General considerations for skin test procedures in …

1 RostrumGeneral considerations for skin test procedures in the diagnosis ofdrug hypersensitivityK. Brockow1, A. Romano2,M. Blanca3, J. Ring1, W. Pichler4,P. Demoly5*1 Klinik und Poliklinik fu r Dermatologie undAllergologie, Muenchen, Germany;2 Department ofInternal Medicine and Geriatrics, UCSC, Allergy Unit,CI Columbus, Rome and IRCS Oasi Maria SS, Troina,Italy;3 Research Unit for Allergic Diseases, Carlos HayaHospital, Malaga, Spain;4 Clinic for Rheumatology andClinical Immunology/Allergology, Inselspital, Bern,Switzerland.

2 5 Maladies Respiratoires, Ho pital Arnaudde Villeneuve, Montpellier, FrancePascal DemolyMaladies RespiratoiresINSERM U454Ho pital Arnaud de VilleneuveCHU de Montpellier34295 Montpellier cedex 5 FranceAccepted for publication 20 August 2001 Diagnostic procedures in allergy diagnosis can beclassified into the patient s history,in vivoskin testing,in vitrolaboratory tests and provocation tests (1). Indrug hypersensitivity, a reliable diagnosis is particularlydifficult. The history is often not reliable since differentdrugs are often taken simultaneously.

3 Test reagents areneither standardized forin vitronor forin vivo( skin ) tests and provocation tests are cumbersome, possiblyharmful for the patient and possibly not sensitiveenough since crucial cofactors might be absent duringthe procedure. Finally, the clinical picture of drughypersensitivity is very heterogeneous, mirroring manydistinct pathophysiological events. When immunologicmechanisms have been shown, either antibody or cellmediated, the reactions are referred as drug allergy (20).Drug allergy is in the vast majority due to IgE-mediatedimmediate-type reactions or T-cell mediated delayed-type reactions.

4 In a large number of patients, no allergycan be proven, which may be either due to the lack ofadequate test reagents or procedures , or may indicate anon-allergic pathomechanism. Thus, many doctors relyon history and some reference manuals for drug adverseevent diagnosis, without attempting to prove therelationship between drug intake and symptoms or toclarify the underlying pathomechanism of the an attitude leads to a misunderstanding of theepidemiology and the pathophysiology of this highlyrelevant tests can be used for the evaluation of a drughypersensitivity (2 5).

5 The diagnostic value of skintests has not been fully evaluated and the experience indifferent centres has rarely been exchanged during the*ENDA: European Network for Drug Allergy, the EAACI interestgroup on drug hypersensitivity with the following additional members:Drs W. Aberer, B. K. Ballmer-Weber, A. Barbaud, A. Bircher, , P. Campi, A. de Weck, M. Drouet, J. Fernandez, T. Fuchs, , J. L. Gue ant, C. Gutgesell, A. Kapp, M. Kowalski, G. Marone,H. Merk, D. Moneret-Vautrin, C. Pascual-Marcos, B. Przybilla, , F. Rueff, A. Sabbah, J.

6 Sainte Laudy, M. J. Torres, , B. WediAllergy 2002: 57: 45 51 Printed in UK. All rights reservedCopyright#Munksgaard 2002 ALLERGYISSN 0105-453845last decades. Thus, reliable skin test procedures for thediagnosis of drug hypersensitivity are generally missingand test concentrations are unknown or poorlyvalidated for most tests have to be applied according to thesuspected pathomechanism of thedrughypersensitivity (2 5). In immediateb-lactam drugallergy an IgE-mediated reaction can be demonstratedby a positive skin prick and/or intradermal test after20 min (6, 7).

7 On the other hand, non-immediatereactions tob-lactams manifesting by cutaneoussymptoms occurring more than one hour after lastdrug intake, are often T-cell mediated and a positivepatch test and/or a late-reading intradermal test isfound after several hours or days (8). Moreover, skintests have the additional capability to give insightsconcerning the immunologic harmonize our drug hypersensitivity diagnosticprocedures in Europe, members of ENDA (the corepart of the EAACI interest group on drug hypersensi-tivity) have first developed a questionnaire based on adetailed history of the reaction (9).

8 It also includes someprocedures for skin tests , provocation tests andbiological tests . It is available in various languagesand thus utilized in different regions of Europe. Ournext aim is to develop useful test procedures for thediagnosis of drug hypersensitivity, procedures whichare simple and can be used in centres not specialized indrug a first step, we define General principles for skintesting of drugs, to establish the best skin testconcentrations to be used for already well-studied sub-stances. For other substances and through collaborativestudies, we will be able to provide sensitivity andspecificity data for each drug and drug of patients for skin testingA list of common clinical symptoms, for which skintesting is recommended is listed 1.

9 For thepractising allergist, skin testing with SPT, IDT and/orpatch test is especially recommended in adverse drugreactions to beta-lactam antibiotics (mainly penicillins,cephalosporins). SPT and IDT are often positive tomyorelaxants, insulin, protamine, heparin, streptoki-nase and chymopapain. It is also recommended toperform patch tests and IDT in delayed local orexanthematic adverse reactions to other antibiotics,carbamazepine, practolol, pyrazonolines and tetraze-pam. skin tests and provocation tests to localanesthetics should be performed; however, in this casethe purpose is to exclude a reaction to a preparationunder test conditions, rather than to confirm and signs generally indicating drugallergy, as opposed to non-immunologic adversereaction, are the presence of a sensitization period,reaction to low dosages of the drug, and typicalsymptomatology such as urticaria and anaphylaxisimmediately after administration of a drug (Table 1).

10 However, in adverse reactions to drugs, this generalscheme is often unreliable, as sensitization may not beapparent and some reactions may mimic symptoms ofallergy. Thus, centres with a special interest on drugallergies are encouraged to test patients with otherdrugs to gain and publish experience on the value ofskin testing under different are other diseases where immunologicalreactions to drugs could be involved, but skin testinghas generally not been found helpful. For example,renal or hepatic manifestations may occur as a part of ageneralized allergic reaction ( , in Drug Reactionwith Eosinophilia and Systematic Symptoms).