Dermatology Online Journal

Dermatitis herpetiformis and gluten-free diet
Irina Turchin BSc¹, and Benjamin Barankin MD²
Dermatology Online Journal 11 (1): 6

¹Clinical Clerk, Faculty of Medicine, University of Calgary;²Division of Dermatology, Faculty of Medicine, University of Alberta. benbarankin@yahoo.com

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A 35-year-old man presents with an erythematous papulaovesicular rash with secondary excoriations symmetrically distributed to the shoulders, elbows, knees, buttocks, sacrum and posterior hairline. The patient states that this rash appeared 2 weeks ago and complains of severe pruritus. He denies any diarrhea, bloating or abdominal pain. Skin biopsy is performed and sent for H & E and immunopathology. Both confirm the clinical suspicion of dermatitis herpetiformis. The patient is started on Dapsone® and recommended to follow a gluten-free diet. He phones back the next morning stating that his rash is a lot better and challenges you about the usefulness of a hard-to-follow gluten-free diet.

Dermatitis herpetiformis (DH) is associated with an often-asymptomatic gluten-sensitive enteropathy characterized by chronic, intensely pruritic, polymorphic, vesicles usually appearing on extensor surfaces, namely elbows, knees, buttocks, and scalp. It is less common on the upper back, abdomen, groin, face, and very rare to affect oral mucosa [1]. The common age at onset is 30-40; however, it can present in children and elderly. There is a slight male predominance. Both genetic and environmental factors seem to be important in its pathogenesis, with a strong association with HLA DQ2 and HLA DQ8. The risk of DH or celiac disease in first-degree relatives of patients with DH appears to be fifteen times higher than in general population [1]. About 75 percent of the patients with DH have small bowel gluten-sensitive villous atrophy with the remainder of the patients having minor nonspecific changes with increased number of intraepithelial T lymphocytes [1]. It has been recently demonstrated that tissue transglutaminase is the predominant autoantigen in celiac disease [2] and epidermal transglutaminase is the main autoantigen in patients with DH [3]. Sárdy et al. [3] also suggested that patients with DH have IgA transglutaminase antibodies with higher affinity to epidermal than tissue transglutaminase. There are granular IgA deposits in the dermal papillae by the direct immunofluorescence in the perilesional skin of patients with DH, which is the hallmark of the disease.

A gluten-free diet (GFD) is the mainstay of treatment in celiac disease. It alleviates gastrointestinal symptoms much more rapidly than the rash [1]. The rash of DH is gluten-dependent, and there are several advantages to a GFD in the management of DH. After following 133 DH patients who consumed a GFD, Garioch et al. [4] reported that these advantages are (1) the need for medication is reduced or abolished; (2) there is resolution of enteropathy; (3) a general feeling of well-being; and (4) protective effect against development of lymphoma.

Several studies [4, 5, 6] demonstrated that a GFD abrogates the need for medication. Garioch et al. [4] suggest that patients with strict adherence to a GFD should be able to stop their medication after approximately 28 months. In their study, only 3 of 44 (6.8 %) patients required a medication in addition to the strict GFD. One patient was following a strict GFD for 4 years and was unable to reduce the medication, another patient taking a strict GFD for 4 years was able to reduce her medication dose by over a half, and the last patient was an insulin-dependent diabetic diagnosed with celiac disease in early childhood and taking strict GFD since then. All these patients had a normal small bowel biopsy confirming their adherence to GFD. The authors suggest that these patients may have been very sensitive to even minute amounts of gluten in gluten-free products. The other hypothesis is that these patients may react to other antigens, with one report suggesting that milk may play such a role [4]. The authors also showed that 10 of 41 (24 %) patients taking a strict GFD lost the skin IgA deposits in a range between 3-16 months after complete control of the rash by diet alone.

In addition, Garioch et al. [4] suggest that patients who continue to ingest small amounts of gluten may never be able to stop their medication completely but may be able to reduce the dose. In the partial GFD group (off diet no more than twice a year) 13 of 22 (59 %) patients were unable to stop their medication completely. Similar results were obtained for partial GFD (off diet more than twice per year) with 36 of 62 (58 %) patients requiring medication in addition to their diet [4].

Patients with DH often have malabsorption. A GFD improves absorption of essential nutrients and prevents alimentary deficiencies of iron, vitamin B12, and folate [5]. Patients without gastrointestinal symptoms often report a general feeling of well-being on commencement of the GFD [4, 5].

Several studies demonstrated a protective effect of a GFD against the development of lymphoma. Lewis et al. [7] and Collin et al. [8] demonstrated an increased incidence of lymphoma in patients with DH and no increased incidence of lymphoma in DH patients adhering to a strict GFD for more than 5 years.

It has been demonstrated that patients with DH have an increased incidence of other autoimmune conditions (i.e., thyroid disease, vitiligo, type-I diabetes, myasthenia gravis, Sjögren's syndrome, dermatomyositis, and rheumatoid arthritis) [1]. However, at present it is unknown whether long-term adherence to a GFD will decrease the incidence of these concurrent autoimmune conditions.

Even though a gluten-free offers many benefits in the management of DH, in practice, it is not well adopted by many DH patients. A GFD requires scrupulous monitoring of all ingested foods; it is time-consuming and socially restricting. The mainstay of GFD is avoidance of all gluten-containing cereals that include wheat, barley, rye, and oats (mnemonic BROW). Recently some authors [10, 11, 12] have demonstrated that oats may be safely consumed by patients with DH. Close clinical surveillance is advised for patients starting on oats and oat-containing products because some oat products may become contaminated with gluten-containing cereals and therefore provoke the appearance of skin lesions. Strict adherence to a GFD requires extensive knowledge of the diet, therefore a dietician consult and involvement in DH support groups is strongly encouraged. In general, patients following a GFD are advised to read all food labels carefully and avoid products with unfamiliar ingredients. Many food ingredients (i.e., additives, cereal grains, colorings and artificial colorings, emulsifiers, excipients, flavorings and artificial flavorings, malts, hydrolyzed plant protein, hydrolyzed vegetable protein, monosodium glutamate, preservatives, starches and modified food starches, vegetable gum, and vinegar) may be derivatives of gluten-containing products; Rottmann provides a detailed list and description of foods permitted and those to be avoided [9].

In conclusion, DH is a cutaneous manifestation of celiac disease characterized by a chronic, intensely pruritic, polymorphic, blistering rash usually appearing on extensor surfaces. There is a strong evidence to recommend a GFD as a mainstay of treatment in DH for the following reasons: (1) the need for medication is reduced or abolished; (2) there is resolution of enteropathy; (3) a general feeling of well-being; and (4) protective effect against lymphoma development. More studies are required to determine whether a longstanding GFD will decrease the incidence of concurrent autoimmune conditions in patients with DH. For more information on gluten-free diets, please refer to Rottmann [9] or the Gluten Intolerance Group of North America at www.gluten.net.

References

1. Collin P, Reunala T. Recognition and management of the cutaneous manifestations of celiac disease: a guide for dermatologists. Am J Clin Dermatol. 4(1): 13-20, 2003.

2. Dieterich W, Ehnis T, Bauer M, Donner P, Volta U, Reicken EO, Schuppan D. Identification of tissue transglutaminase as the autoantigen of celiac disease. Nat Med. 3(7): 797-801, 1997.

3. Sárdy M, Kárpáti S, Merkl B, Paulsson M, Smyth N.Epidermal transglutaminase (Tgase3) is the autoantigen of dermatitis herpetiformis. J Exp Med. 195(6): 747-757, 2002.

4. Garioch JJ, Lewis HM, Sargent SA, Leonard JN, Fry L. 25 years' experience of a gluten-free diet in the treatment of dermatitis herpetiformis. Br J Dermatol. 131(4): 541-545, 1994.

5. Mobacken H, Andersson H, Gillberg R. Gluten-free diet in clinical practice: a Scandinavian perspective. Clin Dermatol. 9(3): 415-419, 1991.

6. Egan CA, O'Loughlin S, Gormally S, Powell FC. Dermatitis herpetiformis: a review of fifty-four patients. Ir J Med Sci. 166(4): 241-244, 1997.

7. Lewis HM, Renaula TL, Garioch JJ, Leonard JN, Fry JS, Collin P, Evans D et al. Protective effect of gluten-free diet against development of lymphoma in dermatitis herpetiformis. Br J Dermatol.135 (3): 363-367, 1996.

8. Collin P, Pukkala E, Reunala T. Malignancy and survival in dermatitis herpetiformis: a comparison with coeliac disease. Gut. 38(4): 528-530, 1996.

9. Rottmann LH. Details of the gluten-free diet for the patient with dermatitis herpetiformis. Clin Dermatol. 9: 409-414, 1992.

10. Janatuinen EK, Pikkarainen PH, Kemppainen TA, Kosma VM, Jarvinen RM, Uusitupa MI, Julkunen RJ. A comparison of diets with and without oats in adults with celiac disease. N Engl J Med. 333(16):1033-7, 1995.

11. Hardman CM, Garioch JJ, Leonard JN, Thomas HJ, Walker MM, Lortan JE, Lister A, et al. Absence of toxicity of oats in patients with dermatitis herpetiformis. N Engl J Med. 337(26): 1884-7, 1997.

12. Reunala T, Collin P, Holm K, Pikkarainen P, Miettinen A, Vuolteenaho N, Maki M. Tolerance to oats in dermatitis herpetiformis. Gut. 43(4): 490-3, 1998.

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