Background/Objectives: Drug hypersensitivity reactions (DHRs) are an important cause of morbidity in hospitalized patients, but their epidemiology and management in the inpatient setting are not well defined. Mislabeling of drug allergies may lead to inappropriate treatment and reduced antimicrobial stewardship. This study aimed to characterize the clinical profile, diagnostics, and management of inpatients referred for suspected drug allergy in a tertiary care hospital. Methods: We retrospectively reviewed all adult inpatients (≥18 years) at Luigi Sacco Hospital (Milan, Italy) who received allergology consultation between 1 June 2022 and 31 May 2025. Data on demographics, reaction type, culprit drugs, investigations, and management were collected. Immediate reaction severity was graded using the United States Drug Allergy Registry (USDAR) scale; delayed reactions were classified as severe cutaneous adverse reactions (SCARs) or non-SCARs. Logistic regression identified predictors of severity. Results: Among 35,438 admissions, 334 patients (0.9%) were evaluated; median age was 65 years, 51.2% were female, 67.4% had atopic comorbidities, and 55.1% reported prior drug allergy. Immediate reactions occurred in 49.1%, delayed in 43.7%. Cutaneous involvement was present in 86.8%, anaphylaxis in 6.6%, and SCARs in 3.9%. Antibiotics—particularly β-lactams—were most often implicated. In multivariate analysis, antibiotic exposure and older age were linked to more severe immediate reactions, while the absence of atopy predicted SCARs. Desensitization was successfully performed in 16.2% of patients. Conclusions: DHRs in inpatients are frequent and often involve high-risk drugs. Structured inpatient allergology services and an “allergy stewardship” approach may reduce DHR-related risks, support optimal therapy, and improve antimicrobial use strategies in tertiary care settings.

Scombroid syndrome is a frequent cause of fish poisoning and typically presents with mild, self-limiting symptoms. Severe anaphylaxis-like reactions are uncommon, and a biphasic clinical course has not previously been reported. We describe the case of a 19-year-old woman who developed flushing, headache, generalized urticaria, facial edema, dyspnea, and hypotension approximately 30 minutes after ingesting raw amberjack tartare. Emergency treatment with adrenaline, antihistamines, corticosteroids, and intravenous fluids led to initial clinical improvement; however, three hours later, she experienced a recurrence of cutaneous, respiratory, and gastrointestinal symptoms, consistent with a biphasic reaction. The patient subsequently developed chest pain associated with transient electrocardiographic changes and mild troponin elevation, prompting further evaluation for suspected Kounis syndrome. Allergy assessment, including specific IgE testing and skin-prick testing with fresh fish, was negative, supporting a toxic rather than IgE-mediated mechanism. This case expands the clinical spectrum of scombroid syndrome by documenting a biphasic anaphylaxis-like presentation and underscores the importance of considering histamine fish poisoning in the differential diagnosis of severe food-related reactions. Careful evaluation is essential to prevent misdiagnosis and unnecessary long-term dietary restrictions.