Drug Hypersensitivity

The drug hypersensitivity is mediated by the immune system reaction to a drug. Symptoms range from mild to severe reactions and include redness to anaphylaxis and serum sickness. The diagnosis is made clinically; Occasionally skin tests are useful. The treatment consists in the discontinuation of the drug, supportive therapy (eg. B. antihistamines) and occasionally desensitization.

The hypersensitivity to medicines different from toxic and side effects and problems associated with drug interactions.

The drug hypersensitivity is mediated by the immune system reaction to a drug. Symptoms range from mild to severe reactions and include redness to anaphylaxis and serum sickness. The diagnosis is made clinically; Occasionally skin tests are useful. The treatment consists in the discontinuation of the drug, supportive therapy (eg. B. antihistamines) and occasionally desensitization. The hypersensitivity to medicines different from toxic and side effects and problems associated with drug interactions. Some drugs pathophysiology of proteins and large polypeptides (eg. As insulin, therapeutic antibodies) able to stimulate antibody production directly. However, most drugs act as haptens, which bind covalently to serum or cell-bound proteins, including embedded also in the molecules of the major histocompatibility complex (MHC) peptides. The binding proteins makes the immunogenic what the stimulation of antibody formation against the drug or T cell responses, or both the consequence has. hapten can also bind to the MHC-II molecule and thereby activate the T cells directly. Some drugs act as Prohaptene. Prohaptene are converted by metabolic processes in haptens; Penicillin, for example, is not itself antigenic, but his main degradation product, the Benzylpenicillinsäure can react with tissue proteins and benzylpenicilloyl (BPO) form an important antigenic determinant. Some medicines bind and stimulate T-cell receptors (TCR) directly; currently under investigation, the clinical importance of TCR binding with non-hapten. It is still unclear how the primary sensitization and how the innate immune system is initially involved. After stimulation of an immune response, it may, however, lead to cross-reactions with other medications within or between classes of drugs. For example, patients with a penicillin allergy react very likely also to semi-synthetic penicillins (eg. As amoxicillin, carbenicillin, ticarcillin). In the former, poorly designed studies, reacted about 10% of patients with an unclear anamnestich penicillin hypersensitivity to cephalosporins, which have a similar beta-lactam structure; this finding was cited as evidence of cross-reactions between these classes of substances. However, in younger, better-designed studies, only about 2% of patients responded with a penicillin allergy skin tests while proven to cephalosporins, about the same percentage of patients responded to structurally unrelated antibiotics (eg. As sulfonamides). Sometimes these and other obvious cross-reactions go (z. B. between sulfonamides and not microbicidal acting drugs) rather back to a predisposition to allergic reactions than on specific cross reactivity of the immune system. It is also not any visible reaction, an allergic; such as amoxicillin causes a reddening of the skin, which is not immune mediated and therefore does not exclude the later use of the drug. Tips and risks penicillin allergy includes the use of cephalosporins is not always. Symptoms and signs The symptoms of drug allergies differ depending on the patient and drug; so a particular drug in different patients can cause different reactions. Anaphylaxis is the most severe reaction; most common rash (z. B. morbilliform) are, urticaria and fever. Fixed drug reactions – these are reactions that appear after drug exposure repeatedly in the same location of the body – are rare. There are several distinct syndromes: serum sickness: Typically, the reaction is 7-10 days after exposure with fever, arthralgia and skin rashes. In the reaction mechanism drug-antibody complexes and complement activation are involved. In some patients it comes to overt arthritis, edema, or gastrointestinal symptoms. The symptoms are self-limited and do not last longer than 1-2 weeks. Most often they occur after treatment with beta-lactam and sulfonamides, iron dextran, and carbamazepine. Hemolytic anemia: This disorder may develop when an interaction between antibodies, pharmaceuticals and erythrocytes takes place, or it may occur due to changes in the erythrocyte membrane, the drug-induced (e.g., methyldopa.) Is caused. This lead to the exposure of an antigen that stimulates the production of autoantibodies. DRESS (Drug rash with eosinophilia and systemic symptoms): This reaction, which (DHS) is also called drug-induced hypersensitivity syndrome, may begin drug treatment and occur after a dose increase up to 12 weeks after initiation. Symptoms may persist or recur over several weeks after cessation of drug treatment. The patients have predominant eosinophilia and often develop hepatitis, skin rash, facial swelling, generalized edema and lymphadenopathy. Carbamazepine, phenytoin, allopurinol, and lamotrigine are often involved. Pulmonary effects: Some medications cause respiratory symptoms (in contrast to the wheezing that occurs in type I hypersensitivity reaction), deterioration of lung function and other pulmonary changes (lung disease through medication). Renal effects: The most common renal disease due to an allergic reaction to a drug therapy is the tubular interstitial nephritis; usually for methicillin, antibiotics and cimetidine can be held responsible. Other autoimmune phenomena: Hydralazine, propylthiouracil and procainamide can cause an SLE-like syndrome. The syndrome can easily tend not to be affected are (with serositis, high fever and malaise), but the kidneys and the central nervous system (with joint pain, fever and rash) or quite dramatic. The test for antinuclear antibody is positive. SLE-like symptoms and other autoimmune diseases (eg. As myasthenia gravis) can be caused by penicillamine. Some medications can cause vasculitis associated with perinuclear anti-neutrophil cytoplasmic autoantibodies (p-ANCA). These autoantibodies directed against myeloperoxidase (MPO). Diagnosis patients report a reaction soon after taking a drug skin tests Sometimes drug provocation testing Sometimes direct and indirect Coombs tests following may be helpful in differentiating the drug sensitivity of toxic and adverse drug reactions and the problems with drug interactions. Time of occurrence acquaintances effects of a drug The results of a repeated “Drugs Challenge” (drug challenge) For example, a dose-dependent response is often an expression of drug toxicity, not a drug hypersensitivity. Is a suspicion of drug hypersensitivity is when a reaction occurs within a few minutes to a few hours after administration of the drug. However, many patients report already past reactions of unknown type. If in such cases no equivalent replacement can be found (eg. As penicillin to treat syphilis), appropriate investigations must be taken into consideration. Skin test skin tests are suitable for the Identifiizierung of (IgE-mediated) hypersensitivity reactions of the right type of beta-lactam antibiotics (xenograft) foreign serum, some vaccines and polypeptide hormones. Usually show only 10-20% of patients with a penicillin allergy a positive response. (Including cephalosporins) for most other drug skin tests are not reliable enough and since they only detect IgE-mediated reactions, they may not predict as to the occurrence of a morbilliform rash, haemolytic anemia or nephritis. A penicillin skin test is required for patients who have a history of hypersensitivity reactions of immediate type and need to be treated with penicillin. For this purpose, a BPO-polylysine conjugate and penicillin G is available, histamine and saline used as control. The prick test is performed first. If the history result in a very strong reaction, the reagents for the initial testing 1 should be diluted 100th In case of a negative prick test intradermal test can be done. Drop the skin test is positive, there is a risk of an anaphylactic reaction to the patient at Penizillinbehandlung. Negative skin tests reduce the risk of a severe reaction, but does not rule out. Although there is no indication that the penicillin skin test in patients has ever induced sensitization de novo, it is nevertheless advisable to perform the test just before the start of a necessary Penizillintherapie. Is the test result is negative, 0.02 ml of a 1 are: 1000 dilution was injected intradermally. In the case of xenogenic serum (z. B. horse) should be carried out first a prick test with a dilution of 1:10 in patients who are not atopic and have been given no horse serum. If the patient is sensitive, a wheal develops within 15 minutes with a diameter> 0.5 cm. It should first of all patients who have previously received serum – whether they responded or not – and for those with a suspected allergy in medical history, a skin prick test at a dilution of 1: carried out in 1000; if the results are negative, the Verdünung 1: 100 and if the results are negative again 1:10 as used above. Negative skin tests include the possibility of anaphylaxis, but say nothing about the occurrence of a subsequent serum sickness voraus.Weitere test method When drug provocation test is a medicine of which it is believed that it triggers an allergic reaction, given in increasing doses to cause a reaction , Under controlled conditions, performed this test is generally safe and effective. Since drug hypersensitivity is associated with particular HLA class I haplotypes of patient genotyping of certain ethnic groups can identify those with an increased risk of hypersensitivity reactions. Some HLA-based risk factors for drug hypersensitivity drug ethnicity HLA haplotype abacavir White HLA-B * 5701 allopurinol Han Chinese, Japanese, Korean, Thai Less frequently, Europeans HLA-B * 5801 carbamazepine White, Japanese HLA-A * 3101 * 1502 fosphenytoin phenytoin 1502 To hematologic drug reactions to test carbamazepine Asians HLA-B Asians HLA-B * 1502 lamotrigine Asians HLA-B *, the direct and indirect antiglobulin test can be performed. Tests for other specific drug hypersensitivities (z. B. allergen-specific serum IgE assay, histamine release, basophil or mast cell degranulation, lymphocyte transformation) are unreliable or too experimental. The forecast hypersensitivity decreases over time. In 90% of patients IgE antibodies find one year after an allergic reaction, after 10 years but only in 20-30% of cases. Patients with anaphylactic reactions retain antibodies against the causative drug probably longer. Persons with a drug allergy should be advised to avoid the use of the drug and to wear an identification bracelet or warning. Medical records should always be marked accordingly. Treatment discontinuation of the drug Supportive treatment (. For example, antihistamines, corticosteroids, epinephrine) Sometimes desensitization By treatment of drug allergies stops the action of the causative drug; Most symptoms disappear within a few days after discontinuation of the pollutant. Symptomatic and supportive treatment for acute reactions may comprise antihistamines at pruritus NSAIDs for arthralgia corticosteroids in severe reactions (eg. B. exfoliative dermatitis, bronchospasm) epinephrine for anaphylaxis symptoms such as drug fever, a nichtjuckender rash or mild reactions of the organ system require no treatment ( the treatment of specific clinical responses is discussed elsewhere in the MSD Manual). A rapid desensitization desensitization may be necessary if a sensitization was confirmed, treatment is essential and no alternative exists. Rapid desensitization reduces sensitivity only temporary. If possible, desensitization in cooperation with an allergist should be. In patients who had Stevens-Johnson syndrome, however, it should be dispensed with. If desensitization is performed, must be available for immediate countermeasures for anaphylaxis O2, adrenaline and resuscitation equipment. Desensitization is based on a gradual increase in the dose of administered antigen (every 15 to 20 minutes). The starting dose is just strong enough to induce a subclinical anaphylaxis before therapeutic doses follow. The method depends on a constant presence of the drug in serum and must not be interrupted; desensitization immediately follow gifts full therapeutic doses. After stopping the treatment, the hypersensitivity returns again normally within 24-48 hours. weak reactions (eg. B. itching, rash) are usually observed during the desensitization. Desensitization to penicillin can be administered orally or intravenously; subcutaneous or intramuscular treatment is not recommended. If only the intradermal skin test is positive, the first dose should be 100 units (ug) / ml (in a 50 mL bag, a total of 5000 units) i.v. be administered, with a slow onset of infusion (z. B. <1 ml / minute). If any symptoms occur after 20-30 minutes, the infusion rate may be gradually increased until the bag is empty. This is then repeated at concentrations of 1000 units / ml and 10,000 units / ml, followed by the full therapeutic dose. If develop allergic symptoms, the infusion rate should slow down and the patient to be treated accordingly with medication (s. O.). If the prick test was positive for penicillin or the patient had a severe anaphylactic reaction, the initial dose should be chosen lower. Oral desensitization to penicillin begins with an initial dose of 100 U (or ug). The following doses can be doubled every 15 minutes, up to 400,000 units (13 doses). The therapeutic dose of the drug is then administered parenterally for the treatment of infection, and anti-anaphylactic hypersensitivity reactions corresponding drugs are administered. For allergies to trimethoprim-sulfamethoxazole, and vancomycin similar treatment strategies as for penicillin apply. With a positive skin test on foreign serum is a high anaphylaxis. If treatment with serum is essential before desensitization must be performed. Summary The diagnosis can be made a history in general (mainly due to patient reports a reaction soon after taking the drug). Known unwanted and toxic effects of the drug and drug-drug interactions must be excluded. In case of unclear diagnosis can sometimes drug provocation tests or other specific tests to identify some drugs as the cause usually skin tests. Negative skin tests rule out the possibility of anaphylaxis, but do not say anything ahead of the occurrence of a subsequent serum sickness. The hypersensitivity tends to decrease over time. As adjuvant therapy in acute reactions (exfoliative dermatitis, bronchospasm z. B.) corticosteroids and epinephrine anaphylaxis can be given antipruritic antihistamines, arthralgia at NSAIDs, in severe reactions. If the causative drug must be used, it should be wherever possible in cooperation with an allergist, tries a rapid desensitization to reduce drug hypersensitivity temporary.

Health Life Media Team

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