Article Text

other Versions

PDF
Original article
Anti-TNF antibody-induced psoriasiform skin lesions in patients with inflammatory bowel disease are characterised by interferon-γ-expressing Th1 cells and IL-17A/IL-22-expressing Th17 cells and respond to anti-IL-12/IL-23 antibody treatment
  1. Cornelia Tillack1,
  2. Laura Maximiliane Ehmann2,
  3. Matthias Friedrich1,3,
  4. Rüdiger P Laubender4,
  5. Pavol Papay5,
  6. Harald Vogelsang5,
  7. Johannes Stallhofer1,
  8. Florian Beigel1,
  9. Andrea Bedynek6,
  10. Martin Wetzke1,7,
  11. Harald Maier8,
  12. Maria Koburger1,
  13. Johanna Wagner1,3,
  14. Jürgen Glas1,3,9,
  15. Julia Diegelmann1,3,
  16. Sarah Koglin2,
  17. Yvonne Dombrowski2,10,
  18. Jürgen Schauber2,
  19. Andreas Wollenberg2,
  20. Stephan Brand1
  1. 1Department of Medicine II—Grosshadern, Ludwig Maximilians University (LMU), Munich, Germany
  2. 2Department of Dermatology and Allergy, LMU Munich, Munich, Germany
  3. 3Clinic for Preventive Dentistry and Parodontology, LMU Munich, Munich, Germany
  4. 4Institute of Medical Informatics, Biometry, and Epidemiology (IBE), LMU Munich, Munich, Germany
  5. 5Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University Vienna, Vienna, Austria
  6. 6Institute of Clinical Chemistry—Grosshadern, LMU Munich, Munich, Germany
  7. 7Department of Pediatrics, Medizinische Hochschule Hannover, Hannover, Germany
  8. 8Department of General Dermatology, Medical University Vienna, Vienna, Austria
  9. 9Department of Human Genetics, Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen, Aachen, Germany
  10. 10Centre of Infection and Immunity, Queen's University Belfast, Belfast, UK
  1. Correspondence to Dr Stephan Brand, Department of Medicine II, University-Hospital Munich-Grosshadern, Ludwig Maximilians University Munich, Munich D-81377, Germany; stephan.brand{at}med.uni-muenchen.de

Abstract

Background We analysed incidence, predictors, histological features and specific treatment options of anti-tumour necrosis factor α (TNF-α) antibody-induced psoriasiform skin lesions in patients with inflammatory bowel diseases (IBD).

Design Patients with IBD were prospectively screened for anti-TNF-induced psoriasiform skin lesions. Patients were genotyped for IL23R and IL12B variants. Skin lesions were examined for infiltrating Th1 and Th17 cells. Patients with severe lesions were treated with the anti-interleukin (IL)-12/IL-23 p40 antibody ustekinumab.

Results Among 434 anti-TNF-treated patients with IBD, 21 (4.8%) developed psoriasiform skin lesions. Multiple logistic regression revealed smoking (p=0.007; OR 4.24, 95% CI 1.55 to 13.60) and an increased body mass index (p=0.029; OR 1.12, 95% CI 1.01 to 1.24) as main predictors for these lesions. Nine patients with Crohn's disease and with severe psoriasiform lesions and/or anti-TNF antibody-induced alopecia were successfully treated with the anti-p40-IL-12/IL-23 antibody ustekinumab (response rate 100%). Skin lesions were histologically characterised by infiltrates of IL-17A/IL-22-secreting T helper 17 (Th17) cells and interferon (IFN)-γ-secreting Th1 cells and IFN-α-expressing cells. IL-17A expression was significantly stronger in patients requiring ustekinumab than in patients responding to topical therapy (p=0.001). IL23R genotyping suggests disease-modifying effects of rs11209026 (p.Arg381Gln) and rs7530511 (p.Leu310Pro) in patients requiring ustekinumab.

Conclusions New onset psoriasiform skin lesions develop in nearly 5% of anti-TNF-treated patients with IBD. We identified smoking as a main risk factor for developing these lesions. Anti-TNF-induced psoriasiform skin lesions are characterised by Th17 and Th1 cell infiltrates. The number of IL-17A-expressing T cells correlates with the severity of skin lesions. Anti-IL-12/IL-23 antibody therapy is a highly effective therapy for these lesions.

  • IBD
  • Crohn's disease
  • TNF-Alpha
  • T Lymphocytes
  • Ulcerative colitis

Statistics from Altmetric.com

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

Linked Articles