The Effect of Enzyme Therapy on Skin Symptoms and Immune Responses in Patients with Dermatitis Herpetiformis

Agnieszka Zebrowska¹, Hugh J. Cornell², Finlay A. Macrae³, Anna Sysa-Jedrzejowska¹, Elzbieta Waszczykowska¹ and Teodor Stelmasiak⁴

¹Department of Dermatology and Venereology, Lodz Medical University, Lodz, Poland

²School of Applied Science, RMIT University, Melbourne, Victoria, Australia

³Department of Colorectal Medicine and Genetics, and University of Melbourne Department Medicine, The Royal Melbourne Hospital, Parkville, Victoria, Australia

⁴Glutagen Pty Ltd, Maribyrnong, Victoria, Australia

Cite this paper:
Agnieszka Zebrowska, Hugh J. Cornell, Finlay A. Macrae, Anna Sysa-Jedrzejowska, Elzbieta Waszczykowska and Teodor Stelmasiak. The Effect of Enzyme Therapy on Skin Symptoms and Immune Responses in Patients with Dermatitis Herpetiformis. International Journal of Celiac Disease. 2014; 2(2):58-63. doi: 10.12691/ijcd-2-2-7

Abstract

Background: The aetiology of coeliac disease (CD) has many similarities to that of dermatitis herpetiformis (DH), except that DH lesions are mainly manifested in the skin. Mucosal enzyme deficiency plays an important part in CD pathology. Clinical studies indicated that the gluten exposure in CD could be partly corrected by the use of enzyme supplementation. Objective: Enzyme therapy, using enterically coated tablets containing caricain, was investigated as a means of protecting patients with DH against wheat gluten. Methods: A randomized, placebo-controlled clinical trial was carried out on 20 DH patients in clinical remission. The patients were divided into two groups of 10, one group given a placebo daily and the other the enzyme – containing tablets. Both groups were challenged with 6g of gluten daily in a double-blind trial. Symptoms and signs of skin involvement were recorded and graded at the start of the trial, after 7 days and after 14 days. Blood was also taken at the start and after 14 days and assayed for IgA EMA and anti-gliadin antibodies. Results: After 7 days the major features associated with DH were more severe and more common with the placebo compared with enzyme therapy. Before 14 days, seven patients in total, six on placebo, had to withdraw from the trial because of the effects of the gluten challenge whilst 2 patients on therapy developed blisters, erythema and itching. Serological tests indicated that IgA EmA antibodies and anti-gliadin antibodies after 14 days were not affected significantly, but indicated that abnormally high antibodies titers of both types were present in 8 patients at the start of the trial, suggesting the need for enzyme therapy in addition to the normal gluten-free diet for patient well-being. Conclusions: This study supports the use of enzyme supplementation as a safeguard for patients with DH on a nominal gluten-free diet.

Keywords:
dermatitis herpetiformis coeliac disease gluten caricain enzyme therapy IgA endomysial antibodies antigliadin antibodies

This work is licensed under a Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

References:

[1]	Mäki M, Collin P. Coeliac disease. Lancet 1997; 349: 1755-1759.
[2]	Fry L. Dermatitis herpetiformis. In: Coeliac disease: M. Marsh, (Ed.), Oxford, UK, Blackwell Scientific Pub. 1992.
[3]	Duhring L. Dermatitis herpetiformis. JAMA 1884; 3: 225-229.
[4]	Caproni M, Antiga E., Melani L, Fabbri P. Italian Group for Cutaneous Immunopathology. Guidelines for the diagnosis and treatment of dermatitis herpetiformis. J Eur Acad Dermatol Venerol; 2009; 23: 633-638.
[5]	Reunala T. Dermatitis herpetiformis. Clin Dermatol, 2001; 19: 728-736.
[6]	Lewis HM, Renaula TL, Garioch JJ, et al. Protective effect of gluten-free diet against development of lymphoma in dermatitis herpetiformis. Br J Dermatology 1996; 3: 363-367.
[7]	Puavilai S, Chutha S, Polnikorn N, et al. Incidence of anemia in leprosy patients treated with dapsone. J Med Assoc Thai. 1984; 67: 404-407.
[8]	Turchin I, Barankin B. Dermatitis herpetiformis and gluten-
[9]	Molberg O, Mc Adam S, Korner R. Tissue transglutaminase selectively modifies gliadin peptides that are recognized by gut-derived T cells in celiac disease. Nat Med 1998; 4: 713-717.
[10]	Van der Wal Y, Kooy Y, Veelen P. Cutting Edge: Selective deamidation by tissue transglutaminase strongly enhances gliadin-specific T cell reactivity. J Immunol 1998; 161: 1585-1588.
[11]	Dietrich W, Ehnis T, Bauer M. Identification of tissue transglutaminase as the autoantigen of celiac disease. Nature Med 1997; 3: 797-801.
[12]	Kumar V, Zane H, Kaul N. Serologic markers of gluten-sensitive enteropathy in bullous diseases. Arch. Dermatol. 1992; 128 (11): 1474-1478.
[13]	Ko CJ, Collegio OR, Moss JE, McNiff JM. Fibrillar IgA deposition in dermatitis herpetiformis - an underreported pattern with potential clinical significance. Journal of cutaneous pathology. 2010; 37: 475-477.
[14]	Van L, Browning JC, Krishnan RS, Kenner-Bell BM, Hsu S. Dermatitis herpetiformis: potential for confusion with linear IgA bullous dermatosis on direct immunofluorescence. Dermatol on line Journal 2008; 14: (1), 21.
[15]	Holm K, Mäki M, Savilathi E. Intraepithelial γ/δ T- cell receptor lymphocytes and genetic susceptibility to coeliac disease. Lancet 1992; 339: 1500-1503.
[16]	Vecchi M, Crosti L, Berti E. Increased jejunal intraepitelial lymphocytes bearning γ/δ T-cell receptor in dermatitis herpetiformis. Gastroenterology 1992; 102: 1499-1505.
[17]	Caproni M, Feliciani C, Fuligni A. Th2-like cytokine activity in dermatitis herpetiformis. Br J Dermatol 1998; 138: 242-247.
[18]	Einstein WM, Brow JR, Parker F. The small intestinal mucosa in dermatitis herpetiformis. Relationship of the small intestinall lesion to gluten. Gastroenterology 1971; 60: 362-369.
[19]	Cornell HJ, Stelmasiak T. A unified hypothesis of coeliac disease with implications for management of patients. Amino Acids 2007; 33: 43-49.
[20]	Cornell HJ, Macrae FA, Melny J, et al. Enzyme therapy for management of coeliac disease. Scand. J. Gastroent 2005; 40: 1304-1312.
[21]	Stepniak D, Spaenij-Dekking L, Mitea C, et al. Highly efficient gluten degradation with a newly identified prolyl endoprotease: implications for celiac disease. Am J Physiol Gastrointest Liver Physiol 2006; 291: G621-G629.
[22]	Cornell HJ, Stelmasiak T. Caricain: A basis for enzyme therapy for coeliac disease. S Afr J Sci 2011; 107: (09/10)
[23]	Templet JT, Welsh JP, Cusack CA. Childhood dermatitis: a case report and review of the literature. Cutis. 2007; 80 (6): 473-476.
[24]	Garioch JJ, Lewis HM, Sargent SA, Leonard JN, Fry L. 25 years’ experience of a glute-free diet in the treatment of dermatitis herpetiformis. Br. J. Dermatol. 1994; 131 (4): 541-545.
[25]	Gregory J, Foster K, Tyler H. The dietary and nutritional survey of British adults HMSO, London. 1990.
[26]	Gajewska J, Ambroszkiewicz J, Hozyasz K. Biochemical markers of bone turnover In children with celiac disease on gluten free-diet. Med Wieku Rozwoj. 2005; 9 (4): 675-683.
[27]	Fry L, Mcminn R, Cowan J. Effect of Gluten- free diet on dermatological, intestinal and haematological manifestations of dermatitis herpetiformis. Lancet 1968; i: 557-561.
[28]	Fry L, Seath P, Riches D. Clearance of skin lesions in dermatitis herpetiformis after gluten withdrawal. Lancet 1973; i: 288-291.