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Treatment of aspirin idiosyncracy
222
J. ALLERGY
Correspondence
CLIN. IMMUNOL. SEPTEMBER 1982
therapyor to other mechanisms not involving IgE. Thuswe agreewith Dr. Sullivan’scalculationof a 0.7% (two out of 290)frequencyof immediatereactionsin patientwith negative skin tests.The reactionsin the remainingpatientsoccurredlaterthan24 hr; thesemaybe dueto sensitizationasa consequence of therapyor to mechanisms involving cellular immunity. In the abstractwe usedthe term “allergy” to referto all of thesereactions,but mostof thesewerenot due to the presenceof preexisting(prior to therapy) IgE antibodies. ConcerningDr. Sullivan’squestions,almostall the patients were treatedwithin 24 to 48 hr after skin testing, many within hours. In this group of patientswe did not examinethe relationshipbetweentheprevalenceof positive skin test reactionsandthe time sincethe allergicreaction. We analyzedthis data in the first 123 patientsand had reportedthis previously.’ Our resultsshowed,in keeping with prior studies,an inverserelationship,i.e., that the frequencyof positiveskin testsdecreased asthe time after the clinical reactionincreased.
tally insignificant,which never happenedlater than the fourth day. The studywascarriedout in six ASA-asthmaticpatients. Within 20daystolerancewasinducedin all of themwithout anytrouble.Thisrefractoryconditionlastedaslongasthese patientskept taking 500 mg of ASA every day or every other day. During this period, indomethacinwastolerated aswell. WhenASA wasstoppedfor morethan 2 to 3 days the sensitivitygraduallyreappeared; 20 to 30daysof interruption were neededfor full recuperation.No impressive improvementof asthmaticsymptomswasobservedin any patientduringASA treatment,whichlastedfrom 1 wk to 3 mo. Theseresultswere publishedearly in 1977(Bianco et al., IRCSJ Med Sci, 5: 129, 1977).Our paperwasquoted by Dr. Stevensonand hiscolleaguesin their article (J ALLERGYCLIN IMMUNOL66:82, 1980)but not in a proper way. Clearly we did more thanobservethat “a refractory period to further adverseeffects of aspirinpersistedafter original inhalationchallenge.” More recentexperiencesenableus to add that (1) ASA tolerancecanbe inducedby giving increasingdosesof other Richard G. Van Dellen, M.D. nonsteroidalanti-inflammatoryasthmogenic drugs,(2) tarGerald J. Gleich, M.D. trazine is toleratedby ASA-asthmaticpatients(negativereMayo Clinic sultsin 45 ASA-asthmaticpatientschallengedwith 500 to Rochester. Minn. 2000mg of tartrazine), (3) the challengewith lysine acetylsalicylateby inhalationispreferableto the oralchallenge REFERENCE becauseresponses are faster, confinedonly to the respira1. VanDellenRG,GleichGJ:Penicillinskintestsaspredictive tory tree, and alwayseasilycontrollable,and (4) we doubt anddiagnostic aidsin penicillinallergy.MedClinNorthAm that inducingandkeepingASA tolerancehave any thera54997, 1970. peutic implicationin ASA-asthmaticpatients.
Treatment
of aspirin
Bianco Sebastian0 Robuschi Mariella Petrigni Giuseppe Istituto de Tisiologia e delle Malattie dell’Apparato Respiratorio Milan University Milan, Italy
idiosyncracy
To the Editor:
With referenceto the letter of Dr. Basombaet al. andto Dr. Stevenson’s reply (J ALLERGYCLINIMMUNOL 68:484, 1981),we muststressthat in the history of the discoveryof aspirin(ASA)-induced“desensitization”we alsodeservea place. In fact, we were the first to carry out systematic studieson thisphenomenon, sothatwhenthepaperby Zeiss andLackey (J ALLERGYCLINIMMUNOL57:440, 1976) appeared,we alreadyknew that what they observedin one patientwasnot an exceptionbut the rule. Our experiencewith this phenomenon startedin 1955, when, after developinga new challengetest with ASA (as an aerosolsolutionof lysine acetylsalicylate)by inhalation (Pasargiklian et al., Respiration34:79, 1977),we wantedto check its reproducibility. In two ASA-asthmaticpatients, the challengewith the samedoseof ASA wasrepeatedon 4 consecutivedays. To our great surprise,the bronchialresponseprogressivelyfadedandon the lastdaywe couldnot get any response at all. This originalobservationprompted us to try to “desensitize” ASA-asthmaticpatientsby administeringincreasingdosesof ASA. The sequence of the doseswasas follows: 1.3, 2.6, 5.2, 10.5, and 21 mg of ASA by inhalationandthen 50, 100,200,400, and500mg of ASA by mouth.Eachnew dosewasintroducedwhenthe response. to the previous one (assessed by meansof a body-plethysmograph) had vanishedor had becomeclini-
Reply To the Editor:
Actually, the first reportof aspirin(ASA) desensitization of which I am awareappearedin the French literaturein 1922(Widal MF et al: Anaphylaxieet idiosyncrasie.Eresse Med 30:189, 1922). In the U.S. literature, Zeiss and Lackey (J ALLERGYCLIN IMMIJNOL57:440, 1976)made their own observationsindependently,as did Dr. Sebastiano’sgroup, as indicatedin the letter. The point for our readersis that ASA desensitization andinductionof refractorinessto ASA wasobservedby a numberof independent investigatorsandappearsto be a universalfindingin ASAsensitiverhinosinusitis/asthma patients(J ALLERGYCLIN IMMUNOL69: 11, 1982). With respectto Dr. Sebastiano’s additionalobservations: (1) ASA tolerancecanbe inducedwith other nonstemida1anti-inflammatorydrugs. At our institution we have been able to achieve desensitization with Indocin in 8/8 patients.
J. ALLERGY
Correspondence
CLIN. IMMUNOL. SEPTEMBER 1982
therapyor to other mechanisms not involving IgE. Thuswe agreewith Dr. Sullivan’scalculationof a 0.7% (two out of 290)frequencyof immediatereactionsin patientwith negative skin tests.The reactionsin the remainingpatientsoccurredlaterthan24 hr; thesemaybe dueto sensitizationasa consequence of therapyor to mechanisms involving cellular immunity. In the abstractwe usedthe term “allergy” to referto all of thesereactions,but mostof thesewerenot due to the presenceof preexisting(prior to therapy) IgE antibodies. ConcerningDr. Sullivan’squestions,almostall the patients were treatedwithin 24 to 48 hr after skin testing, many within hours. In this group of patientswe did not examinethe relationshipbetweentheprevalenceof positive skin test reactionsandthe time sincethe allergicreaction. We analyzedthis data in the first 123 patientsand had reportedthis previously.’ Our resultsshowed,in keeping with prior studies,an inverserelationship,i.e., that the frequencyof positiveskin testsdecreased asthe time after the clinical reactionincreased.
tally insignificant,which never happenedlater than the fourth day. The studywascarriedout in six ASA-asthmaticpatients. Within 20daystolerancewasinducedin all of themwithout anytrouble.Thisrefractoryconditionlastedaslongasthese patientskept taking 500 mg of ASA every day or every other day. During this period, indomethacinwastolerated aswell. WhenASA wasstoppedfor morethan 2 to 3 days the sensitivitygraduallyreappeared; 20 to 30daysof interruption were neededfor full recuperation.No impressive improvementof asthmaticsymptomswasobservedin any patientduringASA treatment,whichlastedfrom 1 wk to 3 mo. Theseresultswere publishedearly in 1977(Bianco et al., IRCSJ Med Sci, 5: 129, 1977).Our paperwasquoted by Dr. Stevensonand hiscolleaguesin their article (J ALLERGYCLIN IMMUNOL66:82, 1980)but not in a proper way. Clearly we did more thanobservethat “a refractory period to further adverseeffects of aspirinpersistedafter original inhalationchallenge.” More recentexperiencesenableus to add that (1) ASA tolerancecanbe inducedby giving increasingdosesof other Richard G. Van Dellen, M.D. nonsteroidalanti-inflammatoryasthmogenic drugs,(2) tarGerald J. Gleich, M.D. trazine is toleratedby ASA-asthmaticpatients(negativereMayo Clinic sultsin 45 ASA-asthmaticpatientschallengedwith 500 to Rochester. Minn. 2000mg of tartrazine), (3) the challengewith lysine acetylsalicylateby inhalationispreferableto the oralchallenge REFERENCE becauseresponses are faster, confinedonly to the respira1. VanDellenRG,GleichGJ:Penicillinskintestsaspredictive tory tree, and alwayseasilycontrollable,and (4) we doubt anddiagnostic aidsin penicillinallergy.MedClinNorthAm that inducingandkeepingASA tolerancehave any thera54997, 1970. peutic implicationin ASA-asthmaticpatients.
Treatment
of aspirin
Bianco Sebastian0 Robuschi Mariella Petrigni Giuseppe Istituto de Tisiologia e delle Malattie dell’Apparato Respiratorio Milan University Milan, Italy
idiosyncracy
To the Editor:
With referenceto the letter of Dr. Basombaet al. andto Dr. Stevenson’s reply (J ALLERGYCLINIMMUNOL 68:484, 1981),we muststressthat in the history of the discoveryof aspirin(ASA)-induced“desensitization”we alsodeservea place. In fact, we were the first to carry out systematic studieson thisphenomenon, sothatwhenthepaperby Zeiss andLackey (J ALLERGYCLINIMMUNOL57:440, 1976) appeared,we alreadyknew that what they observedin one patientwasnot an exceptionbut the rule. Our experiencewith this phenomenon startedin 1955, when, after developinga new challengetest with ASA (as an aerosolsolutionof lysine acetylsalicylate)by inhalation (Pasargiklian et al., Respiration34:79, 1977),we wantedto check its reproducibility. In two ASA-asthmaticpatients, the challengewith the samedoseof ASA wasrepeatedon 4 consecutivedays. To our great surprise,the bronchialresponseprogressivelyfadedandon the lastdaywe couldnot get any response at all. This originalobservationprompted us to try to “desensitize” ASA-asthmaticpatientsby administeringincreasingdosesof ASA. The sequence of the doseswasas follows: 1.3, 2.6, 5.2, 10.5, and 21 mg of ASA by inhalationandthen 50, 100,200,400, and500mg of ASA by mouth.Eachnew dosewasintroducedwhenthe response. to the previous one (assessed by meansof a body-plethysmograph) had vanishedor had becomeclini-
Reply To the Editor:
Actually, the first reportof aspirin(ASA) desensitization of which I am awareappearedin the French literaturein 1922(Widal MF et al: Anaphylaxieet idiosyncrasie.Eresse Med 30:189, 1922). In the U.S. literature, Zeiss and Lackey (J ALLERGYCLIN IMMIJNOL57:440, 1976)made their own observationsindependently,as did Dr. Sebastiano’sgroup, as indicatedin the letter. The point for our readersis that ASA desensitization andinductionof refractorinessto ASA wasobservedby a numberof independent investigatorsandappearsto be a universalfindingin ASAsensitiverhinosinusitis/asthma patients(J ALLERGYCLIN IMMUNOL69: 11, 1982). With respectto Dr. Sebastiano’s additionalobservations: (1) ASA tolerancecanbe inducedwith other nonstemida1anti-inflammatorydrugs. At our institution we have been able to achieve desensitization with Indocin in 8/8 patients.