What are the other Names for this Condition? (Also known as/Synonyms)

• MCTD (Mixed Connective Tissue Disease)
• Mixed Connective Tissue Disorder
• Sharp Syndrome

What is Mixed Connective Tissue Disease? (Definition/Background Information)

• Mixed Connective Tissue Disease (MCTD) is a rare autoimmune disorder that is characterized by features commonly seen in three different connective tissue disorders: systemic lupus erythematosus, scleroderma, and polymyositis. Some affected people may also have symptoms of rheumatoid arthritis
• Although MCTD can affect people of all ages, it appears to be most common in women under age 30
• Signs and symptoms vary but may include Raynaud's phenomenon; arthritis; heart, lung and skin abnormalities; kidney disease; muscle weakness, and dysfunction of the esophagus
• The cause of Mixed Connective Tissue Disease is currently unknown. There is no cure but certain medications such as nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids and immunosuppresive drugs may help manage the symptoms

(Source: Mixed Connective Tissue Disease; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Who gets Mixed Connective Tissue Disease? (Age and Sex Distribution)

• Mixed Connective Tissue Disease is a rare immune disorder. The presentation of symptoms most commonly occur between ages 15-21
• Both males and females may be affected. However, the condition is more prevalent among women in a ratio of 3:1 (female-male ratio)
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for Mixed Connective Tissue Disease? (Predisposing Factors)

• Currently, no risk factors have been clearly identified for Mixed Connective Tissue Disease

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Mixed Connective Tissue Disease? (Etiology)

• The exact cause of Mixed Connective Tissue Disease is not known at the present time
• It is an autoimmune disorder, in which an affected individual’s immune cells target and destroy his/her own healthy cells, leading to the signs and symptoms of the disorder

What are the Signs and Symptoms of Mixed Connective Tissue Disease?

The signs and symptoms of Mixed Connective Tissue Disease may overlap with several connective tissue disorders, including systemic lupus erythematosus, polymyositis, scleroderma, and rheumatoid arthritis.

A condition called Raynaud's phenomenon sometimes occurs months or years before other symptoms of MCTD develop. Most people with MCTD have pain in multiple joints, and/or inflammation of joints (arthritis). Muscle weakness, fevers, and fatigue are also common.

Other signs and symptoms of Mixed Connective Tissue Disease may include:

• Accumulation of fluid in the tissue of the hands that causes puffiness and swelling (edema)
• Skin findings including lupus-like rashes (including reddish brown patches), reddish patches over the knuckles, violet coloring of the eyelids, loss of hair (alopecia), and dilation of small blood vessels around the fingernails (periungual telangiectasia)
• Dysfunction of the esophagus (hypomotility)
• Abnormalities in lung function which may lead to breathing difficulties, and/or pulmonary hypertension
• Heart involvement (less common in MCTD than lung problems) including pericarditis, myocarditis, and aortic insufficiency
• Kidney disease
• Neurologic abnormalities (in about 10 percent of people with MCTD) such as organic brain syndrome; blood vessel narrowing causing "vascular" headaches; a mild form of meningitis; seizures; blockage of a cerebral vessel (cerebral thrombosis) or bleeding; and/or various sensory disturbances in multiple areas of the body (multiple peripheral neuropathies)
• Anemia and leukopenia (in 30 to 40 percent of cases)
• Lymphadenopathy, enlargement of the spleen (splenomegaly), enlargement of the liver (hepatomegaly), and/or intestinal involvement in some cases

Based on the frequency of symptoms observed, the following information may be noted:

Very frequently present symptoms in 80-99% of the cases:

• Arthritis 
• Autoimmunity
• Chest pain 
• Dyspnea 
• Elevated erythrocyte sedimentation rate
• Fatigue 
• Gastritis
• Gastroesophageal reflux
• Myalgia   
• Pulmonary fibrosis 
• Scleroderma 
• Skin rash

Frequently present symptoms in 30-79% of the cases:

• Arthralgia
• Fever 
• Joint swelling 
• Keratoconjunctivitis sicca
• Myositis
• Pleuritis 
• Psychosis 
• Xerostomia

Occasionally present symptoms in 5-29% of the cases:

• Alopecia
• Aseptic necrosis 
• Gastrointestinal hemorrhage
• Hemolytic anemia 
• Hepatomegaly
• Interstitial pulmonary abnormality
• Joint stiffness
• Leukopenia
• Mediastinal lymphadenopathy
• Meningitis 
• Myocarditis  
• Nephropathy 
• Osteolysis 
• Pericarditis 
• Peripheral neuropathy 
• Prolonged bleeding time 
• Pulmonary arterial hypertension 
• Purpura 
• Seizures
• Splenomegaly

(Source: Mixed Connective Tissue Disease; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

How is Mixed Connective Tissue Disease Diagnosed?

Mixed Connective Tissue Disease is diagnosed on the basis of the following information:

• Complete physical examination
• Thorough medical history evaluation
• Assessment of signs and symptoms
• Laboratory tests, including blood test to check for specific antibodies that are known to be elevated in MCTD
• Imaging studies
• Biopsy studies, if necessary

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Mixed Connective Tissue Disease?

The complications of Mixed Connective Tissue Disease may include:

• Extreme arthritic pain 
• Difficulty with movement
• Myositis
• Pleurisy
• Pericarditis
• Myocarditis
• Pulmonary hypertension
• Severe respiratory distress
• Risk of fall injuries, if seizures are present
• Aseptic meningitis 
• Permanent damage to brain
• Poor quality of life

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is Mixed Connective Tissue Disease Treated?

There is no cure for Mixed Connective Tissue Disease, and generally, treatment is given to address signs and symptoms. The treatment methods for MCTD may include the following:

• Over-the-counter pain medication, such as non-steroidal anti-inflammatory drugs (NSAIDs)
• Glucocorticoids, when there is a flare-up, or when complications arise
• Immune-suppressing medications

How can Mixed Connective Tissue Disease be Prevented?

• Currently, the cause of Mixed Connective Tissue Disease is not known, and therefore, no methods or guidelines are available for its prevention
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders
• Regular medical screening at periodic intervals with tests and physical examinations are recommended

What is the Prognosis of Mixed Connective Tissue Disease? (Outcomes/Resolutions)

The prognosis of Mixed Connective Tissue Disease is dependent upon the severity of the signs and symptoms and associated complications, if any.

• The overall 10-year survival after diagnosis is approximately 80%
• Whereas some of those affected may be symptoms-free for lengthy periods of time, others (about 13%) may develop life-threatening complications even with treatment and succumb to the disorder (within 6-12 years after diagnosis)
• Pulmonary hypertension is often the cause of fatalities in individuals with MCTD. The outcomes may be unfavorable in individuals with systemic sclerosis and polymyositis too
• The prognosis may be assessed on a case-by-case basis

Additional and Relevant Useful Information for Mixed Connective Tissue Disease:

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/