Fellow’s Forum Case Report: New Sarcoidosis Cases in Patients Treated with Tumor Necrosis Factor–Alpha Inhibitors

TNF-α inhibitors have been thought to suppress granuloma formation and have been tried in the treatment of refractory sarcoidosis, with varying results.⁴ Therefore, the development of sarcoidosis in our patients treated with TNF-α inhibitors is an unexpected occurrence. To our knowledge, this is the first case of sarcoidosis development in a psoriatic arthritis patient treated with adalimumab.

There are differences among the different classes of TNF-α inhibitors and the way they can be related to the development of sarcoidosis.^5,6 For example, the TNF-α monoclonal antibodies, infliximab and adalimumab, can cause cytotoxic complement-induced lysis of cells expressing membrane-linked TNF-α and cell apoptosis in T cells. In contrast, the soluble TNF-α receptor, etanercept, does not fix complement and does not induce apoptosis.^2,4 This may explain etanercept’s more frequent association with the formation of granulomas.2 When TNF-α inhibitors were used in the treatment of sarcoidosis, infliximab was associated with significant improvement, whereas etanercept was associated with worsening disease in patients with progressive pulmonary sarcoidosis.^4,7

There has also been a suggestion of an infectious etiology, mainly mycobacterial infection, being associated with the development of sarcoidosis.¹ Mycobacterial infections have been reported as an adverse event of treatment with TNF-α inhibitors. It is possible that TNF-α inhibitors may allow or reactivate a mycobacterial infection, which could be linked to sarcoidosis pathophysiology.

In summary, we report two cases of sarcoidosis in patients with psoriatic arthritis following the use of TNF-α inhibitors—one with etanercept, a soluble receptor, and one with adalimumab, a monoclonal antibody. As physicians, we need to be aware of the possibility of sarcoidosis development while treating patients who have psoriatic arthritis with TNF-α inhibitors.

Dr. Cote is a fellow in the department of rheumatology, Dr. Harrington is assistant director of rheumatology, Dr. Meadows is a fellow in the department of internal medicine, Dr. Lin is director of anatomic pathology, and Dr. Bili is a rheumatologist and investigator; all are at Geisinger Medical Center in Danville, Pa.

References

1. Hamzeh, N. Sarcoidosis. Med Clin N Am. 2011;95: 1223-1234.
2. Massara A, Cavazzini L, Corte, R, et al. Sarcoidosis appearing during anti-tumor necrosis alpha therapy: A new “class effect” paradoxical phenomenon. Two case reports and literature review. Semin Arthritis Rheum. 2010;39:313-319.
3. Antoniu S. Targeting the TNF-α pathway in sarcoidosis. Expert Opin Ther Targets. 2010;14:21-29.
4. Doty J, Mazur J, Judson M. Treatment of sarcoidosis with infliximab. Chest. 2005; 127:1064-1071.
5. Wallis R, Ehlers S. Tumor necrosis factor and granuloma biology: Explaining the differential infection risk of etanercept and infliximab. Semin Arthritis Rheum. 2005; 34:34-38.
6. Mitoma H, Horiuchi T, Tsukamoto H, et al. Mechanisms for cytotoxic effects of anti-tumor necrosis factor agents on transmembrane tumor necrosis factor α-expressing cells. Comparison among infliximab, etanercept and adalimumab. Arthritis Rheum. 2008;58:1248-1257.
7. Utz JP, Mazur JE, Judson MA. Etanercept for the treatment of stage II and III progressive pulmonary sarcoidosis. Chest. 2003;124:177-185.