An online survey of pelvic congestion support group members regarding comorbid symptoms and syndromes

Abstract:

Objectives: Patients with pelvic congestion syndrome (PCS) often report overlapping somatic symptoms and syndromes. The objective of this study was to explore the prevalence of co-existing symptoms and self-reported syndrome diagnoses among women with PCS and to inform future research hypotheses.

Methods: A brief online survey was offered to members of a PCS support group website. Responses were assessed for self-reported co-existing symptoms and formal diagnoses, including: chronic fatigue syndrome, fibromyalgia, postural tachycardia syndrome, irritable bowel syndrome, migraines, interstitial cystitis, and temporomandibular joint dysfunction.

Results: Of a total of 6000 members, there were 398 respondents; 232 (59%) had not yet been treated for PCS. Among these, the most prevalent co-existing symptoms were as follows: severe fatigue (72%), dizziness (63%), IBS symptoms (61%), brain fog (33%), migraines (49%), polyuria or dysuria (41%), excessive sweating (31%), TMJ pain (31%), and loose skin or lax joints (18%). These are much higher than reported for the general female population. The most commonly self-reported comorbid syndrome diagnoses for the overall group of 398 were: irritable bowel syndrome (29%), fibromyalgia (13%), spinal nerve problems (18%), interstitial cystitis (10%), postural tachycardia syndrome (9%), hypertension (11%), chronic fatigue syndrome (10%), and Ehlers-Danlos syndrome (6%). Other than with hypertension, these rates are variably higher than in the general population.

Conclusion: Several self-reported co-existing symptoms and syndromes are more prevalent in members of a PCS support group relative to the reported prevalence in the general population. More formal investigation is warranted to evaluate this finding and to investigate potential etiologic links. Ehlers-Danlos Syndrome appears to be common in self identifying PCS women.

Source: Smith SJ, Sichlau M, Sewall LE, Smith BH, Chen B, Khurana N, Rowe PC. An online survey of pelvic congestion support group members regarding comorbid symptoms and syndromes. Phlebology. 2022 Jul 13:2683555221112567. doi: 10.1177/02683555221112567. Epub ahead of print. PMID: 35831253. https://pubmed.ncbi.nlm.nih.gov/35831253/

Prevalence of fibromyalgia 10 years after infection with Giardia lamblia: a controlled prospective cohort study

Abstract:

Objectives: To investigate whether acute infection with Giardia lamblia is associated with fibromyalgia 10 years after infection and whether fibromyalgia is associated with irritable bowel syndrome (IBS) and chronic fatigue (CF) in this setting.

Methods: A cohort study was established after an outbreak of G. lamblia in Bergen, Norway, 2004. Laboratory-confirmed cases and a matched control group were followed for 10 years. The main outcome was fibromyalgia 10 years after giardiasis, defined by the 2016 revisions of the fibromyalgia diagnostic criteria using the Fibromyalgia Survey Questionnaire (FSQ).

Results: The prevalence of fibromyalgia was 8.6% (49/572) among Giardia exposed compared to 3.1% (21/673) in controls (p<0.001). Unadjusted odds for having fibromyalgia was higher for Giardia exposed compared to controls (odds ratio (OR): 2.91, 95% confidence interval (CI): 1.72, 4.91), but adjusted for IBS and CF it was not (OR: 1.05, 95% CI: 0.57, 1.95). Among participants without CF the odds for fibromyalgia was 6.27 times higher for participants with IBS than those without (95% CI: 3.31, 11.91) regardless of exposure. Among participants without IBS the odds for fibromyalgia was 4.80 times higher for those with CF than those without (95% CI: 2.75, 8.37).

Conclusions: We found a higher prevalence of fibromyalgia among Giardia exposed compared to controls 10 years after the acute infection. Fibromyalgia was strongly associated with IBS and CF, and the difference between the exposed and controls can be attributed to the high prevalence of IBS and CF among the Giardia exposed. Notably, this study was not designed to establish causality between Giardia exposure and the outcomes.

Source: Hunskar GS, Rortveit G, Litleskare S, Eide GE, Hanevik K, Langeland N, Wensaas KA. Prevalence of fibromyalgia 10 years after infection with Giardia lamblia: a controlled prospective cohort study. Scand J Pain. 2021 Oct 21;22(2):348-355. doi: 10.1515/sjpain-2021-0122. PMID: 34679267. https://www.degruyter.com/document/doi/10.1515/sjpain-2021-0122/html (Full text)

No difference in serum levels of B-cell activating receptor and antibodies against cytolethal distending toxin B and flagellin in post-infectious irritable bowel syndrome and chronic fatigue syndrome after Giardia infection

Abstract :

Background and Aim: Functional gastrointestinal disorders (FGIDs) and chronic fatigue syndrome (CFS) frequently occur as comorbid conditions to each other. A shared etiology of these syndromes has been proposed because of their shared symptomatology and triggering by infections.

Antibodies against the bacterial antigens cytolethal distending toxin B (CdtB) and flagellin have been proposed to be biomarkers of irritable bowel syndrome (IBS), especially diarrhea-predominant IBS (IBS-D). It is unknown if they may also be associated with comorbid conditions such as CFS. On the other hand, elevated level of B-cell activating factor (BAFF) has been associated with CFS and inflammatory bowel disease (IBD) and subjective food intolerance.

Methods: We evaluated serum levels of anti-flagellin and anti-CdtB using an in-house enzyme-linked immunosorbent assay (ELISA) and BAFF with a commercially available ELISA kit in a cohort of patients who developed fatigue syndromes and/or FGIDs after Giardia infection, by comparing them with healthy controls without these conditions.

Results: We did not find significant differences in circulating BAFF, anti-CdtB, or anti-flagellin antibody levels in these patient groups compared to healthy controls. Therefore, our results do not support a role for BAFF, anti-CdtB, or anti-flagellin antibodies as universal biomarkers for IBS or CFS.

Conclusion: BAFF, anti-CdtB, or anti-flagellin antibodies cannot be considered as universal biomarkers for IBS or CFS.

Source: Hanevik, K., Saghaug, C., Aaland, M., Morch, K. and Langeland, N. (2022), No difference in serum levels of B-cell activating receptor and antibodies against cytolethal distending toxin B and flagellin in post-infectious irritable bowel syndrome and chronic fatigue syndrome after Giardia infection. JGH Open, 6: 185-188. https://doi.org/10.1002/jgh3.12724 (Full text)

Review article: Physical and psychological comorbidities associated with irritable bowel syndrome

Abstract:

Irritable bowel syndrome (IBS) is one of the most common gastrointestinal disorders encountered by physicians in primary and secondary care. Patients with IBS commonly present with various extraintestinal complaints, which account for a substantial clinical and economic burden. The common extraintestinal comorbidities associated with IBS include anxiety, depression, somatisation, fibromyalgia, chronic fatigue syndrome, chronic pelvic pain, interstitial cystitis, sexual dysfunction and sleep disturbance. The presence of comorbidity in IBS poses a diagnostic and therapeutic challenge with patients frequently undergoing unnecessary investigations and interventions, including surgery. This review discusses the different physical and psychological comorbidities associated with IBS, the shared pathophysiological mechanisms and potential management strategies

Source: Shiha MG, Aziz I. Review article: Physical and psychological comorbidities associated with irritable bowel syndrome. Aliment Pharmacol Ther. 2021 Dec;54 Suppl 1:S12-S23. doi: 10.1111/apt.16589. PMID: 34927759. https://pubmed.ncbi.nlm.nih.gov/34927759/

Local immune response to food antigens drives meal-induced abdominal pain

Abstract:

Up to 20% of people worldwide develop gastrointestinal symptoms following a meal1, leading to decreased quality of life, substantial morbidity and high medical costs. Although the interest of both the scientific and lay communities in this issue has increased markedly in recent years, with the worldwide introduction of gluten-free and other diets, the underlying mechanisms of food-induced abdominal complaints remain largely unknown. Here we show that a bacterial infection and bacterial toxins can trigger an immune response that leads to the production of dietary-antigen-specific IgE antibodies in mice, which are limited to the intestine.

Following subsequent oral ingestion of the respective dietary antigen, an IgE- and mast-cell-dependent mechanism induced increased visceral pain. This aberrant pain signalling resulted from histamine receptor H1-mediated sensitization of visceral afferents. Moreover, injection of food antigens (gluten, wheat, soy and milk) into the rectosigmoid mucosa of patients with irritable bowel syndrome induced local oedema and mast cell activation. Our results identify and characterize a peripheral mechanism that underlies food-induced abdominal pain, thereby creating new possibilities for the treatment of irritable bowel syndrome and related abdominal pain disorders.

Source: Aguilera-Lizarraga, J., Florens, M.V., Viola, M.F. et al. Local immune response to food antigens drives meal-induced abdominal pain. Nature (2021). https://doi.org/10.1038/s41586-020-03118-2 https://www.nature.com/articles/s41586-020-03118-2#Abs1

Chronic Pain Syndromes and Their Laryngeal Manifestations

Abstract:

IMPORTANCE: Fibromyalgia syndrome (FMS), irritable bowel syndrome (IBS), and chronic fatigue syndrome (CFS) are traditionally considered as distinct entities grouped under chronic pain syndrome (CPS) of an unknown origin. However, these 3 disorders may exist on a spectrum with a shared pathophysiology.

OBJECTIVE: To investigate whether the clinical presentation of FMS, IBS, and CFS is similar in a population presenting with voice and laryngeal disorders.

DESIGN, SETTING, AND PARTICIPANTS: This case series was a retrospective review of the medical records and clinical notes of patients treated between January 1, 2016, and December 31, 2017, at the Johns Hopkins Voice Center in Baltimore, Maryland. Patients with at least 1 CPS of interest (FMS, IBS, or CFS) were included (n = 215), along with patients without such diagnoses (n = 4034). Diagnoses, demographic, and comorbidity data were reviewed. Diagnoses related to voice and laryngeal disorders were subdivided into 5 main categories (laryngeal pathology, functional voice disorders, airway problems, swallowing problems, and other diagnoses).

MAIN OUTCOMES AND MEASURES: Prevalence and odds ratios of 45 voice and laryngeal disorders were reviewed. Odds ratios (ORs) were calculated by comparing patients with CPS with control patients.

RESULTS: In total, 4249 individuals were identified; 215 (5.1%) had at least 1 CPS and 4034 (94.9%) were control participants. Patients with CPS were 3 times more likely to be women compared with the control group (173 of 215 [80.5%] vs 2318 of 4034 [57.5%]; OR, 3.156; 95% CI, 2.392-4.296), and the CPS group had a mean (SD) age of 57.80 (15.30) years compared with the mean (SD) age of 55.77 (16.97) years for the control group. Patients with CPS were more likely to present with functional voice disorders (OR, 1.812; 95% CI, 1.396-2.353) and less likely to present with laryngeal pathology (OR, 0.774; 95% CI, 0.610-0.982) or airway problems (OR, 0.474; 95% CI, 0.285-0.789).

CONCLUSIONS AND RELEVANCE: The voice and airway presentation of patients with FMS, IBS, and/or CFS appears to be indistinguishable from each other. This finding suggests that these 3 diseases share upper airway symptoms.

Source: Piersiala K, Akst LM, Hillel AT, Best SR. Chronic Pain Syndromes and Their Laryngeal Manifestations. JAMA Otolaryngol Head Neck Surg. 2020 Apr 30. doi: 10.1001/jamaoto.2020.0530. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/32352483

Symptom frequency and development of a generic functional disorder symptom scale suitable for use in studies of patients with irritable bowel syndrome, fibromyalgia syndrome or chronic fatigue syndrome

Abstract:

OBJECTIVES: To describe the extent to which irritable bowel syndrome (IBS), fibromyalgia syndrome (FMS), and chronic fatigue syndrome (CFS) exhibit symptom overlap, and to validate a patient-derived, generic symptom questionnaire.

METHODS: A patient-derived 61-item symptom-frequency questionnaire was completed by participants recruited through IBS, FMS and CFS self-help websites. Principal axis factor analysis with oblimin rotation was performed separately for those reporting an IBS, FMS or CFS diagnosis.

RESULTS: Questionnaires were completed by 1751 participants of whom 851 reported more than one of the three diagnoses. Stomach pain on at least a weekly basis was reported by 79% of IBS, 52% of FMS, and 43% of CFS single diagnosis participants. Pain increasing the day after activity was reported by 32% of IBS, 94% of FMS, and 85% of CFS single diagnosis participants. Waking still tired at least once weekly was reported by 75% of IBS, 97% of FMS, and 95% of CFS single diagnosis participants. Exploratory factor analysis produced consistent results across all three diagnostic groups, the 61 items loading on 12 correlated factors with a single higher order factor on which all items loaded. Frequency analysis led to the rejection of one item (cold sores on or near lips), and freeform reporting by participants of additional symptoms identified an additional five, namely, restless legs, hair loss/brittle hair/thinning, dizziness/balance problems, blurred vision and urination problems.

CONCLUSIONS: IBS, FMS and CFS are polysymptomatic spectrum disorders with a wide range of overlapping symptoms, many of which are unrelated to diagnostic criteria. Frequency analysis and factor analysis confirm the validity of using the same questionnaire across different diagnostic categories. The 65-item general symptom questionnaire (GSQ-65) is a valid generic symptom scale suitable for assessing the many different symptoms of people with IBS, FMS and CFS.

Source: Hyland ME, Bacon AM, Lanario JW, Davies AF. Symptom frequency and development of a generic functional disorder symptom scale suitable for use in studies of patients with irritable bowel syndrome, fibromyalgia syndrome or chronic fatigue syndrome. Chronic Dis Transl Med. 2019 Jun 24;5(2):129-138. doi: 10.1016/j.cdtm.2019.05.003. eCollection 2019 Jun. https://www.sciencedirect.com/science/article/pii/S2095882X18300987?via%3Dihub (Full article)

A Systematic Review of Probiotic Interventions for Gastrointestinal Symptoms and Irritable Bowel Syndrome in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME)

Abstract:

Gastrointestinal (GI) symptoms and irritable bowel (IB) symptoms have been associated with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). The aim of this study was to conduct a systematic review of these symptoms in CFS/ME, along with any evidence for probiotics as treatment. Pubmed, Scopus, Medline (EBSCOHost) and EMBASE databases were searched to source relevant studies for CFS/ME. The review included any studies examining GI symptoms, irritable bowel syndrome (IBS) and/or probiotic use.

Studies were required to report criteria for CFS/ME and study design, intervention and outcome measures. Quality assessment was also completed to summarise the level of evidence available. A total of 3381 publications were returned using our search terms. Twenty-five studies were included in the review. Randomised control trials were the predominant study type (n = 24). Most of the studies identified examined the effect of probiotic supplementation on the improvement of IB symptoms in IBS patients, or IB symptoms in CFS/ME patients, as well as some other significant secondary outcomes (e.g. quality of life, other gastrointestinal symptoms, psychological symptoms).

The level of evidence identified for the use of probiotics in IBS was excellent in quality; however, the evidence available for the use of probiotic interventions in CFS/ME was poor and limited. There is currently insufficient evidence for the use of probiotics in CFS/ME patients, despite probiotic interventions being useful in IBS. The studies pertaining to probiotic interventions in CFS/ME patients were limited and of poor quality overall. Standardisation of protocols and methodology in these studies is required.

Source: Corbitt M, Campagnolo N, Staines D, Marshall-Gradisnik S. A Systematic Review of Probiotic Interventions for Gastrointestinal Symptoms and Irritable Bowel Syndrome in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME). Probiotics Antimicrob Proteins. 2018 Feb 20. doi: 10.1007/s12602-018-9397-8. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/29464501

Prevalence of Irritable Bowel Syndrome and Chronic Fatigue 10 Years after Giardia Infection

Abstract:

BACKGROUND & AIMS: Irritable bowel syndrome (IBS) is a complication that can follow gastrointestinal infection, but it is not clear if patients also develop chronic fatigue. We investigated the prevalence and odds ratio of IBS and chronic fatigue 10 years after an outbreak of Giardia lamblia, compared with a control cohort, and changes in prevalence over time.

METHODS: We performed a prospective follow-up study of 1252 laboratory-confirmed cases of giardiasis (exposed), which developed in Bergen, Norway in 2004. Statistics Norway provided us with information from 2504 unexposed individuals from Bergen, matched by age and sex (controls). Questionnaires were mailed to participants 3, 6, and 10 years after the outbreak. Results from the 3- and 6-year follow-up analyses have been published previously. We report the 10-year data and changes in prevalence among time points, determined by logistic regression using generalized estimating equations.

RESULTS: The prevalence of IBS 10 years after the outbreak was 43% (n=248) among 576 exposed individuals and 14% (n=94) among 685 controls (adjusted odds ratio for development of IBS in exposed individuals, 4.74; 95% CI, 3.61-6.23). At this time point, the prevalence of chronic fatigue was 26% (n=153) among 587 exposed individuals and 11% (n=73) among 692 controls (adjusted odds ratio, 3.01; 95% CI, 2.22-4.08). The prevalence of IBS among exposed persons did not change significantly from 6 years after infection (40%) to 10 years after infection (43%; adjusted odds ratio for the change 1.03; 95% CI, 0.87-1.22). However, the prevalence of chronic fatigue decreased from 31% at 6 years after infection to 26% at 10 years after infection (adjusted odds ratio for the change 0.74; 95% CI, 0.61-0.90).

CONCLUSION: The prevalence of IBS did not change significantly from 6 years after an outbreak of Giardia lamblia infection in Norway to 10 years after. However, the prevalence of chronic fatigue decreased significantly from 6 to 10 years afterward. IBS and chronic fatigue were still associated with giardiasis 10 years after the outbreak.

Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

Source: Litleskare S, Rortveit G, Eide GE, Hanevik K, Langeland N, Wensaas KA. Prevalence of Irritable Bowel Syndrome and Chronic Fatigue 10 Years after Giardia Infection. Clin Gastroenterol Hepatol. 2018 Jan 25. pii: S1542-3565(18)30088-0. doi: 10.1016/j.cgh.2018.01.022. [Epub ahead of print]

Chronic fatigue syndrome linked to imbalanced microbiome

Press Release: Columbia University's Mailman School of Public Health, April 26. 2017. Scientists at the Center for Infection and Immunity (CII) at Columbia University's Mailman School of Public Health have discovered abnormal levels of specific gut bacteria related to chronic fatigue syndrome/myalgic encephalomyelitis, or ME/CFS, in patients with and without concurrent irritable bowel syndrome, or IBS. Findings are published in the journal Microbiome.

The study is among the first to disentangle imbalances in the gut bacteria in individuals with ME/CFS and IBS. ME/CFS is a complex, debilitating disorder characterized by extreme fatigue after exertion and other symptoms including muscle and joint pain, cognitive dysfunction, sleep disturbance, and orthostatic intolerance. Up to 90 percent of ME/CFS patients also have IBS.

The researchers followed 50 patients and 50 matched healthy controls recruited at four ME/CFS clinical sites. They tested for bacterial species in fecal samples, and for immune molecules in blood samples.

They report:

  • Levels of distinct intestinal bacterial species — Faecalibacterium, Roseburia, Dorea, Coprococcus, Clostridium, Ruminococcus, Coprobacillus — were strongly associated with ME/CFS; their combined relative abundance appeared to be predictive of diagnosis

  • Increased abundance of unclassified Alistipes and decreased Faecalibacterium were the top biomarkers of ME/CFS with IBS; while increased unclassified Bacteroides abundance and decreased Bacteroides vulgatus were the top biomarkers of ME/CFS without IBS

  • An analysis of bacterial metabolic pathways associated with disturbances in gut bacteria revealed distinct differences between ME/CFS and ME/CFS subgroups relative to healthy controls

  • In ME/CFS subgroups, symptom severity measures, including pain and fatigue, correlated with the abundance of distinct bacterial types and metabolic pathways

  • No changes were observed in immune markers — a finding that may reflect the dearth of participants who had been ill for a short time; earlier research suggests immune changes may only be evident when comparing short and long duration cases

"Individuals with ME/CFS have a distinct mix of gut bacteria and related metabolic disturbances that may influence the severity of their disease," says co-lead investigator Dorottya Nagy-Szakal, postdoctoral research scientist at CII.

"Our analysis suggests that we may be able to subtype patients with ME/CFS by analyzing their fecal microbiome," says co-lead investigator Brent L. Williams, assistant professor of Pathology and Cell Biology at CII. "Subtyping may provide clues to understanding differences in manifestations of disease."

"Much like IBS, ME/CFS may involve a breakdown in the bidirectional communication between the brain and the gut mediated by bacteria, their metabolites, and the molecules they influence," says senior author W. Ian Lipkin, director of CII and John Snow Professor of Epidemiology at Columbia's Mailman School. "By identifying the specific bacteria involved, we are one step closer to more accurate diagnosis and targeted therapies."

Journal Reference: Dorottya Nagy-Szakal, Brent L. Williams, Nischay Mishra, Xiaoyu Che, Bohyun Lee, Lucinda Bateman, Nancy G. Klimas, Anthony L. Komaroff, Susan Levine, Jose G. Montoya, Daniel L. Peterson, Devi Ramanan, Komal Jain, Meredith L. Eddy, Mady Hornig, W. Ian Lipkin. Fecal metagenomic profiles in subgroups of patients with myalgic encephalomyelitis/chronic fatigue syndrome. Microbiome, 2017; 5 (1) DOI: 10.1186/s40168-017-0261-y https://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-017-0261-y