Mixed Connective Tissue Disease

Excerpt

Mixed connective tissue disease (MCTD) is a rare systemic autoimmune disease with the main features of at least 2 overlapping connective tissue diseases, including systemic lupus erythematosus, systemic sclerosis, polymyositis, dermatomyositis, and rheumatoid arthritis. The disease is also defined by the presence of anti-U1-ribonucleoprotein (RNP) antibodies and Raynaud phenomenon. The condition was initially described by Sharp in 1972 through a case series of 25 patients with features of systemic lupus erythematosus, systemic sclerosis, and inflammatory muscle disease associated with anti-U1-RNP antibodies. However, at that time, MCTD was not described as a separate entity from undifferentiated connective tissue disease, and its characteristics have evolved since then. Although most authors describe MCTD as an independent entity, some believe it may represent an early stage of a definite connective tissue disease, such as systemic lupus erythematosus, systemic sclerosis, or overlap syndrome. MCTD has no unique clinical features, and considerable interindividual variation in clinical manifestations exists.

Multiple attempts have been made to develop classification criteria, but there are currently no internationally agreed-upon diagnostic criteria. Most clinicians agree on a diagnosis if the following criteria are met:

1. The presence of a high titer of positive anti-U1-RNP, and

2. Raynaud phenomenon, puffy digits, or hand edema

And at least 2 of the following:

1. Synovitis

2. Myositis

3. Leukopenia

4. Esophageal dysmotility

5. Pleuritis

6. Pericarditis

7. Interstitial lung disease

In 2019, a consensus panel in Japan proposed another revised set of diagnostic criteria for MCTD, which divides the disease features into 4 categories.

1. The presence of a high titer of positive anti-U1-RNP, and

2. Raynaud phenomenon, puffy digits, or hand edema

And either 1 of the following organ involvements or at least 2 overlapping manifestations:

Organ involvement includes:

1. Pulmonary arterial hypertension

2. Aseptic meningitis

3. Trigeminal neuropathy

Overlapping manifestations include:

1. Systemic lupus erythematosus: polyarthritis, lymphadenopathy, malar rash, pericarditis or pleuritis, leukopenia or thrombocytopenia

2. Systemic sclerosis: sclerodactyly, interstitial lung disease, esophageal dysmotility or dilatation

3. Inflammatory myositis: muscle weakness, elevated levels of myogenic enzymes, myogenic abnormalities on electromyogram

Diagnosis is based on at least 1 common manifestation, immunological manifestation, and either 1 characteristic organ involvement or at least 1 feature in 2 or more overlapping manifestations. These criteria have a sensitivity of 90.6% and a specificity of 98.4%, although they have not been formally adopted by the international community.