Diagnosing and Managing Drug Allergy

REVIEW CPD

Diagnosing and managing drug allergy

Elissa M. Abrams, MD, David A. Khan MD n Cite as: CMAJ 2018 April 30;190:E532-8. doi: 10.1503/cmaj.171315

dverse drug reactions are common both in outpatient and inpatient settings. A meta-analysis of 39 prospec- KEY POINTS tive studies from American hospitals that was pub- • Cutaneous manifestations are the most common presentation lishedA in 1998 reported an incidence of serious adverse drug of allergic drug reactions. reactions of 6.7% and fatal adverse drug reactions of 0.32%, • Diagnosis of drug allergy is largely based on clinical history which places these reactions around the fourth to sixth leading because diagnostic tests are limited. causes of death in the United States.3 A review published in • Most patients who are labelled as having penicillin allergy can 2005 found that adverse drug reactions affected 10%–20% of tolerate penicillins after allergy evaluation. patients admitted to hospital and more than 7% of the general • Cross-reactivity between cephalosporins and penicillins is rare. population.4 • Maculopapular rashes with amoxicillin are common and not an Health Canada has documented an increase in reported absolute contraindication for future use. adverse drug reactions, with nearly 30 000 reports of adverse 5 drug reactions in 2009 (up 35% from the year before). In addi- tion, adverse drug reactions are more common among older How are adverse drug reactions classified? patients. The Canadian Institute for Health Information (CIHI) reported that patients 65 years or older accounted for 57.6% of Adverse drug reactions can be classified into predictable hospital admissions related to adverse drug reactions in Canada (“type A”) and unpredictable (“type B”) reactions.7 Predictable between 2006/07 and 2011/12, even though they accounted for reactions account for 80% of all adverse drug reactions; they are only 14.2% of the Canadian population.6 common, dose-dependent and caused by the pharmacologic Adverse drug reactions are defined by the World Health Orga- actions of the drug.1 In contrast, unpredictable reactions are nization (WHO) as, “all intended pharmacologic effects of a drug uncommon, independent of dose and unrelated to pharmaco- except therapeutic failures, intentional over-dosage, abuse of logic effects of the drug (Table 1).1 Allergic drug reactions the drug, or errors in administration.”1 The WHO defines adverse account for about 5%–10% of adverse drug reactions overall.9 drug events as “an injury resulting from medical intervention Although the term “drug allergy” has often been used exclusively related to a drug,” which, in contrast to adverse drug reactions, for immunoglobulin E (IgE)-mediated reactions, more recently, also includes in its definition errors in medication use, such as an expert panel on drug allergy discussed whether or not the overdose.2 term drug allergy should also include other forms of hypersensi- In this review, we focus on allergic drug reactions and address tivity reactions that are not IgE mediated.7 key issues in diagnosis and management. The articles referenced in this review include guidelines, cohort and case–control studies, What are the clinical manifestations of and surveys (Box 1). allergic drug reactions?

Although allergic reactions to medications can affect any organ Box 1: Evidence used in this review system, cutaneous manifestations are by far the most com- 8,10 We used recent American and international practice parameters mon. A 2017 meta-analysis and systematic review of 53 studies and guidelines as primary bases to inform this review, (126 306 participants) found cutaneous manifestations to be supplemented with a search for systematic reviews for supporting present in 68.2% of allergic drug reactions (with anaphylactic or information. Additional clinical points or examples are based on systemic reactions in 10.8%).11 Determining the characteristics of reviews, case–control and cohort studies, and surveys. We restricted our results to articles in English. Where possible, we the cutaneous manifestation, if present, is one of the strongest selected the most recent articles and the articles with the most diagnostic clues in a drug-induced allergic reaction. robust level of evidence. A 2016 review on cutaneous allergic drug reactions noted that most of these eruptions are benign in nature.12 The most common

E532 CMAJ | APRIL 30, 2018 | VOLUME 190 | ISSUE 17 © 2018 Joule Inc. or its licensors REVIEW E533 Example 1,8 ASA-induced tinnitus ASA-induced hemolytic Primaquine-induced anemia in glucose-6-phosphate deficiency dehydrogenase 1: anaphylaxis Type anemia 2: thrombocytopenia, Type 3: serum sickness, vasculitis Type 4: benign drug exanthems, Type dermatitis contact AGEP, DRESS, urticaria Opiate-induced ISSUE 17 ISSUE | Clinical manifestations Clinical How is drug allergy diagnosed? allergy is drug How History medical his- with the patient’s to diagnosis begins The approach identify of the reaction, may identify the etiology tory, which details of symptoms and provide as a possible cause drug allergy VOLUME 190 VOLUME | 1,7,8,10,13 Description APRIL 30, 2018 | Table 2 describes

8 Unrelated to intended pharmacologic intended to Unrelated and is of the drug, is reproducible, action of abnormalities usually due to or bioavailability excretion metabolism, Immune mediated: 1 (IgE-mediated) Type 2 (cytotoxic) Type 3 (immune complex) Type hypersensitivity; 4 (delayed Type (IVa), monocytes subclassified into (IVc),eosinophils (IVb), CD8+ T lymphocytes (IVd) neutrophils with reactions type I allergic Similar to pathophysiology (direct different from histamine, often release, mediator and basophils) cells mast Occurs at very low doses and is not due due very at doses and is not low Occurs of underlying abnormalities to or excretion bioavailability metabolism, CMAJ Fine macules and papules that occur days after drug initiation and resolve a few days after discontinuing the discontinuing few days after a resolve and drug initiation after days occur that Fine macules and papules symptoms systemic lack of other medication; to one syncope and/or hypotension wheeze, cough, diarrhea, angioedema, vomiting, of urticaria, Combination prior sensitization requires usually a medication; starting after six hours a medication; starting after three weeks one to lymphadenopathy arthralgias, fever, (usually urticarial), Rash with sensitization be earlier could SJS/TEN < 10% epidermal detachment; lesions (SJS: and bullous target cutaneous fever, involvement, Mucosal of liver, possible involvement TEN: > 30% epidermal detachment); 10%–30% epidermal detachment; overlap: lungs kidney, multiple different dysfunction, possible renal dysfunction, liver eosinophilia, lymphadenopathy, Fever, weeks or for and may persist a medication starting after 12 weeks up to possible; starts eruptions cutaneous ) (Figure 1 the medication stopping months after ) (Figure 2 prior sensitization days; requires over evolves that contact of cutaneous in area Dermatitis plaques erythematous photodistributed Cutaneous: drug initiation after weeks malaise several arthralgias, fever, myalgias, sudden onset Systemic: ) (Figure 3 the same site at recur plaques that Hyperpigmented nephritis), pulmonary (interstitial renal jaundice), cholestatic (hepatitis, hepatic (cytopenia), Hematologic vasculitis (pneumonitis, fibrosis), Note: AGEP = acute generalized exanthematous pustulosis, ASA = acetylsalicylic acid, DRESS = drug reaction with eosinophilia and = drug reaction acid, DRESS ASA = acetylsalicylic pustulosis, exanthematous generalized = acute AGEP Note: IgE = immunoglobulin E. symptoms, systemic Table 1: Classification of unpredictable adverse drug reactions adverse unpredictable of 1: Classification Table Classification Idiosyncracy Allergy “Pseudoallergy” Intolerance The most severe reactions are Stevens–Johnson Stevens–Johnson severe reactions are The most 4,13,14 Note: DRESS = drug reaction with eosinophilia and systemic symptoms, IgE = immunoglobulin E, SJS = Stevens–Johnson syndrome, TEN= toxic epidermal necrolysis. TEN= toxic syndrome, = Stevens–Johnson IgE = immunoglobulin E, SJS symptoms, with eosinophilia and systemic = drug reaction DRESS Note: Reaction drug exanthem Delayed IgE-mediated reaction Serum sickness-like SJS/TEN DRESS dermatitis contact Allergic lupus erythematosus Drug-induced drug eruption Fixed Other Table 2: Clinical features of drug hypersensitivity reactions drug hypersensitivity of features 2: Clinical Table clinical features of the more common types of allergic drug drug allergic of types common more the of features clinical reactions. cutaneous eruption is a generalized maculopapular exanthem, exanthem, maculopapular is a generalized eruption cutaneous caused all cutaneous eruptions for up to 90% of which accounts by drugs. syndrome and toxic epidermal necrolysis. and toxic epidermal syndrome REVIEW vincing reaction history. serum-specific IgEtestingifskin testingisnegativedespiteacon- value. penicillin reagentsbecauseofitshighnegativepredictive tion ofskinpricktestingandthenintradermaltesting)with the and Immunologyguideline, recommend skin testing (a combina- guidelines, includingtheAmericanAcademyofAllergy,Asthma E534 the otherlow-molecular-weightdrugs. skin testingreagentsexistonlyforpenicillinandnotanyof In thediagnosisofapotentialIgE-mediatedreaction,validated Skin testing largely fromobservationalstudies. levels normalize,althoughthisisbasedonlow-qualityevidence elevated serumtryptaseisrelativelyspecific,especiallyifserial els in the diagnosis of a potential IgE-mediated reaction, because and CareExcellencerecommendsobtainingserumtryptaselev- for mostallergicdrugreactions.TheNationalInstituteHealth Laboratory investigationsaresupportiveandnotconfirmatory Laboratory tests adverse drugreaction. mine thelikelihoodthatsymptomsdescribedrepresentan patient’s history,asavalidatedprobabilityscaletohelpdeter- Drug ReactionProbabilityScalecanbeused,basedonthe tors areessentialinarrivingatadiagnosis.TheNaranjoAdverse toms, previousexposureandunderlyingconditionsasriskfac- (i.e., time of onset and its duration), the constellation of symp- tory. In particular, establishing the time frame of the reaction provides a list of useful components of the - medical his Table 3 suggesting thepossibletypeofdrug-inducedallergicreaction. tolerance inpatientswhohavenegativeskintesting. toprove usuallyofamoxicillinorpenicillininchildren — lenge — neous drug-inducedlupus). drug-induced lupus, and anti-Ro/SSA and anti-La/SSB for cuta antibody) ordrug-inducedlupus(antihistonelevelsinsystemic there isconcern aboutvasculitis (antineutrophil cytoplasmic induced allergicreactions.Testingforautoantibodiesisusefulif of internalorgans,inparticularwithseverenonimmediatedrug- function, completebloodcellcount)maydetermineinvolvement absence ofeosinophiliadoesnotexcludeit. ports adiagnosisofanIgE-mediatedreaction,althoughthe well described or validated, mon antibiotics;however, their sensitivityandspecificityarenot both oral doses of penicillin tive penicillintesting.Patientshavebeenreportedtotolerate ate hypersensitivityreactions. spective review,repeatedintravenouspenicillinwithoutimmedi - 68%). higher specificity(90%ormore) thansensitivity(29% to monly inclinicalpractice. drug allergicreactionsintheliterature,butitisnotusedcom- tively simpletouseandisfrequentlycitedwhenreportingnew Other laboratoryinvestigations(e.g.,liverenzymes,renal In vitro serum-specific IgE assays are available for some com- The riskoforreacquiringapenicillinallergyislowafternega- 8,18 1,8,21 This is followed by an allergist-administered oral chal Someguidelinesdorecommend theinclusionof 16 18 This scale based on 10 questions isrela- Thisscalebasedon10 questions 1,8 20 8 and, according to a recent retro- although studies have found a 17 Serumeosinophiliasup- 1,8 CMAJ Severalinternational | APRIL30, 2018 19 - - | VOLUME 190 and systemicsymptoms. Figure 1:Maculopapularexanthemaindrugreactionwitheosinophilia Figure 3:Fixeddrugeruption onthepalms. Figure 2:Contactdermatitisontherightshoulder. matitis, fixeddrugeruptionandmaculopapularexanthem,skin it isnotavailableroutinelyatthistime. shows promiseinthediagnosisofIgE-mediateddrugallergy,but expression, is being reported increasingly because this test stimulation withanallergenandsubsequentCD63orCD203c For somenonimmediatereactions,inparticularcontactder- The basophilactivationtest,whichlooksatinvitrobasophilic | ISSUE 17 22 REVIEW - In E535 1,28 but 90% or more but 90% or more 1,27 -lactam allergy was -lactam allergy was Recent initiatives have suggested Recent initiatives have suggested 30 31,32 1 In a 2016 Canadian retrospective chart review review In a 2016 Canadian retrospective chart 29 ISSUE 17 ISSUE | Some studies have suggested that the rate of confirmed peni- Some studies have suggested that the rate ism of the reaction. Induction of drug tolerance does modify does modify tolerance of drug Induction the reaction. ism of -lactam antibiotics of 2.84% (95% confidence interval [CI] interval [CI] -lactam antibiotics of 2.84% (95% confidence -lactam allergy evaluation. 2016, a systematic review and meta-analysis of 14 studies of meta-analysis and review a systematic 2016, drug allergy to reported a low prevalence of IgE-mediated β among adults (7.78%, 1.77%–3.91%), with a higher prevalence (1.98%, 95% CI 95% CI 6.53%–9.04%) than among children 1.35%–2.60%). cillin allergy is decreasing. involving 306 patients in primary care, β after patients of 93.2%–97.5%) CI (95% 96.1% in out ruled β are able to tolerate penicillin after allergy evaluation. are able to tolerate penicillin after allergy Which common drugs are associated with Which common allergic reactions? β-Lactam antibiotics developed About 10% of the population in predominantly countries is thought to be penicillin allergic, an­ while the temporarily response to the medication the immune modifies the It effectively on the medication. patient remains there is an even though to the medication, immune response for both IgE- can be used allergy. This procedure underlying a variety of reactions to drug allergic and non-IgE–mediated chemotherapeutics and biologic drugs, including antibiotics, allopuri and [ASA] acid acetylsalicylic penicillin, (e.g., agents for patients with a history of a severe nol), but it is not used - toxic epi syndrome, as Stevens–Johnson such drug reaction, - drug reaction with eosinophilia and sys dermal necrolysis or temic symptoms. VOLUME 190 VOLUME |

1,23 1,4,7,15 APRIL 30, 2018 | CMAJ 1 26 However, in Europe, both patch However, 8 Allergic reactions to medications have characteristic times of onset, with some (such as IgE-mediated reactions) reactions) as IgE-mediated with some (such times of onset, characteristic have medications to reactions Allergic drug allergies Most in onset. being delayed (such as DRESS) others a dose, and after hours within a few occurring lupus (such as drug-induced some exceptions are there the drug; however, of taking two weeks within the first occur and DRESS). erythematosus is urticaria example, (for and prognosis type of testing aids in determining of the type of skin eruption Knowledge of a type IV reaction). is suggestive rash a maculopapular whereas reaction, of an IgE-mediated suggestive instead was that a reaction is blamed for such as an antibiotic, medication, a newly prescribed It is possible that drugs). anti-inflammatory (such as nonsteroidal medication another by caused although some (such as a reaction, before a period of sensitization require reactions allergic drug-induced Most weeks of use. several after exposure on first occur can DRESS) are of administration routes and cutaneous (parenteral of administration include route Drug-specific risk factors of dose associated duration prolonged administration), than oral of sensitization with a higher degree associated virus, which virus (such as Epstein–Barr and concurrent the medication to exposure risk, repetitive with increased (female), include sex risk factors Host-specific is used concurrently). 100% of the time when amoxicillin rash causes hypersensitivity) the risk of abacavir polymorphisms (such as HLA-B5701, which increases some genetic older age, reactions. the risk of allergic HIV) which increase lupus erythematosus, (systemic and underlying conditions of a instead urticaria), etiology (such as chronic another may be due to such as urticaria, reactions, Some cutaneous the drug, this increases or related with a particular in the past has occurred In addition, if the reaction drug allergy. of drug allergy. likelihood (e.g., penicillin; within some medications to reactions allergic drug-induced of outgrowing is a high rate There tolerant). will be pencillin patients most reaction, an allergic after 10 years A recent retrospective review of patch testing that that testing patch of review retrospective recent A 24,25 In contrast, induction of drug tolerance (e.g., drug desensi- (e.g., drug In contrast, induction of drug tolerance Note: DRESS = drug reaction with eosinophilia and systemic symptoms, IgE = immunoglobulin E. symptoms, with eosinophilia and systemic = drug reaction DRESS Note: Table 3: Useful components of the medical history the medical of components 3: Useful Table of the time frame was What the reaction? symptoms cutaneous What occurred? medications any other Were being used concurrently? been Has the medication used in the past? any patient- there Were specific or drug-specific risk a reaction? for factors occurred Has this reaction before? the was long ago How reaction? tization) involves providing increasing incremental doses of incremental doses of tization) involves providing increasing days, to hours of period a over patient the to medication the hypothesized mech­ using different procedures based on the

In most cases of drug allergy, validated skin or laboratory tests are allergy, validated skin or laboratory tests In most cases of drug isallergy drug of likelihood the whom in patients For available. not challengedrug a rash), benign reaction, remote (e.g., low deemed is not indicative ofcan be performed by an allergist. If the history con- to administered be can dose full allergy (e.g., headache), a an challenge is per- firm tolerance. In most circumstances, a graded that often involves theformed, with the assistance of an allergist, doses of the medi- administration of two graded sub-therapeutic allergic reaction. A UScation to the patient, with monitoring for an if the his- guideline noted that drug challenges are contraindicated such as Stevens– tory is consistent with a severe drug reaction, or drug reaction Johnson syndrome, toxic epidermal necrolysis with eosinophilia and systemic symptoms. Drug challenge - at a nonirritat on the back the allergen placing testing (i.e., patch reported. disk) has been under an aluminum ing concentration included 260 patients der- who received treatment in a European that patch testing was safe and specific, matology clinic found reactions. even for severe nonimmediate In North America, it is not used commonly in the more severe more severe commonly in the it is not used In North America, syn- such as Stevens–Johnson drug reactions, nonimmediate with eosino- or drug reaction epidermal necrolysis drome, toxic systemic symptoms. philia and testing and delayed intradermal testing (i.e., the result is read intradermal testing (i.e., the result is read testing and delayed nonimmediate reactions, including severedays later) are used for reactions. REVIEW lution forpenicillinallergy. ago,becausethereisahighrateofreso- more than5to10 years unnecessary healthcarecosts. eral othermoieties(minordeterminants). moiety (majordeterminant) and theremainder degrade intosev- under physiologic conditions. Most degrade to the penicilloyl lin undergoesspontaneousconversiontoreactiveintermediates more yearsaftertheirclinicalreaction. of patientswithapositivetestresultiftheywereevaluated10or testing ifthereactionwasinpastyear;thisdecreasedto22% found that93%ofthesepatientshadapositiveresultforskin withahistoryofβ study involving740 patients test). results forallergytesting(skinanddrugprovocation 100%) ofthesechildrenwithlow-risksymptomshadnegative a historyofpenicillinallergyfoundthat100%(95%CI96.4%– with pediatric emergencydepartmentthatinvolved100 children oral challenge)penicillinallergy.Anevaluationconductedina suggested even in those with confirmed (based on skin testing or E536 patients withco-existingEpstein–Barrvirus. maculopapular rash in 5%–10% of patients, and in 100% of Amoxicillin and ampicillin are associated with a delayed (type 4) Amoxicillin andcephalosporins ous reaction —eithermacular,morbilliformorurticarial. The most common drug allergic reaction to penicillin is a cutane- Penicillin cillin allergy, the “de-labelling”ofpatientserroneouslydiagnosedwithpeni- spectrum antibioticuse, have notedthaterroneouslabellingisassociatedwithbroad- penicillin. tions, overall the reaction rate is about 10-fold lower than for cation tofutureamoxicillinorampicillinuse. reactions arenotlife-threateningandanabsolutecontraindi- lin isthoughttobeverylow. firmed penicillinoramoxicillinallergy.” the safeuseofcephalosporins inpatientswithisolatedcon- bidity, andconcludedthatthere was“ampleevidencetoallow amoxicillin orpenicillinallergycouldresultinsubstantialmor - reported thatavoidanceofcephalosporinsinpatientswith the tion totheβ penicillin skintestsandwilltoleratepenicillins. with a history of penicillin allergy are found to have negative allergist asaconfirmatorystepifnegative. sis ofIgE-mediated penicillin allergy, with anoralchallenge by an cillin reagents has ahighnegative predictive value inthediagno- ous reaction was not life-threatening. ­second- orthird-generationcephalosporinsaslongtheprevi - reactivity topenicillinoramoxicillincansafelybeprescribed guideline onotitismedianotesthatchildrenwithahistory of Although cephalosporinscanalsocauseacuteallergicreac- Amoxicillin and cephalosporins contain “R” side chains in addi- Recent studieshaveshownthatasmany98%ofpatients β -lactam portion of penicillin would result in sensitization to -lactam portion ofpenicillinwouldresultinsensitization to 37 Evaluationisespeciallyusefulifthereactionoccurred 1 Cross reactivity between cephalosporins and penicil- -lactam ring, which may be allergenic. Sensitization to -lactam ring,whichmaybeallergenic. Sensitizationto 33 includingonefromChoosingWiselyCanada, 1,19 increasedantibioticresistance 41 38–40 19,36 TheCanadianPediatricSociety’s Forexample,aretrospective 38 43 8 CMAJ 42 Skintestingwithpeni- A 2016 review also 8 Theseamoxicillin 36 | Re-evaluationis APRIL30, 2018 -lactam allergy 1 Penicil- 35 34 and and | VOLUME 190 erance followedbyASAtherapy canbeconsideredaswell. refractory to medical and surgical therapy, ASA induction of tol- (COX-2 inhibitors are usually safe); if asthma or rhinosinusitis is provocation test.TreatmentisavoidanceofCOX-1inhibitors It isrelatedtoCOX-1inhibitionanddiagnosedwithanoral lenge, andthereactionswhenpresentweremild. and accurate.Almostallchildren(94.1%)toleratedtheoralchal- pected amoxicillinallergy,agradedoralchallengewasbothsafe with sus- lin allergyinchildrenfindingthatamong818 children an cohort studyalsosuggestedthatagradedoralchallengealonein to ruleoutdefinitivelyIgE-mediatedallergy.ArecentCanadian an oralchallengetoamoxicillinisoftenconsideredbyallergist have negativeresultsforskintestingtothepenicillinreagents, patients withahistoryofunderlyingasthmaandrhinosinusitis. afterNSAIDingestion,mostlyinadult toms withinthree hours tory diseasepresentswithupperandlowerrespiratorysymp - eruptions, arealsopossiblewithNSAIDs. Johnson syndrome,delayedmaculopapularrashorfixeddrug all reaction, ofwhich18.3%wereallergic. period reportedthat17%ofthosepatientshadanadversedrug care system whowereprescribedNSAIDsover an eight-year spective review involving all adult patients in an American health ). Aretro- related tocyclooxygenase-1[COX-1]inhibition)(Table 5 either allergicinnatureor,morecommonly,nonimmune(and monly inNorthAmericaandcancausedifferentreactionsthatare Nonsteroidal anti-inflammatory drugs (NSAIDs) are used com- Nonsteroidal anti-inflammatorydrugs allergy usuallytoleratecarbapenemsandaztreonam. β negative resultsforpenicillinskintestscansafelyreceive patientswith tory consistentwithanIgE-mediatedreaction — other thanpenicillin,itcanstillhavesomeutilityifthereisahis- cutaneous disease, NSAID-induced urticaria/angioedema or exposure mayhaveoneofthree conditions:NSAID-exacerbated gested bytheJointTaskForceonPracticeParameters. , assug- the contextofanallergicreactionisoutlinedinTable 4 ). NSAID-induced) (Table 4 (which couldbeNSAID-exacerbated,NSAID-inducedorsingle– ease, single–NSAID-inducedanaphylaxisorurticaria/­ NSAID-induced reactionsareNSAID-exacerbatedrespiratorydis- validated. sporins; however,theirnegativepredictivevaluehasnotbeen ing reagentshavebeendevelopedforamoxicillinandcephalo- the R-groupsidechaininsteadofcommonβ rins, ifanacuteallergicreactiondoesoccur,itisoftendirectedat and cephalexin;ceftriaxonewithcefotaxime.Forcephalospo- an identicalRsidechainwithcefprozil;ampicillincefaclor those withacommonsidechain).Forexample,amoxicillinshares chain wouldleadtotoleranceofmostβ -lactam antibiotics,andpatientswithconfirmedpenicillin allergy clinic may beaneffective diagnostic testforamoxicil- Nonsteroidal anti-inflammatorydrug–exacerbatedrespira- Although skin testing has not been validated for Patients whopresentwithcutaneous symptomsafterNSAID The approachtoadministrationofcephalosporinsorpenicillinin β -lactam antibiotics;incontrast,sensitizationtotheRside 1 Ifpatientswithahistoryofreactiontoamoxicillin | ISSUE 17 47,48 Delayedreactions,suchasStevens– -lactam antibiotics (except -lactam antibiotics(except 46 The common types of -lactam ring. 45 1 angioedema angioedema 44 β Skintest- -lactams 1 8 47

REVIEW . Curr Curr 5 E537 1200- 279:​ Drug allergy: an Drug allergy: an 1998; JAMA 1 American Academy of Allergy, American Academy of Allergy, ; Incidence of adverse drug events and Incidence of adverse drug events and Incidence of adverse drug reactions in hospi- et al. 47 PN. , N American College of Allergy, Asthma and Immunol- and Asthma Allergy, of College American Symptoms Corey Epidemiology of hypersensitivity drug reactions. Laird . BH, P Reaction to penicillin to Reaction DJ, Demoly Cullen Give cephalosporin if result is negative if result cephalosporin Give give cephalosporin, Avoid or challenge via graded cephalosporin if result cephalosporin to desensitize is positive via graded cephalosporin Give is negative result if challenge cephalosporin to or desensitize Avoid is positive if results or penicillin avoid is positive, If result desensitize penicillin via give is negative, If result challenge ISSUE 17 ISSUE | Pomeranz , 1. Penicillin skin testing 1. Penicillin • • or 2. Cephalosporin skin testing • • skin test Penicillin • • J Upper and lower respiratory Upper and lower Cutaneous Cutaneous or anaphylaxis Cutaneous ER, DW, Joint Council of Allergy, Asthma and Immunology. Lazarou Gomes Joint Task Force on Practice Parameters Practice on Force Task Joint Immunology; and Asthma ogy; updated practice parameter. Ann Allergy Asthma Immunol 2010;105:259-73. Bates potential adverse drug events. Implications for prevention. ADE Prevention Study Group. JAMA 1995;274:29-34. talized patients: a meta-analysis of prospective studies. Opin Allergy Clin Immunol 2005;5:309-16. . 4. Conclusion allergic reactions areAlthough adverse drug reactions are common, uncommon. Cutaneous manifestations are the most common clinical manifestation of an allergic drug reaction. Diagnosis largely relies on medical history, because there are few standardized tests in the diag- nosis of drug allergy, with the exception of skin testing for penicillin. However, evaluation of patients labelled as allergic remains an impor- tant public health goal because mislabelling can have health conse- quences, such as increased morbidity and public health costs. References 1. 2. 3 – – VOLUME 190 VOLUME | - condition Underlying All of Asthma, rhinitis, sinusitis, polyps urticaria Chronic 47 APRIL 30, 2018 | Reaction to cephalosporin to Reaction type Reaction Reaction If result is negative, give via graded via graded give is negative, If result challenge or avoid is positive, If result desensitize If result is negative, give penicillin give is negative, If result drug alternate give is positive, If result penicillin to or desensitize NERD NECD NIUA SNIUAA CMAJ 1. Graded challenge to cephalosporin cephalosporin to challenge 1. Graded side chain with different or cephalosporin different to 2. Skin test • • 1. Graded challenge to penicillin to challenge 1. Graded or penicillin to 2. Skin test • • For NSAID-exacerbated cutaneous dis- 47 Table 4: Administration of penicillin or cephalosporins in the context of a previous reaction a previous of the context in or cephalosporins penicillin of 4: Administration Table Drug administered Cephalosporin Penicillin Note: COX-1 = cyclooxygenase-1, IgE = immunoglobulin E, NECD = NSAID-exacerbated cutaneous disease, NERD = NSAID-exacerbated NERD = NSAID-exacerbated disease, cutaneous IgE = immunoglobulin E, NECD = NSAID-exacerbated = cyclooxygenase-1, COX-1 Note: single-NSAID– drug, SNIUAA = anti-inflammatory nonsteroidal NSAID = urticaria/angioedema, NSAID-induced NIUA = disease, respiratory or anaphylaxis. urticaria/angioedema induced Table 5: Allergic reactions induced by nonsteroidal anti-inflammatory drugs anti-inflammatory nonsteroidal by induced reactions 5: Allergic Table Pathophysiology COX-1 inhibition COX-1 (nonimmune) IgE-mediated (immune-mediated) 1,47 For all of these conditions, COX-2 inhibitors are largely 1,47 Table 4). Distinguishing between these conditions by drug provoca- caria, and the pathophysiology differs between these conditions ( tion testing (to both the implicated NSAID and a chemically unre- lated NSAID) is beneficial as a means of differentiating the condi- tions and predicting the extent of necessary NSAID avoidance according to a 2013 review. these conditions present with angioedema/urticaria; however, thethese conditions present with angioedema/urticaria; time frame differs slightly: NSAID-exacerbated cutaneous disease and NSAID-induced urticaria/angioedema can present up to several hours after NSAID ingestion (although presentation is often immedi- ate), and single-NSAID–induced urticaria/angioedema or anaphalaxis presentation is uniformly immediate. In addition, NSAID-exacerbated cutaneous disease presents in patients with a history of chronic urti ease and NSAID-induced urticaria/angioedema, all COX-1 inhibitors should be avoided (COX-2 inhibitors are usually safe). For single- NSAID–induced urticaria/angioedema or anaphalaxis, only the implicated NSAID and chemically related NSAIDs must be avoided.

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