Mixed Connective Tissue Disease

Mixed connective tissue diseases (MCTD) are a group of rare autoimmune conditions characterized by signs and symptoms seen in three various connective tissue abnormalities: Systemic lupus erythematosus, polymyositis (muscle inflammation), and scleroderma (a state of abnormal hardening and thickening of the skin, tissues, and organs).

Some individuals affected with mixed connective tissue disease may also present symptoms of rheumatoid arthritis. Mixed connective tissue disease (MCTD) is predominantly occurring in women under the age of 50; however other groups have not been written off, as there is a possibility of it affecting men, children, and different age groups.

Mixed connective tissue disease (MCTD) cases, usually vary from mild to moderate to severe, depending on the organ or body system affected, degree of inflammation, and disease progression rate.

It has also been recorded from presented cases that about 27% of patients with a connective tissue disorder also develop another connective tissue disease over several years. These cases are referred to as “overlap syndrome.”

Mixed connective tissue disease (MCTD) has no cure, and treatments are solely targeted at easing symptoms. Since mixed connective tissue disease can also affect various organs and tissues, such as muscles, skin, lungs, digestive system, and joints; Treatment approaches manage the significantly affected areas. 

The National Institutes of Health stipulated a survival rate of 10years for 80% of people with MCTD. That is, about 80% of persons with the disease will still be living 10years after diagnosis.

Symptoms of Mixed Connective Tissue Disease (MCTD)

The Symptoms presented by Mixed connective tissue disease (MCTD) might be continuous or periodic, showing up in sequence over many years.

These symptoms are similar to the symptoms of patients who suffer from connective tissue complications.

Symptoms of MCTD are:

  • Raynaud’s phenomenon: a condition that features severe attacks of cold, puffy and numb fingers that appear blue, white, or purple. In most cases, it is the first presented sign of MCTD, appearing months or even years before other symptoms.
  • Fever
  • Rash
  • Fatigue
  • Swelling in joints
  • Muscle weakness
  • Joint pains
  • Hearing loss
  • Sensitivity to cold with color changes of the hands and feet
  • Chest pains
  • Acid reflux
  • Stomach inflammation
  • Difficulty in breathing, in cases of lung tissue inflammation, due to increase blood pressure.
  • Swollen hands
  • Tightening patches appearing on the skin 
  • Hardening of the skin

In later life stages, disease complications leading to dysfunction of major organs such as the kidneys, the heart, and lungs may arise.

Complications may include:

  • Lung disease
  • Kidney damage
  • Heart disease
  • Myelitis
  • Damage to the gastrointestinal tract
  • Pulmonary High blood pressure
  • Anemia
  • Coronary arterial damage
  • Tissue death (Gangrene)
  • Neuropathy

Causes of Mixed Connective Tissue Disease (MCTD)

The etiology of mixed connective tissue disease is a mystery. But as this much is known, that is an autoimmune disorder; that is, it involves the body’s immune system attacking the healthy tissues.

When antibodies of the immune system begin to attack the connective tissues that provide the framework for organs in the body, it results in MCTD condition. Also, exposure to certain viruses and chemicals such as polyvinyl chloride and silica are other possibilities to cause.

Risk Factors

MCTD is a spondaic condition. It occurs mainly in women, with 75% of cases usually in their late 20s and early 30s. Other research suggests that the onset of MCTD can appear anytime, either in childhood or adulthood, but the hypothetic average age of onset is 37 years.

The Prevalence of Mixed connective tissue disease is 3.8 per 100,000 persons in Norway; this is believed to be similar in other parts of the world. Ethnically, the disease condition has a higher prevalence, notably in Japan.


The three common connective tissue diseases closely related and mostly misinterpreted with MCTD are polymyositis, scleroderma, and systemic lupus erythematosus (SLE).

MCTD symptoms usually occur one after the other over time; it is difficult to give an accurate diagnosis of MCTD. Waiting for a precise diagnosis may take several years.

Diagnosis may be based on thorough clinical examination, investigation of patient’s medical history, blood tests specialized in revealing abnormalities in levels of antibodies to the U1 small nuclear ribonucleoprotein (anti-RNP).

Apart from these, there are also three (3) other features that may direct diagnosis towards an MCTD condition rather than to other connective tissue disorders:

  • Severe arthritis or pulmonary hypertension, which may not be found in either SLE or scleroderma patients.
  • Occurrence of Raynaud phenomenon, and swollen hands or puffed fingers. These symptoms only occur in 25 percent of SLE patients.
  • SLE is often characterized by severe kidney dysfunction and central nervous system problems. An absence of these is a sign of mixed tissue disease.

Treatment of Mixed Connective Tissue Disease (MCTD)

There is no cure for MCTD; however, medications are available to help manage the symptoms and slow the disease progression rate. Some persons may require long-term treatment, while others only need treatment of their disease when it flares up depending on the organ affected and the severity of the condition. Considerably, treatment for MCTD includes the following:


Steroids such as prednisone are used to treat inflammation and stop the immune system from attacking the body. But this treatment might result in many side effects, such as hypertension, weight gain, and cataracts, and due to this reason, they are frequently used only for a brief period to avoid long-term risks.

NSAIDs (Non-steroidal anti-inflammatory drugs)

Medications such as ibuprofen and naproxen (Aleve) are used to treat joint pain and inflammation.

Antimalarial drugs

Antimalarial drugs such as Plaquenil (Hydroxychloroquine) can help with a not-so-severe case of MCTD and help prevent flare-ups.


These drugs are used for long-term treatments of MCTD. An Immunosuppressant is a drug that suppresses the immune system. Examples of immunosuppressants include azathioprine (Azasan, Imuran) and mycophenolate mofetil (CellCept).

However, immunosuppressants are limited in unique conditions, such as pregnancy, due to the potential effect of increase the risk of fetal malformations or toxicity.

Calcium-channel blockers

Nifedipine and amlodipine are some examples of calcium channel blockers used to manage Raynaud’s phenomenon.

Pulmonary Hypertensive Drugs

Increased blood pressure in the lungs is one of the leading causes of death in persons with MCTD. Clinicians may prescribe drugs like bosentan or sildenafil (Revatio, Viagra) to help prevent pulmonary hypertension from getting worse.

Generally, individuals with mixed connective tissue disease (MCTD) are always advised to keep a good health habit and adopt some lifestyle changes to assist medication, such as:

  • Get regular exercises as much as possible to Improve muscle strength, blood pressure and also reduce the risk of heart complications associated with MCTD.
  • Quit smoking because the blood vessels become narrow, which can lead to worsen symptoms of Raynaud’s phenomenon and raise blood pressure.
  • Protecting hands and feet from cold can help reduce the chances of having a Raynaud’s phenomenon flare-up.
  • Try adequate iron in a diet, as it is having been discovered that 75% of persons with MCTD have iron deficiency anemia.
  • A diet rich in whole grain, fruits, and vegetables can help keep a healthy digestive system.  
  • Salt intake should also be limited. Salt tends to increase blood pressure, which presents additional health risks for people with MCTD.

Complications of Mixed Connective Tissue Disease (MCTD)

    Several severe conditions tend to rise in the course of MCTD. Some of these conditions or complications can be fatal, such as:

  • Interstitial lung disease (scarring of lung tissues)
  • High blood pressure of the lungs
  • Heart disease (heart enlargement, myocardium, or pericardium)
  • Kidney damage (chronic kidney failure nephritis)
  • Hearing complications
  • Anemia
  • Chronic Gangrene
  • Sjögren syndrome (deterioration of the trigeminal nerve)


Mixed connective tissue disease may be rare, but it is not a condition to be overlooked as it can present similar symptoms as other connective tissue diseases and significant organs can be involved.

Talk to a doctor or specialist if you are experiencing any of the signs and symptoms to establish a long-term treatment and management plan that works best for you. Due to the complexity of MCTD, a rheumatologist might be very useful.