What Is Progressive Systemic Sclerosis?

Systemic sclerosis (SSc), also known as scleroderma, is a systemic autoimmune disease characterized by localized or diffuse skin thickening and fibrosis. Lesions are characterized by skin fibrous hyperplasia and onion-like changes in blood vessels, which eventually lead to skin sclerosis and blood vessel ischemia. The disease is clinically characterized by localized or diffuse skin thickening and fibrosis. In addition to skin involvement, it can also affect the internal organs (heart, lung, and digestive tract organs). As an autoimmune disease, it is often accompanied by resistance Autoantibodies such as nuclear antibodies, anticentromere antibodies, and anti-Scl-70. It is more common in women, the incidence is about 4 times that of men, and children are relatively rare.

Basic Information

nickname: scleroderma
English name: systemicscleroderma
Visiting department: Internal medicine

Multiple groups: female
Common symptoms: Skin sclerosis, vascular ischemia
Contagious: no

Causes of Systemic Sclerosis

At present, the exact etiology of systemic sclerosis is unknown, but studies have shown that its onset may be related to genetic and environmental factors ^[2] .

Genetic factor

Although systemic sclerosis is not inherited according to the classic Mendelian law, genetic factors are still the biggest risk factor found so far.

2. Environmental factors

Including drugs such as bleomycin can induce fibrosis. The use of bleomycin to induce skin sclerosis in mice has fully demonstrated its pathogenicity. In addition, viral infections such as cytomegalovirus and Epstein-Barr virus are suspected to be related to 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 H. pylori antibodies in serum of patients with systemic sclerosis is higher than that of ordinary people, suggesting that H. 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 of Systemic Sclerosis

According to the condition of skin involvement, systemic sclerosis can be divided into:

Diffuse scleroderma

In addition to the face, distal and proximal limbs, thickening of the skin also affects the trunk.

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

There is no clinical manifestation of skin thickening. However, there are characteristic visceral manifestations and vascular and serological abnormalities.

4. Overlap syndrome

Either of the three conditions mentioned above occurs simultaneously with a diagnosis of rheumatoid arthritis, systemic lupus erythematosus, polymyositis, and / or dermatomyositis.

5. Undifferentiated connective tissue disease

Raynaud's phenomenon with clinical and / or serological features of systemic sclerosis, but without skin thickening and visceral abnormalities of systemic sclerosis.

Among them, CREST syndrome refers to calcification, Raynaud's phenomenon, esophageal dyskinesia, hard finger and telangiectasia.

Clinical manifestations of systemic sclerosis

Early symptoms

The most common early manifestations of systemic sclerosis are Raynaud's phenomenon and swelling of the extremities and face, with gradual thickening of the skin of the fingers. The first symptom of some cases is Raynaud's phenomenon. Raynaud's phenomenon can precede other symptoms of scleroderma (finger swelling, arthritis, visceral involvement) for 1 to 2 years or occur simultaneously with other symptoms. Gastrointestinal dysfunction (burning of the stomach and difficulty swallowing) or respiratory symptoms are occasionally the first manifestations of the disease. Patients may have irregular fever, loss of appetite, and weight loss before onset ^[3] .

Skin

In almost all cases, skin sclerosis begins with the hand. The fingers and back of the hand are shiny and tight, the folds of the fingers disappear, the hair is thin, and the face and neck are affected. The patient has tightness on the upper chest and shoulders. Thick horizontal streaks can appear in front of the neck. When the head is raised, the patient will feel the skin of the neck tight, which is rare in other diseases. Facial skin involvement can be represented by a typical scleroderma face, which is: a mask face; radioactive stripes appear around the mouth, lips become thinner, nose ends become sharper, and mouth opening is restricted. The affected skin may have pigmentation or depigmentation. Skin lesions can be confined to the fingers (toes) and face, or spread concentrically, affecting the upper arms, shoulders, chest, back, abdomen, and legs. Some can involve the whole body's skin within a few months, some progress gradually over a few years, and some progress intermittently. Clinically, skin lesions can be divided into edema, sclerosis and atrophy. The edema is non-concave and swollen, and the skin feels tough. The sclerosis is waxy and sticks to the subcutaneous tissue, which makes it difficult to pick up During the atrophy, the superficial dermis becomes thin and brittle, and the epidermis is loose.

3. Bone and joint

Due to the thickening of the skin and close contact with its lower joints, joint contracture and limited function. Due to fibrosis of the tendon sheath, leather-like friction can be perceived when the affected joint is actively or passively moved, especially at the wrist, ankle, and knee. Arthritis can occur in some patients, and some cases can have invasive joint disease. Due to chronic chronic finger (toe) ischemia, osteolysis of the finger (toe) can occur. X-ray films showed narrowing of joint space and articular surface sclerosis.

4. Digestive system

Digestive tract involvement is the most common visceral lesion of scleroderma. Any part of the digestive tract can be affected, of which the esophagus is the most common, followed by the anus and rectum, and the small intestine and colon are less common.

(1) The mouth opening is limited, and the periodontal space widens, the gums shrink, and the teeth fall off after the secondary Sjogren's syndrome.

(2) Impaired sphincter function in the lower esophagus can cause post-sternal burning and acid reflux. Long-term can cause complications such as erosive esophagitis, bleeding, and lower esophageal stricture. Lower 2/3 esophageal motility can cause swallowing difficulties and pain. Histopathology showed atrophy of esophageal smooth muscle, fibrosis of the submucosa and lamina propria, and the mucosa became thinner and eroded to varying degrees. The nutritional blood vessels of the esophagus changed fibrosis. Barrett's esophagus can occur in one third of patients with scleroderma, and these patients are at increased risk for complications such as adenocarcinoma. Esophageal function can be checked by esophageal manometry, barium meal imaging and gastroscopy.

(3) The small intestine can often cause abdominal pain, diarrhea, weight loss and malnutrition. Malnutrition is caused by slow intestinal motility and excessive growth of microorganisms in the intestinal fluid. Application of broad-spectrum antibiotics such as tetracycline often works. Occasionally, pseudointestinal obstruction may occur. Presented as abdominal pain, bloating and vomiting. Similar to esophageal involvement, fibrosis and muscle atrophy are the main causes of these symptoms. Intestinal wall mucosal muscle layer degeneration, after the air enters the intestinal wall mucosa, intestinal wall cystic effusion can 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, bloating, and occasional diarrhea can occur after involvement. Due to atrophy of the intestinal wall muscles, characteristic enteritis (dividenda) with large openings in the transverse and descending colons. If the anal sphincter is involved, rectal prolapse and fecal incontinence may occur. Patients with CREST syndrome can develop biliary cirrhosis.

5. Lungs

Lung involvement is common in scleroderma. The most common symptoms are shortness of breath during exercise, decreased activity tolerance, and dry cough. Pulmonary interstitial fibrosis and pulmonary vascular disease can coexist, but often one of them predominates.

6. Heart

Clinical manifestations are shortness of breath, chest tightness, palpitations, and edema. Clinical examination may have ventricular galloping rhythm, sinus tachycardia and congestive heart failure, occasionally pericardial friction sounds can be heard. Echocardiography revealed pericardial hypertrophy or effusion in about half of the cases, but clinical myocarditis and pericardial tamponade were rare.

7. Kidney

The renal lesions of scleroderma are most prominent in the interlobular arteries, arcuate arteries, and arterioles, the most important of which are the interlobular arteries. There are fibroblast hyperplasia, mucus-like changes, acidic mucopolysaccharide deposition, and edema in the vascular endometrium; hyaline degeneration of vascular smooth muscle cells; fibrosis in the adventitia and surrounding stroma; irregular thickening of the glomerular basement membrane. The clinical manifestations of scleroderma nephropathy vary, and some patients have many years of skin and other internal organ involvement without renal damage; some have a renal crisis during the course of the disease, that is, sudden severe hypertension and rapid renal failure. If left untreated, they often die of heart failure and uremia within a few weeks. Although the initial stage of renal crisis may be asymptomatic, most patients feel tired and exacerbated, with symptoms such as shortness of breath, severe headache, blurred vision, convulsions, and unconsciousness. Laboratory tests revealed increased creatinine, proteinuria, and / or microscopic hematuria, which may have microvascular hemolytic anemia and thrombocytopenia.

Systemic sclerosis test

1. General laboratory inspection

No special exceptions. ESR can be normal or slightly faster. Anemia can be caused by peptic ulcers, malabsorption, kidney involvement, or chronic disease. There may be a slight decrease in serum albumin and an increase in globulin ^[4] .

2. Immunological test

Serum ANA positive rate was over 90%, and the karyotypes were mainly spotted and nucleoli. Among patients with CREST syndrome, 50% to 90% are positive for anticentromere antibodies, and only 10% of cases are positive for diffuse scleroderma. 20% to 40% of patients with systemic sclerosis have positive anti-Scl-70 antibodies. Rheumatoids are positive in about 30% of cases. There are also patients with anti-RNA polymerase III antibodies and anti-fibrin antibodies.

3. Pathology and nailfold microcirculation examination

Biopsy of sclerotic skin showed increased reticular dense collagen fibers, thinning of the epidermis, disappearance of epidermal processes, and atrophy of skin appendages; large accumulation of T lymphocytes was seen in the dermis and subcutaneous tissues (also in extensive fibrosis sites). Microscopic examination of the nailfolds showed that the capillaries were dilated and normal blood vessels disappeared.

4. High-resolution CT examination

Patients with interstitial lung disease can find pulmonary exudative lesions or fibrotic changes or stretched bronchiectasis.

5. Lung function test

Patients with interstitial lung disease can find that the patient's forced vital capacity, total lung capacity, and carbon monoxide dispersion have decreased.

6. Cardiac catheterization

As a screening test for patients with pulmonary hypertension, echocardiography can detect pulmonary hypertension, but the diagnosis is performed by cardiac catheterization, which is the only gold standard for the diagnosis of pulmonary hypertension.

Systemic sclerosis diagnosis

According to the American College of Rheumatology's diagnostic criteria for the disease in 1980, anyone who meets one or two of the following secondary criteria can be diagnosed with scleroderma, which is systemic sclerosis.

Main criteria

Proximal scleroderma, where the skin is symmetrically thickened, taut, and hardened above the finger and metacarpophalangeal or metatarsophalangeal joints. Such changes can affect the entire limb, face, neck and torso (chest and abdomen).

2. Minor criteria

(1) Standard chest radiographs showing bilateral fibrosis at the base of the lungs show bilateral reticulated linear or linear nodular shadows, which are most obvious at the base of the lungs, and can have a diffuse ground-glass shadow or "honeycomb lung" appearance. These changes cannot be attributed to primary lung disease.

(2) Scleroderma of the fingers The above skin changes are limited to the fingers.

(3) The sunken scars of the fingers or the tissues of the finger pads disappear. The sunken fingertips or the tissues of the finger pads (finger belly) disappear.

3.CREST syndrome criteria

Diagnosis can be confirmed with 3 of 5 items including calcification, Raynaud's phenomenon, esophageal dyskinesia, hard finger and capillary dilation.

Differential diagnosis of systemic sclerosis

This disease should be distinguished from eosinophilic fasciitis, scleredema, and renal-derived systemic fibrosis.

Systemic sclerosis treatment

There is no specific medicine for this disease. The extent of skin involvement and the extent of lesions are important basis for diagnosis and assessment of prognosis, and the extent and severity of important organ involvement determine its prognosis. Early treatment aims to prevent new skin and organ involvement, while late treatment aims to improve existing symptoms ^[5] .

General treatment

(1) Glucocorticoids and immunosuppressive agents Generally speaking, glucocorticoids have no significant effect on this disease, but they have a certain effect on the inflammatory phase of inflammatory myopathy and interstitial lung disease; in the early edema phase, joint pain and Myalgia is also effective. The dose is 30 to 40 mg / d of prednisone, which is continuously used for 3 to 4 weeks, and gradually reduced to a maintenance amount of 10 to 15 mg / d. There is not much literature on the treatment of skin sclerosis with immunosuppressants. Cyclosporine A, cyclophosphamide, and azathioprine are commonly used. It has been reported to have certain effects on skin joints and kidney diseases. Combined application with glucocorticoids can often improve the efficacy and reduce the amount of glucocorticoids.

(2) In the process of penicillamine converting from procollagen to collagen, monoamine oxidase needs to participate in polymerization and cross-linking. Penicillamine can complex copper ions in monoamine oxidase, thereby inhibiting the maturation of new collagen, and can activate collagenase to degrade the formed collagen fibers. Common adverse reactions include fever, anorexia, nausea, vomiting, mouth ulcers, abnormal taste, rash, white blood cells and thrombocytopenia, proteinuria and hematuria.

3. Methotrexate The European Anti-Rheumatoid Alliance's recommended treatment guidelines The only treatment recommendation for skin sclerosis is methotrexate. The results of two high-quality randomized controlled trials show that methotrexate can improve the system by oral or intramuscular injection. Progression of skin lesions related to sclerosis is recommended for skin lesions of systemic sclerosis.

4. In recent years, there have been reports in the literature that various new treatment methods such as relaxin, imatinib, CD20 monoclonal antibody, and TGF- antibody have achieved good results in the treatment of skin sclerosis, but they have not yet been widely used and can be used. Considered for refractory patients.

Symptomatic treatment

(1) Do not smoke the Raynaud phenomenon , keep your hands and feet away from cold and keep warm. If the symptoms are severe and there is a tendency to necrosis, the endothelin receptor antagonist bosentan or sildenafil can be added. Intravenous prostaglandin analogs can also relieve Raynaud's phenomenon and are used to treat fingertip ulcers. Finger gangrene can be considered sympathetic nerve block.

(2) Gastrointestinal involvement Proton pump blockers; Gastrointestinal motility drugs; Antibiotics.

(3) Scleroderma-related pulmonary hypertension Bosentan; Sildenafil; Epoprostenol.

(4) Scleroderma-related pulmonary fibrosis For systemic sclerosis-related interstitial lung disease, cyclophosphamide intravenous shock or daily oral treatment can be selected.

(5) Although the results of randomized controlled trials are lacking in scleroderma renal crisis , the results of two prospective non-controlled studies show that Kaibotong and Enalapril can reduce the dialysis dependence rate of scleroderma renal crisis and improve it. Survival; angiotensin-converting enzyme inhibitors are recommended for scleroderma renal crisis (recommended intensity C). Retrospective studies have shown that using medium and large doses of glucocorticoids (15 mg / d prednisone or equivalent doses of glucocorticoids) may be a risk factor for scleroderma renal crisis. Therefore, for the system using glucocorticoids Patients with sclerosis should closely monitor blood pressure and renal function (recommended intensity C). Although blood purification treatment is not included in the European Anti-Rheumarrheal Alliance treatment recommendations, it is also an important part of scleroderma renal crisis treatment.

3. Other treatments

In recent years, peripheral hematopoietic stem cell transplantation using CD34 cell sorting at home and abroad has achieved certain results, but it is expensive and has a high risk of adverse transplant reactions. It is only recommended for refractory patients. Domestic professor Sun Lingyun firstly used mesenchymal stem cells to treat systemic sclerosis and achieved good early results. More studies are needed to confirm its efficacy.

Prognosis of systemic sclerosis

It usually develops slowly and the outcome is difficult to predict. Most patients eventually develop visceral disease. If heart, lung or kidney damage occurs early in the disease, the prognosis is poor. In patients with CREST syndrome, the lesions can be localized and not developed for a long time, and the prognosis is good, but those with severe pulmonary hypertension may have sudden death.

Systemic sclerosis prevention

For people with Raynaud's phenomenon, try to avoid cold, mental stress, and smoking. For patients with abnormal gastrointestinal dynamics, pay attention to easy-to-absorb diet and avoid supine position after meals. For patients with interstitial lung disease, try to avoid colds and, if necessary, long-term low-flow oxygen inhalation to prevent further pulmonary fibrosis. For those with pulmonary hypertension, pay attention to avoid strenuous exercise and prevent sudden death.

References:

1. Chinese Medical Association Rheumatology Society. Guidelines for the diagnosis and treatment of systemic sclerosis (draft). Chinese Journal of Rheumatology, 2004, 8 (6): 377-379.

2. Yu Huimin, Zhang Fengshan. Research progress on the pathogenesis of systemic sclerosis. Chinese Journal of Rheumatology, 2005, 9 (6): 362-365.

3.BroenJC, CoenenMJ, RadstakeTR. Genetics ofsystemicsclerosis: anupdate, 2012, 14 (1): 11-21.

4. Kowal-BieleckaO, LandewéR, AvouacJ, etal. EULARrecommendations for the treatment of systemicsclerosis: areport from the EULARSclerodermaTrialsand Researchgroup (EUSTAR). AnnRheumDis, 2009, 68 (5): 620-8.

5. Radi M, Martinovi KaliternaD, Radi J. Infectiousdiseaseasaetiologicalfactorinthepathogenesisofsystemicsclerosis.NethJMed, 2010, 68 (11): 348-53.