Severe Mixed Hypersensitivity Reaction Induced by Antivenom: Diagn ostic Challenges and Precision Management

Objectives To report a rare, life-threatening mixed hypersensitivity reaction (Types I and III) induced by snake antivenom and describe a precision management strategy. Clinical features and outcome A 55-year-old woman with a history of plant allergy received antivenom treatment(6 vials total) for a Trimeresurus stejnegeri bite, with initial symptom resolution. On post-serum day 7, she developed syncope, fever, generalized pruritus, and urticaria, followed by recurrent rash, pruritus, nausea, vomiting, abdominal pain, myalgia, arthralgia, and hypotension on day 8. Laboratory findings included leukocytosis, neutrophilia, elevated D-dimer, IgE (155.0 IU/mL), and serum creatinine (123 μmol/L). Multidisciplinary consultation diagnosed a mixed hypersensitivity reaction (anaphylaxis + serum sickness). Management employed a “Shock control—Inflammation suppression—Volume optimization” strategy: epinephrine (intramuscular/intravenous) for shock, dexamethasone and antihistamines for inflammation, and aggressive crystalloid resuscitation. Hemodynamic stability and symptom resolution were achieved. Conclusions This represents the first documented case of severe mixed hypersensitivity (co-occurring Type I anaphylaxis and Type III serum sickness) triggered by antivenom. It highlights the diagnostic challenge posed by overlapping biphasic features and multi-system involvement occurring within the typical serum sickness window. Precision management addressing both pathogenic pathways simultaneously, specifically via combined hemodynamic stabilization, anti-inflammatory therapy, and volume support, was critical for successful recovery. Enhanced vigilance for this synergistic reaction pattern is warranted.