Granular Deposits of IgA in the Skin of Coeliac Patients Without Dermatitis Herpetiformis: A Prospective Multicentric Analysis
DOI:
https://doi.org/10.2340/00015555-3742Keywords:
general dermatology, direct immunofluorescence, coeliac disease, gastroenterology, dermatitis herpetiformis, immunoglobulin A, granular deposit, epidermal transglutaminaseAbstract
Granular deposits of IgA represent the specific cutaneous marker of dermatitis herpetiformis. The prevalence of IgA deposits in the skin of patients with coeliac disease without dermatitis herpetiformis remains unknown. In this prospective case-control study, skin biopsies from newly diagnosed coeliac patients without dermatitis herpetiformis were analysed by direct immunofluorescence. Controls included healthy volunteers and patients with both bowel symptoms and skin eruptions unrelated to coeliac disease. Clinical data and serum level of anti-tissue transglutaminase and anti-epidermal transglutaminase IgA antibodies were collected from patients and controls. Granular deposits of IgA or IgA1 in the skin were found in 29 out of 45 patients with coeliac disease (64.4%), and in none of the included controls (specificity 100%; sensitivity 64.4%). Positive direct immunofluorescence correlated significantly with an increased serum level of anti-epidermal transglutaminase IgA antibodies (p < 0.005). This study shows that granular deposits of IgA represent a low sensitive, but highly specific, cutaneous marker of coeliac disease independent of dermatitis herpetiformis.
Downloads
References
Lebwohl B, Sanders DS, Green PHR. Coeliac disease. Lancet Lond Engl 2018; 391:70-81.
DOI: https://doi.org/10.1016/S0140-6736(17)31796-8
Graziano M, Rossi M. An update on the cutaneous manifestations of coeliac disease and non-coeliac gluten sensitivity. Int Rev Immunol 2018; 37: 291-300.
DOI: https://doi.org/10.1080/08830185.2018.1533008
Rodrigo L, Beteta-Gorriti V, Alvarez N, Gomez De Castro C, de Dios A, Placios L, et al. Cutaneous and mucosal manifestations associated with celiac disease. Nutrients 2018; 10: 800
DOI: https://doi.org/10.3390/nu10070800
Antiga E, Maglie R, Quintarelli L, Verdelli A, Bonciani D, Bonciolini V, et al. Dermatitis herpetiformis: novel perspectives. Front Immunol 2019; 10: 1290.
DOI: https://doi.org/10.3389/fimmu.2019.01290
Sárdy M, Kárpáti S, Merkl B, Paulsson M, Smyth N. Epidermal transglutaminase (TGase 3) is the autoantigen of dermatitis herpetiformis. J Exp Med 2002; 195: 747-757.
DOI: https://doi.org/10.1084/jem.20011299
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 Venereol 2009; 23: 633-638.
DOI: https://doi.org/10.1111/j.1468-3083.2009.03188.x
Penny HA, Raju SA, Lau MS, Marks LJ, Baggus EM, Bai JC, et al. Accuracy of a no-biopsy approach for the diagnosis of coeliac disease across different adult cohorts. Gut 2020 Nov 2 [Epub ahead of print].
DOI: https://doi.org/10.1136/gutjnl-2020-320913
Hietikko M, Hervonen K, Salmi T, Ilus T, Zone J J, Laukinen K, et al. Disappearance of epidermal transglutaminase and IgA deposits from the papillary dermis of patients with dermatitis herpetiformis after a long-term gluten-free diet. Br J Dermatol 2018; 178: e198-e201.
DOI: https://doi.org/10.1111/bjd.15995
Cannistraci C, Lesnoni La Parola I, Cardinali G, Bolasco G, Aspite N, Stigliano V, Picardo M, et al. Co-localization of IgA and TG3 on healthy skin of coeliac patients. J Eur Acad Dermatol Venereol 2007; 21: 509-514.
DOI: https://doi.org/10.1111/j.1468-3083.2006.02017.x
Bonciolini V, Antiga E, Bianchi B, Del Bianco E, Ninci A, Maio V, et al. Granular IgA deposits in the skin of patients with coeliac disease: is it always dermatitis herpetiformis? Acta Derm Venereol 2019; 99: 78-83.
DOI: https://doi.org/10.2340/00015555-3001
Oberhuber G. Histopathology of celiac disease. Biomed Pharmacother Biomedecine Pharmacother 2000; 54: 368-372.
DOI: https://doi.org/10.1016/S0753-3322(01)80003-2
Wojnarowska F, Delacroix D, Gengoux P. Cutaneous IgA subclasses in dermatitis herpetiformis and linear IgA disease. J Cutan Pathol 1988; 15: 272-275.
DOI: https://doi.org/10.1111/j.1600-0560.1988.tb00558.x
Barghuthy FS, Kumar V, Valeski E, Beutner EH, Chorzelski TP. Identification of IgA subclasses in skin of dermatitis herpetiformis patients. Int Arch Allergy Appl Immunol 1988; 85: 268-271.
DOI: https://doi.org/10.1159/000234516
Antiga E, Quaglino P, Pierini I, Volpi W, Lami G, Bianchi B, et al. Regulatory T cells as well as IL-10 are reduced in the skin of patients with dermatitis herpetiformis. J Dermatol Sci 2015; 77: 54-62.
DOI: https://doi.org/10.1016/j.jdermsci.2014.11.003
Barnadas MA. Dermatitis herpetiformis: a review of direct immunofluorescence findings. Am J Dermatopathol 2016; 38: 283-288.
DOI: https://doi.org/10.1097/DAD.0000000000000420
Ohata C, Ishii N, Hamada T, Shimomura Y, Niizeki H, Dainichi T, et al. Distinct characteristics in Japanese dermatitis herpetiformis: a review of all 91 Japanese patients over the last 35 years. Clin Dev Immunol 2012; 2012: 562168.
DOI: https://doi.org/10.1155/2012/562168
Zhang F, Yang B, Lin Y, Chen S, Zhou G, Wang G, et al. Dermatitis herpetiformis in China: a report of 22 cases. J Eur Acad Dermatol Venereol 2012; 26: 903-907.
DOI: https://doi.org/10.1111/j.1468-3083.2011.04204.x
Hashimoto T, Tsuruta D, Yasukochi A, Imanishi H, Sekine H, Fujita T, et al. Granular C3 dermatosis. Acta Derm Venereol 2016; 96: 748-753.
Salmi T, Hervonen K. Current concepts of dermatitis herpetiformis. Acta Derm Venereol 2020; 100: adv00056.
DOI: https://doi.org/10.2340/00015555-3401
Collin P, Salmi TT, Hervonen K, Kaukinen K, Reunala T. Dermatitis herpetiformis: a cutaneous manifestation of coeliac disease. Ann Med 2017; 49: 23-31.
DOI: https://doi.org/10.1080/07853890.2016.1222450
Paek SY, Steinberg SM, Katz SI. Remission in dermatitis herpetiformis: a cohort study. Arch Dermatol 2011; 147: 301-305.
DOI: https://doi.org/10.1001/archdermatol.2010.336
Shalom G, Kridin K, Raviv K-O, Freud T, Comaneshter D, Friedland R et al. Atopic dermatitis and celiac disease: a cross-sectional study of 116,816 patients. Am J Clin Dermatol 2020; 21: 133-138.
DOI: https://doi.org/10.1007/s40257-019-00474-2
Acharya P, Mathur M. Association between psoriasis and celiac disease: a systematic review and meta-analysis. J Am Acad Dermatol 2020; 82: 1376-1385.
DOI: https://doi.org/10.1016/j.jaad.2019.11.039
Lebwohl B, Söderling J, Roelstraete B, Lebwohl MG, Green PH, Ludvigsson JF. Risk of skin disorders in patients with celiac disease: a population-based cohort study. J Am Acad Dermatol 2020 Oct 31 [Epub ahead of print].
DOI: https://doi.org/10.1016/j.jaad.2020.10.079
Kauppi S, Jokelainen J, Timonen M, Tasanen K, Huilaja L. Atopic dermatitis is associated with dermatitis herpetiformis and celiac disease in children. J Invest Dermatol 2021; 141: 191-193.e2.
DOI: https://doi.org/10.1016/j.jid.2020.05.091
Hietikko M, Hervonen K, Ilus T, Salmi T, Hihtaòa H, Laurila K, et al. Ex vivo culture of duodenal biopsies from patients with dermatitis herpetiformis indicates that transglutaminase 3 antibody production occurs in the gut. Acta Derm Venereol 2018; 98: 366-372.
DOI: https://doi.org/10.2340/00015555-2849
Görög A, Németh K, Kolev K, Zone JJ, Mayer B, Silló P, et al. Circulating transglutaminase 3-immunoglobulin A immune complexes in dermatitis herpetiformis. J Invest Dermatol 2016; 136: 1729-1731.
DOI: https://doi.org/10.1016/j.jid.2016.03.039
Graziano M, Rossi M. An update on the cutaneous manifestations of coeliac disease and non-coeliac gluten sensitivity. Int Rev Immunol 2018; 37: 291-300.
DOI: https://doi.org/10.1080/08830185.2018.1533008
Antiga E, Verdelli A, Calabrò A, Fabbri P, Caproni M. Clinical and immunopathological features of 159 patients with dermatitis herpetiformis: an Italian experience. G Ital Dermatol Venereol 2013; 148: 163-169.
West J, Fleming KM, Tata LJ, Card TR, Crooks CJ. Incidence and prevalence of celiac disease and dermatitis herpetiformis in the UK over two decades: population-based study. Am J Gastroenterol 2014; 109: 757-768.
Published
How to Cite
License
Copyright (c) 2021 Emiliano Antiga, Roberto Maglie, Gabriele Lami, Alessandro Tozzi, Veronica Bonciolini, Francesca Calella, Beatrice Bianchi, Elena Del Bianco, Daniela Renzi, Edoardo Mazzarese, Antonino S. Calabrò, Marzia Caproni
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
All digitalized ActaDV contents is available freely online. The Society for Publication of Acta Dermato-Venereologica owns the copyright for all material published until volume 88 (2008) and as from volume 89 (2009) the journal has been published fully Open Access, meaning the authors retain copyright to their work.
Unless otherwise specified, all Open Access articles are published under CC-BY-NC licences, allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material for non-commercial purposes, provided proper attribution to the original work.
