Dermatology MCQ - Inflammatory Dermatoses - Dermatitis herpetiformis

A 32-year-old man presents with a several-month history of extremely pruritic, grouped vesicles and excoriated papules distributed symmetrically over his elbows, knees, and buttocks. Which of the following diagnostic findings is considered the gold standard for confirming dermatitis herpetiformis?

A. Circulating anti-tissue transglutaminase (tTG) IgA antibodies
B. Granular deposition of IgA in the dermal papillae on direct immunofluorescence
C. A positive response to a gluten-free diet
D. Subepidermal blister with neutrophilic microabscesses on histology
E. HLA-DQ2 or HLA-DQ8 haplotype positivity

Correct Answer: B. Granular deposition of IgA in the dermal papillae on direct immunofluorescence

Explanation

Dermatitis herpetiformis (DH) is the cutaneous manifestation of gluten sensitivity and is considered a specific immunopathologic entity. While it is intimately associated with celiac disease, its diagnosis is confirmed by a distinct dermatopathological finding.

• Gold Standard Diagnostic Test: The definitive diagnosis of dermatitis herpetiformis is established by direct immunofluorescence (DIF) performed on a perilesional skin biopsy (taken from normal-appearing skin immediately adjacent to a lesion). This test reveals pathognomonic granular or fibrillar deposits of IgA in the dermal papillae. This finding is present in almost 100% of active, untreated cases and is unique to DH.

Why other options are incorrect

• A. Circulating anti-tissue transglutaminase (tTG) IgA antibodies: This is a highly sensitive and specific serological test for celiac disease and is almost always positive in patients with active DH. It is an excellent screening tool and supports the diagnosis, but it is not the definitive gold standard for diagnosing the skin disease itself. A patient could have celiac disease without DH.

• C. A positive response to a gluten-free diet: The clinical response to a gluten-free diet is characteristic and provides strong supportive evidence, but it is not a diagnostic test. A therapeutic trial is not a substitute for a definitive histological diagnosis.

• D. Subepidermal blister with neutrophilic microabscesses on histology: This is the characteristic finding on routine histology (H&E stain) of a fully developed lesion. It is highly suggestive of DH but is not entirely specific, as it can be seen in other neutrophilic dermatoses like Linear IgA disease and bullous lupus. DIF is required for definitive differentiation.

• E. HLA-DQ2 or HLA-DQ8 haplotype positivity: Over 90% of patients with DH carry these haplotypes. However, this is a genetic susceptibility marker, not a diagnostic test for the active disease, as a significant portion of the healthy population also carries these haplotypes.

Key Associations for Dermatitis Herpetiformis (DH)

• Pathogenesis: DH is an autoimmune disorder triggered by gluten ingestion in genetically predisposed individuals. The immune response involves the production of IgA autoantibodies against tissue transglutaminase (tTG) in the skin, which leads to neutrophil recruitment and subsequent microabscess formation.

• Clinical Presentation: The hallmark is intense, burning, or stinging pruritus. Primary lesions are vesicles, but they are often destroyed by scratching, so patients typically present only with excoriations, erosions, and crusted papules grouped symmetrically on extensor surfaces (elbows, knees, buttocks, shoulders, and scalp).

• Systemic Association: Virtually all patients with DH have an associated gluten-sensitive enteropathy (Celiac Disease), though it may be asymptomatic or subclinical. All patients should be evaluated by a gastroenterologist.

• Histopathology: A lesional biopsy shows a subepidermal blister with neutrophilic microabscesses at the tips of the dermal papillae. This is the histological correlate of the DIF finding.

• Differential Diagnosis: Includes scabies, atopic dermatitis, linear IgA disease, bullous pemphigoid, and neurotic excoriations. The distribution and DIF findings are key to differentiation.

• Management:

  1. Strict, lifelong gluten-free diet: This is the cornerstone of management, which controls the skin disease over time and reduces the long-term risk of intestinal lymphoma associated with celiac disease.

  2. Pharmacologic Therapy: Dapsone is the first-line drug for rapid symptomatic control, providing relief within 24-48 hours. It suppresses the neutrophil-mediated inflammation but does not treat the underlying enteropathy.