Sarcoid-related Uveitis Occurring During Adalimumab Therapy

Abstract

Purpose: To report the first case of sarcoid-related uveitis in a patient receiving adalimumab.

Design: Case report.

Methods: A 61-year-old woman with rheumatoid arthritis treated with adalimumab for 4 years presented with a 1-year history of bilateral panuveitis with venous vasculitis and peripheral multifocal choroiditis. A small papular lesion was found on her forehead, which upon biopsy showed noncaseating granulomas. No systemic involvement was observed.

Results: An ophtalmological and clinical improvement was seen after (TNF) antagonist withdrawal plus a course of prednisone.

Conclusions: Ophthalmologists should know that a sarcoid-like granulomatosis can develop during TNFα blockade therapy.

Keywords:

• adalimumab
• anti-TNF
• sarcoidosis
• uveitis

The development of sarcoid-like granulomatosis during treatment with tumor necrosing factor α (TNFα) blocking agents (infliximab, etanercept, adalimumab) is a rare and paradoxical adverse effect.¹ A recent literature review found 28 cases of proved granulomatosis in patients receiving anti-TNFα, 4 of whom had ocular involvement (including 3 cases with etanercept and 1 with infliximab).² Herein, we describe a patient with rheumatoid arthritis (RA) who developed chronic bilateral panuveitis and cutaneous nodule on the face, 5 years after administration of adalimumab. Noncaseating granulomas were present in the skin. Uveitis resolved upon discontinuation of adalimumab and systemic administration of corticosteroids.

CASE REPORT

In November 2010, a 61-year-old white woman was referred to our ophthalmological department for a 1-year history of bilateral panuveitis. At the age of 41 she was diagnosed with RA based on widespread polyarthritis, erosions of small joints in her hand, and rheumatoid factor positivity. During the following years, several courses of antirheumatic treatment were given, including injectable gold and methotrexate. In January 2006, due to persistent disease activity, she was started on adalimumab, 40 mg every other week, in association with methotrexate 15 mg weekly. Adalimumab treatment gave rise to a rapid and sustained amelioration of joint symptoms.

At examination the anterior segment showed inferior granulomatous precipitates with moderate Tyndall, whereas funduscopic examination showed bilateral posterior uveitis with moderate hyalitis, retinal periphlebitis, and peripheral multifocal choroiditis. Fluorescein and indocyanine green angiographies confirmed these observations on both eyes, compatible with sarcoidosis. The only significant laboratory data was a raised angiotensin-converting enzyme level (118 U/mL; normal value, 8–69). Imaging tests (including chest computed tomography scan), purified protein derivative skin test, quantiFERON testing, and serological tests for Borellia, Bartonella, Toxoplasma, and syphilis were performed with negative results. The patient was subsequently referred to the Department of Internal Medicine. A small papular lesion was found on her forehead, which upon biopsy showed noncaseating epithelioid cell granulomas. Because of the existing case reports describing sarcoid-like granulomatosis during treatment with TNFα blocking agents, adalimumab was stopped. The patient was started on prednisone (1 mg/kg/d) for 1 month then slowly tapered to 5 mg over the following 3 months with rapid resolution of skin involvement, while ophthalmological evaluation revealed an improvement without complete resolution; bilateral hyalitis was less important but still present.

DISCUSSION

TNFα is a proinflammatory cytokine that plays a major role in the pathogenesis of both RA and sarcoidosis.³ Anti-TNFα drugs, especially infliximab, have been successfully used for treating refractory sarcoidosis, including therapy resistant uveitis.⁴ In contrast, cases of sarcoidosis and granulomatosis after TNF blocker introduction have been described. Daien et al. estimated the frequency of this adverse event to be at least 0.04% (1/2800).¹ A study published last year found 28 cases, including 16 cases with etanercept, 8 cases under infliximab, and 4 with adalimumab.² The median delay between anti-TNFα agent introduction and granulomatosis diagnosis was 19 (range 1–60) months. Clinical symptoms were mainly pulmonary (86%) and cutaneous (29%). Four patients had ocular involvement, including bilateral anterior uveitis (n = 2), acute panuveitis (n = 1), and nerve palsy of the left eye and papilledema (n = 1). Anti-TNFα was discontinued, except in 2 cases. All but 2 cases showed clinical improvement after anti-TNFα discontinuation with (n = 12) or without (n = 14) systemic corticosteroids.

There have been anecdotal reports that implicate etanercept as a cause of uveitis.⁵ Lim et al. have recently relied on a database of 2 drug events to assess reported cases of uveitis associated with the use of anti-TNFα.⁵ They found that etanercept was associated with a significantly greater number of uveitis in comparison with infliximab and adalimumab. An analysis of ankylosing spondylitis studies by Braun and colleagues⁶ suggested that both etanercept and could prevent episodes of uveitis, but the data suggest that infliximab might be superior in this regard. Overall, these findings do not support the use of infliximab over etanrecept; rather, if a patient with ankylosing spondylitis develops uveitis during etanercept therapy, then a change to infliximab or adalimumab may be warranted.

In conclusion, our case report shows that adalimumab, like other TNFα blocking agents, can induce sarcoid-related uveitis. The occurrence of cases with all 3 anti-TNFα agents suggests it could be a “class effect” linked to the dysregulatory features of TNFα inhibition rather than a molecule side effect.⁷ Ophthalmologists should keep in mind that a sarcoid-like granulomatosis can develop during TNFα blockade therapy.

ACKNOWLEDGMENT

We thank Doctor Emmanuel Vignot and Doctor Charlotte Deroo-Berger who cared for the patient. We thank Marie-Agnes Charrier for administrative assistance.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.