Category: Etiology

Precipitating factors for the chronic fatigue syndrome

Abstract:

The etiology of the Chronic Fatigue Syndrome (CFS) is unknown but it is usually considered to be postinfectious or postviral. Many infecting agents have been suspected as causative but none has been proven.

We investigated precipitating factors in 134 CFS patients through the use of a questionnaire, interview, clinical examination and serology for infecting agents; 35 healthy controls completed a similar questionnaire. CFS started with an apparently infectious illness in 96 (72%) but a definite infection was only found in seven of these 96 (7%). Thirty-eight (28%) had no apparent infectious onset: 15/38 (40%) had noninfectious precipitants (trauma, allergy, surgery).

There was no apparent precipitating event in 23/38 (61%). Immunization was not a significant precipitant. Stressful events were very common in the year preceding the onset of CFS (114/134, 85%) but these occurred in only 2/35 (6%) of the controls (p < .0001). The onset of CFS may be associated with preceding stressful events and multiple other precipitants. An infectious illness is not uniformly present at the onset and no single infectious agent has been found; CFS is most likely multifactorial in origin.

 

Source: Salit IE. Precipitating factors for the chronic fatigue syndrome. J Psychiatr Res. 1997 Jan-Feb;31(1):59-65. http://www.ncbi.nlm.nih.gov/pubmed/9201648

 

Postinfectious chronic fatigue: a distinct syndrome?

Abstract:

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.

 

Source: Buchwald D, Umali J, Pearlman T, Kith P, Ashley R, Wener M. Postinfectious chronic fatigue: a distinct syndrome? Clin Infect Dis. 1996 Aug;23(2):385-7. http://cid.oxfordjournals.org/content/23/2/385.long (Full article)

 

A case-control study to assess possible triggers and cofactors in chronic fatigue syndrome

Abstract:

PURPOSE: To assess possible triggers and cofactors for chronic fatigue syndrome (CFS) and to compare levels of selected cytokines between cases and an appropriately matched control group.

PATIENTS AND METHODS: We conducted a case-control study of 47 cases of CFS obtained through a regional CFS research program maintained at a tertiary care medical center. One age-, gender-, and neighborhood-matched control was identified for each case through systematic community telephone sampling. Standardized questionnaires were administered to cases and controls. Sera were assayed for transforming growth factor-beta (TGF-beta), interleukin-1 beta, interleukin-6, tumor necrosis factor-alpha, and antibody to Borrelia burgdorferi and Babesia microti.

RESULTS: Cases were more likely to have exercised regularly before illness onset than controls (67% versus 40%; matched odds ratio (MOR) = 3.4; 95% CI = 1.2 to 11.8; P = 0.02). Female cases were more likely to be nulliparous prior to onset of CFS than controls (51% versus 31%; MOR = 8.0; 95% CI = 1.03 to 170; P = 0.05). History of other major factors, including silicone-gel breast implants (one female case and one female control), pre-morbid history of depression (15% of cases, 11% of controls) and history of allergies (66% of cases, 51% of controls) were similar for cases and controls. However, cases were more likely to have a diagnosis of depression subsequent to their diagnosis of CFS compared to a similar time frame for controls (MOR = undefined; 95% CI lower bound = 2.5; P < 0.001). Positive antibody titers to B burgdorferi (one case and one control) and B microti (zero cases and two controls) were also similar.

CONCLUSIONS: Further investigation into the role of prior routine exercise as a cofactor for CFS is warranted. This study supports the concurrence of CFS and depression, although pre-morbid history of depression was similar for both groups.

Comment in: Etiology of chronic fatigue syndrome. [Am J Med. 1997]

 

Source: MacDonald KL, Osterholm MT, LeDell KH, White KE, Schenck CH, Chao CC, Persing DH, Johnson RC, Barker JM, Peterson PK. A case-control study to assess possible triggers and cofactors in chronic fatigue syndrome. Am J Med. 1996 May;100(5):548-54. http://www.ncbi.nlm.nih.gov/pubmed/8644768

 

Demonstration of Borna disease virus RNA in peripheral blood mononuclear cells derived from Japanese patients with chronic fatigue syndrome

Abstract:

CFS, a recently named heterogeneous disorder, is an illness of unknown etiology. The association of CFS with viral infections has been suggested. A common association between CFS and several viruses examined has not been confirmed.

Here, we centered on the possible link between CFS and BDV infection. By nested RT-PCR followed by hybridization, BDV RNA was demonstrated as a clear signal in PBMCs in 3 out of 25 CFS patients. The amplified cDNA fragments were cloned and sequenced. A total of 16 clones were studied. Intra-patients divergencies of the p24 were 2-9%, 3-20%, and 3-11% in the deduced amino acids. Inter-patient divergencies among the 16 clones were 3-24%. Antibodies to recombinant BDV p24 protein were detected in 6 CFS patients including one carrying BDV RNA.

Overall, these gave the prevalence of 32% (8/25) in Japanese CFS patients, suggesting that Japanese CFS is highly associated with active infection of BDV, or a related agent.

 

Source: Nakaya T, Takahashi H, Nakamura Y, Asahi S, Tobiume M, Kuratsune H, Kitani T, Yamanishi K, Ikuta K. Demonstration of Borna disease virus RNA in peripheral blood mononuclear cells derived from Japanese patients with chronic fatigue syndrome. FEBS Lett. 1996 Jan 8;378(2):145-9. http://onlinelibrary.wiley.com/doi/10.1016/0014-5793(95)01439-X/epdf (Full article)

 

New pathogens, and diseases old and new. I) Afipia felis and Rochalimaea. II) Parvovirus B 19. III) herpesvirus 6

Abstract:

The paper describes events that in the last fifteen years, have led to the identification of the aetiological agents of three widely known diseases: cat scratch disease, erythema infectiosum and exanthem subitum. The particular features of Afipia felis and Rochalimaea, Parvovirus B 19 and Herpesvirus 6 are presented.

The paternity of new diseases (i.e. bacillary angiomatosis, bacillary peliosis hepatitis, LES-like syndrome, chronic fatigue syndrome, petechial glove and sock syndrome, etc.) has also been attributed to some of these pathogens as has the paternity of some older ones (i.e. aplastic crisis, erythroblastosis fetalis, trench fever, hepatitis, opportunistic infection, etc.).

It has been argued that the same pathogen can cause different diseases depending on the immunogenic state of the subject. To date, persisting difficulties in isolating the pathogen or differentiating between latent or active infection, still in some cases raises doubts concerning the attribution of the disease to a specific agent.

New immunological or molecular techniques, allowing the direct detection of in vivo replication, are still needed in order to establish a sure connection between some of these agents and some of these diseases. Progress here will both give more accurate data about the epidemiology of some diseases and allow us to apply more appropriate treatment and prevention techniques.

 

Source: Zannolli R, Morgese G. New pathogens, and diseases old and new. I) Afipia felis and Rochalimaea. II) Parvovirus B 19. III) herpesvirus 6. Panminerva Med. 1995 Dec;37(4):238-47. http://www.ncbi.nlm.nih.gov/pubmed/8710408

 

Reducing heterogeneity in chronic fatigue syndrome: a comparison with depression and multiple sclerosis

Abstract:

Chronic fatigue syndrome (CFS) is a heterogeneous illness characterized by a high prevalence of psychiatric problems. We reasoned that we could reduce heterogeneity by excluding patients with psychiatric problems preceding CFS.

We compared the functional status, mood, fatigue level, and psychiatric status of this more homogeneous group of CFS patients with the same parameters in patients with mild multiple sclerosis and in patients with major depression or dysthymia.

Patients with CFS and those with multiple sclerosis were similar in terms of level of anger, severity of depression, level of anxiety, and frequency of current psychiatric diagnoses. Patients with CFS resembled depressed patients in having impaired vigor and experiencing substantial fatigue and confusion–problems constituting part of the case definition of CFS.

The group with CFS was not psychologically vulnerable before the development of this condition and maintained adequate networks of social support despite disabling illness.

Stratification to exclude patients with prior psychiatric disease and those with mild CFS allowed us to define a group of patients with CFS who more resembled patients with mild MS than patients with major depression or dysthymia and thus were more likely to have illness with an infectious or immunologic cause. Use of such a stratification strategy should prove important in testing of the viral/immunologic hypothesis of the etiology of CFS.

 

Source: Natelson BH, Johnson SK, DeLuca J, Sisto S, Ellis SP, Hill N, Bergen MT. Reducing heterogeneity in chronic fatigue syndrome: a comparison with depression and multiple sclerosis. Clin Infect Dis. 1995 Nov;21(5):1204-10. http://www.ncbi.nlm.nih.gov/pubmed/8589144

 

A preliminary investigation of chlorinated hydrocarbons and chronic fatigue syndrome

Abstract:

OBJECTIVE: To determine whether serum levels of chlorinated hydrocarbons are elevated in patients with chronic fatigue syndrome.

METHODS: Chlorinated hydrocarbon levels were measured in 22 patients with chronic fatigue syndrome (CFS) (as defined by the Centers for Disease Control [CDC]); in 17 patients with CFS symptoms whose history of exposure to toxic chemicals excluded them from the research definition of CFS; and in 34 non-CFS control subjects matched for age and sex.

RESULTS: DDE (1,1-dichloro-2,2-bis (p-chlorophenyl) ethene) was detected in all serum samples at levels over 0.4 ppb. The incidence of hexachlorobenzene (HCB) contamination (> 2.0 ppb) was 45% in the CFS group, compared with 21% in the non-CFS control group (P < 0.05). The CFS group had a significantly higher total organochlorine level (15.9 ppb; SEM, 4.4) than the control group (6.3 ppb; SEM, 1.1; P < 0.05). The toxic exposure group also had a higher mean organochlorine level (13.6 ppb; SEM, 6.2) than the control group, but the difference was not statistically significant. DDE and HCB comprised more than 90% of the total organochlorines measured in each of the groups.

CONCLUSION: The results suggest that recalcitrant organochlorines may have an aetiological role in CFS. There were no significant differences in serum organochlorine concentrations between CFS patients and chronic fatigue patients with a history of toxic chemical exposure. Therefore, exclusion of patients from the CDC research definition of CFS on the basis of a reported history of known exposure to toxic chemicals is not valid. The role of low-level organochlorine bioaccumulation in the development of CFS symptoms requires further investigation.

 

Source: Dunstan RH, Donohoe M, Taylor W, Roberts TK, Murdoch RN, Watkins JA, McGregor NR. A preliminary investigation of chlorinated hydrocarbons and chronic fatigue syndrome. Med J Aust. 1995 Sep 18;163(6):294-7. http://www.ncbi.nlm.nih.gov/pubmed/7565234

 

Can the chronic fatigue syndrome be defined by distinct clinical features?

Abstract:

To determine whether patients diagnosed as having chronic fatigue syndrome (CFS) constitute a clinically homogeneous class, multivariate statistical analyses were used to derive symptom patterns and potential patient subclasses in 565 patients. The notion that patients currently diagnosed as having CFS constitute a single homogeneous class was rejected.

An alternative set of clinical subgroups was derived. The validity of these subgroups was assessed by sociodemographic, psychiatric, immunological and illness behaviour variables. A two-class statistical solution was considered most coherent, with patients from the smaller class (27% of the sample) having clinical characteristics suggestive of somatoform disorders. The larger class (73% of sample) presented a more limited combination of fatigue and neuropsychological symptoms, and only moderate disability but remained heterogeneous clinically. The two patient groups differed with regard to duration of illness, spontaneous recovery, severity of current psychological morbidity, utilization of medical services and CD8 T cell subset counts. The distribution of symptoms among patients was not unimodal, supporting the notion that differences between the proposed subclasses were not due simply to differences in symptom severity.

This study demonstrated clinical heterogeneity among patients currently diagnosed as CFS, suggesting aetiological heterogeneity. In the absence of discriminative clinical features, current consensus criteria do not necessarily reduce the heterogeneity of patients recruited to CFS research studies.

 

Source: Hickie I, Lloyd A, Hadzi-Pavlovic D, Parker G, Bird K, Wakefield D. Can the chronic fatigue syndrome be defined by distinct clinical features? Psychol Med. 1995 Sep;25(5):925-35. http://www.ncbi.nlm.nih.gov/pubmed/8588011

 

The validity and reliability of the fatigue syndrome that follows glandular fever

Abstract:

The validity and reliability of an empirically defined fatigue syndrome were tested in a prospective cohort study of 245 primary care patients, with glandular fever or an upper respiratory tract infection. Subjects were interviewed three times in the 6 months after onset. Subjects with the empirically defined fatigue syndrome were compared with those who were well and those who had a psychiatric disorder.

The validity of the fatigue syndrome was supported, separate from psychiatric disorders in general and depressive disorders in particular. Only 16% of subjects with the principal component derived fatigue factor also met criteria for a psychiatric disorder (excluding pre-morbid phobias). Compared with subjects with psychiatric disorders, subjects with the operationally defined fatigue syndrome reported more severe physical fatigue, especially after exertion, were just as socially incapacitated, had fewer mental state abnormalities, and showed little overlap on independent questionnaires. A more mild fatigue state also existed.

Both fatigue syndrome and state were more reliable diagnoses over time than depressive disorders. The empirically defined syndrome probably is a valid and reliable condition in the six months following glandular fever.

 

Source: White PD, Grover SA, Kangro HO, Thomas JM, Amess J, Clare AW. The validity and reliability of the fatigue syndrome that follows glandular fever. Psychol Med. 1995 Sep;25(5):917-24. http://www.ncbi.nlm.nih.gov/pubmed/8588010

 

The existence of a fatigue syndrome after glandular fever

Abstract:

This prospective cohort study was designed to test whether a distinct fatigue syndrome existed after the onset of glandular fever.

Two hundred and fifty primary care patients, with either glandular fever or an ordinary upper respiratory tract infection (URTI) were interviewed three times in the 6 months after the clinical onset of their infection. At each interview a standardized psychiatric interview was given and physical symptoms were assessed. There were 108 subjects with and Epstein-Barr virus (EBV) infection; 83 subjects had glandular fever not caused by EBV and 54 subjects had an ordinary URTI. Five subjects were excluded because they had no evidence of an infection.

Principal components analyses of symptoms supported the existence of a fatigue syndrome, particularly in the two glandular fever groups. The addition of symptoms not elicited by the standard interviews gave the full syndrome. This included physical and mental fatigue, excessive sleep, psychomotor retardation, poor concentration, anhedonia, irritability, social withdrawal, emotional lability, and transient sore throat and neck gland swelling with pain. A fatigue syndrome probably exists after glandular fever.

 

Source: White PD, Thomas JM, Amess J, Grover SA, Kangro HO, Clare AW. The existence of a fatigue syndrome after glandular fever. Psychol Med. 1995 Sep;25(5):907-16. http://www.ncbi.nlm.nih.gov/pubmed/8588009