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 deforming
- 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.
- 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.
- 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.
- 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.
- Verny C, de Gennes C, Sébastien P, et al. [Heart conduction disorders in long-term treatment with chloroquine. Two new cases]. Presse Med 1992; 21:800.
- 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.
- Francioni C, Galeazzi M, Fioravanti A, et al. Long-term i.v. Ig treatment in systemic lupus erythematosus. Clin Exp Rheumatol 1994; 12:163.
- Sany J. Intravenous immunoglobulin therapy for rheumatic diseases. Curr Opin Rheumatol 1994; 6:305.
- Chan AC, Sack K. Danazol therapy in autoimmune hemolytic anemia associated with systemic lupus erythematosus. J Rheumatol 1991; 18:280.
- 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.
- A randomized study of the effect of withdrawing hydroxychloroquine sulfate in systemic lupus erythematosus. The Canadian Hydroxychloroquine Study Group. N Engl J Med 1991; 324:150.