A 52-year-old woman comes to the office due to a 2-month history of oral lesions that cause pain with chewing and swallowing food. The patient did not seek treatment because she thought the lesions would go away on their own, but they have persisted. On examination, there are erosions of the buccal and gingival mucosa, as shown in the image below. There are several flaccid bullae with erosions scattered over her trunk. The blisters spread laterally with pressure, and traction on seemingly uninvolved skin produces blistering. Autoantibodies directed against which of the following structures are most likely responsible for this process?

Question

A 52-year-old woman comes to the office due to a 2-month history of oral lesions that cause pain with chewing and swallowing food.  The patient did not seek treatment because she thought the lesions would go away on their own, but they have persisted.  On examination, there are erosions of the buccal and gingival mucosa, as shown in the image below.  There are several flaccid bullae with erosions scattered over her trunk.  The blisters spread laterally with pressure, and traction on seemingly uninvolved skin produces blistering.  Autoantibodies directed against which of the following structures are most likely responsible for this process?

Quizplus · Accepted Answer

11ec160b_3900_3986_9249_7bdeeb653097_MD0001_00 This patient has pemphigus vulgaris (PV), an autoimmune bullous disease characterized by painful, flaccid bullae and erosions of the skin and mucosal membranes. Any mucosal site can be involved, but the oral mucosa is the most common. The bullae are structurally weak and often rupture prior to presentation, with only erosions remaining. The bullae spread laterally when pressure is applied on top (ie, Asboe-Hansen sign), and new blisters may form with gentle traction or rubbing (ie, Nikolsky sign). The underlying pathophysiology of PV involves autoantibodies directed against desmosomes, specifically desmogleins 1 and 3, which disrupt cohesion of keratinocytes. Biopsy of an active PV lesion will show intraepithelial cleavage with detached keratinocytes (acantholysis), retained keratinocytes along the basement membrane and an eosinophilic inflammatory infiltrate. Direct immunofluorescence of unaffected skin adjacent to PV lesions will show epidermal intercellular IgG and C3 deposits. Circulating autoantibodies against desmogleins are present in many patients and can aid diagnosis. (Choice A) Autoantibodies against cutaneous basement membrane proteins are characteristic of epidermolysis bullosa acquisita (forms tense acral bullae) and cicatricial pemphigoid (causes chronic conjunctivitis and scarring). (Choice B) No known cutaneous diseases result from connexin autoimmunity, but connexin defects do underlie some specific forms of palmoplantar keratoderma, which causes epidermal hyperproliferation of the palms and soles, or deafness-associated ichthyosis. (Choice D) Autoantibodies against hemidesmosomal proteins cause bullous pemphigoid, in which the bullae are usually tense and remain intact as the entire epidermis separates from the dermis (no intraepithelial cleavage). In addition, mucosal involvement is less common and Nikolsky sign is usually negative. (Choice E) Autoantibodies against tissue transglutaminase result in celiac disease and dermatitis herpetiformis, an autoimmune cutaneous eruption associated with gluten sensitivity. The eruption is characterized by grouped (herpetiform) erythematous papulovesicles that are intensely pruritic, not painful; oral mucosal involvement is rare. Educational objective: Pemphigus vulgaris is an autoimmune bullous disease characterized by autoantibodies directed against desmosomal proteins (eg, desmogleins). It presents with painful, flaccid bullae and erosions affecting the skin and mucosal membranes. The bullae spread laterally with pressure, and new blisters may form with gentle rubbing.

A 52-Year-Old Woman Comes to the Office Due to a 2-Month