Pemphigus vulgaris and bullous pemphigoid — SAQ

Stem

A 48-year-old woman presents with a three-month history of painful oral erosions (buccal mucosa and gingiva) and, over the past two weeks, flaccid cutaneous blisters on the chest and axillae that rupture to leave large raw erosions. Applying lateral pressure to apparently normal skin shears off the superficial epidermis. She is systemically well but losing weight because eating is painful. ^[1]

a) What is the diagnosis, and which two bedside signs support it? (2 marks)

Pemphigus vulgaris (mucocutaneous type).^[1] Bedside signs: a positive Nikolsky sign — lateral pressure on normal-looking skin shears off the superficial epidermis, indicating an intraepidermal split; and a positive Asboe-Hansen sign — vertical pressure on an intact blister extends it laterally onto adjacent unblistered skin. Flaccid blisters with oral erosions preceding skin lesions by weeks to months complete the picture (oral manifestations in about 80 to 90 percent of PV patients at some stage; the sole presenting symptom in 60 percent or more).^[1]

b) List the investigations that confirm the diagnosis. (3 marks)

1. Skin biopsy for H&E from the edge of a fresh blister — PV shows a suprabasal intraepidermal split with acantholytic cells ("row of tombstones").
2. Perilesional biopsy for direct immunofluorescence (in Michel's medium, not formalin) — the diagnostic gold standard; PV shows intercellular fishnet IgG ± C3.
3. Serum ELISA for anti-desmoglein 3 and anti-desmoglein 1 (± indirect immunofluorescence) — confirms the diagnosis and quantifies titres that track disease activity and predict relapse.^[1]

c) Outline the management. (3 marks)

First-line for moderate-severe PV: rituximab plus short-term prednisone — rituximab 1000 mg IV on days 0 and 14 (with 500 mg at months 12 and 18) plus prednisone 0.5 to 1.0 mg/kg/day tapered over 3 to 6 months (Ritux 3: complete remission off-therapy at 24 months in 89 versus 34 percent versus prednisone alone, with fewer grade 3 to 4 adverse events). Rituximab is approved as first-line for moderate and severe PV in Europe and the United States.^[2] Supportive care: analgesia, oral care with antiseptic rinses and topical anaesthesia, nutritional support, aseptic wound dressing, infection surveillance, and steroid-safety prophylaxis (bone, gastric, glycaemic).

d) What are the key complications and prognostic factors? (2 marks)

Complications: secondary bacterial infection and sepsis, fluid-electrolyte loss and hypoalbuminaemia from extensive erosions, malnutrition from painful oral disease, and treatment complications of long-term steroids/rituximab (infection including HBV reactivation, diabetes, osteoporosis).^[2] Before immunosuppression pemphigus was almost always fatal; treated PV still carries about three times the risk of death of matched controls. Prognostic factors: disease severity/extent, anti-Dsg3 titre control (rising titre heralds relapse), mucosal (especially laryngeal/oesophageal) involvement, and comorbidity.

References3ShowHide

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