AUTHOR AND EDITOR INFORMATION

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• Medication
• Follow-up
• Miscellaneous
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INTRODUCTION

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Background

Rocky Mountain spotted fever (RMSF) is the most common rickettsial infection and the second most commonly reported tick-borne disease (after Lyme disease) in the United States.

The causative agent is Rickettsia rickettsii (named after Howard T. Ricketts, the discoverer of the organism), an Alphaproteobacteria and member of the spotted fever groups of rickettsial infections. RMSF was first described in the late 1800s in the Bitterroot Valley of Idaho. For several decades, it was thought to be limited to the Rocky Mountain area; however, it now has a high documented prevalence in the eastern United States.

The disease was so problematic because of its mortality of £30% that the Rocky Mountain Laboratory was established in Hamilton, Montana to help investigate it. This laboratory is now part of the National Institute of Allergy and Infectious Diseases (NIAID). RMSF has the highest mortality of any tick-borne illness in the United States.

RMSF is a reportable disease in the United States.

Pathophysiology

RMSF is a diffuse small-vessel vasculitis. R rickettsii is a small, gram-negative, obligate intracellular coccobacillus with a tropism for human endothelial cells. This bacterium causes membrane disruption and increased permeability.

Rickettsiae can be demonstrated in the cytoplasm and the nucleus of cells. Possible mechanisms for cellular injury include injury to the cell membrane, depletion of adenosine 5-triphosphate (which leads to failure of the sodium pump), and damage to the cell caused by toxic products of rickettsial metabolism.

Vascular lesions are responsible for the clinical manifestations, including rash, headache, alteration in the level of consciousness, heart failure, and shock. Vascular lesions can be found everywhere, with highest predilection for the skin, gonads, and adrenal glands. Profound hyponatremia is common. Several mechanisms have been postulated, including (1) a shift in water from the intracellular spaces to the extracellular spaces, (2) increased loss of sodium in the urine, and (3) an exchange of sodium for potassium at the cellular level.

Edema of the medulla oblongata may contribute to fatality in some patients.

Concentrations of antidiuretic hormone and aldosterone are increased in some patients.

Frequency

United States

RMSF has been reported in almost every state in the continental United States, with an age-related annual incidence of 0.5-3 cases per million population. In 1997-2002, the mean incidence of was 2.2 cases per million per year.¹

States reporting the highest rate of disease include North Carolina, South Carolina, Tennessee, Oklahoma, and Arkansas; these states accounted for more than half the total cases in recent years. The term RMSF is a misnomer because it is relatively rare in the Rocky Mountain states. About 90% of cases occur between April and September, the time of the year when ticks have maximal activity and when people participate in outdoor recreational activities. See Media file 1.

International

The disease is also found in Canada, Mexico, Central America, and South America. However, the arthropod vector differs by location (see the table below). Other illnesses similar to RMSF are also found worldwide.

Human Disease Around the World Caused by Spotted Fever Group Rickettsiae.

Mortality/Morbidity

The mortality rate during the preantibiotic era was as high as 30%; however, the mortality rate now ranges from approximately 2% in children to 9% in elderly persons. The case-fatality rate is higher (6.2%) for persons whose treatment begins more than 3 days after onset of symptoms than for those treated within the first 3 days of illness (1.3%). Patients with glucose-6-phosphate dehydrogenase (G-6-PD) deficiency tend to have a severe course of RMSF.

Race

People of African descent have reportedly had a high mortality rate partly due to the 12% rate of G-6-PD deficiency in male African Americans. RMSF may also be diagnosed later in African American individuals than in others because of the difficulty in detecting the early macular rash.

Sex

The incidence is higher in male individuals than in female individuals, with a male-to-female ratio of 1.7:1.

Age

Children are at greater risk of acquiring RMSF than are adults. The highest incidence occurs in children aged 5-9 years. However, the highest mortality is in those aged 50 years or older.

CLINICAL

Section 3 of 11  

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History

• The incubation period for Rocky Mountain spotted fever (RMSF) is 2-8 days after the tick bite.
• History of tick bite is only present in two thirds of cases.
• Symptoms can begin gradually or abruptly.
• Fever, headache, rash, toxicity, myalgia, and mental confusion are the major clinical manifestations.
• • The patient's body temperature is usually higher than 38.8°C (101.8°F)
  • Headache is the most common neurologic manifestation. In older children and adults, the headache may be intractable and may be ongoing day and night. Young children may not complain of headache.
  • Nausea, vomiting, and abdominal pain may occur.
  • Conjunctival hyperemia and photophobia may be observed.
• The rash of RMSF is an important pathognomonic feature of the disease and is present in 80-90% of patients.
• • Rash begins as blanching maculopapular lesions. These lesions become petechial or purpuric in approximately one half of patients, accounting for its former name of black measles.
  • The rash first appears peripherally on the wrists and ankles. It spreads centripetally over the next 2-3 days.
  • Involvement of the palms and soles is an important diagnostic feature.
  • In most patients, rash usually appears by the second or third day. However, it may be delayed until the sixth day.
  • Early recognition of the blanching macular eruption is vital, because the classic petechial rash does not typically appear until 6 days or so after the initial symptoms become apparent.

Physical

Physical signs vary and include the following:

• Body temperature is higher than 38.8°C (101.8°F).
• Patient might have a toxic appearance.
• A characteristic skin rash appears. It may be absent in 10-20% of infected individuals.
• Hepatomegaly and splenomegaly are present in approximately 33% of patients.
• Signs of meningoencephalitis include restlessness, irritability, mental confusion, and delirium.
• Meningismus may occur. Findings may include neck stiffness, photophobia, a positive Kernig sign (pain on knee extension when hips flexed to 90°), and a positive Brudzinski sign (knee and hip flexion when the is neck flexed).
• Ataxia may be present.
• Spastic paralysis may occur.
• Sixth nerve palsy may be observed.
• Muscle tenderness is a common feature.

Causes

Ticks are the natural hosts, reservoirs, and vectors of R rickettsii. The species of tick acting as the vector varies by geographic location. R rickettsii is transmitted to humans by the bite of an infected tick. Adult ticks transmit the disease to humans during feeding. At least 6 hours of tick attachment is needed for the transmission of R rickettsii.

• Primary hosts of R rickettsii
• • Dermacentor variabilis (dog tick) in the eastern United States and eastern Canada
  • Dermacentor andersoni (wood tick) in the western United States and western Canada
  • Amblyomma americanum (Lone Star tick) in the southwestern United States
• Transmissions
• • Humans usually acquire infection through the bite of an infected tick.
  • On occasion, transmission occurs by scratching or rubbing infectious tick feces into the skin.
  • Laboratory personnel can be infected by inoculation or inhalation of aerosolized infectious specimens. For this reason, only specially equipped laboratories should attempt to culture and isolate Rickettsia species. Detection by other means (eg, serology) is more readily available than culture and isolation.

DIFFERENTIALS

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Other Problems to be Considered

Typhoid fever
Atypical measles
Hypersensitivity reactions to drugs
Murine typhus
Rickettsial pox

WORKUP

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Lab Studies

• Laboratory findings may be nonspecific.
• • The total leukocyte count may be normal, elevated, or decreased but usually shows a left shift.
  • Mild anemia and thrombocytopenia of less than 150 X 10⁹/L (<150 X 10³/µL) occur in approximately one third of patients.
  • Severe thrombocytopenia of less than 20 X 10⁹L (<20 X 10³µL) occurs in approximately 10% of patients.
  • Hyponatremia (<130 mEq/L) is noted in 20% of patients.
  • The serum alanine aminotransferase level is usually increased.
  • Serum albumin values may be low.
  • The BUN level is increased.
  • Results of CSF analysis are generally normal. However, mild pleocytosis may be present, and approximately 50% of patients have a predominance of polymorphonuclear cells. An elevated CSF protein level may also be observed.
• Serologic assays to detect anti–R rickettsii immunoglobulin G (IgG) antibodies are usually performed for definitive diagnosis. Testing of acute- and convalescent-phase sera is recommended to demonstrate a 4-fold or higher increase in the titer.
• Enzyme immunoassays (EIAs) and immunoglobulin M (IgM) antibody-capture immunoassays are new serologic tests that potentially allow for early diagnosis.
• In research laboratories, isolation of rickettsiae from tissues or direct detection of rickettsiae in tissues by means of direct immunofluorescence is used to confirm the diagnosis.
• Polymerase chain reaction tests have been developed but are not widely available.

TREATMENT

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Medical Care

• Early treatment is critical to the patient's outcome and must be started on the basis of clinical diagnosis. Consider Rocky Mountain spotted fever (RMSF) and promptly begin medical treatment in any person with a potential exposure to the pathogen who develops fever, myalgia, or headache, even if they do not have of a rash. The best outcomes are achieved when treatment is started within 4 days of symptom onset.
• Provide supportive care. Doxycycline is the antibiotic of choice.² Chloramphenicol was previously recommended for the treatment of children younger than 9 years. However, in national surveillance data, patients treated with chloramphenicol were more likely to die than those treated with tetracycline. Staining of teeth caused by one or more courses of tetracyclines (particularly doxycycline) is negligible.
• For children who weigh less than 45 kg, the dose is 2 mg/kg given orally or intravenously twice daily on the first day of treatment and once or twice daily thereafter. Older children and adults should receive 100 mg twice daily on the first day and once or twice daily thereafter.
• Antibiotics should be continued for a minimum of 5-7 days and until the patient has been afebrile for at least 1 day.
• Some have advocated the use of corticosteroids, but the specific therapeutic benefits of these drugs are not known. Physicians should be aware that sulfonamide treatment given empirically in a febrile child can worsen RMSF.

Consultations

• Patients with RMSF should be treated in consultation with an infectious disease specialist.

MEDICATION

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Drug Category: Antibiotic agents

Tetracyclines are the drug of choice. Although tetracyclines should not be routinely prescribed to children younger than 8 years, the benefits far exceed the risks in treating Rocky Mountain spotted fever (RMSF). Doxycycline is the agent of choice because the risk of dental staining is less than that of other tetracyclines. Chloramphenicol was previously recommended for use in children younger than 8 years (to avoid teeth staining), but it poses a risk of permanent aplastic anemia and should be avoided if at all possible

FOLLOW-UP

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Further Inpatient Care

• Delayed diagnosis and delayed initiation of specific antirickettsial therapy (eg, on or after day 5 of the illness) is associated with substantially increased risk of a fatal outcome.
• Rocky Mountain spotted fever (RMSF) should be considered in any person who has fever and a history of tick bite or exposure.
• Never delay treatment while awaiting a confirmatory laboratory diagnosis.
• Doxycycline is the antibiotic of choice in almost all clinical situations, including disease in children younger than 8 years.
• Also, other supportive measures (eg, intravenous administration of fluids, oxygenation, correction of electrolyte impairments, management of disseminated intravascular coagulation) should be provided according to the patient's clinical situation.

Deterrence/Prevention

• Avoidance of tick-infested areas is the first line of defense against RMSF.
• After a tick bite occurs, use of antimicrobial prophylaxis has no role in the prevention of RMSF.
• If tick-infested areas cannot be avoided, wearing light-colored shirts and trousers that fit tightly around the waist and ankles can minimize the risk of being bitten.
• Exposed areas of the skin should be covered with insect repellents containing N-N-diethyl-M-toluamide (DEET). In children, insect repellents should be used carefully on exposed skin. Application to the face and hands should be avoided.
• After people leave an endemic area, they should inspect their bodies for attached ticks, with particular attention on areas containing hair.
• If ticks are found, any of several commercial removal devices should be used if possible. Otherwise, ticks should be removed by grasping them with fine tweezers at the point of attachment and by pulling them out slowly and steadily. The aim is to remove the tick's mouthparts from the site of insertion without damaging the arachnid.
• • After the tick is removed, the skin should be disinfected. Check to make sure that the head of the tick is not still embedded.
  • Some recommended keeping the removed tick in a jar along with a dampened paper towel in the refrigerator for a month. This way, if symptoms develop, the tick may be used to help identify what (if any) infection it may have transmitted.
  • Burning the tick, smothering it in alcohol or petroleum jelly (or another substance), or twisting or rubbing it off is not recommended. These methods have not been shown to decrease the time the tick remains embedded. In addition, they may pose of risk breaking the body of the tick open and releasing bacteria that were otherwise contained within it.

Complications

• Meningitis
• Renal failure
• Pulmonary involvement
• Liver impairment with development of jaundice
• Splenomegaly
• Myocarditis
• Thrombocytopenia

Prognosis

• The outcome greatly depends on the early start of appropriate treatment.
• Outcomes can vary from complete resolution to death.
• Severe disease may result in long-term sequelae, such as the following:
• • Partial paralysis of the lower extremities
  • Gangrene requiring amputation of fingers, toes, arms, or legs
  • Hearing loss
  • Blindness
  • Loss of bowel or bladder control
  • Movement disorders
  • Speech disorders

Patient Education

• For excellent patient education resources, visit eMedicine's Bites and Stings Center. Also, see eMedicine's patient education article Ticks.

MISCELLANEOUS

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Medical/Legal Pitfalls

• Rocky Mountain spotted fever (RMSF) is a life-threatening disease. Therefore, paying meticulous attention when patients with potential RMSF are treated is important. Clinicians should have a low threshold for treatment if RMSF is clinical suspected.
• Signs and symptoms can mimic those of other diseases. Therefore, a history of traveling to endemic areas, having tick bites, or having exposures to ticks is an important clue.
• A negative history for tick bites should not exclude the diagnosis if the index of clinical suspicion is high.
• Antibiotics (doxycycline) should be promptly administered.
• Waiting for the classic petechial rash to develop may seriously worsen the patient's outcome because antibiotics are best administered before day 5 of the illness, and the rash may not appear until day 6.

MULTIMEDIA

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• Follow-up
• Miscellaneous
• Multimedia
• References

Media file 1:  Annual incidence per million population for Rocky Mountain spotted fever by state in the United States for 2002, as determined on the basis of cases reported to the National Electronic Telecommunications System for Surveillance. Image courtesy of the Centers for Disease Control and Prevention.
	View Full Size Image
Media type:  Image

REFERENCES

Section 11 of 11

• Authors and Editors
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1. Chapman AS, Bakken JS, Folk SM, et al. Diagnosis and management of tickborne rickettsial diseases: Rocky Mountain spotted fever, ehrlichioses, and anaplasmosis--United States: a practical guide for physicians and other health-care and public health professionals. MMWR Recomm Rep. Mar 31 2006;55(RR-4):1-27. [Medline]. [Full Text].
2. Cale DF, McCarthy MW. Treatment of Rocky Mountain spotted fever in children. Ann Pharmacother. Apr 1997;31(4):492-4. [Medline].
3. Abramson JS, Givner LB. Rocky Mountain spotted fever. Pediatr Infect Dis J. Jun 1999;18(6):539-40. [Medline].
4. American Academy of Pediatrics Committee on Infectious Diseases. Rocky Mountain spotted fever. In: Red Book. 27th Ed. Elk Grove Village, IL: AAP; 2006:570-2.
5. Azad AF, Beard CB. Rickettsial pathogens and their arthropod vectors. Emerg Infect Dis. Apr-Jun 1998;4(2):179-86. [Medline].
6. Kostman JR. Laboratory diagnosis of rickettsial diseases. Clin Dermatol. May-Jun 1996;14(3):301-6. [Medline].
7. Thorner AR, Walker DH, Petri WA. Rocky mountain spotted fever. Clin Infect Dis. Dec 1998;27(6):1353-9; quiz 1360. [Medline].

Article Last Updated: Feb 14, 2008