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Rocky Mountain Spotted Fever

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
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

Updated: Oct 19, 2009

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 Rocky Mountain 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 Bitterroot Valley. 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 Rocky Mountain 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.

Differential Diagnoses

Babesiosis
Q Fever
Dengue Fever
Rickettsialpox
Ehrlichiosis
Streptococcus Group A Infections
Enteroviruses
Streptococcus Group B Infections
Hepatitis, Viral
Streptococcus Group D Infections
Infectious Mononucleosis
Syphilis
Leptospirosis
Thrombotic Thrombocytopenic Purpura
Lyme Disease
Toxic Shock Syndrome
Malaria
Tularemia
Mediterranean Spotted Fever
Typhus
Meningitis
Meningococcemia

Other Problems to Be Considered

Acute surgical abdomen
Allergic vasculitis
Brill-Zinsser disease
Drug hypersensitivity
Atypical measles
Murine typhus
Rubeola
Undifferentiated viral illness
Drug reactions
Other acute rickettsial infections (eg, Mediterranean spotted fever, North Asian tick typhus, Siberian tick typhus, Astrakhan fever, African tick bite fever, Japanese spotted fever, Queensland tick typhus, Flinders Island spotted fever, Israeli tick typhus, Marseilles tick bite fever)

Workup

Laboratory Studies

  • Rocky Mountain spotted fever (RMSF) diagnosis relies on clinical (fever, rash, myalgia) and epidemiologic (tick exposure) criteria.
  • After exposure to vector ticks, patients who develop fever, petechial rash, and vomiting require antibiotic therapy. Antibiotic therapy should be initiated before laboratory confirmation is available.
  • A clinical diagnosis of RMSF is difficult to establish, and laboratory findings are nonspecific. Immunologic methods for detection of rickettsiae are unavailable in most clinics.
  • White blood cell count  
    • Leukopenia is present initially, then mild leukocytosis.
    • Patients usually have a normal WBC count.
  • Platelets  
    • Thrombocytopenia (<150,000 cells/µL) occurs in 32-52% of patients.
    • Abnormalities indicative of DIC are present in severely ill patients.
  • Hemoglobin and hematocrit: Anemia is present in 5-24% of patients.
  • Serology
    • Diagnosis is confirmed based on indirect immunofluorescent antibody (IFA) test results, latex agglutination, or enzyme immunoassay.
    • Serology specific for R rickettsii infection develops within 6-8 weeks.
    • Serological test results are negative prior to until convalescence.
  • Other laboratory findings  
    • Mildly elevated aminotransferase levels are present in 36-62% of patients.
    • Hyponatremia is present in 19-56% of cases.
    • Increased bilirubin levels are present in 8-9% of patients.
    • Mild cerebrospinal fluid pleocytosis with monocyte predominance may be present.
    • Azotemia develops in 12-14% of cases.
    • Elevated prothrombin time and activated partial thromboplastin time may be present.

Imaging Studies

  • Chest radiographs that show an early pulmonary infiltrate should prompt consideration of a different diagnosis.

Other Tests

  • Electrocardiography may indicate myocardial or conduction abnormalities.
  • The Weil-Felix test is used to detect cross-reacting antibodies against Proteus vulgaris antigens OX-2 and OX-19.
    • This test lacks sensitivity and specificity, and better tests are now available.
    • If the Proteus titer is greater than or equal to 1:320 or if a 4-fold or greater rise to either Proteus OX-19 or OX-2 antigens is observed, an RMSF case that is clinically compatible is considered probable.

Procedures

  • Skin biopsy
    • Direct immunofluorescent microscopy, if available, may be used for rapid histologic diagnosis of RMSF.
    • Immunofluorescent or immunoperoxidase staining of R rickettsii in a biopsy skin or organ specimen is both sensitive (73%) and specific (100%).5
    • Antibodies to specific rickettsial antigens are detected by indirect immunofluorescence (most specific), latex agglutination, and enzyme immunoassay. The diagnostic titer is 1:64 for indirect immunofluorescence and latex agglutination.
    • Polymerase chain reaction amplification of R rickettsii DNA has not been proven to be a sensitive diagnostic method except for later in the disease course, particularly fatal cases. It has been successful when applied to biopsy skin samples during rickettsioses and to ticks. According to Walker and Raoult in 2000, the primers used amplify genes of the 17-kD protein citrate synthetase and rickettsial OmpA and allow the identification of any rickettsial organism.
  • Lumbar puncture is not routinely indicated but is important to rule out meningitis in some patients with RMSF who have CNS findings.

Treatment

Medical Care

Initiating antibiotics early significantly reduces the mortality rate of Rocky Mountain spotted fever (RMSF) from 20% to approximately 5%. In addition, it prevents early complications.

  • Patients may require oxygen or intubation.
  • Fluids  
    • Dehydration due to high fever and vomiting may occur.
    • Appropriate and aggressive fluid management with isotonic fluids should be instituted.
    • Monitor urine output and blood pressure.
  • A Swan-Ganz catheter may be needed to monitor hemodynamics in some patients.

Consultations

  • Always report tick-borne illnesses to public health authorities.
  • Consultation with an infectious disease specialist is advised.
  • A dermatologist should be consulted to obtain a skin biopsy specimen for immunofluorescent staining, if available.

Medication

In adults with Rocky Mountain spotted fever (RMSF), the preferred drug of choice is doxycycline. Chloramphenicol is an alternative. In vitro and in ovo R rickettsii are also susceptible to rifampin.

In 1997, the American Academy of Pediatrics revised treatment options for children with RMSF. Doxycycline became the preferred drug choice for treating children of any age because of the potential for severe or fatal cases.

Short courses of doxycycline to treat RMSF do not cause significant dental staining.6 Doxycycline is preferable to chloramphenicol because tetracyclines have been shown to be associated with a higher survival rate.

Beta-lactam antibiotic coverage does not treat RMSF. Some new quinolones have antirickettsial effects in vitro, but the clinical experience in RMSF is limited.

Antibiotics

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.


Doxycycline (Bio-Tab, Doryx, Vibramycin)

Drug of choice for RMSF. Inhibits protein synthesis and thus bacterial growth by binding to 30S and possibly 50S ribosomal subunits of susceptible bacteria.

Dosing

Adult

200 mg/d PO/IV for 7 d or through third day of defervescence; 200 mg PO/IV q12h for 72 h loading dose should be given, followed by 100 mg q12h

Pediatric

>45 kg: 2 mg/kg PO/IV loading dose, followed by 1 mg/kg PO/IV q12h; administer for 7 d and for at least 48 h after defervescence

Interactions

Bioavailability decreases with antacids containing aluminum, calcium, magnesium, iron, or bismuth subsalicylate; tetracyclines can increase hypoprothrombinemic effects of anticoagulants; tetracyclines can decrease effects of oral contraceptives, causing breakthrough bleeding and increased risk of pregnancy

Contraindications

Documented hypersensitivity; severe hepatic dysfunction

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Photosensitivity may occur with prolonged exposure to sunlight or tanning equipment; reduce dose in renal impairment; consider drug serum level determinations in prolonged therapy; tetracycline use during tooth development (last one half of pregnancy through age 8 y) can cause permanent discoloration of teeth; Fanconilike syndrome may occur with outdated tetracyclines


Chloramphenicol (Chloromycetin)

Alternative choice for RMSF in pregnant women and patients allergic to tetracyclines. Binds to 50S bacterial ribosomal subunits and inhibits bacterial growth by inhibiting protein synthesis.

Dosing

Adult

500 mg IV divided qid for 7 d

Pediatric

50 mg/kg PO or 75 mg/kg IV divided qid for 7 d and for at least 48 h after defervescence

Interactions

Concurrently with barbiturates, serum levels may decrease while barbiturate levels may increase; rifampin may reduce serum levels; may increase effects of anticoagulants; may increase serum hydantoin levels, chloramphenicol levels may be increased or decreased

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Use only for indicated infections or as prophylaxis for bacterial infections; serious and fatal blood dyscrasias (aplastic anemia, hypoplastic anemia, thrombocytopenia, granulocytopenia) can occur; evaluate baseline and perform periodic blood studies approximately every 2 d while in therapy; discontinue upon appearance of reticulocytopenia, leukopenia, thrombocytopenia, anemia, or findings attributable to chloramphenicol; adjust dose in liver or kidney dysfunction; caution in pregnancy at term or during labor because of potential toxic effects on fetus (gray syndrome)

Follow-up

Transfer

Proper personnel trained in complicated airway intervention and treatment of shock should be available to patients with Rocky Mountain spotted fever (RMSF)who are comatose, convulsing, or hypotensive.

Deterrence/Prevention

  • The best means of prevention is to avoid contact with ticks by using protective clothing and repellants.
  • Currently, research is underway to develop an effective vaccine using OmpA expressed in baculovirus to be used among high-risk patients in endemic areas.
  • See Patient Education.

Complications

  • Disseminated intravascular coagulation
  • Noncardiogenic pulmonary edema
  • Acute tubular necrosis
  • Shock with myocarditis
  • Skin necrosis and gangrene, particularly in fingers, toes, elbows, ears, and scrotum
  • Myocarditis - Usual cause of death
  • Other possible complications include the following:  
    • Seizures
    • Encephalopathy
    • Peripheral neuropathy
    • Bowel and bladder incontinence
    • Cerebellar and vestibular dysfunction
    • Hearing loss
  • Hemophagocytic histiocytosis - Described in fatal cases of RMSF

Prognosis

  • Mortality rates vary according to the following criteria:  
    • Delay in diagnosis
    • Delay in effective antibiotic treatment
    • Age
    • Race
    • Severity of the disease
  • Mortality rates can be as low as 5% with proper antibiotic therapy and as high as 70% in untreated elderly individuals.
  • Risk factors for fatal outcome in RMSF include the following:  
    • Age older than 40 years
    • Delay in treatment
    • No treatment within the first 5 days of illness3

Patient Education

  • To promote prevention, educate the public about transmission of ticks and means of personal protection.
    • Avoid dogs with ticks and tick-infected areas.
    • Use protective light-colored clothing that covers arms and legs. Tuck pants in socks to protect legs.
    • Apply tick-repellent chemicals such as diethyltoluamide (DEET, Autan) or permethrin to pants and sleeves.
    • Search the entire body every 3-4 hours when in an infested area. Common areas of attachment are in scalp, pubic, or axillary hair.
    • Without crushing the tick, remove it promptly using gentle steady traction with tweezers. Be careful not to leave any mouthparts. Protect hands with gloves.
    • Because the tick needs 6-10 hours of feeding to transmit the disease, early discovery and removal of ticks can prevent infection.
    • Prophylaxis with doxycycline for 7 days is recommended after tick removal.
  • For excellent patient education resources, visit eMedicine's Bites and Stings Center. Also, see eMedicine's patient education article Ticks.

Miscellaneous

Medicolegal Pitfalls

  • Failure to promptly evaluate and treat patients with acute febrile illnesses and tick exposure
  • Failure to consider Rocky Mountain spotted fever (RMSF) in a febrile patient in an endemic area, regardless of tick exposure

Special Concerns

  • Pregnancy  
    • Whether R rickettsii can cross the placenta and adversely affect the fetus remains unknown.
    • In a case report, a pregnant patient with RMSF was treated with chloramphenicol successfully with no apparent adverse maternal or neonatal effects.7
  • Human ehrlichiosis caused by Ehrlichia canis mimics RMSF in its clinical manifestations and geographic and seasonal distribution. Rash is not present with ehrlichiosis. Spotless RMSF is usually ehrlichiosis. Doxycycline is the preferred drug for human ehrlichiosis.

References

  1. Sexton DJ, Corey GR. Rocky Mountain "spotless" and "almost spotless" fever: a wolf in sheep's clothing. Clin Infect Dis. Sep 1992;15(3):439-48. [Medline].

  2. Salgo MP, Telzak EE, Currie B, et al. A focus of Rocky Mountain spotted fever within New York City. N Engl J Med. May 26 1988;318(21):1345-8. [Medline].

  3. Kirkland KB, Wilkinson WE, Sexton DJ. Therapeutic delay and mortality in cases of Rocky Mountain spotted fever. Clin Infect Dis. May 1995;20(5):1118-21. [Medline].

  4. Byrd RP Jr, Vasquez J, Roy TM. Respiratory manifestations of tick-borne diseases in the Southeastern United States. South Med J. Jan 1997;90(1):1-4. [Medline].

  5. Procop GW, Burchette JL Jr, Howell DN, et al. Immunoperoxidase and immunofluorescent staining of Rickettsia rickettsii in skin biopsies. A comparative study. Arch Pathol Lab Med. Aug 1997;121(8):894-9. [Medline].

  6. Lochary ME, Lockhart PB, Williams WT Jr. Doxycycline and staining of permanent teeth. Pediatr Infect Dis J. May 1998;17(5):429-31. [Medline].

  7. Markley KC, Levine AB, Chan Y. Rocky Mountain spotted fever in pregnancy. Obstet Gynecol. May 1998;91(5 Pt 2):860. [Medline].

  8. Beers MH, Berkow R, eds. Rocky Mountain Spotted Fever. In: The Merck Manual. 17th ed. Whitehouse Station, NJ: Merck & Co; 1999:1230-1.

  9. Brouqui P. Tick-borne Rickettsioses of the Eastern Hemisphere. In: Strickland GT, ed. Hunter's Tropical Medicine and Emerging Infectious Diseases. 8th ed. Philadelphia, Pa: WB Saunders; 2000:438-42.

  10. Centers for Disease Control and Prevention. Rocky Mountain spotted fever--United States, 1990. MMWR Morb Mortal Wkly Rep. Jul 12 1991;40(27):451-3, 459. [Medline].

  11. Chen LF, Sexton DJ. What's new in Rocky Mountain spotted fever?. Infect Dis Clin North Am. Sep 2008;22(3):415-32, vii-viii. [Medline].

  12. Cunha BA. Clinical features of Rocky Mountain spotted fever. Lancet Infect Dis. Mar 2008;8(3):143-4. [Medline].

  13. Cunha BA. Key Clinical Features of Rocky Mountain Spotted Fever. Lancet Infectious Disease. 2008;7:143-144.

  14. Cunha BA. Rocky Mountain spotted fever revisited. Arch Intern Med. Jan 26 2004;164(2):221-2. [Medline].

  15. Getfand MS, Daniel CB Jr, Killebrew L. Rocky Mountain spotted fever: legal duty to warn for noncontagious disease. JAMA. Nov 22-29 1995;274(20):1586-7. [Medline].

  16. Gudiol F, Pallares R, Carratala J, et al. Randomized double-blind evaluation of ciprofloxacin and doxycycline for Mediterranean spotted fever. Antimicrob Agents Chemother. Jun 1989;33(6):987-8. [Medline].

  17. Harrell GT, Aikawa JK. Rocky Mountain spotted fever. Medicine (Baltimore). Dec 1949;28(4):333-70. [Medline].

  18. Hazard GW, Ganz RN, Nevin RW, et al. Rocky mountain spotted fever in the eastern United States. N Engl J Med. Jan 9 1969;280(2):57-62. [Medline].

  19. Helmick CG, Bernard KW, D'Angelo LJ. Rocky Mountain spotted fever: clinical, laboratory, and epidemiological features of 262 cases. J Infect Dis. Oct 1984;150(4):480-8. [Medline].

  20. Holman RC, McQuiston JH, Haberling DL, Cheek JE. Increasing incidence of Rocky Mountain spotted fever among the American Indian population in the United States. Am J Trop Med Hyg. Apr 2009;80(4):601-5. [Medline].

  21. Jain SK, Khan JA, Mittal V, Kumar K, Venkatesh S, Jain DC, et al. Indian tick typhus mimicking as Rocky Mountain Spotted Fever: a case report. J Commun Dis. Mar 2008;40(1):83-5. [Medline].

  22. Kirk JL, Fine DP, Sexton DJ, et al. Rocky Mountain spotted fever. A clinical review based on 48 confirmed cases, 1943-1986. Medicine (Baltimore). Jan 1990;69(1):35-45. [Medline].

  23. Lackman DB, Gerloff RK. The effects of antibiotic therapy upon diagnostic, serologic tests for Rocky Mountain spotted fever. Public Health Laboratory. 1953;11:97-100.

  24. Minnick K, Schleupner CJ. Rocky Mountain Spotted Fever. In: Rakel RE, ed. Conn's Current Therapy. Philadelphia, Pa: WB Saunders; 1997:144.

  25. Raoult D, Parola P. Rocky Mountain spotted fever in the USA: a benign disease or a common diagnostic error?. Lancet Infect Dis. Oct 2008;8(10):587-9. [Medline].

  26. Saah AJ. Introduction to Rickettsioses and Ehrlichioses. In: Mandel GL, Bennett JE, Dolin R, eds. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases. 5th ed. Philadelphia, Pa: Churchill Livingstone; 2000:2033-5.

  27. Sexton DJ. Rocky Mountain Spotted Fever. In: Strickland GT, ed. Hunter's Tropical Medicine and Emerging Infectious Diseases. 8th ed. Philadelphia, Pa: WB Saunders; 2000:435-8.

  28. Thorner AR, Walker DH, Petri WA Jr. Rocky mountain spotted fever. Clin Infect Dis. Dec 1998;27(6):1353-9; quiz 1360. [Medline].

  29. Tierney LM, McPhee SJ, Papadakis MA, eds. Rocky Mountain Spotted Fever. In: CURRENT Medical Diagnosis & Treatment. . 38th ed. New York, NY: McGraw-Hill; 1999:1287-8.

  30. Toerner JG, Kumar PN, Garagusi VF. Guillain-Barré syndrome associated with Rocky Mountain spotted fever: case report and review. Clin Infect Dis. Jun 1996;22(6):1090-1. [Medline].

  31. Torres J, Humphreys E, Bisno AL. Rocky Mountain spotted fever in the Mid-South. Arch Intern Med. Sep 1973;132(3):340-7. [Medline].

  32. Walker DH. Rocky Mountain spotted fever: a seasonal alert. Clin Infect Dis. May 1995;20(5):1111-7. [Medline].

  33. Walker DH, Burday MS, Folds JD. Laboratory diagnosis of Rocky Mountain spotted fever. South Med J. Nov 1980;73(11):1443-6, 1449. [Medline].

  34. Walker DH, Lane TW. Rocky Mountain spotted fever; clinical signs, symptoms, and pathophysiology. In: Walker DH, ed. Biology of Rickettsial Diseases. Vol 1. Boca Raton, Fla: CRC Press; 1988:63-78.

  35. Walker DH, Peacock MG. Laboratory diagnosis of rickettsial diseases. In: Walker DH, ed. Biology of Rickettsial Diseases. Vol 1. Boca Raton, Fla: CRC Press;. 1988:135-55.

  36. Walker DH, Raoult D. Rickettsia rickettsii and Other Spotted Fever Group Rickettsiae. In: Mandel GL, Bennett JE, Dolin R, eds. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases. 4th ed. Philadelphia, Pa: Churchill Livingstone; 1995:1719-27.

  37. Walker DH, Raoult D, Brouqui P. Rickettsial Diseases. In: Fauci AS, Braunwald E, Isselbacher KJ, et al, eds. Harrison's Principles of Internal Medicine. 14th ed. New York, NY: McGraw-Hill; 1998:1045-6.

  38. White DJ, Flynn MK. Rocky Mountain spotted fever in New York State. Ann N Y Acad Sci. 1990;590:248-55. [Medline].

  39. Woodward TE. Rickettsia. In: Fauci AS, Braunwald E, Isselbacher KJ, et al, eds. Harrison's Principles of Internal Medicine. 13th ed. New York, NY: McGraw-Hill; 1994:747-57.

  40. Woodward TE. Rickettsial diseases. In: Weatherall DJ, Ledingham JGG, Warrel DA, eds. Oxford Textbook of Medicine. Vol 1. 2nd ed. London, UK: Oxford University Press; 1987:341-8.

  41. Woodward TE, Cunha BA. Rocky Mountain spotted fever. Infect Dis Pract. 1999;23:73-80.

  42. Woodward TE, Cunha BA. Rocky Mountain Spotted Fever. In: Cunha BA, ed. Tickborne Infectious Diseases. New York, NY: Marcel Dekker; 2000:121-37.

  43. Zavala-Castro JE, Dzul-Rosado KR, León JJ, Walker DH, Zavala-Velázquez JE. An increase in human cases of spotted fever rickettsiosis in Yucatan, Mexico, involving children. Am J Trop Med Hyg. Dec 2008;79(6):907-10. [Medline].

Keywords

Rocky Mountain spotted fever, RMSF, tick fever, spotted fever, tick typhus, New World spotted fever, Rickettsia rickettsii, R rickettsii, Sao Paulo fever, fiebre manchada, fiebre petechial, fiebre maculosa brasiliensis, dog tick, wood tick, the great imitator

Contributor Information and Disclosures

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
Burke A Cunha, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

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
Richard H Snyder, MD is a member of the following medical societies: American College of Physicians
Disclosure: Nothing to disclose.

Marie Spevak O'Brien, DO, Assistant Clinical Professor of Medicine, Arthritis and Rheumatology, Lehigh Valley Physician Group
Marie Spevak O'Brien, DO is a member of the following medical societies: American College of Physicians, American College of Rheumatology, American Medical Association, American Osteopathic Association, International Society for Clinical Densitometry, and Pennsylvania Medical Society
Disclosure: Nothing to disclose.

Medical Editor

Gary L Gorby, MD, Program Director of Adult Infectious Diseases Fellowship, Associate Professor, Department of Internal Medicine, Division of Infectious Disease, St Joseph Medical Center, Creighton University School of Medicine
Gary L Gorby, MD is a member of the following medical societies: Alpha Omega Alpha, American Medical Association, American Society for Microbiology, Infectious Diseases Society of America, and New York Academy of Sciences
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Aaron Glatt, MD, Professor of Clinical Medicine, New York Medical College; President and CEO, Former Chief Medical Officer, Departments of Medicine and Infectious Diseases, New Island Hospital
Aaron Glatt, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physician Executives, American College of Physicians, American College of Physicians-American Society of Internal Medicine, American Medical Association, American Society for Microbiology, American Thoracic Society, American Venereal Disease Association, Infectious Diseases Society of America, International AIDS Society, and Society for Healthcare Epidemiology of America
Disclosure: Nothing to disclose.

CME Editor

Eleftherios Mylonakis, MD, Clinical and Research Fellow, Department of Internal Medicine, Division of Infectious Diseases, Massachusetts General Hospital
Eleftherios Mylonakis, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American Society for Microbiology, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Chief Editor

Michael Stuart Bronze, MD, Professor, Stewart G Wolf Chair in Internal Medicine, Department of Medicine, University of Oklahoma Health Science Center
Michael Stuart Bronze, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physician Executives, American College of Physicians, American College of Physicians-American Society of Internal Medicine, American Federation for Clinical Research, American Medical Association, American Society for Microbiology, Association of Professors of Medicine, Association of Program Directors in Internal Medicine, Infectious Diseases Society of America, Oklahoma State Medical Association, and Southern Society for Clinical Investigation
Disclosure: Nothing to disclose.

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