Pemphigus vulgaris and bullous pemphigoid — Viva

Q1: Definition and clinical presentation (2 min)

Pemphigus vulgaris: IgG against desmoglein 3 ± desmoglein 1 producing suprabasal intraepidermal acantholysis — flaccid blisters, raw erosions, oral ulceration typically preceding skin lesions, positive Nikolsky sign; adults 4th to 6th decade. Bullous pemphigoid: IgG against BP180 and BP230 of the hemidesmosome producing a subepidermal split — tense pruritic bullae on flexural skin of the elderly (median age 80 in UK data), oral mucosa typically spared (10-30 percent mild involvement), Nikolsky negative. The examiner may push on the level of the split and the mechanical consequence: thin friable roof (PV) versus thick durable roof (BP).^[1]

Q2: Differential diagnosis (3 min)

TEN/SJS (drug history, target lesions, full-thickness necrosis, DIF negative); dermatitis herpetiformis (young coeliac patient, intensely pruritic grouped vesicles on elbows/knees/buttocks, granular IgA at papillae); linear IgA disease (annular string-of-pearls, vancomycin, linear IgA BMZ); epidermolysis bullosa acquisita (trauma-prone, milia and scarring, floor binding on salt-split); staphylococcal scalded skin syndrome (infant, exfoliative toxin cleaves Dsg1, mucosa spared). Discriminate by blister type, mucosal involvement, Nikolsky sign, DIF pattern and salt-split binding.^[1]

Q3: Investigations (2 min)

Biopsy triad: H&E from blister edge (PV: suprabasal split, acantholytic cells; BP: subepidermal blister with eosinophils); perilesional DIF in Michel's medium — the gold standard (PV fishnet intercellular IgG/C3; BP linear BMZ IgG/C3); serum ELISA (anti-Dsg3/Dsg1 in PV; anti-BP180 NC16A in BP) with titres tracking activity. Indirect IF on monkey oesophagus (PV) and salt-split skin (BP roof; EBA floor). Pre-immunosuppression safety: FBC, U&E, LFTs, TPMT before azathioprine, G6PD before dapsone, HBV/HCV/HIV/TB screen and immunoglobulins before rituximab.^[1]

Q4: Management (3 min)

Moderate-severe PV: first-line rituximab 1000 mg IV days 0 and 14 plus short-term prednisone 0.5 to 1.0 mg/kg/day tapered over 3 to 6 months — Ritux 3 showed 89 versus 34 percent complete remission off-therapy at 24 months with fewer grade 3 to 4 adverse events; rituximab is approved first-line in Europe and the United States.^[2][4] BP: high-potency topical corticosteroids are the mainstay; doxycycline 200 mg/day is a non-inferior and significantly safer initial strategy than prednisolone 0.5 mg/kg/day (BLISTER: 18 versus 36 percent related severe, life-threatening and fatal events at 52 weeks).^[3] Severe pemphigus with extensive skin loss is managed like a burn — fluids, electrolytes, nutrition, aseptic wound care, infection surveillance.

Q5: Complications and prognosis (2 min)

PV: before immunosuppression almost always fatal; treated disease still carries about three times the mortality of controls — sepsis, electrolyte loss, malnutrition, and steroid/rituximab complications. BP: pooled 1-year mortality 23.5 percent (Europe 26.7, Asia 20.5, US 15.1) driven by age, neurological comorbidity and iatrogenic harm — the rationale for topical-first and doxycycline-first strategies. MMP: ocular scarring is irreversible — early aggressive therapy to prevent symblepharon and blindness. Pemphigoid gestationis: flares at delivery, recurs in later pregnancies, transient neonatal blistering.^[1]

References4ShowHide

1. [1]van Beek N, Holtsche MM, Atefi I, et al. State-of-the-art diagnosis of autoimmune blistering diseases. Front Immunol, 2024.PMID 38903493
2. [2]Joly P, Maho-Vaillant M, Prost-Squarcioni C, et al. First-line rituximab combined with short-term prednisone versus prednisone alone for the treatment of pemphigus (Ritux 3): a prospective, multicentre, parallel-group, open-label randomised trial. Lancet, 2017.PMID 28342637
3. [3]Williams HC, Wojnarowska F, Kirtschig G, et al. Doxycycline versus prednisolone as an initial treatment strategy for bullous pemphigoid: a pragmatic, non-inferiority, randomised controlled trial. Lancet, 2017.PMID 28279484
4. [4]Joly P, Horvath B, Patsatsi A, et al. Updated S2K guidelines on the management of pemphigus vulgaris and foliaceus initiated by the european academy of dermatology and venereology (EADV). J Eur Acad Dermatol Venereol, 2020.PMID 32830877