Chr. Fatigue Syn
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Diagnosis for Chronic Fatigue Syndrome (CFS): 1) Have severe chronic fatigue of six months or longer with other known medical conditions excluded, and 2) concurrently have four or more of the following eight symptoms: substantial impairment in short-term memory or concentration, sore throat, tender lymph nodes, muscle pain, multi-joint pain without swelling or redness, headaches of a new type, pattern or severity, unrefreshing sleep, and post-exertional malaise lasting more than 24 hours. 

One in 500 people nationally suffers from CFS. The CDC Seattle study found that 59% of CFS patients were women. CDC's San Francisco study found that CFS-like disease was most prevalent among women, persons with household annual incomes of under $40,000, and African-Americans, and was least common among Asians and European-Americans. 

CFS often follows a cyclical course, alternating between periods of illness and relative well being. 50% report recovery, and most of these recover within the first 5 years.  No characteristics have been identified that made one patient more likely to recover than another.  At illness onset, the most commonly reported CFS symptoms are sore throat, fever, muscle pain, and muscle weakness.  As the illness progresses, muscle pain and forgetfulness increase and the reporting of depression decreases.

Research on the treatment of CFS has been disappointingly sparse.  However, there are quite a few approaches worth pursuing.  These are listed on another page under Treatment for Chronic Fatigue Syndrome.

Risk Factors for Chronic Fatigue Syndrome

Some risk factors for developing CFS are depression, endometriosis, being a Gulf War Veteran, positive test for Lyme disease, history of mononucleosis or Q fever, mycoplasma infection, phosphate depletion, and sinusitis.

Angiotensin-Converting Enzyme Gene Polymorphism Much More Common in Gulf War CFS: In a study of 49 Gulf War veterans and 61 nonveterans with chronic fatigue syndrome (CFS) or idiopathic chronic fatigue (ICF) and 30 veterans and 45 nonveterans who served as healthy controls, increased risk for CFS/ICF was associated with alterations of the insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme gene within the Gulf War veteran sample only. Veterans with the DD genotype were eight times more likely to develop CFS/ICF than were those with the II genotype (OR, 8.30; P = 0.009). Association of medically unexplained fatigue with ACE insertion/deletion polymorphism in Gulf War veterans. Vladutiu GD, Natelson BH. State University of New York at Buffalo. Muscle Nerve. 2004 Jul;30(1):38-43

Chemical Trigger Effect Not Found: In a DB PC study of 36 CFS patients who reported having chemical triggers, no difference was found in neuropsychological tests scores when patients were exposed to the offending chemical or a placebo. Int J Behav Med. 2003;10(2):162-73. 

Depression and Fatigue Tend to Lead to Each Other: 3,201 adults in 14 countries were followed for 12 months. Patients with depression were found to have an increased risk of developing a new episode of unexplained fatigue at follow-up with an adjusted odds ratio of 4.15. Unexplained fatigue had an increased risk of developing a new episode of depression with an OR of 2.76. Temporal relations between unexplained fatigue and depression: longitudinal data from an international study in primary care. Skapinakis P, Lewis G, Mavreas V. University of Ioannina, Greece. Psychosom Med. 2004 May-Jun;66(3):330-5

Endometriosis Connected to CFS, MS, SLE, and Many Autoimmune Diseases: In a cross-sectional survey of 3680 women with endometriosis, all members of a national endometriosis organization, almost all responders had pain (99%), and many infertility (41%). Compared national norms, women with endometriosis had higher rates of hypothyroidism (9.6 vs. 1.5%, P < 0.0001), fibromyalgia (5.9 vs. 3.4%, P < 0.0001), chronic fatigue syndrome (4.6 vs. 0.03%, P < 0.0001), rheumatoid arthritis (1.8 vs. 1.2%, P = 0.001), systemic lupus erythematosus (0.8 vs. 0.04%, P < 0.0001), Sjogren's syndrome (0.6 vs. 0.03%, P < 0.0001) and multiple sclerosis (0.5 vs. 0.07%, P < 0.0001), but not hyperthyroidism or diabetes. Allergies and asthma were more common among women with endometriosis (61% and 12%) and still higher in those with fibromyalgia or chronic fatigue syndrome in addition (88% and 25%) than in the USA female population (18% and 5%). High rates of autoimmune and endocrine disorders, fibromyalgia, chronic fatigue syndrome and atopic diseases among women with endometriosis: a survey analysis. Sinaii N, Cleary SD, Ballweg ML, Nieman LK, Stratton P. National Institute of Child Health and Human Development, Bethesda. Hum Reprod. 2002 Oct;17(10):2715-24

Gulf War Vets More CFS and PTSD: In a population-based sample of 15,000 Gulf War veterans and 15,000 non-Gulf veteran controls, Gulf War veterans reported significantly higher rates of PTSD (OR=3.1) and CFS (OR=4.8). Post-traumatic stress disorder and chronic fatigue syndrome-like illness among Gulf War veterans: a population-based survey of 30,000 veterans. Kang HK, Natelson BH, Mahan CM, Lee KY, Murphy FM. VA, Washington, DC, USA. Am J Epidemiol. 2003 Jan 15;157(2):141-8  

Immune Abnormalities: Evidence of Infection or Toxicity in CFS: Many patients with chronic fatigue syndrome (CFS) have symptoms that are consistent with an underlying viral or toxic illness. Neutrophil apoptosis occurs in patients with infection. In a study, the 47 patients with CFS had higher numbers of apoptotic neutrophils, lower numbers of viable neutrophils, increased annexin V binding, and increased expression of the death receptor, tumour necrosis factor receptor-I, on their neutrophils than did 34 healthy controls. Patients with CFS also had raised concentrations of active TGFbeta1 (p < 0.005). Patients with CFS have an underlying detectable abnormality in their immune cells. Increased neutrophil apoptosis in chronic fatigue syndrome. Kennedy G, Spence V, Underwood C, Belch JJ. Dundee, UK J Clin Pathol. 2004 Aug;57(8):891-3 

Joint Hypermobility Common in CFS Children: 60% of CFS children have hypermobile joints vs. 24% of healthy children. Hypermobility is measured by being able to hyperextend knees and elbows over 190 degrees, touch palms to floor, touch thumb to forearm, hyperextend pinkie past 90 degrees. CFS chidlren often have orthostatic intolerance (dizziness on standing) with headaches and dizziness similar to Ehlers-Danlos Syndrome, a connective tissue disorder with hypermobility and orthostatic hypotension. Johns Hopkins, J Pediatrics 9/02

Lyme Disease Seropositives More Fatigue, Malaise: German study of 1,156 healthy young males. Eur Neurol. 2000;43(2):107- 

Mercury: No Relationship Dental Amalgam and CFS: In a retrospective cohort study of New Zealand Defense Force covering 20 000 young adults, 84% males, of conditions allegedly associated with amalgam, multiple sclerosis had a slightly increased risk: an adjusted hazard ratio (HR) of 1.24 (P = 0.06), but neither chronic fatigue syndrome nor kidney diseases were associated at all with amalgam. Further follow-up of the cohort will permit investigation of diseases more common in the elderly. Health effects of dental amalgam exposure: a retrospective cohort study. Bates MN, Fawcett J, Garrett N, Cutress T, Kjellstrom T. Porirua, New Zealand. Int J Epidemiol. 2004 Aug;33(4):894-902 

Mono Can Cause Chronic Fatigue: 150 Americans with infectious mononucleosis were followed for 2 and 6 months and 50 for 4 years. There were four different groups: most subjects with few symptoms, a few with many symptoms, a group with predominantly mood symptoms and some subjects with fatigue symptoms. Some fatigue was still demonstrable 4 years after onset. The nosology of sub-acute and chronic fatigue syndromes that follow infectious mononucleosis. White PD, Thomas JM, Sullivan PF, Buchwald D. University of London, UK. Psychol Med. 2004 Apr;34(3):499-507

Mycoplasma: Evidence of Infection in Many CFS Patients: The presence of Mycoplasma fermentans, M. penetrans, M. pneumoniae and M. hominis in the blood of 261 European CFS patients and 36 healthy volunteers was examined using a polymerase chain reaction. 69% of patients were infected by at least one species of Mycoplasma, vs. 6% of controls (P<0.001). M. hominis was found in 37%, M. pneumoniae 26% and M. fermentans 26%. M. penetrans infections were not found. Multiple mycoplasmal infections were detected in 17.2%. High prevalence of Mycoplasma infections among European chronic fatigue syndrome patients. Examination of four Mycoplasma species in blood of chronic fatigue syndrome patients. Nijs J, Nicolson GL, De Becker P, Coomans D, De Meirleir K. Vrije Universiteit Brussel. FEMS Immunol Med Microbiol. 2002 Nov 15;34(3):209-14. Similar American research is available. 

Mycoplasma, Chlamydia, HHV-6 Infections Higher in CFS: In a study of 200 CFS patients, 52% had PCR evidence of mycoplasmal infections, Chlamydia pneumoniae (7.5%) and/or active human herpes virus-6 (HHV-6, 30.5%). The incidence of C. pneumoniae or HHV-6 was similar in Mycoplasma-positive and -negative patients. Control subjects (n=100) had low rates of mycoplasmal (6%), active HHV-6 (9%) or chlamydial (1%) infections. There was no correlation between the type of co-infection and severity of signs and symptoms. Multiple co-infections (Mycoplasma, Chlamydia, human herpes virus-6) in blood of chronic fatigue syndrome patients: association with signs and symptoms. Nicolson GL, Gan R, Haier J. Huntington Beach, California. APMIS. 2003 May;111(5):557-66 

Phosphate Diabetes Can Cause CFS: Phosphate depletion is associated with neuromuscular dysfunction due to changes in mitochondrial respiration that result in a defect of intracellular oxidative metabolism. Phosphate diabetes causes phosphate depletion due to abnormal renal re-absorption of phosphate in the proximal renal tubule. Most of the symptoms presented by patients with phosphate diabetes such as myalgia, fatigue and mild depression. Of the 87 patients with chronic fatigue syndrome, 9 had phosphate diabetes. Phosphate diabetes should be considered in differential diagnosis with chronic fatigue syndrome; further studies are needed to investigate the incidence of phosphate diabetes in patients with chronic fatigue syndrome and the possible beneficial effect of vitamin D and oral phosphate supplements. Phosphate diabetes in patients with chronic fatigue syndrome. De Lorenzo F, Hargreaves J, Kakkar VV. London, UK. Postgrad Med J. 1998 Apr;74(870):229-32

Q Fever Linked to Increased Risk of CFS: Of 108 Q-exposed subjects 10 years after exposure, 65% had fatigue and 34% idiopathic chronic fatigue vs. 36.% and 15.% in controls. Chronic fatigue syndrome was present in 19% of Q-exposed patients vs. 4% of controls (p=0.003). Chronic fatigue following infection by Coxiella burnetii (Q fever): ten-year follow-up of the 1989 UK outbreak cohort. Wildman MJ, Smith EG, Groves J, Beattie JM, Caul EO, Ayres JG. Birmingham, UK. QJM. 2002 Aug;95(8):527-38 

Sinusitis Linked to Chronic Fatigue Syndrome: Sinus symptoms were nine times more common on average in patients with unexplained chronic fatigue than the control group, and six times more common in patients with unexplained chronic pain. In addition, sinus symptoms were more common in patients with unexplained fatigue than in patients with fatigue explained by a mental or physical illness, suggesting the syndrome of unexplained fatigue is more closely associated with sinusitis than are other types of fatigue. 

Sleep Apnea Might Be Increased with Antidepressants with Antihypertensives: In a retrospective analysis of data on 212,972 patients for prescriptions for antihypertensive medications, antidepressant medications, and the diagnosis of obstructive sleep apnea, the likelihood of having a diagnosis of OSA increased when either antihypertensive or antidepressant medications were prescribed. The probability was highest in the young and middle-age groups receiving prescriptions for both medications. Simultaneous use of antidepressant and antihypertensive medications increases likelihood of diagnosis of obstructive sleep apnea syndrome. Farney RJ, Lugo A, Jensen RL, Walker JM, Cloward TV., Salt Lake City. Chest. 2004 Apr;125(4):1279-85

Viral: Twin Study Finds No Evidence of Viral Infections Connected to CFS: In 22 monozygotic twin pairs where one twin had CFS, polymerase chain reaction assays for viral DNA of peripheral blood mononuclear cell specimens to detect infection with HHV-6, HHV-7, HHV-8, cytomegalovirus, Epstein-Barr virus, herpes simplex virus, varicella zoster virus, JC virus, BK virus, and parvovirus B19 found results did not differ between the group of twins with CFS and the healthy twins. Markers of viral infection in monozygotic twins discordant for chronic fatigue syndrome. Koelle DM, Barcy S, Huang ML, Ashley RL, Corey L, Zeh J, Ashton S, Buchwald D. University of Washington, Seattle. Clin Infect Dis. 2002 Sep 1;35(5):518-25.

Viral: Herpesvirus No Difference: Human herpesviruses (HHVs) HHV-6, HHV-7, Epstein-Barr virus (EBV), and cytomegalovirus were studied intensively and no differences were found between CFS patients and controls in PCR testing for viral presence. Clin Diagn Lab Immunol. 1999 Mar;6(2):216-23 

Viral: Coxsackie B Virus: Muscle biopsy samples from 10 of the 48 chronic fatigue patients were positive for enterovirus RNA, 10/03 J Neurology, Neurosurgery, and Psychiatry. All 29 human tissue controls were negative for enterovirus sequences. The RNA most closely that from coxsackie B virus 


Chronic Fatigue in Teens: In a 5-year follow-up of 34 teens with chronic fatigue syndrome, idiopathic chronic fatigue, or unexplained fatigue for less than 6 months, 25% of the chronic fatigue syndrome group showed near to complete improvement, 31% showed partial improvement, and 44% showed no improvement. The idiopathic chronic fatigue group had near to complete recovery in 50%, partial in 10%, and no improvement in 40%. Those with unexplained fatigue for less than 6 months had all recovered. Chronic fatigue syndrome in adolescents: a follow-up study. Gill AC, Dosen A, Ziegler JB. Sydney Children's Hospital, Australia. Arch Pediatr Adolesc Med. 2004 Mar;158(3):225-9

Pregnancies No Worse with CFS: In a survey of 86 women regarding 252 pregnancies that occurred before or after the onset of CFS, during pregnancy, there was no change in CFS symptoms in 41%, an improvement in 30%, and a worsening in 29%. After pregnancy, there was no change in CFS in 30%, an improvement in 20%, and a worsening in 20%. The rates of many complications were similar in pregnancies occurring before and after the onset of CFS. There was a higher frequency of spontaneous abortions in the pregnancies occurring after, vs before, the onset of CFS 30% vss 8%; P<.001), but no differences in the rates of other complications. Developmental delays or learning disabilities were reported more often in the offspring of women who became pregnant after, vs before, the onset of CFS: 21% vs. 8%; P =.01). The higher rates of spontaneous abortions and of developmental delays in offspring could be explained by maternal age or parity differences. A comparison of pregnancies that occur before and after the onset of chronic fatigue syndrome. Schacterle RS, Komaroff AL. Harvard. Arch Intern Med. 2004 Feb 23;164(4):401-4