Description

• Dermatitis herpetiformis (DH) is a chronic, intensely pruritic, papulovesicular eruption involving primarily extensor skin surfaces of elbows, knees, buttocks, back, and the scalp.
• DH is a multifactorial disease 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.
• System(s) affected: Skin
• Synonym(s): Duhring disease

Epidemiology

• Occurs most frequently in those of Northern European origin
• Rare in persons of Asian or African American origin
• Predominant age: Most common between the ages of 30 and 40 years, but may present at any age
• Predominant sex: Male > Female (1.4:1 in the US, 2:1 worldwide)

Incidence
1/100,000 persons per year in the US

Prevalence
11/100,000 persons in the US population; as high as 39/100,000 persons worldwide

Risk Factors

• Gluten-sensitive enteropathy (GSE): >90% of those with DH will have GSE, which may be asymptomatic.
• Family history of DH or celiac disease (CD)

• High association with human leukocyte antigen DQ2 (90%) 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

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.

Pathophysiology

• Evidence suggests that epidermal transglutaminase (eTG) 3, a keratinocyte enzyme involved in cell envelope formation, is the autoantigen in DH.
• eTG is highly homologous with tissue transglutaminase (tTG), which is the antigenic target in CD 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 tTGs 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 blistering.
• Skin eruption may be delayed 5–6 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.

Etiology

Thought to be immune complex–mediated disease

Commonly Associated Conditions

• Gluten-sensitive enteropathy, gluten ataxia
• Gastric atrophy, hypochlorhydria, pernicious anemia
• GI lymphoma, non-Hodgkin lymphoma
• Hypothyroidism, hyperthyroidism, thyroid nodules, thyroid cancer
• Down syndrome, Turner syndrome
• Glomerulopathy
• Autoimmune disorders, including systemic lupus erythematosus, dermatomyositis, Sjögren syndrome, rheumatoid arthritis, Raynaud phenomenon, insulin-dependent diabetes mellitus, myasthenia gravis, Addison disease, vitiligo, alopecia areata, primary biliary cirrhosis and psoriasis