Clinical features with anti fibroblast growth factor receptor 3 (FGFR3) antibody-related polyneuropathy: a retrospective study

Abstract

Background Despite its initial association with sensory neuropathies, anti-fibroblast growth factor receptor 3 (FGFR3) antibodies have been since reported with a broad range of neuropathies and clinical features. The aim of the study is to report the clinical and electro diagnostic findings in a cohort of patients with sensory or sensorimotor polyneuropathy and anti-FGFR3 antibodies. Methods We performed a retrospective chart review to assess the clinical characteristics of patients with sensory or sensorimotor neuropathy related to FGFR3 antibodies. Descriptive statistics were reported using frequencies and percentages for categorical variables and median and interquartile range (IQR) for continuous variables. Results This study included 14 patients (9 women) with a median age of 51.9 years (IQR 48–57). The most common presenting symptoms were painful paresthesia (100%), gait instability (42.9%), constitutional symptoms (42.9%), and autonomic symptoms (28.6%). Onset of symptoms was chronic (≥12 weeks) in eight patients (57.1%). Examination showed a distal loss of sensation to pin prick (100%), as well as impaired vibration sensation (78.6%) and proprioception (35.7%), in the distal extremities. We also observed mild weakness in the distal lower-extremities (42.9%). Three patients (21.4%) had trigeminal neuralgia, three patients (21.4%) had co-existing autoimmune disease, and one patient (7.1%) had a history of renal cell carcinoma. The mean titer of FGFR3 antibody was 14,285.71 (IQR 5000–16,750). All 14 patients produced normal results in the neuropathy workup. Nerve conduction study and electromyography showed sensory axonal neuropathy in four patients (28.6%), sensorimotor axonal neuropathy in seven patients (50%), and a normal result in three patients (21.4%). For those with a normal NCS/EMG, a skin biopsy showed a non-length-dependent small fiber neuropathy. Conclusions Neuropathy related to FGFR3 antibodies can potentially involve small and large fibers, sensory and motor fibers, and even the trigeminal nerve, which contributes to a highly variable clinical presentation.

Non‐length‐dependent small fiber neuropathy: Not a matter of stockings and gloves

“…168,169 Antibodies binding to trisulfated heparin disaccharide (TS-HDS), 191,192 and the intracellular domain of the fibroblast growth factor receptor 3 (FGFR3) 193 have been detected in patients with apparently idiopathic sensory neuropathy, often with features of sensory neuronopathy, 193 including NLD-SFN. [170][171][172][173][174] It is still unclear whether these are autoantibodies playing a pathogenic role or are only biomarkers of a dysimmune process, and whether they can identify patients who would respond to immune intervention. 194 Finally, predispositions towards dysimmunity in some patients with idiopathic SFN is suggested by findings of minor abnormalities of immune and inflammatory biomarkers, 42,115,195 as also observed in NLD-SFN.…”

Sensory neuronopathies, diagnostic criteria and causes

“…Abs recognizing the TK domain correspond to a more severe disease. Other studies have associated anti-FGFR3 Abs with a wider spectrum of neuropathy [72][73][74][75]. The method used for the Abs detection is certainly crucial for the specificity of the results [76].…”

Small fiber neuropathies: expanding their etiologies

“…It can be a manifestation of an underlying systemic disease, like sarcoidosis [11 ▪ ,12 ▪ ] or Sjögren syndrome [13 ▪ ,14 ▪ ]. In addition, various auto-antibodies have been linked to SFN, in the absence of systemic diseases [15 ▪ ,16 ▪▪ ,17 ▪▪ ]. Besides, postinfectious and postvaccination cases of SFN have been described, in which immune-mediated mechanisms are supposed to be causative [18 ▪ ,19 ▪ ,20 ▪ ,21 ▪ ,22 ▪ ,23 ▪ ,24 ▪ ,25 ▪ ,26 ▪ ].…”

“…Antibodies against FGFR3 were already linked to purely sensory-predominant neuropathies or neuronopathies. A recently conducted retrospective study, showed a broader clinical spectrum with involvement of both small and large fibers, sensory, and motor fibers, and the trigeminal nerves [15 ▪ ].…”