On physical examination, symmetric urticarial plaques are identified on both knees and the extensor surfaces of both arms.
A 46-year-old woman presents to the clinic with a 6-week history of a bumpy, itchy rash on her arms and legs. She is otherwise healthy and has no known family history of skin conditions. On physical examination, symmetric urticarial plaques are identified on both knees with overlying grouped vesicles and erosions. The patient also has symmetrically grouped vesicles and erosions over the extensor surfaces of both arms. Skin biopsy reveals subepidermal vesicles filled with neutrophils and eosinophils.
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Dermatitis herpetiformis is a chronic skin eruption that presents as a cutaneous manifestation in patients with celiac disease, a gluten-sensitive enteropathy. The rash presents as pruritic papulovesicles in a characteristic distribution, mainly across the elbows, knees, and buttocks.1 Patients typically present with skin manifestations as the only complaint and are often unaware of the underlying small bowel disease.2
Like celiac disease, dermatitis herpetiformis is most common in individuals of European descent and can be diagnosed at any age. However, unlike celiac disease, dermatitis herpetiformis rarely presents in early childhood, with most diagnoses made in the third or fourth decades of life. While celiac disease is more common in women, studies have shown dermatitis herpetiformis to be slightly more prevalent in men.3
Dermatitis herpetiformis can be caused by genetic or environmental factors. Genetic screening has shown a strong association between dermatitis herpetiformis and HLA-DQ2 in 95% of patients.1 The rash is generated by immunocomplexes of gluten-induced IgA autoantibodies against the autoantigen, epidermal transglutaminase, accumulating in the superficial papillary dermis.4 Due to the genetic predisposition for both dermatitis herpetiformis and celiac disease, screening close family members for the presence of antibodies against transglutaminases is indicated to identify forms of gluten sensitivity. Dietary gluten is the main environmental cause of the immunologic reaction; however, exposure to iodine can also precipitate severe clinical manifestations.1
Dermatitis herpetiformis can be diagnosed clinically if the typical distribution pattern of grouped papulovesicles on an erythematous base is seen across the elbows, knees, buttocks, shoulders, and scalp. While not always present, petechiae may be observed on the fingertips and toes.5 The diagnosis is confirmed with histopathologic examination of the skin and direct immunofluorescence. Histopathology reveals subepidermal blister formation with accumulations of neutrophils and scant eosinophils at the papillary tips. Immunopathology can reveal granular deposits of IgA in the papillary dermis, the basement membrane, or a combination of both.6 The most sensitive diagnostic marker, serologic testing, can be performed to detect the presence of IgA antibodies against transglutaminases.1 Small bowel biopsy is unnecessary but may serve as additional evidence of celiac disease if the characteristic villous atrophy is seen on microscopic examination.
While dermatitis herpetiformis is the best characterized extraintestinal manifestation of celiac disease, other mucocutaneous symptoms associated with celiac disease — such as urticaria, atopic dermatitis, psoriasis, or rosacea — may present similarly.7 The differential diagnosis may also include scabies, impetigo, or bullous pemphigoid. Therefore, the characteristic distribution pattern in addition to histopathology and direct immunofluorescence are used to differentiate dermatitis herpetiformis from similar presentations.6 Because patients typically present in the absence of gastrointestinal symptoms, identifying these skin manifestations may lead to a diagnosis of latent or silent celiac disease.
The treatment associated with the best prognosis and eventual remission is a strict gluten-free diet. The gastrointestinal symptoms are relieved more rapidly than the skin manifestations, which require an average of 2 years to resolve completely. Patients may also take oral dapsone to alleviate pruritus and inflammation in the period before improvements are seen as a result of a gluten-free diet. Sulfasalazine, sulfamethoxypyridazine, or potent topical steroids can be used as second-line treatment for alleviating symptoms if the desired effects are not achieved with dapsone therapy.6
After initiating a gluten-free diet and observing its effects, following up with patients can allow for confirmation of the diagnosis and prevention of other related comorbidities. In order to ensure adherence to a gluten-free diet, patients must be monitored regularly and consult with dietitians. Strict adherence to a gluten-free diet has shown a reduction in the risk for developing B-cell or T-cell lymphomas associated with dermatitis herpetiformis.8 Additionally, monitoring is advised as patients with dermatitis herpetiformis are at risk of developing other autoimmune diseases, such as type I diabetes, vitiligo, pernicious anemia, and alopecia areata, as well as disorders related to malabsorption, such as microcytic or megaloblastic anemias.1 Patients receiving dapsone therapy require regular blood monitoring in the early stages due to possible hematologic adverse effects, such as hemolytic anemia or methemoglobinemia.6
The patient in the case above adhered to a strict gluten-free diet and received 25 mg oral dapsone daily. At 6-month follow-up, dramatic regression of her skin lesions was noted.
Rachel Graubard, BS, is a medical student; Talia Noorily, BA, is a medical student; and Christopher Rizk, MD, is a dermatology fellow at Baylor College of Medicine, in Houston, Texas.
- Kárpáti S. Dermatitis herpetiformis. Clin Dermatol. 2012;30(1):56-59.
- Krishnareddy S, Lewis SK, Green PH. Dermatitis herpetiformis: clinical presentations are independent of manifestations of celiac disease. Am J Clin Dermatol. 2013;15(1):51-56.
- Reunala T, Salmi TT, Hervonen K, Kaukinen K, Collin P. Dermatitis herpetiformis: a common extraintestinal manifestation of coeliac disease. Nutrients. 2018;10(5):602.
- Borroni G, Biagi F, Ciocca O, et al. IgA anti-epidermal transglutaminase autoantibodies: a sensible and sensitive marker for diagnosis of dermatitis herpetiformis in adult patients. J Eur Acad Dermatol Venereol. 2012;27(7):836-841.
- Zaghi D, Witheiler D, Menter AM. Petechial eruption on fingers. JAMA Dermatol. 2014;150(12):1353-1354.
- Caproni M, Antiga E, Melani L, Fabbri P. Guidelines for the diagnosis and treatment of dermatitis herpetiformis. J Eur Acad Dermatol Venereol. 2009;23(6):633-638.
- Rodrigo L, Beteta-Gorriti V, Alvarez N, et al. Cutaneous and mucosal manifestations associated with celiac disease. Nutrients. 2018;10(7):800.
- Hervonen K, Vornanen M, Kautiainen H, Collin P, Reunala T. Lymphoma in patients with dermatitis herpetiformis and their first-degree relatives. Br J Dermatol. 2005;152(1):82-86.