Pediatric Mixed Connective Tissue Disease Clinical Presentation

The most frequent presentation of mixed connective tissue disease (MCTD) is a child with polyarthritis, general malaise, and Raynaud phenomenon.

Patients may present with the following:

• Sclerodermatous skin (usually limited to fingers but can be more extensive)

• Sausage-shaped fingers

• Proximal muscle weakness

• Rash (finger ulcers or pits, Gottren papules)

• Vasculitic rashes (usually palpable purpuric rashes)

• Dysphagia

• Gastroesophageal reflux disease (GERD) symptoms

• Fever

• Rheumatoid nodules

• Lymphadenopathy

• Alopecia

• Telangiectasia

• Headache

Detailed physical examination is critical. ^[13]  Classification criteria other than autoantibody status rely on clinical examination and diagnostic tests. Consider the following to make the diagnosis:

• Alopecia

• Pleuritic chest pain

• Pericardial rub

• Arthritis

• Raynaud phenomenon

• Malar rash

• Petechial rash

• Muscle weakness

• Swollen hands (especially dorsal surface)

• Trigeminal neuropathy

• Acrosclerosis or sclerodermatous skin changes

• Epigastric tenderness

Diagnostic criteria

The following lists, published by several authors, are the criteria for making a diagnosis of mixed connective tissue disease. ^{[1, 2, 3, 14]}

Sharp criteria

• Definite diagnosis requires 4 major criteria with positive anti-U1 RNP greater than 1:4000 and a negative anti-Sm Ab. U1 RNP is the specific RNP protein associated with this syndrome.

• Probable diagnosis requires either 3 major criteria or 2 major criteria (which must come from the first 3 major criteria listed) and 2 minor criteria plus an anti-U1 RNP greater than 1:1000.

• Possible diagnosis requires 3 major criteria without serologic evidence of disease or, if anti-U1 RNP is greater than 1:100, 2 major criteria or 1 major and 3 minor criteria.

  • Major criteria include severe myositis, pulmonary involvement (diffusing capacity of lung for carbon monoxide 70% of normal, pulmonary hypertension, proliferating vascular lesions on lung biopsy), Raynaud phenomenon or esophageal hypomotility, swollen hands or sclerodactyly, and highest observed anti-U1 RNP (>1:10,000) with negative anti-Sm Ab.

  • Minor criteria include alopecia, leukopenia (4000 WBC/mL), anemia (< 10 g/dL for females, < 12 g/dL for males), pleuritis, pericarditis, arthritis, trigeminal neuralgia, malar rash, thrombocytopenia (< 100,000/mL), mild myositis, and history of swollen hands.

Alarcon-Segovia and Villareal classification

• Serologic criterion is a positive anti-RNP at a titer of 1:1600 or higher.

• Clinical criteria (at least 3) are edema of the hands, Raynaud phenomenon (ie, 2 or 3 color changes), acrosclerosis, synovitis, and myositis (laboratory or biopsy evidence).

Kasukawa criteria

• Diagnosis requires the following 3 conditions: (1) positive in either 1 of 2 common symptoms, (2) positive anti-RNP antibody, and (3) positive in 1 or more findings in 2 of 3 disease categories of A, B, and C. The following are disease findings A, B, and C:

  • SLE-like conditions (polyarthritis, lymphadenopathy, facial erythema, pericarditis or pleuritis, leukopenia [< 4000/mL], or thrombocytopenia [< 100,000/mL])

  • Progressive systemic sclerosislike findings (sclerodactyly, pulmonary fibrosis, restrictive lung disease [vital capacity < 80%] or reduced diffusion capacity [< 70%], hypomotility, or dilation of the esophagus)

  • Polymyositislike findings (muscle weakness, increased serum level of myogenic enzymes [creatine kinase], myogenic pattern on electromyogram)

• Common symptoms include Raynaud phenomenon and swollen fingers or hands.

Japanese consensus panel criteria

A consensus panel in Japan in 2019 offered a revised set of diagnostic criteria for MCTD, which divides the features of the disease into the following four categories:

1. Common manifestations: Raynaud phenomenon, Puffy fingers and/or swollen hands
2. Immunologic manifestation: Anti–U1-RNP antibody positivity
3. Characteristic organ involvement: Pulmonary arterial hypertension, aseptic meningitis, trigeminal neuropathy
4. Overlapping manifestations: (A) SLE-like, (B) systemic sclerosis–like, (C) polymyositis/dermatomyositis-like 

SLE-like manifestations include the following:

• Polyarthritis
• Lymphadenopathy
• Malar rash
• Pericarditis or pleuritis
• Leukopenia (4,000/μL or less) or thrombocytopenia (100,000/μL or less)

Systemic sclerosis–like manifestations include the following:

• Sclerodactyly
• Interstitial lung disease
• Esophageal dysmotility or dilatation

Polymyositis/dermatomyositis-like manifestations include the following:

• Muscle weakness
• Elevated levels of myogenic enzymes
• Myogenic abnormalities on electromyogram

For diagnosis of MCTD, the patient must have the following:

• At least one common manifestation
• Anti–U1-RNP antibodies
• At least one characteristic organ involvement,  or at least one feature of at least two of the three disorders in the overlapping manifestations category (A, B, and C) 

Other conditions to consider in the differential diagnosis of MCTD include the following:

• Pleuritis
• Respiratory distress syndrome
• Stroke