A controlled trial of intravenous immunoglobulin G in chronic fatigue syndrome

Abstract:

PURPOSE: Currently, there is no established therapy for chronic fatigue syndrome (CFS), a recently defined illness that has been associated with a variety of immunologic abnormalities. Based on the hypothesis that a chronic viral infection or an immunoregulatory defect is involved in the pathogenesis of CFS, the therapeutic benefit of intravenous immunoglobulin G (IV IgG) was evaluated in a group of patients with CFS. Additionally, serum immunoglobulin concentrations and peripheral blood lymphocyte subset numbers were measured at the outset of the study, and the effect of IV IgG therapy on IgG subclass levels was determined.

PATIENTS AND METHODS: Thirty patients with CFS were enrolled in a double-blind, placebo-controlled trial of IV IgG. The treatment regimen consisted of IV IgG (1 g/kg) or intravenous placebo (1% albumin solution) administered every 30 days for 6 months. Participants completed a self-assessment form prior to each of the six treatments, which was used to measure severity of symptoms, functional status, and health perceptions. Patients were also asked to report adverse experiences defined as worsening of symptoms occurring within 48 hours of each treatment.

RESULTS: Twenty-eight patients completed the trial. At baseline, all 28 patients complained of moderate to severe fatigue, and measures of social functioning and health perceptions showed marked impairment. Low levels of IgG1 were found in 12 (42.9%), and 18 (64.3%) had low levels of IgG3. At the end of the study, no significant therapeutic benefit could be detected in terms of symptom amelioration or improvement in functional status, despite restoration of IgG1 levels to a normal range. Major adverse experiences were observed in 20% of both the IV IgG and placebo groups.

CONCLUSION: The results of this study indicate that IV IgG is unlikely to be of clinical benefit in CFS. In addition to the ongoing need for placebo-controlled trials of candidate therapies for CFS, an expanded research effort is needed to define the etiology and pathogenesis of this disorder.

Comment in:

Intravenous immunoglobulin treatment for the chronic fatigue syndrome. [Am J Med. 1990]

 

Source: Peterson PK, Shepard J, Macres M, Schenck C, Crosson J, Rechtman D, Lurie N. A controlled trial of intravenous immunoglobulin G in chronic fatigue syndrome. Am J Med. 1990 Nov;89(5):554-60. http://www.ncbi.nlm.nih.gov/pubmed/2239975

 

A double-blind, placebo-controlled trial of intravenous immunoglobulin therapy in patients with chronic fatigue syndrome

Abstract:

PURPOSE: The chronic fatigue syndrome (CFS) is characterized by profound fatigue, neuropsychiatric dysfunction, and frequent abnormalities in cell-mediated immunity. No effective therapy is known.

PATIENTS AND METHODS: Forty-nine patients (40 with abnormal cell-mediated immunity) participated in a randomized, double-blind, placebo-controlled trial to determine the effectiveness of high-dose intravenously administered immunoglobulin G. The patients received three intravenous infusions of a placebo solution or immunoglobulin at a dose of 2 g/kg/month. Assessment of the severity of symptoms and associated disability, both before and after treatment, was completed at detailed interviews by a physician and psychiatrist, who were unaware of the treatment status. In addition, any change in physical symptoms and functional capacity was recorded using visual analogue scales, while changes in psychologic morbidity were assessed using patient-rated indices of depression. Cell-mediated immunity was evaluated by T-cell subset analysis, delayed-type hypersensitivity skin testing, and lymphocyte transformation with phytohemagglutinin.

RESULTS: At the interview conducted by the physician 3 months after the final infusion, 10 of 23 (43%) immunoglobulin recipients and three of the 26 (12%) placebo recipients were assessed as having responded with a substantial reduction in their symptoms and recommencement of work, leisure, and social activities. The patients designated as having responded had improvement in physical, psychologic, and immunologic measures (p less than 0.01 for each).

CONCLUSION: Immunomodulatory treatment with immunoglobulin is effective in a significant number of patients with CFS, a finding that supports the concept that an immunologic disturbance may be important in the pathogenesis of this disorder.

Comment in:

Intravenous immunoglobulin treatment for the chronic fatigue syndrome. [Am J Med. 1990]

Immunoglobulin treatment for chronic fatigue syndrome. [Am J Med. 1991]

Intravenous immunoglobulin treatment of chronic fatigue syndrome. [Am J Med. 1991]

Placebo responses in patients complaining of chronic fatigue. [Am J Med. 1991]

 

Source: Lloyd A, Hickie I, Wakefield D, Boughton C, Dwyer J. A double-blind, placebo-controlled trial of intravenous immunoglobulin therapy in patients with chronic fatigue syndrome.  Am J Med. 1990 Nov;89(5):561-8. http://www.ncbi.nlm.nih.gov/pubmed/2146875

 

A chronic “postinfectious” fatigue syndrome associated with benign lymphoproliferation, B-cell proliferation, and active replication of human herpesvirus-6

Abstract:

A 17-year-old, previously healthy woman developed an acute “mononucleosis-like” illness with an associated “atypical” pneumonitis, followed by years of debilitating chronic fatigue, fevers, a 10-kg weight loss, night sweats, and neurocognitive symptoms. Thereafter, her sister developed a similar but less severe illness.

The patient developed marked, chronic lymphadenopathy and splenomegaly, with associated persistent relative lymphocytosis and atypical lymphocytosis and with thrombocytopenia. After 3 years of illness, a splenectomy was performed, which resulted in some symptomatic improvement, prompt weight gain, and resolution of all hematologic abnormalities. Serial immunologic studies revealed a strikingly elevated number of activated B lymphocytes and a T lymphopenia, which improved but did not return to normal postsplenectomy. No causal association was found with any of several infectious agents that could produce such a lymphoproliferative illness.

However, both the patient and her sister had evidence of active infection with the recently discovered human herpesvirus-6. Seven years after the onset of the illness, the patient and her sister remain chronically ill.

 

Source:  Buchwald D, Freedman AS, Ablashi DV, Sullivan JL, Caligiuri M, Weinberg DS, Hall CG, Ashley RL, Saxinger C, Balachandran N, et al. A chronic “postinfectious” fatigue syndrome associated with benign lymphoproliferation, B-cell proliferation, and active replication of human herpesvirus-6. J Clin Immunol. 1990 Nov;10(6):335-44. http://www.ncbi.nlm.nih.gov/pubmed/1964694

 

Aerobic work capacity in patients with chronic fatigue syndrome

Abstract:

OBJECTIVE: To determine the aerobic work capacity of patients with the chronic fatigue syndrome and compare it with that of two control groups, and to assess the patients’ perception of their level of activity before and during illness.

DESIGN: A symptom limited exercise treadmill test with on line gas analysis and blood sampling was used. Subjects were assessed by one investigator, who was blind to the group which they were in.

SETTING: Department of medicine, Royal Victoria Hospital, Belfast.

SUBJECTS: 13 Patients (10 women, three men) who fulfilled the diagnostic criteria for chronic fatigue syndrome. Two control groups of similar age, sex, and body weight: 13 normal subjects (10 women, three men) and seven patients (five women, two men) with the irritable bowel syndrome.

MAIN OUTCOME MEASURES: Aerobic work capacity as assessed by several variables such as length of time on treadmill, heart rate, and biochemical measurements; Borg score; and visual analogue scores of perceived level of physical activity.

RESULTS: The patients with the chronic fatigue syndrome had a reduced exercise capacity compared with that of the other subjects, spending a significantly shorter time on the treadmill. They had a significantly higher heart rate at submaximal levels of exertion and at stage III exertion had significantly higher blood lactate concentrations. Using a Borg score, they showed a significantly altered perception of their degree of physical exertion with a mean score of 8.2 compared with 6.6 and 5.3 for the normal subjects and patients with the irritable bowel syndrome respectively. Using a visual analogue scale they indicated that they had a greater capacity for activity before illness than had the patients with the irritable bowel syndrome, but the scores were not significantly different between the two groups. Both groups of patients indicated reduced activity at the time of testing. Normal controls and patients with the irritable bowel syndrome aspired to a greater level of activity than their current level, but the patients with the chronic fatigue syndrome aspired to a level similar to that which they had had before their illness.

CONCLUSIONS: Patients with the chronic fatigue syndrome have reduced aerobic work capacity compared with normal subjects and patients with the irritable bowel syndrome. They also have an altered perception of their degree of exertion and their premorbid level of physical activity.

 

Source: Riley MS, O’Brien CJ, McCluskey DR, Bell NP, Nicholls DP. Aerobic work capacity in patients with chronic fatigue syndrome. BMJ. 1990 Oct 27;301(6758):953-6. http://www.ncbi.nlm.nih.gov/pubmed/2249024

Note: You can read the full article here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1664147/

 

Postviral syndrome

Note: This comment appeared in the Journal of the Royal Society of Medicine, Volume 83, October 1990 in reference to The diagnosis of postviral syndrome. [J R Soc Med. 1990]

 

Postviral syndrome Dr D J D Perrins writes (June 1990 JRSM, p 413) of the difficulty in making a definitive diagnosis of postviral syndrome (myalgic encephalomyelitis, ME) echoing the paper by Dr Bowman et aL (December 1988 JRSM, p 712) and goes on to affirm ‘the clinical pattern of ME has much in common with multiple sclerosis (1). No neurologist of experience would agree with this statement. Dr Perrins admits that some of the patients he himself reported upon may in fact have had MS. Seven out of 10 MS patients will tell you the diagnosis if you listen carefully (the late Henry Miller); ‘a blind neurologist is better than a deaf one’ (Mumenthaler, Berne). The clinical course of ME and MS is usually quite different, though occasional ‘difficult’ similarities may be met with.

You can read the rest of this comment here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1292897/pdf/jrsocmed00131-0089b.pdf

 

Source:  E. J. Field. Postviral syndrome. J R Soc Med. 1990 Oct;83(10):675-6. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1292897/

 

Chronic fatigue syndrome and the psychiatrist

Abstract:

The number of patients who are identified as having chronic fatigue syndrome (CFS) has increased, and as a result, chronic fatigue syndrome has received widespread attention. Research has demonstrated that cognitive, affective and behavioural symptoms are prominent in CFS. Psychiatrists are therefore being asked to participate in the assessment and management of patients with this syndrome. This paper will provide an overview of the clinical characteristics of CFS and the current empirical findings related to its pathology, and will conclude with a discussion of the management of these patients.

 

Source:  Abbey SE, Garfinkel PE. Chronic fatigue syndrome and the psychiatrist. Can J Psychiatry. 1990 Oct;35(7):625-33. http://www.ncbi.nlm.nih.gov/pubmed/2268845

 

Asthenic symptoms in a rural family practice. Epidemiologic characteristics and a proposed classification

Abstract:

Asthenic symptoms (eg, fatigue, lassitude, weakness) are of major concern in family practice setting, yet relatively little research has addressed this issue. A retrospective chart review over a 10-year period was conducted to better characterize these symptoms in a rural family practice providing health care to 508 adult patients.

Asthenic complaints were recorded at least once in the medical charts of 164 patients (32%) with a preponderance of female patients. Peak prevalence occurred in the third decade of age and during the summer months. Associated symptoms, mainly pain and dizziness, were reported in 75% of the cases. A cause or diagnosis was not identified by the practicing physician in nearly 50% of the encounters; nevertheless, most episodes resolved spontaneously.

Patients could be subclassified into three categories according to the recurrence pattern of their asthenic symptoms during the study period. The largest category (64%) included patients who had a single or two episodes and was thus termed “episodic asthenia.” Forty-five patients (27%) with recurrent episodes (mean 4.4, range 3 to 10) were classified as having “recurrent episodic asthenia.”

A third small group (14 patients, 9%) with persistent complaints over the years but no evidence of the chronic fatigue syndrome were classified as having “chronic persistent asthenia.” The proposed classification may help future research of asthenic symptoms in the family practice setting.

 

Source: Shahar E, Lederer J. Asthenic symptoms in a rural family practice. Epidemiologic characteristics and a proposed classification. J Fam Pract. 1990 Sep;31(3):257-61; discussion 261-2. http://www.ncbi.nlm.nih.gov/pubmed/2391456

 

Life insurance MDs sceptical when chronic fatigue syndrome diagnosed

There’s no middle ground when it comes to chronic fatigue syndrome (CFS) – it is either a bona fide clinical entity or a trendy media-made disease with no basis in fact.

This division was evident during the recent annual meeting of the Canadian Life Insurance Medical Officers Association (CLIMOA), the doctors who advise health and life insurance companies on the morbidity and mortality risks of every disease state.

CLIMOA’s members meet annually for an update on therapeutic and laboratory diagnostic testing developments. There are currently 187 members from 128 North American companies and this year’s meeting in Toronto was the largest to date, with 112 members attending.

Dr. Richard Proschek shed more heat than light on the CFS issue with a presentation that concluded family physicians are diagnosing CFS in patients who clearly have other medical conditions that would account for their fatigue.

With an alleged epidemic of CFS looming, insurance companies are caught in a dilemma. Should they pay disability benefits to people being diagnosed with the controversial syndrome? They want to know if it’s a real disease and how much it’s going to cost them if large numbers of people become afflicted.

You can read the rest of this article here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1452254/pdf/cmaj00222-0063.pdf

 

Source:  Olga Lechky. Life insurance MDs sceptical when chronic fatigue syndrome diagnosed. CMAJ. 1990 Sep 1; 143(5): 413–415. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1452254/

 

Effect of high doses of essential fatty acids on the postviral fatigue syndrome

Abstract:

Sixty-three adults with the diagnosis of the postviral fatigue syndrome were enrolled in a double-blind, placebo-controlled study of essential fatty acid therapy. The patients had been ill for from one to three years after an apparently viral infection, suffering from severe fatigue, myalgia and a variety of psychiatric symptoms.

The preparation given contained linoleic, gamma-linolenic, eicosapentaenoic and docosahexaenoic acids and either it, or the placebo, was given as 8 x 500 mg capsules per day over a 3-month period. The trial was parallel in design and patients were evaluated at entry, one month and three months. In consultation with the patient the doctors assessed overall condition, fatigue, myalgia, dizziness, poor concentration and depression on a 3-point scale. The essential fatty acid composition of their red cell membrane phospholipids was analysed at the first and last visits.

At 1 month, 74% of patients on active treatment and 23% of those on placebo assessed themselves as improved over the baseline, with the improvement being much greater in the former. At 3 months the corresponding figures were 85% and 17% (p less than 0.0001) since the placebo group had reverted towards the baseline state while those in the active group showed continued improvement.

The essential fatty acid levels were abnormal at the baseline and corrected by active treatment. There were no adverse events. We conclude that essential fatty acids provide a rational, safe and effective treatment for patients with the post-viral fatigue syndrome.

 

Source:  Behan PO, Behan WM, Horrobin D. Effect of high doses of essential fatty acids on the postviral fatigue syndrome. Acta Neurol Scand. 1990 Sep;82(3):209-16. http://www.ncbi.nlm.nih.gov/pubmed/2270749

 

Clinical and laboratory findings in the Paul-Bunnell negative glandular fever-fatigue syndrome

Abstract:

Forty-one patients with recurrent fatigue were studied for evidence of symptom clustering, abnormal laboratory findings and infection with novel viruses. Symptom enquiry and investigations were repeated 4 months later.

Four patients were found to have diseases compatible with their symptoms. In those remaining, an initial acute onset of symptoms was associated with an intermittent course, tender glands and a raised number of T suppressor lymphocytes. Raised numbers of T suppressor lymphocytes at follow-up correlated with resolution of symptoms. Antibodies to human herpesvirus 6 (HHV-6) were found in 75% of the patients as compared to 53% of a control group and more patients than controls were strongly seropositive.

Some patients with chronic fatigue have a pattern of illness which suggests glandular fever, although acute infection with Epstein-Barr virus (EBV) is not demonstrated. Primary or reactivation infection with HHV-6 may have a role in this syndrome.

 

Source:  Read R, Larson E, Harvey J, Edwards A, Thomson B, Briggs M, Fox J. Clinical and laboratory findings in the Paul-Bunnell negative glandular fever-fatigue syndrome. J Infect. 1990 Sep;21(2):157-65. http://www.ncbi.nlm.nih.gov/pubmed/2172387