Skin involvement

Introduction Skin involvement is common in systemic sclerosis. Systemic sclerosis is an unexplained connective tissue disease 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). The disease is more common in women, the incidence rate is about 4 times that of men, and children are relatively rare. The severity and development of the disease vary widely, from diffuse skin thickening (diffuse scleroderma) with rapid development and often fatal visceral damage, to only a small part of the skin (usually limited to fingers) And the face) can be seen. The latter progresses slowly and can last for decades before the typical lesions of the internal organs are fully revealed. It is called localized scleroderma or CREST (C, calcinosis; R, raynaud's phenomenon; E, esophageal dysmotility; S, sclerodactyly; T, telangiectasia) syndrome (calcacalcification, Raynaud's phenomenon, esophageal dysfunction, fingertip hardening, and telangiectasia). In addition, there are overlapping syndromes (such as scleroderma and dermatomyositis overlap) and undifferentiated connective tissue diseases.

Cause

Systemic sclerosis is an unexplained diffuse connective tissue disease that has been shown to be related to:

(1) Genetic factors:

1 Family history: The survey showed that the proportion of patients with systemic sclerosis (or another connective tissue disease such as systemic lupus erythematosus, Sjogren's syndrome, polymyositis) was higher than that of the general population. Therefore, the family's genetic predisposition is related to the pathogenesis of this disease.

2HLA correlation: Some studies have suggested that HLA-II genes are associated with this disease, including HLA-DR1, HLA-DR2, HLA-DR3, HLA-DR5, HLA-DR8, HLA-DR52, among which HLA-DR1 The correlation is particularly evident.

(2) Gender: There are more female patients than males, especially women of childbearing age. Therefore, estrogen may have a certain effect on the onset of this disease.

(3) Environmental factors: It has been clarified that some chemicals can cause scleroderma-like changes, such as silicon, polyvinyl chloride, organic solvents, bleomycin, epoxy resin, L-tryptophan, pentazocine, etc. The prevalence of this disease is higher in people who have been exposed to these substances for a long time.

(4) Abnormal immune function: patients with this disease have a wide range of immune dysfunction: this disease often coexists with or with autoimmune diseases such as systemic lupus erythematosus, Sjogren's syndrome, and polymyositis; sometimes it can occur during the course of the disease Other autoimmune diseases, such as autoimmune hemolytic anemia, Hashimoto's thyroiditis, etc.; laboratory tests such as lymphocyte function, pathological biopsy, serum antibodies, cytokines, etc. may indicate abnormal immune function.

(5) Infectious factors: In recent years, studies have shown that the self-components of certain viruses have homology with the target antigens targeted by the characteristic autoantibodies of systemic sclerosis, suggesting immunity caused by the crossover of viral antigens and patients' own antigens. The reaction may contribute to the disease.

an examination

Related inspection

Skin test white blood cell count (WBC) blood routine

First, clinical manifestations

1. Early symptoms: The most common initial manifestations of systemic sclerosis are Raynaud's phenomenon and insidious swelling of the extremities and face, and the skin of the fingers gradually thickens. The first symptom of about 70% of cases is Raynaud's phenomenon. The 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. Polyarticular disease is also an outstanding early symptom. Gastrointestinal dysfunction (stomach burning and difficulty swallowing) or respiratory symptoms, and occasionally the first manifestation of the disease. Patients may have irregular fever, decreased appetite, and weight loss before onset.

2. Skin: In almost all cases, skin hardening starts from the hand. The fingers and back of the hand are bright and tight, the folds of the fingers disappear, the hair is sparse, and the face and neck are affected. The patient has a tight feeling on the upper part of the chest and the shoulder. The horizontal thick stripe can appear in front of the neck. When the head is raised, the patient feels the neck skin is tight. This disease is rare in other diseases. Facial skin involvement can be expressed as a mask-like face. Radiation groove appeared on the mouth, the lips became thinner, and the nose became sharp. 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, some have intermittent progress, and the extent and severity of skin involvement usually peaks within three years. Clinically, skin lesions can be divided into edema phase, hardening phase and atrophic phase. During the edema period, the skin is non-concave and swollen, and it has a tough feeling. The hardened skin has a waxy luster and is close to the subcutaneous tissue, which is not easy to pinch; the superficial dermis becomes thin and brittle, and the epidermis is slack.

3, bones and joints: polyarticular pain and muscle pain are often early symptoms, but also obvious arthritis. About 29% can have erosive joint disease. 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. Long-term chronic finger (toe) ischemia can occur in the fingertip osteolysis. X-ray showed joint space stenosis and articular surface sclerosis. Osteoporosis is often caused by poor intestinal absorption, disuse, and decreased perfusion.

4, digestive system: digestive tract involvement is a common manifestation of scleroderma, second only to skin involvement and Raynaud's phenomenon. Any part of the digestive tract can be affected, with the most common esophageal involvement (90%), followed by the anus and rectum (50% to 70%), and the small intestine and colon (40% and 10% to 50%).

(1) Oral: The mouth is restricted, the tongue band is shortened, the periodontal space is widened, the gums are retracted, the teeth are detached, and the alveolar bone is atrophied.

(2) Esophagus: impaired sphincter function in the lower esophagus can lead to burning sensation in the back of the sternum and acid reflux. Long-term can cause complications such as erosive esophagitis, hemorrhage, and lower esophageal stricture. Lower 2/3 esophageal peristalsis can cause difficulty swallowing and swallowing pain. Histopathology showed atrophy of the esophageal smooth muscle, fibrosis of the submucosa and lamina propria, and the mucosa was thinned and eroded to varying degrees. The nutrient vessels of the esophagus are fibrotic. Barrett metaplasia can occur in the esophagus of 1/3 scleroderma patients, and these patients have an increased risk of complications such as stenosis and adenocarcinoma. Esophageal function can be examined by esophageal manometry, supine dilute meal angiography, esophagoscopy and other methods.

(3) Small intestine: often causes mild 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. Occasionally, there may be pseudo-intestinal obstruction, which is manifested as abdominal pain, bloating and vomiting. Similar to esophageal involvement, fibrosis and muscle atrophy are the main causes of these symptoms. Muscle layer of the intestinal wall is degenerated, and after the air enters the mucosa of the intestinal wall, a cystic gas deposit 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 clinical symptoms are often mild. Constipation can occur after the infection, the lower abdomen is full, and occasionally diarrhea. Due to atrophy of the intestinal wall muscle, there may be a large opening of characteristic enteritis (diverticulum) in the transverse colon and descending colon, such as anal sphincter involvement, rectal prolapse and fecal incontinence may occur.

(5) CREST syndrome: patients can develop biliary cirrhosis.

5, the lungs: lung involvement is common in scleroderma. The most common symptoms at the beginning of the disease are shortness of breath during exercise and a decrease in activity tolerance; dry cough appears later. As the disease progresses, the chances of lung involvement increase, and once it is involved, it progresses progressively and does not respond well to treatment. Pulmonary interstitial fibrosis and pulmonary vascular disease often coexist, but often one of the pathological processes predominates. In patients with diffuse scleroderma with anti-Scl-70 positive, pulmonary interstitial fibrosis is often more severe; in CREST syndrome, pulmonary hypertension is often more pronounced. Pulmonary interstitial fibrosis is often preceded by eosinophilic alveolitis. In the alveolitis phase, high-resolution CT can show a drusen-like change in the lungs, and bronchoalveolar lavage can increase the number of cells in the lavage fluid. The X-ray showed that the interstitial texture of the lungs was thickened, and in the case of severe reticular nodular changes, it was most prominent at the base. Pulmonary function tests showed restrictive ventilatory disorders, reduced lung capacity, decreased lung compliance, and reduced gas diffusion. The physical examination can smell small cracking sounds, especially at the bottom of the lungs. Occlusion, fibrosis, and inflammatory changes are the causes of lung involvement. Pulmonary hypertension is often a thorny problem as a result of long-term fibrosis around the interstitial and peribronchial or intimal hyperplasia of the pulmonary arterioles. Pulmonary hypertension often progresses slowly, unless it is severely irreversible in the later stages, which is generally not clinically detectable. Non-invasive echocardiography can detect early pulmonary hypertension. The autopsy showed that about 29 to 47% of patients had small intima pulmonary intimal hyperplasia and mesothelioma-like changes. Cardiac catheterization revealed 33% of patients with pulmonary hypertension.

6, the heart: pathological examination 80% of patients have flaky myocardial fibrosis. Clinical manifestations of shortness of breath, chest tightness, palpitations, edema. Clinical examination may have ventricular gallop, sinus tachycardia, congestive heart failure, and occasional vocal friction. Echocardiography showed that about half of the cases had pericardial hypertrophy or effusion, but clinical myocarditis and pericardial tamponade were rare.

7, kidney: scleroderma nephropathy with interlobular artery, arcuate artery and small artery is the most important, the most important of which is the interlobular artery. The intima of the blood vessels has fibroblast proliferation, mucoidosis, acid mucopolysaccharide deposition and edema. Vascular smooth muscle cells undergo hyaline degeneration. The adventitia and surrounding stroma are fibrotic. The glomerular basement membrane is irregularly thickened and cleft. 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, ie sudden severe hypertension, rapid renal failure, such as 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 have found normal or elevated creatinine, proteinuria and/or microscopic hematuria, and may have microvascular hemolytic anemia and thrombocytopenia. The predictors of renal crisis are as follows: 1 systemic scleroderma; 2 less than 4 years; 3 disease progression; 4 anti-RNA polymerase III antibody positive; 5 taking large amounts of hormone or small dose of cyclosporine; The serum renin level suddenly increased.

Second, laboratory inspection

(1) There are no special abnormalities in general tests. ESR can be normal or slightly increased. Anemia can be caused by peptic ulcers, malabsorption, and kidney involvement, which are rare in general. There may be a decrease in mild serum albumin and an increase in globulin.

(2) Immunological tests showed that the positive rate of serum ANA was over 90%, and the karyotype was spot type and nucleolus type. Using HEP-2 cells as a negative film, about 50-90% of patients with CREST syndrome were positive for anti-filament antibody, and only 10% of patients with diffuse scleroderma were positive. Anti-centromere antibody-positive patients tend to have skin telangiectasia and subcutaneous calcareous deposition, which is less restrictive than the antibody-negative lung disease, and its titer does not change with time and disease, which helps hard Diagnosis and classification of skin diseases. About 20 to 40% of patients with systemic sclerosis have positive anti-Scl~70 antibodies. About 30% of cases are RF positive, and about 50% of cases have low titer cryoglobulinemia.

(3) Pathology and pleats examination: Hard skin biopsy showed increased dense collagen fibers in the reticular dermis, thinning of the epidermis, disappearance of the epidermis, and atrophy of the skin appendage. Large accumulation of T lymphocytes can be seen in the dermis and subcutaneous tissue (also in the extensive fibrosis site). Microscopic examination of the pleats showed capillary dilation and disappearance of normal blood vessels.

Third, the diagnostic criteria

The classification criteria for systemic sclerosis (scleroderma) proposed by the American College of Rheumatology (ARA) in 1980 played an important role in ensuring the consistency of clinical research cases. Currently, this classification standard is used as a diagnostic criterion. It should be noted, however, that not all systemic sclerosis meets this criterion. On the other hand, other diseases can also have proximal skin sclerosis. This standard does not include eosinophilic fasciitis and various types of pseudo-scleroderma. The classification criteria for ARA systemic sclerosis (scleroderma) are as follows:

A. Main conditions:

Proximal skin sclerosis: thickening, tightness, and swelling of the proximal skin of the fingers and metacarpophalangeal joints. This change can affect the entire limb, face, neck and torso (chest, abdomen).

B. Secondary conditions:

(1) refers to hardening: the above skin changes are limited to fingers.

(2) Depressed scars on the fingertips, or the disappearance of the finger pad: a depressed scar on the fingertip due to ischemia, or the finger pad disappears.

(3) Fibrosis of the basal fibrosis of the lungs: On the chest radiograph, a strip-like or nodular dense shadow can be seen, which is also located at the bottom of both lungs, and can also be diffuse or honeycomb-like. This change caused by primary lung disease should be excluded.

Judgment: Patients with major conditions or more than two secondary conditions can be diagnosed as systemic sclerosis. In addition, Raynaud's phenomenon, polyarthritis or joint pain, abnormal esophageal motility, skin biopsy showed swelling and fibrosis of collagen fibers, serum ANA, anti-Scl~70 antibody and anti-centromere antibody are helpful for diagnosis.

Differential diagnosis

Differential diagnosis of skin involvement:

(1) Adult scleredema: The skin lesions mostly develop from the head and neck to the shoulder and back, and the deep dermis is swollen and stiff. Local non-pigmentation, no atrophy and hair loss, and self-healing tendency.

(2) mixed connective tissue disease: patients with systemic lupus erythematosus, scleroderma, dermatomyositis or polymyositis and other mixed manifestations, including Raynaud's phenomenon, face, hand non-recessed edema, finger-shaped sausage Swelling, fever, non-destructive polyarthritis, muscle weakness or myalgia. Both leaching nuclear antigen (ENA) and RNP antibodies are highly titer positive.

(3) Systemic lupus erythematosus: Raynaud's phenomenon and skin damage can also occur, and systemic lupus erythematosus is complex and variable, with early atypical symptoms and high misdiagnosis rate. Systemic lupus erythematosus changes to discoid erythema or butterfly erythema. Other skin lesions are complex and variable. In addition to the identification of systemic sclerosis, it can be identified by laboratory tests such as antinuclear antibody spectrum and biopsy. Systemic lupus erythematosus is positive for ANA, anti-ds-DNA antibody, anti-Sm antibody, anti-u1RNP antibody, and rare in systemic sclerosis. Patients with overlap syndrome and early atypical patients need to be vigilant.

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