Bullous pemphigoid (BP) is the most common autoimmune blistering skin disease.1 The term “pemphigoids” refers to a group of autoimmune bullous diseases characterized by subepidermal blistering.1 Lever first described the histopathologic subepidermal split and acantholysis characteristic of pemphigoid diseases in 1953.2,3 The mean age of presentation is between 75 and 85 years, and the risk of developing BP increases with age.4,5 In Europe, the estimated incidence of BP is between 4.5 and 14.0 new cases per million per year.1,2
BP is an autoimmune disorder in which immunoglobulin G (IgG) autoantibodies attack BP180 (BPAG2, type XVIII collagen) and BP230 (BPAG1-e) antigens found on hemidesmosomes, which are responsible for the tight barrier between the epidermis and dermis.5-7 Many triggers are associated with BP, some of which include medications and viral infections. Certain drugs, such as loop diuretics and neuroleptics, are thought to alter the immune response to specific antigens or, conversely, modify the antigenic properties of the epidermal basement membrane leading to the development of BP.1,2,8 Infections such as human herpesvirus, hepatitis B and C viruses, Helicobacter pylori, and Toxoplasma gondii have also been associated with the development of BP.1 Other triggers linked to the development of this disease include trauma, burns, radiotherapy, ultraviolent radiation, various autoimmune disorders, psoriasis, and certain neurologic disorders.2
Patients with BP often present with an intensely pruritic eruption of tense vesicles/bullae and annular urticarial plaques that overlie either normal or inflamed, erythematous skin.2,9 The bullae tend to develop on the trunk and flexural surfaces, often in a symmetrical distribution.8 As many as 10% to 20% of patients have mucosal involvement, with the oral mucosa most commonly affected.8 BP bullae are usually preceded by a prodromal nonbullous phase characterized by intense pruritus and eczematous patches and/or fixed urticarial-like lesions.1,2 This prodromal phase can sometimes persist for months to years prior to bullae development.8
The gold standard in establishing a diagnosis of BP is by lesional fixed tissue histopathology and perilesional direct immunofluorescence (DIF) analysis.10 Light microscopy usually shows subepidermal blister formation with a superficial dermal eosinophilic infiltrate.1 DIF analysis shows linear IgG and/or complement C3 deposition at the epithelial basement membrane zone.1-3,8 Enzyme-linked immunosorbent assay (ELISA) has recently become more widely used for the detection of recombinant BP180 circulating antibodies, given its high sensitivity (~92%) and specificity (~98%).3 At present, there are no generally accepted criteria for the diagnosis of BP; however, according to Vaillant et al, diagnosis of BP can be made when 3 of the 4 clinical criteria are present: (1) age >70 years, (2) absence of atrophic scars, (3) absence of mucosal involvement, and (4) absence of predominant bullous lesions on the neck and head.3,8
BP can bear close resemblance to a variety of dermatoses including localized or generalized drug reactions, contact and allergic dermatitis, urticarial vasculitis, arthropod reactions, scabies, ecthyma, or even pityriasis lichenoides. In addition, several other autoimmune blistering diseases can mimic BP, including linear IgA dermatosis, pemphigoid gestationis, and epidermolysis bullosa acquisita. Therefore, a detailed patient history, clinical evaluation, histopathologic examination displaying the characteristic findings of BP, and DIF studies are crucial components necessary to distinguish BP from other similarly presenting disorders.2
Linear IgA dermatosis and BP both present with subepidermal splitting; therefore, DIF must be used to distinguish between these 2 diseases. In BP, DIF shows C3 and IgG deposition, whereas C3 and IgA deposits are present in linear IgA dermatosis.11,12 Furthermore, bullous pemphigoid has a predominantly eosinophilic infiltrate, while linear IgA dermatosis has a largely neutrophilic infiltrate.3
Pemphigoid gestationis is an autoimmune bullous dermatosis that occurs in the second or third trimester of pregnancy.13 BP cannot be differentiated from pemphigoid gestationis in the urticarial or bullous stage of the disease, and the histopathology of pemphigoid gestationis is similar to cell-rich BP.12 However, the diseases can be distinguished clinically as BP usually affects the thighs and lower legs of the elderly and has not been reported in pregnancy.13 Epidermolysis bullosa acquisita can be distinguished from BP by the detection of IgG autoantibodies to type VII collagen at the cutaneous basement membrane zone.14
Because bullous pemphigoid is a chronic fluctuating disease, the primary goal of treatment is to reduce the symptomatic blister burden and to improve the patient’s quality of life. The standard of care for the treatment of disease involves either high-potency topical corticosteroids or systemic corticosteroids, both of which have been found to lead to a significant reduction in BP180 and BP230 autoantibodies.8 Due to the poor tolerability and side effects of systemic corticosteroids, especially in elderly patients, more dermatologists are preferring high-potency topical corticosteroids, such as clobetasol propionate, for the management of patients with moderate disease.4,8 However, if topical steroids fail to provide adequate relief, systemic corticosteroids are an appropriate option.15 Systemic antibiotics, such as tetracyclines, and adjunctive immunosuppressants, such as azathioprine, are also used as adjunctive treatment.15,16 A few cases have even reported benefits with therapy targeting anti-BP180 IG3 through omalizumab use. This method of immunoadsorption resulted in rapid decreases of circulating antibodies; however, this method is not widely used.8
In the case presented here, the patient underwent biopsy of one of his lesions, the findings of which were consistent with a diagnosis of bullous pemphigoid. The patient was initiated on oral prednisone. At his follow-up appointment 3 weeks later, the patient’s blister burden had substantially decreased and his pruritus had diminished. He was instructed to continue the prednisone with an extended-taper dosing schedule in place.
Click to the next page for Case 2.