Mixed Connective Tissue Disease (MCTD)

Pediatric mixed connective tissue disease (MCTD) is a rare disease in children that has symptoms of arthritis along with 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 primarily works to protect the body from infections. However, in autoimmune diseases, immune cells attack the body's own tissues, resulting in inflammation and tissue damage.

Pediatric MCTD occurs in children under the age of 16. MCTD is three times more frequent in girls than boys.

We do not know the cause of MCTD; although a number of factors have been investigated, no single factor has been identified.

One theory is that development of MCTD requires the combination of two factors: infection and genetics. In this theory, the body has an abnormal response to 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 partially inherited.

However, 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. So you cannot get MCTD from touching someone who has it.

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 characteristic findings in MCTD at the time of diagnosis are arthritis and Raynaud's phenomenon. Arthritis is painful, swollen joints with tenderness, loss of motion, and heat or redness. Raynaud's phenomenon is a sudden, reversible sequence of skin color changes (pale, blue and/or red) commonly affecting fingers and toes that may happen after cold exposure. Raynaud's may also occur in other inflammatory connective tissue diseases such as scleroderma.

Pulmonary hypertension is an uncommon but very dangerous complication of pediatric MCTD, typically developing slowly and silently. Its symptoms, like shortness of breath and chest pain, must be reported to your doctor immediately.

The following is a list of the most common disease characteristics in pediatric MCTD and the percentage of children who may experience them.

Disease characteristicsAffected
Arthritis93%
Raynaud's phenomenon85%
Muscle disease61%
Fever56%
Lung disease (initially often "silent")40-50%
Thickened skin of scleroderma49%
Dry eyes and dry mouth36%
Rash of lupus (SLE)33%
Rash of juvenile dermatomyositis33%
Kidney disease26%
Central nervous system disease23%
Heart disease15%
Pulmonary hypertension7%

The diagnosis of pediatric MCTD is made by a careful review of a person's medical history, physical examination, laboratory 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 definitely prove your child has MCTD.

Since all people with MCTD have RNP antibodies, this is a requirement for diagnosis. RNP is a nuclear protein in the blood that some scientists believe could be involved in causing the disease. When a child is suspected of having MCTD, pulmonary function tests will be done, which require breathing into a tube. An abnormal result suggests lung involvement.

There is no known cure for pediatric MCTD. However, there is effective treatment which can reduce or eliminate symptoms, allowing 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 require steroids and other immune-suppressing medications.

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.

The following are a list of medications used to treat children with MCTD.

NSAIDs (Nonsteroidal Anti-Inflammatory Drugs)

Drugs like ibuprofen, naproxen and nabumetone are used to control the mild arthritis commonly seen in MCTD. Up to one-third of children get adequate disease control with the use of NSAIDs alone. These drugs are very well tolerated in children and uncommonly cause side effects like upset stomach.

Prednisone

Prednisone is the most commonly used drug in the group of medications 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 unresponsive to NSAIDs, or to treat pulmonary hypertension.

Prednisone works quickly to calm the immune system and control inflammation. This drug is similar to cortisone, a natural hormone produced by our bodies. At first, high doses of this drug may be given for quick reduction of inflammation in the joints or lungs. As your child improves, the steroid dose will be reduced gradually to prevent side effects common at higher doses; side effects depend on both the dose and duration 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 lupus, dosed as a once daily pill. Although hydroxychloroquine is generally well-tolerated, some children may develop stomach upset.

Approximately 1 in every 3,000-5,000 people who take high doses of hydroxychloroquine will accumulate pigment in the retina of the eye. If this is allowed to progress, it could interfere with a person's vision. For this reason, an ophthalmologist (eye doctor) needs to check your child's eyes once a year while your child is taking hydroxychloroquine. If the eye doctor finds any pigment accumulation, 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. Immunosuppressive drugs calm the immune system by preventing new autoimmune cells from being formed.

Cyclophosphamide (brand name Cytoxan) is a type of immunosuppressive drug that is frequently used in combination with prednisone to treat kidney inflammation, central nervous system disease or pulmonary hypertension. Children receiving cyclophosphamide need to have their blood counts monitored carefully.

Side effects may include nausea, vomiting, hair loss, blood in the urine, decreased fertility or an increased risk of cancer or infection.

Pediatric MCTD is a treatable disease. The long-term outcome depends on a child’s disease characteristics and response to medications. Therefore, the outcome is variable and unpredictable.

Some children achieve remission and may discontinue their medications.

However, 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, the majority of children grow up to lead an active, productive life.


Last Updated 07/2013