Definition and Epidemiology

Bullous pemphigoid (BP) is the most common of the auto­immune blistering diseases affecting primarily the elderly population.^1,2 It belongs to the group of pemphigoid diseases characterized by the presence of circulating immunoglobulin G (IgG) autoantibodies against structural proteins of the dermal-epidermal junction leading to tissue damage and blister formation.³ Incidence increases in older adults, with the majority of patients diagnosed older than 70 years.^1,3–5 Males and females are equally affected, and there is no apparent racial predilection. Childhood-onset BP has been reported in the literature; however, is it generally self-limited.⁶

Pathophysiology

The hallmark of BP is the presence of circulating and tissue-bound IgG autoantibodies specific for the hemidesmosomal BP antigens BP230 and BP180.^1,7 These autoantibodies along with complement components bind to the basement membrane at the dermal-epidermal junction of the perilesional skin. Complement activation attracts inflammatory cells (lymphocytes, histiocytes, eosinophils) to the skin basement membrane, initiating release of proteolytic enzymes that lead to degradation of the hemidesmosomal proteins, resulting in blister formation.⁷

Clinical Presentation and Physical Examination

Patients with BP often experience a nonbullous prodromal phase characterized by mild to severe pruritus accompanied by erythematous, eczematous papules and/or urticarial lesions. These nonspecific skin eruptions lasting several weeks to months may be the only early signs of the disease and often delay the diagnosis of BP.^3,4 Constitutional symptoms are absent except in severe widespread disease.

The bullous phase may appear suddenly with intense pruritus and widespread blister formation symmetrically distributed primarily on the abdomen and the flexor aspects of the extremities (axillae, medial aspects of groin, thighs, flexor aspects of forearms and lower legs). The tense oval or round blisters are filled with either clear or hemorrhagic exudate erupting on either normal or erythematous skin accompanied by urticarial plagues and papules. Blisters may persist for several days, either rupturing or collapsing, resulting in oozing erosions and crusts.⁷ Oral lesions develop in 10% to 20% of patients; however, eyes, nose, esophagus, and anogenital areas are rarely affected.^1,3

Triggers that have been reported to precipitate the onset of BP include traumatic, pharmacologic, or infectious agents. Trauma to the skin such as burns, radiotherapy, and ultraviolet radiation can trigger BP. Drugs associated with the onset of BP include furosemide, phenacetin, enalapril, ibuprofen, influenza vaccine, and several antibiotics (penicillamine, ampicillin, penicillin, and cephalexin).^1,3,7 Infections such as human herpesvirus (HHV), Epstein-Barr virus, cytomegalovirus, and hepatitis B and C may contribute to the induction of BP.⁷

Physical examination begins with general appearance and vital signs, observing for signs of discomfort or toxicity. Although skin lesions may involve any part of the body in BP, inspection of the skin should focus on the axillae, groin, and flexor aspects of the extremities and lower legs for papular or urticarial lesions, excoriations, hemorrhagic crusts, vesicles, and erosions. Mucous membranes must be inspected for blisters or erosions in the oropharynx, conjunctiva, and genitalia. Nikolsky sign (ability to split or dislodge the epidermis from the dermis by applying lateral pressure with a finger resulting in an erosion) is negative in patients with BP.^2,8