Rocky Mountain spotted fever (RMSF) is
one of the severest infectious disease, with a mortality in previously healthy
persons of 20% before the advent of antimicrobial therapy.
RMSF is the
most important rickettsiosis in the United States from the aspects of
morbidity and mortality. However, contrary to its name, cases occur
throughout the U.S.A. as well as in Central and South America with the
majority of cases occurring in the Southeastern states.
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R.
rickettsii are released from the salivary glands of a feeding
Dermacentor variabilis, D. andersoni, Rhipicephalus sanguineus, or
Amblyomma cajennense tick and are injected into the feeding blood pool
in the host’s skin.
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Clinical
presentation:
After an incubation period of 2 to 12 days the patient develops severe
headache, fever, and frequently nausea, vomiting, or abdominal pain.
A
maculopapular rash appears on the wrists and ankles 2 to 5 days later,
usually spreads to involve the trunk, palms, and may become petecheal.
Delay or absence of rash and frequent lack of a history of tick bite
make misdiagnosis and fatality a genuine problem.
In severe
cases the patient may manifest signs of encephalitis, noncardiogenic
pulmonary edema, skin necrosis, coagulopathy with bleeding, acute
renal failure failure, jaundice, hypovolemic shock.
In fatal
cases death usually ensues 8 to 15 days after onset of symptoms.
There is a
fulminant form of RMSF observed most often in glucose-6-phosphate
dehydrogenase deficient black males in which the patient may die
before the fifth day of illness.
Early
treatment with tetracycline or chloramphenicol cures most patients ;
however, late diagnosis and inappropriate treatment result in an
overall mortality of 3% to 8%.
Pathological presentation:
Rickettsiae spread via the
blood stream, enter endothelial cells, proliferate within the
cytoplasm and nuclei of endothelial and vascular smooth muscle cells
of the microcirculation of virtually all organs, and directly injure
the foci of infected cells.
The consequence is systemic
vascular damage that is the pathologic basis for the rash,
interstitial pneumonia, interstitial myocarditis, meningoencephalitis,
hepatic portal triaditis, and interstitial nephritis.
Microscopically the
vasculitis consists of swollen or necrotic endothelial cells ;
intramural and perivascular infiltration, predominantly by macrophages
and T-lymphocytes with few polymorphonuclear leukocytes ;
focal extravasation of erythrocytes ; and occasionally, usually
nonocclusive, eccentric thrombi in the foci of rickettsial infection.
In the skin these foci are located principally in the dermis.
In the brain the lesions
assume a characteristic appearance, so-called typhus nodules, found
most frequently in the brain stem. These perivascular
accumulations of mononuclear cells, which measure 100 to 180
micrometer in diameter, indicate a probable rickettsial infection
though they are not pathognomonic. Other neuropathologic lesions
include microinfarcts of white matter and a mild mononuclear cell-rich
leptomeningitis.
Lungs are congested and heavy.
Microscopic pulmonary lesions include mononuclear interstitial
pneumonia and interstitial and alveolar edema and hemorrhages.
The heart is grossly normal except for
epicardial petechiae, but it usually manifests a mild mononuclear
interstitial myocarditis on microscopic examination.
The hepatic portal triaditis and
multifocal perivascular interstitial nephritis correspond to foci of
infection of hepatic portal blood vessels and the renal
microcirculation near the corticomedullary junction, respectively.
Erythrophagocytosis occurs in Kupffer cells and macrophages within
sinus of lymph nodes.
In fulminant RMSP there are more
thrombi and fewer intramural and perivascular leukocytes in foci of
vascular injury.
Disseminated vascular foci of
rickettsial infection and microvascular injury result in leakage of
intravascular fluid into the interstitial space with consequent edema
and hypovoluemia.
Consumption of platelets and
coagulation factors in thrombi at the sites of injury can cause
thrombocytopenia and in very severe cases more severe coagulopathy.
Focal lesions in the skin are the cause
of rash. Vasodilatation and petechiae are the basis of the cutaneous
erythematous macules and central “spots” respectively.
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Increased vascular permeability of the
infected pulmonary microcirculation may result in noncardiogenic
pulmonary edema. Myocardial injury is not a significant factor.
Central nervous system lesions are the
cause of coma, seizures, multifocal, neurologic signs, and probably
cardiorespiratory arrest.
Jaundice correlates with hemolysis and
portal triadal inflammation.
Acute renal failure results from
hypovolemic prerenal azotemia or, in more severe cases, acute tubular
necrosis.
Vasculitis in the gastrointestinal
tract is the apparent pathologic basis for nausea, vomiting, and
abdominal pain and tenderness.
Pathogenesis:
Thrombosis
and activation of the kallikrein-kinin pathways may exacerbate the
disease and the acute-phase response presumably mediated by
interleukin-1 is observed. R. rickettsii does not seem to
produce a toxin. Direct injury of infected cells by rickettsiae has
been documented. The pathogenic mechanisms of the host cell injury
have not been elucidated though cell membrane injury by phospholipase
A and protease enzymes has been proposed.
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