Chapter 056. Cutaneous Drug Reactions (Part 8)

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Allopurinol Together with sulfonamides and antiepileptics, allopurinol is one of the "usual suspects" that induce frequently mild maculopapular eruptions (in at least 3% of users) and may also cause more severe reactions including hypersensitivity/DRESS and SJS/TEN. Because of increasing utilization it is one of the most frequent causes of life-threatening reactions. Anti-HIV Medications In clinical trials, combinations of highly active antiretroviral treatments were frequently associated with ≥10% "drug eruptions." Two drugs, nevirapine and abacavir, have been associated with specific risks. Nevirapine has both a high risk of maculopapular eruptions and a very high risk (about 1 in 1000) of SJS or TEN. Progressive escalation...

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Chapter 056. Cutaneous Drug Reactions (Part 8) DRUGS OF SPECIAL INTEREST Allopurinol Together with sulfonamides and antiepileptics, allopurinol is one of the "usual suspects" that induce frequently mild maculopapular eruptions (in at least 3% of users) and may also cause more severe reactions including hypersensitivity/DRESS and SJS/TEN. Because of increasing utilization it is one of the most frequent causes of life-threatening reactions. Anti-HIV Medications
In clinical trials, combinations of highly active antiretroviral treatments were frequently associated with ≥10% "drug eruptions." Two drugs, nevirapine and abacavir, have been associated with specific risks. Nevirapine has both a high risk of maculopapular eruptions and a very high risk (about 1 in 1000) of SJS or TEN. Progressive escalation of daily doses has been shown to decrease the risk of mild eruption but does not abrogate the risk of severe reactions. Abacavir is associated with a 4–5% risk of a hypersensitivity reaction, which is remarkable because of the association of symptoms suggesting a type I reaction (dyspnea, diarrhea, low blood pressure, shock on rechallenge) and signs of delayed hypersensitivity (rash, late onset, hepatitis). The risk is lower in patients of African ancestry and strongly correlated with HLAB*5701. Penicillin The utilization rate of penicillin has decreased markedly since it has been the subject of many investigations and a model for "drug allergy." Incidence of cutaneous reactions is about 1%. About 85% of cutaneous reactions to penicillin are morbilliform, and about 10% are urticaria or angioedema. Anaphylaxis and serum sickness appear to be due to IgE antibodies in serum.
Delayed reactions, mainly maculopapular eruptions, are much more common with aminopenicillins, involving 4–7% of users. The question of cross- reactivity between β-lactam antibiotics and preventing the risk of anaphylaxis is discussed below ("Management of a Patient with a Drug Eruption"). Nonsteroidal Anti-Inflammatory Drugs Most NSAIDs, including aspirin, cause immediate allergy-like symptoms in susceptible individuals. Approximately 1% of persons experience urticaria or angioedema, and about half as many (0.5%) experience rhinosinusitis and asthma. Urticaria/angioedema may be delayed up to 24 h and may occur at any age. The rhinosinusitis-asthma syndrome generally develops within 1 h of drug administration. Recurrences are frequent and can be complicated by nasal and sinus infection, polyposis, bloody discharge, and nasal eosinophilia. In many individuals with this syndrome, asthma that can be life-threatening eventually ensues whenever NSAIDs are subsequently ingested. Proof of the association of symptoms and NSAID use requires either clear-cut history of symptoms following drug ingestion or an oral challenge. That procedure must be conducted only in a hospital setting by experienced personnel. Cross-reactivity between NSAIDs that inhibit cyclooxygenase (COX) 1 is common, while reactivity to COX-2 inhibitors is less frequent. The reaction is pharmacologic, and patients who are sensitive to
NSAIDs cannot be identified by assessment of IgE antibody to aspirin, lymphocyte sensitization, or in vitro immunologic testing. Other reactions can also occur with NSAIDs, including phototoxicity with many agents, a pattern of pseudoporphyria being often related to naproxen, hypersensitivity/DRESS (oxicam derivatives, COX-2 inhibitors), and SJS or TEN (phenylbutazone, oxicam derivatives, diclofenac). Radiocontrast Media Large numbers of patients are exposed to radiocontrast agents. High- osmolality radiocontrast media were about five times more likely to induce urticaria (1%) or anaphylaxis than were newer low-osmolality media. Severe reactions are rare with either type of contrast media. About one-third of those with mild reactions to previous exposure re-react on re-exposure. In most cases, these reactions are probably not immunologic. Pretreatment with prednisone and diphenhydramine reduces reaction rates. Persons with a reaction to a high- osmolality contrast media should be given low-osmolality media if later contrast studies are required. Anticonvulsants Along with sulfonamide antibiotics, phenobarbital, phenytoin, and carbamazepine among the older anticonvulsants, and lamotrigine among the
newer, are associated with many types of severe reactions and a high incidence of less severe reactions, particularly in children. These drugs have among the highest risk of SJS, TEN, and hypersensitivity syndrome in immunologically normal patients. The aromatic anticonvulsants can induce a pseudolymphoma syndrome and induce gingival hyperplasia.