Mixed Connective Tissue Disease (MCTD)
What is Pediatric 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 (SLE). It is characterized by the presence of specific antibodies to nuclear proteins (RNP).
MCTD is a type of autoimmune disease. The immune system is a group of cells that functions to protect the body from infections. In autoimmune diseases like MCTD, these cells fight the body's own tissues and cells, resulting in inflammation and tissue damage.
Who gets Pediatric MCTD?
Pediatric MCTD occurs in children under the age of 16. The disease is extremely rare. MCDT is three times more frequent in girls than in boys.
What causes Pediatric MCTD?
We do not know what causes MCTD. Although a number of factors have been investigated, no single factor has been identified as the cause. One view commonly held by researchers in this area (but not scientifically proven) 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 virus infection. The immune system attacks and clears the virus, but does not stop this process and begins attacking the body's own tissue(s). There is some evidence to show that some individuals are more likely to have this type of abnormal immune response and that this tendency for the immune system to react in this way is at least partially inherited. This is not a simple genetic inheritance as seen in other forms of muscle disease such as muscular dystrophy, as it is very, very rare for other family members to develop MCTD. In some individuals there appear to be genes or groups of genes which either allow for the immune system to cause the illness to occur or fail to protect the person from developing it.
We do know that MCTD is not contagious. This means you can not get MCTD from touching a patient with MCTD.
What are the 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 characteristic findings in MCTD at the time of diagnosis are arthritis and Raynaud's phenomenon.
Arthritis is the development of painful, swollen joints with loss of motion. Raynaud's phenomenon is a sudden, reversible "dead-white" uniform coloring of the hands caused frequently by exposure to cold. There is usually a three-part response with the hands turning white, then purple or blue and finally red. Raynaud's phenomenon is often a finding seen in other connective tissue diseases like scleroderma.
Pulmonary hypertension is the most dangerous complication seen in pediatric MCTD. Pulmonary hypertension often develops slowly and silently. 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 experience them.
| Disease characteristics | Percentage of Cases |
|---|
| Arthritis | 93 |
| Raynaud's phenomenon | 85 |
| Muscle disease | 61 |
| Fever | 56 |
| Thickened skin of scleroderma | 49 |
| Dry eyes and dry mouth | 36 |
| Rash of lupus (SLE) | 33 |
| Rash of juvenile dermatomyositis | 33 |
| Central nervous system disease | 23 |
| Pulmonary hypertension | 7 |
| Heart disease | 30 |
How is Pediatric MCTD diagnosed?
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 put together evolving symptoms and diagnose pediatric MCTD. There is no single test that can definitely prove your child has MCTD. All people with MCTD test positive for RNP antibodies (presence of RNP antibodies is required to make the diagnosis of MCTD). RNP is a nuclear protein in the blood that some scientists believe could be involved in causing the disease. Pulmonary function testing, which requires a child to breathe into a tube, is performed when the diagnosis is suspected. An abnormal result suggests lung involvement.
How is Pediatric MCTD treated?
There is no known cure for pediatric MCTD. However, there are effective treatments that can reduce or eliminate the symptoms and allow children with MCTD to lead healthy, productive lives.
There is no specific treatment for MCTD. The treatment depends entirely on the pattern of symptoms. Some patients develop mild arthritis over time and need only symptomatic relief. Other patients develop lung disease and require steroids and medications that suppress the immune system.
Raynaud's phenomenon responds well to simple conservative measures like mittens. At times, children with Raynaud's phenomenon will need to use drugs like calcium channel blockers for better control. The following are a list of medications used to treat Pediatric MCTD.
- NSAIDs (Non Steroidal Anti-Inflammatory Drugs):
- Drugs like Ibuprofen, Naprosyn, and Relafen are used to control mild arthritis commonly seen in MCTD. Up to 1/3 of children have the disease adequately controlled with only the use of NSAIDs. These drugs are very well tolerated in children and infrequently cause side effects like abdominal pain.
- Prednisone:
- Prednisone is the most commonly used drug in the group of medications called steroids, corticosteroids, or glucocorticoids. Other drugs in this group are Solumedrol or Prednisolone. Prednisone (or one of the other steroids) is sometimes used to treat severe arthritis that does not respond to NSAIDs. It is also used to treat pulmonary hypertension. Prednisone works quickly to slow down the immune system and help control inflammation in the body. This drug is similar to cortisone, a hormone produced naturally in the body. At first, high doses of this drug are given in order to quickly reduce inflammation in the joints or in the lungs. As your child gets better, the dose will be gradually reduced in order to prevent side effects seen with higher doses. Side effects depend on both the dose used and the 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 can also cause decreased calcium content in the bones, cataracts, high blood pressure, and slowed growth rate. The doctor will try to lower the dose as soon as possible to lessen the side effects, while keeping the disease under control.
- Hydroxychloroquine (brand name Plaquenil):
- This is an antimalarial drug that is sometimes used to treat rash and arthritis in lupus. This drug is given as a pill and usually only once a day. Hydroxychloroquine is generally tolerated very well. Some will develop stomach upset. Approximately 1 in every 3000-5000 people who take Hydroxychloroquine will accumulate pigment in the retina of the eye. If this is allowed to progress then it could interfere with a person's vision. For this reason, an ophthalmologist (eye doctor) needs to check your child's eyes every six months while your child is taking Hydroxychloroquine. If the eye doctor detects any pigment accumulation, the Hydroxychloroquine will be stopped before any visual problems develop.
- Immunosuppressives:
- For patients with more severe symptoms like lung disease, kidney disease, or central nervous system disease, drugs called immunosuppressives may be used. Immunosuppressive drugs slow down the immune system by preventing new immune 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, and pulmonary hypertension. Children receiving Cyclophosphamide need to have their blood counts monitored carefully. Side effects may include nausea, vomiting, hair loss, bladder problems, decreased fertility and increased risk of cancer and infection.
What is the outcome of Pediatric MCTD?
Pediatric MCTD is a treatable disease. The long-term outcome of MCTD in children depends on the disease characteristics your child has and the response to medications. The outcome therefore is varied and unpredictable. Some children go into remission and have their medications eliminated. However, other children may have active disease for many years and some may have more severe symptoms than others. Pulmonary hypertension is the most feared complication.
Overall, children with MCTD have a more favorable prognosis than children with lupus. Despite the challenges children with MCTD and their families face, the majority of children grow up to lead an active, productive life.
Written 2/07
