National Center for Advancing and Translational Sciences Genetic and Rare Diseases Information Center, a program of the National Center for Advancing and Translational Sciences

Mixed connective tissue disease

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.[1] Although MCTD can affect people of all ages, it appears to be most common in women under age 30.[2] 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.[3][1] The cause of MCTD is currently unknown. Treatment may include medications such as nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids and immune-suppressing drugs to help manage symptoms.[2]
Last updated: 12/29/2014
People with mixed connective tissue disease (MCTD) have symptoms that overlap with several connective tissue disorders, including systemic lupus erythematosus, polymyositis, scleroderma, and rheumatoid arthritis.[3]

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.[3]

Other signs and symptoms may include:[1][3][4]
  • 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 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
Last updated: 12/29/2014

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Showing of 40 |
Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Arthritis
Joint inflammation
0001369
Autoimmunity
Autoimmune disease
Autoimmune disorder
[ more ] 		0002960
Chest pain 0100749
Dyspnea
Trouble breathing
0002094
Elevated erythrocyte sedimentation rate
High ESR
0003565
Fatigue
Tired
Tiredness
[ more ] 		0012378
Gastritis
Stomach inflammation
0005263
Gastroesophageal reflux
Acid reflux
Acid reflux disease
Heartburn
[ more ] 		0002020
Myalgia
Muscle ache
Muscle pain
[ more ] 		0003326
Pulmonary fibrosis 0002206
Scleroderma 0100324
Skin rash 0000988
30%-79% of people have these symptoms
Arthralgia
Joint pain
0002829
Fever 0001945
Joint swelling 0001386
Keratoconjunctivitis sicca
Dry eyes
0001097
Myositis
Muscle inflammation
0100614
Pleuritis
Inflammation of tissues lining lungs and chest
0002102
Psychosis 0000709
Xerostomia
Dry mouth
Dry mouth syndrome
Reduced salivation
[ more ] 		0000217
5%-29% of people have these symptoms
Alopecia
Hair loss
0001596
Avascular necrosis
Death of bone due to decreased blood supply
0010885
Gastrointestinal hemorrhage
Gastrointestinal bleeding
0002239
Hemolytic anemia 0001878
Hepatomegaly
Enlarged liver
0002240
Interstitial pulmonary abnormality
Abnormality in area between air sacs in lung
0006530
Joint stiffness
Stiff joint
Stiff joints
[ more ] 		0001387
Leukopenia
Decreased blood leukocyte number
Low white blood cell count
[ more ] 		0001882
Mediastinal lymphadenopathy
Swollen lymph nodes in center of chest
0100721
Meningitis 0001287
Myocarditis
Inflammation of heart muscle
0012819
Nephropathy 0000112
Osteolysis
Breakdown of bone
0002797
Pericarditis
Swelling or irritation of membrane around heart
0001701
Peripheral neuropathy 0009830
Prolonged bleeding time 0003010
Pulmonary arterial hypertension
Increased blood pressure in blood vessels of lungs
0002092
Purpura
Red or purple spots on the skin
0000979
Seizure 0001250
Splenomegaly
Increased spleen size
0001744
Showing of 40 |
Last updated: 7/1/2020
The exact underlying cause of mixed connective tissue disease (MCTD) is currently unknown. It is an autoimmune disorder, which means the immune system mistakes normal, healthy cells for those that that body should "fight off." There are ongoing studies exploring how immune system dysfunction may be involved in the development of this condition.[1][3]
Last updated: 12/29/2014
The role of genetics in the onset of mixed connective tissue disease (MCTD) is still unclear. Some people with MCTD have family members who are also affected by the condition. This suggests that in some cases, an inherited predisposition may contribute to the development of MCTD. People with an inherited or genetic predisposition have an increased risk of developing a certain condition due to their genes.[3][5]
Last updated: 12/29/2014
Mixed connective tissue disease (MCTD) is often suspected after a physical examination reveals signs and symptoms associated with the condition. The diagnosis is supported by a blood test that shows high levels of antibodies associated with MCTD.[1][3][6]
Last updated: 12/29/2014
There is currently no cure for mixed connective tissue disease (MCTD). However, treatments can help manage symptoms of the condition. For example, medications such as over-the-counter or prescription nonsteroidal anti-inflammatory drugs may help with inflammation and pain of the muscles or joints. Glucocorticoids may be recommended in certain situations, such as during disease flares or when complications arise (e.g., aseptic meningitis, myositis, pleurisy, pericarditis, and myocarditis). Some people with MCTD require long term use of immunosuppressant medications.[1][7]

Additional medications may be prescribed based on the signs and symptoms present in each person. For example, if a person with MCTD has developed symptoms similar to those of lupus, medications typically prescribed for people with lupus may be recommended.[2]

For additional information about the treatment of MCTD, visit the Mayo Foundation for Medical Education and Research Web site.
Last updated: 12/30/2014
In general, the long-term outlook (prognosis) for people with mixed connective tissue disease (MCTD) is favorable, but it mostly depends on the signs and symptoms present in each person.[8][1]

The overall 10-year survival rate of the disease is about 80%.[8] Some people have symptom-free periods lasting for many years with no treatment. Despite treatment, the disease gets worse in about 13% of people and can cause potentially fatal complications in six to 12 years.[9] The prognosis is worse for people with features of systemic sclerosis and/or polymyositis. Pulmonary hypertension is the most common MCTD-associated cause of death.[8]
Last updated: 12/30/2014
Mixed connective tissue disease (MCTD) has been reported in all races and does not seem to occur more often in any racial or ethnic population. The clinical signs, symptoms and manifestations of MCTD are similar among different ethnic groups. MCTD is more common in females, with a female to male ration of 3:1. MCTD may affect any age, but typical age of onset is between 15-25 years old.
Last updated: 1/13/2016

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
Differential diagnoses include other connective tissue diseases such as SLE, SSc, PM and/or RA, and other systemic diseases such as sarcoidosis, periarteritis nodosa, or Still's disease (see these terms).
Visit the Orphanet disease page for more information.

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

  • ClinicalTrials.gov lists trials that are related to Mixed connective tissue disease. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

    Please note: Studies listed on the ClinicalTrials.gov website are listed for informational purposes only; being listed does not reflect an endorsement by GARD or the NIH. We strongly recommend that you talk with a trusted healthcare provider before choosing to participate in any clinical study.

Patient Registry

  • The Autoimmune Registry supports research for Mixed connective tissue disease by collecting information about patients with this and other autoimmune diseases. You can join the registry to share your information with researchers and receive updates about participating in new research studies. Learn more about registries.

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

Organizations Providing General Support

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

  • The Mayo Clinic Web site has an information page on mixed connective tissue disease that can be found at the following link. Click on The Mayo Clinic to view the information page.
  • The Merck Manuals Online Medical Library provides information on this condition for patients and caregivers. 
  • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

In-Depth Information

  • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
    Mixed Connective-Tissue Disease
    Pediatric Mixed Connective Tissue Disease
    Dermatologic Manifestations of Mixed Connective Tissue Disease
  • The Merck Manual for health care professionals provides information on Mixed connective tissue disease.
  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Mixed connective tissue disease. Click on the link to view a sample search on this topic.

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know.

  1. Eric L Greidinger, MD. Mixed Connective-Tissue Disease. Medscape Reference. February 2013; http://emedicine.medscape.com/article/335815-overview.
  2. Mixed Connective Tissue Disease. Mayo Foundation for Medical Education and Research. May 2012; http://www.mayoclinic.org/diseases-conditions/mixed-connective-tissue-disease/basics/definition/con-20026515?METHOD=print.
  3. Mixed Connective Tissue Disease (MCTD). NORD. October 2007; http://www.rarediseases.org/rare-disease-information/rare-diseases/byID/338/viewAbstract.
  4. Robert M Bennett, MD, FRCP, MACR. Clinical manifestations of mixed connective tissue disease. UpToDate. September 2014; Accessed 12/29/2014.
  5. Robert A Schwartz, MD, MPH. Dermatologic Manifestations of Mixed Connective Tissue Disease. Medscape Reference. May 2014; http://emedicine.medscape.com/article/1066445-overview.
  6. Robert M Bennett, MD, FRCP, MACR. Definition and diagnosis of mixed connective tissue disease. UpToDate. October 2014; Accessed 12/29/2014.
  7. Robert M Bennett, MD, FRCP, MACR. Prognosis and treatment of mixed connective tissue disease. UpToDate. December 2013;
  8. Zahir Amoura and Laurent Arnaud. Mixed connective tissue disease. Orphanet. October, 2009; http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=809.
  9. Rula A. Hajj-ali. Mixed Connective Tissue Disease (MCTD). Merck Manuals. August, 2013; http://www.merckmanuals.com/home/bone_joint_and_muscle_disorders/autoimmune_disorders_of_connective_tissue/mixed_connective_tissue_disease_mctd.html?qt=&sc=&alt=#top.
  10. Eric L Greidinger, MD. Mixed Connective-Tissue Disease - Epidemiology. Medscape Reference. March 25, 2015; http://emedicine.medscape.com/article/335815-overview#a6.