New onset sarcoid-like granulomatosis developing during anti-TNF therapy: an under-recognised complication

Intern Med J. 2012 Jan;42(1):89-94. doi: 10.1111/j.1445-5994.2011.02612.x.


Tumour necrosis factor-alpha (TNF-a) antagonists have advanced the treatment of inflammatory arthropathies, and are even considered for use in refractory sarcoidosis with some success. Paradoxically, cases of new onset sarcoidosis-like diseases are increasingly reported in patients receiving TNF-a antagonists. Here, we report three cases of sarcoid-like granulomatosis that developed during treatment with TNF-a antagonists. Review of the Biologics clinic data base at Westmead, Sydney, Australia identified three patients whom, during anti-TNF therapy, developed non-caseating granulomas consistent with sarcoidosis. These three cases are described with review of the literature from 2000 to 2009 using PubMed. One hundred and sixty-nine patients within our data base were reviewed for the period 2003–2009. Sarcoidosis-like granulomas developed in three patients within a period of 3 to 36 months of treatment with etanercept and/or adalimumab. All cases demonstrated non-infective, non-caseating granulomas on renal or lymph node biopsy. Improvement was seen in two cases upon cessation of TNF-a antagonist and steroid therapy. Interestingly, clinical deterioration was noted upon re-challenge with the same TNF-a antagonist in one patient. To date, a total of 37 cases of sarcoid-like granuloma development after anti-TNF therapy have been reported in the literature. Development of sarcoidosis-like granulomatosis in patients treated with TNF-a antagonists is a phenomenon previously under-recognised. All three anti-TNF agents have been observed to cause this phenomenon, suggesting a ‘class effect’ rather than being drug specific.

Publication types

  • Case Reports

MeSH terms

  • Adalimumab
  • Adult
  • Antibodies, Monoclonal, Humanized / adverse effects*
  • Antirheumatic Agents / adverse effects*
  • Arthritis, Psoriatic / complications
  • Arthritis, Psoriatic / drug therapy
  • Arthritis, Rheumatoid / complications
  • Arthritis, Rheumatoid / drug therapy
  • Australia / epidemiology
  • Etanercept
  • European Continental Ancestry Group
  • Female
  • Granuloma / chemically induced*
  • Granuloma / pathology
  • Humans
  • Immunoglobulin G / adverse effects*
  • Kidney / pathology
  • Lymph Nodes / pathology
  • Male
  • Middle Aged
  • Nephritis, Interstitial / chemically induced*
  • Nephritis, Interstitial / pathology
  • Oceanic Ancestry Group
  • Receptors, Tumor Necrosis Factor
  • Recurrence
  • Sarcoidosis / chemically induced*
  • Sarcoidosis / pathology
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*


  • Antibodies, Monoclonal, Humanized
  • Antirheumatic Agents
  • Immunoglobulin G
  • Receptors, Tumor Necrosis Factor
  • Tumor Necrosis Factor-alpha
  • Adalimumab
  • Etanercept