Small fiber neuropathy associated with ANCA positivity: a case series and brief literature review.

INTRODUCTION: Small fiber neuropathy [SFN] is a common peripheral neurologic disorder with a vast array of implicated etiologies. It has previously been proposed that some forms of immune-mediated small fiber neuropathy are driven by vasculitis, though antinuclear cytoplasmic antibodies [ANCA] antibodies have not commonly been reported in association with SFN, thus far. We present this case series to discuss the observation of a possible novel association between ANCA and SFN. METHODS: This is a retrospective case series of 6 patients with SFN and ANCA positivity, with and without systemic manifestations. Patients included were diagnosed with SFN by skin biopsy or autonomic function testing and were seropositive for ANCA by ELISA. RESULTS: Six patients are outlined, including 4 females and 2 males. Antigen specific antibodies were MPO alone in 4 cases, PR3 alone in 1 case and both MPO and PR3 in 1 case. Systemic vasculitis was noted in 2 patients. Five patients received immunosuppression. Three patients experienced partial improvement, while symptoms stabilized in 3 patients. DISCUSSION: This is the first series of patients with suspected immune-mediated SFN and ANCA antibody positivity, raising the possibility of ANCA mediated isolated SFN. This is in contradistinction to the more typical ANCA-mediated peripheral neuropathy manifestations of mononeuropathy multiplex or axonal sensorimotor neuropathy. We cannot unequivocally prove ANCA-associated vasculitis [AAV] causality in these cases; however, the stabilization in SFN symptomatology and associated improvement in ANCA antibody titer, after AAV treatment, may be indicative of an association.

Paraneoplastic Glomerular Diseases.

Paraneoplastic glomerular diseases (GNs) are rare manifestations in patients with underlying hematologic and solid organ malignancies and can occur before or after the detection of cancer. In the absence of established algorithms for investigation and reliable tests, they remain difficult to diagnose. Given the heterogeneity and infrequency of cases, the pathogenesis of most paraneoplastic GNs is poorly understood. Most of our recent understanding of paraneoplastic GNs has emerged from the discovery of target antigens in membranous nephropathy such as thrombospondin type-1 domain-containing protein 7A and neural epidermal growth factor-like 1 protein that appear to be promising in differentiating a primary vs paraneoplastic cause of membranous nephropathy. Treatment of paraneoplastic GNs is usually directed at the underlying malignancy. This review will focus on the epidemiology, pathogenesis, and diagnosis of paraneoplastic glomerular processes.