Skip to main content

Advertisement

SpringerLink
Log in

Anti-Tumor Necrosis Factor-α-Induced Dermatological Complications in a Large Cohort of Inflammatory Bowel Disease Patients

  • Original Article
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

Background/Aims

The broader use of anti-tumor necrosis factor (TNF) agents in inflammatory bowel disease (IBD) has been associated with a high rate of adverse reactions. Dermatological complications are among the most common adverse events. We assessed the incidence, risk factors, management, and outcome of anti-TNF-induced dermatological complications in a large cohort of IBD patients.

Methods

This was an observational retrospective study at a single tertiary referral center. All consecutive adult IBD patients treated with anti-TNF agents between 2005 and 2015 were identified. Patients who developed at least one dermatological complication while on anti-TNF therapy were included.

Results

From the 732 patients treated with anti-TNF agents, 211 (29%) developed at least one dermatological complication: 52% women (mean age of 42 ± 13 years), 85% with Crohn’s disease, 67% were under infliximab. Median follow-up time under anti-TNF therapy was 53 (27–77) months. Dermatological complications recorded were: infections (13.5%), psoriasiform lesions (5.3%), injection/infusion reactions (3.8%), skin cancer (0.5%), and miscellaneous (5.6%). Overall, female gender (OR = 1.658, p = 0.029), smoking (OR = 2.021, p = 0.003), and treatment with an infliximab dose of 10 mg/kg (OR = 2.012, p = 0.007) were independent risk factors for dermatological complications in multivariable analysis. Female gender (OR = 3.63, p = 0.017), smoking (OR = 2.846, p = 0.041), and treatment with adalimumab (OR = 8.894, p < 0.001) were independently associated with development of psoriasiform lesions. Three (3%) patients with infectious complications and 12 (31%) patients with psoriasiform lesions discontinued anti-TNF therapy definitively.

Conclusions

Dermatological manifestations occurred in almost one-third of our population. Infections were the most common complication, but anti-TNF-induced psoriasiform lesions were the most common cause for anti-TNF therapy definitive discontinuation.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Podolsky DK. Inflammatory bowel disease. N Engl J Med. 2002;347:417–429.

    Article  CAS  PubMed  Google Scholar 

  2. Hanauer SB, Feagan BG, Lichtenstein GR, et al. Maintenance infliximab for Crohn’s disease: the ACCENT I randomised trial. Lancet. 2002;359:1541–1549.

    Article  CAS  PubMed  Google Scholar 

  3. Colombel JF, Sandborn WJ, Rutgeerts P, et al. Adalimumab for maintenance of clinical response and remission in patients with Crohn’s disease: the CHARM trial. Gastroenterology. 2007;132:52–65.

    Article  CAS  PubMed  Google Scholar 

  4. Rutgeerts P, Sandborn WJ, Feagan BG, et al. Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2005;353:2462–2476.

    Article  CAS  PubMed  Google Scholar 

  5. Mocci G, Marzo M, Papa A, et al. Dermatological adverse reactions during anti-TNF treatments: focus on inflammatory bowel disease. J Crohns Colitis. 2013;7:769–779.

    Article  PubMed  Google Scholar 

  6. Kerbleski JF, Gottlieb AB. Dermatological complications and safety of anti-TNF treatments. Gut. 2009;58:1033–1039.

    Article  CAS  PubMed  Google Scholar 

  7. Nagy G, Lukàcs K, Sziray A, et al. Adverse events during biological therapy: focusing on dermatological side effects. Orv Hetil. 2011;152:212–220.

    Article  PubMed  Google Scholar 

  8. Flendrie M, Vissers WH, Creemers MC, et al. Dermatological conditions during TNF-alpha-blocking therapy in patients with rheumatoid arthritis: a prospective study. Arthritis Res Ther. 2005;7:R666–R676.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Lee HH, Song IH, Friedrich M, et al. Cutaneous side effects in patients with rheumatic diseases during application of tumour necrosis factor-alpha antagonists. Br J Dermatol. 2007;156:486–491.

    Article  CAS  PubMed  Google Scholar 

  10. Llao J, Gomez-Pastrana B, Gordillo J, et al. Skin lesions in patients with inflammatory bowel disease treated with immunomodulators and/or anti-tumor necrosis factor. J Crohns Colitis. 2011;P223:5:106.

    Google Scholar 

  11. Torres J, Buche S, Delaporte E, et al. Skin side effects of inflammatory bowel disease therapy. Inflamm Bowel Dis. 2013;19:1086–1098.

    Article  PubMed  Google Scholar 

  12. Fidder H, Schnitzler F, Ferrante M, et al. Long-term safety of infliximab for the treatment of inflammatory bowel disease: a single-centre cohort study. Gut. 2009;58:501–508.

    Article  CAS  PubMed  Google Scholar 

  13. Afzali A, Wheat CL, Hu JK, et al. 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;8:480–488.

    Article  PubMed  Google Scholar 

  14. Fréling E, Baumann C, Cuny 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;110:1186–1196.

    Article  PubMed  Google Scholar 

  15. Mälkönen T, Wikström A, Heiskanen K, et al. Skin reactions during anti-TNFα therapy for pediatric inflammatory bowel disease: a 2-year prospective study. Inflamm Bowel Dis. 2014;20:1309–1315.

    Article  PubMed  Google Scholar 

  16. 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 Th 1 cells and IL-17 A/IL-22-expressing Th 17 cells and respond to anti-IL-12/IL-23 antibody treatment. Gut. 2014;63:567–577.

    Article  CAS  PubMed  Google Scholar 

  17. Rahier J-F, Buche S, Peyrin-Biroulet L, et al. Severe skin lesions cause patients with inflammatory bowel disease to discontinue anti-tumor necrosis factor therapy. Clin Gastroenterol Hepatol Off Clin Pract J Am Gastroenterol Assoc. 2010;8:1048–1055.

    Google Scholar 

  18. Broge T, Nguyen N, Sacks A, et al. Infliximab-associated psoriasis in children with Crohn’s disease may require withdrawal of anti-tumor necrosis factor therapy. Inflamm Bowel Dis. 2013;19:75–77.

    Article  Google Scholar 

  19. Collamer AN, Battafarano DF. Psoriatic skin lesions induced by tumor necrosis factor antagonist therapy: clinical features and possible immunopathogenesis. Semin Arthritis Rheum. 2010;40:233–240.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  21. Cleynen I, Van Moerkercke W, Billiet T, et al. Characteristics of skin lesions associated with anti tumor necrosis factor therapy in patients with inflammatory bowel disease: a cohort study. Ann Intern Med. 2016;5:10–22.

    Article  Google Scholar 

  22. Hellstrom EA, Farkkila M, Kolho KL. Infliximab-induced skin manifestations in patients with inflammatory bowel disease. Scand J Gastroenterol. 2016;51:563–571.

    Article  PubMed  Google Scholar 

  23. Ortiz A, Grando SA. Smoking and the skin. Int J Dermatol. 2012;51:250–262.

    Article  CAS  PubMed  Google Scholar 

  24. Peyrin-Biroulet L, Deltenre P, De Suray N, et al. Efficacy and safety of tumor necrosis factor antagonists in Crohn’s disease: meta-analysis of placebo controlled trials. Clin Gastroenterol Hepatol. 2008;6:644–653.

    Article  CAS  PubMed  Google Scholar 

  25. Lichtenstein G, Feagan B, Cohen R, et al. Serious infections and mortality in association with therapies for Crohn’s disease: TREAT registry. Clin Gastroenterol Hepatol. 2006;4:621–630.

    Article  CAS  PubMed  Google Scholar 

  26. Listing J, Strangfeld A, Kary S, et al. Infections in patients with rheumatoid arthritis treated with biologic agents. Arthritis Rheum. 2005;52:3403–3412.

    Article  CAS  PubMed  Google Scholar 

  27. Dixon WG, Watson K, Lunt M, et al. Rates of serious infection, including site-specific and bacterial intracellular infection, in rheumatoid arthritis patients receiving anti-tumor necrosis factor therapy: results from the British Society for Rheumatology Biologics Register. Arthritis Rheum. 2006;54:2368–2376.

    Article  CAS  PubMed  Google Scholar 

  28. Rahier JF, Ben-Horin S, Chowers Y, et al. European evidence based consensus on the prevention, diagnosis and management of opportunistic infections in inflammatory bowel disease. J Crohns Colitis. 2009;3:47–91.

    Article  CAS  PubMed  Google Scholar 

  29. Toruner M, Loftus EV Jr, Harmsen WS, et al. Risk factors for opportunistic infections in patients with inflammatory bowel disease. Gastroenterology. 2008;134:929–936.

    Article  PubMed  Google Scholar 

  30. Guerra I, Algaba A, Pérez-Calle JL, et al. Induction of psoriasis with anti-TNF agents in patients with inflammatory bowel disease: a report of 21 cases. J Crohns Colitis. 2012;6:518–523.

    Article  PubMed  Google Scholar 

  31. 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;29:921–927.

    Article  CAS  PubMed  Google Scholar 

  32. Cullen G, Kroshinsky D, Cheifetz AS, et al. Psoriasis associated with anti-tumour necrosis factor therapy in inflammatory bowel disease: a new series and a review of 120 cases from the literature. Aliment Pharmacol Ther. 2011;34:1318–1327.

    Article  CAS  PubMed  Google Scholar 

  33. Guerra I, Péres-Jeldres T, Iborra M, et al. Incidence, clinical characteristics, and management of psoriasis induced by anti-TNF therapy in patients with inflammatory bowel disease: a nationwide cohort study. Inflamm Bowel Dis. 2016;22:894–901.

    Article  PubMed  Google Scholar 

  34. Denadai R, Teixeira FV, Steinwurz F, et al. Induction or exacerbation of psoriatic lesions during anti-TNF-α therapy for inflammatory bowel disease: a systematic literature review based on 222 cases. J Crohns Colitis. 2013;7:517–524.

    Article  PubMed  Google Scholar 

Download references

Funding

Authors did not receive any funding sources.

Author information

Authors and Affiliations

  1. Gastroenterology Department, Centro Hospitalar São João, University of Porto Medical School, Alameda Prof. Hernani Monteiro, 4200-319, Porto, Portugal

    P. Andrade, S. Lopes, R. Gaspar, A. Nunes & G. Macedo

  2. Dermatology Department, Centro Hospitalar São João, University of Porto Medical School, Porto, Portugal

    S. Magina

Authors
  1. P. Andrade
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S. Lopes
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. R. Gaspar
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. A. Nunes
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. S. Magina
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. G. Macedo
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

PA and SL were responsible for study design. PA and RG were responsible for data collection. PA and RG were responsible for statistical analyses. PA and SL wrote the manuscript. SM, AN, and GM revised and approved the final manuscript. All the named authors, contributing directly to the work described, have agreed on the respective roles of each author, read the manuscript, and approved submission.

Corresponding author

Correspondence to P. Andrade.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Additional information

Conference Presentation

24th United European Gastroenterology Week 2016. Vienna, October 15–19, 2016.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 83 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

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 63, 746–754 (2018). https://doi.org/10.1007/s10620-018-4921-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10620-018-4921-y

Keywords

Search

Navigation