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April 2007
An Evidence-Based Approach
To The Diagnosis And
Treatment Of Rocky Mountain
Spotted Fever In The
Emergency Department
Volume 9, Number 4
Authors
Benjamin P. Davis, MD
Attending Physician, Carle Foundation Hospital,
Urbana IL; Clinical Instructor, College of Medicine,
University of Illinois at Urbana-Champaign,
Champaign, IL
John A. Marx, MD
Chair, Department of Emergency Medicine,
Carolinas Medical Center; Adjunct Professor of
Emergency Medicine, University of North Carolina at
Chapel Hill, Charlotte, NC
A 21-year-old man presents with headache, fever, myalgias, and vomiting for two
days. You think to yourself that it is unusual for a young man to have the flu in
the summertime. Being the ever-astute clinician, you discover that he has not
traveled outside of the country, but did spend last weekend camping with some
friends in a nearby state park. You think that he probably didn’t get much sleep on
the trip and caught a virus. He feels much better after a liter of normal saline so
you discharge him home with NSAIDs and instructions to drink plenty of fluids.
One week later, as you go to sign out, your partner says,”Remember that guy
with the viral illness that you saw last week…”
F
ever. Muscles aches. Vomiting. Headache. Each is a nonspecific complaint that may imply a diagnosis in isolation, but
taken together often lead to the general diagnosis of viral syndrome. Only rarely does a constellation of nonspecific complaints
lead to a specific diagnosis. Rocky Mountain Spotted Fever (RMSF)
is a disease with protean manifestations. The classic presentation is
a patient complaining of fever, headache, myalgias, nausea, and a
petechial rash involving the palms and soles. Although RMSF,
among the tick-borne illnesses, has taken a back seat to Lyme disease in terms of national attention due to its relatively low prevalence, it has a high incidence of mortality and substantive associated morbidity. Failure to diagnose RMSF in a timely manner is the
primary explanation for this. RMSF must be in the front of the
Editor-in-Chief
Andy Jagoda, MD, FACEP, Professor
and Vice-Chair of Academic Affairs,
Department of Emergency Medicine;
Mount Sinai School of Medicine;
Medical Director, Mount Sinai Hospital,
New York, NY.
Associate Editor
Health Science Center, New Orleans,
LA.
Wyatt W. Decker, MD, Chair and
Associate Professor of Emergency
Medicine, Mayo Clinic College of
Medicine, Rochester, MN.
Francis M. Fesmire, MD, FACEP,
Director, Heart-Stroke Center,
Erlanger Medical Center; Assistant
Professor, UT College of Medicine,
Chattanooga, TN.
HSC/Jacksonville, FL.
Gregory L. Henry, MD, FACEP, CEO,
Medical Practice Risk Assessment,
Inc; Clinical Professor of Emergency
Medicine, University of Michigan, Ann
Arbor.
Keith A. Marill, MD, Instructor,
Department of Emergency Medicine,
Massachusetts General Hospital,
Harvard Medical School, Boston, MA.
John M. Howell, MD, FACEP, Clinical
Charles V. Pollack, Jr, MA, MD, FACEP,
Professor of Emergency Medicine,
Michael J. Gerardi, MD, FAAP, FACEP,
Professor and Chair, Department of
George Washington University,
Director, Pediatric Emergency
Emergency Medicine, Pennsylvania
Washington, DC; Director of Academic
Medicine, Children’s Medical Center,
Hospital, University of Pennsylvania
Affairs, Best Practices, Inc, Inova
Atlantic Health System; Department of
Health System, Philadelphia, PA.
Fairfax Hospital, Falls Church, VA.
Emergency Medicine, Morristown
Memorial Hospital, NJ.
Michael S. Radeos, MD, MPH,
Editorial Board
Assistant Professor of Emergency
Michael A. Gibbs, MD, FACEP, Chief,
Medicine, Lincoln Health Center,
William J. Brady, MD, Associate
Department of Emergency Medicine,
Bronx, NY.
Professor and Vice Chair, Department
Maine Medical Center, Portland, ME.
of Emergency Medicine, University of
Robert L. Rogers, MD, FAAEM,
Steven A. Godwin, MD, FACEP,
Virginia, Charlottesville, VA.
Assistant Professor and Residency
Assistant Professor and Emergency
Director, Combined EM/IM Program,
Peter DeBlieux, MD
Medicine Residency Director,
University of Maryland, Baltimore,
Professor of Clinical Medicine, LSU
University of Florida
MD.
Peer Reviewers
Peter DeBlieux, MD
Professor of Clinical Medicine, LSU Health Science
Center, New Orleans, LA.
Denis Pauze, MD, FACEP
Inova Faifax Hospital, Falls Church, Virginia; Clinical
Assistant Professor of Emergency Medicine, The
George Washington University School of Medicine,
Washington, DC
CME Objectives
Upon completion of this article, you should be able to:
1. Understand the epidemiologic and historical features of RMSF.
2. Understand the utility and limitations of diagnostic
testing for RMSF.
3. Describe the clinical features of RMSF.
4. Discuss the appropriate treatment for patients
with suspected RMSF.
Date of original release: April 1, 2007
Date of most recent review: March 1, 2007
See “Physician CME Information” on back page.
Alfred Sacchetti, MD, FACEP,
Assistant Clinical Professor,
Department of Emergency Medicine,
Thomas Jefferson University,
Philadelphia, PA.
Corey M. Slovis, MD, FACP, FACEP,
Professor and Chair, Department of
Emergency Medicine, Vanderbilt
University Medical Center, Nashville,
TN.
Jenny Walker, MD, MPH, MSW,
Assistant Professor; Division Chief,
Family Medicine, Department of
Community and Preventive Medicine,
Mount Sinai Medical Center, New
York, NY.
Ron M. Walls, MD, Professor and
Chair, Department of Emergency
Medicine, Brigham & Women’s
Hospital, Boston, MA.
Research Editors
Nicholas Genes, MD, PhD, Mount
Sinai Emergency Medicine Residency.
Beth Wicklund, MD, Regions Hospital
Emergency Medicine Residency,
EMRA Representative.
International Editors
Valerio Gai, MD, Senior Editor,
Professor and Chair, Dept of EM,
University of Turin, Italy.
Peter Cameron, MD, Chair, Emergency
Medicine, Monash University; Alfred
Hospital, Melbourne, Australia.
Amin Antoine Kazzi, MD, FAAEM,
Associate Professor and Vice Chair,
Department of Emergency Medicine,
University of California, Irvine;
American University, Beirut, Lebanon.
Hugo Peralta, MD, Chair of Emergency
Services, Hospital Italiano, Buenos
Aires, Argentina.
Maarten Simons, MD, PhD,
Emergency Medicine Residency
Director, OLVG Hospital, Amsterdam,
The Netherlands.
Commercial Support: Emergency Medicine Practice does not accept any commercial support. All faculty participating in this activity report no significant
financial interest or other relationship with the manfacturer(s) of any commercial product(s) discussed in this educational presentation.
minds of clinicians, even those who do not practice
in endemic regions. This issue of Emergency Medicine
Practice will provide a systematic approach to the
diagnosis and treatment of RMSF.
zoan pathogen as the infecting microorganism and
demonstrated that the wood tick (Dermacentor andersoni) was the vector for the disease.3,4
The reported annual incidence of RMSF in the
United States is extremely low, approximately 2.2
cases per million. This number appears to be increasing. In 2004, 1514 cases of RMSF were reported, compared to only 365 cases in 1998.5 However, the reported numbers may still be artificially low for several
reasons. First, most confirmed diagnoses are based on
serologic tests that are typically not positive until the
second or third week of the disease and may never be
positive in patients treated early in the course of disease.6,7 Second, several patients may have mild disease and recover without proper diagnosis or treatment, as demonstrated by a recent study by Marshall
which showed that 12% of a random sample of children were found positive for serum antibodies reactive to Rickettsia rickettsii.8 Third, cases may be drastically underreported. Paddock et al compared cases
reported to the CDC on standard forms to national
mortality statistics from death certificates. They
found that an estimated 400 cases of fatal RMSF went
unreported from 1983 - 1998. The nature of passive
surveillance makes it difficult to improve the quantity
and quality of national reported RMSF data.9,10
Critical Appraisal Of The Literature
RMSF has been referenced in the medical literature
for over 100 years. Unfortunately, there is still a
paucity of robust studies to assist clinical decision
making. Most reports are retrospective analyses.
While some of these contain large patient cohorts,
such as those from the Centers for Disease Control
and Prevention (CDC), there are very few high grade
evidence-based studies.
While the National Guideline Clearinghouse provides a link to Infectious Disease Society of America
recommendations for the diagnosis and treatment of
Lyme Disease, no such guidelines exist for RMSF in
adults. The American Academy of Pediatric
Committee on Infectious Diseases, however, does
publish guidelines for the treatment of RMSF in children.1 A search of the Cochrane Database of
Systematic Reviews, Cochrane Central Register of
Clinical Trials, ACP Journal Club, and Database of
Abstracts of Reviews and Effects revealed only three
articles relevant to RMSF and these are of marginal
significance to emergency practitioners.
This paper will attempt to tease out reasonably
evidence-based recommendations from groundless
and traditional dogma. We will endeavor to provide
recommendations based upon the strongest evidence, and to dispel any myths that may remain.
Table 1. Incidence of RMSF
Epidemiology
RMSF was first described by physicians during the
1880s in the Snake River Valley of Idaho. The disease
was called the “black measles” in reference to the
petechial rash seen later in the course of the disease.
In the nearby Bitter Root Valley in Western Montana,
Native Americans told stories of the “evil spirits” that
occupied the Bitter Root Valley during the spring.2 In
the early 1900s, much controversy surrounded the etiological agent of RMSF. Several scientists believed
that ticks were a possible vector and protozoa were
the infecting agent. Others saw no evidence of protozoa, and concluded that ticks could not be the vector.
In 1909, Howard Ricketts, a microbiologist at the
University of Chicago, published a series of landmark
epidemiologic studies that elucidated a non-proto-
Emergency Medicine Practice©
Incidence of RMSF in the US since 1920 from Dumler “Rocky Mountain
Spotted Fever—Changing Ecology and Persisting Virulence” NEJM
2005. 353;6:551-553]
Geography plays a major role in the epidemiology of RMSF. Although originally described in the
Rocky Mountains, the name Rocky Mountain Spotted
Fever is something of a misnomer and a potential
source of confusion. The majority of reported cases
actually occur in the Southeast and Midwest, while
the disease is only sporadically reported in the Rocky
Mountain region. Furthermore, RMSF has been
reported in all the contiguous United States, with the
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April 2007 • EBMedicine.net
exception of Maine and Vermont.7 North Carolina
and Oklahoma consistently have the highest reported
incidence.11 In one surveillance report from two highly endemic counties in North Carolina, the mean
annual incidence was nearly 20 cases per 100,000.12
The disease also occurs in South and Central
America, where it goes largely unrecognized.
Table 2. Seasonal Variation
Figure 1. Incidence Within US
reported a case of a man from Tennessee who died of
RMSF. After his funeral, his wife, brother, sister, and
son all developed symptoms compatible with RMSF
and were seropositive for the disease.17 Similarly, in
2003, the CDC reported three separate fatal cases of
RMSF in which family members developed similar
illness.18 The phenomenon of familial clustering is
probably the result of shared exposure to R. rickettsii.
Some epidemiologists have proposed that there may
be “foci of disease hyperendemicity” (areas in which
R. rickettsii-infected ticks are especially prevalent)
which are responsible for the clusters.17
Around the turn of the 20th Century, R. rickettsii
killed up to 75% of infected patients.5 Case fatality
ratios for RMSF in the pre-antibiotic era of the 1920s
and 30s ranged from 18 - 28%.19 This number was cut
in half by the discovery of tetracycline and chloramphenicol in the late 1940s. Despite the improved use
of antibiotics and improvements in supportive care,
approximately 5% of infected individuals will die from
the disease and many more suffer from its sequelae.20,21
Exposure to the outdoors, particularly woody
areas, increases the risk of contracting RMSF. In one
study, 95 of 96 subjects reported exposure to woody
areas in the 14 days prior to symptom onset.12
Although RMSF may occur at any age, historically,
children ages five to nine have the highest incidence
of disease, presumably because they are more likely
to be playing outdoors. This may be changing, however, as surveillance data from 2003 demonstrated
that patients in the 40 - 65 year age range had the
highest incidence of disease.13 One report demonstrated that men greater than 60 years of age have a
high risk of disease as well. The case fatality rate is
highest for those greater than age 40.14 Persons ages
20 - 29 have the lowest incidence.
Seasonal variation is important in the epidemiology of RMSF. Not surprisingly, seasonal peaks in
RMSF occur when people are more likely to be in the
outdoors, i.e., the summer months. This also corresponds to the period of highest tick activity. Ticks
are usually dormant during the winter, unless they
are disturbed.15 According to CDC data from 1981 to
1992, 90% of confirmed cases had symptom onset
between April 1 and September 30.11 Wilfert et al
corroborated these findings.16 However, sporadic
cases are still reported throughout the year, even in
colder climates.11
Rocky Mountain Spotted Fever is not contagious
and is generally a sporadic illness. However, familial clustering of RMSF has been reported. Jones et al
EBMedicine.net • April 2007
Etiology And Pathophysiology
R. rickettsii are small, obligate intracellular bacteria,
and are the etiologic agents of RMSF. The species
has evolved through a symbiotic relationship with
ticks. The primary tick vectors are the Rocky
Mountain wood tick (Dermacentor andersonii) in the
western U.S. and the American dog tick (D. variabilis)
in the Midwestern and Eastern U.S. However, a
recent investigation reported the presence of RMSF
in Arizona, with the brown dog tick (Rhipicephalus
sanguineus) as the vector.22
Ticks infected with R. rickettsii transmit the infection to humans through salivary secretions during a
blood meal. The ticks also transmit the infection to
their progeny, maintaining R. rickettsii in nature.23
Interestingly, more than 90% of infected tick larvae die
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from the infection prior to becoming adults.24 Some
studies estimate that less than 1% of ticks carry pathogenic R. rickettsii, even in endemic areas.17 Because the
tick bite is painless, many persons never know that a
tick was attached. After at least 6 - 10 hours of attachment, rickettsiae begin to be injected from the salivary
glands. In some cases, transmission may not occur for
24 hours or longer.25 According to unpublished case
reports, humans can also be infected when removing
ticks from another person or from an animal.26 Dogs
are at risk for clinical infection with RMSF, and concurrent rickettsial infection in a dog and its owner has
been reported.27 Other small mammals, and even
birds, may also be infected with rickettsiae.23
Once a human is infected, the rickettsiae initiate a
devastating pathogenic sequence; the hallmark is a
vasculitis that may occur anywhere in the body. The
bacteria spread via the lymphatics into the circulation. Once in the circulation, they establish numerous foci of infection within the vascular endothelium
of small vessels. This leads to endothelial cell injury
and a profound inflammatory response.28 The net
result is increased vascular permeability causing
edema and hypovolemia. In addition, this setting
promotes a hypercoagulable state, which may play a
role in the end organ damage that may include the
skin, CNS, myocardium, lungs, liver, and kidneys.29,30
The mean incubation period from tick bite to symptoms is seven days.31
gitis. Some authors have argued that any patient
hospitalized for suspected RMSF should also receive
coverage for meningococcal meningitis until the
diagnosis of RMSF is secure and that of meningococcal disease is eliminated.35,36,37
Gastroenteritis
Nausea and vomiting may be present in more than
50% of RMSF patients. Diarrhea may be present in
20 - 30%.31,32 Without careful history taking, it is easy
to dismiss a patient with RMSF as having gastroenteritis. One should approach the diagnosis of gastroenteritis in children with extreme caution, as the
enteroviral season overlaps with that of RMSF.38
Acute Abdomen
Abdominal pain may be a significant feature of
RMSF. Davis and Bradford reported two patients
with severe RLQ pain who had appendectomies with
pathologically normal appendices and were later
diagnosed with RMSF; one of whom died postoperatively.39 Walker et al reported two similar cases of
elderly patients with fever and abdominal pain, one
of whom underwent a cholecystectomy and one of
whom underwent appendectomy. Pathology
demonstrated infection with R. rickettsii in the
respective organs.40
Toxic Shock Syndrome
Toxic shock syndrome (TSS) also overlaps significantly with RMSF. The defining characteristics of TSS are
fever, rash, hypotension, and multisystem involvement. The classic rash for TSS is diffuse, blanching,
macular erythroderma and may involve desquamation of the palms and soles. As with RMSF, the rash
may also be faint and not noticed on initial exam.41
Barson reported a case of confluent macular rash in
the setting of headache and fever that was ultimately
diagnosed clinically with RMSF.42 Similarly, TSS may
affect any organ system and cause GI symptoms,
myalgias, CNS abnormalities, hepatic, and renal
abnormalities. Although hypotension is a requirement for a diagnosis of TSS, it may also be seen in
severe RMSF. In a patient who presents with fever,
rash, and hypotension, it is prudent for the emergency physician to treat for both toxic shock and
severe RMSF until the true etiology is discovered.
Differential Diagnosis
Given the often nonspecific presentation of patients
with RMSF, the differential is vast. The emergency
physician should consider life-threatening as well as
benign presentations as potential harbingers of RMSF.
Meningitis
It is difficult, if not impossible, to differentiate bacterial or viral meningitis from RMSF by history and
physical exam alone. Fever and headache are the
two most prevalent symptoms in RMSF; meningismus can also be present.31,32 Furthermore, the rash of
RMSF is classically petechial, as is the rash of
meningococcal meningitis. A history of tick bite or
recollection that the rash began on the wrists and
ankles, spreading to the trunk, palms, and soles may
point towards RMSF, though these findings are
absent in up to 20% of confirmed RMSF cases.33,34
Emergency physicians should perform a lumbar
puncture if there is any clinical suspicion for meninEmergency Medicine Practice©
Measles
Measles generally occurs during the winter and
spring, while RMSF is more common in the summer
4
April 2007 • EBMedicine.net
syphilis (VDRL and RPR) are readily available to
help rule out this diagnosis.
months. The rash of measles typically appears after
three to five days of fever, coryza, cough, and conjunctival injection. It is typically maculopapular and
coalesces, spreading from the face to the trunk and
extremities. Koplik spots are small white spots on the
buccal surface of the oropharynx and are pathognomonic for measles. It is important to ask about
immunization history and any possible exposure to
measles. Nieburg et al reported positive measles
antibodies in the sera of 6 of 46 children originally
suspected to have RMSF but who, in fact, had
measles.43
Allergic Reaction
The rash of RMSF may be indistinguishable from a
drug reaction. However, urticaria and pruritis are
uncommon with RMSF. Some patients will
inevitably present after being prescribed antibiotics
in the preceding days, such that it is important to
keep RMSF in the differential diagnosis.
Other Tick-borne Illnesses
The signs and symptoms of several other tick-borne
illnesses may overlap with RMSF, including ehrlichiosis, anaplasmosis (formerly human granulocytic
ehrlichiosis), and Lyme Disease. Headache, myalgias, and fever are particularly nonspecific findings
in these disorders. Like RMSF, each of these exhibits
a seasonal predisposition for the summer months.
Ehrlichiosis and anaplasmosis are increasingly
recognized disease entities in the United States.
Headache, fever, myalgias, and malaise are the main
presenting symptoms of these disorders.44 Rash may
be present in children with ehrlichiosis, although it
does not follow the typical pattern of RMSF. Adults
with ehrlichiosis are unlikely to have a rash.45,46 Some
authors have suggested that some cases presumed to
be RMSF were, in fact, ehrlichiosis.47 Sexton et al
even reported a case of simultaneous infection with
rickettsia and ehrlichial agents.48 Fortunately for
emergency physicians, these diseases are treated with
the same antibiotic as RMSF: doxycycline.
Lyme disease is the most common tick-borne disease in the United States. Caused by Borrelia burgdorferi, Lyme disease classically presents with the rash
of erythema migrans, an expanding erythematous
lesion surrounding the tick bite. The majority of
patients present with a solitary lesion, but up to 20%
may present with secondary lesions which may raise
suspicion for RMSF. Additional symptoms are similar to RMSF and include fatigue, chills, fever,
headache, myalgias, and arthralgias.49 Unlike RMSF,
untreated Lyme Disease is rarely fatal. Long term
morbidity is high; 60% of patients develope arthritis,
10% have a neurologic manifestation (most commonly facial nerve palsy), and approximately 5% develop
a cardiac complication (usually AV block).50 Hughes
reported an interesting case of RMSF in which the
patient presented with an erythematous rash at the
site of the tick bite consistent with erythema
migrans, but serology suggested that the offending
Carbon Monoxide Poisoning
CO poisoning is generally a winter malady.
However, it is always important to consider in a
patient with headache and flu-like symptoms. You
must obtain a thorough exposure history, and consider a carboxyhemoglobin level by co-oximetry if
there is any doubt.
Viral Illness
One must consider RMSF in ANY patient presenting
with a constellation of symptoms consistent with
viral illness. Several viruses may present with a maculopapular rash and similar symptoms to RMSF.
Enteroviruses, such as coxsackie virus and echovirus,
may cause symptoms which may be impossible to
distinguish from RMSF. Human herpes virus 6 infections (roseola infantum) may have a similar presentation to RMSF with two to three days of febrile illness
followed by rash. However, the child typically defervesces and symptoms improve soon after appearance
of the rash. Parvovirus B19 (erythema infectiosum)
may also present with a prodrome of fever and nonspecific symptoms followed by a rash.
Kawasaki Disease
Kawasaki Disease may be confused with RMSF, particularly because of a rash and changes in the extremities.
However, several of the classic criteria for Kawasaki
Disease, such as cracked or fissured lips, conjunctivitis,
and cervical lymphadenopathy, are not common with
RMSF. Nonetheless, both diseases are diagnosed clinically and should not be excluded prematurely.
Syphilis
Secondary syphilis should be considered in the differential of any rash that involves the palms and
soles. Like RMSF, symptoms of secondary syphilis
may be nonspecific. Fortunately, blood tests for
EBMedicine.net • April 2007
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Emergency Medicine Practice©
agent was R. rickettsii.51 Babesiosis is another emerging tick borne illness. Like Lyme disease, babesiosis
is endemic to the northeastern United States; it is
transmitted by the Ixodes tick. Babesiosis usually
presents as a nonspecific flu-like illness. Unlike
RMSF, rash is extremely uncommon in babesiosis.52
A final consideration in the patient with suspected RMSF and neurological findings is tick paralysis.
Tick paralysis typically presents with neurologic
symptoms as a result of a neurotoxin released by an
attached tick. These symptoms include flaccid paralysis and ataxia, although ataxia may be seen in isolation. Although Dermacentor species are known to
secrete the toxin responsible for this disease, it is a
completely separate disease from RMSF. Unlike
RMSF, tick paralysis is treated not with antibiotics,
but by removing the tick. Symptoms will typically
resolve within 48 hours of tick removal. Any patient
presenting with suspected RMSF and neurologic
findings should be thoroughly searched for the continued presence of a tick.53
Prehospital Care
Prehospital care of the patient with suspected RMSF
is primarily supportive. In stable patients with a
febrile illness and rash, IV access may not be necessary. In contrast, patients may present with respiratory compromise, hypotension, or even cardiac
arrest.54 In these situations, EPs should pay careful
attention to the ABCs, and initiate ACLS protocols if
indicated. Because ill patients with petechial rash
may in fact have meningococcal disease, it is imperative to observe universal precautions in the provision
of care to these patients.55
If a tick is present, it should be removed promptly. Timely removal of the tick may limit infectivity..26
There are several anecdotal reports of prehospital
providers responding to calls for “emergent” tick
removal.
There is no evidence that prophylactic treatment
of an asymptomatic tick bite victim is helpful in preventing RMSF. Some experts suggest that prophylactic treatment may prolong the incubation period.
However, practical circumstances in the backcountry
setting, such as long distance from a health care facility, may require prophylaxis rather than waiting for
symptoms to develop.
Table 3. Differential Features of
Common Tickborne Infections*
Clinical/Laboratory
Finding
Symptom
Headache
Meningismus
Abdominal pain
Myalgias
Signs
Temperature >38.9°C
(>102°F)
Relative bradycardia
Ankle/wrist rash
Periorbital edema
Conjunctival suffusion
Edema of dorsum of
the hands/feet
Calf tenderness
RMSF
HME/
HGE
Lyme
Disease Babesiosis
+
+
+
+
+
+
+
+
+
+
+
-
+
+
+
+
+
+
+
-
-
-
+
-
-
-
ED Evaluation
Initial Assessment
There are several important considerations when a
patient with a syndrome consistent with RMSF presents to the ED. First and foremost, the ABCs must be
addressed. Because of multisystem involvement,
RMSF patients may present in extremis and should
be managed with airway measures including intubation, aggressive intravenous fluids, and careful monitoring. In these acutely ill patients, meningococcal
disease will often be a consideration and universal
precautions and isolation should be considered.
Triage nurses must be careful to not be dismissive of
a febrile illness with a rash.
Abnormal laboratory finding
Leukocytosis
+
Anemia
+
Thrombocytopenia
+
+
+
+
+
+
ÇAST/ALT
+
ÇLDH
+
WBC inclusions
+
(morulae)
RBC inclusions
+
(Maltese crosses)
Confirmation
ÇlgM
ÇlgM
ÇlgM
Strained
diagnostic test serology serology serology peripheral
smear
History
In an emergency department evaluation of possible
RMSF, the greatest challenge is first considering the
diagnosis. In a waiting room full of patients with
headaches and vague complaints or children with a
suspected summer virus, looking for RMSF may
seem akin to searching for a needle in a haystack.
Knowing the suggestive history and the frequency of
physical findings is essential. In a survey by
Abreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; HGE, human granulocytic ehrlichiosis; HME, human monocytic
ehrlichiosis; LDH, lactate dehydrogenase; RBC, red blood cell; RMSF,
Rocky Mountain Spotted Fever; WBC, white blood cell; +, usually present; -, may be present; Ç, increased levels.
* Table adapted from Woodward and Cunha and Cunha.
Emergency Medicine Practice©
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April 2007 • EBMedicine.net
O’Reilly et al assessing physician knowledge of
RMSF, less than 50% of physicians surveyed knew
that most patients with RMSF do not present with
the classic constellation of tick bite, fever, and rash.56
When taking a history, several key elements can help
to keep RMSF in the differential.
should remain in the minds of practitioners in all
parts of the country.
When did symptoms begin?
Traditional dogma is that RMSF has an abrupt onset
of symptoms. However, up to one-third of patients
will describe a gradual onset.31 If a definite tick bite or
exposure took place, symptoms usually begin within
seven days, although the incubation period may range
from 2 to 14 days.25 The incubation period tends to be
shorter in those with more severe disease.59
Is there a history of tick bite or tick exposure?
Every patient presenting with a febrile illness should
be asked about recent tick bite. If there has not been
known tick bite, inquire about occupational or recreational exposure to ticks. Young children often do
not give a thorough history. If the weather is nice,
assume that they have been playing outside and
have been exposed to ticks. Ticks may also be found
inside the home, particularly on dogs and other
pets.31 Unfortunately, many patients will not report a
history of tick bite. There are several possible reasons for this: ticks are very small, they attach in
places on the body that are difficult to observe, and
they usually inflict a painless bite.35 In a CDC report
from 1981 to 1992, only 66% of over 4000 confirmed
cases of RMSF reported tick attachment in the 14
days prior to illness.11 In a review by Kirk et al, only
56% confirmed cases reported tick bite.32 In a retrospective study by Helmick et al, 80% of confirmed
cases reported tick bite or attachment. They compared those 158 patients with 31 persons without
tick exposure. Patients without a history of tick
exposure had significant delays in diagnosis and
prolonged hospitalization.31
Physical
Constitutional signs and symptoms
As the name Rocky Mountain Spotted Fever implies,
fever is a nearly ubiquitous symptom in RMSF.
Approximately 94 - 100% of patients will experience
a fever at some time in their illness.11,32,33 Fever is
reported by 73% during the first three days of illness.
Similarly, headache is found in 60 - 80% of cases.
The reported severity of headache varies among
patients, though more reported mild to moderate
pain than severe. The symptoms at presentation are
most commonly fever, headache, or both.31
Skin Findings
The rash of RMSF is classically described as blanching erythematous macules, beginning on the ankles
and wrists, eventually including involvement of the
palms and soles, and spreading rapidly to the trunk
and face. The rash is believed to result from the diffuse vasculitis and is usually observed two to five
days after symptom onset. The rash then becomes
petechial over days six to nine.60,61 Although these
are the most characteristic findings in RMSF, the rash
may occur in myriad ways, or be completely absent,
or the patient may present prior to developing the
rash. National surveillance studies indicate that up
to 20% of confirmed cases may never have a rash
during the course of their illness.11 Sexton and Corey
reported that 10% of 90 cases of RMSF had no rash
or had fleeting rash. They urge clinicians to beware
of the “wolf in sheep’s clothing.”33 In a retrospective
cohort study, Kirkland et al reported only 39% of
patients presented with rash. They found that the
absence of the typical rash was associated with
delays in therapy.57 Still, it is imperative that the
emergency physician diligently search for the presence of any rash. A rash appearing after three days
of fever should strongly suggest RMSF. Some
authors have suggested that the slightly higher case
Is the season right for RMSF?
Not surprisingly, the majority of tick bites occur in
warmer months, when humans venture into the outdoors with greater frequency and ticks are active.
While 90% of cases occur between April 1 and
September 30, it is imperative that the emergency
physician be cognizant of the fact that cases present
year round. In Kirkland’s retrospective cohort study,
28% of RMSF cases presented during the “off-season,” though they defined the season as May 1
through July 31.57
Is this an endemic area for RMSF?
Dorland’s Medical Dictionary defines endemic as
“present or usually present in a population or geographical area at all times.”58 Cases of RMSF have
been reported in every state in the continental U.S.
except for Vermont and Maine. You must know the
prevalence in your local area. However, RMSF
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fatality ratio in African-Americans is due to dark
skin color causing a delay in the detection of a rash.7
The skin findings of RMSF can also progress
beyond the rash. Skin necrosis has been noted to
occur, and the literature contains several cases of
gangrene. Though limited by small sample size,
there do not appear to be any features to distinguish
the patients who developed gangrene from other
the course of the disease, and 30% will have abdominal pain during the first three days of the disease.31
Febrile patients in whom abdominal pain is the chief
complaint present a clinical challenge. RMSF may be
misdiagnosed as appendicitis or cholecystitis.39,40 It is
unclear if this is secondary to inflammation of the
abdominal wall or vasculitic involvement of a specific organ. Similarly, nausea, vomiting, and diarrhea
may all occur in 20 - 60% of cases, leading to a misdiagnosis of gastroenteritis.31 Hepatobiliary involvement may occur, ranging from mild elevations in
LFTs to frank jaundice.34
Figure 2. RMSF Rash
Neurologic Findings
Neurologic manifestations of RMSF are numerous.
These are generally attributed to the effects of the vasculitis on brain tissue.64 Common findings are
headache and meningismus. Seizure may occur in up
to 10% of cases.31 Many will present with altered
mental status, even progressing to coma. Other common neurologic manifestations include ataxia, cranial
nerve findings, peripheral neuropathy, and hearing
loss.64 In a retrospective review, neurological involvement was associated with an odds ratio of 8.3 for mortality.65 However, the authors’ definition of neurological involvement was very broad, such that the majority of critical patients would be considered to have
“neurological involvement.” Furthermore, this finding was limited by a very large confidence interval
(4.6 - 28). Recent case reports have suggested a relation between rickettsial infection and demyelinating
diseases, such as Guillain-Barre and Acute
Disseminated Encephalomyelitis.66,67 In any patient
presenting with suspected RMSF and neurological
findings, perform a careful search for any attached
ticks. These should be removed promptly to exclude
tick paralysis as the etiology of the neurologic symptoms.53 As a result of the neurotoxin released by an
attached tick, tick paralysis typically presents with
flaccid paralysis, acute ataxia, or a combination.
Symptoms improve within hours of tick removal, and
usually resolve within 48 hours.68
Dumler JS NEJM 2005
patients with RMSF.62
Musculoskeletal Findings
Myalgias are the third most prevalent symptom after
fever and headache, occurring in up to 83% of
cases.31 Arthralgias were reported by patients in one
series, occurring 10% of the time.32 An acute,
monoarticular arthritis may also be observed.63
Cardiovascular Findings
Clinically obvious rickettsial myocardial involvement is an unusual complication of RMSF. These
patients may present with classic signs and symptoms of left ventricular dysfunction, i.e., dyspnea,
orthopnea, chest pain, jugular venous distension,
and crackles on lung exam. According to one case
report, the symptoms may even mimic acute MI.69
Gastrointestinal Findings
Abdominal pain may be a prominent finding in
RMSF. Up to 50% will have abdominal pain during
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Cardiac involvement may not be readily apparent on
examining the patient with suspected RMSF. In a
classic pathological study, Bradford described 16
children who died of RMSF; all had some evidence
of myocardial involvement.70 However, because
these patients had widespread multisystem involvement, it is difficult to determine the significance of
these findings. In a small study, Feltes et al performed echocardiograms on nine children admitted
with a diagnosis of RMSF. Seven of the nine had
varying degrees of left ventricular dysfunction,
though not all were symptomatic. When Feltes performed repeat echocardiograms 10 months after resolution of the disease, all patients had regained normal ventricular function.71 In a similar small cohort
of children, Marin-Garcia found that nine of thirteen
patients have various abnormalities on echocardiogram. In contrast to Feltes’ study, half of these
patients had persistent LV dysfunction at five month
follow up.72 However, symptoms of left ventricular
dysfunction are not commonly observed in the acute
setting.73 The long term clinical significance is
unknown. Patients with RMSF should be considered
at risk for cardiac decompensation.
Diagnostic Studies
Laboratory Tests
Complete Blood Count
A CBC with differential is necessary in any patient
with moderate to severe RMSF, and may be helpful
in the diagnosis. Thrombocytopenia is present in
more severe cases, but may be seen in those with
mild disease.74 In the majority of cases, the thrombocytopenia is mild to moderate, with typical ranges
from 21,000 – 150,000.75 The etiology of thrombocytopenia is not entirely clear. Most experts have postulated that it is due to peripheral platelet aggregation and adherence to Rickettsia-infected endothelial
cells, rather than a direct injury to bone marrow.36,74
However, a recent dog study by Grindem et al found
elevated levels of anti-platelet antibodies; this suggests a possible immunological component for
thrombocytopenia.76 To the authors’ knowledge, no
study has attempted to correlate the appearance of
the rash with the platelet count.
Classic teaching is that RMSF is associated with a
low or normal white blood cell count (WBC). This is
largely based upon a single retrospective study of 78
cases by Haynes et al in 1970.77 Unlike the elevated
WBC (greater than 10,000) typically seen with infectious processes, RMSF is associated with a low to normal WBC with a predominance of immature forms.
Hall and Schwartz reported 27 confirmed cases of
RMSF in which 78% had a WBC less than 10,000, 89%
had at least 10% bands, and 67% had greater than
20% bands.75 They proposed that using the WBC may
help distinguish between RMSF and meningitis, i.e.,
patients with a WBC greater than 10,000 should be
suspected to have meningococcemia while patients
with a WBC less than 10,000 are more likely to have
RMSF. In their study, the calculated sensitivity would
be 78%. The specificity for RMSF would be horrendous given that most “healthy” patients would be
expected to have a WBC less than 10,000. One must
remember that the WBC is a nonspecific test and its
utility in the ED setting is debatable.
Pulmonary Findings
Pulmonary edema may be observed, and is present
in many cases of fatal RMSF. In an autopsy study by
Roggli et al, 15 of 16 children with RMSF had
histopatholgic changes identified.29 Pulmonary
edema is non-cardiogenic and multifactorial, resulting from the diffuse vasculitic process.
Renal Findings
Severe RMSF is also associated with acute renal failure (ARF). In a retrospective review of 114 patients
with RMSF by Conlon et al, nearly 20% developed
ARF, defined as a serum creatinine greater than
2 mg/dL. Of these patients, 52% died. The mechanism of renal failure is probably due to intravascular
thrombosis, hypotension, and possibly rhabdomyolysis, in addition to direct infection of kidney
endothelial cells with R. rickettsii. This study’s findings are undermined by a mortality rate of 14%,
which is two to three times higher than is typically
reported. Thus, the patients who developed ARF
were probably much sicker than the typical patient
admitted with RMSF.65
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Coagulation Studies
Abnormalities of coagulation times are unusual in
RMSF and are usually clinically insignificant.
Fibrinogen and fibrin split product levels should be
ordered in patients suspected of disseminated
intravascular coagulation, although this is also a rare
complication.30
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Chemistries
Blood chemistries are often abnormal in RMSF
patients. Hyponatremia is a common finding, occurring in an estimated 20% of cases.36 Reported mean
sodium values for two retrospective studies were 124
and 129.32,65 The etiology of hyponatremia is probably multifactorial, although SIADH may play a role
in some cases.78
Derangements of liver function tests are often
reported with RMSF. This is likely due to rickettsial
infection of the hepatic vasculature, as pathology
studies have shown microscopic involvement of the
liver in up to 75% of cases. 49 Transaminase elevations
are generally mild, with mean AST around 200 - 300.
However, in Conlon’s retrospective review, higher
elevations (greater than 500) were associated with an
odds ratio of 2.3 having a fatal outcome. This study
is limited by its small size.65 Hyperbilirubinemia is
also generally mild, with mean elevation to a level of
1.6 mg/dL, and rarely high enough to cause jaundice.34 BUN and creatinine may also be abnormal. In
Conlon’s study creatinine greater than 2 mg/dL was
associated with an increased risk of mortality.65
meningitis.”32,64 The CSF in meningococcal disease
typically demonstrates a neutrophilic pleocytosis
(often greater than 100 wbc/microliter), very low
glucose (less than 20 - 30 mg/dL), and gram-negative diplococci on gram stain.80
RMSF Serology
Serology is the usual method for confirmation of the
diagnosis of RMSF. However, serology is unlikely to
be helpful in the emergency department, as serologic
tests may take several days to return and are typically not positive until the convalescent phase of illness.
The Weil-Felix agglutination test, the original
serologic test for R. rickettsii, is insensitive and nonspecific. This test is based on the principle that
serum antibodies agglutinate antigens which are
shared by Proteus vulgaris, R. rickettsii, and various
other Rickettsiae. The sensitivity of Weil-Felix for
RMSF is, at best, 70%.81 In addition, the specificity is
very low as many healthy persons have the antibodies and will have false positive results. The WeilFelix test should not be ordered for suspected RMSF
cases. Newer methods of serological diagnosis
include indirect fluorescent antibody (IFA), latex
agglutination (LA), complement fixation (CF),
enzyme immunoassay (EIA), indirect hemagglutination (IHA), polymerase chain reaction (PCR), and
enzyme-linked immunosorbent assay (ELISA).82-85
LA can be performed as a rapid screening test in
some labs with a turnaround time of one to two
hours.86 Unfortunately, it is severely limited by a
sensitivity of only 50 - 70%.82,83 IFA is the most sensitive, specific, and widely used test. Sensitivities for
IFA are reported to be approximately 94%.83,84,87
However, the turnaround time for IFA is several days
in most centers.86
There are several drawbacks to the use of serological tests in the emergency department. Most
importantly, all the tests, including IFA, have very
poor sensitivities if drawn during the first one to two
weeks of symptoms. Second, it is difficult to distinguish between active or past infection when convalescent titers are positive.88 Finally, the tests require
long turnaround times, and are unlikely to affect
emergent management. The routine use of serological tests for RMSF is not recommended unless performed in coordination with a consultant who can
follow up on the results and the condition of the
patient.
Table 4. Factors Associated With
Need For ICU Admission
• Age greater than 40
• Symptoms for five days or more
• Neurological involvement
• AST greater than 500
• Bilirubin greater than 3.0
• Creatinine greater than 2.0
• Sodium less than 130
Cerebrospinal Fluid
Because of the overlap of clinical presentation with
bacterial meningitis, lumbar puncture is commonly
performed in patients with RMSF. Kirk et al found
that 21 of 32 patients with RMSF who underwent
lumbar puncture had abnormalities. Unfortunately,
the indication for lumbar puncture is not explicitly
stated. The most commonly noted was an elevated
CSF white blood count (usually less than 100
wbc/microliter) with a predominance of mononuclear cells.32 Massey et al reported a similar CSF
pleocytosis.64 The CSF protein is often mildly elevated (100 - 200 mg/dL) and the CSF glucose is usually
normal. Gram stain will typically not show any
organisms as Rickettsia are not well differentiated by
gram stain.79 Thus, the CSF composition in RMSF is
usually either negative or compatible with “aseptic
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Biopsy
Skin biopsy in patients with a rash is recommended
by some authors.87 Immunohistochemistry staining
of tissue samples may be a valuable technique for
making an early diagnosis of RMSF, even during the
acute phase of the illness.19 Again, this should be performed in coordination with a consulting physician.
old male with fever, headache, myalgias, and vomiting in mid-June after being bit by a tick), “possible
RMSF” (e.g., 20-year-old with fever and myalgias in
August), or “probably not RMSF” (e.g., 35-year-old
in mid-December, in non-endemic location, with
fever, chills, myalgias). Patients in the “probable” or
“possible” groups should be treated with antibiotics.
Patients in the “probably not” group can be managed expectantly. A recent report from Chapman
and the Tickborne Rickettsial Disease Working
Group with the CDC introduced the idea of a “watch
and wait” strategy for 24 hours in a patient with an
acute febrile illness, who appears well, and has an
unrevealing history and physical examination.80
Emergency physicians should be very cautious about
using this approach.
Perhaps the highest risk for mortality in RMSF is
delay in initiating treatment. Multiple studies have
reported a much higher risk of death for those
patients in whom antibiotics were not started until
more than five days of symptoms.11,31,92 Emergency
physicians must focus on recognizing the possibility
of RMSF, and initiating early antibiotic treatment.
Many commonly prescribed antibiotics lack activity
against the intracellular rickettsiae. Although multiple drugs may have activity against R. rickettsiae,
doxycycline is considered the drug of choice in suspected cases of RMSF.
Imaging
Chest X-ray
Chest x-ray may be useful in suspected RMSF cases
with pulmonary symptoms. In a retrospective study
of 70 confirmed RMSF cases, McCook et al found
that 27% had abnormalities on chest x-ray. Of these
abnormalities, more than 50% showed a pulmonary
edema pattern.89 This study is limited by small sample size and selection bias. Routine radiographs are
not necessary in suspected RMSF cases without
objective evidence of pulmonary involvement.
Neuroimaging
Given the multitude of neurological manifestations
of RMSF, one would suspect that imaging of the
brain, either by computed tomography (CT) or by
magnetic resonance imaging (MRI), may be useful.
However, Bonawitz et al reviewed 44 CT scans and
six MRIs in confirmed RMSF cases and found abnormalities on only 4 of 44 CTs and four of six MRIs.
The abnormalities included infarctions, cerebral
edema, meningeal enhancement, and prominent
perivascular spaces. All abnormalities were considered “subtle.” In addition, none of the abnormal
findings altered clinical treatment.90 Although there
is a case report suggesting that MRI may be useful in
patients with RMSF, routine neuroimaging in the
emergency department is unnecessary. However, in
cases where there are significant neurological findings, other diagnoses are under consideration, or
both, CT or MRI may provide useful information.91
Doxycycline
Doxycycline is the drug of choice for the treatment of
RMSF in adults AND children. Historically, chloramphenicol and doxycycline were felt to be equally
efficacious in treating RMSF. However, several
recent large epidemiologic studies suggest that
patients treated only with chloramphenicol have a
higher mortality rate than those treated with either
doxycycline alone or both drugs concurrently.11,31,92
Holman et al conducted a large analysis (6388
patients) of confirmed cases of RMSF reported to the
CDC from 1981 to 1998 and found that chloramphenicol was associated with a three-fold risk of
death, compared to treatment with tetracyclines.92
Results were similar for patients from 1981 to 1989,
when chloramphenicol use was much more common, and for patients from 1990 to 1998. Similar
older studies by Dalton et al and Fishbein et al produced similar results.11,93 Unfortunately, inherent in
these study designs is an inability to control for
severity of illness. Therefore, sicker patients may be
more likely to be treated with chloramphenicol.
Treatment
The decision of whom to treat for RMSF is a difficult
one. Because of the varied symptoms and signs,
RMSF is not amenable to the simple algorithms often
used by emergency physicians. We recommend a
conservative approach to the use of antibiotics for
RMSF. Although it is impossible to list the possible
combinations of variables that may be present in an
individual case, most patients can be divided into
these categories: “probable RMSF” (e.g., nine-yearEmergency Medicine Practice©
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break, and many physicians continue to be unaware
of the recommendations.56 In one case series, only
one of 35 children was given a tetracycline class
antibiotic as initial therapy despite the fact that rickettsial infection was a diagnostic consideration.95
There have been no controlled studies on dosage
or duration of treatment in RMSF.
Recommendations for dosage are 100 mg every 12
hours for adults and 2 - 4 mg/kg/day divided every
12 hours for children.60,87 Duration is typically 7 to
10 days, or until the patient has been afebrile for at
least three days.1 Given the dose-dependent relation
to side effects, some authors have proposed shorter
courses of doxycycline. Yagupsky et al showed efficacy of a much shorter course of doxycycline in a
randomized trial of children with rickettsial spotted
fever.101 However, there was no blinding in this trial
and no placebo used to equalize the two treatment
groups. Furthermore, they studied Mediterranean
spotted fever, a related but much less severe rickettsial disease caused by Rickettsia conorii. Thus,
these results can not be generalized to patients with
RMSF. Nevertheless, if close follow up with a primary care physician is assured, it may be reasonable
to stop the antibiotic in a low risk patient prior to
finishing the full 7 to 10 day course.
Moreover, chloramphenicol has a poor safety profile
in comparison with doxycycline.94
Previously, the use of tetracyclines was contraindicated in children. In the 2003 edition of Red
Book, the American Academy of Pediatrics
Committee on Infectious Diseases unequivocally stateed that doxycycline is the drug of choice.1
Tetracycline antibiotics have several adverse effects
that have limited their use, including phototoxic
eruptions, hypersensitivity reactions, esophagitis,
and staining of teeth and fingernails.95,96 Although
these adverse reactions rarely occur, the risk of teeth
staining is commonly cited as a reason not to prescribe tetracyclines to children. Recent data suggest
that the risk of teeth staining may be exaggerated.97,98
In a study by Lochary et al, there was no statistically
significant difference in teeth staining between controls and patients less than nine years of age who
received doxycycline for treatment of RMSF.98 This
study is limited by a very small sample size and its
retrospective nature. However, it is the only study of
its kind and certainly suggests that doxycycline may
not cause significant staining.
Data from Grossman and colleagues suggest that
the risk of teeth staining is directly proportional to
the frequency of tetracycline exposure. In their
study of 160 children, a single six-day course of
tetracycline caused an exceedingly small amount of
teeth darkening. Even those children who received
five courses of tetracycline had a difference in shading that was nearly imperceptible. However, children who received eight or more courses were more
likely to have moderate darkening. These authors
also suggest that, after age five, the risk of staining
can be ignored because the “cosmetically important
anterior teeth” have already been formed. Moreover,
they suggest that doxycycline may cause less staining than other tetracyclines because of less calcium
binding.97 This study is well-designed, but lacks any
calculation of inter-observer reliability. In addition,
the number of patients with tetracycline exposure is
hinted at, but never clearly stated.
The concern of teeth staining can be further
repudiated when one considers the advances of
modern cosmetic dentistry. Dentists can now use
bleaching to improve mild cases of tetracycline-related teeth staining.99 Ayaslioglu even describes four
adults with tooth discoloration secondary to doxycycline in whom abrasive dental cleaning led to complete recovery of original tooth color.100
Despite the evidence, old habits are hard to
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Chloramphenicol
Chloramphenicol was the first antibiotic used to treat
rickettsial diseases.102 However, due to its safety profile, lack of availability, and evidence that it is less
efficacious than RMSF, use of chloramphenicol for
RMSF has markedly declined.11,94 Major side effects
include aplastic anemia, other hematologic abnormalities, and cardiovascular collapse, known as
“gray baby syndrome” in neonates. Aplastic anemia
is idiopathic, irreversible, non-dose-related, and
occurs in approximately one in 40,000. Other hematologic abnormalities which are dose-related and
reversible include isolated thrombocytopenia, anemia, and leucopenia.103 The only current recommended indications for chloramphenicol are in pregnant patients and in those with documented hypersensitivity to doxycycline.87
The recommended dose of chloramphenicol is
50 mg/kg/day divided every six hours.104 Duration
is 7 to 10 days. The oral form of chloramphenicol is
no longer manufactured in the United States. The
parenteral formulation may be administered orally,
but its efficacy has not been thoroughly studied.103
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Corticosteroids
The use of steroids in the treatment of RMSF is controversial. Some authors have advocated their use in
critically ill patients with widespread vasculitis or
encephalitis.112 In a case series from the 1950s, cortisone added to chloramphenicol subjectively
improved the clinical course.113 A canine study
showed no improvement with prednisolone used in
conjunction with doxycycline.114 Until more studies
are performed, steroids are not recommended in the
routine management of RMSF.
Other Antibiotics
In addition to tetracyclines and chloramphenicol,
other antibiotics, such as fluoroquinolones,
macrolides, and rifampin, have shown some promise
in the treatment of RMSF. The fluoroquinolones
trovafloxacin and enrofloxacin have proven efficacious in treating RMSF in dogs.105,106 In addition,
ciprofloxacin is commonly used to treat
Mediterranean spotted fever.107 Though R. rickettsii is
susceptible to clarithromycin in vitro, azithromycin
was less efficacious than doxycycline and
trovafloxacin in one dog study.87,106 Finally, in vitro
studies suggest that new antimicrobials that target
the methods by which rickettsia spread throughout
the body may be on the horizon.108 These studies
show promise, but until further analyses are performed, there is no clinical role for these antibiotics
in the usual treatment of RMSF.
Prophylaxis
Patients may present to the emergency department
requesting antibiotics after tick exposure, even if they
are asymptomatic. Some studies have demonstrated
success in preventing Lyme Disease when prophylactic treatment is initiated after tick exposure in an
endemic area.115,116 In contrast, prophylactic treatment
for RMSF of patients sustaining a tick bite is believed
to prolong the incubation period without mitigating
the disease course.25 Data are scarce, and one guineapig study suggested that single-dose prophylaxis
may be useful if given in the first 24 - 48 hours after
the tick bite.117 Until further studies are performed,
prophylactic treatment is not recommended for
patients with tick exposure who are asymptomatic.
Antibiotics To Avoid (Sulfonamides)
It has been reported for over 50 years that sulfonamides may increase the severity of RMSF.109
Recently, reports have emerged showing similar
severe cases of ehrlichiosis treated with sulfonamides.109,110 One theory is that sulfa drugs have an
enhancing effect on the multiplication of rickettsia.111
Unfortunately, this concept is largely anecdotal.
Poor outcomes in patients treated with sulfonamides
may be due to delay in treatment with doxycycline
rather than an effect of the sulfonamides. Despite
any compelling evidence, use caution when prescribing sulfonamides to any patient with a syndrome
consistent with RMSF.
Avoidance
The best prophylaxis against RMSF is avoidance and
early tick removal. Patients should be educated on
avoidance strategies. The first and most obvious is
keeping away from wooded areas. If time must be
spent in wooded areas, thoroughly inspect the head,
body, and clothes for ticks after exposure.118,119
Table 5. Recommended Antibiotics For Rocky Mountain Spotted Fever
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Finally, the use of clothing that thoroughly covers the
entire body and the use of tick repellents, such as
DEET (N,N-diethyl-m-toluamide), will help prevent
tick bites.31
severe RMSF may be mistaken for preeclampsia,
HELLP syndrome, thrombotic thrombocytopenic
purpura (TTP), or sepsis.123 RMSF must also be differentiated from several diseases transmitted from
mother to fetus, such as measles, rubella, toxoplasmosis, leptospirosis, enteroviruses, Epstein-Barr
virus, and syphilis. It is not known if R. rickettsii can
cross the placenta and infect the fetus. In one case of
serologically proven RMSF at 28 weeks gestation
treated with chloramphenicol, the patient delivered a
full-term healthy infant and pathologic evaluation of
the placenta revealed no evidence of rickettsial infection.124 As in non-pregnant adults, RMSF is a clinical
diagnosis. In addition to a high false negative rate in
the early stages of the disease, serologic tests may
have a high rate of false-positive results in pregnancy.125 The cause of the high false-positive rate is
unclear, but it appears to only occur with latex
agglutination and not with indirect fluorescent antibody testing.
Treat the pregnant patient with RMSF as soon as
the diagnosis is suspected. Tetracyclines are contraindicated during pregnancy in the first and second
trimesters due to concerns about limb hypoplasia and
growth abnormalities, and in the third trimester due
to concerns about hepatotoxicity. However, while
tetracyclines as a class are associated with the aforementioned concerns, doxycycline has not been linked
to specific problems during pregnancy, and short
courses are considered unlikely to cause harm.
Nevertheless, at this time, chloramphenicol remains
the drug of choice for rickettsial infection during
pregnancy.124,126 The side effects are essentially the
same as in the adult patient, the most untoward
being aplastic anemia. “Gray baby syndrome” has
not been reported in newborns of mothers treated for
RMSF, though this theoretically could occur.126
Tick Removal
At least 6 to 10 hours of tick attachment are required
before rickettsiae are transferred to a human host.
Furthermore, in the laboratory setting, dormant ticks
attached for more than 10 hours have shown a tendency to revert to a more virulent state.120 Therefore,
an attached tick should be removed as soon as possible to minimize the risk of infection. Several methods
have been proposed for the removal of an attached
tick. Some of these include petroleum jelly, burning
the tick with a match, fingernail polish, isopropyl
alcohol, forceps, and even commercial removal
devices. Needham et al compared several of these
techniques and found that grasping the tick with
curved forceps as close to the skin as possible and
pulling straight up achieved the best results.26 Three
commercially available tick removal tools compared
favorably with forceps in a study by Stewart et al.121
In a systematic review of the topic, Teece confirmed
that straight slow pressure was best for removal.122
Table 6. Recommended Procedure
For Tick Removal26
1. Use blunt curved forceps or tweezers.
2. Grasp the tick as close to the skin surface as possible and
pull upward with steady even pressure. Do not twist or jerk
the tick.
3. Do not squeeze or crush the body of the tick as its fluids
may also be infective.
4. Do not handle the tick with bare hands.
5.Thoroughly irrigate the bite site after tick removal, and wash
with soap and water.
6. Ticks may be safely disposed of by placing in a container of
alcohol or flushing them down the toilet.
Elderly
Elderly patients are much more likely to present with
atypical features of RMSF.11,127 In addition, the elderly
have a higher risk of other infections, making arrival
at the correct diagnosis even more difficult. In
patients who are untreated because the diagnosis
was missed, mortality is greater than 50%. Maintain
a very low threshold for treating patients greater
than age 60 who present with a flu-like illness without another definite source.
Special Populations
Pregnancy
The diagnosis and treatment of RMSF in pregnancy
is especially difficult. The nonspecific symptoms of
early RMSF are easily dismissed as the common ailments that accompany pregnancy. In addition,
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related rickettsiae which may share antigens.129,130
However, there is no commercially available vaccine
against R. rickettsii at this time.
Glucose-6-Phosphate Dehydrogenase
Deficiency (G6PD)
Fulminant RMSF is more commonly reported in
African-American males with G6PD deficiency.
Presumably, this is due to more severe hemolysis
than usually occurs with Rickettsial infection.59 Since
these patients may present with severe illness, or
even in extremis, the clinician must remember that
African Americans are less likely to have a rash on
presentation.7
Bioterrorism
Rickettsial pathogens have been used in the past as
bioweapons. The USSR and Japan developed
Rickettsia prowazekii, the agent of epidemic typhus, as
a biologic weapon in the 1930s and 1940s. The danger in rickettsial agents is that they may achieve high
infectivity as stable, small particle aerosols. In addition, it would theoretically be simple to confer resistance to tetracyclines and chloramphenicol to any
Rickettsiae in a laboratory environment, rendering the
antibiotics of choice useless. Furthermore, the low
level of immunity and the absence of an effective
vaccine make a high attack rate likely after exposure
to an infectious aerosol.131 Emergency physicians
must be aware of the potential malicious use of rickettsial pathogens.
Controversies And Cutting Edge
Immunization
Vaccination of high risk groups for RMSF, such as
children in endemic areas, is not a novel concept.
History of infection with R. rickettsii provides strong
protective immunity, but studies evaluating killed R.
rickettsii vaccines have demonstrated incomplete
immunity on reexposure.128 Recently, immunization
with rickettsial surface antigens has shown promise
as well as the possibility of vaccines using distantly
Ten Pitfalls To Avoid
in RMSF. Beware of patients with severe abdominal
pain and multiple other symptoms.
1. “He had no history of a tick bite, so it must have just
been the flu.” Approximately half of confirmed RMSF
cases recall a history of tick bite. Patients without such
a history are at risk for delays in diagnosis and worse
outcomes.
7. “I didn’t want to stain his teeth, so I held off on writing for any antibiotics.” Doxycycline is the drug of
choice for treatment of suspected RMSF in children of
all ages. There is reasonable evidence that a short
course will not cause permanent staining of teeth.
2. “I sent a RMSF test to lab, which came back negative.
So I sent the patient home.” RMSF serologies are commonly falsely negative during the first one to two
weeks of illness. In addition, there is significant turnaround time associated with the more sensitive tests.
8. “I treated one child with doxycycline, but now his
brother is in the ICU with fulminant RMSF. Why are
they blaming me?” Familial clustering of RMSF cases
has been reported multiple times, probably as a result
of natural foci of ticks infected with R. rickettsia.
Although RMSF is not a contagious disease, family
members need to be warned about the symptoms and
the need to seek early treatment.
3. “I considered RMSF, but she didn’t have a rash.”
Over half of patients with RMSF present without a
rash, and 10 - 20% will never develop a rash during the
course of their disease.
4. “Sure I would have thought about Rocky Mountain
Spotted Fever, if I lived in Montana or Colorado.”
RMSF has been reported in all contiguous United
States except Vermont and Maine. Physicians in all
states must consider this diagnosis.
9. “I covered him with ceftriaxone for his meningitis,
but the internist says his CSF culture was negative
and he’s getting worse.” There is significant overlap in
symptoms of bacterial meningitis and RMSF.
Furthermore, RMSF may show increased WBC on CSF
analysis. Thus, it is important to consider treatment
with doxycycline for any patient in whom the clinical
diagnosis of bacterial meningitis is in doubt.
5. “It’s April, ticks aren’t even around yet.” Cases of
RMSF have been reported in every month of the year.
The diagnosis should strongly be considered between
April 1 and September 30.
10. “I knew that she could have RMSF, but nobody dies
from that anymore.” Despite efforts to increase physician education about the appropriate use of doxycycline for RMSF, the mortality rate remains around 5%.
6. “At first I thought it was the flu, but because of the
severe right lower quadrant pain, I called the surgeon.” Abdominal pain may be a prominent symptom
Emergency Medicine Practice©
16
April 2007 • EBMedicine.net
independently. Other clear reasons for admission
include altered mental status, immunocompromised
state, pain management, inability to tolerate oral
antibiotics, and evidence of multi-organ-system
involvement. Patients greater than 60 years of age
should be strongly considered for admission for
observation. All probable cases of RMSF should be
reported to the state health department for follow up.
Patients who are discharged home must have
close follow up within the next two to three days. If
a “watch and wait” approach is used, those patients
should be reevaluated within the next 24 - 48 hours.
The first dose of doxycycline should be given in the
emergency department, and arrangements should be
made to ensure that patients are compliant with therapy. Patients should receive detailed information
regarding the disease, the reason for the antibiotics,
and the importance of taking the entire course. The
patient’s family members should be educated on the
early symptoms of the disease and seek medical care
if symptoms occur.
Medicolegal Concerns
In 1993, a case before the Tennessee Supreme Court
brought forth the issue of physicians’ duty to warn
third parties (i.e., family members and close contacts)
of the risk of contracting RMSF. In Bradshaw v.
Daniel, the court ruled that a physician treating a
patient with documented or suspected RMSF has a
legal duty to “act to protect identifiable third persons
from foreseeable risks emanating from a patient’s
disease.” Physicians are generally aware of their
medical and legal duty to warn and sometimes treat
family members of patients with contagious diseases,
such as meningococcemia or tuberculosis.132
However, RMSF is not transmitted from one person
to the other, and rarely has RMSF been transmitted
via blood transfusion or transplantation.133,134 It is
counterintuitive that emergency physicians be
required to warn family members in close contact.
However, because of the Bradshaw Case, it is important that physicians be aware of this statute as it
establishes a legal duty to warn third parties about
the risk of non-contagious diseases, such as RMSF.135
Summary
Disposition
Rocky Mountain Spotted Fever remains the leading
killer among the tick-borne diseases in the United
States. Delay in the diagnosis and failure to initiate
treatment with antibiotics lead to significant morbidity and mortality. It is a difficult diagnosis to make
as it may present in a variety of ways, in nearly any
geographic location, and at any time of year. Many
patients will not remember a tick bite, and several
will not present with any classic findings. Despite
advances in laboratory and radiographic tests, the
preliminary diagnosis of RMSF remains clinical.
Therapy should be initiated as soon as the diagnosis
is considered, with doxycycline as the treatment of
choice for both adults and children, and chloram-
The decision to admit a patient with suspected RMSF
is largely based on “clinical gestalt.” In general, any
patient with a probable case of RMSF should strongly
be considered for admission. Similarly, patients with
more severe symptoms (e.g., intractable vomiting) or
abnormal vital signs should be admitted, even if they
are considered to “possibly” vs. “probably” have
RMSF. However, the majority of cases of possible
RMSF can be treated as outpatients with oral doxycycline. The line between a possible and probable case
is difficult to draw, and each case must be examined
Cost Effective Care
Key Points
• Diagnostic tests should be used judiciously in patients
with suspected RMSF. The main indication for testing
is to rule out other potential conditions. For the emergency physician, the diagnosis of RMSF is made on
clinical grounds.
• The incidence of RMSF peaks between April and
September and it primarily occurs in specific regions
of the country; however, it can occur at any time of the
year.
• Treating all possible and probable cases of RMSF with
doxycycline will limit morbidity and mortality. A "watch
and wait" approach in low-suspicion cases can be
used only if close 24-hour follow up is ensured.
EBMedicine.net • April 2007
• RMSF is a disease with protean manifestations that
compel the emergency physician to consider RMSF in
the differential diagnosis.
• Helpful and specific findings from the history and physical examination, such as tick bite and rash, are often
absent in patients with RMSF.
• Despite advances in testing for RMSF, the diagnosis
remains a clinical one based on history and physical
examination.
• Doxycycline is the treatment of choice for RMSF in
both adults and children. If RMSF is a possibility, it is
appropriate to initiate treatment with doxycycline.
17
Emergency Medicine Practice©
phenicol reserved for pregnant patients and those
with known hypersensitivity.
6.
7.
Case Conclusions
The 21-year-old man returned two days after your initial
encounter. This time, he was brought by his girlfriend for
fever and altered mental status. Your partner was very
concerned for meningitis and immediately initiated ceftriaxone prior to performing a lumbar puncture. CSF
showed a 65 WBC/microliter, 2 RBC/microliter, protein of
75 mg/deciliter, and glucose of 60 mg/dL. Upon receiving
the results and reviewing your note, your partner astutely
initiated empiric doxycycline prior to consulting the critical care team for admission. The patient’s mental status
improved over the next two days and he was discharged
home on oral doxycycline after four days in the hospital.
Two weeks later, results from IFA and PCR testing confirmed the diagnosis of Rocky Mountain Spotted Fever.
8.
9.
10.
11.
References
Evidence-based medicine requires a critical appraisal
of the literature based upon study methodology and
number of subjects. Not all references are equally
robust. The findings of a large, prospective, randomized, and blinded trial should carry more weight
than a case report.
To help the reader judge the strength of each reference, pertinent information about the study, such
as the type of study and the number of patients in
the study, will be included in bold type following the
reference, where available.
1.
2.
3.
4.
5.
12.
13.
14.
15.
American Academy of Pediatrics. Rocky Mountain
Spotted Fever. In: Pickering LK, ed. 2003 Red Book:
Report of the Committee on Infectious Disease. Elk
Grove Village, IL: American Academy of Pediatrics;
2005:532-533. (Textbook chapter)
Heyneman D. The blight of the Bitterroot, the mysterious Rocky Mountain spotted fever, and the significant
role of Wilson and Chowning—a commentary.
Wilderness and Environmental Medicine 2001;12:118-120.
(Commentary)
Centers for Disease Control. Rocky Mountain Spotted
Fever. 20 May 2005. Available at:
http://www.cdc.gov/ncidod/dvrd/rmsf/index.htm.
Accessed 3 March 2006.
Ricketts, HT. Some Aspects of Rocky Mountain Spotted
Fever as Shown by Recent Investigations. Medical
Record 1909;76: 843-55. (Review Article, reprinted in
Reviews of Infectious Diseases 1991;13:1227-1240.)
Dumler JS, Walker DH. Rocky Mountain Spotted
Fever—Changing Ecology and Persisting Virulence. N
Engl J Med 2005;353:551-553. (Commentary)
Emergency Medicine Practice©
16.
17.
18.
19.
20.
21.
18
Kostman JR. Laboratory Diagnosis of Rickettsial
Diseases. Clin Dermatol 1996;14:301-306. (Review
Article, 58 references)
Treadwell TA, Holman RC, Clarke MJ, et al. Rocky
Mountain Spotted Fever in the United States, 19931996. Am J Trop Med Hyg 2000;63:21-26. (Retrospective
epidemiologic, 2313 cases)
Marshall GS, Gordon G, Stout BS, et al. Antibodies
Reactive to Rickettsia rickettsii Among Children Living
in the Southeast and South Central Regions of the
United States. Arch Pediatr Adolesc Med 2003;157:443448. (Retrospective, 300 patients)
Paddock CD, Holman RC, Krebs JW, et al. Assessing
the Magnitude of Fatal Rocky Mountain Spotted Fever
in the United States: Comparison of Two National Data
Sources. Am J Trop Med Hyg 2002;67:349-354.
(Retrospective epidemiologic )
Childs JE, Paddock CD. Passive Surveillance as an
Instrument to Identify Risk Factors for Fatal Rocky
Mountain Spotted Fever: Is There More to Learn? Am J
Trop Med Hyg 2002;66:450-457. (Review Article)
Dalton MJ, Clarke MJ, Holman RC, et al. National
Surveillance for Rocky Mountain Spotted Fever, 19811991: Epidemiologic Summary and Evaluation of Risk
Factors for Fatal Outcome. Am J Trop Med Hyg
1995;52:405-413. (Retrospecitive epidemiologic, 9223
cases)
Wilfert CM, MacCormack JN, Kleeman K.
Epidemiology of Rocky Mountain Spotted Fever as
Determined by Active Surveillance. J Infect Dis
1984;150:469-479. (Prospective epidemiologic)
CDC. Summary of Notifiable Diseases—United States,
2003. MMWR Morbid Mortal Wkly Rep 2005;52.
Current Trends Rocky Moutain Spotted Fever—United
States, 1990. MMWR Morb Mortal Wkly Rep 1991;40:451453. (Epidemiologic)
Sonenshine DE. Zoogeography of the American dog
tick, Demacentor variabilis. Recent Adv Acarol
1979;2:123-134.
Wilfert CM, MacCormack JN, Kleeman K.
Epidemiology of Rocky Mountain Spotted Fever as
Determined by Active Surveillance. J Infect Dis
1984;150:469-479. (Prospective epidemiologic)
Jones TF, Allen SC, Paddock CD, et al. Family Cluster
of Rocky Mountain Spotted Fever. Clin Infect Dis
1999;28:853-859. (Case Series)
Fatal Cases of Rocky Mountain Spotted Fever in
Family Clusters—Three States, 2003. MMWR Morb
Mortal Wkly Rep 2004;53:407-410. (Case Series)
Paddock CD, Greer PW, Ferebee TL, et al. Hidden
Mortality Attributable to Rocky Mountain Spotted
Fever: Immunohistochemical Detection of Fatal,
Serologically Unconfirmed Disease. J Infect Dis
1999;179:1469-1478. (Retrospective, 16 patients)
Archibald LK, Sexton DJ. Long-Term Sequelae of
Rocky Mountain Spotted Fever. Clin Infect Dis
1995;20:1122-1125. (Retrospective, 25 patients)
Bergeron JW, Braddom RL, Kaelin DL. Persisting
Impairment Following Rocky Mountain Spotted Fever:
April 2007 • EBMedicine.net
22.
23.
24.
25.
26.
27.
28.
29.
30.
31.
32.
33.
34.
35.
36.
37.
38.
39.
A Case Report. Arch Phys Med Rehabil 1997;78:12771280. (Case Report)
Demma LJ, Traeger MS, Nicholson WL, et al. Rocky
Moutain Spotted Fever from an Unexpected Tick
Vector in Arizona. N Engl J Med 2005;353:587-594.
(Retrospective)
Azad AF, Beard CF. Rickettsial Pathogens and their
Arthropod Vectors. Emerg Infect Dis 1998;4:179-185.
(Review Article, 31 references)
Niebylski ML, Peacock MG, Schwan TG. Lethal Effect
of Rickettsia ricketsii on Its Tick Vector. Appl Environ
Microbiol 1999;65:773-778. (Epidemiologic)
Thorner AR, Walker DH, Petri WA. Rocky Mountain
Spotted Fever. Clin Infect Dis 1998;27:1353-1360.
(Review Article, 50 references)
Needham GR. Evaluation of Five Popular Methods for
Tick Removal. Pediatrics 1985;75:997-1002.
Paddock CD, Brenner O, Vaid C, et al. Short
Report:Concurrent Rocky Mountain Spotted Fever in A
Dog and Its Owner. Am J Trop Med Hyg 2002;66:197199.
Walker DH, Valbuena GA, Olano JP. Pathogenic
Mechanisms of Diseases Caused by Rickettsia. Ann NY
Acad Sci 2003;990:1-11. (Basic Science Review Article,
63 references)
Roggli VL, Keener S, Bradford WD et al. Pulmonary
Pathology of Rocky Mountain Spotted Fever in
Children. Pediatr Pathol 1985;4:47-57. (Case Control)
Elghetany MT, Walker DH. Hemostatic Changes in
Rocky Mountain Spotted Fever and Mediterranean
Spotted Fever. Am J Clin Pathol 1999;112:159-168. (Basic
Science Review Article, 91 references)
Helmick CG, Bernard KW, D’Angelo LJ. Rocky
Mountain Spotted Fever: Clinical, Laboratory, and
Epidemiological Features of 262 Cases. J Infect Dis
1984;150:480-488. (Retrospective)
Kirk JL, Fine DP, Sexton DJ, et al. Rocky Mountain
Spotted Fever A Clinical Review Based on 48
Confirmed Cases, 1943-1986. Medicine 1990;69:35-45.
(Retrospective)
Sexton DJ, Corey GR. Rocky Mountain “Spotless” and
“Almost Spotless” Fever: A Wolf in Sheep’s Clothing.
Clin Infect Dis 1992;15:439-448. (Retrospective, 93
patients)
Verne GN, Myers BM. Jaundice in Rocky Mountain
Spotted Fever. Am J Gastroenterol 1994;89:446-448. (Case
Report)
Masters EJ, Olson GS, Weiner SJ, et al. Rocky Mountain
Spotted Fever—A Clinician’s Dilemma. Arch Intern
Med 2003;163:769-773. (Review Article, 73 references)
Razzaq S, Schurtze GE. Rocky Mountain Spotted
Fever: A Physicians’ Challenge. Pediatr Rev 2005;26:125129. (Review Article)
Benson P. Rocky Mountain Spotted Fever, Another
Important Cause of Fever and Rash. J Emerg Med
2004;27:415-418. (Letter)
Cunha BA. Rocky Mountain Spotted Fever Revisited.
Arch Intern Med 2004;164:221-222. (Letter)
Davis AE, Bradford WD. Abdominal Pain Resembling
EBMedicine.net • April 2007
40.
41.
42.
43.
44.
45.
46.
47.
48.
49.
50.
51.
52.
53.
54.
55.
19
Acute Appendicitis in Rocky Mountain Spotted Fever.
JAMA 1982;247:2811-2812. (Case Report)
Walker DH, Lesesne HR, Varma VA, et al. Rocky
Mountain Spotted Fever Mimicking Acute
Cholecystitis. Arch Intern Med 1985;145:2194-2196.
(Case Report)
Stevens DL. Streptococcal Toxic-Shock Syndrome:
Spectrum of Disease, Pathogenesis, and New Concepts
in Treatment. Emerg Infect Dis 1995;1:69-78. (Review
Article)
Nieburg PI. D’Angelo LJ, Herrmann KL. Measles in
Patients Susptected of Having Rocky Mountain
Spotted Fever. JAMA 1980;244:808-809. (Case Control
Study)
Nieburg PI. D’Angelo LJ, Herrmann KL. Measles in
Patients Susptected of Having Rocky Mountain
Spotted Fever. JAMA 1980;244:808-809. (Case Control
Study)
Current Trends Rocky Mountain Spotted Fever and
Human Ehrlichiosis—United States, 1989. MMWR
Morb Mortal Wkly Rep 1990;39:281-284. (Retrospective,
603 patients)
Centers for Disease Control. Human Ehrlichiosis in the
United States. 5 April 2000. Available at:
http://www.cdc.gov/ncidod/dvrd/ehrlichia/Signs/S
igns.htm. Accessed 18 April 2006.
Jacobs RF. Human Monocytic Ehrlichiosis: Similar to
Rocky Mountain Spotted Fever But Different. Pediatric
Annals 2002;31:181-184. (Review article, 24 references)
Carpenter CF, Gandhi TK, Kong LK, et al. The
Incidence of Ehrlichial and Rickettsial Infection in
Patients with Unexplained Fever and Recent History of
Tick Bite in Central North Carolina. J Infect Dis
1999;180:900-903. (Prospective, 35 patients)
Sexton DJ, Corey GR, Carpenter C, et al. Dual Infection
with Ehrlichia chaffeensis and a Spotted Fever Group
Rickettsia: A Case Report. Emerg Infect Dis 1998;4:311316. (Case Report)
Centers for Disease Control. Lyme Disease Symptoms.
13 October 2005. Available at:
http://www.cdc.gov/ncidod/dvbid/lyme/ld_humandisease_symptoms.htm Accessed 20 April 2006.
Wormser GP. Early Lyme Disease. N Engl J Med
2006;354:2794-801. (Review article, 51 references)
Hughes C. Rocky Mountain “Spotless” Fever with an
Erythema Migrans-Like Skin Lesion. Clin Infect Dis
1995;21:1328-1329. (Case Report)
Krause PJ. Babesiosis. Med Clin North Am 2002;86:36173. (Review Article)
Zhongzeng L, Turner RP. Pediatric Tick Paralysis:
Discussion of Two Cases and Literature Review. Pediatr
Neurol 2004;31:304-307. (Case Report)
Hattwick MAW, Retailliau H, O’Brien RJ, et al. Fatal
Rocky Mountain spotted fever. JAMA 1978;240:14991503. (Retrospective, 44 patients)
Centers for Disease Control. Meningococcal Disease. 12
October 2005. Available at: http://www.cdc.gov/ncidod/dbmd/diseaseinfo/meningococcal_g.htm
Accessed 20 April 2006.
Emergency Medicine Practice©
56. O’Reilly M, Paddock C, Elchos B, et al. Physician
Knowledge of the Diagnosis and Management of
Rocky Mountain Spotted Fever. Ann NY Acad Sci
2003;990:295-301. (Survey, 148 physicians)
57. Kirkland KB, Wilkinson WE, Sexton DJ. Therapeutic
Delay and Mortality in Cases of Rocky Mountain
Spotted Fever. Clin Infect Dis 1995;20:1118-1121.
(Retrospective, 148 patients)
58. Dorland’s Illustrated Medical Dictionary. Philadelphia:
W.B. Saunders; 2000:591-592.
59. Walker DH, Hawkins HK, Hudson P. Fulminant Rocky
Mountain Spotted Fever. Arch Pathol Lab Med
1983;107:121-125. (Retrospective, 3 patients)
60. Buckingham SC. Rocky Mountain Spotted Fever: A
Review for the Pediatrician. Pediatric Annals
2002;31:163-168. (Review article, 24 references)
61. Harrell GT. Rocky Mountain Spotted Fever. Medicine.
1949;28:333-370. (Review article)
62. Kirkland KB, Marcom PK, Sexton DJ, et al. Rocky
Mountain Spotted Fever Complicate by Gangrene:
Report of Six Cases and Review. Clin Infect Dis
1993;16:629-634. (Case Series, 6 patients)
63. Sundy JS, Allen NB, Sexton DJ. Rocky Mountain
Spotted Fever presenting with Acute Monartciular
Arthritis. Arthritis Rheum 1996;39:175-176. (Case
Report)
64. Massey EW, Thames T, Coffey CE, et al. Neurologic
Complications of Rocky Mountain Spotted Fever. South
Med J 1985;78:1288-1290. (Retrospective, 16 patients)
65. Conlon PJ, Procop GW, Fowler V, et al. Predictors of
Prognosis and Risk of Acute Renal Failure in Patients
with Rocky mountain Spotted Fever. Am J Med
1996;101:621-626. (Retrospective, 114 cases)
66. Toerner JG, Kumar PN, Garagusi WF. Guillain-Barre
Syndrome Associated with Rocky Mountain Spotted
Fever: Case Report and Review. Clin Infect Dis
1996;22:1090-1091. (Case Report)
67. Wei TY, Baumann RJ. Acute Disseminated
Encephalomyelitis After Rocky Mountain Spotted
Fever. Pediatr Neurol 1999;21:503-505. (Case Report)
68. Bolgiano EB, Sexton J. Tick-Borne Illnesses. In: Marx
JA, Hockberger RS, Walls RM, eds. Rosen’s Emergency
Medicine: Concepts and Clinical Practice. St. Louis:
Mosby; 2002:1879-1902. (Textbook chapter)
69. Doyle A, Bhalla KS, Jones JM, et al. Myocardial
Involvement in Rocky Mountain Spotted Fever: A Case
Report and Review. Am J Med Sci 2006;332:208-210.
(Case Report)
70. Bradford WD, Hackel DB. Myocardial Involvement in
Rocky Mountain Spotted Fever. Arch Pathol Lab Med
1978;102:357-9. (Case Series, 16 patients)
71. Feltes TF, Wilcox WD, Feldman WE, et al. M-mode
Echocardiographic Abnormalities in Rocky Mountain
Spotted Fever. South Med J 1984;77:1130-2. (Case Series,
9 patients)
72. Marin-Garcia J. Left ventricular dysfunction in Rocky
Mountain Spotted Fever. Clin Cardiol 1983;6:501-6.
73. Marin-Garcia J, Mirvis DM. Myocardial Disease in
Rocky Mountain Spotted Fever: Clinical, Functional,
Emergency Medicine Practice©
74.
75.
76.
77.
78.
79.
80.
81.
82.
83.
84.
85.
86.
87.
88.
89.
20
and Pathologic Findings. Pediatr Cardiol 1984;5:149-154.
(Review Article, 34 references)
Woodard BH, Farnham R, Bradford WD. Fatal Rocky
Mountain Spotted Fever. Arch Pathol Lab Med
1981;105:452-453.
Hall GW, Schwartz RP. White Blood Cell Count and
differential in Rocky Mountain Spotted Fever. NC Med
J 1979;40:212-214. (Retrospective, 27 patients)
Grindem CB, Breitschwerdt EB, Perkins PC, et al.
Platelet-associated Immunoglobulin (antiplatelet antibody) in Canine Rocky Mountain Spotted Fever and
Ehrlichiosis. J Am Anim Hosp Assoc 1999;35:56-61.
Haynes RE. Rocky Mountain Spotted Fever in
Children. J Pediatr 1970;76:685.
Sexton DJ, Clapp J. Inappropriate antidiuretic hormone
secretion. Occurence in a patient with Rocky
Mountain Spotted Fever. Arch Intern Med 1977;137:362363. (Case Report)
Abedon ST. Eubacterial Classification. 14 May 1998.
Available at: http://www.mansfield.ohiostate.edu/~sabedon/biol3018.htm Accessed 22 October
2006.
Chapman AS, Bakken JS, Folk SM, et al. Diagnosis and
Management of Tickborne Rickettsial Disease: Rocky
Mountain Spotted Fever, Ehrlichioses, and
Anaplasmosis—United States. MMWR Morbid Mortal
Wkly Rep 2006;55(RR04):1-27.
Walker DH. Rocky Mountain Spotted Fever:A Disease
in Need of Microbiological Concern. Clin Microbiol Rev
1989;2:227-40.
Greene CE, Marks MA, Lappin MR. Comparison of
Latex Agglutination, Indirect Immunofluorescent
Antibody, and Enzyme Immunoassay Methods for
Serodiagnosis of Rocky Mountain Spotted Fever in
Dogs. Am J Vet Res 1993;54:20-28. (Basic Science)
Kaplan JE, Schonberger LB. The Sensitivity of Various
Serologic Tests in the Diagnosis of Rocky Mountain
Spotted Fever. Am J Trop Med Hyg 1986;35:840-844.
(Basic Science)
Kostman JR. Laboratory Diagnosis of Rickettsial
Diseases. Clin Dermatol 1996;14:301-306. (Review article, 58 references)
Eremeeva ME, Dasch GA, Silverman DJ. Evaluation of
a PCR Assay for Quantitation of Rickettsia ricketsii and
Closely Related Spotted Fever Group Rickettsiae. J Clin
Microbiol 2003;41:5466-5472. (Basic Science)
University of North Carolina. Rocky Mountain Spotted
Fever Serologies. 24 September 2004. Available at:
http://www.pathology.unc.edu/labs/test/r/rmsf_ifa.
htm Accessed 26 October 2006.
Walker DH, Raoult D. Rickettsia rickettsii and Other
Spotted Fever Group Rickettsiae. In: Mandell GL,
Bennett JE, Dolin R, eds. Principles and Practice of
Infectious Diseases. Philadelphia: Elsevier; 2005:22872295. (Textbook chapter)
Hechemy KA. Correspondence. Am J Trop Med Hyg
1987;37:205-207. (Letter)
McCook TA, Briley C, Ravin CE. Roentgenographic
Abnormalities in Rocky Mountain Spotted Fever. South
April 2007 • EBMedicine.net
Mountain Spotted Fever in Dogs. Antimicrob Agents
Chemother 1991;35:2375-2381. (Prospective)
106.Breitschwerdt EB Papich MG, Hegarty, et al. Efficacy of
Doxycycline, Azithromycin, or Trovafloxacin for
Treatment of Experimental Rocky Mountain Spotted
Fever in dogs. Antimicrob Agents Chemother 1999;43:813821. (Prospective)
107.Tsai TF, Olson JG. Rickettsial Spotted Fever Infections:
Another Pediatric Indication for Fluoroquinolones?
Pedatr Infect Dis J 1995;14:635. (Letter)
108.Walker DH. Targetting Rickettsia. N Engl J Med
2006;354:1418-1420. (Commentary)
109.Peters TR, Edwards KM, Standaert SM. Severe
Ehrlichiosis in an Adolescent Taking TrimethoprimSulfamethoxazole. Pediatr Infect Dis J 2000;19:170-71.
(Case Report)
110.Brantley RK. Trimethoprim-Sulfamethoxazole and
Fulminant Ehrlichiosis. Pediatr Infect Dis J 2001;20:231233. (Letter)
111. Steigman AJ. Rocky Mountain Spotted Fever and the
Avoidance of Sulfonamides. J Pediatr 1977;91:163-164.
(Letter)
112.Woodward TE. Rocky Mountain Spotted Fever:
Epidemiological and Early clinical Signs are Keys to
Treatment and Reduced Mortality. J Infect Dis
1984;150:465-468. (Editorial)
113.Workman JB, Hightower JA, Borges FJ, et al. Cortisone
as an adjunct to chloramphenicol in the treatment of
Rocky Mountain Spotted Fever. New Engl J Med
1952;246:962-966.
114.Breitschwerdt EB, Davidson MG, Hegarty BC, et al.
Prednisolone at Anti-Inflammatory of
Immunosuppressive Dosages in Conjunction with
Doxycycline Does Not Potentiate the Severity of
Rickettsia ricketsii Infection in Dogs. Antimicrob Agents
Chemother 1997;41:141-147. (Prospective)
115.Donovan BJ, Weber DJ, Rublein JC, et al. Treatment of
Tick-Borne Diseases. Ann Pharmacother 2002;36:15901597. (Review article, 72 references)
116.Nadelman RB, Nowakowski J, Fish D, et al.
Prophylaxis with single-dose doxycycline for the prevention of Lyme disease after an Ixodes scapularis tick
bite. N Engl J Med 2001;345:79-84. (Prospective
Double-blind RCT, 482 patients)
117.Kenyon RH, Williams RG, Oster CN, et al. Prophylactic
Treatment of Rocky Mountain Spotted Fever. J Clin
Microbiol 1978;8:102-104. (Prospective)
118.Centers for Disease Control and Prevention. MMWR
Morb Mortal Wkly Rep 2000;49:885-888. (Case Report)
119.Rotz L, Callejas L, McKechnie D, et al. An epidemiologic and Entomologic Investigation of a Cluster of
Rocky Mountain Spotted Fever Cases in Delaware. Del
Med Jrl 1998;70:285-291. (Retrospective, 7 patients)
120.Hayes SF, Burgdorfer W. Reactivation of Rickettsia
rickettsii in Dermacentor andersoni Ticks: an
Ultrastructural Analysis. Infect Immun 1982;37:779-785.
121.Stewart RL, Burgdorger W, Needham GR. Evaluation
of Three Commerical Tick Removal Tools. Wilderness
and Environmental Medicine 1998;9:137-142.
Med J 1982;75:156-160. (Retrospective, 70 cases)
90. Bonawitz C, Castillo M, Mukherji SK. Comparison of
CT and MR Features with Clinical Outcome in Patients
with Rocky Mountain Spotted Fever. Am J Neuroradiol
1997;18:459-464. (Retrospective, 54 patients)
91. Baganz MD, Dross PE, Reinhardt JA. Rocky Mountain
Spotted Fever Encephalitis: MR Findings. Am J
Neuroradiol 1996;16:919-922.
92. Holman RC, Paddock CD, Curns AT, et al. Analysis of
Risk Factors for Fatal Rocky Mountain Spotted Fever:
Evidence for Superiority of Tetracyclines for Therapy. J
Infect Dis 2001;184:1437-1444. (Retrospective 213
patients)
93. Fishbein DB, Frontini MG, Giles R, Vernon LL. Fatal
Cases of Rocky Mountain Spotted Fever in the United
States, 1981-1988. Ann NY Acad Sci 1990;590:246-247.
(Retrospective)
94. Marks MI, LaFerriere C. Chloramphenicol: Recent
Developments and Clinical Indications. Clin Pharm
1982;1:315-320. (Review article, 29 references)
95. Purvis JJ, Edwards MS. Doxycycline Use for Rickettsial
Disease in Pediatric Patients. Pediatr Infect Dis J
2000;19:871-874. (Retrospective, 35 patients)
96. Akcam M, Artan R, Akcam FZ, et al. Nail Discoloration
Induced by Doxycycline. Pediatr Infect Dis J
2005;24:845. (Case Report)
97. Grossman ER, Walchek A, Freeman H. Tetracyclines
and Permanent Teeth: The Relation Between Dose and
Tooth Color. Pediatrics 1971;47:567-570. (Retrospective,
160 patients)
98. Lochary ME, Lockhart PB, Williams WT. Doxycycline
and Staining of Permanent Teeth. Pediatr Infect Dis J
1998;17:429-431. (Retrospective, 10 patients)
99. Ship JA. Tooth Discoloration. 27 October 2005.
Available at:
http://www.emedicine.com/derm/topic646.htm
Accessed 15 May 2006.
100.Ayaslioglu E, Erkek E, Oba AA, et al. Doxycyclineinduced Staining of Permanent Adult Dentition. Aust
Dent J 2005;50:273-275. (Case Series)
101.Yagupsky P, Gross EM, Alkan M, et al. Comparison of
Two Dosage Schedules of Doxycycline in Children
with Rickettsial Spotted Fever. J Infect Dis
1987;155:1215-1219. (Prospective Randomized, 60
patients)
102.DuPont HL, Hornick RB, Weiss CF. Evaluation of
Chloramphenicol Acid Succinate Therapy of Induced
Typhoid Feer and Rocky Mountain Spotted Fever. N
Engl J Med 1970;282:53-58. (Prospective, 8 patients)
103.Cale DF, McCarthy MW. Treatment of Rocky Mountain
Spotted Fever in Children. Ann Pharmacother
1997;31:492-494. (Review article, 23 references)
104.American Society of Health-System Pharmacists.
Chloramphenicol. Available at:
http://www.ashp.org/emergency/chloramphenicol.p
df Accessed 3 March 2006.
105.Breitschwerdt EB, Davidson MG, Aucoin DP, et al.
Efficacy of chloramphenicol, Enrofloxacin, and
Tetracycline for Treatment of Experimental Rocky
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122.Teece S, Crawford I. How to Remove a Tick. Emerg Med
J 2002;19:323-324. (Systematic review, 2 references)
123.Stallings SP. Rocky Mountain Spotted Fever and
Pregnancy: A Case Report and Review of the
Literature. Obstet Gynecol Surv 2001;56:37-42. (Review
Article, 20 references)
124.Markley KC, Levine AB, Chan Y. Rocky Mountain
Spotted Fever in Pregnancy. Obstet Gynecol 1998;91:860.
(Case Report)
125.Welch KJ, Rumley RL, Levine JA. False-Positive
Results in Serologic Tests for Rocky Mountain Spotted
Fever During Pregnancy. South Med J 1991;84:307-311.
(Prospective, 195 patients)
126.Gallis HA, Agner RC, Painter CJ. Rocky Mountain
Spotted Fever in Pregnancy. N C Med J 1984;45:187-188.
(Case Report)
127.Morrison RE, Lancaster L, Lancaster DJ, et al. Rocky
Mountain Spotted Fever in the Elderly. J Am Geriatrics
Soc 1991;39:205-208. (Case Reports)
128.Dumler JS, Wisseman CL, Fiset P, et al. Cell-mediated
Immune Responses of Adults to Vaccination,
Challenge with Rickettsia Rickettsii, or Both. Am J Trop
Med Hyg 1992;46:105-115. (Prospective)
129.Crosquet-Valdes PA, Diaz-Montero CM, Feng HM, et
al. Immunization with a Portion of Rickettsial Outer
Membrane Protein A Stimulates Protective Immunity
Against Spotted Fever Rickettsiosis. Vaccine
2002;20:979-988. (Basic Science)
130.Feng HM, Walker DH. Cross-protection Between
Distantly Related Spotted Fever Group Rickettsiae.
Vaccine 2003;21:3901-3905. (Basic Science)
131.Walker DH. Principles of the Malicious Use of
Infectious Agents to Create Terror: Reasons for
Concern for Organisms of the Genus Rickettsia. Ann
NY Acad Sci 2003;990:739-742. (Review Article, 15 references)
132.Bradshaw v Daniel, 854 SW2d 865 (Tenn 1993). (Legal
decision)
133.Arguin PM, Singleton J, Rotz LD, et al. An
Investigation into the Possibility of Transmission of
Tick-borne Pathogens via Blood Transfusion.
Transfusion 1999;39:828-833. (Retrospective)
134.Rallis RM, Kriesel JD, Dumler JS, et al. Rocky
Mountain Spotted Fever Following Cardiac
Transplantation. West J Med 1993;158:625-628. (Case
Report)
135.Gelfand MS, Chalmers BD, Killebrew L. Rocky
Mountain Spotted Fever: Legal Duty to Warn for
Noncontagious Disease. JAMA 1995;274:1586-1587.
(Letter)
CME Questions
49. Rocky Mountain Spotted Fever most commonly
occurs in which of the following seasons?
a. Summer
b. Spring
c. Fall
d. Winter
50. The most common symptom of RMSF is:
a. Fever
b. Headache
c. Rash
d. Myalgias
51. Which states consistently have the highest
reported incidence of RMSF?
a. Colorado and Wyoming
b. Idaho and Montana
c. North Carolina and Oklahoma
d. Vermont and Maine
e. Wisconsin and Indiana
52. Regarding serologic testing for RMSF:
a. Tests are often falsely negative in the first
one to two weeks
b. Weil-Felix has the greatest sensitivity and
specificity
c. Turnaround times are rapid
d. Antibiotics should be withheld until the test
results are known
53. The drug of choice for Rocky Mountain Spotted
Fever in children is:
a. Doxycycline
b. Chloramphenicol
c. Amoxicillin
d. Azithromycin
e. Ciprofloxacin
54. A 15-year-old male presents after a week long
camping trip in the Blue Ridge Mountains of
North Carolina with complaints of fever, muscle aches, headache, and nausea. He has no
rash, vital signs are stable, and he does not
appear severely ill. Which is of the following
is the best course of action?
a. Discharge home with reassurance and return
precautions
b. Treat empirically with doxycycline
c. Treat empirically with chloramphenicol
d. Send RMSF serologies and await results
prior to initiating treatment
Emergency Medicine Practice©
22
April 2007 • EBMedicine.net
60. In regards to its use in the treatment of RMSF,
doxycycline:
55. A 22-year-old man presents after a two week
hiking trip in the Ouachita Mountains of
Arkansas complaining of a tick bite. He denies
any complaints, and he removed the tick
immediately after finding it. Which of the following is the best course of action?
a. Frequently causes severe and irreversible
tooth staining
b. Is the second line therapy behind chloramphenicol
c. May cause severe side effects, such as aplastic anemia and “gray baby syndrome”
d. Is often still not used in children despite
being the drug of choice according to the
American Academy of Pediatrics
a. Discharge home with reassurance and return
precautions
b. Treat empirically with doxycycline
c. Treat empirically with chloramphenicol
d. Send RMSF serologies and await results
prior to initiating treatment
56. The best method of removing a tick is:
a. Burning with a match
b. Petroleum jelly
c. Cyanoacrylate glue
d. Steady pressure with forceps
57. The drug of choice for Rocky Mountain Spotted
Fever in the pregnant patient is:
Jump Ahead of the Class!
a. Doxycycline
b. Chloramphenicol
c. Amoxicillin
d. Azithromycin
e. Ciprofloxacin
EB Medicine's 2007 Lifelong Learning and SelfAssessment is designed exclusively to save you
time and money while preparing for this years
58. A 63-year-old man presents with fever, rash,
myalgias and shortness of breath. His vital
signs are T 102, P 110, R 24, BP 225/120, SaO2
86%. He relates a five day history of progressively worsening orthopnea, pedal edema, and
dyspnea on exertion. His wife recalls that he
was bitten by a tick while working in the yard
a week ago. After initial stabilization and
treatment, which of the following is the best
course of action?
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a. Discharge home with high dose chloramphenicol
b. Empiric IV doxycycline and admission
c. Send RMSF titers and admit
d. Discharge home with empiric doxycycline
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59. A 35-year-old woman presents in late summer
with fever, headache, and myalgias. You perform a lumbar puncture which shows 65
wbc/microliter, 10 rbc/microliter, glucose 54
milligrams/deciliter, protein 105
milligrams/deciliter. CSF gram stain is negative. Treatment should include:
a. Chloramphenicol
b. Doxycycline
c. Prednisone
d. Supportive care as this is aseptic meningitis
EBMedicine.net • April 2007
23
Emergency Medicine Practice©
Physician CME Information
Binders
Accreditation: This activity has been planned and implemented in accordance with the
Essentials and Standards of the Accreditation Council for Continuing Medical
Education (ACCME) through the joint sponsorship of Mount Sinai School of Medicine
and Emergency Medicine Practice. The Mount Sinai School of Medicine is accredited
by the ACCME to provide continuing medical education for physicians.
Emergency Medicine Practice has handsome
binders that are great for storing all your issues.
To order your binder for just $15, please email
[email protected], call 1-800-249-5770, or go
to www.empractice.com, scroll down, and click
"Binders" on the left side of the page.
Credit Designation: The Mount Sinai School of Medicine designates this educational
activity for a maximum of 48 AMA PRA Category 1 Credit(s)TM per year. Physicians
should only claim credit commensurate with the extent of their participation in the
activity.
Credit may be obtained by reading each issue and completing the printed post-tests
administered in June and December or online single-issue post-tests administered at
EBMedicine.net.
Target Audience: This enduring material is designed for emergency medicine physicians.
If you have any questions or comments, please
call or email us. Thank you!
Needs Assessment: The need for this educational activity was determined by a survey
of medical staff, including the editorial board of this publication; review of morbidity
and mortality data from the CDC, AHA, NCHS, and ACEP; and evaluation of prior
activities for emergency physicians.
Date of Original Release: This issue of Emergency Medicine Practice was published
April 1, 2007. This activity is eligible for CME credit through April 1, 2010. The
latest review of this material was March 1, 2007.
Discussion of Investigational Information: As part of the newsletter, faculty may be
presenting investigational information about pharmaceutical products that is outside
Food and Drug Administration approved labeling. Information presented as part of
this activity is intended solely as continuing medical education and is not intended to
promote off-label use of any pharmaceutical product. Disclosure of Off-Label Usage:
This issue of Emergency Medicine Practice discusses no off-label use of any pharmaceutical product.
Coming In Future Issues:
Complications in Pregnancy
Pediatric Toxicology
Faculty Disclosure: It is the policy of Mount Sinai School of Medicine to ensure objectivity, balance, independence, transparency, and scientific rigor in all CME-sponsored
educational activities. All faculty participating in the planning or implementation of a
sponsored activity are expected to disclose to the audience any relevant financial
relationships and to assist in resolving any conflict of interest that may arise from the
relationship. Presenters must also make a meaningful disclosure to the audience of
their discussions of unlabeled or unapproved drugs or devices.
Class Of Evidence Definitions
Each action in the clinical pathways section of Emergency Medicine
Practice receives a score based on the following definitions.
Class I
• Always acceptable, safe
• Definitely useful
• Proven in both efficacy and
effectiveness
Level of Evidence:
• One or more large prospective
studies are present (with rare
exceptions)
• High-quality meta-analyses
• Study results consistently positive
and compelling
Class II
• Safe, acceptable
• Probably useful
Level of Evidence:
• Generally higher levels of evidence
• Non-randomized or retrospective
studies: historic, cohort, or casecontrol studies
• Less robust RCTs
• Results consistently positive
Class III
• May be acceptable
• Possibly useful
• Considered optional or alternative
treatments
Level of Evidence:
• Generally lower or intermediate
In compliance with all ACCME Essentials, Standards, and Guidelines, all faculty for this
CME activity were asked to complete a full disclosure statement. The information
received is as follows: Dr. Davis, Dr. Marx, Dr. DeBileux, and Dr. Pauze report no significant financial interest or other relationship with the manufacturer(s) of any commercial product(s) discussed in this educational presentation.
levels of evidence
• Case series, animal studies, consensus panels
• Occasionally positive results
For further information, please see The Mount Sinai School of Medicine website at
www.mssm.edu/cme.
ACEP Accreditation: Emergency Medicine Practice is approved by the American
College of Emergency Physicians for 48 hours of ACEP Category 1 credit per annual
subscription.
Indeterminate
• Continuing area of research
• No recommendations until further
research
AAFP Accreditation: Emergency Medicine Practice has been reviewed and is acceptable for up to 48 Prescribed credits per year by the American Academy of Family
Physicians. AAFP Accreditation begins August 1, 2006. Term of approval is for two
years from this date. Each issue is approved for 4 Prescribed credits. Credits may
be claimed for two years from the date of this issue.
Level of Evidence:
• Evidence not available
• Higher studies in progress
• Results inconsistent, contradictory
• Results not compelling
AOA Accreditation: Emergency Medicine Practice has been approved for 48 Category
2B credit hours per year by the American Osteopathic Association.
Significantly modified from: The
Emergency Cardiovascular Care
Committees of the American Heart
Association and representatives
from the resuscitation councils of
ILCOR: How to Develop EvidenceBased Guidelines for Emergency
Cardiac Care: Quality of Evidence
and Classes of Recommendations;
also: Anonymous. Guidelines for
cardiopulmonary resuscitation and
emergency cardiac care. Emergency
Cardiac Care Committee and
Subcommittees, American Heart
Association. Part IX. Ensuring effectiveness of community-wide emergency cardiac care. JAMA
1992;268(16):2289-2295.
Earning Credit: Two Convenient Methods
Print Subscription Semester Program: Paid subscribers with current and valid licenses in the United States who read all CME articles during each Emergency Medicine
Practice six-month testing period, complete the post-test and the CME Evaluation
Form distributed with the December and June issues, and return it according to the
published instructions are eligible for up to 4 hours of CME credit for each issue. You
must complete both the post test and CME Evaluation Form to receive credit. Results
will be kept confidential. CME certificates will be delivered to each participant scoring
higher than 70%.
Online Single-Issue Program: Current, paid subscribers with current and valid licenses
in the United States who read this Emergency Medicine Practice CME article and
complete the online post-test and CME Evaluation Form at EBMedicine.net are eligible for up to 4 hours of Category 1 credit toward the AMA Physician’s Recognition
Award (PRA). You must complete both the post-test and CME Evaluation Form to
receive credit. Results will be kept confidential. CME certificates may be printed
directly from the Web site to each participant scoring higher than 70%.
Emergency Medicine Practice is not affiliated with any pharmaceutical firm or medical device manufacturer.
CEO: Robert Williford President and Publisher: Stephanie Williford Director of Member Services: Liz Alvarez
Direct all editorial or subscription-related questions to EB Medicine: 1-800-249-5770 • Fax: 1-770-500-1316 • Non-U.S. subscribers, call: 1-678-366-7933
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Emergency Medicine Practice (ISSN Print: 1524-1971, ISSN Online: 1559-3908) is published monthly (12 times per year) by EB Practice, LLC, 305 Windlake Court, Alpharetta, GA 30022. Opinions
expressed are not necessarily those of this publication. Mention of products or services does not constitute endorsement. This publication is intended as a general guide and is intended to supplement, rather than substitute, professional judgment. It covers a highly technical and complex subject and should not be used for making specific medical decisions. The materials contained herein
are not intended to establish policy, procedure, or standard of care. Emergency Medicine Practice is a trademark of EB Practice, LLC. Copyright © 20076 EB Practice, LLC. All rights reserved. No
part of this publication may be reproduced in any format without written consent of EB Practice, LLC. Subscription price: $299, U.S. funds. (Call for international shipping prices.)
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April 2007 • EBMedicine.net