Overview of the disease
It is a group of autoimmune-related diseases involving multiple systems and organs, with a high degree of heterogeneity. In mild cases, fever and malaise may occur, while in severe cases, systemic organ failure may occur. The cause of the disease is unknown, and it is closely related to genetic factors, environmental factors, and abnormalities in immune function.
Definition
Connective tissue disorders are a group of immune system-related diseases with multi-system and multi-organ involvement, in which any connective tissue in the body is the primary target of the pathology.
Narrowly defined connective tissue disorders include systemic lupus erythematosus, dry syndrome, inflammatory myopathies (dermatomyositis/polymyositis), scleroderma (systemic sclerosis), antiphospholipid syndrome, mixed connective tissue disorders, and undifferentiated connective tissue disorders.
Broader connective tissue diseases also include rheumatoid arthritis and various systemic vasculitides.
This article refers only to connective tissue diseases in the narrow sense.
Incidence
The incidence and prevalence of connective tissue diseases vary by region, race, and gender. Overall, the prevalence is higher in women than in men and is more common in women between the ages of 20 and 40 years.
Diseases such as systemic lupus erythematosus (SLE) and desiccation syndrome are all most common in adult women.
People with a family history of the disease and those with immune system abnormalities are at higher risk.
Causes
Connective tissue diseases are a group of autoimmune disorders that include systemic lupus erythematosus, dry syndrome, inflammatory myopathies (dermatomyositis/polymyositis), systemic sclerosis, antiphospholipid syndromes, mixed connective tissue disorders, and undifferentiated connective tissue disorders.
The causes of these diseases are complex and varied, and some are unknown. They are usually closely related to genetic factors, environmental factors, hormone levels, and immune dysfunction.
Causes
Genetic factors
Connective tissue diseases have a tendency to run in families, suggesting that they are related to genetic factors.
Environmental factors
Bacterial, fungal, and viral infections cause damage to connective tissue, which can lead to the development of connective tissue diseases such as lupus erythematosus.
Hydralazine, procainamide, isoniazid, etc. can cause drug-associated lupus erythematosus.
Long-term exposure to chemicals, catheters, artificial joints and orthopedic surgery metal fixation brackets and other medical implants, long-term smoking and alcoholism, exposure to sunlight, ultraviolet rays or radiation, long-term exposure to heavily polluted air, chemical materials or other toxins, and other environmental factors that act on susceptible individuals, causing immune disorders, can lead to the development of connective tissue disease.
Hormone Levels
Connective tissue disease occurs in adult women, and some patients may experience a relapse or aggravation of the disease during pregnancy, suggesting that changes in sex hormone levels and an imbalance in the ratio of estrogen to progesterone may be related to the development of the disease.
Abnormal immune function
Abnormalities in the regulatory system of immune function induce the production of autoantibodies and the release of inflammatory mediators, which can lead to a disruption of the immune system and an attack on the normal connective tissues of the body, resulting in the corresponding symptoms.
Symptoms
Connective tissue diseases, including systemic lupus erythematosus, sclerosis, dermatomyositis/polymyositis, and desiccation syndrome, can affect the skin, joints and muscles, as well as multiple organs such as the kidneys, heart, lungs, and liver, and multiple systems such as the blood system and the nervous system, and the symptoms vary from disease to disease.
Main Symptoms
Systemic Symptoms
Systemic symptoms, such as generalized weakness or fever, night sweats, poor appetite and weight loss, can be seen in systemic lupus erythematosus and inflammatory myelopathy.
Unexplained fever may be the most prominent clinical manifestation and the first symptom of diffuse connective tissue disease, and prolonged low-grade fever is more common.
Bone, Joint, and Muscle Symptoms
Joint pain and stiffness is one of the early symptoms in almost all patients, and may also be characterized by joint erythema, weakness, and myalgia, but most patients do not have definite muscle weakness.
Patients with SLE can develop aseptic osteonecrosis, with femoral head necrosis being the most common. Scleroderma may manifest as osteoporosis and sclerosis.
Skin and mucosal damage
Raynaud’s phenomenon is one of the early manifestations of systemic scleroderma, mixed connective tissue disease, etc. It is manifested as discoloration of the fingertips of the extremities upon contact with cold water, intermittent whitening, purplish, and reddening, often accompanied by swelling of the fingers or swelling of the whole hand.
Lupus erythematosus, dermatomyositis, scleroderma, and desiccation syndrome may manifest as a rash, especially erythema of the cheeks and discoid erythema in a butterfly-shaped distribution, which are characteristic changes of systemic lupus erythematosus.
Typical lesions of dermatomyositis include periorbital edematous violet erythema, erythema of the V-zone of the anterior chest, erythema of the back of the neck and neck (shawl sign), Gaucher’s rash/Gaucher’s sign (erythema of the proximal interphalangeal joints, metacarpophalangeal joints, elbows, and extensor measurements of the knees), and perinail erythema.
Scleroderma can present with dilated capillaries.
Dry syndrome may present with skin purpura of the lower extremities due to hyperglobulinemia.
Mucosal damage includes buccal mucosal ulcers, which can occur in systemic lupus erythematosus; dry mouth and dry eyes are seen primarily in dry syndrome.
Ocular symptoms
Patients with systemic lupus erythematosus and dry syndrome may have conjunctivitis, uveitis, fundus changes, and optic neuropathy, which are mainly characterized by decreased visual acuity, eye pain, tearing, and dry eyes.
Cardiac manifestations
Systemic lupus erythematosus, dermatomyositis/polymyositis, etc. may have circulatory system involvement, which may be manifested as chest pain and palpitations with dyspnea. Pericarditis is the most common clinical manifestation of cardiac involvement, and cardiomyopathy, cardiac valvular disease, and coronary artery disease can also be seen.
Pulmonary manifestations
The main symptoms of lung involvement in patients with systemic lupus erythematosus, scleroderma, and dermatomyositis/polymyositis are dry cough, dyspnea, and pleuritic chest pain manifesting as pleurisy/pleural effusion, interstitial pneumonia, and pulmonary hypertension, and pulmonary embolism can be seen in antiphospholipid syndrome.
Renal manifestations
Renal lesions in patients with SLE, dry syndrome, and scleroderma are glomerulonephritis (lupus nephritis), tubular acidosis (tubulointerstitial lesions), and renal microangiopathy (scleroderma renal crisis).
Patients with SLE may also present with urinary frequency, urgency, and pain (lupus cystitis), as well as dilatation of the upper ureter and hydronephrosis.
The main manifestations are hematuria, proteinuria, generalized edema, hypertension and renal insufficiency.
Digestive tract manifestations
Digestive system involvement in SLE, systemic scleroderma, and inflammatory myelopathy is manifested by abdominal pain, diarrhea, gagging after eating, and dysphagia.
Systemic lupus erythematosus, dry syndrome, and limited scleroderma may present with liver lesions, including hepatocellular damage (hepatitis) and/or cholestasis (cholangitis).
Neurologic manifestations
Central nervous system involvement in patients with SLE and dry syndrome manifests as migraine headaches, personality changes, memory loss, seizures, impaired consciousness, stroke, myelitis, and schizophrenia. Headache is a common symptom and most may be vascular.
Secondary vasculitis in SLE can lead to single or multiple mononeuritis.
Hematologic manifestations
Hematocrit is one of the common manifestations in patients with SLE, dry syndrome, and antiphospholipid syndrome, with leukopenia, autoimmune hemolytic anemia, and immune thrombocytopenia, predominantly of the lymphocytic lineage, being the most typical and common.
Patients with SLE may present with multiple superficial lymph node enlargement and splenomegaly.
Venous thrombosis and/or arterial thromboembolic events are common in patients with antiphospholipid syndrome and are usually recurrent.
Vascular manifestations
Gangrene of the extremities can occur in SLE secondary to vasculitis and in severe vascular lesions in systemic scleroderma, manifesting as localized pain, decreased skin temperature, and gangrene.
Medical treatment
Department of Medicine
Rheumatology
Joint discomfort, swelling, heat and pain, etc. Prompt consultation is recommended.
Nephrology
Symptoms such as hematuria (blood in the naked eye) and pain in the lower back suggest prompt medical attention.
Dermatology
Consultation is recommended when multiple skin rashes occur.
Neurology
When symptoms such as abnormal sensation and weakness in the limbs, headache, epilepsy, or stroke occur, timely consultation is recommended.
Preparation for medical treatment
Preparation for consultation: registration, preparation of documents, common problems
Consultation Tips
Patients with joint pain and difficulty walking are advised to be accompanied by family members.
Avoid self-medication.
Preparation List
Symptom list
Particular attention should be paid to the time of onset of symptoms, special manifestations, etc.
Are there any skin abnormalities, such as erythema of the skin?
Are there joint problems, such as joint pain, joint swelling, and morning stiffness?
Is there a chronic, recurrent fever? What is the highest degree? Is there any regularity?
Is there any weakness around the body?
Medical History Checklist
Is there a family history of lupus erythematosus, dry syndrome, etc.?
Is there arthritis?
Has there ever been a diagnosis of thrombocytopenic purpura, or anemia?
Any recent infectious diseases (e.g., malaria, tuberculosis, typhoid, etc.)?
Are there any cases of high blood pressure or diabetes?
Checklist
Test results of the last six months, which can be brought to the doctor’s office
General laboratory tests: routine blood test, urine test, blood biochemistry, blood sedimentation, C-reactive protein, serum immunoglobulin, complement, etc.
Specialized laboratory tests: autoantibodies (anti-nuclear antibody, anti-ds-DNA antibody, anti-Sm antibody, anti-rRNP antibody, anti-RNP antibody, anti-SSA antibody, anti-SSB antibody, anti-cardiolipin antibody, anti-B2 glycoprotein 1 antibody, lupus anticoagulant, etc.) tests.
Imaging examination: ultrasound, CT, X-ray, MRI examination, etc.
Other tests: pathologic examination, such as renal puncture biopsy pathology, muscle biopsy pathology, etc.
Medication list
Medication used in the last three months, if available in boxes or packages, carry with you to the doctor’s office
Non-steroidal anti-inflammatory drugs: aspirin, ibuprofen, etc.
Glucocorticoids: prednisone, methylprednisolone, etc.
Immunosuppressants: leflunomide, azathioprine, cyclophosphamide, tacrolimus, etc.
Biological agents: rituximab, abatacept, belimumab, etc.
Diagnosis
Diagnosis is based on
Medical history
Family history of lupus erythematosus, dry syndrome, etc.
Recent infectious diseases.
Suffers from hypertension, diabetes.
Suffers from arthritis.
Suffers from thrombocytopenic purpura.
Have hemolytic anemia.
Have nephritis.
Suffers from mental illness.
Clinical manifestations
Systemic symptoms: persistent fever.
Bones, joints, and muscles: joint pain, osteonecrosis, muscle pain, etc.
Skin and mucous membranes: discoloration of fingertips after contact with cold water, rash, skin and mucous membrane ulcers, etc.
Eyes: loss of vision, eye pain, tearing, dry eyes, and other symptoms.
Lung manifestations: dry cough, dyspnea, pleuritic chest pain, etc.
Cardiac manifestations: chest pain with dyspnea.
Gastrointestinal manifestations: abdominal pain, choking after eating and dysphagia, etc.
Kidney manifestations: hematuria, proteinuria, edema, etc.
Neurological manifestations: headache, memory loss or mild cognitive impairment.
Hematologic manifestations: thrombocytopenia, anemia, and leukopenia predominantly of the lymphocyte lineage.
General Laboratory Tests
Routine blood tests
Find out if the patient has developed hematologic impairment.
The presence of leukopenia, erythrocytopenia and thrombocytopenia may indicate hematologic damage and may assist in the diagnosis of connective tissue diseases such as active systemic lupus erythematosus and dry syndrome.
Urine examination
To find out whether the patient has kidney damage.
The presence of red blood cells and proteins in the urine often suggests kidney damage and may assist in the diagnosis of connective tissue diseases such as SLE. Active urinary sediment and 24-hour urine protein quantification can help determine the activity of SLE.
Blood biochemistry
It mainly includes liver and kidney function, blood glucose, blood lipids, electrolytes, blood sedimentation, C-reactive protein, immunoglobulin and complement.
Find out whether the patient has inflammation, myositis, liver damage, kidney injury.
If serum aminotransferase is elevated, blood sedimentation is increased, or C-reactive protein is increased, it can indicate the occurrence of inflammatory diseases and assist in the diagnosis of connective tissue diseases such as polymyositis, dry syndrome, and systemic lupus erythematosus.
If the blood creatinine, blood glucose, blood lipids increase, or immunoglobulin and complement abnormalities, it may suggest renal lesions or diabetes, hyperlipidemia and other diseases, and may assist in the diagnosis of systemic lupus erythematosus, dry syndrome, scleroderma and other connective tissue diseases.
Specialized Laboratory Tests
Autoantibody test, including anti-nuclear antibody, anti-ds-DNA antibody, anti-Sm antibody, anti-rRNP antibody, anti-RNP antibody, anti-SSA antibody, anti-SSB antibody, anti-cardiolipin antibody, anti-B2 glycoprotein 1 antibody, and lupus anticoagulant. The presence of specific autoantibodies can be observed by autoantibody tests.
Antinuclear antibodies are screening antibodies for connective tissue disease. If the result suggests an elevated titer of antinuclear antibodies, it suggests the possibility of connective tissue disease.
Anti-dsDNA positivity is highly specific for SLE, is pathogenic and correlates with disease activity; anti-Sm positivity is a marker antibody for SLE.
Anti-rRNP (ribosomal P protein) antibodies are most often seen in SLE and are associated with neuropsychiatric symptoms; anti-Scl-70 antibodies are specific for systemic sclerosis; anti-Jo-1 antibodies are specific for dermatomyositis/polymyositis.
Anti-RNP, anti-SSA, and anti-SSB antibodies can be seen in a variety of connective tissue diseases; anti-RNP antibodies are associated with Raynaud’s phenomenon, and positive anti-SSA and anti-SSB antibodies are helpful in the diagnosis of dry syndrome.
Anti-cardiolipin antibodies, anti-B2 glycoprotein 1 antibodies, and positive lupus anticoagulant are associated with thromboembolic events and morbid pregnancies (habitual abortion, intrauterine death), suggesting the possibility of antiphospholipid syndrome, which may be accompanied by elevated rheumatoid factor titers in some patients.
Imaging
Ultrasound
Ultrasound can help determine the thickness of the joint capsule, synovium, and effusion.
Thickening of the joint capsule, synovial thickness, or the presence of fluid may help in the diagnosis of diseases such as polymyositis.
X-ray
X-rays can be used to visualize lesions in joints, bones, or other organs.
Examination that reveals soft tissue swelling, bone damage, or fluid in the pericardium or pleural cavity can help in the diagnosis of connective tissue diseases such as inflammatory myopathies.
CT
Can be used to look for lesions in the joints, brain, or other organs.
If the examination reveals bone destruction, infarctive or hemorrhagic lesions in the brain, etc., it helps in the early diagnosis and treatment of connective tissue diseases such as systemic lupus erythematosus and inflammatory myopathies.
MRI examination
It can be used to observe damage to joints and organs as well as lesions.
If the examination result suggests synovial membrane thickening, bone marrow edema and slight joint surface erosion, diffuse or focal edema in muscles, or hemorrhage and other lesions in organs, it can assist in the diagnosis of connective tissue diseases such as polymyositis and systemic lupus erythematosus.
Pathologic examination
Arthrocentesis biopsy can be used to see if the patient has developed an infection. If the test results suggest that a pathogenic infection has occurred, it can help to clarify the cause of the disease.
Renal puncture biopsy pathology helps to clarify the type (glomerulonephritis, interstitial tubulopathy, renal microangiopathy), activity, and severity of kidney damage.
Muscle biopsy pathology helps in the diagnosis and differential diagnosis of inflammatory myopathies.
Differential diagnosis
Osteoarthritis
Similarities: Both present with joint pain and stiffness.
Differences: Osteoarthritis is more common in the elderly, mainly in the spine and joints (knees, hips, distal hands and proximal interphalangeal joints), and is usually caused by fluid accumulation after exertion, which can be differentiated by auxiliary tests.
Systemic vasculitis
Similarities: Systemic symptoms such as fatigue, fever, joint and muscle pain, weight loss, and multi-organ and multi-system damage may occur.
Differences: The pathological findings of systemic vasculitis may suggest the presence of fibrin deposition, fibrous degeneration, endothelial necrosis, etc. In some patients, ANCA is found in the serum. Some patients are positive for ANCA in serum, and ANA is usually negative.
Dry mouth and eyes caused by other diseases
Similarity: Both may present with dry mouth and dry eyes.
Differences: mainly differentiated from dry syndrome, which can be identified by history.
Treatment
Aim of treatment: Relieve symptoms, control disease progression, prevent and minimize complications.
Treatment principle: Connective tissue disease is mostly a chronic disease, so it is necessary to make a clear diagnosis, assess the activity and severity of the disease, and carry out standardized treatment. Treatment should be individualized and based on symptomatic drug therapy.
General treatment
Patients with Raynaud’s phenomenon, photosensitivity and other manifestations should pay attention to keep warm.
Patients with skin rashes and photosensitivity should pay attention to avoiding light.
Pay attention to the selection of appropriate exercise, activity training should emphasize the functional activities of the joints, can be given to joint rehabilitation training, physiotherapy and so on.
Medication
Non-steroidal anti-inflammatory drugs
Suitable for fever and arthritis. They can control body temperature and reduce joint pain.
Commonly used drugs include aspirin, ibuprofen and so on.
Adverse drug reactions include abdominal discomfort, vomiting, and in severe cases, stomach bleeding and stomach ulcers.
Glucocorticoid
It is suitable for systemic lupus erythematosus, systemic scleroderma, dermatomyositis/polymyositis, dry syndrome, etc., which have important internal organ involvement, with powerful anti-inflammatory and immunosuppressive effects.
Commonly used drugs include prednisone and methylprednisolone.
Long-term use of large amounts of glucocorticoids have many adverse effects, including Cushing’s face (i.e., full-moon face, buffalo back, centripetal obesity, and the appearance of purple lines on the skin), hypertension, hyperlipidemia, hyperglycemia, lowering of body resistance and secondary infections, causing aseptic osteonecrosis, osteoporosis, cataracts, etc., and will inhibit the development of children.
Immunosuppressant
It is suitable for systemic lupus erythematosus, dermatomyositis/polymyositis, dry syndrome, systemic scleroderma, etc. with internal organ involvement, and combined with high-dose glucocorticoid to strengthen the effect of immunosuppressant.
Commonly used drugs include leflunomide, azathioprine, cyclophosphamide, and tacrolimus.
Adverse drug reactions include nausea, vomiting, rash, alopecia, diarrhea, bone marrow suppression, leukopenia, and liver damage. It is contraindicated in infected persons.
Biological agents
Applicable to rheumatoid arthritis, systemic lupus erythematosus, etc., with the effect of controlling disease activity, reducing recurrence and improving body function.
Commonly used drugs include rituximab, abatacept, belimumab and so on.
Common adverse reactions include infection and allergic reaction. It should be used under physician’s supervision and is contraindicated in patients with uncontrolled chronic infections (hepatitis B, tuberculosis, etc.).
Prognosis
Cure
Connective tissue diseases are generally not curable, and some of the symptoms of connective tissue diseases can be relieved through early and regular treatment.
Scleroderma, if the lesions are limited to the skin and do not involve organs, generally has a better prognosis.
Dry syndrome generally has a good prognosis if the lesions are limited to exocrine glands such as salivary glands, lacrimal glands, and mucous membranes of the skin.
Dermatomyositis/polymyositis has a low recurrence rate after prompt treatment and generally has a good prognosis.
Systemic lupus erythematosus can lead to long-term remission of symptoms with rational treatment.
Hazards
Connective tissue diseases can involve multiple systems, have a long and complex course, and have an adverse effect on daily life.
Scleroderma can cause skin lesions and joint damage.
Desiccation syndrome may recur when treatment is discontinued if internal organs are involved.
Dermatomyositis/polymyositis may cause swallowing dysfunction and dyspnea if the respiratory and pharyngeal muscles are involved. Severe involvement of the heart, lungs and other organs may lead to pulmonary fibrosis and myocarditis.
SLE may involve multiple organs, causing severe damage to multiple organs and secondary infections.
Daily
Daily Management
Dietary management
Pay attention to light diet and balanced nutrition; quit smoking and drinking to avoid irritation to the body.
Ensure that the body has sufficient water intake every day.
Consume foods rich in vitamins, minerals and monounsaturated fatty acids/polyunsaturated fatty acids, e.g. fresh vegetables, fruits.
Life management
Patients with SLE, dermatomyositis, and systemic sclerosis should avoid sun exposure or freezing of the skin to reduce damage to muscles and skin. Outdoor attention to shade or sunscreen, etc..
Patients with Raynaud’s phenomenon should try to stay away from the cold environment and pay attention to the warmth of fingers, toes and other parts of the body.
Pay attention to rest, avoid overwork, pay attention to personal hygiene, prevent infection.
Exercise appropriately, such as walking, brisk walking, etc., to maintain good health and enhance the body’s resistance.
Avoid contact with chemical reagents, paints, rubber products, pigments, etc. on a daily basis.
Psychological support
Due to the long duration of the disease, patients may experience anxiety, depression and other adverse emotions, relatives should strengthen communication with patients and encourage them to maintain an optimistic mindset.
Follow-up
Connective tissue disease requires regular review, which allows the doctor to dynamically assess the changes in the patient’s condition and prevent complications.
According to the doctor’s instructions, patients with stabilized conditions can have their relevant indicators reviewed every 1 to 3 months, and any changes in their conditions should be followed up in time.
Blood tests, urine tests, liver and kidney functions, blood sedimentation, C-reactive protein, autoantibodies and other tests may be needed.
Prevention
The causes of this group of diseases are complex and varied, and there is still a lack of effective prevention methods. However, early intervention against factors related to this group of diseases may play a positive role in preventing the development of the disease.
People with family history: they should know about the disease and seek medical treatment when they have suspected symptoms, so as to achieve early diagnosis and early treatment, and take the initiative to inform the doctor of their family history of the disease when seeking medical treatment.
Environmental factors: pay attention to diet and environmental hygiene, avoid infection and contact with special chemical substances.