Prognosis and treatment of mixed connective tissue disease
- Robert M Bennett, MD, FRCP, MACR
Robert M Bennett, MD, FRCP, MACR
- Professor of Medicine
- Oregon Health & Science University
Mixed connective tissue disease (MCTD) is a generalized connective tissue disorder that includes clinical features commonly seen in systemic lupus erythematosus (SLE), scleroderma, and polymyositis (referred to as overlap syndrome) (table 1) . Almost any organ system can be involved in MCTD. There are, however, several clinical features that, taken together, suggest the presence of MCTD rather than another connective tissue disorder:
●Raynaud phenomenon and swollen hands or puffy fingers
●A high titer speckled pattern antinuclear antibody (ANA) (usually ≥1280)
●The absence of severe renal and central nervous system (CNS) disease
●More severe arthritis, which is sometimes deformingTo continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- Bennett, RM. Overlap Syndromes. In: Textbook of Rheumatology, 8th ed, Firestein (Ed), W.B. Saunders Co, Philadelphia 2009. p.1381.
- Hoffman RW, Maldonado ME. Immune pathogenesis of Mixed Connective Tissue Disease: a short analytical review. Clin Immunol 2008; 128:8.
- Sharp GC, Irvin WS, Tan EM, et al. Mixed connective tissue disease--an apparently distinct rheumatic disease syndrome associated with a specific antibody to an extractable nuclear antigen (ENA). Am J Med 1972; 52:148.
- Piirainen HI, Kurki PT. Clinical and serological follow-up of patients with polyarthritis, Raynaud's phenomenon, and circulating RNP antibodies. Scand J Rheumatol 1990; 19:51.
- Piirainen HI. Patients with arthritis and anti-U1-RNP antibodies: a 10-year follow-up. Br J Rheumatol 1990; 29:345.
- Sharp GC, Anderson PC. Current concepts in the classification of connective tissue diseases. Overlap syndromes and mixed connective tissue disease (MCTD). J Am Acad Dermatol 1980; 2:269.
- Burdt MA, Hoffman RW, Deutscher SL, et al. Long-term outcome in mixed connective tissue disease: longitudinal clinical and serologic findings. Arthritis Rheum 1999; 42:899.
- Aringer M, Smolen JS. Mixed connective tissue disease: what is behind the curtain? Best Pract Res Clin Rheumatol 2007; 21:1037.
- Sharp GC, Irvin WS, May CM, et al. Association of antibodies to ribonucleoprotein and Sm antigens with mixed connective-tissue disease, systematic lupus erythematosus and other rheumatic diseases. N Engl J Med 1976; 295:1149.
- Bennett RM, Spargo BH. Immune complex nephropathy in mixed connective tissue disease. Am J Med 1977; 63:534.
- Bennett RM, Bong DM, Spargo BH. Neuropsychiatric problems in mixed connective tissue disease. Am J Med 1978; 65:955.
- Shi YH, Li R, Chen S, et al. [Analysis of clinical features and the outcome in 91 cases of mixed connective tissue diseases]. Beijing Da Xue Xue Bao 2012; 44:270.
- Nimelstein SH, Brody S, McShane D, Holman HR. Mixed connective tissue disease: a subsequent evaluation of the original 25 patients. Medicine (Baltimore) 1980; 59:239.
- Miyawaki S, Onodera H. Clinical course and prognosis of patients with mixed connective tissue disease. In: Mixed Connective Tissue Disease and Antinuclear Antibodies, Kasukawa R, Sharp G (Eds), Excerpta Medica, Amsterdam 1987. p.331.
- Gendi NS, Welsh KI, Van Venrooij WJ, et al. HLA type as a predictor of mixed connective tissue disease differentiation. Ten-year clinical and immunogenetic followup of 46 patients. Arthritis Rheum 1995; 38:259.
- Szodoray P, Hajas A, Kardos L, et al. Distinct phenotypes in mixed connective tissue disease: subgroups and survival. Lupus 2012; 21:1412.
- Hajas A, Szodoray P, Nakken B, et al. Clinical course, prognosis, and causes of death in mixed connective tissue disease. J Rheumatol 2013; 40:1134.
- Hant FN, Herpel LB, Silver RM. Pulmonary manifestations of scleroderma and mixed connective tissue disease. Clin Chest Med 2010; 31:433.
- Bennett RM, O'Connell DJ. Mixed connective tisssue disease: a clinicopathologic study of 20 cases. Semin Arthritis Rheum 1980; 10:25.
- Gunnarsson R, Andreassen AK, Molberg Ø, et al. Prevalence of pulmonary hypertension in an unselected, mixed connective tissue disease cohort: results of a nationwide, Norwegian cross-sectional multicentre study and review of current literature. Rheumatology (Oxford) 2013; 52:1208.
- Gunnarsson R, Aaløkken TM, Molberg Ø, et al. Prevalence and severity of interstitial lung disease in mixed connective tissue disease: a nationwide, cross-sectional study. Ann Rheum Dis 2012; 71:1966.
- Lundberg IE. Cardiac involvement in autoimmune myositis and mixed connective tissue disease. Lupus 2005; 14:708.
- Graf WD, Milstein JM, Sherry DD. Stroke and mixed connective tissue disease. J Child Neurol 1993; 8:256.
- Kuwana M, Kaburaki J, Okano Y, et al. Clinical and prognostic associations based on serum antinuclear antibodies in Japanese patients with systemic sclerosis. Arthritis Rheum 1994; 37:75.
- Morand EF, Miller MH, Whittingham S, Littlejohn GO. Fibromyalgia syndrome and disease activity in systemic lupus erythematosus. Lupus 1994; 3:187.
- Middleton GD, McFarlin JE, Lipsky PE. The prevalence and clinical impact of fibromyalgia in systemic lupus erythematosus. Arthritis Rheum 1994; 37:1181.
- Bennett RM, O'Connell DJ. The arthritis of mixed connective tissue disease. Ann Rheum Dis 1978; 37:397.
- Halla JT, Hardin JG. Clinical features of the arthritis of mixed connective tissue disease. Arthritis Rheum 1978; 21:497.
- Ramos-Niembro F, Alarcón-Segovia D, Hernández-Ortíz J. Articular manifestations of mixed connective tissue disease. Arthritis Rheum 1979; 22:43.
- Kitridou RC, Akmal M, Turkel SB, et al. Renal involvement in mixed connective tissue disease: a longitudinal clinicopathologic study. Semin Arthritis Rheum 1986; 16:135.
- Bulpitt KJ, Clements PJ, Lachenbruch PA, et al. Early undifferentiated connective tissue disease: III. Outcome and prognostic indicators in early scleroderma (systemic sclerosis). Ann Intern Med 1993; 118:602.
- De Clerck LS, Meijers KA, Cats A. Is MCTD a distinct entity? Comparison of clinical and laboratory findings in MCTD, SLE, PSS, and RA patients. Clin Rheumatol 1989; 8:29.
- Kim P, Grossman JM. Treatment of mixed connective tissue disease. Rheum Dis Clin North Am 2005; 31:549.
- Yoshida S. Pulmonary arterial hypertension in connective tissue diseases. Allergol Int 2011; 60:405.
- Fares WH, Trow TK. Targeted approaches to the treatment of pulmonary hypertension. Ther Adv Respir Dis 2012; 6:147.
- Ueda Y, Yamauchi Y, Makizumi K, et al. Successful treatment of acute right cardiac failure due to pulmonary thromboembolism in mixed connective tissue disease. Jpn J Med 1991; 30:568.
- Dahl M, Chalmers A, Wade J, et al. Ten year survival of a patient with advanced pulmonary hypertension and mixed connective tissue disease treated with immunosuppressive therapy. J Rheumatol 1992; 19:1807.
- Sullivan WD, Hurst DJ, Harmon CE, et al. A prospective evaluation emphasizing pulmonary involvement in patients with mixed connective tissue disease. Medicine (Baltimore) 1984; 63:92.
- Sharp GC. Therapy and prognosis of MCTD. In: Mixed Connective Tissue Disease and Antinuclear Antibodies, Kasukawa R, Sharp G (Eds), Excerpta Medica, Amsterdam 1987. p.315.
- Alpert MA, Pressly TA, Mukerji V, et al. Acute and long-term effects of nifedipine on pulmonary and systemic hemodynamics in patients with pulmonary hypertension associated with diffuse systemic sclerosis, the CREST syndrome and mixed connective tissue disease. Am J Cardiol 1991; 68:1687.
- McLaughlin VV, Genthner DE, Panella MM, et al. Compassionate use of continuous prostacyclin in the management of secondary pulmonary hypertension: a case series. Ann Intern Med 1999; 130:740.
- Alpert MA, Pressly TA, Mukerji V, et al. Short- and long-term hemodynamic effects of captopril in patients with pulmonary hypertension and selected connective tissue disease. Chest 1992; 102:1407.
- Jais X, Launay D, Yaici A, et al. Immunosuppressive therapy in lupus- and mixed connective tissue disease-associated pulmonary arterial hypertension: a retrospective analysis of twenty-three cases. Arthritis Rheum 2008; 58:521.
- de Perrot M, Granton JT, McRae K, et al. Outcome of patients with pulmonary arterial hypertension referred for lung transplantation: a 14-year single-center experience. J Thorac Cardiovasc Surg 2012; 143:910.
- Végh J, Soós G, Csipõ I, et al. Pulmonary arterial hypertension in mixed connective tissue disease: successful treatment with Iloprost. Rheumatol Int 2006; 26:264.
- Naclerio C, D'Angelo S, Baldi S, et al. Efficacy of bosentan in the treatment of a patient with mixed connective tissue disease complicated by pulmonary arterial hypertension. Clin Rheumatol 2010; 29:687.
- Sjogren RW. Gastrointestinal motility disorders in scleroderma. Arthritis Rheum 1994; 37:1265.
- Pope JE. Other manifestations of mixed connective tissue disease. Rheum Dis Clin North Am 2005; 31:519.
- Ulmer A, Kötter I, Pfaff A, Fierlbeck G. Efficacy of pulsed intravenous immunoglobulin therapy in mixed connective tissue disease. J Am Acad Dermatol 2002; 46:123.
- Hahn BH, Grossman J, Chen W, McMahon M. The pathogenesis of atherosclerosis in autoimmune rheumatic diseases: roles of inflammation and dyslipidemia. J Autoimmun 2007; 28:69.
- Canadian Hydroxychloroquine Study Group. A randomized study of the effect of withdrawing hydroxychloroquine sulfate in systemic lupus erythematosus. N Engl J Med 1991; 324:150.
- Vereckei A, Fazakas A, Baló T, et al. Chloroquine cardiotoxicity mimicking connective tissue disease heart involvement. Immunopharmacol Immunotoxicol 2013; 35:304.