Mixed connective-tissue disease (MCTD) is a rare systemic autoimmune disease with overlapping features of at least two connective tissue diseases, including systemic lupus erythematosus (SLE), systemic sclerosis, polymyositis, dermatomyositis, and rheumatoid arthritis.[1] MCTD was first recognized by Sharp and colleagues (1972) in a group of patients with overlapping clinical features of SLE, scleroderma, and myositis, with the presence of a distinctive antibody against what now is known to be U1-ribonucleoprotein (RNP).[2]
MCTD has since been more completely characterized and is now recognized to consist of the following core clinical and laboratory features[3, 4] :
Raynaud phenomenon
Swollen hands
Arthritis/arthralgia
Acrosclerosis
Esophageal dysmotility
Myositis
Lung fibrosis[5]
Pulmonary hypertension
High level of anti–U1-RNP antibodies
Antibodies against U1-70 kd small nuclear ribonucleoprotein (snRNP)
Different classification and diagnostic criteria for MCTD have been developed.[6] These include the Alarcón-Segovia diagnostic criteria[7, 8] and, more recently, a set of criteria from a Japanese multispecialty consensus panel.[9] See DDx/Diagnostic Considerations.
Nevertheless, whether MCTD is a distinct disease entity has been in question since shortly after its original description. A minority of authors continues to suggest that MCTD would be better characterized as subgroups or early stages of disorders such as SLE or systemic sclerosis.[10] Other authors propose that MCTD cases should not be distinguished from undifferentiated autoimmune rheumatic disease.[11, 12]
The overall goals of therapy for MCTD are to control symptoms, to maintain function, and to reduce the risk of future disease consequences. Medical therapy targets control of disease activity in general and management of specific organ involvement, while monitoring for and mitigating the risks of complications either of the condition itself (eg, pulmonary hypertension, interstitial lung disease) or of its treatment (eg, infection).
Pathophysiologic abnormalities that are believed to play a role in MCTD include the following:
B-lymphocyte hyperactivity, resulting in high levels of anti–U1-RNP and anti–U1-70 kd autoantibodies
T-lymphocyte activation, with anti–U1-70 kd–reactive T lymphocytes circulating in the peripheral blood
Apoptotic modification of the U1-70 kd antigen
Immune response against apoptotically modified self-antigens
Genetic association with major histocompatibility genes human leukocyte antigen (HLA)–DRB1*04/*15[13]
Vascular endothelial pathology, including features of hyperproliferation and increased endothelial apoptosis[14]
Lymphocytic and plasmacytic infiltration of tissues
Activation of Toll-like receptors in a pattern that may differ from that of classic SLE
A strong Type I Interferon activation signature in circulating cells[15, 16, 17]
In a study of a nationwide MCTD cohort in Norway, Flåm and colleagues found that HLA-B*08 and DRB1*04:01 were risk alleles for MCTD, while DRB1*04:04, DRB1*13:01 and DRB1*13:02 were protective. Risk alleles for SLE, systemic sclerosis, and polymyositis/dermatomyositis were distinct from those for MCTD.[18]
Oka and colleagues performed genotyping of HLA-DRB1 and -DQB1 in 116 Japanese MCTD patients and 413 controls and analyzed the genotype frequencies. The analysis showed that HLA-DRB1*04:01 and DRB1*09:01 were risk alleles for Japanese MCTD. DRB1*13:02 was also confirmed to be protective against MCTD in Japanese patients.[19]
Over time, some patients with MCTD also develop anti-Sm autoantibodies—an expansion of the autoimmune response known as epitope spreading. Escolà-Vergé reported that epitope spreading occurred in 13 (43%) of 40 patients with MCTD, mainly during the first 2 years after diagnosis. Compared with patients who did not have epitope spreading, patients with epitope spreading had a significantly lower prevalence of skin sclerosis (0% vs 44%, P = 0.004) and a higher prevalence of interstitial lung disease (46% vs 15%, P = 0.05).[20]
The fundamental cause of MCTD remains unknown. Autoimmunity to components of the U1-70 kd snRNP is a hallmark of disease. Anti-RNP antibodies can precede overt clinical manifestations of MCTD, but overt disease generally develops within 1 year of anti-RNP antibody induction.
The loss of T-lymphocyte and B-lymphocyte tolerance, due to cryptic self-antigens, abnormalities of apoptosis, or molecular mimicry by infectious agents, and driven by U1-RNA–induced innate immune responses and other danger signal sensors induced by end-organ injury, are proposed current theories of pathogenesis.
It is notable that the RNA component unique to the U1-small nuclear ribonucleoprotein, U1-RNA, is among the most prevalent RNAs present in cellular apoptotic debris, and that U1-RNA is an agonist for autoimmunity-associated endosomal Toll-lIke receptors, including TLR7 and TLR3.[21, 22] These observations promote the hypothesis that immune recognition of apoptotic debris may play a key role in the etiology of anti-RNP autoimmunity, as in MCTD.
A population-based study from Olmsted County, Minnesota found that MCTD occurred in about 2 persons per 100,000 per year. Diagnosis was frequently delayed, with a median of 3.6 years elapsing from first symptom to fulfillment of diagnostic criteria.[23] A study in American Indian and Alaska Native adults found a prevalence of 6.4 per 100,000 (95% confidence interval 2.8-12.8).[24]
International
In an epidemiologic survey in Japan, MCTD has a reported prevalence of 2.7 cases per 100,000 population.[25] A population-based study in Norway found the point prevalence rate to be 3.8 cases per 100,000 adult population, with a female-to-male ratio of 3.3:1, and an annual incidence rate of 2.1 per million population.[26]
Mortality/morbidity
Long-term outcome studies have established pulmonary hypertension as the most common disease-related cause of death.[27] Immunoglobulin G (IgG) anticardiolipin antibodies are a marker for development of pulmonary hypertension. Infections are also a major cause of death.
Cardiac disease, most often pericarditis, is also common in MCTD patients, with prevalence estimates ranging from 13% to 65%. Other cardiac abnormalities include conduction abnormalities, pericardial effusion, mitral valve prolapse, diastolic dysfunction, and accelerated atherosclerosis. In three prospective studies with 13-15 years of follow-up, MCTD patients had an overall mortality rate of 10.4%, and 20% of these deaths were directly attributable to cardiac causes.[28]
Race-, sex-, and age-related variances
MCTD has been reported in all races. The clinical manifestations of MCTD are similar among various ethnic groups; however, one study observed ethnic differences in the frequency of end-organ involvement; gastroesophageal reflux, sclerodactyly, and malar rash were significantly more common in a White group than in a group consisting of 57% Hispanics, 29% Blacks, and 14% Whites.[29]
MCTD is far more common in females than in males. Estimates of the female-to-male ratio vary from approximately 3:1 to 16:1.[26, 25]
The onset of MCTD is typically at 15-25 years of age, but can occur at any age.
Most patients with MCTD have a favorable outcome. Cases of MCTD with typical clinical or serologic features occasionally evolve into scleroderma, SLE, or another rheumatic disease.
Pulmonary hypertension is the most common disease-associated cause of death. Careful monitoring and aggressive treatment may improve the outcome of pulmonary hypertension.
A long-term observational nationwide cohort study from Norway found that interstitial lung disease (ILD) was present in 41% of MCTD patients and progressed in 19% of patients across the observation period of a mean of 6.4 years.[30] The following were the strongest predictors of ILD progression:
Male sex (hazard ratio [HR] = 4.0, 95% confidence interval [CI]: 1.4, 11.5; P = 0.011)
Presence of anti-ro52 antibodies (HR = 3.5, 95% CI: 1.2, 10.2; P = 0.023)
Education about MCTD and its treatment is essential. Active participation in the decision-making process empowers patients in their own care. Education about disease decreases the risk of patients developing learned helplessness and improves functional outcomes. For patient education information, see What Is Mixed Connective Tissue Disease (MCTD)?.
Manifestations of mixed connective-tissue disease (MCTD) can be protean. The principal features of early MCTD are Raynaud phenomenon, inflammatory arthritis, swollen hands, and myalgia/myositis.[31] The following may be revealed by history or physical examination:
Raynaud phenomenon (96% cumulatively, 74% at presentation); see the image below
Arthralgia/arthritis (96% cumulatively, 68% at presentation)
Esophageal hypomotility (66% cumulatively, 9% at presentation)
Pulmonary dysfunction (66% cumulatively, rare at presentation)
Swollen hands (66% cumulatively, 45% at presentation)
Myositis (51% cumulatively, 2% at presentation)
Rash (53% cumulatively, 13% at presentation)
Leukopenia (53% cumulatively, 9% at presentation)
Sclerodactyly (49% cumulatively, 11% at presentation)
Pleuritis/pericarditis (43% cumulatively, 19% at presentation)
Pulmonary hypertension (23% cumulatively, rare at presentation)
View Image
Raynaud phenomenon is a common feature of mixed connective tissue disease.
The experience with a large single-center cohort of MCTD patients suggests that the following three clinical subclusters of MCTD manifestations may exist[32] :
Predominantly vascular manifestations, including Raynaud phenomenon, pulmonary hypertension, and antiphospholipid syndrome with thromboses (this group is at the greatest risk of mortality)
A polymyositislike picture, including interstitial lung disease, esophageal dysmotility, and myositis
Erosive polyarthritis with anti–cyclic citrullinated peptide (anti-CCP) antibodies and sclerodactyly
Physical examination is helpful in confirming or identifying features of MCTD. Seek the following features on examination:
Fever should prompt a careful search for infection; however, infection may be present in the absence of fever and is one of the primary disease-related causes of mortality and/or morbidity in MCTD; the use of corticosteroids and immunosuppressive agents further increases the risk of infection[33]
Corticosteroids may mask serious intra-abdominal processes, including appendicitis, vasculitis, pancreatitis, and bowel perforation
Cardiopulmonary symptoms or findings should prompt a careful evaluation for pulmonary hypertension
Capillary microscopy can assist in finding sclerodermatous-type nailfold changes
Severe Raynaud phenomenon may result in digital vascular infarcts and ulcerations
Pericarditis may be occult and can progress rapidly to cardiac tamponade
Trigeminal neuralgia is common in MCTD; it may be the initial manifestation and is often bilateral[34]
Secondary Sjögren syndrome occurs in 25% of patients with MCTD and may cause both ocular symptoms and oral dryness
Protein-losing gastroenteropathy is a rare feature of MCTD, but may be the initial manifestation of the disorder. Patients present with generalized edema, ascites, and pleural and pericardial effusions due to to hypoproteinemia from leakage of serum protein into the gastrointestinal tract.[35]
Laboratory studies used in the workup for mixed connective-tissue disorder (MCTD) are as follows:
Complete blood cell count (CBC)
Urinalysis
Routine blood chemistry
Indicators of acute phase response (erythrocyte sedimentation rate [ESR] or C-reactive protein [CRP])
Muscle enzymes if myositis is suspected clinically
Antinuclear antibodies
Anti–U1-ribonucleoprotein (RNP) antibodies
Amylase and lipase - To assess for pancreatitis if clinically indicated
Serologic indicators of pulmonary hypertension (such as brain natriuretic peptide [BNP]) if clinically indicated
Antibody study results
High-titer speckled pattern fluorescent antinuclear antibody (FANA) is typical of MCTD. However, the presence of FANA is not specific to MCTD.
Anti-RNP antibodies are required for diagnosis of MCTD. Titers are typically high. The presence of anti–U1-70 kd is characteristic of MCTD but not specific.
MCTD can enter sustained remission later in the clinical course. Anti-RNP autoantibodies typically become undetectable in patients in remission.
Other immune studies
Further results are as follows:
Antiphospholipid antibodies (including anticardiolipin antibodies and lupus anticoagulant) may be associated with pulmonary hypertension
Rheumatoid factor is frequently detected
Other lupus-specific antibodies (eg, anti–double-stranded DNA antibodies) are typically absent
Scleroderma-specific antibodies, including anticentromere, anti–Scl-70 (topoisomerase), and anti–PM-1 (Pm-Scl), are typically absent
C3 and C4 complement levels are more likely to be depleted in lupus than in MCTD
Imaging studies used in the workup of patients with MCTD include the following:
Chest radiography - To assess for infiltrates, effusion, or cardiomegaly (see the image below)
Echocardiography - In patients with effusion or chest pain, used to evaluate for pulmonary hypertension or valvular disease (exercise echocardiography may have increased sensitivity for identifying pulmonary hypertension)[37]
Ultrasonography/CT scanning - Used to evaluate abdominal pain (indicated for evidence of serositis, pancreatitis, or visceral perforation related to vasculitis)
MRI - Used to assess neuropsychiatric signs or symptoms
View Image
Chest radiograph in a patient with pulmonary hypertension reveals enlarged pulmonary arteries.
The following tests may be part of the workup for MCTD:
Pulmonary function testing is used to screen for declining diffusing capacity of lung for carbon monoxide (DLCO), possibly indicating pulmonary hypertension,[38] or to assess lung volumes and forced vital capacity to screen for suspicion/progression of interstitial lung disease.
Electrocardiogram and/or cardiac enzyme assays are helpful to assess for myocardial ischemia and myocarditis.
Infection, stroke, or neuropsychiatric manifestations may be monitored with cerebrospinal fluid (CFS) analysis.
The six-minute walk can be helpful to assess for cardiopulmonary insufficiency, possibly indicating pulmonary hypertension.[39]
Right-sided heart catheterization is the criterion standard for confirming the diagnosis of pulmonary hypertension
The overall goals of therapy for mixed connective-tissue disease (MCTD) are to control symptoms, to maintain function, and to reduce the risk of future disease consequences. Medical therapy targets control of disease activity in general and management of specific organ involvement (see Medication), while monitoring for and mitigating the risks of complications either of the condition itself (eg, pulmonary hypertension, interstitial lung disease) or of its treatment (eg, infection) (see Long-Term Monitoring).
Patients with MCTD may require hospital admission while undergoing assessment for suspected infection or complications related to disease or treatment. Admit patients to the appropriate service with rheumatology care, if available. Obtain subspecialty consultations as indicated.
Whenever possible, a rheumatologist experienced in diagnosis and treatment of the disease should co-manage all patients with mixed connective-tissue disease (MCTD). Consultation with other specialists or subspecialists may be indicated for the evaluation and/or treatment of specific aspects of disease, such as pulmonary hypertension, interstitial lung disease, gastroesophageal reflux, or acute ischemia due to Raynaud phenomenon.
Patients with MCTD that involves esophageal reflux, malabsorption, or other sclerodermatous-type bowel involvement may need special consideration with respect to diet. Because atherosclerotic heart disease remains a major risk in all patients, advocate a heart-healthy diet. However, no specific dietary manipulations have been demonstrated to be effective in treating MCTD.
High-dose omega-3 fatty acids have been reported to inhibit the production of pro-inflammatory prostaglandins, and clinical trials have reported benefits of dietary supplementation with omega-3 fatty acids in several inflammatory and autoimmune diseases.[40] Omega-3 fatty acids may thus have similar benefits to the long-term use of NSAIDs, with less risk of worsening of hypertension and less risk of gastrointestinal or kidney toxicity. However, omega-3 fatty acids at this dose have platelet inhibitory effects that can increase bleeding risk in susceptible patients.
Convincing data support the value of an active lifestyle and an exercise program tailored to the needs of patients with arthritis of various types.[41] This approach also appears to be appropriate in MCTD.
Scrupulous cold avoidance may help to reduce the risk of flares of Raynaud phenomenon.
Given that other inflammatory rheumatic diseases—including rheumatoid arthritis, lupus, and scleroderma—are reported to be independent risk factors for the development of atherosclerosis and related conditions, patients with MCTD may also be at increased risk for atherosclerosis. As in those other conditions (and modeled after recommendations developed for diabetes mellitus), more aggressive targets for blood pressure and cholesterol control may be appropriate.
Patients with stable disease and no recent changes in medications should be seen approximately every 2-4 months and undergo routine laboratory evaluation, including a complete blood cell count and chemistry studies. Patients with active disease are typically seen approximately every 3-6 weeks, depending on the severity of disease.
Recommendations for screening and early detection of pulmonary artery hypertension (PAH) associated with connective tissue diseases, including MCTD, have been published by the Scleroderma Foundation and Pulmonary Hypertension Association.[38] Although these guidelines do not recommend screening of asymptomatic patients with MCTD who lack features of scleroderma, the following studies are recommended for symptomatic patients:
Pulmonary function testing (spirometry with lung volumes) with single-breath diffusing capacity for carbon monoxide (DLCO)
Use of 6-minute walk stress echocardiography has also been proposed as a means of predicting the development of PAH in patients with connective tissue disorders.[39]
Abnormalities on noninvasive tests require confirmation with right heart catheterization, which remains the gold standard for diagnosis of PAH.
Therapeutic options in mixed connective-tissue disease (MCTD) include the following:
Arthritis/arthralgia can often be controlled with nonsteroidal anti-inflammatory drugs (NSAIDs); antimalarials (hydroxychloroquine); and, if needed, infrequent oral or intra-articular corticosteroid courses, typically at low dose.
Disease-modifying antirheumatic drug (DMARD) therapy is reserved for more refractory synovitis, particularly if showing features of erosive/deforming risk.
Proton pump inhibitors can control esophageal reflux symptoms.
In patients with Raynaud phenomenon, calcium channel blockers are used.
Phosphodiesterase inhibitors, endothelin receptor antagonists, or prostaglandins can be used for pulmonary hypertension.
In some cases, pulmonary hypertension in MCTD may also respond to aggressive immunosuppression, similar to that used in interstitial lung disease therapy.[42]
MCTD-related interstitial lung disease (ILD) is conventionally treated with corticosteroids in combination with steroid-sparing agents such as cyclophosphamide, azathioprine, or mycophenolate.[43] The RECITAL trial, which included patients with MCTD, found that rituximab was noninferior to cyclophosphamide for treatment of ILD, and was associated with fewer adverse effects.[44] The INBUILD trial, which included patients with MCTD, reported that treatment with the antifibrotic tyrosine kinase inhibitor nintedanib can significantly slow the annual rate of decline in forced vital capacity (FVC) in patients with progressive fibrosing ILDs.[45]
DMARDs used in the management of rheumatoid arthritis can be relevant in MCTD, in which a significant subset of patients have clinical manifestations that include those of chronic erosive polyarthritis, as is seen in rheumatoid arthritis. These drugs include the following:
Agents with immunosuppressive effects (eg, methotrexate, leflunomide)
Agents without immunosuppressive effects (sulfasalazine)
Biologics (anti-TNF, anti-IL-6, anti–T-cell second signaling [abetacept], anti–B-cell)
Targeted enzyme antagonists (JAK inhibitors)
Increasingly, targeted therapies effective against other rheumatic diseases are emerging that may find a place in therapy for the overlapping rheumatic features in MCTD patients. A notable example is belimumab, a B-cell survival inhibitor that is approved for use in lupus.
Clinical Context:
Used to treat musculoskeletal manifestation of MCTD, including arthralgia and arthritis. Inhibits inflammatory reactions and pain by decreasing cyclooxygenase (COX) activity, thus reducing prostaglandin synthesis.
Clinical Context:
Used to treat musculoskeletal manifestations of MCTD, including arthralgia and arthritis. Inhibits primarily cyclooxygenase-2 (COX-2), which is considered an inducible isoenzyme (ie, induced during pain and inflammatory stimuli). At therapeutic concentrations, celecoxib does not inhibit the COX-1 isoenzyme; thus, risk of gastrointestinal bleeding may be lower than with traditional NSAIDs. However, as with traditional NSAIDs, risk of serious cardiovascular events is elevated. Seek lowest dose of celecoxib for each patient.
These agents reduce pain and inflammation and allow for improvement in mobility and function. Adverse effects of this class include serious cardiovascular events; serious gastrointestinal events, including bleeding, ulceration, and gastric or intestinal perforation; and renal injury. NSAIDs may be associated with increased risk of aseptic meningitis in MCTD.
Clinical Context:
Inhibits gastric acid secretion by inhibition of the H+/K+ -ATPase enzyme system in gastric parietal cells. May be effective to treat reflux symptoms in MCTD. As in scleroderma, high dose PPI therapy may be needed. Other Proton Pump Inhibitors are used with similar clinical efficacy.
Esophageal reflux symptoms can be controlled effectively with these agents. Patients requiring long term PPIs should be co-managed with a gastroenterologist.
Clinical Context:
Antimalarials are believed to exert their major antirheumatic effect by inhibiting the function of endosomal Toll-like receptors (a group that includes TLRs -3, -7, -8, and -9).
Inhibits chemotaxis of eosinophils and locomotion of neutrophils, and impairs complement-dependent antigen-antibody reactions.
Hydroxychloroquine sulfate 200 mg is equivalent to 155 mg hydroxychloroquine base and 250 mg chloroquine phosphate.
Mild MCTD can often be controlled with hydroxychloroquine. Hydroxychloroquine may also help prevent disease flares. Though often well tolerated, antimalarials can cause anemia in G6PD-deficient patients, and chronic use can lead to retinal toxicity in a modest percentage of patients. Regular ophthalmomogy follow-up is recommended for long-term users.
These agents are reserved for more active or severe disease. They are used in moderate to high doses for major organ involvement. They are often used in combination with other drugs. While helpful for their ability to have fast-acting immunosuppressive/anti-inflammatory effects in the treatment of severe flares, corticosteroids have a multitude of potential adverse effects with long-term use. As in scleroderma, high-dose corticosteroids may be a risk factor for the development of scleroderma renal crisis in MCTD patients.
Clinical Context:
Promotes selective smooth-muscle relaxation in lung vasculature, possibly by inhibiting phosphodiesterase type 5 (PDE-5). This reduces pulmonary arterial pressure and increases cardiac output.
Phosphodiesterase inhibitors can ameliorate symptoms of pulmonary hypertension and Raynaud phenomenon in patients with MCTD. These agents may not be as durable as other drug classes in improving pulmonary hypertension, but the adverse effect profile of phosphodiesterase inhibitors is often more favorable than that of prostaglandin or anti-endothelin therapies.
Clinical Context:
Endothelin receptor antagonist indicated for pulmonary arterial hypertension in patients with World Health Organization (WHO) class II or III symptoms. Improves exercise ability and decreases progression of clinical symptoms. Inhibits vessel constriction and blood pressure elevation by competitively binding to endothelin-1 receptors ETA and ETB in endothelium and vascular smooth muscle. This leads to significant increase in cardiac index associated with significant reduction in pulmonary artery pressure, pulmonary vascular resistance, and mean right atrial pressure. Because of the risks of hepatic injury and teratogenic potential, available only through the Letairis Education and Access Program (LEAP). Prescribers and pharmacies must register with LEAP in order to prescribe and dispense. For more information, see http://www.letairis.com or call (866) 664-LEAP (5327).
These agents may be helpful for managing pulmonary hypertension in patients with MCTD. The risk of liver toxicity with endothelin receptor antagonists dictates that these drugs must be prescribed by experts. They are contraindicated in pregnancy.
Clinical Context:
Strong vasodilator of all vascular beds. May decrease thrombogenesis and platelet clumping in the lungs by inhibiting platelet aggregation.
These agents may be useful for managing pulmonary hypertension in patients with MCTD, although dose titration and administration should be managed by an expert in this drug.
Clinical Context:
Chemically related to nitrogen mustards. As an alkylating agent, the mechanism of action of the active metabolites may involve cross-linking of DNA, which may interfere with growth of normal and neoplastic cells.
Administered as monthly IV infusion or, less commonly, as daily PO medication for severe MCTD.
Cyclophosphamide has serious short- and long-term adverse effect risks, and should be prescribed by an expert in its use.
Clinical Context:
This purine antagonist inhibits the proliferation of activated lymphocytes. It is contraindicated in pregnancy. It has been found to have effectiveness often similar to cyclophosphamide in the management of rheumatic diseases, with a somewhat less extensive adverse effect profile; for example, while also highly immunosuppressive, mycophenolate does not share cyclophosphamide's risk of bladder toxicity.
What is mixed connective-tissue disorder (MCTD)?What is the pathophysiology of mixed connective-tissue disorder (MCTD)?What causes mixed connective-tissue disorder (MCTD)?What is the US prevalence of mixed connective-tissue disorder (MCTD)?What is the global prevalence of mixed connective-tissue disorder (MCTD)?What is the morbidity and mortality associated with mixed connective-tissue disorder (MCTD)?What are the racial predilections of mixed connective-tissue disorder (MCTD)?What are the sexual predilections of mixed connective-tissue disorder (MCTD)?Which age groups have the highest prevalence of mixed connective-tissue disorder (MCTD)?What is the prognosis of mixed connective-tissue disorder (MCTD)?Which clinical history findings are characteristic of mixed connective-tissue disorder (MCTD)?Which physical findings are characteristic of mixed connective-tissue disorder (MCTD)?What are the diagnostic criteria for mixed connective-tissue disorder (MCTD)?Which conditions are included in the differential diagnoses of mixed connective-tissue disorder (MCTD)?What are the differential diagnoses for Mixed Connective-Tissue Disease (MCTD)?What is the role of lab tests in the workup of mixed connective-tissue disorder (MCTD)?Which immune studies are performed in the workup of mixed connective-tissue disorder (MCTD)?What is the role of imaging studies in the workup of mixed connective-tissue disorder (MCTD)?What is the role of cardiac tests in the workup of mixed connective-tissue disorder (MCTD)?What is the role of CFS analysis in the workup of mixed connective-tissue disorder (MCTD)?What is the role of a six-minute walk test in the workup of mixed connective-tissue disorder (MCTD)?What is the role of pulmonary function testing in the workup of mixed connective-tissue disorder (MCTD)?How is hypertension assessed in the workup of mixed connective-tissue disorder (MCTD)?How is mixed connective-tissue disorder (MCTD) treated?Which specialist consultations are beneficial to patients with mixed connective-tissue disorder (MCTD)?Which dietary modifications are used in the treatment of mixed connective-tissue disorder (MCTD)?Which activity modifications are used in the treatment of mixed connective-tissue disorder (MCTD)?How is mixed connective-tissue disorder (MCTD) prevented?What is the role of medications in the treatment of mixed connective-tissue disorder (MCTD)?Which medications in the drug class Immunosuppressive agents are used in the treatment of Mixed Connective-Tissue Disease (MCTD)?Which medications in the drug class Prostaglandins are used in the treatment of Mixed Connective-Tissue Disease (MCTD)?Which medications in the drug class Endothelin receptor antagonists are used in the treatment of Mixed Connective-Tissue Disease (MCTD)?Which medications in the drug class Phosphodiesterase (type 5) enzyme inhibitor are used in the treatment of Mixed Connective-Tissue Disease (MCTD)?Which medications in the drug class Corticosteroids are used in the treatment of Mixed Connective-Tissue Disease (MCTD)?Which medications in the drug class Antimalarial agents are used in the treatment of Mixed Connective-Tissue Disease (MCTD)?Which medications in the drug class Proton pump inhibitors are used in the treatment of Mixed Connective-Tissue Disease (MCTD)?Which medications in the drug class Nonsteroidal anti-inflammatory drugs (NSAIDs) are used in the treatment of Mixed Connective-Tissue Disease (MCTD)?Which medications in the drug class Pulmonary, Tyrosine Kinase Inhibitors are used in the treatment of Mixed Connective-Tissue Disease (MCTD)?
Eric L Greidinger, MD, Associate Professor, Department of Medicine, Division of Rheumatology and Immunology, University of Miami, Leonard M Miller School of Medicine, Miami Veterans Affairs Medical Center
Disclosure: Received research grant from: Corbus Pharmaceuticals; Eli Lilly & Company; Horizon Pharmaceuticals; INFLARX GBMH, Mitsubishi Pharmaceuticals, Reatta Pharmaceuticals, Swedish Orphan Biovitrum AB.
Specialty Editors
Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Received salary from Medscape for employment. for: Medscape.
Elliot Goldberg, MD, Dean of the Western Pennsylvania Clinical Campus, Professor, Department of Medicine, Lewis Katz School of Medicine at Temple University
Disclosure: Nothing to disclose.
Chief Editor
Herbert S Diamond, MD, Visiting Professor of Medicine, Division of Rheumatology, State University of New York Downstate Medical Center; Chairman Emeritus, Department of Internal Medicine, Western Pennsylvania Hospital
Disclosure: Nothing to disclose.
Additional Contributors
Bryan L Martin, DO, Associate Dean for Graduate Medical Education, Designated Institutional Official, Associate Medical Director, Director, Allergy Immunology Program, Professor of Medicine and Pediatrics, Ohio State University College of Medicine
Disclosure: Nothing to disclose.
Acknowledgements
Robert W Hoffman, DO, FACP, FACR Chief, Division of Rheumatology and Immunology, Professor, Departments of Medicine and Microbiology & Immunology, University of Miami, Leonard M Miller School of Medicine
Robert W Hoffman, DO, FACP, FACR is a member of the following medical societies: American Association for the Advancement of Science, American Association of Immunologists, American College of Physicians, American College of Rheumatology, and Clinical Immunology Society
About Physical Activity and Arthritis. U.S. Centers for Disease Control and Prevention. Available at https://www.cdc.gov/arthritis/prevention/index.html. Accessed: October 31, 2024.
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