Penicillin allergy T88.7

Allergy to penicillins or other beta-lactam antibiotics can occur as an IgE-mediated anaphylactic immediate reaction or as a non-IgE-mediated exanthematic late reaction (Trautmann A et al. 2018). S.a. under antibiotic allergy.

Up to 10% of the population reports a "penicillin allergy". The available figures in the literature vary between 2% and 25% of suspected cases (Arroliga ME et al. 2003; Macy E et al. 2014). The main cause for these discrepancies is often infectious exanthema that was associated with the intake of the antibiotic (Trautmann A 2018).

In principle, a penicillin allergy can affect any patient. However, certain factors increase the individual risk.

These include:

• Allergic diathesis
• Multiple previous penicillin therapies.
• Virus infections (e.g. Epstein-Barr virus infections) increase the probability of "hypersensitivity" to an aminopenicillin (e.g. ampicillin, amoxicillin); they are often not reproducible later (see below mononucleosis infectious)

The actual antigenic components of penicillins are either the aminobenzyl-R side chain at carbon atom 6 of the beta-lactam ring or certain structures extending over other parts of the ring. Since these antigenically relevant side chains are found in versch. Since these antigenically relevant side chains are structurally similar in various penicillins and cephalosporins, they are suspected to be the cause of cross-reactivity.

Cross-Reactivity:

• Amoxicillin and ampicillin are structurally 100% cross-reactive (see structural formula).
• Cross-reactions between aminopenicillins and cephalosporins (cefalexin, cefaclor) are mainly caused by similar R1 side chain structures at C7 of the cepaholosporin molecule and at C6 of the beta-lactam ring of ampicillin or amoxicillin.
• Allergic patients to aminopenicillins usually tolerate cephalosporins with different R1 side chains, such as cefpodoxime, ceftriaxone, or cefuroxime.
• 40% of allergic patients to benzyl-/phenoxymethylpenicillin react cross-reactive with aminobenzylpenicillins (e.g. ampicillin).

The most common penicillin allergies are caused by the aminopenicillins amoxicillin or ampicillin. As triggers of the less frequent IgE-mediated anaphylaxis, certain cephalosporins play a greater role, e.g. cefazolin, ceftriaxone, cefuroxime.

A general allergic reaction to all beta-lactam antibiotics has only been detected in a few individual cases, although the common chemical-pharmacological group name suggests the opposite (Romano A et al. 2004).

IgE-mediated immediate reactions induce urticarial and anaphylactic reactions(angioedema) which may develop within a few minutes.

Exanthematic late reactions, predominantly maculo-papular exanthema, are clinically heterogeneous. They occur in presensitized patients a few hours after application of the drug. In the phase of initial sensitization it takes 7-10 days until dermatologically relevant manifestations occur.

So-called uncomplicated exanthema are most frequent. By definition, these are maculo-papular exanthems without significant systemic components.

Rarer are:

• Symmetrical drug related intertriginous and flexural exanthema.
• Acute generalized pustulosis
• Fixed drug reactions.
• In isolated cases: Hypersensitivity reactions with hepatitis and nephritis.
• DRESS
• Stevens-Johnson syndrome

IgE determination: Specific IgE against certain beta-lactam antibiotics can be determined using validated immunoassays.

Skin test: Prick tests and intradermal tests allow, as with other allergies, the short-term diagnosis of IgE-mediated immediate reactions to penicillin. With epicutaneous tests or late readings of the intradermal test, late reactions can also be detected after 2-4 days.

Exposure test: The controlled administration of beta-lactams is the most meaningful. It should be performed under controlled inpatient conditions. The patient receives the active substances in ascending doses as a test.

Basophil activation test and lymphocyte transformation test: Both test procedures are controversially discussed with regard to their biological and methodological variability. They are not suitable for routine clinical diagnosis (Ebo DG et al. 2011).

Non-irritating skin test concentrations (prick test concentrations) of beta-lactam antibiotics

Benzylpenicilloyl octa-lysine - Prick test: 8,6x10¯5 mol/l

Minor determinant benzylpenicilloate - Prick test: 1,5x 10¯3 mol/l

Benzylpenicillin (Penicillin G) - prick test: 10.000I.U./ml

Amoxicillin - prick test: 20mg/ml

Ampicillin - Prick test: 20mg/ml

Cephalosporins - Prick test: 2mg/ml

The catchy term "penicillin allergy" is most commonly used. However, it is inaccurate in view of the large group of beta-lactam antibiotics. The term "beta-lactam antibiotic allergy" would be more correct. It is currently hardly enforceable due to its poor legibility.

In the allergy documentation an exact designation is to be demanded (e.g. amoxicillin/ampicillin allergy).

If a confirmed (clinic, serology, skin test, provocation test) penicillin allergy exists, the patient should mention this before any medical treatment (allergy pass).

The penicillin allergy must be clearly documented in the emergency ID card with the name of the medication causing it.

In no case should the "suspicion of a pencillin allergy" be expressed lightly, as in this case the patient is denied a large number of clinically valuable antibiotics due to the (theoretically possible) cross-reactivity with other antibiotics of the beta-lactam group.

1. Ebo DG et al (2011) The in vitro diagnosis of drug allergy: status and perspectives. Allergy 66:1275-1286.
2. Macy E (2014) Penicillin and beta-lactam allergy: epidemiology and diagnosis. Curr Allergy Asthma Rep 14: 476.
3. Romano A et al (2004) Cross-reactivity and tolerability of cephalosporins in patients with immediate hypersensitivity to penicillins. Ann Intern Med 141:16-22.

4. Romano A et al. (1997) Aminopenicillin allergy Arch Dis Child 76: 513-517.

5. Stephanie A et al (2014) Prevalence and characteristics of reported penicillin allergy in an urban outpatient adult population. Allergy Asthma Proc 35: 489-494.
6. Trautmann A et al (2018) Allergies to penicillins and other beta-lactam antibiotics - Recommendations for diagnosis and patient management. Allergo J 27: 103-113
7. Trcka, J et al (2004) Penicillin therapy despite penicillin allergy? Plea for an allergological diagnosis in case of suspected penicillin allergy. Dtsch Ärztebl 101: A-2888 / B-2444 / C-2331