Common cutaneous drug reactions
- Overview
- Theory
- Diagnosis
- Management
- Follow up
- Resources
Treatment algorithm
Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer
serious cutaneous adverse reactions
withdrawal of suspected drug
Withdrawal of the suspected drug is essential.
epinephrine (adrenaline) + supportive care
Treatment recommended for ALL patients in selected patient group
Call for help and treat as an emergency.[45]Resuscitation Council UK. Emergency treatment of anaphylactic reactions: guidelines for healthcare providers. May 2021 [internet publication]. https://www.resus.org.uk/library/additional-guidance/guidance-anaphylaxis/emergency-treatment See Anaphylaxis (Treatment algorithm).
Key considerations are as follows.
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 recovering position if they are unconscious.[45]Resuscitation Council UK. Emergency treatment of anaphylactic reactions: guidelines for healthcare providers. May 2021 [internet publication]. https://www.resus.org.uk/library/additional-guidance/guidance-anaphylaxis/emergency-treatment The offending drug should be withdrawn, and intramuscular epinephrine given as soon as possible.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]Resuscitation Council UK. Emergency treatment of anaphylactic reactions: guidelines for healthcare providers. May 2021 [internet publication]. https://www.resus.org.uk/library/additional-guidance/guidance-anaphylaxis/emergency-treatment [55]Shaker MS, Wallace DV, Golden DBK, et al. Anaphylaxis-a 2020 practice parameter update, systematic review, and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) analysis. J Allergy Clin Immunol. 2020 Apr;145(4):1082-123. https://www.jacionline.org/article/S0091-6749(20)30105-6/fulltext http://www.ncbi.nlm.nih.gov/pubmed/32001253?tool=bestpractice.com
Take an ABCDE approach and give high-flow supplemental oxygen and intravenous fluids (e.g., normal saline) if indicated.[45]Resuscitation Council UK. Emergency treatment of anaphylactic reactions: guidelines for healthcare providers. May 2021 [internet publication]. https://www.resus.org.uk/library/additional-guidance/guidance-anaphylaxis/emergency-treatment [56]Muraro A, Worm M, Alviani C, et al. EAACI guidelines: anaphylaxis (2021 update). Allergy. 2022 Feb;77(2):357-77. https://onlinelibrary.wiley.com/doi/10.1111/all.15032 http://www.ncbi.nlm.nih.gov/pubmed/34343358?tool=bestpractice.com [57]Lieberman PL. Recognition and first-line treatment of anaphylaxis. Am J Med. 2014 Jan;127(1 suppl):S6-11. http://www.ncbi.nlm.nih.gov/pubmed/24384138?tool=bestpractice.com 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]Resuscitation Council UK. Emergency treatment of anaphylactic reactions: guidelines for healthcare providers. May 2021 [internet publication]. https://www.resus.org.uk/library/additional-guidance/guidance-anaphylaxis/emergency-treatment [56]Muraro A, Worm M, Alviani C, et al. EAACI guidelines: anaphylaxis (2021 update). Allergy. 2022 Feb;77(2):357-77. https://onlinelibrary.wiley.com/doi/10.1111/all.15032 http://www.ncbi.nlm.nih.gov/pubmed/34343358?tool=bestpractice.com [57]Lieberman PL. Recognition and first-line treatment of anaphylaxis. Am J Med. 2014 Jan;127(1 suppl):S6-11. http://www.ncbi.nlm.nih.gov/pubmed/24384138?tool=bestpractice.com
Biphasic reactions can occur.[45]Resuscitation Council UK. Emergency treatment of anaphylactic reactions: guidelines for healthcare providers. May 2021 [internet publication]. https://www.resus.org.uk/library/additional-guidance/guidance-anaphylaxis/emergency-treatment Antihistamines and/or corticosteroids are not reliable in preventing biphasic anaphylaxis but may be considered as secondary treatment.[45]Resuscitation Council UK. Emergency treatment of anaphylactic reactions: guidelines for healthcare providers. May 2021 [internet publication]. https://www.resus.org.uk/library/additional-guidance/guidance-anaphylaxis/emergency-treatment [55]Shaker MS, Wallace DV, Golden DBK, et al. Anaphylaxis-a 2020 practice parameter update, systematic review, and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) analysis. J Allergy Clin Immunol. 2020 Apr;145(4):1082-123. https://www.jacionline.org/article/S0091-6749(20)30105-6/fulltext http://www.ncbi.nlm.nih.gov/pubmed/32001253?tool=bestpractice.com
Primary options
epinephrine (adrenaline): consult specialist for guidance on dose
topical dressings + supportive management
Treatment recommended for ALL patients in selected patient group
Withdrawal of the suspected drug is essential. 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]Seminario-Vidal L, Kroshinsky D, Malachowski SJ, et al. Society of Dermatology Hospitalists supportive care guidelines for the management of Stevens-Johnson syndrome/toxic epidermal necrolysis in adults. J Am Acad Dermatol. 2020 Jun;82(6):1553-67. http://www.ncbi.nlm.nih.gov/pubmed/32151629?tool=bestpractice.com Transfer to a burn center, a specialized wound care center, or a dermatology intensive care unit is recommended for patients with SJS/TEN.[58]Seminario-Vidal L, Kroshinsky D, Malachowski SJ, et al. Society of Dermatology Hospitalists supportive care guidelines for the management of Stevens-Johnson syndrome/toxic epidermal necrolysis in adults. J Am Acad Dermatol. 2020 Jun;82(6):1553-67. http://www.ncbi.nlm.nih.gov/pubmed/32151629?tool=bestpractice.com [59]Creamer D, Walsh SA, Dziewulski P, et al. U.K. guidelines for the management of Stevens-Johnson syndrome/toxic epidermal necrolysis in adults 2016. Br J Dermatol. 2016 Jun;174(6):1194-227. https://academic.oup.com/bjd/article/174/6/1194/6617016
Exact treatment will depend on the extent of skin involvement. See Stevens-Johnson syndrome and toxic epidermal necrolysis (Management approach).
corticosteroid
Treatment recommended for ALL patients in selected patient group
Systemic treatment may be required in severe cases such as severe liver dysfunction. A topical corticosteroid (e.g., betamethasone) may be used in mild cases.
Care should be taken not to withdraw corticosteroid too early as this might result in reoccurrence.
Primary options
betamethasone valerate topical: (0.1%) children and adults: apply sparingly to the affected area(s) once daily for 7-14 days
OR
prednisone: children and adults: 0.5 to 1 mg/kg/day orally, taper gradually according to response
nonserious cutaneous adverse reactions
withdrawal of suspected drug
Withdrawal of the suspected drug is essential. In many cases, the lesions will resolve spontaneously thereafter, within 1 to 2 weeks.
corticosteroid
Treatment recommended for ALL patients in selected patient group
Topical corticosteroids are often used when skin eruptions are symptomatic (especially for itch). In mild cases, hydrocortisone can be used. For more severe problems, alternatives include betamethasone, clobetasol, fluocinolone, and triamcinolone.
In severe reactions unresponsive to withdrawal of the drug, oral prednisone can be used.
Severity refers to the intensity of the reaction. A severe (intense) headache need not be serious, and a mild arrhythmia (e.g., a ventricular extra beat) can have a serious outcome (a fatal cardiac arrhythmia).
A serious cutaneous adverse reaction affects the structure or function of the skin, its appendages, or mucous membranes.
Primary options
hydrocortisone topical: (0.5 to 1%) apply sparingly to the affected area(s) twice daily
OR
betamethasone valerate topical: (0.1%) apply sparingly to the affected area(s) once or twice daily
OR
clobetasol topical: (0.05%) apply sparingly to the affected area(s) twice daily
OR
fluocinolone topical: (0.025%) apply sparingly to the affected area(s) twice daily
OR
triamcinolone topical: (0.1%) apply sparingly to the affected area(s) twice daily
Secondary options
prednisone: children: 1-2 mg/kg/day orally, taper gradually over 3 weeks according to response; adults: 30-60 mg orally once daily, taper gradually over 3 weeks according to response
antihistamine
Treatment recommended for ALL patients in selected patient group
Treatment of drug-induced urticaria is withdrawal of the suspected drug, and an antihistamine if needed.
A nonsedating antihistamine (e.g., cetirizine, loratadine, fexofenadine) is preferred for daytime use; if nocturnal symptoms are a problem, a sedating antihistamine (e.g., hydroxyzine) can be used at night.
Primary options
cetirizine: 10 mg orally once daily
OR
loratadine: 10 mg orally once daily
OR
fexofenadine: 180 mg orally once daily
OR
hydroxyzine: 25 mg orally once daily at night
following acute episode
avoidance of offending drug where possible
Avoidance of the offending drug is essential where possible.
self-administered epinephrine (adrenaline) + action plan
Treatment recommended for ALL patients in selected patient group
All adverse drug reactions need to be meticulously recorded and the patient fully informed. For possible future anaphylactic reactions, the patient should be equipped with 2 epinephrine autoinjectors.[55]Shaker MS, Wallace DV, Golden DBK, et al. Anaphylaxis-a 2020 practice parameter update, systematic review, and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) analysis. J Allergy Clin Immunol. 2020 Apr;145(4):1082-123. https://www.jacionline.org/article/S0091-6749(20)30105-6/fulltext http://www.ncbi.nlm.nih.gov/pubmed/32001253?tool=bestpractice.com
After receiving epinephrine, the patient should present to the emergency department for monitoring and further treatment as required until stable.
Primary options
epinephrine (adrenaline): children <30 kg: 0.15 mg intramuscularly as a single dose, may repeat in 10-20 minutes; children >30 kg and adults: 0.3 mg intramuscularly as a single dose, may repeat in 10-20 minutes
drug desensitization
Treatment recommended for ALL patients in selected patient group
Patients who have had an allergic reaction to a drug can prevent future reactions by strictly avoiding the drug. Attempting desensitization is rarely necessary; 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 other alternative therapy. Recommendations for alternative therapy and desensitization are available for specific drugs and drug classes (e.g., antibiotics, nonsteroidal anti-inflammatory drugs, chemotherapy, immune checkpoint inhibitors, biologic agents).[42]Khan DA, Banerji A, Blumenthal KG, et al. Drug allergy: a 2022 practice parameter update. J Allergy Clin Immunol. 2022 Dec;150(6):1333-93. https://www.jacionline.org/article/S0091-6749(22)01186-1/fulltext http://www.ncbi.nlm.nih.gov/pubmed/36122788?tool=bestpractice.com [43]Haanen J, Obeid M, Spain L, et al. Management of toxicities from immunotherapy: ESMO clinical practice guideline for diagnosis, treatment and follow-up. Ann Oncol. 2022 Dec;33(12):1217-38. https://www.annalsofoncology.org/article/S0923-7534(22)04187-4/fulltext [44]Jeimy S, Ben-Shoshan M, Abrams EM, et al. Practical guide for evaluation and management of beta-lactam allergy: position statement from the Canadian Society of Allergy and Clinical Immunology. Allergy Asthma Clin Immunol. 2020 Nov 10;16(1):95. https://aacijournal.biomedcentral.com/articles/10.1186/s13223-020-00494-2 http://www.ncbi.nlm.nih.gov/pubmed/33292466?tool=bestpractice.com
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Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer
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