Autoimmune nodopathies (AN) are a recently defined group of demyelinating neuropathies characterized by antibodies targeting nodal and paranodal proteins such as neurofascin-155 (NF155) and neurofascin-186 (NF186). Unlike classic chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) or Guillain-Barré syndrome (GBS), ANs often present with overlapping clinical and electrophysiologic features but show limited response to conventional immunotherapies. To date, nodopathy coexisting with systemic lupus erythematosus (SLE) has not been reported. We describe the first documented case of dual-positive anti-NF155 and anti-NF186 autoimmune nodopathy (a “pan-neurofascin” nodopathy) occurring in new-onset SLE, presenting with a fulminant GBS-like syndrome with cranial nerve involvement and respiratory failure.

An 18-year-old woman presented with rapidly progressive ascending flaccid quadriparesis, bulbar dysfunction, and respiratory failure requiring mechanical ventilation shortly after being diagnosed with SLE (ANA, anti-dsDNA, anti-Sm positivity, and low complement). Nerve conduction studies demonstrated a demyelinating polyneuropathy, and cerebrospinal fluid analysis revealed albuminocytologic dissociation. Despite intensive treatment with intravenous immunoglobulin (IVIG), plasmapheresis, corticosteroids, and cyclophosphamide (for concurrent SLE), neurological improvement was minimal. Given the refractory course, a sural nerve biopsy and extended paranodal antibody panel were obtained.

Nerve biopsy showed patchy axonal degeneration, and subsequent antibody testing identified serum anti-NF155 and anti-NF186 positivity, confirming autoimmune nodopathy. Rituximab was initiated as targeted therapy, but neurological recovery remained minimal. This case underscores the diagnostic overlap between GBS and autoimmune nodopathy and highlights the limited efficacy of standard and advanced immunotherapies in paranodal antibody–mediated disease. The coexistence of SLE suggests an autoimmune milieu predisposing to epitope spreading and dual antibody formation.

This case expands the clinical spectrum of autoimmune nodopathies with dual-positive anti-NF155 and anti-NF186 nodopathy in new-onset SLE. It emphasizes the importance of early antibody screening in atypical or treatment-refractory GBS presentations and the need for continued investigation into optimal immunotherapeutic strategies for nodopathies associated with systemic autoimmunity.