Rocky Mountain Spotted Fever (Rickettsia rickettsii)

Etiology

Rickettsia rickettsii, the most well-described and most lethal of the spotted group rickettsiae, causes Rocky Mountain spotted fever (RMSF). It is a coccobacillary, obligate, intracellular organism that accidentally infects human hosts after a bite with an infected tick vector. Transmission is believed to occur very quickly after a bite from an infected tick, with a rapid entry of the bacteria into human endothelial cells.[4][5][6]

Epidemiology

R. rickettsia transmits into human hosts by the bite of an infected tick. Humans are not a natural reservoir of disease. The Rickettsia does not harm the tick. In the United States, transmission occurs most often after a bite of the American dog tick (Dermacentor variabilis), the Rocky Mountain wood tick (Dermacentor andersoni), or the brown dog tick (Rhipicephalus sanguineus). Because of its association with tick bites, diagnosis more likely in the summer months in people with outdoor exposure. Despite its name, the diagnosis is most common in the southeastern and south-central United States. Importantly, because the tick bite may be brief, a lack of history of a tick bite should not exclude this diagnosis in a patient residing in or with a history of travel to an endemic area.[7][8]

Pathophysiology

Rickettsia preferentially infects the vascular endothelial cells lining small and medium vessels throughout the body, causing the systemic symptoms and high mortality occurs with Rocky Mountain spotted fever. The infection of endothelial cells leads to disseminated inflammation, loss of barrier function, and altered vascular permeability throughout the body. This condition leads to fever, myalgias, central nervous system symptoms such as headache and confusion, rash, and cardiovascular instability that can be present in patients with Rocky Mountain spotted fever. The mechanisms involved in the rapid entry of the organisms into the cell and the downregulation of immune pathways allowing for persistence of infection are targets of studies to identify new therapeutic targets in these illnesses.

History and Physical

Patients typically present with symptoms four to ten days after exposure to the Rickettsia via tick bite. Patients may or may not recall the tick bite, as the tick does not need to have prolonged contact with the host to cause infection. A detailed travel history is important to identify any outdoor activities in endemic areas and areas with other endemic Rickettsia, as symptoms overlap between the various Rickettsial infections. Symptoms classically include the triad of fever, headache, and a petechial or maculopapular rash but may also include lymphadenopathy, central nervous system changes such as confusion or nuchal rigidity, myalgias and arthralgias, hepatitis, vomiting, and cardiovascular instability. The rash often begins as a maculopapular rash around the wrists and ankles that progresses to petechia. It is essential to have a high index of suspicion for rickettsial infection when patients present with these "influenza-like" symptoms during the summer months, regardless of known tick or insect exposure.

Evaluation

Currently, most cases of Rocky Mountain spotted fever are diagnosed based on immunoglobulin M (IgM) and IgG serologic responses to R. rickettsiae, in conjunction with a high degree of clinical suspicion. It is crucial to consider repeat testing after the resolution of symptoms, as serologic tests may be negative if testing occurs early in the course of illness. A rise in Rocky Mountain spotted fever IgG in the weeks after symptoms when comparing acute and convalescent testing is suggestive of infection. While Rickettsia can be cultured in the microbiology laboratory, this approach is not often used for clinical diagnosis as the technique is difficult and requires a high level of biosafety containment due to the risk of exposure. Other diagnostic options include molecular tests, such as polymerase chain reaction (PCR), in some centers, and skin biopsy. Given its low sensitivity and specificity, the Weil-Felix agglutination assay is no longer the recommended test for diagnosing of Rocky Mountain spotted fever. In addition to suggestive or positive serologic tests, patients with rickettsial infections may also have thrombocytopenia, hyponatremia, and cerebrospinal fluid pleocytosis. On a peripheral white blood cell count, it is important to note that this may be elevated, normal, or low and thus may not help to rule out Rickettsial infection. Given the possibility of negative serologic testing early in the illness and otherwise non-specific laboratory abnormalities, it is essential to have a high index of suspicion for Rocky Mountain spotted fever in patients with influenza-like symptoms in the warmer months if they reside in or have a history of travel to endemic areas.[9][10]

Treatment / Management

Doxycycline is the drug of choice for the treatment of Rocky Mountain spotted fever, including in children. Defervescence typically occurs within three days of starting appropriate antibiotic therapy, although other symptoms may be slower to resolve. The treatment course is usually seven to ten days, or for at least three days after defervescence. It is important to note than in severe rickettsial disease, such as Rocky Mountain spotted fever, mortality rates are as high as 20% to 30% without prompt antibiotic treatment. Thus, treatment should not delay while awaiting confirmatory laboratory testing in a patient with a suspected rickettsial infection; this is particularly important in children, who are at high risk of morbidity and mortality but may experience delays in treatment due to concerns with doxycycline use in children younger than age 8. The risk of dental staining in the treatment of Rocky Mountain spotted fever is very low, as dental staining is a cumulative dose effect, and treatment for Rocky Mountain spotted fever is typically seven to ten days. Thus, concerns regarding tooth staining should not delay treatment in suspected Rocky Mountain spotted fever.[11][12][13][14](B3)

Differential Diagnosis

• Babesiosis

• Boutonneuse fever

• Dengue

• Drug hypersensitivity

• Disseminated gonococcal infection

• Enteroviruses

• Ehrlichiosis

• Epstein-Barr virus infectious mononucleosis

• Immune complex vasculitis

• Influenza

• Lyme disease

• Leptospirosis

• Luetic exanthem

• Malaria

• Typhus