A Child With Recurrent Bullous Lesions and Allergic Predisposition

A 5-year-old boy presented with a 48-hour history of painful lesions on the left lower limb, without fever or systemic symptoms, following a recent course of amoxicillin for otitis 1 week prior. A similar episode had occurred earlier in the year, resolving with a tapering regimen of oral prednisolone (1 mg/kg/day) for 8 days and topical betamethasone dipropionate/gentamicin 0.5 mg/g + 1 mg/g, applied twice daily for 14 days. No infection or antibiotic exposure preceded that episode. The patient's history was notable for atopy, including IgE-mediated food allergies, recurrent anaphylaxis, asthma, atopic dermatitis, and urticaria. His management included dietary restrictions, inhaled corticosteroids, and omalizumab. On physical examination, the distal left lower limb exhibited a well-defined reddish-brown erythematous plaque, without epidermal involvement and with vesiculobullous lesions (Figures 1 and 2). A punch biopsy was obtained for histopathological evaluation (Figures 3 and 4). Histopathological examination revealed a dermal infiltrate composed of eosinophils and histiocytes surrounding amorphous collagen deposits, forming flame figures and without vasculitis (H&E; Figure 3, ×40; Figure 4, ×200). The patient was treated with oral prednisolone (1 mg/kg/day for 5 days, then 0.5 mg/kg/day for 5 days), resulting in marked improvement with resolution of vesiculobullous lesions and residual erythematous-brown discoloration. Amoxicillin had previously been well tolerated by our patient but given the temporal relationship with symptom onset and the child's complex allergic background, the patient was advised to be assessed by an allergist regarding future avoidance of amoxicillin. Eosinophilic cellulitis (EC), first described in 1971, is a rarely reported inflammatory dermatosis, particularly in children [1, 2]. It presents with sudden onset of well-defined, erythematous, edematous plaques with vesicles or bullae, mainly on the trunk and limbs [1, 3, 4]. Lesions begin with itching or burning, expand over days, and resolve in 4–6 weeks [1, 3, 5]. However, recurrences are common [1]. Systemic symptoms are infrequent, and prognosis is favorable [1]. Fewer than 200 cases of EC have been reported with approximately one quarter being children [3, 6]. The etiology remains unknown, though a hypersensitivity reaction to triggers such as infections, insect bites, drugs, vaccines, or allergens is suspected [1, 3, 7]. Most of the EC cases are idiopathic, with no identifiable precipitating factor [3]. In children, when a trigger is identified, vaccinations are the most commonly reported cause [3, 7]. Although drug-induced EC is rare in pediatrics, the recent treatment of our patient with amoxicillin cannot be disregarded as a potential contributing factor. β-lactam antibiotics, including penicillin and ampicillin are well-documented triggers [1-3, 5]. Other associated antibiotics include tetracycline, bleomycin, lincomycin, minocycline, clindamycin and erythromycin [1-3, 5]. Since 2016, only one antibiotic-related case has been reported: a 28-year-old man with bilateral erythematous, edematous plaques at a benzathine penicillin injection site, which showed histopathological features consistent with EC and resolved with systemic corticosteroids [3, 8]. EC is marked by dysregulated tissue eosinophilia, driven by increased CD3+ and CD4+ T cells that spontaneously release IL-5—critical for eosinophil maturation, activation, and survival [1, 7, 9]. Triggers, such as amoxicillin, may upregulate IL-2, IL-5, and eosinophilic cationic protein, enhancing eosinophil and T-cell activation [9]. EC disproportionately affects children with atopic backgrounds, as in our case [6]. This suggests that an underlying hyperreactive immune state may increase susceptibility to eosinophil-mediated hypersensitivity [1, 9]. The differential diagnosis includes bacterial cellulitis, parasitic infections, arthropod bites, hypereosinophilic syndrome, chronic idiopathic urticaria, and Churg–Strauss syndrome [1, 3, 4]. Given the wide clinical spectrum, evolving morphology, and overlap with other conditions, EC is frequently misdiagnosed. In 2013, diagnostic criteria were proposed for the drug-induced variant of EC, although these have neither been validated in large series nor updated since publication [5]. Skin biopsy is crucial for establishing the diagnosis, typically showing an infiltrate of eosinophils within the dermis, with marked edema and flame figures, without evidence of vasculitis [3, 4]. Although flame figures are a hallmark of EC, they are not pathognomonic and may also appear in conditions such as eczema and parasitic infections [6, 9]. Treatment remains uncertain, relying primarily on case reports and small series [2, 3, 6]. If a causative factor is identified, its removal is the best treatment option [1-3]. Topical corticosteroids are first-line for localized or residual lesions, while systemic therapy with oral prednisone (1–2 mg/kg/day) is recommended for extensive disease, followed by tapering over two to three weeks [2, 3, 7, 8]. Second-generation H1-antihistamines are commonly used, primarily to alleviate pruritus, given their known inhibitory action on eosinophils and neutrophils, as seen in acute urticaria [2, 3]. A recent review suggests a shift in EC management, with therapies such as dupilumab, omalizumab, mepolizumab, and JAK inhibitors providing effective, steroid-sparing options for relapsing cases [3]. Seven cases to date report successful use of omalizumab in refractory EC, including only adults [10]. Omalizumab, approved for chronic spontaneous urticaria, binds free IgE, downregulates FcεRI on mast cells and basophils, and inhibits their activation [10]. However, its role in EC remains unclear, as shown by our patient, who developed EC despite ongoing omalizumab therapy. EC is a rare, often misdiagnosed condition in children, with drug-induced forms being particularly uncommon. In our case, amoxicillin and underlying atopy may have triggered a hypersensitivity reaction. Diagnosis relies on biopsy, and topical and/or systemic corticosteroids remain first-line treatment. Biologic medications and allergen avoidance may help, but more research is needed to understand pediatric EC and its triggers. The authors declare no conflicts of interest.