alpha-Interferon treatment of patients with chronic fatigue syndrome

Abstract:

Thirty patients who fulfilled clinical criteria defined by the CDC for Chronic Fatigue Syndrome were treated with alfa 2a interferon or placebo in a double-blind crossover study. Outcome was evaluated by Natural Killer (NK) cell function, lymphocyte proliferation to mitogens and soluble antigens, CD4/CD8 counts and a 10 item Quality of Life (QOL) survey.

Although mean NK function rose from 87.8 +/- 19.6 to 129.3 +/- 20.7 lytic untis (LU; p < .05) with 12 weeks of interferon therapy, there was no significant change in the other immunologic parameters or QOL scores. When the 26 patients who completed the study were stratified according to their baseline NK function and lymphocyte proliferation, 4 groups were identified: 3 patients had normal NK cell function and lymphocyte proliferation when compared to normal, healthy controls, 9 had isolated deficiency in lymphocyte proliferation, 7 had diminished NK function only, and 7 had abnormalities for both parameters.

QOL scores were not significantly different for the four groups at baseline. After 12 weeks of interferon therapy, QOL score significantly improved in each of the seven patients with isolated NK cell dysfunction (mean score, 16.3 +/- 7.9) compared to baseline (39.7 +/- 12.1; p < .05). In these patients the mean NK function increased from 35.1 +/- 11.7 to 91.5 +/- 22.7 LU (p < .01). Significant improvement was not recorded for QOL in the other three groups. Thus, therapy with alpha interferon has a significant effect on the QOL of that subgroup of patients with CFS manifesting an isolated decrease in NK function.

 

Source: See DM, Tilles JG. alpha-Interferon treatment of patients with chronic fatigue syndrome. Immunol Invest. 1996 Jan-Mar;25(1-2):153-64. http://www.ncbi.nlm.nih.gov/pubmed/8675231

 

Chronic fatigue complaints in primary care: incidence and diagnostic patterns

Abstract:

The complaint of chronic fatigue is ubiquitous in the primary care setting. Because of the nonspecific nature of chronic fatigue, practitioners do not focus on this complaint. Furthermore, most physicians use a problem-based approach. Such a prematurely narrowed focus could overlook the chronic fatigue complaint. Omissions in the data collection process would prove this oversight.

Therefore, we postulated that a retrospective review of evaluations for chronic fatigue would demonstrate significant categorical deficiencies. These deficiencies would indicate a problem focus different than the chronic fatigue complaint itself.

The authors reviewed the current literature to establish historical, physical, and laboratory findings pertinent to the evaluation of chronic fatigue. Six major categories and the associated data elements were identified for use in analyzing patient records. The patient records from the preceding 6 months were reviewed to find those containing a complaint of chronic fatigue. These records were analyzed to determine if a complete data set had been sought and if an associated diagnosis was made.

A total of 425 consecutive charts from an academic family practice clinic were retrospectively reviewed; 9.9% (42) mentioned chronic fatigue. Physicians were lax in performing the mental status and physical examinations; taking the patient’s psychiatric and sleep history, as well as the history of chief complaint; and ordering laboratory evaluations. The physician diagnoses included: depression (40.4%), nonspecific fatigue (35.7%), general medical disorders (16.6%), chronic fatigue syndrome (2.4%), fibromyalgia (2.4%), and sleep apnea (2.4%).

From these data, the investigators conclude that the workup for chronic fatigue is often incomplete or lacks documentation. This oversight is likely due to a problem focus not directed at the chronic fatigue complaints. Also complicating the evaluation process are the multiple associated disorders, the prevalence of the complaint, and cost/benefit issues facing the primary care physician.

 

Source: Ward MH, DeLisle H, Shores JH, Slocum PC, Foresman BH. Chronic fatigue complaints in primary care: incidence and diagnostic patterns. J Am Osteopath Assoc. 1996 Jan;96(1):34-46, 41. http://www.ncbi.nlm.nih.gov/pubmed/8626230

 

An examination of the working case definition of chronic fatigue syndrome

Abstract:

PURPOSE: Chronic fatigue syndrome (CFS) currently is defined by a working case definition developed under the leadership of the United States Centers for Disease Control and Prevention (CDC) based on a consensus among experienced clinicians. We analyzed the experience from one large center to examine the adequacy of the case definition.

PATIENTS AND METHODS: Predefined clinical and laboratory data were collected prospectively from 369 patients with debilitating fatigue, of whom 281 (76%) met the major criteria of the original CDC case definition for CFS: (1) fatigue of at least 6 months’ duration, seriously interfering with the patient’s life; and (2) without evidence of various organic or psychiatric illnesses that can produce chronic fatigue. The same clinical data were obtained from 311 healthy control subjects and two comparison groups with diseases that can present in a similar fashion; relapsing-remitting multiple sclerosis (n = 25) and major depression (n = 19).

RESULTS: All of the minor criteria symptoms from the original CDC case definition distinguished patients with debilitating chronic fatigue from healthy control subjects, and many distinguished the patients with chronic fatigue from the comparison groups with multiple sclerosis and depression: myalgias, postexertional malaise, headaches, and a group of infectious-type symptoms (ie, chronic fever and chills, sore throat, swollen glands in the neck or underarm areas). In addition, two other symptoms not currently part of the case definition discriminated the chronic fatigue patients from the control/comparison groups: anorexia and nausea. Physical examination criteria only infrequently contributed to the diagnosis. Patients meeting the CDC major criteria for CFS also met the minor criteria in 91% of cases.

CONCLUSION: Patients meeting the major criteria of the current CDC working case definition of CFS reported symptoms that were clearly distinguishable from the experience of healthy control subjects and from disease comparison groups with multiple sclerosis and depression. Eliminating three symptoms (ie, muscle weakness, arthralgias, and sleep disturbance) and adding two others (ie, anorexia and nausea) would appear to strengthen the CDC case definition of CFS.

 

Source: Komaroff AL, Fagioli LR, Geiger AM, Doolittle TH, Lee J, Kornish RJ, Gleit MA, Guerriero RT. An examination of the working case definition of chronic fatigue syndrome. Am J Med. 1996 Jan;100(1):56-64. http://www.ncbi.nlm.nih.gov/pubmed/8579088

 

Double-blind placebo-controlled study of the efficacy of oral terfenadine in the treatment of chronic fatigue syndrome

Abstract:

BACKGROUND: There is no established treatment for chronic fatigue syndrome (CFS), an illness characterized by disabling fatigue exacerbated by physical activity. A variety of immunologic abnormalities have been reported, including a high incidence of atopy and hypoergy or anergy.

OBJECTIVE: Because of anecdotal reports and uncontrolled trials showing antihistamine efficacy in CFS, we evaluated the clinical efficacy of the antihistamine terfenadine (60 mg twice daily) in a placebo-controlled study.

METHODS: Thirty patients with CFS were enrolled in a 2-month, double-blind, placebo-controlled trial of terfenadine. Participants underwent a battery of both immediate- and delayed-type hypersensitivity skin tests and completed a self-assessment questionnaire used to measure severity of symptoms, physical and social functioning, health perceptions, and mental health before each of six biweekly visits.

RESULTS: Twenty-eight patients completed the trial. History of atopy and positive immediate skin test results were prevalent, 73% and 53%, respectively. No evidence for hypoergy or anergy after delayed-type hypersensitivity skin testing was found. No therapeutic benefit from terfenadine could be detected in terms of symptom amelioration, improved physical or social functioning, health perceptions, or mental health. A high incidence of atopy in patients with CFS was confirmed.

CONCLUSION: Although this trial involved a small number of patients, the results suggest that terfenadine is unlikely to be of clinical benefit in treating CFS symptoms.

 

Source: Steinberg P, McNutt BE, Marshall P, Schenck C, Lurie N, Pheley A, Peterson PK. Double-blind placebo-controlled study of the efficacy of oral terfenadine in the treatment of chronic fatigue syndrome. J Allergy Clin Immunol. 1996 Jan;97(1 Pt 1):119-26. http://www.ncbi.nlm.nih.gov/pubmed/8568124

 

Corticotropin releasing hormone in the pathophysiology of melancholic and atypical depression and in the mechanism of action of antidepressant drugs

Abstract:

Hypercortisolism in depression seems to preferentially reflect activation of hypothalamic CRH secretion. Although it has been postulated that this hypercortisolism is an epiphenomenon of the pain and stress of major depression, our data showing preferential participation of AVP in the hypercortisolism of chronic inflammatory disease suggest specificity for the pathophysiology of hypercortisolism in depression.

Our findings that imipramine causes a down-regulation of the HPA axis in experimental animals and healthy controls support an intrinsic role for CRH in the pathophysiology of melancholia and in the mechanism of action of psychotropic agents. Our data suggest that hypercortisolism is not the only form of HPA dysregulation in major depression.

In a series of studies, commencing in patients with Cushing’s disease, and extending to hyperimmune fatigue states such as chronic fatigue syndrome and examples of atypical depression such as seasonal affective disorder, we have advanced data suggesting hypofunction of hypothalamic CRH neurons. These data raise the question that the hyperphagia, hypersomnia, and fatigue associated with syndromes of atypical depression could reflect a central deficiency of a potent arousal-producing anorexogenic neuropeptide.

In the light of data presented elsewhere in this symposium regarding the role of a hypofunctioning hypothalamic CRH neuron in susceptibility to inflammatory disease, these data also raise the question of a common pathophysiological mechanism in syndromes associated both with inflammatory manifestations and atypical depressive symptoms. This concept of hypofunctioning of hypothalamic CRH neurons in these disorders also raises the question of novel forms of neuropharmacological intervention in both inflammatory diseases and atypical depressive syndromes.

 

Source: Gold PW, Licinio J, Wong ML, Chrousos GP. Corticotropin releasing hormone in the pathophysiology of melancholic and atypical depression and in the mechanism of action of antidepressant drugs. Ann N Y Acad Sci. 1995 Dec 29;771:716-29. http://www.ncbi.nlm.nih.gov/pubmed/8597444

 

Seroepidemiology of chronic fatigue syndrome: a case-control study

Abstract:

We performed serological testing for a large number of infectious agents in 26 patients from Atlanta who had chronic fatigue syndrome (CFS) and in 50 controls matched by age, race, and sex. We did not find any agent associated with CFS. In addition, we did not find elevated levels of antibody to any of a wide range of agents examined. In particular, we did not find elevated titers of antibody to any herpesvirus, nor did we find evidence of enteroviral exposure in this group of patients.

 

Source: Mawle AC, Nisenbaum R, Dobbins JG, Gary HE Jr, Stewart JA, Reyes M, Steele L, Schmid DS, Reeves WC. Seroepidemiology of chronic fatigue syndrome: a case-control study. Clin Infect Dis. 1995 Dec;21(6):1386-9. http://www.ncbi.nlm.nih.gov/pubmed/8749620

 

Auditory brain stem evoked potentials in the evaluation of chronic fatigue syndrome

Abstract:

The Chronic Fatigue Syndrome (CFS) was formally defined to describe disabling fatigue of multifactorial ethology with depression and immunologic dysfunctions linked to some currently recognized infectious agents. In most cases neurophysiological tests reveal abnormalities.

In this paper the Authors use low (11 pps) and high (51-71 pps) frequency ABR to evaluate the electrophysiological function of auditory brainstem responses. Eighteen patients with suspected CFS, between the ages of 17 and 63, were examined. Eleven subjects had clinically diagnosed “true” CFS (CDC criteria modified by Fukuda). The 11 pps frequency test did not reveal a high number of abnormalities in the patients in question.

However, the high frequency stimulation test (with 51 and 71 pps) which was statistically significant (P = 0.009) revealed numerous aberrations in 7 patients; absence of the first wave in 1 case, in 5 numerous wave gap delays and in 1 patient absence of the first wave and numerous wave gap delays. The high frequency test did not show many abnormalities for the 4 remaining patients. For the 7 “non CFS” subjects, the clinical-audiological comparison showed no statistical significance (P = 0.920).

The Authors hypothesize that the absence of the first wave in the CFS Subject may well indicate a cyto-neural junction disease in the organ of Corti. The combined analysis of clinical and audiological data showed that the described tests are more reliable when employed in dealing with patients with clinically assessed “true” CFS.

 

Source: Bianchedi M, Croce A, Moretti A, Neri G, Barberio A, Iezzi A, Pizzigallo E. Auditory brain stem evoked potentials in the evaluation of chronic fatigue syndrome. Acta Otorhinolaryngol Ital. 1995 Dec;15(6):403-10. [Article in Italian] http://www.ncbi.nlm.nih.gov/pubmed/8711992

 

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

 

Life-events and the course of chronic fatigue syndrome

Abstract:

Life-events have been implicated in the onset and course of various illnesses. The present study examined their role in chronic fatigue syndrome, in the context of the ongoing illness. Using the PERI list, events experienced during the past year were elicited in interviews with 130 patients. The analyses were restricted to those events implying moderate or major life change, and separate analyses were carried out for positive and negative events.

Positive events were found to be associated with lower scores for fatigue, impairment, anxiety and depression, as assessed at the time of the life-events interview, and these relationships were also significant when prior scores at the beginning of the year were statistically controlled. Negative life-events were associated with higher anxiety, but were unrelated to the other measures.

It was concluded that positive life-events and experiences may contribute to the process of recovery in chronic fatigue syndrome, though their occurrence may also be facilitated by a preceding lifting of symptoms.

 

Source: Ray C, Jefferies S, Weir WR. Life-events and the course of chronic fatigue syndrome. Br J Med Psychol. 1995 Dec;68 ( Pt 4):323-31. http://www.ncbi.nlm.nih.gov/pubmed/8688371

 

Exercise responses in the chronic fatigue syndrome. Objective assessment of study is difficult without knowledge of data

Comment on: Exercise responses and psychiatric disorder in chronic fatigue syndrome. [BMJ. 1995]

 

EDITOR,-In their study of exercise responses and psychiatric disorder in the chronic fatigue syndrome Russell J M Lane and colleagues claim to have detected abnormal lactate responses to subanaerobic threshold exercise in 31 of 96 patients. As no data are offered to support this statement, however, objective assessment of the validity of their findings is difficult.

The authors’ definition of an abnormal response is “lactate concentrations exceeding the upper 99% reference limit for normal control subjects at two or more time points.” However, only three samples were taken (before, immediately after, and 30 minutes after exercise), and a raised lactate concentration in the sample obtained before exercise began cannot be described as an abnormal response to exercise. Neither the method used to measure lactate nor its precision is given; assessment of the importance of the “abnormal” lactate concentrations could not be guessed at without this information, even if the authors had given details of the patients’ concentrations.

You can read the full comment along with the authors’ reply here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2551191/pdf/bmj00618-0070a.pdf

 

Source: Hutchison AS. Exercise responses in the chronic fatigue syndrome. Objective assessment of study is difficult without knowledge of data. BMJ. 1995 Nov 11;311(7015):1304. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2551191/pdf/bmj00618-0070a.pdf