Abstract
To report our experience in using rituximab (RTX) for treating refractory rapidly progressive interstitial lung disease (RP-ILD) complicating anti-melanoma differentiation-associated gene 5 antibody (anti-MDA5 Ab)-positive amyopathic dermatomyositis (ADM). Medical records of four ADM patients with refractory RP-ILD treated with RTX therapy were reviewed retrospectively. All four patients were tested positive for anti-MDA5 Ab and failed to respond to high-dose systemic steroid and other intensive immunosuppressive therapies. Respiratory symptoms, lung function tests, and high-resolution computed tomography (HRCT) of the chest were compared before and after the first course of RTX. After RTX treatment, all four patients had improvement in the respiratory symptoms in terms of New York Heart Association classification. Two patients successfully had their supplementary oxygen therapy weaned off. The lung function tests were significantly better in all patients. The HRCT showed improvement in three patients while the other one remained static. The recalcitrant vasculitic rashes associated with the anti-MDA5 Ab were also better in all patients. The average daily prednisolone dose dropped from 20 to 6.25 mg post-treatment. None of the patients died throughout the follow-up period which ranged from 6 months to 2 years. However, two patients developed chest infection and one wound infection within 6 months after the RTX infusion. Our results suggest that RTX may be a useful therapy for anti-MDA5 Ab-positive ADM associated with RP-ILD. However, infection is the major risk.
References
Sontheimer RD (2010) Clinically myopathic dermatomyositis: what can we now tell our patients? Arch Dermatol 146:76–80
Betterridge Z, McHugh N (2016) Myositis-specific autoantibodies: an important tool to support diagnosis of myosis. J Internal Med 280:8–23
Sato S, Hoshino K, Satoh T, Fujita T, Kawakami Y, Kuwana M (2009) RNA helicase encoded by melanoma differentiation-associated gene 5 is a major autoantigen in patients with clinically amypathic dermatomyositis: association with rapidly progressive ILD. Arthritis Rheum 60:2193–2200
Moghadam-Kia S, Oddis C, Sato S, Kuwana M, Aggarwal R (2016) Anti-melanoma differentiation-associated gene 5 is associated with rapidly progressive lung disease and poor survival in US patients with myopathic and myopathic dermatomyositis. Arthritis Care Res 68:689–694
Gil B, Merav L, Pnina L, Chagai G (2016) Diagnosis and treatment of clinically myopathic dermatomyositis (CADM): a case series and literature review. Clin Rheumatol 35:2125–2130
Kawasumi H, Gono T, Kawaguchi Y, Yamanaka H (2015) Recent treatment of interstitial lung disease with idiopathic inflammatory myopathies. Clin Med Insights Cir Respir Pulm Med 9:9–17
Marie I, Dominique S, Janvresse A, Levesque H, Menard JF (2013) Rituximab therapy for refractory interstitial lung disease related to antisynthetase syndrome. Respir Med 106:582–587
Andersson H, Sem M, Lund MB, Aalokken TM, Gunther A, Walle-Hansen R et al (2015) Long-term experience with rituximab in anti-synthetase syndrome-related interstitial lung disease. Rheumatology 54:1420–1428
Aggarwal R, Bandos A, Reed AM, Ascherman DP, Barohn RJ, Feldman BM, Miller FW, Rider LG, Harris-Love MO, Levesque MC, the RIM Study Group, Oddis CV (2014) Predictors of clinical improvement in rituximab-treated refractory adult and juvenile dermatomyositis and adult polymyositis. Arthritis Rheumatol 66:740–749
American Thoracic Society (2000) Idiopathic pulmonary fibrosis: diagnosis and treatment. International consensus statement. American Thoracic Society (ATS), and the European Respiratory Society (ERS). Am J Respir Crit Care Med 161:646–664
Kameda H, Nagaswa H, Ogawa H, Sekiguchi N, Takei H, Tokuhira M et al (2005) Combination therapy with corticosteroid, cyclosporin A, and intravenous pulse cyclophosphamide for acute/subacute interstitial pneumonia in patients with dermatomyositis. J Rheumatol 32:1719–1726
Hamada-Ode K, Taniguchi Y, Kimata T et al (2015) High-dose intravenous immunoglobulin therapy for rapidly progressive interstitial pneumonitis accompanied by anti-melanoma differentiation-associated gene 5 antibody positive amyopathic dermatomyositis. Eur J Rheumatol 2:83–85
Ichiyasu H, Sakamoto Y, Yoshida C, Kawaguchi Y, Shimamura Y, Kuwana M et al (2017) Rapidly progressive interstitial lung disease due to anti-MDA-5 antibody-positive clinically amyopathic dermatomyositis complicated with cervical cancer: successful treatment with direct hemoperfusion using polymyxin B-immobilized fibre column therapy. Respir Med Case Reports 20:50–54
Fasano S, Gordon P, Hajji R, Loyo E, Isenberg D (2017) Rituximab in the treatment of inflammatory myopathies: a review. Rheumatology 56:26–36
Watanabe R, Ishii T, Araki K, Ishizuka M, Kamogawa Y, Fujita Y, Shirota Y, Fujii H, Harigae H (2016) Successful multi-target therapy using corticosteroid, tacrolimus, cyclophosphamide, and rituximab for rapidly progressive interstitial lung disease in a patient with clinically amyopathic dermatomyositis. Mod Rheumatol 26:465–466
Yamaguchi K, Yamaguchi A, Uchida M, Kono S, Suzuki M, Masubuchi H et al (2017) A case of anti-MDA5-positive rapidly progressive interstitial lung disease in a patient with clinically amyopathic dermatomyositis ameliorated by rituximab, in addition to standard immunosuppressive treatment. Mod Rheumatol 27:536–540
Ogawa Y, Kishida D, Shimojima Y, Hayashi K, Sekijima Y (2017) Effective administration of rituximab in anti-MDA5 antibody-positive dermatomyositis with rapidly progressive interstitial lung disease and refractory cutaneous involvement: a case report and literature review. Case Rep Rheumatol 2017:1–6. https://doi.org/10.1155/2017/5386797
Tokunaga K, Hagino N (2017) Dermatomyositis with rapidly progressive interstitial lung disease treated with rituximab: a report of 3 cases in Japan. Intern Med 56:1399–1403
Chen Z, Cao M, Plana M, Liang J, Cai H, Kuwana M et al (2013) Utility of anti-melanoma differentiation-associated gene 5 antibody measurement in identifying patients with dermatomyositis and a high risk for developing rapidly progressive interstitial lung disease: a review of the literature and a meta-analysis. Arthritis Care Res 65:1316–1324
Sato S, Kuwana M, Fujita T, Suzuki Y (2013) Anti-CADM-140/MDA5 autoantibody titre correlates with disease activity and predicts disease outcome in patients with dermatomyositis and rapidly progressive interstitial lung disease. Mod Rheumatol 23:496–502
Aggarwal R, Oddis C, Goudeau D, Koontz D, Qi Z, Reed AM et al (2016) Autoantibody levels in myositis patients correlate with clinical response during B cell depletion with rituximab. Rheumatology 55:991–999
Narang N, Casciola-Rosen L, Li S, Chung L, Fiorentino D (2015) Cutaneous ulceration in dermatomyositis: association with anti-melanoma differentiation-associated gene 5 antibodies and interstitial lung disease. Arthritis Care Res 67:667–672
Gono T, Y. Kawaguchi Y, Hara M, Masuda I, Katsumata Y, Shinozaki M, Ota Y., Ozeki E., Yamanaka H. (2010) Increased ferritin predicts development and severity of acute interstitial lung disease as a complication of dermatomyositis. Rheumatology 49:1354–1360
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So, H., Wong, V.T.L., Lao, V.W.N. et al. Rituximab for refractory rapidly progressive interstitial lung disease related to anti-MDA5 antibody-positive amyopathic dermatomyositis. Clin Rheumatol 37, 1983–1989 (2018). https://doi.org/10.1007/s10067-018-4122-2
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DOI: https://doi.org/10.1007/s10067-018-4122-2