Complications of therapy
Sarcoidosis Appearing During Anti-Tumor Necrosis Factor α Therapy: A New “Class Effect” Paradoxical Phenomenon. Two Case Reports and Literature Review

https://doi.org/10.1016/j.semarthrit.2008.11.003Get rights and content

Objectives

To report 2 cases of sarcoidosis that developed during treatment with tumor necrosis factor α (TNFα) 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-TNFα 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-TNFα agents and a brief course of steroids, the clinical picture resolved. Thirteen additional cases of sarcoidosis that developed after anti-TNFα treatment have been reported, and in 9 of these the causative agent was etanercept.

Conclusions

The development of sarcoidosis during treatment with TNFα 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-TNFα treatment.

Section snippets

Methods

In addition to the cases presented, we performed a PubMed search with the following keywords: “infliximab,” “adalimumab,” “etanercept,” and “anti-TNF” coupled by the Boolean operator “OR.” This search was subsequently coupled with the entry-term “sarcoidosis” by the Boolean operator “AND.” No start date was used for the research strategy that was performed up to August 2008. An additional search through the references of the retrieved papers was performed. We evaluated all series, reviews, and

Case Report 1

The patient was a 45-year-old white man with a 10-year history of severe psoriatic arthritis. The past medical history was unremarkable except for an episode of nephrolithiasis at the age of 20 years. His disease was formerly treated with cyclosporin (3 mg/kg) and methotrexate (MTX) 10 mg/weekly, both stopped due to inefficacy and side effects. Because of the persistence of high disease activity, in January 2002 he was started on intravenous infliximab 5 mg/kg every 6 weeks. Concurrent

Discussion

We describe here 2 cases of pulmonary sarcoidosis that occurred during treatment with anti-TNFα agents (infliximab, adalimumab) for refractory chronic arthritis. Anti-TNFα agents are widely used in the management of many chronic inflammatory diseases, such as rheumatoid arthritis, the spondyloarthritides, Crohn's disease, and psoriasis. Recently, various pulmonary complications have been reported in patients receiving these drugs, including interstitial pneumonitis and worsening of preexisting

Acknowledgment

This research was supported by a grant from Fondazione Cassa di Risparmio di Ferrara.

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