Description

• Dermatitis herpetiformis (DH) presents as a chronic, relapsing, polymorphous, intensely pruritic, erythematous papulovesicular eruption with symmetrical distribution primarily involving extensor skin surfaces of the elbows, knees, buttocks, back, and scalp.
• DH is an autoimmune disease associated with gluten sensitivity with genetic, environmental, and immunologic influences.
• DH is distinguished from other bullous diseases by characteristic histologic and immunologic findings as well as associated gluten-sensitive enteropathy (GSE).
• System(s) affected: skin
• Synonym(s): Duhring disease, Duhring-Brocq disease

Epidemiology

• Occurs most frequently in those of Northern European origin
• Rare in persons of Asian or African American origin
• Predominant age: most common in 4th and 5th decades but may present at any age
• Childhood DH is rare in most countries, although an Italian study showed 27% of patients were age of <10 years and 36% age of <20 years.
• Predominant gender: adults: male > female (1.5:1 in the United States, 2:1 worldwide); children: female > male

Incidence
1/100,000 persons per year in the United States

Prevalence
11/100,000 persons in the U.S. population; as high as 39/100,000 persons worldwide

Etiology and Pathophysiology

• Evidence suggests that epidermal transglutaminase (eTG) 3, a keratinocyte enzyme involved in cell envelope formation and maintenance, is the autoantigen in DH.
• eTG is highly homologous with tissue transglutaminase (tTG), which is the antigenic target in celiac disease and GSE.
• The initiating event for DH is presumed to be the interaction of wheat peptides with tTGs, which results in the formation of an autoantigen with high affinity for particular class II major histocompatibility complex (MHC) molecules.
• Presentation of the autoantigen leads to activation of T cells and the humoral immune system.
• IgA antibodies against tTG cross-react with eTG and result in IgA-eTG immune complexes that are deposited in the papillary dermis. Subsequent activation of complement and recruitment of neutrophils to the area result in inflammation and microabscesses.
• Skin eruption may be delayed up to 5 to 6 weeks after exposure to gluten.
• Gluten applied directly to the skin does not result in the eruption, whereas gluten taken by mouth or rectum does. This implies necessary processing by the GI system.
• Thought to be immune complex–mediated disease

Genetics

• High association with human leukocyte antigen (HLA)-DQ2 (95%), with remaining patients being positive for DQ8, DR4, or DR3
• Strong association with combination of alleles DQA1*0501 and DQB1*0201/0202, DRB1*03 and DRB1*05/07, or DQA1*0301 and DQB1*0302

Risk Factors

• GSE: >90% of those with DH will have GSE, which may be asymptomatic.
• Family history of DH or celiac disease

General Prevention

Gluten-free diet (GFD) results in improvement of DH and reduces dependence on medical therapy. GFD also may reduce the risk of lymphomas associated with DH.

Commonly Associated Conditions

• Hypothyroidism is the most common condition associated with DH.
• GSE, gluten ataxia
• Gastric atrophy, hypochlorhydria, pernicious anemia
• GI lymphoma, non-Hodgkin lymphoma
• Hyperthyroidism, thyroid nodules, thyroid cancer
• IgA nephropathy
• Autoimmune disorders, including systemic lupus erythematosus, dermatomyositis, Sjögren syndrome, rheumatoid arthritis, sarcoidosis, Raynaud phenomenon, insulin-dependent diabetes mellitus, myasthenia gravis, Addison disease, vitiligo, alopecia areata, primary biliary cirrhosis, and psoriasis