Is a gluten-free diet sufficient in the treatment of Duhring’s Disease? - A Review
DOI:
https://doi.org/10.12775/QS.2024.36.56447Keywords
dermatitis herpetiformis, celiac disease, gluten free diet, direct immunofluorescence, dapsone, sulfonamidesAbstract
Introduction
Dermatitis herpetiformis is a chronic autoimmune blistering disease characterized by intensely pruritic,
symmetrically distributed skin lesions and an association with gluten-sensitive enteropathy. Despite advances in
diagnostic methods, delayed diagnosis remains a challenge due to its overlapping features with other dermatoses.
Aim of Study
This study aims to provide a comprehensive overview of the diagnostic methods, associated conditions, and
differential diagnosis of dermatitis herpetiformis, focusing on recent advancements in serological,
histopathological, and immunological testing.
Material and methods
A comprehensive review of the literature on dermatitis herpetiformis was performed using the PubMed database.
Results and Conclusions
Direct immunofluorescence remains the gold standard in diagnosing dermatitis herpetiformis, revealing granular
IgA deposits in the dermal papillae. Histopathological findings are supportive but nonspecific, with early lesions
showing subepidermal vesicles and neutrophilic infiltrates. Serological markers, including anti-TG2 and anti-
TG3 antibodies, provide valuable diagnostic support but exhibit variable sensitivity. HLA-DQ2/DQ8 haplotypes
are present in most dermatitis herpetiformis patients, offering high negative predictive value for exclusion.
Associated autoimmune conditions, such as autoimmune thyroid disease and type 1 diabetes, are prevalent, and
dermatitis herpetiformis patients face an elevated risk of non-Hodgkin lymphoma within the first five years after
diagnosis. The diagnosis of dermatitis herpetiformis relies on a combination of direct immunofluorescence,
serological testing, and clinical features. Increased awareness of dermatitis herpetiformis and its associated
conditions is critical for timely diagnosis and management. Advances in immunological and genetic testing may
further refine diagnostic accuracy, while screening for associated autoimmune disorders and malignancies
remains an integral part of patient care.
References
Duhring LA. Landmark article, Aug 30, 1884: Dermatitis herpetiformis. By Louis A. Duhring. JAMA.
;250(2):212-16. doi: 10.1001/jama.250.2.212
Bolotin D, Petronic-Rosic V. Dermatitis herpetiformis. Part I. Epidemiology, pathogenesis, and clinical
presentation. J Am Acad Dermatol. 2011;64(6):1017-24; quiz 25-6. doi: 10.1016/j.jaad.2010.09.777
Collin P, Salmi TT, Hervonen K, Kaukinen K, Reunala T. Dermatitis herpetiformis: a cutaneous manifestation
of coeliac disease. Ann Med. 2017;49(1):23-31. doi: 10.1080/07853890.2016.1222450
Barnadas MA. Dermatitis Herpetiformis: A Review of Direct Immunofluorescence Findings. Am J
Dermatopathol. 2016;38(4):283-8. doi: 10.1097/DAD.0000000000000420
Bolotin D, Petronic-Rosic V. Dermatitis herpetiformis. Part II. Diagnosis, management, and prognosis. J Am
Acad Dermatol. 2011;64(6):1027-33; quiz 33-4. doi: 10.1016/j.jaad.2010.09.776
Leonard J, Haffenden G, Tucker W, Unsworth J, Swain F, McMinn R, et al. Gluten challenge in dermatitis
herpetiformis. N Engl J Med. 1983;308(14):816-9. doi: 10.1056/NEJM198304073081406
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. 1994;131(4):541-5. doi: 10.1111/j.1365-
1994.tb08557.x
Savilahti E, Reunala T, Maki M. Increase of lymphocytes bearing the gamma/delta T cell receptor in the
jejunum of patients with dermatitis herpetiformis. Gut. 1992;33(2):206-11. doi: 10.1136/gut.33.2.206
Grainge MJ, West J, Solaymani-Dodaran M, Card TR, Logan RF. The long-term risk of malignancy following
a diagnosis of coeliac disease or dermatitis herpetiformis: a cohort study. Aliment Pharmacol Ther.
;35(6):730-9. doi: 10.1111/j.1365-2036.2012.04998.x
Graziano M, Rossi M. An update on the cutaneous manifestations of coeliac disease and non-coeliac gluten
sensitivity. Int Rev Immunol. 2018;37(6):291-300. doi: 10.1080/08830185.2018.1533008
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(7):903-7. doi: 10.1111/j.1468-3083.2011.04204.x
Leffler DA, Green PH, Fasano A. Extraintestinal manifestations of coeliac disease. Nat Rev Gastroenterol
Hepatol. 2015;12(10):561-71. doi: 10.1038/nrgastro.2015.131
Salmi TT, Hervonen K, Kautiainen H, Collin P, Reunala T. Prevalence and incidence of dermatitis
herpetiformis: a 40-year prospective study from Finland. Br J Dermatol. 2011;165(2):354-9. doi: 10.1111/j.1365-
2011.10385.x
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.
;109(5):757-68. doi: 10.1038/ajg.2014.55
Kang JY, Kang AH, Green A, Gwee KA, Ho KY. Systematic review: worldwide variation in the frequency
of coeliac disease and changes over time. Aliment Pharmacol Ther. 2013;38(3):226-45. doi: 10.1111/apt.12373
Salmi TT, Hervonen K, Kurppa K, Collin P, Kaukinen K, Reunala T. Celiac disease evolving into dermatitis
herpetiformis in patients adhering to normal or gluten-free diet. Scand J Gastroenterol. 2015;50(4):387-92. doi:
3109/00365521.2014.974204
Rampertab SD, Pooran N, Brar P, Singh P, Green PH. Trends in the presentation of celiac disease. Am J
Med. 2006;119(4):355 e9-14. doi: 10.1016/j.amjmed.2005.08.044
Spurkland A, Ingvarsson G, Falk ES, Knutsen I, Sollid LM, Thorsby E. Dermatitis herpetiformis and celiac
disease are both primarily associated with the HLA-DQ (alpha 1*0501, beta 1*02) or the HLA-DQ (alpha 1*03,
beta 1*0302) heterodimers. Tissue Antigens. 1997;49(1):29-34. doi: 10.1111/j.1399-0039.1997.tb02706.x
Clarindo MV, Possebon AT, Soligo EM, Uyeda H, Ruaro RT, Empinotti JC. Dermatitis herpetiformis:
pathophysiology, clinical presentation, diagnosis and treatment. An Bras Dermatol. 2014;89(6):865-75; quiz 76-
doi: 10.1590/abd1806-4841.20142966
Dieterich W, Ehnis T, Bauer M, Donner P, Volta U, Riecken EO, et al. Identification of tissue
transglutaminase as the autoantigen of celiac disease. Nat Med. 1997;3(7):797-801. doi: 10.1038/nm0797-797
Antiga E, Maglie R, Quintarelli L, Verdelli A, Bonciani D, Bonciolini V, et al. Dermatitis Herpetiformis:
Novel Perspectives. Front Immunol. 2019;10:1290. doi: 10.3389/fimmu.2019.01290
Hietikko M, Hervonen K, Ilus T, Salmi T, Huhtala 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(3):366-72. doi: 10.2340/00015555-2849
Sardy M, Karpati S, Merkl B, Paulsson M, Smyth N. Epidermal transglutaminase (TGase 3) is the
autoantigen of dermatitis herpetiformis. J Exp Med. 2002;195(6):747-57. doi: 10.1084/jem.20011299
Salmi T, Hervonen K. Current Concepts of Dermatitis Herpetiformis. Acta Derm Venereol.
;100(5):adv00056. doi: 10.2340/00015555-3401
Alakoski A, Hervonen K, Mansikka E, Reunala T, Kaukinen K, Kivela L, et al. The Long-Term Safety and
Quality of Life Effects of Oats in Dermatitis Herpetiformis. Nutrients. 2020;12(4). doi: 10.3390/nu12041060
Collin P, Reunala T. Recognition and management of the cutaneous manifestations of celiac disease: a guide
for dermatologists. Am J Clin Dermatol. 2003;4(1):13-20. doi: 10.2165/00128071-200304010-00002
Mistry A, Mistry N. Persistent pruritic papulovesicles. Dermatitis herpetiformis. Am Fam Physician.
;90(6):407-8.
Al-Toma A, Volta U, Auricchio R, Castillejo G, Sanders DS, Cellier C, et al. European Society for the Study
of Coeliac Disease (ESsCD) guideline for coeliac disease and other gluten-related disorders. United European
Gastroenterol J. 2019;7(5):583-613. doi: 10.1177/2050640619844125
Vale E, Dimatos OC, Porro AM, Santi CG. Consensus on the treatment of autoimmune bullous dermatoses:
dermatitis herpetiformis and linear IgA bullous dermatosis - Brazilian Society of Dermatology. An Bras
Dermatol. 2019;94(2 Suppl 1):48-55. doi: 10.1590/abd1806-4841.2019940208
Reunala T, Kosnai I, Karpati S, Kuitunen P, Torok E, Savilahti E. Dermatitis herpetiformis: jejunal findings
and skin response to gluten free diet. Arch Dis Child. 1984;59(6):517-22. doi: 10.1136/adc.59.6.517
Haffenden GP, Blenkinsopp WK, Ring NP, Wojnarowska F, Fry L. The potassium iodide patch test in the
dermatitis herpetiformis in relation to treatment with a gluten-free diet and dapsone. Br J Dermatol.
;103(3):313-7. doi: 10.1111/j.1365-2133.1980.tb07250.x
Hassan S, Dalle S, Descloux E, Balme B, Thomas L. [Dermatitis herpetiformis associated with progesterone
contraception]. Ann Dermatol Venereol. 2007;134(4 Pt 1):385-6. doi: 10.1016/s0151-9638(07)89198-8
Grimwood RE, Guevara A. Leuprolide acetate-induced dermatitis herpetiformis. Cutis. 2005;75(1):49-52.
Marakli SS, Uzun S, Ozbek S, Tuncer I. Dermatitis herpetiformis in a patient receiving infliximab for
ankylosing spondylitis. Eur J Dermatol. 2008;18(1):88-9. doi: 10.1684/ejd.2007.0323
Mochel MC, Ming ME, Imadojemu S, Gangadhar TC, Schuchter LM, Elenitsas R, et al. Cutaneous
autoimmune effects in the setting of therapeutic immune checkpoint inhibition for metastatic melanoma. J Cutan
Pathol. 2016;43(9):787-91. doi: 10.1111/cup.12735
Shigeta M, Saiki M, Tsuruta D, Ohata C, Ishii N, Ono F, et al. Two Japanese cases of dermatitis
herpetiformis associated each with lung cancer and autoimmune pancreatitis but showing no intestinal symptom
or circulating immunoglobulin A antibodies to any known antigens. J Dermatol. 2012;39(12):1002-5. doi:
1111/j.1346-8138.2012.01663.x
Fuertes I, Mascaro JM, Bombi JA, Iranzo P. [A retrospective study of clinical, histological, and
immunological characteristics in patients with dermatitis herpetiformis. The experience of Hospital Clinic de
Barcelona, Spain, between 1995 and 2010 and a review of the literature]. Actas Dermosifiliogr.
;102(9):699-705. doi: 10.1016/j.ad.2010.11.007
Zone JJ, Meyer LJ, Petersen MJ. Deposition of granular IgA relative to clinical lesions in dermatitis
herpetiformis. Arch Dermatol. 1996;132(8):912-8. doi:
Hadjivassiliou M, Duker AP, Sanders DS. Gluten-related neurologic dysfunction. Handb Clin Neurol.
;120:607-19. doi: 10.1016/B978-0-7020-4087-0.00041-3
Alonso-Llamazares J, Gibson LE, Rogers RS, 3rd. Clinical, pathologic, and immunopathologic features of
dermatitis herpetiformis: review of the Mayo Clinic experience. Int J Dermatol. 2007;46(9):910-9. doi:
1111/j.1365-4632.2007.03214.x
Rose C, Brocker EB, Zillikens D. Clinical, histological and immunpathological findings in 32 patients with
dermatitis herpetiformis Duhring. J Dtsch Dermatol Ges. 2010;8(4):265-70, -71. doi: 10.1111/j.1610-
2009.07292.x
Bresler SC, Granter SR. Utility of direct immunofluorescence testing for IgA in patients with high and low
clinical suspicion for dermatitis herpetiformis. Am J Clin Pathol. 2015;144(6):880-4. doi:
1309/AJCPXIVSR6OZK1HU
Mansikka E, Hervonen K, Salmi TT, Kautiainen H, Kaukinen K, Collin P, et al. The Decreasing Prevalence
of Severe Villous Atrophy in Dermatitis Herpetiformis: A 45-Year Experience in 393 Patients. J Clin
Gastroenterol. 2017;51(3):235-9. doi: 10.1097/MCG.0000000000000533
Mansikka E, Hervonen K, Kaukinen K, Collin P, Huhtala H, Reunala T, et al. Prognosis of Dermatitis
Herpetiformis Patients with and without Villous Atrophy at Diagnosis. Nutrients. 2018;10(5). doi:
3390/nu10050641
Pasternack C, Kaukinen K, Kurppa K, Maki M, Collin P, Hervonen K, et al. Gastrointestinal Symptoms
Increase the Burden of Illness in Dermatitis Herpetiformis: A Prospective Study. Acta Derm Venereol.
;97(1):58-62. doi: 10.2340/00015555-2471
Caproni M, Antiga E, Melani L, Fabbri P, Italian Group for Cutaneous I. Guidelines for the diagnosis and
treatment of dermatitis herpetiformis. J Eur Acad Dermatol Venereol. 2009;23(6):633-8. doi: 10.1111/j.1468-
2009.03188.x
Araya M, Oyarzun A, Lucero Y, Espinosa N, Perez-Bravo F. DQ2, DQ7 and DQ8 Distribution and Clinical
Manifestations in Celiac Cases and Their First-Degree Relatives. Nutrients. 2015;7(6):4955-65. doi:
3390/nu7064955
Dieterich W, Laag E, Bruckner-Tuderman L, Reunala T, Karpati S, Zagoni T, et al. Antibodies to tissue
transglutaminase as serologic markers in patients with dermatitis herpetiformis. J Invest Dermatol.
;113(1):133-6. doi: 10.1046/j.1523-1747.1999.00627.x
Reunala T, Salmi TT, Hervonen K, Laurila K, Kautiainen H, Collin P, et al. IgA antiepidermal
transglutaminase antibodies in dermatitis herpetiformis: a significant but not complete response to a gluten-free
diet treatment. Br J Dermatol. 2015;172(4):1139-41. doi: 10.1111/bjd.13387
Hull CM, Liddle M, Hansen N, Meyer LJ, Schmidt L, Taylor T, et al. Elevation of IgA anti-epidermal
transglutaminase antibodies in dermatitis herpetiformis. Br J Dermatol. 2008;159(1):120-4. doi: 10.1111/j.1365-
2008.08629.x
Sar-Pomian M, Rudnicka L, Olszewska M. Trichoscopy - a useful tool in the preliminary differential
diagnosis of autoimmune bullous diseases. Int J Dermatol. 2017;56(10):996-1002. doi: 10.1111/ijd.13725
Hervonen K, Viljamaa M, Collin P, Knip M, Reunala T. The occurrence of type 1 diabetes in patients with
dermatitis herpetiformis and their first-degree relatives. Br J Dermatol. 2004;150(1):136-8. doi: 10.1111/j.1365-
2004.05642.x
Maglie R, Hertl M. Pharmacological advances in pemphigoid. Curr Opin Pharmacol. 2019;46:34-43. doi:
1016/j.coph.2018.12.007
Varpuluoma O, Jokelainen J, Forsti AK, Timonen M, Huilaja L, Tasanen K. Dermatitis Herpetiformis and
Celiac Disease Increase the Risk of Bullous Pemphigoid. J Invest Dermatol. 2019;139(3):600-4. doi:
1016/j.jid.2018.10.010
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(1):191-3 e2. doi:
1016/j.jid.2020.05.091
Iyer A, Rathnasabapathi D, Elsone L, Mutch K, Terlizzo M, Footitt D, et al. Transverse myelitis associated
with an itchy rash and hyperckemia: neuromyelitis optica associated with dermatitis herpetiformis. JAMA
Neurol. 2014;71(5):630-3. doi: 10.1001/jamaneurol.2013.6277
Mansikka E, Salmi T, Kaukinen K, Collin P, Huhtala H, Reunala T, et al. Diagnostic Delay in Dermatitis
Herpetiformis in a High-prevalence Area. Acta Derm Venereol. 2018;98(2):195-9. doi: 10.2340/00015555-2818
Mirza HA, Gharbi A, Bhutta BS. Dermatitis Herpetiformis. StatPearls. Treasure Island (FL)2024.
Gorog A, Antiga E, Caproni M, Cianchini G, De D, Dmochowski M, et al. S2k guidelines (consensus
statement) for diagnosis and therapy of dermatitis herpetiformis initiated by the European Academy of
Dermatology and Venereology (EADV). J Eur Acad Dermatol Venereol. 2021;35(6):1251-77. doi:
1111/jdv.17183
Turchin I, Barankin B. Dermatitis herpetiformis and gluten-free diet. Dermatol Online J. 2005;11(1):6. doi:
Paek SY, Steinberg SM, Katz SI. Remission in dermatitis herpetiformis: a cohort study. Arch Dermatol.
;147(3):301-5. doi: 10.1001/archdermatol.2010.336
Mansikka E, Hervonen K, Kaukinen K, Ilus T, Oksanen P, Lindfors K, et al. Gluten Challenge Induces Skin
and Small Bowel Relapse in Long-Term Gluten-Free Diet-Treated Dermatitis Herpetiformis. J Invest Dermatol.
;139(10):2108-14. doi: 10.1016/j.jid.2019.03.1150
Coleman MD. Dapsone: modes of action, toxicity and possible strategies for increasing patient tolerance. Br
J Dermatol. 1993;129(5):507-13. doi: 10.1111/j.1365-2133.1993.tb00476.x
Wolverton SE, Remlinger K. Suggested guidelines for patient monitoring: hepatic and hematologic toxicity
attributable to systemic dermatologic drugs. Dermatol Clin. 2007;25(2):195-205, vi-ii. doi:
1016/j.det.2007.02.001
Ghaoui N, Hanna E, Abbas O, Kibbi AG, Kurban M. Update on the use of dapsone in dermatology. Int J
Dermatol. 2020;59(7):787-95. doi: 10.1111/ijd.14761
Fry L, Seah PP, Riches DJ, Hoffbrand AV. Clearance of skin lesions in dermatitis herpetiformis after gluten
withdrawal. Lancet. 1973;1(7798):288-91. doi: 10.1016/s0140-6736(73)91539-0
Reunala T, Hervonen K, Salmi T. Dermatitis Herpetiformis: An Update on Diagnosis and Management. Am
J Clin Dermatol. 2021;22(3):329-38. doi: 10.1007/s40257-020-00584-2
Bilgin H, Ozcan B, Bilgin T. Methemoglobinemia induced by methylene blue pertubation during
laparoscopy. Acta Anaesthesiol Scand. 1998;42(5):594-5. doi: 10.1111/j.1399-6576.1998.tb05173.x
Antiga E, Caproni M. The diagnosis and treatment of dermatitis herpetiformis. Clin Cosmet Investig
Dermatol. 2015;8:257-65. doi: 10.2147/CCID.S69127
Albers LN, Zone JJ, Stoff BK, Feldman RJ. Rituximab Treatment for Recalcitrant Dermatitis Herpetiformis.
JAMA Dermatol. 2017;153(3):315-8. doi: 10.1001/jamadermatol.2016.4676
Cinats AK, Parsons LM, Haber RM. Facial Involvement in Dermatitis Herpetiformis: A Case Report and
Review of the Literature. J Cutan Med Surg. 2019;23(1):35-7. doi: 10.1177/1203475418795818
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2024 Jakub Zwardoń, Alicja Kapciak, Julia Górny, Gabriela Witas, Artur Hawajski, Natalia Jankowska, Oliwia Kamieniecka, Katarzyna Naja, Adrianna Świerzyńska
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
Stats
Number of views and downloads: 53
Number of citations: 0