26th January 2024

Differential Diagnosis 

MCTD was initially thought to be a type of overlap syndrome, and thus, other autoimmune illnesses can present similarly. 

Systemic Lupus Erythematosus (SLE)

 Both MCTD and SLE patients have similar symptoms of arthritis and synovitis. However, symptoms such as photosensitivity are prominent with SLE but not MCTD and antibodies such Anti-ds DNA would be expected to be positive in SLE while Anti- U1 RNP would be positive in MCTD. 

Rheumatoid Arthritis (RA)

Both RA and MCTD may present with symptoms such as fatigue, arthralgia and some degree of swelling. However, in RA, the swelling would be more around the joints, whereas in MCTD, the swelling would be more in the subcutaneous connective tissue of the hands. This swelling can be determined both on physical examination as well as on radiographs of the hands. In addition, the auto-antibodies again will differ where Anti-CCP would be more specific with RA and Anti-U1 RNP more specific for MCTD. 

Inflammatory Myopathy – Polymyositis

 In both polymyositis and MCTD, there are features of myositis and end-organ involvement, such as interstitial lung disease and oesophageal dysmotility. However, there are significantly elevated inflammatory markers such as CK and CRP in polymyositis, but in MCTD, these markers would be expected to be within the normal range or mildly elevated. 

Systemic Sclerosis

 Raynaud’s phenomenon can occur both in systemic sclerosis and MCTD. However, it tends to be more severe in systemic sclerosis, and the characteristic skin changes seen in systemic sclerosis, such as skin thickening and telangiectasia, are not seen in MCTD. In addition, renal involvement is rarely seen in MCTD and is a more common feature of systemic sclerosis. Laboratory testing again would help differentiate by testing for autoantibodies where Anti-centromere or Anti-Scl-70 would be expected to be positive in systemic sclerosis while Anti-U1 RNP is positive in MCTD.