Chapter VI.27. Rocky Mountain Spotted Fever
Niket V. Gandhi, MD
April 2013

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The editors and current author would like to thank and acknowledge the significant contribution of the previous author of this chapter from the 2004 first edition, Douglas K. Kwock, MD. This current second edition chapter is a revision and update of the original author's work .

A 10 year old male presents to the ED 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 ago with a two day history of fever, headaches, nausea and abdominal pain. He was diagnosed with acute gastroenteritis and given instructions for home symptomatic care. He comes to the ED because the headaches, 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.

Physical Examination: T39.8 degrees C, P 104, RR 22, BP 120/85. He is lying in a hospital gurney, awake and responsive, but tired and ill appearing. 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 thigh is moderately tender. His head is nontender and atraumatic. He has no mucosal lesions. He has negative Kernig’s and Brudzinski’s signs. 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. His serum sodium is 130 mEq/L. His aspartate aminotransferase and alanine aminotransferase 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" 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 commonly reported and most severe rickettsial infection in the U.S. Overall, it is the second most common tick transmitted disease in the United States. This tick-borne illness is caused by Rickettsia rickettsii, an aerobic, obligate intracellular, gram-negative coccobacillus, with a particular predilection towards vascular endothelial cells (more on this later).

It was initially known as "black measles", and was first recognized in Idaho and Montana during the 1890s. It was initially thought to be limited only to the Rocky Mountain region. However, RMSF is seen in various geographic areas within the United States. Most cases today occur in the southern and mid-Atlantic states, although they have also been found in Canada as well as Central and South America. The highest rates of disease are reported in North Carolina and Oklahoma.

The incidence of RMSF has increased to over 8 cases per million people in 2008. However, the case fatality rate has declined to 0.5% (versus 1.4% in 1997-2002).

Rocky mountain spotted fever, like all rickettsial illnesses, is a zoonosis; that is, they require an animal vector to spread to humans. Common tick vectors known to transmit RMSF include Dermacentor variabilis (the dog tick), Dermacentor andersoni (the wood tick), and Amblyomma americanum (the Lone Star tick). Infected female ticks can transmit the infection by laying infected eggs and perpetuating infection from generation to generation. Ticks can also acquire the infection while feeding on an infected rickettsemic host. Tick nymph and larva stages primarily feed on small mammals. Adult ticks feed on large domestic mammals, including humans. Once a tick becomes infected, it will maintain the infection for life.

R. rickettsii is released from salivary glands of an adult tick, however, it requires about 12-24 hours of feeding and attachment for transmission to occur. Transmission can also occur during tick removal as well, with an increased risk if the tick is crushed. The risk of exposure to R. rickettsii is low. Even in areas of increased cases of RMSF, only about 1% to 3% of the tick population are infected with R. rickettsii.

The tick bite often is unnoticed, since it is not painful. A history of tick bite or exposure to tick infested areas may not be recalled by the patient. The median incubation time is 7 days, though this varies depending on the size of the rickettsial inoculum. It 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, as the appearance of the rash is a later sign, with fewer than half of patients developing this feature by 72 hours. Fever usually develops as the first sign of illness. 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 diagnoses such as appendicitis or bowel obstruction are often made. Because the rash typically appears late in the course of illness (3 to 5 days after fever onset), and may be absent in 10-15% of patients, the classic triad is rarely useful in assisting with an early diagnosis.

Rickettsiae infect vascular endothelial cells. As such, infection leads to direct vascular injury, 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 petchial. The rash starts at the wrists and ankles and tends to initially spare the palms and soles, and spreads inward to involve the trunk. Palms and soles become involved later in the course. Despite a coagulopathic etiology, 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/treatment and a potentially fatal outcome. Initiation of therapy beyond day 5 of illness is associated with a nearly 4-fold increase in mortality (6.5% vs 22.9%).

The initial presentation of RMSF is nonspecific and can easily be mistaken for nonspecific febrile or viral illnesses. Given that fever and headache are often present, meningococcal meningitis is a common misdiagnosis, as is (in non-toxic patients) viral meningitis. Fever and the petchial rash are often misdiagnosed as meningococcemia, thrombotic thrombocytopenic purpura (TTP), Lyme disease, and sepsis. In tropical regions, dengue, typhoid fever, and leptospirosis are often included in the differential.

The diagnosis of RMSF is heavily based on a compelling clinical presentation, suggestive laboratory data and a high index of suspicion (for example, exposure to ticks or arrival from an area endemic to ticks). There is no laboratory test that definitively diagnoses RMSF in the early phase of illness. The WBC count may be high, low or normal. Thrombocytopenia and hyponatremia are often noticed in those affected with RMSF. R. rickettsii does not readily stain with gram stain. The CSF is usually normal but may show a mild pleocytosis. A skin biopsy of a rash lesion can detect the organism by immunofluorescence staining with a high specificity of 100% (sensitivity of 70%). Enzyme immunoassay and complement fixation tests can also be used. Antibodies usually develop about 7 to 10 days after onset of illness (diagnostic immunofluorescence antibody titer is 1:64). Other serologic studies include latex agglutination test, indirect hemagglutination and microagglutination. However, the immunofluorescence assay generally is considered the standard utilized by the Centers for Disease Control and Prevention (CDC) and most state health department laboratories.

Early treatment is necessary and often empiric based on a high index of suspicion considering history, clinical course, and epidemiology. Treatment should not be withheld until a definitive diagnosis is made. Without treatment, death occurs about 7 to 15 days after symptom onset. Thus, early treatment is important for full recovery, as case fatality reports have suggested 10% to 25% mortality rate without early intervention. Doxycycline has been shown to be the best treatment against R. rickettsii (2 mg/kg twice daily for those under 45 kg for 7 days, but should be lengthened to allow treatment for 3 days after the patient becomes afebrile, or 100 mg twice a day for those over 45 kg). Tetracycline and doxycycline were not favored initially because they bind to calcium in developing teeth and bones, thus causing permanent discoloration. However, there are several reasons why doxycycline is the recommended first-line therapy. Doxycycline’s risk of teeth staining is very low compared to older tetracyclines. A single course of doxycycline treatment carries little risk of teeth staining. Doxycycline is also active against ehrlichiosis, which may be clinically indistinguishable from RMSF. Chloramphenicol may be used in those allergic to doxycycline, although the former has been associated with aplastic anemia, pancytopenia, and gray baby syndrome. Drugs containing sulfa-groups may worsen the infection. No study has demonstrated doxycycline prophylaxis to be effective. Duration of treatment depends on the resolution of fever, and should be continued for 3-5 days after this resolves. Typically, 5-7 days of antibiotics are sufficient. If other differentials are present, e.g., meningococcal infection, it is appropriate to treat both conditions empirically.

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.

Limiting exposure to ticks is the most effective method of decreasing the risk of disease. Using insect repellents, particularly those containing N-N-dietyl-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. 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.


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. Lin L, Decker CF. Rocky Mountain spotted fever. Dis Mon. 2012;58:361-369.

2. Raoult D, Parola P. Rocky mountain spotted fever in the USA: a benign disease or a common diagnostic error? Lancet Infect Dis. 2008;8(10):587–589.

3. Dahlgren FS, Holman RC, Paddock CD, Callinan LS, McQuiston JH. Fatal Rocky Mountain Spotted Fever in the United States, 1997-2007. Am J Trop Med Hyg. 2012;86:713-719.

4. Cunha A. Clinical features of Rocky Mountain spotted fever. Lancet Infect Dis. 2008;8(3):143–144

5. Volovitz B, Shkap R, Amir J, Calderon S, Varsano I, Nussinovitch M. Absence of tooth staining with doxycycline in young children. Clin Pediatr. 2007;46: 121–126.

6. Kirkland KB, Wilkinson WE, Sexton DJ. Therapeutic delay and mortality in cases of Rocky Mountain spotted fever. Clin Infect Dis. 1995;20(5):1118.

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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