What types of muscle involvement can occur in Mixed Connective Tissue Disease (MCTD)?

Muscle Involvement in Mixed Connective Tissue Disease

Mixed connective tissue disease (MCTD) can affect both striated and smooth muscle, resulting in proximal muscle weakness (polymyositis-like pattern), esophageal dysmotility affecting the entire length of the esophagus, and occasionally atypical patterns involving facial, neck, wrist, or finger muscles. 1

Types of Muscle Involvement

Skeletal Muscle Myositis

Proximal muscle weakness is the most common skeletal muscle manifestation, presenting similarly to polymyositis with symmetric involvement of the upper and lower extremities 2, 3. However, MCTD myositis demonstrates several distinctive features:

• Atypical distribution patterns occur frequently, with involvement of facial muscles, neck flexors, wrist extensors, or finger muscles in addition to or instead of classic proximal weakness 2, 4
• Severity ranges from subclinical (elevated muscle enzymes without weakness) to severe myositis requiring intensive immunosuppression 5, 6, 3
• Clinical presentation typically includes elevated creatine kinase levels, though the degree of elevation may be variable 5, 6

Esophageal Smooth and Striated Muscle Involvement

MCTD uniquely affects both the proximal (striated) and distal (smooth) portions of the esophagus, distinguishing it from systemic sclerosis which predominantly affects smooth muscle 1:

• Dysphagia is common due to involvement of both muscle types throughout the esophageal length 1
• Esophageal dysmotility may be more variable and less severe compared to systemic sclerosis, though it can still significantly impact quality of life 1
• Cricopharyngeal involvement can occur as part of the striated muscle dysfunction affecting swallowing 1

Histopathological Patterns

The muscle biopsy findings in MCTD myositis are heterogeneous and often nonspecific 2:

• Mild myogenic changes with increased necrotic and regenerating fibers are common 2
• Inflammatory infiltrates predominantly in the perivascular region, distinguishing it from classic polymyositis 2, 4
• Some cases resemble dermatomyositis with perifascicular atrophy, while others show features of immune-mediated necrotizing myopathy (IMNM) 2
• Poor muscle regeneration has been reported in some cases, with scarcity of alkaline phosphatase positivity in connective tissue 4

Clinical Severity and Red Flags

Severe myositis presentations require intensive therapy beyond standard corticosteroids 2, 5, 6:

• Dysphagia and cervical muscle weakness indicate more severe disease requiring escalation to pulse methylprednisolone, IVIG, or additional immunosuppressants 5, 6
• Refractory cases may not respond to initial corticosteroid doses and require combination therapy with methotrexate, azathioprine, or mycophenolate 5, 6
• Respiratory muscle involvement, while less commonly emphasized in MCTD literature, should be assessed as it represents a medical emergency in any inflammatory myopathy 7, 8

Prognosis

The prognosis of MCTD-associated myositis is generally favorable compared to other forms of inflammatory myopathy 2, 3:

• Therapeutic responses are consistently good with appropriate immunosuppression 2
• Mortality is rare during standard observation periods, contrasting with more severe forms of myositis 2
• Long-term outcomes appear better than isolated polymyositis or dermatomyositis, though this requires confirmation in larger studies 3

Important Clinical Pitfall

The subclinical nature of early muscle involvement can lead to delayed diagnosis—elevated muscle enzymes may be the only manifestation initially, preceding overt weakness by months or years 3. Clinicians should maintain a high index of suspicion for muscle involvement even in the absence of weakness, particularly given that MCTD is an overlap syndrome with features of systemic sclerosis, SLE, and polymyositis 1.