Resident Program - Case of the Month

March 2023 – Presented by Dr. Yuden Pemba (Mentored by Dr. Maija Kiuru)

Discussion

B) Bullous Pemphigoid

Introduction

Bullous pemphigoid is the most common autoimmune subepidermal blistering disorder. It most commonly affects elderly patients over the age of 60. In the early stage of bullous pemphigoid, patients often experience pruritus, either by itself or in combination with urticarial plaques and bullae on the trunk and extremities. The bullae are tense (in contrast to pemphigus vulgaris, where bullae are flaccid) ranging in size from 1 to 4 cm and containing clear fluid. They may take several days to heal and can leave behind erosions and crusts. Constitutional symptoms, such as fatigue or fever, are not typical unless the disease is widespread and severe.

Etiology

Autoantibodies directed against basement membrane zone hemidesmosomal proteins cause most cases of bullous pemphigoid. However, certain medications can contribute to a subset of cases of bullous pemphigoid. Drug-induced bullous pemphigoid tends to develop within a few months of starting a new medication and is more likely to occur in younger patients. The most common medications linked to drug-induced bullous pemphigoid are spironolactone, furosemide, NSAIDs, amoxicillin, PD-1/PD-L1 inhibitors, gliptins, and TNF-alpha inhibitors.

Pathophysiology

The pathophysiology of bullous pemphigoid involves two main components: immunologic and inflammatory. The immunologic component involves the formation of autoantibodies against two parts of the hemidesmosomal proteins, BP antigen 230 (BPAG1) and BP antigen 180 (BPAG2 or type XVII collagen), which play a crucial role in adhesion between the epidermis and the dermis. These autoantibodies trigger the inflammatory response, activating complement and mast cells and leading to the release of proteolytic enzymes from neutrophils and eosinophils, resulting in damage to the boundary between the dermal and epidermal layers.

Histopathology

The histopathological findings in bullous pemphigoid typically reveal a subepidermal split with a separation between the epidermis and the underlying dermis. There is an infiltration of inflammatory cells, including eosinophils and lymphocytes, in the blister cavity and in the upper dermis as seen this case. In the early stages of the disease, bullae may be absent, but eosinophils are present around vessels, in between collagen bundles in the dermis, and along the epidermal-dermal junction. Direct immunofluorescence microscopy can be used to demonstrate the presence of linear IgG and C3 deposits at the basement membrane zone, which confirms the diagnosis of bullous pemphigoid.

Differential Diagnosis

The differential diagnosis for bullous pemphigoid includes other immunobullous diseases, urticaria, drug reactions, or arthropod bite reactions.

Arthropod bite reaction (A) presents as a pruritic papule or plaque, occasionally with vesiculation. Histologically it is characterized by a superficial and deep dermal inflammatory cell infiltrate containing many eosinophils, accompanied by spongiosis.

Epidermolysis bullosa (C) is a genetic bullous skin disease that typically presents at birth or in childhood. It is caused by mutations in genes involved in the formation and stability of the basement membrane zone proteins. Direct immunofluorescence is negative.

Linear IgA bullous dermatosis (D) is an autoimmune subepidermal bullous skin disease, characterized by linear deposits of IgA along the basement membrane zone under direct immunofluorescence examination.

Pemphigus vulgaris (E) is characterized by autoantibodies against desmosomal proteins, which can affect skin and mucous membranes, resulting in flaccid blisters with positive Nikolsky sign and under immunofluorescence, revealing intercellular deposits of IgG within the epidermis and adnexal epithelium.

Treatment

The treatment approach for bullous pemphigoid primarily consists of topical corticosteroids, systemic corticosteroids, and doxycycline; depending on the presence of any accompanying health conditions and the severity of the disease. In refractory disease, other immunosuppressive therapies may be considered as an alternative treatment option.

Prognosis

Bullous pemphigoid is a chronic disease characterized by exacerbations and remissions over months to years. Appropriate treatment can help alleviate symptoms and reduce the risk of life-threatening complications.

References

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