Specific Inhibition of Allergic Reactions to Penicillin in Man by a Monovalent Hapten

Weck, A.L. de; Girard, Jean‐Pierre

doi:10.1159/000230659

Cited by 43 publications

(1 citation statement)

References 5 publications

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“…Hapten inhibition of reactions, impractical on a large scale, may become feasible to avoid or arrest reactions in high-risk patients. 13 The recognition of a propensity to drug allergy in a large fraction of patients who express allergic reactions to antimicrobial drugs, the "multiple drug allergy syndrome," has led to a perception of drug allergy as a 364 recurrent disease rather than an isolated event. Many of these patients will make new immune responses to structurally dissimilar antimicrobial drugs in the future, with reactions ranging from anaphylaxis to rashes to "serum sickness" to life-endangering mucocutaneous bullous lesions.…”

Section: Discussionmentioning

confidence: 99%

Management of Patients Allergic to Antimicrobial Drugs

Sullivan¹

1991

allergy asthma proc

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Allergic reactions to antimicrobial drugs cause significant morbidity in approximately 1% of treated patients. Those who express allergic reactions to antimicrobial drugs or who are at increased risk of reacting also can present difficult diagnostic and management problems. Recent studies suggest that patients who have expressed allergic reactions to antimicrobial drugs in the past or who are the offspring oj antimicrobial drug-allergic parents are at increased risk of antimicrobial drug allergy. This propensity to antimicrobial drug allergy is not restricted to specific classes of drug or to specific patterns of allergic reactions. The concept that antimicrobial drug allergy often is a recurrent disease rather than an isolated event has generated new approaches to the comprehensive management of high-risk patients. This concept also has suggested new areas for investigation that may provide fundamental new insights into why some persons express immune responses to haptens and others do not. (Allergy Proc 12, 6:361-364,1991.) A llergic reactions occur in a predictable, small fraction of patients exposed to specific classes of antimicrobial drugs}02 Until recently no clinical or laboratory assessments have been available that allowed accurate prediction of which patients treated with a specific agent are destined to express immune responses to drug determinants. HLA genotype and drug metabolism polymorphisms are theoretical risk factors for reactions to specific antimicrobial drugs, 3 but data clarifying the importance of these possible markers are not yet available. Allergy Proc.Recently, a history of allergy to one class of antimicrobial drug has been proposed as a marker identifying patients at increased risk of reacting to other classes of antimicrobial drugs. A prospective study in our institution demonstrated a reaction rate of 13.5% in historypositive patients receiving one course of in-hospital parenteral antimicrobial drug therapy and 1.4% in matched history-negative patients, a lO-fold increased risk. 4 A family history of antimicrobial drug allergy has been proposed as a second general risk factor for antimicrobial drug allergy. Studies at our institution detected significantly increased risk of antimicrobial drug allergy in the offspring of drug-allergic parents in one study and in the parents of drug-allergic children in a second study.5 Twenty-six percent of the children of drug-allergic parents had experienced an allergic reaction to an antimicrobial drug by age 16. These children had a IS-fold increased risk of antimicrobial drug allergy when compared with the offspring of parents who had tolerated antimicrobial drug therapy without incident.This propensity to antimicrobial drug allergy appears to consist of an enhanced reaction to haptenating drugs during an infection. 6 These reactions are not restricted to specific classes of antimicrobial drugs and are not restricted to specific forms of reactions. Although pleiomorphic rashes were common, anaphylaxis occurred in 3%, toxic epidermal necroly...

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Section: Discussionmentioning

confidence: 99%

Management of Patients Allergic to Antimicrobial Drugs

Sullivan¹

1991

allergy asthma proc

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Aspects of Formation of the D‐Penicillamine‐Antigenic Determinant from Penicilloyl Compounds

Schneider¹,

Pfeuti²,

Weck³

1973

Helvetica Chimica Acta

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Summavy. The formation of D-penicillamine-L-cystcine mixed disulfide from benzylpenicilloic acid, benzylpenilloic acid and benzylpenicilloyl amide derivatives in 1.-cysteine suspensions a t pH 7,6 and 37" was studied. Thc reaction is faster than direct penicilloylation of proteins known to be a route to penicilloyl antigenic determinants. The production of S-bound penicillamine on protein from penicilloyl compounds must therefore definitely be considered as a potential antigenforming step. The reaction may be partly if not fully blocked by acylation of the thiazolidine nitrogen of penicilloyl compounds. When formylation is applied a considerable rcduction of the capacity of penicilloyl antigenic determinants to interact with anti-penicilloyl antibody is noted. In a number of patients hypersensitive to penicillin, allergic wheal and erythema reactions can be elicited by intracutaneous administration of relatively high doses of sodium benzylpenicilloate. These skin responses do not involve the penicilloyl antigenic determinant because, inter alia, they cannot be correlated with the penicilloyl-specific reactions elicited at the same time by penicilloylated polylysine l) . It has been postulated that D-penicillamine-L-cysteine mixed disulfides may form from penicilloic acid and cysteine residues of host proteins and function as antigenic determinants. According to Leuine [l] , monosodium D-a-benzylpenicilloate reacts in aqueous solution at pH 7.5 with cystine and a product which seems to be D-penicillamine-cysteine mixed disulfide can be separated by paper chromatography. The mechanism could function via an initial disulfide exchange between cystine and penamaldate, present in small amounts in equilibrium with penicilloate. The penamaldic acid-cysteine mixed disulfide thus produced should decompose yielding the observed D-penicillaniine-cysteine mixed disulfide (scheme 1).Our interest in penicillamine determinants is due to the fact, demonstrated in this paper, that in addition to penicilloic acid, functional derivatives of its a-carboxyl group can produce penicillamine-cysteine mixed disulfides in the presence of cystine. Therefore, any penicilloylated carrier within the body has to be regarded as a potential source for the penicillamine determinant. Furthermore, this determinant may arise from low molecular weight penicilloyl derivatives such as e(benzylpenicilloy1)-cr-formyl-L-lysine introduced into the body in large amounts in order to inhibit penicilloyl specific allergic manifestations during penicillin therapy (21. I)The penicilloyl compounds in this paper are functional derivatives of the a-carboxyl group of penicilloic acid. Their isomeric form is ~-a .Acid treated penicilloyl derivatives such as the formvlated ones are isomeric mixtures.

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Approaches to prevention and treatment of drug allergy

Weck

1979

Drugs and Immune Responsiveness

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Specific Inhibition of Allergic Reactions to Penicillin in Man by a Monovalent Hapten

Cited by 43 publications

References 5 publications

Management of Patients Allergic to Antimicrobial Drugs

Management of Patients Allergic to Antimicrobial Drugs

Aspects of Formation of the D‐Penicillamine‐Antigenic Determinant from Penicilloyl Compounds

Approaches to prevention and treatment of drug allergy

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