The number of existing functional somatic syndromes (FSSs) is an important risk factor for new, different FSSs

Abstract

Objective

The objective of this study is to test the hypothesis that the number of functional somatic syndromes (FSSs) predicts new, additional FSSs.

Methods

In a recent case–control study of interstitial cystitis/painful bladder syndrome (IC/PBS), we used symptom-based consensus definitions to identify these FSSs: fibromyalgia (FM), chronic fatigue syndrome (CFS), irritable bowel syndrome (IBS), chronic pelvic pain, migraine, sicca syndrome and panic disorder. Those present before the incidence year were called antecedent FSSs; those with onset during the incidence year were called incident FSSs. In each of two groups, 312 IC/PBS cases and 313 controls, rates of incident FSSs were compared among those with 0, 1, 2, or ≥ 3 antecedent FSSs. Confounding was assessed using logistic regression analyses that included the individual antecedent FSSs, published correlates of these FSSs, and demographic variables.

Results

The incidence of a new FSS increased with the number of antecedent FSSs, as did that of incident FM, CFS and IBS studied separately. These findings were not confounded by other variables. The presence of multiple antecedent FSSs generally had the highest odds ratio for new, different, incident FSSs.

Conclusions

This study revealed that the number of antecedent FSSs was among the strongest risk factors for other FSSs, especially incident FM, CFS and IBS. This suggests that the FSSs are linked through a polysyndromic phenotype. If each FSS is heterogeneous, to seek a pathogenesis common to all FSSs, individuals with multiple FSSs should be sought; to seek a pathogenesis unique to a specific FSS, mature persons who have only that FSS should be studied.

Introduction

Functional somatic syndromes (FSSs) are often discussed as a group because they have many similarities: absent or incidental local pathology, non-diagnostic laboratory tests, over-representation in women, association with childhood adversities, exacerbation with stress and menstruation, chronicity, co-morbidity and unknown etiology [1]. Fibromyalgia (FM), chronic fatigue syndrome (CFS) and irritable bowel syndrome (IBS) are almost always included as FSSs; chronic pelvic pain (CPP) and migraine sometimes are; and sicca syndrome and panic disorder have similar characteristics including association with these syndromes [1].

Interstitial cystitis/painful bladder syndrome (IC/PBS) is a chronic disorder diagnosed by bladder pain and urinary symptoms that has many of the characteristics of an FSS and, indeed, some experts include it in discussions of FSSs [1], [2]. In a recent case–control study of over 600 women, Events Preceding Interstitial Cystitis (EPIC), we showed that 11 syndromes were risk factors for IC/PBS; these syndromes included the seven above plus depression, allergies, asthma and vulvodynia [3]. These antecedent syndromes generally were associated with each other, e.g. a woman who had FM was more likely to have IBS than if she did not have FM [3]. The risk of IC/PBS increased as the number of these antecedent syndromes increased [4]. Indeed, the presence of multiple syndromes had the largest odds ratio for IC/PBS of any variable tested and this association was not confounded by other variables [5].

These findings generated the hypothesis that patients who had IC/PBS and multiple syndromes shared a pathogenesis that was common to IC/PBS and each of the other syndromes [4], [6]. If such a shared pathogenesis existed, then a corollary hypothesis would be that the presence of multiple syndromes is a marker for the shared pathogenesis and would emerge as a risk factor for each of the remaining syndromes, just as it had for IC/PBS. The study design allowed testing of this hypothesis.