Chapter 056. Cutaneous Drug Reactions (Part 8)

AllopurinolTogether 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 includinghypersensitivity/DRESS and SJS/TEN. Because of increasing utilization it is one of the most frequent causes of life-threatening reactions.Anti-HIV MedicationsIn 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) Chapter 056. Cutaneous Drug Reactions (Part 8) DRUGS OF SPECIAL INTEREST Allopurinol Together with sulfonamides and antiepileptics, allopurinol is one of theusual suspects that induce frequently mild maculopapular eruptions (in at least3% of users) and may also cause more severe reactions includinghypersensitivity/DRESS and SJS/TEN. Because of increasing utilization it is oneof the most frequent causes of life-threatening reactions. Anti-HIV Medications In clinical trials, combinations of highly active antiretroviral treatmentswere frequently associated with ≥10% drug eruptions. Two drugs, nevirapineand abacavir, have been associated with specific risks. Nevirapine has both a high risk of maculopapular eruptions and a very highrisk (about 1 in 1000) of SJS or TEN. Progressive escalation of daily doses hasbeen shown to decrease the risk of mild eruption but does not abrogate the risk ofsevere 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 Ireaction (dyspnea, diarrhea, low blood pressure, shock on rechallenge) and signsof delayed hypersensitivity (rash, late onset, hepatitis). The risk is lower inpatients of African ancestry and strongly correlated with HLAB*5701. Penicillin The utilization rate of penicillin has decreased markedly since it has beenthe subject of many investigations and a model for drug allergy. Incidence ofcutaneous reactions is about 1%. About 85% of cutaneous reactions to penicillinare morbilliform, and about 10% are urticaria or angioedema. Anaphylaxis andserum sickness appear to be due to IgE antibodies in serum. Delayed reactions, mainly maculopapular eruptions, are much morecommon with aminopenicillins, involving 4–7% of users. The question of cross-reactivity between β-lactam antibiotics and preventing the risk of anaphylaxis isdiscussed below (Management of a Patient with a Drug Eruption). Nonsteroidal Anti-Inflammatory Drugs Most NSAIDs, including aspirin, cause immediate allergy-like symptomsin susceptible individuals. Approximately 1% of persons experience urticaria orangioedema, 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 drugadministration. Recurrences are frequent and can be complicated by nasal andsinus infection, polyposis, bloody discharge, and nasal eosinophilia. In manyindividuals with this syndrome, asthma that can be life-threatening eventuallyensues whenever NSAIDs are subsequently ingested. Proof of the association ofsymptoms and NSAID use requires either clear-cut history of symptoms followingdrug ingestion or an oral challenge. That procedure must be conducted only in ahospital setting by experienced personnel. Cross-reactivity between NSAIDs thatinhibit cyclooxygenase (COX) 1 is common, while reactivity to COX-2 inhibitorsis less frequent. The reaction is pharmacologic, and patients who are sensitive toNSAIDs 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 withmany 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 induceurticaria (1%) or anaphylaxis than were newer low-osmolality media. Severereactions are rare with either type of contrast media. About one-third of those withmild reactions to previous exposure re-react on re-exposure. In most cases, thesereactions are probably not immunologic. Pretreatment with prednisone anddiphenhydramine reduces reaction rates. Persons with a reaction to a high-osmolality contrast media should be given low-osmolality media if later contraststudies are required. Anticonvulsants Along with sulfonamide antibiotics, phenobarbital, phenytoin, andcarbamazepine among the older anticonvulsants, and lamotrigine among thenewer, are associated with many types of severe reactions and a high incidence ofless severe reactions, particularly in children. These drugs have among the highestrisk of SJS, TEN, and hypersensitivity syndrome in immunologically normalpatients. The aromatic anticonvulsants can induce a pseudolymphoma s ...