Rocky Mountain Spotted Fever


Rocky Mountain spotted fever (RMSF) is one of about a dozen spotted fever illnesses found in the Americas, Europe, Asia and Australia. All are caused by bacteria belonging to the genus Rickettsia, a group of pleomorphic (shape-changing), non-motile microbes that replicate only inside of eukaryotic host cells.

Incidence of Rocky Mountain spotted fever cases per million population, 1993-1996, based on national surveillance figures. Reprinted from Treadwell TA, Holman RC, Clarke MJ, et al. Rocky Mountain spotted fever in the United States, 1993-1996. Am J Trop Med Hyg 2000;63:21-26.

Although first described in the Snake River Valley region of Idaho in 1896 (hence its name), Rocky Mountain spotted fever is actually more common in the south Atlantic and south central parts of the United States. It is caused by Rickettsia rickettsii and is transmitted to humans in the United States by two primary tick vectors, the American dog tick (Dermacentor variabilis) and the Rocky Mountain wood tick (Dermacentor andersoni). The brown dog tick, Rhipicephalus sanguineus, has been implicated in some cases of RMSF as well.

Prior to the antibiotic era, Rocky Mountain spotted fever had a mortality rate of up to 30%. Even today, it remains the most common fatal tick-borne disease in the United States; about three to five percent of patients who acquire the infection will die from it. Most of these fatalities occur in the very young and very old and are due to delayed diagnosis and treatment.

The Centers for Disease Control typically receives somewhere between 300-1200 case reports of RMSF each year, although the number has been increasing in recent years. As with many tick-borne infections, there is a seasonal peak in the late spring and summer months, with May, June, and July accounting for the most cases. More than 90% of cases are reported from April through September. The disease strikes children disproportionately — peak incidence is in the five to nine age group, and more than half of all reported cases involve children under 15 years old.

Signs and Symptoms

The usual incubation time between tick bite and symptom onset is five to ten days. Only about half of patients recall a preceding tick bite. Initial symptoms of Rocky Mountain spotted fever are usually non-specific, consisting of fever, severe headache, myalgias, nausea, and loss of appetite. Many patients will present to physicians before the hallmark rash develops, which complicates diagnosis and increases the disease’s potential deadliness.

Rash onset is subtle and usually develops within two to five days after symptoms begin. The rickettsiae spread through the lymphatic system, eventually parasitizing and multiplying within endothelial cells. As the host cells die, blood leaks into adjacent tissues, causing both rash and damage to internal organs. Typically, pale spots first appear on the patient’s extremities (hands, feet, forearms, and ankles) and eventually spread inward, toward the trunk.

A spotted rash on a person's arm.

Classic rash of Rocky Mountain spotted fever. Photo courtesy of the Centers for Disease Control and Prevention.

The “classic” RMSF rash, consisting of small, bright red petechial (spotted) lesions, does not usually appear until almost a week after symptom onset. Estimates vary as to its prevalence, with most sources stating that it presents eventually in about half of all RMSF patients. Close to 5% of patients will develop gangrene or skin necrosis, sometimes requiring amputation of the affected extremities.

Around 10-15% of RMSF patients will not develop rash at any stage.

Rocky Mountain spotted fever is multisystemic and potentially severe. Central nervous system manifestations include lethargy and confusion (about 25% of all cases), ataxia (18%), coma (9-10%), and seizures (8%). Other neurologic manifestations include meningitis, cranial neuropathies, deafness, paralysis, spasticity, vertigo, aphasia, and photophobia. Ophthalmologic complications can also occur. In addition, RMSF affects the respiratory system, the gastrointestinal system, and the renal system. Pulmonary involvement includes edema, pneumonia, and respiratory distress syndrome. Microcirculatory vasculitis can lead to myocarditis. Close to 10% of patients develop jaundice during the course of their illness; a similar percentage will produce stools positive for occult blood. Hospitalization is frequently required in advanced cases of RMSF.

African-American males are at particular risk for serious complications of Rocky Mountain spotted fever, as they are genetically more likely to be deficient in glucose-6-phosphate dehydrogenase (G6PD), an enzyme associated with the maintenance of membrane integrity in red blood cells.


While a number of laboratory tests are available for Rocky Mountain spotted fever, none are both rapid and sensitive enough to provide useful diagnostic assistance to the examining physician. As prompt treatment of RMSF is critical to a positive outcome, diagnosis should be made on clinical grounds — i.e., history, epidemiology, and clinical exam. This can be challenging, as many patients will not recall the tick bite.

Conventional blood tests can produce results that hint at RMSF. Among the typical findings are hypoanotremia (low sodium), thrombocytopenia, white blood cell abnormalities, and/or elevated liver enzymes.

Serological assays are used mostly to confirm the diagnosis after treatment has been initiated. Indirect immunofluorescence assays (IFA) of both IgM and IgG antibodies are most commonly employed, but enzyme linked immunosorbent assays (ELISA) and dot immunoassays are also available. Complement fixation is less sensitive, and less frequently used. Immunostaining of biopsied skin rashes can also be performed and is very rapid; results are available in a few hours. However, the test is only 70% sensitive, so a negative result does not exclude the diagnosis.

Polymerase chain reaction (PCR) assays for R. rickettsii DNA are considered perhaps the most timely and specific test for RMSF overall, but are still not widely available.