Paeds · paediatric-dermatology
Drug eruptions including DRESS and AGEP
Also known as Cutaneous adverse drug reaction · Drug rash · DRESS syndrome · Drug-induced hypersensitivity syndrome · AGEP · Acute generalised exanthematous pustulosis · Morbilliform drug eruption
Fellowship guide to drug eruptions in children: how to tell the common benign morbilliform rash from the three severe cutaneous adverse reactions (DRESS, AGEP and SJS-TEN) at the bedside, the drugs and the timing that point to each, the role of eosinophilia, hepatitis and HHV-6 reactivation in DRESS, the sterile pinhead pustules and rapid course of AGEP, and the management of stopping the drug, assessing severity, excluding infection and supporting the child.
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- Fever plus a rash after a new drug is a severe cutaneous adverse reaction until proven otherwise — morbilliform rashes are common and benign, but fever, mucosal involvement, blistering, skin pain, facial oedema or epidermal peeling signal DRESS, AGEP or SJS-TEN and demand urgent assessment
- A rash that appears two to eight weeks after starting an anticonvulsant, sulfonamide, allopurinol or minocycline, with fever, facial oedema, lymphadenopathy, eosinophilia or hepatitis, is DRESS (drug-induced hypersensitivity syndrome) — it is delayed, systemic and carries up to 10 per cent mortality, so never dismiss a long-latency rash as a simple drug allergy
- Hundreds of tiny pinhead sterile pustules erupting over hours to a day on a red, oedematous skin after a beta-lactam or macrolide is acute generalised exanthematous pustulosis (AGEP) — the rapid onset and the non-follicular pinhead pustules on an erythematous base distinguish it from folliculitis and from DRESS
- Skin pain, a positive Nikolsky sign, target lesions, mucosal erosions or epidermal detachment point to Stevens-Johnson syndrome or toxic epidermal necrolysis, not DRESS or AGEP — recognise the overlap early because this group needs fluid resuscitation, specialist transfer and burn-unit or intensive-care principles
- Reintroducing the culprit drug after a severe cutaneous adverse reaction can be fatal — document the allergy, counsel the family, check cross-reactivity (especially among aromatic anticonvulsants and sulfonamides), report to pharmacovigilance, and never re-challenge a confirmed SCAR
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- Dermatology
- Allergy and immunology
- Adverse drug reactions and drug eruptions
- General Paediatrics learning goal — distinguish a benign morbilliform rash from DRESS, AGEP and SJS-TEN
- Severe cutaneous adverse reactions: recognition, immediate management and referral
- Drug-induced hypersensitivity syndrome and the role of HHV-6 reactivation
- Clinical Applications
- Severe drug eruptions and dermatological emergencies
- Short Cases
- Emergency scenarios
- Dermatology: recognises severe cutaneous adverse drug reactions
- Allergy: understands drug hypersensitivity mechanisms and cross-reactivity
- Safe prescribing and medication-related harm
- Foundation of Practice (FOP)
- Applied Knowledge in Practice (AKP)
- Drug eruptions, DRESS and AGEP
- Clinical
- History
- Communication
- Dermatological examination
- General Pediatrics Content Outline — Dermatology
- Adverse drug reactions and drug hypersensitivity
- Severe cutaneous adverse reactions
- Patient Care 1: History and Physical Examination
- Patient Care 4: Clinical Reasoning
- Medical Knowledge 1: Clinical Knowledge of drug eruptions
- Systems-Based Practice 1: pharmacovigilance and reporting
- Medical Expert
- Collaborator
- Pediatrics: Core EPA — recognise and manage severe cutaneous adverse drug reactions
Overview & Definition
Picture the six-year-old started on a cephalosporin for tonsillitis who, ten days in, develops a fever and a widespread pink rash that begins on his trunk and spreads to his limbs. His mother is frightened and wants to know whether the antibiotic is to blame and whether he is safe. That scenario — a child with a rash after a new drug — is one of the most common and most anxiety-provoking presentations in general paediatrics, and the clinician's job is to separate, calmly and quickly, the benign majority from the dangerous few. [1]
A drug eruption is any cutaneous reaction caused by a medication, whether systemic or topical. The vast majority are benign exanthems, of which the morbilliform (measles-like) pattern is by far the commonest, but a small and critically important minority are severe cutaneous adverse reactions that carry significant morbidity and mortality. The two severe reactions covered in this topic are DRESS, the drug reaction with eosinophilia and systemic symptoms, also called drug-induced hypersensitivity syndrome or DIHS, and AGEP, acute generalised exanthematous pustulosis. Stevens-Johnson syndrome and toxic epidermal necrolysis are covered in a dedicated topic because they form a distinct mechanistic and prognostic entity, but they belong to the same severe family and must be excluded at the bedside whenever a drug eruption looks worrying. [2] [3]
Three ideas anchor the whole topic and drive every clinical decision. First, timing is the strongest single clue to the type of reaction, because a morbilliform rash takes days, AGEP takes hours, DRESS takes weeks, and each latency points to a different mechanism. Second, the presence of systemic features — fever, mucosal involvement, lymphadenopathy, eosinophilia, hepatitis or skin pain — is the dividing line between a benign exanthem and a severe cutaneous adverse reaction, and a child who is systemically unwell with a drug rash is never a simple allergy. Third, the first action in any suspected drug eruption, benign or severe, is to stop the culprit drug and to take a precise, chronological medication history, because the drug itself is both the cause and the diagnostic thread. [1] [9]
References12ShowHide
- [1]Nguyen E, Gabel CK, Yu J Pediatric drug eruptions. Clin Dermatol, 2020.PMID 33341197
- [2]Del Pozzo-Magaña BR, Liy-Wong C Drugs and the skin: A concise review of cutaneous adverse drug reactions. Br J Clin Pharmacol, 2024.PMID 35974692
- [3]Wei BM, Fox LP, Kaffenberger BH, et al. Drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms. Part II diagnosis and management. J Am Acad Dermatol, 2024.PMID 37516356
- [4]Awad A, Goh MS, Trubiano JA Drug Reaction With Eosinophilia and Systemic Symptoms: A Systematic Review. J Allergy Clin Immunol Pract, 2023.PMID 36893848
- [5]Calle AM, Aguirre N, Ardila JC, et al. DRESS syndrome: A literature review and treatment algorithm. World Allergy Organiz J, 2023.PMID 37082745
- [6]Sharifzadeh S, Mohammadpour AH, Tavanaee A, et al. Antibacterial antibiotic-induced drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome: a literature review. Eur J Clin Pharmacol, 2021.PMID 33025080
- [7]Halevy S Acute generalized exanthematous pustulosis. Curr Opin Allergy Clin Immunol, 2009.PMID 19458527
- [8]Bhat YJ, Akhtar S, Ahmad M, et al. Etiopathological and Clinical Study of Acute Generalized Exanthematous Pustulosis: Experience from a Tertiary Care Hospital in North India. Indian Dermatol Online J, 2020.PMID 32695700
- [9]Brockow K, Wurpts G, Trautmann A, et al. Guideline for allergological diagnosis of drug hypersensitivity reactions: S2k Guideline of the German Society for Allergology and Clinical Immunology (DGAKI) in cooperation with the German Dermatological Society (DDG). Allergologie Select, 2023.PMID 37705676
- [10]Levi N, Bastuji-Garin S, Mockenhaupt M, et al. Medications as risk factors of Stevens-Johnson syndrome and toxic epidermal necrolysis in children: a pooled analysis. Pediatrics, 2009.PMID 19153164
- [11]Ramien ML Stevens-Johnson syndrome in children. Curr Opin Pediatr, 2022.PMID 35836393
- [12]Saper VE, Ombrello MJ, Tremoulet AH, et al. Severe delayed hypersensitivity reactions to IL-1 and IL-6 inhibitors link to common HLA-DRB1*15 alleles. Ann Rheum Dis, 2022.PMID 34789453