Bullous pemphigoid

Abstract

Bullous pemphigoid is the most frequent autoimmune bullous disease and mainly affects elderly individuals. Increase in incidence rates in the past decades has been attributed to population aging, drug-induced cases and improvement in the diagnosis of the nonbullous presentations of the disease. A dysregulated T cell immune response and synthesis of IgG and IgE autoantibodies against hemidesmosomal proteins (BP180 and BP230) lead to neutrophil chemotaxis and degradation of the basement membrane zone. Bullous pemphigoid classically manifests with tense blisters over urticarial plaques on the trunk and extremities accompanied by intense pruritus. Mucosal involvement is rarely reported. Diagnosis relies on (1) the histopathological evaluation demonstrating eosinophilic spongiosis or a subepidermal detachment with eosinophils; (2) the detection of IgG and/or C3 deposition at the basement membrane zone using direct or indirect immunofluorescence assays; and (3) quantification of circulating autoantibodies against BP180 and/or BP230 using ELISA. Bullous pemphigoid is often associated with multiple comorbidities in elderly individuals, especially neurological disorders and increased thrombotic risk, reaching a 1-year mortality rate of 23%. Treatment has to be tailored according to the patient's clinical conditions and disease severity. High potency topical steroids and systemic steroids are the current mainstay of therapy. Recent randomized controlled studies have demonstrated the benefit and safety of adjuvant treatment with doxycycline, dapsone and immunosuppressants aiming a reduction in the cumulative steroid dose and mortality.

Figure 1

Classic bullous pemphigoid - Tense blisters with hemorrhagic (A) and hyaline (B) content on the trunk and limbs with erythematous and edematous background; hyaline blisters without inflammatory signs (C); excoriated papules and blisters with crusts in the axillary region (D); brownish and erythematous plaques with overlying purulent and hyaline blisters (E). Mucosal involvement - blisters and erosions on the palate (F); blister in the esophagus (G)

Figure 2

Nonbullous pemphigoid - Urticariform: confluent erythematous and edematous papules on the trunk (A). Erythema multiforme-like: targetoid plaques on the thighs (B). Prurigo-like: lichenified papules on the dorsum of the hand (C). Excoriations on the frontal region (D). Eczematous: erythematous-brownish confluent plaques on the trunk and upper limbs (E). Toxic epidermal necrolysis-like: erosions on the dorsum (F)

Figure 3

Bullous pemphigoid presenting as exfoliative erythroderma without blisters

Figure 4

Childhood bullous pemphigoid - Confluent urticarial plaques with blisters on the trunk (A). Disidrosiform vesicles on the hands (B)

Figure 5

Bullous pemphigoid triggered by UVB-NB phototherapy in a patient with psoriasis - Erythematous and brownish patches with blisters on the upper (A) and lower (B) limbs; psoriatic plaque on the thigh (C)

Figure 6

Lichen planus - Violaceous flat papules with mild desquamation on the upper (A) and lower (B) limbs, and feet (C). Lichen planus pemphigoid - Confluent macules and papules on the trunk (D) and lower limbs (E) with tense hyaline blisters on the feet (F)

Figure 7

Histopathological features of bullous pemphigoid - A. Eosinophilic spongiosis with eosinophilic dermal infiltrate (Hematoxycilin & eosin, x20); B. Subepidermal detachment filled with eosinophils and fibrin (Hematoxycilin & eosin, x20). Immunofluorescence characteristics in bullous pemphigoid - C. Linear C3 deposition at the BMZ; D. IgG bound to the epidermal side of the detachment using the salt-split skin technique