The following letter was published along with an answer from the authors.

CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 69
NUMBER 1 JANUARY 2002
Human herpesvirus 6
(JULY 2001)

TO THE EDITOR: The article by Drs. Chemaly and
Rehm on human herpesvirus 6 (HHV-6)
infection 1 was very interesting but left out
one particular associated symptom of this
insidious virus. This symptom is chronic
fatigue, which is markedly debilitating.

When HHV-6 was first defined by
Salahuddin et al in 1986, 2 the virus was
ubiquitous and the symptoms of the disease it
causes were nebulous. Although little knowl-edge
about HHV-6 has been added over the
years, it seems that more than 90% of the
population is exposed, most exposure does
not lead to prolonged disease, and its common
manifestations are low-grade infection,
usually mild, accompanied by lymphadenopathy,
debilitating fatigue, and retro-orbital
headache. In some patients the malaise can
be prolonged and can be the initial manifestation
of chronic fatigue syndrome, the exact
cause of which is still unknown.

It is possible that the HHV-6 virus, like
its fellow herpesviruses, lurks in tissues or
that in sensitized patients it produces elevated
cytokines or other immune system effects
that can manifest in prolonged symptoms.

DEREK ENLANDER, MD, MRCS, LRCP
New York

REFERENCES
1. Chemaly RF, Rehm SJ. A young woman with fever,
headache, and lymphadenopathy. Cleve Clin J
Med 2001; 68:584593.
2. Salahuddin SZ, Ablashi DV, Markham PD, et al. Isolation
of a new virus, HBLV, in patients with lymphopro-liferative
disorders. Science 1986; 234:596601.

IN REPLY: We appreciate Dr. Enlander's query
regarding possible links between human herpesvirus
6 (HHV-6) and chronic fatigue syndrome,
a well-characterized illness of
unknown etiology.

Because patients with chronic fatigue
syndrome may have an abnormal immunologic
status suggestive of immunosuppression,
several ubiquitous viruses, especially
the herpesviruses (ie, Epstein-Barr virus and
HHV-6), were implicated in its pathogenesis.
However, multiple studies in patients
with chronic fatigue syndrome, using a variety
of markers of HHV-6 infection, produced
results that were at best contradictory, with
few suggesting an association between these
diseases.14 A recent case-control study 5
compared rates of infection with HHV-6A,
HHV-6B, or HHV-7 among patients with
chronic fatigue syndrome and control subjects.
The authors found no evidence that
infection with these herpesviruses is associated
with chronic fatigue syndrome.

Furthermore, an association between
HHV-6 and multiple sclerosis generated a
considerable interest for the past few years
but no causal link has been established.

Because of lack of compelling evidence
linking HHV-6 infection with chronic
fatigue syndrome or multiple sclerosis, we
elected not to discuss this issue in our review
of HHV-6 and infectious mononucleosis-like
syndrome.

ROY F. CHEMALY, MD
The Cleveland Clinic
Foundation

SUSAN J. REHM, MD
The Cleveland Clinic
Foundation

REFERENCES
1. Josephs SF, Henry B, Balachandran N, et al. HHV-6 reactivation
in chronic fatigue syndrome. Lancet 1991;
337:13461347.
2. Buchwald D, Ashley RL, Pearlman T, et al. Viral serologies
in patients with chronic fatigue and chronic
fatigue syndrome. J Med Virol 1996; 50:2530.
3. DiLuca D, Zorzenon M, Mirandola P, et al. Human herpesvirus
6 and human herpesvirus 7 in chronic
fatigue syndrome. J Clin Microbiol 1995;
33:16601661.
4. Patnaik M, Komaroff AL, Conley E, et al. Prevalence of
IgM antibodies to human herpesvirus 6 early antigen
(p41/38) in patients with chronic fatigue syndrome.
J Infect Dis 1995; 172:13641367.
5. Reeves WC, Stamey FR, Black JB, Mawle AC, Stewart JA,
Pellett PE. Human herpesviruses 6 and 7 in chronic
fatigue syndrome: a case-control study. Clin Infect
Dis 2000; 31:4852.

Letter to British Medical Journal Jan 2002

Sir, I am dismayed at the editorial of Steven Strauss and his current knowledge of ME/ CFS. He promotes the thought again that this disease is a shallow mainifestation of a patient's mind, and the only treatment therefore is cognitive therapy, pacing and graded exercise. In fact grading of exercise is very difficult, more often overexercise produces relapse. He further shows his lack of knowledge by purveying the notion that the disease is a 1980's invention. Ramsay's seminal work in the Royal Free Hospital seemingly is unknown to him or is to be sloughed aside.

His position as chief of the Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Disease certainly was not obvious in his thinking related to research approaches in this disease.

The NIH credo in ME/ CFS is not new but continues to be immersed in old doctrine rather than new ideas.

Derek Enlander

1 Stephen E Straus BMJ 2002; 324: 124-125

2 Ramsay M The saga of the Royal Free Disease 1955 ME Assoc.