Mixed connective tissue disease

It is sometimes said to be the same as undifferentiated connective tissue disease, but other experts specifically reject this idea because undifferentiated connective tissue disease is not necessarily associated with serum antibodies directed against the U1 RNP, and MCTD is associated with a more clearly defined set of signs/symptoms. (with some sources adding myositis, dermatomyositis, and inclusion body myositis) and is thus considered an overlap syndrome. The initial clinical manifestations of MCTD usually are unspecific. They can consist of general malaise, arthralgias, myalgias, and fever. The specific signs to suspect this disease is the presence of positive antinuclear antibodies (ANA), specifically anti RNP, associated with Raynaud's phenomenon. As MCTD can present with comorbid connective tissue diseases there must be a genetic link, however it has not yet been discovered. DNA methylation may affect the as yet unknown genetic risks of this disease as patients with MCTD have decreased DNA methylation levels in opposition to their healthy counterparts.

MCTD is an autoimmune disorder. Anti RNP antibodies develop against RNP when RNP is found outside of the nucleus. RNP is immunologically protected due to its location, however if a cell dies and RNP is no longer contained in the nucleus and thus unprotected, the immune system can respond by forming antibodies due to cellular mimicry. Risk to develop MCTD can increase if the body has been exposed to molecules or viruses with a similar structure to RNP in the past. There are currently no known environmental factors or triggers contributing to MCTD. It has been associated with HLA DR4.

Although MCTD was originally described as a disease with a good treatment response to corticosteroids, the treatment of the disease is based on the specific manifestations and clinical complications, similar to how other signs and symptoms are treated in other connective tissue disease. Higher doses of corticosteroids (0.25 to 1 mg/kg/day) are used in complications such as myositis, meningitis, pleuritis, pericarditis, myocarditis, interstitial lung disease, or hematologic abnormalities. On the contrary, Raynaud's phenomenon, acrosclerosis or peripheral neuropathies are usually resistant to corticosteroids. Cyclophosphamide are useful in interstitial lung disease and in the eventual serious renal involvement. In cases of myositis or thrombocytopenias resistant to corticosteroids, intravenous immunoglobulins may be useful. For Raynaud, general measures (such as tobacco cessation, protection against the cold), calcium antagonists, endovenous prostaglandins or endothelin 2 antagonists may be useful. In patients with gastroesophageal reflux, proton pump inhibitors and H2 receptor antagonists can be used, following protocol for the usual treatment of these scleroderma problems. The presence of anticardiolipin antibodies is a more serious risk factor for the disease, as well as the presence of more scleroderma and polymyositis signs and symptoms. Morbidity is quite high in patients with MCTD. In addition to fatigue and recurrent musculoskeletal complaints, patients can develop a fibromyalgia symptom as a result of occasional outbreaks requiring medium high doses of corticosteroid. The steroids, in combination with their adverse effects, frequently cause fibromyalgia symptoms and thus complicate treatment. Such progression is, in part, determined genetically, thus SLE is more likely in patients with HLA DR3 and scleroderma in patients with HLA DR5. In a 2011 Norwegian study, the prevalence of MCTD was 3.8 per 100,000 adults, with an incidence of 2.1 per million per year. MCTD is much more frequent in women than in men at between a 3:1 to 16:1 ratio, and in women younger than 50. The general age at onset is around 15–25 years old.