AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Rocky Mountain spotted fever (RMSF) is the most common rickettsial disease in the United States; it also occurs throughout the Western hemisphere. RMSF is caused by Rickettsia rickettsii, an obligate intracellular gram-negative coccobacilli that contains both DNA and RNA. Ticks serve as both vectors and reservoirs for RMSF. The organism usually is harbored by the wood tick Dermacentor andersoni in the Rocky Mountain states; the American dog tick Dermacentor variabilis in the eastern, central, southern, and Pacific coastal states; the cayenne tick Amblyomma americanum in Texas and in Central and South America; and the brown dog tick Rhipicephalus sanguineus in Arizona and in Mexico.

RMSF is characterized by fever, myalgias, headache, and a petechial rash. Early symptoms are nonspecific. Ocular manifestations include petechial conjunctivitis, anterior uveitis, retinal hemorrhages, cotton-wool spots, retinal vascular engorgement and tortuosity, branch retinal arteriolar occlusion, and optic disc edema.

RMSF is a potentially fatal disease with a mortality rate as high as 30% in the preantibiotic era. Early treatment with appropriate antibiotics is the key prognostic factor. Therapy should be instituted as soon as the disease is suspected clinically. Further, RMSF should be considered in family members and contacts who have febrile illness and share environmental exposures with the patient.

An ophthalmologist rarely participates in the treatment of patients with RMSF where fulminant systemic symptoms overwhelm mild ocular manifestations. The ocular changes probably are underestimated and underdiagnosed, usually resolving within 3 weeks of systemic antibiotic therapy.

Pathophysiology

The disease is transmitted to humans through tick bites, which often occurs unnoticed. The organism invades the endothelial and smooth muscle cells of the blood vessels, producing a systemic vasculitis with increased vascular permeability. Loss of serum proteins, decreased blood volume, and thrombi result in edema, hypovolemia, hypoperfusion, and circulatory failure. Ocular manifestations are due to ischemia and increased vascular permeability.

Frequency

United States

According to the Centers for Disease Control and Prevention (CDC), approximately 600-800 new cases per year occur, with an annual incidence of 3.8 cases per 1 million persons in 2002. The incidence was lowest among persons younger than 5 years and 10-29 years, and the incidence was highest among adults aged 60-69 years. Seasonal outbreaks parallel tick activity. Most cases occur during the spring and summer with rare sporadic cases throughout the year. Risk factors include exposure to wooded areas and to dogs.

Geographic distribution of RMSF shows that more than one half of reported cases are from only 5 states: North Carolina, South Carolina, Tennessee, Oklahoma, and Arkansas.

International

RMSF is endemic in Central and South America.

Mortality/Morbidity

• Untreated cases usually result in death within 15 days of symptom onset.
• The overall mortality rate is currently 1.4%. Children who are younger than 5 years have a case-fatality rate of 5%.
• Mortality increases dramatically if treatment is delayed.
• Even with treatment, the hospitalization rate is as high as 72%.

Race

No racial predilection exists for RMSF.

Sex

The male-to-female ratio is 1.7:1.

Age

In a survey of children, the findings from immunofluorescence antibody assays suggest infection with R rickettsii or the related spotted fever group rickettsiae may be subclinical and occur more commonly than previously thought. Children have been thought to have a high incidence, perhaps because of a high mortality rate in the young age groups. Data from 1997-2002 from the CDC showed the incidence was lowest among persons younger than 5 years and 10-29 years, and the incidence was highest among adults aged 60-69 years.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

Early diagnosis is based on clinical and epidemiologic grounds. The clinician must always have a high index of suspicion, because the early signs and symptoms are nonspecific. A history of tick bite or tick exposure and recent travel to endemic regions are risk factors. The incubation period is 2-14 days following a tick bite.

• High fever (>102°F), headaches, and myalgias occur in greater than 85% of patients.
• Central nervous system (CNS): Of patients with RMSF, 25% develop signs of encephalitis, including lethargy and confusion.
• Gastrointestinal symptoms include abdominal pain, diarrhea, nausea, and vomiting.

Physical

• High fever (>102°F)
• Skin
• • Ninety percent of patients develop a maculopapular rash between days 3-5 of the illness.
  • The rash gradually becomes petechial and progresses to ecchymoses.
  • The rash may have a variable distribution, although classically it first involves the distal extremities (including the palms and soles) and subsequently spreads toward the trunk.
• Central nervous system
• • Confusion and lethargy occur in about 25% of patients.
  • Encephalitis also may produce ataxia, seizures, cranial nerve palsies, hearing loss, photophobia, severe vertigo, dysarthria, aphasia, paralysis, and nystagmus.
• Lungs
• • Findings consistent with pulmonary edema and interstitial pneumonitis may be present.
  • Patients may be short of breath, or develop respiratory compromise.
• Abdomen
• • Signs and symptoms of acute abdomen, splenomegaly, and hepatomegaly may occur.
  • RMSF is included in the differential diagnosis of the acute surgical abdomen.
• Eyes
• • Petechial conjunctivitis occurs as part of the generalized rash.
  • Anterior uveitis has been reported.
  • Retinal vascular dysfunction may result in retinal hemorrhages, retinal ischemia manifested by cotton-wool spots and nerve fiber layer hemorrhages, retinal vascular engorgement and tortuosity, and branch retinal arteriolar occlusion.
  • Optic disc edema due to ischemia and inflammation and orbital edema from increased extravascular volume may be present. Optic disc edema may be associated with peripapillary subretinal fluid extending into the macula (neuroretinitis).
  • The incidence of ocular changes is considered low but probably is underestimated.

Causes

R rickettsii causes RMSF.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Luetic exanthem

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• Early diagnosis is based on clinical and epidemiologic evidence.
• • CBC, differential, prothrombin time/activated partial thromboplastin time (PT/aPTT), chemistry, urinalysis
  • Immunofluorescence test on skin biopsy is specific but not highly sensitive.
  • Serologic tests will not become reliably positive for 7-10 days after symptom onset, because serum antibodies to the organism only become detectable during convalescence.
  • Polymerase chain reaction (PCR) has high sensitivity and specificity.

Imaging Studies

• Chest x-ray and brain magnetic resonance imaging (MRI) as needed

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

Ophthalmic care: Supportive therapy according to the needs of individual patients is indicated.

• Moderate-to-severe uveitis may be treated with topical cycloplegics and corticosteroids, although no reliable information on efficacy is available.
• Artificial tears and ocular lubricating ointment may help relieve discomfort from periorbital edema and petechial conjunctivitis.
• Patients with RMSF usually do not present initially to an ophthalmologist. They are typically already under the care of an internist or infectious disease physician.

Consultations

An infectious disease specialist and/or internist are the appropriate primary physicians to manage these patients.

Activity

• Bed rest
• Activity as tolerated
• Avoid bright lights

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Start IV tetracyclines as soon as possible with chloramphenicol as an alternative. Doxycycline is the drug of choice for oral treatment. Topical cycloplegics, such as cyclopentolate 1% (1 gtt bid/tid), reduce discomfort from uveitis. Topical ophthalmic steroids, such as prednisolone acetate 1% (1 drop bid/tid/qid), reduce ocular inflammation. Artificial tears and lubricating ointment may be used prn or frequently, depending on the amount of discomfort.

Drug Category: Antibiotics

Tetracyclines are the treatment of choice for adults and children older than 9 years. A course of doxycycline in children younger than 9 years is usually recommended because of better efficacy in treating this potentially life-threatening disease and no risk of aplastic anemia; doxycycline also binds less strongly to calcium than tetracycline does and, thus, is considered less likely to stain teeth. The American Academy of Pediatrics and the CDC recommend chloramphenicol for children younger than 9 years to avoid permanent staining of teeth.

Drug Category: Cycloplegics

These agents relax any ciliary muscle spasm that can cause a deep aching pain and photophobia. Cycloplegic agents are also mydriatics, and the practitioner should make sure that the patient does not have glaucoma. This medication could provoke an acute angle-closure attack.

Drug Category: Topical corticosteroids

Suppresses active disease, which is assumed to be due to inflammatory mechanisms.

Drug Category: Nonsteroidal anti-inflammatory agents

Have analgesic and anti-inflammatory activities. Their mechanism of action is not known but may inhibit cyclooxygenase activity and prostaglandin synthesis. Other mechanisms may exist as well, such as inhibition of leukotriene synthesis, lysosomal enzyme release, lipoxygenase activity, neutrophil aggregation, and various cell membrane functions.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• Most patients with RMSF are treated on an inpatient basis.
• The frequency of long-term ocular sequelae is low, and, in most cases, good binocular visual acuity is preserved.

Further Outpatient Care

• As needed

In/Out Patient Meds

• As needed

Deterrence/Prevention

• Minimize exposure to ticks

Complications

• Sequelae of encephalitis
• Pulmonary damage
• Retinal and optic nerve ischemia

Prognosis

• Prognosis usually is excellent if the patient was treated early in disease.

Patient Education

• People in endemic areas should avoid tick exposure by wearing well-covered clothing. A thorough body inspection should be performed after activity in a known or high-risk tick area. Tick repellants are readily available.
• For excellent patient education resources, visit eMedicine's Bites and Stings Center. Also, see eMedicine's patient education article Ticks.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• To prevent delay in diagnosis and treatment, consider RMSF in any febrile patient in an endemic area.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

• Centers for Disease Control and Prevention (CDC). Fatal cases of Rocky Mountain spotted fever in family clusters--three states, 2003. MMWR Morb Mortal Wkly Rep. May 21 2004;53(19):407-10. [Medline].
• Chapman AS, Murphy SM, Demma LJ, et al. Rocky Mountain spotted fever in the United States, 1997-2002. Vector Borne Zoonotic Dis. 2006;6(2):170-8. [Medline].
• 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. 2006;55:1-27. [Medline]. [Full Text].
• Cherubini TD, Spaeth GL. Anterior nongranulomatous uveitis associated with Rocky Mountain spotted fever. First report of a case. Arch Ophthalmol. Mar 1969;81(3):363-5. [Medline].
• Duffey RJ, Hammer ME. The ocular manifestations of Rocky Mountain spotted fever. Ann Ophthalmol. Aug 1987;19(8):301-3, 306. [Medline].
• Eremeeva ME, Dasch GA, Silverman DJ. Evaluation of a PCR assay for quantitation of Rickettsia rickettsii and closely related spotted fever group rickettsiae. J Clin Microbiol. Dec 2003;41(12):5466-72. [Medline].
• Kamper C. Treatment of Rocky Mountain spotted fever. J Pediatr Health Care. Jul-Aug 1991;5(4):216-22. [Medline].
• Kirk JL, Fine DP, Sexton DJ, Muchmore HG. Rocky Mountain spotted fever. A clinical review based on 48 confirmed cases, 1943-1986. Medicine (Baltimore). Jan 1990;69(1):35-45. [Medline].
• 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].
• Marshall GS, Stout GG, Jacobs RF, et al. Antibodies reactive to Rickettsia rickettsii among children living in the southeast and south central regions of the United States. Arch Pediatr Adolesc Med. May 2003;157(5):443-8. [Medline].
• Miller NR. Rickettsiae and rickettsial diseases. In: Miller NR, Newman NJ, eds. Walsh and Hoyt's Clinical Neuro-Ophthalmology. 5th ed. Baltimore: Williams and Wilkins;1998: 4739-4748.
• Presley GD. Fundus changes in Rocky Mountain spotted fever. Am J Ophthalmol. Feb 1969;67(2):263-7. [Medline].
• Raab EL, Leopold IH, Hodes HL. Retinopathy in Rocky Mountain spotted fever. Am J Ophthalmol. Jul 1969;68(1):42-6. [Medline].
• Smith TW, Burton TC. The retinal manifestations of Rocky Mountain spotted fever. Am J Ophthalmol. Aug 1977;84(2):259-62. [Medline].
• Spach DH, Liles WC, Campbell GL, et al. Tick-borne diseases in the United States. N Engl J Med. Sep 23 1993;329(13):936-47. [Medline].
• Stenos J, Graves SR, Unsworth NB. A highly sensitive and specific real-time PCR assay for the detection of spotted fever and typhus group Rickettsiae. Am J Trop Med Hyg. Dec 2005;73(6):1083-5. [Medline].
• Vaphiades MS. Rocky Mountain Spotted Fever as a cause of macular star figure. J Neuroophthalmol. Dec 2003;23(4):276-8. [Medline].
• Weber DJ, Walker DH. Rocky Mountain spotted fever. Infect Dis Clin North Am. Mar 1991;5(1):19-35. [Medline].

Article Last Updated: Nov 1, 2006