MCTD is a rare systemic rheumatic disease characterized by presence of anti-U1 RNP autoantibodies, with clinical features overlapping SLE, systemic sclerosis, RA, and polymyositis.
Epidemiology
Occurs worldwide, affects all races, and peak incidence is in adolescence and 20s. More common in females than males, from 3:1 to 16:1.
Diagnostic Criteria
These are in debate. Common themes are:
- Positive anti U1 RNP antibodies
- Three or more of the following:
- Swollen or puffy hands
- Synovitis
- Myositis
- Raynaud phenomenon
- Acrosclerosis
RF is positive in 70%, anti CCP positive in 50%.
Pathogenesis
U1 RNP is uniquely linked to MCTD in terms of unique clinical presentations. One might argue that MCTD is then a disease defined by the presence of U1 RNP, but not all patients with U1 RNP have MCTD.
Little is known about the etiology of MCTD. It has been associated with vinyl chloride and silica, HLA-DRB1 polymorphism.
Natural History of Disease
Timelines
MCTD often takes several years before enough features present that MCTD is the most likely diagnosis. In early stages, MCTD may present with features of undifferentiated connective tissue disease (UCTD).
Clinical Presentation
Early clinical features are nonspecific: puffy fingers, fatigue, arthralgias, myalgias, low-grade fever, and Raynaud syndrome. Patients may be found to have a positive ANA/ENA for RNP.
Any organ system can be involved. Most commonly the following would suggest MCTD over another rheumatic disease: (1) Raynaud phenomenon or swollen or puffy hands, (2) absence of severe renal and CNS disease, (3) more severe arthritis, (4) insidious onset of pulmonary hypertension, (5) U1 RNP antibodies.
| System | Manifestations |
|---|---|
| skin | Raynaud phenomenon, swollen fingers and hands, Chillblain lesions, calcinosis cutis, malar rash, discoid plaques, panniculitis, oral ulcerations, sicca complex, nasal septal perforation |
| joints | arthritis with RA-esque deformities |
| pulmonary (75%) | ILD (50%), pulmonary hypertension |
| vascular | Raynaud, abnormal nailfold capillaroscopy |
| muscle | polymyositis-like myopathy |
| cardiac | conduction disorder, pericarditis, MVP, pericardial effusion, accelerated atherosclerosis |
| kidney | severe renal dysfunction is ABSENT, but patients can develop membranous nephropathy, nephrotic range proteinuria |
| gastrointestinal | dysmotility of the UGI |
| CNS | Trigeminal neuropathy, headaches, sensorineural hearing loss |