Allergic purpura Allergic purpura is an autoimmune disease that causes increased capillary permeability and fragility due to the body’s metamorphic reaction to certain allergic substances, resulting in bleeding and edema in subcutaneous tissues, mucous membranes and internal organs. Allergens can be caused by a variety of factors, but it is often difficult to find the exact cause for each specific case. It is usually believed that it may be related to a variety of predisposing factors, but the direct causative factors are often difficult to identify. (1) Infectious factors The most common bacterial infection is β-hemolytic streptococcus, followed by Staphylococcus aureus, Mycobacterium tuberculosis, Mycobacterium typhi, Pneumococcus and Pseudomonas, etc. The above respiratory tract infections are more common and can also be seen in pneumonia, tonsillitis, scarlet fever, bacillary dysentery, urinary tract infections, impetigo, tuberculosis and focal infections (skin, teeth, mouth, middle ear). Viral infections include rubella, influenza, measles, chickenpox, mumps, hepatitis, etc. Parasitic infections can also cause this disease, roundworm infection is common, as well as hookworm, whipworm, tapeworm, schistosome, trichomonas vaginalis, Plasmodium infection, etc. (2) Food factors Mainly due to animal allergic protein to the body, fish, shrimp, crab, clams, eggs, chicken and milk can cause this disease. (3) Drug factors such as chloramphenicol, streptomycin, isoniazid, aminopyrine, aspirin, sulfonamides and other drugs have been reported to cause this disease. (4) Other factors Insect bites, plant pollen, cold, trauma, menopause, tuberculin testing, vaccination, and psychological factors can cause the disease. It has also been reported to cause allergic purpura in hemodialysis patients, patients after chemotherapy for lymphoma, and patients with Guillain-Barre syndrome. The lesions are quite extensive and can involve the skin, joints, gastrointestinal tract, kidneys, heart, pleura, respiratory organs, central nervous system, pancreas, testes, etc. (B) Pathogenesis Under the sensitizing effect of the above-mentioned factors, metabolic reactions occur in the body, and the mechanisms are possible as follows: 1. Rapid metabolic reactions After the allergens enter the body, they combine with proteins in the body to form antigens, which, after a certain incubation period (5-20 days), stimulate immune tissues and plasma cells to produce IgE. IgE adsorbs on mast cells in various organs throughout the body (perivascular, gastric cavity, skin). skin). When stimulated by the same antigen, the antigen combines with IgE adsorbed on mast cells and activates the enzyme system in the cells, causing them to release a series of bioactive substances, such as histamine, 5-TH, bradykinin, slow-response substances for allergy (SRS-A), and also excite sympathetic nerves and release acetylcholine. This series of bioactive substances, mainly acting on smooth muscle, cause dilation of small arteries and capillaries, increased permeability, hemorrhage and edema in tissues and organs. 2, antigen-antibody complex reaction This is the main pathogenesis. Allergens stimulate plasma cells to produce IgG (also IgM and IgA), which binds with the corresponding antigen to form an antigen-antibody complex, the small molecule part of which is soluble and can be precipitated in the blood on the vessel wall or glomerular basement membrane, activating the complement system to produce C3a, C5a, C5, C6, C7 can attract neutrophils, which phagocytose the antigen-antibody complex, releasing lysosomal enzymes, causing vasculitis and involvement of the corresponding organs. In the other part of the immune complex, there are more antibodies than antigens, and the complexes have a large molecular weight and are non-soluble and precipitated, which are cleared by the monocyte macrophage system and generally do not produce pathological changes. 3, the role of cytokines It has been reported that TNFα and soluble TNF receptor (sTNFR) in the serum of patients with allergic purpura are in the normal range, while the level of sIL-2R is elevated. In the local tissue cells of the kidney of patients with allergic purpura with renal injury, there is expression of various inflammatory factors such as IL-1α, IL-1β, TNF-α and LT. IL-4 promotes IgE synthesis and may be an important factor in the process of the disease. Clinical manifestations】 1. Symptoms and signs A. Prodromal symptoms There are often symptoms such as low fever, sore throat, upper respiratory tract infection and general discomfort 1 to 3 weeks before the onset of the disease. B. Typical symptoms and signs Clinically, there are different manifestations due to different sites of lesions. (1) Skin symptoms: symmetrically distributed maculopapular purpura of different sizes appearing in batches near the large joints of the lower limbs and buttocks, mainly on the extensor side of the lower limbs and buttocks, often symmetrical, with a few involving the face and trunk. The purpura can be prominent on the skin surface, with a slight itching, at first bright red, then dark red, brown, but also can show urticaria, angioneurotic edema, erythema multiforme, and even ulcerative necrosis and hemorrhagic macules. The rash varies in size and may fuse into patches, appear in batches, or recur, and some may be accompanied by limited or diffuse edema, such as head, face, eyelids, etc. The skin purpura usually fades away after about 2 weeks. (2) Joint symptoms: The clinical term is joint type. The joints may have mild pain to obvious redness, swelling, pain and mobility disorders, and may have single or multiple, wandering joint swelling and pain or arthritis, sometimes with localized pressure pain, the lesions often involve large joints, the knee, ankle, elbow, wrist and other joints, may be wandering, often easily mistaken for “rheumatism”. This disease is also called Schönlein type. In children, there are joint symptoms with scrotal involvement, which can help to identify and diagnose atypical allergic purpura. (3) Gastrointestinal symptoms: about 2/3 of patients can present with abdominal pain often in the form of colic, mostly in the right lower abdomen and around the umbilicus, but also throughout the abdomen, due to the leakage of bloody fluid into the intestinal wall, but rarely with abdominal muscle tension, which can be accompanied by nausea, vomiting, blood in the stool and mucus-like stools, irregular peristalsis of the intestine, which can also lead to intussusception, which is common in children, if the abdominal symptoms are not accompanied by purpura, it is often misdiagnosed “Acute abdomen”. The abdominal symptom type is also known as Henoch type. The clinical term is abdominal type. (4) Renal symptoms: usually appear around 2 to 4 weeks after purpura with hematuria of the naked eye or microscopic hematuria, proteinuria and tubular urine, but also after the rash subsides or during the disease quiescence. Recovery usually occurs within a few weeks. In severe cases, hyperalgesia, azotemia and hypertensive encephalopathy may occur. In rare cases, hematuria, proteinuria, or hypertension may persist for more than 2 years. The clinical term is renal type. (5) Neurological symptoms In a few patients, after the appearance of purpura, the lesion may also involve the brain and meningeal vessels, manifesting as symptoms of the central nervous system, such as headache, vomiting, dizziness, blurred vision, confusion, irritability, delirium, paralysis, intracranial hemorrhage, coma, etc. 2. Common complications may include intussusception, intestinal obstruction, intestinal perforation, hemorrhagic necrosis, enterocolitis, intracranial hemorrhage, polyneuritis, myocarditis, acute pancreatitis, orchitis, and pulmonary hemorrhage, etc. Diagnostic criteria] 1, blood often returned to the examination: blood cells mild to moderate increase, eosinophils normal or increased, bleeding can be more anemic, clotting time, platelet count, clot contraction time are normal. 2.Blood sedimentation: most patients have increased blood sedimentation. 3.Anti-O: may be increased. 4.Serum immunoglobulin: serum LGA may be increased. 5.Urinary routine: protein, red blood cells or tubular type may appear in the urine of those with kidney involvement. 6.Blood urea nitrogen and kegan: increased in renal insufficiency. 7.Fecal occult blood: positive type in case of gastrointestinal bleeding. 8.Capillary fragility test: positive in about half of the patients. 9, renal tissue biopsy: can determine the nature of nephritis lesions, and has a guiding significance for the determination of treatment and prognosis. There are no uniform diagnostic criteria for this disease. (1) The diagnostic criteria established by the American College of Rheumatology in 1990 include the following 4: ① skin purpura above the skin surface, not accompanied by thrombocytopenia; ② age of first occurrence ≤ 20 years; ③ intestinal colic, diffuse, intensifying after meals, or intestinal ischemia, usually accompanied by bloody diarrhea; ④ tissue biopsy, small arteries and small vein walls with neutrophil infiltration. The disease can be diagnosed if 2 or more of the above 4 items are met. (2) The domestic diagnostic criteria formulated in the book “Diagnostic and efficacy criteria for hematologic diseases” edited by Zhang Zhinan contain the following points: ① Clinical manifestations: A. Symptoms such as low fever, sore throat, upper respiratory tract infection and general malaise are often present 1 to 3 weeks before the onset of the disease. B. Symmetrically distributed maculopapular purpura of varying sizes appearing in batches near the large joints of the lower limbs and buttocks, may be accompanied by urticaria or edema, polymorphic erythema. C. There may be hemorrhagic enteritis or arthralgia during the course of the disease. In a few patients, abdominal pain or arthralgia may occur 2 weeks before the appearance of purpura. There is often purpura nephritis. ②Laboratory examination: normal platelet count, normal platelet function and clotting time. ③Histological examination: neutrophil aggregation around small vessels in the dermis of the affected skin, focal fibrous necrosis in the vessel wall, epithelial cell hyperplasia and erythrocyte exudation outside the vessels, immunofluorescence examination shows vasculitis lesions with IgA and C3 deposition in the vessel wall of the dermis. ④ Excluding vasculitis caused by other diseases: e.g. cold globulin syndrome, benign hyperglobulin purpura, circumscribed capillary dilated purpura, pigmented purpura mossy dermatitis, etc. The diagnosis can be confirmed if the clinical manifestations are consistent, especially non-thrombocytopenic purpura with palpable typical rash, and if other types of purpura can be excluded. If the differential diagnosis is really difficult, pathological examination can be done. The sensitivity of the diagnostic criteria of the American College of Rheumatology is 87.1% and the specificity is 87.7%. However, the significance of each criterion is not equal, with typical skin purpura being the most sensitive and specific, followed by age at first onset. In addition, almost all patients had skin purpura at the onset of the disease, either mildly or severely. Therefore, it seems more reasonable to replace “diagnostic if 2 or more items are met” with “diagnostic if ① plus 1 or more other items are present”. The pathological manifestations of tissue biopsy are not specific and therefore not necessary for diagnosis. The disease is generally diagnosed with typical clinical manifestations and routine laboratory findings, and pathological examination is considered only when there is a genuine difficulty in differential diagnosis. In addition, renal damage is present in about 30% of patients, but this is not included in the criteria of the American College of Rheumatology, which is its shortcoming. Although the domestic diagnostic criteria formulated in the book “Diagnostic and efficacy criteria for hematologic diseases” edited by Zhang Zhinan is longer, it seems more reasonable considering the above-mentioned shortcomings. In the past, the disease was often divided into skin type (simple purpura type), abdominal type, joint type and nephritis type (purpura nephritis) according to the main clinical manifestations, and if more than 2 types exist together, it is called mixed type. Because of the insidious nature of some organ injuries, it is sometimes difficult to exclude them, and the emphasis on typing is no longer emphasized. However, it should be clear that the prognosis is very different depending on the site and degree of involvement. For example, the prognosis of those with kidney damage is the worst. Therefore, the site and degree of involvement should be continuously re-evaluated for those with recurrent disease. (a) Treatment 1. Treatment of the cause Eliminating the causative factors, controlling infection, eliminating parasites, avoiding allergic foods and drugs, etc. are the fundamental measures to prevent recurrence and cure the disease. Deworming treatment can be carried out. 2, general therapy (1) antihistamines: can use promethazine hydrochloride (non-nagin), chlorpheniramine (paracetamol), phenothiazine, dechloroxazine (ketamine) or terfenadine tablets, etc.. Calcium gluconate 10% can also be given intravenously, but its efficacy is variable. Paracetamol: 8mg, 3 times/d, orally; Xithromax: 10mg, 2 times/d, orally. (2) Rutin and vitamin C: applied as adjuvants, generally the dose should be large, and vitamin C is better to be injected intravenously. (3) Hemostatic drugs: Carbacrol (Antenoxin, Anloxin) 10mg, 2-3 times/d, intramuscularly, or 40-60mg added to glucose solution intravenously. Phenolsulfonamide (hemostat) 0.25-0.5g, intramuscular injection, 2-3 times/d or sedation. If there are renal lesions, antifibrinolytic drugs should be used with caution. 3.Adrenocorticotropic hormone Inhibits antigen-antibody reaction and has anti-allergic and improving vascular permeability effects. It is effective for joint type, abdominal type and skin type, but the hormone is not effective for renal lesions, and some people think that it cannot shorten the course of the disease. 30mg/d of prednisone (prednisone) is generally used, divided into oral doses, and if the rash does not subside in 1 week, it can be increased to 40-60mg/d, and the dose is gradually reduced until it is discontinued after the symptoms are controlled. 100-200mg/d of hydrocortisone can also be used, and oral doses are changed after the condition improves. 4, Immunosuppressants Allergic purpura complicated by nephritis, to hormone therapy is not good or the disease is prolonged can add immunosuppressants, usually often combined with hormones, can choose cyclophosphamide, azathioprine, etc., but should pay attention to the complication of infection. 5, anticoagulation therapy For cases of acute nephritis, nephrotic syndrome, in addition to corticosteroids, cyclophosphamide (CTX), anticoagulation therapy is also available, such as heparin 10-20U/(kg-h) × 4 weeks, so that the APTT is maintained to 1.5-2.0 times the normal value. 6, patients with renal impairment to improve renal microcirculation: 654-2 (20-30mg/d) + Chuanxiongzine (300mg/d) or Danshen injection, intravenous drip, 10d as a course, 1~2 times a month. 7.Other At present, it has been reported abroad that for patients with severe allergic purpura in which hormones and immunosuppressants are ineffective, aminophene may be an effective therapeutic drug. The therapeutic dose is 100mg/d, and the G-6-PD level should be checked before treatment. Blood ortho-ferritin levels should be noted during treatment. The typical symptoms can be largely controlled after 2 weeks of treatment. It has not been reported in China. (B) Prognosis The prognosis of this disease is mostly good, the course of the disease is usually 3-6 months, and an attack can last from 1 week to 6 months. The duration of the disease is shorter for those with only joint and skin symptoms, and longer for those with significant abdominal symptoms. The prognosis is serious if the disease is complicated by nephritis and progresses to renal failure, or if there are brain lesions complicated by cerebral hemorrhage. Ruijin Hospital had statistics of 350 cases of allergic purpura, 181 cases (57.71%) were cured at discharge, 153 cases (43.72%) were improved, 15 cases (4.29%) were not cured, and 1 case (0.28%) died. The cause of death was progression of nephritis to renal failure with pulmonary infection and sepsis.