acrosclerosis
Introduction
Introduction Acromegaly syndrome is also known as systemic scleroderma and progressive systemic sclerosis. The disease is a diffuse lesion of connective tissue characterized by inflammatory, fibrous, and degenerative changes associated with vascular disease. Mainly involved in the skin (scleroderma), synovial membrane and some internal organs (such as esophagus, intestine, heart, lung, kidney, etc.). The etiology of this disease is still unclear. At present, most people think that PSS may be an autoimmune disease caused by a chronic infection based on a certain genetic background.
Cause
Cause
The etiology of this disease is still unclear. At present, most people think that PSS may be an autoimmune disease caused by a chronic infection based on a certain genetic background. To sum up, the following aspects are involved:
1. Genetic and environmental factors: The disease has a clear family history and may be related to genes such as HLA-DR3, DR6, and C4null.
2. Connective tissue metabolism abnormalities: The disease has extensive connective tissue lesions. Fibroblast culture shows that the activity of collagen synthesis is significantly increased, and it is found that the fibronectin gene has a mutation, which leads to abnormal metabolism of connective tissue and leads to the occurrence of PSS.
3. Infection factors: Many patients often have acute infections before onset, such as sinusitis, angina, tonsillitis, pneumonia, scarlet fever. Paramyxovirus-like inclusion bodies were detected in the patient's striated muscle and kidney.
4. Cytokines: Many cytokines can regulate the expression of collagen components. For example, TGF not only has a strong regulatory effect on extracellular matrix, but also affects other cytokines, including IL-1, TNF1, PDGF, and basic fibroblast growth factor.
5. Immune abnormalities: A variety of autoantibodies (such as anti-nuclear antibodies, anti-DNA antibodies, anti-ssR-NA antibodies, antibodies against scleroderma skin extract) can be detected in patients with PSS, and the number of B cells is increased. The humoral immunity is obviously enhanced, and the CIC positive rate is as high as 50% or more. Most patients have hypergammaglobulinemia, and some cases often form with systemic lupus erythematosus, dermatomyositis, rheumatoid arthritis, and Sjogren's syndrome. Overlap syndrome.
Examine
an examination
Related inspection
Anti-RNP antibody rheumatoid factor serum globulin (G, GL0)
According to the PSS classification standard established by the American College of Rheumatology in 1980: PSA can be diagnosed by having one of the following main indicators or two secondary indicators.
1. Main indicators: proximal hard skin, symmetrical fingers and palmar or proximal toe skin thickened, tight, similar lesions are also seen in the entire limbs, face, neck, trunk (chest and abdomen).
2. Secondary indicators:
(1) The above skin changes are limited to the fingers.
(2) The fingertip may be concavely scarred or the finger pad thinned. The finger pad tissue is lost due to the depressed area at the ischemic fingertip.
(3) Fibrosis at the base of the lung: in patients with no primary pulmonary disease, there are reticular cues, nodules, and increased density at the bottom of both lungs. They may also be diffusely spotted or honeycomb.
PSS kidney damage can be diagnosed when PSS patients develop proteinuria, hypertension, or azotemia. However, many patients, especially in the early stages of the disease, often have no obvious renal damage and are missed. Patients with PSS should be combined with clinical manifestations, renal angiography, and renal biopsy to improve the diagnosis of renal damage.
Laboratory inspection:
1. Urine check proteinuria hematuria and granule cast.
2. Some blood samples can be found in the blood of lupus cells, the erythrocyte sedimentation rate is normal or slightly elevated; about half of the patients with protein electrophoresis have elevated gamma globulin; blood BUN, Scr increased, blood urea nitrogen >25mg/dl, Ccr decreased; Plasma renin levels are elevated.
3. Immunological examination:
(1) Rheumatoid factor (RF): 1/3 PSS patients were RF positive.
(2) ANA: 70% PSS patients were positive for ANA.
(3) Anti-Scl-70 antibody: a labeled antibody to diffuse PSS, found in 50% to 60% of patients.
(4) anti-centromere antibody: a labeled antibody for localized PSS, 70% to 80% of patients with localized PSS are positive for anti-filament antibody.
(5) Anti-nucleoside antibody: 30% to 40% of patients with PSS are positive for this antibody, and the positive rate of diffuse PSS is high.
(6) Anti-ribonucleoprotein antibodies (anti-RNP antibodies) and anti-SS-A (Ro) antibodies are sometimes positive.
Other auxiliary inspections:
1. Renal biopsy: Renal biopsy is an important way to evaluate renal damage in patients with PSS. Histologically, renal damage is divided into acute and chronic forms, which helps to assess the severity and classification of kidney damage. Acute lesions (arterial mucin-like edema, small arterial fibrinoid necrosis, glomerular capillary thrombosis, and renal infarction) are often seen in acute oliguric renal failure, most of which suggest a serious condition. Chronic inactive lesions (arterial intimal sclerosis, glomerular sclerosis, tubular atrophy, and renal interstitial fibrosis) suggest that the patient has impaired renal function after acute renal failure.
Moderate chronic lesions are usually seen in patients with long-term disease, chronic menstruation, or stable disease characterized by renal insufficiency and mild proteinuria with or without mild hypertension. In some patients without a history of clinical nephropathy, these inactive lesions were only discovered at the time of autopsy.
2. Indications for renal biopsy: indications for renal biopsy in patients with PSS are limited and not well defined. For the identification of patients with PSS, lupus nephritis and mixed connective tissue disease, renal biopsy is of considerable value. PSS patients with acute renal failure, if not clearly diagnosed as PSS kidney crisis, and can not rule out interstitial nephritis and other diseases, can be diagnosed by renal biopsy. Because renal lesions in patients with PSS cannot be estimated from clinical and other laboratory data, renal biopsy can provide useful information for the prognosis of PSS.
Progressive systemic sclerosis
3. Renal pathology: The actual incidence of renal pathological changes in patients with PSS is difficult to determine, estimated at 58% to 100%. The anatomical features of the kidneys of patients with PSS vary with the length and severity of renal vascular injury. In patients with acute renal failure with or without severe hypertension, the size of the kidney is normal because of the rapid onset of kidney damage. The renal surface of patients with acute renal failure is fine-grained or smooth, but when the acute renal failure occurs on the basis of the original chronic lesions, the renal surface appears as coarse particles. In acute renal failure, the kidney is bright red, and the renal cortex has a large number of sputum, ecchymosis and small wedge-shaped hemorrhage or pale yellow infarct area. In some cases, cortical infarcts are very numerous and fused to each other, making the cortical surface a plaque. In patients with mild chronic renal insufficiency, the kidneys are slightly shrunk, the surface of the cortex is finely granulated, and the color is pale or brown.
(1) Arterial histological changes: The main lesions of histological changes in renal vasculature in PSS patients are in interlobular arteries and arterioles. Vascular lesions can be divided into acute and chronic. There are two types of acute vascular disease: one is mucosal edema for endometrial proliferation, and this type mainly affects larger arteries. The other is cellulose-like necrosis, which mainly affects small arteries. These lesions may be focal or systemic.
1 acute phase: mucinous edematous endometrial proliferation first appeared in the interlobular artery, a small number appeared in the small arch artery, large arch artery and interlobular artery are often not involved. The typical lesion of vascular involvement is concentric epithelial hypertrophic edema hyperplasia, cells are relatively rare, and the lumen becomes narrow. Endothelial cell edema, partial shedding, loose endometrial stroma, hematoxylin-eosin-stained matrix is mildly basophilic or transparent, and the three-color stained mucoid matrix is transparent or light blue. A small amount of elongated endomysial cells are present in the matrix, and these cells are arranged in a spiral concentric shape, a so-called "onion skin"-like structure.
Some arterial mucin-like matrices contain basophils and fossil-like small clusters of fibrin-like substances that are positive for fibrin staining. A number of different fibrin deposits in the narrow lumen, the narrow lumen is often filled with deposited red blood cells, and the debris red blood cells are deposited in the deep intimal matrix, which provides a morphological basis for the involvement of microangiopathic hemolytic anemia in the pathogenesis of this disease. .
The middle layer of the blood vessel is thinned and expanded, and the outer diameter of the blood vessel is increased around the dilated inner membrane, and the three-color staining method shows that the middle layer of the blood vessel is slightly hardened. The outer membrane changes were not obvious, and some of the outer membranes were mildly fibrotic, showing a very small amount of monocytes. There are few reports of renal ultrastructural changes in patients with PSS. Consistent with the mucin-like intimal proliferation observed under light microscopy, the ultrastructure of acute interlobular arterial lesions is concentrically lined and has a medium electron density. The middle layer of the interlobular artery is thinner, with only 1 or 2 layers of cells, some of which are atrophied, the endoplasmic reticulum is swollen, and the phagosomes are increased. The outer membrane ultrastructure did not change significantly.
2 Chronic phase: Chronic arterial damage is narrowed due to the dense concentric inner membrane fiber elastic tissue of the lumen, and there is no mucosal edematous intimal hyperplasia. The hyperplastic fibrous elastic tissue is dark blue under trichromatic staining, indicating the presence of a rich matrix. The middle layer of the blood vessels is generally normal or mildly hardened, has a normal thickness, and has no expansion as seen in acute arterial injury. The outer membrane changes were not obvious.
Ultrastructural examination showed that chronic arterial lesions showed thickening of the intima. The thickened intima consisted of a dense concentric inner layer of endomysial cells. The endometrial cells were densely bounded by the intimal matrix and thickened. Separated by elastic tissue membranes and collagen bundles.
The basement membrane sheath of the slightly thickened surrounding muscle fibers can be seen in the middle layer of the blood vessel. Small arteries with an outer diameter of 50 to 15 m are less likely to exhibit mucin-like intimal hyperplasia. PSS arterioles mainly show fibrinoid necrosis, both endothelial cells and middle muscle fibers are swollen and necrotic. Strong eosinophilic cellulose-like substances occupy the vascular lumen and intima, and the affected vessels are severely narrowed or blocked. Occasionally, a small amount of polymorphonuclear leukocytes, Lymphocytes infiltrate the damaged intima or attach to the vessel wall. This is the second characteristic lesion of PSS vascular damage.
(2) Kidney glomerule:
1 acute phase: patients with severe PSS have different manifestations of glomerular damage in the acute phase. Fibrin thrombosis can be seen in some small bulb capillaries, which is segmental or small spherical. Red blood cell deposits and endothelial cell swelling and degeneration in capillaries are common in these areas. Occasionally, there are more cells in the mild capillaries or mesangial areas. Partial or complete necrosis of the glomeruli in the acute infarcted area. In patients with PSS renal crisis, the paracellular cells may develop hyperplasia.
2 Chronic phase: PSS chronic glomerular pathological changes are glomerular sclerosis, visible intravascular coagulation, glomerular ischemia, glomerular capillary wall thickening. Electron microscopy showed thickening of the glomerular basement membrane, which may have mild and irregular foot process fusion.
(3) renal tubules and interstitial: changes in renal tubules and interstitium in patients with PSS depend on the distribution, severity, and duration of vascular and glomerular damage. Cortical necrosis is seen in acute vascular injury, interstitial edema and lymphocytic infiltration occur, and red blood cells, white blood cells and detached tubular epithelial cells can be seen in the collecting duct. In the chronic lesions, mild to severe tubular atrophy, a small amount of lymphocytic infiltration, and interstitial fibrosis can be seen.
There are a variety of changes in glomerular and vascular immunofluorescence in patients with PSS. Similar to histological changes, immunofluorescence staining of vascular injuries is usually focal. In acute injury, IgM, C3, and fibrinogen were strongly positive in the intima, and IgG, IgA, C1q, and C4 deposition were also observed. Chronic vascular injury showed a small amount of deposition of IgM and C3, but no fibrinogen deposition. The lesions of the glomerulus and tubules are the same as the arteries, and the deepest staining, the most common are IgM and C3. In a few cases, IgG, IgA, C1q, and C4 deposits were observed.
4. X-ray examination: systemic patients often show periodontal membrane widening; esophageal and gastrointestinal tract peristalsis disappear, lower end stenosis, proximal widening, small bowel peristalsis, proximal small intestine dilatation, colonic bag spherical change; Bone resorption; thickening of the two lungs, or seeing cystic changes; soft tissue deposits within the soft tissue.
Diagnosis
Differential diagnosis
Limb keratosis: hemiplegic keratosis, also known as Hopf disease. The disease is a localized skin keratosis and excessive formation of granules, hereditary skin diseases caused by the formation of echinoderma and papilloma. The disease is autosomal dominant, usually one of the parents is a patient (heterozygous), the child's risk of recurrence is 50%, and men and women have equal opportunities.
Limb cyanosis: Cyanosis refers to an increase in the reduction of hemoglobin in the blood, which causes the skin and mucous membranes to change in shades of blue and purple. It can also be called purpura. Acromegaly, the onset of symptoms is cold limbs and cyanosis in the limbs. More common in young women.
Acromegaly: It is an important complication of systemic scleroderma. Persistent and recurrent ulcers can cause severe pain, infection, gangrene, dysfunction and declining quality of life, causing great pain to patients. Because of this, the research on acral ulcers in scleroderma has become a hot issue in recent years.
Limb ischemia: Symptoms caused by insufficient blood supply at the extremities of the extremities. A physical examination can be diagnosed.
