By Gary M. White, MD
Itchy tiny vesicles on the knees.
Dermatitis herpetiformis (DH) is an intensely pruritic papulovesicular skin disease caused by gluten sensitivity. Epidermal transglutaminase (eTG) (transglutaminase 3) is the major autoantigen in DH. Tissue transglutaminase (tTG) (transglutaminase 2) is the major autoantigen in celiac disease. IgA antibodies to tissue-transglutaminase (T-TG) form in the gut and cross react with epidermal-TG (e-TG). Deposition of IgA/e-TG complexes in the papillary dermis lead to activation of complement and neutrophils. The average age of onset is between 20 and 40 but children and the elderly may be affected. In Finland, up to 4.4% of DH patients have a first-degree relative with DH and up to 6.1% have relatives with celiac disease (CD). Thus, more than 10% have a relative with DH or CD [BJD 1996;134;394].
A chronic, intensely pruritic vesicular rash that affects the knees, sacrum, back, posterior axillary folds and the elbows symmetrically is characteristic of DH. Small vesicles or excoriated papules are most common. Mucous membrane involvement is rare. Palmar plantar petechie/purpura can accompany or be the sole manifestation of DH .
Deposition of IgA in a granular pattern at the top of the dermal papilla in both healthy and affected skin is seen. The biopsy of unaffected skin adjacent to an active lesion and sent for DIF is recommended to diagnose DH.
DH should be considered a manifestation of and pathognomonic for celiac disease. In the case of documented DH, biopsy of the small intestine is not necessary. If performed however, most but not all will show villous atrophy. Only 20% of patients with DH develop intestinal symptoms. Conversely, only 24% of patients with celiac disease develop DH. The incidence of small bowel lymphoma is increased.
Gluten, the causative antigen for the GI disease and the skin, is a protein found in most cereals, e.g. wheat, barley, oats, malt and rye--and not rice and corn. Interestingly, patch testing with a potassium iodine mixture may produce bulla.
Patients with DH may have other autoimmune disease especially thyroid (5-11%), pernicious anemia (1-2%), type I diabetes (1-2%) and collagen vascular disease.
Workup may include CBC, G6PD, creatinine, SGPT, TSH, T3, T4, ANA, Ro, La, HbA1c and cryofibrinogens. Referral to gastroenterology is in order.
Measuring IgA anti-tissue transglutaminase antibody is 98% reliable for detecting celiac disease. Celiac disease is characterized by inflammation of the small intestinal mucosa that occurs with the ingestion of gluten. It is separate and distinct from DH.
A long-term follow-up study showed that patients with DH live longer. There was a significantly reduced all-cause and cerebrovascular disease mortality. Strict adherence to a gluten-free diet, less smoking and a lower incidence of hypercholesterolemia may play a role in the observed health benefit. [Br J Dermatol. 2012 Dec;167:1331-7].
Every patient should be explained the role of gluten in their disease and educated with printed material about a gluten-free diet. Referral to a dietician is in order. Strict adherence to such a diet may allow for complete control of the rash, although the diet is very difficult to follow. Even taking small amounts of gluten per week can make it ineffective. Patients should know that strict adherence to the diet can reduce their risk of death by 30%.
In Fry's experience, the average time to stop drug therapy is 24 months (range 6-48 months) [CED 1982; 7; 633-642]. In other words, at the onset of the disease, one may start both dapsone and adherence to the diet. If the patient is faithful to the diet, he/she may be able to stop the medication after 6-48 months. Even partial adherence can reduce the need for medication. There is some evidence to suggest that following a gluten-free diet will also decrease the likelihood of small bowel lymphoma and this fact should be explained to the patient in order to encourage compliance.
For most patients, some amount of dapsone, sulfapyridine or sulphamethoxypyridaze will need to be given. All of these medications act rapidly, within days to just 1-2 weeks. Dapsone may be started at 50-100 mg/day and increased until symptoms are controlled. Doses of 100-200 are typical. It is unusual to have to go above 300 mg/day. If hemolysis is a problem, don't forget to give vitamin E as it has been shown that vitamin E 800 Units/day can partially reduce the hemolysis associated with dapsone [AD 1992;128;210].
Topical steroids may be prescribed for localized areas of itching. For acute attacks of itching, e.g., in suspected cases before the DIF is back, systemic prednisone or IM kenalog can give great relief.
Sulfapyridine can be started at 1000 mg - 2000 mg/day with the usual maximum dose of 4000 mg/day. Sulphamethoxypyridaxine can be given 0.5 - 1.0 g/day with the maximum dose of 1500 mg/day. Once the symptoms are controlled, the patient should periodically attempt to taper to the lowest possible effective dose. Some patients may even be able to reduce to alternate day dosing. The use of asulfadiazine (e.g., 500 mg twice a day) may be useful in patients with deficient G6PD.
Rituximab 4 weekly infusions of 375 mg/m2 followed by maintenance azathioprine completely cleared one patient after 13 months [JAMADerm 2017;153;315].
A small vesicle of DH.
An Bras Dermatol. 2014 Nov-Dec; 89(6): 865–877
Purpuric lesions on the fingers. Arch Dermatol. 2011;147(11):1313-1316.