The plethora of names and the frequency of descriptions in the medical and lay press are evidence of the confusion about Chronic Fatigue Syndrome and Post Viral Fatigue Syndrome (PVFS), but there can be no doubt that one or more syndromes of chronic fatigue certainly do exist, and the personal testimonies of some of the sufferers highlight how painful and disabling it can be. There can be few conditions with such a varied and extensive nomenclature, but through the confusion can be discerned two distinct groupings: the epidemic cases (including epidemic neuromyaesthenia, Adelaide epidemic, Royal Free disease, Iceland disease, Los Angeles flu, Lake Tahoe disease) and the sporadic cases (including myalgic encephalomyelitis (ME), fibrositis myalgia, 'Yuppie' flu, idiopathic chronic fatigue syndrome, Epstein Barr disease/chronic infectious mononucleosis). In addition to their historical and epidemiological distinctions, there are a number of significant differences in the clinical features that they present.
Most of the cases of the PVFS which present to general practitioners, specialist with an interest in the field and self-help organizations such as the ME Association, are of the sporadic type. Indeed, virtually all of the information presented in this issue derives from the study of patients with this form of fatigue syndrome. In contrast to the epidemics, sporadic cases occur apparently at random within the community and have no obvious relation to each other. The name 'postviral fatigue syndrome' indicates a temporal association between a viral infection and the onset of the fatigue syndrome, and most sufferers will testify to this. It also suggests a possible causal association, but as we shall see, viral infections are so common that chance association is almost inevitable, and the jury is still out on their role in the etiology of this condition.
On the face of it, there is a substantial body of knowledge on the epidemiology of the postviral fatigue syndrome. Estimates of its yearly incidence range from 140 cases in 6 months from a general practice population for 10,000 (annual rate 2,800/100,000) to a hospital estimate of an incidence of 3-5 per 100,000. The total number of such cases in the UK is not known, but reports of the condition to specialist centers and private health insurance companies are increasing rapidly and the ME Association estimates the overall prevalence in the UK at around 150,000 cases. Most studies have shown a strikingly consistent predominance of females compared with males of around 2:1 and the large majority of cases are said to occur between the ages of 18 and 60 (the mean age in most series is around 35 years). There is a common perception that the disorder predominantly affects individuals from the middle socio-economic classes and of professional occupation, hence the name Yuppie flu' coined, somewhat uncharitably, by the press. In the great majority of cases, there are no abnormalities on clinical examination and routine laboratory testing. Patients almost always report having been quite well before the onset of the condition, and usually relate the start of the illness to a non-specific 'viral' infection, hence the term 'postviral fatigue syndrome.' A number or organisms, including Candida and molds have been implicated in the causation of the condition; in the UK, interest has mostly centered on the enteroviruses and in particular the Coxsackie viruses, while in the USA the focus of attention has been primarily the Epstein-Barr virus (EBV). Those studies which have examined psychiatric status reveal that between 50-80% fulfill operational criteria for psychiatric disorder. The natural history appears to be of a persistent condition with a generally poor prognosis: 'Most of the cases do not improve, give up their work and become permanent invalids.'
On the face of it, the epidemiology of the postviral fatigue syndrome would thus appear to be relatively straightforward. But a critical appraisal of the design of the studies from which this information is derived, usually on groups of patients thought to be suffering from the syndrome and typically recruited by self-help organizations or referred to centers with a known interest in the condition readily reveals a number of fundamental flaws which suggest the need to question almost all of the above findings.
By general agreement, postviral fatigue syndrome is a diagnosis of exclusion. Indeed, one of the universally accepted criteria is the absence of normal results on routine laboratory testing. Although the hunt is on to identify a biological marker (and some claims have been made to have found one), most doctors and sufferers alike would agree that at present no such marker exists. In its absence, a precise case definition together with the use of reliable, valid and reproducible measures is essential in order to ensure that different studies include comparable patients. Until recently no attempt was made to reach agreement on any of these, with the result that it is impossible to be sure that different investigators have described the same syndrome. The Center for Disease Control (CDC) in Atlanta has proposed an operational definition defined largely to discourage the assumption that patients are suffering with 'chronic EB virus syndrome.' Although this represents an important advance, a number of problems with the definition have been identified, including the exclusion of patients with minor psychiatric morbidity. A further definition was advanced by Lloyd, and more recently a report was published of a consensus meeting held in Green College, Oxford in March 1990. Modeled on an earlier MRC workshop on Alzheimer's Disease, the meeting included representation from a wide variety of disciplines including biochemistry, general medicine, general practice, microbiology, neurology, physiology, psychiatry and psychology. The agreed guidelines can be summarized as follows:
Chronic fatigue syndrome (CFS)
Post-infectious fatigue syndrome (PIFS)
Chronic Epstein-Barr virus (EBV)
Antibody tests for EBV are of no value in diagnosing the syndrome.
Two especially noteworthy treatments for Chronic Fatigue Syndrome and Post-Viral Fatigue Syndrome have been reported in the literature and are recommended by our office:
The EFAs were given in research setting as capsules of "Primrosa" (or "Efamol Marine"): this is a mixture of Epogam and concentrated fish oil. Epogam itself consists of oil from seeds of evening primrose, Oenothera spp, the strains having been selected to yield oil of constant quality and composition. The patients took eight capsules a day in four divided doses. The effect of high doses of essential fatty acids on symptoms postviral fatigue syndrome was marked. At one month 74% of patients on active treatment and 23% on placebo assessed themselves as improved over baseline. No adverse events were reported. (Behan P, Behan W and Horrobin D. Effect of high doses of essential fatty acids on the postviral fatigue syndrome Acta Neurol Scand 1990;82:209-216.)
Research subjects were given 10 mg of nicotinamide adenine dinucleotide (NADH) in its stabilized, oral absorbable form (NADA). Nicotinamide adenine dinucleotide is known to trigger energy production through ATP generation which may for the basis for its potential effects. No adverse effects were reported. 31% of patients responded favorably to NADH compared to 8% for the placebo group. (Forsyth, et al. Therapeutic effects to oral NADH on the symptoms of patients with chronic fatigue syndrome. Ann Allergy Asthma Immunol. 1999;82: 185-191.)