Mixed Connective Tissue Disease


Definition/Description[edit | edit source]

Mixed connective tissue disease (MCTD) is a systemic disease which consists of clinical symptoms observed in the following three disorders: systemic lupus erythematosus, polymyositis, and systemic sclerosis (also known as systemic scleroderma).[1] [2] MCTD is considered an "overlapping disease" as it contains features of these three disorders. The features can be categorized broadly as arthritic changes, cardiopulmonary dysfunctions, skin changes, muscle weakness, kidney disease, and dysfunctions of the oesophagus.[3]

The symptoms associated with the three underlying disorders do not generally present simultaneously.[4] It usually takes several years before the symptoms of each individual disorder present, which ultimately complicates the diagnosis of MCTD.[4] Typically, the first symptom to present is swelling of the fingers or the presentation of “sausage fingers”.[5] As the disease progresses, it can often affect multiple organs such as the lungs, heart, and/or kidneys.[3] There is no cure for MCTD, however side effects can be managed through the use of medications.[5]

Prevalence[edit | edit source]

It has been reported that 80% of individuals diagnosed with MCTD are women, with the highest prevalence in the age group under thirty.[4] Other sources have reported statistics collected from patients ages 5 through 80, with the peak prevalence around 20 years of age. [6] Estimates of this disease show it occurs in between 2-6.4out of every 100,000 individuals. [2] 

Aetiology/Causes[edit | edit source]

The exact cause of MCTD is unknown, but it has been classified as an autoimmune disorder. Individuals with this disease have high levels of antinuclear antibodies (ANAs) and antibodies to U1 snRNP.[3] 

A genetic link can be seen in MCTD in that some individuals diagnosed with MCTD report having a family member who also has a connective tissue disease.[5] Also, exposures to certain chemicals or viruses such as silica or polyvinyl chloride have been found as potential causes of MCTD.[5]

Characteristics/Clinical Presentation[edit | edit source]

The initial sign of MCTD may be shown as a presentation of puffy and swollen hands, Raynaud’s phenomenon, and polyarthritis.[1][2][3][7][8]

Some of the classical conditions or "signs” of MCTD include[5]:

Raynaud phenomenon
  • Inflammation of muscles and joints
  • Pulmonary hypertension
  • Raynaud phenomenon
  • Swollen fingers, often “sausage-like”, can be a temporary stage of the disease, or may progress into limited movement of the fingers due to thinning of fingers and thickening of the skin[2]

The chart below lists some of the symptoms common versus uncommon symptoms in early stages of MCTD.[5]


Associated Co-morbidities[edit | edit source]

Medical Management[edit | edit source]

Medical management is undertaken by a range of specialist working together. Since there is no cure yet for the disease, management is focussed on control of symptoms and minimising systemic involvement. A variety of medications will be used to manage the various symptoms associated with the disease (s)

  • Corticosteroids[4][6]- may be used to manage synovitis ( active, or more severe disease)
  • Anti-malarial drugs- may be used it manage synovitis, may help prevent disease flares [4]
  • Nonsteroidal anti-inflammatory drugs - may be used to manage arthritis/ arthralgia[2][6]-
  • Immunosuppressive drugs[6]- may be used to manage refractory synovitis and pulmonary hypertension in some patients
  • Calcium channel blockers[2][4]- may be used to treat Raynaud’s ( Vasodilation and possible antiplatelet effects)
  • Phosphodiesterase inhibitors[2]- may be used to treat pulmonary hypertension
  • Endothelial receptor antagonists [2] - may be used to treat pulmonary hypertension
  • Prostaglandins- may be used to treat pulmonary hypertension [2]
  • Proton pump inhibitors[2]- may be used for heartburn or swallowing problems

Diagnostic Tests/Lab Tests/Lab Values[edit | edit source]

Laboratory Testing Often Includes:[2]

  • Anti-U1-RNP (ribonucleoprotein) antigens
  • Urinalysis
  • Muscle enzymes (myositis involvement)
  • Complete blood count (CBC)
  • Antinuclear antibodies
  • Lipase and amylase (pancreatitis involvement)
  • Routine blood chemistry

To check for systemic involvement, the following imaging testing can be performed[2]

  • Chest radiography- assesses for infiltrates, effusions, and cardiomegaly
  • MRI- assess for neuropsychiatric signs or symptoms
  • CT scan/ultrasound- evaluates abdominal pain in cases of suspected serositis, pancreatitis, and/or visceral perforation related to vasculitis
  • Echocardiography- assesses for effusion, chest pain, pulmonary hypertension, or valvular disease

Systemic involvement tests may also include cardiopulmonary testing, such as:[10]

Currently, there are three different criteria classification systems that are associated with predicting the probability that an individual may have MCTD. These three classification systems are set forth by Modified Sharp et al (1987), Alarcon Segovia et al (1987), and Kauskawa et al (1987).[9] Listed below are the criteria sets that are presently used in the diagnosing MCTD.




Malar rash

Physical Therapy Management[edit | edit source]

Since there has been limited research regarding physical therapy treatment in patients with MCTD, interventions should be tailored to address the impairments of each individual. Although each person presents differently, there are some common areas that need to be addressed in nearly all cases. Individuals with MCTD often present with decreased aerobic capacity and weakness of the proximal musculature.[10] Physical therapists should treat according to the common deficits seen in the disease, as well as personal impairments that arise with each case.

Common areas of focus may include:

  • Patient education regarding joint protection
  • Aerobic and endurance training
  • Range of motion exercises to maintain available range
  • Passive stretching, including splinting for joint protection
  • Strengthening total-body exercises (including proximal musculature)
  • Skin education and management
  • Energy conservation techniques

Differential Diagnosis [2][edit | edit source]

  • Systemic Lupus Erythematosus - a chronic inflammatory disease characterized by protean manifestations with a relapsing and remitting course
  • Scleroderma- progressive skin hardening and induration
  • Dermatomyositis- idiopathic inflammatory myopathy with characteristic signs commonly present in the skin, muscles, and joints
  • Polymyositis- idiopathic inflammatory myopathy which results in symmetrical proximal muscle weakness
  • Primary pulmonary hypertension- elevated pulmonary artery pressure with no known cause, if left untreated will lead to right-sided heart failure
  • Raynaud phenomenon- recurrent vasospasms of the fingers or toes which usually occurs as a result of stress or exposure to the cold
  • Bacterial sepsis- the presence of infection along with the systemic inflammatory response syndrome
  • Pleuritis- inflammation in the lining of the lungs
  • Rheumatoid arthritis- chronic systemic inflammatory disease with an unknown cause

Case Reports/ Case Studies[edit | edit source]

Karmacharya P, Mainali N, Aryal M, Lloyd B. Recurrent case of ibuprofen-induced aseptic meningitis in mixed connective tissue disease. Case Reports [Internet]. 2013 [2016 Apr 8];2013(apr30 1):bcr2013009571-bcr2013009571. [12][12][12][12][12][12][12][12][12][12][12][12]

Souto Filho J, de Barros P, da Silva A, Barbosa F, Ribas G. Thrombotic Thrombocytopenic Purpura Associated with Mixed Connective Tissue Disease: A Case Report. Case Reports in Medicine [Internet]. 2011 [Cited 2016 Apr 8];2011:1-5.[13][13][13][13][13][13][13][13][13][13][13][13]

Fantò M, Salemi S, Socciarelli F, Bartolazzi A, Natale G, Casorelli I et al. A Case of Subacute Cutaneous Lupus Erythematosus in a Patient with Mixed Connective Tissue Disease: Successful Treatment with Plasmapheresis and Rituximab. Case Reports in Rheumatology [Internet]. 2013 [Cited 2016 Apr 8];2013:1-4. [14][14][14][14][14][14][14][14][14][14][14][14]

Resources[edit | edit source]

Lupus Foundation of America, Inc.

References[edit | edit source]

  1. 1.0 1.1 Fagundes MN, Caleiro MT, Navarro-rodriguez T, et al. Esophageal involvement and interstitial lung disease in mixed connective tissue disease. Respir Med [Internet]. 2009 [cited 2016 Mar 12];103(6):854-60. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19201182
  2. 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 2.11 2.12 2.13 2.14 2.15 Mixed Connective-Tissue Disease: Background, Pathophysiology, Etiology [Internet]. Emedicine.medscape.com. 2016 [cited 8 April 2016]. Available from: http://emedicine.medscape.com/article/335815-overview
  3. 3.0 3.1 3.2 3.3 3.4 Mixed Connective Tissue Disease (MCTD) - NORD (National Organization for Rare Disorders) [Internet]. NORD (National Organization for Rare Disorders). 2016 [cited 8 April 2016]. Available from: http://rarediseases.org/rare-diseases/mixed-connective-tissue-disease-mctd/
  4. 4.00 4.01 4.02 4.03 4.04 4.05 4.06 4.07 4.08 4.09 4.10 4.11 4.12 4.13 4.14 Mixed connective tissue disease - Mayo Clinic [Internet]. Mayoclinic.org. 2016 [cited 2016 Apr 8]. Available from: http://www.mayoclinic.org/diseases-conditions/mixed-connective-tissue-disease/basics/definition/con-20026515
  5. 5.0 5.1 5.2 5.3 5.4 5.5 5.6 5.7 5.8 Mixed Connective Tissue Disease [Internet]. My.clevelandclinic.org. 2016 [cited 2016 Apr 8]. Available from: https://my.clevelandclinic.org/health/diseases_conditions/hic_Mixed_Connective_Tissue_Disease
  6. 6.0 6.1 6.2 6.3 Mixed Connective Tissue Disease (MCTD) [Internet]. Merck Manuals Consumer Version. 2016 [cited 2016 Apr 8]. Available from: https://www.merckmanuals.com/home/bone,-joint,-and-muscle-disorders/autoimmune-disorders-of-connective-tissue/mixed-connective-tissue-disease-(mctd)
  7. 7.0 7.1 Tani C, Carli L, Vagnani S, et al. The diagnosis and classification of mixed connective tissue disease. J Autoimmun [Internet]. 2014 [Cited 2016 Mar 12];48-49:46-9. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24461387
  8. 8.0 8.1 8.2 Cappelli S, Bellando randone S, Martinović D, et al. "To be or not to be," ten years after: evidence for mixed connective tissue disease as a distinct entity. Semin Arthritis Rheum [Internet]. 2012 [cited 2016 Mar 12];41(4):589-98. Available from http://www.ncbi.nlm.nih.gov/pubmed/21959290
  9. 9.0 9.1 9.2 Ungprasert P, Wannarong T, Panichsillapakit T, et al. Cardiac involvement in mixed connective tissue disease: a systematic review. Int J Cardiol [Internet]. 2014 [Cited 2016 Mar 12];171(3):326-30. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24433611
  10. 10.0 10.1 Van der net J, Wissink B, Van royen A, Helders PJ, Takken T. Aerobic capacity and muscle strength in juvenile-onset mixed connective tissue disease (MCTD). Scand J Rheumatol [Internet]. 2010 [Cited 2016 Mar 12];39(5):387-92. Available from: http://www.ncbi.nlm.nih.gov/pubmed/20604672
  11. Marigliano B, Soriano A, Margiotta D, Vadacca M, Afeltra A. Lung involvement in connective tissue diseases: a comprehensive review and a focus on rheumatoid arthritis. Autoimmun Rev [Internet]. 2013[Cited 2016 Mar 12];12(11):1076-84. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23684699