title: 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.
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).
  
  
  METHODS
  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.
authors.affiliation: Department of Medicine II-Grosshadern, Ludwig Maximilians University (LMU), , Munich, Germany.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Tillack
authors.forename: Laura Maximiliane
authors.initials: LM
authors.lastname: Ehmann
authors.forename: Matthias
authors.initials: M
authors.lastname: Friedrich
authors.forename: Rüdiger P
authors.initials: RP
authors.lastname: Laubender
authors.forename: Pavol
authors.initials: P
authors.lastname: Papay
authors.forename: Harald
authors.initials: H
authors.lastname: Vogelsang
authors.forename: Johannes
authors.initials: J
authors.lastname: Stallhofer
authors.forename: Florian
authors.initials: F
authors.lastname: Beigel
authors.forename: Andrea
authors.initials: A
authors.lastname: Bedynek
authors.forename: Martin
authors.initials: M
authors.lastname: Wetzke
authors.forename: Harald
authors.initials: H
authors.lastname: Maier
authors.forename: Maria
authors.initials: M
authors.lastname: Koburger
authors.forename: Johanna
authors.initials: J
authors.lastname: Wagner
authors.forename: Jürgen
authors.initials: J
authors.lastname: Glas
authors.forename: Julia
authors.initials: J
authors.lastname: Diegelmann
authors.forename: Sarah
authors.initials: S
authors.lastname: Koglin
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Dombrowski
authors.forename: Jürgen
authors.initials: J
authors.lastname: Schauber
authors.forename: Andreas
authors.initials: A
authors.lastname: Wollenberg
authors.forename: Stephan
authors.initials: S
authors.lastname: Brand
mesh_terms: D000328:Adult; D000906:Antibodies / Q000276:immunology / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000276:immunology / Q000627:therapeutic use; D005260:Female; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000150:complications / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D007371:Interferon-gamma / Q000276:immunology* / Q000502:physiology; D018664:Interleukin-12 / Q000276:immunology* / Q000502:physiology; D020381:Interleukin-17 / Q000276:immunology* / Q000502:physiology; D053759:Interleukin-23 / Q000276:immunology* / Q000502:physiology; D007378:Interleukins / Q000276:immunology* / Q000502:physiology; D008297:Male; D011446:Prospective Studies; D011565:Psoriasis / Q000209:etiology / Q000276:immunology* / Q000503:physiopathology; D012867:Skin / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D018417:Th1 Cells / Q000276:immunology / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology* / Q000502:physiology; D000069549:Ustekinumab; D000097043:Interleukin-22
chemical_list: D000906:Antibodies; D061067:Antibodies, Monoclonal, Humanized; D007371:Interferon-gamma; D018664:Interleukin-12; D020381:Interleukin-17; D053759:Interleukin-23; D007378:Interleukins; D014409:Tumor Necrosis Factor-alpha; D000069549:Ustekinumab; D000097043:Interleukin-22
keywords: CROHN'S DISEASE; IBD; T LYMPHOCYTES; TNF-ALPHA; ULCERATIVE COLITIS