Chronic fatigue syndrome: an immunological perspective

Abstract:

OBJECTIVE: The aim of this study is to review research examining an immunological basis for chronic fatigue syndrome (CFS) and to discuss how a disturbance in immunity could produce central nervous system (CNS)-mediated symptoms.

METHOD: Data relevant to the hypothesis that abnormal cytokine release plays a role in the pathogenesis of CFS are reviewed as well as recent evidence relating to potential mechanisms by which immune products may enter the brain and produce a disturbance in CNS processes.

RESULTS: Examinations of cytokine levels in patients with CFS have produced inconclusive results. Recent evidence suggests that abnormal release of cytokines within the CNS may cause neural dysfunction by a variety of complex mechanisms.

CONCLUSION: Neuropsychiatric symptoms in patients with CFS may be more closely related to disordered cytokine production by glial cells within the CNS than to circulating cytokines. This possibility is discussed in the context of unresolved issues in the pathogenesis of CFS.

 

Source: Vollmer-Conna U, Lloyd A, Hickie I, Wakefield D. Chronic fatigue syndrome: an immunological perspective. Aust N Z J Psychiatry. 1998 Aug;32(4):523-7. http://www.ncbi.nlm.nih.gov/pubmed/9711366

 

Hormonal influences on stress-induced neutrophil mobilization in health and chronic fatigue syndrome

Abstract:

This investigation tested the hypotheses that women diagnosed with chronic fatigue syndrome (CFS) would exhibit significantly greater systemic indices of exercise-induced leukocyte mobilization and inflammation (neutrophilia, lactoferrin release, complement activation) than controls matched for age, weight, and habitual activity and that responses in the luteal phase of the menstrual cycle would be greater than in the follicular phase.

Subjects stepped up and down on a platform adjusted to the height of the patella for 15 min, paced by metronome. Blood samples were collected under basal conditions (the day before exercise) and following exercise for determination of circulating neutrophils and plasma concentrations of lactoferrin, C3a des arg, and creatine kinase. Complete, 24-hr urine collections were made for determination of cortisol excretion.

For all subjects, circulating neutrophil counts increased 33% (P < 0.0001) and lactoferrin increased 27% (P = 0.0006) after exercise, whereas plasma C3a des arg and creatine kinase did not increase. No indication of an exaggerated or excessive response was observed in the CFS patients compared to the controls.

In healthy women, circulating neutrophil numbers exhibited previously described relationships with physiological variables: basal neutrophil counts correlated with plasma progesterone concentrations (R = 0.726, P = 0.003) and the exercise-induced neutrophilia correlated with both urinary cortisol (R = 0.660, P = 0.007) and plasma creatine kinase (R = 0.523, P = 0.038) concentrations. These relationships were not observed in the CFS patients (R = 0.240, P = 0.370; R = 0.042, P = 0.892; and R = 0.293, P = 0.270; respectively).

These results suggest that normal endocrine influences on the circulating neutrophil pool may be disrupted in patients with CFS.

 

Source: Cannon JG, Angel JB, Abad LW, O’Grady J, Lundgren N, Fagioli L, Komaroff AL. Hormonal influences on stress-induced neutrophil mobilization in health and chronic fatigue syndrome. J Clin Immunol. 1998 Jul;18(4):291-8. http://www.ncbi.nlm.nih.gov/pubmed/9710746

 

Chronic fatigue disorders: an inappropriate response to arginine vasopressin?

Abstract:

Chronic fatigue disorders are characterized by a subjectively defined group of symptoms such as chronic fatigue, mental confusion, exertional malaise, weight changes, and/or diffuse multi-joint pains.

Significant clinical overlap exists between chronic fatigue disorders and the syndrome of serum inappropriate anti-diuretic hormone (SIADH). Both chronic fatigue disorders and SIADH are characterized by lethargy and mental confusion. Both disorders can be induced or exacerbated by viral illnesses, physical exertion, emotional stress and/or hypotension. Both can be treated with salt loading and glucocorticoids.

Therefore, altered water metabolism resulting from inappropriate release and/or response to arginine vasopressin (AVP) is proposed as a pathophysiological basis of certain chronic fatigue disorders. Moreover, these data suggest that salt loading and/or direct inhibition of AVP may be an effective therapeutic approach in individuals with chronic fatigue disorders.

 

Source: Peroutka SJ. Chronic fatigue disorders: an inappropriate response to arginine vasopressin? Med Hypotheses. 1998 Jun;50(6):521-3. http://www.ncbi.nlm.nih.gov/pubmed/9710328

 

Sociosomatics and illness in chronic fatigue syndrome

Abstract:

OBJECTIVE: This study examines social processes that construct the course of chronic illness. Specifically, it identifies and describes mechanisms that constitute the process of role constriction in employment for individuals with chronic illness.

METHOD: Sixty-six persons meeting the Centers for Disease Control case definition of chronic fatigue syndrome (CFS) participated in a longitudinal study involving three waves of data collection over 3 years. Qualitative and quantitative methods were combined in the research, which included face-to-face semistructured interviews, telephone interviews, and self-report questionnaires. Materials presented in this study are drawn principally from the Year 1 face-to-face and telephone interviews.

RESULTS: When patterns of symptoms and of the illness course in CFS intersect with work requirements, they impede performance and place ill individuals at risk for job loss. Persons with CFS devise and implement specific strategies to resist role constriction and remain in the work force.

CONCLUSIONS: Role constriction is a social process of marginalization in chronic illness. Opposing forces of marginalization and resistance define the social course in chronic illness and suggest that chronicity can be thought of as a marginalized position in social space.

Comment in: Sociosomatics and illness in CFS. [Psychosom Med. 1999]

 

Source: Ware NC. Sociosomatics and illness in chronic fatigue syndrome. Psychosom Med. 1998 Jul-Aug;60(4):394-401. http://www.ncbi.nlm.nih.gov/pubmed/9710284

 

Serum neopterin and somatization in women with chemical intolerance, depressives, and normals

Abstract:

The symptom of intolerance to low levels of environmental chemicals (CI, chemical intolerance) is a feature of several controversial polysymptomatic conditions that overlap symptomatically with depression and somatization, i.e., chronic fatigue syndrome, fibromyalgia, multiple chemical sensitivity, and Persian Gulf syndrome. These syndromes can involve many somatic symptoms consistent with possible inflammation. Immunological or neurogenic triggering might account for such inflammation.

Serum neopterin, which has an inverse relationship with l-tryptophan availability, may offer a marker of inflammation and macrophage/monocyte activation. This study compared middle-aged women with CI (who had high levels of affective distress; n = 14), depressives without CI (n = 10), and normals (n = 11).

Groups did not differ in 4 p.m. resting levels of serum neopterin. However, the CI alone had strong positive correlations between neopterin and all of the scales measuring somatization. These preliminary findings suggest the need for additional research on biological correlates of ‘unexplained’ multiple somatic symptoms in subtypes of apparent somatizing disorders.

 

Source: Bell IR, Patarca R, Baldwin CM, Klimas NG, Schwartz GE, Hardin EE. Serum neopterin and somatization in women with chemical intolerance, depressives, and normals. Neuropsychobiology. 1998;38(1):13-8. http://www.ncbi.nlm.nih.gov/pubmed/9701717

 

A 56-Year-Old Woman With Chronic Fatigue Syndrome, 1 Year Later

In June 1997, at the Medicine Grand Rounds, Dr Anthony Komaroff discussed Ms H, an educator unable to work because of debilitating symptoms associated with a 2-year history of chronic fatigue. Her ailment, which began shortly after a flu-like illness, was marked primarily by weakness, fatigue, chronic insomnia, and depression that she felt was in response to her symptoms. In recent years she had felt somewhat less depressed, and wondered also if the disease might be slowly diminishing in its severity.

You can read the rest of this article here: http://jama.jamanetwork.com/article.aspx?articleid=187800

 

Source: Thomas L. Delbanco, MD; Jennifer Daley, MD; Erin E. Hartman, MS. A 56-Year-Old Woman With Chronic Fatigue Syndrome, 1 Year Later. JAMA. 1998;280(4):372. doi:10.1001/jama.280.4.372. http://jama.jamanetwork.com/article.aspx?articleid=187800

Course and outcome of chronic fatigue in children and adolescents

Abstract:

PURPOSE: To describe the epidemiology, symptoms, and psychosocial characteristics of children and adolescents evaluated in a chronic fatigue program and determine the course and outcome of the syndrome in these patients.

METHODS: During the summer of 1994, chart review was performed for the 58 patients evaluated between 1990 and 1994 and a telephone follow-up was conducted with 42 of the 58 families. Patients were predominantly female (71%) and white (94%), with 50% between the ages of 7 and 14 years and 50% between the ages of 15 and 21 years (mean age 14.6 years).

RESULTS: At time of presentation, 50% of patients had been fatigued for 1 to 6 months and 50% had been fatigued for 7 to 36 months. Sixty percent indicated the fatigue had begun with an acute illness and 60% had a history of allergies. Most commonly reported symptoms were fatigue (100%), headache (74%), sore throat (59%), abdominal pain (48%), fever (36%), and difficulties with concentration and/or memory (33%). Most patients had a worsening of school performance and a decrease in social activities. On follow-up, there was significant improvement in many patients during the summer after the first visit, with continued improvement in most patients during the second and third years. At time of the follow-up telephone call, 43% of families considered their child “cured” and 52% considered their child “improved,” whereas only 5% considered their child to be “the same.” Statistical analyses demonstrated no demographic or clinical factors that distinguished between those who did or did not participate in the follow-up study, or between those who did or did not do well on follow-up.

CONCLUSIONS: These data demonstrate that children and adolescents with chronic fatigue have a syndrome that is similar to that described in adults, but that the syndrome differs in several ways, most specifically, presentation earlier in the course of the illness and a more optimistic outcome.

 

Source: Krilov LR, Fisher M, Friedman SB, Reitman D, Mandel FS. Course and outcome of chronic fatigue in children and adolescents. Pediatrics. 1998 Aug;102(2 Pt 1):360-6. http://www.ncbi.nlm.nih.gov/pubmed/9685439

 

Phosphate diabetes in patients with chronic fatigue syndrome

Abstract:

Phosphate depletion is associated with neuromuscular dysfunction due to changes in mitochondrial respiration that result in a defect of intracellular oxidative metabolism. Phosphate diabetes causes phosphate depletion due to abnormal renal re-absorption of phosphate be the proximal renal tubule. Most of the symptoms presented by patients with phosphate diabetes such as myalgia, fatigue and mild depression, are also common in patients with chronic fatigue syndrome, but this differential diagnosis has not been considered.

We investigated the possible association between chronic fatigue syndrome and phosphate diabetes in 87 patients who fulfilled the criteria for chronic fatigue syndrome. Control subjects were 37 volunteers, who explicitly denied fatigue and chronic illness on a screening questionnaire.

Re-absorption of phosphate by the proximal renal tubule, phosphate clearance and renal threshold phosphate concentration were the main outcome measures in both groups. Of the 87 patients with chronic fatigue syndrome, nine also fulfilled the diagnostic criteria for phosphate diabetes.

In conclusion, we report a previously undefined relationship between chronic fatigue syndrome and phosphate diabetes. Phosphate diabetes should be considered in differential diagnosis with chronic fatigue syndrome; further studies are needed to investigate the incidence of phosphate diabetes in patients with chronic fatigue syndrome and the possible beneficial effect of vitamin D and oral phosphate supplements.

Comment in: Chronic fatigue syndrome. [Postgrad Med J. 1998]

 

Source: De Lorenzo F, Hargreaves J, Kakkar VV. Phosphate diabetes in patients with chronic fatigue syndrome. Postgrad Med J. 1998 Apr;74(870):229-32. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2360873/ (Full article)

 

Dysfunction of natural killer activity in a family with chronic fatigue syndrome

Abstract:

A family was identified with 5 of 6 siblings and 3 other immediate family members who had developed chronic fatigue syndrome (CFS) as adults. All 8 met criteria for the CFS case definition as recommended by the Centers for Disease Control and Prevention.

Sixty-eight blood samples were obtained over a period of 2 years from 20 family members (8 affected, 12 unaffected) and 8 normal controls. All blood samples were tested for NK activity in 4-h 51Cr-release assays and for the number of circulating CD3-CD56(+) and CD3-CD16(+) by flow cytometry.

NK activity of the affected immediate family members (cases, n = 8) was significantly lower (P = 0.006, two-sided) than that of the concurrently tested normal controls. The results for unaffected family members were intermediate between these two groups, and the pairwise comparison of unaffected family members to either cases or controls showed no statistically significant difference (P = 0.29, two-sided). No differences were seen between the groups in the absolute number of CD3-CD56(+) or CD3-CD16(+) lymphocytes in the peripheral blood.

Familial CFS was associated with persistently low NK activity, which was documented in 6/8 cases and in 4/12 unaffected family members. In the family with 5 of 6 siblings who had documented CFS, 2 of their offspring had pediatric malignancies. Low NK activity in this family may be a result of a genetically determined immunologic abnormality predisposing to CFS and cancer.

 

Source: Levine PH, Whiteside TL, Friberg D, Bryant J, Colclough G, Herberman RB. Dysfunction of natural killer activity in a family with chronic fatigue syndrome. Clin Immunol Immunopathol. 1998 Jul;88(1):96-104. http://www.ncbi.nlm.nih.gov/pubmed/9683556

 

Incidence and clinical relevance of antibodies to phospholipids, serotonin and ganglioside in patients with sudden deafness and progressive inner ear hearing loss

Abstract:

Immunoserological assays of patients with sudden deafness and progressive hearing losses have revealed the presence of different antibodies, leading to the assumption that immunological processes may be involved. Recent investigations have demonstrated that these patients have phospholipid antibodies that can cause venous or arterial vasculopathies.

In the present study we analyzed the incidence of these antibodies in patients with inner ear disorders. Sera of 55 patients with sudden deafness and 80 patients with progressive hearing loss were tested.

Phospholipid antibodies were demonstrable in 49% of the patients with sudden hearing loss and 50% of the patients with progressive hearing loss. Serotonin and ganglioside antibodies were found in 53% of the patients with sudden hearing loss and 63% of the patients with progressive hearing loss.

Since these three antibodies are also frequently found in patients with fibromyalgia syndrome (FMS) and chronic fatigue syndrome (CFS), 28 of the patients studied displayed symptoms typical for these disorders, including fatigue, myalgia, arthralgia, depressions, sicca symptoms and diarrhea.

We now recommend questioning patients suffering from inner ear disorders for symptoms typical for FMS or CFS, since these diseases are often closely related to inner ear disorders. If symptoms are present, antibodies should be tested against phospholipids, serotonin and gangliosides. If present, the antibodies are diagnostic for each syndrome. Additionally these immunologic and serologic findings show that these antibodies may play a role in the etiology of hearing loss disorders.

 

Source: Heller U, Becker EW, Zenner HP, Berg PA. Incidence and clinical relevance of antibodies to phospholipids, serotonin and ganglioside in patients with sudden deafness and progressive inner ear hearing loss. HNO. 1998 Jun;46(6):583-6. [Article in German] http://www.ncbi.nlm.nih.gov/pubmed/9677490