Drug Allergy

A stepwise approach is essential for accurate diagnosis:

[1] Collect clinical information related to drug hypersensitivity

Analyze the pattern of the reaction, evaluate peripheral blood eosinophil count, liver function tests, serum tryptase levels, and assess risk factors (e.g., sex, age, personal or family history of drug hypersensitivity, atopy, comorbidities, and concurrent medications).

[2] Identify suspected causative drugs

Evaluate the temporal relationship between drug administration and reaction onset, and consult drug adverse reaction databases.

[3] Discontinue suspected drug and monitor

Stop the suspected drug and observe clinical progress. If necessary, administer medications such as antihistamines or corticosteroids to alleviate symptoms.

[4] Perform diagnostic tests

Depending on the suspected immune mechanism, conduct skin tests, specific IgE measurements, or other relevant allergy tests.

[5] Drug re-administration through graded challenge or desensitization

If the drug is essential and no alternatives are available, and if the hypersensitivity reaction was not life-threatening, the drug may be reintroduced in gradually increasing doses while monitoring for adverse reactions.

1. Immediate-type reactions

• Skin prick tests and intradermal tests: Limited to certain agents such as β-lactam antibiotics (e.g., penicillin, cephalosporins), insulin, and latex.  
• For drug-specific IgE antibodies, ImmunoCAP assays can be performed for penicilloyl G, penicilloyl V, ampicilloyl, amoxicilloyl, and cefaclor
• The sensitivity of these tests is low, and a negative result cannot exclude an immediate-type allergic reaction to the drug.

2. Delayed-type reactions

• Patch testing: The drug is applied to a Finn chamber and placed on the skin; reactions are assessed at 48 and 72 (or 96) hours. Erythema alone is considered weakly positive, erythema with papules is mildly positive, papules alone are strongly positive, and vesicles are very strongly positive. 
• Delayed intradermal test readings: The reaction should be assessed at 24 and 72 hours, recording not only the wheal size but also the extent of erythema, presence of papules, eczema, or vesicles.

3. Drug provocation testing (DPT) (The most accurate method for identifying or excluding the causative drug)

• It can be performed for both immediate and delayed-type reactions by re-administering the suspected drug and observing the patient’s response, or by confirming the safety of an alternative medication. 
• Ability to determine drug-reaction causality by gradually increasing the drug dose starting from a low concentration. 
• It must only be performed after careful evaluation of indications and risks, under the supervision of an experienced allergist and in a setting equipped for emergency intervention. 
• SCARs: Absolute contraindication 

1. Principles of Management 

• Discontinuing the suspected drug is the most effective approach for both diagnosis and treatment. 
• Supportive care: In cases of SJS or TEN, although controversial, high-dose corticosteroids or intravenous immunoglobulin (IVIG) may be helpful. Corticosteroids may also reduce the risk of organ damage in conditions like DRESS.

2. Change of Therapeutic Drug

• A different medication should be used. 
• If no alternative is available, or if the alternative is less effective or causes severe side effects, or if the reaction was mild, the original drug may sometimes be continued with close monitoring—often with concurrent administration of antihistamines. 
• If a drug from the same class must be used, skin testing can be performed first, followed by cautious dose escalation.

3. Education

• Patients with drug hypersensitivity should be informed of the causative drug and the type of reaction they experienced. 
• They should be educated to avoid re-exposure to the same drug or related agents with potential cross-reactivity and to inform healthcare providers of their drug allergy history in future medical encounters.

4. Desensitization

• If no alternatives exist, the therapeutic efficacy of alternatives is significantly lower, or the substitute is much more expensive or causes severe adverse effects, desensitization therapy may be considered. 
• The repeated administration of the causative drug to induce temporary immune tolerance
• Before starting desensitization, the necessity of treatment and the potential risks of allergic reactions must be thoroughly evaluated and discussed with the patient.