Dermatitis Herpetiformis

Natalia Plotnikova, BS; Jami L. Miller, MD


Skin Therapy Letter. 2013;18(3) 

In This Article

Pathology and Diagnosis

Characteristically, a biopsy taken from an area near an active DH lesion will show a neutrophilic infiltrate within the dermal papillae and a subepidermal blister with neutrophils (if intact vesicle was captured), as well as a superficial perivascular lymphocytic infiltrate (Figure 2). Direct immunofluorescence reveals granular immunoglobulin A (IgA) deposits, compared to linear IgA deposits in linear IgA bullous dermatosis (Figure 3). Eighty-five percent of deposits are located in dermal papillae or, less commonly, along the basement membrane in granular or fibrillar patterns.[5,6] Biopsy and direct immunofluorescence are often required for a definitive diagnosis considering the various clinical presentations of DH. In view of the hardship for a patient that is imposed by the restrictive diet and rigorous treatment regiment, a correct diagnosis is very important.

Figure 2A.

Light microscopy at low power magnification shows subepidermal bullae accentuated within dermal papillae.

Figure 2B.

Light microscopy at high power magnification shows subepidermal bullae with numerous neutrophils.

Figure 3.

Direct immunofluorescence shows granular IgA deposits at the tips of dermal papillae.

Serologic studies are also helpful in the diagnosis of DH. Direct immunofluorescence tests for anti-endomysium antibodies have high specificity and moderate sensitivity. Anti-tissue transglutaminase (tTG) or transglutaminase 2 (TG2) IgA is an enzyme-linked immunosorbent assay (ELISA) test with reported specificity of 97.6 to 100% and sensitivity of 48.8 to 89.1%.[7,8] A more recent ELISA test for anti-epidermal transglutaminase (eTG) or transglutaminase 3 (TG3) IgA provides even higher sensitivity of 60 to 80.8% and comparable specificity of 92.8 to 100%.[7,9] eTG was also shown to be detected for longer periods of time while on a gluten free diet (GFD) compared to tTG.[9] At this point, serologic testing does not replace a biopsy; however, it provides valuable information. Tests for both types of TG antibodies correlate with intestinal involvement by disease and all three tests can be used to monitor compliance with a strict GFD.[7,9,10] Laboratory testing of total IgA immunoglobulin levels can be monitored but there is an increased prevalence of partial IgA deficiency in DH patients (10-15 times more in CD than in the general population).[11] Human leukocyte antigen (HLA) haplotype testing is not routinely recommended at this time but could be considered if other evaluations are equivocal. HLA-DQ2, present in 95% of DH patients, and DQ8 are associated with DH with high negative predictive value but low specificity considering the high prevalence of these haplotypes in the general population.[12]

While present in more than 90% of CD cases, DH is also observed in other autoimmune conditions, such as Hashimoto's thyroiditis, and, less often, other thyroid dysfunctions.[13,14] It has also been reported in patients with Sjögren's syndrome, rheumatoid arthritis, sarcoidosis, lupus erythematosus, type I diabetes, vitiligo, primary biliary cirrhosis, pernicious anemia, alopecia areata, and Addison's disease.[15–18] Patients with DH have a higher incidence of non-Hodgkin's lymphomas compared to the general population, although no increase in mortality from cancer has been documented.[19,20] The risk of lymphoma appears to be reduced with a strict GFD.[21] Upon DH diagnosis, screening for thyroid disease, anti-thyroid peroxidase antibody titers and blood glucose are recommended.[7] Workup for rheumatologic and connective tissue conditions should also be considered, especially with pertinent systemic symptoms.[7]