There are many confusing terms in the world of autoimmune diseases like lupus. One condition that we will attempt to clarify is multiple connective tissue disorder (MCTD). We have enlisted the help of rheumatologist, Dr. Donald Thomas, author of The Lupus Encyclopedia, to assist us in making sense of this complicated medical issue so that we can better explain it to you!
What is a connective tissue disease?
First off, let’s define what a connective tissue disease, or disorder, is. Connective tissue diseases (CTDs) actually refer to a large group of diseases that primarily target the body’s connective tissue (the “glue” that supports organs and other parts of the body). Examples of connective tissue include bone, cartilage (tendons, ligaments, the hyaline at the tip of your nose etc.), fat (adipose tissue) and even blood.
Connective tissue diseases can arise from many causes including infections, metabolic issues, and genetic disorders (such as Marfan Syndrome and Ehlers-Danlos syndromes) as well as autoimmune diseases such as the mixed connective tissue disorders. What is more, any of these can be associated with systemic lupus erythematosis.
Dr. Thomas clarifies the term system autoimmune disease; “The immune system is that part of our body, primarily the white blood cells, that usually protects us from foreign invaders. However, the immune system of a person with an autoimmune disease (“auto” is Greek meaning “self”) attacks the body itself. If a disease can cause this in more than one organ, we consider it a “systemic” problem since it is occurring in more than one organ or in multiple systems of the body. -Dr. Thomas
What is MCTD?
Simply stated, when someone is diagnosed as having mixed connective tissue disease (MCTD), it refers the fact that the person has features of more than one of the connective tissue diseases. “There is a lot of overlap between these [types of] disorders. This probably has to do with the fact that these are genetic diseases, and many of the same genes can cause the same illnesses. There are numerous genes involved, and the various combinations of these genes inherited by a person probably help to determine which problems end up occurring.”-Dr. Thomas Many people with systemic autoimmune diseases, such as lupus, can also have symptoms characteristic of one or more of other connective tissue diseases. When this occurs, a physician may use the term “overlap” to describe the illness. Here is a list of common connective tissue diseases/disorders, also known as “overlap” diseases:
- Systemic Lupus Eyrthematosus (SLE): SLE is a widespread and chronic autoimmune condition that, for unknown reasons, causes the immune system to attack the body’s own tissues and organs, including joints, kidneys, heart, lungs, brain, blood, and skin.
- Sjogren’s Syndrome: In Sjögren’s, white blood cells attack moisture-producing glands, such as the tear ducts and salivary glands, making it difficult for your body to produce saliva and tears.
- Systemic sclerosis (also known as scleroderma): Scleroderma can cause the tightening and hardening of the skin and the connective tissues. The word “scleroderma” derives from two Greek words: “sclero” meaning hard, and “derma” meaning skin.
- Rheumatoid Arthritis (RA): RA is a chronic inflammatory condition and autoimmune disorder that generally affects the lining of the joints in your hands and feet. Rheumatoid arthritis causes a painful swelling that can eventually lead to deformity and erosion of your joints and bones.
- Polymyositis: Plymyositis (pol-e-mi-o-SI-tis) is a persistent inflammatory muscle disease that causes weakness of the skeletal muscles, which control movement. “Without proper treatment, it can cause progressive, debilitating weakness of the arms and legs and can even cause problems with using the muscles of the chest to breath.”-Dr. Thomas
- Dermatomyositis: Dermatomyositis (dur-muh-toe-my-uh-SY-tis) is an uncommon inflammatory disease marked by muscle weakness and a distinctive skin rash.
“It is not uncommon to have more than one well-defined connective tissue disease at a time. This makes sense, since the same genes can cause the same disorders. If someone meets specific classification criteria for more than one of these diseases, then that person is said to have an “overlap syndrome.” By far, the most common overlap syndrome with SLE is Sjögren’s syndrome. 30% to 50% of people affected by SLE will also have Sjögren’s syndrome.” -Dr. Thomas Each of the above disorders can cause the following ‘overlap’ disorders as well:
- Raynaud’s Phenomenon: Raynaud’s, simply put, is a problem with blood flow. This means that your body is not able to send enough blood to your extremities, like your hands and feet, so they tend to feel very cold, numb or tingly and can even discolor due to lack of circulation.
- Neuropathy (or peripheral neuropathy): Peripheral Neuropathy, is nerve damage that often causes weakness, numbness and pain, usually in your hands and feet, but may also occur in other areas of your body, it may also signal lupus.
- Anemia: Anemia is a condition in which your blood has a lower than normal number of red blood cells causing symptoms such as weakness, fatigue, dizziness, shortness of breath, or headaches. Long-lasting or severe anemia can damage the body’s vital organs and in extreme cases, death.
- Pleurisy (also called pleuritis): Pleurisy is an inflammation of the moist, double-layered membrane that surrounds the lungs and lines the rib cage, making breathing extremely painful.
“I think that one of the most important things for the person with MCTD to keep in mind is that there is one major organ system that becomes commonly involved in people who have MCTD, and that is the lungs. Seventy five percent of all MCTD patients will develop lung problems, and this is a major source of their possibly not doing well. It is essential not to smoke cigarettes, to get all vaccines preventing lung infections (the flu shot, Pneumovax, and Prevnar), and to report any symptoms of shortness of breath, cough, and chest pain to their doctor.” -Dr. Thomas Other names for different types of MCTD: To make things even more confusing, these disorders are often also identified by the following alternative terms that are used to clarify specific differences in each patient’s unique diagnosis:
- Collagen vascular disease: Collagen is a protein-based connective tissue that forms a support system for your skin. The connective tissue holds bones, ligaments, and muscles together.
- Diffuse connective tissue diseases: The diffuse connective tissue diseases constitute a group of inflammatory diseases with the potential of involvement of many organ systems.
- Undifferentiated connective tissue disease: Unclassifiable symptoms, physical examination findings, or test results suggestive of a connective tissue disease frequently lead to diagnoses such as incomplete lupus, latent lupus, overlap syndrome, and undifferentiated connective-tissue disease (UCTD)
What are some signs and symptoms of MCTD?
Here are some early signs and symptoms of connective tissue disease:
- General feeling of being unwell: This might include a mild fever and increased fatigue.
- Swollen/Puffy Fingers: Swelling in the hands and fingers is a common symptom of mixed connective tissue disease.
- Raynaud’s Phenomenon: This is experienced as cold/numb fingers, toes, tip of the nose, and ears that may change color in response to cold. This is caused by a reduction in blood flow to these areas
- Muscle and joint pain: The symptoms of rheumatoid arthritis including muscle aches and joint swelling/pain are common in MCTD.
- Pulmonary hypertension (PH): This condition means that there is an increased pressure in the pulmonary arteries. These are the arteries that carry blood from your heart to your lungs to pick up oxygen. PH can cause symptoms such as shortness of breath during routine activity, fatigue, chest pain, and a racing heartbeat. As the condition gets worse, its symptoms may limit all physical activity.
“[Pulmonary hypertension] is an especially ominous problem. This occurs due to the arteries in the lungs becoming inflamed and thickened, causing an elevation in blood pressure in the blood vessels. People who have MCTD are especially at increased risk for developing this. Without early identification, this can lead to heart problems, shortness of breath, blood clots in the heart, and even death. Early diagnosis in order to provide prompt treatments is very important. A person with MCTD should have pulmonary function tests and an ultrasound of the heart (called an echocardiogram) yearly in order to identify pulmonary hypertension at an early stage if they develop it. This worrisome complication is very treatable when caught early.”-Dr. Thomas
How is it diagnosed?
Often, testing for mixed connective tissue disorder is called for when a patient is experiencing a rheumatologic disease, such as rheumatoid arthritis, along with several other overlap disease features. Diagnosing specific connective tissue disorders can be tricky because often the same lab abnormalities exist in several connective tissue conditions. For example, someone could test positive for certain abnormalities and still the specific diagnosis may be unclear (although the treatment, in fact, may be the same). When the diagnosis is unclear, but it is evident that a systemic disorder is present, the physician may call it an undifferentiated connective tissue disorder (UCTD).
“The rheumatologist will recognize that the person indeed has a systemic autoimmune disorder and will usually use the term “undifferentiated connective tissue disease or UCTD.” This term is used because the disorder has not fully declared itself yet. However, it does not prevent the doctor from treating it properly as the problems shared by these illnesses are usually treated similarly… These autoimmune disorders can come on slowly and not completely reveal what the final problem will be.” –Dr. Thomas
Dr. Thomas explains how the physician may use the present symptoms in addition to lab tests to pinpoint a specific diagnosis for some of these connective tissue disorders: “Problems can be specific for a disease, helping to identify exactly which one is going on. For example, if someone develops enlargement of the glands that secrete saliva in the mouth (salivary glands) due to inflammation and also develops dry mouth or dry eyes, this person has Sjogren’s syndrome. If a person’s inflammatory arthritis shows large areas of bone “eaten away” on x-rays (called erosions) and has a high positive CCP antibody, that person has rheumatoid arthritis. If someone develops a red butterfly rash on the face and is positive for anti-Smith and anti-ds DNA antibodies, then that person has SLE. Rheumatologists often use “classification criteria” to help determine exactly which connective tissue disease someone has.”- Dr. Thomas
Here are some of the lab/blood tests that may be ordered to help diagnose a connective tissue disorder:
Antinuclear antibody (ANA): The immune system makes a lot of proteins called antibodies. Antibodies are made by white blood cells and they identify and fight infectious organisms in the body like bacteria and viruses. Sometimes these antibodies make a mistake and identify normal, naturally-occurring proteins in our bodies as being “foreign” and dangerous. These antibodies are called antinuclear antibodies (ANA). A positive ANA test means that the antibodies are present. By itself, an ANA test DOES NOT mean that a person has an auto-immune disease.
Rheumatoid factor (RF): This is present in 80% of adults with rheumatoid arthritis but not often present in the normal individual. It is also often positive in people with MCTD. A high level can indicate a tendency toward more aggressive disease activity.
SS-A/RO: Anti-SSA autoantibodies (also called anti-Ro, or the combination anti-SSA/Ro or anti-Ro/SSA autoantibodies): These are anti-nuclear autoantibodies (see above) that are associated with many autoimmune diseases, such as systemic lupus erythematosus. This particular antibody often occurs in patients with Sjogren’s Syndrome.
Ribonucleoprotein (RNP) or Anti-RNP antibodies: Anti-RNP antibodies are strongly associated with MCTD, and the majority of patients diagnosed with MCTD test high positive for RNP antibodies. These patients often also have Raynaud’s. “It is important to realize that everyone who is RNP antibody positive does not have MCTD. RNP antibody commonly occurs in all of the CTD disorders (for example, 30% of SLE patients are RNP positive, but the vast majority of people with SLE do not have MCTD).” Clarifies Dr. Thomas.
Immunoglobulins: An immunoglobulin test measures the level of certain immunoglobulins, or antibodies, in the blood. Antibodies are proteins made by the immune system to fight antigens, such as bacteria, viruses, and toxins. This test is used to diagnose immunodeficiencies (when the immune system is not working properly). “These autoimmune disorders can come on slowly and not completely reveal what the final problem will be. In these cases, nonspecific problems may occur that do not point to one disease over another. For example, if someone has an inflammatory arthritis, Raynaud’s phenomenon and is positive for antinuclear antibody (ANA), RNP antibody and SSA antibody; it is impossible to know which disorder the person actually has. This particular group of problems can be seen in all of them (SLE, RA, scleroderma, and polymyositis).”-Dr. Thomas
- High concentrations of the RNP antibody (see above for description)
- Raynaud’s Phenomenon
- Swelling of the fingers
- Inflammatory arthritis
- Myositis or muscle inflammation
“An often confusing situation can arise when different rheumatologists label the same patient differently. For example, one doctor may say a patient has mixed connective tissue disease, while another physician may diagnose the same exact patient as having an overlap of SLE and scleroderma, especially if this person meets the criteria for both SLE and scleroderma. These two separate ways of diagnosing the patient would be correct as the problems the patient has and the treatments would be exactly the same. This can, of course, cause confusion to the patient when they hear these different diagnoses from different doctors. Another common, confusing situation can occur when someone starts off appearing to have one disorder, then evolve over time to be more similar to another disorder. For example, someone may start out fulfilling criteria for MCTD, yet over time, evolve into either classic SLE or classic systemic sclerosis and require a change in their diagnosis. I have also noted that even doctors often use these terms incorrectly. I have seen many patients labeled as having mixed connective tissue disease then the person actually had an undifferentiated connective tissue disease. If it can be so confusing for the doctors, no wonder it can be so confusing for your patients.” -Dr. Thomas
What is the cause of MCTD and can it be prevented?
As with most autoimmune diseases, pinpointing the cause of MCTD is very difficult. It is likely that they stem from a combinations of genetic and environmental factors, but doctors do not know why people get these types of immune disorders. Because there is no way to know why people get them, it is very difficult to say how they can be prevented.
How is mixed connective tissue disease treated?
The goal of treatment for MCTD is to suppress the immune-related inflammation of tissues. This is a very similar approach to the [treatment of lupus]. Often corticosteroids such as prednisone are prescribed to accomplish this. Cases that are less severe can often be treated with nonsteroidal anti-inflammatory drugs (NSAIDs), hydroxychoroquine (such as Plaquenil) and lower doses of corticosteroids. More severe cases of MCTD might require the use of immunosuppressive medications like cytoxin, for example. It is very important to note- If you are on Prednisone, please have your physician monitor you closely and never reduce your dosage or stop taking it without first consulting with your medical provider. There are side effects and important things to know about corticosteroids, please find that information in our blog on the topic.
Like in lupus, symptoms may come and go and you may experience periods of remission. Unfortunately in about 13% of patients, the MCTD will progress in spite of treatment. This being said, the outcome for MCTD is usually very good. There are many feelings that go along with learning to cope with a chronic illness and they are all normal. You may not know where to turn to for advice, support, or information. Your family, friends, and caregivers may feel the same way. The first thing to understand is that a person with MCTD, scleroderma, lupus, fibromyalgia, or any other chronic illness is just that. A person. The disease should not become your identity. There is so much more to each individual than their diagnosis, so maintaining a positive but realistic attitude can really help when learning to live with any chronic disease. Lead as full of a life as possible and understand that this is just a part of your life, meaning that the disease is what you have, not who you are. If you are feeling depressed or hopeless, or having trouble accepting your diagnosis, please seek counseling from a professional to help provide the tools to help you cope with these complicated feelings. Here are some things that might help you along the journey:
- Maintain good communication with your treating physician(s) and be your own best advocate.
- Keep organized medical records, bring a support person along to visits when you can to help you digest and remember information and advice, and be open and honest with your doctor, following the recommended protocol.
- A network, or team of friends, family, medical providers, support groups, and resources can help you successfully navigate through your disease.
- Protect your hands from cold temperatures by wearing gloves or taking other measures to keep your core temperature warm.
- Reduce stress- Yoga, breathing techniques, relaxation and meditation can help your mind/body connection.
- Stop smoking! Get help here: Smokefree.gov
A new diagnosis of MCTD, or UCTD may feel overwhelming, but it doesn’t have to be. It is a complex disease and the symptoms and severity can vary widely between those diagnosed, depending on which CTD’s are diagnosed as well as which overlapping diseases and symptoms are involved. If you or someone you care about is showing any of the above signs or symptoms, getting a quick, accurate diagnosis and early treatment, can help to minimize the symptoms of MCTD, thereby decreasing the chances of irreversible damage and creating the best possible outcome and quality of life. We would like to thank Dr. Donald Thomas for taking the time to helping us hopefully clarify this very confusing topic. We greatly appreciate his insight and expertise in this field!
Author: Karrie Sundbom
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