Question:

A 14-month-old girl is brought to the clinic by her parents due to sores on her feet. Since she took her first steps 3 months ago, she has had blisters involving the soles of the feet, which subsequently break down and heal slowly. The patient had failure to thrive as an infant due to frequent oral ulcerations but otherwise has been healthy and has achieved normal developmental milestones. Examination shows small bullae at the soles with faint erythema and no scarring. Biopsy taken at the margin of a blister shows an intraepidermal cleavage plane. Which of the following most likely contributes to the pathogenesis of this patient's condition?

Autoantibodies against tissue transglutaminase

Impaired keratin filament assembly

Loss of function mutation in filaggrin

T-cell–mediated hypersensitivity reaction

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Epidermolysis bullosa
Etiology	Inherited disorders Mutations involving intraepidermal & dermoepidermal adhesion complexes
Clinical features	Onset in infancy/childhood Bullae, erosions & ulcers Lesions triggered by friction or minor trauma Histopathology: intraepidermal cleavage most common
Complications	Malnutrition Infection

Epidermolysis bullosa (EB) is a group of inherited disorders caused by mutations involving intraepidermal and dermoepidermal adhesion complexes in the basement membrane zone. It is characterized by epithelial fragility (eg, bullae, erosions, ulcers) triggered by minor trauma. Light microscopy of skin biopsy typically shows intraepidermal cleavage, although the plane of cleavage can vary based on subtype.

The most common form of EB, EB simplex, is caused by mutations in keratin genes that impair the assembly of keratin into filaments. It presents early in life with friction-induced blisters at the palms and soles and other exposed areas. Lesions typically heal with no residual scarring, although patients may have chronic thickening of the skin of the feet. Infants with EB simplex may develop oral blisters with bottle-feeding.

(Choice A) Dermatitis herpetiformis is caused by autoantibodies against tissue transglutaminase. It presents with small, intensely pruritic vesicles on the elbows, knees, and buttocks and is typically seen in patients with gluten-sensitive enteropathy (ie, celiac disease).

(Choice C) Atopic dermatitis is a multifactorial disorder but is commonly seen in association with loss of function mutations in filaggrin and other epidermal barrier proteins. Infants have red, crusted lesions at the extensor surfaces and face, whereas older children and adults have pruritic patches and lichenification at flexural areas.

(Choice D) A delayed T-cell–mediated hypersensitivity reaction is responsible for allergic contact dermatitis (eg, poison ivy/rhus dermatitis), which presents acutely with pruritic vesicles at sites of contact.

Educational objective:
Epidermolysis bullosa is a group of inherited disorders characterized by epithelial fragility (eg, bullae, erosions, ulcers) triggered by minor trauma. It is caused by mutations affecting proteins in the intraepidermal and dermoepidermal adhesion complexes; keratin mutations are responsible for the most common form (EB simplex).