Category: Etiology

The temporal stability and co-morbidity of prolonged fatigue: a longitudinal study in primary care

Abstract:

BACKGROUND: Depression, anxiety and fatigue are among the most common symptoms presented in primary care. Whether such symptoms indicate discrete psychological syndromes or whether they result from a common vulnerability is not clear. This study examined longitudinally the patterns of co-morbidity between prolonged fatigue and other forms of psychological distress in patients attending general practitioners.

METHODS: Adults attending primary care completed questionnaires designed to detect cases of prolonged fatigue and psychological distress at presentation and 12 months later.

RESULTS: Of 652 patients, the prevalence rates of ‘prolonged fatigue’ alone, ‘psychological distress’ alone, ‘prolonged fatigue + psychological distress’ and ‘no disorder’ were 7%, 19%, 15% and 59% respectively at initial assessment. Of those patients with any prolonged fatigue syndrome initially, 58% still reported fatigue 12 months later (representing 13% of the total sample). Most importantly, the risk of developing prolonged fatigue was not increased in patients who initially had psychological distress (OR = 0.95; 95% CI 0.2-3.6), neither was the risk of developing psychological distress increased in patients who initially had prolonged fatigue (OR = 1.4; 95% CI 0.6-3.4).

CONCLUSIONS: This study indicates that prolonged fatigue is a persistent diagnosis over time. The longitudinal patterns of co-morbidity with psychological distress do not support an aetiological model that proposes a common vulnerability factor for these disorders. Psychiatric classification systems may be better served by treating prolonged fatigue and psychological distress as independent disorders.

 

Source: Hickie I, Koschera A, Hadzi-Pavlovic D, Bennett B, Lloyd A. The temporal stability and co-morbidity of prolonged fatigue: a longitudinal study in primary care. Psychol Med. 1999 Jul;29(4):855-61. http://www.ncbi.nlm.nih.gov/pubmed/10473312

 

Fungal spores: hazardous to health?

Abstract:

Fungi have long been known to affect human well being in various ways, including disease of essential crop plants, decay of stored foods with possible concomitant production of mycotoxins, superficial and systemic infection of human tissues, and disease associated with immune stimulation such as hypersensitivity pneumonitis and toxic pneumonitis. The spores of a large number of important fungi are less than 5 microm aerodynamic diameter, and therefore are able to enter the lungs. They also may contain significant amounts of mycotoxins. Diseases associated with inhalation of fungal spores include toxic pneumonitis, hypersensitivity pneumonitis, tremors, chronic fatigue syndrome, kidney failure, and cancer.

 

Source: Sorenson WG. Fungal spores: hazardous to health? Environ Health Perspect. 1999 Jun;107 Suppl 3:469-72. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1566211/ (Full article)

 

Single aetiological agent may not be feasible in CFS patients

Comment on: Cortisol deficiency may account for elevated apoptotic cell population in patients with chronic fatigue syndrome. [J Intern Med. 1999]

 

Dear Sir, I would like to thank Dr Baschetti for his very interesting letter. I hope clinicians and CFS patients will be able to benefit from its contents. We agree that chronic fatigue syndrome (CFS) is an illness with uncertain aetiology. Although it is true that no single infectious agent has been identified as a primary cause of CFS, a variety of pathogens, including HTLV-II, EBV, cytomegalovirus, herpes simplex viruses 1 and 2, and human herpes viruses 6, 7 and 8, have been identified in CFS patients [1–7]. In addition to the pathogens previously mentioned, a recent study by our laboratory has identified Mycoplasma fermentans in a statistically significant number of CFS patients over non-CFS control subjects [8]. Further investigation is necessary to determine whether these pathogens are occurring secondarily to some immunological disturbances, as some investigators believe, or whether they are involved as a primary cause of symptoms characteristic of CFS. As mentioned by Dr Baschetti, various measures of immune function have been reported to be altered in CFS subjects, thereby suggesting an association rather than demonstrating a causative link. Abnormalities that have been reported include increased circulating immune complexes, reduced CD4 and CD8 T-lymphocyte subsets, diminished natural killer cell activity, reduction in IgG subclasses, reduced mitogenic response of lymphocytes, altered cytokine production, elevated titres of antibodies to a number of viruses and abnormal production of IFN [9–15]. However, similar immune functional abnormalities have been reported in patients exposed to toxic chemicals without evidence of viral infection or reactivation [16, 17]. Moreover, the symptomatologies described in these patients overlap with CFS patients, thus making the differentiation between the two groups extremely difficult [18–21]. In these articles, the substantial overlap between chemical sensitivity, fibromyalgia and CFA was discussed. It was concluded that the latter two conditions may involve chemical sensitivity and may even be the same disorder. In fact, in a separate study strictly with CFS patients without evidence of viral reactivation but exposed to methyl tertiary-butyl ether (MTBE) and benzene, we showed that programmed cell death and cell cycle were abnormal in both groups [22]. Similarly, in our original article published in this journal, we reported elevated apoptosis and abnormal cell cycle in CFS patients without a history of exposure to toxic chemicals. The interferon-induced protein kinase RNA (PKR) was found to be elevated in these patients as well and was therefore proposed as a possible mechanism of induction of apoptosis and cell cycle abnormalities [23].

 

You can read the rest of this comment here: http://onlinelibrary.wiley.com/doi/10.1046/j.1365-2796.1999.00479.x/full

 

Source: Vojdani A. Single aetiological agent may not be feasible in CFS patients. J Intern Med. 1999 Apr;245(4):410-2. http://onlinelibrary.wiley.com/doi/10.1046/j.1365-2796.1999.00479.x/full

 

Chronic fatigue syndrome and nickel allergy

Abstract:

50 patients with chronic fatigue syndrome (CFS) and 73 controls were patch tested with 8 metal allergens. We found an overrepresentation of allergies among the CFS patients, which was not significant. However, allergy to nickel occurred in 36% of patients in the CFS group and in 19% of subjects in the control group (p<0.05). The high frequency of nickel allergy was more noteworthy in females in the CFS group than among female controls (52% and 24%, respectively, p<0.05). Similarly, in the males the figures were 14% and 9%. We suggest that in vivo immunoactivation by ions of nickel, or metal cross-reacting with nickel, could be an etiological factor in CFS.

 

Source: Marcusson JA, Lindh G, Evengård B. Chronic fatigue syndrome and nickel allergy. Contact Dermatitis. 1999 May;40(5):269-72. http://www.ncbi.nlm.nih.gov/pubmed/10344482

 

What causes chronic fatigue?

Comment on:

Chronic fatigue syndrome comes out of the closet. [CMAJ. 1998]

Chronic fatigue syndrome or just plain tired? [CMAJ. 1998]

Chronic fatigue syndrome get court’s nod of approval as legitimate disorder. [CMAJ. 1998]

 

Even though the 3 articles on chronic fatigue syndrome 1–3 in the Sept. 8 issue commendably demolish the obsolete claim that chronic fatigue syndrome is a psychiatric illness, they also offer outdated biological explanations for the syndrome, namely, either a chronic viral infection or a weakened immune system. Although the first of these explanations seemed convincing until a few years ago, it is hardly tenable now, because no specific virus has been identified in these patients.4

You can read the rest of this comment here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1230107/pdf/cmaj_160_5_636.pdf

 

Source: Baschetti R. What causes chronic fatigue? CMAJ. 1999 Mar 9;160(5):636, 638. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1230107/pdf/cmaj_160_5_636.pdf (Full article)

 

Chronic fatigue syndrome among overseas development workers: A qualitative study

Abstract:

BACKGROUND: A relatively high proportion of overseas development workers may develop chronic fatigue syndrome (CFS). A qualitative study was conducted in order to investigate how such people perceived their condition.

METHODS: Twelve people who had developed CFS while working overseas with development organizations, or shortly after visiting development projects, were interviewed about their experiences. Their responses were analyzed using a grounded theory approach.

RESULTS: Most of the participants considered themselves to have been extremely healthy before they developed CFS. The syndrome did not appear to have been caused by depression. The symptoms which were reported covered the range of symptoms typically found in studies of CFS. Respondents described difficulty in receiving, and accepting, a diagnosis. All of the participants attributed the CFS to multiple causes, the principal causes being overwork, stress and infections. Among the consequences of CFS reported to be the most difficult were having to leave the development project prematurely; pain; powerlessness; loss of independence, and the unpredictability of CFS. Factors which had helped respondents cope with these difficulties included religious beliefs; comparisons with people who were worse off than they were; thinking about positive consequences of the condition, and talking with supportive people.

CONCLUSIONS: Some theories have suggested that CFS symptoms arise as a result of depression or other emotional difficulties, which the individual is not able to acknowledge. The results indicated that such theories may not apply to this subgroup of people with CFS. Further research on the etiology of CFS is warranted. Respondents described high levels of work-related stress as common to the experience of development work. It might be beneficial to train development workers in stress management techniques. Development organizations should be encouraged to ensure that their workers take sufficient time to rest, and attempts should be made to reduce work pressures.

 

Source: Lovell DM. Chronic fatigue syndrome among overseas development workers: A qualitative study. J Travel Med. 1999 Mar;6(1):16-23. http://jtm.oxfordjournals.org/content/6/1/16.long (Full article)

 

Incidence, risk and prognosis of acute and chronic fatigue syndromes and psychiatric disorders after glandular fever

Abstract:

BACKGROUND: The role of viruses in the aetiology of both chronic fatigue syndrome (CFS) and depressive illness is uncertain.

METHOD: A prospective cohort study of 250 primary care patients, presenting with glandular fever or an ordinary upper respiratory tract infection (URTI).

RESULTS: The incidence of an acute fatigue syndrome was 47% at onset, after glandular fever, compared with 20% with an ordinary URTI (relative risk 2.3, 95% CI 1.3-4.1). The acute fatigue syndrome lasted a median (interquartile range) of eight weeks (4-16) after glandular fever, but only three weeks (2-4) after an URTI. The prevalence of CFS was 9-22% six months after glandular fever, compared with 0-6% following an ordinary URTI, with relative risks of 2.7-5.1. The most conservative measure of the incidence of CFS was 9% after glandular fever, compared with no cases after an URTI. A conservative estimate is that glandular fever accounts for 3113 (95% CI 1698-4528) new cases of CFS per annum in England and Wales. New episodes of major depressive disorder were triggered by infection, especially the Epstein-Barr virus, but lasted a median of only three weeks. No psychiatric disorder was significantly more prevalent six months after onset than before.

CONCLUSIONS: Glandular fever is a significant risk factor for both acute and chronic fatigue syndromes. Transient new major depressive disorders occur close to onset, but are not related to any particular infection if they last more than a month.

 

Source: White PD, Thomas JM, Amess J, Crawford DH, Grover SA, Kangro HO, Clare AW. Incidence, risk and prognosis of acute and chronic fatigue syndromes and psychiatric disorders after glandular fever. Br J Psychiatry. 1998 Dec;173:475-81. http://www.ncbi.nlm.nih.gov/pubmed/9926075

 

Yersinia enterocolitica and the chronic fatigue syndrome

Abstract:

OBJECTIVES: To investigate the potential role of Yersinia enterocolitica in patients with chronic fatigue syndrome (CFS).

METHODS: An immunoblot technique was used to detect antibodies to various Yersinia outer membrane proteins (YOPs) in serum samples from 88 patients with CFS and 77 healthy neighbourhood controls, matched for gender and age.

RESULTS: The prevalence of IgG and IgA antibodies to various Yersinia outer membrane proteins (YOPs) did not differ between patients with CFS and healthy controls. Twenty-four patients (27%) and nineteen controls (25%) had IgG antibodies to one or more YOPs. Four patients and two controls had both serum IgG and IgA antibodies to at least two different YOPs, compatible with a recent or persistent infection. Although all patients with positive IgG and IgA reactions to two or more YOPs had symptoms that could point to persistent Yersinia infection, these symptoms were also found frequently in patients without antibodies to YOPs.

CONCLUSIONS: We conclude that Y. enterocolitica is unlikely to play a major role in the aetiology of CFS.

Source: Swanink CM, Stolk-Engelaar VM, van der Meer JW, Vercoulen JH, Bleijenberg G, Fennis JF, Galama JM, Hoogkamp-Korstanje JA. Yersinia enterocolitica and the chronic fatigue syndrome. J Infect. 1998 May;36(3):269-72. http://www.ncbi.nlm.nih.gov/pubmed/9661935

Demonstration on Borna disease virus in patients with chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS), a recently named heterogeneous disorder, is an illness of unknown etiology. The association between CFS and several viral infection has been suggested. Here, we centered on the possible link between CFS and Borna disease virus (BDV) infection.

BDV is a neurotropic, nonsegmented negative-strand (NNS) RNA virus. Recent epidemiological data have suggested that BDV may be closely associated with depression and schizophrenia in humans.

In Japanese patients with CFS, the prevalence of BDV infection was 34% (30/89) and 12% (7/57) by immunoblotting and PCR analysis, respectively. Furthermore, anti-BDV antibodies and BDV RNA were detected in a family cluster with CFS. These results suggested that this virus contributes to or initiates CFS, although the single etiologic role of BDV is unlikely.

 

Source: Nakaya T, Kuratsune H, Kitani T, Ikuta K. Demonstration on Borna disease virus in patients with chronic fatigue syndrome. Nihon Rinsho. 1997 Nov;55(11):3064-71. [Article in Japanese] http://www.ncbi.nlm.nih.gov/pubmed/9396313

 

Chronic fatigue syndrome–aetiological aspects

Abstract:

The chronic fatigue syndrome (CFS) has been intensively studied over the last 40 years, but no conclusions have yet been agreed as to its cause. Most cases nowadays are sporadic. In the established chronic condition there are no consistently abnormal physical signs or abnormalities on laboratory investigation.

Many physicians remain convinced that the symptoms are psychological rather than physical in origin. This view is reinforced by the emotional way in which many patients present themselves. The overlap of symptoms between CFS and depression remains a source of confusion and difficulty. But even if all CFS patients were rediagnosed as depressives, this would not negate the possibility of an underlying organic cause for the condition, in view of the growing evidence that depression itself has a physical cause and responds best to physical treatments.

There is some evidence both for active viral infection and for an immunological disorder in the CFS. Many observations suggest that the syndrome could derive from residual damage to the reticular activating system (RAS) of the upper brain stem and/or to its cortical projections. Such damage could be produced by a previous viral infection, leaving functional defects unaccompanied by any gross histological changes.

In animal experiments activation of the RAS can change sleep state and activate or stimulate cortical functions. RAS lesions can produce somnolence and apathy. Studies by modern imaging techniques have not been entirely consistent, but many magnetic resonance imaging (MRI) studies already suggest that small discrete patchy brain stem and subcortical lesions can often be seen in CFS.

Regional blood flow studies by single photon-emission computerized tomography (SPECT) have been more consistent. They have revealed blood flow reductions in many regions, especially in the hind brain. Similar lesions have been reported after poliomyelitis and in multiple sclerosis–in both of which conditions chronic fatigue is characteristically present. In the well-known post-polio fatigue syndrome, lesions predominate in the RAS of the brain stem. If similar underlying lesions in the RAS can eventually be identified in CFS, the therapeutic target for CFS would be better defined than it is at present. A number of logical approaches to treatment can already be envisaged.

Comment in:

Chronic fatigue syndrome. [Eur J Clin Invest. 1997]

Similarity of symptoms in chronic fatigue syndrome and Addison’s disease. [Eur J Clin Invest. 1997]

 

Source: Dickinson CJ. Chronic fatigue syndrome–aetiological aspects. Eur J Clin Invest. 1997 Apr;27(4):257-67. http://www.ncbi.nlm.nih.gov/pubmed/9134372