Mixed Connective Tissue Disease (MCTD)

Raynaud syndrome Raynaud Syndrome Raynaud syndrome is vasospasm of parts of the hand in response to cold or emotional stress, causing reversible discomfort and color changes (pallor, cyanosis, erythema, or a combination) in... read more (Raynaud phenomenon) may precede other manifestations by years. Frequently, the first manifestations resemble early SLE Systemic Lupus Erythematosus (SLE) Systemic lupus erythematosus is a chronic, multisystem, inflammatory disorder of autoimmune etiology, occurring predominantly in young women. Common manifestations may include arthralgias and... read more , systemic sclerosis Systemic Sclerosis Systemic sclerosis is a rare chronic disease of unknown cause characterized by diffuse fibrosis and vascular abnormalities in the skin, joints, and internal organs (especially the esophagus... read more , polymyositis Autoimmune Myositis Autoimmune myositis is characterized by inflammatory and degenerative changes in the muscles (polymyositis, necrotizing immune-mediated myopathy) or in the skin and muscles (dermatomyositis)... read more , or even rheumatoid arthritis Rheumatoid Arthritis (RA) Rheumatoid arthritis is a chronic systemic autoimmune disease that primarily involves the joints. Rheumatoid arthritis causes damage mediated by cytokines, chemokines, and metalloproteases.... read more . Many patients appear to have an undifferentiated connective tissue disease initially. The disease manifestations may progress and become widespread, and the clinical pattern changes over time.

Initial, diffuse swelling of the hands is typical but not universal. Skin findings include lupus or dermatomyositis-like rashes. Diffuse systemic sclerosis–like skin changes and ischemic necrosis or ulceration of the fingertips may develop.

Almost all patients have polyarthralgias, and 75% have frank arthritis. Often the arthritis is nondeforming, but erosive changes and deformities similar to those in rheumatoid arthritis (eg, boutonnière Boutonnière Deformity A boutonnière deformity consists of flexion of the proximal interphalangeal (PIP) joint accompanied by hyperextension of the distal interphalangeal (DIP) joint. (See also Overview and Evaluation... read more and swan-neck deformities Swan-Neck Deformity A swan-neck deformity consists of hyperextension of the proximal interphalangeal (PIP) joint, flexion of the distal interphalangeal (DIP) joint, and sometimes flexion of the metacarpophalangeal... read more ) may be present. Proximal muscle weakness with or without tenderness is common, typically among people who have elevated levels of muscle enzymes (eg, creatine kinase).

Renal involvement (most commonly membranous nephropathy Membranous Nephropathy Membranous nephropathy is deposition of immune complexes on the glomerular basement membrane (GBM) with GBM thickening. Cause is usually unknown, although secondary causes include medications... read more ) occurs in about 25% of patients and is typically mild; severe involvement, with morbidity or mortality, is atypical for MCTD. The lungs are affected in up to 75% of patients with MCTD. Interstitial lung disease Overview of Interstitial Lung Disease Interstitial lung diseases are a heterogeneous group of disorders characterized by alveolar septal thickening, fibroblast proliferation, collagen deposition, and, if the process remains unchecked... read more is the most common lung manifestation; pulmonary hypertension Pulmonary Hypertension Pulmonary hypertension is increased pressure in the pulmonary circulation. It has many secondary causes; some cases are idiopathic. In pulmonary hypertension, pulmonary vessels may become constricted... read more is a major cause of death. Heart failure Heart Failure (HF) Heart failure (HF) is a syndrome of ventricular dysfunction. Left ventricular (LV) failure causes shortness of breath and fatigue, and right ventricular (RV) failure causes peripheral and abdominal... read more can occur. Sjögren syndrome Sjögren Syndrome Sjögren syndrome is a relatively common chronic, autoimmune, systemic, inflammatory disorder of unknown cause. It is characterized by dryness of the mouth, eyes, and other mucous membranes ... read more may develop.

MCTD should be suspected when additional overlapping features are present in patients appearing to have systemic lupus erythematosus Diagnosis Systemic lupus erythematosus is a chronic, multisystem, inflammatory disorder of autoimmune etiology, occurring predominantly in young women. Common manifestations may include arthralgias and... read more (SLE), systemic sclerosis Systemic Sclerosis Systemic sclerosis is a rare chronic disease of unknown cause characterized by diffuse fibrosis and vascular abnormalities in the skin, joints, and internal organs (especially the esophagus... read more , or polymyositis Autoimmune Myositis Autoimmune myositis is characterized by inflammatory and degenerative changes in the muscles (polymyositis, necrotizing immune-mediated myopathy) or in the skin and muscles (dermatomyositis)... read more .

Tests for ANA and antibody to U1 RNP antigen are done first. Almost all patients have high titers of fluorescent ANA that produce a speckled pattern. Antibodies to U1 RNP are present, usually at very high titers. Antibodies to the ribonuclease-resistant Sm component of extractable nuclear antigen (anti-Sm antibodies) and to double-stranded DNA (negative in MCTD by definition) are measured to exclude other disorders. The presence of anti-RNP antibodies is not sufficient to make the diagnosis of MCTD; typical clinical findings are also required.

Rheumatoid factors are frequently present, and titers may be high. The erythrocyte sedimentation rate is frequently elevated.

Pulmonary hypertension Diagnosis Pulmonary hypertension is increased pressure in the pulmonary circulation. It has many secondary causes; some cases are idiopathic. In pulmonary hypertension, pulmonary vessels may become constricted... read more should be detected as early as possible with pulmonary function testing and echocardiography. Further evaluation depends on symptoms and signs; manifestations of myositis, renal involvement, or pulmonary involvement prompt tests of those organs.

Creatine kinase, MRI, electromyogram, or muscle biopsy can help confirm the presence of myositis as part of MCTD.

The overall 10-year survival rate is about 80%, but prognosis depends largely on which manifestations predominate. Patients with features of systemic sclerosis and polymyositis have a worse prognosis. Patients are at increased risk of atherosclerosis Atherosclerosis Atherosclerosis is characterized by patchy intimal plaques (atheromas) that encroach on the lumen of medium-sized and large arteries. The plaques contain lipids, inflammatory cells, smooth muscle... read more . Causes of death include pulmonary hypertension, renal failure, myocardial infarction, colonic perforation, disseminated infection, and cerebral hemorrhage. Some patients have sustained remissions for many years without treatment.

General management and initial drug therapy are tailored to the specific clinical problem and are similar to those of SLE Treatment Systemic lupus erythematosus is a chronic, multisystem, inflammatory disorder of autoimmune etiology, occurring predominantly in young women. Common manifestations may include arthralgias and... read more or the dominant clinical phenotype. Most patients with moderate or severe disease respond to corticosteroids, particularly if treated early, and other immunosuppressants (eg, methotrexate, azathioprine, mycophenolate mofetil). Mild disease is often controlled by NSAIDs, antimalarials (eg, hydroxychloroquine, chloroquine), or sometimes low-dose corticosteroids. Severe major organ involvement usually requires higher doses of corticosteroids (eg, oral prednisone 1 mg/kg once a day) and additional immunosuppressants. If patients develop features of myositis Autoimmune Myositis Autoimmune myositis is characterized by inflammatory and degenerative changes in the muscles (polymyositis, necrotizing immune-mediated myopathy) or in the skin and muscles (dermatomyositis)... read more or systemic sclerosis Systemic Sclerosis Systemic sclerosis is a rare chronic disease of unknown cause characterized by diffuse fibrosis and vascular abnormalities in the skin, joints, and internal organs (especially the esophagus... read more , treatment is as for those diseases.

Patients with Raynaud syndrome Raynaud Syndrome Raynaud syndrome is vasospasm of parts of the hand in response to cold or emotional stress, causing reversible discomfort and color changes (pallor, cyanosis, erythema, or a combination) in... read more should be treated based on their symptoms and as tolerated by their blood pressure with calcium channel blockers (eg, nifedipine) and phosphodiesterase inhibitors (eg, tadalafil).

All patients should be closely monitored for atherosclerosis Diagnosis Atherosclerosis is characterized by patchy intimal plaques (atheromas) that encroach on the lumen of medium-sized and large arteries. The plaques contain lipids, inflammatory cells, smooth muscle... read more . Patients on long-term corticosteroid therapy should receive osteoporosis prophylaxis Prevention Osteoporosis is a progressive metabolic bone disease that decreases bone mineral density (bone mass per unit volume), with deterioration of bone structure. Skeletal weakness leads to fractures... read more . If combination immunosuppressive therapy is used, patients should be given prophylaxis for opportunistic infections, such as Pneumocystis jirovecii (see prevention of Pneumocystis jirovecii pneumonia Prevention Pneumocystis jirovecii is a common cause of pneumonia in immunosuppressed patients, especially in those infected with human immunodeficiency virus (HIV) and in those receiving systemic... read more ), and vaccines against common infections (eg, streptococcal pneumonia Overview of Pneumonia Pneumonia is acute inflammation of the lungs caused by infection. Initial diagnosis is usually based on chest x-ray and clinical findings. Causes, symptoms, treatment, preventive measures, and... read more , influenza Influenza Influenza is a viral respiratory infection causing fever, coryza, cough, headache, and malaise. Mortality is possible during seasonal epidemics, particularly among high-risk patients (eg, those... read more , COVID-19 COVID-19 Vaccine COVID-19 vaccines provide protection against COVID-19, the disease caused by infection with the SARS-CoV-2 virus. Vaccination is the most effective strategy to prevent severe illness and death... read more ).

Some experts encourage screening for pulmonary hypertension Diagnosis Pulmonary hypertension is increased pressure in the pulmonary circulation. It has many secondary causes; some cases are idiopathic. In pulmonary hypertension, pulmonary vessels may become constricted... read more on a periodic basis with pulmonary function testing and/or echocardiography every 1 to 2 years, depending on symptoms.