6th July 2023

Autoimmune Blistering Disorders

Pemphigus Vulgaris

A potentially fatal autoimmune blistering disorder, typically presenting between the ages of 30 and 60 years. The condition occurs due to intraepithelial blisters caused by IgG antibodies against adhesion proteins desmoglein 3 and/or desmoglein 1. Painful mucosal erosions which can precede skin involvement by months. However, note that mucosal involvement may be the only manifestation of this disorder in some patients. Skin involvement is characterised by flaccid, easily ruptured blisters that quickly evolve into itchy and painful erosions and crusting.

Pemphigus vulgaris

Image Source: Wikimedia Commons (2018). Pemphgoid vulgaris, Licensed under a creative commons licence. Available for free at: https://commons.wikimedia.org/wiki/File:Pemphgoid_vulgaris.jpg (Accessed on: 10 March 2022).

Skin biopsy is sent for histology and direct immunofluorescence. Diagnosis is confirmed on viewing intraepidermal deposition of IgG antibodies and suprabasal epidermal acantholysis. Serum antibody levels can also be taken.

Management involves high dose corticosteroids for disease control followed by a step-down regime. Other immunosuppressive agents such as azathioprine and cyclophosphamide are used as adjuvant or second-line.

Table 8: Variants of pemphigus

Bullous Pemphigoid

The most common autoimmune blistering disorder, typically affecting the elderly. IgG autoantibodies attack the basement membrane (specifically BP180 and BP230 proteins), resulting in subepidermal blistering. Bullous pemphigoid has been associated with:

• Neurological disorders: stroke, Parkinson’s disease, dementia, epilepsy and multiple sclerosis.
• Medications: antibiotics, penicillamine, ACE inhibitors, Beta-blockers, DPP-4 inhibitors (e.g. sitagliptin), diuretics, immune checkpoint inhibitors
• Physical triggers: trauma and burns

The onset of blisters is preceded by a non-bullous phase lasting weeks or months. This presents as intense itching which may be accompanied by erythema and/or urticated plaques. The bullous phase consists of localised or widespread tense bullae on erythematous or normal-looking skin. The trunk and flexor aspect of the limbs are typically affected. Mucosal involvement is uncommon.

Bullous pemphigoid

Image Source: Wikimedia Commons (2018). Drugs induce pemphigoud bullous, Licensed under a creative commons licence. Available for free at: https://commons.wikimedia.org/wiki/File:Drugs_induce_pemphigoud_bullous.jpg (Accessed on: 10 March 2022).

Investigation involves checking serum antibodies and skin biopsies for histology and direct immunofluorescence. Histology and immunofluorescence will demonstrate subepidermal blistering and IgG deposition at the basement membrane, respectively. Super-potent topical steroids can treat localised disease, whereas widespread disease will require oral prednisolone +/- immunosuppressants (e.g. Azathioprine). Doxycycline 200 mg daily is an alternative to immunosuppressive therapy, due to its anti-inflammatory properties, and it has fewer side effects compared to oral prednisolone.

Dermatitis Herpetiformis

A rare chronic autoimmune blistering skin condition that is associated with coeliac disease (a gluten-sensitive enteropathy) in 90% of patients. More common in men and typically presents between 15-40 years old. Loss of immune tolerance to gluten peptides triggers the production of IgA antibodies and an autoimmune process targeting both the skin and intestinal submucosa.

Classically presents as intensely itchy clusters of vesicles on erythematous or normal-looking skin. Vesicles are often broken through scratching leaving erosions. Distribution is symmetrical and commonly affects the extensors, including the elbows, knees, buttocks and scalp. Symptoms of gastrointestinal disturbance and malabsorption may also be present.

Dermatitis herpetiformis on the abdomen

Image Source: Wikimedia Commons (2010). Dermatitis-herpetiformis, Licensed under a creative commons licence. Available for free at: https://commons.wikimedia.org/wiki/File:Dermatitis-herpetiformis.jpg (Accessed on: 10 March 2022).

Skin biopsy demonstrates IgA deposits at the dermal papillae and subepidermal blisters on direct immunofluorescence. Coeliac disease should also be tested for. A lifelong gluten-free diet is strongly recommended in these patients. Dapsone is the first choice in cases that cannot be managed with dietary changes alone and will control eruptions and itch. However, regular blood monitoring is required due to the risk of haemolytic anaemia and agranulocytosis.