Introduction
Systemic sclerosis(SSc) is also known asscleroderma, is a systemic autoimmune disease characterized by localized or diffuse skin thickening and fibrosis. The lesions are characterized by skin fibrosis and vascular onion skin-like changes, which eventually lead to skin sclerosis and vascular ischemia. The disease is characterized by localized or diffuse skin thickening and fibrosis. In addition to skin involvement, it can also affect internal organs (hearts, lungs, and digestive tracts). As an autoimmune disease, it is often associated with resistance. Nuclear antibodies, anti-centromere antibodies, autoantibodies such as anti-Scl-70. The disease is more common in women, the incidence rate is about 4 times that of men, and children are relatively rare.
Basic Information
Also known as scleroderma English name systemicscleroderma treatment department indoors multiple groups of women common symptoms of skin sclerosis, vascular ischemic infectivity
Cause
At present, the exact cause of systemic sclerosis is unclear, but studies have shown that its pathogenesis may be related to genetic and environmental factors.
Genetic factor
Although systemic sclerosis is not inherited by the classical Mendelian law, genetic factors remain the largest risk factor found so far.
2. Environmental factors
Including drugs such as bleomycin can induce fibrosis, and the use of bleomycin to induce skin sclerosis in mice is sufficient to prove its pathogenicity. In addition, viral infections such as cytomegalovirus and Epstein-Barr virus are suspected to be associated with the onset of systemic sclerosis.
In recent years, the role of Helicobacter pylori in the pathogenesis of systemic sclerosis has attracted much attention. Studies have shown that the positive rate of Helicobacter pylori antibodies in patients with systemic sclerosis is higher than that of normal people, suggesting that Helicobacter pylori may be involved in the pathogenesis of systemic sclerosis. .
3. Chemicals
Such as polyvinyl chloride, organic solvents, silicon, silicon dioxide, epoxy resin, etc. are also suspected to be involved in the pathogenesis of systemic sclerosis.
classification
According to the skin involvement, systemic sclerosis can be divided into:
Diffuse scleroderma
In addition to the face, distal and proximal limbs, skin thickening also affects the torso.
2. Localized scleroderma
Skin thickening is limited to the distal end of the elbow (knee), but can affect the face and neck.
3. Scleroderma without skin sclerosis
Clinically no skin thickening performance. However, there are characteristic visceral manifestations and vascular and serological abnormalities.
Overlap syndrome
Any of the above three conditions occurs simultaneously with the well-diagnosed rheumatoid arthritis, systemic lupus erythematosus, polymyositis, and/or dermatomyositis.
5. Undifferentiated connective tissue disease
Renault phenomenon with clinical and/or serological features of systemic sclerosis, but no skin thickening and visceral abnormalities in systemic sclerosis.
Among them, CREST syndrome refers to calcification, Raynaud's phenomenon, esophageal dyskinesia, hard fingers and telangiectasia.
Clinical manifestation
Early symptoms
The most common initial manifestations of systemic sclerosis are Raynaud's phenomenon and swelling of the extremities and face, and the skin of the fingers gradually thickens. The first symptom of some cases is Raynaud's phenomenon. Raynaud's phenomenon may precede other symptoms of scleroderma (swelling of the fingers, arthritis, visceral involvement) for 1 to 2 years or with other symptoms. Gastrointestinal dysfunction (stomach burning and difficulty swallowing) or respiratory symptoms are occasionally the first manifestations of this disease. Patients may have irregular fever, loss of appetite and weight loss before onset.
2. Skin
Skin hardening begins in the hands of almost all cases. The fingers, the back of the hand are shiny and tight, the folds of the fingers disappear, the hair is sparse, and the face and neck are affected. The patient has a tight fit on the upper chest and shoulders. Lateral thick stripes can appear in front of the neck. When looking up, the patient will feel tight skin in the neck. This is rarely the case with other diseases. Facial skin involvement can be expressed as a typical scleroderma face, which is characterized by: mask face; radioactive streaks appear around the mouth, the lips are thinner, the nose is sharpened, and the mouth is restricted. The affected skin may have pigmentation or pigment loss. Skin lesions can be limited to the fingers (toes) and face, or centripetal extension, involving the upper arms, shoulders, chest, back, abdomen and legs. Some may involve the whole body skin within a few months, some gradually progress in a few years, and some progress intermittently. Clinically, skin lesions can be divided into edema stage, hardening stage and atrophic stage. The skin in edema stage is non-concave and swollen, and has a tough feeling. The skin in the hardening stage is waxy and lustrous, which is close to the subcutaneous tissue and is not easy to pinch; In the atrophic period, the superficial dermis becomes thin and brittle, and the epidermis is relaxed.
3. Bone and joints
As the skin thickens and is in close contact with its lower joints, the joints contract and function are limited. Due to the fibrosis of the tendon sheath, when the affected joint is actively or passively moved, especially at the wrist, ankle, and knee, a leather-like rubbing sensation is perceived. Some patients may develop joint inflammation, and some cases may have invasive joint disease. Due to chronic chronic finger (toe) ischemia, osteolysis of the finger end can occur. X-ray films showed joint space stenosis and articular surface sclerosis.
4. Digestive system
Digestive tract involvement is the most common visceral damage to scleroderma. Any part of the digestive tract can be affected, with esophageal involvement being the most common, followed by the anus and rectum, and the small intestine and colon.
(1) Oral mouth opening is limited. After the dry syndrome, the periodontal space is widened, the gums are atrophied, and the teeth are detached.
(2) impaired sphincter function in the lower esophagus esophagus can cause burning sensation and acid reflux in the sternum. Long-term can cause complications such as erosive esophagitis, hemorrhage, and lower esophageal stricture. Attenuation of the lower 2/3 esophageal peristalsis can cause difficulty swallowing and swallowing pain. Histopathology showed atrophy of esophageal smooth muscle, submucosa and lamina propria fibrosis, and the mucosa was thinned and eroded to varying degrees. The nutrient vessels of the esophagus are fibrotic. Barrett's esophagus can occur in 1/3 of patients with scleroderma, and these patients have an increased risk of complications such as adenocarcinoma. The esophageal function can be examined by esophageal manometry, barium meal imaging and gastroscope.
(3) The small intestine can often cause abdominal pain, diarrhea, weight loss and malnutrition. Malnutrition is caused by slow peristalsis and excessive growth of microorganisms in intestinal fluid. It is often effective with broad-spectrum antibiotics such as tetracycline. Even pseudo-intestinal obstruction can occur. It is characterized by abdominal pain, bloating and vomiting. Similar to esophageal involvement, fibrosis and muscle atrophy are the main causes of these symptoms. Mucosal degeneration of the mucosa of the intestinal wall, after the air enters the mucosa of the intestinal wall, a cystic gas accumulation sign of the intestinal wall may occur.
(4) Large intestine barium enema can be found in 10% to 50% of patients with large intestine involvement, but the clinical symptoms are often mild. Constipation, lower abdominal fullness, and occasional diarrhea may occur after involvement. Due to atrophy of the intestinal wall muscle, characteristic enteritis (diverticulum) with a large opening in the transverse colon and descending colon, such as anal sphincter involvement, may occur with rectal prolapse and fecal incontinence. Biliary cirrhosis can occur in patients with CREST syndrome.
5. Lungs
Lung involvement is common in scleroderma. The most common symptoms are shortness of breath during exercise, reduced activity tolerance, and dry cough. Pulmonary interstitial fibrosis and pulmonary vascular disease can coexist, but often one of them dominates.
6. Heart
Clinical manifestations of shortness of breath, chest tightness, palpitations, edema. Clinical examination may have ventricular gallop, sinus tachycardia and congestive heart failure, and occasionally hear pericardial friction. Echocardiography showed that about half of the cases had pericardial hypertrophy or effusion, but clinical myocarditis and pericardial tamponade were rare.
7. Kidney
Renal lesions of scleroderma are most prominent in interlobular arteries, arcuate arteries, and small arteries, the most important of which is the interlobular artery. Endothelium has fibroblast proliferation, mucoidosis, acid mucopolysaccharide deposition and edema; vascular smooth muscle cells undergo hyaline degeneration; fibrosis of the adventitia and surrounding interstitial; glomerular basement membrane irregular thickening. The clinical manifestations of scleroderma nephropathy are different. Some patients have clinical symptoms of skin and other visceral involvement without renal damage. Some kidney crises appear in the course of the disease, that is, sudden high blood pressure and rapid renal failure suddenly occur. If not treated in time, often died of heart failure and uremia within a few weeks. Although the kidney crisis can be asymptomatic at the beginning, most patients feel fatigue and aggravation, such as shortness of breath, severe headache, blurred vision, convulsions, and unconsciousness. Laboratory tests revealed increased creatinine, proteinuria, and/or microscopic hematuria with microvascular hemolytic anemia and thrombocytopenia.
an examination
1. General laboratory inspection
No special exceptions. ESR can be normal or slightly increased. Anemia can be caused by peptic ulcers, malabsorption, kidney involvement or chronic diseases. There may be a decrease in mild serum albumin and an increase in globulin [4].
2. Immunological testing
The positive rate of serum ANA is over 90%, and the karyotype is mainly spot type and nucleolus type. In patients with CREST syndrome, 50% to 90% are positive for anti-filament antibodies, and only 10% of cases with diffuse scleroderma are positive. 20% to 40% of patients with systemic sclerosis, serum anti-Scl-70 antibody positive. About 30% of cases are positive for rheumatoid. There are also patients with anti-RNA polymerase III antibodies and anti-fibrin antibodies.
3. Pathology and nailfold microcirculation examination
Hard skin biopsy showed increased dense collagen fibers in the reticular dermis, thinning of the epidermis, loss of epidermal processes, and atrophy of the skin appendages; large accumulation of T lymphocytes was observed in the dermis and subcutaneous tissues (also in the extensive fibrosis site). Microscopic examination of the pleats showed capillary dilation and disappearance of normal blood vessels.
4. High resolution CT examination
Pulmonary exudative lesions or fibrotic changes or stretch bronchiectasis can be found in patients with interstitial lung disease.
5. Pulmonary function test
Patients with interstitial lung disease can be found to have a strong lung capacity, a decrease in total lung volume, and a decrease in carbon monoxide diffusion.
6. Cardiac catheterization
As a screening test for patients with pulmonary hypertension, echocardiography can detect pulmonary hypertension, but the diagnosis is to perform a cardiac catheterization, which is the only gold standard for the diagnosis of pulmonary hypertension.
diagnosis
According to the 1980 American College of Rheumatology diagnostic criteria for this disease, any of the following major criteria or two minor criteria can be diagnosed as scleroderma, systemic sclerosis.
Main standard
There is proximal scleroderma, that is, the skin of the finger and metacarpophalangeal joints or any part of the metatarsophalangeal joint is symmetrically thickened, tightened and hardened. Such changes can affect the entire limb, face, neck and torso (chest and abdomen).
2. Secondary criteria
(1) Bilateral lung basal fibrosis The standard chest radiograph shows a bilateral reticular linear or linear nodular shadow, which is most prominent in the base of the lung and may be a diffuse ground glass or "honeycomb lung" appearance. These changes cannot be attributed to primary lung disease.
(2) Finger scleroderma The above skin changes are limited to the fingers.
(3) The depressed scar of the finger or the tissue of the finger pad disappears. The fingertip depression or the finger pad (finger belly) tissue disappears.
3. CREST syndrome standard
Three of the five items of calcification, Raynaud's phenomenon, esophageal dyskinesia, hard finger and telangiectasia, and anti-centromere antibodies can be diagnosed.
Differential diagnosis
The disease should be differentiated from eosinophilic fasciitis, scleredema, and systemic fibrosis of the kidney.
treatment
There is no specific drug for this disease. The extent of skin involvement and the extent of lesions are important evidence for the diagnosis and assessment of prognosis, and the extent and severity of the involvement of important organs determines the prognosis. The purpose of early treatment is to prevent new skin and organ involvement, while the purpose of the late stage is to improve existing symptoms.
General treatment
(1) Glucocorticoids and immunosuppressive agents In general, glucocorticoids have no significant effect on this disease, but have a certain effect on the inflammatory phase of inflammatory myopathy and interstitial lung disease; in early edema, joint pain and Myalgia is also effective. The dose is prednisone 30 ~ 40mg / d, used for 3 ~ 4 weeks, gradually reduced to the maintenance amount l0 ~ 15mg / d. There are few studies on the treatment of skin sclerosis by immunosuppressive agents. Commonly usedCyclosporin A,Cyclophosphamide,AzathioprineEtc. It has been reported to have a certain effect on skin joints and kidney lesions. Combined with glucocorticoids, it can often improve the efficacy and reduce the amount of glucocorticoids.
(2) Penicillamine requires monoamine oxidase to participate in polymerization and cross-linking in the process of converting procollagen into collagen. Penicillamine can complex copper ions in monoamine oxidase, thereby inhibiting the maturation of new collagen and activating collagenase to degrade the formed collagen fibers. Common adverse reactions are fever, anorexia, nausea, vomiting, mouth ulcers, abnormal taste, rash, white blood cells and thrombocytopenia, proteinuria and hematuria.
3.MethotrexateThe recommended treatment guidelines for the European Anti-Rheum Alliance recommend methotrexate for the only treatment for skin sclerosis. Two high-quality randomized controlled trials have shown that methotrexate can improve systemic sclerosis-associated skin by oral or intramuscular injection. The lesion progresses and, therefore, is recommended for skin lesions of systemic sclerosis.
4. Others In recent years, there have been reports in the literature on the use of relaxin,ImatinibVarious new treatments such as CD20 monoclonal antibody and TGF-β antibody have achieved good curative effect on skin hardening, but they have not been widely used and can be considered for refractory patients.
2. Symptomatic treatment
(1) Reynolds phenomenon does not smoke, hands and feet to avoid cold and keep warm. If the symptoms are heavier and there is a tendency to necrosis, the endothelin receptor antagonist bosentan or sildenafil may be added. Intravenous prostaglandin analogs can also alleviate the Raynaud's phenomenon and are used to treat fingertip ulcers. Sympathetic nerve blockade can be considered for finger gangrene.
(2) gastrointestinal involvement 1 proton pump blocker; 2 gastrointestinal motility drugs; 3 antibiotics.
(3) scleroderma relatedpulmonary hypertension1Bosentan;2Sildenafil; 3 by prostacyclin.
(4) Scleroderma-associated pulmonary fibrosis For systemic sclerosis-related interstitial lung disease, cyclophosphamide intravenous shock or daily oral treatment may be used.
(5) Although scleroderma renal crisis lacks randomized controlled trials, two prospective uncontrolled studies have shown that Kaibotong and enalapril can reduce dialysis dependence and improve scleroderma renal crisis. Survival; angiotensin-converting enzyme inhibitors are recommended for use in scleroderma kidney crisis (recommended strength C). Retrospective studies have shown that the use of large doses of glucocorticoids (≥15 mg / d prednisone or equivalent dose of glucocorticoids) may be a risk factor for scleroderma kidney crisis, therefore, for the system using glucocorticoids In patients with sclerosing disease, blood pressure and renal function should be closely monitored (recommended strength C). Although blood purification treatment is not included in the European Anti-Rheum Union treatment recommendations, it is also an important part of the treatment of scleroderma kidney crisis.
3. Other treatments
In recent years, peripheral hematopoietic stem cell transplantation by CD34 cell sorting has achieved certain effects at home and abroad, but it is expensive and has a high risk of adverse reactions. It is only recommended for refractory patients. Professor Sun Lingyun first achieved better pre-effects with mesenchymal stem cells in the treatment of systemic sclerosis, and more research is needed to confirm its efficacy.
Prognosis
Often slow development, the outcome is unpredictable, most patients eventually develop visceral lesions, such as heart and lung or kidney damage in the early stage of the disease, the prognosis is poor. In patients with CREST syndrome, the lesion can be localized for a long time without development, and the prognosis is good, but sudden death can occur in patients with severe pulmonary hypertension.
prevention
For patients with Raynaud's phenomenon, try to avoid cold, mental stress and smoking. For patients with abnormal gastrointestinal motility, pay attention to eating easy to absorb diet, avoid post-meal relocation. For patients with interstitial lung disease, try to avoid a cold, if necessary, long-term low-flow oxygen, to prevent further increase in pulmonary fibrosis. For those with pulmonary hypertension, pay attention to avoid strenuous exercise and prevent sudden death.
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