Approach

Dermatitis herpetiformis is not a life-threatening disease, but its symptoms and signs, particularly pruritus, may deeply affect the patient's quality of life. Moreover, as it is associated with celiac disease, patients with dermatitis herpetiformis may develop complications typically found in patients with celiac disease, including celiac sprue, ulcerative ileitis, and lymphoma.[17][41] Patients with dermatitis herpetiformis are also at higher risk of autoimmune comorbidities such as autoimmune thyroiditis, as well as a lesser risk of other inflammatory skin conditions, such as vitiligo, psoriasis, atopic dermatitis, and bullous pemphigoid.[42] The main goals of treatment are therefore to provide symptomatic relief of dermatologic symptoms, resolve associated skin lesions, and prevent the occurrence of potential complications.

It is important to give only symptomatic therapy until all diagnostic steps have been carried out, as a gluten-free diet and treatment with dapsone can modify diagnostic results.[2]

Once the diagnosis is confirmed, a lifelong gluten-free diet is the main treatment option for patients with the condition.[2][11][20][21] However, elimination of gluten from the diet may take from a few months to several years to impact skin lesions, and therefore other therapeutic strategies aimed at relieving the skin manifestations of the disease, such as dapsone, may be used in the interim.[2][11][17][20][21]

Monitor patients with dermatitis herpetiformis to assess:

  • The clinical course of the disease

  • The effectiveness and the potential adverse effects of the suggested treatment

  • The adherence to gluten-free diet and the occurrence of potential complications or associated diseases.

Perform frequent follow-up visits (every 2-4 weeks, if possible) following the initial diagnosis depending on treatment modalities used and response to treatment. When disease control is achieved, follow-up visits every 3-6 months are sufficient.[2]

Gluten-free diet

Advise all patients with confirmed dermatitis herpetiformis to follow a strict and lifelong gluten-free diet.[2][11][20][21]

  • Dermatitis herpetiformis is the specific cutaneous manifestation of celiac disease and gluten is the main trigger for both conditions; a lifelong gluten-free diet is necessary to switch off the autoimmune process causing the disease and may help to prevent potential complications, such as lymphoma.[2][43][44]

Refer all patients starting a gluten-free diet to a dietitian with training in gluten-free diets.[2][20][45] Dietary counseling is important because a gluten-free diet has been associated with:

  • Potential vitamin B deficiency[46][47]

  • Reduced fiber intake

  • Risk of rebound weight gain.[48]

Advise all patients on a gluten-free diet to follow a healthy and well balanced diet.[2]

  • Micronutrient and vitamin supplementation may also be a consideration on a case-by-case basis.[2]

  • Some experts recommend avoidance of excessive iodine intake (i.e., via excessive seafood consumption/iodine supplementation), as this may increase risk of flares/relapse in patients with dermatitis herpetiformis.[2]

    • Although an inconsistent manifestation, potassium iodide (ingested or applied topically) may induce a flare-up of symptoms in some patients with dermatitis herpetiformis.[49]​ When applied topically, potassium iodide may cause lesions similar to dermatitis herpetiformis (note these may also occur with trauma and other chemical irritants, due to a mechanism known as the Koebner phenomenon).

Around 15% to 20% of people with dermatitis herpetiformis show gastrointestinal symptoms resembling those of celiac disease.[2][11]​ A gluten-free diet alone is usually able to induce the resolution of intestinal signs and symptoms in people with dermatitis herpetiformis (and those with celiac disease) within 3-6 months.[21][50]​

  • If intestinal symptoms persist following 6 months of gluten-free diet or recur despite adherence to diet, referral for exclusion of other gastrointestinal conditions should be considered.

By contrast, its effects on resolving cutaneous lesions and pruritus is slower, in some instances taking several years; an average of 1-2 years on a gluten-free diet may be required for complete resolution of skin lesions.[21][51]​ 

  • Deposited immunoglobulin A (IgA) autoantibodies may be detected in the dermis for up to 10 years after starting a strict gluten-free diet.[2]

  • One study of 237 patients with dermatitis herpetiformis showed that 38% of patients continued to have cutaneous symptoms after 2 years of a gluten-free diet, while 14% had skin symptoms after a longer term (mean duration 24 years) gluten-free diet.[52]

Adherence to gluten-free diet is challenging, with one study reporting dietary lapses in approximately 25% of long-term treated patients with dermatitis herpetiformis.[53] In addition, gluten contamination can be present in food that is intended to be gluten free; one meta-analysis of gluten contamination in naturally gluten-free foods, gluten-free labelled foods, and meals prepared in food services found the overall prevalence of gluten contamination in these foods to be over 15%.[54]

For these reasons, other therapeutic strategies are often required in people with dermatitis herpetiformis.

Dapsone

Consider starting dapsone in addition to lifelong gluten-free diet in patients who:[2][11][20][21]

  • Have intolerable or severe skin involvement at initial presentation, or

  • Continue to have skin signs and symptoms despite adhering to a strict gluten-free diet.

Dapsone is also an alternative treatment option in patients who cannot adhere to/cannot tolerate a gluten-free diet.[2]

Despite the lack of randomized clinical trials on its efficacy, dapsone is considered to be an essential treatment option in these patients as per current guidelines and general expert consensus, with treatment often resulting in the clearance of skin lesions and reduction in pruritus within a few days of treatment.[2][11][21][44][55] Dapsone has no effect on gastrointestinal signs and symptoms.

In patients starting dapsone, continue treatment until cutaneous signs and symptoms have completely resolved.[2]​ Monitor the patient closely for adverse effects related to dapsone therapy.

  • Dapsone may cause hemolytic anemia. Measure serum glucose-6-phosphate-dehydrogenase (G6PD) levels before treatment as severe hemolytic anemia is possible in patients with G6PD deficiency and dapsone should be avoided or used with caution in these patients.

  • All patients should also have complete blood count (CBC) with differential, liver function tests, renal function tests, urinalysis, and reticulocyte count performed at baseline and then periodically during treatment to monitor for dapsone-related adverse effects.[2][20][21]​ CBC with differential should be checked weekly for the first month, monthly for 6 months, and semi-annually thereafter, when feasible. Discontinue dapsone if there is a significant reduction in leukocytes, platelets, or hemopoiesis.

  • The majority of dapsone-related adverse effects (including methemoglobinemia, peripheral neuropathy, dizziness, headache, fatigue, nausea, and vomiting) are dose-dependent and for the most part can be rapidly reverted with dose reduction/discontinuation of therapy.

  • In about 1% to 2% of patients, and usually within the first few weeks of treatment, dapsone can cause a potentially life-threatening idiosyncratic hypersensitivity syndrome resembling drug reaction with eosinophilia and systemic symptoms (DRESS), characterized by fever, skin rash, and organ involvement.[56] Close monitoring of the patient with a particular focus on liver function is advised.

  • A rare adverse effect of dapsone therapy is idiosyncratic agranulocytosis, which may lead to life-threatening neutropenic sepsis; if affected, the patient typically presents with a fever and evidence of infection 1-3 months following initiation of dapsone.[57]​ Regular monitoring of CBC with differential aims to detect early phases of agranulocytosis before severe effects of neutropenia such as fever and infection occur.

Other therapeutic options

Consider other therapeutic options to help manage skin manifestations:

  • Sulfasalazine is a second-line option if dapsone is contraindicated or not effective in controlling the disease despite adherence to a gluten-free diet.[2][11][20][21]

    • Sulfasalazine is considerably less effective than dapsone and only anecdotal case reports are available to support its use in this setting.[2][11][20][21][58][59][60][61]

  • For patients with localized disease, consider the use of ultrapotent topical corticosteroids (e.g., clobetasol propionate) alongside dapsone (or sulfasalazine, if dapsone is contraindicated or not effective) and a gluten-free diet for short-term symptomatic relief of pruritus and to reduce the appearance of new lesions.[8][11][17][20][21]

    • Topical corticosteroids can be used in children; however, higher potency corticosteroids should be used with caution.

  • A third-generation antihistamine (e.g., desloratadine, levocetirizine, fexofenadine) can be considered as an alternative/adjunctive therapy if dapsone (or sulfasalazine, if dapsone is contraindicated or not effective) alone is ineffective at controlling pruritus symptoms.[2][11][20][21]

    • However, the role of antihistamines in the treatment of dermatitis herpetiformis is very limited and their efficacy has not been robustly demonstrated.

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