# Autonomic dysfunction and its associations with clinical parameters in Familial Mediterranean Fever: a cross-sectional study

## TL;DR

This study found that people with Familial Mediterranean Fever have more autonomic nervous system issues, which may affect their quality of life and mental health.

## Contribution

The study is the first to show parasympathetic dysfunction in FMF patients and its links to disease markers and quality of life.

## Key findings

- FMF patients had higher autonomic dysfunction scores compared to healthy controls.
- Parasympathetic function was reduced in FMF patients, with correlations to inflammation and disease activity.
- Autonomic dysfunction in FMF was associated with worse quality of life and mental health outcomes.

## Abstract

This study aimed to assess autonomic dysfunction in patients with Familial Mediterranean Fever (FMF), and to explore its association with disease characteristics and comorbidities. Thirty FMF patients and 30 healthy controls were enrolled in this cross-sectional study. Disease features and quality of life were recorded using the Familial Mediterranean Fever Quality of Life Scale (FMF-QoL). The Composite Autonomic Symptom Score-31 (COMPASS-31), Hospital Anxiety and Depression Scale (HADS), Fatigue Severity Scale (FSS), Jenkins Sleep Scale (JSS), and Fibromyalgia Rapid Screening Tool (FiRST) were noted. Parasympathetic nervous system was evaluated by R-R interval variability (RRIV) during normal and deep breathing and 30:15 ratio tests with electromyography, while the sympathetic nervous system was assessed by sympathetic skin response (SRR), blood pressure response to standing and sustained handgrip tests. FMF patients had higher total median COMPASS-31 scores than controls (15.09 vs. 5.12, p = 0.001), with significantly higher secretomotor, gastrointestinal, bladder, and pupillomotor subdomain scores (p < 0.05). RRIV during normal breathing was lower in the FMF group compared with controls (17.29 vs. 21.27, p = 0.015). No between-group differences were observed in sympathetic function tests (p > 0.05). In correlation analyses, RRIV during normal breathing correlated negatively with CRP (r = − 0.378, p = 0.04). Sympathetic parameters showed negative correlations with CRP (left plantar SSR latency: r = − 0.398, p = 0.03; blood pressure response to handgrip: r = − 0.405, p = 0.026) and with annual attack frequency (left plantar SSR amplitude: r = − 0.449, p = 0.01). Total COMPASS-31 scores correlated with FMF-QoL (r > 0.5, p < 0.001), HADS-anxiety (r = 0.550, p = 0.002), HADS-depression (r = 0.633, p < 0.001), FSS (r = 0.600, p < 0.001), JSS (r = 0.705, p < 0.001), and FiRST (r = 0.598, p < 0.001). FMF patients showed predominant parasympathetic dysfunction, while sympathetic findings were limited to correlations suggesting possible subclinical involvement. These autonomic alterations may contribute to reduced quality of life and associated symptoms such as fatigue, depression, and sleep disturbance.

The online version contains supplementary material available at 10.1007/s00296-026-06076-6.