Small Fiber Polyneuropathy Is Associated With Non–Bladder-Centric Interstitial Cystitis/Bladder Pain Syndrome Patients

Abstract

Objectives Interstitial cystitis/bladder pain syndrome (IC/BPS) comprises at least 2 phenotypes. Bladder centric patients typically demonstrate low bladder capacity (BC), often with Hunner lesion (HL), whereas non–bladder-centric patients typically have normal cystoscopic findings and more co-occurring nonurologic symptoms/syndromes (NUS), contributing to widespread pain beyond the bladder. Small fiber polyneuropathy (SFPN) is significantly associated with fibromyalgia, a frequent IC/BPS codiagnosis and may play an etiologic role in IC/BPS. We assessed SFPN status in bladder-centric versus non–bladder-centric IC/BPS patients. Methods Distal leg biopsies were obtained from 11 IC/BPS patients after therapeutic hydrodistention. Specimens were embedded/sectioned per standard protocol and stained for protein gene product 9.5, an intraepidermal nerve fiber marker. To determine SFPN status, intraepidermal nerve fiber density was calculated and compared with normative reference values stratified by age/sex. The SFPN prevalence and reported comorbidities were compared between low BC and/or HL-positive (bladder-centric) versus non–low BC, HL (non–bladder-centric) patients. Results Seven patients (63.6%) were SFPN positive. Non–bladder-centric patients demonstrated significantly more SFPN (6/7, 85.7%) compared with bladder-centric patients (1/4, 25.0%; P = 0.027). Non–bladder-centric patients also reported more comorbid NUS overall (1.25 ± 0.83 vs 5.86 ± 2.47; P = 0.003), including fibromyalgia (P = 0.010), migraines (P = 0.035), anxiety/panic disorder (P = 0.035), allergies (P = 0.027), and asthma (P = 0.035). Conclusions In this pilot study, SFPN was significantly more common in non–bladder-centric IC/BPS, that is, those patients who also reported greater prevalence of NUS, including fibromyalgia, migraines, anxiety/panic disorders, allergies, and asthma. These findings suggest that SFPN may have an etiologic role in a larger, systemic pain syndrome and should be explored further.

Urodynamic autonomic bladder dysfunction in women with complex chronic pelvic pain is associated with small fiber polyneuropathy

“…30 Another recent small study found biopsy + SFN in 64% (7/11) of patients with non-bladder centric interstitial cystitis/bladder pain syndrome (those without classic Hunner's ulcer and with the co-occurrence of other widespread pain beyond the bladder, such as fibromyalgia, migraine, anxiety, and asthma). 31 Overall, our cohort of complex CPP patients with urologic abnormalities associated with autonomic dysfunction on VUDS (detrusor underactivity and/or BNO) were more likely to have a diagnosis of SFN. Pinprick testing, symptoms of urgency, and elevated postvoid residual volume were also associated with SFN.…”

“…Another recent small study found biopsy + SFN in 64% (7/11) of patients with non‐bladder centric interstitial cystitis/bladder pain syndrome (those without classic Hunner's ulcer and with the co‐occurrence of other widespread pain beyond the bladder, such as fibromyalgia, migraine, anxiety, and asthma) 31 …”

Small Fiber Polyneuropathy May Be a Nexus Between Autonomic Nervous System Dysregulation and Pain in Interstitial Cystitis/Bladder Pain Syndrome

“…Several small case series studies have reported a similarly high incidence, up to 63%, of SFPN in women with IC/BPS ( 6 , 40 ), even when controlling for comorbid FMS. Further, several of the other disorders, beyond FMS, that commonly co-occur with IC/BPS have also been found to exhibit high rates of SFPN.…”

“…Although bladder pain is the defining characteristic, IC/BPS frequently co-occurs with numerous non-urological symptoms and syndromes including psychiatric disorders such as depression, vague symptoms such as chronic fatigue and sleep disturbances, as well as other poorly understood chronic functional pain disorders such as irritable bowel syndrome (IBS), fibromyalgia syndrome (FMS), and migraines ( 5 ). The clustering of these comorbidities, along with evidence stemming from physiologic and anatomic studies, including the high frequency of small fiber polyneuropathy (SFPN) ( 6 ), point to widespread neurologic abnormalities in this patient population. Many of the symptomatic and functional changes described in patients with IC/BPS are related to the autonomic nervous system, i.e., the system responsible for the regulation of a wide variety of bodily systems and functions ( Figure 1 ).…”

Interstitielle Zystitis: Was gibt es Neues zur Ätiopathogenese?

“…Eine Schädigung überwiegend der peripheren kleinen Nerven und myelinisierten (Aδ) Fasern oder der unmyelinisierten C-Fasern, wie sie bei der Small Fiber Polyneuropathie (SFP) auftritt, wurde in kleiner Fallzahl auch bei IC/BPS Patienten beschrieben [57]. Die SFP könnte als Mitbeteiligung bei der IC/BPS auftreten oder auch nur eine Untergruppe der IC/BPS Patienten vorzugsweise vom Nicht-Hunner Type definieren.…”