What is the Difference Between Overlap Syndrome and Mixed Connective Tissue Disease?

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Overlap syndrome and mixed connective tissue disease (MCTD) are both conditions that involve the presence of symptoms and signs of multiple connective tissue diseases. However, they have distinct characteristics and are differentiated by certain criteria.

Mixed connective tissue disease (MCTD) is an uncommon autoimmune disorder with signs and symptoms of a combination of disorders, primarily lupus, scleroderma, and polymyositis. Many people with MCTD also have Sjogren's syndrome, and it is sometimes referred to as an overlap disease. MCTD is distinguished from other overlap syndromes by a laboratory result: MCTD patients have rheumatic overlap syndrome plus anti-RNP antibodies.

On the other hand, overlap syndromes are a heterogeneous group of disorders characterized by the presence of symptoms and signs of multiple connective tissue diseases. These patients often do not meet the criteria for classification of a particular disease but have symptoms and laboratory findings consistent with a systemic connective tissue disease. As many as 25% of connective tissue disease patients present with an overlap syndrome.

In summary, the main differences between overlap syndrome and mixed connective tissue disease are:

  • MCTD is a specific autoimmune disorder with a combination of symptoms from lupus, scleroderma, and polymyositis, while overlap syndromes involve symptoms and signs of multiple connective tissue diseases without meeting the criteria for a specific disease.
  • MCTD is distinguished by the presence of rheumatic overlap syndrome plus anti-RNP antibodies, while overlap syndromes can have various antibody markers and clinical features.

Comparative Table: Overlap Syndrome vs Mixed Connective Tissue Disease

Overlap syndrome and mixed connective tissue disease (MCTD) are both conditions characterized by the presence of multiple autoimmune rheumatic diseases. However, there are some differences between the two:

Feature Overlap Syndrome Mixed Connective Tissue Disease (MCTD)
Definition A condition where a patient meets the criteria for more than one defined connective tissue disease (CTD) or has several symptoms characteristic of autoimmune diseases but does not meet the criteria for a specific CTD. A distinct entity characterized by the presence of clinical features of systemic lupus erythematosus (SLE), rheumatoid arthritis, polymyositis, and overlap syndrome, with high titers of serum anti-U1 ribonucleoprotein (U1-RNP) antibody.
Clinical Features Patients may have a mixed clinical picture with symptoms and signs of systemic sclerosis, rheumatoid arthritis, or SLE, depending on the disease combination. MCTD is characterized by overlapping manifestations of systemic sclerosis, polymyositis, and high titers of serum anti-U1 ribonucleoprotein (U1-RNP) antibody.
Autoantibodies Autoimmunity in overlap syndromes is often antigen-driven by RNA-associated components and may nucleosomal components. The presence of anti-U1 ribonucleoprotein (U1-RNP) antibody is characteristic of MCTD.
Diagnosis Diagnosis is based on the presence of clinical features of at least two connective tissue diseases. Diagnosis is based on the presence of organ involvement, immunological manifestations, and at least one feature from items A, B, or C in overlapping manifestations.

In summary, overlap syndrome is a broader term that covers situations where several autoimmune rheumatic diseases coexist, while MCTD is a specific condition characterized by the presence of clinical features of SLE, rheumatoid arthritis, polymyositis, and overlap syndrome, with high titers of serum anti-U1-RNP antibody.