Approach

All adverse drug reactions need to be meticulously recorded and the patient fully informed. Withdrawal of the suspected drug is essential, after which in many cases the lesions will resolve spontaneously within 1 to 2 weeks. Fixed drug eruptions resolve on withdrawal but can leave residual scarring or pigmentation.[54] Otherwise, treatment should be the same as for nondrug-induced skin lesions.

Serious adverse cutaneous reactions

Adverse cutaneous reactions can be considered to be serious if they affect the structure or function of the skin, its appendages, or mucous membranes. The main potentially serious drug-induced cutaneous allergic reactions are Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), exfoliative dermatitis, hypersensitivity DRESS (drug reaction with eosinophilia and systemic symptoms; also called drug hypersensitivity syndrome), serum sickness and vasculitis, and anaphylaxis.

Acute anaphylactic reactions

Attending healthcare professionals should call for help as this is a medical emergency.[45] See Anaphylaxis (Management approach).

Key considerations

Acute anaphylactic reactions are treated by having the patient lie down if they are hypotensive, sitting them up if they are having trouble breathing, or lying them in the recovery position if they are unconscious.[45]​The offending drug should be withdrawn, and intramuscular epinephrine (adrenaline) given as soon as possible. A further follow-up dose of intramuscular epinephrine can be given after 5 to 15 minutes if necessary (guidelines vary on the precise timing of repeat dose[s] so check your local protocol). If required, intravenous epinephrine should be given under the guidance of a physician experienced in the use and titration of vasopressors.​[45][55]​​​​ ​​Take an ABCDE approach and give high-flow supplemental oxygen and intravenous fluids (e.g., normal saline) if indicated.[45][56]​​​​[57]​ ​​If there is marked stridor, nebulized epinephrine should be administered. If the patient has persistent bronchospasm despite epinephrine, an inhaled beta-2 agonist (e.g., albuterol) is indicated.[45][56]​​​​​[57]

Biphasic reactions can occur.[45]  Antihistamines and/or corticosteroids are not reliable in preventing biphasic anaphylaxis but may be considered as secondary treatment.[45]​​[55]

For possible future anaphylactic reactions, the patient should be equipped with 2 epinephrine autoinjector pens and taught how to use them correctly.[55] A warning bracelet is advisable. Information about drug allergy status (drug name; signs, symptoms, and severity of reaction; and date when the reaction occurred) should be updated and included in hospital discharge letters and medical records.

Stevens-Johnson syndrome and toxic epidermal necrolysis

Patients with Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) should be assessed in the same way as a patient with cutaneous burns, using a structured approach to evaluate airway, breathing, and circulation. See Cutaneous burns (Diagnosis approach).

Treatment requires a multidisciplinary team so that patients receive optimal daily wound care, nutrition, critical care, pain management, and supportive care.[58] Transfer to a burn center, a specialized wound care center, or a dermatology intensive care unit is recommended.[58][59]​​​

Exact treatment will depend on the extent of skin involvement. See Stevens-Johnson syndrome and toxic epidermal necrolysis (Management approach). 

Hypersensitivity reactions

Systemic corticosteroids may be required in acute hypersensitivity reactions (e.g., DRESS).

Nonserious reactions unresponsive to withdrawal of drug

Topical corticosteroids are often used when drug-induced lesions do not resolve spontaneously; oral corticosteroids are used in severe cases.

In mild cases, topical hydrocortisone can be used. For more severe disease, alternatives include betamethasone, clobetasol, fluocinolone, and triamcinolone.

In severe reactions unresponsive to withdrawal of the drug, oral prednisone can be used.

Management of drug-induced urticaria

Treatment of drug-induced urticaria is withdrawal of the suspected drug, and an antihistamine if needed. A nonsedating antihistamine is preferred for daytime use. If nocturnal symptoms are a problem, a sedating antihistamine can be used at night.

Desensitization

Patients who have had an allergic reaction to a drug can prevent future reactions by strictly avoiding the drug. It is rarely necessary to attempt desensitization, and it should not be attempted unless the benefit of continuing to use the drug outweighs the potential harm of desensitization and when there is no alternative therapy.

Recommendations for alternative therapy and desensitization are available for specific drugs and drug classes (e.g., antibiotics, nonsteroidal anti-inflammatory drugs [NSAIDs], chemotherapy, immune checkpoint inhibitors, biologic agents).[42][43][44]

Specialist referral

Referral to a specialist drug allergy service should be considered for: suspected anaphylaxis; severe/life-threatening episodes (e.g., DRESS, Stevens-Johnson syndrome, toxic epidermal necrolysis); severe reactions to NSAIDs with ongoing need for NSAID therapy; suspected beta-lactam allergy (if alternative antibiotics are not available); and problems related to general and local anesthesia.[53]

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