris (EADV/EDF S2k pemphigus guideline, JEADV 2020; PMID 32830877); Flaccid, easily ruptured bullae on non-erythematous skin leaving raw painful erosions, with a positive Nikolsky sign — the intraepidermal acantholytic phenotype (EADV/EDF S2k 2020; PMID 32830877); Superficial scaly-crusted "corn-flake" erosions on the scalp/face/upper trunk with NO mucosal involvement — pemphigus foliaceus (anti-Dsg1 only) (Murrell international consensus, JAAD 2018; PMID 29438767).

Objective

- No vitals, labs, or imaging entered for this encounter.

Assessment

**Pemphigus (vulgaris & foliaceus)** (derm.pemphigus-vulgaris.core.v1).
Phenotype framing: Terminal autoimmune/blistering/erosive differential with named pivots: pemphigus vulgaris/foliaceus vs bullous pemphigoid (tense, non-mucosal, elderly, Nikolsky−, LINEAR-BMZ DIF, anti-BP180 pivot — route derm.bullous-pemphigoid.core.v1) vs mucous-membrane pemphigoid (scarring predominantly-mucosal, linear-BMZ pivot) vs paraneoplastic pemphigus (severe stomatitis + polymorphous + occult neoplasm + anti-plakin/rat-bladder pivot — route to onc.lymphoproliferative-malignancy.core.v1) vs SJS/TEN (acute drug latency, dusky targetoid, full-thickness, DIF-negative pivot — route derm.sjs-ten.core.v1) vs erosive oral lichen planus / aphthous / herpetic / Behçet (erosive-oral pivots — route derm.lichen-planus.core.v1) vs Hailey-Hailey / Darier (familial acantholytic, DIF-negative pivot) vs IgA pemphigus (intercellular IgA, pustular pivot) vs bullous impetigo / SSSS (subcorneal toxin, paediatric pivot). Drug-induced status is a within-pemphigus modifier, not an alternative.
Scope: Frame as the prototypic INTRAEPIDERMAL IgG-anti-desmoglein acantholytic autoimmune blistering disease — pemphigus VULGARIS (mucosal-dominant, anti-Dsg3 ± Dsg1, flaccid, Nikolsky+, suprabasal split, historically fatal untreated) vs pemphigus FOLIACEUS (superficial, anti-Dsg1, no mucosa) — managed on a RITUXIMAB-FIRST evidence-based ladder. PARANEOPLASTIC pemphigus (severe stomatitis + polymorphous + occult neoplasm) is the not-to-miss recognised here; drug-induced (thiol/ACEi) is reconciled here; secondary infection/sepsis from erosions is the leading cause of death and is escalated/routed.

No severity triggers fired against current inputs.

Plan

Regimen axis: **Pemphigus (vulgaris & foliaceus) — rituximab-first severity-tiered ladder (EADV/EDF S2k 2020 / Joly Ritux 3 Lancet 2017)** — step "Step 1 — Withdraw culprit drug + erosion/oral/nutrition supportive care (every patient)".
1. withdraw_offending_thiol_or_acei_drug (culprit_withdrawal, first line) — EADV/EDF S2k pemphigus 2020 (PMID 32830877) — thiol drugs (D-penicillamine, thiopronine) and ACE inhibitors / other non-thiol drugs can induce pemphigus; withdrawing the culprit can be disease-modifying and may obviate or reduce immunosuppression.
2. erosion_wound_oral_care_nutrition_and_infection_surveillance (supportive_care, first line) — EADV/EDF S2k 2020 (PMID 32830877) — non-adherent dressings + atraumatic wound care, oral antiseptic/anaesthetic care + analgesia + nutrition for painful oral/oesophageal erosions, and active surveillance for secondary infection (the leading cause of pemphigus death).
3. treat_underlying_neoplasm_and_route_oncology_if_paraneoplastic (paraneoplastic_directed, rescue) — Pan J Peking Univ 2022 (PMID 36241242) + Choi J Dermatol 2012 (PMID 22938021) — paraneoplastic pemphigus prognosis depends on the underlying neoplasm; treat/resect it (Castleman/NHL/CLL/thymoma) and route to oncology; bronchiolitis obliterans + fungal infection are independent mortality risks.

Setting playbook (outpatient) — Confirm pemphigus + PV/PF phenotype (perilesional intercellular DIF + lesional acantholytic H&E + anti-Dsg1/Dsg3 ELISA), reconcile/withdraw any culprit drug, exclude paraneoplastic pemphigus, and treat RITUXIMAB-FIRST for moderate–severe disease with anti-Dsg-titre-guided monitoring and a short corticosteroid taper (EADV/EDF S2k pemphigus 2020 PMID 32830877; Joly Ritux 3 Lancet 2017 PMID 28342637)
4. withdraw culprit thiol/ACEi drug + erosion/oral/nutrition supportive care n/a n/a immediate — Drug-induced pemphigus suspected (EADV/EDF S2k 2020 PMID 32830877) (Culprit withdrawal can be disease-modifying; supportive oral/wound care + infection surveillance throughout)
5. rituximab 1000 mg IV d0 + d14 (M12 + M18) + SHORT tapering prednisone 1000 mg ×2 + prednisone 0.5–1.0 mg/kg/day tapered 3–6 mo IV + PO induction d0/d14; maintenance M12/M18 — Moderate–severe newly diagnosed PV/PF (Joly Ritux 3 Lancet 2017 PMID 28342637) (First-line rituximab + short prednisone: CR off-therapy 89% vs 34% with fewer steroid adverse events)
6. azathioprine (TPMT-guided) or mycophenolate mofetil (steroid-sparing / rituximab-ineligible) AZA 1–3 mg/kg/day or MMF 2–3 g/day PO daily / BID — Steroid-sparing need or rituximab unavailable/contraindicated (Beissert Arch Dermatol 2006 PMID 17116835) (MMF and azathioprine give equivalent steroid-sparing efficacy as adjuvants)
7. IVIG / immunoadsorption / plasmapheresis / cyclophosphamide / repeat rituximab (refractory) per protocol IV per agent — Refractory to rituximab + corticosteroid ± adjuvant (Amagai JAAD 2009 PMID 19293008) (IVIG (RCT-supported) / autoantibody removal / cyclophosphamide / repeat rituximab for treatment-resistant disease; reassess diagnosis)
8. clobetasol / dexamethasone oral rinse / intralesional betamethasone (localised mild adjunct) topical/intralesional topical / oral rinse / intralesional BID then taper — Localised mild or residual lesions (EADV/EDF S2k 2020 PMID 32830877) (Local control of limited/residual disease as an adjunct; most PV still needs systemic therapy)

Non-pharmacologic actions:
- Atraumatic wound care + non-adherent dressings; oral antiseptic/anaesthetic care + soft diet for oral erosions (EADV/EDF S2k 2020 PMID 32830877)
- Relapse-recognition education (new oral/skin erosions) + anti-Dsg ELISA trend counselling (Hébert/Joly J Invest Dermatol 2018 PMID 30301637)
- Pre-rituximab vaccination + permanent culprit-drug avoidance flag if drug-induced (EADV/EDF S2k 2020 PMID 32830877)
- Oncology referral + CT/lymphoproliferative workup if paraneoplastic pemphigus suspected (Pan J Peking Univ 2022 PMID 36241242)

AVOID / contraindication checks:
- Pre rituximab screen hbv hcv latent tb and vaccinate before immunosuppression (EADV/EDF S2k pemphigus 2020 PMID 32830877 — HBV reactivation can be fatal; live vaccines avoided once immunosuppressed)
- Rituximab hypogammaglobulinaemia and infection vigilance rare pml (EADV/EDF S2k 2020 PMID 32830877 — monitor immunoglobulins + infection; the rituximab first strategy is chosen specifically to reduce cumulative corticosteroid harm per Ritux 3 PMID 28342637)
- Azathioprine check tpmt activity or genotype before starting (EADV/EDF S2k 2020 PMID 32830877 — absent/low TPMT → severe myelosuppression; use MMF instead)
- Mycophenolate cyclophosphamide methotrexate teratogenic contraindicated in pregnancy and conception (EADV/EDF S2k 2020 PMID 32830877)
- Long term systemic corticosteroid requires bone gi glucose prophylaxis and taper (Joly Ritux 3 Lancet 2017 PMID 28342637 — cumulative steroid harm; rituximab first short course taper minimises exposure)
- Secondary infection and sepsis from eroded skin is the leading cause of death treat do not only escalate immunosuppression (EADV/EDF S2k 2020 PMID 32830877)
- Paraneoplastic pemphigus treat the underlying neoplasm route oncology and monitor for bronchiolitis obliterans (Pan J Peking Univ 2022 PMID 36241242; Choi J Dermatol 2012 PMID 22938021)
- Drug induced pemphigus withdraw thiol d penicillamine thiopronine or acei culprit first (EADV/EDF S2k 2020 PMID 32830877)

Monitoring

Regimen monitoring:
- anti Dsg1 and Dsg3 ELISA evolution tracks skin disease activity rising titre precedes relapse and guides taper (Hébert/Joly J Invest Dermatol 2018 PMID 30301637)
- PDAI or ABSIS activity plus new erosion count plus mucosal survey at each visit (Hébert/Joly J Invest Dermatol 2018 PMID 30301637 — schema-blocked scores captured narratively)
- rituximab: B-cell + immunoglobulin levels, infusion reactions, infection + HBV-reactivation vigilance (rare PML); re-screen HBV before redosing (EADV/EDF S2k 2020 PMID 32830877)
- systemic corticosteroid: glucose/BP/bone/GI/infection during induction and taper-to-off (Joly Ritux 3 Lancet 2017 PMID 28342637)
- azathioprine/MMF/cyclophosphamide: CBC + LFT periodic; TPMT-guided azathioprine; cyclophosphamide urinalysis for haemorrhagic cystitis (EADV/EDF S2k 2020 PMID 32830877)
- infection surveillance throughout leading cause of death + nutrition/oral status if oral-oesophageal involvement (EADV/EDF S2k 2020 PMID 32830877)
- paraneoplastic: oncology-led neoplasm surveillance + pulmonary (bronchiolitis obliterans) monitoring (Pan J Peking Univ 2022 PMID 36241242)

Setting (outpatient) monitoring:
- anti-Dsg1/Dsg3 ELISA + new-erosion count + PDAI/ABSIS at each visit (Hébert/Joly J Invest Dermatol 2018 PMID 30301637)
- Drug-class safety labs (rituximab B-cell/Ig + HBV; steroid glucose/BP/bone; AZA/MMF/cyclophosphamide CBC/LFT) (EADV/EDF S2k 2020 PMID 32830877)

Follow-up plan: Chronic relapsing-remitting maintenance: taper corticosteroid/immunosuppressant to the lowest effective dose guided by clinical remission + anti-Dsg ELISA trend, relapse-recognition education (new oral/skin erosions), planned/relapse-triggered repeat-rituximab strategy, periodic immunosuppressant + immunoglobulin + HBV surveillance, infection precautions, oral/dental and nutrition care, and — for drug-induced pemphigus — a permanent culprit-avoidance flag. For confirmed/treated paraneoplastic pemphigus, oncology-led neoplasm surveillance + pulmonary (bronchiolitis obliterans) monitoring. Dermatology continuity for any systemic agent; reassess the diagnosis (repeat biopsy/serology, rat-bladder IIF) if the course is atypical or treatment-refractory.
- Close-out criterion: taper plan + relapse education + repeat-rituximab strategy + anti-Dsg surveillance + culprit-avoidance flag + paraneoplastic/pulmonary surveillance (if applicable) documented

Monitoring phase: Disease: PDAI/ABSIS activity + new-erosion count + anti-Dsg1/Dsg3 ELISA at follow-up — the ELISA evolution tracks skin disease activity and a rising titre predicts/precedes relapse (Hébert/Joly J Invest Dermatol 2018; informs taper). Drug safety: rituximab → B-cell/immunoglobulin levels, infusion reactions, infection + HBV reactivation vigilance (rare PML); systemic corticosteroid → glucose/BP/bone/GI/infection during induction & taper; azathioprine/MMF/cyclophosphamide → CBC + LFT (TPMT-guided azathioprine); cyclophosphamide → urinalysis (haemorrhagic cystitis). Infection surveillance throughout (leading cause of death). Taper corticosteroid and immunosuppressant guided by remission + anti-Dsg trend.

Disposition

Current setting: outpatient — Confirm pemphigus + PV/PF phenotype (perilesional intercellular DIF + lesional acantholytic H&E + anti-Dsg1/Dsg3 ELISA), reconcile/withdraw any culprit drug, exclude paraneoplastic pemphigus, and treat RITUXIMAB-FIRST for moderate–severe disease with anti-Dsg-titre-guided monitoring and a short corticosteroid taper (EADV/EDF S2k pemphigus 2020 PMID 32830877; Joly Ritux 3 Lancet 2017 PMID 28342637)

Disposition criteria:
- Continue rituximab-first ladder + anti-Dsg-titre-guided monitoring + derm follow-up if responding (EADV/EDF S2k 2020 PMID 32830877)
- Step up the ladder if rituximab + corticosteroid ± adjuvant fails after adherence/diagnosis review
- Admit only for infection/sepsis, large-BSA fluid loss, intake impairment/failure to thrive, or a rituximab infection/HBV-reactivation event

Escalation triggers (move to higher acuity):
- Extensive PV with secondary infection / sepsis or large-BSA erosions with fluid/protein loss → admit + infection/sepsis pathway (EADV/EDF S2k 2020 PMID 32830877)
- Severe oral/oesophageal erosions impairing intake / failure to thrive → admit + nutrition support (Pan J Peking Univ 2022 PMID 36241242)
- Severe refractory stomatitis + polymorphous eruption → urgent paraneoplastic-pemphigus malignancy workup + oncology (Pan J Peking Univ 2022 PMID 36241242)

Earlier-Return Triggers

Return-precaution thresholds (watch for):
- [LIFE_THREATENING] Extensive eroded/denuded pemphigus with secondary skin infection, purulent crust/pustules, fever, large-BSA fluid/protein loss, or systemic toxicity / sepsis physiology
- [LIFE_THREATENING] Severe intractable haemorrhagic stomatitis + polymorphous lichenoid/EM-like (± palmoplantar, conjunctival, nail) eruption, treatment-resistant — paraneoplastic pemphigus / paraneoplastic autoimmune multiorgan syndrome
- [SEVERE] Rapidly progressive widespread flaccid blistering, or pemphigus refractory to/intolerant of rituximab + corticosteroid ± a steroid-sparing adjuvant

Citations

- EADV/EDF updated S2k guideline for the management of pemphigus vulgaris and foliaceus (Joly, Hertl, Schmidt et al, JEADV 2020; PMID 32830877, DOI 10.1111/jdv.16752) — rituximab is FIRST-LINE for moderate-to-severe pemphigus vulgaris (approved in Europe and the USA); systemic corticosteroid for rapid control; azathioprine/MMF as steroid-sparing adjuvants; IVIG / immunoadsorption / plasmapheresis / cyclophosphamide / repeat rituximab for refractory disease; diagnosis per the autoimmune-bullous canon (perilesional intercellular DIF + lesional acantholytic H&E + anti-Dsg1/Dsg3 ELISA + IIF, rat-bladder for paraneoplastic). Concordant international expert consensus (Murrell et al, JAAD 2018; PMID 29438767 — IV CD20 inhibitor first-line). Cornerstone RCTs: Joly Ritux 3 first-line rituximab (Lancet 2017; PMID 28342637); Beissert azathioprine-vs-MMF steroid-sparing (Arch Dermatol 2006; PMID 17116835); Amagai high-dose IVIG (JAAD 2009; PMID 19293008). Activity/serology: Hébert/Joly PDAI/ABSIS validation + anti-Dsg correlation (J Invest Dermatol 2018; PMID 30301637). Paraneoplastic-pemphigus prognosis: Pan (J Peking Univ 2022; PMID 36241242) + Choi (J Dermatol 2012; PMID 22938021). [PMID:32830877](https://pubmed.ncbi.nlm.nih.gov/32830877/)
- Cited evidence (PMID 29438767) [PMID:29438767](https://pubmed.ncbi.nlm.nih.gov/29438767/)
- Cited evidence (PMID 28342637) [PMID:28342637](https://pubmed.ncbi.nlm.nih.gov/28342637/)
- Cited evidence (PMID 17116835) [PMID:17116835](https://pubmed.ncbi.nlm.nih.gov/17116835/)
- Cited evidence (PMID 19293008) [PMID:19293008](https://pubmed.ncbi.nlm.nih.gov/19293008/)

Last reconciled with current guidelines: 2026-05-22.
References
  • EADV/EDF updated S2k guideline for the management of pemphigus vulgaris and foliaceus (Joly, Hertl, Schmidt et al, JEADV 2020; PMID 32830877, DOI 10.1111/jdv.16752) — rituximab is FIRST-LINE for moderate-to-severe pemphigus vulgaris (approved in Europe and the USA); systemic corticosteroid for rapid control; azathioprine/MMF as steroid-sparing adjuvants; IVIG / immunoadsorption / plasmapheresis / cyclophosphamide / repeat rituximab for refractory disease; diagnosis per the autoimmune-bullous canon (perilesional intercellular DIF + lesional acantholytic H&E + anti-Dsg1/Dsg3 ELISA + IIF, rat-bladder for paraneoplastic). Concordant international expert consensus (Murrell et al, JAAD 2018; PMID 29438767 — IV CD20 inhibitor first-line). Cornerstone RCTs: Joly Ritux 3 first-line rituximab (Lancet 2017; PMID 28342637); Beissert azathioprine-vs-MMF steroid-sparing (Arch Dermatol 2006; PMID 17116835); Amagai high-dose IVIG (JAAD 2009; PMID 19293008). Activity/serology: Hébert/Joly PDAI/ABSIS validation + anti-Dsg correlation (J Invest Dermatol 2018; PMID 30301637). Paraneoplastic-pemphigus prognosis: Pan (J Peking Univ 2022; PMID 36241242) + Choi (J Dermatol 2012; PMID 22938021). — PMID:32830877
  • Cited evidence (PMID 29438767) — PMID:29438767
  • Cited evidence (PMID 28342637) — PMID:28342637
  • Cited evidence (PMID 17116835) — PMID:17116835
  • Cited evidence (PMID 19293008) — PMID:19293008