edited by Elisa Magnanelli M.D.
Dermatitis Herpetiformis is a cutaneous manifestation of Celiac disease and comes up in vesicular rash pathognomonic cutaneous IgA deposits. Dermatitis Herpetiformis, named by Duhring in 1884, was formerly described as part of a set of pathologies including pemphigus and erythema multiforme.
Dermatitis Herpetiformis mainly affects individuals of European origin. Prevalence is nearly 1 in 10,000 in the United Kingdom and in the United States, as far as white population of European origin is concerned, even though higher rates, equal to 4 and 6 in 10,000, have been reported in Switzerland and in Finland, respectively. Dermatitis Herpetiformis rarely affects Asian and African people. Dermatitis Herpetiformis may arise at any age, but rarely affects children and elderly people; the most ordinary age of onset is nearly 40. Unlike Celiac disease, Dermatitis Herpetiformis is more common in men than in women (with a ratio 1.5-1.9:1). Familiarity studies show that 5% of first degree relatives will experience Dermatitis Herpetiformis too, while a further 5% will be affected by Celiac Disease. Both Dermatitis Herpetiformis and Celiac disease show the same high prevalence of haplotypes HLA-DQ2 (90%) and HLA-DQ8 (5%).
Only some of the patients suffering from Celiac disease also develop Dermatitis Herpetiformis, but this mechanism has not been understood yet, as we still ignore which factors link intestinal and cutaneous lesions together. In case of Dermatitis Herpetiformis, IgA are at cutaneous level and inflammatory cells and cytokines can be observed in lesions. Moreover, anti-EMA and anti-tTG antibodies can be found in serum and the rash is gluten-induced. The importance of these factors still remains unknown, as the way how they interact causing cutaneous lesions; nevertheless, antibodies directed against epidermal transglutaminase (TG3) in patients affected by Dermatitis Herpetiformis have recently been identified, and it could represent the main autoantigen regarding this pathology.
The first cutaneous alterations consist of small erythematous macules which rapidly evolve into urticarial papules. Later vesicles arise, which could break, dry up and form scabs. The main symptoms are intense itching and burning sensation. Rash has a characteristic symmetric distribution. Elbows and upper part of forearms are affected in more than 90% of patients. Other body location which are frequently affected are glutei, knees, shoulders, sacrum, face, scalp, neck and torso. The eruption can be widespread or restricted to one or two locations. Once appeared, rash remain stable in the main part of patients, but can have an intermittent course in 10% of cases. Only a small number of patients, nearly 10%, show gastrointestinal symptoms, usually soft. Nevertheless, in 65-70% of patients affected by Dermatitis Herpetiformis a celiac villous atrophy in the upper section of the small intestine mucosa can be detected. Even in case of apparently normal bioptic evidence, light mucosa variations, such as increase in intraepithelial lymphocytes number (IELs), indicate a gluten sensitization. In the serum of patients affected by Dermatitis Herpetiformis a celiac disease autoantibody pattern (antibodies anti-tTG, anti-EMA and anti-DGP) is generally observed. Similarly, patients suffering from Dermatitis Herpetiformis can show the same pattern of clinical manifestations, associated disorders and complications as patients affected by Celiac disease (autoimmune diseases, iron deficiency anaemia, osteoporosis and malignant tumour).
The diagnosis of Dermatitis Herpetiformis consists in IgA identification in non-affected skin on bioptic samples analysed by immunofluorescence method with colouring technique. Dermal papillae are the most common location, where IgA appear as granular or fibrillary deposits. Besides, IgA can form linear granular deposits along the basal membrane. It is important to differentiate between this pattern and homogeneous linear IgA deposits detected in linear IgA disease, which is not gluten-dependent. The diagnosis of Dermatitis Herpetiformis is based on cutaneous biopsies and on the identification of a celiac disease autoimmunity in serum. Since Dermatitis Herpetiformis is the cutaneous counterpart of Celiac disease (“Cutaneous celiac disease”), a definite diagnosis of Dermatitis Herpetiformis in a patient should be considered as an indirect sign of a small bowel damage. According to that, duodenal biopsy is not necessary for those patients diagnosed with Dermatitis Herpetiformis.