ME and CFS Medical Abnormalities – Related Conditions

 

Following is a list of articles about abnormalities in ME and CFS compared to those in other medical conditions.

Links to the more than 1,000 peer-reviewed journal articles are listed on the M.E. and CFS Medical Abnormalities page of this website.

 

Uhde M, Indart A, Fallon BA, Wormser GP, Marques AR, Vernon SD, Alaedini A. C-Reactive Protein Response in Patients With Post-Treatment Lyme Disease Symptoms Versus Those With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Clin Infect Dis. 2018 May 8. PMID: 29741589

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Maness C, Saini P, Bliwise DL, Olvera V, Rye DB, Trotti LM. Systemic exertion intolerance disease/chronic fatigue syndrome is common in sleep centre patients with hypersomnolence: A retrospective pilot study. J Sleep Res. 2018 Apr 6:e12689. PMID: 29624767

The authors sought to determine the frequency and correlates of systemic exertion intolerance disease in a hypersomnolent population. One-hundred and eighty-seven hypersomnolent patients completed questionnaires regarding sleepiness and fatigue; questionnaires and clinical records were used to assess for systemic exertion intolerance disease. Twenty-one percent met systemic exertion intolerance disease criteria, and the frequency of systemic exertion intolerance disease was not different across sleep diagnoses.

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Natelson BH, Vu D, Coplan JD, Mao X, Blate M, Kang G, Soto E, Kapusuz T, Shungu DC. Elevations of Ventricular Lactate Levels Occur in Both Chronic Fatigue Syndrome and Fibromyalgia. Fatigue. 2017;5(1):15-20. PMID: 29308330

While patients with CFS, fibromyalgia (FM) and comorbid CFS and FM can be differentiated from healthy subjects based on measures of CFS lactate, this neuroimaging outcome measure is not a viable biomarker for differentiating CFS from FM or from patients in whom symptoms of the two disorders overlap.

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Higgins JNP, Pickard JD, Lever AML. Chronic fatigue syndrome and idiopathic intracranial hypertension: Different manifestations of the same disorder of intracranial pressure? Med Hypotheses. 2017 Aug;105:6-9. PMID: 28735654

The authors hypothesise that idiopathic intracranial hypertension (IIH), IIH without papilloedema (IIHWOP), lesser forms of IIH and an undetermined proportion of chronic fatigue cases are all manifestations of the same disorder of intracranial pressure across a spectrum of disease severity, in which this subset of chronic fatigue syndrome would represent the most common and least severe and IIH the least common and most extreme.

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McManimen SL, Jason LA. Post-Exertional Malaise in Patients with ME and CFS with Comorbid Fibromyalgia. SRL Neurol Neurosurg. 2017;3(1):22-27. Epub 2017 Mar 10. PMID: 28603794

The purpose of this study was to determine if the PEM differences seen between patients with and without comorbid fibromyalgia (FM) exist for the Muscle or General PEM factors. The secondary diagnosis of FM in addition to ME and CFS appears to amplify the PEM symptomatology and worsen patients’ physical functioning.

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Castro-Marrero J, Faro M, Aliste L, Sáez-Francàs N, Calvo N, Martínez-Martínez A, de Sevilla TF, Alegre J. Comorbidity in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: A Nationwide Population-Based Cohort Study. Psychosomatics. 2017 Sep – Oct;58(5):533-543. PMID: 28596045

A total of 1757 Spanish CFS/ME patients completed surveys were collected. Over 80% presented comorbidities. The researchers identified 5 CFS/ME clusters: group 1-fibromyalgia, myofascial pain, multiple chemical hypersensitivity, sicca syndrome, epicondylitis, and thyroiditis; group 2-alterations of ligaments and subcutaneous tissue, hypovitaminosis D, psychopathology, ligamentous hyperlaxity, and endometriosis. These 2 subgroups comprised mainly older women, with low educational level, unemployment, high levels of fatigue, and poor quality of life; group 3-with hardly any comorbidities, comprising mainly younger women, university students or those already employed, with lower levels of fatigue, and better quality of life; group 4-poorly defined comorbidities; and group 5-hypercholesterolemia.

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Hakim A, De Wandele I, O’Callaghan C, Pocinki A, Rowe P. Chronic fatigue in Ehlers-Danlos syndrome-Hypermobile type. Am J Med Genet C Semin Med Genet. 2017 Mar;175(1):175-180. PMID: 28186393

There is overlap in the symptoms and findings of Ehlers-Danlos syndrome (EDS) and chronic fatigue syndrome. A proportion of those with CFS likely have EDS that has not been identified.

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Bakken IJ, Tveito K, Aaberg KM, Ghaderi S, Gunnes N, Trogstad L, Magnus P, Stoltenberg C, Håberg SE. Comorbidities treated in primary care in children with chronic fatigue syndrome / myalgic encephalomyelitis: A nationwide registry linkage study from Norway. BMC Fam Pract. 2016 Sep 2;17(1):128. PMID: 27590471

The authors studied primary care diagnoses for Norwegian children with CFS/ME, with children with another hospital diagnosis (type 1 diabetes mellitus [T1DM]) and the general child population as comparison groups. This large nationwide registry linkage study confirms that the clinical picture in CFS/ME is complex. Children with CFS/ME were frequently diagnosed with infections, supporting the hypothesis that infections may be involved in the causal pathway. The long time span often observed from the first diagnosis of weakness / general tiredness to the diagnosis of CFS/ME might indicate that the treatment of these patients is sometimes not optimal.

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Lau CI, Lin CC, Chen WH, Wang HC, Kao CH. Increased risk of chronic fatigue syndrome in patients with migraine: A retrospective cohort study. J Psychosom Res. 2015 Dec;79(6):514-8. PMID: 26505533

The current study demonstrated an increased risk of CFS in patients with migraines. Proposed mechanisms in previous studies such as mitochondrial dysfunction and central sensitization may underlie the shared pathophysiology of these seemingly distinct but potentially overlapping disorders.

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Yang TY, Kuo HT, Chen HJ, Chen CS, Lin WM, Tsai SY, Kuo CN, Kao CH. Increased Risk of Chronic Fatigue Syndrome Following Atopy: A Population-Based Study. Medicine (Baltimore). 2015 Jul;94(29):e1211. PMID: 26200644

Atopy is associated with CFS, particularly in patients with numerous atopic syndromes.

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Gaber TA, Oo WW, Ringrose H. Multiple Sclerosis/Chronic Fatigue Syndrome overlap: When two common disorders collide. NeuroRehabilitation. 2014;35(3):529-34. PMID: 25238862

MS and CFS/ME are two common conditions with increased prevalence in middle aged females. The study results suggest that the two conditions may co-exist.

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Morris G, Maes M. Myalgic encephalomyelitis/chronic fatigue syndrome and encephalomyelitis disseminata/multiple sclerosis show remarkable levels of similarity in phenomenology and neuroimmune characteristics. BMC Med. 2013 Sep 17;11:205. PMID: 24229326

Mitochondrial dysfunctions, including lowered levels of ATP, decreased phosphocreatine synthesis and impaired oxidative phosphorylation, are heavily involved in the pathophysiology of both MS and ME/CFS. The findings produced by neuroimaging techniques are quite similar in both illnesses and show decreased cerebral blood flow, atrophy, gray matter reduction, white matter hyperintensities, increased cerebral lactate and choline signaling and lowered acetyl-aspartate levels.

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Morris G, Anderson G, Galecki P, Berk M, Maes M. A narrative review on the similarities and dissimilarities between myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and sickness behavior. BMC Med. 2013 Mar 8;11(1):64. PMID: 23497361

Differences and similarities between sickness behavior (an adaptive response induced by proinflammatory cytokines) and ME/CFS are discussed. The article concludes that these are two different conditions.

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Abbi B, Natelson BH. Is chronic fatigue syndrome the same illness as fibromyalgia: evaluating the ‘single syndrome’ hypothesis. QJM. 2013 Jan;106(1):3-9. PMID: 22927538

This review presents data showing differences between CFS and FM across a number of parameters.

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Castro-Marrero J, Cordero MD, Sáez-Francas N, Jimenez-Gutierrez C, Aguilar-Montilla FJ, Aliste L, Alegre-Martin J. Could mitochondrial dysfunction be a differentiating marker between chronic fatigue syndrome and fibromyalgia? Antioxid Redox Signal. 2013 Nov 20;19(15):1855-60. PMID: 23600892

The researchers looked at the possible association between mitochondrial biogenesis and oxidative stress in patients with CFS vs. patients with fibromyalgia (FM) and healthy controls. Compared to controls, both CFS and FM patients had decreased levels of Coenzyme Q10, decreased ATP levels, and increased levels of lipid peroxidation.  Several measures (mitochondrial citrate synthase activity, mitochondrial DNA content and expression levels of peroxisome proliferator-activated receptor gamma-coactivator 1-alpha and transcription factor A, mitochondrial by immunoblotting) were significantly lower in FM patients than either CFS patients or controls.

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Smylie AL, Broderick G, Fernandes H, Razdan S, Barnes Z, Collado F, Sol C, Fletcher MA, Klimas N. A comparison of sex-specific immune signatures in Gulf War illness and chronic fatigue syndrome. BMC Immunol. 2013 Jun 25;14:29. PMID: 23800166

Common to both Gulf War Illness and CFS, IL-10 and IL-23 expression contributed in an illness and time-dependent manner, accompanied in male subjects by NK and Th1 markers IL-12, IL-15, IL-2 and IFNγ. In female GWI and CFS subjects IL-10 was again identified as a delineator but this time in the context of IL-17 and Th2 markers IL-4 and IL-5. Exercise response also differed between sexes: male GWI subjects presented characteristic cytokine signatures at rest but not at peak effort whereas the opposite was true for female subjects.

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Itoh Y, Shigemori T, Igarashi T, Fukunaga Y. Fibromyalgia And Chronic Fatigue Syndrome In Children. Pediatr Int. 2011 Nov 24. PMID: 22115414

In a group of children, ANA titers were higher and the prevalence of anti-Sa was far more frequent in CFS patients than in FM cases. The authors conclude that CFS and FM are different from each other at least in childhood from the immunological aspects, although a few patients were suffering from both conditions.

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Schutzer SE, Angel TE, Liu T, Schepmoes AA, Clauss TR, Adkins JN, Camp DG, Holland BK, Bergquist J, Coyle PK, Smith RD, Fallon BA, Natelson BH. Distinct cerebrospinal fluid proteomes differentiate post-treatment lyme disease from chronic fatigue syndrome. PLoS One. 2011 Feb 23;6(2):e17287. PMID: 21383843

Analysis of cerebral spinal fluids accurately distinguished CFS, Chronic Lyme and healthy subjects, and thus has potential as a biomarker.

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Nickel JC, Tripp DA, Pontari M, Moldwin R, Mayer R, Carr LK, Doggweiler R, Yang CC, Mishra N, Nordling J. Interstitial cystitis/painful bladder syndrome and associated medical conditions with an emphasis on irritable bowel syndrome, fibromyalgia and chronic fatigue syndrome. J Urol. 2010 Oct;184(4):1358-63. PMID: 20719340

CFS and interstitial cystitis/painful bladder syndrome are related.

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Baraniuk JN, Zheng Y. Relationships among rhinitis, fibromyalgia, and chronic fatigue. Allergy Asthma Proc. 2010 May-Jun;31(3):169-78. PMID: 20615318

There is a high prevalence of idiopathic nonallergic rhinopathy in CFS. CFS also has significant overlap with systemic hyperalgesia (fibromyalgia), autonomic dysfunction (irritable bowel syndrome and migraine headaches), sensory hypersensitivity (dyspnea; congestion; rhinorrhea; and appreciation of visceral nociception in the esophagus, gastrointestinal tract, bladder, and other organs), and central nervous system maladaptations (central sensitization) recorded by functional magnetic resonance imaging (fMRI). Neurological dysfunction may account for the overlap of CFS with idiopathic nonallergic rhinopathy.

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Meeus M, Mistiaen W, Lambrecht L, Nijs J. Immunological similarities between cancer and chronic fatigue syndrome: the common link to fatigue? Anticancer Res. 2009 Nov;29(11):4717-26. PMID: 20032425

CFS patients display a number of immunological abnormalities also seen in cancer, including abnormalities of ribonuclease (RNase) L, hyperactivation of nuclear factor kappa beta (NF-kappa B), high oxidative stress and natural killer cell malfunction.

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Ciccone DS, Weissman L, Natelson BH. Chronic fatigue syndrome in male Gulf war veterans and civilians: a further test of the single syndrome hypothesis. J Health Psychol. 2008 May;13(4):529-36. PMID: 18420761

CFS was more likely to present in a sudden flu-like manner in civilians than Gulf War veterans. Comorbid fibromyalgia was more prevalent in civilians.

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Bennett B, Goldstein D, Friedlander M, Hickie I, Lloyd A. The experience of cancer-related fatigue and chronic fatigue syndrome: a qualitative and comparative study. J Pain Symptom Manage. 2007 Aug;34(2):126-35. PMID: 17544246

Qualitatively, cancer related fatigue appears closely related to CFS.

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Ferré Ybarz L, Cardona Dahl V, Cadahía García A, Ruiz E, Vázquez A, Fernández de Sevilla T, Alegre Martín J. Prevalence of atopy in chronic fatigue syndrome. Allergol Immunopathol (Madr). 2005 Jan-Feb;33(1):42-7. PMID: 15777523

Atopy was not more prevalent in patients with CFS than in healthy controls, although the CFS group tended to report more respiratory symptoms and drug allergies.

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Sinaii N, Cleary SD, Ballweg ML, Nieman LK, Stratton P. High rates of autoimmune and endocrine disorders, fibromyalgia, chronic fatigue syndrome and atopic diseases among women with endometriosis: a survey analysis. Hum Reprod. 2002 Oct;17(10):2715-24. PMID: 12351553

A survey showed that about 4.6% of endometriosis sufferers also reported having CFS.

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Aaron LA, Herrell R, Ashton S, Belcourt M, Schmaling K, Goldberg J, Buchwald D. Comorbid clinical conditions in chronic fatigue: a co-twin control study. J Gen Intern Med. 2001 Jan;16(1):24-31. PMID: 11251747

Compared to their nonfatigued co-twins, CFS twins had higher rates of fibromyalgia and irritable bowel syndrome. The strongest associations were observed between chronic fatigue and fibromyalgia, irritable bowel syndrome, chronic pelvic pain, multiple chemical sensitivities, and temporomandibular disorder.

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White KP, Speechley M, Harth M, Ostbye T. Co-existence of chronic fatigue syndrome with fibromyalgia syndrome in the general population. A controlled study. Scand J Rheumatol. 2000;29(1):44-51. PMID: 10722257

There is significant clinical overlap between CFS and FMS.

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Evengard B, Nilsson CG, Lindh G, Lindquist L, Eneroth P, Fredrikson S, Terenius L, Henriksson KG. Chronic fatigue syndrome differs from fibromyalgia. No evidence for elevated substance P levels in cerebrospinal fluid of patients with chronic fatigue syndrome. Pain. 1998 Nov;78(2):153-5. PMID: 9839828

Unlike fibromyalgia patients, CFS patients have normal levels of Substance P in their cerebrospinal fluid.

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De Lorenzo F, Hargreaves J, Kakkar VV. Phosphate diabetes in patients with chronic fatigue syndrome. Postgrad Med J. 1998 Apr;74(870):229-32. PMID: 9683977

The authors report a relationship between chronic fatigue syndrome and phosphate diabetes.

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Baraniuk JN, Clauw DJ, Gaumond E. Rhinitis symptoms in chronic fatigue syndrome. Ann Allergy Asthma Immunol. 1998 Oct;81(4):359-65. PMID: 9809501

In a CFS population, 24% had no significant rhinitis complaints, 30% had positive skin tests suggesting the potential for allergic rhinitis complaints, and 46% had nonallergic rhinitis.

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Gomborone JE, Gorard DA, Dewsnap PA, Libby GW, Farthing MJ. Prevalence of irritable bowel syndrome in chronic fatigue. J R Coll Physicians Lond. 1996 Nov-Dec;30(6):512-3. PMID: 8961203

63% of people belonging to a group for chronic fatigue sufferers fulfilled a diagnosis of irritable bowel syndrome (recurrent abdominal pain and at least three Manning criteria). This greatly exceeds estimates of irritable bowel syndrome prevalence of up to 22% in the general population.

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Auger PL, Gourdeau P, Miller JD. Clinical experience with patients suffering from a chronic fatigue-like syndrome and repeated upper respiratory infections in relation to airborne molds. Am J Ind Med. 1994 Jan;25(1):41-2. PMID: 8116649

 

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