Allergic purpura nephritis

Introduction to allergic purpura nephritis Anaphylactoid purpura, also known as hemorrhagic capillary venom, is a capillary allergic hemorrhagic disease that may be associated with autoimmune damage to blood vessels. Clinical features In addition to purpura, there are often rash and angioedema, arthritis, abdominal pain and nephritis. Clinically, the kidney damage caused by allergic purpura is called allergic purpura nephritis. basic knowledge The proportion of illness: 0.006% Susceptible people: no specific population Mode of infection: non-infectious Complications: nephrotic syndrome hypertension

Causes of allergic purpura nephritis

(1) Causes of the disease

Upper respiratory tract infection (30%):

Allergic purpuric nephritis is a secondary disease of allergic purpura, and the cause of allergic purpura is not clear, and may be related to toxins and allergies. Some cases have infections before onset, the most common being upper respiratory tract infections (non-specific or streptococcal infections).

Drug factors (30%):

Drug antibiotics (such as tetracycline, Vancomycine, etc.), sulfonamides, isoniazid, salicylic acid, barbital, quinine, iodide, streptokinase, vaccination (measles vaccine, epidemic cerebrospinal meningitis vaccine, etc.), tuberculosis The bacteriocin test has become the cause of this disease.

Other factors (28%):

Pollen or insect bites, cold stimulation. There are also a small number of patients with no obvious incentives. A large amount of data indicates that the disease is an immune complex disease.

(two) pathogenesis

It is currently believed that this disease is an immune complex disease, and allergic purpura nephritis caused by various causes is a process including the formation, circulation and deposition of immune complexes. The circulating immune complex can be measured in the serum of patients, mainly IgA, IgA increased more obviously after infection, IgA and C3 granules were detected in diseased blood vessels and glomeruli. Therefore, data indicate that IgA plays an important role in the pathogenesis of allergic purpura nephritis, and immunopathological techniques confirm that The deposited IgA has no secretory tablets but has a J chain, suggesting that it is poly-IgA deposition. The deposition rate of IgA in the kidney, mesentery and skin is higher than that of other organ tissues. As for the exact mechanism of IgA in the pathogenesis of this disease, it is unclear. It is an antigen, and it is also considered to be an antibody or a non-specific antibody. It is produced when an antigen is stimulated by the body to produce the corresponding antibody. Currently, there are two opinions on the effect of IgA. One thinks that IgA may be the body's response to different antigens. The resulting antibody, which then forms an immune complex, is deposited on the mesangial membrane, and the other is considered to be IgA, which is directed against the glomerular mesangial Or an antigen that has been fixed to the mesangium and deposited in the mesangium. Recently, it has been suggested that IgA is not an antibody but an antigen, and IgG is an antibody of IgA. Since C3 and properdin are often found in the lesion, C1q is not easily found. C4 et al. believe that it is possible to cause immune damage to tissues by activating the complement bypass system. Other immune abnormalities include increased B cells secreted by IgA, T-regulated cell changes, and some studies have found that renal tissue exists in patients with allergic purpura nephritis. A large number of lymphocytes and monocytes infiltrate, and the clinical and pathological diversification, the response to treatment is not the same, so the pathogenesis of allergic purpura nephritis is not a single factor, cell-mediated tissue damage in the pathogenesis of allergic purpura nephritis makes an important impact.

In addition, the intravascular coagulation mechanism is also involved in the pathogenesis, the patient's fibrin degradation products (FDP) increased, platelet aggregation and fibrin deposition and thrombosis were found in the glomerular capillary lumen, suggesting that there is microvascular coagulation leading to the kidney. damage.

Recent studies have found that cytokines play an important role in mediating the development of vasculitis. IL-1 can affect the function of mesangial cells through autocrine or paracrine formation. In addition to promoting mesangial cell proliferation, IL-1 can promote mesangial cell proliferation. Increased release of cytokines (1L-6, IL-8, MCP-1, PDGF) and adhesion molecules (ICAM-1, VCAM-1) and the role of extracellular matrix, as well as glomerular crescents Form related.

Domestic studies have found that the rate of interleukin-1 receptor antagonist allele (IL-1 RN*2) in patients with allergic purpura nephritis is significantly higher than that of normal people, due to the inflammation caused by genetic specific background, The body can not effectively antagonize the inflammatory effect of IL-1, and may be one of the most important factors in the pathogenesis of allergic purpura nephritis. In addition, the carrying rate of IL-1 RN*4 allele in patients with allergic purpura nephritis is also significantly higher. In normal people and patients with IgA nephropathy, its clinical significance remains to be elucidated.

Allergic purpura nephritis prevention

First of all, you should avoid contact with various "unjust qi" that induces this disease, avoid fish, shrimp, crab, pollen, milk and other diets that may induce allergies. Secondly, you should pay attention to cold and warmth, prevent colds, pay attention to exercise, enhance physical fitness, and improve The body's disease resistance, bed rest after illness, avoid overwork, avoid eating alcohol and tobacco, diet should be rich in nutrition, easy to digest, eat more fresh vegetables, fruits, for patients with hematuria, should not eat spicy, fragrant and irritant And seafood and hair such as cock, sea fish, beef, lamb, goose, etc., so as not to help heat the fire to aggravate the condition, more urine protein, should pay attention to not eat high-protein diet, to prevent deficiency.

Allergic purpura nephritis complications Complications nephrotic syndrome hypertension

Allergic purpura nephritis is mainly complicated by severe nephrotic syndrome, hypertension and acute renal failure.

Allergic purpura nephritis symptoms common symptoms skin purpura pimples gastrointestinal bleeding proteinuria nausea and vomiting blood urinary angioedema low heat convulsions repeated hematemesis

In addition to extrarenal manifestations, the disease, clinical manifestations, especially immunopathological changes are very similar to IgA nephropathy.

Extrarenal performance

(1) skin purpura: one of the main reasons for the clinical diagnosis of this disease is that the majority of patients with skin purpura as the first symptom, skin purpura often occurs in the distal extremities of the extremities, buttocks and lower abdomen, mostly symmetric distribution, skin The size of the lesion is not equal, it is a hemorrhagic spot, slightly protruding the skin, can be fused into a piece, itchy, no pain, may have one or more recurrences, or may appear in batches, gradually disappear after 1 to 2 weeks, there are also 4 ~ 6 weeks of delayed remission, sometimes urticaria and hemorrhagic maculopapular rash, angioedema and other symptoms may occur in batches.

(2) joint symptoms: 1/2 ~ 2 / 3 patients have joint symptoms, mostly in the larger joints, such as the knee, ankle joint, followed by the wrist and finger joints, often expressed as tender and swollen around the joints, but No red, hot, no deformity.

(3) digestive system symptoms: about 2 / 3 patients have gastrointestinal symptoms, abdominal dislocation is more common, physical examination of the abdomen has tenderness, generally no abdominal muscle tension or rebound tenderness, accompanied by nausea, vomiting, often There are gastrointestinal bleeding, intestinal edema, hemorrhage or stiffness, can form intussusception, intestinal perforation, clinical manifestations of hematemesis or melena, there are reports of pancreatitis.

(4) Other manifestations: Those with a history of upper respiratory tract infection may have headache, low fever, general malaise, occasional nosebleed or hemoptysis, nervous system involvement as headache, behavioral abnormalities and convulsions, and a small number of patients have myocarditis.

2. Intrarenal performance

The renal involvement rate of allergic purpura is extremely high. Even in patients with normal urine examination, glomerular inflammatory lesions are found in renal histological examination. Kidney symptoms can be seen at any time of the disease, but within 4 weeks after the occurrence of purpura More common, can also appear later, even after the onset of the disease for several months to more than 2 years, occasionally a small number of patients, first under the microscope hematuria, after the emergence of rash and other symptoms, the severity of kidney involvement and skin, joints, There was no significant correlation between the extent of gastrointestinal involvement, and the main clinical manifestations of renal involvement were as follows:

(1) Hematuria: The most common clinical manifestations of renal involvement are gross hematuria or microscopic hematuria, which can occur continuously or intermittently. It is more common in children with gross hematuria than in adults, and is exacerbated after infection or cyanosis. Most cases are different. Degree of proteinuria, hematuria is mostly caused by nephritis, occasionally due to bleeding from the ureter, bladder or urethra mucosal surface.

(2) proteinuria: most cases have different degrees of proteinuria, proteinuria is mostly moderate, quantitative more than 2g / d, and hematuria severity is not necessarily proportional, serum protein levels decreased more than proteinuria, The reason may be that in addition to leakage through the kidney, the protein may also leak from other parts such as the gastrointestinal tract, subcutaneous tissue, etc. In some cases, proteinuria may be present in the range of nephrotic syndrome.

(3) Hypertension: generally mild hypertension, obvious hypertension and poor prognosis.

(4) Others: A small number of patients have edema, most of which are mild. The cause of edema is related to proteinuria, gastrointestinal protein loss and capillary permeability changes. The renal function is generally normal, and a small number of patients have a transient increase in serum creatinine.

3. Clinical classification

According to the renal histological changes of allergic purpura nephritis, the severity of the disease is very different, and the clinical manifestations are generally divided into 5 types:

(1) acute purpura nephritis syndrome: the clinical features of this type are hematuria, proteinuria, edema and hypertension, acute onset, similar to acute nephritis, most of which are of this type, histological changes are mostly focal proliferative nephritis or diffuse Proliferative nephritis.

(2) mild purpuric nephritis: manifested as asymptomatic hematuria, proteinuria, edema, hypertension or renal dysfunction, the incidence of this type is second only to acute purpura nephritis syndrome, the prognosis is good, pathologically mostly minor abnormalities Or focal segmental changes.

(3) Chronic purpura nephritis syndrome: this type of onset is slow, the symptoms of nephritis persist after skin changes, often accompanied by varying degrees of renal dysfunction, more common in adults, poor prognosis, pathological changes in diffuse proliferative changes, May be associated with crescent formation or glomerular sclerosis.

(4) purpura nephrotic syndrome: this type has typical nephrotic syndrome, most of which are associated with renal dysfunction, poor prognosis, severe glomerular lesions, diffuse proliferative nephritis, often accompanied by varying degrees of crescent formation.

(5) Rapid progressive purpura nephritis: patients with acute onset, early oliguria or no urine, progressive renal damage, rapid progressive nephritis, rapid deterioration of the disease, often died of renal failure in a short time, This type is rare, more than 50% of pathological examinations have crescent formation.

Examination of allergic purpura nephritis

Blood routine examination

Platelets, bleeding time, clotting time, clot retraction time and prothrombin time are normal, and severe bleeding may be associated with anemia.

2. Immunological examination

Serum IgA increased, IgG, IgM was normal, IgA began to increase 2 weeks after onset, C3, C4, CH50 mostly normal or increased, interleukin-6 (IL-6) and tumor necrosis factor (TNF-a) Raise.

3. Renal function

Blood urea nitrogen, creatinine can be increased, and creatinine clearance can be reduced.

4. Urine check

Hematuria, proteinuria and tubular urine can be seen.

Renal biopsy: The main pathological condition of allergic purpura nephritis is the proliferation of mesangial cells, often accompanied by different degrees of proliferation of endothelial cells and epithelial cells. The proliferation of epithelial cells often adheres to the balloon and forms a small crescent. Most of the affected glomeruli are below 50%. Although some very light focal lesions may also have crescent formation, most scholars believe that crescent formation is a prominent pathological manifestation.

Other inspection

Light mirror

Mesangial lesions are mainly caused by mild to severe changes. The main lesions of the small spheres are focal segmental mesangial hyperplasia with various degrees of cell proliferation, small focal necrosis, exudation, and capillary Intravascular thrombosis, glomerular hyalinosis, capillary double-track changes, etc., often accompanied by varying degrees of crescent, acute glomeruli may have focal segmental scar formation Hardening, more severe cases of renal tubular and interstitial lesions, tubular epithelial cell swelling, vacuolization, necrosis, atrophy, interstitial inflammatory cell infiltration or fibrosis (Figure 1).

Zollinger summarized 349 cases of allergic purpura nephritis pathological changes and divided them into 4 types:

(1) focal proliferative nephritis, 49%.

(2) mild lesions or mesangial proliferative nephritis type, 37%.

(3) crescentic nephritis type, 5%.

(4) Mesangial capillary nephritis type, 1%.

According to the lesions from mild mesangial hyperplasia to different degrees of crescent formation, according to the International Children's Nephrology Society (ISKDC) standards, combined with the pathological features of Chinese allergic purpura nephritis, can change the light microscopy of allergic purpura nephritis Divided into 6 levels,

Grade I: minor lesions.

Grade II: focal or diffuse mesenteric hyperplasia.

Grade III: focal or diffuse mesangial hyperplasia, <25% crescent formation and/or glomerular sclerosis.

Grade IV: Same as III, crescent formation and/or glomerular sclerosis, the ratio is between 25% and 50%.

Grade V: Same as III, crescentic and/or glomerular sclerosis, with a ratio of 50% to 75%.

Grade VI: Same as III, crescentic and/or glomerular sclerosis >75%, or membrane proliferative nephritis.

2. Immunofluorescence

Immunofluorescence is mainly IgA deposition, the positive rate is 90% to 100%, mostly distributed in the mesangial area, also in the blood vessel wall, a few may be accompanied by IgG, IgM, C3, properdin and fibrin diffuse granular or Bulk deposits, fibrin-associated antigen deposition in the crescent or necrotic area, with fewer C4 or C1q deposits (13/104, 12.5%), Uab, IGH, R-GH pathology II, III The majority of the grades, while NS, HT, RPGN type pathology is more IV ~ VI grade, the first three types of clinical simple IgA deposition, while the latter three clinical IgA, IgG, IgM simultaneous deposition, Muda focused laser Scanning microscopy (CLSM) was used to observe the main components of immune complexes as IgA and C3. The spatial structure of IgA outer layer was lightly damaged, while the immune complex was exposed without IgA. The renal damage was heavy, suggesting that the complement components were in direct contact. Cell or mesangial interstitial receptors cause cell breakdown and inflammation. Skin biopsy revealed IgA deposition in the capillary wall, whether in the rash or non-rash site.

3. Electron microscopy

It can be seen that mesangial cells proliferate, the matrix increases, there are extensive mesangial areas and irregular electron dense deposits under endothelial cells. IgA components in the electron dense substance are confirmed by immunoelectron microscopy. Occasionally, electron density is dense under epithelial cells. Deposition with basement membrane rupture and luminal neutrophil infiltration.

Diagnosis and differentiation of allergic purpura nephritis

Allergic purpura nephritis must have the characteristics of allergic purpura and nephritis in order to confirm the diagnosis. Because the disease has special skin, joint, gastrointestinal and kidney involvement, the kidney has mesangial proliferative pathological changes mainly based on IgA deposition. It is not difficult to diagnose the diagnosis. About 25% of the patients have mild renal involvement. Repeated urine examination is needed to detect the main basis of renal involvement. If necessary, the pathological examination of the kidney can help confirm the diagnosis. The serum test for IgA and IgM is mostly elevated, IgG. Normal, in many cases, the amount of cryoglobulin in the blood increases. The pathological changes of the kidney in this disease are similar to those of IgA nephropathy, but the glomerular capillary necrosis and the degree of cellulose deposition are heavier, so it should be distinguished.

Differential diagnosis

Acute nephritis

The disease is different from purpura nephritis in that serum C3 is mostly decreased; there is no rash, arthritis and colic; skin biopsy and renal biopsy can help identify.

2. Lupus nephritis

Lupus nephritis rash has characteristic butterfly erythema or discoid erythema, mostly congestive erythema; lupus in addition to joints, rash, abdomen and kidney performance, there are many systemic damage including photoallergic, oral ulcer, serositis, nerve Systemic manifestations, abnormal blood system examination, immunological examination showed decreased serum C3, anti-dsDNA positive, anti-Smith antibody positive, anti-nuclear antibody positive; skin biopsy: lupus positive; renal biopsy: lupus kidney with V-type pathological changes, small renal The capillary wall of the ball was changed by "Platinum ear", and the immunofluorescence showed "full hall bright". IgG, IgM, IgA, C3 co-deposited, mainly IgG, IgM.

3. Primary vasculitis (micro polyarteritis, Wegener granuloma)

In addition to rash, kidney damage, upper respiratory tract, lung performance, skin or nodule biopsy showed swelling of the endothelial cells of the blood vessel wall, hyperplasia, middle cell necrosis with inflammatory cell infiltration, edema, sometimes accompanied by a large number of lymphocytes , monocytes, multinucleated giant cells and neutrophil infiltration, even granulomatous lesions, no immunoglobulin deposition, immunofluorescence negative, renal biopsy: glomerular segmental necrosis with peripheral inflammatory cell infiltration, and even granuloma Formation, may be associated with crescentic body, most negative immunofluorescence, sometimes manifested as necrotizing arteriitis, anti-leukocyte cytoplasmic antigen autoantibodies (ANCA) can be found in the blood, micro-polyarteritis is mainly perinuclear PANCA, The target antigen is myeloperoxidase (MPO), the Wegener granuloma is mainly cytoplasmic C-ANCA, and the target antigen is protease 3 (PR3).

4.IgA nephropathy (IgAN)

IgA nephropathy is mainly caused by repeated gross hematuria, with few rashes, joint pain and abdominal manifestations; IgAN is more common in adulthood; pathological examination is more common in IgA, IgG, IgM deposition, and the proportion of C4/C1q deposition in classical complement activation is significantly increased. Sexual purpura nephritis is difficult to distinguish from IgA nephropathy according to changes in renal pathology and immunopathology. Most authors believe that the clinical and pathological process of renal allergic purpura nephritis is very similar to IgA nephropathy, so they are considered to be two different diseases of the same disease. Performance, IgA nephropathy is mainly affected by kidney involvement, allergic purpura nephritis in addition to kidney involvement and systemic system damage, further genetic studies found that the two diseases occurred in the same family, homozygous ineffective C4 genetic phenotype (homozygous Null C4 phenotype) increased in frequency, all of which showed IgA immunoregulatory abnormalities, such as IgA and macromolecular (poly) IgA increased, the ratio of IgA plasma cells / IgG plasma cells in the tonsil lymphoid tissue increased in both patients, allergies Sexual purpura nephritis is a systemic vasculitis, also a secondary IgA nephropathy, which is pathologically associated with IgA nephropathy with mesangial disease. Mainly, with crescent formation and glomerular sclerosis, especially in patients with IgA nephropathy, recurrent episodes of hematuria, regardless of clinical manifestations or genetic background, compared with other clinical types of IgA nephropathy and allergies There are many similarities in purpura nephritis, but although there are many similarities between allergic purpura nephritis and IgA nephropathy, there are still significant differences between the two (Table 1).

5. Blood disease caused by purpura

Due to platelet count and hemorrhage of allergic purpura nephritis, the clotting time is normal, so it can be distinguished from purpura caused by blood diseases.

6. Acute abdomen

Because abdominal allergic purpura is prone to nephritis, especially before the appearance of purpura, it should be differentiated from acute appendicitis, hemorrhagic enteritis, intestinal perforation, acute pancreatitis or kidney stones; if there is hemoptysis, renal failure and Goodpaschu (Goodpasture) syndrome identification.

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