RMSF occurs in 47 states (with the highest prevalence in the south-central and southeastern states) as well as in Canada, Mexico, and Central and South America. The infection is transmitted by:
- Dermacentor variabilis, the American dog tick, in the eastern two-thirds of the United States and California;
- D. andersoni, the Rocky Mountain wood tick, in the western United States;
- Rhipicephalus sanguineus in Mexico, Arizona, and probably Brazil; and
- Amblyomma cajennense in Central and South America.
Maintained principally by transovarian transmission from one generation of ticks to the next, R. rickettsii can be acquired by uninfected ticks through the ingestion of a blood meal from rickettsemic small mammals.
Humans become infected during tick season (in the Northern Hemisphere, from May to September), although some cases occur in winter. The mortality rate was 20–25% in the preantibiotic era and remains at 3–5% principally because of delayed diagnosis and treatment. The case-fatality ratio increases with each decade of life above age 20.
Pathogenesis
R. rickettsii organisms are inoculated into the dermis along with secretions of the tick's salivary glands after 6 h of feeding. The rickettsiae spread lymphohematogenously throughout the body and infect numerous foci of contiguous endothelial cells. The dose-dependent incubation period is 1 week (range, 2–14 days). Occlusive thrombosis and ischemic necrosis are not the fundamental pathologic basis for tissue and organ injury. Instead, increased vascular permeability, with resulting edema, hypovolemia, and ischemia, is responsible. Consumption of platelets results in thrombocytopenia in 32–52% of patients, but disseminated intravascular coagulation with hypofibrinogenemia is rare. Activation of platelets, generation of thrombin, and activation of the fibrinolytic system all appear to be homeostatic physiologic responses to endothelial injury.
Clinical Manifestations
- Early in the illness, when medical attention usually is first sought, RMSF is difficult to distinguish from many self-limiting viral illnesses. Fever, headache, malaise, myalgia, nausea, vomiting, and anorexia are the most common symptoms during the first 3 days.
- The progressive nature of the infection is clearly manifested in the skin. Macules (1–5 mm) appear first on the wrists and ankles and then on the remainder of the extremities and the trunk. Later, more severe vascular damage results in frank hemorrhage at the center of the maculopapule, producing a petechia that does not disappear upon compression. This sequence of events is sometimes delayed or aborted by effective treatment.
- Renal failure, often reversible with rehydration, is caused by acute tubular necrosis in severe cases with shock.
- Hepatic injury with increased serum aminotransferase concentrations is due to focal death of individual hepatocytes without hepatic failure. Jaundice is recognized in 9% of cases and an elevated serum bilirubin concentration in 18–30%.
- Life-threatening bleeding is rare. Anemia develops in 30% of cases and is severe enough to require transfusions in 11%. Blood is detected in the stools or vomitus of 10% of patients, and death has followed massive upper gastrointestinal hemorrhage.
- Other characteristic clinical laboratory findings include increased plasma levels of proteins of the acute-phase response (C-reactive protein, fibrinogen, ferritin, and others), hypoalbuminemia, and hyponatremia (in 56% of cases) due to the appropriate secretion of antidiuretic hormone in response to the hypovolemic state.
- Myositis occurs occasionally, with marked elevations in serum creatine kinase levels and multifocal rhabdomyonecrosis.
- Ocular involvement includes conjunctivitis in 30% of cases and retinal vein engorgement, flame hemorrhages, arterial occlusion, and papilledema with normal CSF pressure in some instances.
- In untreated cases, the patient usually dies 8–15 days after onset. A rare presentation, fulminant RMSF, is fatal within 5 days after onset. This fulminant presentation is seen most often in male black patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency and may be related to an undefined effect of hemolysis on the rickettsial infection. Although survivors of RMSF usually return to their previous state of health, permanent sequelae, including neurologic deficits and gangrene necessitating amputation of extremities, may follow severe illness.
Diagnosis
The diagnosis of RMSF during the acute stage is more difficult than is generally appreciated. The most important epidemiologic factor is a history of exposure to a potentially tick-infested environment within the 12 days preceding disease onset during a season of possible tick activity.
The differential diagnosis for early clinical manifestations of RMSF (fever, headache, and myalgia without a rash) includes:
- influenza,
- enteroviral infection,
- infectious mononucleosis,
- viral hepatitis,
- leptospirosis,
- typhoid fever,
- gram-negative or gram-positive bacterial sepsis,
- HME,
- HGA,
- murine typhus,
- sylvatic flying-squirrel typhus,
- rickettsialpox,
- enterocolitis (may be suggested by nausea, vomiting, and abdominal pain),
- bacterial or viral meningoencephalitis (may be suggested by CNS involvement),
- bronchitis or pneumonia (may be suggested by cough, pulmonary signs, and chest radiographic opacities).
At presentation during the first 3 days of illness, only 3% of patients exhibit the classic triad of fever, rash, and history of tick exposure. When a rash appears, a diagnosis of RMSF should certainly be considered. However, many illnesses considered in the differential diagnosis may also be associated with a rash, including:
- rubeola,
- rubella,
- meningococcemia,
- disseminated gonococcal infection,
- secondary syphilis,
- toxic shock syndrome,
- drug hypersensitivity,
- idiopathic thrombocytopenic purpura,
- thrombotic thrombocytopenic purpura,
- Kawasaki syndrome,
- immune complex vasculitis.
The most common serologic test for confirmation of the diagnosis is the indirect immunofluorescence assay. Not until 7–10 days after onset is a diagnostic titer of 1:64 usually detectable. The sensitivity and specificity of the indirect immunofluorescence assay are 94–100% and 100%, respectively.
The only diagnostic test that is useful during the acute illness is immunohistologic examination of a cutaneousbiopsy sample from a rash lesion for R. rickettsii. Examination of a 3-mm punch biopsy from such a lesion is 70% sensitive and 100% specific.
The sensitivity of polymerase chain reaction (PCR) amplification and detection of R. rickettsii DNA in peripheral blood is improving.
Cultivation of rickettsiae in cell culture is feasible but is seldom undertaken because of biohazard concerns.
Treatment
- The drug of choice for the treatment of both children and adults with RMSF is doxycycline, except when the patient is pregnant or allergic to this drug. Doxycycline is administered orally (or, in the presence of coma or vomiting, intravenously) at 200 mg/d in two divided doses. For children with suspected RMSF, up to five courses of doxycycline may be administered with minimal risk of dental staining.
- Other regimens include oral tetracycline (25–50 mg/kg per day) in four divided doses.
- Treatment with chloramphenicol, a less effective drug, is advised only for patients who are pregnant or allergic to doxycycline.
- The antirickettsial drug should be administered until the patient has been afebrile and improving clinically for 2–3 days.
Prevention
Avoidance of tick bites is the only available preventive approach. Use of protective clothing and tick repellents, inspection of the body once or twice a day, and removal of ticks before they inoculate rickettsiae reduce the risk of infection.
Reference:
Harrison's Principles of Internal Medicine 18th Edition.