Infliximab

Abstract

Infliximab, a chimeric (humanized mouse) monoclonal antibody which specifically inhibits TNF-[alpha], has recently shown efficacy in the treatment of refractory sarcoidosis (1,2). The manifestations of sarcoidosis are diverse; however, the long-term effects on the lungs are often the most life-threatening. We describe a patient with sarcoidosis who experienced the complete resolution of her cutaneous disease and stabilization of her pulmonary symptoms after initiation of infliximab.

Case Report

A 37-year-old black female with a 12 year history of sarcoidosis presented with stage II lung disease and generalized granulomatous skin lesions with lupus pernio (Fig. 1). She was originally diagnosed after an episode of anterior uveitis and findings of sarcoidal granulomas in her skin and salivary glands. Her lung disease was rapidly progressive resulting in significant obstructive disease (FEV1 64% of predicted) and a diminished lung diffusing capacity (DLCO 58% of predicted). On examination of her skin, she was found to have diffuse hyperpigmented and skin colored papules as well as plaques primarily over her elbows and extremities. In addition, she had violaceous papules involving the nasal tip and nares without nasopharyngeal involvement.

[FIGURE 1 OMITTED]

The course of her disease was characterized by multiple flares that were partially controlled with pulse doses of prednisone. Steroid sparing agents were added to include hydroxychloroquine and methotrexate. Despite aggressive management, her cutaneous disease continued to progress while the assessment of her lung disease was difficult due to the extent of fibrosis and obstructive changes resulting from the repeated flares. At the time of initiation of infliximab, the patient was treated with corticosteroids (oral prednisone 20 mg/day and topical 0.05% clobetasol propionate ointment), methotrexate (15 mg/week), and hydroxychloroquine (400 mg/day). Given her poor response to steroid sparing agents in the context of documented osteoporosis, progressive lung disease, and her young age, she was started on intravenous infliximab.

The patient received four intravenous infusions of infliximab (5 mg/kg): at baseline, 2 weeks, 4 weeks, and 12 weeks. There was improvement in her skin lesions after the first and second treatments; there was complete resolution of her cutaneous disease after her third dose, leaving residual hypopigmented macules and patches at the sites of previous inflammation. The most dramatic consequence of the infliximab infusions was the disappearance of her lupus pernio (Fig. 2).

[FIGURE 2 OMITTED]

After her dramatic clinical improvement, her prednisone and plaquenil were stopped and the methotrexate was decreased to 10 mg weekly. Her laboratory values paralleled her clinical response with a drop in her serum ACE level from 84 U/L (normal 9-67 U/L) to 26 U/L. Additionally, she had dramatic improvement in her exercise tolerance and subjective complaints of dyspnea.

Comment

This case report describes a new exciting new intervention for the treatment of refractory sarcoidosis. The clinical response parallels the understanding of the importance of TNF-[alpha] in granuloma formation (3). Additionally, the use of infliximab complements findings by Lee et al. (4) that thalidomide, another proposed TNF inhibitor, can be used to treat cutaneous sarcoidosis. Long-term follow up and the durability of the response to infliximab will require further study for this exciting new medication.

References

(1.) Baughman RP, Lower EE. Infliximab for refractory sarcoidosis. Sarcoidosis Vase Diffuse Lung Dis 2001; 18(1):70-4.

(2.) Yee AM, Pochapin MB. Treatment of complicated sarcoidosis with infliximab anti-tumor necrosis factor-alpha therapy. Ann Intern Med 2001; 135:27-31.

(3.) Senaldi G, Yin S, Shaklee CL, Piguet PF, Mak TW, Ulich TR. Corynebacterium parvum- and Mycobacterium bovis bacillus Calmette-Guerin-induced granuloma formation is inhibited in TNF receptor I (TNF-RI) knockout mice and by treatment with soluble TNF-RI. J Immunol 1996; 157(11):5022-6.

(4.) Lee JB, Koblenzer PS. Disfiguring cutaneous manifestation of sarcoidosis treated with thalidomide: a case report. J Am Acad Dermatol 1998; 39(5 Pt 2):835-8.

ADDRESS FOR CORRESPONDENCE:

Jon Meyerle MD

Department of Internal Medicine, Section of Dermatology

Walter Reed Army Medical Center

4515 Willard Avenue #1018

Chevy Chase, MD 20815

Phone: (202) 246-3262

Fax: (202) 782-9118

Email: jon.meyerle@verizon.net

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