Hypersensitivity to the B�talactames

Moutaouakkil Y; Tadlaoui Y; Fettah H; Moukafih B; Bennana A; Taoufik J; Lamsaouri J; Cherrah Y; Bousliman Y

Review Article

Austin J Allergy. 2017; 4(2): 1030.

Hypersensitivity to the Bêtalactames

Moutaouakkil Y¹*, Tadlaoui Y², Fettah H², Moukafih B², Bennana A², Taoufik J², Lamsaouri J², Cherrah Y¹ and Bousliman Y¹

¹Laboratory of Pharmacology-Toxicology, Faculty of Medicine and Pharmacy, Rabat Institute, University Mohamed V, Rabat-Morocco

²Laboratory of Medicinal Chemistry, Faculty of Medicine and Pharmacy, Rabat Institute, University Mohamed V, Rabat-Morocco

*Correspoing author: Youssef Moutaouakkil, Laboratory of Pharmacology-Toxicology, Faculty of Medicine and Pharmacy, Rabat Institute, University Mohamed V, Rabat-Morocco

Received: July 24, 2017; Accepted: August 28, 2017; Published: September 04, 2017

Abstract

Bêtalactames are the antibiotic family the most commonly used both in prophylaxy and therapy. Allergic reactions to penicillin’s have been reported since the 1950s, shortly after their introduction as therapeutic agents. An increasing number of reported anaphylactic reactions and other adverse effects proved this to be a serious public health problem. Hypersensitivity to the Bêtalactames is often overestimated with 80% to 90% of patients who report an allergy even without arguments. Documented allergy to betalactames antibiotics is rare but it can be seriously lethal. We are going through this present review, detailing the semiological aspects, the etiopathogenic mechanisms, as well as the risk factors of the Hypersensitivity to the Bêtalactames.

Keywords: Drug; Bêtalactames; Hypersensitivity; Allergy

Introduction

Drug hypersensitivity his immunological reaction characterized by two essential characteristics: it is unpredictable and it is independent of antibiotic dose administered [1]. It constitutes a major clinical problem. Its prevalence remains little known. It is estimated that it affects approximately 10% of hospitalized patients and 7% of ambulatory patient [2]. All medicines may be responsible of a hypersensitivity reaction, although the frequency and the severity of the reaction depend on the molecule. The bêtalactames antibiotics are the most frequently drugs involved in severe reactions [3]. It is classically admitted that almost 10% of the subjects treated by the bêtalactames report suspected bêtalactames allergic reactions to [4].

Bêtalactames

The β-lactam antibiotics represent a broad class of antibiotics which includes: penicillin’s; cephalosporin’s; the monobactams; the carbapenems;

Their common structure is molecular defined by a β-lactam ring to which is added a pénéme kernel /cephem and the side chains, allowing to define the different classes cited above (Figure 1).

Figure 1: Chemical structure of β-lactam antibiotics.

    
    
    Figure 1:  Chemical structure of β-lactam antibiotics.

Mechanisms of allergy to penicillin’s

Because of their low molecular weight, the β-lactams can induce a humoral and cellular immunological response. They are capable to cause all types of immunological reactions described by Gell and Coombs. The allergy mediated by immunoglobulin E (IgE) is the most frequent form. It is responsible for the immediate reaction occurring in the hour following the drug therapy. The Delayed hypersensitivity reactions are responsible of Delayed reactions [5]. The clones T as the specific IgE, of allergic patients, recognize the kernel β-lactame as much as the rest of the molecule, which explains the heterogeneity of immune responses [5-9].

The mechanisms involved are numerous and are linked to both the drug chemical properties and the host and are not yet well known

Mechanisms related to the molecule

The penicillin’s are responsible of a large number of allergic reactions due to the high chemical reactivity of the kernel β-lactame and its derivatives [4]. During the penicillin metabolism, it appears that intermediate compounds reagents are able to attach on proteins, to change the structure and thus become immunogenic by production of specific antibodies. Moreover, the native penicillin can also be set directly, on proteins as the HLA molecules antigen presenting cells, to modify the structure and reactivate some specifically clones specific T [10].

Mechanisms related to the host

The risk to develop drug hypersensitivity depends also on the host itself because of the stimulation level of immune system during antibiotic administration [10].

The Classifications

The Gell and Coombs classification distinguishes between four types of hypersensitivity (Table 1) [11,12].

Table 1: Classification of immunological reactions caused by antibiotics [12].




  
    Classification    of Gell and Coombs scope
    Type of immune response 
    The pathophysiological    characteristics 
    Clinical signs 
    Usual period of onset of symptoms (after the beginning of    treatment)
  
  
    Type I 
    IgE 
    Activation of mast cells and basophils, and
    Anaphylactic Shock
    From a few minutes to 1 hour after the last drug therapy
  
  
    Angiedema
  
  
    Urticaria
  
  
    Bronchospasm
  
  
    Type II 
    IgG and FCR* 
    Dependent cytotoxicity of    the RCF 
    Cytopenias 
    5-15 days 
  
  
    Type III 
    IgG or IgM and complement or rcfs
    Filing of Immune Complex 
    Serum sickness
    7-8 days for the serum sickness
  
  
    Urticaria
  
  
    Vasculitis
    7-21 days for vasculitis
  
  
    Induced lupus
  
  
    Type IV 
    Has 
    Th1 (INF?) 
    Activation of monocytes 
    Eczemas 
    5-21days 
  
  
    B 
    Th2 (IT-4 and IT-5) 
    Eosinophilic inflammation 
    Rash maculopapular bullous    and 
    2-6 weeks for the syndrome of hypersensitivity drug    (DRESS**)
  
  
    C 
    T lymphocyte (LT) cytotoxic. 
    Lysis of keratinocytes mediated by the LT CD4 or    CD8
    Rash maculopapular bullous    pustular and 
    < 2 days for the pigmented erythema fixed; 
      7-21 days for the Stevens-Johnson syndrome and toxic    epidermal necrolysis
  
  
    Of 
    LT (IT-8/CXCL8) 
    Recruitment and activation of the Neutrophil
    Pustulose exanthématique acute    generalized 
    < 2 days 
  
  
    *rcfs    : Receiver cell membrane for the immunoglobulins; 
      **Dress:    Drug reaction with Eosinophilia and Systemic Symptoms.



Table 1: Classification of immunological reactions caused by antibiotics [12].

Epidemiology

The hypersensitivity to BL is the most reported in the literature. Penicillin are the most purveyor of allergic reactions. It is reported that 1 to 10% of patients developed a clinical history of penicillin allergy [4], with 0.02% of Anaphylaxis Severe and sometimes fatal [5]. The cephalosporin’s allergy varies from 1 to 3% [13]. Now, Amoxicillin is the most beta lactam involved in allergy reaction because of its high prescription [4].

Risk factor

There are several risk factors associated to development of allergy:

• Treatment itself: character immunogenic of the drug, administration route, repeated exposures

• Environmental factors: in particular viral infections in the Drug Allergies delayed

• Genetic predisposition: The first study, published in 1998 by an Italian team. Romano et al. [14], had showed an association between certain alleles of the CMH (HLA-A2, DRw52) and a delayed hypersensitivity medicinal. Later, it had demonstrated the association between particular alleles and penicillin allergy [14].

The betalactames antibiotics have the capacity to bind to the amino acids present on various antigenicepitopes of the same protein carrier [15]. These epitopes are modified by a connection of bêtalactams and are presented to the surface of the CPA by HLA molecules of the patient to T lymphocytes. The activation of lymphocytes therefore depends on presence of these epitopes modified and of the alleles HLA-specific HAS capable to present this complex. The molecular heterogeneity of modified epitopes and of HLAalleles could explain the allergic symptoms variations induced by bêtalactames antibiotics. Furthermore, the heterogeneity of allergenic determinants related to penicillin’s also explains the absence of associations described up to now with the HLA specificallele.

Conclusion

The waning of symptoms of suspected hypersensitivity to betalactam antibiotics: exploration by skin tests validated more or less a challenge test can often rule out a true hypersensitivity. Anamnestic information is often insufficient to clear hypersensitivity. For benign eruptions delayed onset, the most common, reintroduction can be achieved in the absence of skin tests, but it is recommended under medical supervision, at least the first outlet. Hypersensitivity to the true therapeutic alternative should be sought, and in some cases, the proposed desensitization protocols.

References

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Citation: Moutaouakkil Y, Tadlaoui Y, Fettah H, Moukafih B, Bennana A, Taoufik J, et al. Hypersensitivity to the Bêtalactames. Austin J Allergy. 2017; 4(2): 1030.

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