title: Sarcoidosis appearing during anti-tumor necrosis factor alpha therapy: a new "class effect" paradoxical phenomenon. Two case reports and literature review.
abstract: OBJECTIVE
  To report 2 cases of sarcoidosis that developed during treatment with tumor necrosis factor alpha (TNFalpha) antagonists, infliximab and adalimumab, used for inflammatory rheumatic disease and to review previously reported cases.
  
  
  METHODS
  We describe 2 patients, the first with psoriatic arthritis, the second with rheumatoid arthritis, who developed noncaseating granulomas of the lungs consistent with sarcoidosis while being treated with anti-TNFalpha drugs. A retrospective review of the literature was performed using the PubMed database.
  
  
  RESULTS
  In our patients sarcoidosis developed after 2 years of continuous treatment with infliximab and adalimumab. Both patients presented with low-grade fever, chest pain, and dyspnea. The diagnosis of sarcoidosis was established by the typical well-formed noncaseating granulomas on transbronchial biopsy, after excluding all other granulomatous conditions. Following withdrawal of anti-TNFalpha agents and a brief course of steroids, the clinical picture resolved. Thirteen additional cases of sarcoidosis that developed after anti-TNFalpha treatment have been reported, and in 9 of these the causative agent was etanercept.
  
  
  CONCLUSIONS
  The development of sarcoidosis during treatment with TNFalpha antagonists represents a rare and paradoxical adverse event. The occurrence of sarcoidosis with all 3 available agents suggests a new "class effect" probably linked to a cytokine disequilibrium in patients receiving anti-TNFalpha treatment.
authors.affiliation: Sezione di Reumatologia, Dipartimento di Medicina Clinica e Sperimentale, Università degli Studi di Ferrara, Ferrara, Italy. alfmass@yahoo.it
authors.forename: Alfonso
authors.initials: A
authors.lastname: Massara
authors.forename: Luigi
authors.initials: L
authors.lastname: Cavazzini
authors.forename: Renato
authors.initials: R
authors.lastname: La Corte
authors.forename: Francesco
authors.initials: F
authors.lastname: Trotta
mesh_terms: D000068879:Adalimumab; D000328:Adult; D000911:Antibodies, Monoclonal / Q000009:adverse effects*; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents / Q000009:adverse effects; D015535:Arthritis, Psoriatic / Q000628:therapy*; D001172:Arthritis, Rheumatoid / Q000628:therapy*; D005260:Female; D006801:Humans; D000069285:Infliximab; D008297:Male; D008875:Middle Aged; D012507:Sarcoidosis / Q000139:chemically induced* / Q000175:diagnosis; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068879:Adalimumab