Background
Skin tests
β-Lactam antibiotics
Immediate reactions
American perspective | European perspective | Comment | |
---|---|---|---|
General rules | Evaluation mainly by signs and symptoms In history of severe reactionsa: avoidance of allergy tests In history of non-severe reactions: diagnostic approach can be applied | Evaluation by clinical history and allergy tests | Different |
DPTs | Recommended if other diagnostic tools are negative Consider contraindications | Recommended if other diagnostic tools are negative Consider contraindications | Similar |
Desensitization | Recommended Consider indications and contraindications | Recommended Consider indications and contraindications | Similar |
Immediate reactions
| |||
General rules | SPTs followed by IDTs are the first to perform Perform DPTs if STs are negative | SPTs followed by IDTs are the first to perform Perform DPTs if STs and in vitro tests are negative | Similar |
STs |
Penicillins
| ||
Recommended: PPL: 5 × 10−5 mol/L MDM: 2 × 10−2 mol/L BP: 10,000 IU/mL | Recommended PPL: 5 × 10−5 mol/L MDM: 2 × 10−2 mol/L BP: 10,000 IU/mL | Similar | |
Semisynthetic penicillins
| |||
Not routinely recommendeda
| Recommended AX: 20 mg/mL AMP: 20 mg/mL | Different | |
β-Lactamase inhibitors
| |||
Not recommendeda
| Recommended with original drug and the individual components of the antibiotic combination | Different | |
Cephalosporins
| |||
Not recommendeda
| Recommended with original drug (max: 2–20 mg/mL) | Different | |
Aztreonam/carbapenems
| |||
Not recommendeda
| Recommended Aztreonam: 2 mg/mL; Imipenem/cilastatin: 0.5 mg/mL of each component; Meropenem: 1 mg/mL; Ertapenem: 1 mg/mL | Different | |
Commercially available kits
| |||
PRE-PEN® (AllerQuest LLC, Plainville, CT, USA) PPL: 6.0 × 10−5 mol/L | DAP® (Diater, Leganés, Madrid, Spain) BP-OL: 0.04 mg/mL (8.64 × 10−5 mol/L) MD: Benzylpenilloate 0.5 mg/mL (1.5 × 10−3 mol/L) AX: 20 mg/mL | Different | |
In vitro tests |
Serum specific IgE assays
| ||
Not recommended | Testing with penicillins is recommended | Different | |
Basophil activation tests
| |||
Not recommended | Recommended as complementary to sIgE | Different | |
Non-immediate reactions
| |||
STs/PTs | Not recommended | PTs followed by delayed-reading IDTs are recommended in routine approach In case of positive PTs, IDTs may be avoided | Different |
In vitro tests | Not recommended | Not recommended | Similar |
Retest
| |||
Repeating penicillin STs routinely is not indicated in patients with a history of non-severe penicillin reactions who have tolerated 1 or more oral penicillin courses | Weakly recommended: retesting (2–4 weeks later) patients who suffered severe immediate reactions to BLs and display negative results in the first allergy evaluation, including DPTs |
Non-immediate reactions
Non-β-lactam antibiotics
Non-steroidal anti-inflammatory drugs (NSAIDs)
Cancer chemotherapeutic agents
Perioperative agents
ENDA proposal | American proposal | |||
---|---|---|---|---|
SPT (mg/mL) | IDT (mg/mL) | SPT (mg/mL) | IDT (mg/mL) | |
Thiopental | 25 | 2.5 | 0.2 | |
Propofol | 10 | 1 | 10–1 | 10–0.1 |
Ketamine | 10 | 1 | 10 | 0.25 |
Etomidate | 2 | 0.2 | 2 | 0.2–0.002 |
Midazolam | 5 | 0.5 | 5 | 0.5–0.25 |
Fentanyl | 0.05 | 0.005 | 0.05 | 0.005–0.000005 |
Alfentanil | 0.5 | 0.05 | ||
Sufentanil | 0.005 | 0.0005 | ||
Remifentanil | 0.05 | 0.005 | ||
Morphine | 1 | 0.01 | ||
Atracurium | 1 | 0.01 | 10 | 0.01 |
Cis-atracurium | 2 | 0.02 | 2 | 0.01–0.001 |
Mivacurium | 0.2 | 0.002 | ||
Rocuronium | 10 | 0.05 | 10 | 0.01–0.001 |
Vecuronium | 4 | 0.4 | 10 | 0.1–0.001 |
Pancuronium | 2 | 0.2 | 2 | 0.02 |
Suxamethonium | 10 | 0.1 | ||
Chlorhexidine | 5 | 0.002 | 1.2 | 0.00048 |
Alcuronium | 0.005 | |||
Methohexital | 0.1 | |||
Metocurine | 0.002 | |||
Succinylcholine | 20 | 0.02–0.05 | ||
Thioamyl | 0.1 | |||
Tubocuranine | 0.0003–0.0001 |
Local anaesthetics
Iodinated contrast media, gadolinium chelates and dyes
Other drugs
In vitro tests
Effector cells | Test | Detection | Drug studied | Limitations | |
---|---|---|---|---|---|
Immediate reactions | Mast cells and basophils | Immunoassay | Serum tryptase (normal values: <11.4 ng/mL) | Any drug involved in grade 2–3 anaphylactic reactions | Samples must be obtained within 60–90 min after the reaction |
Specific IgE | β-Lactams, NMBAs, chlorhexidine, and biological agents | Available for few drugs Low sensitivity | |||
Basophil activation test | Activated basophils | β-Lactams, NMBAs, pyrazolones, and fluoroquinolones Potentially available for any injectable drug | Need for fresh blood Low sensitivity | ||
Non-immediate reactions | Cell-mediated: T-cells, NK cells, neutrophils, monocytes | HLA-allele determination | Allele determination | Abacavir, carbamazepine | Associations are very specific for particular drugs and/or types of DHRs Variable sensitivity |
Lymphocyte transformation test | Lymphocyte proliferation | Potentially available for any injectable drug | Limited supportive data Low sensitivity/specificity | ||
ELISpot | Number of cells producing inflammatory markers | Potentially available for any injectable drug | Limited supportive data Low sensitivity/specificity |
Tryptase level
Specific IgE determination
Basophil activation test
HLA-allele determination
Lymphocyte transformation test
Enzyme-linked immunosorbent spot
Drug provocation tests
DPTs are contraindicated in non-controllable and/or severe life-threatening DHRs | Severe cutaneous reactions, such as SJS, TEN, DRESS, vasculitis, AGEP Systemic reactions such as DRESS, any internal organ involvement, hematological reactions Anaphylaxis may be tested after discussion with patient of risk and benefits |
DPTs are not indicated | The offending drug is unlikely to be needed and several structurally unrelated alternatives exist Severe concurrent illness or pregnancy (unless the drug is essential for the concurrent illness or required during pregnancy or delivery) |
DPTs should be performed under the highest safety conditions | Trained staff that are: familiar with allergy tests, can identify early signs of a positive reaction, and can manage life-threatening allergic reactions Emergency resuscitative equipment should be available |
American perspective | European perspective | |
---|---|---|
General rules for management | Based on clinical evaluation For immediate reactions, STs are applied first; if they are negative, DPT is performed unless contraindication exists STs are not recommended for non-immediate reactions No allergy tests are recommended in history of severe reactions* Desensitization is recommended in indicated cases | Allergy tests are strongly recommended if there are no contraindications. STs are applied first; if they are negative, DPT is performed unless contraindication exists Selection of STs depends on underlying mechanisms (SPTs/IDTs for immediate reactions, PTs and delayed-reading IDTs for non-immediate reactions) Desensitization is recommended in indicated cases |
Immediate reactions
| ||
SPTs/IDTs | Recommended for BLs, other antibiotics, NMBAs, chlorhexidine, chemotherapeutic agents, insulin, heterologous antisera, and streptokinase at non-irritating concentrations | Recommended based on sensitivity and specificity of the tests BLs, pyrazolones, NMBAs, chlorhexidine, LAs, RCM (strong recommendation) Should be performed at non-irritating concentrations |
In vitro tests | Not recommended | Serum specific IgE assays are recommended for BLs, NMBAs, and chlorhexidine BAT is recommended for BLs and NMBAs (complementary to sIgE assays), as well as for pyrazolones, fluoroquinolones, and RCM |
Non-immediate reactions
| ||
General rules for management | PTs and IDTs are not recommended routinely | PTs and IDTs are recommended routinely PTs are performed first; if negative, delayed-reading IDTs are performed if no contraindications exist |
PTs | May have a role in delayed DHRs, such as MPE, AGEP, and FDE | Recommended In severe cases, lower drug concentrations are recommended |
Delayed-reading IDTs | Not recommended | In severe cases, such as DRESS, AGEP, and TEN/SJS, can be performed after negative PTs and at higher drug dilutions |
In vitro tests | Pre-screening with certain HLA alleles before introduction of abacavir and carbamazepine Other tests (e.g., LTT and ELISpot) are not recommended | Pre-screening with certain HLA alleles before introduction of abacavir and carbamazepine Other tests (e.g., LTT and ELISpot) arenot recommended |
Non allergic drug hypersensitivity
| ||
Skin tests | Not recommended | Not recommended |
In vitro tests | Not recommended | Not recommended |
Drug provocation tests/challenges
| ||
Indication | To exclude DHR in non-suggestive histories or provide safe alternatives | To exclude DHR in non-suggestive histories or provide safe alternatives To confirm diagnosis |
Methods | Similar contraindications and precautions | Similar contraindications and precautions |
Comment on a negative test result | “Patients who tolerate a graded challenge are considered to not be allergic to the drug and are not at increased risk for future reactions compared with the general population” | “A negative test does not prove tolerance to the drug in the future, but rather that there is no DHR at the time of the challenge and to the doses challenged” |