Acyclovir treatment of the chronic fatigue syndrome. Lack of efficacy in a placebo-controlled trial

Abstract:

Twenty-seven adults with a diagnosis of the chronic fatigue syndrome were enrolled in a double-blind, placebo-controlled study of acyclovir therapy. The patients had had debilitating fatigue for an average of 6.8 years, accompanied by persisting antibodies to Epstein-Barr virus early antigens (titers greater than or equal to 1:40) or undetectable levels of antibodies to Epstein-Barr virus nuclear antigens (titers less than 1:2) or both.

Each course of treatment consisted of intravenous placebo or acyclovir (500 mg per square meter of body-surface area) administered every eight hours for seven days. The same drug was then given orally for 30 days (acyclovir, 800 mg four times daily). There were six-week observation periods before, between, and after the treatments. Three patients had acyclovir-induced nephrotoxicity and were withdrawn from the study.

Of the 24 patients who completed the trial, similar numbers improved with acyclovir therapy and with placebo (11 and 10, respectively). Neither acyclovir treatment nor clinical improvement correlated with alterations in laboratory findings, including titers of antibody to Epstein-Barr virus or levels of circulating immune complexes or of leukocyte 2′,5′-oligoadenylate synthetase. Subjective improvement correlated with various measures of mood.

We conclude that acyclovir, as used in this study, does not ameliorate the chronic fatigue syndrome. We believe that the clinical improvement observed in most patients reflected either spontaneous remission of the syndrome or a placebo effect.

 

Source: Straus SE, Dale JK, Tobi M, Lawley T, Preble O, Blaese RM, Hallahan C, Henle W. Acyclovir treatment of the chronic fatigue syndrome. Lack of efficacy in a placebo-controlled trial. N Engl J Med. 1988 Dec 29;319(26):1692-8. http://www.ncbi.nlm.nih.gov/pubmed/2849717

 

Epstein-Barr virus and the chronic fatigue syndrome: a short review

Abstract:

Chronic Fatigue Syndrome (CFS), previously known as neuroasthenia is often considered to be due to psychiatric causes. Evidence for a possible role for the Epstein-Barr virus in CFS is summarized. A plea is made for physicians to accept CFS as a non-psychiatric chronic illness to encourage further research into a clear definition of the syndrome.

 

Source: Jones JF. Epstein-Barr virus and the chronic fatigue syndrome: a short review. Microbiol Sci. 1988 Dec;5(12):366-9.  http://www.ncbi.nlm.nih.gov/pubmed/2856301

 

The chronic fatigue syndrome (myalgic encephalomyelitis)–myth or mystery?

Abstract:

The chronic fatigue syndrome (CFS) or myalgic encephalomyelitis has caused great confusion, misunderstanding and perhaps even mismanagement of many persons presenting with a variety of combinations of ill-defined complaints. The history, possible pathogenesis and clinical features, of what is probably in most instances a post-viral infection syndrome, are reviewed. The recent Centers for Disease Control case definition is summarised and simplified. The need for such uniformity of definition, acceptable to most workers in the field, is emphasised in order to facilitate further studies into the cause, diagnosis, course and treatment of CFS. The difficulty in treating this condition and the currently recommended management are described. Double-blind controlled studies are essential in assessing any proposed new treatment.

 

Source: Spracklen FH. The chronic fatigue syndrome (myalgic encephalomyelitis)–myth or mystery? S Afr Med J. 1988 Nov 5;74(9):448-52. http://www.ncbi.nlm.nih.gov/pubmed/3055363

 

Sleep and symptoms in fibrositis syndrome after a febrile illness

Abstract:

Sleep physiology and symptoms of 9 patients with fibrositis syndrome secondary to a febrile illness were compared to 9 patients with fibrositis syndrome who did not attribute their symptoms to a febrile illness and to 10 healthy controls.

Both patient groups showed an alpha EEG (7.5 to 11 Hz) nonrapid eye movement sleep anomaly, had similar observed tender points, and self-ratings of musculoskeletal pain.

These findings suggest that patients with postfebrile fibrositis have a nonrestorative sleep disorder characteristic of patients with fibrositis syndrome and share similar symptoms with patients who have a “chronic fatigue syndrome.”

 

Source: Moldofsky H, Saskin P, Lue FA. Sleep and symptoms in fibrositis syndrome after a febrile illness. J Rheumatol. 1988 Nov;15(11):1701-4. http://www.ncbi.nlm.nih.gov/pubmed/3236304

 

The frequency of the chronic fatigue syndrome in patients with symptoms of persistent fatigue

Abstract:

STUDY OBJECTIVE: To determine the frequency of the chronic fatigue syndrome among patients with symptoms of fatigue.

DESIGN: Prospective, cohort study.

SETTING: Referral clinic, based in a primary care general internal medicine faculty practice of a university medical center.

PATIENTS: Consecutive sample of 135 patients (53 men, 82 women) with 6 months or more of debilitating fatigue.

INTERVENTIONS: All patients had a complete history taken, had a physical examination and a comprehensive battery of blood tests, and were given the Diagnostic Interview Schedule of the National Institute of Mental Health, a highly-structured 260-item instrument designed to enable accurate psychiatric diagnoses. Other diagnostic studies (for example, sleep studies and electroencephalography) were ordered if necessary for individual patients.

MEASUREMENTS AND MAIN RESULTS: Six of the one hundred thirty-five patients met criteria for chronic fatigue syndrome (95% CI, 0 to 10). Ninety-one (67%) patients (CI, 56 to 78) had clinically active psychiatric disorders and 4 (3%) patients (CI, 0 to 8) had medical disorders that were considered a major cause of their fatigue. Thirty-four (25%) patients (CI, 14 to 36) had insufficient symptoms or objective findings of the chronic fatigue syndrome.

CONCLUSION: The chronic fatigue syndrome is rare among patients with symptoms of persistent fatigue. Most of these patients have psychiatric disorders.

 

Source: Manu P, Lane TJ, Matthews DA. The frequency of the chronic fatigue syndrome in patients with symptoms of persistent fatigue. Ann Intern Med. 1988 Oct 1;109(7):554-6. http://www.ncbi.nlm.nih.gov/pubmed/3421564

 

Chronic fatigue syndrome–a diagnosis for consideration

Abstract:

Chronic fatigue syndrome (CFS) is an illness which may be mild or completely disabling. Clients who return with recurring non-related symptoms and no specific diagnosis may suffer from CFS. The symptoms of CFS are numerous and varied, including fatigue, malaise, myalgias, difficulty concentrating, headaches and sore throat. Patient complaints seem out of proportion to the physical findings, which may be normal. There is no cure for this chronic disease. Therapy is primarily symptomatic. The role of the health care provider is to recognize this confusing disorder and help the patient and family cope with its many effects.

 

Source: Portwood MF. Chronic fatigue syndrome–a diagnosis for consideration. Nurse Pract. 1988 Feb;13(2):11-2, 15-8, 23. http://www.ncbi.nlm.nih.gov/pubmed/2830563

 

Chronic fatigue syndrome: a working case definition

Abstract:

The chronic Epstein-Barr virus syndrome is a poorly defined symptom complex characterized primarily by chronic or recurrent debilitating fatigue and various combinations of other symptoms, including sore throat, lymph node pain and tenderness, headache, myalgia, and arthralgias.

Although the syndrome has received recent attention, and has been diagnosed in many patients, the chronic Epstein-Barr virus syndrome has not been defined consistently. Despite the name of the syndrome, both the diagnostic value of Epstein-Barr virus serologic tests and the proposed causal relationship between Epstein-Barr virus infection and patients who have been diagnosed with the chronic Epstein-Barr virus syndrome remain doubtful.

We propose a new name for the chronic Epstein-Barr virus syndrome–the chronic fatigue syndrome–that more accurately describes this symptom complex as a syndrome of unknown cause characterized primarily by chronic fatigue. We also present a working definition for the chronic fatigue syndrome designed to improve the comparability and reproducibility of clinical research and epidemiologic studies, and to provide a rational basis for evaluating patients who have chronic fatigue of undetermined cause.

 

Source: Holmes GP, Kaplan JE, Gantz NM, Komaroff AL, Schonberger LB, Straus SE, Jones JF, Dubois RE, Cunningham-Rundles C, Pahwa S, et al. Chronic fatigue syndrome: a working case definition. Ann Intern Med. 1988 Mar;108(3):387-9. http://www.ncbi.nlm.nih.gov/pubmed/2829679

 

“Chronic Epstein-Barr virus infection” syndrome and polymyalgia rheumatica

Abstract:

Twenty-three patients with polymyalgia rheumatica (PMR) followed in an academic rheumatology practice frequently reported symptoms commonly found in the recently described “chronic fatigue syndrome” or “chronic Epstein-Barr infection syndrome.” These symptoms persisted for months after treatment had reduced the severity of the myalgias and lowered the sedimentation rate: periodically disabling fatigue (33%), recurrent pharyngitis (30%), sleep disorder (65%) and arthralgias (70%). However, antibody titers to Epstein-Barr virus in the patients with PMR were not significantly different from those in age and sex matched control subjects.

 

Source: Buchwald D, Sullivan JL, Leddy S, Komaroff AL. “Chronic Epstein-Barr virus infection” syndrome and polymyalgia rheumatica. J Rheumatol. 1988 Mar;15(3):479-82. http://www.ncbi.nlm.nih.gov/pubmed/2837573

 

Allergy and the chronic fatigue syndrome

Abstract:

The chronic fatigue syndrome is a heterogeneous disorder characterized by easy fatigability, feverishness, diffuse pains, and depression. Many patients also report inhalant, food, or drug allergies.

This article reviews the clinical features of the syndrome and hypotheses of its pathogenesis, especially those regarding the Epstein-Barr virus and cellular immune mechanisms. Also summarized are recent studies of the validity of atopic complaints in the syndrome.

The results of epicutaneous skin testing demonstrated a high correlation with history in 24 patients. Atopy coexists with the chronic fatigue syndrome in greater than 50% of patients.

 

Source: Straus SE, Dale JK, Wright R, Metcalfe DD. Allergy and the chronic fatigue syndrome. J Allergy Clin Immunol. 1988 May;81(5 Pt 1):791-5. http://www.ncbi.nlm.nih.gov/pubmed/2836490

 

Chronic fatigue syndromes: relationship to chronic viral infections

Abstract :

Chronic fatigue syndrome (CFS) is a newly-recognized clinical entity characterized by chronic, debilitating fatigue lasting longer than six months. Common associated findings are chronic and recurrent fever, pharyngitis, myalgias, adenopathy, arthralgias, difficulties in cognition and disorders of mood. In the majority of patients, the illness starts suddenly with an acute, ‘flu-like’ illness.

The following abnormalities are seen with some frequency although none are seen in all patients: lymphocytosis, atypical lymphocytosis, monocytosis, elevation of hepatocellular enzymes, low levels of antinuclear antibodies, low levels of immune complexes.

Clinical and serologic studies suggest an association of CFS with all of the human herpesviruses, particularly Epstein-Barr virus (EBV) and the recently-discovered human B-lymphotropic virus (HBLV) or human herpesvirus-6; neither EBV nor HBLV has yet been shown to play a causal role in the illness.

 

Source: Komaroff AL. Chronic fatigue syndromes: relationship to chronic viral infections. J Virol Methods. 1988 Sep;21(1-4):3-10. http://www.ncbi.nlm.nih.gov/pubmed/2846619