Can Mixed Connective Tissue Disease (MCTD) cause muscle weakness?

From the Guidelines

Yes, Mixed Connective Tissue Disease (MCTD) can cause muscle weakness, as it is an overlap syndrome that can have features of polymyositis, which affects proximal striated muscle and can lead to muscle weakness. This condition combines features of several disorders including lupus, scleroderma, and polymyositis, with muscle weakness being a common symptom 1. The weakness typically affects proximal muscles (those closer to the trunk of the body), making activities like climbing stairs, rising from a chair, or lifting objects above the head difficult.

Key Points to Consider

• MCTD is an autoimmune condition that can cause esophageal involvement, resembling those with systemic sclerosis (SSc), and can manifest proximally and distally due to its capability to affect both striated and smooth muscle 1.
• The muscle weakness in MCTD results from inflammation of muscle tissue (myositis) caused by the immune system inappropriately attacking healthy muscle cells.
• Treatment typically involves immunosuppressive medications such as corticosteroids, methotrexate, or mycophenolate mofetil to reduce inflammation and prevent further muscle damage.
• Physical therapy is also important to maintain strength and function.
• Patients should monitor for worsening weakness, particularly if it affects breathing or swallowing, as this requires prompt medical attention.

Diagnostic Considerations

• Upper endoscopy with biopsies and High-resolution esophageal manometry may be used to evaluate esophageal involvement in MCTD 1.
• Creatine kinase blood tests may be used to track muscle inflammation levels during treatment.
• A thorough medical history and physical examination are essential to diagnose MCTD and rule out other conditions that may cause muscle weakness.

From the Research

Muscle Weakness in Mixed Connective Tissue Disease (MCTD)

• Muscle weakness is a symptom that can be associated with MCTD, as evidenced by several studies 2, 3, 4, 5.
• A study from 1997 described a 13-year-old girl with MCTD who presented with muscle weakness, arthritis, and myositis, and was effectively treated with low-dose methotrexate pulses 2.
• Another study from 2025 analyzed the clinical and myopathological findings of nine myositis patients with U1-RNP antibodies who fulfilled the diagnostic criteria for MCTD, and found that eight patients had muscle weakness in the proximal extremities 3.
• A case report from 2000 described a 29-year-old woman with MCTD who experienced muscle weakness, mental disturbance, and recto-urinary disturbance, and was successfully treated with cyclophosphamide combined with prednisolone 4.
• A study from 2010 reported a rare case of a patient with MCTD who presented with severe onset of myositis characterized by dysphagia, an increase in myopathy, and a weakening of the cervical musculature, and was refractive to corticotherapy 5.

Characteristics of Muscle Weakness in MCTD

• Muscle weakness in MCTD can be severe and refractory to treatment, as reported in several studies 2, 3, 4, 5.
• The muscle weakness can be associated with other symptoms such as myositis, arthritis, and sclerodactyly 2, 3.
• The distribution of muscle weakness can be axial or atypical, and may require intensive therapy 3.
• Histological studies have shown that MCTD myositis can have a heterogeneous myopathology, with features resembling those of immune-mediated necrotizing myopathy (IMNM) or dermatomyositis (DM) 3.