ASCIA Consensus Cephalosporin Allergy

Drug (Medication) Allergy Terms

This document has been developed by the ASCIA Drug Allergy Committee to assist clinical

immunology/allergy specialists and other health professionals who manage drug allergy.

It is based on expert consensus and references listed on page 9. ASCIA Drug Allergy Committee

members are listed on the ASCIA website www.allergy.org.au/members/committees#dac

SUMMARY OF ADVERSE DRUG REACTIONS AND DRUG ALLERGY

ASCIA Information for Health Professionals - Drug Allergy Terms

TERMS ASSOCIATED WITH DRUG ALLERGY

Acute generalised

exanthematous

pustulosis (AGEP)

• Acute generalised exanthematous pustulosis (AGEP), also known as

pustular drug eruption and toxic pustuloderma, is a rare severe

cutaneous adverse skin reaction (SCAR), that is mostly related to

medication administration.

• AGEP appears on average five days after a medication is started.

Adverse drug

reactions (ADRs)

• Adverse drug reactions (ADRs) is a general term that includes all

unintended effects of a drug except for therapeutic failures, intentional

overdose, abuse of the drug or errors in administration. ADRs can be

classified into two types:

- Type A reactions are predictable reactions and are based on known

pharmacological properties of the drug.

- Type B reactions are unpredictable and include drug allergy, drug

intolerance and idiosyncratic reactions to drugs.

Anaphylaxis

• Anaphylaxis is a severe and immediate Immunoglobulin E (IgE)

mediated allergic reaction.

• Anaphylaxis can affect breathing and/or the heart and blood pressure.

• Anaphylaxis is potentially life threatening and requires urgent medical

attention.

• Whist anaphylaxis is more likely when medication is given by intravenous

(IV) or intramuscular injection (IMI), anaphylaxis to oral medications can

also occur.

• The most common causes of anaphylaxis are allergies to drugs

(medications), foods and insect bites or stings.

Angioedema

• Angioedema is a swelling (oedema) of the structures of the skin (dermis,

subcutaneous tissue), mucosa and submucosal tissues.

Benign rash

• In the context of drug allergy, a benign rash is a transient morbilliform or

maculopapular rash that may be mildly pruritic and is not associated with

other symptoms.

Beta-lactam

antibiotics

• Beta-lactam antibiotics are antibiotics that contain a chemical structure

called a beta-lactam ring. They include:

- Penicillin derivatives (penams)

- Cephalosporins (cephems)

- Monobactams

- Carbapenems

- Carbacephems

Cephalosporin

antibiotics

• Cephalosporins are a large group of beta-lactam antibiotics.

• Some cephalosporins share side chains attached to the beta-lactam ring

with penicillins, which can lead to cross reactivity.

• Cephalosporins bind to and block the activity of enzymes responsible for

making peptidoglycan, an important component of the bacterial cell wall.

• Cephalosporins are effective against a wide range of bacteria.

ASCIA Information for Health Professionals - Drug Allergy Terms

Complementary and

alternative medicine

allergy (unproven

medicines)

• While so-called complementary and alternative medicines (CAM),

including herbal medicines, are often considered to be safe, ADRs

including allergic reactions can occur.

• It is therefore important to include questions about CAM in the patient’s

clinical history.

Co-reactivity

• Co-reactivity is rare and refers to if a patient reacts to structurally

unrelated drugs. This has been described for T-cell mediated reactions,

especially for drug reaction with eosinophilia and systemic symptoms

(DRESS).

Cross-reactivity

• Cross-reactivity is an important clinical problem and may result in an

ADR in some patients who are allergic to structurally related drugs.

• For example, some patients who are sensitised to penicillin may also

have allergic reactions to cephalosporins, due to side chain cross-

reactivity and rarely due to beta-lactam ring allergy.

Cutaneous

symptoms

• Cutaneous (skin) symptoms of a mild or moderate allergic reaction to a

drug can include urticaria (hives) and angioedema.

• Rashes due to infections can be mistaken as an allergic reaction to a

drug.

• Non-immediate severe cutaneous adverse reactions (SCAR) are life

threatening and are described on page 6.

De-labelling

• Drug allergy de-labelling is the process of removing a drug allergy

diagnosis from the patient medical record, after assessment.

• Assessment is achieved by allergy testing or subsequent safe exposure

to the drug.

• The patient should receive a written and dated confirmation if their drug

allergy diagnosis ‘label’ is removed.

• It is important that the updated drug allergy status is recorded in all

medical records for each patient.

Drug-induced liver

injury (DILI)

• Drug-induced liver injury is a drug allergy and a leading cause of acute

liver failure.

• Antibiotics are the most common cause for DILI worldwide.

• DILI can clinically present with hepatocellular, cholestatic or mixed liver

dysfunction.

Drug allergy

• Drug allergies are immune mediated ADRs.

• In drug allergies, IgE or other antibodies or activated T cells are directed

against the drug and its metabolite, which can be bound to serum

proteins (haptens).

• Allergic reactions to pain killers, anti-inflammatories and antibiotics are

the most common drug allergies.

• Symptoms range from mild rashes through to potentially life-threatening

anaphylaxis and SCAR.

• Failure to accurately diagnose drug allergy, particularly to antibiotics,

may result in the unnecessary use of less effective medications, which is

associated with negative patient outcomes.

ASCIA Information for Health Professionals - Drug Allergy Terms

Drug challenge

(provocation test)

• Drug challenges are medically supervised tests using protocols in which

a drug is administered (parenteral or oral), while the patient is being

monitored for adverse effects at each stage.

• Drug challenges are also known as provocation tests and are considered

to be the gold standard for drug allergy assessment.

• Location of challenges depends on the pre-existing risk profile of the

patient and should be performed in a suitably equipped hospital or clinic,

which can manage severe reactions.

• If a true drug allergy is diagnosed after a drug challenge, the drug must

be avoided. Documentation of a diagnosed drug allergy should be in My

Health Record, GP and hospital records. People with a diagnosed drug

allergy should carry or wear medical identification jewellery or a card

listing their drug allergies.

Drug

desensitisation

• Drug desensitisation is a medically supervised treatment, using protocols

for rapid administration of incremental does (parenteral or oral), of

allergenic drugs.

• The aim is to induce temporary immune drug tolerance, by which effector

cells are rendered less reactive to allergic immune responses.

Drug

hypersensitivity

reactions (DHRs)

• Drug hypersensitivity reactions (DHRs) are unpredictable adverse effects

of drugs that are allergic (immune mediated) or non-allergic (non-immune

mediated).

• DHRs can be classified as immediate and non-immediate, based on the

timing when the reaction occurs.

• Immediate allergic DHRs develop as a result of IgE production by

antigen-specific B lymphocytes after sensitisation, and occur typically

within one hour, or up to six hours following exposure.

• Most non-immediate allergic DHRs are mediated through the actions of T

lymphocytes, and typically occur after six hours following exposure.

• DHRs can be life-threatening, may require or prolong hospitalisation, and

may require changes in therapy.

Drug idiosyncrasy

• Idiosyncratic reactions to drugs are abnormal and unexpected ADRs.

• These reactions can be allergic or non-allergic and are often reproducible

on re-administration of the drug.

Drug intolerance

• Drug intolerance is an undesirable pharmacologic effect that may occur

at low or usual doses of the drug.

• Immune mechanisms are not thought to be involved, and a scientific

explanation has not yet been established.

Drug reaction with

eosinophilia and

systemic symptoms

(DRESS)

• Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome

is a severe idiosyncratic drug reaction.

• DRESS typically occurs two to eight weeks following exposure to the

drug.

• DRESS has been linked to infection with human herpes virus 6 (HHV 6).

Drug tolerance

• Drug tolerance is defined as a state in which a patient will tolerate a drug

without an adverse reaction.

• Desensitisation can induce temporary, but not permanent drug tolerance.

ASCIA Information for Health Professionals - Drug Allergy Terms

Eosinophilia

• Eosinophilia is a condition in which the eosinophil count in the peripheral

blood exceeds the laboratory reference range.

• In drug allergy, eosinophilia is often accompanied by a skin rash.

• Eosinophilia and skin rashes are common, whereas systemic DRESS is

rare.

Exanthema

• Exanthema describes a skin eruption, which can be caused by a range of

reasons, including toxins, drugs, infections and autoimmune disease.

• Viral exanthem is a widespread rash usually occurring in children.

Extrapyramidal

symptoms (EPS)

• Extrapyramidal symptoms (EPS) are various movement disorders

(including acute dystonic reactions, pseudoparkinsonism and akathisia)

which can result from taking dopamine antagonists. These are usually

antipsychotic (neuroleptic) drugs, that are often used to control

psychosis.

• EPS can also be symptoms of metabolic diseases.

Fixed drug eruption

(FDE)

• A fixed drug eruption (FDE) is an allergic reaction to a medication that

usually recurs at the same site/s each time a particular drug is taken.

• The number of involved sites may increase over time.

Generalised bullous

fixed drug eruption

(GBFDE)

• Generalised bullous fixed drug eruption (GBFDE) is a bullous type of

fixed drug eruption (FDE), characterised by sharply defined bullae at the

same site following administration of offending drug.

• Unlike FDE, GBFDE requires aggressive treatment.

Human Leucocyte

Antigen (HLA)

• Certain non-immediate drug allergies are associated with the carriage of

defined HLA (e.g. ADR to abacavir with HLA B*57:01).

Immunoglobulin E

(IgE)

• Immunoglobulin E (IgE) is one of the five subclasses of antibody related

to allergic reactions present in the blood, usually in very low

concentrations and bound to the surface of cells such as mast cells.

• Cross linking of bound IgE on the surface of mast cells leads to the

release of allergic mediators, including histamine. This can trigger mild,

moderate or severe (anaphylaxis) allergic reactions.

• These reactions are known as IgE-mediated allergies.

• Allergen specific IgE can be measured using skin testing or blood tests.

Maculopapular rash

• Maculopapular rash is a skin rash with a combination of macular (flat, red

areas) and papules (raised bumps).

Multiple drug

intolerance

syndrome

• Multiple drug intolerance syndrome occurs in patients with intolerance to

three or more neither structurally nor pharmacologically related drugs,

with no confirmation of allergy after evaluation, and can possibly be

driven by patient anxiety.

Non-IgE mediated

allergy

• In non-IgE -mediated allergic reactions a patient may have similar clinical

symptoms to IgE-mediated reactions, ranging from mild or moderate to

severe allergic reactions, including anaphylaxis.

• These reactions do not involve IgE antibodies against the allergens.

ASCIA Information for Health Professionals - Drug Allergy Terms

Non-steroidal anti-

inflammatory drug

(NSAID) allergy

(intolerance)

• Aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) can

cause reactions in some people. Symptoms include flushing, itchy

rashes, blocked/runny nose and sometimes severe asthma, usually

within an hour of taking a tablet.

• Aspirin allergy (more correctly referred to as aspirin intolerance) is more

common in people with nasal polyps and asthma (AERD or Samter’s

Triad).

• Aspirin-induced respiratory disease (AERD) is characterised by aspirin or

non-steroidal anti-inflammatory drug (NSAID) induced respiratory

reactions in a patient with underlying asthma and/or rhinitis or sinusitis.

Penicillin antibiotic

allergy

• Penicillin antibiotics were among the first medications to be effective

against many bacterial infections. They are still widely used today,

despite some bacteria developing resistance following extensive use.

• Approximately 10% of people report that they are allergic to penicillin,

however, up to 90% of this group have an unconfirmed allergy and may

not actually be allergic to penicillin.

• Penicillin allergy de-labelling is the process of removing an unconfirmed

allergy diagnosis from the patient medical record. This may be achieved

by allergy testing or subsequent safe exposure to the drug.

Perioperative

allergic reactions

• Allergic reactions, including anaphylaxis, can occur during surgical and

interventional procedures involving anaesthetics and antibiotics.

• Allergic reactions to antiseptics, latex and anaesthetic drugs given during

operations are rare, but can be serious.

• Allergic reactions to chlorhexidine antiseptics are increasing in frequency

and may be due to common usage of chlorhexidine-containing products.

Pharmacologic

interaction with

immune receptors

(P-i) concept

• The p-i concept (pharmacologic interaction with immune receptors) is a

recently proposed drug hypersensitivity classification in which a drug

binds noncovalently to an immune receptor, such as a T cell receptor.

This may lead to an immune response via interaction with a major

histocompatibility complex molecule.

Pharmacovigilance

(drug safety)

• Pharmacovigilance (also known as drug safety), is the pharmacological

science relating to the collection, detection, assessment, monitoring and

prevention of adverse effects with pharmaceutical products.

Pseudoallergic

(anaphylactoid)

reactions

• Pseudoallergic (anaphylactoid) reactions are immediate systemic

reactions that mimic anaphylaxis, but are caused by non IgE-mediated

reactions with the release of mediators from mast cells and basophils.

• This term is rarely used and is incorrect as the anaphylaxis that results

has the same characteristics as an IgE-mediated reaction.

Severe cutaneous

adverse reaction

(SCAR)

• Non-immediate severe cutaneous adverse reactions (SCAR) are rashes

that are associated with fever, flu-like and other systemic symptoms.

• SCAR are potentially life-threatening, and require urgent specialist care.

• SCAR often involve mucosal surfaces as well as the skin and include:

- Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN)

- Drug reaction with eosinophilia and systemic symptoms (DRESS)

- Acute generalised exanthematous pustulosis (AGEP)

- Generalised bullous fixed drug eruptions (GBFDE)

ASCIA Information for Health Professionals - Drug Allergy Terms

Skin tests

• Skin prick tests

(SPT)

• Intradermal tests

(IDT)

• A skin prick test (SPT) introduces a tiny amount of allergen into the skin,

via a prick into the skin.

• Intradermal skin testing (IDT) injects a defined amount of allergen into

the dermal layer of the skin.

• IDT is more sensitive than SPT as it delivers a larger amount of allergen

but can carry a risk of anaphylaxis in highly sensitised individuals.

• SPT and IDT elicit a localised allergic response in the form of a wheal

(bump) and flare (redness) at the site of testing.

• IDT can also elicit a delayed inflammatory reaction in the skin in non-

immediate drug reactions.

• When drug allergy is uncertain, SPT or IDT or a medically supervised

drug challenge can be conducted by clinical immunology/allergy

specialists.

Stevens–Johnson

syndrome (SJS)

• Stevens–Johnson syndrome (SJS) is a life-threatening skin condition, in

which cell death causes the epidermis to separate from the dermis.

• SJS is thought to be a hypersensitivity complex that affects the skin and

the mucous membranes.

• The most well-known causes of SJS are certain medications, but it can

also be due to infections, or more rarely, cancers.

Symmetrical drug-

intertriginous and

flexural exanthema

(SDRIFE)

• Symmetrical drug-related intertriginous and flexural exanthema

(SDRIFE) is also known as Baboon syndrome because of its

resemblance to the distinctive red buttocks displayed by female baboons,

• SDRIFE is a systemic contact dermatitis with well-demarcated patches of

erythema distributed symmetrically on the buttocks.

• The cause of SDRIFE may be drug-related, induced by systemic

administration of drugs, including hydroxyzine, penicillin and iodinated

radio contrast media.

Toxic epidermal

necrolysis (TEN)

• Toxic epidermal necrolysis (TEN) is a type of severe skin reaction.

• Symptoms include fever and flu-like symptoms, followed by blister and

peel.

Tryptase

• Tryptase is a proteinase that is abundant in human mast cells and

basophils.

• Serum Tryptase is used as a marker for mast cell activation and rises in

anaphylaxis particularly when caused by drugs and stings.

Urticaria (hives)

• Urticaria (also known as hives or welts) is a raised, itchy rash that

appears on the skin.

• Urticaria can be limited to one part of the body or spread across large

areas of the body.

ASCIA Information for Health Professionals - Drug Allergy Terms

ACRONYMS AND ABBREVIATIONS ASSOCIATED WITH DRUG ALLERGY

ADR Adverse drug reaction

AERD Aspirin-exacerbated respiratory

disease

AGEP Acute generalized

exanthematous pustulosis

AMP Ampicillin

AX Amoxicillin

BAT Basophil activation test

BP Benzyl penicillin

COX-1 Cyclooxygenase 1

COX-2 Cyclooxygenase 2

DMARDS Disease modifying

anti-rheumatic drugs

DRESS Drug rash with eosinophilia and

systemic symptoms

DHR Drug hypersensitivity reactions

DIHS Drug-induced hypersensitivity

syndrome

DILI Drug-induced liver injury

DPT Drug provocation (challenge)

test

DRESS Drug reaction with eosinophilia

and systemic symptoms

FDE Fixed drug eruption

GBFDE Generalised bullous fixed drug

eruption

HHV 6 Human herpes virus 6

HLA Human leukocyte antigen

HSS Hypersensitivity syndrome

iDILI Idiosyncratic drug-induced liver

injury

IDT Intradermal test

IgE Immunoglobulin E

LTT Lymphocyte transformation test

MDH Multiple drug hypersensitivity

MDM Minor determinant mixture

MHC Major histocompatibility

complex (HLA in humans)

NMBA Neuromuscular blocking agent

NSAIDs Non-steroidal anti-inflammatory

drugs

OPC Oral provocation challenge

RCM Radio contrast media

SCAR Severe cutaneous

adverse reaction

SDRIFE Symmetrical drug-related

intertriginous and flexural

exanthema

SJS Stevens-Johnson syndrome

SPT Skin prick test

TEN Toxic epidermal necrolysis

ASCIA Drug Allergy Terms Consensus Statement

REFERENCES

International Consensus (ICON) on Drug Allergy 2014

European Academy of Allergy and Clinical Immunology (EAACI), the American Academy of Allergy,

Asthma and Immunology (AAAAI), the American College of Allergy, Asthma and Immunology

(ACAAI), and the World Allergy Organization (WAO).

Demoly, P., Adkinson, N.F., Brockow, K., …. Thong, B.Y-H. (2014) Allergy. European Journal of

Allergy and Clinical Immunology, Vol 69, pp 420-437.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/all.12350

Drug Allergy: An Updated Practice Parameter 2010

American Academy of Allergy, Asthma and Immunology (AAAAI), and the American College of

Allergy, Asthma and Immunology (ACAAI).

Solensky, R., and Khan, D.A. editors, (2010) Annals of Allergy, Asthma & Immunology, Vol 105,

pp273e78

https://www.aAAAAI.org/AAAAAI/media/MediaLibrary/PDF%20Documents/Practice%20and%20Para

meters/drug-allergy-updated-practice-param.pdf

World Allergy Organisation (WAO) 2014

Thong, B., and Vervolet, D., https://www.worldallergy.org/education-and-programs/education/allergic-

disease-resource-center/professionals/drug-allergies

Drug Allergy: Diagnosis and Management of Drug Allergy in Adults, Children and Young

People (2014)

National Institute for Health and Care Excellence UK, Clinical Guidelines, No. 183.

https://www.ncbi.nlm.nih.gov/books/NBK274156/

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