Markers of inflammation and immune activation in chronic fatigue and chronic fatigue syndrome

Abstract:

OBJECTIVE: Chronic fatigue syndrome (CFS) has been hypothesized to result from immune activation. We examined the role of serum markers of inflammation and immune activation among patients with CFS and in those with chronic fatigue (CF) not meeting the case definition.

METHODS: Assays for soluble interleukin 2 (IL-2) receptor, IL-6, C-reactive protein, beta 2-microglobulin, and neopterin were performed in 153 fatigued patients in a referral clinic. Patients were classified according to whether they met criteria for CFS, reported onset of illness with a viral syndrome or had a temperature > 37.5 degrees C on examination.

RESULTS: Compared to control subjects, mean concentrations of C-reactive protein, beta 2-microglobulin, and neopterin were higher in patients with CFS (p < or = 0.01) and CF (p < or = 0.01). Results did not distinguish CFS from CF. IL-6 was elevated among febrile patients compared to those without this finding (p < or = 0.001), but other consistent differences between patient subgroups were not observed. The presence of several markers was highly correlated (p < 0.01).

CONCLUSION: Our findings that levels of several markers were significantly correlated points to a subset of patients with immune system activation. Whether this phenomenon reflects an intercurrent, transient, common condition, such as an upper respiratory infection, or is the result of an ongoing illness associated process is unknown. Overall, serum markers of inflammation and immune activation are of limited diagnostic usefulness in the evaluation of patients with CFS and CF.

 

Source: Buchwald D, Wener MH, Pearlman T, Kith P. Markers of inflammation and immune activation in chronic fatigue and chronic fatigue syndrome. J Rheumatol. 1997 Feb;24(2):372-6. http://www.ncbi.nlm.nih.gov/pubmed/9034999

 

Chronic fatigue syndrome criteria in patients with other forms of unexplained chronic fatigue

Abstract:

To determine the prevalence of chronic fatigue syndrome (CFS) criteria in other forms of unexplained chronic fatigue, 297 consecutive outpatients under the age of 40 from a general medicine practice were studied. After excluding the three with chronic fatigue syndrome, the remaining 294 individuals were divided into those with unexplained chronic fatigue (64 patients) those without (the remaining 230 patients).

Chronic fatigue syndrome criteria noted to be significantly more common in those with unexplained fatigue compared to those without include: fever, painful adenopathy, muscle weakness, myalgia, headache, migratory arthralgia, neuropsychologic symptoms, and sleep disorder. Like chronic fatigue syndrome, unexplained chronic fatigue often started suddenly.

I conclude that the CFS criteria are noted more commonly than expected in other forms of unexplained chronic fatigue.

 

Source: Chester AC. Chronic fatigue syndrome criteria in patients with other forms of unexplained chronic fatigue. J Psychiatr Res. 1997 Jan-Feb;31(1):45-50. http://www.ncbi.nlm.nih.gov/pubmed/9201646

 

Screening for psychiatric disorders in chronic fatigue and chronic fatigue syndrome

Abstract:

Psychiatric disorders are common in chronic fatigue (CF) and chronic fatigue syndrome (CFS). To determine the usefulness of the General Health Questionnaire (GHQ), a self-report measure of psychological distress, in identifying those with psychiatric illnesses, a structured psychiatric interview and the GHQ were administered to 120 CF and 161 CFS patients seen in a referral clinic.

Overall, 87 (35%) patients had a current and 210 (82%) a lifetime psychiatric disorder. Compared to patients without psychiatric disorders, GHQ scores above the threshold (> or = 12) were more frequent among patients with current (p < 0.001) and lifetime (p < 0.05) diagnoses; scores among patients with CF and CFS were similar.

Longer illness duration, greater fatigue severity, and current psychiatric disorders were significant predictors of the GHQ score. In CF and CFS, the best sensitivity (0.69-0.76) and specificity (0.51-0.62) were achieved for current psychiatric diagnoses using a threshold score of > or = 12. Thus, patients scoring < 12 on the GHQ are significantly less likely to have a psychiatric disorder.

 

Source: Buchwald D, Pearlman T, Kith P, Katon W, Schmaling K. Screening for psychiatric disorders in chronic fatigue and chronic fatigue syndrome. J Psychosom Res. 1997 Jan;42(1):87-94. http://www.ncbi.nlm.nih.gov/pubmed/9055216

 

Prevalence of irritable bowel syndrome in chronic fatigue

Abstract:

The aetiologies of irritable bowel syndrome and chronic fatigue are unknown. Psychological as well as physical factors have been implicated in both. Fatigue is common in irritable bowel syndrome patients. The purpose of the study was to determine the prevalence of irritable bowel syndrome in chronic fatigue sufferers.

A bowel symptom questionnaire was sent to all 4,000 members of a self-help group for fatigue sufferers. Of the 1,797 who responded, 1,129 (63%) 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.

Furthermore, irritable bowel syndrome sufferers within this chronic fatigue population reported more Manning criteria (14% had all six Manning criteria) than irritable bowel syndrome sufferers in the general population. This study demonstrates an overlap of symptoms in chronic fatigue and irritable bowel syndrome. In chronic fatigue, irritable bowel symptoms may be one aspect of a more generalised disorder.

 

Source: 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. http://www.ncbi.nlm.nih.gov/pubmed/8961203

 

Psychosocial risk factors for chronic fatigue and chronic fatigue syndrome following presumed viral illness: a case-control study

Abstract:

This study investigated psychosocial morbidity, coping styles and health locus of control in 64 cases with and without chronic fatigue identified from a cohort of primary care patients recruited 6 months previously with a presumed, clinically diagnosed viral illness. A significant association between chronic fatigue and psychosocial morbidity, somatic symptoms and escape-avoidance coping styles was shown.

Chronic fatigue cases were significantly more likely to have a past psychiatric history and a current psychiatric diagnosis based on a standardized clinical interview. Twenty-three of the cases fulfilled criteria for chronic fatigue syndrome (CFS). Such cases were significantly more fatigued than those not fulfilling criteria, but had little excess psychiatric disorder.

A principal components analysis provided some evidence for chronic fatigue being separable from general psychosocial morbidity but not from the tendency to have other somatic complaints. Past psychiatric history and psychological distress at the time of the viral illness were risk factors for psychiatric ‘caseness’ 6 months later, while presence of fatigue, psychologising attributional style and sick certification were significant risk factors for CFS. These findings extend a previous questionnaire study of predictors of chronic ‘post-viral’ fatigue.

 

Source: Cope H, Mann A, Pelosi A, David A. Psychosocial risk factors for chronic fatigue and chronic fatigue syndrome following presumed viral illness: a case-control study. Psychol Med. 1996 Nov;26(6):1197-209. http://www.ncbi.nlm.nih.gov/pubmed/8931166

 

Functional status in patients with chronic fatigue syndrome, other fatiguing illnesses, and healthy individuals

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) is a condition that may be associated with substantial disability. The Medical Outcomes Study Short-Form General Health Survey (SF-36) is an instrument that has been widely used in outpatient populations to determine functional status. Our objectives were to describe the usefulness of the SF-36 in CFS patients and to determine if subscale scores could distinguish patients with CFS from subjects with unexplained chronic fatigue (CF), major depression (MD), or acute infectious mononucleosis (AIM), and from healthy control subjects (HC). An additional goal was to ascertain if subscale scores correlated with the signs and symptoms of CFS or the presence of psychiatric disorders and fibromyalgia.

DESIGN: Prospectively collected case series.

SETTING: Patients with CFS and CF were seen in a university-based referral clinic and had undergone a complete medical and psychiatric evaluation. Other study subjects were recruited from the community to participate in research studies.

PARTICIPANTS: The study included 185 patients with CFS, 246 with CF, 111 with AIM, and 25 with MD. There were 99 HC subjects.

MEASURES: The SF-36 and a structured psychiatric interview were used. The SF-36 contains 8 subscales: physical, emotional, social, and role functioning, body pain, mental health, vitality, and general health- and a structured psychiatric interview.

RESULTS: Performance characteristics (internal reliability coefficients, convergent validity) of the SF-36 were excellent. A strikingly consistent pattern was found for the physical functioning, role functioning, social functioning, general health, and body pain subscales, with the lowest scores in CFS patients, intermediate scores in AIM patients, and the highest scores in the HC subjects. The CFS patients had significantly lower scores than patients with CF alone on the physical functioning (P < or = 0.01), role functioning (P < or = 0.01), and body pain (P < or = 0.001) subscales. The emotional functioning and mental health scores were worst among those with MD. The presence of fibromyalgia, being unemployed, and increasing fatigue severity all were associated with additional functional limitations across multiple functional domains, with increasing fatigue appearing to have the greatest effect.

CONCLUSIONS: The SF-36 is useful in assessing functional status in patients with fatiguing illnesses. Patients with CFS and CF have marked impairment of their functional status. The severity and pattern of impairment as documented by the SF-36 distinguishes patients with CFS and CF from those with MD and AIM, and from HC, but does not discriminate between CF and CFS.

 

Source: Buchwald D, Pearlman T, Umali J, Schmaling K, Katon W. Functional status in patients with chronic fatigue syndrome, other fatiguing illnesses, and healthy individuals. Am J Med. 1996 Oct;101(4):364-70. http://www.ncbi.nlm.nih.gov/pubmed/8873506

 

Viral serologies in patients with chronic fatigue and chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is an illness characterized by disabling fatigue associated with complaints of fevers, sore throat, myalgia, lymphadenopathy, sleep disturbances, neurocognitive difficulties, and depression. A striking feature of CFS is its sudden onset following an acute, presumably viral, illness and the subsequent recurrent “flu-like” symptoms. It has been speculated that both CFS and debilitating chronic fatigue (CF) that does not meet strict criteria for CFS may be the direct or indirect result of viral infections.

We therefore tested 548 chronically fatigued patients who underwent a comprehensive medical and psychiatric evaluation for antibodies to 13 viruses. Our objectives were to compare the seroprevalence and/or geometric mean titer (GMT) of antibodies to herpes simplex virus 1 and 2, rubella, adenovirus, human herpesvirus 6, Epstein-Barr virus, cytomegalovirus, and Cox-sackie B virus, types 1-6 in patients with CF to healthy control subjects. Other goals were to determine if greater rates of seropositivity or higher GMTs occurred among subsets of patients with CFS, fibromyalgia, psychiatric disorders, a self-reported illness onset with a viral syndrome, and a documented temperature > 37 degrees C on physical examination.

Differences in the seroprevalence or GMTs of antibodies to 13 viruses were not consistently found in those with CF compared with control subjects, or in any subsets of patients including those with CFS, an acute onset of illness, or a documented fever. These particular viral serologies were not useful in evaluating patients presenting with CF.

 

Source: Buchwald D, Ashley RL, Pearlman T, Kith P, Komaroff AL. Viral serologies in patients with chronic fatigue and chronic fatigue syndrome. J Med Virol. 1996 Sep;50(1):25-30. http://www.ncbi.nlm.nih.gov/pubmed/8890037

 

Chronic fatigue, chronic fatigue syndrome, and fibromyalgia. Disability and health-care use

Abstract:

OBJECTIVES: Disabling chronic fatigue that does not meet criteria for chronic fatigue syndrome (CFS) or fibromyalgia (FM) is a condition thought to be associated with substantial disability and an apparently high use of health-care services. The authors compare patients who have chronic fatigue, CFS, FM, or CFS and FM together (CFS+FM) on employment status, self-reported disability, number of medical care visits, type of services obtained, and other diagnoses received.

METHODS: The authors studied 402 patients from a university-based chronic fatigue clinic. All patients underwent an initial structured diagnostic assessment. One hundred forty-seven patients met case criteria for CFS, 28 for FM, 61 for CFS+FM, and 166 fell in the residual chronic fatigue group. Of these patients, 388 completed a follow-up questionnaire an average of 1.7 years later. Chi-squared tests and analysis of variance were used to compare groups on follow-up measures of health-care use and disability.

RESULTS: Patients with chronic fatigue, CFS, FM, and CFS+FM were similar in terms of disability and health-care use, though those with CFS+FM were significantly more likely to be unemployed and to use more chiropractic and “other” provider services. Rates of unemployment ranged from 26% (chronic fatigue) to 51% (CFS+FM). Overall, patients reported a mean of 21 visits to a wide variety health-care providers during the previous year, with no significant differences between groups.

CONCLUSIONS: Chronic fatigue, CFS, and FM are associated with considerable personal and occupational disability and low rates of employment. The potentially large economic burden of these disorders underscores the need for accurate estimates of direct and indirect costs, the relative contribution of individual factors to disability, and the need to develop targeted rehabilitation programs.

 

Source: Bombardier CH, Buchwald D. Chronic fatigue, chronic fatigue syndrome, and fibromyalgia. Disability and health-care use. Med Care. 1996 Sep;34(9):924-30. http://www.ncbi.nlm.nih.gov/pubmed/8792781

 

Chronic fatigue, arthralgia, and malaise

A 25 year old female veterinary nurse presented with a six year history of general malaise and severe fatigue. Associated with this she described frequent (monthly) episodes of polyarthralgia affecting all joints but with a predilection for the small joints of the hands and the wrists. When present this was accompanied by mild morning stiffness. In addition she experienced colicky abdominal pain, sometimes with diarrhoea, occasionally with blood mixed with her faeces. Other complaints consisted of low back pain, sore gritty eyes, and an inability to perform any physical exercise at the time of these symptoms. Her symptoms had been remarkably consistent, with no recent change to their pattern.

Six years ago she had been on a working holiday at a veterinary practice situated in New York state, USA. After eating a dish made with “blue fish” she had immediately developed severe nausea, vomiting, and malaise. Although all her acute symptoms resolved, her other symptoms started on return to the United Kingdom. She was investigated twice, at different hospitals, before being referred to this department. It had been found that her symptoms were helped by treatment with 30 mg prednisolone daily for the severe episodes and a maintenance dose of 5 mg daily. Severe episodes were occurring three to four times a year. Non-steroidal anti-inflammatory drugs, sulphasalazine, and other treatments of inflammatory bowel disease had not helped her symptoms. On all occasions the examination and investigations had been reported as normal including markers of inflammation, connective tissue disease, and radiological and histological gastrointestinal studies. No blood had been seen in her faeces. No diagnosis was made other than a seronegative arthralgia.

You can read the rest of this article here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1010225/pdf/annrheumd00353-0014.pdf

 

Source: Gompels MM, Spickett GP. Chronic fatigue, arthralgia, and malaise. Ann Rheum Dis. 1996 Aug;55(8):502-3. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1010225/

 

Psychological symptoms, somatic symptoms, and psychiatric disorder in chronic fatigue and chronic fatigue syndrome: a prospective study in the primary care setting

Abstract:

OBJECTIVE: This study assessed relationships among psychological symptoms, past and current psychiatric disorder, functional impairment, somatic symptoms, chronic fatigue, and chronic fatigue syndrome.

METHOD: A prospective cohort study was followed by a nested case-control study. The subjects, aged 18-45 years, had been in primary care for either clinical viral infections or a range of other problems. Questionnaire measures of fatigue and psychological symptoms were completed by 1,985 subjects 6 months later; 214 subjects with chronic fatigue were then compared with 214 matched subjects without fatigue. Assessments were made with questionnaires, interviews, and medical records of fatigue, somatic symptoms, psychiatric disorder, and functional impairment.

RESULTS: Subjects with chronic fatigue were at greater risk than those without chronic fatigue for current psychiatric disorder assessed by standardized interview (60% versus 19%) or by questionnaire (71% versus 31%). Chronic fatigue subjects were more likely to have received psychotropic medication or experienced psychiatric disorder in the past. There was a trend for previous psychiatric disorder to be associated with comorbid rather than noncomorbid chronic fatigue. Most subjects with chronic fatigue syndrome also had current psychiatric disorder when assessed by interview (75%) or questionnaire (78%). Both the prevalence and incidence of chronic fatigue syndrome were associated with measures of previous psychiatric disorder. The number of symptoms suggested as characteristics of chronic fatigue syndrome was closely related to the total number of somatic symptoms and to measures of psychiatric disorder. Only postexertion malaise, muscle weakness, and myalgia were significantly more likely to be observed in chronic fatigue syndrome than in chronic fatigue.

CONCLUSIONS: Most subjects with chronic fatigue or chronic fatigue syndrome in primary care also meet criteria for a current psychiatric disorder. Both chronic fatigue and chronic fatigue syndrome are associated with previous psychiatric disorder, partly explained by high rates of current psychiatric disorder. The symptoms thought to represent a specific process in chronic fatigue syndrome may be related to the joint experience of somatic and psychological distress.

 

Source: Wessely S, Chalder T, Hirsch S, Wallace P, Wright D. Psychological symptoms, somatic symptoms, and psychiatric disorder in chronic fatigue and chronic fatigue syndrome: a prospective study in the primary care setting. Am J Psychiatry. 1996 Aug;153(8):1050-9. http://www.ncbi.nlm.nih.gov/pubmed/8678174