Bizarre Localization of Amlodipine‐Induced <scp>AGEP</scp> Over Infiltrated Plaques of Borderline Lepromatous Leprosy in a Patient With Type‐1 Lepra Reaction: An Uncanny Immunological Phenomenon

Acute generalized exanthematous pustulosis (AGEP) is an uncommon severe cutaneous adverse reaction, predominantly drug induced, most frequently associated with antibiotics [1]. In patients with leprosy, diagnostic difficulty may arise due to clinical overlap with lepra reactions. We report a rare case of amlodipine-induced AGEP in a patient with borderline lepromatous (BL) Hansen disease with type 1 reaction, confirmed through withdrawal, controlled rechallenge, and repeat histopathology. A 38-year-old woman with biopsy-proven BL Hansen disease (slit-skin smear positivity of 4+), on multidrug therapy (MDT) recommended by the World Health Organization third pack (without dapsone) with severe anemia was hospitalized for management of a type 1 lepra reaction. During admission, she was started on i.v dexamethasone 2 cc daily along with oral iron supplementation, levocetirizine, paracetamol as required, calcium with vitamin D, and methylcobalamin. Persistently elevated blood pressure readings prompted initiation of amlodipine 5 mg once daily following medical consultation. Within 48 h of drug initiation, she developed abrupt onset of numerous small, sterile, non-follicular pustules predominantly distributed along the peripheral margins of pre-existing leprosy plaques and on previously uninvolved skin (Figure 1A,B). The eruption was associated with bilateral pedal edema, low-grade fever, and neutrophilic leukocytosis, without mucosal involvement. Pustules were superficial and non-tender. Gram staining demonstrated abundant neutrophils (Figure 1C) without microorganisms and bacterial culture was sterile. Histopathological examination of biopsies taken from pustular lesions over both leprosy plaques and newly affected skin revealed subcorneal collections of neutrophils consistent with AGEP (Figure 1D). Based on clinical morphology, histopathology, temporal relationship with drug exposure, and rapid resolution following drug withdrawal, a diagnosis of drug-induced AGEP was established. All recently introduced medications except dexamethasone were discontinued, resulting in marked regression of pustules and erythema within 48 h with desquamation. A structured stepwise drug rechallenge was subsequently performed under close observation. Reintroduction of each agent was tolerated without recurrence until amlodipine was administered, which led to reappearance of pustules within 24 h, confirming causality. In view of the rarity of this association, a repeat rechallenge was undertaken with informed monitoring, again inducing recurrence of lesions. A subsequent skin biopsy reconfirmed features of AGEP. Amlodipine was permanently withdrawn and antihypertensive therapy was modified to telmisartan and metoprolol, after which no further cutaneous reactions occurred. AGEP is characterized by rapid onset of sterile non-follicular pustules on an erythematous base, frequently accompanied by fever and neutrophilia, with prompt resolution following removal of the offending agent [1]. The short latency period observed aligns with classical drug-induced AGEP and rules out a sometimes similar drug eruption, generalized pustular figurate erythema (GPFE), which has a longer latency and lesions of various morphologies like urticarial, targetoid, and arcuate plaques [2]. Although rechallenge is generally discouraged in severe cutaneous adverse reactions, its controlled application in this setting provided definitive diagnostic confirmation. A distinctive aspect of this case was the preferential localization of pustules at the advancing margins of BL leprosy plaques, sparing their centers. In BL disease, immunological activity is known to be heterogeneous within lesions, with heightened cell-mediated immune responses at peripheral borders characterized by increased T-cell infiltration and interferon-γ production, while plaque centers remain relatively immunologically inert due to heavy bacillary burden [3]. The concomitant type 1 lepra reaction likely further intensified this localized immune activation. We hypothesize that amlodipine acted as a Hapten, triggering drug-specific CD4+ and CD8+ T-cell responses that synergized with the heightened inflammatory milieu at plaque margins, leading to keratinocyte apoptosis via perforin/granzyme B and Fas–FasL, with subsequent CXCL8/IL-8-mediated neutrophil recruitment, IFN-γ amplification, GM-CSF-prolonged neutrophil survival, and Th17 (IL-17/IL-22)-driven keratinocyte activation culminating in subcorneal pustule formation. A prior report described amlodipine-associated hypersensitivity in a patient with graft-versus-host disease, later diagnosed as pseudolymphoma, wherein the underlying immune dysregulation was proposed to have facilitated an enhanced T-cell-mediated hypersensitivity response to amlodipine [4]. This case expands the spectrum of drugs implicated in AGEP and underscores the influence of underlying immunologic dermatoses on the morphological expression of drug reactions. Recognition of AGEP in patients with Hansen disease is crucial to prevent misinterpretation as lepra reactions, as highlighted by the comparison table (Table 1) so as to ensure prompt withdrawal of the offending agent. The observed site-specific predilection further highlights the role of local immune microenvironments in shaping hypersensitivity responses. The authors have nothing to report. The authors declare no conflicts of interest. The data that support the findings of this study are available from the corresponding author upon reasonable request.