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FOR MORE LETTERS SEE BELOW: To the Editor: Relapsing polychondritis (RP) is a rare autoinflammatory disorder characterized by recurrent inflammation and destruction of cartilage and connective tissue1. Although the etiology of the disease is unknown, the pathogenesis appears to be mediated by an immune reaction to type II collagen, which is abundant in cartilage and the sclera1-2. Despite its episodic nature, RP is a progressive disease and most patients have significant disabilities during later stages, including impairments in hearing and vision, as well as cardiorespiratory problems1. Treatments are not standardized and generally consist of nonsteroidal antiinflammatory drugs and/or immunosuppressive therapies such as corticosteroids, methotrexate (MTX), or cyclophosphamide. Treatment may relieve the immediate symptoms of RP, but longterm therapy does not generally prevent disease progression, and prognosis is usually poor2. This report describes the successful treatment of episodic symptoms and cessation of flares with the tumor necrosis factor (TNF) antagonist etanercept in a patient with refractory RP. The first undiagnosed episode of illness in this patient, a 46-year-old white woman, consisted of a 2-week episode of pain and inflammation involving the bridge of the nose, which had spontaneously resolved. This event occurred approximately 1 year before her presentation with pain and erythema in the left ear, sparing the earlobe. She was originally diagnosed with cellulitis, but antibiotic treatment was ineffective and the symptoms resolved spontaneously after completion of the antibiotic regimen. Three months later, the patient developed scleritis of the right eye and recurrence of pain and inflammation in the left ear, again sparing the earlobe. At that time she was diagnosed with RP. Other features of RP, including cardiovascular and joint manifestations, were absent. Laboratory tests for antinuclear antibodies and all other lupus serologies were negative. Oral corticosteroids were prescribed (60 mg prednisone daily) and the symptoms resolved; however, when the prednisone dose was tapered to 30 mg daily, the symptoms returned. Azathioprine was added to her therapeutic regimen and titrated up to 150 mg daily. Attempts to taper her prednisone to 30 mg daily were unsuccessful; symptoms of scleritis, with or without ear inflammation, always returned at that dosage. Azathioprine was discontinued after 1.5 months. MTX was added and rapidly titrated up to 20 mg weekly. The patient remained on MTX (20 mg orally per week) and prednisone (varying doses) for 6 months. Scleritis, and frequently pain and erythema of the ear and nose, would recur whenever her prednisone dose was tapered to 25–30 mg daily. Etanercept therapy was initiated at 25 mg subcutaneously (SC) twice weekly (BIW) for her refractory RP, in addition to MTX and prednisone. Her corticosteroid dosage was subsequently tapered and ultimately discontinued without the appearance of flares. She remains on etanercept (25 mg SC BIW) and MTX (15 mg weekly), and had no recurrence of symptoms in the ensuing year. The level of plasma C-reactive protein (CRP), a marker of inflammation, was slightly elevated (2.6 mg/dl; normal: 0-1.0 mg/dl) during combination therapy with MTX (20 mg weekly) and prednisone (25 mg daily). Following the initiation of etanercept therapy, CRP levels were reduced to 0.02, 0.05, and 0.03 mg/dl at 3, 6, and 9 months, respectively. Based on a growing body of evidence, the pathophysiology of RP is apparently mediated by an autoimmune reaction to cartilage components1,2. Autoantibodies to collagen are seen in the serum of patients with RP following an inflammatory episode, and histological studies have suggested the presence of immune complexes in affected tissues1. An animal model of experimental collagen-induced arthritis resembles RP3 and data from this model suggest that the binding of anti-collagen antibodies to cartilage results in complement-mediated inflammation and the release of inflammatory cytokines, including TNF. These studies support the use of biologic therapies designed to modulate TNF function in treatment of RP. Etanercept therapy in this patient resulted in rapid relief of eye and cartilage inflammation, with no recurrence of RP symptoms to date. An additional benefit of instituting this biologic therapy was the subsequent ability to taper her prednisone dosage, reducing the risk of side effects associated with longterm systemic steroid therapy. There are currently 4 reports of successful treatment of RP symptoms, including laryngotracheal chondritis with respiratory complications4, scleritis5 arthritis6-7, and chondritis7 with an anti-TNF monoclonal antibody, infliximab. These reports, together with the case reported here, strongly suggest that the pathophysiology of RP is mediated by the proinflammatory cytokine TNF. It remains to be seen if anti-TNF therapies will be able to slow or prevent longterm progression of this disease. Longterm studies are clearly warranted. JOHN D. CARTER, MD, Division of Rheumatology, Department of Internal Medicine, College of Medicine, University of South Florida, Tampa, Florida, USA. REFERENCES 1. Molina JF, Espinoza LR. Relapsing polychondritis. Best Pract Res Clin Rheumatol 2000;14:97-109. 2. Letko E, Zafirakis P, Baltatzis S, Voudouri A, Livir-Rallatos C, Foster CS. Relapsing polychondritis: a clinical review. Semin Arthritis Rheum 2002;31:384-95. 3. Cremer MA, Rosloniec EF, Kang AH. The cartilage collagens: a review of their structure, organization, and role in the pathogenesis of experimental arthritis in animals and in human rheumatic disease. J Mol Med 1998;76:275-88. 4. Mpofu S, Estrach C, Curtis J, Moots RJ. Treatment of respiratory complications in recalcitrant relapsing polychondritis with infliximab. Rheumatology 2003;42:1117-8. 5. Cazabon S, Over K, Butcher J. The successful use of infliximab in resistant relapsing polychondritis and associated scleritis. Eye 2005;19:222-4. 6. Matzkies FG, Manger B, Schmitt-Haendle M, et al. Severe septicaemia in a patient with polychondritis and Sweet's syndrome after initiation of treatment with infliximab. Ann Rheum Dis 2003;62:81-2. 7. Saadoun D, Deslandre CJ, Allanore Y, Charlier C, Pham X-V, Kahan A. Sustained response to infliximab in 2 patients with refractory relapsing polychondritis. J Rheumatol 2003;30:1394-5. |
