eMedicine Specialties > Ophthalmology > Infectious Disease

Rocky Mountain Spotted Fever

Byron L Lam, MD, Professor, Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami School of Medicine

Updated: Oct 30, 2009

Introduction

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.¹

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), 3908 cases of RMSF were reported in 2002-2004.² The numbers of reported cases are increasing in the United States with declining mortality rates. This may be because other rickettsial diseases are being grouped under the general term of Rocky Mountain spotted fever. 

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.³

Geographic distribution of RMSF shows that more than one half of reported cases are from Oklahoma, Tennessee, Arkansas, Maryland, Virginia, North Carolina, and South Carolina.⁴

International

RMSF is endemic in Central and South America.

Mortality/Morbidity

• Untreated cases may result in death within 15 days of symptom onset.
• Even with treatment, the hospitalization rate is as high as 72%.
• Mortality increases if treatment is delayed. 
• The overall case-fatality rate in the United States was 0.7% in 2002-2004.²
• The recent declining mortality rates in the United States may be because of improved early treatment or in part to other rickettsial diseases being grouped under the general term of Rocky Mountain spotted fever.

Race

No racial predilection exists for RMSF.

Sex

The male-to-female ratio is near 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. 
 
According to the CDC, the incidence was highest among persons aged 5-9 years and in those aged 40-64 years.

Clinical

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.¹ 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.

Differential Diagnoses

Other Problems to Be Considered

Luetic exanthem

Workup

Laboratory 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

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

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.

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.

Doxycycline (Doryx, Bio-Tab, Vibramycin)

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

Dosing

Adult

200 mg PO/IV divided bid

Pediatric

<100 lb: 2 mg/lb divided bid PO/IV
>100 lb: 200 mg divided bid PO/IV

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)

Binds to 50 S bacterial-ribosomal subunits and inhibits bacterial growth by inhibiting protein synthesis. Effective against gram-negative and gram-positive bacteria.

Dosing

Adult

Not recommended

Pediatric

50-75 mg/kg PO qid

Interactions

Administered concurrently with barbiturates, chloramphenicol serum levels may decrease while barbiturate levels may increase causing toxicity; manifestations of hypoglycemia may occur with sulfonylureas; rifampin may reduce serum chloramphenicol levels, presumably through hepatic enzyme induction; may increase effects of anticoagulants; may increase serum hydantoin levels, possibly resulting in toxicity; chloramphenicol levels may be increased or decreased

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

D - Fetal risk shown in humans; use only 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)

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.

Cyclopentolate 1% (AK-Pentolate, Cyclogyl)

DOC in corneal abrasions. Blocks muscle of ciliary body and sphincter muscle of iris from responding to cholinergic stimulation, thus causing mydriasis and cycloplegia.
Induces mydriasis in 30-60 min and cycloplegia in 25-75 minutes. These effects last up to 24 hours.

Dosing

Adult

1 gtt bid/tid in affected eye(s)

Pediatric

Administer as in adults; use 0.5% instead of 1% in infants

Interactions

Decreases effects of carbachol and cholinesterase inhibitors

Contraindications

Documented hypersensitivity; narrow-angle glaucoma

Precautions

Pregnancy

A - Fetal risk not revealed in controlled studies in humans

Precautions

Exercise caution in patients (eg, elderly persons) where increased intraocular pressure may be present; can cause toxic anticholinergic systemic adverse effects (common in children especially infants) but incidence rare when used sparingly; compressing lacrimal sac by digital pressure for 1-3 min, following application, may minimize systemic absorption

Topical corticosteroids

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

Prednisolone acetate 1% (AK-Pred, Delta-Cortef, Econopred)

Decreases autoimmune reactions, possibly by suppressing key components of immune system.

Dosing

Adult

1 gtt qd/qid in affected eye(s)

Pediatric

Administer as in adults

Interactions

None reported

Contraindications

Documented hypersensitivity; viral, fungal, or tubercular infections

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

Caution in hyperthyroidism, osteoporosis, cirrhosis, nonspecific ulcerative colitis, peptic ulcer, diabetes, and myasthenia gravis; may increase IOP; prolonged use may result in glaucoma

Loteprednol etabonate (Lotemax, Alrex)

Decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reversing increased capillary permeability. Topical ester steroid drop with decreased risk of glaucoma. Available in 0.2% and 0.5% drops.

Dosing

Adult

1 gtt tid up to q1h in both eyes; well shaken to suspend particles

Pediatric

Administer as in adults

Interactions

None reported

Contraindications

Documented hypersensitivity; viral, fungal, or tubercular infections

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

Caution in hypertension; known to cause cataract formation with chronic use; fungal invasion should be suspected in any persistent corneal ulceration where a corticosteroid has been used or is in use (fungal cultures should be taken when appropriate); may increase IOP; prolonged use may result in glaucoma

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.

Diclofenac (Voltaren)

Inhibits prostaglandin synthesis by decreasing activity of enzyme cyclooxygenase, which in turn decreases formation of prostaglandin precursors. May facilitate outflow of aqueous humor and decreases vascular permeability.

Dosing

Adult

1 gtt in affected eye(s) qid or prn for pain and photophobia

Pediatric

Administer as in adults

Interactions

Additive effect with systemic NSAIDs may occur

Contraindications

Documented hypersensitivity; avoid during pregnancy

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Corneal thinning may occur (Voltaren from CibaVision, Duluth, GA is not associated with this increased risk)

Ketorolac (Acular)

Available in preserved bottle as well as PF (preservative free) single dose unit (SDU) containers.

Dosing

Adult

1 gtt in affected eye(s) qid or prn for pain and photophobia

Pediatric

Administer as in adults

Interactions

None reported

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Perform ophthalmologic studies in patients who develop eye complaints during therapy; discontinue therapy if changes are noted; changes may include blurred or diminished vision, corneal deposits and retinal disturbances, scotomata, changes in color vision, and macula degeneration

Follow-up

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

Inpatient & Outpatient Medications

• 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 and by using tick repellants. A thorough body inspection should be performed after activity in a known or high-risk tick area.
• For excellent patient education resources, visit eMedicine's Bites and Stings Center. Also, see eMedicine's patient education article Ticks.

Miscellaneous

Medicolegal Pitfalls

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

References

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3. Labruna MB, Kamakura O, Moraes-Filho J, Horta MC, Pacheco RC. Rocky Mountain spotted fever in dogs, Brazil. Emerg Infect Dis. Mar 2009;15(3):458-60. [Medline].

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16. Presley GD. Fundus changes in Rocky Mountain spotted fever. Am J Ophthalmol. Feb 1969;67(2):263-7. [Medline].

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Keywords

Rocky Mountain spotted fever, RMSF, rickettsial disease, ticks, wood ticks, dog ticks,

Contributor Information and Disclosures

Author

Byron L Lam, MD, Professor, Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami School of Medicine
Byron L Lam, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Ophthalmology, American Medical Association, and Phi Beta Kappa
Disclosure: Nothing to disclose.

Medical Editor

John D Sheppard Jr, MD, MMSc, Professor of Ophthalmology, Microbiology and Molecular Biology, Clinical Director, Thomas R Lee Center for Ocular Pharmacology, Program Director, Ophthalmology Residency Training, Eastern Virginia Medical School; President, Virginia Eye Consultants
John D Sheppard Jr, MD, MMSc is a member of the following medical societies: American Academy of Ophthalmology, American Society for Microbiology, American Society of Cataract and Refractive Surgery, American Uveitis Society, and Association for Research in Vision and Ophthalmology
Disclosure: Nothing to disclose.

Pharmacy Editor

Simon K Law, MD, PharmD, Assistant Professor of Ophthalmology, Jules Stein Eye Institute; Chief of Section of Ophthalmology Surgical Services, Department of Veterans Affairs Healthcare Center, West Los Angeles
Simon K Law, MD, PharmD is a member of the following medical societies: American Academy of Ophthalmology, American Glaucoma Society, and Association for Research in Vision and Ophthalmology
Disclosure: Nothing to disclose.

Managing Editor

R Christopher Walton, MD, Professor, Director of Uveitis and Ocular Inflammatory Disease Service, Department of Ophthalmology, Assistant Dean for Graduate Medical Education, University of Tennessee College of Medicine; Consulting Staff, Regional Medical Center, Memphis Veterans Affairs Medical Center, St Jude Children's Research Hospital
R Christopher Walton, MD is a member of the following medical societies: American Academy of Ophthalmology, American College of Healthcare Executives, American Uveitis Society, Association for Research in Vision and Ophthalmology, and Retina Society
Disclosure: Nothing to disclose.

CME Editor

Lance L Brown, OD, MD, Ophthalmologist, Affiliated With Freeman Hospital and St John's Hospital, Regional Eye Center, Joplin, Missouri
Disclosure: Nothing to disclose.

Chief Editor

Hampton Roy Sr, MD, Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences
Hampton Roy Sr, MD is a member of the following medical societies: American Academy of Ophthalmology, American College of Surgeons, and Pan-American Association of Ophthalmology
Disclosure: Nothing to disclose.

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