Vancomycin-Induced Linear IgA Bullous Disease in a Neonate

Dear Editor, Linear IgA bullous dermatosis (LABD) is an autoimmune subepidermal blistering disorder, rarely reported in neonates. Although LABD is well-documented in adults and older children, neonatal cases are limited and often present diagnostic and therapeutic challenges. To the best of our knowledge, this is the first reported case of vancomycin-induced LABD in a neonate. A 3.1 kg male neonate, now weighing 3.5 kg (day 21), the firstborn of non-consanguineous parents, presented with widespread blistering on the extremities, which had progressed in size and number over the preceding 1–2 days. The neonate was being treated for septic arthritis of the right knee with parenteral vancomycin (15 mg/kg/dose) and meropenem (20 mg/kg/dose) for the past 5 days. There was no family history of skin lesions, and the first 2 weeks of life were uneventful. On examination, approximately 8–10 scattered vesicular lesions, measuring 0.2 cm–2 cm were noted on the extremities, sparing the face and genitocrural region [Figure 1a and b]. Grouping of lesions was evident, and mucosal and nail examinations were normal. Darier’s sign was negative. A bulla spread sign performed on a lesion on the elbow demonstrated peripheral extension with a regular, rounded border. A Tzanck smear revealed numerous neutrophils, and the Gram stain showed no organisms. A complete blood count showed hemoglobin of 14.8 g/dL, white blood cell count of 19,000/μL (78% neutrophils), and platelet count of 650,000/μL. Repeated blood cultures were negative. Histopathology revealed a paucicellular subepidermal bulla with sparse perivascular lymphohistiocytic infiltrates [Figure 2a]. Direct immunofluorescence demonstrated linear immunoglobulin A (IgA) deposits with focal discontinuity along the basement membrane zone [Figure 2b].Figure 1: (a) Tense bullae on normal-looking skin on the right forearm and right axilla, along with grouped vesicles (suggestive of abortive “crown of jewels”) on the right upper limb. Prominent surrounding erythema is noted. (b) A spontaneously ruptured bulla producing a shallow ulcer on the left medial malleolusFigure 2: (a) Hematoxylin and eosin stain (100×) showing a paucicellular subepidermal bulla. (b) Direct immunofluorescence shows linear immunoglobulin A deposits along the basement membrane zoneThe neonate was managed in the neonatal intensive care unit with dermatology consultation. While biopsy and immunofluorescence results were awaited, supportive care continued. Vancomycin was promptly discontinued and was replaced by linezolid. New lesions ceased developing within 12 hours, and the ruptured lesions began to heal over the next 2–3 days without the need for topical or systemic immunosuppressive therapy. Follow-up confirmed resolution of septic arthritis. LABD is a rare autoimmune blistering disorder in neonates, with only 12 cases reported in the literature.[1] Neonatal LABD typically presents with severe cicatrizing mucosal involvement, including blindness, airway compromise, and feeding difficulties, often requiring systemic therapy.[2-4] However, recent reports suggest that some cases may follow an uncomplicated, self-healing course.[2] The pathogenesis of neonatal LABD is often idiopathic or attributed to the transfer of pathogenic IgA autoantibodies via breast milk, explaining the non-relapsing course in some cases.[1-4] Vancomycin-induced LABD is well-documented in adults but to our knowledge, has not been reported in neonates until now.[5] Histopathology in our case revealed a paucicellular subepidermal bulla, differing from the more robust inflammatory infiltrate characteristic of idiopathic LABD. This could be explained by the known attenuated inflammation in drug-induced LABD, especially in early lesions, as well as the inherently less developed immune response in neonates.[5] The diagnosis of vancomycin-induced LABD was supported by the history of vancomycin exposure, characteristic bullae, subepidermal split on histopathology, and linear IgA deposits. A Naranjo adverse drug reaction probability score of six (“probable”) further supported this, based on the temporal association, rapid resolution upon withdrawal, and absence of alternative causes. Differential diagnoses considered included other immunobullous diseases, disseminated listeriosis, cutaneous herpes simplex, and epidermolysis bullosa [Table 1].[6] Disseminated listeriosis, though rare, can present with pustules and petechiae involving the skin and mucosa, but localized joint involvement with vesiculobullous lesions is not a feature.[7] Cutaneous herpes simplex, which can present with grouped vesicles, was ruled out by the absence of multinucleate giant cells on the Tzanck smear and the lack of viral cytopathic effect on histopathology. Epidermolysis bullosa, an inherited skin fragility disorder, was also considered but was unlikely given the absence of lesions on trauma-prone sites and the rapid resolution.Table 1: Common vesiculopustular lesions in neonates and infantsThis case highlights the importance of considering drug-induced dermatoses, particularly LABD, in neonates presenting with acute blistering lesions. Early recognition and discontinuation of the offending agent can lead to rapid resolution without the need for additional therapy. Clinicians should maintain a high index of suspicion for drug-induced dermatoses when evaluating neonates with blistering dermatosis, especially in the context of systemic antibiotic use. Declaration of patient consent The authors certify that they have obtained all appropriate parent consent forms. In the form a parent has given their consent for her images and other clinical information to be reported in the journal. The parent understands that her name and initials will not be published and due efforts will be made to conceal her identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest. Use of artificial intelligence (AI) The preparation of this manuscript was carried out entirely by the authors without the use of artificial intelligence technologies.