Description

• Dermatitis herpetiformis (DH) is an autoimmune disease that 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 associated with autoimmune diseases, especially celiac disease, in addition to 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 the 4th decade of life but may present at any age
• Equal male-to-female incidence, in comparison to celiac disease which is female dominant.
• >90% have evidence of GSE, whereas only 20% are symptomatic of celiac disease.

Incidence
As high as 2.6/100,000 people per year (1)

Prevalence
As high as 39.2/100,000 people (1)

Etiology and Pathophysiology

• Evidence suggests that epidermal transglutaminase (eTG) 3, 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 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 (1)
• Strong association with a combination of alleles DQA1*0501 and DQB1*0201/0202, DRB1*03 and DRB1*05/07, or DQA1*0301 and DQB1*0302 (2)

Risk Factors

• GSE: >90% of those with DH will have GSE, which may be asymptomatic (1),(3).
• Family history of DH or celiac disease

General Prevention

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

Commonly Associated Conditions

• Hypothyroidism, hyperthyroidism, thyroid nodules, thyroid cancer
• Celiac disease, GSE, gluten ataxia
• Gastric atrophy, hypochlorhydria, pernicious anemia
• GI lymphoma, non-Hodgkin lymphoma
• 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