title: Correlations between skin lesions induced by anti-tumor necrosis factor-α and selected cytokines in Crohn's disease patients.
abstract: OBJECTIVE
  To investigate the correlation between the appearance of skin lesions and concentration of interleukin (IL)-17A, IL-23 and interferon-γ (IFN-γ) in Crohn's disease (CD) patients during anti-tumor necrosis factor-α (TNF-α) therapy
  
  
  METHODS
  A prospective study included 30 adult patients with CD of Caucasian origin (19 men and 11 women; mean age ± SD 32.0 ± 8.6 years) during biological therapy with anti-TNF-α antibodies from January 2012 to March 2013. Eighteen patients were treated with infliximab, seven with adalimumab and five with certolizumab. Inclusion criteria were exacerbation of the underlying disease, Crohn's Disease Activity Index over 300 and the ineffectiveness of previously used non-biological therapies. Patients with a history of psoriasis, atopic dermatitis and other autoimmune skin lesions were excluded from the study. The control group consisted of 12 healthy subjects. A diagnostic survey was carried out, blood tests and careful skin examination were performed, and the serum levels of IL-17, IL-23 and IFN-γ were measured using an enzyme-linked immunosorbent assays technique. Dermatoses that have developed in the course of biological therapy in patients who had no pre-existing skin lesions of similar character were qualified as skin lesions induced by anti-TNF-α therapy.
  
  
  RESULTS
  Skin manifestations occurred in 18 of CD patients during the anti-TNF-α therapy (60%), in the average time of 10.16 ± 3.42 mo following the beginning of the 52-wk treatment cycle. Skin lesions observed in CD patients during biological therapy included psoriasiform lesions (44.4%), and eczema forms lesions (22.2%). In CD patients with drug induced skin lesions significantly higher levels of hemoglobin (13.3 ± 1.5 g/dL vs 10.8 ± 1.9 g/dL, P = 0.018) and hematocrit (39.9% ± 4.5% vs 34.3% ± 5.4%, P = 0.01), as well as a significantly lower level of platelets (268 ± 62 × 10(3)/μL vs 408 ± 239 × 10(3)/μL, P = 0.046) was observed compared with CD patients without skin manifestations. The concentrations of IL-17A and IL-23 in CD patients with skin lesions developed under anti-TNF-α therapy were significantly higher compared to those in patients without lesions (IL-17A: 39.01 ± 7.03 pg/mL vs 25.71 ± 4.90 pg/mL, P = 0.00004; IL-23: 408.78 ± 94.13 pg/mL vs 312.15 ± 76.24 pg/mL, P = 0.00556).
  
  
  CONCLUSIONS
  Skin lesions in CD patients during biological therapy may result from significantly increased concentrations of IL-17A and IL-23, which are strongly associated with TNF-α/Th1 immune pathways.
authors.affiliation: Marcin Włodarczyk, Aleksandra Sobolewska, Bartosz Wójcik, Karolina Loga, Maria Wiśniewska-Jarosińska, Department of Gastroenterology, Medical University of Lodz, 90-647 Lodz, Poland.
authors.forename: Marcin
authors.initials: M
authors.lastname: Włodarczyk
authors.affiliation: Marcin Włodarczyk, Aleksandra Sobolewska, Bartosz Wójcik, Karolina Loga, Maria Wiśniewska-Jarosińska, Department of Gastroenterology, Medical University of Lodz, 90-647 Lodz, Poland.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Sobolewska
authors.affiliation: Marcin Włodarczyk, Aleksandra Sobolewska, Bartosz Wójcik, Karolina Loga, Maria Wiśniewska-Jarosińska, Department of Gastroenterology, Medical University of Lodz, 90-647 Lodz, Poland.
authors.forename: Bartosz
authors.initials: B
authors.lastname: Wójcik
authors.affiliation: Marcin Włodarczyk, Aleksandra Sobolewska, Bartosz Wójcik, Karolina Loga, Maria Wiśniewska-Jarosińska, Department of Gastroenterology, Medical University of Lodz, 90-647 Lodz, Poland.
authors.forename: Karolina
authors.initials: K
authors.lastname: Loga
authors.affiliation: Marcin Włodarczyk, Aleksandra Sobolewska, Bartosz Wójcik, Karolina Loga, Maria Wiśniewska-Jarosińska, Department of Gastroenterology, Medical University of Lodz, 90-647 Lodz, Poland.
authors.forename: Jakub
authors.initials: J
authors.lastname: Fichna
authors.affiliation: Marcin Włodarczyk, Aleksandra Sobolewska, Bartosz Wójcik, Karolina Loga, Maria Wiśniewska-Jarosińska, Department of Gastroenterology, Medical University of Lodz, 90-647 Lodz, Poland.
authors.forename: Maria
authors.initials: M
authors.lastname: Wiśniewska-Jarosińska
mesh_terms: D000068879:Adalimumab; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000009:adverse effects*; D000911:Antibodies, Monoclonal / Q000009:adverse effects*; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects*; D016022:Case-Control Studies; D003424:Crohn Disease / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D016207:Cytokines / Q000097:blood*; D003875:Drug Eruptions / Q000175:diagnosis / Q000209:etiology* / Q000276:immunology; D005260:Female; D005765:Gastrointestinal Agents / Q000009:adverse effects*; D006801:Humans; D000069285:Infliximab; D007371:Interferon-gamma / Q000097:blood; D020381:Interleukin-17 / Q000097:blood; D053759:Interleukin-23 / Q000097:blood; D008297:Male; D011446:Prospective Studies; D012307:Risk Factors; D012720:Severity of Illness Index; D012867:Skin / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D013997:Time Factors; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D055815:Young Adult
chemical_list: D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D016207:Cytokines; D005765:Gastrointestinal Agents; C573415:IFNG protein, human; D020381:Interleukin-17; D053759:Interleukin-23; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D000069285:Infliximab; D000068879:Adalimumab
keywords: Biological therapy; Crohn’s disease; Interferon γ; Interleukin 17A; Interleukin 23; Tumor necrosis factor-α