[8] The early clinical features of MCTD are nonspecific and may include fatigue, low-grade fever, myalgias, Raynaud phenomenon, swelling of the fingers or hands, arthralgia, esophageal reflux or dysmotility, acrosclerosis (also known as sclerodactyly), mild myositis, and various forms of pulmonary involvement.
Early indications of pulmonary involvement include dyspnea, dry cough, and pleuritic chest pain.
[29] Diagnosing MCTD involves identification of inflammatory myopathy that is histologically and clinically identical to polymyositis (PM).
People with MCTD typically have mild myositis, with normal muscle enzymes and electromyographic results.
[37] Tubulointerstitial nephritis, mesangioproliferative glomerulonephritis, and hypertensive episodes resembling scleroderma renal crisis have also been observed.
[44][45] The most common central nervous system manifestation is trigeminal (fifth cranial) nerve neuropathy, which may be a patient’s first symptom.
[10] In MCTD, major histocompatibility complex (MHC) and non-MHC genes have been linked to disease vulnerability.
[56] Genome-wide association studies have revealed that there are parts of a patient’s genetic material which cause production of these anti-RNP antibody.
[63][64] Beyond antibody formation, B cells can serve in a variety of other important immunological pathways, including as antigen presentation, pathogenic cytokine secretion, and tissue harm via antibody-directed mechanisms.
Both anti-RNP and anti-U1-RNA antibodies identified in patients' serum have typically undergone isotope shift to immunoglobulin G (IgG) subtypes.
In addition, there is intense lymphocyte infiltration, with many T cells detected in the locations of tissue injury at autopsy and in patient biopsy specimens.
[65] In vitro studies have also revealed that human RNP reactive T cells can aid in the generation of anti-RNP autoantibodies.
VEGF levels were higher in MCTD individuals who had pulmonary arterial hypertension and myositis, which may indicate a more severe course of disease.
[66] There are also uncompleted versions of recognized connective tissue diseases, in which clinical and serological symptoms allow for a diagnosis but classification criteria are not met.
Management should address the individual's primary issues, such as arthritis, skin disease, or visceral involvement.
Low-dose glucocorticoids, nonsteroidal anti-inflammatory medications, hydroxychloroquine, or a combination of these therapies can effectively treat many patients.
[65] Fever, tiredness, unspecific arthralgias, or myalgias are commonly treated with nonsteroidal anti-inflammatory medications (NSAIDs), hydroxychloroquine, or a low dose of prednisone, depending on the severity.
[44][73] Topical steroids, prednisone, and/or hydroxychloroquine are useful in treating SLE-like skin rash, oral ulcers, and photosensitivity.
Raynaud's phenomenon in MCTD typically responds to vasodilator therapy such as calcium channel blockers, as well as preventive measures including avoiding cold temperatures, smoking, and sympathomimetic drugs.
[68] To ensure early detection, all individuals with MCTD must have screening echocardiography and high-resolution computed tomography upon diagnosis.
[68] Traditional therapies such as calcium channel blockers, ACE inhibitors, immunosuppression, and heart failure medications can be used.
For moderate to severe myocarditis, high-dose steroid therapy should be combined with standard congestive heart failure treatment.
First-line treatment for chronic reflux symptoms includes proton-pump inhibitors, H2-receptor antagonists, lifestyle changes, and oesophageal PH monitoring.
Long-term follow-up studies have shown that MCTD can progress to a moderate disease with a favorable prognosis, or patients can acquire a significant condition with vascular alterations driven by pulmonary hypertension and increased mortality.
The prevalence of pulmonary hypertension was related with the worst prognosis and a high mortality rate, making it the most significant complication in MCTD.
[44][71] Gordon C. Sharp first described mixed connective tissue disease (MCTD) in 1972 as an entity with mixed features of systemic sclerosis (SSc), systemic lupus erythematosus (SLE), polymyositis/dermatomyositis (PM/DM), and rheumatoid arthritis (RA) along with an elevated level of high-titre anti-U1small nuclear (sn) anti-ribonucleoprotein (anti-RNP) antibodies.