Mixed connective tissue disease (MCTD): symptoms, tests and treatment

Connective tissue diseases are autoimmune conditions in which the immune system attacks the body's own tissues, particularly the skin, joints, muscles and blood vessels. MCTD was first described as a distinct entity in 1972. Patient says the original group of patients had overlapping features of systemic lupus erythematosus, scleroderma and myositis, and it has since been defined as overlapping features of two or more systemic autoimmune diseases in the presence of anti-U1-ribonucleoprotein antibody.

It is different from undifferentiated connective tissue disease, where a person has features of a connective tissue disorder but does not meet the criteria for any specific condition. Patient also notes that MCTD sometimes evolves into other connective tissue disorders, and that the idea that MCTD is a distinct clinical entity has historically been criticised, although few authors reject it entirely.

Because the condition is rare, there are no large controlled clinical trials, and treatments have been borrowed from other rheumatic diseases. That is one reason it is usually looked after by a rheumatology team with experience of overlap conditions.

Patient says females are affected more often than males and it can occur at any age. The precise incidence is unknown, as in some cases it may be diagnosed as other connective tissue disorders or overlap syndromes. It cites a Norwegian study reporting a female-to-male ratio of 3.3 to 1 and a mean age at diagnosis of 37.9 years for adult-onset disease, and a Taiwanese study reporting a mean age of onset of 10.7 years in the paediatric form.

In children, Patient says Raynaud's phenomenon, fatigue and pain in the muscles and joints are important presenting symptoms, and that all children presenting with Raynaud's should be regularly assessed for other signs and symptoms of MCTD.

Patient lists Raynaud's phenomenon, arthralgia, swollen joints, oesophageal dysfunction, muscle weakness and fingers with a sausage-like appearance as the most common clinical manifestations. It adds that people may also present with a combination of other features.

• Raynaud's phenomenon, in which fingers turn white, blue or red in the cold.

• Painful, swollen joints and muscle weakness or aching.

• Swollen, "sausage-shaped" fingers and tight or thickened skin.

• Rashes and hair loss, as Patient lists among other possible features.

• Difficulty swallowing, probably related to effects on the muscle of the oesophagus.

• Lethargy, fever and swollen glands, with pleuritic chest pain and heart involvement, most often pericarditis, which can be present without obvious symptoms.

Bristol says the diagnosis is based on symptoms, physical examination findings and blood tests. Patient lists the investigations that may be used: a full blood count which may show anaemia, low platelets and low white cells; kidney and liver tests and urinalysis, which may show blood or protein if the kidneys are involved; markers such as CRP and ESR; and antibody tests. Antinuclear antibody is usually raised, anti-double-stranded DNA is usually but not always negative, and anti-U1-RNP is almost always raised.

Imaging and heart tests depend on symptoms. Patient lists a chest X-ray, ECG, echocardiogram to check for effusion or pulmonary hypertension, and a high-resolution CT scan of the lungs, which may help to differentiate MCTD from other connective tissue diseases.

Classification criteria exist, including the original Sharp criteria, but the same source acknowledges the differential diagnosis is broad. It includes scleroderma, Still's disease, polymyositis and dermatomyositis, systemic lupus erythematosus, sarcoidosis and others.

Bristol says treatment depends on your symptoms, the organs involved and the severity of disease. The medicines used overlap with those for lupus, scleroderma and myositis and may include steroids to reduce inflammation and drugs to suppress the immune system. Other medicines may be given to treat or reduce the risk of complications affecting internal organs.

Patient describes a stepped approach. For mild disease, initial treatment is likely to be with non-steroidal anti-inflammatory medicines for pain and inflammation, and hydroxychloroquine may also help. In more severe cases, or with secondary organ involvement, systemic corticosteroids are used, and steroid-sparing agents such as cyclophosphamide and ciclosporin may be used when prolonged high-dose steroids would otherwise be required.

Bristol says self-care is important in helping control symptoms and includes healthy lifestyle changes such as stopping smoking, reducing stress and protecting the hands from the cold. Patient adds that people should be encouraged to keep active and mobile but to avoid over-exertion, and to avoid cold exposure, especially of the hands and feet.

Practical measures such as insulated gloves, warm socks and avoiding sudden temperature changes are commonly used for Raynaud's. The sources used here give the principle, and a rheumatology nurse or occupational therapist can advise on specifics, including joint protection and energy pacing.

Patient says all patients with MCTD should be regularly reviewed and reassessed, as some will go on to develop other connective tissue diseases such as SLE, scleroderma or an overlap syndrome. The prognosis is variable. It states that one third of patients go into long-term remission, one third have intermittent chronic disabilities such as arthritis, chronic fatigue and breathlessness on exertion, and one third have severe systemic involvement. The mortality rate is lower in children than in adults, and the most common cause of death is pulmonary hypertension, so careful management of the pulmonary complications improves prognosis.

Because the lungs are the main concern, new breathlessness or chest pain should be reported promptly to the rheumatology team or GP.

On the NHS, MCTD is diagnosed and managed by rheumatology services, often with input from respiratory, cardiology and dermatology teams and specialist nurses. Patient says all patients should be regularly reviewed and reassessed.

Private rheumatology consultations are used by some people for faster assessment or second opinions. Because treatment relies on the same medicines and monitoring in both settings, the main differences are access, waiting times and the level of continuity.