Dermatology MCQ - Inflammatory Dermatoses - Mixed connective tissue disease
(MCTD)

A 30-year-old woman presents with puffy fingers, Raynaud's phenomenon, and polyarthralgias. Her laboratory workup is significant for a high-titer positive ANA with a speckled pattern. Which of the following autoantibody specificities is most specific for confirming a diagnosis of Mixed Connective Tissue Disease (MCTD)?

A. Anti-dsDNA
B. Anti-Smith (Anti-Sm)
C. Anti-U1-RNP
D. Anti-Scl-70 (Topoisomerase I)
E. Anti-Jo-1

Correct Answer: C. Anti-U1-RNP

Explanation

Mixed Connective Tissue Disease (MCTD) is defined by the presence of high titers of a specific autoantibody: anti-U1-ribonucleoprotein (RNP). This antibody is considered the serologic hallmark of the disease.

• Diagnostic Significance: While various diagnostic criteria exist (e.g., Alarcón-Segovia, Kahn, Sharp), the presence of a high-titer anti-U1-RNP antibody is a central and obligatory feature in all of them. It is the key finding that distinguishes MCTD from other overlapping connective tissue diseases like SLE, systemic sclerosis, and polymyositis. The clinical features of puffy fingers, Raynaud's, and arthritis form a classic triad seen in MCTD.

Why other options are incorrect

• A. Anti-dsDNA: This is a highly specific antibody for Systemic Lupus Erythematosus (SLE). While it can be present in some MCTD patients, its presence should strongly point toward SLE as the primary diagnosis.

• B. Anti-Smith (Anti-Sm): This is also a highly specific antibody for SLE and is part of the classification criteria. It is not associated with MCTD.

• D. Anti-Scl-70 (Topoisomerase I): This is a specific antibody for Diffuse Cutaneous Systemic Sclerosis (Scleroderma) and is associated with a high risk of pulmonary fibrosis.

• E. Anti-Jo-1: This is a myositis-specific antibody associated with the antisynthetase syndrome, which includes myositis, interstitial lung disease, fever, mechanic's hands, and polyarthritis.

Key Associations for Mixed Connective Tissue Disease (MCTD)

• Clinical Presentation: MCTD is characterized by overlapping features of SLE, Systemic Sclerosis (Scleroderma), and Polymyositis. Common initial symptoms include:

  • Puffy, sausage-like fingers

  • Raynaud's phenomenon (often severe)

  • Inflammatory polyarthritis

  • Other features can include myositis, esophageal dysmotility, and lymphadenopathy.

• Serology: The high-titer anti-U1-RNP antibody is the defining feature. The ANA is almost always positive, typically with a speckled pattern.

• Major Organ Involvement & Prognosis: The prognosis of MCTD is largely determined by the development of major organ complications. The most serious and characteristic life-threatening complication is Pulmonary Arterial Hypertension (PAH). Other significant complications include interstitial lung disease, renal disease (less common and severe than in SLE), and cardiac involvement.

• Differential Diagnosis: The main differential is with other defined and undifferentiated connective tissue diseases (UCTD). The high-titer anti-U1-RNP helps differentiate it from UCTD. It must also be distinguished from SLE, Systemic Sclerosis, and Polymyositis individually.

• Management:

  • Treatment is tailored to the specific organ systems involved and is often similar to the therapy for the disease it mimics (e.g., SLE, scleroderma).

  • Mild Disease (Arthritis, Raynaud's): NSAIDs, antimalarials (hydroxychloroquine), and calcium channel blockers.

  • Moderate-Severe Disease (Myositis, Scleroderma-like lung disease): Corticosteroids and steroid-sparing agents like methotrexate, mycophenolate mofetil, or azathioprine.

  • Pulmonary Arterial Hypertension (PAH): Requires specific PAH-directed therapies (e.g., endothelin receptor antagonists, phosphodiesterase-5 inhibitors) and aggressive immunosuppression.

  • Regular screening for PAH with echocardiograms is a critical part of long-term management.