Guideline sources The following summarized guidelines for the evaluation and management of dermatitis herpetiformis are prepared by our editorial team based on guidelines from the European Academy of Dermatology and Venereology (EADV 2021) and the European Society for the Study of Coeliac Disease (ESsCD 2019). 1 2 Guidelines 1. Screening and diagnosis Diagnosis: As per EADV 2021 guidelines: Diagnose dermatitis herpetiformis if both major diagnostic criteria are fulfilled - clinical manifestation compatible with dermatitis herpetiformis and positive DIF microscopy. B Recognize that HLA-DQ2/DQ8 positivity does not confirm the diagnosis of dermatitis herpetiformis. B As per ESsCD 2019 guidelines: Confirm the diagnosis of dermatitis herpetiformis by DIF examination of perilesional skin showing granular IgA deposits in the papillary dermis. A https://web.pathway.md/diseases/recomDblZ3foWk3l5 1/6 6/29/23, 10:08 PM Dermatitis herpetiformis Pathway Consider confirming the diagnosis of celiac disease and dermatitis herpetiformis by typical results from DIF examination of perilesional skin and positive anti-tissue transglutaminase. B Differential diagnosis: Differentiate dermatitis herpetiformis from the following autoimmune bullous diseases: linear IgA dermatosis bullous pemphigoid anti-laminin gamma-1 pemphigoid epidermolysis bullosa acquisita bullous SLE pemphigus herpetiformis igA pemphigus. Differentiate dermatitis herpetiformis from the following non-autoimmune disease: atopic dermatitis and other types of eczema multiple folliculitis nodular or subacute prurigo scabies arthropod bite reactions (papular urticaria, strophulus). 2. Diagnostic investigations History and physical examination: elicit a medical history, perform a complete physical examination and obtain gastroenterological assessment in patients with suspected dermatitis herpetiformis. B Show 3 more Serologic testing (general principles): Recognize that: there are circulating IgA antibodies directed against two different transglutaminase isoenzymes (tissue transglutaminase-2 and tissue transglutaminase-3) only IgA antibody-based serological immunoassays (IDIF microscopy or ELISA) play a significant role in the diagnosis of dermatitis herpetiformis. Show 4 more Serologic testing (endomysial antibodies): recognize that IDIF microscopy is used for qualitative and semi-quantitative detection of endomysial antibodies in the sera of patients with dermatitis herpetiformis. Show 2 more Serologic testing (tissue transglutaminase antibodies): obtain IgA antibodies against tissue transglutaminase-2 in all patients with suspected dermatitis herpetiformis, as they are specific markers of gluten-induced enteropathy in patients with dermatitis herpetiformis and celiac disease. B Show 5 more Serologic testing (epidermal transglutaminase antibodies): consider obtaining epidermal transglutaminase ELISA in addition to tissue transglutaminase-2. C https://web.pathway.md/diseases/recomDblZ3foWk3l5 2/6 6/29/23, 10:08 PM Dermatitis herpetiformis Pathway Show 2 more Serologic testing (gliadin antibodies): do not obtain antibodies against gliadin or deamidated gliadin as primary tests in the diagnostic work-up for dermatitis herpetiformis or celiac disease. D HLA genotyping: Do not obtain routine HLA-DQ2/DQ8 typing for the diagnosis of dermatitis herpetiformis. D Consider obtaining HLA-DQ2/DQ8 to exclude dermatitis herpetiformis or celiac disease in selected situations due to its high negative predictive value. C Baseline laboratory tests: Obtain the following laboratory tests at baseline: CBC including reticulocyte count LFTs renal function tests serum G6PD level (if not available, reduce starting dapsone dose). B Evaluation for comorbidities: consider assessing thyroid function and thyroid autoimmunity at diagnosis and during follow-up. C Show 4 more 3. Diagnostic procedures Skin biopsy: As per EADV 2021 guidelines: Perform lesional biopsy for histopathology in patients with suspected dermatitis herpetiformis. B Use a standardized (buffered) 4% formaldehyde (10% formalin) solution for storage and transport. B As per ESsCD 2019 guidelines: Perform perilesional skin biopsy with DIF examination to identify granular IgA deposits in the papillary dermis for the diagnosis of dermatitis herpetiformis. A Perform perilesional skin biopsy after at least 1 month of initiating gluten-containing diet in patients already following a gluten-free diet. B Direct immunofluorescence microscopy: perform DIF microscopy as the gold-standard for diagnosis in all patients with suspected dermatitis herpetiformis. B Show 2 more Small bowel biopsy: Perform small bowel biopsy in patients with dermatitis herpetiformis to evaluate the degree of enteropathy. B Consider taking at least four specimen from the distal duodenum and at least one from the duodenal bulb by upper gastrointestinal endoscopy. C 4. Medical management https://web.pathway.md/diseases/recomDblZ3foWk3l5 3/6 6/29/23, 10:08 PM Dermatitis herpetiformis Pathway Dapsone: As per EADV 2021 guidelines: Initiate dapsone in patients with dermatitis herpetiformis in the following situations: intolerable and/or severe skin involvement skin manifestation not responding to a correct gluten-free diet patients not accepting or unable to adhere to a gluten-free diet. B Do not use dapsone in patients with any of the following: G6PD deficiency low blood cell counts, especially anemia or neutropenia any cardiac or pulmonary disease leading to significantly impaired tissue oxygenation. D As per ESsCD 2019 guidelines, consider initiating dapsone for the management of patients with dermatitis herpetiformis during the 6-24 month period until the gluten-free diet is effective. B Second-line therapy: Offer the following agents as additional options in patients with dermatitis herpetiformis: sulfasalazine potent topical corticosteroids antihistamines. B Offer the following agents as alternative therapies in patients with dermatitis herpetiformis: sulfasalazine (1-4 g/day), sulfamethoxipyridazine (0.25-1.5 g/day), sulfapyridine tetracycline plus nicotinamide (500 mg/500 mg QID) potent topical corticosteroids. B Agents with no evidence for benefit: Do not use the following agents in patients with dermatitis herpetiformis: cyclosporine systemic corticosteroids. D Insufficient evidence to suggest the use of colchicine in patients with dermatitis herpetiformis. I 5. Nonpharmacologic interventions Gluten-free diet: As per EADV 2021 guidelines, offer lifelong gluten-free diet with/without dapsone as the main therapeutic option in patients with dermatitis herpetiformis. B Show 4 more As per ESsCD 2019 guidelines, offer a gluten-free diet for the management of patients with dermatitis herpetiformis. A Supplements: consider offering micronutrient and vitamin supplementation case-by-case. C 6. Follow-up and surveillance https://web.pathway.md/diseases/recomDblZ3foWk3l5 4/6 6/29/23, 10:08 PM Dermatitis herpetiformis Pathway Follow-up: Obtain the following at according intervals: Situation Guidance History and clinical review Weekly at 1st month CBC including reticulocyte count Every 2 weeks at 2nd and 3rd months MetHgb if the daily dose of dapsone is > 150 mg weekly LFTs Every 2 weeks at 1st 3 months Renal function tests History and clinical review including peripheral motor neurological examination Every 3rd month CBC including reticulocyte count MetHgb if the daily dose of dapsone is > 150 mg LFTs Renal function tests. B 7. Quality improvement Labelling regulations: Recognize the following regulations on gluten-free diets in Europe: gluten-free labels guarantee safety for consumers with dermatitis herpetiformis and celiac disease foods labeled as "very low gluten content" are not suitable for consumers with dermatitis herpetiformis and celiac disease hidden gluten contamination should be avoided as it is easy to reach toxicity thresholds. Clinical findings Symptoms Past medical history Abdominal pain Celiac disease Diarrhea Gluten-sensitive enteropathy Itching Iron deficiency anemia Integument exam Serological findings Hyperpigmentation anti-epidermal transglutaminase Hypopigmentation anti-gliadin antibodies Papulovesicular rash anti-tissue transglutaminase Skin blisters antiendomysial antibody Skin erythema Skin excoriations https://web.pathway.md/diseases/recomDblZ3foWk3l5 5/6 6/29/23, 10:08 PM Dermatitis herpetiformis Pathway Skin plaques References 1. A G r g, E Antiga, M Caproni et al. S2k guidelines (consensus statement) for diagnosis and therapy of dermatitis herpetiformis initiated by the European Academy of Dermatology and Venereology EADV . J Eur Acad Dermatol Venereol. 2021 Jun;35 6 1251 1277. Open 2. Abdulbaqi Al-Toma, Umberto Volta, Renata Auricchio et al. European Society for the Study of Coeliac Disease ESsCD guideline for coeliac disease and other gluten-related disorders. United European Gastroenterol J. 2019 Jun;7 5 583 613. Open https://web.pathway.md/diseases/recomDblZ3foWk3l5 6/6