Chapter VI.27. Rocky Mountain Spotted Fever
Jason C. Seto
May 2022

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The editors and current author would like to thank and acknowledge the significant contribution of the previous authors of this chapter from the 2004 first edition, Dr. Douglas Kwock, and the 2013 second edition Dr. Niket Gandhi. This current third edition chapter is a revision and update of the original authors' work.

A 10-year-old male presents to the Emergency Department with a rash that started on his wrists and ankles, spreading up his arms and legs and also involves his palms and soles. He was seen in the office two days prior with a two-day history of fever, headache, nausea and abdominal pain. He was diagnosed with acute gastroenteritis and given instructions for home symptomatic care. He comes to the Emergency Department because the headache, nausea and abdominal pain have persisted. His mother states that her son today has not been himself and that she is concerned that he is getting worse.

Exam: T39.8, P 104, RR 22, BP 120/85. He is lying in a hospital gurney, awake and responsive but tired and ill appearing. His pupils are equal and reactive. Extraocular movements are full and intact. Fundi show sharp optic disc margins. Moderate photophbia is noted on funduscopy. His skin has a blanching, maculopapular rash on the upper and lower extremities as well as palms and soles. There are several sites of scattered petechiae located on his back. There is a small 2 mm irregular healed scab lesion on his right thigh. His right thigh is moderately tender. He has no mucosal lesions. He has negative Kernig and Brudzinski signs. His neck is supple with full range of motion. His heart has a regular rate and rhythm with a normal S1 and S2. His lungs are clear to auscultation bilaterally with good aeration and he is not in any respiratory distress. His abdomen is soft, mildly tender to palpation in all four quadrants, with normal bowel sounds. No masses are palpable during his abdominal examination. He is oriented to person, place and time.

Laboratory studies reveal a mildly elevated white blood cell count with a slight left shift. His platelet count is 95,000 per mm3. His serum sodium is 130 mEq/L. His aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels are also mildly elevated.

He is asked about the scab on his thigh. Four days prior to the onset of illness, while hiking to observe deer with friends, he noticed an engorged tick on his thigh. The tick was removed by squeezing and scratching it, causing a small abrasion that he soon forgot about. He is started on doxycycline. Rocky mountain spotted fever serologies are ordered on his blood.

Rocky Mountain Spotted Fever (RMSF) is the most representative of the large group of illnesses known as the Spotted Fever (characterized by a rash) Group Rickettsioses; RMSF is considered to be the most severe and most common among this group (1). RMSF is caused by Rickettsia rickettsii, a small (0.3 to 0.5 micron by 1 to 2 micron), obligate intracellular bacterium, with a particular predilection towards vascular endothelial cells (2,3).

RMSF was formerly known as "black measles" and was first recognized in Idaho and Montana during the 1890s. It was initially thought to be limited to the Rocky Mountain region (hence its name); however, RMSF is seen in various geographic areas within the United States. Most cases today occur in the southern and mid-Atlantic states, mostly during the months April to September (1).

The incidence of RMSF has increased over the past two decades from 495 cases in 2000 to a peak of 6,248 cases in 2017; with a slight subsequent decrease in 2018 and 2019. The case fatality rate declined from 2.2% in 2000 to 0.3% in 2007, and it has remained roughly unchanged since then (3). Still, the case fatality rate remains high (about 7%) in several Native American reservations in Arizona (4), possibly due to delayed initiation of antimicrobial therapy.

Like all rickettsioses, RMSF is a zoonosis; that is, they require animal contact. Common reservoirs of R. rickettsii include rodents, ungulates (hoofed mammals), and various other mammals. The infection is then transmitted by a tick that feeds on the animal reservoir and then bites the human host. Common tick vectors known to transmit RMSF include Dermacentor variabilis (the dog tick), Dermacentor andersoni (the wood tick), Rhipicephalus sanguineus (the brown dog tick) and Amblyomma americanum (the Lone Star tick) (2,3). Tick nymph and larva stages primarily feed on small mammals; adult ticks feed on large domestic mammals, including humans. In addition, infected female ticks can transmit the infection transovarial to their offspring by laying infected eggs and perpetuating infection from generation to generation. Once a tick becomes infected, it will maintain the infection for life.

At the time of bite, R. rickettsii is released from salivary glands of the adult tick; however, it requires about 12 to 24 hours of feeding and attachment for transmission to occur. Transmission can also occur during tick removal, with the risk increasing if the tick is crushed. Overall, the risk of exposure to R. rickettsii is low, even in endemic areas where only 1% to 3% of ticks are found to carry the infection. The tick bite is not painful and, hence, frequently goes unnoticed. Consequently, a history of tick bite or exposure to tick infested areas may not be recalled by the patient (2).

Symptom onset is typically 5 to 7 days after inoculation, though this varies depending on the size of the rickettsial inoculum. RMSF classically presents with a triad of fever, rash and headache. The triad is seen in approximately two-thirds of patients; however, it should not be relied upon, since the appearance of the rash is a later sign, with fewer than half of patients developing this feature by 72 hours. Because the rash typically appears late in the course of illness (3 to 5 days after fever onset), and may be absent in 10% to 15% of patients, the classic triad is rarely useful in assisting with an early diagnosis. Fever usually is the first sign of illness (2). Other symptoms include myalgia (specifically bilateral calf pain), arthralgia, photophobia, nausea, vomiting, abdominal pain, and malaise. In children in particular, the abdominal pain is severe enough that it may be confused with appendicitis or bowel obstruction.

R. ricketsii preferentially targets vascular endothelial cells, leading to vascular injury, and triggering release of prostaglandins which increase vascular permeability; clotting factors then become activated. The rash seen in RMSF arises secondary to this process. Typically, a rash develops between the 3rd and 5th day of illness, and is comprised of erythematous, blanchable macules which later become petechial. The rash starts at the wrists and ankles and spreads inward to involve the trunk; palms and soles become involved later in the course (2,3). Despite this coagulopathy, disseminated intravascular coagulation (DIC) is rarely observed. During convalescence, desquamation may occur in the most affected skin areas. Importantly, in up to 10% of cases, a rash never occurs, potentially leading to a delay in diagnosis and treatment, and a potentially fatal outcome. Therapy initiation delayed beyond day 5 of illness is associated with a nearly 4-fold increase in mortality (6.5% vs 22.9%) (2).

The initial presentation of RMSF is nonspecific and can be mistaken for a viral illness. Given that fever and headache are often present, meningococcal meningitis is a common alternative consideration, as is viral meningitis. Fever and petechial rash are often confused with meningococcemia, idiopathic thrombocytopenic purpura (ITP), Lyme disease, and sepsis. In tropical regions, dengue, typhoid fever, and leptospirosis are often included in the differential.

Central nervous system complications include disorientation, meningoencephalitis, meningismus, seizures, and coma. If the cardiac system is involved, complications such as myocarditis, arrhythmias, and congestive heart failure may occur. Other potential complications include retinal vasculitis, pulmonary edema, hepatic dysfunction, splenomegaly, and renal failure (3).

The diagnosis of RMSF should be suspected based on the epidemiology (e.g., exposure to ticks or arrival from an area endemic to ticks), the clinical presentation (as noted above), and suggestive laboratory results. There is no laboratory test that definitively diagnoses RMSF in the early phase of illness. The peripheral white blood cell count may be high, low, or normal; thrombocytopenia and hyponatremia are often seen, as well as elevated transaminases and hyperbilirubinemia (2,3). R. rickettsii does not readily stain with Gram-stain. The cerebrospinal fluid (CSF) is usually normal but may show a mild pleocytosis. Various serologic tests can be used, such as enzyme immunoassay, complement fixation, latex agglutination, indirect hemagglutination, and microagglutination; however, the indirect immunofluorescence antibody (IFA) assay is considered the gold standard (2) utilized by the Centers for Disease Control and Prevention (CDC) and most state health department laboratories. Since antibodies are late to appear (usually about 7 to 10 days after onset of illness), acute phase specimens are usually negative and it is the convalescent phase specimens (taken 2 to 3 weeks later) that are diagnostic (3). Polymerase chain reaction (PCR) tests in whole blood, serum, or tissue are available but considered less sensitive. Finally, if done, a skin biopsy of a rash lesion can detect the organism by immunofluorescence staining with high specificity (100%) and moderate sensitivity (70%) (2,3).

To avoid unnecessary morbidity and mortality, early treatment is necessary and usually started before a definitive diagnosis is made (2,3). Without treatment, death occurs about 7 to 15 days after symptom onset. Early treatment is important for full recovery; without early intervention, the mortality rate may rise to 10% to 25% or higher (4,5). Doxycycline is the preferred treatment against R. rickettsii dosed as 2.2 mg/kg/dose (maximum 100 mg) twice daily for at least 7 days, and at least for 3 days after the patient has become afebrile. The previous concern about doxycycline causing tooth staining has been found not to be valid, and the benefit of treating a potentially lethal disease far outweighs any theoretical concern. Chloramphenicol is the only listed alternative but it is scarcely available in the U.S and it has a lower efficacy with more frequent and serious side effects (2).

Limiting exposure to ticks is the most effective method of decreasing the risk of disease. Using insect repellents, particularly those containing N-N-diethyl-M-toluamide (DEET), and performing tick checks, especially on the head and scalp, can help in reducing the risk of tick-related infections. Light colored clothing should cover a large surface area to minimize exposed skin and reduce tick attachment. Proper skin removal of ticks is important in decreasing the risk of infection (2,3). The best way to remove an attached tick is with a fine-tipped tweezer, grasping as close to the skin as possible and pulling upwards with a slow steady pressure. The skin site should be cleaned and disinfected after this is done. Squeezing, crushing, pinching, or the folk remedy of burning the tick with a cigarette may actually facilitate rickettsiae transmission. There are no studies to support or disprove a possible prophylactic role (e.g., following a tick bite in an endemic area) of doxycycline to prevent RMSF (2). No vaccine is available.


1. True/False: Bacterial transmission cannot occur when the tick is crushed.

2. True/False: RMSF can be associated with thrombocytopenia and hyponatremia.

3. True/False: The best treatment for RMSF is chloramphenicol.

4. True/False: Rash typically starts on the wrists and ankles, and eventually can involve the palms and soles.

5. Which is the preferred method of removing an attached tick?
. . . . a. Use a lit match or cigarette to burn the tick stimulating it to detach and flee.
. . . . b. Gently pinch the body of the tick with fingers and lift straight off.
. . . . c. Use fine-tipped tweezers to grasp the tick as close to the skin as possible and pull upward with slow steady pressure.
. . . . d. Apply petroleum jelly (Vaseline) over the tick and wait for the tick to suffocate or detach for air.
. . . . e. Don't remove, leave the tick alone

6. Which of the following is NOT a recommended means of RMSF prevention?
. . . . a. Insect or tick repellants to clothing and exposed skin.
. . . . b. Prophylactic doxycycline prior to exposure to tick infested areas.
. . . . c. Minimize exposed skin with light-colored clothing.
. . . . d. Avoid known tick infested areas.
. . . . e. Survey skin and scalp after exposure to tick infested areas

1. Centers for Disease Control and Prevention. Rocky Mountain Spotted Fever. Available at:, accessed on March 22, 2022
2. Biggs HM, Behravesh CB, Bradley KK, et al. Diagnosis and Management of Tickborne Rickettsial Diseases: Rocky Mountain Spotted Fever and Other Spotted Fever Group Rickettsioses, Ehrlichioses, and Anaplasmosis – United States. MMWR Morb Mortal Wkly Rep 2016;65,RR.2:1-44
3. Committee on Infectious Diseases American Academy of Pediatrics. Rocky Mountain Spotted Fever. In: Kimberlin DW, Barnett ED, Lynfield R, Sawyer MH (eds). Red Book: 2021 Report of the Committee on Infectious Diseases. 32nd edition. 2021. Itasca, IL, American Academy of Pediatrics: pp. 641-644.
4. Jay R, Armstrong PA. Clinical characteristics of Rocky Mountain spotted fever in the United States: A literature review. J Vector Borne Dis. 2020;57(2):114-120. doi: 10.4103/0972-9062.310863. PMID: 34290155
5. Álvarez-López DI, Ochoa-Mora E, Nichols Heitman K, et al. Epidemiology and Clinical Features of Rocky Mountain Spotted Fever from Enhanced Surveillance, Sonora, Mexico: 2015-2018. Am J Trop Med Hyg. 2021;104(1):190-197.

Answers to questions
1. False. Bacterial transmission increases if the tick is crushed.
2. True. Thrombocytopenia (especially due to involvement of vascular endothelium) and hyponatremia is often noticed in those affected with RMSF.
3. False. The best treatment for RMSF is doxycycline. Its teeth staining properties are much less than those of older tetracyclines. Chloramphenicol may be used in those allergic to doxycycline. Chloramphenicol is not first line as it has been associated with aplastic anemia, pancytopenia, and gray baby syndrome.
4. True. Rash typically starts on the wrists and ankles, spreads to the trunk, and can involve the palms and soles.
5. c. Use fine-tipped tweezers to grasp the tick as close to the skin as possible and pull upward with slow steady pressure.
6. b. Prophylactic doxycycline prior to exposure to tick infested areas has not been demonstrated to be effective.

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