What is Mixed Connective Tissue Disease (MCTD)?
Mixed connective tissue disease (MCTD) is a rare disease in children. It has symptoms of arthritis and features of scleroderma, dermatomyositis and lupus. It is characterized by lab tests showing the presence of specific antibodies to nuclear proteins (specifically, RNP).
MCTD is a type of autoimmune disease. The immune system works to protect the body from infections. But, in autoimmune diseases, immune cells attack the body's own tissues. This results in inflammation (swelling) and if not controlled then tissue damage may occur.
Who gets pediatric MCTD?
Pediatric MCTD starts in children under the age of 16 but the symptoms may continue into adulthood. MCTD is three times more frequent in girls than boys. MCTD is a very rare disease overall and one of the least frequent rheumatic diseases occurring in children.
Causes of Pediatric MCTD
We do not know the cause of MCTD. A number of factors have been researched, but no single factor has been found.
One theory is that development of MCTD requires a blend of environmental factors and a genetic risk factor. In this theory, the body has an abnormal response to an environmental exposure such as a viral infection. The immune system attacks and clears the virus, but it does not stop the attacking process. Instead, it begins to attack the body's own tissue(s). There is evidence that some people are more likely to have this type of abnormal immune response. Also, the tendency for the immune system to react this way is part inherited.
MCTD does not occur from inheriting a single gene mutation, since it is very rare for other family members to develop MCTD. In some people, there appear to be several genes or groups of genes which either allow the immune system to cause the illness or fail to protect the person from developing it.
We do know MCTD is not contagious and there is no treatment to prevent it. So you cannot get MCTD from touching someone who has it and the person with MCTD cannot spread it to others. Also, you cannot prevent MCTD by getting a vaccine.
Signs and Symptoms of Pediatric MCTD
MCTD often begins with fever, decreased energy, and weakness. The symptoms can range from mild to life-threatening.
Pediatric MCTD can go into periods of remission where symptoms are not present. The two most common findings in MCTD at the time of diagnosis are arthritis and Raynaud's phenomenon. Arthritis is painful, swollen and tender joints, loss of motion, and heat or redness. Raynaud's is a sudden, reversible sequence of skin color changes (pale, blue and/or red). This often affects fingers and toes, and may happen after being in the cold. Raynaud's may also occur in other inflammatory connective tissue diseases such as scleroderma.
Pulmonary hypertension is not common, but is a very dangerous complication of pediatric MCTD. It most often develops slowly and silently. Its symptoms, like shortness of breath and chest pain, must be reported to your doctor right away.
The most common disease characteristics in pediatric MCTD and the percent of children who may have them are:
| Disease characteristics | Affected |
|---|---|
| Arthritis | 93% |
| Raynaud's phenomenon | 85% |
| Muscle disease | 61% |
| Fever | 56% |
| Lung disease (Often "silent" at first) | 40-50% |
| Thickened skin of scleroderma | 49% |
| Dry eyes and dry mouth | 36% |
| Rash of lupus (SLE) | 33% |
| Rash of juvenile dermatomyositis | 33% |
| Kidney disease | 26% |
| Central nervous system disease | 23% |
| Heart disease | 15% |
| Pulmonary hypertension | 7% |
Diagnosis of Pediatric MCTD
The diagnosis of pediatric MCTD is made by a careful review of a person's medical history, physical exam, lab tests (blood and urine) and imaging.
It may take months or even years for doctors to conclude that evolving symptoms represent pediatric MCTD. There is no single test that can prove your child has MCTD.
Since all people with MCTD have RNP antibodies, this is required for diagnosis. RNP is a nuclear protein in the blood that some experts believe could be involved in causing the disease. When a child is suspected of having MCTD, pulmonary function tests will be done. This requires breathing into a tube. An abnormal result suggests lung involvement.
Treatment of Pediatric MCTD
There is no known cure for pediatric MCTD. But, there is effective treatment which can reduce or stop symptoms. This allows children with MCTD to lead healthy, productive lives.
There is no specific treatment for MCTD. Treatment will be tailored to a child’s pattern of symptoms. Over time, some patients develop mild arthritis and need only symptom relief. Patients who develop lung disease will need steroids and other immune-suppressing medicines.
Raynaud's phenomenon responds well to protection from the cold, such as wearing mittens. Some children with Raynaud's may need drugs, like calcium channel blockers.
Medications used to treat children with MCTD include:
NSAIDs (Nonsteroidal Anti-Inflammatory Drugs)
Drugs like ibuprofen, naproxen, meloxicam and nabumetone are used to control the mild arthritis often seen in MCTD. Up to one-third of children get adequate disease control with the use of NSAIDs alone. Children tolerate these drugs very well. They uncommonly cause side effects like upset stomach.
Prednisone
Prednisone is the drug most often used in the group of medicines called steroids, corticosteroids or glucocorticoids. Other drugs in this group are methylprednisolone or prednisolone. Prednisone (or one of the other steroids) may be used to treat severe arthritis that does not respond to NSAIDs. It is also used to treat pulmonary hypertension.
Prednisone works quickly to calm the immune system and control inflammation. This drug is like cortisone, a natural hormone made by our bodies. At first, high doses of this drug may be given to quickly reduce swelling in the joints, muscles, skin or lungs. As your child improves, the steroid dose will be reduced over time to prevent side effects that are common at higher doses. Side effects depend on both the dose and length of therapy.
Common side effects include weight gain, increased appetite, increased risk for infections and facial swelling. Over a long period of time, the drug may cause decreased bone calcium content, cataracts, high blood pressure and a slowed growth rate. The doctor will try to lower the dose as soon as possible to decrease the risk of side effects, while keeping the disease under control.
Hydroxychloroquine (brand name Plaquenil)
This antimalarial drug is used to treat MCTD and also lupus. It is a pill or pills taken one time a day. Though hydroxychloroquine is most often well-tolerated, some children may have stomach upset.
About one in each 3,000-5,000 people who take hydroxychloroquine will accumulate pigment in the retina of the eye. If this is allowed to progress, it can interfere with a person's eyesight. For this reason, an ophthalmologist (eye doctor) needs to check your child's eyes once a year while your child is taking this medicine. If the eye doctor finds any pigment build up, hydroxychloroquine will be stopped before any visual problems develop.
Immunosuppressives
For patients with more severe symptoms like lung, kidney or central nervous system disease, drugs called immunosuppressives may be used. These drugs calm the immune system by preventing new autoimmune cells from being formed.
Long-Term Outlook for Children with MCTD
Pediatric MCTD can be treated. The long-term outcome depends on a child’s disease characteristics and response to medicine. Therefore, the outcome varies and can't be predicted.
Some children achieve remission and may stop their medicines.
Other children may have active disease for many years. Some may have more severe symptoms than others.
Despite the challenges children with MCTD and their families face, most grow up to lead an active, productive life.
