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A. Definition [1]navigator

  1. Well characterized rheumatologic overlap syndrome
  2. Overlapping clinical features including:
    1. Systemic Lupus Erythematosus (SLE)
    2. Scleroderma (Systemic Sclerosis)
    3. Polymyositis / Dermatomyositis (Inflammatory Myositis)
  3. Very high titers of circulating anti-ribonuclear antibodies (Abs) required for diagnosis [4]

B. Laboratory Findingsnavigator

  1. Marked hypergammaglobulinemia
  2. Antibodies (Abs) [2]
    1. Anti-RNP in high titer with low to moderate titer ANA
    2. Anti-73kd Heat Shock Protein Abs
  3. Mild to moderate hypocomplementemia in 25% of patients
  4. Circulating Immune complexes in active disease
  5. Deposition of these immune complexes in blood vessels, muscle fibers, glomeruli
  6. Chronic inflammatory infiltration (lymphocytes, plasma cells) in various tissues

C. Symptomsnavigator

  1. May present as fever of unknown origin
  2. Polyarthralgias (~100%) or arthritis (75%)
  3. Raynaud's Phenomenon and Swollen hands
  4. Proximal inflammatory myopathy is major component
    1. All patients with suspected MCTD should have creatinine kinase levels checked
    2. Aldolase is muscle-specific and may also be checked
  5. Esophageal hypomotility - similar to scleroderma
  6. Pulmonary Disease
    1. Pulmonary hypertension is most common (probably related to Raynaud's)
    2. May have parenchymal inflammation (similar to scleroderma)
    3. Diffuse alveolar damage, interstitial disease, uncommon [5]
    4. However, these kinds of pathology are not uncommon in myositis and systemic sclerosis

D. Treatment navigator

  1. High dose glucocorticoids (prednisone 1mg/kg) initially
    1. Primarily improves myopathy
    2. May improve parenchymal pulmonary disease, but this is not common
  2. Consider cytotoxic therapy (Cyclophosphamide or Chlorambucil ?) if prednisone fails
  3. Azathioprine - may be used as a steroid sparing agent
  4. Methotrexate may be useful in patients with myositis
  5. Raynaud's Disease
    1. Treatment with vasodilators, particularly calcium blockers is first line
    2. Nitropaste (nitroglycerin gel) applied to affected fingers may be helpful
    3. alpha1-antagonists may also be effective

E. Pulmonary Hypertension [6] navigator

  1. Major cause of morbidity and mortality in MCTD
  2. Patients often have significant Raynaud's disease and severe pulmonary hypertension
  3. Present with subacute dyspnea on exertion
  4. Evaluation [7]
    1. Should establish that MCTD is the cause of pulmonary HTN
    2. Rule out coexistant infection or pneumoconiosis or emphysema or pulmonary embolism
    3. Evaluation of vasodilatory response to nitric oxide or prostaglandins often useful
  5. Most patients have difficulty tolerating nifedipine treatment due to systemic hypotension
  6. Combined therapy with diltiazem and oxygen may be effective [3]
    1. Calcium blockers alone may worsen V/Q mismatch and lower Arterial oxygenation
    2. Exogenous O2 administration leads to pulmonary vasodilatation, improved oxygenation
  7. Aerosolized prostacyclin (Iloprost) is effective in early studies and well tolerated [6,8]

References navigator

  1. Sharp GC et al. 1976. NEJM. 295:1149 abstract
  2. Mairesse N, Kahn MF, Appelboom T. 1993. Am J Med. 95(6):595 abstract
  3. Shinohara S. et al. 1994. J Rheum. 21(9):1763 abstract
  4. Sharp GC, Irwin WS, Tan EM, et al. 1972. Am J Med. 52:148 abstract
  5. Lazarus DS, and Mark EJ. 1995. NEJM. 333(6):369 (Case Report)
  6. Olschewski H, Walmrath D, Schermuly R. et al. 1996. Ann Intern Med. 124(9):820 abstract
  7. Rubin LJ. 1997. NEJM. 336(2):111 abstract
  8. Rolla G, Colagrande P, Brussino, et al. 1998. Lancet. 351(9114):1491 abstract