Download Remember Rocky Mountain Spotted Fever

165
Editorial: Remember Rocky Mountain Spotted Fever-A Lesson in Ethical
Principles
In the preceding article, DiNubile reports an atypical case
record that conveys several lessons with regard to good medicine and high ethics [1]. To his great credit, he did not forget
the experience and bury it in the mothballs of oblivion. Instead,
his courage and conviction, combined with what I regard as
commitment to the highest ethical principles, guided him to
make a full report.
See article by DiNubile on pages 160-4.
The first lesson is one of honesty and forthrightness (not
self-satisfaction), which prompted the author to openly report
what he regarded as a mistake. Perhaps it was a mistake, but
it was the kind that does not result from a lack of knowledge
or interest and invites no indictment or incrimination. We have
all made errors, and the person who fails to acknowledge them
is simply blind to himself.
The candor and humility of the reporting physician are admirable. He delivers a potent message to our profession as well
as to the legal profession. The fundamental principles of the
medical profession, which he exemplifies, are of the highest
order.
In this particularly difficult clinical dilemma, the responsible
physician carefully considered plausible diagnostic possibilities
and, when unsure, consulted with others. His mind was open
to various acceptable possibilities during the course of the
patient's illness, and he took appropriate diagnostic and therapeutic steps. The fatal outcome could have been attributed to
AIDS and serious superimposed infections. Yet, the physician
followed through, obtained a postmortem examination, and
took the necessary steps that led to a final diagnosis.
It is true that the patient had a treatable infectious disease.
Yet, we do not know that he would have recovered because,
as is well known, serious infectious diseases in immunocompromised persons, such as those with AIDS, respond differently to specific treatment. Examples include the horrible
outcomes for patients with AIDS and tuberculosis, fungal infections, or other superimposed infections.
A second lesson is simply that so-called classic clinical signs
and symptoms of a specific infectious disease are not always
present. It is obvious that the sudden onset of fever, severe
headache, myalgia, and a pink macular rash on the extremities
Received 9 April 1996.
Reprints or correspondence: Dr. Theodore E. Woodward, University of
Maryland Hospital, 22 South Green Street, Room N3W40, Baltimore, Maryland 21201-7914.
Clinical Infectious Diseases 1996; 23:165-6
© 1996 by The University of Chicago. All rights reserved.
1058--4838/96/2301-0022$02.00
of a febrile patient on the third or fourth day after a tick bite
or exposure to a wooded area during the spring and summer
months is pathognomic. Yet, this was not the case for DiNubile's patient. There was no history of a tick bite or exposure
outside a large metropolitan area. Indeed, only ~20%-30%
of patients with Rocky Mountain spotted fever (RMSF) have
a known history of tick exposure. Headache may be minimal
or absent, and in ~ 5%- 8% of patients, a rash does not occur.
The rash is visualized with difficulty in dark-skinned patients.
Absence of these clinical and epidemiological considerations
makes diagnosis quite difficult.
Not long ago, I successfully defended a physician who practiced in a populous eastern state. The patient had the only case
ofRMSF reported in a particular county during a 5-year period.
The physician reacted promptly, thoroughly, and correctly.
Nevertheless, the patient died of a cardiac arrest that resulted
from severe, complicated rickettsial myocarditis. This was a
tragic death, but it was hardly an example of unacceptable
practice.
A third interesting feature of DiNubile's case is whether it
represents a recurrent type of rickettsial infection, similar to
Brill-Zinsser disease, or recurring epidemic typhus fever. This
finding has never been reported for RMSF. In 1910, Brill [2]
described 221 patients with a typhus-typhoid-like illness in
New York. These patients were studied carefully, and Brill
came to the conclusion that the patients had neither typhus nor
typhoid fever, but an illness similar to typhus of unknown
cause. This illness became known as Brill's disease and for
many years was confused with endemic typhus in the southern
United States.
Zinsser evaluated this problem carefully and concluded in
1934 that Brill's disease represented an example of recurrent
epidemic typhus fever, which developed in persons who had
emigrated to the United States from areas (e.g., Poland, Yugoslavia, or Russia) where typhus was endemic [3]. The second
attacks, usually milder than the initial infection, occurred several decades after the immigrants arrived in the New World.
Zinsser's hypothesis, which was confirmed by Murray [4], was
correct in that rickettsiae continued to be viable in the human
host even though most patients remained fully convalescent.
This example, like that of Mycobacterium tuberculosis, illustrated the ability of a pathogenic organism to persist in the
human host. The concept of cell-mediated immunity, which
came along much later, explains why most patients remained
fully convalescent. For many years, a few of our dying breed
of rickettsiologists have been searching for a recurring type of
RMSF. In 1954, we isolated a pathogenic strain of spottedfever-group rickettsiae from a lymph node of a patient who
had had RMSF and who had been in the convalescent phase
of illness for> 1 year [5]. However, no second cases ofRMSF
have been definitively reported.
166
Woodward
The case reported by DiNubile may represent just such an
infection, since the patient related that he had experienced a
similar illness a number of months previously and had fully
recovered. Studies of the postmortem tissue samples from this
current patient showed widespread vasculitis in many organs
including the skin, kidneys, and lungs, as well as in the muscles.
In addition, Dr. David Walker, an authority in this field, identified many rickettsiae in the vessels of these organs by means
of appropriate staining techniques (immunoperoxidase). The
serological findings for the patient are highly informative, since
the titer of IgG antibodies to Rickettsia rickettsii on the day of
death (lith day of illness) was 1:2,028. This is a high titer of
IgG antibodies, which usually is detected later in the course
of RMSF during convalescence. These IgG antibodies persist.
It is plausible, although conjectural, that DiNubile's case
represents a recurrence of a primary illness. In this instance,
the high levels of IgG developed immediately because of the
presence of antigenic memory. This immunologic pattern occurs in patients with Brill-Zinsser disease.
Another aspect of this case interests me considerably. The
rickettsial diseases, including RMSF, are model examples of
vasculitis with localization of rickettsiae in endothelial cells (a
secondary inflammatory vasculitis with fibrinoid changes in
vessel walls). For many years, I have believed that glucocorticoid steroids were helpful in treating severely ill patients during
the late stages of RMSF, and I have stated this belief. However,
a controlled trial of this therapy has not been conducted. Furthermore, I have commented that during the late states ofRMSF
or epidemic typhus, when the vasculitis is most severe, it might
be possible to treat a patient with high-dose steroids alone,
without a specific antibiotic.
In other words, at this stage of illness, the pathological
changes appear to be the damaging influence: the rickettsiemia
usually disappears in 10-12 days. However, I always stated
that this experiment could never be performed on any sensible
or ethical basis; use of antibiotics was always essential. It is
em
1996;23 (July)
conceivable this experiment could be conducted in primates,
but it is of low priority.
The patient described by DiNubile inadvertently provides
partial answers to the question of corticosteroid treatment.
Steroids were given at "stress levels" late in the patient's
illness, but these drugs did not appear to provide any beneficial effect or influence the unfavorable outcome. We must
again remind ourselves that the patient had AIDS and that
his whole immune system, including his ability to mobilize
host defenses and cellular immune mechanisms, was seriously altered.
In conclusion, it is most likely that the HIV infection in
DiNubile's patient could have accounted for the overwhelming
clinical abnormalities, since his ability to respond to treatment
was compromised by the immunosuppression.
I am grateful to DiNubile for making such an important
clinical experience available to other physicians. We all become better persons when we hear a colleague discuss pressing
personal experiences. Such candidness is the mark of a special,
concerned physician.
Theodore E. Woodward
University of Maryland Hospital, Baltimore, Maryland
References
1. DiNubile MJ. Reliving a nightmare: a hard (and tragic) lesson in humility.
Clin Infect Dis 1996;23:160-4.
2. Brill NE. An acute infectious disease of unknown origin: a clinical study
based on 221 cases. Am J Med Sci 1910; 139:484-502.
3. Zinsser H. Varieties of typhus virus and the epidemiology of the American
form of European typhus fever (Brill's disease). American Journal of
Hygiene 1934;20:513-32.
4. Murray ES, Baehr G, Shwartzman G, et al. Brill's Disease: 1. Clinical and
laboratory diagnosis. JAMA 1950; 142:1059-66.
5. Parker RI, Menon PG, Meredith AM, Snyder MJ, Woodward IE. Persistence of Rickettsia rickettsii in a patient recovered from Rocky Mountain
spotted fever. J Immunol 1954; 73:383-6.