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Background We analysed incidence, predictors, histological features and specific treatment options of anti-tumour necrosis factor a (TNF-a) 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)-?-secreting Th1 cells and IFN-a- 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. [ABSTRACT FROM AUTHOR]

Eur J Clin Invest 2011; 41 (10): 1071-1076 Abstract Background IFN-γ release assays (IGRA), widely used for latent tuberculosis screening prior to anti-TNF-α treatment, are limited by indeterminate results in patients under immunomodulatory (IM) therapy. The aim of our observational study was to delineate factors associated with indeterminate IGRA results. Methods A total of 190 patients with inflammatory bowel disease were included. IGRA was indeterminate if the result of IFN-γ concentration was < 0·35 IU mL−1 for tuberculosis-specific antigens and < 0·5 IU mL−1 for the positive control. Predictors for indeterminate results were delineated from multivariate logistic regression. Results IFN-γ release assays was indeterminate in 26/190 (13·7%) patients. Indeterminate IGRA were associated with lower serum albumin levels (odds ratio [OR] 0·88, 95% confidence interval [CI] 0·79-0·96), lower absolute lymphocyte count (OR 0·39, 95% CI 0·18-0·75) and double IM therapy (OR 2·98, 95% CI 0·95-8·90). Sub-analysis of IM therapy revealed an association of steroid therapy with indeterminate IGRA (OR 3·19, 95% CI 1·35-7·70). Hypoalbuminaemia increased the risk of indeterminate IGRA by (OR 2·97, 95% CI 1·03-8·61) and lymphopaenia by (OR 3·28, 95% CI 1·41-7·65). After a mean of 18·5 ± 14·4 days, retesting of IGRA in 18 patients with indeterminate results yielded 9 negative vs. 9 indeterminate results. Conclusions Our results reveal associations of indeterminate IGRA with low serum albumin levels and absolute lymphocyte count and double IM therapy. IGRA testing appears best to be performed prior to initiation of IM therapy in patients with inflammatory bowel disease. [ABSTRACT FROM AUTHOR]