Editorial

Functional somatic syndromes may be either “polysyndromic” or “monosyndromic”

To test the hypothesis that risk factors for bladder pain syndrome/interstitial cystitis (BPS/IC) in women differ between those with and without the BPS/IC prodrome.

Incident cases of BPS/IC and healthy controls were recruited nationally. More than half the BPS/IC cases reported subsyndromal urinary symptoms for decades before onset of BPS/IC and were identified as having the prodrome. Risk factors for BPS/IC were examined separately for cases with and without the prodrome using a set of matched controls.

Two risk factors distinguished 178 prodrome from 134 non-prodrome cases. One was “UTIs” in the year before BPS/IC onset, possibly a manifestation of the prodrome itself. The other was the presence of the maximal number of nonbladder syndromes (NBSs): prodrome cases were 12 times more likely than non-prodrome cases to have ≥4 NBSs. Additional risk factors for prodrome and/or non-prodrome cases were the direct association of exogenous female hormones, as well as 3 inverse associations: type 2 diabetes mellitus, multiple pregnancies, and current daily smoking.

Prodrome cases developed urinary symptoms in their early 20s (ie, the prodrome) and were at very high risk of numerous NBSs. Non-prodrome cases developed urinary symptoms in their early 40s (ie, full-blown BPS/IC) and were no more likely than controls to have the maximal number of NBSs. These findings are consistent with recent suggestions of two BPS/IC phenotypes: one with systemic and psychosocial manifestations and the other more specific to the bladder. Additionally, several risk factors identified here might be hints of related or causal nervous system pathophysiologies.

The current delimitation of functional somatic syndromes (FSS) is inconsistent. We aimed to investigate somatic symptom profiles in the general adult population to contribute to a new, data-driven delimitation of FSS.

Information on 31 self-reported somatic symptoms used in the delimitation of various FSS and bodily distress syndrome (BDS) was obtained from the DanFunD study—a population-based cohort study on 9656 adults (participation 33.6%) from Greater Copenhagen, Denmark. Latent class analysis was used to identify symptom profiles. The profiles were described by their relation with sex, age, chronic disease, self-perceived health, symptom impact, self-reported FSS, and BDS case-status.

Eight symptom profiles were identified. The largest profile had no symptoms (49% of the population). Three profiles were characterized by a few, specific symptoms: muscle and joint pain (17%), gastrointestinal symptoms (6%), and general symptoms (13%). Three profiles had multiple symptoms in specific combinations: musculoskeletal and general symptoms (7%); fatigue, musculoskeletal and gastrointestinal symptoms (3%); and cardiopulmonary, gastrointestinal and general symptoms (3%). Lastly, one profile (2%) had high probability of all symptoms. The last four profiles (15%) were strongly associated with BDS case-status, poor self-perceived health and high impact of symptoms. Analyses excluding persons with multi-symptomatic chronic disease showed similar results.

We identified eight symptom profiles characterized by specific combinations of symptoms. Four of these had multiple symptoms from several bodily systems showing large overlap with BDS, possibly indicating subtypes of FSS. The profiles contribute to a new delimitation of FSS by illustrating the importance of specific symptom combinations.

Somatoform disorders (SD) are common medical disorders with prevalence rates between 3.5% and 18.4%, depending on country and medical setting. SD as outlined in the ICD-10 exhibits various biological, social, and psychological pathogenic factors. Little is known about the neural correlates of SD. The aims of this meta-analysis are to identify neuronal areas that are involved in SD and consistently differ between patients and healthy controls. We conducted a systematic literature research on neuroimaging studies of SD. Ten out of 686 studies fulfilled the inclusion criteria and were analyzed using activation likelihood estimation. Five neuronal areas differ between patients with SD and healthy controls namely the premotor and supplementary motor cortexes, the middle frontal gyrus, the anterior cingulate cortex, the insula, and the posterior cingulate cortex. These areas seem to have a particular importance for the occurrence of SD. Out of the ten studies two did not contribute to any of the clusters. Our results seem to largely overlap with the circuit network model of somatosensory amplification for SD. It is conceivable that functional disorders, independent of the clinical impression, show similar neurobiological processes. While overlaps do occur it is necessary to understand single functional somatic syndromes and their aetiology for future research, terminology, and treatment guidelines.

Functional somatic syndromes are common and disabling conditions that all include chronic pain, and which may be related to central nervous system sensitisation. Here, we address the concept of central sensitisation as a physiological basis for the functional somatic syndromes.

A narrative review of the current literature on central sensitisation and physiological studies in the functional somatic syndromes.

Central sensitisation may be a common neurophysiological process that is able to explain non-painful as well as painful symptoms in these disorders. Furthermore, central sensitisation may represent an endophenotypic vulnerability to the development of these syndromes that potentially explains why they cluster together.

Further research is needed to verify these findings, including prospective studies and the standardisation of combined methods of investigation in the study of central sensitisation in functional somatic syndromes. In turn, this may lead to new explanatory mechanisms and treatments being evaluated. Our conclusions add to the debate over the nomenclature of these syndromes but importantly also provide an explanation for our patients.

To determine whether bladder pain syndrome/interstitial cystitis (BPS/IC) has the characteristics of a functional somatic syndrome (FSS).

There is no accepted definition of an FSS. Consequently, this paper reviewed the literature for common FSS characteristics and for reports that BPS/IC has these characteristics.

Eleven articles met inclusion and exclusion criteria and yielded 18 FSS characteristics. BPS/IC patients manifest all but two: the exceptions were normal light microscopic anatomy (after hydrodistention under anesthesia, some BPS/IC bladders have Hunner's lesions and most have petechial hemorrhages) and normal laboratory tests (many BPS/IC patients have hematuria). Petechial hemorrhages and hematuria are probably related and may appear during naturally-occurring bladder distention. Without such distention, then, the 90% of BPS/IC patients without a Hunner's lesion have all the characteristics of an FSS. Comparisons in the opposite direction were consistent: several additional features of BPS/IC were found in FSSs.

This systematic but untested method is consistent with but does not test the hypothesis that BPS/IC in some patients might best be understood as an FSS. Like most conditions, BPS/IC is probably heterogeneous; hence only a proportion of BPS/IC cases are likely to be manifestations of an FSS. This hypothesis has several implications. Explorations of processes that connect the FSSs might contribute to understanding the pathogenesis of BPS/IC. Patients with FSSs are at risk for BPS/IC and may benefit from future preventive strategies. Therapies that are useful in FSSs also may be useful in some cases of BPS/IC.

To test the hypothesis that more bladder pain syndrome/interstitial cystitis (BPS/IC) cases than controls report pre-onset urinary symptoms.

In a risk factor study, the date of BPS/IC onset (index date) was systematically determined in 312 female incident cases; the mean age at onset was 42.3 years. Frequency-matched controls were compared on pre–index date medical history.

Three pre–index date symptoms were more common in BPS/IC cases: pelvic pain with urinary features, frequency, and bladder pain; 178 cases (57%) vs 56 controls (18%) had at least 1 symptom (P <.001). Several perspectives suggested that prodromal symptoms were different from BPS/IC symptoms. In prodromal women, the median age of the earliest urinary symptom “more than other people” was 20 years. Women with the prodrome were significantly more likely than those without to have pre–index date nonbladder syndromes (NBSs). The prodrome predicted not only BPS/IC but also a worse prognosis for it.

Before the onset of BPS/IC, pelvic pain with urinary features, frequency, and/or bladder pain were reported by more than half the cases. Prodromal women recalled abnormal urinary symptoms decades before the onset of BPS/IC. The prodrome was associated with prior NBSs and predicted not only BPS/IC but also its poor prognosis. These data generated 2 hypotheses: that (1) prodromal symptoms are different from BPS/IC symptoms and (2) pain amplification links NBSs, the prodrome, the appearance of BPS/IC, and its poor prognosis. Recognition of the prodrome might provide opportunities for prevention of fully developed BPS/IC.