Hello, my name is Dr. Paige Armstrong,
Medical Epidemiologist with the Rickettsial Zoonoses Branch
at the CDC.
I am also an Emergency Medicine Physician.
Today, I'm going to discuss RMSF and provide information
to help frontline healthcare providers recognize
and treat this rapidly progressive, fatal disease.
Rocky Mountain spotted fever, or RMSF,
is the most severe rickettsiosis in the United States,
with mortality rates as high as 25 percent in untreated cases.
RMSF poses a diagnostic challenge for providers
because early symptoms are often similar
to other febrile illnesses, and yet decision to treat is based
on clinical diagnosis.
The sudden onset of fever and headache at the beginning
of illness prompts most people to visit a healthcare provider
in the first few days of symptoms.
Since most deaths occur within the first eight days of illness,
clinical consideration and early treatment during these initial
encounters are critical
to prevent severe disease and death.
The most important thing frontline providers can do is
to keep RMSF in the differential,
because if you are not thinking about it, you will miss it!
Here are the key clinical messages every provider should
know about RMSF: -It's a rapidly progressing tickborne disease
with non-specific clinical findings during early illness;
-Doxycycline is the drug of choice for treating people
of all ages; -Treatment is most effective at preventing death
and severe disease when started within the first five days
of symptoms; and -Never wait for the rash to begin treatment.
RMSF is caused by infection with Rickettsia rickettsii,
an obligate intracellular bacterium,
transmitted through the bite of an infected tick.
It is spread by at least three species of ticks
in the United States, including the American dog tick,
the Rocky Mountain wood tick, and,
in parts of the southwestern United States
and Mexico, the brown dog tick.
RMSF cases occur throughout the United States,
but are most commonly reported from North Carolina, Tennessee,
Missouri, Arkansas, and Oklahoma.
The first manifestations of RMSF begin 3 to 12 days
after the bite of an infected tick.
However, about half
of all affected people don't report a tick bite.
Initial symptoms include abrupt onset of high fever,
headache, myalgia, and malaise.
Children with RMSF are less likely to report a headache
than adults, but more likely to experience periorbital edema
or edema involving the dorsum of the hands.
If laboratory tests are performed,
white blood cell count, platelets, and electrolytes tend
to fall within normal limits during early illness.
By days two through four of clinical illness,
symptoms will often include abdominal pain, nausea,
vomiting, cough, rash, and worsening myalgia.
Laboratory diagnostics may show elevated hepatic transaminases
or mild thrombocytopenia.A classic case
of RMSF involves a rash that appears two to four days
after the onset of fever as small, flat, pink macules
on the wrists, forearms, ankles,
and spreads to include the trunk
and sometimes the palms and soles.
While most patients develop a rash during the course
of illness, less than 50 percent
of patients have a rash during the first three days,
when most first seek medical care.
In fact, late-onset rash is a risk factor for fatal outcome,
so the clinician should never wait for a rash
to appear to treat for RMSF.
Doxycycline is the treatment of choice
for RMSF for all age groups.
It's most effective at preventing severe disease
if administered within the first five days of illness.
The use of antibiotics other than doxycycline is associated
with a higher risk of fatality.
Doxycycline has not been shown to cause tooth staining
in children when used in the dose
and duration recommended for RMSF.
Minimum treatment duration is five to seven days,
or at least three days after fever subsides
and until there is evidence of clinical improvement.
If treatment is not initiated, and the disease is allowed
to progress, days five through seven
of illness are characterized by high fever;
worsening abdominal pain, which can mimic acute appendicitis
or cholecystitis; and worsening respiratory status.
The rash becomes petechial and more widespread.
These symptoms are a reflection
of the widespread vasculitis caused by R. rickettsii.
Laboratory tests around days five
to seven reflect worsening thrombocytopenia,
elevated hepatic transaminases,
and electrolyte abnormalities, such as hyponatremia.
Beyond day seven of illness, irreversible damage
to vascular endothelium leads to diffuse purpura,
necrosis of digits, septic shock, renal failure,
pulmonary edema, cerebral edema, altered mental status, and coma.
People who survive can experience severe sequela,
such as necrosis, necessitating amputation;
persistent neurologic deficits; and permanent organ damage.
The most frequently used method for confirmation is serology,
which measures the immune response,
and requires a four-fold or greater rise
in IgG antibody titer between acute
and convalescent-phase sera.
Acute serum samples should be taken in the first week
of illness or while exhibiting symptoms,
and convalescent two to four weeks later.
A single serology result cannot confirm RMSF infection.
Polymerase chain reaction (PCR) assays are also used
to detect R. rickettsii in whole blood
or tissue during the first week of illness.
Positive PCR results indicate the presence
of R. rickettsii in the sample.
Rickettsia circulate in low numbers
in the bloodstream early in infection.
A negative PCR test in the first few days
of illness may not definitively rule out infection.
Because RMSF can progress rapidly to severe illness,
the decision to treat should be based on clinical suspicion.
Prophylactic use of doxycycline following tick bites is not
recommended to prevent RMSF, and may confound
or delay presentation, making it more difficult
to diagnose correctly.
It's true that RMSF can pose a diagnostic dilemma, however,
there are things that can help guide clinical decisions.
Number one - Assess for risk factors.
Was the person exposed to ticks?
Are they around dogs?
Have they been to an endemic area?
Number Two - Look for red flags.
Persistent high fever, subtle laboratory abnormalities,
failed initial treatment, patient appears toxic or unwell.
Remember, this is a widespread vasculitis
so patients usually feel ill.
Number three - Treat based on level of clinical suspicion.
Even if you decide not to treat initially,
consider next-day follow-up, and educate patients or care takers
about the symptoms to watch for and the importance
of returning for care.
Thank you for your time and attention.
Please share this knowledge
with other providers and your patients.