Contents

Search

mixed connective tissue disease; Sharp's syndrome (MCTD)

- A term proposed in 1972 to describe 20 patients with a combination of clinical manifestations generally associated with systemic lupus erythematosus (SLE), scleroderma & polymyositis/dermatomyositis - It is felt by some that MCTD is not a separate entity, but an overlap syndrome of SLE, scleroderma & polymyositis - The original patients diagnosed with MCTD tended to evolve to a single disease entity, generally scleroderma. Epidemiology: 1) female > male (9:1 ratio); 88 % women 2) peak onset in 2nd & 3rd decade, can occur at any age - median age at diagnosis 35 years [11] 3) occurs worldwide & in all races 4) rare: prevalence 1 in 1,000,000 [4] Clinical manifestations: 1) manifestations of SLE, scleroderma & dermatomyositis 2) presenting symptoms a) most common: 1] Raynaud's phenomenon (85-91%) [11] 2] hand edema, puffy hands (66%), puffy fingers (46%), sclerodactyly (33%) - palmar telangiectasias noted in case presentation [4] - abnormal nailfold capillaroscopy (~50%) [11] 3] arthralgias, arthritis, synovitis (83-95%) 4] myalgias (31%) [11], myositis 5] fatigue b) less comon 1] high fever 2] polymyositis, inflammatory myopathy (proximal muscle weakness) 3] arthritis, serositis (27%) 4] neurologic manifestations a] trigeminal neuralgia (10%) b] aseptic meningitis 3) pulmonary involvement a) often asymptomatic b) pleurisy (common) c) pleural effusions are generally small & resolve spontaneously d) interstitial lung disease (28%) e) aspiration pneumonia f) pulmonary hypertension (67%), (8%) [11] 1] most serious complication 2] most common cause of death in MCTD 4) renal disease in 10-25% a) glomerulonephritis (most common) b) nephrotic syndrome 5) GI manifestations (70%) a) esophageal dysmotility b) gastroesophageal reflux (GERD) c) bowel manifestations similar to scleroderma 6) cardiac manifestations a) pericarditis (30%), pericardial effusion b) myocarditis, arrhythmias, mitral valve prolapse Diagnostic criteria: - at least 2 of - systemic lupus erythematosus - systemic sclerosis - autoimmune myositis (dermatomyositis) with anti-U1 RNP Ab Laboratory: 1) positive antinuclear antibody (ANA) restricted to: a) anti U1-snRNP, anti U1-RNP (all) [11] b) anti-U1 RNP antibodies (high titer) [4] c) may be referred to as extractable nuclear ribonucleoprotein antigen (ENA) 2) complete blood count (CBC): anemia of chronic inflammation 3) positive direct Coomb's test (60%) 4) serum creatinine kinase: hyperCKemia 5) muscle biopsy not necessary if muscle strength is normal [4] 6) serum complement: normal 7) serum creatinine generally normal 8) see ARUP consult [6] Special laboratory: 1) pulmonary function testing: a) diminished DLCO (67%) b) restrictive pattern (50%) 2) pulmonary artery catheter - diagnosis of pulmonary hypertension [4] Complications: - pulmonary hypertension is the leading cause of death [9] - thrombotic thrombocytopenic purpura [9] Management: 1) good response to low dose oral glucocorticoids 2) treatment is the same as for the connective tissue diseases comprising the manifestations of MCTD 3) patients with pulmonary hypertension a) combination of glucocorticoids plus cyclophosphamide [7] b) add pulmonary vasodilator for more severe cases [7] 4) most patients have a favorable course of the disease - after 8 years, 26% progressed to a differentiated connective tissue disease, mostly systemic lupus erythematosis or scleroderma [11] - patients who do not progress to a differentiated connective tissue disease, are more likely to be in remission after 8 years (52% vs 26 [11] 5) 10 year survival rate is 80%

Related

dermatomyositis scleroderma (diffuse cutaneous systemic sclerosis) systemic lupus erythematosus

General

connective tissue disease; soft tissue disease overlap syndrome

References

  1. Clinical Diagnosis & Management by Laboratory Methods, 19th edition, J.B. Henry (ed), W.B. Saunders Co., Philadelphia, PA. 1996, pg 1021
  2. Harrison's Principles of Internal Medicine, 14th ed. Fauci et al (eds), McGraw-Hill Inc. NY, 1998, pg 1895
  3. Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 789
  4. Medical Knowledge Self Assessment Program (MKSAP) 14, 15, 16, 17, 18, 19. American College of Physicians, Philadelphia 2006, 2009, 2012, 2015, 2018, 2022. - Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022
  5. Venables PJ Mixed connective tissue disease. Lupus, 2006 15:132 PMID: 16634365
  6. ARUP Consult: Mixed Connective Tissue Disease - MCTD The Physician's Guide to Laboratory Test Selection & Interpretation https://www.arupconsult.com/content/mixed-connective-tissue-disease
  7. Jais X, Launay D, Yaici A, Le Pavec J 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 Feb;58(2):521-31 PMID: 18240255
  8. Tsai YY, Yang YH, Yu HH, Wang LC, Lee JH, Chiang BL. Fifteen-year experience of pediatric-onset mixed connective tissue disease. Clin Rheumatol. 2010 Jan;29(1):53-8. PMID: 19756834
  9. Hajas A, Szodoray P, Nakken B et al Clinical course, prognosis, and causes of death in mixed connective tissue disease. J Rheumatol. 2013 Jul;40(7):1134-42 PMID: 23637328
  10. Swanton J, Isenberg D. Mixed connective tissue disease: still crazy after all these years. Rheum Dis Clin North Am. 2005 Aug;31(3):421-36 PMID: 16084316
  11. Chevalier K et al. Clinical presentation, course, and prognosis of patients with mixed connective tissue disease: A multicenter retrospective cohort. J Intern Med 2024 Apr; 295:532. PMID: 38013625 https://onlinelibrary.wiley.com/doi/10.1111/joim.13752