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354 The frequency of reactivity to side chain determinants in immediate hypersensitivity to penicillins, as detected by skin testing
228 Abstracts
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354
DIFFERENCES IN RAST VALUE TO BENZYL PENICILLIN AND AMOXICILLIN MEASURED IN SERA FROM PATIENTS ALLERGIC TO BETALACTAMS. S Femandez M Blanca. JM Veaa. A Miranda, MJ Carmona JJ Garcia. E Perez, MC Mova. A Garcia. Carlos Haya Hospital, Malaga, Spain. II has been reported that the cross-reactivity between betalactams can be related to the variation of the acyl side chain structure in the penicillin molecule. Futhermore clinical evidence of anaphylaxis to amoxicillin with good tolerance to benzyl penicllio has been reported. In this study RAST to BP and AX was determined in the sera of allergic patients to penicillins. Concentration effect curves and RAST inhibition studies were made in order to determine the role of the side chain in the specificity of the IgE antibodies. Twcnly four sera containing Ig!3 antibodies to BP and/or AX were studied. RAST was made in parallel lo all the sera; 16 proved to be more positive lo BPO-PLL, 6 to AX-PLL and in 2 [he RAST was similar with a coefficient of variation lower than 15%. Pools were made with the sera more positive to BP (A) or AX (B) and another pool with similar value to both haptens (C). Concentration effect curves with increasing concentrations of BP and AX coupled to polylisine on the discs indicated that at 25 mM of hapten concentration a plateau was reached with any of the pools used that was higher when pool A was used with the BPO-PLL discs and pool B with the AX-PLL discs. When pool C was used similar RAST value was obtained with either BPO-PLL or AX-PLL discs. RAST inhibition studies showed that with pool A and BPO-PLL discs, 82% inhibition was obtained with BPO-EAC conjugates and 40% with AX-EAC conjugates. With pool B and AX-PLL discs 42% was obtained with BP-EAC conjugates and 85% with AXEAC conjugates al the same molar concentration (100 mM). With pool C a similar value in inhibition was obtained using either BP0 or AX-PLL discs in the solid phase. These lindings indicate that the side chain structure of penicillins is relevani in the constitution of the antigenic determinant. We are at present studying the clinical relevance of these findings
355
THE FREQUENCYOF REACTIVITY TO SIDE CHAIN DETERMINANTS IN IMMEDIATE HYPERSENSITIVITY TO PENICILLINS. AS DETECTED BY SKIN TESTING. Fanny
356
Silviu-6an, Warrington,
MD, Shawn McPhillips, MB, BS, PhD, University
RN,
&Richard
of Manitoba. The value of skin testinn to detect immediate hypersensitivity to the ienicillins has been amply proven in clinical studies. Testing is usually with the major determinant of benzyl penicillin, benzyl-penicilloyl (BPO) and a minor determinant mixture of benzyl penicillin (BP-MDM). The frequency with which patients react to penicillins at side chain determinants is uncertain. We have examined this question in a survey of patients attending an adult allergy outpatient clinic. 228 patients have been tested by prick and intradermal testing for penicillin allergy. Tests were carried out with BPO-poly-L-lysine (6x10-5M), BP-MD?I (1x10m2M) and ?IDM of the clinically implicated penicillin derivative (l~lO-~i9. Negative and positive controls were included. The (168 F; 60 M) had an average age of 34.3 atients r 15.6 yrs. 40 (17.5%) of this group were positive on skin testing. 35% of these reacted only to BPO-PL, 17.5% reacted to BP-MDM and 32.4% reacted to both. But 6 patients (2.6% of the whole group and 15% of all positive reactors) reacted only to the XDM of ampicillin with a mean response of 4.3 * 1.2 mm. In these 6 patients the clinical reactions were urticaria(2), angioedema (l), respiratory difficulty(2), and m/p rash(l) and occurred 35.3 f 42 months before testing. It therefore appears that a significant number of patients with immediate hypersensitivity to the penicillins react only to the minor determinant mixture of the implicated antibiotic, suggesting side-chain specific reactions.
ANAFHYLACTOID REACTIONS (AK) ‘TO QlilNO LOPES. Dieter Vwluf. M. D.. Repine Rw..swurrn* A_ M-. D -:, Bernhard Prwbilla**. M. D. and Johan~~-Riiy~..?$.. p Ph.., Hamburg/*Frankfurt a. M./**Munich. FRG Quinolones such as ofloxacin and ciprotluxacm .tie LXWIX antibiotics with a broad antibacterial spectrum 'Their lwz ha> been significantly increased in the last few .veari and some few cases of AR to quinolones have 5e~r; : rracrions in the skin prick and i. d. test to ofloxacm and c!profiowacun even 111dilutions up to l:l@ 3 ,md l-10 4 r~:~p~c~~v~~I~This may he due to toxic effects or a part!) ,hr’e~~r histatnmc release by other up to now unknown ~ICC~:~IISII~X I+c,~e quinolones are autofluorescent it is irnp<>sSittle (0 in~‘~su~e hasophil histamine release with a specrrofluurolnr:ti K .IS?;.II Measurement of histamine release $1~ &: ,XWL~ (vi qumoiones was only possible with ‘I >pt~~~! RI.4 usmg chemical ! )fi<;x;ii.:n modification of histarnim and ciprofloxacin did not induce histamine rclea$c Iron! !~soph~l leucocytes of control individuals ‘rfter I:? vm~.~ mcut,;&r)i! Ihr pathomechanisms of AR tcb qu~~~lont~~ .~IZ ne! rstahlished. Some facts argue for posslbli: p~udo liiergi; mechanisms (e. g. immediate onset of ~yrnptom~ attrr tirvt o~-dl administration, direct histamine relzav f:om S~VStlt.ti.,t cells). other for allergic mechanisms (e. 3 T.iiC Llil IdfXlir' (if’ AR. possible sensitization tluv to prcvrrtt:\ ~..up,~ur~~ tl; qulnolones~.
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COVWNG
ENZYME (ACE) s. Lee, n.o*.. c., M. J&e;& M.D. L. Bielorv. M.D,, Newark, N.J. rare but AngioeTdyersLANG) is a serious effect of the ACE inhibitors. We report 4 cases of ANG induced by a long-acting ACE inhibitor (duration of action 24h). Pt. I is a 73 y/o BF who presented with ANG & severe 24h after her 1st dose of dyspnea lisinopril (L). Pt. 2 is a 82 y/o BF, on her last dose L for 2 wks, who 24h after developed severe ANC. Both pts. were admitted to the ICU & Pt. 1 received a tracheostomy. Pt. 3 is a 66 y/o BM, presented with tongue swelling & dysphagia 12h after his first dose of enalapril (E). Pt. 4 is a 58 y/o BM, who after 2 wks. of E, noted ANG of his face, lips & tongue 24h after his last dose of E. We determined serum tryptase (Tl I IFIE (kU/ml), C3&C4 (mg/dl), CH50 (U/ml) & Cl esterase inhibitor antigenic (mg/dl) & functional (+/-) levels in these pts. Pt. T IgE c3/c4 Cl-INH CM50 1 0 210 47128 107 13/+ 2 0 0 99135 185 15/+ 3 0 850 llO/47 301 22/+ 4 0 0 106/32 15/+ 262 ANG 2" to ACE inhibitors are not associated with complement or mast cell activation. The common use & the severe side effects (potentially fatal ANG) of ACE inhibitors require further analyses to elucidate the mechanism & assist in treatment. ~~~.
353
354
DIFFERENCES IN RAST VALUE TO BENZYL PENICILLIN AND AMOXICILLIN MEASURED IN SERA FROM PATIENTS ALLERGIC TO BETALACTAMS. S Femandez M Blanca. JM Veaa. A Miranda, MJ Carmona JJ Garcia. E Perez, MC Mova. A Garcia. Carlos Haya Hospital, Malaga, Spain. II has been reported that the cross-reactivity between betalactams can be related to the variation of the acyl side chain structure in the penicillin molecule. Futhermore clinical evidence of anaphylaxis to amoxicillin with good tolerance to benzyl penicllio has been reported. In this study RAST to BP and AX was determined in the sera of allergic patients to penicillins. Concentration effect curves and RAST inhibition studies were made in order to determine the role of the side chain in the specificity of the IgE antibodies. Twcnly four sera containing Ig!3 antibodies to BP and/or AX were studied. RAST was made in parallel lo all the sera; 16 proved to be more positive lo BPO-PLL, 6 to AX-PLL and in 2 [he RAST was similar with a coefficient of variation lower than 15%. Pools were made with the sera more positive to BP (A) or AX (B) and another pool with similar value to both haptens (C). Concentration effect curves with increasing concentrations of BP and AX coupled to polylisine on the discs indicated that at 25 mM of hapten concentration a plateau was reached with any of the pools used that was higher when pool A was used with the BPO-PLL discs and pool B with the AX-PLL discs. When pool C was used similar RAST value was obtained with either BPO-PLL or AX-PLL discs. RAST inhibition studies showed that with pool A and BPO-PLL discs, 82% inhibition was obtained with BPO-EAC conjugates and 40% with AX-EAC conjugates. With pool B and AX-PLL discs 42% was obtained with BP-EAC conjugates and 85% with AXEAC conjugates al the same molar concentration (100 mM). With pool C a similar value in inhibition was obtained using either BP0 or AX-PLL discs in the solid phase. These lindings indicate that the side chain structure of penicillins is relevani in the constitution of the antigenic determinant. We are at present studying the clinical relevance of these findings
355
THE FREQUENCYOF REACTIVITY TO SIDE CHAIN DETERMINANTS IN IMMEDIATE HYPERSENSITIVITY TO PENICILLINS. AS DETECTED BY SKIN TESTING. Fanny
356
Silviu-6an, Warrington,
MD, Shawn McPhillips, MB, BS, PhD, University
RN,
&Richard
of Manitoba. The value of skin testinn to detect immediate hypersensitivity to the ienicillins has been amply proven in clinical studies. Testing is usually with the major determinant of benzyl penicillin, benzyl-penicilloyl (BPO) and a minor determinant mixture of benzyl penicillin (BP-MDM). The frequency with which patients react to penicillins at side chain determinants is uncertain. We have examined this question in a survey of patients attending an adult allergy outpatient clinic. 228 patients have been tested by prick and intradermal testing for penicillin allergy. Tests were carried out with BPO-poly-L-lysine (6x10-5M), BP-MD?I (1x10m2M) and ?IDM of the clinically implicated penicillin derivative (l~lO-~i9. Negative and positive controls were included. The (168 F; 60 M) had an average age of 34.3 atients r 15.6 yrs. 40 (17.5%) of this group were positive on skin testing. 35% of these reacted only to BPO-PL, 17.5% reacted to BP-MDM and 32.4% reacted to both. But 6 patients (2.6% of the whole group and 15% of all positive reactors) reacted only to the XDM of ampicillin with a mean response of 4.3 * 1.2 mm. In these 6 patients the clinical reactions were urticaria(2), angioedema (l), respiratory difficulty(2), and m/p rash(l) and occurred 35.3 f 42 months before testing. It therefore appears that a significant number of patients with immediate hypersensitivity to the penicillins react only to the minor determinant mixture of the implicated antibiotic, suggesting side-chain specific reactions.
ANAFHYLACTOID REACTIONS (AK) ‘TO QlilNO LOPES. Dieter Vwluf. M. D.. Repine Rw..swurrn* A_ M-. D -:, Bernhard Prwbilla**. M. D. and Johan~~-Riiy~..?$.. p Ph.., Hamburg/*Frankfurt a. M./**Munich. FRG Quinolones such as ofloxacin and ciprotluxacm .tie LXWIX antibiotics with a broad antibacterial spectrum 'Their lwz ha> been significantly increased in the last few .veari and some few cases of AR to quinolones have 5e~r; :
-ION
COVWNG
ENZYME (ACE) s. Lee, n.o*.. c., M. J&e;& M.D. L. Bielorv. M.D,, Newark, N.J. rare but AngioeTdyersLANG) is a serious effect of the ACE inhibitors. We report 4 cases of ANG induced by a long-acting ACE inhibitor (duration of action 24h). Pt. I is a 73 y/o BF who presented with ANG & severe 24h after her 1st dose of dyspnea lisinopril (L). Pt. 2 is a 82 y/o BF, on her last dose L for 2 wks, who 24h after developed severe ANC. Both pts. were admitted to the ICU & Pt. 1 received a tracheostomy. Pt. 3 is a 66 y/o BM, presented with tongue swelling & dysphagia 12h after his first dose of enalapril (E). Pt. 4 is a 58 y/o BM, who after 2 wks. of E, noted ANG of his face, lips & tongue 24h after his last dose of E. We determined serum tryptase (Tl I IFIE (kU/ml), C3&C4 (mg/dl), CH50 (U/ml) & Cl esterase inhibitor antigenic (mg/dl) & functional (+/-) levels in these pts. Pt. T IgE c3/c4 Cl-INH CM50 1 0 210 47128 107 13/+ 2 0 0 99135 185 15/+ 3 0 850 llO/47 301 22/+ 4 0 0 106/32 15/+ 262 ANG 2" to ACE inhibitors are not associated with complement or mast cell activation. The common use & the severe side effects (potentially fatal ANG) of ACE inhibitors require further analyses to elucidate the mechanism & assist in treatment. ~~~.