To describe an unusual initial presentation of Systemic Lupus Erythematosus (SLE) that highlights three key features: combined cord and nerve-root involvement, extreme CSF inflammation in an autoimmune myelitis, and a parainfectious bacterial trigger.

SLE is an autoimmune disease that can present with neuropsychiatric manifestations, including inflammatory myelitis in 1-2% of patients. Radiculomyelitis, with nerve-root extension, is uncommon. Although viral parainfectious lupus myelitis has been reported, bacterial triggers are rare and can be difficult to differentiate from infectious myelitis.

A 27-year-old previously healthy Hmong female presented initially with Salmonella enterica bacteremia and was treated with ceftriaxone. Two weeks later, in the context of new-onset Clostridium difficile colitis, she developed bilateral weakness of hip flexors and ankles, absent lower extremity reflexes, and lumbar radicular pain. MR spine showed multifocal gadolinium enhancement in the cervical and thoracic cord, conus, and ventral cauda equina nerve roots. Initial lumbar puncture was notable for 2020 WBC/µL (68% neutrophils), protein 274 mg/dL, and glucose 28 mg/dL. CNS infectious studies were negative, and she progressed to flaccid bilateral leg and deltoid weakness despite broad antimicrobial coverage. Autoimmune testing and renal biopsy confirmed class III lupus nephritis. She was started on 1000 mg IV methylprednisolone with rapid and significant improvement. At six months, on rituximab, there was complete resolution of MRI lesions and near complete clinical recovery.

Dual spinal cord and nerve-root involvement is atypical and frequently associated with infectious etiologies in immunocompromised and septic patients. Lack of clinical response to antimicrobial therapy but marked improvement with steroids confirmed the diagnosis of lupus radiculomyelitis. Bacterial antigens may amplify lupus autoimmunity via Toll-like receptor and type I interferon pathways, and bacterial lipopolysaccharide can induce spinal microglial activation resulting in demyelination. This case highlights potential overlap between autoimmune and infectious etiologies, and the importance of early recognition and corticosteroid therapy.