ROCKY MOUNTAIN SPOTTED FEVER
Demetre C. Daskalakis, MD
September 6, 2002
History
Rocky Mountain Spotted Fever (RMSF) was first recognized in 1896 in the Snake River Valley of Idaho.
It was originally referred to as “black measles” because of its characteristic rash. The causative organism, Rickettsia
rickettsii, was discovered several years later by Howard Taylor Ricketts (who tragically died of endemic typhus,
another rickettsial disease, shortly after he completed his research on RMSF). The severity of the RMSF problem
led to the creation of the Rocky Mountain Laboratory in Hamilton, Montana in the early 20 th century to research this
often fatal disease.
The Organism/Reservoirs/Pathophysiology
Rickettsia rickettsii is an obligate intracellular bacterium. In humans, rickettsiae invade endothelia of small
and medium-size blood vessels. The endothelial cells are damaged by this infection and necrose leading to
extravisation of blood through these defects into surrounding tissue. The infection induces an acute vasculitic
process that leads to increased vascular permeability. It is this increased vascular permeability that leads to several
features of RMSF:
 Characteristic rash of RMSF
 Activation of clotting factors
 Edema,
 Hypotension,
 Hypoalbuminemia,
 Reduced tissue perfusion leading to end-organ damage.
RMSF is a zoonosis. Ticks are the natural hosts, acting as reservoirs and vectors. Only hard ticks are
infected with this organism, most commonly the American Dog Tick in the eastern U.S. (Dermacentor variabilis)
and The Rocky Mountain Wood Tick in the western U.S.(Dermacentor andersoni). Other ticks may be infected, but
their role in the epidemiology of RMSF is minor. The disease is transmitted between ticks and between ticks and
the animals on which they feed. Interestingly the organism is transmitted sexually and vertically (transovarial
transmission) between ticks. Humans are accidentally infected in the course of arthropod attack. They are not
thought to be a link in the natural life cycle the disease. Exposure to tick fluids and aerosol can also transmit RMSF.
The organism takes about six hours to travel from the salivary glands of ticks to the host, so prolonged
attachment is necessary to transmit the disease. Incorrect removal of ticks allows for injection of infected material
into the host and potentially adequate organism burden for infection.
Epidemiology
RMSF has been a reportable disease since 1920s. 500-1200 cases are reported annually. The majority
(90%) of infections occur April through September because of the increased numbers of Dermacentor ticks, though
winter cases have been reported. The name Rocky Mountain Spotted Fever is a geographic misnomer. The disease
is most common in the South Atlantic states of the US. Oklahoma and North Carolina account for 34% of all US
cases of RMSF. Though pacific states are still affected, only 3% of cases occur in the Rocky Mountain area.
Incidence of RMSF is higher in Caucasian males and children. Dog exposure and residence near wooded
areas with high grass are risk factors. Fatalities occur more commonly in:
 Patients older than 40 y/o
 Non-Caucasians
 Males
 Patients with no headache, rash or tick exposure history (likely because of treatment delay).
 Patients not treated for >5 days after onset of symptoms
Clinical Manifestations
The classic triad of fever, rash and history of tick bite is cited frequently in the clinical diagnosis of RMSF.
It is present in only 3-18% of presenting patients. Generally the incubation of the disease is 2-14 days, mean
incubation of 7 days. 66% of patients develop fevers >102F in the first three days of illness. Other non-specific
complaints such as nausea, vomiting, severe headache, abdominal pain, diarrhea, muscle pain, and lack of appetite
predominate in the early phase of the disease. A history of tick exposure is identified in 85% of patients.
Beth Israel Deaconess Medical Center Residents’ Report
Skin rash appears 2-3 days after the onset of illness. It starts off as a macular, blanching rash on the wrist
and ankles that later becomes petechial. The palms and soles are often not spared. The rash can become confluent
and areas of skin supplied by terminal arteries (fingers, toes, nose, ears, genitals) may become necrotic. Younger
patients will tend to form the rash earlier and 10-15% of patients may actually never develop the rash (spotless
RMSF). In general adults are more likely to present with atypical symptoms and no rash. Lab abnormalities are
usually non-specific and include:
 Hyponatremia
 Elevated LFTs,
 Thrombocytopenia.
Complications of infection are caused by the vasculitic nature of the infection.
 Encephalitis

Non-cardiogenic pulmonary edema
 Cardiac arrhythmia
 ARDS
 GI bleed
 Skin necrosis

Long-term effects are mainly neurologic or related to loss of limb from ischemia.
A group of African –American patients with G6PD-deficiency suffer a far more fulminant course when afflicted
with RMSF. Death often occurrs within 5 days of the onset of illness. Hemolysis is the likely cause of this
accelerated decompensation.
The mortality associated with RMSF is very high with 20-25% of patients dying if untreated and 5% dying
even with appropriate antibiotics. Delay in treatment is a major factor in outcome primarily since the diagnosis
during the critical part of the illness is a clinical one.
Diagnosis
The diagnosis is a clinic and based on H and P. Direct immunofluorescence or immunoperoxidase staining
of skin biopsies for detection of R. rickettsii is 70-90% sensitive, but is not useful in patients without a rash or if they
have been treated with antibiotics for greater than 48 hours. PCR is usually negative early in the disease when
therapeutic decisions are made. Serology becomes positive 7-10 days after onset of symptoms. Usually acute and
convalescent titers are compared. A fourfold rise constitutes a serologic diagnosis. Other less sensitive tests like the
Weil-Felix test exist but should not be used.
Therapy
Tetracycline and chloramphenicol are the standby therapies for RMSF. One study that may be confounded
by several factors indicates that outcome may be better with tetracyclines. MICs for doxycycline (0.06-0.1) are
lower than tetracycline or chloramphenicol ( 0.25 and 0.3-0.5, respectively), so it should be our antibiotic of choice
to treat RMSF. Some sources recommend using chloramphenicol in cases with severe CNS infection or if N.
meningitides is a serious part of the differential. Doxycycline has the added benefit of being active against Erlichia
chaffeensis that may have a very similar clinical presentation and be confused for RMSF. There may also be a role
for the fluoroquinilones. Therapy should be based on clinical suspicion rather than serology or other RMSF-specific
data since delay in therapy increases risk of mortality.
Prevention
Common sense tick preventative measures and adequate removal of ticks when attached are the best
advice.
Bibliography
Thorner, A. et al. “Rocky Mountain Spotted Fever.” CID. 1998; 27: 1353-60.
CDC Web Site
Beth Israel Deaconess Medical Center Residents’ Report
Beth Israel Deaconess Medical Center Residents’ Report