Background: Differentiating febrile rash can be challenging due to overlapping systemic symptoms. SSLR is a rare, immune-mediated condition that can be triggered by drugs, infections, or vaccines. Due to its heterogenous presentation, SSLR it often misdiagnosed as other conditions. The classical triad of SSLR is fever, rash and lymphadenopathy and polyarthritis, closely resembled infections and inflammatory conditions such as Kawasaki disease (KD).

Case presentation: We present a 17-year-old male, with a history of prematurity, mono-kidney function, bilateral deafness and epilepsy, who experienced 3 admissions to the pediatric intensive care unit (PICU) over two years due to sepsis-like symptoms. In 2022, he was diagnosed with KD after presenting with classical symptoms of fever, rash, conjunctivitis, swollen and painful hands and cervical lymphadenopathy, normal echocardiography, corresponding well to intravenous immunoglobulin (IVIG) and methylprednisolone. In April 2024, he was suspected of having TSS and treated with antibiotics, IVIG and methylprednisolone with good clinical response. In June 2024, he presented again with suspicion of septic shock, combined with fever, rash, vomiting and hypotension requiring inotropic support, antibiotics and methylprednisolone. Inflammatory markers were mildly elevated and no infectious etiology was found on any occasion. Notably, he was treated with amoxicillin or amoxicillin/clavulanate prior to each admission. Oral provocation with amoxicillin-clavulanate ultimately confirmed the diagnosis SSLR.

Conclusion: This case highlights the diagnostic challenges in distinguishing SSLR from conditions such as KD and TSS. SSLR is a self-limiting condition often triggered by certain antibiotics like amoxicillin/clavulanate mimicking other infectious and inflammatory conditions. Early recognition is crucial to avoid unnecessary treatments and misdiagnosis, particularly in pediatric patients with recurrent sepsis-like presentations with unknown infectious etiology.