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Comorbidities of Myalgic Encephalomyelitis
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A '''comorbidity''' is a diagnosis that commonly occurs independently of, and at the same time as another condition.<ref>{{Cite web | url = https://www.merriam-webster.com/dictionary/comorbid | title = Definition of COMORBID | website = Merriam-Webster|language=en|access-date=2019-05-05}}</ref> For example, [[Hashimoto's thyroiditis]] is a comorbidity of ME/CFS because they are independent conditions, but [[Postural orthostatic tachycardia syndrome|postural orthostatic tachychardia syndrome]] is a symptom used to aid the diagnosis of ME/CFS is not a comorbidity even though both are distinct disorders and both frequently occur together.<ref name="canadianconsensus" /><ref name="ICP2011primer" /> Symptoms of ME/CFS that are not a separate diagnosis are not counted as comorbidities. Patients with [[myalgic encephalomyelitis]] frequently meet the criteria for one or more other conditions including: [[Postural orthostatic tachycardia syndrome|postural orthostatic tachychardia syndrome]] and other forms of [[orthostatic intolerance]];<ref>{{Cite book | title = Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness|isbn=978-0-309-31689-7 | url = http://www.nap.edu/catalog/19012 | date =2015-03-16| publisher = National Academies Press|doi=10.17226/19012|location=Washington,D.C.}}</ref> [[mast cell activation syndrome]];<ref>{{Cite journal | last = Rönnberg|first = E | last2 = Calounova | first2 = G | last3 = Pejler | first3 = G | date = June 2017 | title = Novel characterisation of mast cell phenotypes from peripheral blood mononuclear cells in chronic fatigue syndrome/myalgic encephalomyelitis patients |url =https://www.ncbi.nlm.nih.gov/pubmed/27362406 | journal = Asian Pac J Allergy Immunol|volume=35 | issue = 2 | pages = 75-81|via=}}</ref> [[Ehlers-Danlos syndrome]];<ref>{{Cite journal | title = Orthostatic intolerance and chronic fatigue syndrome associated with Ehlers-Danlos syndrome | url =http://www.sciencedirect.com/science/article/pii/S0022347699701733 | journal = The Journal of Pediatrics | date = 1999-10-01|issn=0022-3476 | pages = 494–499|volume=135 | issue = 4|doi=10.1016/S0022-3476(99)70173-3|first = Peter C. | last = Rowe | first2 = Diana F. | last2 = Barron | first3 = Hugh | last3 = Calkins | first4 = Irene H. | last4 = Maumenee | first5 = Patrick Y. | last5 = Tong | first6 = Michael T. | last6 = Geraghty}}</ref> [[fibromyalgia]];<ref name="canadianconsensus" /> [[endometriosis]];<ref>{{Cite journal | last = Boneva | first = Roumiana S. | authorlink = | last2 = Lin | first2 = Jin-Mann S. | authorlink2 = Jin-Mann Sally Lin | last3 = Wieser | first3 = Friedrich | author-link3 = | last4 = Nater | first4 = Urs M. | author-link4 = | last5 = Ditzen | first5 = Beate | author-link5 = | last6 = Taylor | first6 = Robert N. | author-link6 = | last7 = Unger | first7 = Elizabeth R. | author-link7 = Elizabeth Unger | date = Apr 2018 | title = Endometriosis as a Comorbid Condition in Chronic Fatigue Syndrome (CFS): Secondary Analysis of Data from a CFS Case-Control study | url = https://www.frontiersin.org/articles/10.3389/fped.2019.00195/abstract | journal = Frontiers in Pediatrics|volume= | issue = | pages = |doi=10.3389/fped.2019.00195|quote=|via=}}</ref> and a variety of [[Autoimmune disease|autoimmune diseases.]]<ref name="canadianconsensus" /> It is not yet known whether these are true co-morbidities that share underlying genetic or environment risk factors, or if they are artifacts of diagnosis and disease definition. ==Canadian Consensus Criteria == The Canadian Consensus Criteria recognizes the following comorbidities for [[ME/CFS]]: [[fibromyalgia]], [[myofascial pain syndrome]] (MPS), [[temporomandibular joint syndrome]] (TMJ), [[irritable bowel syndrome]] (IBS), [[interstitial cystitis]], [[painful bladder syndrome|irritable bladder syndrome]], [[Raynaud's syndrome|Raynaud's phenomenon]], [[prolapsed mitral valve]], [[depression]], [[migraine]], [[allergy|allergies]], [[multiple chemical sensitivity|multiple chemical sensitivities]] (MCS), [[Hashimoto's thyroiditis]], and [[Sjögren's syndrome|sicca syndrome]] (Sjögren's syndrome).<ref name="canadianconsensus">{{Citation | last1 = Carruthers | first1 = Bruce M. | author-link1 = Bruce Carruthers | last2 = Jain | first2 = Anil Kumar | authorlink2 = Anil Kumar Jain | last3 = De Meirleir | first3 = Kenny L. | author-link3 = Kenny De Meirleir | last4 = Peterson | first4 = Daniel L. | author-link4 = Daniel Peterson | last5 = Klimas | first5 = Nancy G. | author-link5 = Nancy Klimas | last6 = Lerner | first6 = A. Martin | author-link6 = Martin Lerner | last7 = Bested | first7 = Alison C. | author-link8 = Alison Bested | last8 = Flor-Henry | first8 = Pierre | author-link8 = Pierre Flor-Henry | last9 = Joshi | first9 = Pradip | author-link9 = Pradip Joshi | last10 = Powles | first10 = AC Peter | author-link10 = A C Peter Powles | last11 = Sherkey | first11 = Jeffrey A. | author-link11 = Jeffrey Sherkey | last12 = van de Sande | first12 = Marjorie I. | author-link12 = Marjorie van de Sande | title = Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Clinical Working Case Definition, Diagnostic and Treatment Protocols | journal =Journal of Chronic Fatigue Syndrome | volume = 11 | issue = 2 | page = 13 | date = 2003 | doi = 10.1300/J092v11n01_02 | url = http://www.investinme.org/Documents/PDFdocuments/CanadianDefinitionME-CFS.pdf }}</ref> ===Preceding conditions === Conditions that begin many years before [[ME/CFS]] but then become associated with it, such as irritable bowel syndrome, migraines and depression, are regarded as more loosely associated. [[ME/CFS]] and [[fibromyalgia]] are regarded by the Canadian Consensus Criteria as often closely connected overlapping syndromes.<ref name="canadianconsensus" /> ==International Consensus Criteria== The primer for the [[International Consensus Criteria]] for [[myalgic encephalomyelitis]], which is based on the earlier Canadian Consensus Criteria gives the following comorbidities: [[myofascial pain syndrome]], [[temporomandibular joint syndrome]] (TMJ), [[interstitial cystitis]], [[Raynaud's syndrome|Raynaud's phenomenon]], [[prolapsed mitral valve]], [[irritable bladder syndrome]], [[Hashimoto's thyroiditis]], [[Sjögren's syndrome|sicca syndrome]] (Sjögren's syndrome), [[secondary depression]], [[allergy|allergies]], and [[multiple chemical sensitivity|multiple chemical sensitivities]]. [[Fibromyalgia]] (FMS) is considered "an overlap condition." ===Preceding conditions=== [[Irritable bowel syndrome]] and [[migraine]] "may precede [[myalgic encephalomyelitis|ME]] and then become associated with it."<ref name="ICP2011primer">{{citation | last1 = Carruthers | first1 = BM | author-link1 = Bruce Carruthers | last2 = van de Sande | first2 = MI | authorlink2 = Marjorie van de Sande | last3 = De Meirleir | first3 = KL | author-link3 = Kenny de Meirleir | last4 = Klimas | first4 = NG | author-link4 = Nancy Klimas | last5 = Broderick | first5 = G | author-link5 = Gordon Broderick | last6 = Mitchell | first6 = T | author-link6 = Terry Mitchell | last7 = Staines | first7 = D | author-link8 = Donald Staines | last8 = Powles | first8 = ACP | author-link8 = A C Peter Powles | last9 = Speight | first9 = N | author-link9 = Nigel Speight | last10 = Vallings | first10 = R | author-link10 = Rosamund Vallings | last11 = Bateman | first11 = L | author-link11 = Lucinda Bateman | last12 = Bell | first12 = DS | author-link12 = David Bell | last13 = Carlo-Stella | first13 = N | author-link13 = Nicoletta Carlo-Stella | last14 = Chia | first14 = J | author-link14 = John Chia | last15 = Darragh | first15 = A | author-link15 = Austin Darragh | last16 = Gerken | first16 = A | author-link16 = Anne Gerken | last17 = Jo | first17 = D | author-link17 = Daehyun Jo | last18 = Lewis | first18 = DP | author-link18 = Donald Lewis | last19 = Light | first19 = AR | author-link19 = Alan Light | last20 = Light | first20 = KC | authorlink20 = Kathleen Light | last21 = Marshall-Gradisnik | first21 = S | authorlink21 = Sonya Marshall-Gradisnik | last22 = McLaren-Howard | first22 = J | authorlink22 = John McLaren-Howard | last23 = Mena | first23 = I | authorlink23 = Ismael Mena | last24 = Miwa | first24 = K | authorlink24 = Kunihisa Miwa | last25 = Murovska | first25 = M | authorlink25= Modra Murovska | last26 = Stevens | first26 = SR | authorlink26 = Staci Stevens | title = Myalgic encephalomyelitis: Adult & Paediatric: International Consensus Primer for Medical Practitioners | page = 12 | date = 2012 | isbn = 978-0-9739335-3-6 | url = http://www.investinme.org/Documents/Guidelines/Myalgic%20Encephalomyelitis%20International%20Consensus%20Primer%20-2012-11-26.pdf }}</ref> == Theories == [[RCCX Genetic Module Theory|RCCX Theory]] == Epidemiology == {| class="wikitable" |+ ! !Percentage of ME/CFS patients |- |POTS |10-70% |- |hEDS |20%<ref name=":2">{{Cite web | url = https://osf.io/qwn5h/ | title = Bragee Bertilson et al. - ME CFS and Intracranial Hypertension | website = osf.io|access-date=2020-02-05}}</ref> |- |Fibromyalgia |67%<ref name=":2" /> |} {| class="wikitable" |+Percentage of patients in row X who also meet the diagnostic criteria for column Y ! !ME/CFS !POTS !Orthostatic intolerance (all types) !MCAS !Fibromyalgia !hEDS |- |ME/CFS |* |10-70% | | |67%<ref name=":2" /> |20%<ref name=":2" /> |- |POTS |64%<ref>{{Cite journal | last = Okamoto|first = Luis E. | last2 = Raj | first2 = Satish R. | last3 = Peltier | first3 = Amanda | last4 = Gamboa | first4 = Alfredo | last5 = Shibao | first5 = Cyndya | last6 = Diedrich | first6 = André | last7 = Black | first7 = Bonnie K. | last8 = Robertson | first8 = David | last9 = Biaggioni | first9 = Italo | date = 2012-02-01 | title = Neurohumoral and haemodynamic profile in postural tachycardia and chronic fatigue syndromes |url =https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3203411/ | journal = Clinical Science (London, England : 1979)|volume=122 | issue = Pt 4 | pages = 183–192|doi=10.1042/CS20110200|issn=0143-5221|pmid=21906029|via=}}</ref> |* | | | |31%<ref>{{Cite journal | last = Miller | first = Amanda J. | last2 = Stiles | first2 = Lauren E. | last3 = Sheehan | first3 = Timothy | last4 = Bascom | first4 = Rebecca | last5 = Levy | first5 = Howard P. | last6 = Francomano | first6 = Clair A. | last7 = Arnold | first7 = Amy C. | date = 2020-03-01 | title = Prevalence of hypermobile Ehlers-Danlos syndrome in postural orthostatic tachycardia syndrome | url =http://www.sciencedirect.com/science/article/pii/S1566070219303029 | journal = Autonomic Neuroscience|language=en|volume=224 | pages = 102637|doi=10.1016/j.autneu.2020.102637|issn=1566-0702}}</ref> |- |MCAS | | | |* | | |- |Fibromyalgia | | | | |* | |- |hEDS | | |74%<ref>{{Cite journal | last = Malfait | first = Fransiska | last2 = Calders | first2 = Patrick | last3 = De Paepe | first3 = Anne | last4 = De Mits | first4 = Sophie | last5 = Da Silva | first5 = Hellen | last6 = Peersman | first6 = Wim | last7 = De Backer | first7 = Tine | last8 = Rombaut | first8 = Lies | last9 = De Wandele | first9 = Inge | date = 2016-08-01 | title = Orthostatic intolerance and fatigue in the hypermobility type of Ehlers-Danlos Syndrome | url =https://academic.oup.com/rheumatology/article/55/8/1412/2566504 | journal = Rheumatology|language=en|volume=55 | issue = 8 | pages = 1412–1420|doi=10.1093/rheumatology/kew032|issn=1462-0324}}</ref><ref>{{Cite journal | last = De Wandele | first = Inge | last2 = Rombaut | first2 = Lies | last3 = Leybaert | first3 = Luc | last4 = Van de Borne | first4 = Philippe | last5 = De Backer | first5 = Tine | last6 = Malfait | first6 = Fransiska | last7 = De Paepe | first7 = Anne | last8 = Calders | first8 = Patrick | date = 2014-08-01 | title = Dysautonomia and its underlying mechanisms in the hypermobility type of Ehlers–Danlos syndrome | url =http://www.sciencedirect.com/science/article/pii/S0049017213002928 | journal = Seminars in Arthritis and Rheumatism|volume=44 | issue = 1 | pages = 93–100|doi=10.1016/j.semarthrit.2013.12.006|issn=0049-0172}}</ref> to 78%<ref>{{Cite journal | last = Gazit | first = Yael | last2 = Nahir | first2 = A. Menahem | last3 = Grahame | first3 = Rodney | last4 = Jacob | first4 = Giris | date = 2003-07-01 | title = Dysautonomia in the joint hypermobility syndrome | url =http://www.sciencedirect.com/science/article/pii/S0002934303002353 | journal = The American Journal of Medicine|volume=115 | issue = 1 | pages = 33–40|doi=10.1016/S0002-9343(03)00235-3|issn=0002-9343}}</ref> | | |* |} == Clinical perspectives == * In “The Nightingale Research Foundation Definition of Myalgic Encephalomyelitis (M.E.),”<ref>{{Cite book | url = https://docs.wixstatic.com/ugd/5b307e_b3a662c05f174937b9516d473a994c41.pdf | title=The Nightingale Research Foundation Definition of Myalgic Encephalomyelitis (M.E.) | last = Hyde | first = Byron| publisher = Cornell University| year = |isbn=|location= | pages = }}</ref> ME physician [[Byron Hyde]] has describes the relationship between ME, POTS/dyaustonomia, and EDS in terms of disease severity: ** “Patients with [[dysautonomia]] and/or [[Postural orthostatic tachycardia syndrome|POTS]] dysfunctions invariably demonstrated [[Cerebral hypoperfusion|hypoperfusion]] in the operculum area overlying the insular cortex as in the above patient, suggesting an insular cortex injury in our dysautonomia patients.” ** “Patients with pre-existing or newly-discovered (a) [[Ehlers-Danlos syndrome|Ehlers-Danlos Hypermobility Syndrome]], (b) Collagen diseases... are among the most disabled patients we have seen.” * A case series by [[Peter Rowe]] of adolescents referred to his clinic found 12 patients who also met the criteria for Ehlers-Danlos Syndrome and had orthostatic intolerance (postural orthostatic tachycardia or neurally-mediated hypotension). He concluded that “Among patients with CFS and orthostatic intolerance, a subset also has EDS.”<ref>{{Cite journal | title = Orthostatic intolerance and chronic fatigue syndrome associated with Ehlers-Danlos syndrome | url =http://www.sciencedirect.com/science/article/pii/S0022347699701733 | journal = The Journal of Pediatrics | date = 1999-10-01|issn=0022-3476 | pages = 494–499|volume=135 | issue = 4|doi=10.1016/S0022-3476(99)70173-3|first = Peter C. | last = Rowe | first2 = Diana F. | last2 = Barron | first3 = Hugh | last3 = Calkins | first4 = Irene H. | last4 = Maumenee | first5 = Patrick Y. | last5 = Tong | first6 = Michael T. | last6 = Geraghty}}</ref> * At a two-day physician summit in Salt Lake City, Utah March 2018, physicians discussed the relationship between “Chronic Fatigue Syndrome” and mast cell activation syndrome.<ref>{{Cite web | url = https://www.medscape.com/viewarticle/893858 | title = Medscape Log In | website = Medscape|access-date=2018-09-25}}</ref> ** [[David Kaufman]]: "ME/CFS is a descriptive diagnosis of a bunch of symptoms, but it says nothing about what's causing the symptoms, which is probably part of the reason it's so hard for it to get recognition. So, the question becomes, What other pathology is driving this illness and making the person feel so ill? I think mast cell activation is one of those drivers, whether cause, effect, or perpetuator, I don't know." ** [[Charles Lapp]]: "I see a lot of this. I think it's one of the many overlap syndromes that we've been missing for years." ** [[Susan Levine]]: "I suspect 50% to 60% of ME/CFS patients have it. It's a very new concept."...In Levine's experience, MCAS often manifests in patients being unable to tolerate certain foods or medications. "If we can reduce the mast cell problem, we can facilitate taking other drugs to treat ME/CFS," she said. However, she also cautioned, "It's going to be a subset, not all ME/CFS patients." == Studies and collaborations == * A lab at the [[Stanford Genome Technology Center]] is currently studying the genetic relationship between EDS and ME/CFS. Early data show a possible relationship.<ref>{{Cite news |url =https://www.omf.ngo/2017/09/09/molecular-underpinnings/ | title = Molecular Underpinnings of ME/CFS Explored at the Open Medicine Foundation Symposium {{!}} Open Medicine Foundation | date = 2017-09-09|work=Open Medicine Foundation|access-date=2018-09-25|language=en-US}}</ref> == Research findings == Recent research has focused on the possible relationships between EDS, POTS, and MCAS. In particular, these disorders were associated in a sample of 25 families. {| class="wikitable" !Findings ![[ME/CFS]] ![[Postural orthostatic tachycardia syndrome|POTS]] !MCAS ![[Fibromyalgia]] ![[hEDS]] |- |'''[[Central nervous system]]''' | | | | | |- |[[Ventricular lactate]] |increased<ref name=":53">{{Cite journal | last = Mathew|first = Sanjay J. | last2 = Mao | first2 = Xiangling | last3 = Keegan | first3 = Kathryn A. | last4 = Levine | first4 = Susan M. | last5 = Smith | first5 = Eric L.P. | last6 = Heier | first6 = Linda A. | last7 = Otcheretko | first7 = Viktor | last8 = Coplan | first8 = Jeremy D. | last9 = Shungu | first9 = Dikoma C. | date = Apr 2009 | title = Ventricular cerebrospinal fluid lactate is increased in chronic fatigue syndrome compared with generalized anxiety disorder: anin vivo3.0 T1H MRS imaging study | url = https://onlinelibrary.wiley.com/doi/full/10.1002/nbm.1315 | journal = NMR in Biomedicine|language=en|volume=22 | issue = 3 | pages = 251–258|doi=10.1002/nbm.1315|issn=0952-3480}}</ref><ref>{{Cite journal | last = Murrough|first = James W. | last2 = Mao | first2 = Xiangling | last3 = Collins | first3 = Katherine A. | last4 = Kelly | first4 = Chris | last5 = Andrade | first5 = Gizely | last6 = Nestadt | first6 = Paul | last7 = Levine | first7 = Susan M. | last8 = Mathew | first8 = Sanjay J. | last9 = Shungu | first9 = Dikoma C. | date = Jul 2010 | title = Increased ventricular lactate in chronic fatigue syndrome measured by 1H MRS imaging at 3.0 T. II: comparison with major depressive disorder |url =https://www.ncbi.nlm.nih.gov/pubmed/20661876 | journal = NMR in biomedicine|volume=23 | issue = 6 | pages = 643–650|doi=10.1002/nbm.1512|issn=1099-1492|pmid=20661876}}</ref><ref>{{Cite journal | last = Shungu|first = Dikoma C. | last2 = Weiduschat | first2 = Nora | last3 = Murrough | first3 = James W. | last4 = Mao | first4 = Xiangling | last5 = Pillemer | first5 = Sarah | last6 = Dyke | first6 = Jonathan P. | last7 = Medow | first7 = Marvin S. | last8 = Natelson | first8 = Benjamin H. | author-link8 = Benjamin Natelson | last9 = Stewart | first9 = Julian M. | date = Sep 2012 | title = Increased ventricular lactate in chronic fatigue syndrome. III. Relationships to cortical glutathione and clinical symptoms implicate oxidative stress in disorder pathophysiology | url = https://www.ncbi.nlm.nih.gov/pubmed/22281935 | journal = NMR in biomedicine|volume=25 | issue = 9 | pages = 1073–1087|doi=10.1002/nbm.2772|issn=1099-1492|pmc=3896084|pmid=22281935}}</ref><ref>{{Cite journal | last = Natelson | first = Benjamin H. | last2 = Vu | first2 = Diana | last3 = Coplan | first3 = Jeremy D. | last4 = Mao | first4 = Xiangling | last5 = Blate | first5 = Michelle | last6 = Kang | first6 = Guoxin | last7 = Soto | first7 = Eli | last8 = Kapusuz | first8 = Tolga | last9 = Shungu | first9 = Dikoma C. | date = 2017-01-02 | title = Elevations of ventricular lactate levels occur in both chronic fatigue syndrome and fibromyalgia | url = https://www.tandfonline.com/doi/abs/10.1080/21641846.2017.1280114?journalCode=rftg20|journal = Fatigue: Biomedicine, Health & Behavior |language=en|volume=5 | issue = 1 | pages = 15–20|doi=10.1080/21641846.2017.1280114|issn=2164-1846|pmc=5754037|pmid=29308330}}</ref> | | | | |- |Neuroinflammmation | | | | | |- |Grey matter | | | | | |- |White matter | | | | | |- |[[Intracranial hypertension]] |Present in a subset<ref>{{Cite journal | last = Higgins | first = Nicholas | authorlink = Nicholas Higgins | last2 = Pickard | first2 = John | authorlink2 = John Pickard | last3 = Lever | first3 = Andrew | author-link3 = Andrew Lever | author-link4 = | author-link5 = | date = 2013-11-21 | title = Lumbar puncture, chronic fatigue syndrome and idiopathic intracranial hypertension: a cross-sectional study | url = http://journals.sagepub.com/doi/10.1177/2042533313507920 | journal = JRSM Short Reports|language=en|volume=4 | issue = 12 | pages = 204253331350792|doi=10.1177/2042533313507920|issn=2042-5333|quote=|via=}}</ref> | | | | |- |'''[[Autonomic nervous system]]''' | | | | | |- |[[Small fiber peripheral neuropathy]] | |37.5%<ref>{{Cite journal | last = Gibbons | first = Christopher H. | last2 = Bonyhay | first2 = Istvan | last3 = Benson | first3 = Adam | last4 = Wang | first4 = Ningshan | last5 = Freeman | first5 = Roy | date = 2013-12-27 | title = Structural and Functional Small Fiber Abnormalities in the Neuropathic Postural Tachycardia Syndrome | url =https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0084716 | journal = PLoS ONE|language=en|volume=8 | issue = 12| pages = e84716|doi=10.1371/journal.pone.0084716|issn=1932-6203|pmc=3874039|pmid=24386408}}</ref> | |30-50%<ref>{{Cite journal | title = Objective evidence that small-fiber polyneuropathy underlies some illnesses currently labeled as fibromyalgia | url = https://www.sciencedirect.com/science/article/pii/S0304395913002947 | journal = PAIN® | date = 2013-11-01|issn=0304-3959 | pages = 2310–2316|volume=154 | issue = 11|doi=10.1016/j.pain.2013.06.001|language=en}}</ref><ref>{{Cite journal | title = Objective evidence that small-fiber polyneuropathy underlies some illnesses currently labeled as fibromyalgia | url = https://www.sciencedirect.com/science/article/pii/S0304395913002947 | journal = PAIN® | date = 2013-11-01|issn=0304-3959 | pages = 2310–2316|volume=154 | issue = 11|doi=10.1016/j.pain.2013.06.001|language=en}}</ref><ref>{{Cite journal | title = Routine use of punch biopsy to diagnose small fiber neuropathy in fibromyalgia patients |url =https://link.springer.com/article/10.1007/s10067-014-2850-5 | journal = Clinical Rheumatology | date = 2014-12-24|issn=0770-3198|pmc=4348533|pmid=25535201 | pages = 413–417|volume=34 | issue = 3|doi=10.1007/s10067-014-2850-5|language=en | first = ToddD. | last = Levine | first2 = David S. | last2 = Saperstein}}</ref> |100%<ref>{{Cite journal | last = Cazzato|first = Daniele | last2 = Castori | first2 = Marco | last3 = Lombardi | first3 = Raffaella | last4 = Caravello | first4 = Francesca | last5 = Bella | first5 = Eleonora Dalla | last6 = Petrucci | first6 = Antonio | last7 = Grammatico | first7 = Paola | last8 = Dordoni | first8 = Chiara | last9 = Colombi | first9 = Marina | date = 2016-06-15 | title = Small fiber neuropathy is a common feature of Ehlers-Danlos syndromes |url =http://n.neurology.org/content/early/2016/06/15/WNL.0000000000002847 | journal = Neurology|language=en | pages = 10.1212/WNL.0000000000002847|doi=10.1212/WNL.0000000000002847|issn=0028-3878|pmid=27306637}}</ref> |- |Incidence of [[Postural orthostatic tachycardia syndrome|POTS]] |11-70% |100% | | | |- |Incidence of [[Neurally mediated hypotension|NMH]] | | | | | |- |Incidence of OI |57%<ref>{{Cite journal | date = 2002-04-01 | title = Impaired postural cerebral hemodynamics in young patients with chronic fatigue with and without orthostatic intolerance | url =https://www.sciencedirect.com/science/article/pii/S0022347602157878 | journal = The Journal of Pediatrics|language=en|volume=140 | issue = 4 | pages = 412–417|doi=10.1067/mpd.2002.122725|issn=0022-3476}}</ref> | | | | |- |'''Musculoskeletal system''' | | | | | |- |mitochondria |[[mitochondrion|mitochondrial]] abnormalities found via [[muscle biopsy]] including: mitochondrial degeneration,<ref>{{Cite journal | last = Behan | first = W. M.H. | last2 = More | first2 = I.A.R. | last3 = Behan | first3 = P.O. | date = Dec 1991 | title = Mitochondrial abnormalities in the postviral fatigue syndrome | url =https://link.springer.com/article/10.1007/BF00294431 | journal = Acta Neuropathologica|language=en|volume=83 | issue = 1 | pages = 61–65|doi=10.1007/bf00294431|issn=0001-6322}}</ref> deletions of mitochondrial DNA,<ref name=":0">{{Cite journal | date = 1996-04-19 | title = Sensory characterization of somatic parietal tissues in humans with chronic fatigue syndrome | url =https://www.sciencedirect.com/science/article/abs/pii/0304394096125593 | journal = Neuroscience Letters|language=en|volume=208 | issue = 2 | pages = 117–120|doi=10.1016/0304-3940(96)12559-3|issn=0304-3940}}</ref><ref>{{Cite journal | last = Zhang|first = C. | last2 = Baumer | first2 = A. | last3 = Mackay | first3 = I.R. | last4 = Linnane | first4 = A.W. | last5 = Nagley | first5 = P. | date = Apr 1995 | title = Unusual pattern of mitochondrial DNA deletions in skeletal muscle of an adult human with chronic fatigue syndrome | url =https://www.ncbi.nlm.nih.gov/pubmed/7633428 | journal = Human Molecular Genetics|volume=4 | issue = 4 | pages = 751–754|issn=0964-6906|pmid=7633428}}</ref> the reduction of mitochondrial activity<ref name=":0" /> | | | | |- |creatine | * Increased urinary [[creatine]] excretion during relapses<ref>{{Cite journal | last = Albrecht | first = Robert | date = March 21, 1964 | title = Epidemic Neuromyasthenia Outbreak in a Convent in New York State | url =https://www.ncbi.nlm.nih.gov/pubmed/14100144 | journal = Journal of the American Medical Association|volume=187 | pages = 904-907|via=}}</ref> * Increased [[creatine kinase]] ([[postviral fatigue syndrome]]) | | | | |- |'''Cell & metabolism''' | | | | | |- |[[Lipid raft]] |decreased [[Sphingolipid|sphingolipids]] and [[Glycosphingolipid|glycosphingolipids]], building blocks of lipid rafts.<ref>{{Cite journal | last = Naviaux | first = Robert K. | last2 = Naviaux | first2 = Jane C. | last3 = Li | first3 = Kefeng | last4 = Bright | first4 = A. Taylor | last5 = Alaynick | first5 = William A. | last6 = Wang | first6 = Lin | last7 = Baxter | first7 = Asha | last8 = Nathan | first8 = Neil | last9 = Anderson | first9 = Wayne | date = 2016-09-13 | title = Metabolic features of chronic fatigue syndrome | url =http://www.pnas.org/content/113/37/E5472 | journal = Proceedings of the National Academy of Sciences|language=en|volume=113 | issue = 37| pages = E5472–E5480|doi=10.1073/pnas.1607571113|issn=0027-8424|pmid=27573827}}</ref> |autoimmunoreactive [[IgG]]s to lipid raft proteins in the heart.<ref>{{Cite journal | date = 2013-07-01 | title = Autoimmunoreactive IgGs against cardiac lipid raft-associated proteins in patients with postural orthostatic tachycardia syndrome | url =https://www.sciencedirect.com/science/article/pii/S1931524413000753 | journal = Translational Research|language=en|volume=162 | issue = 1 | pages = 34–44|doi=10.1016/j.trsl.2013.03.002|issn=1931-5244}}</ref> | | | |- |'''Immune system''' | | | | | |- |[[Acetylcholine]] receptor autoantibodies |29% |24% | | | |- |Other autoantibodies |elevated anti-cholinergic [[Muscarinic acetylcholine receptor|muscarinic]], Β-adrenergic,<ref>{{Cite journal | last = Loebel|first = Madlen | last2 = Grabowski | first2 = Patricia | last3 = Heidecke | first3 = Harald | last4 = Bauer | first4 = Sandra | last5 = Hanitsch | first5 = Leif G. | last6 = Wittke | first6 = Kirsten | last7 = Meisel | first7 = Christian | last8 = Reinke | first8 = Petra | last9 = Volk | first9 = Hans-Dieter | date = Feb 2016 | title = Antibodies to β adrenergic and muscarinic cholinergic receptors in patients with Chronic Fatigue Syndrome | url =https://www.ncbi.nlm.nih.gov/pubmed/26399744 | journal = Brain, Behavior, and Immunity|volume=52 | pages = 32–39|doi=10.1016/j.bbi.2015.09.013|issn=1090-2139|pmid=26399744}}</ref> [[phosphatidylinositol]]<ref>{{Cite journal | last = Maes | first = Michael | last2 = Mihaylova | first2 = Ivanka | last3 = Leunis | first3 = Jean-Claude | date = Dec 2007 | title = Increased serum IgM antibodies directed against phosphatidyl inositol (Pi) in chronic fatigue syndrome (CFS) and major depression: evidence that an IgM-mediated immune response against Pi is one factor underpinning the comorbidity between both CFS and depression | url =https://www.ncbi.nlm.nih.gov/pubmed/18063934 | journal = Neuro Endocrinology Letters|volume=28 | issue = 6 | pages = 861–867|issn=0172-780X|pmid=18063934}}</ref> and [[serotonin]]<ref>{{Cite journal | last = Maes | first = Michael | last2 = Ringel | first2 = Karl | last3 = Kubera | first3 = Marta | last4 = Anderson | first4 = George | last5 = Morris | first5 = Gerwyn | last6 = Galecki | first6 = Piotr | last7 = Geffard | first7 = Michel | date = 2013-09-05 | title = In myalgic encephalomyelitis/chronic fatigue syndrome, increased autoimmune activity against 5-HT is associated with immuno-inflammatory pathways and bacterial translocation | url =https://www.ncbi.nlm.nih.gov/pubmed/23664637 | journal = Journal of Affective Disorders|volume=150 | issue = 2 | pages = 223–230|doi=10.1016/j.jad.2013.03.029|issn=1573-2517|pmid=23664637}}</ref> [[antibodies]] | | | | |- |mast cells |increased [[mast cell]] populations<ref>{{Cite journal | last = Rönnberg|first = E | last2 = Calounova | first2 = G | last3 = Pejler | first3 = G | date = June 2017 | title = Novel characterisation of mast cell phenotypes from peripheral blood mononuclear cells in chronic fatigue syndrome/myalgic encephalomyelitis patients |url =https://www.ncbi.nlm.nih.gov/pubmed/27362406 | journal = Asian Pac J Allergy Immunol|volume=35 | issue = 2 | pages = 75-81|via=}}</ref> | | | | |- |natural killer cells |[[Natural killer cell]] function is reduced<ref>{{Cite journal | last = Brenu|first = Ekua Weba | last2 = Huth | first2 = Teilah K. | last3 = Hardcastle | first3 = Sharni L. | last4 = Fuller | first4 = Kirsty | last5 = Kaur | first5 = Manprit | last6 = Johnston | first6 = Samantha | last7 = Ramos | first7 = Sandra B. | last8 = Staines | first8 = Don R. | last9 = Marshall-Gradisnik | first9 = Sonya M. | date = Apr 2014 | title = Role of adaptive and innate immune cells in chronic fatigue syndrome/myalgic encephalomyelitis |url =http://www.ncbi.nlm.nih.gov/pubmed/24343819 | journal = International Immunology|volume=26 | issue = 4 | pages = 233–242|doi=10.1093/intimm/dxt068|issn=1460-2377|pmid=24343819}}</ref><ref>{{Cite journal | last = Victoria Scott | first = David Strayer | date = 2015 | title=Low NK Cell Activity in Chronic Fatigue Syndrome (CFS) and Relationship to Symptom Severity | url = https://www.omicsonline.org/open-access/low-nk-cell-activity-in-chronic-fatigue-syndrome-cfs-and-relationship-to-symptom-severity-2155-9899-1000348.php?aid=59415 | journal = Journal of Clinical & Cellular Immunology|language=en|volume=06 | issue = 04|doi=10.4172/2155-9899.1000348|issn=2155-9899}}</ref> | | | | |- |'''Cardiovascular system''' | | | | | |- |[[Preload failure]] |Yes |Yes | | | |- |[[Low blood volume]] |Yes |Yes | | |Yes |- | | | | | | |- |'''Gastrointestinal system''' | | | | | |- | | | | | | |- |'''Genetics''' | | | | | |- |''[[TPSAB1]]'' |Unknown |Mutation found in a sample of 35 families<ref name=":1">{{Cite journal | last = Lyons | first = Jonathan J. | last2 = Yu | first2 = Xiaomin | last3 = Hughes | first3 = Jason D. | last4 = Le | first4 = Quang T. | last5 = Jamil | first5 = Ali | last6 = Bai | first6 = Yun | last7 = Ho | first7 = Nancy | last8 = Zhao | first8 = Ming | last9 = Liu | first9 = Yihui | date = Dec 2016 | title = Elevated basal serum tryptase identifies a multisystem disorder associated with increased TPSAB1 copy number |url =https://www.ncbi.nlm.nih.gov/pubmed/27749843 | journal = Nature Genetics|volume=48 | issue = 12 | pages = 1564–1569|doi=10.1038/ng.3696|issn=1546-1718|pmc=5397297|pmid=27749843}}</ref> |Mutation found in a sample of 35 families<ref name=":1" /> |Unknown |Mutation found in a sample of 35 families<ref name=":1" /> |} ==<span id="symptoms">Diagnoses that are symptoms of ME/CFS</span>== A number of illnesses and diseases are not regarded as true comorbidities, but are so common that they classed as diagnostic [[:Category:Signs and symptoms|signs and symptoms]] instead:<!--- Autogenerated, sorted list based on use of categories --> Symptoms that are also a diagnosis include:<br> <dynamicpagelist> category = Diagnoses category = Signs and symptoms mode = unordered ordermethod=sortkey order=ascending </dynamicpagelist> == See also == * [[Fibromyalgia]] * [[Postural orthostatic tachycardia syndrome|POTS]] * [[Mast cell activation syndrome]] == References == {{reflist}} [[Category:Potential comorbidities]]
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