I. Definition Urticaria is a limited edematous reaction due to the dilation and increased permeability of small blood vessels in the skin and mucous membranes. It is characterized clinically by itchy, itchy, angioedema-prone clusters of varying size. Chronic urticaria is defined as at least 2 episodes of urticaria per week, lasting ≥ 6 weeks. A small number of patients with chronic urticaria may also show intermittent attacks. The cause of acute urticaria can often be found, but the cause of chronic urticaria is more difficult to define. The causes are usually divided into exogenous and endogenous. Exogenous factors are mostly temporary and include physical stimuli (friction, pressure, cold, heat, sunlight exposure, etc.), food (animal proteins such as fish, shrimp, crab, shellfish, eggs, etc., plant or fruit such as lemon, mango, plum, apricot, strawberry, pecan, cocoa, garlic, tomato, etc., spoiled food and food additives), drugs (immune-mediated such as penicillin, sulfonamides, serum preparations, various vaccines, or non-immune-mediated mast cell releasing agents such as morphine, codeine, aspirin, etc.), implants (artificial joints, anastomoses, heart valves, orthopedic plates, steel nails, and gynecological birth control devices, etc.), and exercise. Endogenous factors are mostly persistent and include mast cell hypersensitivity to IgE, chronic occult infections (bacterial, fungal, viral, parasitic, etc., e.g., Helicobacter pylori infection may be important in a minority of patients), exertion or stress, autoimmunity against IgE or high-affinity IgE receptors, and chronic diseases such as rheumatic fever, systemic lupus erythematosus, thyroid disease, lymphoma leukemia, inflammatory bowel disease, etc. In particular, chronic urticaria is rarely caused by allergen-mediated causes. The pathogenesis of urticaria is still not well understood and may involve infection, allergic reactions, pseudo-allergic reactions and auto-reactivity. Mast cells play a central role in the pathogenesis, and their activation and degranulation, leading to the release of histamine, leukotrienes, prostaglandins, etc., are key to the occurrence, development, prognosis and therapeutic response of urticaria. Mechanisms that induce mast cell activation and degranulation include immunologic, nonimmunologic, and idiopathic. Immune mechanisms include autoimmunity against IgE or high-affinity IgE receptors, IgE-dependent, and antigen-antibody complex and complement system-mediated pathways; nonimmune mechanisms include direct induction by mast cell releasing agents, pseudoallergenic responses induced by small molecule compounds in food, or altered arachidonic acid metabolism by nonsteroidal anti-inflammatory drugs; there are a few patients with urticaria whose pathogenesis cannot be elucidated yet The mechanism may not even depend on mast cell activation. The clinical manifestation of urticaria is a wind cluster with various forms of attacks, mostly accompanied by pruritus, and a few patients may be combined with angioedema. Urticaria can be clinically classified according to the pathogenesis pattern, combined with clinical manifestations. The clinical manifestations of different types of urticaria have certain differences, see Table 1. Diagnosis and differential diagnosis 1. History and physical examination: A thorough history and physical examination should be taken, including possible triggering and relieving factors, duration of the disease, frequency of attacks, duration of lesions, diurnal pattern of attacks, size and number of clusters, shape and distribution of clusters, whether angioedema is combined, degree of accompanying pruritus or pain, after remission Whether there is pigmentation, previous personal or family history of allergy, infection, internal organs disease, trauma, surgery, medication, psychological and mental conditions, menstrual history, lifestyle, work and living environment, and previous treatment response. 2, laboratory tests: usually urticaria does not require additional tests. Acute patients can be checked for blood tests to see if the onset is related to infection or allergy. In chronic patients with severe disease, long duration of disease or poor response to conventional doses of antihistamines, relevant tests can be considered, such as routine blood, eggs, liver and kidney function, immunoglobulins, erythrocyte sedimentation rate, C-reactive protein, complement and various autoantibodies. The role of IgE-mediated food allergens in the pathogenesis of urticaria is limited, and the results of allergen testing should be properly analyzed. Double-blind, placebo-controlled food provocation tests can be conducted in units where appropriate. 3. Classification and diagnosis: Combining history and physical examination, urticaria is classified as spontaneous or induced. The former is divided into acute and chronic according to whether the duration of the disease is ≥ 6 weeks, and the latter is divided into physical and non-physical urticaria according to whether the onset is related to physical factors, and further classified according to the definition in Table 1. There can be two or more types of urticaria present in the same patient, such as chronic spontaneous urticaria combined with artificial urticaria. 4. Differential diagnosis: The main differentiation is with urticarial vasculitis, which usually lasts for more than 24 h. The lesions recover with pigmentation and pathology suggesting vasculitis changes. It also needs to be differentiated from other diseases that manifest as urticaria or angioedema formation, such as urticarial drug rash, serum sickness-like reaction, papular urticaria, Staphylococcus aureus infection, adult Still disease, hereditary angioedema, etc. Treatment 1. Patient education: Patients with urticaria, especially chronic urticaria, should be educated, the cause of the disease is unknown, the disease is recurrent, the course of the disease is prolonged, except for a very small number of complications of respiratory or other system symptoms, the vast majority of benign. 2, etiological treatment: the elimination of causative or suspected causes is conducive to the natural regression of urticaria. Treatment is mainly considered from the following aspects: ① detailed medical history is the most important method to discover possible causes or triggers; ② for patients with induced urticaria, including physical and non-physical urticaria, avoiding the corresponding stimulus or triggering factors can improve clinical symptoms or even self-healing; ③ when drug-induced urticaria is suspected, especially non-steroidal anti-inflammatory drugs and angiotensin-converting enzyme inhibitors, avoidance can be considered ( including drugs with similar chemical structures) or replace them with other drugs; ④ chronic urticaria clinically suspected to be associated with various infections and/or chronic inflammation may benefit in some patients by considering treatment such as anti-infection or inflammation control when other treatments are resistant or ineffective, as appropriate. For example, anti-H. pylori treatment is effective for urticaria associated with H. pylori-associated gastritis; ⑤ For patients with suspected food-related urticaria, patients are encouraged to keep a food diary to look for possible foods and avoid them, especially since some natural food components or certain food additives can cause non-allergic urticaria; ⑥ For patients with positive ASST or confirmed presence of autoantibodies against FcεRIa (6) For patients with positive ASST or confirmed presence of autoantibodies against FcεRIa chain or IgE, if conventional treatment is ineffective and the condition is severe, additional immunosuppressive agents, autologous serum injection therapy or plasma exchange can be considered as appropriate. 3. Symptom control: Drug selection should follow the principles of safety, effectiveness and regular use to improve the quality of life of patients. It is recommended to develop and adjust the treatment plan according to the patient’s condition and response to treatment. (1) First-line treatment: second-generation non-sedating or hypo-sedating antihistamines are preferred, and the dose is gradually reduced after effective treatment to achieve effective control of the onset of the wind cluster as the standard. To improve the patient’s quality of life, the course of treatment for chronic urticaria is generally not less than 1 month, and can be extended to 3 ~ 6 months or longer if necessary. First-generation antihistamines are effective in the treatment of urticaria, but their clinical application is limited by adverse effects such as central sedation and anticholinergic effects. They can be selected at discretion with attention to contraindications, adverse effects and drug-drug interactions. Commonly used first-generation antihistamines include chlorpheniramine, diphenhydramine, doxepin, ipratropium, ketotifen, etc. Second-generation antihistamines include cetirizine, levocetirizine, loratadine, desloratadine, fexofenadine, avastin, epinastine, epinastine, imipramine, olopatadine, etc. (2) Second-line treatment: If the symptoms cannot be effectively controlled after 1 to 2 weeks of conventional dosing, considering the differences in response to treatment in different individuals or types of urticaria, the following options are available: change the species or increase the dose by 2 to 4 times with informed consent of the patient; combine with first-generation antihistamines, which can be taken at bedtime to reduce adverse effects; combine with second-generation antihistamines, and advocate the combination of drugs of the same structure such as loratadine combined with desloratadine to enhance the anti-inflammatory effect; combined with anti-leukotriene drugs, especially for NSAID-induced urticaria. (3) Third-line treatment: For patients who fail to respond to the above treatment, the following treatment options can be considered: cyclosporine, 3-5 mg/kg/day in 2-3 oral doses. Because of its high incidence of adverse reactions, it should only be used for severe cases that do not respond to any dose of antihistamines. Glucocorticoids, for acute, severe or laryngeal edema urticaria, prednisone 30-40 mg (or equivalent) orally for 4-5 days and then discontinued, are not recommended for routine use in chronic urticaria. Immunoglobulins, such as intravenous immunoglobulins at 2 g daily for 5 d, are appropriate for severe autoimmune urticaria. Biologic agents, such as omalizumab (anti-IgE monoclonal antibody), have shown positive efficacy in refractory chronic urticaria in foreign studies. Phototherapy, for chronic spontaneous urticaria and artificial urticaria patients in the antihistamine treatment at the same time can try UVA and UVB treatment for 1 to 3 months. (4) Treatment of acute urticaria: When the cause is actively clarified and removed and the symptoms cannot be effectively controlled by oral antihistamines, glucocorticoids can be chosen: prednisone 30-40 mg, discontinued after 4-5 days of oral administration, or an equivalent dose of dexamethasone intravenously or intramuscularly, especially for severe urticaria or urticaria with laryngeal edema; 1:1,000 epinephrine solution 0,2 to 0,4 ml subcutaneously or intramuscularly, can be used for acute urticaria with shock. For acute urticaria with shock or severe urticaria with angioedema. (5) Treatment of induced urticaria: Induced urticaria is relatively poorly treated with conventional antihistamines, and if treatment is ineffective, some special treatment methods should be chosen. (6) Treatment of pregnant and lactating women and children: In principle, antihistamines should be avoided during pregnancy as much as possible. However, if symptoms recur and seriously affect the patient’s life and work, and antihistamines must be used for treatment, the patient should be informed that there are no absolutely safe and reliable drugs available, and relatively safe and reliable drugs such as loratadine should be chosen on the balance of pros and cons. Most antihistamines can be secreted into breast milk. In comparison, cetirizine and loratadine are secreted at lower levels in breast milk and may be recommended at the discretion of lactating women, using lower doses if possible. Chlorpheniramine can be secreted through breast milk, reduce the infant’s appetite and cause drowsiness, etc., and should be avoided. Non-sedating antihistamines are also a first-line choice for the treatment of urticaria in children. The minimum age limits and doses vary significantly among drugs and should be administered according to the drug instructions. Similarly, in children who have failed to respond to treatment, first-generation (nighttime use) and second-generation (daytime use) antihistamines can be combined, with concern for the effects of sedating antihistamines on the child’s learning, etc. (7) Traditional Chinese medicine: Traditional Chinese medicine has some efficacy in the treatment of urticaria, which requires evidence-based treatment.