Introduction: Acute Generalized Exanthematous Pustulosis (AGEP) is a rare, severe cutaneous eruption characterized by the numerous pustules on an erythematous base. Typically, AGEP occurs as an adverse reaction triggered by specific medications, most notably antibiotics, hydroxychloroquine, and diltiazem. However, in this case series, six patients presented with presumed AGEP secondary to developing systemic loxoscelism, systemic effects of a brown recluse spider bite. Methods: Retrospective chart review in University of Missouri-Columbia healthcare system’s electronic medical record (EMR) analyzing each case for pertinent information regarding patient demographics, medical history, presenting symptoms, clinical findings, diagnosis, and management. Results: In all six cases, patients presented with systemic symptoms including peak fevers ranging from 39.3°C to 40.8°C, malaise, chills, hypotension, a widespread erythematous pruritic rash with pustules and signs and symptoms of hemolytic anemia, which can be seen in severe cases of systemic loxoscelism. Other abnormal lab values see in our patients included leukocytosis with granulocyte predominance and an elevated CRP. Conclusion: AGEP is a cutaneous adverse reaction that may manifest with systemic symptoms in severe cases. Although not inherently life-threatening, AGEP can cause secondary complications such as bacterial infection, psychological distress or can exist as a sequela of a life-threatening condition such as systemic loxoscelism. Proper identification, cessation of the offending agent if applicable, and appropriate supportive measures remain crucial in AGEP management
