Tests
Investigations to avoid
Tests to consider
blood (whole blood, plasma, serum) drug concentration
Test
Can be useful when the usual target blood (whole blood, plasma, or serum) concentration range of the suspected drug is known.
Result
concentration above the usual target range increases suspicion of drug-induced cause
serum tryptase concentration (anaphylaxis)
Test
The 2023 American Academy of Allergy, Asthma & Immunology practice parameter on anaphylaxis recommends taking one sample as soon as possible (ideally within 2 hours of symptom onset) and a second sample at a later time to establish the baseline value.[46] UK guidance recommends ideally taking 3 samples: one as soon as possible after starting emergency treatment, a second 1-2 hours (but no later than 4 hours) after symptom onset, and a third at least 24 hours later to establish the baseline value.[45]
An acute tryptase level that is elevated above the (laboratory-defined) upper limit of normal is supportive of a diagnosis of anaphylaxis, as is an acute level that shows significant elevation from the patient’s baseline tryptase level (even where the acute level is still within the normal range, i.e., an acute tryptase level in the normal range does not rule out anaphylaxis).[46]
Elevation of tryptase levels may also exist in non-anaphylactic conditions, such as systemic mastocytosis.
Result
elevated during the first few hours after an anaphylactic reaction, both IgE and non-IgE mediated, due to mast cell degranulation
complement pathway assay
Test
C4 measures should be taken during an attack in angioedema alone (no urticaria). If C4 is low, C1-esterase levels should be measured. Occasionally, C1-esterase function needs to be measured if the enzyme is not low but inactive.
C1 esterase levels can be low in hereditary angioedema and autoimmune disorders. C4 can be normal in bradykinin-mediated angioedema.
Result
low levels of C4 are a strong indication of complement pathway problems such as acquired or inherited deficiency of C1-esterase inhibitor
histology of lesion biopsy
Test
A sample of the lesion and the surrounding normal skin is taken.
Some drug-induced skin rashes have a characteristic histology, whereas others are indistinguishable from nondrug-induced forms.
Result
infiltration of eosinophilic polymorphonuclear leukocytes may suggest drug-induced lesion
CBC and differential
Test
Anemia, leukopenia, thrombocytopenia, and rarely pancytopenia can be caused by adverse drug effects, but eosinophilia can be a useful sign of drug allergy.
Result
CBC usually normal in drug-induced lupus; peripheral blood eosinophilia may suggest a drug allergy reaction
antihistone antibodies to single-stranded DNA (lupus-like syndrome)
Test
Systemic lupus erythematosus is associated with antibodies to double-stranded DNA; drug-induced lupus is associated with antihistone antibodies.
Result
drug-induced lupus is associated with antibodies to histones
skin tests (prick tests, intradermal tests, patch tests)
Test
Specialist advice should be sought. Skin tests can help identify a causative drug after an allergic reaction; mainly useful in contact dermatitis.
Skin tests may also be useful adjuncts for establishing causality and cross-reactivity for delayed hypersensitivity reactions.[42] However, skin tests are limited by low sensitivity and thus results should be interpreted with caution, particularly in the setting of severe reactions given the imperfect negative predictive value. Due to the risk of relapse, skin tests for DRESS should be delayed for at least 6 months after the acute reaction and/or 1 month after discontinuation of corticosteroids.[42]
Result
identification of causative drug after an allergic reaction
drug-specific IgE
Test
Specialist advice should be sought. Drug-specific IgE testing can be helpful, particularly in the case of negative skin tests or severe life-threatening reactions (e.g., anaphylactic reactions to beta-lactam antibiotics).[53]
However, do not perform a battery of nonspecific IgE tests.[49]
Result
positive drug-specific IgE results are strongly supportive of anaphylaxis on re-exposure to the drugs; however, false negative results are a common problem with this assay. Test results should only be interpreted in conjunction with patient history and clinical findings
Emerging tests
basophil activation test
Test
Can be helpful, particularly in the case of negative skin tests or severe life-threatening reactions (e.g., anaphylactic reactions to beta-lactam antibiotics). Specialist advice should be sought. Remains largely a research tool at present.
Result
drug-induced basophil activation; test results should only be interpreted in conjunction with patient history and clinical findings
lymphocyte proliferation assay (LPA/LTT)
Test
Can be helpful, particularly in the case of negative skin tests or severe life-threatening reactions (e.g., anaphylactic reactions to beta-lactam antibiotics). Specialist advice should be sought. Remains largely a research tool at present.
Result
drug-induced in vitro proliferation of T cells with a stimulation index greater than 2 is widely regarded as a useful cut-off threshold for determining positive test results. The test results should only be interpreted in conjunction with patient history and clinical findings
enzyme-linked immunospot assay (ELISPOT test)
Test
Can be helpful, particularly in the case of negative skin tests or severe life-threatening reactions (e.g., anaphylactic reactions to beta-lactam antibiotics). Specialist advice should be sought. Remains largely a research tool at present.
Result
drug-induced cytokine detection above background cytokine release is the minimum threshold for positive test results; test results should only be interpreted in conjunction with patient history and clinical findings
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