Note: This letter by Dr. Ray Holland, published in the Canadian Medical Association Journal on August 1, 1988, generated several responses. Dr. Salit’s response appears below.
There appears to be a scarcity of information in medical and psychiatric journals (although not in the lay press) on what was initially termed the Epstein-Barr syndrome but was later renamed chronic fatigue syndrome because it can be caused by infective agents other than the Epstein-Barr virus (EBV). For example, the last article on the subject in CMAJ appeared in 1985.(1) There the syndrome, consisting of fatigue, depression, myalgia, muscle weakness, headaches and paresthesia, was named sporadic postinfectious neuromyasthenia (PIN), a term preferable to chronic fatigue syndrome because it is not ambiguous and because the condition can be of both infectious and psychologic origin.
Presumably the condition was named chronic fatigue syndrome because fatigue is the main presenting symptom, but in psychologic depression fatigue can also be the main manifestation. It is unfortunate, therefore, that the American Medical Association appears to have adopted such an ambiguous term while lamenting that the lack of a definitive diagnosis leaves both patients and health care providers frustrated.(2)
To confuse matters further, the media have labelled the condition chronic fatigue in overachievers or Yuppie flu. In fact, traditional psychiatrists have for some timed called chronic fatigue in overachievers anhedonia (inability to experience pleasure), which, if untreated, may lead to fatigue, depression and the other symptoms mentioned.
While the clinical picture may be ambiguous, the serologic findings may be more so, even when interpreted along with the clinical findings, because those exposed to EBV may have positive serologic results but no chronic sequelae, in much the same way as most people exposed to tuberculosis have subclinical infection. How high does the antibody titre have to be for a definite diagnosis of chronic fatigue syndrome in those who were apparently well before the acute viral attack, even if one excludes those with a previous psychiatric history, as Salit did? One must suspect that a high antibody titre that does not correlate with the clinical findings implies a psychologic origin, as does a low antibody titre. However, it appears that many patients who are told that they have positive but inconclusive serologic results of testing for EBV are choosing to believe that they have the disease. The local medical laboratory has informed me that there is not even a range of titres for EBV but that patients must find their own range by correlating values with how they feel! The media seem to infer that cases with negative results of EBV testing either have not been diagnosed because of lack of the necessary technology or have been misdiagnosed, because there is no mention that the cause may be psychologic.
Such a state of affairs is only too likely in today’s society, in which people are actually healthier than ever before but are more disease conscious and in which the media have a lively interest in medical matters. Rather than an epidemic of the disease, there appears to be an epidemic of the diagnosis, such that EBV should be named “virus of the year”.
May primum non nocere prevail as high-tech medicine continues to advance, at an alarming rate.
~Ray G.L. Holland, MD, FRCPC Box 458 Port Colbome, Ont.
References
- Salit IE: Sporadic postinfectious neuromyasthenia. Can Med Assoc J 1985; 133: 659-663
- Straus SE: EB or not EB – that is the question [E]. JAMA 1987; 257: 2335- 2336
[Dr. Salit responds:]
I too believe that the lack of information in medical journals on PIN [postinfectious neuromyasthenia] is a problem. There appears to be confusion about the condition among physicians, granting agencies and medical journals; they are unable to neatly classify the ailment into a nosologic category. The comment has been that the illness is “too vague” or “ill-defined”. This translates into an inability to have studies related to this subject published. Indeed, last year CMAJ rejected my article on immunologic aberrations in PIN, citing similar reasons.
The term chronic fatigue syndrome (1) was probably chosen by US investigators because it is a generic term. In 1985 these investigators thought that the illness was due to EBV; hence the common designation chronic EBV infection.(2) At that time I felt that the illness was induced by many etiologic agents, so I used the term PIN.(3) Most investigators in this area have come around to this way of thinking but have chosen not to use the term PIN.
Dr. Holland indicates that this disease has been acknowledged by psychiatrists in the past under other designations. Indeed, very similar illnesses have been known to different specialists by different names for decades. I have suggested a unifying hypothesis concerning a common pathophysiologic mechanism.(4)
EBV serologic findings have been the most confusing diagnostic aspect of this illness. Some patients after typical acute infectious mononucleosis have a form of chronic mononucleosis that symptomatically resembles PIN.(5) The serologic findings strongly suggest chronic active EBV infection. However, in most cases of PIN the illness probably did not start with acute infectious mononucleosis, and the patients probably do not have continuing active EBV infection. Using a sensitive DNA probe we found that PIN patients were not excreting EBV.(6) Furthermore, there is such extensive overlap between PIN patients and healthy controls that EBV serologic findings cannot be used to make the diagnosis.(7) It is also likely that such patients have moderately elevated titres of antibodies to a variety of other antigens. Most adults in Canada have EBV antibodies from a prior infection. Too often a diagnosis of chronic EBV infection is made on the basis of certain symptoms and the findings of any EBV antibody. This is inappropriate.
Holland says that “there appears to be an epidemic of the diagnosis”. What has become very apparent to me is that there are a large number of people in the community with illnesses that might be included under the rubric PIN. Physicians argue about the existence of this disease, but it is clear to me that PIN patients have an illness (or a deviation from a normal state of health). Despite the fact that we do not understand the disease process that results in this illness, the patients still require appropriate medical care, consisting of empathy, an acknowledgement that they are ill, reassurance that there is an absence of a more severe disease and, finally, guidelines on how best to manage the condition.(4’8’9)
I do not think that primum non nocere should prevail, although I can accept secundum non nocere. First we should show some understanding and compassion.
~ Irving E. Salit, MD, FRCPC Division of Infectious Diseases Toronto General Hospital Toronto, Ont.
References
- Holmes GP, Kaplan JE, Gantz NM et al: Chronic fatigue syndrome: a working case definition. Ann Intern Med 1988; 108: 387-389
- Jones JF, Ray CG, Minnich LL et al: Evidence for active Epstein-Barr virus infection in patients with persistent, unexplained illnesses: elevated antiearly antigen antibodies. Ann Intern Med 1985; 102: 1-7 3. Salit IE: Sporadic postinfectious neuromyasthenia. Can Med Assoc J 1985; 133: 659-663
- Idem: Chronic EBV infections (postinfectious neuromyasthenia). Med North Am 1987; 10: 1944-1950
- Straus SE: The chronic mononucleosis syndrome. J Infect Dis 1988; 157: 405- 412
- Salit IE, Diaz-Mitoma F, Walmsley S et al: Absence of Epstein-Barr virus excretion in post-infectious neuromyopathies. Presented at the American Society for Microbiology annual meeting, Miami Beach, May 9, 1988
- Buchwald D, Sullivan JL, Komaroff AL: Frequency of “chronic active Epstein-Barr virus infection” in a general medical practice. JAMA 1987; 257: 2303-2307
- Salit IE: Post-infectious fatigue. Can Fam Physician 1987; 133: 1217-1219 9. Taerk GS, Toner B, Salit IE et al: Depression in patients with neuromyasthemia. Int J Psychiatry Med 1987; 17: 49-56
Source: R G Holland. “Virus of the year”? CMAJ. 1988 Aug 1; 139(3): 198–199. PMCID: PMC1268060 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1268060/?page=1 and http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1268061/