Tag: fibromyalgia

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

Systemic Hyperalgesia in Females with Gulf War Illness, Chronic Fatigue Syndrome and Fibromyalgia

Abstract:

Pain is a diagnostic criterion for Gulf War Illness (GWI), Chronic Fatigue Syndrome (CFS), and fibromyalgia (FM). The physical sign of systemic hyperalgesia (tenderness) was assessed in 920 women who were stratified by 2000 Kansas GWI, 1994 CFS, and 1990 FM criteria.

Pressure was applied by dolorimetry at 18 traditional tender points and the average pressure causing pain determined. GWI women were the most tender (2.9 ± 1.6 kg, mean ± SD, n = 70), followed by CFS/FM (3.1 ± 1.4 kg, n = 196), FM (3.9 ± 1.4 kg, n = 56), and CFS (5.8 ± 2.1 kg, n = 170) compared to controls (7.2 ± 2.4 kg, significantly highest by Mann-Whitney tests p < 0.0001, n = 428). Receiver operating characteristics set pressure thresholds of 4.0 kg to define GWI and CFS/FM (specificity 0.85, sensitivities 0.80 and 0.83, respectively), 4.5 kg for FM, and 6.0 kg for CFS.

Pain, fatigue, quality of life, and CFS symptoms were equivalent for GWI, CFS/FM and CFS. Dolorimetry correlated with symptoms in GWI but not CFS or FM. Therefore, women with GWI, CFS and FM have systemic hyperalgesia compared to sedentary controls.

The physical sign of tenderness may complement the symptoms of the Kansas criteria as a diagnostic criterion for GWI females, and aid in the diagnosis of CFS. Molecular mechanisms of systemic hyperalgesia may provide new insights into the neuropathology and treatments of these nociceptive, interoceptive and fatiguing illnesses.

Source: Surian AA, Baraniuk JN. Systemic Hyperalgesia in Females with Gulf War Illness, Chronic Fatigue Syndrome and Fibromyalgia. Sci Rep. 2020 Apr 1;10(1):5751. doi: 10.1038/s41598-020-62771-9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7113257/ (Full text)

Characterization of Cortisol Dysregulation in Fibromyalgia and Chronic Fatigue Syndromes: A State-Space Approach

Abstract:

OBJECTIVE: Fibromyalgia syndrome (FMS) and chronic fatigue syndrome (CFS) are complicated medical disorders, with little known etiologies. The purpose of this research is to characterize FMS and CFS by studying the variations in cortisol secretion patterns, timings, amplitudes, the number of underlying pulses, as well as infusion and clearance rates of cortisol.

METHODS: Using a physiological state-space model with plausible constraints, we estimate the hormonal secretory events and the physiological system parameters (i.e., infusion and clearance rates).

RESULTS: Our results show that the clearance rate of cortisol is lower in FMS patients as compared to their matched healthy individuals based on a simplified cortisol secretion model. Moreover, the number, magnitude, and energy of hormonal secretory events are lower in FMS patients. During early morning hours, the magnitude and energy of the hormonal secretory events are higher in CFS patients.

CONCLUSION: Due to lower cortisol clearance rate, there is a higher accumulation of cortisol in FMS patients as compared to their matched healthy subjects. As the FMS patient accumulates higher cortisol residues, internal inhibitory feedback regulates the hormonal secretory events. Therefore, the FMS patients show a lower number, magnitude, and energy of hormonal secretory events. Though CFS patients have the same number of secretory events, they secrete lower quantities during early morning hours. When we compare the results for CFS patients against FMS patients, we observe different cortisol alteration patterns.

SIGNIFICANCE: Characterizing CFS and FMS based on the cortisol alteration will help us to develop novel methods for treating these disorders.

Source: Pednekar DD, Amin MR, Fekri Azgomi H, Aschbacher K, Crofford LJ, Faghih RT. Characterization of Cortisol Dysregulation in Fibromyalgia and Chronic Fatigue Syndromes: A State-Space Approach. IEEE Trans Biomed Eng. 2020 Mar 5. doi: 10.1109/TBME.2020.2978801. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/32149617

From IBS to ME – The dysbiotic march hypothesis

Abstract:

Irritable bowel syndrome (IBS) is often associated with other unexplained complaints like chronic fatigue syndrome (CFS), fibromyalgia and myalgic encephalopathy (ME). The pathogenesis of the relationship is unknown. Intestinal dysbiosis may be a common abnormality, but based on 1100 consecutive IBS patients examined over a nine years period, we hypothesize that the development of the disease, often from IBS to ME, actually manifests a “dysbiotic march”. In analogy with “the atopic march” in allergic diseases, we suggest “a dysbiotic march” in IBS; initiated by extensive use of antibiotics during childhood, often before school age. Various abdominal complaints including IBS may develop soon thereafter, while systemic symptom like CFS, fibromyalgia and ME may appear years later.

Source: Berstad A, Hauso O, Berstad K, Berstad JER. From IBS to ME – The dysbiotic march hypothesis. Med Hypotheses. 2020 Feb 26;140:109648. doi: 10.1016/j.mehy.2020.109648. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/32126475

Activation of Transposable Elements in Immune Cells of Fibromyalgia Patients

Abstract:

Advancements in nucleic acid sequencing technology combined with an unprecedented availability of metadata have revealed that 45% of the human genome constituted by transposable elements (TEs) is not only transcriptionally active but also physiologically necessary. Dysregulation of TEs, including human retroviral endogenous sequences (HERVs) has been shown to associate with several neurologic and autoimmune diseases, including Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). However, no study has yet addressed whether abnormal expression of these sequences correlates with fibromyalgia (FM), a disease frequently comorbid with ME/CFS.

The work presented here shows, for the first time, that, in fact, HERVs of the H, K and W types are overexpressed in immune cells of FM patients with or without comorbid ME/CFS. Patients with increased HERV expression (N = 14) presented increased levels of interferon (INF-β and INF-γ) but unchanged levels of TNF-α. The findings reported in this study could explain the flu-like symptoms FM patients present with in clinical practice, in the absence of concomitant infections. Future work aimed at identifying specific genomic loci differentially affected in FM and/or ME/CFS is warranted.

Source: Ovejero T, Sadones O, Sánchez-Fito T, Almenar-Pérez E, Espejo JA, Martín-Martínez E, Nathanson L, Oltra E. Activation of Transposable Elements in Immune Cells of Fibromyalgia Patients. Int J Mol Sci. 2020 Feb 18;21(4). pii: E1366. doi: 10.3390/ijms21041366. https://www.mdpi.com/1422-0067/21/4/1366 (Full text)

A System Theoretic Investigation of Cortisol Dysregulation in Fibromyalgia Patients with Chronic Fatigue

Abstract:

Fibromyalgia Syndrome (FMS) and Chronic Fatigue Syndrome (CFS) are complex medical conditions with similar symptoms such as anxiety, fatigue, depression, headaches, muscle aches and joint pain. The etiology of both these syndromes is unknown. The objective of this study is to characterize FMS, both in the presence and in the absence of CFS, by analyzing variations in cortisol secretion patterns, timings, amplitudes, and the number of the underlying pulses as well as infusion and clearance rates.

The comparison is performed against matched healthy control subjects. We estimate the hormonal secretory events by deconvolving cortisol data using a two-step coordinate descent approach. The first step implements a sparse recovery approach to infer the amplitudes and the timings of the cortisol secretion events from limited cortisol hormone data. The main advantage of this method is estimating the cortisol secretory events using a system theoretic approach. The second step is to estimate the physiological system parameters (i.e. infusion and clearance rates). This approach has been verified on healthy individuals previously.

Our results show that the clearance rate of cortisol by the liver is relatively lower in patients as compared to the matched healthy individuals. This suggests that there is a relatively higher accumulation of serum cortisol in patients when compared to matched healthy subjects.

Source: Pednekar DD, Amin MR, Azgomi HF, Aschbacher K, Crofford LJ, Faghih RT. A System Theoretic Investigation of Cortisol Dysregulation in Fibromyalgia Patients with Chronic Fatigue. Conf Proc IEEE Eng Med Biol Soc. 2019 Jul;2019:6896-6901. doi: 10.1109/EMBC.2019.8857427. https://www.ncbi.nlm.nih.gov/pubmed/31947425

Intimate Partner Violence and the Risk of Developing Fibromyalgia and Chronic Fatigue Syndrome

Abstract:

Intimate partner violence (IPV) is a global public health issue with a variety of ill health consequences associated with exposure. Due to the stimulation of chronic stress and inflammatory pathways, childhood abuse has been associated with the subsequent development of functional syndromes such as fibromyalgia and chronic fatigue syndrome (CFS). Although IPV in women appears to elicit similar biochemical responses, this association has not been tested thoroughly in IPV survivors. These functional syndromes are complex in etiology and any indication of their risk factors would benefit health care professionals managing this population. Therefore, we aimed to investigate the association between exposure to IPV with functional syndromes: fibromyalgia and CFS.

We conducted a retrospective open cohort study using “The Heath Improvement Network” database between January 1, 1995 and December 1, 2017. A total of 18,547 women who were exposed to IPV were each matched by age to four controls who were not exposed (n = 74,188). The main outcome measures were the risk of developing fibromyalgia and CFS. These were presented as adjusted incidence rate ratios (aIRR) with 95% confidence intervals (CIs).

We found that 97 women in the exposed group developed fibromyalgia (incidence rate [IR] = 1.63 per 1,000 person-years) compared to 239 women in the unexposed group (IR = 0.83 per 1,000 person-years). Following adjustment, this translated to an IRR of 1.73 (95% CI = [1.36, 2.22]). Similarly, 19 women developed CFS in the exposed group (IR = 0.32 per 1,000 person-years), compared to 53 in the unexposed group (0.18 per 1,000 person-years), which translates to an aIRR of 1.92 (95% CI = [1.11, 3.33]).

Therefore, we have identified an association between a history of IPV in women and the development of these functional syndromes, which may provide more information to inform the biopsychosocial pathway precipitating the development of fibromyalgia and CFS.

Source: Chandan JS, Thomas T, Raza K, Bradbury-Jones C, Taylor J, Bandyopadhyay S1, Nirantharakumar K. Intimate Partner Violence and the Risk of Developing Fibromyalgia and Chronic Fatigue Syndrome. J Interpers Violence. 2019 Dec 6:886260519888515. doi: 10.1177/0886260519888515. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/31805821

Neuroimmunology: What Role for Autoimmunity, Neuroinflammation, and Small Fiber Neuropathy in Fibromyalgia, Chronic Fatigue Syndrome, and Adverse Events after Human Papillomavirus Vaccination?

Abstract:

Fibromyalgia is a disorder characterized by chronic widespread pain and non-pain symptoms, such as fatigue, dysautonomia, and cognitive and sleep disturbances. Its pathogenesis and treatment continue to be the subject of debate. We highlight the role of three mechanisms-autoimmunity, neuroinflammation, and small fiber neuropathy in the pathogenesis of the disease. These mechanisms are shown to be closely interlinked (also on a molecular level), and the review considers the implementation of this relationship in the search for therapeutic options.

We also pay attention to chronic fatigue syndrome, which overlaps with fibromyalgia, and propose a concept of “autoimmune hypothalamopathy” for its pathogenesis. Finally, we analyze the molecular mechanisms underlying the neuroinflammatory background in the development of adverse events following HPV vaccination and suggesting neuroinflammation, which could exacerbate the development of symptoms following HPV vaccination (though this is hotly debated), as a model for fibromyalgia pathogenesis.

Source: Ryabkova VA, Churilov LP, Shoenfeld Y. Neuroimmunology: What Role for Autoimmunity, Neuroinflammation, and Small Fiber Neuropathy in Fibromyalgia, Chronic Fatigue Syndrome, and Adverse Events after Human Papillomavirus Vaccination? Int J Mol Sci. 2019 Oct 18;20(20). pii: E5164. doi: 10.3390/ijms20205164. https://www.mdpi.com/1422-0067/20/20/5164 (Full article)

Scientific Advances in and Clinical Approaches to Small-Fiber Polyneuropathy: A Review

Abstract:

IMPORTANCE: Small-fiber polyneuropathy involves preferential damage to the thinly myelinated A-delta fibers, unmyelinated C sensory fibers, or autonomic or trophic fibers. Although this condition is common, most patients still remain undiagnosed and untreated because of lagging medical and public awareness of research advances. Chronic bilateral neuropathic pain, fatigue, and nausea are cardinal symptoms that can cause disability and dependence, including pain medication dependence.

OBSERVATIONS: Biomarker confirmation is recommended, given the nonspecificity of symptoms. The standard test involves measuring epidermal neurite density within a 3-mm protein gene product 9.5 (PGP9.5)-immunolabeled lower-leg skin biopsy. Biopsies and autonomic function testing confirm that small-fiber neuropathy not uncommonly affects otherwise healthy children and young adults, in whom it is often associated with inflammation or dysimmunity. A recent meta-analysis concluded that small-fiber neuropathy underlies 49% of illnesses labeled as fibromyalgia. Initially, patients with idiopathic small-fiber disorders should be screened by medical history and blood tests for potentially treatable causes, which are identifiable in one-third to one-half of patients. Then, secondary genetic testing is particularly important for familial and childhood cases. Treatable genetic causes include Fabry disease, transthyretin and primary systemic amyloidosis, hereditary sensory autonomic neuropathy-1, and ion-channel mutations. Immunohistopathologic evidence suggests that small-fiber dysfunction and denervation, especially of blood vessels, contributes to diverse symptoms, including postexertional malaise, postural orthostatic tachycardia, and functional gastrointestinal distress. Preliminary evidence implicates acute or chronic autoreactivity in some cases, particularly in female patients and otherwise healthy children and young adults. Different temporal patterns akin to Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathy have been described; here, corticosteroids and immunoglobulins, which are often efficacious for inflammatory neuropathic conditions, are increasingly considered.

CONCLUSIONS AND RELEVANCE: Because small fibers normally grow throughout life, improving contributory conditions may permit regrowth, slow progression, and prevent permanent damage. The prognosis is often hopeful for improving quality of life and sometimes for abatement or resolution, particularly in the young and otherwise healthy individuals. Examples include diabetic, infectious, toxic, genetic, and inflammatory causes. The current standard of care requires prompt diagnosis and treatment, particularly in children and young adults, to restore life trajectory. Consensus diagnostic and tracking metrics should be established to facilitate treatment trials.

Source: Oaklander AL, Nolano M. Scientific Advances in and Clinical Approaches to Small-Fiber Polyneuropathy: A Review. JAMA Neurol. 2019 Sep 9. doi: 10.1001/jamaneurol.2019.2917. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/31498378

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)