Z Gastroenterol 2012; 50 - K198
DOI: 10.1055/s-0032-1324133

Anti-TNF antibody-induced psoriasiform skin lesions in patients with inflammatory bowel disease are characterized by interferon-gamma-expressing Th1 and IL-17/IL-22-expressing Th17 cell infiltrates and respond to anti-IL-12/IL-23 antibody treatment

C Tillack 1, L Ehmann 1, S Koglin 2, J Schauber 2, A Wollenberg 2, S Brand 3
  • 1Klinikum der Universität München – Großhadern, Munich, Germany
  • 2Klinikum der Universität München, Munich, Germany
  • 3Klinikum der Universität München – Großhadern, Medizinische Klinik II, Munich, Germany

Background and aims: Anti-TNF antibodies may cause psoriasiform skin lesions. Currently, the pathogenesis of these lesions is only poorly understood. We analyzed incidence, predictors, histological features and specific treatment options of anti-tumor necrosis factor (TNF)-alpha antibody-induced psoriasiform skin lesions in patients with inflammatory bowel diseases (IBD).

Methods: Anti-TNF antibody-treated IBD patients were prospectively screened for anti-TNF-induced psoriasiform skin lesions. Patients were genotyped for IBD- and psoriasis-associated IL23R and IL12B single nucleotide polymorphisms (SNPs). Skin lesions were histologically examined for infiltrating Th1 and Th17 cells. Patients with severe lesions were treated with the anti-IL-12/IL-23 p40 antibody ustekinumab.

Results: Among 434 anti-TNF treated IBD patients, 21 patients (4.8%) developed psoriasiform skin lesions, including 19 patients (90.5%) with Crohn's disease (CD) and 2 patients (9.5%) with ulcerative colitis (UC). The majority of these patients developed palmoplantar psoriasis or guttate psoriasis. Multivariate analysis demonstrated smoking (p=0.007; OR 4.24, CI 1.55–13.60) and an increased body mass index (p=0.029; OR 1.12, CI 1.01–1.24) as predictors for these lesions. IL12B and IL23R genotyping did not reveal a specific risk genotype. Nine CD patients with severe psoriasiform skin 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 characterized by infiltrates of IL-17A/IL-22-secreting Th17 cells and IFN-gamma-secreting Th1 cells. Strong IL-17A expression was significantly more often found in very severe psoriasiform skin lesions requiring ustekinumab therapy than in less severe lesions responding to topical therapy (p=0.0047).

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