Managing chronic fatigue conditions with overlapping symptoms, and the health policies and social services supporting those affected
Main Article Content
Abstract
Complex chronic conditions present a formidable challenge to clinicians to diagnose and manage for their patients, and the diseases are still relatively poorly understood. The chronic fatigue conditions, Myalgic Encephalomyelitis/Chronic fatigue syndrome, Long COVID, Fibromyalgia, Ehlers-Danlos syndromes and Multiple sclerosis, share many overlapping symptoms that reflect similar physiological responses, sometimes leading to misdiagnosis, yet the conditions are distinct and are being managed as separate diseases. The characteristics of what is known about each condition are described here, and as well for two comorbidities, Postural Orthostatic Tachycardia Syndrome and Mast cell Activation Syndrome intimately linked to the physiological dysfunctions of the chronic conditions. The pathophysiological changes in immunological function, neurological regulation, metabolism and energy production, and the microbiome affecting the gut-immune brain axis are discussed and compared for each condition. The difficulties encountered for diagnosis, and the current lack of effective treatment options are highlighted. Evidence is presented that affected patients have pressing needs, and that there are currently barriers that prevent access to more effective health support, result in patients being isolated lifelong from employment, and that block access to the essential social services. Effective public health policy is needed to ensure these inadequacies in public health support are overcome, and financial support is provided to ensure all patients have an enhanced quality of life. There may be significant benefit for affected patients if research and collective knowledge of these conditions and comorbidities are shared and more integrated, to promote better understanding for their management, provide a wider range of common treatment options, and stimulate more co-ordinated health policies for the management of patient support. Multiple sclerosis is far better served than the other conditions and could provide the model for how chronic conditions could be managed better.
Keywords:
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), Long COVID, Fibromyalgia, Ehlers-Danlos Syndromes, Multiple Sclerosis, Postural Orthostatic Tachycardia Syndrome (POTS), Mast Cell Activation Syndrome (MCAS), Chronic illness management, Health policy, Social support services
Article Details
How to Cite
TATE, Warren et al.
Managing chronic fatigue conditions with overlapping symptoms, and the health policies and social services supporting those affected.
Medical Research Archives, [S.l.], v. 13, n. 11, dec. 2025.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/7104>. Date accessed: 26 dec. 2025.
doi: https://doi.org/10.18103/mra.v13i11.7104.
Section
Review Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
1. Shepherd C. ME/CF/PVFS. The MEA Clinical & Research Guide. An Exploration of the Key Clinical Issues. 13th ed. The ME association, UK; 2022:316.
2. Staff M. AN OUTBREAK of encephalomyelitis in the Royal Free Hospital Group, London, in 1955. Br Med J. Oct 19 1957;2(5050):895-904.
3. Levine PH, Jacobson S, Pocinki AG, et al. Clinical, epidemiologic, and virologic studies in four clusters of the chronic fatigue syndrome. Arch Intern Med. Aug 1992;152(8):1611-6.
4. Vallings R. Chronic Fatigue Syndrome M.E.Symptoms, Diagnosis, Management. Calico Publishing; 2020.
5. Davis HE, McCorkell L, Vogel JM, Topol EJ. Long COVID: major findings, mechanisms and recommendations. Nat Rev Microbiol. Mar 2023;21(3):133-146. doi: 10.1038/s41579-022-00846-2
6. Gentilotti E, Górska A, Tami A, et al. Clinical phenotypes and quality of life to define post-COVID-19 syndrome: a cluster analysis of the multinational, prospective ORCHESTRA cohort. eClinicalMedicine. 2023/08/01/ 2023;62:102107. doi:https://doi.org/10.1016/j.eclinm.2023.102107
7. Tate WP, Walker MOM, Peppercorn K, Blair ALH, Edgar CD. Towards a Better Understanding of the Complexities of Myalgic Encephalomyelitis /Chronic Fatigue Syndrome and Long COVID. Int J Mol Sci. 2023;24(6):5124.
8. Komaroff AL, Lipkin WI. ME/CFS and Long COVID share similar symptoms and biological abnormalities: road map to the literature. Front Med (Lausanne). 2023;10:1187163. doi:10.3389/ fmed.2023.1187163
9. Eckey M, Li P, Morrison B, et al. Patient-reported treatment outcomes in ME/CFS and long COVID. Proc Natl Acad Sci U S A. Jul 15 2025;122(28): e2426874122. doi:10.1073/pnas.2426874122
10. Marshall-Gradisnik S, Eaton-Fitch N. Understanding myalgic encephalomyelitis. Science. Sep 9 2022;37 7(6611):1150-1151. doi:10.1126/science.abo1261
11. Peppercorn K, Edgar CD, Kleffmann T, Tate WP. A pilot study on the immune cell proteome of long COVID patients shows changes to physiological pathways similar to those in myalgic encephalomyelitis/chronic fatigue syndrome. Sci Rep. Dec 12 2023;13(1):22068. doi:10.1038/s4159 8-023-49402-9
12. Peppercorn K, ; Edgar, C.; Al Momani, S,; Rodger, E. J.; Tate, W.P.; Chatterjee, A. Application of DNA methylome analysis to patients with ME/CFS. Methods in Molecular Biology. Spinger; 2025.
13. Shah KM, Shah RM, Sawano M, et al. Factors Associated with Long COVID Recovery among US Adults. Am J Med. Sep 2024;137(9):896-899. doi:10.1016/j.amjmed.2024.04.017
14. Ballouz T, Menges D, Anagnostopoulos A, et al. Recovery and symptom trajectories up to two years after SARS-CoV-2 infection: population based, longitudinal cohort study. Bmj. May 31 2023;381:e074425. doi:10.1136/bmj-2022-074425
15. Hartung TJ, Bahmer T, Chaplinskaya-Sobol I, et al. Predictors of non-recovery from fatigue and cognitive deficits after COVID-19: a prospective, longitudinal, population-based study. EClinicalMedicine. Mar 2024;69:102456. doi:10.1016/j.eclinm.2024.102456
16. Al-Aly Z, Davis H, McCorkell L, et al. Long COVID science, research and policy. Nat Med. Aug 2024;30(8):2148-2164. doi:10.1038/s41591-024-03173-6
17. Walitt B, Nahin RL, Katz RS, Bergman MJ, Wolfe F. The Prevalence and Characteristics of Fibromyalgia in the 2012 National Health Interview Survey. PLoS One. 2015;10(9):e0138024. doi:10.13 71/journal.pone.0138024
18. Arnold LM, Fan J, Russell IJ, et al. The fibromyalgia family study: a genome-wide linkage scan study. Arthritis Rheum. Apr 2013;65(4):1122-8. doi:10.1002/art.37842
19. Rahman MS, Winsvold BS, Chavez Chavez SO, et al. Genome-wide association study identifies RNF123 locus as associated with chronic widespread musculoskeletal pain. Ann Rheum Dis. Sep 2021;80 (9):1227-1235. doi:10.1136/annrheumdis-2020-219624
20. Pan Q, Cai T, Tao Y, et al. Genome-wide association study identifies novel genetic variants associated with widespread pain in the UK Biobank (N = 172,230). Mol Pain. Jan-Dec 2025;21:1744806 9251346603. doi:10.1177/17448069251346603
21. Das S, Taylor K, Kozubek J, Sardell J, Gardner S. Genetic risk factors for ME/CFS identified using combinatorial analysis. J Transl Med. Dec 14 2022; 20(1):598. doi:10.1186/s12967-022-03815-8
22. Taylor K, Pearson M, Das S, et al. Genetic risk factors for severe and fatigue dominant long COVID and commonalities with ME/CFS identified by combinatorial analysis. Journal of Translational Medicine. 2023/11/01 2023;21(1):775. doi:10.1186 /s12967-023-04588-4
23. Boutin T, Bretherick A, Dibble J, et al. Initial findings from the DecodeME genome-wide association study of myalgic encephalomyelitis/chronic fatigue syndrome. 2025.
24. Cortini F, Villa C. Ehlers-Danlos syndromes and epilepsy: An updated review. Seizure. Apr 2018;57:1-4. doi:10.1016/j.seizure.2018.02.013
25. Malfait F, Francomano C, Byers P, et al. The 2017 international classification of the Ehlers-Danlos syndromes. Am J Med Genet C Semin Med Genet. Mar 2017;175(1):8-26. doi:10.1002/ajmg.c.31552
26. Lawrence EJ. The clinical presentation of Ehlers-Danlos syndrome. Adv Neonatal Care. Dec 2005;5(6):301-14. doi:10.1016/j.adnc.2005.09.006
27. Mudie K, Ramiller A, Whittaker S, Phillips LE. Do people with ME/CFS and joint hypermobility represent a disease subgroup? An analysis using registry data. Front Neurol. 2024;15:1324879. doi: 10.3389/fneur.2024.1324879
28. Malfait F, Wenstrup RJ, De Paepe A. Clinical and genetic aspects of Ehlers-Danlos syndrome, classic type. Genet Med. Oct 2010;12(10):597-605. doi:10.1097/GIM.0b013e3181eed412
29. Bakalidou D, Giannopapas V, Giannopoulos S. Thoughts on Fatigue in Multiple Sclerosis Patients. Cureus. Jul 2023;15(7):e42146. doi:10.7759/cureus.42146
30. Travers BS, Tsang BK, Barton JL. Multiple sclerosis: Diagnosis, disease-modifying therapy and prognosis. Aust J Gen Pract. Apr 2022;51 (4):199-206. doi:10.31128/ajgp-07-21-6103
31. Venkatesan A, Johnson RT. Infections and multiple sclerosis. Handb Clin Neurol. 2014;122: 151-71. doi:10.1016/b978-0-444-52001-2.00007-8
32. Riise T, Mohr DC, Munger KL, et al. Stress and the risk of multiple sclerosis. Neurology. May 31 2011;76(22):1866-71. doi:10.1212/WNL.0b013e31821d74c5
33. Mohr DC, Hart SL, Julian L, Cox D, Pelletier D. Association between stressful life events and exacerbation in multiple sclerosis: a meta-analysis. Bmj. Mar 27 2004;328(7442):731. doi:10.1136/bmj .38041.724421.55
34. Tate W, Walker M, Sweetman E, et al. Molecular Mechanisms of Neuroinflammation in ME/CFS and Long COVID to Sustain Disease and Promote Relapses. Front Neurol. 2022;13:877772. doi:10.3389/fneur.2022.877772
35. Sharma S, Hodges LD, Peppercorn K, et al. Precision Medicine Study of Post-Exertional Malaise Epigenetic Changes in Myalgic Encephalomyelitis/Chronic Fatigue Patients During Exercise. Int J Mol Sci. Sep 3 2025;26(17)doi:10.33 90/ijms26178563
36. Compston A, Coles A. Multiple sclerosis. Lancet. Oct 25 2008;372(9648):1502-17. doi:10.10 16/s0140-6736(08)61620-7
37. Wootla B, Eriguchi M, Rodriguez M. Is multiple sclerosis an autoimmune disease? Autoimmune Dis. 2012;2012:969657. doi:10.1155/2012/969657
38. Vilisaar J, Harikrishnan S, Suri M, Constantinescu CS. Ehlers-Danlos syndrome and multiple sclerosis: a possible association. Mult Scler. May 2008;14(4): 567-70. doi:10.1177/1352458507083187
39. Mar PL, Raj SR. Neuronal and hormonal perturbations in postural tachycardia syndrome. Front Physiol. 2014;5:220. doi:10.3389/fphys.2014.00220
40. van Campen C, Rowe PC, Visser FC. Low Sensitivity of Abbreviated Tilt Table Testing for Diagnosing Postural Tachycardia Syndrome in Adults With ME/CFS. Front Pediatr. 2018;6:349. doi:10.3389/fped.2018.00349
41. Roma M, Marden CL, De Wandele I, Francomano CA, Rowe PC. Postural tachycardia syndrome and other forms of orthostatic intolerance in Ehlers-Danlos syndrome. Auton Neurosci. Dec 2018;215:89-96. doi:10.1016/j.autneu.2018.02.006
42. Adamec I, Lovrić M, Žaper D, et al. Postural orthostatic tachycardia syndrome associated with multiple sclerosis. Auton Neurosci. Jan 2013;173 (1-2):65-8. doi:10.1016/j.autneu.2012.11.009
43. Staud R. Autonomic dysfunction in fibromyalgia syndrome: postural orthostatic tachycardia. Curr Rheumatol Rep. Dec 2008;10(6):463-6. doi:10.100 7/s11926-008-0076-8
44. Theoharides TC, Tsilioni I, Ren H. Recent advances in our understanding of mast cell activation - or should it be mast cell mediator disorders? Expert Rev Clin Immunol. Jun 2019;15(6):639-656. doi:10.1080/1744666x.2019.1596800
45. Afrin LB, Ackerley MB, Bluestein LS, et al. Diagnosis of mast cell activation syndrome: a global "consensus-2". Diagnosis (Berl). May 26 2021;8(2):137-152. doi:10.1515/dx-2020-0005
46. Hatziagelaki E, Adamaki M, Tsilioni I, Dimitriadis G, Theoharides TC. Myalgic Encephalomyelitis /Chronic Fatigue Syndrome-Metabolic Disease or Disturbed Homeostasis due to Focal Inflammation in the Hypothalamus? J Pharmacol Exp Ther. Oct 2018;367(1):155-167. doi:10.1124/jpet.118.250845
47. Theoharides TC, Tsilioni I, Arbetman L, et al. Fibromyalgia syndrome in need of effective treatments. J Pharmacol Exp Ther. Nov 2015;355 (2):255-63. doi:10.1124/jpet.115.227298
48. Akin C. Mast cell activation syndromes. J Allergy Clin Immunol. Aug 2017;140(2):349-355. doi:10.1016/j.jaci.2017.06.007
49. Nguyen T, Johnston S, Chacko A, et al. Novel characterisation of mast cell phenotypes from peripheral blood mononuclear cells in chronic fatigue syndrome/myalgic encephalomyelitis patients. Asian Pac J Allergy Immunol. Jun 2017;35(2):75-81. doi:10.12932/ap0771
50. Mandarano AH, Maya J, Giloteaux L, et al. Myalgic encephalomyelitis/chronic fatigue syndrome patients exhibit altered T cell metabolism and cytokine associations. J Clin Invest. Mar 2 2020; 130(3):1491-1505. doi:10.1172/jci132185
51. Walker MOM, Peppercorn K, Kleffmann T, Edgar CD, Tate WP. An understanding of the immune dysfunction in susceptible people who develop the post-viral fatigue syndromes Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Long COVID. Medical Research Archives. 2023-07-06 2023;11(7.1)doi:10.18103/mra.v11i7.1.4083
52. Walitt B, Singh K, LaMunion SR, et al. Deep phenotyping of post-infectious myalgic encephalomyelitis/chronic fatigue syndrome. Nat Commun. Feb 21 2024;15(1):907. doi:10.1038/ s41467-024-45107-3
53. Eaton-Fitch N, Rudd P, Er T, et al. Immune exhaustion in ME/CFS and long COVID. JCI Insight. Oct 22 2024;9(20)doi:10.1172/jci.insight.183810
54. Cervia-Hasler C, Brüningk SC, Hoch T, et al. Persistent complement dysregulation with signs of thromboinflammation in active Long Covid. Science. Jan 19 2024;383(6680):eadg7942. doi:10. 1126/science.adg7942
55. Altmann DM, Whettlock EM, Liu S, Arachchillage DJ, Boyton RJ. The immunology of long COVID. Nat Rev Immunol. Oct 2023;23(10): 618-634. doi:10.1038/s41577-023-00904-7
56. Yin K, Peluso MJ, Luo X, et al. Long COVID manifests with T cell dysregulation, inflammation and an uncoordinated adaptive immune response to SARS-CoV-2. Nat Immunol. Feb 2024;25(2):218-225. doi:10.1038/s41590-023-01724-6
57. Clauw D, Sarzi-Puttini P, Pellegrino G, Shoenfeld Y. Is fibromyalgia an autoimmune disorder? Autoimmun Rev. Jan 2024;23(1):103424. doi:10.1016/j.autrev. 2023.103424
58. Paroli M, Gioia C, Accapezzato D, Caccavale R. Inflammation, Autoimmunity, and Infection in Fibromyalgia: A Narrative Review. Int J Mol Sci. May 29 2024;25(11)doi:10.3390/ijms25115922
59. International statistical classification of diseases, injuries, and causes of death. (World Health Organisation) (1969).
60. Nakatomi Y, Mizuno K, Ishii A, et al. Neuroinflammation in Patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: An (1)(1)C-(R)-PK11195 PET Study. J Nucl Med. Jun 2014; 55(6):945-50. doi:10.2967/jnumed.113.131045
61. Bynke A, Julin P, Gottfries CG, et al. Autoantibodies to beta-adrenergic and muscarinic cholinergic receptors in Myalgic Encephalomyelitis (ME) patients - A validation study in plasma and cerebrospinal fluid from two Swedish cohorts. Brain Behav Immun Health. Aug 2020;7:100107. doi:10.1016/j.bbih.2020.100107
62. Talkington GM, Kolluru P, Gressett TE, et al. Neurological sequelae of long COVID: a comprehensive review of diagnostic imaging, underlying mechanisms, and potential therapeutics. Front Neurol. 2024;15:1465787. doi:10.3389/fneur .2024.1465787
63. Peppercorn K, Sharma S, Edgar CD, et al. Comparing DNA Methylation Landscapes in Peripheral Blood from Myalgic Encephalomyelitis /Chronic Fatigue Syndrome and Long COVID Patients. Int J Mol Sci. Jul 10 2025;26(14)doi:10. 3390/ijms26146631
64. Clauw DJ, Arnold LM, McCarberg BH. The science of fibromyalgia. Mayo Clin Proc. Sep 2011;86(9):907-11. doi:10.4065/mcp.2011.0206
65. Fitzcharles MA, Cohen SP, Clauw DJ, et al. Nociplastic pain: towards an understanding of prevalent pain conditions. Lancet. May 29 2021;397(10289):2098-2110. doi:10.1016/s0140-6736(21)00392-5
66. Becker S, Schweinhardt P. Dysfunctional neurotransmitter systems in fibromyalgia, their role in central stress circuitry and pharmacological actions on these systems. Pain Res Treat. 2012; 2012:741746. doi:10.1155/2012/741746
67. Fernandez A, Jaquet M, Aubry-Rozier B, et al. Functional neurological signs in hypermobile Ehlers-Danlos syndrome and hypermobile spectrum disorders with suspected neuropathic pain. Brain Behav. Feb 2024;14(2):e3441. doi:10.1002/brb3.3441
68. Oudejans E, Luchicchi A, Strijbis EMM, Geurts JJG, van Dam AM. Is MS affecting the CNS only? Lessons from clinic to myelin pathophysiology. Neurol Neuroimmunol Neuroinflamm. Jan 2021;8 (1)doi:10.1212/nxi.0000000000000914
69. Holden S, Maksoud R, Eaton-Fitch N, et al. A systematic review of mitochondrial abnormalities in myalgic encephalomyelitis/chronic fatigue syndrome/systemic exertion intolerance disease. J Transl Med. Jul 29 2020;18(1):290. doi:10.1186/s1 2967-020-02452-3
70. Annesley SJ, Missailidis D, Heng B, Josev EK, Armstrong CW. Unravelling shared mechanisms: insights from recent ME/CFS research to illuminate long COVID pathologies. Trends Mol Med. May 2024;30(5):443-458. doi:10.1016/j.molmed.2024.02.003
71. Syed AM, Karius AK, Ma J, Wang PY, Hwang PM. Mitochondrial Dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Physiology (Bethesda). Jul 1 2025;40(4):0. doi:10. 1152/physiol.00056.2024
72. Sweetman E, Kleffmann T, Edgar C, et al. A SWATH-MS analysis of Myalgic Encephalomyelitis /Chronic Fatigue Syndrome peripheral blood mononuclear cell proteomes reveals mitochondrial dysfunction. J Transl Med. Sep 24 2020;18(1):365. doi:10.1186/s12967-020-02533-3
73. Missailidis D, Annesley SJ, Allan CY, et al. An Isolated Complex V Inefficiency and Dysregulated Mitochondrial Function in Immortalized Lymphocytes from ME/CFS Patients. Int J Mol Sci. Feb 6 2020;21(3)doi:10.3390/ijms21031074
74. Arnold DL, Bore PJ, Radda GK, Styles P, Taylor DJ. Excessive intracellular acidosis of skeletal muscle on exercise in a patient with a post-viral exhaustion/fatigue syndrome. A 31P nuclear magnetic resonance study. Lancet. Jun 23 1984;1(8 391):1367-9. doi:10.1016/s0140-6736(84)91871-3
75. Naviaux RK, Naviaux JC, Li K, et al. Metabolic features of chronic fatigue syndrome. Proc Natl Acad Sci U S A. Sep 13 2016;113(37):E5472-80. doi:10.1073/pnas.1607571113
76. Fluge Ø, Mella O, Bruland O, et al. Metabolic profiling indicates impaired pyruvate dehydrogenase function in myalgic encephalopathy/chronic fatigue syndrome. JCI Insight. Dec 22 2016;1(21):e89376. doi:10.1172/jci.insight.89376
77. Germain A, Ruppert D, Levine SM, Hanson MR. Metabolic profiling of a myalgic encephalomyelitis/chronic fatigue syndrome discovery cohort reveals disturbances in fatty acid and lipid metabolism. Mol Biosyst. Jan 31 2017; 13(2):371-379. doi:10.1039/c6mb00600k
78. Mueller C, Lin JC, Sheriff S, Maudsley AA, Younger JW. Evidence of widespread metabolite abnormalities in Myalgic encephalomyelitis/ chronic fatigue syndrome: assessment with whole-brain magnetic resonance spectroscopy. Brain Imaging Behav. Apr 2020;14(2):562-572. doi:10.1007/s116 82-018-0029-410.1007/s11682-018-0029-4.
79. Thapaliya K, Marshall-Gradisnik S, Eaton-Fitch N, et al. Imbalanced Brain Neurochemicals in Long COVID and ME/CFS: A Preliminary Study Using MRI. Am J Med. Mar 2025;138(3):567-574.e1. doi: 10.1016/j.amjmed.2024.04.007
80. Macchi C, Giachi A, Fichtner I, et al. Mitochondrial function in patients affected with fibromyalgia syndrome is impaired and correlates with disease severity. Sci Rep. Dec 4 2024;14(1): 30247. doi:10.1038/s41598-024-81298-x
81. Jung YH, Kim H, Seo S, et al. Central metabolites and peripheral parameters associated neuroinflammation in fibromyalgia patients: A preliminary study. Medicine (Baltimore). Mar 31 2023;102(13):e33305. doi:10.1097/md.0000000000033305
82. Davis L, Higgs M, Snaith A, et al. Dysregulation of lipid metabolism, energy production, and oxidative stress in myalgic encephalomyelitis/chronic fatigue syndrome, Gulf War Syndrome and fibromyalgia. Front Neurosci. 2025;19:1498981. doi:10.3389/ fnins.2025.1498981
83. Shirvani P, Shirvani A, Holick MF. Mitochondrial Dysfunction and Its Potential Molecular Interplay in Hypermobile Ehlers-Danlos Syndrome: A Scoping Review Bridging Cellular Energetics and Genetic Pathways. Curr Issues Mol Biol. Feb 19 2025;47 (2)doi:10.3390/cimb47020134
84. Ravera S, Panfoli I, Calzia D, et al. Evidence for aerobic ATP synthesis in isolated myelin vesicles. Int J Biochem Cell Biol. Jul 2009;41(7):1581-91. doi:10.1016/j.biocel.2009.01.009
85. Ravera S, Panfoli I, Aluigi MG, Calzia D, Morelli A. Characterization of Myelin Sheath F(o)F(1)-ATP synthase and its regulation by IF(1). Cell Biochem Biophys. Mar 2011;59(2):63-70. doi:10.1007/s1201 3-010-9112-1
86. Morelli AM, Ravera S, Panfoli I. The aerobic mitochondrial ATP synthesis from a comprehensive point of view. Open Biol. Oct 2020;10(10):200224. doi:10.1098/rsob.200224
87. Mishra G, Townsend KL. The metabolic and functional roles of sensory nerves in adipose tissues. Nat Metab. Sep 2023;5(9):1461-1474. doi: 10.1038/s42255-023-00868-x
88. Greeck VB, Williams SK, Haas J, Wildemann B, Fairless R. Alterations in Lymphocytic Metabolism-An Emerging Hallmark of MS Pathophysiology? Int J Mol Sci. Jan 20 2023;24(3)doi:10.3390/ijms24032094
89. König RS, Albrich WC, Kahlert CR, et al. The Gut Microbiome in Myalgic Encephalomyelitis (ME) /Chronic Fatigue Syndrome (CFS). Front Immunol. 2021;12:628741. doi:10.3389/fimmu.2021.628741
90. El-Sehrawy A, Ayoub, II, Uthirapathy S, et al. The microbiota-gut-brain axis in myalgic encephalomyelitis/chronic fatigue syndrome: a narrative review of an emerging field. Eur J Transl Myol. Mar 31 2025;35(1)doi:10.4081/ejtm.2025.13690
91. Jurek JM, Castro-Marrero J. A Narrative Review on Gut Microbiome Disturbances and Microbial Preparations in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Implications for Long COVID. Nutrients. May 21 2024;16(11)doi:10.3390/nu16111545
92. Fallah A, Sedighian H, Kachuei R, Fooladi AAI. Human microbiome in post-acute COVID-19 syndrome (PACS). Curr Res Microb Sci. 2025;8:10 0324. doi:10.1016/j.crmicr.2024.100324
93. Minerbi A, Khoutorsky A, Shir Y. Decoding the connection: unraveling the role of gut microbiome in fibromyalgia. Pain Rep. Feb 2025;10(1):e1224. doi:10.1097/pr9.0000000000001224
94. Choudhary A, Fikree A, Ruffle JK, et al. A machine learning approach to stratify patients with hypermobile Ehlers-Danlos syndrome/ hypermobility spectrum disorders according to disorders of gut brain interaction, comorbidities and quality of life. Neurogastroenterol Motil. Jan 2025;37(1):e14957. doi:10.1111/nmo.14957
95. Parodi B, Kerlero de Rosbo N. The Gut-Brain Axis in Multiple Sclerosis. Is Its Dysfunction a Pathological Trigger or a Consequence of the Disease? Front Immunol. 2021;12:718220. doi:10. 3389/fimmu.2021.718220
96. Sharifa M, Ghosh T, Daher OA, et al. Unraveling the Gut-Brain Axis in Multiple Sclerosis: Exploring Dysbiosis, Oxidative Stress, and Therapeutic Insights. Cureus. Oct 2023;15(10):e47 058. doi:10.7759/cureus.47058
97. Mohsen E, Haffez H, Ahmed S, Hamed S, El-Mahdy TS. Multiple Sclerosis: A Story of the Interaction Between Gut Microbiome and Components of the Immune System. Mol Neurobiol. Jun 2025;6 2(6):7762-7775. doi:10.1007/s12035-025-04728-5
98. Carruthers BM, Jain AK, De Meirleir KL, et al. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Journal of Chronic Fatigue Syndrome. 2003/01/01 2003;11(1):7-115. doi:10.1300/J092v11n01_02
99. Carruthers BM, van de Sande MI, De Meirleir KL, et al. Myalgic encephalomyelitis: International Consensus Criteria. J Intern Med. Oct 2011;270(4): 327-38. doi:10.1111/j.1365-2796.2011.02428.x
100. Vallings R. How a Clinician Makes a Diagnosis for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Methods Mol Biol. 2025;292 0:3-11. doi:10.1007/978-1-0716-4498-0_1
101. WHO. A clinical case definition of post COVID-19 condition by a Delphi consensus, 6 October 2021. 2021.
102. RECOVER. RECOVER: Researching COVID to Enhance Recovery. NIH. Accessed 14 October 2025, 2025. https://recovercovid.org
103. Häuser W, Perrot S, Sommer C, Shir Y, Fitzcharles MA. Diagnostic confounders of chronic widespread pain: not always fibromyalgia. Pain Rep. May 2017;2(3):e598. doi:10.1097/pr9.000000 0000000598
104. Jones EA, Asaad F, Patel N, Jain E, Abd-Elsayed A. Management of Fibromyalgia: An Update. Biomedicines. Jun 6 2024;12(6)doi:10.339 0/biomedicines12061266
105. Hardmeier M, Leocani L, Fuhr P. A new role for evoked potentials in MS? Repurposing evoked potentials as biomarkers for clinical trials in MS. Mult Scler. Sep 2017;23(10):1309-1319. doi:10.117 7/1352458517707265
106. Society TNMS. Relapsing-Remitting Multiple Sclerosis (RRMS). Accessed 14 Oct 2025, 2025. https://www.nationalmssociety.org/understanding-ms/what-is-ms/types-of-ms/relapse-remitting-ms
107. Kingdon CC, Bowman EW, Curran H, Nacul L, Lacerda EM. Functional Status and Well-Being in People with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Compared with People with Multiple Sclerosis and Healthy Controls. Pharmacoecon Open. Dec 2018;2(4):381-392. doi:10.1007/s41669-018-0071-6
108. Nacul LC, Lacerda EM, Campion P, et al. The functional status and well being of people with myalgic encephalomyelitis/chronic fatigue syndrome and their carers. BMC Public Health. May 27 2011;11:402. doi:10.1186/1471-2458-11-402
109. Bae J, Lin JS. Healthcare Utilization in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): Analysis of US Ambulatory Healthcare Data, 2000-2009. Front Pediatr. 2019;7:185. doi:10 .3389/fped.2019.00185
110. Pheby DFH, Araja D, Berkis U, et al. A Literature Review of GP Knowledge and Understanding of ME/CFS: A Report from the Socioeconomic Working Group of the European Network on ME/CFS (EUROMENE). Medicina (Kaunas). Dec 24 2020;57(1)doi:10.3390/medicina57010007
111. Gendelman O, Shapira R, Tiosano S, et al. Utilisation of healthcare services and drug consumption in fibromyalgia: A cross-sectional analysis of the Clalit Health Service database. Int J Clin Pract. Nov 2021;75(11):e14729. doi:10.1111/ijcp.14729
112. Jones JT, Black WR, Cogan W, Callen E. Resource utilization and multidisciplinary care needs for patients with Ehlers-Danlos syndrome. Mol Genet Genomic Med. Nov 2022;10(11):e2057. doi:10.1002/mgg3.2057
113. O'Sullivan S. It's all in your head: Stories from the frontline of psychosomatic illness. Random House; 2016.
114. Valdez AR, Hancock EE, Adebayo S, et al. Estimating Prevalence, Demographics, and Costs of ME/CFS Using Large Scale Medical Claims Data and Machine Learning. Front Pediatr. 2018;6:412. doi:10.3389/fped.2018.00412
115. Goodin DS, Frohman EM, Garmany GP, Jr., et al. Disease modifying therapies in multiple sclerosis: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and the MS Council for Clinical Practice Guidelines [RETIRED]. Neurology. Jan 22 2002;58(2):169-78. doi:10.1212/wnl.58.2.169
116. Hauser SL, Cree BAC. Treatment of Multiple Sclerosis: A Review. Am J Med. Dec 2020;133(12): 1380-1390.e2. doi:10.1016/j.amjmed.2020.05.049
117. Jason LA, Benton MC, Valentine L, Johnson A, Torres-Harding S. The economic impact of ME/ CFS: individual and societal costs. Dyn Med. Apr 8 2008;7:6. doi:10.1186/1476-5918-7-6
118. Bowden N, McLeod, K., Anns, F., Catchpole, L., Charlton, F., Taylor, B. S., Vallings, R., Vu, H., Tate, W. Health, Labour Market, And Social Service Outcomes For People With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome On A Health Or Disability Related Benefit: An Aotearoa | New Zealand Nationwide Cross-Sectional Study Using The Integrated Data Infrastructure. OSF Preprints. 2025;
119. Khan G, Hashim MJ. Epidemiology of Multiple Sclerosis: Global, Regional, National and Sub-National-Level Estimates and Future Projections. J Epidemiol Glob Health. Feb 10 2025;15(1):21. doi:10.1007/s44197-025-00353-6
120. Schubart JR, Mills SE, Francomano CA, Stuckey-Peyrot H. A qualitative study of pain and related symptoms experienced by people with Ehlers-Danlos syndromes. Front Med (Lausanne). 2023;10:1291189. doi:10.3389/fmed.2023.1291189
121. Berger A, Dukes E, Martin S, Edelsberg J, Oster G. Characteristics and healthcare costs of patients with fibromyalgia syndrome. Int J Clin Pract. Sep 2007;61(9):1498-508. doi:10.1111/j.174 2-1241.2007.01480.x
122. Tene L, Bergroth T, Eisenberg A, David SSB, Chodick G. Risk factors, health outcomes, healthcare services utilization, and direct medical costs of patients with long COVID. Int J Infect Dis. Mar 2023;128:3-10. doi:10.1016/j.ijid.2022.12.002
123. Palstam A, Mannerkorpi K. Work Ability in Fibromyalgia: An Update in the 21st Century. Curr Rheumatol Rev. 2017;13(3):180-187. doi:10.2174/ 1573397113666170502152955
124. Taylor RR, Kielhofner GW. Work-related impairment and employment-focused rehabilitation options for individuals with chronic fatigue syndrome: A review. Journal of Mental Health. 2005/06/01 2005;14(3):253-267. doi:10.1080/09638230500136571
125. Bøe Lunde HM, Telstad W, Grytten N, et al. Employment among patients with multiple sclerosis-a population study. PLoS One. 2014;9(7): e103317. doi:10.1371/journal.pone.0103317
126. Collin SM, Crawley E, May MT, Sterne JA, Hollingworth W. The impact of CFS/ME on employment and productivity in the UK: a cross-sectional study based on the CFS/ME national outcomes database. BMC Health Serv Res. Sep 15 2011;11:217. doi:10.1186/1472-6963-11-217
127. Schubart JR, Schaefer EW, Mills SE, et al. The Financial Impact of Ehlers-Danlos Syndromes on Patients in the United States in 2022. Mayo Clin Proc Innov Qual Outcomes. Feb 2025;9(1):100586. doi:10.1016/j.mayocpiqo.2024.11.003
128. Stevelink SAM, Fear NT, Hotopf M, Chalder T. Factors associated with work status in chronic fatigue syndrome. Occup Med (Lond). Oct 1 2019;69(6):453-458. doi:10.1093/occmed/kqz108
129. Ottiger M, Poppele I, Sperling N, Schlesinger T, Müller K. Work ability and return-to-work of patients with post-COVID-19: a systematic review and meta-analysis. BMC Public Health. Jul 7 2024;24(1):1811. doi:10.1186/s12889-024-19328-6
130. Amris K, Ibsen R, Duhn PH, et al. Health inequities and societal costs for patients with fibromyalgia and their spouses: a Danish cohort study. RMD Open. Feb 2 2024;10(1)doi:10.1136/ rmdopen-2023-003904
131. Henriksson CM, Liedberg GM, Gerdle B. Women with fibromyalgia: work and rehabilitation. Disabil Rehabil. Jun 17 2005;27(12):685-94. doi:10. 1080/09638280400009089
132. Vitturi BK, Rahmani A, Dini G, et al. Spatial and temporal distribution of the prevalence of unemployment and early retirement in people with multiple sclerosis: A systematic review with meta-analysis. PLoS One. 2022;17(7):e0272156. doi:10.1 371/journal.pone.0272156
133. Vitturi BK, Rahmani A, Dini G, et al. Occupational outcomes of people with multiple sclerosis: a scoping review. BMJ Open. Jul 1 2022; 12(7):e058948. doi:10.1136/bmjopen-2021-058948
134. Black WR, Black LL, Jones JT. Barriers to the Diagnosis, Care, and Management of Pediatric Patients With Ehlers-Danlos Syndrome in the United States: A Qualitative Analysis. Glob Pediatr Health. 2023;10:2333794x231212081. doi:10.117 7/2333794x231212081
135. Pheby DFH, Araja D, Berkis U, et al. The Development of a Consistent Europe-Wide Approach to Investigating the Economic Impact of Myalgic Encephalomyelitis (ME/CFS): A Report from the European Network on ME/CFS (EUROMENE). Healthcare (Basel). Apr 7 2020;8(2) doi:10.3390/healthcare8020088
136. Wilson N, Beasley MJ, Pope C, et al. UK healthcare services for people with fibromyalgia: results from two web-based national surveys (the PACFiND study). BMC Health Serv Res. Aug 3 2022;22(1):989. doi:10.1186/s12913-022-08324-4
137. NICE. National Institute for Health and Care Excellence: Guidelines. Multiple sclerosis in adults: management. National Institute for Health and Care Excellence (NICE); 2022.
138. ANZMES. National advisory on me releases best practice guidance with clinician and researcher support. Accessed 14 Oct 2025, https://anzmes.org.nz/national-advisory-on-me-releases-best-practice-guidance-with-clinician-and-researcher-support/
139. Castro-Marrero J, Faro M, Zaragozá MC, et al. Unemployment and work disability in individuals with chronic fatigue syndrome/myalgic encephalomyelitis: a community-based cross-sectional study from Spain. BMC Public Health. Jun 28 2019;19(1):840. doi:10.1186/s12889-019-7225-z
140. Wolfe F, Walitt BT, Katz RS, Häuser W. Social security work disability and its predictors in patients with fibromyalgia. Arthritis Care Res (Hoboken). Sep 2014;66(9):1354-63. doi:10.1002/acr.22305
141. Kavaliunas A, Wiberg M, Tinghög P, et al. Earnings and Financial Compensation from Social Security Systems Correlate Strongly with Disability for Multiple Sclerosis Patients. PLoS One. 2015;10 (12):e0145435. doi:10.1371/journal.pone.0145435
142. Bebo B, Cintina I, LaRocca N, et al. The Economic Burden of Multiple Sclerosis in the United States: Estimate of Direct and Indirect Costs. Neurology. May 3 2022;98(18):e1810-e1817 . doi:10.1212/wnl.0000000000200150
143. MSNZ. Supporting New Zealanders to Live Well with MS. Accessed 14th October, 2025. https://www.msnz.org.nz
144. Falk Hvidberg M, Brinth LS, Olesen AV, Petersen KD, Ehlers L. The Health-Related Quality of Life for Patients with Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME/CFS). PLoS One. 2015;10(7):e0132421. doi:10.1371/journal.pone.0132421
145. Excellence NNIfHaC. Myalgic encephalomyelitis (or encephalopathy) / chronic fatigue syndrome: diagnosis and management (NG206). Accessed 15 oct 2025, https://www.nice.org.uk/guidance/ng206
146. Malfait F, Castori M, Francomano CA, et al. The Ehlers-Danlos syndromes. Nat Rev Dis Primers. Jul 30 2020;6(1):64. doi:10.1038/s41572-020-0194-9
147. Burling F, Callear, R., Campbell-Stokes, P., Bromhead, C., Crawford, L., Preston, M., Robertson, S., & Taylor, W. . Hypermobility and ehlers-danlos syndromes (EDS) - New Zealand guideline 2019. 2019. https://ehlers-danlos.org.nz/wp-content/uploads/2023/01/NZ-EDS-Guideline-V1-2019-1.pdf
148. Ministry of Health MH. Health care and rare disorders: Evidence brief. 2024b. https://www.health.govt.nz/system/files/2024-12/health-care-and-rare-disorders.pdf
149. Zealand E-DSAN. How is Ehlers-Danlos Syndrome and Hypermobility Spectrum Disorder diagnosed? https://ehlers-danlos.org.nz/eds-info/
150. Aotearoa AN-M. Fibromyalgia. Accessed 15 Oct 2025, 2025. https://www.arthritis.org.nz/newly-diagnosed/types-of-arthritis/fibromyalgia
151. Qureshi AG, Jha SK, Iskander J, et al. Diagnostic Challenges and Management of Fibromyalgia. Cureus. Oct 2021;13(10):e18692. doi:10.7759/cureus.18692
152. Devan H, Davies, C., Grainger, R., Perry, M. A., Hale, L. A., & Ingham, T. . Partnering with whānau to address inequities in pain management. Ministry of Health. Ministry of Health, NZ. https://www.health.govt.nz/system/files/2024-05/day_2_-_3.1_hem_devan_and_cheryl_davies.pdf
153. Health Mo. Models of Care for People Living with Long COVID. New Zealand government. https://www.health.govt.nz/system/files/2025-05/models-care-people-living-with-long-covid.pdf
154. Minister of Health NZg. Government policy statement on health 2024-2027. Manatu Hauora, Ministry of Health,. 14th October 2025, 2024. Accessed 14th October 2025, 2025. https://www.health.govt.nz/system/files/2024-06/government-policy-statement-on-health-2024-2027-v4.pdf
155. NICE. Myalgic encephalomyelitis (or encephalopathy)/chronic fatigue syndrome: diagnosis and management. https://www.nice.org.uk/guidance/ng206
156. Health NDo. National strategy for ME/CFS. https://www.helsedirektoratet.no
157. Health AGDo. Long COVID National Plan. 15th October 2025. https://www.health.gov.au
158. Whitwell M. ME/CFS and Long COVID support in New Zealand. 14th October, 2025. https://tatou.health.govt.nz/the-future-of-the-health-system/me-cfs-long-covid-support-in-new-zealand
159. Development MoS. Very high needs service for people with a disability or health conditions. 14th October, 2025. https://www.msd.govt.nz/what-we-can-do/disability-services/very-high-needs-service-for-people-with-a-disability-or-health-conditions.html
160. ANZMES. Transforming ME/CFS Care: A Call to Action for Aotearoa New Zealand. Associated New Zealand Myalgic Encephalomyelitis Society Incorporated. 14th October, 2025. https://anzmes.org.nz/wp-content/uploads/2025/05/Transforming-ME_CFS-Care_-A-Call-to-Action-for-Aotearoa-New-Zealand.pdf
161. Jorgensen D, Parsons M, Jacobs S, Arksey H. The New Zealand informal caregivers and their unmet needs. N Z Med J. Jun 25 2010;123(1317):9-16.
162. Synergia. The state of caring in Aotearoa. 2022. https://carers.net.nz/wp-content/uploads/2022/07/State-of-Caring-Report-Aug2022.pdf
163. Bradely L. Is fibromyalgia a disability? https://www.moregooddays.com/post/is-fibromyalgia-a-disability
164. sällskapet SM. THE SWEDISH MS-ASSOCIATION. https://www.mssallskapet.se/information-in-english/
165. Zar. Ambulante reha bei Long COVID. 14th October, 2025. https://www.zar.de/long-covid/#!/s?services=Long-COVID%20Rehahttps://www.pharmac.govt.nz/news-and-resources/consultations-and-decisions/decision-for-funded-multiple-sclerosis-treatments
166. CAN-PCC. Canadian guidelines for post COVID-19 condition. https://canpcc.ca/home/
167. Zealand. E-DSAN. How is Ehlers-Danlos Syndrome and Hypermobility Spectrum Disorder diagnosed? https://ehlers-danlos.org.nz/eds-info/
168. Development MoS. A breakdown of financial support for specific health conditions. 14th October, 2025. https://www.msd.govt.nz/documents/about-msd-and-our-work/publications-resources/official-information-responses/2023/october/25102023-a-breakdown-of-financial-support-for-specified-health-conditions-rates-eligibility-and-funding-allocation-inclusive.pdf
169. Kela. 14th October, 2025. https://www.kela.fi
170. trust BaWGyc. PIP health condition guides: Claim PIP for fibromyalgia. https://www.benefitsandwork.co.uk/personal-independence-payment-pip/pip-health-conditions/claim-pip-for-fibromyalgia
2. Staff M. AN OUTBREAK of encephalomyelitis in the Royal Free Hospital Group, London, in 1955. Br Med J. Oct 19 1957;2(5050):895-904.
3. Levine PH, Jacobson S, Pocinki AG, et al. Clinical, epidemiologic, and virologic studies in four clusters of the chronic fatigue syndrome. Arch Intern Med. Aug 1992;152(8):1611-6.
4. Vallings R. Chronic Fatigue Syndrome M.E.Symptoms, Diagnosis, Management. Calico Publishing; 2020.
5. Davis HE, McCorkell L, Vogel JM, Topol EJ. Long COVID: major findings, mechanisms and recommendations. Nat Rev Microbiol. Mar 2023;21(3):133-146. doi: 10.1038/s41579-022-00846-2
6. Gentilotti E, Górska A, Tami A, et al. Clinical phenotypes and quality of life to define post-COVID-19 syndrome: a cluster analysis of the multinational, prospective ORCHESTRA cohort. eClinicalMedicine. 2023/08/01/ 2023;62:102107. doi:https://doi.org/10.1016/j.eclinm.2023.102107
7. Tate WP, Walker MOM, Peppercorn K, Blair ALH, Edgar CD. Towards a Better Understanding of the Complexities of Myalgic Encephalomyelitis /Chronic Fatigue Syndrome and Long COVID. Int J Mol Sci. 2023;24(6):5124.
8. Komaroff AL, Lipkin WI. ME/CFS and Long COVID share similar symptoms and biological abnormalities: road map to the literature. Front Med (Lausanne). 2023;10:1187163. doi:10.3389/ fmed.2023.1187163
9. Eckey M, Li P, Morrison B, et al. Patient-reported treatment outcomes in ME/CFS and long COVID. Proc Natl Acad Sci U S A. Jul 15 2025;122(28): e2426874122. doi:10.1073/pnas.2426874122
10. Marshall-Gradisnik S, Eaton-Fitch N. Understanding myalgic encephalomyelitis. Science. Sep 9 2022;37 7(6611):1150-1151. doi:10.1126/science.abo1261
11. Peppercorn K, Edgar CD, Kleffmann T, Tate WP. A pilot study on the immune cell proteome of long COVID patients shows changes to physiological pathways similar to those in myalgic encephalomyelitis/chronic fatigue syndrome. Sci Rep. Dec 12 2023;13(1):22068. doi:10.1038/s4159 8-023-49402-9
12. Peppercorn K, ; Edgar, C.; Al Momani, S,; Rodger, E. J.; Tate, W.P.; Chatterjee, A. Application of DNA methylome analysis to patients with ME/CFS. Methods in Molecular Biology. Spinger; 2025.
13. Shah KM, Shah RM, Sawano M, et al. Factors Associated with Long COVID Recovery among US Adults. Am J Med. Sep 2024;137(9):896-899. doi:10.1016/j.amjmed.2024.04.017
14. Ballouz T, Menges D, Anagnostopoulos A, et al. Recovery and symptom trajectories up to two years after SARS-CoV-2 infection: population based, longitudinal cohort study. Bmj. May 31 2023;381:e074425. doi:10.1136/bmj-2022-074425
15. Hartung TJ, Bahmer T, Chaplinskaya-Sobol I, et al. Predictors of non-recovery from fatigue and cognitive deficits after COVID-19: a prospective, longitudinal, population-based study. EClinicalMedicine. Mar 2024;69:102456. doi:10.1016/j.eclinm.2024.102456
16. Al-Aly Z, Davis H, McCorkell L, et al. Long COVID science, research and policy. Nat Med. Aug 2024;30(8):2148-2164. doi:10.1038/s41591-024-03173-6
17. Walitt B, Nahin RL, Katz RS, Bergman MJ, Wolfe F. The Prevalence and Characteristics of Fibromyalgia in the 2012 National Health Interview Survey. PLoS One. 2015;10(9):e0138024. doi:10.13 71/journal.pone.0138024
18. Arnold LM, Fan J, Russell IJ, et al. The fibromyalgia family study: a genome-wide linkage scan study. Arthritis Rheum. Apr 2013;65(4):1122-8. doi:10.1002/art.37842
19. Rahman MS, Winsvold BS, Chavez Chavez SO, et al. Genome-wide association study identifies RNF123 locus as associated with chronic widespread musculoskeletal pain. Ann Rheum Dis. Sep 2021;80 (9):1227-1235. doi:10.1136/annrheumdis-2020-219624
20. Pan Q, Cai T, Tao Y, et al. Genome-wide association study identifies novel genetic variants associated with widespread pain in the UK Biobank (N = 172,230). Mol Pain. Jan-Dec 2025;21:1744806 9251346603. doi:10.1177/17448069251346603
21. Das S, Taylor K, Kozubek J, Sardell J, Gardner S. Genetic risk factors for ME/CFS identified using combinatorial analysis. J Transl Med. Dec 14 2022; 20(1):598. doi:10.1186/s12967-022-03815-8
22. Taylor K, Pearson M, Das S, et al. Genetic risk factors for severe and fatigue dominant long COVID and commonalities with ME/CFS identified by combinatorial analysis. Journal of Translational Medicine. 2023/11/01 2023;21(1):775. doi:10.1186 /s12967-023-04588-4
23. Boutin T, Bretherick A, Dibble J, et al. Initial findings from the DecodeME genome-wide association study of myalgic encephalomyelitis/chronic fatigue syndrome. 2025.
24. Cortini F, Villa C. Ehlers-Danlos syndromes and epilepsy: An updated review. Seizure. Apr 2018;57:1-4. doi:10.1016/j.seizure.2018.02.013
25. Malfait F, Francomano C, Byers P, et al. The 2017 international classification of the Ehlers-Danlos syndromes. Am J Med Genet C Semin Med Genet. Mar 2017;175(1):8-26. doi:10.1002/ajmg.c.31552
26. Lawrence EJ. The clinical presentation of Ehlers-Danlos syndrome. Adv Neonatal Care. Dec 2005;5(6):301-14. doi:10.1016/j.adnc.2005.09.006
27. Mudie K, Ramiller A, Whittaker S, Phillips LE. Do people with ME/CFS and joint hypermobility represent a disease subgroup? An analysis using registry data. Front Neurol. 2024;15:1324879. doi: 10.3389/fneur.2024.1324879
28. Malfait F, Wenstrup RJ, De Paepe A. Clinical and genetic aspects of Ehlers-Danlos syndrome, classic type. Genet Med. Oct 2010;12(10):597-605. doi:10.1097/GIM.0b013e3181eed412
29. Bakalidou D, Giannopapas V, Giannopoulos S. Thoughts on Fatigue in Multiple Sclerosis Patients. Cureus. Jul 2023;15(7):e42146. doi:10.7759/cureus.42146
30. Travers BS, Tsang BK, Barton JL. Multiple sclerosis: Diagnosis, disease-modifying therapy and prognosis. Aust J Gen Pract. Apr 2022;51 (4):199-206. doi:10.31128/ajgp-07-21-6103
31. Venkatesan A, Johnson RT. Infections and multiple sclerosis. Handb Clin Neurol. 2014;122: 151-71. doi:10.1016/b978-0-444-52001-2.00007-8
32. Riise T, Mohr DC, Munger KL, et al. Stress and the risk of multiple sclerosis. Neurology. May 31 2011;76(22):1866-71. doi:10.1212/WNL.0b013e31821d74c5
33. Mohr DC, Hart SL, Julian L, Cox D, Pelletier D. Association between stressful life events and exacerbation in multiple sclerosis: a meta-analysis. Bmj. Mar 27 2004;328(7442):731. doi:10.1136/bmj .38041.724421.55
34. Tate W, Walker M, Sweetman E, et al. Molecular Mechanisms of Neuroinflammation in ME/CFS and Long COVID to Sustain Disease and Promote Relapses. Front Neurol. 2022;13:877772. doi:10.3389/fneur.2022.877772
35. Sharma S, Hodges LD, Peppercorn K, et al. Precision Medicine Study of Post-Exertional Malaise Epigenetic Changes in Myalgic Encephalomyelitis/Chronic Fatigue Patients During Exercise. Int J Mol Sci. Sep 3 2025;26(17)doi:10.33 90/ijms26178563
36. Compston A, Coles A. Multiple sclerosis. Lancet. Oct 25 2008;372(9648):1502-17. doi:10.10 16/s0140-6736(08)61620-7
37. Wootla B, Eriguchi M, Rodriguez M. Is multiple sclerosis an autoimmune disease? Autoimmune Dis. 2012;2012:969657. doi:10.1155/2012/969657
38. Vilisaar J, Harikrishnan S, Suri M, Constantinescu CS. Ehlers-Danlos syndrome and multiple sclerosis: a possible association. Mult Scler. May 2008;14(4): 567-70. doi:10.1177/1352458507083187
39. Mar PL, Raj SR. Neuronal and hormonal perturbations in postural tachycardia syndrome. Front Physiol. 2014;5:220. doi:10.3389/fphys.2014.00220
40. van Campen C, Rowe PC, Visser FC. Low Sensitivity of Abbreviated Tilt Table Testing for Diagnosing Postural Tachycardia Syndrome in Adults With ME/CFS. Front Pediatr. 2018;6:349. doi:10.3389/fped.2018.00349
41. Roma M, Marden CL, De Wandele I, Francomano CA, Rowe PC. Postural tachycardia syndrome and other forms of orthostatic intolerance in Ehlers-Danlos syndrome. Auton Neurosci. Dec 2018;215:89-96. doi:10.1016/j.autneu.2018.02.006
42. Adamec I, Lovrić M, Žaper D, et al. Postural orthostatic tachycardia syndrome associated with multiple sclerosis. Auton Neurosci. Jan 2013;173 (1-2):65-8. doi:10.1016/j.autneu.2012.11.009
43. Staud R. Autonomic dysfunction in fibromyalgia syndrome: postural orthostatic tachycardia. Curr Rheumatol Rep. Dec 2008;10(6):463-6. doi:10.100 7/s11926-008-0076-8
44. Theoharides TC, Tsilioni I, Ren H. Recent advances in our understanding of mast cell activation - or should it be mast cell mediator disorders? Expert Rev Clin Immunol. Jun 2019;15(6):639-656. doi:10.1080/1744666x.2019.1596800
45. Afrin LB, Ackerley MB, Bluestein LS, et al. Diagnosis of mast cell activation syndrome: a global "consensus-2". Diagnosis (Berl). May 26 2021;8(2):137-152. doi:10.1515/dx-2020-0005
46. Hatziagelaki E, Adamaki M, Tsilioni I, Dimitriadis G, Theoharides TC. Myalgic Encephalomyelitis /Chronic Fatigue Syndrome-Metabolic Disease or Disturbed Homeostasis due to Focal Inflammation in the Hypothalamus? J Pharmacol Exp Ther. Oct 2018;367(1):155-167. doi:10.1124/jpet.118.250845
47. Theoharides TC, Tsilioni I, Arbetman L, et al. Fibromyalgia syndrome in need of effective treatments. J Pharmacol Exp Ther. Nov 2015;355 (2):255-63. doi:10.1124/jpet.115.227298
48. Akin C. Mast cell activation syndromes. J Allergy Clin Immunol. Aug 2017;140(2):349-355. doi:10.1016/j.jaci.2017.06.007
49. Nguyen T, Johnston S, Chacko A, et al. Novel characterisation of mast cell phenotypes from peripheral blood mononuclear cells in chronic fatigue syndrome/myalgic encephalomyelitis patients. Asian Pac J Allergy Immunol. Jun 2017;35(2):75-81. doi:10.12932/ap0771
50. Mandarano AH, Maya J, Giloteaux L, et al. Myalgic encephalomyelitis/chronic fatigue syndrome patients exhibit altered T cell metabolism and cytokine associations. J Clin Invest. Mar 2 2020; 130(3):1491-1505. doi:10.1172/jci132185
51. Walker MOM, Peppercorn K, Kleffmann T, Edgar CD, Tate WP. An understanding of the immune dysfunction in susceptible people who develop the post-viral fatigue syndromes Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Long COVID. Medical Research Archives. 2023-07-06 2023;11(7.1)doi:10.18103/mra.v11i7.1.4083
52. Walitt B, Singh K, LaMunion SR, et al. Deep phenotyping of post-infectious myalgic encephalomyelitis/chronic fatigue syndrome. Nat Commun. Feb 21 2024;15(1):907. doi:10.1038/ s41467-024-45107-3
53. Eaton-Fitch N, Rudd P, Er T, et al. Immune exhaustion in ME/CFS and long COVID. JCI Insight. Oct 22 2024;9(20)doi:10.1172/jci.insight.183810
54. Cervia-Hasler C, Brüningk SC, Hoch T, et al. Persistent complement dysregulation with signs of thromboinflammation in active Long Covid. Science. Jan 19 2024;383(6680):eadg7942. doi:10. 1126/science.adg7942
55. Altmann DM, Whettlock EM, Liu S, Arachchillage DJ, Boyton RJ. The immunology of long COVID. Nat Rev Immunol. Oct 2023;23(10): 618-634. doi:10.1038/s41577-023-00904-7
56. Yin K, Peluso MJ, Luo X, et al. Long COVID manifests with T cell dysregulation, inflammation and an uncoordinated adaptive immune response to SARS-CoV-2. Nat Immunol. Feb 2024;25(2):218-225. doi:10.1038/s41590-023-01724-6
57. Clauw D, Sarzi-Puttini P, Pellegrino G, Shoenfeld Y. Is fibromyalgia an autoimmune disorder? Autoimmun Rev. Jan 2024;23(1):103424. doi:10.1016/j.autrev. 2023.103424
58. Paroli M, Gioia C, Accapezzato D, Caccavale R. Inflammation, Autoimmunity, and Infection in Fibromyalgia: A Narrative Review. Int J Mol Sci. May 29 2024;25(11)doi:10.3390/ijms25115922
59. International statistical classification of diseases, injuries, and causes of death. (World Health Organisation) (1969).
60. Nakatomi Y, Mizuno K, Ishii A, et al. Neuroinflammation in Patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: An (1)(1)C-(R)-PK11195 PET Study. J Nucl Med. Jun 2014; 55(6):945-50. doi:10.2967/jnumed.113.131045
61. Bynke A, Julin P, Gottfries CG, et al. Autoantibodies to beta-adrenergic and muscarinic cholinergic receptors in Myalgic Encephalomyelitis (ME) patients - A validation study in plasma and cerebrospinal fluid from two Swedish cohorts. Brain Behav Immun Health. Aug 2020;7:100107. doi:10.1016/j.bbih.2020.100107
62. Talkington GM, Kolluru P, Gressett TE, et al. Neurological sequelae of long COVID: a comprehensive review of diagnostic imaging, underlying mechanisms, and potential therapeutics. Front Neurol. 2024;15:1465787. doi:10.3389/fneur .2024.1465787
63. Peppercorn K, Sharma S, Edgar CD, et al. Comparing DNA Methylation Landscapes in Peripheral Blood from Myalgic Encephalomyelitis /Chronic Fatigue Syndrome and Long COVID Patients. Int J Mol Sci. Jul 10 2025;26(14)doi:10. 3390/ijms26146631
64. Clauw DJ, Arnold LM, McCarberg BH. The science of fibromyalgia. Mayo Clin Proc. Sep 2011;86(9):907-11. doi:10.4065/mcp.2011.0206
65. Fitzcharles MA, Cohen SP, Clauw DJ, et al. Nociplastic pain: towards an understanding of prevalent pain conditions. Lancet. May 29 2021;397(10289):2098-2110. doi:10.1016/s0140-6736(21)00392-5
66. Becker S, Schweinhardt P. Dysfunctional neurotransmitter systems in fibromyalgia, their role in central stress circuitry and pharmacological actions on these systems. Pain Res Treat. 2012; 2012:741746. doi:10.1155/2012/741746
67. Fernandez A, Jaquet M, Aubry-Rozier B, et al. Functional neurological signs in hypermobile Ehlers-Danlos syndrome and hypermobile spectrum disorders with suspected neuropathic pain. Brain Behav. Feb 2024;14(2):e3441. doi:10.1002/brb3.3441
68. Oudejans E, Luchicchi A, Strijbis EMM, Geurts JJG, van Dam AM. Is MS affecting the CNS only? Lessons from clinic to myelin pathophysiology. Neurol Neuroimmunol Neuroinflamm. Jan 2021;8 (1)doi:10.1212/nxi.0000000000000914
69. Holden S, Maksoud R, Eaton-Fitch N, et al. A systematic review of mitochondrial abnormalities in myalgic encephalomyelitis/chronic fatigue syndrome/systemic exertion intolerance disease. J Transl Med. Jul 29 2020;18(1):290. doi:10.1186/s1 2967-020-02452-3
70. Annesley SJ, Missailidis D, Heng B, Josev EK, Armstrong CW. Unravelling shared mechanisms: insights from recent ME/CFS research to illuminate long COVID pathologies. Trends Mol Med. May 2024;30(5):443-458. doi:10.1016/j.molmed.2024.02.003
71. Syed AM, Karius AK, Ma J, Wang PY, Hwang PM. Mitochondrial Dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Physiology (Bethesda). Jul 1 2025;40(4):0. doi:10. 1152/physiol.00056.2024
72. Sweetman E, Kleffmann T, Edgar C, et al. A SWATH-MS analysis of Myalgic Encephalomyelitis /Chronic Fatigue Syndrome peripheral blood mononuclear cell proteomes reveals mitochondrial dysfunction. J Transl Med. Sep 24 2020;18(1):365. doi:10.1186/s12967-020-02533-3
73. Missailidis D, Annesley SJ, Allan CY, et al. An Isolated Complex V Inefficiency and Dysregulated Mitochondrial Function in Immortalized Lymphocytes from ME/CFS Patients. Int J Mol Sci. Feb 6 2020;21(3)doi:10.3390/ijms21031074
74. Arnold DL, Bore PJ, Radda GK, Styles P, Taylor DJ. Excessive intracellular acidosis of skeletal muscle on exercise in a patient with a post-viral exhaustion/fatigue syndrome. A 31P nuclear magnetic resonance study. Lancet. Jun 23 1984;1(8 391):1367-9. doi:10.1016/s0140-6736(84)91871-3
75. Naviaux RK, Naviaux JC, Li K, et al. Metabolic features of chronic fatigue syndrome. Proc Natl Acad Sci U S A. Sep 13 2016;113(37):E5472-80. doi:10.1073/pnas.1607571113
76. Fluge Ø, Mella O, Bruland O, et al. Metabolic profiling indicates impaired pyruvate dehydrogenase function in myalgic encephalopathy/chronic fatigue syndrome. JCI Insight. Dec 22 2016;1(21):e89376. doi:10.1172/jci.insight.89376
77. Germain A, Ruppert D, Levine SM, Hanson MR. Metabolic profiling of a myalgic encephalomyelitis/chronic fatigue syndrome discovery cohort reveals disturbances in fatty acid and lipid metabolism. Mol Biosyst. Jan 31 2017; 13(2):371-379. doi:10.1039/c6mb00600k
78. Mueller C, Lin JC, Sheriff S, Maudsley AA, Younger JW. Evidence of widespread metabolite abnormalities in Myalgic encephalomyelitis/ chronic fatigue syndrome: assessment with whole-brain magnetic resonance spectroscopy. Brain Imaging Behav. Apr 2020;14(2):562-572. doi:10.1007/s116 82-018-0029-410.1007/s11682-018-0029-4.
79. Thapaliya K, Marshall-Gradisnik S, Eaton-Fitch N, et al. Imbalanced Brain Neurochemicals in Long COVID and ME/CFS: A Preliminary Study Using MRI. Am J Med. Mar 2025;138(3):567-574.e1. doi: 10.1016/j.amjmed.2024.04.007
80. Macchi C, Giachi A, Fichtner I, et al. Mitochondrial function in patients affected with fibromyalgia syndrome is impaired and correlates with disease severity. Sci Rep. Dec 4 2024;14(1): 30247. doi:10.1038/s41598-024-81298-x
81. Jung YH, Kim H, Seo S, et al. Central metabolites and peripheral parameters associated neuroinflammation in fibromyalgia patients: A preliminary study. Medicine (Baltimore). Mar 31 2023;102(13):e33305. doi:10.1097/md.0000000000033305
82. Davis L, Higgs M, Snaith A, et al. Dysregulation of lipid metabolism, energy production, and oxidative stress in myalgic encephalomyelitis/chronic fatigue syndrome, Gulf War Syndrome and fibromyalgia. Front Neurosci. 2025;19:1498981. doi:10.3389/ fnins.2025.1498981
83. Shirvani P, Shirvani A, Holick MF. Mitochondrial Dysfunction and Its Potential Molecular Interplay in Hypermobile Ehlers-Danlos Syndrome: A Scoping Review Bridging Cellular Energetics and Genetic Pathways. Curr Issues Mol Biol. Feb 19 2025;47 (2)doi:10.3390/cimb47020134
84. Ravera S, Panfoli I, Calzia D, et al. Evidence for aerobic ATP synthesis in isolated myelin vesicles. Int J Biochem Cell Biol. Jul 2009;41(7):1581-91. doi:10.1016/j.biocel.2009.01.009
85. Ravera S, Panfoli I, Aluigi MG, Calzia D, Morelli A. Characterization of Myelin Sheath F(o)F(1)-ATP synthase and its regulation by IF(1). Cell Biochem Biophys. Mar 2011;59(2):63-70. doi:10.1007/s1201 3-010-9112-1
86. Morelli AM, Ravera S, Panfoli I. The aerobic mitochondrial ATP synthesis from a comprehensive point of view. Open Biol. Oct 2020;10(10):200224. doi:10.1098/rsob.200224
87. Mishra G, Townsend KL. The metabolic and functional roles of sensory nerves in adipose tissues. Nat Metab. Sep 2023;5(9):1461-1474. doi: 10.1038/s42255-023-00868-x
88. Greeck VB, Williams SK, Haas J, Wildemann B, Fairless R. Alterations in Lymphocytic Metabolism-An Emerging Hallmark of MS Pathophysiology? Int J Mol Sci. Jan 20 2023;24(3)doi:10.3390/ijms24032094
89. König RS, Albrich WC, Kahlert CR, et al. The Gut Microbiome in Myalgic Encephalomyelitis (ME) /Chronic Fatigue Syndrome (CFS). Front Immunol. 2021;12:628741. doi:10.3389/fimmu.2021.628741
90. El-Sehrawy A, Ayoub, II, Uthirapathy S, et al. The microbiota-gut-brain axis in myalgic encephalomyelitis/chronic fatigue syndrome: a narrative review of an emerging field. Eur J Transl Myol. Mar 31 2025;35(1)doi:10.4081/ejtm.2025.13690
91. Jurek JM, Castro-Marrero J. A Narrative Review on Gut Microbiome Disturbances and Microbial Preparations in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Implications for Long COVID. Nutrients. May 21 2024;16(11)doi:10.3390/nu16111545
92. Fallah A, Sedighian H, Kachuei R, Fooladi AAI. Human microbiome in post-acute COVID-19 syndrome (PACS). Curr Res Microb Sci. 2025;8:10 0324. doi:10.1016/j.crmicr.2024.100324
93. Minerbi A, Khoutorsky A, Shir Y. Decoding the connection: unraveling the role of gut microbiome in fibromyalgia. Pain Rep. Feb 2025;10(1):e1224. doi:10.1097/pr9.0000000000001224
94. Choudhary A, Fikree A, Ruffle JK, et al. A machine learning approach to stratify patients with hypermobile Ehlers-Danlos syndrome/ hypermobility spectrum disorders according to disorders of gut brain interaction, comorbidities and quality of life. Neurogastroenterol Motil. Jan 2025;37(1):e14957. doi:10.1111/nmo.14957
95. Parodi B, Kerlero de Rosbo N. The Gut-Brain Axis in Multiple Sclerosis. Is Its Dysfunction a Pathological Trigger or a Consequence of the Disease? Front Immunol. 2021;12:718220. doi:10. 3389/fimmu.2021.718220
96. Sharifa M, Ghosh T, Daher OA, et al. Unraveling the Gut-Brain Axis in Multiple Sclerosis: Exploring Dysbiosis, Oxidative Stress, and Therapeutic Insights. Cureus. Oct 2023;15(10):e47 058. doi:10.7759/cureus.47058
97. Mohsen E, Haffez H, Ahmed S, Hamed S, El-Mahdy TS. Multiple Sclerosis: A Story of the Interaction Between Gut Microbiome and Components of the Immune System. Mol Neurobiol. Jun 2025;6 2(6):7762-7775. doi:10.1007/s12035-025-04728-5
98. Carruthers BM, Jain AK, De Meirleir KL, et al. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Journal of Chronic Fatigue Syndrome. 2003/01/01 2003;11(1):7-115. doi:10.1300/J092v11n01_02
99. Carruthers BM, van de Sande MI, De Meirleir KL, et al. Myalgic encephalomyelitis: International Consensus Criteria. J Intern Med. Oct 2011;270(4): 327-38. doi:10.1111/j.1365-2796.2011.02428.x
100. Vallings R. How a Clinician Makes a Diagnosis for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Methods Mol Biol. 2025;292 0:3-11. doi:10.1007/978-1-0716-4498-0_1
101. WHO. A clinical case definition of post COVID-19 condition by a Delphi consensus, 6 October 2021. 2021.
102. RECOVER. RECOVER: Researching COVID to Enhance Recovery. NIH. Accessed 14 October 2025, 2025. https://recovercovid.org
103. Häuser W, Perrot S, Sommer C, Shir Y, Fitzcharles MA. Diagnostic confounders of chronic widespread pain: not always fibromyalgia. Pain Rep. May 2017;2(3):e598. doi:10.1097/pr9.000000 0000000598
104. Jones EA, Asaad F, Patel N, Jain E, Abd-Elsayed A. Management of Fibromyalgia: An Update. Biomedicines. Jun 6 2024;12(6)doi:10.339 0/biomedicines12061266
105. Hardmeier M, Leocani L, Fuhr P. A new role for evoked potentials in MS? Repurposing evoked potentials as biomarkers for clinical trials in MS. Mult Scler. Sep 2017;23(10):1309-1319. doi:10.117 7/1352458517707265
106. Society TNMS. Relapsing-Remitting Multiple Sclerosis (RRMS). Accessed 14 Oct 2025, 2025. https://www.nationalmssociety.org/understanding-ms/what-is-ms/types-of-ms/relapse-remitting-ms
107. Kingdon CC, Bowman EW, Curran H, Nacul L, Lacerda EM. Functional Status and Well-Being in People with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Compared with People with Multiple Sclerosis and Healthy Controls. Pharmacoecon Open. Dec 2018;2(4):381-392. doi:10.1007/s41669-018-0071-6
108. Nacul LC, Lacerda EM, Campion P, et al. The functional status and well being of people with myalgic encephalomyelitis/chronic fatigue syndrome and their carers. BMC Public Health. May 27 2011;11:402. doi:10.1186/1471-2458-11-402
109. Bae J, Lin JS. Healthcare Utilization in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): Analysis of US Ambulatory Healthcare Data, 2000-2009. Front Pediatr. 2019;7:185. doi:10 .3389/fped.2019.00185
110. Pheby DFH, Araja D, Berkis U, et al. A Literature Review of GP Knowledge and Understanding of ME/CFS: A Report from the Socioeconomic Working Group of the European Network on ME/CFS (EUROMENE). Medicina (Kaunas). Dec 24 2020;57(1)doi:10.3390/medicina57010007
111. Gendelman O, Shapira R, Tiosano S, et al. Utilisation of healthcare services and drug consumption in fibromyalgia: A cross-sectional analysis of the Clalit Health Service database. Int J Clin Pract. Nov 2021;75(11):e14729. doi:10.1111/ijcp.14729
112. Jones JT, Black WR, Cogan W, Callen E. Resource utilization and multidisciplinary care needs for patients with Ehlers-Danlos syndrome. Mol Genet Genomic Med. Nov 2022;10(11):e2057. doi:10.1002/mgg3.2057
113. O'Sullivan S. It's all in your head: Stories from the frontline of psychosomatic illness. Random House; 2016.
114. Valdez AR, Hancock EE, Adebayo S, et al. Estimating Prevalence, Demographics, and Costs of ME/CFS Using Large Scale Medical Claims Data and Machine Learning. Front Pediatr. 2018;6:412. doi:10.3389/fped.2018.00412
115. Goodin DS, Frohman EM, Garmany GP, Jr., et al. Disease modifying therapies in multiple sclerosis: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and the MS Council for Clinical Practice Guidelines [RETIRED]. Neurology. Jan 22 2002;58(2):169-78. doi:10.1212/wnl.58.2.169
116. Hauser SL, Cree BAC. Treatment of Multiple Sclerosis: A Review. Am J Med. Dec 2020;133(12): 1380-1390.e2. doi:10.1016/j.amjmed.2020.05.049
117. Jason LA, Benton MC, Valentine L, Johnson A, Torres-Harding S. The economic impact of ME/ CFS: individual and societal costs. Dyn Med. Apr 8 2008;7:6. doi:10.1186/1476-5918-7-6
118. Bowden N, McLeod, K., Anns, F., Catchpole, L., Charlton, F., Taylor, B. S., Vallings, R., Vu, H., Tate, W. Health, Labour Market, And Social Service Outcomes For People With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome On A Health Or Disability Related Benefit: An Aotearoa | New Zealand Nationwide Cross-Sectional Study Using The Integrated Data Infrastructure. OSF Preprints. 2025;
119. Khan G, Hashim MJ. Epidemiology of Multiple Sclerosis: Global, Regional, National and Sub-National-Level Estimates and Future Projections. J Epidemiol Glob Health. Feb 10 2025;15(1):21. doi:10.1007/s44197-025-00353-6
120. Schubart JR, Mills SE, Francomano CA, Stuckey-Peyrot H. A qualitative study of pain and related symptoms experienced by people with Ehlers-Danlos syndromes. Front Med (Lausanne). 2023;10:1291189. doi:10.3389/fmed.2023.1291189
121. Berger A, Dukes E, Martin S, Edelsberg J, Oster G. Characteristics and healthcare costs of patients with fibromyalgia syndrome. Int J Clin Pract. Sep 2007;61(9):1498-508. doi:10.1111/j.174 2-1241.2007.01480.x
122. Tene L, Bergroth T, Eisenberg A, David SSB, Chodick G. Risk factors, health outcomes, healthcare services utilization, and direct medical costs of patients with long COVID. Int J Infect Dis. Mar 2023;128:3-10. doi:10.1016/j.ijid.2022.12.002
123. Palstam A, Mannerkorpi K. Work Ability in Fibromyalgia: An Update in the 21st Century. Curr Rheumatol Rev. 2017;13(3):180-187. doi:10.2174/ 1573397113666170502152955
124. Taylor RR, Kielhofner GW. Work-related impairment and employment-focused rehabilitation options for individuals with chronic fatigue syndrome: A review. Journal of Mental Health. 2005/06/01 2005;14(3):253-267. doi:10.1080/09638230500136571
125. Bøe Lunde HM, Telstad W, Grytten N, et al. Employment among patients with multiple sclerosis-a population study. PLoS One. 2014;9(7): e103317. doi:10.1371/journal.pone.0103317
126. Collin SM, Crawley E, May MT, Sterne JA, Hollingworth W. The impact of CFS/ME on employment and productivity in the UK: a cross-sectional study based on the CFS/ME national outcomes database. BMC Health Serv Res. Sep 15 2011;11:217. doi:10.1186/1472-6963-11-217
127. Schubart JR, Schaefer EW, Mills SE, et al. The Financial Impact of Ehlers-Danlos Syndromes on Patients in the United States in 2022. Mayo Clin Proc Innov Qual Outcomes. Feb 2025;9(1):100586. doi:10.1016/j.mayocpiqo.2024.11.003
128. Stevelink SAM, Fear NT, Hotopf M, Chalder T. Factors associated with work status in chronic fatigue syndrome. Occup Med (Lond). Oct 1 2019;69(6):453-458. doi:10.1093/occmed/kqz108
129. Ottiger M, Poppele I, Sperling N, Schlesinger T, Müller K. Work ability and return-to-work of patients with post-COVID-19: a systematic review and meta-analysis. BMC Public Health. Jul 7 2024;24(1):1811. doi:10.1186/s12889-024-19328-6
130. Amris K, Ibsen R, Duhn PH, et al. Health inequities and societal costs for patients with fibromyalgia and their spouses: a Danish cohort study. RMD Open. Feb 2 2024;10(1)doi:10.1136/ rmdopen-2023-003904
131. Henriksson CM, Liedberg GM, Gerdle B. Women with fibromyalgia: work and rehabilitation. Disabil Rehabil. Jun 17 2005;27(12):685-94. doi:10. 1080/09638280400009089
132. Vitturi BK, Rahmani A, Dini G, et al. Spatial and temporal distribution of the prevalence of unemployment and early retirement in people with multiple sclerosis: A systematic review with meta-analysis. PLoS One. 2022;17(7):e0272156. doi:10.1 371/journal.pone.0272156
133. Vitturi BK, Rahmani A, Dini G, et al. Occupational outcomes of people with multiple sclerosis: a scoping review. BMJ Open. Jul 1 2022; 12(7):e058948. doi:10.1136/bmjopen-2021-058948
134. Black WR, Black LL, Jones JT. Barriers to the Diagnosis, Care, and Management of Pediatric Patients With Ehlers-Danlos Syndrome in the United States: A Qualitative Analysis. Glob Pediatr Health. 2023;10:2333794x231212081. doi:10.117 7/2333794x231212081
135. Pheby DFH, Araja D, Berkis U, et al. The Development of a Consistent Europe-Wide Approach to Investigating the Economic Impact of Myalgic Encephalomyelitis (ME/CFS): A Report from the European Network on ME/CFS (EUROMENE). Healthcare (Basel). Apr 7 2020;8(2) doi:10.3390/healthcare8020088
136. Wilson N, Beasley MJ, Pope C, et al. UK healthcare services for people with fibromyalgia: results from two web-based national surveys (the PACFiND study). BMC Health Serv Res. Aug 3 2022;22(1):989. doi:10.1186/s12913-022-08324-4
137. NICE. National Institute for Health and Care Excellence: Guidelines. Multiple sclerosis in adults: management. National Institute for Health and Care Excellence (NICE); 2022.
138. ANZMES. National advisory on me releases best practice guidance with clinician and researcher support. Accessed 14 Oct 2025, https://anzmes.org.nz/national-advisory-on-me-releases-best-practice-guidance-with-clinician-and-researcher-support/
139. Castro-Marrero J, Faro M, Zaragozá MC, et al. Unemployment and work disability in individuals with chronic fatigue syndrome/myalgic encephalomyelitis: a community-based cross-sectional study from Spain. BMC Public Health. Jun 28 2019;19(1):840. doi:10.1186/s12889-019-7225-z
140. Wolfe F, Walitt BT, Katz RS, Häuser W. Social security work disability and its predictors in patients with fibromyalgia. Arthritis Care Res (Hoboken). Sep 2014;66(9):1354-63. doi:10.1002/acr.22305
141. Kavaliunas A, Wiberg M, Tinghög P, et al. Earnings and Financial Compensation from Social Security Systems Correlate Strongly with Disability for Multiple Sclerosis Patients. PLoS One. 2015;10 (12):e0145435. doi:10.1371/journal.pone.0145435
142. Bebo B, Cintina I, LaRocca N, et al. The Economic Burden of Multiple Sclerosis in the United States: Estimate of Direct and Indirect Costs. Neurology. May 3 2022;98(18):e1810-e1817 . doi:10.1212/wnl.0000000000200150
143. MSNZ. Supporting New Zealanders to Live Well with MS. Accessed 14th October, 2025. https://www.msnz.org.nz
144. Falk Hvidberg M, Brinth LS, Olesen AV, Petersen KD, Ehlers L. The Health-Related Quality of Life for Patients with Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME/CFS). PLoS One. 2015;10(7):e0132421. doi:10.1371/journal.pone.0132421
145. Excellence NNIfHaC. Myalgic encephalomyelitis (or encephalopathy) / chronic fatigue syndrome: diagnosis and management (NG206). Accessed 15 oct 2025, https://www.nice.org.uk/guidance/ng206
146. Malfait F, Castori M, Francomano CA, et al. The Ehlers-Danlos syndromes. Nat Rev Dis Primers. Jul 30 2020;6(1):64. doi:10.1038/s41572-020-0194-9
147. Burling F, Callear, R., Campbell-Stokes, P., Bromhead, C., Crawford, L., Preston, M., Robertson, S., & Taylor, W. . Hypermobility and ehlers-danlos syndromes (EDS) - New Zealand guideline 2019. 2019. https://ehlers-danlos.org.nz/wp-content/uploads/2023/01/NZ-EDS-Guideline-V1-2019-1.pdf
148. Ministry of Health MH. Health care and rare disorders: Evidence brief. 2024b. https://www.health.govt.nz/system/files/2024-12/health-care-and-rare-disorders.pdf
149. Zealand E-DSAN. How is Ehlers-Danlos Syndrome and Hypermobility Spectrum Disorder diagnosed? https://ehlers-danlos.org.nz/eds-info/
150. Aotearoa AN-M. Fibromyalgia. Accessed 15 Oct 2025, 2025. https://www.arthritis.org.nz/newly-diagnosed/types-of-arthritis/fibromyalgia
151. Qureshi AG, Jha SK, Iskander J, et al. Diagnostic Challenges and Management of Fibromyalgia. Cureus. Oct 2021;13(10):e18692. doi:10.7759/cureus.18692
152. Devan H, Davies, C., Grainger, R., Perry, M. A., Hale, L. A., & Ingham, T. . Partnering with whānau to address inequities in pain management. Ministry of Health. Ministry of Health, NZ. https://www.health.govt.nz/system/files/2024-05/day_2_-_3.1_hem_devan_and_cheryl_davies.pdf
153. Health Mo. Models of Care for People Living with Long COVID. New Zealand government. https://www.health.govt.nz/system/files/2025-05/models-care-people-living-with-long-covid.pdf
154. Minister of Health NZg. Government policy statement on health 2024-2027. Manatu Hauora, Ministry of Health,. 14th October 2025, 2024. Accessed 14th October 2025, 2025. https://www.health.govt.nz/system/files/2024-06/government-policy-statement-on-health-2024-2027-v4.pdf
155. NICE. Myalgic encephalomyelitis (or encephalopathy)/chronic fatigue syndrome: diagnosis and management. https://www.nice.org.uk/guidance/ng206
156. Health NDo. National strategy for ME/CFS. https://www.helsedirektoratet.no
157. Health AGDo. Long COVID National Plan. 15th October 2025. https://www.health.gov.au
158. Whitwell M. ME/CFS and Long COVID support in New Zealand. 14th October, 2025. https://tatou.health.govt.nz/the-future-of-the-health-system/me-cfs-long-covid-support-in-new-zealand
159. Development MoS. Very high needs service for people with a disability or health conditions. 14th October, 2025. https://www.msd.govt.nz/what-we-can-do/disability-services/very-high-needs-service-for-people-with-a-disability-or-health-conditions.html
160. ANZMES. Transforming ME/CFS Care: A Call to Action for Aotearoa New Zealand. Associated New Zealand Myalgic Encephalomyelitis Society Incorporated. 14th October, 2025. https://anzmes.org.nz/wp-content/uploads/2025/05/Transforming-ME_CFS-Care_-A-Call-to-Action-for-Aotearoa-New-Zealand.pdf
161. Jorgensen D, Parsons M, Jacobs S, Arksey H. The New Zealand informal caregivers and their unmet needs. N Z Med J. Jun 25 2010;123(1317):9-16.
162. Synergia. The state of caring in Aotearoa. 2022. https://carers.net.nz/wp-content/uploads/2022/07/State-of-Caring-Report-Aug2022.pdf
163. Bradely L. Is fibromyalgia a disability? https://www.moregooddays.com/post/is-fibromyalgia-a-disability
164. sällskapet SM. THE SWEDISH MS-ASSOCIATION. https://www.mssallskapet.se/information-in-english/
165. Zar. Ambulante reha bei Long COVID. 14th October, 2025. https://www.zar.de/long-covid/#!/s?services=Long-COVID%20Rehahttps://www.pharmac.govt.nz/news-and-resources/consultations-and-decisions/decision-for-funded-multiple-sclerosis-treatments
166. CAN-PCC. Canadian guidelines for post COVID-19 condition. https://canpcc.ca/home/
167. Zealand. E-DSAN. How is Ehlers-Danlos Syndrome and Hypermobility Spectrum Disorder diagnosed? https://ehlers-danlos.org.nz/eds-info/
168. Development MoS. A breakdown of financial support for specific health conditions. 14th October, 2025. https://www.msd.govt.nz/documents/about-msd-and-our-work/publications-resources/official-information-responses/2023/october/25102023-a-breakdown-of-financial-support-for-specified-health-conditions-rates-eligibility-and-funding-allocation-inclusive.pdf
169. Kela. 14th October, 2025. https://www.kela.fi
170. trust BaWGyc. PIP health condition guides: Claim PIP for fibromyalgia. https://www.benefitsandwork.co.uk/personal-independence-payment-pip/pip-health-conditions/claim-pip-for-fibromyalgia