Skip to main content

Advertisement

Log in

Current clinical issue of skin lesions in patients with inflammatory bowel disease

  • Clinical Review
  • Published:
Clinical Journal of Gastroenterology Aims and scope Submit manuscript

Abstract

Inflammatory bowel disease (IBD) is associated with a number of extraintestinal complications, including skin lesions. Most reports have shown that skin lesions are found in 10–15% of IBD cases, although this depends on the definition of skin lesions. The representative skin lesions in patients with IBD are erythema nodosum, pyoderma gangrenosum, Sweet’s syndrome, and so on. These lesions are often associated with IBD progression, and intestinal lesions in particular require appropriate treatment. Recently, another clinical issue regarding skin lesions in patients with IBD, a so-called paradoxical reaction, during the treatment with anti-tumor necrosis factor (TNF)-α agents has emerged. These reactions are termed paradoxical reactions because the skin lesions sometimes resemble psoriasis, although the anti-TNF-α agents have been historically used to treat psoriasis. Paradoxical reactions are reportedly found in approximately 5–10% of patients using anti-TNF-α agents and are no longer rare. Now that the use of biologics is at its culmination, reports regarding paradoxical reactions are predicted to increase in number; thus, we must recognize skin lesions with IBD patients including this type of adverse events and manage them appropriately while consulting with dermatologists.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Molodecky NA, Soon IS, Rabi DM, et al. Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review. Gastroenterology. 2012;142:46–54.

    PubMed  Google Scholar 

  2. Ottaviano G, Salvatore S, Salvatoni A, et al. Ocular manifestations of paediatric inflammatory bowel disease: a systematic review and meta-analysis. J Crohns Colitis. 2018;12:870–9.

    PubMed  Google Scholar 

  3. Fine S, Nee J, Thakuria P, et al. Ocular, auricular, and oral manifestations of inflammatory bowel disease. Dig Dis Sci. 2017;62:3269–79.

    PubMed  Google Scholar 

  4. Troncoso LL, Biancardi AL, de Moraes HV Jr, et al. Ophthalmic manifestations in patients with inflammatory bowel disease: a review. World J Gastroenterol. 2017;23:5836–48.

    PubMed  PubMed Central  Google Scholar 

  5. Lee HJ, Song HJ, Jeong JH, et al. Ophthalmologic manifestations in patients with inflammatory bowel disease. Intest Res. 2017;15:380–7.

    PubMed  PubMed Central  Google Scholar 

  6. Hammoudeh M, Elsayed E, Al-Kaabi S, et al. Rheumatic manifestations of inflammatory bowel diseases: a study from the Middle East. J Int Med Res. 2018;46:3837–47.

    PubMed  PubMed Central  Google Scholar 

  7. Pouillon L, Bossuyt P, Vanderstukken J, et al. Management of patients with inflammatory bowel disease and spondyloarthritis. Expert Rev Clin Pharmacol. 2017;10:1363–74.

    CAS  PubMed  Google Scholar 

  8. Vavricka SR, Brun L, Ballabeni P, et al. Frequency and risk factors for extraintestinal manifestations in the Swiss inflammatory bowel disease cohort. Am J Gastroenterol. 2011;106:110–9.

    PubMed  Google Scholar 

  9. Vavricka SR, Schoepfer A, Scharl M, et al. Extraintestinal manifestations of inflammatory bowel disease. Inflamm Bowel Dis. 2015;21:1982–92.

    PubMed  PubMed Central  Google Scholar 

  10. Monsén U, Sorstad J, Hellers G, et al. Extracolonic diagnoses in ulcerative colitis: an epidemiological study. Am J Gastroenterol. 1990;85:711–6.

    PubMed  Google Scholar 

  11. Lo B, Julsgaard M, Vester-Andersen MK, et al. Disease activity, steroid use and extraintestinal manifestation are associated with increased disability in patients with inflammatory bowel disease using the inflammatory bowel disease disability index: a cross-sectional multicentre cohort study. Eur J Gastroenterol Hepatol. 2018;30:1130–6.

    CAS  PubMed  Google Scholar 

  12. Godat S, Fournier N, Safroneeva E, et al. Frequency and type of drug-related side effects necessitating treatment discontinuation in the Swiss Inflammatory Bowel Disease Cohort. Eur J Gastroenterol Hepatol. 2018;30:612–20.

    PubMed  Google Scholar 

  13. Cleynen I, Vermeire S. Paradoxical inflammation induced by anti-TNF agents in patients with IBD. Nat Rev Gastroenterol Hepatol. 2012;9:496–503.

    CAS  PubMed  Google Scholar 

  14. Lichtenstein L, Ron Y, Kivity S, et al. Infliximab-related infusion reactions: systematic review. J Crohns Colitis. 2015;9:806–15.

    PubMed  PubMed Central  Google Scholar 

  15. Duron C, Goutte M, Pereira B, et al. Factors influencing acute infusion reactions in inflammatory bowel disease patients treated with infliximab in the era of scheduled maintenance therapy. Eur J Gastroenterol Hepatol. 2015;27:705–11.

    CAS  PubMed  Google Scholar 

  16. Keane J, Gershon S, Wise RP, et al. Tuberculosis associated with infliximab, a tumor necrosis factor alpha-neutralizing agent. N Engl J Med. 2001;345:1098–104.

    CAS  PubMed  Google Scholar 

  17. Park DI, Hisamatsu T, Chen M, et al. Asian Organization for Crohn’s and Colitis and Asian Pacific Association of Gastroenterology consensus on tuberculosis infection in patients with inflammatory bowel disease receiving anti-tumor necrosis factor treatment. Part 1: risk assessment. J Gastroenterol Hepatol. 2018;33:20–9.

    PubMed  Google Scholar 

  18. Greenstein AJ, Janowitz HD, Sachar DB. The extra-intestinal complications of Crohn’s disease and ulcerative colitis: a study of 700 patients. Medicine. 1976;55:401–12.

    CAS  PubMed  Google Scholar 

  19. Rankin GB, Watts HD, Melnyk CS, et al. National Cooperative Crohn’s Disease Study: extraintestinal manifestations and perianal complications. Gastroenterology. 1979;77:914–20.

    CAS  PubMed  Google Scholar 

  20. Veloso FT, Carvalho J, Magro F. Immune-related systemic manifestations of inflammatory bowel disease. A prospective study of 792 patients. J Clin Gastroenterol. 1996;23:29–34.

    CAS  PubMed  Google Scholar 

  21. Jose FA, Garnett EA, Vittinghoff E, et al. Development of extraintestinal manifestations in pediatric patients with inflammatory bowel disease. Inflamm Bowel Dis. 2009;15:63–8.

    PubMed  Google Scholar 

  22. Ott C, Schölmerich J. Extraintestinal manifestations and complications in IBD. Nat Rev Gastroenterol Hepatol. 2013;10:585–95.

    CAS  PubMed  Google Scholar 

  23. Marzano AV, Borghi A, Stadnicki A, et al. Cutaneous manifestations in patients with inflammatory bowel diseases: pathophysiology, clinical features, and therapy. Inflamm Bowel Dis. 2014;20:213–27.

    PubMed  Google Scholar 

  24. Alreheili KM, Alsaleem KA, Almehaidib AI. Natural history and outcome of inflammatory bowel diseases in children in Saudi Arabia: a single-center experience. Saudi J Gastroenterol. 2018;24:171–6.

    PubMed  PubMed Central  Google Scholar 

  25. Burgdorf W. Cutaneous manifestations of Crohn’s disease. J Am Acad Dermatol. 1981;5:689–95.

    CAS  PubMed  Google Scholar 

  26. Palamaras I, El-Jabbour J, Pietropaolo N, et al. Metastatic Crohn’s disease: a review. J Eur Acad Dermatol Venereol. 2008;22:1033–43.

    CAS  PubMed  Google Scholar 

  27. Freeman HJ. Erythema nodosum and pyoderma gangrenosum in 50 patients with Crohn’s disease. Can J Gastroenterol. 2005;19:603–6.

    PubMed  Google Scholar 

  28. Farhi D, Cosnes J, Zizi N, et al. Significance of erythema nodosum and pyoderma gangrenosum in inflammatory bowel diseases: a cohort study of 2402 patients. Medicine. 2008;87:281–93.

    PubMed  Google Scholar 

  29. Saltman AP, Kuriya B. Löfgren syndrome in acute sarcoidosis. CMAJ. 2017;189:E1230.

    PubMed  PubMed Central  Google Scholar 

  30. Davatchi F, Chams-Davatchi C, Shams H, et al. Adult Behcet’s disease in Iran: analysis of 6075 patients. Int J Rheum Dis. 2016;19:95–103.

    CAS  PubMed  Google Scholar 

  31. Passarini B, Infusino SD. Erythema nodosum. G Ital Dermatol Venereol. 2013;148:413–7.

    CAS  PubMed  Google Scholar 

  32. Apgar JT. Newer aspects of inflammatory bowel disease and its cutaneous manifestations: a selective review. Semin Dermatol. 1991;10:138–47.

    CAS  PubMed  Google Scholar 

  33. Timani S, Mutasim DF. Skin manifestations of inflammatory bowel disease. Clin Dermatol. 2008;26:265–73.

    PubMed  Google Scholar 

  34. Lakatos PL, Lakatos L, Kiss LS, et al. Treatment of extraintestinal manifestations in inflammatory bowel disease. Digestion. 2012;86:28–35.

    CAS  PubMed  Google Scholar 

  35. Clayton TH, Walker BP, Stables GI. Treatment of chronic erythema nodosum with infliximab. Clin Exp Dermatol. 2006;31:823–4.

    CAS  PubMed  Google Scholar 

  36. Quin A, Kane S, Ulitsky O. A case of fistulizing Crohn’s disease and erythema nodosum managed with adalimumab. Nat Clin Pract Gastroenterol Hepatol. 2008;5:278–81.

    PubMed  Google Scholar 

  37. Vavricka SR, Gubler M, Gantenbein C, et al. Anti-TNF treatment for extraintestinal manifestations of inflammatory bowel disease in the Swiss IBD Cohort Study. Inflamm Bowel Dis. 2017;23:1174–81.

    PubMed  Google Scholar 

  38. Greuter T, Navarini A, Vavricka SR. Skin manifestations of inflammatory bowel disease. Clin Rev Allergy Immunol. 2017;53:413–27.

    CAS  PubMed  Google Scholar 

  39. Polcz M, Gu J, Florin T. Pyoderma gangrenosum in inflammatory bowel disease: the experience at Mater Health Services’ Adult Hospital 1998–2009. J Crohns Colitis. 2011;5:148–51.

    PubMed  Google Scholar 

  40. Bennett ML, Jackson JM, Jorizzo JL, et al. Pyoderma gangrenosum. A comparison of typical and atypical forms with an emphasis on time to remission. Case review of 86 patients from 2 institutions. Medicine (Baltimore). 2000;79:37–46.

    CAS  Google Scholar 

  41. Powell FC, Su WP, Perry HO. Pyoderma gangrenosum: classification and management. J Am Acad Dermatol. 1996;34:395–409.

    CAS  PubMed  Google Scholar 

  42. Lora V, Cerroni L, Cota C. Skin manifestations of rheumatoid arthritis. G Ital Dermatol Venereol. 2018;153:243–55.

    PubMed  Google Scholar 

  43. Chasset F, Francès C. Cutaneous manifestations of medium- and large-vessel vasculitis. Clin Rev Allergy Immunol. 2017;53:452–68.

    CAS  PubMed  Google Scholar 

  44. Ahn C, Negus D, Huang W. Pyoderma gangrenosum: a review of pathogenesis and treatment. Expert Rev Clin Immunol. 2018;14:225–33.

    CAS  PubMed  Google Scholar 

  45. Callen JP. Pyoderma gangrenosum. Lancet. 1998;351:581–5.

    CAS  PubMed  Google Scholar 

  46. Rothfuss KS, Stange EF, Herrlinger KR. Extraintestinal manifestations and complications in inflammatory bowel diseases. World J Gastroenterol. 2006;12:4819–31.

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Huang W, McNeely MC. Neutrophilic tissue reactions. Adv Dermatol. 1997;13:33–64.

    CAS  PubMed  Google Scholar 

  48. Weizman A, Huang B, Berel D, et al. Clinical, serologic, and genetic factors associated with pyoderma gangrenosum and erythema nodosum in inflammatory bowel disease patients. Inflamm Bowel Dis. 2014;20:525–33.

    PubMed  PubMed Central  Google Scholar 

  49. Thomas KS, Ormerod AD, Craig FE, et al. UK Dermatology Clinical Trials Network’s STOP GAP Team. Clinical outcomes and response of patients applying topical therapy for pyoderma gangrenosum: a prospective cohort study. J Am Acad Dermatol. 2016;75:940–9.

    PubMed  Google Scholar 

  50. Rice SA, Woo PN, El-Omar E, et al. Topical tacrolimus 0.1% ointment for treatment of cutaneous Crohn’s disease. BMC Res Notes. 2013;6:19.

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Jolles S, Niclasse S, Benson E. Combination oral and topical tacrolimus in therapy-resistant pyoderma gangrenosum. Br J Dermatol. 1999;140:564–5.

    CAS  PubMed  Google Scholar 

  52. Friedman S, Marion JF, Scherl E, et al. Intravenous cyclosporine in refractory pyoderma gangrenosum complicating inflammatory bowel disease. Inflamm Bowel Dis. 2001;7:1–7.

    CAS  PubMed  Google Scholar 

  53. Carp JM, Onuma E, Das K, et al. Intravenous cyclosporine therapy in the treatment of pyoderma gangrenosum secondary to Crohn’s disease. Cutis. 1997;60:135–8.

    CAS  PubMed  Google Scholar 

  54. Sapienza MS, Cohen S, Dimarino AJ. Treatment of pyoderma gangrenosum with infliximab in Crohn’s disease. Dig Dis Sci. 2004;49:1454–7.

    CAS  PubMed  Google Scholar 

  55. Brooklyn TN, Dunnill MG, Shetty A, et al. Infliximab for the treatment of pyoderma gangrenosum: a randomised, double blind, placebo controlled trial. Gut. 2006;55:505–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Vavricka SR, Scharl M, Gubler M, et al. Biologics for extraintestinal manifestations of IBD. Curr Drug Targets. 2014;15:1064–73.

    CAS  PubMed  Google Scholar 

  57. Hurabielle C, Schneider P, Baudry C, et al. Certolizumab pegol - A new therapeutic option for refractory disseminated pyoderma gangrenosum associated with Crohn’s disease. J Dermatolog Treat. 2016;27:67–9.

    CAS  PubMed  Google Scholar 

  58. Afifi L, Sanchez IM, Wallace MM, et al. Diagnosis and management of peristomal pyoderma gangrenosum: a systematic review. J Am Acad Dermatol. 2018;78:1195–204.e1.

    PubMed  Google Scholar 

  59. Ohmori T, Yamagiwa A, Nakamura I, et al. Treatment of pyoderma gangrenosum associated with Crohn’s disease. Am J Gastroenterol. 2003;98:2101–2.

    PubMed  Google Scholar 

  60. Ohno M, Koyama S, Ohara M, et al. Pyoderma gangrenosum with ulcerative colitis successfully treated by the combination of granulocyte and monocyte adsorption apheresis and corticosteroids. Intern Med. 2016;55:25–30.

    CAS  PubMed  Google Scholar 

  61. Sweet D. An acute febrile neutrophilic dermatosis. Br J Dermatol. 1964;76:350–6.

    Google Scholar 

  62. Salmon P, Rademaker M, Edwards L. A continuum of neutrophilic disease occurring in a patient with ulcerative colitis. Australas J Dermatol. 1998;39:116–8.

    CAS  PubMed  Google Scholar 

  63. Becuwe C, Delaporte E, Colombel JF, et al. Sweet’s syndrome associated with Crohn’s disease. Acta Derm Venereol. 1989;69:444–5.

    CAS  PubMed  Google Scholar 

  64. Travis S, Innes N, Davies MG, et al. Sweet’s syndrome: an unusual cutaneous feature of Crohn’s disease or ulcerative colitis. Eur J Gastroenterol Hepatol. 1997;9:715–20.

    CAS  PubMed  Google Scholar 

  65. Ali M, Duerksen DR. Ulcerative colitis and Sweet’s syndrome: a case report and review of the literature. Can J Gastroenterol. 2008;22:296–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  66. Shin OR, Lee Y, Bak S, et al. Gastroenterology: sweet’s syndrome in a patient with acutely exacerbated ulcerative colitis. J Gastroenterol Hepatol. 2015;30:965.

    PubMed  Google Scholar 

  67. Lopes CR, Soares M, Cardoso C, et al. Sweet’s syndrome complicating ulcerative colitis: a rare association. BMJ Case Rep. 2016;2016:pii: bcr2015212990.

    Google Scholar 

  68. Calixto R, Menezes Y, Ostronoff M, et al. Favorable outcome of severe, extensive, granulocyte colony-stimulating factor-induced, corticosteroid-resistant Sweet’s syndrome treated with high-dose intravenous immunoglobulin. J Clin Oncol. 2014;32:e1–2.

    PubMed  Google Scholar 

  69. Fukutoku M, Shimizu S, Ogawa Y, et al. Sweet’s syndrome during therapy with granulocyte colony-stimulating factor in a patient with aplastic anaemia. Br J Haematol. 1994;86:645–8.

    CAS  PubMed  Google Scholar 

  70. Fujii A, Mizutani Y, Hattori Y, et al. Sweet’s syndrome successfully treated with granulocyte and monocyte adsorption apheresis. Case Rep Dermatol. 2017;9:13–8.

    PubMed  PubMed Central  Google Scholar 

  71. Yasuda F, Fujio Y, Kakuta R, et al. Use of cyclosporin A for successful management of steroid-resistant Sweet’s syndrome patient with possible myelodysplastic syndrome. J Dermatol. 2014;41:465–6.

    CAS  PubMed  Google Scholar 

  72. Martínez Andrés B, Sastre Lozano V, Sánchez Melgarejo JF. Sweet syndrome after treatment with vedolizumab in a patient with Crohn’s disease. Rev Esp Enferm Dig. 2018;110:530.

    PubMed  Google Scholar 

  73. Maeda K, Okada M, Yao T, et al. Intestinal and extraintestinal complications of Crohn’s disease: predictors and cumulative probability of complications. J Gastroenterol. 1994;29:577–82.

    CAS  PubMed  Google Scholar 

  74. Letsinger JA, McCarty MA, Jorizzo JL. Complex aphthosis: a large case series with evaluation algorithm and therapeutic ladder from topicals to thalidomide. J Am Acad Dermatol. 2005;52:500–8.

    PubMed  Google Scholar 

  75. Basu MK, Asquith P. Oral manifestations of inflammatory bowel disease. Clin Gastroenterol. 1980;9:307–21.

    CAS  PubMed  Google Scholar 

  76. Kurtzman DJ, Jones T, Lian F, et al. Metastatic Crohn’s disease: a review and approach to therapy. J Am Acad Dermatol. 2014;71:804–13.

    PubMed  Google Scholar 

  77. Guest GD, Fink RL. Metastatic Crohn’s disease: case report of an unusual variant and review of the literature. Dis Colon Rectum. 2000;43:1764–6.

    CAS  PubMed  Google Scholar 

  78. Marotta PJ, Reynolds RP. Metastatic Crohn’s disease. Am J Gastroenterol. 1996;9:373–5.

    Google Scholar 

  79. Sabbadini C, Banzato C, Schena D, et al. Metastatic Crohn’s disease in childhood. J Dtsch Dermatol Ges. 2016;14:431–4.

    PubMed  Google Scholar 

  80. Siroy A, Wasman J. Metastatic Crohn disease: a rare cutaneous entity. Arch Pathol Lab Med. 2012;136:329–32.

    PubMed  Google Scholar 

  81. Chiba M, Iizuka M, Horie Y, et al. Metastatic Crohn’s disease involving the penis. J Gastroenterol. 1997;32:817–21.

    CAS  PubMed  Google Scholar 

  82. Albuquerque A, Magro F, Rodrigues S, et al. Metastatic cutaneous Crohn’s disease of the face: a case report and review of the literature. Eur J Gastroenterol Hepatol. 2011;23:954–6.

    PubMed  Google Scholar 

  83. Carranza DC, Young L. Successful treatment of metastatic Crohn’s disease with cyclosporine. J Drugs Dermatol. 2008;7:789–91.

    PubMed  Google Scholar 

  84. Kiuru M, Camp B, Adhami K, et al. Treatment of metastatic cutaneous Crohn disease with certolizumab. Dermatol Online J. 2015;21.

  85. Wylomanski S, Bouquin R, Dréno B, et al. Spectacular response of metastatic vulval Crohn’s disease to infliximab treatment. Int J Dermatol. 2016;55:1146–8.

    PubMed  Google Scholar 

  86. Williams N, Scott NA, Watson JS, et al. Surgical management of perineal and metastatic cutaneous Crohn’s disease. Br J Surg. 1993;80:1596–8.

    CAS  PubMed  Google Scholar 

  87. Zouboulis CC, Desai N, Emtestam L, et al. European S1 guideline for the treatment of hidradenitis suppurativa/acne inversa. J Eur Acad Dermatol Venereol. 2015;29:619–44.

    CAS  PubMed  Google Scholar 

  88. Zouboulis CC, Del Marmol V, Mrowietz U, et al. Hidradenitis suppurativa/acne inversa: criteria for diagnosis, severity assessment, classification and disease evaluation. Dermatology. 2015;231:184–90.

    PubMed  Google Scholar 

  89. van der Zee HH, de Winter K, van der Woude CJ, et al. The prevalence of hidradenitis suppurativa in 1093 patients with inflammatory bowel disease. Br J Dermatol. 2014;171:673–5.

    PubMed  Google Scholar 

  90. Yadav S, Singh S, Edakkanambeth Varayil J, et al. Hidradenitis suppurativa in patients with inflammatory bowel disease: a population-based cohort study in Olmsted County, Minnesota. Clin Gastroenterol Hepatol. 2016;14:65–70.

    PubMed  Google Scholar 

  91. van der Zee HH, van der Woude CJ, Florencia EF, et al. Hidradenitis suppurativa and inflammatory bowel disease: are they associated? Results of a pilot study. Br J Dermatol. 2010;162:195–7.

    PubMed  Google Scholar 

  92. Deckers IE, Benhadou F, Koldijk MJ, et al. Inflammatory bowel disease is associated with hidradenitis suppurativa: Results from a multicenter cross-sectional study. J Am Acad Dermatol. 2017;76:49–53.

    PubMed  Google Scholar 

  93. Lukach AJ, Saul MI, Ferris LK, et al. Risk factors for hidradenitis suppurativa in patients with inflammatory bowel disease. Dig Dis Sci. 2018;63:755–60.

    PubMed  Google Scholar 

  94. Ortiz-Masiá D, Cosín-Roger J, Calatayud S, et al. M1 Macrophages activate notch signalling in epithelial cells: relevance in Crohn’s disease. J Crohns Colitis. 2016;10:582–92.

    PubMed  PubMed Central  Google Scholar 

  95. Schlapbach C, Hänni T, Yawalkar N, et al. Expression of the IL-23/Th17 pathway in lesions of hidradenitis suppurativa. J Am Acad Dermatol. 2011;65:790–8.

    CAS  PubMed  Google Scholar 

  96. Ingram JR. The genetics of hidradenitis suppurativa. Dermatol Clin. 2016;34:23–8.

    CAS  PubMed  Google Scholar 

  97. Alikhan A, Lynch PJ, Eisen DB. Hidradenitis suppurativa: a comprehensive review. J Am Acad Dermatol. 2009;60:539–61 (quiz 562–3).

    PubMed  Google Scholar 

  98. Knowles SR, Graff LA, Wilding H, et al. Quality of life in inflammatory bowel disease: a systematic review and meta-analyses—part I. Inflamm Bowel Dis. 2018;24:742–51.

    PubMed  Google Scholar 

  99. Knowles SR, Graff LA, Wilding H, et al. Quality of life in inflammatory bowel disease: a systematic review and meta-analyses—part II. Inflamm Bowel Dis. 2018;24:966–76.

    PubMed  Google Scholar 

  100. Kimball AB, Kerdel F, Adams D, et al. Adalimumab for the treatment of moderate to severe Hidradenitis suppurativa: a parallel randomized trial. Ann Intern Med. 2012;157:846–55.

    PubMed  Google Scholar 

  101. Gottlieb A, Menter A, Armstrong A, et al. Adalimumab treatment in women with moderate-to-severe hidradenitis suppurativa from the placebo-controlled portion of a phase 2, randomized, double-blind study. J Drugs Dermatol. 2016;15:1192–6.

    CAS  PubMed  Google Scholar 

  102. Kimball AB, Okun MM, Williams DA, et al. Two phase 3 trials of adalimumab for hidradenitis suppurativa. N Engl J Med. 2016;375:422–34.

    CAS  PubMed  Google Scholar 

  103. Kerbleski JF, Gottlieb AB. Dermatological complications and safety of anti-TNF treatments. Gut. 2009;58:1033–9.

    CAS  PubMed  Google Scholar 

  104. Fréling E, Baumann C, Cunty JF, et al. Cumulative incidence of, risk factors for, and outcome of dermatological complications of anti-TNF therapy in inflammatory bowel disease: a 14-year experience. Am J Gastroenterol. 2015;110:1186–96.

    PubMed  Google Scholar 

  105. Cleynen I, Moerkercke WV, Billiet T, et al. Characteristics of skin lesions associated with anti-tumor necrosis factor therapy in patients with inflammatory bowel disease. Ann Intern Med. 2016;164:10–22.

    PubMed  Google Scholar 

  106. Verea MM, Del Pozo J, Yebra-Pimental MT, et al. Psoriasiform eruption induced by infliximab. Ann Pharmacother. 2004;38:54–5.

    PubMed  Google Scholar 

  107. Sfikakis PP, Ilipoulos A, Elezoglou A, et al. Psoriasis induced by anti-tumor necrosis factor therapy: a paradoxical adverse reaction. Arthritis Rheum. 2005;52:2513–8.

    CAS  PubMed  Google Scholar 

  108. Gottlieb AB, Evans R, Li S, et al. Infliximab induction therapy for patients with severe plaque-type psoriasis: a randomized, double-blind, placebo-controlled trial. J Am Acad Dermatol. 2004;51:534–42.

    PubMed  Google Scholar 

  109. Asahina A, Nakagawa H, Etoh T, Adalimumab M04-688 Study Group, et al. Adalimumab in Japanese patients with moderate to severe chronic plaque psoriasis: efficacy and safety results from a Phase II/III randomized controlled study. J Dermatol. 2010;37:299–310.

    CAS  PubMed  Google Scholar 

  110. Andrade P, Lopes S, Gaspar R, et al. Anti-tumor necrosis factor-α-induced dermatological complications in a large cohort of inflammatory bowel disease patients. Dig Dis Sci. 2018;63:746–54.

    CAS  PubMed  Google Scholar 

  111. Bae JM, Lee HH, Lee BI, et al. Incidence of psoriasiform diseases secondary to tumour necrosis factor antagonists in patients with inflammatory bowel disease: a nationwide population-based cohort study. Aliment Pharmacol Ther. 2018;48:196–205.

    CAS  PubMed  Google Scholar 

  112. Afzali A, Wheat CL, Hu JK, Olerud JE, Lee SD. The association of psoriasiform rash with anti-tumor necrosis factor (anti-TNF) therapy in inflammatory bowel disease: a single academic center case series. J Crohns Colitis. 2014;8:480–8.

    PubMed  Google Scholar 

  113. Rahier JF, Buche S, Peyrin-Biroulet L, et al. Groupe d’Etude Thérapeutique des Affections Inflammatoires du Tube Digestif (GETAID). Severe skin lesions cause patients with inflammatory bowel disease to discontinue anti-tumor necrosis factor therapy. Clin Gastroenterol Hepatol. 2010;8:1048–55.

    PubMed  Google Scholar 

  114. Collamer AN, Battafarano DF. Psoriatic skin lesions induced by tumor necrosis factor antagonist therapy: clinical features and possible immunopathogenesis. Semin Arthritis Rheum. 2010;40:233–40.

    CAS  PubMed  Google Scholar 

  115. Shmidt E, Wetter DA, Ferguson SB, et al. Psoriasis and palmoplantar pustulosis associated with tumor necrosis factor-α inhibitors: the Mayo Clinic experience, 1998 to 2010. J Am Acad Dermatol. 2012;67:e179-85.

    PubMed  Google Scholar 

  116. Tillack C, Ehmann LM, Friedrich M, et al. Anti-TNF antibody-induced psoriasiform skin lesions in patients with inflammatory bowel disease are characterized by interferon-γ expressing Th1 cells and IL-17A/IL-22-expressing Th17 cells and respond to anti-IL-12/IL-23 antibody treatment. Gut. 2014;63:567–77.

    CAS  PubMed  Google Scholar 

  117. Pugliese D, Guldi L, Ferraro PM, et al. Paradoxical psoriasis in a large cohort of patients with inflammatory bowel disease receiving treatment with anti-TNF alpha: 5-year follow-up study. Aliment Pharmacol Ther. 2015;42:880–8.

    CAS  PubMed  Google Scholar 

  118. Ko JM, Gottlieb AB, Kerbleski JF. Induction and exacerbation of psoriasis with TNF-blockade therapy: a review and analysis of 127 cases. J Dermatolog Treat. 2009;20:100–8.

    CAS  PubMed  Google Scholar 

  119. Numakura T, Tamada T, Nara M, et al. Simultaneous development of sarcoidosis and cutaneous vasculitis in a patient with refractory Crohn’s disease during infliximab therapy. BMC Pulm Med. 2016;16:30.

    PubMed  PubMed Central  Google Scholar 

  120. Gîlcă GE, Diaconescu S, Bălan GG, et al. Sarcoidosis associated with infliximab therapy in ulcerative colitis: a case report. Medicine (Baltimore). 2017;96:e6156.

    Google Scholar 

  121. Decock A, Van Assche G, Vermeire S, et al. Sarcoidosis-like lesions: another paradoxical reaction to anti-TNF therapy? J Crohns Colitis. 2017;11:378–83.

    PubMed  Google Scholar 

  122. Amano H, Matsuda R, Shibata T, et al. Paradoxical SAPHO syndrome observed during anti-TNFα therapy for Crohn’s disease. Biologics. 2017;11:65–9.

    PubMed  PubMed Central  Google Scholar 

  123. Marzano AV, Tavecchio S, Berti E, et al. Paradoxical autoinflammatory skin reaction to tumor necrosis factor alpha blockers manifesting as amicrobial pustulosis of the folds in patients with inflammatory bowel diseases. Medicine (Baltimore). 2015;94:e1818.

    CAS  Google Scholar 

  124. Keohane SG, Hayes PC, Hunter JA. Lichen planus and Crohn’s disease. Acta Derm Venereol. 1997;77:488.

    CAS  PubMed  Google Scholar 

  125. Kumar KM, Nachiammai N, Madhushankari GS. Association of oral manifestations in ulcerative colitis: a pilot study. J Oral Maxillofac Pathol. 2018;22:199–203.

    PubMed  PubMed Central  Google Scholar 

  126. Alice Sy N, Khalidi N, Dehghan, et al. Vasculitis in patients with inflammatory bowel diseases: a study of 32 patients and systematic review of the literature. Semin Arthritis Rheum. 2016;45:475–82.

    PubMed  Google Scholar 

  127. Humbert S, Guilpain P, Puéchal X, et al. Inflammatory bowel diseases in anti-neutrophil cytoplasmic antibody-associated vasculitides: 11 retrospective cases from the French Vasculitis Study Group. Rheumatology. 2015;54:1970–5.

    CAS  PubMed  Google Scholar 

  128. Reddy H, Shipman AR, Wojnarowska F. Epidermolysis bullosa acquisita and inflammatory bowel disease: a review of the literature. Clin Exp Dermatol. 2013;38:225–9 (quiz 229–30).

    CAS  PubMed  Google Scholar 

  129. Raab B, Fretzin DF, Bronson DM, et al. Epidermolysis bullosa acquisita and inflammatory bowel disease. JAMA. 1983;250:1746–8.

    CAS  PubMed  Google Scholar 

  130. Fernández-Guarino M, Sáez EM, Gijón RC, et al. Linear IGA dermatosis associated with ulcerative colitis. Eur J Dermatol. 2006;16:692–3.

    PubMed  Google Scholar 

  131. Taniguchi T, Maejima H, Saito N, et al. Case of linear IgA bullous dermatosis-involved ulcerative colitis. Inflamm Bowel Dis. 2009;15:1284–5.

    PubMed  Google Scholar 

  132. Vedak P, Kroshinsky D, St John J, et al. Genetic basis of TNF-α antagonist associated psoriasis in inflammatory bowel diseases: a genotype-phenotype analysis. Aliment Pharmacol Ther. 2016;43:697–704.

    CAS  PubMed  PubMed Central  Google Scholar 

  133. Glimcher LH, Townsend MJ, Sullivan BM, et al. Recent developments in the transcriptional regulation of cytolytic effector cells. Nat Rev Immunol. 2004;4:900–11.

    CAS  PubMed  Google Scholar 

  134. Rácz E, Prens EP. Molecular pathophysiology of psoriasis and molecular targets of antipsoriatic therapy. Expert Rev Mol Med. 2009;11:e38.

    PubMed  Google Scholar 

  135. Nestle FO, Gilliet M. Defining upstream elements of psoriasis pathogenesis: an emerging role for interferon alpha. J Investig Dermatol. 2005;125:xiv–xv.

    CAS  PubMed  Google Scholar 

  136. Niess JH, Danese S. Anti-TNF and skin inflammation in IBD: a new paradox in gastroenterology? Gut. 2014;63:533–5.

    CAS  PubMed  Google Scholar 

  137. Collamer AN, Guerrero KT, Henning JS, et al. Psoriatic skin lesions induced by tumor necrosis factor antagonist therapy: a literature review and potential mechanisms of action. Arthritis Rheum. 2008;59:996–1001.

    CAS  PubMed  Google Scholar 

  138. Matsumoto S, Mashima H. Efficacy of ustekinumab against infliximab-induced psoriasis and arthritis associated with Crohn’s disease. Biologics. 2018;12:69–73.

    CAS  PubMed  PubMed Central  Google Scholar 

  139. Delobeau M, Abdou A, Puzenat E, et al. Observational case series on adalimumab-induced paradoxical hidradenitis suppurativa. J Dermatolog Treat. 2016;27:251–3.

    CAS  PubMed  Google Scholar 

  140. Benzaquen M, Flachaire B, Rouby F, et al. Paradoxical pustular psoriasis induced by ustekinumab in a patient with Crohn’s disease-associated spondyloarthropathy. Rheumatol Int. 2018;38:1297–9.

    CAS  PubMed  Google Scholar 

  141. Lee HY, Woo CH, Haw S. Paradoxical Flare of Psoriasis after Ustekinumab Therapy. Ann Dermatol. 2017;29:794–5.

    PubMed  PubMed Central  Google Scholar 

  142. Fiorino G, Allez M, Malesci A, et al. Review article: anti TNF-alpha induced psoriasis in patients with inflammatory bowel disease. Aliment Pharmacol Ther. 2009;29:921–7.

    CAS  PubMed  Google Scholar 

  143. Soh JS, Yun WJ, Kim KJ, et al. Concomitant use of azathioprine/6-mercaptopurine decreases the risk of anti-TNF-induced skin lesions. Inflamm Bowel Dis. 2015;21:832–9.

    PubMed  Google Scholar 

Download references

Funding

This work was partly supported by Health and Labour Sciences Research Grants for research on intractable diseases from the Ministry of Health, Labour and Welfare of Japan (Investigation and Research for intractable Inflammatory Bowel Disease) (to H.N.), and Japan Society for the Promotion of Science (JSPS) Grants-in-Aid for Scientific Research (KAKENHI) Grant Number JP17J02428 (to T.I.) and JP18H02799 (to H.N.). The funders of the study had no role in the study design, data collection, data analysis, data interpretation, or writing of the report.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Hiroshi Nakase.

Ethics declarations

Conflict of interest

The authors declare no conflict of interest.

Human rights statement

All procedures followed have been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.

Informed consent

Informed consent was obtained from all patients for being included in the study.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Iida, T., Hida, T., Matsuura, M. et al. Current clinical issue of skin lesions in patients with inflammatory bowel disease. Clin J Gastroenterol 12, 501–510 (2019). https://doi.org/10.1007/s12328-019-00958-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12328-019-00958-y

Keywords

Navigation