Development of cutaneous sarcoidosis during treatment with tumour necrosis alpha factor antagonists

Abstract

The use of tumour necrosis factor alpha (TNF-α) antagonists is increasing in the field of dermatology. These agents have been used for multiple inflammatory and immune skin conditions, but most notably, psoriasis. Adverse effects of anti-TNF-α agents have been reported, including the paradoxical development of sarcoidosis. We present an unusual case of limited cutaneous sarcoidosis developing while the patient was on etanercept therapy, and a review of the current literature.

Development of exclusively cutaneous sarcoidosis in patient with rheumatoid arthritis during treatment with etanercept

“…Most cases involved organs other than the skin. 4 In most cases, there was regression after discontinuation of anti-TNF-α therapy, with an average time of 4, 6 and 8 months for IFX, ADA, and ETN, respectively.…”

“…This could be related to the different binding characteristics of each of the three TNF-α inhibitors (ETN, IFX, and ADA), since they present different clearances and binding avidities. 4 ETN is a fusion protein that primarily neutralizes soluble TNF-α, with reduced binding activity to membrane TNF-α compared with IFX. 6,10 Given that TNF-α is only partially neutralized by ETN, there may be a redistribution of bioavailable cytokines that travel to low concentration sites such as the lungs.…”

“…3 Tumor necrosis factor is produced by inflammatory cells such as macrophages, keratinocytes, and T helper 1 (Th1) lymphocytes. 4 It is implicated in the pathogenesis of granulomatous inflammatory diseases. Granuloma formation requires a Th1 pattern of response involving macrophages and CD4+ T lymphocytes activated with interferon (IFN) and IL-2 secretion, and macrophage activation causes increased production of tumor necrosis factor-alpha (TNF-α).…”

“…There is a positive correlation between TNF-α levels and sarcoidotic disease activity. 3,4 Thus, sarcoidosis would be effectively treated with TNF-α blockers. However, cases of cutaneous, pulmonary, and ocular sarcoidosis due to an unexpected and paradoxical effect of these medications have been reported.…”

“…However, cases of cutaneous, pulmonary, and ocular sarcoidosis due to an unexpected and paradoxical effect of these medications have been reported. 3,4 One of the hypotheses that have been reported is that the increased incidence of infections treated with anti-TNF-α could lead to the development of granulomas. 5 We report the case of a patient who developed sarcoidotic skin lesions during treatment with etanercept (ETN), without associated systemic manifestations.…”