Chronic fatigue syndrome: a novel disorder with cutaneous manifestations

Abstract:

Persistent and disabling fatigue associated with low-grade fever and other constitutional symptoms, without any known disorder that accounts for it, is recognized as chronic fatigue syndrome (CFS). Skin lesions occur in 10-35% of patients, but their description is inaccurate. Recurrent aphthous stomatitis or persistent Epstein-Barr virus (EBV)-related erythema multiforme have also been reported. Patients may be diagnosed as having CFS only when they fulfill at least 2 major and 8 minor criteria. Major criteria are the presence of debilitating fatigue persisting or recurring for at least 6 months and the absence of any other medical disorder that may explain it. Although different viral or nonviral etiologies have been documented, evidence implicating EBV is gaining support.

 

Source: Rebora A, Drago F. Chronic fatigue syndrome: a novel disorder with cutaneous manifestations. Dermatology. 1994;188(1):3-5. http://www.ncbi.nlm.nih.gov/pubmed/8305753

 

Upregulation of the 2-5A synthetase/RNase L antiviral pathway associated with chronic fatigue syndrome

Abstract:

Levels of 2′,5′-oligoadenylate (2-5A) synthetase, bioactive 2-5A, and RNase L were measured in extracts of peripheral blood mononuclear cells (PBMCs) from 15 individuals with chronic fatigue syndrome (CFS) before and during therapy with the biological response modifier poly(I).poly(C12U) and were compared with levels in healthy controls.

Patients differed significantly from controls in having a lower mean basal level of latent 2-5A synthetase (P < .0001), a higher pretreatment level of bioactive 2-5A (P = .002), and a higher level of pretherapy RNase L activity (P < .0001). PBMC extracts from 10 persons with CFS had a mean basal level of activated 2-5A synthetase higher than the corresponding control value (P = .009). All seven pretherapy PBMC extracts tested were positive for the replication of human herpesvirus 6 (HHV-6).

Therapy with poly(I).poly(C12U) resulted in a significant decrease in HHV-6 activity (P < .01) and in downregulation of the 2-5A synthetase/RNase L pathway in temporal association with clinical and neuropsychological improvement. The upregulated 2-5A pathway in CFS before therapy is consistent with an activated immune state and a role for persistent viral infection in the pathogenesis of CFS. The response to therapy suggests direct or indirect antiviral activity of poly(I).poly(C12U) in this situation.

 

Source: Suhadolnik RJ, Reichenbach NL, Hitzges P, Sobol RW, Peterson DL, Henry B, Ablashi DV, Müller WE, Schröder HC, Carter WA, et al. Upregulation of the 2-5A synthetase/RNase L antiviral pathway associated with chronic fatigue syndrome. Clin Infect Dis. 1994 Jan;18 Suppl 1:S96-104. http://www.ncbi.nlm.nih.gov/pubmed/8148461

 

A controlled clinical trial with a specifically configured RNA drug, poly(I).poly(C12U), in chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is a physically debilitating illness associated with immunologic abnormalities, viral reactivation, and impairment of cognition.

In a randomized, multicenter, placebo-controlled, double-blind study of 92 patients meeting the CFS case definition of the Centers for Disease Control and Prevention, the response of several laboratory and clinical variables to an antiviral and immunomodulatory drug, poly(I).poly(C12U), was determined.

Measures of clinical response included Karnofsky performance score, a cognition scale derived from a self-administered instrument assessing symptomatology (SCL-90-R), an activities of daily living scale, and exercise treadmill performance.

After 24 weeks, patients receiving poly(I).poly(C12U) had higher scores for both global performance and perceived cognition than did patients receiving placebo. In particular, patients given poly(I).poly(C12U) had increased Karnofsky performance scores (P < .03), exhibited a greater ability to do work during exercise treadmill testing (P = .01), displayed an enhanced capacity to perform the activities of daily living (P < .04), had a reduced cognitive deficit (P = .05), and required less use of other medications (P < .05).

 

Source: Strayer DR, Carter WA, Brodsky I, Cheney P, Peterson D, Salvato P, Thompson C, Loveless M, Shapiro DE, Elsasser W, et al. A controlled clinical trial with a specifically configured RNA drug, poly(I).poly(C12U), in chronic fatigue syndrome. Clin Infect Dis. 1994 Jan;18 Suppl 1:S88-95. http://www.ncbi.nlm.nih.gov/pubmed/8148460

 

Cognitive functioning of patients with chronic fatigue syndrome

Abstract:

Neuropsychological problems are a distressing and frequent component of the symptom complex associated with chronic fatigue syndrome. Objective assessment of these difficulties is essential to understanding the nature of this illness. Results of the studies discussed in this paper suggest that impaired information processing, rather than primary memory dysfunction, may be at the root of the cognitive problems that afflict so many patients with CFS.

 

Source: Johnson SK, DeLuca J, Fiedler N, Natelson BH. Cognitive functioning of patients with chronic fatigue syndrome. Clin Infect Dis. 1994 Jan;18 Suppl 1:S84-5. http://www.ncbi.nlm.nih.gov/pubmed/8148459

 

Measuring the functional impact of fatigue: initial validation of the fatigue impact scale

Abstract:

The fatigue impact scale (FIS) was developed to improve our understanding of the effects of fatigue on quality of life. The FIS examines patients’ perceptions of the functional limitations that fatigue has caused over the past month. FIS items reflect perceived impact on cognitive, physical, and psychosocial functioning.

This study compared 145 patients referred for investigation of chronic fatigue (ChF) with 105 patients with multiple sclerosis (MS) and 34 patients with mild hypertension (HT). Internal consistency for the FIS and its three subscales was > .87 for all analyses. Fatigue impact was highest for the ChF group although the MS group’s reported fatigue also exceeded that of the HT group. Discriminant function analysis correctly classified 80.0% of the ChF group and 78.1% of the MS group when these groups were compared.

This initial validation study indicates that the FIS has considerable merit as a measure of patient’s attribution of functional limitations to symptoms of fatigue.

 

Source: Fisk JD, Ritvo PG, Ross L, Haase DA, Marrie TJ, Schlech. Measuring the functional impact of fatigue: initial validation of the fatigue impact scale. Clin Infect Dis. 1994 Jan;18 Suppl 1:S79-83. http://www.ncbi.nlm.nih.gov/pubmed/8148458

 

Psychosocial correlates of illness burden in chronic fatigue syndrome

Abstract:

We related reported physical symptoms, cognitive appraisals (e.g., negative style of thinking), and coping strategies (e.g., denial/disengagement strategies) with illness burden across several functional domains separately in subsets of chronic fatigue syndrome (CFS) patients with (n = 26) and without (n = 39) concurrently diagnosed major depressive disorder (MDD).

In regard to cognitive appraisal measures, automatic thoughts and dysfunctional attitudes were strongly associated with a higher illness burden, as indicated in sickness impact profile (SIP) scores. Active-involvement coping strategies measured on COPE scales (active coping, planning, and positive reinterpretation and growth) were not associated with SIP scores, while other coping strategies (mental disengagement, behavioral disengagement, and denial) were positively correlated with psychosocial and physical SIP scales, especially those pertaining to interpersonal life-style arenas.

After we accounted for the number of different CFS-specific physical complaints reported and DSM-III-R depression diagnosis status, cognitive appraisals and coping strategies predicted a substantial proportion of the variance in the severity of illness burden. For the most part, the magnitude of these relationships between our predictor model variables and illness burden severity was similar in the MDD and non-MDD subgroups.

 

Source: Antoni MH, Brickman A, Lutgendorf S, Klimas N, Imia-Fins A, Ironson G, Quillian R, Miguez MJ, van Riel F, Morgan R, et al. Psychosocial correlates of illness burden in chronic fatigue syndrome. Clin Infect Dis. 1994 Jan;18 Suppl 1:S73-8. http://www.ncbi.nlm.nih.gov/pubmed/8148457

 

Sleep disorders in patients with chronic fatigue

Abstract:

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.

 

Source: Buchwald D, Pascualy R, Bombardier C, Kith P. Clin Infect Dis. 1994 Jan;18 Suppl 1:S68-72. http://www.ncbi.nlm.nih.gov/pubmed/8148456

 

Acylcarnitine deficiency in chronic fatigue syndrome

Abstract:

One of the characteristic complaints of patients with chronic fatigue syndrome (CFS) is the skeletal muscle-related symptom. However, the abnormalities in the skeletal muscle that explain the symptom are not clear.

Herein, we show that our patients with CFS had a deficiency of serum acylcarnitine. As carnitine has an important role in energy production and modulation of the intramitochondrial coenzyme A (CoA)/acyl-CoA ratio in the skeletal muscle, this deficiency might induce an energy deficit and/or abnormality of the intramitochondrial condition in the skeletal muscle, thus resulting in general fatigue, myalgia, muscle weakness, and postexertional malaise in patients with CFS.

Furthermore, the concentration of serum acylcarnitine in patients with CFS tended to increase to the normal level with the recovery of general fatigue. Therefore, the measurement of acylcarnitine would be a useful tool for the diagnosis and assessment of the degree of clinical manifestation in patients with CFS.

 

Source: Kuratsune H, Yamaguti K, Takahashi M, Misaki H, Tagawa S, Kitani T. Acylcarnitine deficiency in chronic fatigue syndrome. Clin Infect Dis. 1994 Jan;18 Suppl 1:S62-7. http://www.ncbi.nlm.nih.gov/pubmed/8148455

 

An approach to studies of cancer subsequent to clusters of chronic fatigue syndrome: use of data from the Nevada State Cancer Registry

Abstract:

Chronic fatigue syndrome (CFS) has been increasingly associated with immune dysregulation, including depressed natural killer cell activity; this phenomenon is associated with increased susceptibility to cancer. Although anecdotal reports have suggested an association between CFS and cancer, particularly non-Hodgkin’s lymphoma and brain cancer, there has been no a priori justification for evaluating such an association and no consideration of relevant parameters, such as length of latent period vs. tumor type.

We reviewed data from the Nevada State Cancer Registry subsequent to a reported outbreak of a CFS-like illness in Nevada that occurred during 1984-1986. We concentrated on non-Hodgkin’s lymphoma and brain/CNS tumors, with particular emphasis on persons 15-34 and 35-54 years of age.

An upward trend in the incidence of brain/CNS tumors, which could be related to a national upward trend for this disease, was noted. No consistent trends were noted for non-Hodgkin’s lymphoma.

Because of the difficulties inherent in studies of cancer subsequent to various exposures, we evaluated the methodology for determining an association between outbreaks of CFS-like disease and cancer. We propose several approaches that should be considered in future studies for investigation of possible associations between CFS and cancer, including expected latent periods for specific tumors.

 

Source: Levine PH, Atherton M, Fears T, Hoover R. An approach to studies of cancer subsequent to clusters of chronic fatigue syndrome: use of data from the Nevada State Cancer Registry. Clin Infect Dis. 1994 Jan;18 Suppl 1:S49-53. http://www.ncbi.nlm.nih.gov/pubmed/8148453

 

Concurrent sick building syndrome and chronic fatigue syndrome: epidemic neuromyasthenia revisited

Abstract:

Sick building syndrome (SBS) is usually characterized by upper respiratory complaints, headache, and mild fatigue. Chronic fatigue syndrome (CFS) is an illness with defined criteria including extreme fatigue, sore throat, headache, and neurological symptoms.

We investigated three apparent outbreaks of SBS and observed another more serious illness (or illnesses), characterized predominantly by severe fatigue, that was noted by 9 (90%) of the 10 teachers who frequently used a single conference room at a high school in Truckee, California; 5 (23%) of the 22 responding teachers in the J wing of a high school in Elk Grove, California; and 9 (10%) of the 93 responding workers from an office building in Washington, D.C.

In those individuals with severe fatigue, symptoms of mucous membrane irritation that are characteristic of SBS were noted but also noted were neurological complaints not typical of SBS but quite characteristic of CFS. We conclude that CFS is often associated with SBS.

 

Source: Chester AC, Levine PH. Concurrent sick building syndrome and chronic fatigue syndrome: epidemic neuromyasthenia revisited. Clin Infect Dis. 1994 Jan;18 Suppl 1:S43-8. http://www.ncbi.nlm.nih.gov/pubmed/8148452