Peripheral Nervous System Involvement in Sjögren's Syndrome: Analysis of a Cohort From the Italian Research Group on Sjögren's Syndrome.

Giacomo Cafaro,Onorina Berardicurti,Chiara Baldini,Roberto Giacomelli,Angelica Gattamelata,Carlo Perricone,Elena Bartoloni,Roberta Priori,Roberto Gerli,Francesco Carubbi,Francesco Ferro,Luca Quartuccio,Saviana Gandolfo,Salvatore De Vita

doi:10.3389/fimmu.2021.615656

Abstract

PurposeThe prevalence of peripheral nervous system (PNS) involvement in primary Sjögren’s syndrome (pSS) has been reported to range from 2% to over 50%. Bias in study designs, including low number of patients and unclearly defined rheumatological and neurological diagnosis could explain such variability. Consequently, the exact depiction of PNS involvement in pSS is still lacking. This study aimed at analyzing the prevalence and the clinical and laboratory factors associated with PNS involvement in a very large cohort of well-characterized pSS patients with a clearly defined neurological diagnosis.MethodsClinical and serological data of 1,695 pSS patients with specific and accurate information on PNS involvement were analyzed. Comparisons between patients with and without PNS involvement and between patients with distinct subsets of PNS manifestations were performed.ResultsPrevalence of PNS involvement was 3.7%. The most frequent types observed were pure sensory neuropathies and axonal sensorimotor polyneuropathies (SMP). Patients with PNS involvement exhibited a more active disease profile and were more frequently treated with immunosuppressants. Intriguingly, clinical and serological negative prognostic factors, including purpura, extra-glandular manifestations, leukopenia, low complement and cryoglobulinemia, principally characterized patients with SMP, while subjects with pure sensory neuropathy displayed a milder phenotype.ConclusionOur results highlight that PNS involvement is rather rare, but prognostically relevant in pSS. Main adverse prognostic features characterize patients with SMP, while pure sensory neuropathies are usually associated with a mild clinical picture. These findings, useful for patient stratification, may suggest protean pathogenic pathways underlying different types of PNS manifestations in pSS.

Highlights

Primary Sjögren’s syndrome is a systemic autoimmune disease mainly affecting exocrine glands
PNS has a wide spectrum of clinical phenotypes including axonal sensorimotor polyneuropathies (SMP), multiple mononeuropathies and cranial nerve neuropathies that have been described in Primary Sjögren’s syndrome (pSS) [3,4,5]
It is intriguing to note that pure sensory neuropathies, in particular painful small-fiber neuropathy (SFN) and dorsal root ganglionopathy (DRG), seem to be peculiar features of the disease as they represent a considerable proportion of all PNS manifestations in pSS patients, and, pSS is one of the most frequent causes of pure sensory neuropathy among all immunemediated diseases [6,7,8]

Summary

Introduction

Primary Sjögren’s syndrome (pSS) is a systemic autoimmune disease mainly affecting exocrine glands. Neurological involvement represents a clinical challenge due to its heterogeneous presentation and diagnostic complexity [3,4,5]. It may manifest in both central (C) and peripheral (P) nervous system (NS), CNS involvement has been commonly described as a rare complication of pSS, usually affecting a very low proportion of patients. It is intriguing to note that pure sensory neuropathies, in particular painful small-fiber neuropathy (SFN) and dorsal root ganglionopathy (DRG), seem to be peculiar features of the disease as they represent a considerable proportion of all PNS manifestations in pSS patients, and, pSS is one of the most frequent causes of pure sensory neuropathy among all immunemediated diseases [6,7,8]

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