Longitudinal changes associated with improvement in chronic fatigue patients.

Tertiary care patients with chronic fatigue were followed for 2.5 years to determine if changes in physical and psychological status were associated with improvements in chronic fatigue, physical functioning, and return to work. Results indicated that improvement in psychological symptoms, DSM-III-R disorders, physical examination signs, and changes in whether the patient continued to meet criteria for chronic fatigue syndrome (CFS) were associated with recovery from fatigue, improved functioning, and return to work. Patients who never met CFS criteria or only met criteria at the initial assessment, reported improved physical functioning. Patients whose psychiatric disorders and physical examination signs were still present at a mean follow-up time of 2.5 years were more likely to have persistent fatigue and work disability. Loss of physical examination signs was a significant independent predictor of improved functioning and return to work. These results suggest that psychiatric status, as well as physical status, are associated with recovery from chronic fatigue.

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

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 CSF and CF.

Screening for psychiatric disorders in chronic fatigue and chronic fatigue syndrome.

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.

Evaluation of cerebrospinal fluid in Southeast Asian refugees with reactive serologic tests for syphilis.

To determine the prevalence of cerebrospinal fluid abnormalities in Southeast Asian refugees with reactive serologic tests for syphilis, we evaluated 65 patients, 36 prospectively and 29 retrospectively, in a primary care clinic. Information was collected on history of treponemal infections, neurologic symptoms and signs, and total protein concentration, leukocyte count, and the VDRL test in the cerebrospinal fluid. Neurologic symptoms were reported by all patients for whom data were available. Abnormal neurologic signs were found or noted in medical records in 15 (42%) prospectively evaluated patients and 9 (64%) of 14 retrospectively evaluated patients for whom data were available. No patient had evidence of congenital or non-neurologic sequelae such as cutaneous or cardiovascular manifestations of syphilis. No patient had a positive cerebrospinal fluid VDRL test, 1 had more than 5 x 10(6) leukocytes per liter (5 leukocytes per mm3), and 6 (9%) had elevated total protein levels in the cerebrospinal fluid. Previous therapy for syphilis was not associated with lower serum VDRL reactions, neurologic symptoms and signs, or cerebrospinal fluid findings. In the absence of other indications, routine examination of the cerebrospinal fluid in seropositive Southeast Asian refugees who have nonspecific neurologic symptoms has a low yield, perhaps because of the high prevalence of yaws in this population, and may not be warranted.

Viral serologies in patients with chronic fatigue and chronic fatigue syndrome.

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.

Postinfectious chronic fatigue: a distinct syndrome?

Chronic fatigue syndrome (CFS) is often preceded by a viral illness and has recurrent "flu-like" symptoms. We compared demographic, clinical, and laboratory features (markers of inflammation and viral infection) among 717 patients with chronic fatigue (CF) with and without a self-reported postinfectious onset to identify associated clinical and biologic findings and to examine the subset of patients with CFS. Only subjective fever, chills, sore throat, lymphadenopathy, poorer functional status, and attribution of illness to a physical condition were significantly associated with a postinfectious onset. The features of patients with CFS were virtually identical to those of the broader category of patients with CF. We conclude that a postinfectious onset was not associated with a pattern of abnormalities across multiple psychosocial and biologic parameters.

Frequency of thyroid disease among Southeast Asian primary care patients.

We prospectively assessed 99 Southeast Asians for the presence of thyroid disease who were attending a primary care clinic devoted to the care of refugees. Subjects were undergoing evaluation as new patients and had no previously diagnosed thyroid abnormality. Each patient had a physical examination performed by his or her primary-care provider, was given a standardized questionnaire that focused on symptoms of thyroid disease and underwent a venipuncture for total thyroxine, triiodothyronine resin uptake and thyrotropin (TSH) concentration. Those who had an abnormal examination, calculated free thyroxine index (FT4I) or TSH level were re-examined by an endocrinologist and had repeat thyroid studies performed. Although 81% of patients reported > or = 1 symptom compatible with thyroid dysfunction, only 17% were found to have laboratory abnormalities. An abnormal FT4I and TSH level was found in 5% and 13% of subjects, respectively, but only one case of clinically significant hyperthyroidism and no cases of hypothyroidism were confirmed. TSH suppression, noted in 12% of subjects, persisted over a median follow-up of 6 months. Among seven patients with an anatomic abnormality of the thyroid, four had an abnormal FT4I or TSH. We conclude that the clinical prevalence of symptomatic thyroid dysfunction among Southeast Asians is comparable to that reported for non-Asian populations, but that the frequency of subclinical hyperthyroidism may be higher. Although symptoms suggestive of thyroid disease are common, routine screening for thyroid disease is not indicated in this study.

Chronic fatigue and the chronic fatigue syndrome: prevalence in a Pacific Northwest health care system.

OBJECTIVES: To investigate the point prevalence of the chronic fatigue syndrome and unexplained debilitating chronic fatigue in a community-based sample of persons and to describe demographic, clinical, and psychosocial differences among those with the chronic fatigue syndrome, those with chronic fatigue, and healthy controls. DESIGN: Prospective cohort study. SETTING: A health maintenance organization in Seattle, Washington. PARTICIPANTS: A random sample of 4000 members of the health maintenance organization was surveyed by mail for the presence of chronic fatigue. MEASUREMENTS: Persons with chronic fatigue were evaluated using a questionnaire that requested information about medical history and fatigue and related symptoms; validated measures of functional status and psychological distress; a physical examination; and standardized blood tests. A structured psychiatric interview was done in persons who appeared to meet the original Centers for Disease Control and Prevention (CDC) criteria for the chronic fatigue syndrome. Participants completed self-report measures at 12 and 24 months. Those with chronic fatigue were reevaluated in person 1 year after study enrollment. RESULTS: 3066 (77%) of the 4000 members surveyed responded. Chronic fatigue was reported by 590 persons (19%). Of these, 388 (66%) had a medical or psychiatric condition that could account for the fatigue. Of the 74 persons (37%) with chronic fatigue who were enrolled in the study, only 3 met the CDC criteria for the chronic fatigue syndrome. The remaining 71 persons were designated as having chronic fatigue alone. Seventy-four healthy, age- and sex-matched controls who were drawn from the same sample but who denied having chronic fatigue were also studied. Demographic characteristics were similar in persons with the chronic fatigue syndrome, persons with chronic fatigue alone, and controls. Those with the chronic fatigue syndrome or chronic fatigue alone had more frequent cervical and axillary adenopathy, poorer functional status, and greater psychological distress than controls. Women and minorities were not overrepresented among cases with chronic fatigue. CONCLUSIONS: Using different assumptions about the likelihood that persons who did not participate in the study had the chronic fatigue syndrome, the estimated crude point prevalence of the syndrome in this community ranged from 75 to 267 cases per 100,000 persons. The point prevalence of chronic fatigue alone was strikingly higher; it ranged from 1775 to 6321 cases per 100,000 persons.

Chronic fatigue: risk factors for symptom persistence in a 2 1/2-year follow-up study.

BACKGROUND: The prolonged disability of patients suffering from chronic fatigue may be due to sustaining factors that are independent of the cause and subject to intervention. This study reexamined a cohort of patients with chronic fatigue to define medical and psychiatric predictors of persistent symptoms. METHODS: Seventy-eight patients with chronic fatigue present for 6 months or more (not required to meet the Centers for Disease Control case definition for chronic fatigue syndrome [CFS]) completed a self-report, follow-up questionnaire to measure the overall improvement or worsening of their condition at a mean of 2.5 years after their initial examination. At the time of initial evaluation, patients underwent a structured psychiatric examination, physical examination, laboratory studies, and self-report measures of psychological distress and functional disability. The psychiatric examination queried the patient about 28 somatic symptoms that are separate from those associated with CFS. Discriminant analysis was used to determine which variables present at the initial examination were significant predictors of persistent symptoms and disability at 2.5 years. RESULTS: The factors most important at the time of initial presentation in predicting persistent illness were: (1) more than eight medically unexplained physical symptoms separate from those associated with CFS case definition; (2) lifetime history of dysthymia; (3) duration of chronic fatigue symptoms greater than 1.5 years; (4) less than 16 years of formal education; and (5) age older than 38 years. None of the results of the initial physical examination, or immunologic, general laboratory, or viral antibody measurements were significant in predicting persistence of symptoms. Recovery rates for those who met the criteria for CFS by either of two case definitions were lower than the rate of noncases, but the differences were not statistically significant. The five aforementioned variables formed a significant discriminative function, correctly classifying 78% of those who recovered and 74% of those with persistent symptoms. CONCLUSIONS: At initial examination, patients with chronic fatigue, more than eight medically unexplained physical symptoms (excluding symptoms in the case criteria for CFS), a lifetime history of dysthymic disorder, longer than 1.5 years of chronic fatigue, less than 16 years of formal education, and who were older than 38 years were the most likely to have persistence of symptoms of chronic fatigue at the 2.5-year follow-up.

Clinical laboratory test findings in patients with chronic fatigue syndrome.

BACKGROUND: Results of readily available clinical laboratory tests in patients with chronic fatigue syndrome were compared with results in healthy control subjects. METHODS: Cases consisted of all 579 patients who met either the Centers for Disease Control and Prevention, Atlanta, Ga, British, or Australian case definition for chronic fatigue syndrome. They were from chronic fatigue clinics in Boston, Mass, and Seattle, Wash. Control subjects consisted of 147 blood donors who denied chronic fatigue. Outcome measures were the results of 18 clinical laboratory tests. RESULTS: Age- and sex-adjusted odds ratios of abnormal results, comparing cases with control subjects, were as follows: circulating immune complexes, 26.5 (95% confidence interval [CI] 3.4-206), atypical lymphocytosis, 11.4 (95% CI, 1.4-94); elevated immunoglobulin G, 8.5 (95% CI, 2.0-37); elevated alkaline phosphatase, 4.2 (95% CI, 1.6-11); elevated total cholesterol, 2.1 (95% CI, 1.2-3.4); and elevated lactic dehydrogenase, 0.30 (95% CI, 0.16-0.56). Also, antinuclear antibodies were detected in 15% of cases vs 0% in the control subjects. The results of these tests were generally comparable for the cases from Seattle and Boston. Although these tests served to discriminate the population of patients from healthy control subjects, at the individual level they were not as useful. CONCLUSIONS: Patients with chronic fatigue syndrome who were located in two geographically distant areas had abnormalities in the results of several readily available clinical laboratory tests compared with healthy control subjects. The immunologic abnormalities are in accord with a growing body of evidence suggesting chronic, low-level activation of the immune system in chronic fatigue syndrome. While each of these laboratory findings supports the diagnosis of chronic fatigue syndrome, each lacks sufficient sensitivity to be a diagnostic test. Furthermore, the specificity of these findings relative to other organic and psychiatric conditions that can produce fatigue remains to be established.

Gender differences in patients with chronic fatigue syndrome.

OBJECTIVE: To determine whether there are differences between men and women patients who have chronic fatigue syndrome (CFS) and, if so, to ascertain whether a gender-related pattern exists. DESIGN: A descriptive study of demographic, clinical, and psychosocial measures, the results of which were prospectively collected for patients who had CFS. SETTING: A university-based referral clinic devoted to the evaluation and management of chronic fatigue. PATIENTS: 348 CFS patients who had undergone complete medical evaluations. MEASURES: Clinical variables included symptoms, physical examination findings, and laboratory results. Psychosocial assessment consisted of a structured psychiatric interview, the Medical Outcomes Study Short-form General Health Survey to assess functional status, the General Health Questionnaire to ascertain psychological distress, the Multidimensional Health Locus of Control, and measures of attribution, social support, and coping. MAIN RESULTS: Overall, few gender-related differences were identified. Women had a higher frequency of tender or enlarged lymph nodes (60% versus 33%, p < or = 0.01) and fibromyalgia (36% versus 12%, p < or = 0.001) and lower scores on the physical functioning subscale of the Medical Outcomes Study Short-form General Health Survey (37.6 versus 52.2, p < 0.01); men more often had pharyngeal inflammation (42% versus 22%, p < or = 0.001) and reported a higher lifetime prevalence of alcoholism (20% versus 9%, p < or = 0.01). CONCLUSIONS: In general, demographic, clinical, and psychosocial factors do not distinguish men from women CFS patients.

A comparison of case definitions of chronic fatigue syndrome.

We compared three case definitions of chronic fatigue syndrome (CFS) applied to patients followed in CFS clinics at two institutions. All patients had debilitating fatigue without apparent etiology; patients with medical conditions associated with chronic fatigue and with major psychiatric disorders were stratified and presented separately. Patients were classified according to whether they met case definitions developed by a Centers for Disease Control and Prevention (CDC) Working Group, a British group, or an Australian group. When findings for 805 patients followed at the two clinics were combined, 61% met the CDC criteria, 55% met the British criteria, and 56% met the Australian criteria; these proportions were relatively similar at both sites. In addition, similar laboratory abnormalities were found for all case groups and for fatigued patients who met none of the three case definitions. These data suggest that more inclusive case definitions may be superior.

Sleep disorders in patients with chronic fatigue.

This prospective, cohort study examined the prevalence of sleep disorders among highly selected patients with chronic fatigue. On the basis of responses suggestive of sleep pathology on a screening questionnaire, 59 patients from a university-based clinic for chronic fatigue who had undergone a medical and psychiatric evaluation underwent polysomnography. Criteria for chronic fatigue syndrome (CFS) were met by 64% of patients and those for a current psychiatric disorder were met by 41%. Overall, 41% of patients had abnormal results for a multiple sleep latency test and 81% had at least one sleep disorder, most frequently sleep apnea (44%) and idiopathic hypersomnia (12%). In comparing patients who did and did not meet CFS criteria, no significant differences were found in individual sleep symptoms or sleep disorders. Likewise, symptoms and sleep disorders were unrelated to psychiatric diagnoses. In conclusion, chronically fatigued patients with suggestive symptoms may have potentially treatable coexisting sleep disorders that are not associated with meeting criteria for CFS or a current psychiatric disorder.