Last week my partner, Justin Green MD, asked for my opinion about a man with biopsy-proven dermatitis herpetiformis (neutrophilic abscesses and granular IgA deposition) with negative serologic studies for anti-endomysial antibodies (tissue transglutaminase). He had classical lesions on his elbows (grouped vesicles) but the lower extremity lesions were purpuric.
While dermatitis herpetiformis (DH) may present as a purpuric eruption, most characteristically on the palms (1), and rarely the soles, it may also manifest as leukocytoclastic vasculitis (LCV). Naylor et al presented the case of a 58 year-old man with generalized, pruritic and tender macules and papules with features of both DH and LCV on histology, with an elevated serum IgA anti-tissue transglutaminase; he responded to a gluten-free diet (2).
According to Bolotin and Petronic-Rosic, in their excellent review article on DH, serological testing for DH is a useful adjunct for diagnosing DH and may be used to monitor dietary adherence. “IgA antitissue transglutaminase (tTG) testing is performed by a widely available enzyme-linked immunosorbent assay (ELISA)–based test and has a specificity range of 97.6% to 100% and sensitivity of 48.8% to 89.1%” (3).
While it is well known that DH is characterized by granular IgA and epidermal transglutaminase (TG3) deposition in the papillary dermis, associated with celiac disease, the origin of the TG3-IgA immune complexes is uncertain. The prevailing theories are that these TG3-IgA immune complexes would either diffuse trough the epidermis or deposit in the papillary dermis via the circulation.
Görög A et al developed a “sandwich” ELISA assay to detect TG3-IgA immune complexes, comparing 35 patients with DH to 40 control patients (16 healthy people, 12 with pemphigus vulgaris, and 12 with systemic lupus erythematosus). Untreated patients with DH had a statistically significant increase in the TG3-IgA immune complexes compared to all in the control group. Additionally, when 10 DH patients who improved on a gluten-free diet were retested, there was a significant decrease in the complexes (4).
The demonstration of TG3-IgA immune complexes may explain why patients with DH may present with purpuric or vasculitic lesions. Although the mechanism of how the complexes form awaits further elucidation, I agree with the authors’ conclusion that perhaps this newly developed sandwich ELISA could be of diagnostic value in otherwise serologically negative DH patients.
- McGovern TW, Bennion SD. Palmar purpura: an atypical presentation of childhood dermatitis herpetiformis. Pediatr Dermatol 1994; 11: 319-22.
- Naylor E, et al. Leukocytoclastic vasculitis as the presenting feature of dermatitis herpetiformis. Arch Dermatol 2011; 147: 1313-6.
- Bolotin D, Petronic-Rosic V. Dermatitis herpetiformis. Part II. Diagnosis, management, and prognosis. J Am Acad Dermatol 2011; 64: 1027-33.
- Görög A, et al. Circulating transglutaminase 3-immunoglobulin A immune complexes in dermatitis herpetiformis. J Invest Dermatol 2016: 136: 1729-31.