@article{14b6eaeba22642559fc49d1728223654,
title = "Refractory Sarcoidosis Responding to Infliximab",
abstract = "Despite aggressive treatment with conventional therapy, sarcoidosis may be progressive and debilitating. Tumor necrosis factor (TNF)-α is critical in the genesis and maintenance of granulomatous inflammation. Agents developed to inhibit TNF-α have been approved to treat rheumatoid arthritis and inflammatory bowel disease with unprecedented success. As such, physicians are increasingly using these agents to treat patients with other inflammatory diseases, including sarcoidosis. We report a case of refractory sarcoidosis, involving the lung, eyes, skin, and heart, which flared despite aggressive therapy. Oculocutaneous sarcoid dramatically improved after treatment with the anti-TNF antibody infliximab.",
keywords = "Cutaneous, Infliximab, Ocular, Sarcoidosis, Tumor necrosis factor-α, Uveitis",
author = "Roberts, {Scott D.} and Wilkes, {David S.} and Burgett, {Richard A.} and Knox, {Kenneth S.}",
note = "Funding Information: We have described a patient with multisystem sarcoidosis, including pulmonary, cutaneous, ocular, and cardiac involvement, that progressed despite aggressive therapy. Her clinical course included multiple exacerbations of the disease and numerous therapeutic side effects. Only after the institution of infliximab therapy, as part of a multidrug regimen, did the oculocutaneous sarcoid resolve. This case illustrates the impact that targeted anticytokine therapy may have on selected patients with sarcoidosis. There is increasing evidence that TNF-α plays a critical role in the pathophysiology of granulomatous inflammation. In experimental models, 6 7 TNF is critical in the recruitment of T cells and granuloma formation in response to mycobacterial antigens. The sarcoid granuloma may be exquisitely responsive to TNF reduction. Polymorphisms of TNF genes have been suggested as markers of prognosis in patients with sarcoidosis. 8 In addition to infliximab therapy, there have been anecdotal reports 9 10 of sarcoidosis patients being treated with thalidomide and pentoxifylline, medications that reportedly have anti-TNF effects. We decided to use infliximab because published reports 4 have documented successful treatment of cutaneous sarcoidosis with this therapy. Our patient experienced a sarcoid flare with a granulomatous eyelid lesion while receiving thalidomide. Thus, failure with one anti-TNF therapy should not preclude the use of another. Ocular involvement in patients with sarcoidosis is common and can be particularly difficult to manage, with potentially devastating long-term effects. 11 The treatment is often unpleasant. Our patient dreaded the monthly intraocular injections. We did not necessarily expect such a rapid improvement in her longstanding uveitis as few reports are available 12 and it is unknown whether infliximab crosses the blood-eye barrier. Although cardiac involvement is clinically not as common, it is one of the potentially life-threatening manifestations of this systemic disease. 13 The presentation of myocardial sarcoid with ventricular arrhythmia and sudden cardiac death has been well-described. 14 After initiating treatment with infliximab, there was evidence of improvement in our patient{\textquoteright}s cardiac conduction abnormalities on interrogation of her pacemaker/implantable defibrillator. We cannot make definitive statements regarding the use of infliximab in treating this subset of patients. This case provides only a preliminary observation that anti-TNF therapy may be adjunctive. At the time that infliximab therapy was started, our patient{\textquoteright}s lung function was stable on a regimen of systemic steroids and azathioprine. Zabel et al 9 first suggested the benefit of anti-TNF therapy in pulmonary sarcoidosis. In that study, pentoxifylline was the anti-TNF agent used, and the subgroup of patients who benefited from its use were those with active lung disease. Our patient{\textquoteright}s lung disease was stable when infliximab therapy was initiated, and the addition of this therapy provided no further benefit. This observation has implications for future studies, given the heterogeneity of the sarcoid population. The addition of anti-TNF therapy in stable patients who have lung disease may afford no benefit over standard therapy. Alternatively, in patients whose lung function declines despite therapy, treatment with infliximab and other TNF inhibitors may be useful. A double-blinded, placebo-controlled trial studying the use of pentoxifylline in pulmonary sarcoidosis sponsored by the National Institutes of Health is currently enrolling patients. More information regarding this trial can be found on the National Institutes of Health Web site (www.cc.nih.gov). Infliximab is considered to be an immunosuppressive agent, and patients receiving this drug may be at an increased risk of malignancy and infection. 15 16 17 18 Specifically, pulmonologists must be aware of the high incidence of reactivation of latent tuberculosis 17 and the increased risk of pulmonary mycoses. 18 Distinguishing these infectious complications of treatment from the manifestations of underlying pulmonary sarcoid can be difficult. Because the experience with infliximab in patients with sarcoidosis is still limited, it is too early to say how these risks will compare with those of conventional therapy. Meanwhile, close monitoring of these patients is essential. This report describes a patient with recalcitrant, multisystem sarcoidosis who responded to infliximab therapy. Since pulmonologists are often called on to care for sarcoid patients with both lung involvement and other severe manifestations, we will undoubtedly be faced with difficult patients who may benefit from nontraditional therapies. We believe that this case report supports the use of anti-TNF therapies in select sarcoid patients and emphasizes the importance of TNF-α in the pathophysiology of sarcoidosis. Further study is warranted. ",
year = "2003",
month = nov,
doi = "10.1378/chest.124.5.2028",
language = "English (US)",
volume = "124",
pages = "2028--2031",
journal = "CHEST",
issn = "0012-3692",
publisher = "Elsevier Inc.",
number = "5",
}