Paediatric Acute Generalised and Localised Exanthematous Pustulosis: A Systematic Review

Acute generalised exanthematous pustulosis (AGEP) is a severe pustular cutaneous eruption often accompanied by fever and associated with drug triggers or infections. The pathogenesis of AGEP appears to be T-cell-mediated. Many drug-specific T-cells release large amounts of interleukin-8, a potent neutrophil chemoattractant that promotes neutrophil survival and recruitment to the skin, forming intraepidermal pustules [1]. The median age of presentation is approximately 60 years; however, cases are reported in children [1]. Paediatric acute localised exanthematous pustulosis (ALEP) has occurred with infections and vaccines [2]. This study aims to evaluate the characteristics, causes, clinical presentations and treatment outcomes in paediatric cases of AGEP and ALEP. MEDLINE and Embase were searched (inception to January 2025) with the terms ‘AGEP,’ ‘ALEP’ and ‘pediatric’. This review was registered in PROSPERO (ID: 1016727) per PRISMA 2020 guidelines. Full-length English articles reporting AGEP/ALEP in patients < 18 years old were included. Of 268 records identified, 57 articles, consisting of 46 case reports, seven case series and four cohort studies were included (Figure 1). We identified 84 paediatric patients with a mean age of 8.1 years (range: 0–17) and male predominance (61.7%, n = 50/81; Table 1). Most cases were AGEP (81/84, 96.4%) with rare cases of ALEP (3/84, 3.6%). Identified triggers were predominantly drugs (73.8%, n = 62/84) and infection (23.8%, n = 20/84), with upper respiratory tract infections being most common. Among drug-related cases, antibiotics (56.5%, n = 35/62; penicillins [45.7%, n = 16/35], cephalosporins [22.8%, n = 8/35] and sulphonamides [11.4%, n = 4/35]), antifungals (9.7%, n = 6/62) and acetaminophen (8.1%, n = 5/62) were the main therapies implicated in AGEP, while ALEP was triggered by antibiotics and lamotrigine. Mean latency to AGEP and ALEP onset was 5.5 days (range: hours to 42 days) and 2.3 days (range: 2–4 days), respectively. Biopsy confirmed diagnoses in 65.5% of patients (n = 55/84). Laboratory findings frequently included leukocytosis with neutrophilia, elevated CRP, and normal kidney and liver tests. Abnormal liver enzymes were reported in five cases. A EuroSCAR AGEP validation score was reported in 42.9% (n = 36/84) of cases, with a mean of 9.4 (range: 5–12). In drug-induced cases, the mean Naranjo score was 7.3 (range: 4–11), suggesting a probable association with culprit drugs. Drug discontinuation, when feasible, was the primary management in cases of drug-related AGEP/ALEP (74.2%, n = 46/62). Treatments included topical steroids (48.8%, n = 41/84), systemic steroids (28.6%, n = 24/84), antihistamines (33.3%, n = 28/84) and drug withdrawal alone (4.8%, n = 4/84). Nearly all cases achieved complete resolution (92.9%, n = 78/84) within a mean duration of 8.9 days, though 10.7% (n = 9/84) noted residual desquamation or hyperpigmentation. Patients treated with systemic steroids indeed had a longer mean disease duration compared to those treated with topical steroids (12.0 versus 9.2 days), however these patients also had more severe presenting disease characteristics. Two patients had recurrent AGEP after re-exposure, recovering completely, while one progressed to a TEN-like presentation treated with intravenous immunoglobulin; the outcome was unreported. Specific allergological workup for the suspected culprit drug was conducted in select patients, yielding positive results in 72.7% (n = 8/11) of cases with patch test, 50% (n = 1/2) with skin prick test and 100% (n = 2/2) with lymphocyte transformation test. Overall, paediatric AGEP/ALEP presents similarly to that of adults with acute-onset sterile, non-follicular pustules, disseminated lesions and rare mucosal involvement [3]. While visceral involvement occurs in up to 17% of adult AGEP, few cases in this review reported liver involvement, and none reported other organ impacts, likely due to fewer chronic comorbidities in children [4]. Regardless, a basic systemic workup is recommended to detect rare organ involvement. Following recovery, confirmatory allergological workup may be considered, with varying specificity demonstrated in this cohort. Additionally, AGEP/ALEP post-infection may be more common in children and should be considered in cases without a clear drug culprit [3]. Antibiotics were the most common drug cause of paediatric AGEP, led by penicillins, whereas sulphonamide and cephalosporins are more frequent culprits in adult populations [5]. Paediatric-specific considerations include the lack of EuroSCAR score validation in children and ongoing debate regarding systemic corticosteroids in treatment [6]. Limitations include the exclusion of non-English articles and potential reporting bias. Further research into AGEP pathophysiology could improve diagnostic and therapeutic approaches, potentially reducing unnecessary invasive procedures in paediatric populations. Miranda K. Branyiczky: conceptualisation (lead), methodology (lead), investigation (lead), formal analysis (lead), writing – original draft (lead), writing – review and editing (equal). Megan Lowe: investigation (supporting), formal analysis (supporting), writing – review and editing (equal). Eric McMullen: formal analysis (supporting), writing – review and editing (equal), project administration (lead). Shireen Dumont: writing – review and editing (equal). Narachai Julanon: visualisation (lead), writing – review and editing (equal). Vincent Piguet: supervision (supporting), methodology (supporting), writing – review and editing (equal). Cathryn Sibbald: supervision (lead), methodology (supporting), writing – review and editing (equal). The authors have nothing to report. Dr Piguet has received honoraria or fees for consulting and/or speaking for AbbVie, Almirall, Celgene, Janssen, Novartis and Pfizer and has received departmental support for Cardiff University from AbbVie, Almirall, Alliance, Beiersdorf UK Ltd, Biotest, Celgene, Dermal, Eli Lilly, Galderma, Genus Pharma, Globe Micro, Janssen-Celag, La Roche-Posay, L'Oreal, LEO Pharma, Meda, MSD, Novartis, Pfizer, Sinclair Pharma, Spirit, Stiefel, Samumed, Thornton Ross, TyPham and UCB and for University of Toronto from Sanofi. Dr Sibbald has received honoraria for speaking for AbbVie, Incyte, Leo Pharma, Novartis, Pfizer, Sanofi, UCB Pharma, received compensation for advisory board participation from Sanofi, Pfizer, Incyte and Eli Lily and received grant funding from Pfizer International. M.K.B., M.L., E.M., S.D. and N.J. have no conflicts of interest to declare. The data that support the findings of this study are available within the article.

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