Tag: Ehlers-Danlos

A Clinical Qualification Protocol Highlights Overlapping Genomic Influences and Neuro-Autonomic Mechanisms in Ehlers-Danlos and Long COVID-19 Syndromes

Abstract:

A substantial fraction of the 15% with double-jointedness or hypermobility have the traditionally ascertained joint-skeletal, cutaneous, and cardiovascular symptoms of connective tissue dysplasia and its particular manifestation as Ehlers-Danlos syndrome (EDS). The holistic ascertainment of 120 findings in 1261 EDS patients added neuro-autonomic symptoms like headaches, muscle weakness, brain fog, chronic fatigue, dyspnea, and bowel irregularity to those of arthralgia and skin laxity, 15 of these symptoms shared with those of post-infectious SARS-CoV-2 (long COVID-19).

Underlying articulo-autonomic mechanisms guided a clinical qualification protocol that qualified DNA variants in 317 genes as having diagnostic utility for EDS, six of them identical (F2-LIFR-NLRP3-STAT1-T1CAM1-TNFRSF13B) and eighteen similar to those modifying COVID-19 severity/EDS, including ADAMTS13/ADAMTS2-C3/C1R-IKBKG/IKBKAP-PIK3C3/PIK3R1-POLD4/POLG-TMPRSS2/TMPRSS6-WNT3/WNT10A.

Also, contributing to EDS and COVID-19 severity were forty and three genes, respectively, impacting mitochondrial functions as well as parts of an overlapping gene network, or entome, that are hypothesized to mediate the cognitive-behavioral, neuro-autonomic, and immune-inflammatory alterations of connective tissue in these conditions. The further characterization of long COVID-19 natural history and genetic predisposition will be necessary before these parallels to EDS can be carefully delineated and translated into therapies.

Source: Wilson GN. A Clinical Qualification Protocol Highlights Overlapping Genomic Influences and Neuro-Autonomic Mechanisms in Ehlers-Danlos and Long COVID-19 Syndromes. Curr Issues Mol Biol. 2023 Jul 17;45(7):6003-6023. doi: 10.3390/cimb45070379. PMID: 37504295; PMCID: PMC10378515. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10378515/ (Full text)

MTHFR and LC, CFS, POTS, MCAS, SIBO, EDS: Methylating the Alphabet

Abstract:

Long Covid (LC), Chronic Fatigue Syndrome (CFS), Postural Orthostatic Tachycardia Syndrome (POTS), Mast Cell Activation Syndrome (MCAS), Small Intestine Bacterial Overgrowth (SIBO), and Ehlers-Danlos Syndrome (EDS) are all loosely connected, some poorly defined, some with overlapping symptoms.

The female preponderance, the prominence of fatigue and chronic inflammation, and methylenetetrahydrofolate reductase (MTHFR) abnormalities may connect them all. Indeed differential methylation may lie at the root. Two – EDS and MTHFR – are genetic. But epigenetic factors may ultimately determine their phenotypic expression.

Oxidative stress, overloaded mitochondria, an antioxidant and nutrient shortfall, and suboptimal gut microbiome appear to be the primary determinants. A deep dive into the folate and methionine cycles is undertaken in an attempt to connect these syndromes.

The active forms of vitamin D and vitamins B2,3,6,9,12 are shown to be biochemically integral to optimal methylation and control of the epigenome. Their status largely determines the symptoms of abnormal MTHFR in all its phenotypes. The wider implications for aging, cancer, cardiovascular disease, neurodegenerative disease, and autoimmune disease are briefly explored.

Source: Chambers P. MTHFR and LC, CFS, POTS, MCAS, SIBO, EDS: Methylating the Alphabet. Preprint from Qeios, 30 Jun 2023. https://www.qeios.com/read/ZPYS4F (Full text)

Could vascular damage caused by massive inflammatory events underlie a relapse/recovery phenotype of ME/CFS and Long COVID?

Abstract:

I hypothesize that there is a relapse/recovery type of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and Long COVID in which a massive inflammatory event—like the inflammatory cascade prompted by the restoration of blood flow (reperfusion) to tissue that had been deprived of blood (ischemia) or an allergic or pseudoallergic reaction—causes substantial damage to blood vessels, launching a more severe phase of ME/CFS.
People with Ehlers-Danlos syndrome and other connective tissue disorders may be at particular risk of this phenotype due to having connective tissue (a key component of blood vessels) that is more easily and severely injured during inflammatory events and slower to heal, causing a much longer recovery.

Source: Tamara Carnac. Could vascular damage caused by massive inflammatory events underlie a relapse/recovery phenotype of ME/CFS and Long COVID? Patient-Generated Hypotheses Journal | Issue 1, May 2023. https://patientresearchcovid19.com/storage/2023/05/Patient-Generated-Hypotheses-Issue-1-May-2023.pdf#page=30 (Full text)

Female reproductive health impacts of Long COVID and associated illnesses including ME/CFS, POTS, and connective tissue disorders: a literature review

Long COVID disproportionately affects premenopausal women, but relatively few studies have examined Long COVID’s impact on female reproductive health. We conduct a review of the literature documenting the female reproductive health impacts of Long COVID which may include disruptions to the menstrual cycle, gonadal function, ovarian sufficiency, menopause, and fertility, as well as symptom exacerbation around menstruation.

Given limited research, we also review the reproductive health impacts of overlapping and associated illnesses including myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), postural orthostatic tachycardia syndrome (POTS), connective tissue disorders like Ehlers-Danlos syndrome (EDS), and endometriosis, as these illnesses may help to elucidate reproductive health conditions in Long COVID.

These associated illnesses, whose patients are 70%–80% women, have increased rates of dysmenorrhea, amenorrhea, oligomenorrhea, dyspareunia, endometriosis, infertility, vulvodynia, intermenstrual bleeding, ovarian cysts, uterine fibroids and bleeding, pelvic congestion syndrome, gynecological surgeries, and adverse pregnancy complications such as preeclampsia, maternal mortality, and premature birth. Additionally, in Long COVID and associated illnesses, symptoms can be impacted by the menstrual cycle, pregnancy, and menopause.

We propose priorities for future research and reproductive healthcare in Long COVID based on a review of the literature. These include screening Long COVID patients for comorbid and associated conditions; studying the impacts of the menstrual cycle, pregnancy, and menopause on symptoms and illness progression; uncovering the role of sex differences and sex hormones in Long COVID and associated illnesses; and addressing historical research and healthcare inequities that have contributed to detrimental knowledge gaps for this patient population.

Source: Pollack Beth, von Saltza Emelia, McCorkell Lisa, Santos Lucia, Hultman Ashley, Cohen Alison K., Soares Letícia. Female reproductive health impacts of Long COVID and associated illnesses including ME/CFS, POTS, and connective tissue disorders: a literature review. Frontiers in Rehabilitation Sciences, Vol 4, 2023, ISSN=2673-6861. DOI: 10.3389/fresc.2023.1122673 https://www.frontiersin.org/articles/10.3389/fresc.2023.1122673 (Full text)

“I Just Want to Feel Safe Going to a Doctor”: Experiences of Female Patients with Chronic Conditions in Australia

Abstract:

Background: The androcentric history of medicine and medical research has led to an ongoing sex and gender gap in health research and education. Sex and gender gaps in research and education may translate into real-life health inequities for women. This study aimed to explore the experiences of female patients with chronic health conditions in the Australian health system, considering existing sex and gender gaps in medicine.

Methods: This qualitative study used semistructured in-depth interviews with a sample of adult women with chronic conditions in Australia. Thematic analysis was undertaken, guided by Braun and Clarke. Software NVivoX64 assisted in the management of the data. Coding was performed before grouping into subthemes and central themes. To allow for potential researcher biases, the principal researcher engaged in the practice of reflexivity, including the writing of detailed notes during analysis.

Results: Twenty adult Australian women with chronic conditions were interviewed. Diagnoses were varied and included Ehlers-Danlos syndrome, chronic fatigue syndrome, functional neurological disorder, and inflammatory bowel disease. Four central themes emerged: diagnostic difficulties; spectrum of health care experiences; understanding medical complexity; and coping with symptoms.

Conclusions: Women with chronic conditions in Australia report pain, fatigue, and suffering that significantly impacts upon their daily lives. There was a shared experience of feeling that the pain and suffering of women was dismissed or not taken seriously. Many women expressed trauma because of their experiences in health care and often this led to a fear of accessing health services. The participants highlighted a need for more knowledge, understanding, and empathy from health care practitioners.

Source: Merone L, Tsey K, Russell D, Nagle C. “I Just Want to Feel Safe Going to a Doctor”: Experiences of Female Patients with Chronic Conditions in Australia. Womens Health Rep (New Rochelle). 2022 Dec 22;3(1):1016-1028. doi: 10.1089/whr.2022.0052. PMID: 36636320; PMCID: PMC9811844. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9811844/ (Full text)

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/

The Presentation of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Is Not Influenced by the Presence or Absence of Joint Hypermobility

Abstract:

Objective: To examine demographic and clinical characteristics of individuals with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) with and without joint hypermobility We hypothesized that JH+ patients would have an earlier onset of ME/CFS symptoms as well as increased severity, greater number of co-morbid conditions, and lower health related quality of life.

Study design: From an observational cohort study of 55 individuals meeting the Fukuda criteria for ME/CFS, we compared groups using a Beighton score cut-off of 4 or higher to indicate JH. Chart data were collected to examine the age and type of onset of ME/CFS, and the presence of comorbid conditions. The impact on quality of life was assessed through questionnaires that included the Peds QL, Functional Disability Inventory, Peds QL Multidimensional Fatigue Scale, and Anxiety Subscale of the Symptom Checklist 90.

Results: There was no significant difference between groups in mean (SD) age at onset of ME/CFS (13.3 [3.3] years vs 13.3 [2.3] years; P = .92), sex, frequency, and severity of ME/CFS symptoms, orthostatic intolerance symptoms, or comorbid conditions. There was no significant difference between groups in measures of health-related quality of life using a Beighton score cut-off of 4 or a cut-off of 5 to define joint hypermobility.

Conclusions: Despite being a risk factor for the development of ME/CFS, JH as defined in this study was not associated with other clinical characteristics of the illness.

Source: Vogel SK, Primavera IR, Marden CL, Jasion SE, Cranston EM, Flaherty MAK, Violand RL, Rowe PC. The Presentation of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Is Not Influenced by the Presence or Absence of Joint Hypermobility. J Pediatr. 2021 Sep 16:S0022-3476(21)00887-8. doi: 10.1016/j.jpeds.2021.09.014. Epub ahead of print. PMID: 34537220. https://pubmed.ncbi.nlm.nih.gov/34537220/

Beyond bones: The relevance of variants of connective tissue (hypermobility) to fibromyalgia, ME/CFS and controversies surrounding diagnostic classification: an observational study

Abstract:

Background: Fibromyalgia and myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) are poorly understood conditions with overlapping symptoms, fuelling debate as to whether they are manifestations of the same spectrum or separate entities. Both are associated with hypermobility, but this remains significantly undiagnosed, despite impact on quality of life.

Objective: We planned to understand the relevance of hypermobility to symptoms in fibromyalgia and ME/CFS.

Method: Sixty-three patient participants presented with a confirmed diagnosis of fibromyalgia and/or ME/CFS; 24 participants were healthy controls. Patients were assessed for symptomatic hypermobility.

Results: Evaluations showed exceptional overlap in patients between fibromyalgia and ME/CFS, plus 81% met Brighton criteria for hypermobility syndrome (odds ratio 7.08) and 18% met 2017 hypermobile Ehlers-Danlos syndrome (hEDS) criteria. Hypermobility scores significantly predicted symptom levels.

Conclusion: Symptomatic hypermobility is particularly relevant to fibromyalgia and ME/CFS, and our findings highlight high rates of mis-/underdiagnosis. These poorly understood conditions have a considerable impact on quality of life and our observations have implications for diagnosis and treatment targets.

Source: Eccles JA, Thompson B, Themelis K, Amato ML, Stocks R, Pound A, Jones AM, Cipinova Z, Shah-Goodwin L, Timeyin J, Thompson CR, Batty T, Harrison NA, Critchley HD, Davies KA. Beyond bones: The relevance of variants of connective tissue (hypermobility) to fibromyalgia, ME/CFS and controversies surrounding diagnostic classification: an observational study. Clin Med (Lond). 2021 Jan;21(1):53-58. doi: 10.7861/clinmed.2020-0743. PMID: 33479068. https://pubmed.ncbi.nlm.nih.gov/33479068/

Syncope and hypermobile joints: Not rare, but rarely diagnosed

Abstract:

Postural orthostatic tachycardia syndrome (POTS) is a chronic, debilitating condition characterized by heterogeneous symptoms, such as lightheadedness, palpitations, pre-syncope, syncope, and weakness or heaviness, especially of the legs. It is frequently associated with hypermobile joints or conditions such as chronic fatigue syndrome, chronic abdominal pain, migraine headache, and diabetes mellitus. Described is a case of POTS, which though it is not rare, is rarely diagnosed. It can be diagnosed quickly with simple methods.

Source: Tahirovic E. Syncope and hypermobile joints: Not rare, but rarely diagnosed. Turk Kardiyol Dern Ars. 2020 Mar;48(2):177-179. doi: 10.5543/tkda.2019.32624. https://archivestsc.com/jvi.aspx?un=TKDA-32624 (Full text)

Chronic fatigue in Ehlers-Danlos syndrome-hypermobile type

Abstract:

Chronic fatigue is an important contributor to impaired health-related quality of life in Ehlers-Danlos syndrome. There is overlap in the symptoms and findings of EDS and chronic fatigue syndrome. A proportion of those with CFS likely have EDS that has not been identified.

The evaluation of chronic fatigue in EDS needs to include a careful clinical examination and laboratory testing to exclude common causes of fatigue including anemia, hypothyroidisim, and chronic infection, as well as dysfunction of major physiological or organ systems.

Other problems that commonly contribute to fatigue in EDS include sleep disorders, chronic pain, deconditioning, cardiovascular autonomic dysfunction, bowel and bladder dysfunction, psychological issues, and nutritional deficiencies.

While there is no specific pharmacological treatment for fatigue, many medications are effective for specific symptoms (such as headache, menstrual dysfunction, or myalgia) and for co-morbid conditions that result in fatigue, including orthostatic intolerance and insomnia.

Comprehensive treatment of fatigue needs to also evaluate for biomechanical problems that are common in EDS, and usually involves skilled physical therapy and attention to methods to prevent deconditioning.

In addition to managing specific symptoms, treatment of fatigue in EDS also needs to focus on maintaining function and providing social, physical, and nutritional support, as well as providing on-going medical evaluation of new problems and review of new evidence about proposed treatments.

© 2017 Wiley Periodicals, Inc.

 

Source: Hakim A, De Wandele I, O’Callaghan C, Pocinki A, Rowe P. Chronic fatigue in Ehlers-Danlos syndrome-hypermobile type. Am J Med Genet C Semin Med Genet. 2017 Feb 10. doi: 10.1002/ajmg.c.31542. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/28186393