Dermatitis herpetiformis (DH) is and uncommon subepidermal blistering dermatosis, currently regarded as the cutaneous manifestation of celiac disease (CD). The leading theory for DH is that a genetic predisposition (association with HLA-B8, HLA-DR3, and HLA-DQw2) for gluten sensitivity, coupled with the dietary gluten, leads to the formation of IgA antibodies against gluten-tissue transglutaminase (t-TG), a cytosolic enzyme found in the gut. Anti t-TG antibodies cross-react with epidermal transglutaminase (e-TG) which is highly homologous with tTG. Deposition of IgA and epidermal TG complexes in the papillary dermis triggers an immunologic cascade, resulting in neutrophil recruitment and complement activation resulting in subepidermal separation. Clinically, DH is characterized by polymorphic itchy cutaneous eruption, consisting of erythema, urticarial papules and plaques, and herpetiform vesicules followed by excoriations, crusted erosions and residual hyper-, or hypopigmentations. The eruption is with a typical symmetrical distribution on the extensor surfaces, including elbows, knees, shoulders, and buttocks. Morbidity is mainly related to the intense pruritus, scratching, discomfort, and insomnia. Systemic complications consist mainly of the symptoms of the associated gluten-sensitive enteropathy (GSE), which is generally mild or clinically completely absent. However, inflammatory small bowel changes can often be found by histological examination even in the absence of clinical findings. The diagnosis of DH is based on clinical, histological and immunological features and presence of GI disease. Histopathological findings are characterized by subepidermal blisters with predominantly neutrophil infiltrates in the papillary dermis. Direct immunofluorescence (DIF) reveals pathognomonic granular deposits of IgA and C3 in the papillary.

  • Specific challenges associated with the recognition of the condition

The diagnosis of DH can be delayed for several months or years due to the polymorphic nature of the cutaneous eruption, the lack of vesiculo-bullous lesions which are often excoriated due to the severe pruritus. In these cases, DH might not be suspected due to clinical similarity to atopic dermatitis, insect bites, neurotic excoriations, or prurigo-like eruptions. The delay in recognizing DH has severe impact on patients’ quality of life.

  • Specific challengesassociated with the diagnosis

A definitive diagnosis of DH cannot be made without this diagnostic DIF finding. A potential cause for its delay is a false negative result from the DIF, which can occur if lesional skin is biopsied because the inflammatory infiltrate can destroy the IgA. The optimal biopsy site for DIF testing is normal-appearing skin immediately adjacent to a lesion. In cases of clinical signs suggestive of DH and negative DIF, serial sections of the biopsy should be performed and if negative a second biopsy should be taken from surely uninvolved skin and checking that the patient is not on a GFD. DIF testing must be performed in experienced laboratories to minimize both false positive and false negative results.

  • Specific challenges associated with the treatment

The treatment of DH includes avoidance of gluten, and suppressive treatment with dapsone (diamino-diphenyl-sulfone, DADPS) at a dosage of 100 to 200 mg per day. In patients intolerant to dapsone, who are glucose-6-phosphate dehydrogenase deficient, or who have cardiac disease, a second line pharmacological treatment with sulfasalazine (1-2 g/daily) or sulfapyridine (0.25 – 1.5 g/daily) can be considered. Regular screening for dapsone-induced side effects is needed. Strict GFD can clear cutaneous lesions and reverse underlying GSE. Upon reintroduction of gluten the eruption recurs. Although GFD offers many benefits in the management of DH, it is not easy to realize by many DH patients. A GFD requires scrupulous monitoring of all ingested foods; it is time-consuming and socially restricting. Strict adherence to a GFD requires extensive knowledge of foods and diet, thus consultation with a dietician and involvement in DH support groups are strongly encouraged. In general, patients following a GFD are advised to read carefully all food labels and to avoid products with unfamiliar ingredients since many of them (i.e. additives, cereal grains, colourings, emulsifiers, excipients, flavourings, malts, hydrolysed plant and vegetable proteins, etc.) may be derivatives of gluten containing products.

  • Specific challenges associated with care of these patients over their lifespan – Quality of life issues – Gaps across the care continuum

Optimal management of DH patients requires a multidisciplinary approach by highly specialized dermatologists, gastroenterologists and dieticians for evaluation of GSE and formulation of a GFD to help alleviate future symptomatology, and GPs. Other specialists who can be involved are hematologists in the management of dapsone side effects but also to rule out potential lymphoma, endocrinologists in the diagnosis of frequently associated autoimmune diseases (thyroid disease, insulin-dependent diabetes, Addison’s disease, etc.), and neurologists for diagnosis and management of neurologic disease if present. Nursing staff plays also a major role in patients’ educational programs. Dieticians are of outmost importance in the adherence to a strict GFD and alleviation of malabsorption symptoms. Many patients complain of long-lasting symptoms or psychological troubles that frequently needs the intervention of psychologists. Considering the increased incidence of immunomediated diseases and associated conditions, several screening tests should be performed in patients with dermatitis herpetiformis. Nonspecific antibodies, such as antithyroid peroxidase, antigastric parietal cells, antinuclear and anti-Ro/SSA antibodies, should be tested in both DH and CD patients. The presence of such antibodies correlates with autoimmune predisposition of CD/DH patients. Furthermore, testing for thyroid disease (TSH, T3 and T4) and for diabetes (glucose) should be performed.

Intense pruritus, malabsorption, difficulties in following GFD, resulting in impaired quality of life.

Prevalence :  The prevalence of DH has been reported to be 1.2 per 100,000 population in Great Britain (1971), 39.2 per 100,000 population in central Sweden (1984) and 75.3 per 100 000 in Finland (2011).