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Dermatitis Herpetiformis

Basics

  • Autoimmune disease presenting as chronic, relapsing, polymorphous, intensely pruritic erythematous papulovesicular eruption.
  • Symmetric distribution mainly on extensor surfaces: elbows, knees, buttocks, back, scalp.
  • Strong association with gluten-sensitive enteropathy (GSE) and celiac disease (CD).
  • Also called Duhring disease or Duhring-Brocq disease.
  • Equal male-to-female incidence; common in 4th decade; most frequent in Northern European descent.

Epidemiology

  • Incidence: up to 2.6 per 100,000 per year.
  • Prevalence: up to 39.2 per 100,000.

  • 90% have GSE; only 20% symptomatic for celiac disease.

  • Rare in Asian and African American populations.

Etiology and Pathophysiology

  • Epidermal transglutaminase (eTG3) is the key autoantigen; closely related to tissue transglutaminase (tTG).
  • Gluten peptides interact with tTG, forming autoantigens presented via MHC II molecules.
  • IgA antibodies against tTG cross-react with eTG forming immune complexes deposited in papillary dermis.
  • Complement activation and neutrophil recruitment cause inflammation and microabscesses.
  • Skin eruption delayed 5-6 weeks after gluten exposure.
  • Gluten exposure via GI tract necessary; topical gluten does not induce rash.
  • Strong HLA association: HLA-DQ2 (~95%), others DQ8, DR4, DR3.

Risk Factors

  • Gluten-sensitive enteropathy (>90%).
  • Family history of DH or celiac disease.

General Prevention

  • Strict gluten-free diet (GFD) improves symptoms, reduces medication dependence and lymphoma risk.

Commonly Associated Conditions

  • Thyroid disorders (hypo-/hyperthyroidism, nodules, cancer)
  • Celiac disease and gluten ataxia
  • Gastric atrophy, pernicious anemia
  • GI and non-Hodgkin lymphoma
  • IgA nephropathy
  • Other autoimmune disorders: lupus, dermatomyositis, Sjögren’s, rheumatoid arthritis, sarcoidosis, Raynaud, diabetes mellitus type 1, myasthenia gravis, Addison disease, vitiligo, alopecia areata, primary biliary cirrhosis, psoriasis

Diagnosis

History

  • Pruritic, symmetric papulovesicular eruption waxing and waning, worsens with gluten intake.
  • GI symptoms often absent or subtle.

Physical Exam

  • Symmetric, grouped erythematous papules and vesicles on extensor elbows (90%), knees (30%), shoulders, buttocks, sacrum, scalp.
  • Lesions often excoriated, lichenified, or pigmentarily altered from scratching.
  • Rare oral involvement.
  • Children: purpura on digits and palms/soles.

Differential Diagnosis

Adults:
- Bullous pemphigoid (linear C3, IgG deposition)
- Linear IgA disease (linear IgA deposition; no gluten sensitivity)
- Prurigo nodularis
- Urticaria
- Erythema multiforme

Children:
- Atopic dermatitis
- Scabies
- Papular urticaria
- Impetigo

Diagnostic Tests

  • Serology:
  • Serum IgA tTG antibodies (up to 95% sensitive, >90% specific)
  • Serum IgA eTG antibodies (more sensitive than tTG but less widely available)

  • Serum IgA endomysial antibodies (EMA) (50-100% sensitivity, ~100% specificity; expensive and operator-dependent)

  • Genetic testing:

  • HLA-DQ2, HLA-DQ8 haplotypes may help in unclear cases or screening.

  • Gold standard:

  • Direct immunofluorescence (DIF) of perilesional skin: granular IgA deposits in dermal papillae/basement membrane. Sensitivity and specificity ~100%.

  • Histopathology:

  • Neutrophilic microabscesses at dermal papillae tips; subepidermal blisters may be present.

Treatment

General Measures

  • Gluten-free diet (GFD) is mainstay; requires 18-24 months strict adherence to resolve lesions without meds.
  • Lesions may recur within 12 weeks of gluten reintroduction.
  • Some patients may tolerate small amounts after prolonged remission.

Medication

  • First line: Dapsone (FDA approved)
  • Initial dose: 25-50 mg/day, titrate slowly to response (avg maintenance 1 mg/kg/day; up to 300 mg/day).
  • Symptom improvement within 24-72 hours.
  • Mechanism: inhibits neutrophil recruitment, IL-8 release, and respiratory burst.
  • Side effects: nausea, headache, dizziness, hemolysis (Hb drop 1-2 g common at 100 mg).
  • Monitor for sulfone syndrome: fever, jaundice, hepatic necrosis, exfoliative dermatitis, methemoglobinemia, hemolytic anemia.
  • Pediatric: >2 years dosing 0.5-1.0 mg/kg/day; <2 years not established.

  • Pregnancy: category C; avoid if possible; secreted in breast milk causing infant hemolysis.

  • Second line:

  • High-potency topical steroids (short term)
  • Sulfapyridine (1-2 g/day), sulfasalazine metabolite, side effects include nausea, agranulocytosis, hemolysis.
  • Topical steroids and 3rd-gen antihistamines for pruritus.
  • JAK inhibitors (tofacitinib) showing recent promise.

Issues for Referral

  • Dermatology, gastroenterology, dietitian for interdisciplinary management.

Ongoing Care

  • Follow-up every 6-12 months to monitor gluten-free diet adherence and symptom recurrence.
  • Monitor serologic markers (anti-tTG, anti-eTG, EMA).
  • Dapsone lab monitoring weekly (1st month), biweekly (2 months), then quarterly.

Diet

  • Avoid gluten: wheat (spelt, Kamut, semolina, triticale), rye, barley (including malt).
  • Safe gluten-free grains: rice, amaranth, buckwheat, corn, millet, quinoa, sorghum, teff, oats (gluten-free source only).
  • Gluten-free starches: arrowroot, jicama, taro, potato, tapioca.
  • Legumes, nuts, seeds generally safe.

Patient Education

  • Warn about hemolytic anemia and methemoglobinemia symptoms when on dapsone.
  • Support groups and resources provided.

Prognosis

  • Excellent with strict GFD adherence.
  • 10-15 year survival comparable to general population.
  • Remission in 10-15%.
  • Skin disease responds rapidly to dapsone; minor outbreaks common but not requiring dose changes.
  • GFD may reduce lymphoma risk.

Complications

  • Related mostly to gluten-sensitive enteropathy: malnutrition, anemia, osteoporosis, autoimmune disorders, increased lymphoma risk.

ICD10 Codes:
- L13.0 Dermatitis herpetiformis

Clinical Pearls:
- DH is a chronic, intensely pruritic, polymorphic rash with a strong association with gluten-sensitive enteropathy.
- DIF demonstrating granular IgA deposits in dermal papillae is diagnostic gold standard.
- Gluten-free diet is key to long-term control; dapsone is for rapid symptom relief only.