eMedicine Specialties > Infectious Diseases > Bacterial Infections

Rocky Mountain Spotted Fever

Author: Burke A Cunha, MD, Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital
Coauthor(s): Richard H Snyder, MD, Vice-Chair, Program Director, Department of Medicine, Norfolk General Hospital; Clinical Associate Professor, Department of Internal Medicine, East Virginia Medical School; Marie Spevak O'Brien, DO, Assistant Clinical Professor of Medicine, Arthritis and Rheumatology, Lehigh Valley Physician Group
Contributor Information and Disclosures

Updated: Aug 11, 2008

Introduction

Background

Rocky Mountain spotted fever (RMSF) is a tick-borne disease caused by the organism Rickettsia rickettsii. Although RMSF can be lethal, it is curable. RMSF is the most common rickettsial infection. The organism is endemic in parts of North, Central, and South America, especially in the southeastern and south-central United States. Sophisticated microbiologic and serologic methods to distinguish infection by different members of the spotted-fever group reveal that RMSF may be more common in the tropics and subtropical regions of the Americas than previously thought.

RMSF has been described as a "wolf in sheep's clothing" and "the great imitator" of other disease processes.¹ Because of its diverse clinical features, RMSF is often confused with other infections. The hallmark of RMSF is a petechial rash beginning on the palms of the hands and soles of the feet.

The two principal tick vectors of RMSF in North America include Dermacentor variabilis (dog tick) in the eastern United States and Dermacentor andersoni in the RockyMountain region and Canada. Other species also identified include Rhipicephalus sanguineus in Mexico and Central America and Amblyomma cajennense in Central and South America. Amblyomma cooperi, Amblyomma americanum, Ixodes pacificus, and Haemaphysalis leporispalustris are uncommon vectors for human infection.

Major Marshall H. Wood, a US Army physician in Boise, Idaho, first recognized R rickettsii infection and described RMSF in 1896. The first report in the medical literature of a case in the Snake River Valley of Idaho was published in 1899. In 1902, 7 people died of RMSF in BitterrootValley. Then, 111 cases of RMSF were studied on the west side of the Bitterroot River; 69% of these cases were fatal. Based on the history of tick exposure and the season, researchers concluded that the wood tick spreads RMSF.

Howard Ricketts, for whom the etiologic pathogen is named, identified R rickettsii, its vector, and the route of transmission of RMSF. In 1906, Ricketts demonstrated tick transmission of RMSF to guinea pigs, showed that the etiologic agent was present in blood from infected humans, and demonstrated that it could be removed via filtration. Ricketts reported "minute polar staining bacilli" in freshly laid eggs of infected ticks.

In 1916, Wolbach published 2 papers also describing the appearance of R rickettsii using the Giemsa stain. In 1919, he reported that R rickettsii is an intracellular pathogen, and he described the vasculitic lesion.

In the late 1940s, the broad-spectrum antibiotics chloramphenicol and the tetracyclines were first shown to be effective in the treatment of RMSF.

Pathophysiology

R rickettsii is a small (0.3 µm X 1 µm), gram-negative, obligate intracellular coccobacillus.

R rickettsii possesses outer-membrane protein (Omp)A and OmpB, 2 major immunodominant surface-exposed proteins with species-specific conformational epitopes. OmpB is the most abundant outer-membrane protein that shares genetic sequences and limited antigens with typhus group rickettsiae.

Ticks become infected by feeding on the blood of infected animals, through fertilization, or by transovarial passage. Rickettsiae are transmitted from tick to human during feeding. The tick needs to be attached to a host for 6-10 hours for rickettsiae to be released from the salivary glands, although transmission may not occur for 24 hours. In addition, this organism can infect people who remove ticks from other people or animals via contact with tick tissues and fluids.

The organism spreads through the body via both blood and the lymphatic system. The incubation phase of infection ranges from 3-12 days, depending on the volume of the inoculum.

Notable characteristics of R rickettsii include its marked tropism for endothelial cells that line blood vessels and its enhanced ability to invade throughout the body compared with other rickettsiae. The organisms attach via OmpA to the endothelial membrane, where they induce their own engulfment. Once they invade the cell and effectively escape destruction by professional phagocytes, they replicate via binary fission in the cytosol and spread from cell to cell, propelled by polar polymerization of the host cell's actin, without producing cell lysis.

The rickettsial diseases, especially RMSF, are model examples of vasculitis with localization in endothelial cells. The major pathophysiologic effect of endothelial cell injury is increased vascular permeability, which results in edema, hypovolemia, hypotension, and hypoalbuminemia. The organisms also routinely infect vascular smooth-muscle cells.

The distribution of rickettsiae within the blood vessels causes vascular injury and the subsequent development of a host mononuclear-cell tissue response. Consequences of vascular injury include interstitial pneumonia, interstitial myocarditis, and perivascular glial nodules of the CNS, with similar vascular lesions in the skin, gastrointestinal tract, pancreas, liver, skeletal muscles, and kidneys. Large amounts of rickettsiae in damaged cells support the concept of direct injury. The inflammation and damage to the blood vessels and capillaries activate platelets, generate thrombin, and activate the fibrinolytic system as part of the body's homeostatic physiologic response to endothelial injury.

As R rickettsii proliferates in the endothelial lining, it also causes thrombi to form. In severe cases, extensive vasculitis can lead to small-vessel occlusion. Vascular necrosis and thrombosis are more common in RMSF than in typhus and may mimic collagen-vascular disease.

Frequency

United States

RMSF is the most common cause of fatal tick-borne disease in the United States. Anyone who is bitten by an infected dog tick and on whom the infected tick remains for several hours can develop RMSF. In spite of its name, RMSF is more common in the southeastern US tick belt than in the RockyMountain region. The disease is more common in rural and suburban locations; however, it does occur in urban areas such as New York City.²

• The regions with the highest incidences include the Southeast, the western South Central region (including Oklahoma and northern Texas), and selected areas of the Northeast (Cape Cod and Long Island). Most cases are reported from eastern and central states, such as North and South Carolina, Virginia, Georgia, Tennessee, Arkansas, Missouri, Kansas, and Oklahoma. The 2 states with the highest incidence are North Carolina and Oklahoma. Cases have been reported in 48 states, with Vermont and Hawaii being the exceptions. In the northern United States, infections commonly occur in the spring; in the South, cases may occur in any month, including winter months.
• From 1989-1996, more than 4700 cases were reported in 46 states. Of these reported cases, 90% occurred between April and September. More than 1400 cases were reported in 2004.
• A prospective study of RMSF infection in residents of a known endemic area in North Carolina suggests an annual incidence of 42 cases per 100,000 children aged 5-9 years.

International

Canada, Mexico, and Central and South America, particularly Panama, Columbia, Argentina, Costa Rica, Bolivia, and Brazil have reported cases of RMSF. Serologic evidence of RMSF has been found in 6 Brazilian states ranging from Rio Grande de Sol in the south to Bahia in the north. In Brazil, RMSF was unrecognized or unreported for decades in regions such as Espiritu Santo. In southern Brazil, the disease is more common from October to February, but, in the tropics, seasonal variation is less striking.

Mortality/Morbidity

• The mortality rate in untreated cases is 20-25%. The mortality rate in patients treated with appropriate antibiotic therapy is 5%. In a 1995 study, antirickettsial therapy within the first 5 days of illness reduced the risk of mortality 5-fold compared to treatment initiation after the 5-day mark.³
• The mortality rate of untreated RMSF in elderly patients approaches 70%. The mortality rate in untreated children is less than 20%. RMSF tends to be more severe in individuals with glucose-6-phosphate dehydrogenase deficiency.
• The diverse clinical features of RMSF lead clinicians to confuse it with many community-acquired infections. This delays proper therapy and contributes to higher mortality.

Race

• RMSF is more common in blacks, but rash is harder to recognize in dark-skinned individuals.

Sex

• Approximately two thirds of all cases of RMSF occur in males.
• The mortality risk is also higher in males than in females.

Age

• Two thirds of RMSF cases occur in young and middle-aged adults. The second-most-affected age group includes children aged 5-14 years.
• Approximately one third of patients with RMSF are younger than 20 years. The likelihood of mortality increases with each decade of life after 20 years.
• RMSF occurs more often in elderly individuals.

Clinical

History

• Physicians must maintain a high index of suspicion for Rocky Mountain spotted fever (RMSF) in patients with the following:
  • Febrile illness
  • History of potential tick exposure
  • Travel to endemic area
  • Presentation in the spring or fall
• RMSF should also be considered in patients with unexplained febrile illness, even if they have no history of a tick bite or travel to an endemic area.
• History of a tick bite is reported by only 70% of patients.
• People with RMSF generally present within a week after a tick bite.
• The triad of manifestations in RMSF is fever, rash, and history of tick exposure. However, a recent study found that only 18% of patients with RMSF had this triad upon initial presentation. Other common symptoms include chills, severe headache, conjunctival redness, cough, myalgias, gastrointestinal disturbances, and malaise. Patients may report insomnia and photophobia.
• A petechial rash commonly appears 3-5 days into the illness. The absence or delayed appearance of a rash increases the difficulty of diagnosis.

Physical

RMSF presents with a wide clinical spectrum, ranging from mild fever (99-100%), headache (79-91%), and myalgias (72-83%) to disseminated intravascular coagulation (DIC; 32-53%), shock (7-17%), and death (4-8%).

• Adults tend to present with typical symptoms.
• Fever with relative bradycardia is the rule. In mild untreated cases, the fever subsides at the end of the second week.
• Rash
  • Rash is a major diagnostic sign that appears in a low percentage of patients the first day of infection and in only 49% during the first 3 days.
  • In 88-90% of RMSF cases, the maculopapular rash appears 2-6 days after onset of fever and progresses through stages and distribution that are never pathognomonic.
  • The rash begins as a maculopapular eruption on the wrists and ankles and spreads centripetally to involve the trunk and extremities. The rash involves the palms of the hands and soles of the feet.
  • Later in the illness, the rash becomes petechial (45-49%). In dark-skinned patients, the rash is difficult to see.
  • Nonproductive cough may accompany the rash (33%).
  • The rash is absent at presentation in 10-15% of patients. RMSF without a rash (ie, spotless RMSF) should be considered ehrlichiosis until proven otherwise.
  • Later in the illness, purpura and skin necrosis or gangrene may develop, although rarely.
• Head, ears, eyes, nose, and throat
  • Conjunctival suffusion develops in 30% of patients.
  • Bilateral edema is present. Periorbital edema is a key diagnostic finding, especially in children.
  • Transient deafness occurs in 7% of patients.
• Cardiovascular
  • Myocarditis may develop.
  • Relative bradycardia may occur.
  • Arrhythmias are present in 7-16% of patients.
  • Hypotension occurs in 7-17% of patients.
  • RMSF is the only tick-borne disease that can directly cause congestive heart failure secondary to myocarditis (5-26%).
• Pulmonary⁴
  • Pulmonary edema occurs in severe cases.
  • Pneumonitis is present in 12-17% of cases.
• Gastrointestinal
  • Anorexia may develop.
  • Abdominal pain and tenderness (diffuse in right upper quadrant) are present in 34-52% of patients.
  • Jaundice develops in severe cases (8-9%).
  • Hepatomegaly and splenomegaly occur in 12-15% and 14-16% of cases, respectively.
  • Diarrhea develops in 19-20% of patients.
  • Increased aspartate aminotransferase (AST) levels are present in 36-62% of patients.
• Musculoskeletal
  • Severe myalgia may be present, especially in the legs, abdomen, and back (72-82%).
  • Diffuse arthralgias may occur.
  • Edema on the dorsum of the hands and feet is a key sign (18-20%).
  • Lymphadenopathy develops in 27% of cases.
• Central nervous system
  • Restlessness and irritability may occur.
  • Altered mental status may include delirium, lethargy, and coma.
  • Photophobia occasionally develops.
  • Meningoencephalitis may develop (confusion, seizures [8%], focal neurologic deficits).
  • Cranial neuropathies may be present.
  • Patients may have urinary or fecal incontinence.
  • Paralysis may develop.
  • Ataxia is present in 5-18% of cases.
  • Meningismus develops in 18% of patients.
• Miscellaneous presentations include dehydration, generalized edema, and chills.
• Effects of disseminated R rickettsii infection of endothelial cells include increased vascular permeability that leads to edema, hypovolemia, hypotension, and prerenal azotemia.
• In fatal cases of RMSF, myocarditis is the cause of death.

Causes

R rickettsii is the only cause of RMSF.

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