Rocky Mountain Spotted Fever (RMSF)

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. See Epidemiology and the map below.

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In the United States, the American dog tick (Dermacentor variabilis) is the most commonly identified source of transmission. This tick is actually fou....

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. (See Epidemiology.)

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 (see the image below) beginning on the palms of the hands and soles of the feet. (See Clinical and Differentials.)

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The patient's rash is a major diagnostic sign of Rocky Mountain spotted fever (RMSF). Image courtesy of the Centers for Disease Control and Prevention....

See also 7 Bug Bites You Need to Know This Summer, a Critical Images slideshow, for helpful images and information on various bug bites.

The 2 principal tick vectors of RMSF in North America are Dermacentor variabilis (dog tick), in the eastern United States, and D 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. A cooperi, A americanum, Ixodes pacificus, and Haemaphysalis leporispalustris are uncommon vectors for human infection. (See Etiology.)

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

Mortality rates as high as 30% were reported for RMSF in the preantibiotic era. Although its clinical manifestations and treatment of the disease are well known, RMSF still causes significant mortality and morbidity. The current mortality rate is 1.4%. A significant portion of this persistent mortality is likely due to delay in diagnosis and treatment.

Patient education

For patient education information, see Ticks.

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Etiology and Pathophysiology

R rickettsii is a small (0.3 µm X 1 µm), gram-negative, obligate, intracellular coccobacillus. It possesses outer-membrane protein A (OmpA) 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 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 Rocky Mountain spotted fever (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 central nervous system (CNS), with similar vascular lesions in the skin, gastrointestinal (GI) 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.

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Epidemiology

Occurrence in the United States

Rocky Mountain spotted fever (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 (see the map below). The disease is more common in rural and suburban locations; however, it does occur in urban areas such as New York City.^{[2, 3, 4]}

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In the United States, the American dog tick (Dermacentor variabilis) is the most commonly identified source of transmission. This tick is actually fou....

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 at any time of the year, including winter.

From 1989-1996, more than 4700 cases were reported in 46 states. Of these reported cases, 90% occurred between April and September.

A prospective study of RMSF infection in residents of a known endemic area in North Carolina suggested an annual incidence of 42 cases per 100,000 children aged 5-9 years. Asymptomatic infection may be common; in one study, 12% of children living in high-risk zones had positive serology test results, indicating past exposure to RMSF.^[5]

In 2005, 1936 cases were reported—more than 4 times the 365 cases reported in 1998. The reasons for this increase are not known, but wide swings in the incidence of RMSF have occurred since 1920. Due to underdiagnosis, lack of testing, and lack of reporting, it is likely that the actual number of cases is much higher than surveillance data suggest.

International occurrence

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.^[6]

There have been no documented cases of RMSF infection outside of the Americas. However, a wide range of related spotted fever group (SFG) rickettsioses has been described across Europe, Africa, Asia, and Oceania. The true incidence of spotted fever infections internationally is not known.

Race-related demographics

Whites have twice the incidence of African Americans. However, African Americans have a higher case-fatality rate. This may be due to the greater difficulty of appreciating a rash in highly pigmented individuals.

American Indians are at greater risk for RMSF than the general population.^[7] From 2001-2005, the average annual incidence of RMSF reported among American Indians was 16.8 per 1,000,000 persons compared with 4.2 for whites, 2.6 for blacks, and 0.5 for Asian/Pacific Islanders. The incidence of RMSF in American Indians increased at a disproportionate rate during this period, although from 1990-2000, the rate was comparable to those for other races from 1990-2000.^[8]

Sex- and age-related demographics

The male-to-female ratio for RMSF is 1.7:1. The mortality risk is also higher in males than in females.

The incidence of Rocky Mountain spotted fever is highest among adults aged 60-69 years (3.1 cases/million persons) and children aged 5-9 years (an estimated 3.3 cases/million persons).

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Prognosis

Mortality rates in Rocky Mountain spotted fever (RMSF) vary according to the following criteria:

• Delay in diagnosis
• Delay in effective antibiotic treatment - In a 1995 study, antirickettsial therapy within the first 5 days of illness reduced the risk of mortality 5-fold compared with treatment initiation after the 5-day mark^[9]
• Age
• Race
• Gender - Mortality risk is higher in males
• Severity of the disease
• Presence of chronic alcohol abuse
• Presence of glucose-6-phosphate-dehydrogenase deficiency

The mortality rate in untreated cases of RMSF is 20-25%. Mortality rates can be as low as 5% with proper antibiotic therapy and as high as 70% in untreated elderly individuals. Death in 5 days can be expected in fulminant cases.^[3]

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Complications

Complications may include the following^{[10, 11, 12]} :

• 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
• Seizures
• Encephalopathy
• Peripheral neuropathy
• Bowel and bladder incontinence
• Cerebellar and vestibular dysfunction
• Hearing loss
• Blindness - The frequency of long-term ocular sequelae is low; in most cases, good binocular visual acuity is preserved
• Scarring
• Hemophagocytic histiocytosis - Has been described in fatal cases of RMSF

Factors at presentation associated with development of acute renal failure (ARF) include increased bilirubin, advancing age, thrombocytopenia, and the presence of neurologic involvement. Age and decreased platelet count at presentation have been independently associated with the development of ARF by multivariate analysis. ARF development increases the odds ratio of dying by a factor of 17.

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History

People with RMSF generally present within a week after a tick bite. 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 spring, summer, or fall (although not limited to these seasons)

RMSF should 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. (Most tick bites are painless and may be in hidden areas of the body.)

In a case series by Buckingham et al, of 92 patients eventually diagnosed with RMSF, the median delay between first visiting a health care provider and starting antirickettsial therapy was 5 days. Only 49% of the patients reported a tick bite.^[13]

In other studies, 66% of reported cases of RMSF included a history of tick attachment 14 days prior to illness. An additional 26% of patients reported being in a tick-infested area.

The classic clinical triad of fever, headache, and rash may be present in less than 5% of patients in the first 3 days of illness but increases to 60-70% by the second week after tick exposure. The absence or delayed appearance of a rash increases the difficulty of diagnosis.

The most common symptom complaints include the following:

• Fever greater than 102°F - 94% of reported cases
• Fever within 3 days after tick bite - 66% of reported cases
• Headache, frequently severe - 86% of reported cases
• Myalgias - 85% of reported cases
• CNS symptoms - 25% of patients develop signs of encephalitis (ie, confusion, lethargy); this may progress to stupor, delirium, seizures, or coma
• GI symptoms - Some patients present with anorexia, nausea, vomiting, diarrhea, and abdominal pain

Patients may also report insomnia and photophobia.

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Physical Examination

Rocky Mountain spotted fever (RMSF) presents with a wide clinical spectrum, ranging from mild fever (usually greater than 102°F), headache, and myalgia to disseminated intravascular coagulation (DIC; 32-53% of patients), shock (7-17%), hypotension (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.

Skin

Rash is a major diagnostic sign that appears in a low percentage of patients on the first day of infection and in only 49% of patients during the first 3 days. See the images below.

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The patient's rash is a major diagnostic sign of Rocky Mountain spotted fever (RMSF). Image courtesy of Bal AK, Kairys SW. Kawasaki disease following ....

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The patient's rash is a major diagnostic sign of Rocky Mountain spotted fever (RMSF). Image courtesy of the Centers for Disease Control and Prevention....

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.

Classic distribution of RMSF rash on the palms and soles occurs relatively late in the course, appearing in 43% of patients only after the fifth day of symptoms. (The hands and the feet are both involved 49-74% of the time.) Some reports have documented 36-80% of patients with RMSF lack the classic distribution of rash on the palms and soles.

The face is usually spared. Involvement of the scrotum or the vulva is a diagnostic clue. Nonproductive cough may accompany the rash (33%).

In the early phases, the rash may be blanching, nonpruritic, and macular. In 45-49% of patients, it eventually becomes petechial; in rare cases, purpura and skin necrosis or gangrene develop. In dark-skinned patients, the rash is difficult to see.

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. Spotless fever is not synonymous with mild or early illness, because substantial proportions of the deaths occur in patients without a rash.

In older patients and in severe or fatal cases of RMSF, the rash tends to appear later and with less frequency.

Other cutaneous abnormalities that may develop in RMSF include postinflammatory hyperpigmentation, jaundice, and mucosal ulcers. An erythema migrans–like rash has also been reported.

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

Cardiovascular presentations of RMSF can include the following:

• Myocarditis
• Relative bradycardia
• Arrhythmias - 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%).

Pulmonary

Pulmonary edema occurs in severe cases. Pneumonitis is present in 12-17% of patients.^[14]

Gastrointestinal

GI presentations of RMSF can include the following:

• Anorexia
• Abdominal pain and tenderness (diffuse in right upper quadrant) - Present in 34-52% of patients
• Jaundice - Develops in severe cases; it is found in 8-9% of patients
• 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 - Present in 36-62% of patients

Musculoskeletal

Musculoskeletal presentations of RMSF can include the following:

• Severe myalgia - Especially in the legs, abdomen, and back; occurs in 72-82% of patients
• Diffuse arthralgias
• Edema on the dorsum of the hands and feet - A key sign; occurs in 18-20% of patients
• Lymphadenopathy - Develops in 27% of cases

Central nervous system

CNS presentations can include the following:

• Restlessness and irritability
• Altered mental status - May include delirium, lethargy, and coma
• Photophobia
• Meningoencephalitis (confusion, seizures [8%], focal neurologic deficits)
• Cranial neuropathies
• Urinary or fecal incontinence
• Ataxia - Present in 5-18% of cases
• Meningismus - Develops in 18% of patients
• Cranial nerve palsies
• Hearing loss
• Photophobia
• Severe vertigo
• Dysarthria
• Aphasia
• Hemiplegia, paraplegia, or complete paralysis
• Nystagmus
• Hyperreflexia
• Spasticity
• Fasciculations

Eyes

The incidence of ocular changes in RMSF is considered low but probably is underestimated. Such changes can include petechial conjunctivitis, which occurs as part of the generalized rash, and anterior uveitis.

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).

Additional presentations

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.

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Approach Considerations

Rocky Mountain spotted fever (RMSF) diagnosis relies on clinical (fever, rash, myalgia) and epidemiologic (tick exposure) criteria. However, a clinical diagnosis of RMSF is difficult to establish, and laboratory findings are nonspecific. Even so, basic laboratory tests should be obtained, including the following: complete blood count (CBC), electrolytes, renal function tests, liver function tests, and coagulation panel.^[15]

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.

Laboratory findings can include the following:

• White blood cell (WBC) 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
• Aminotransferase levels - Mildly elevated in 36-62% of patients
• Hyponatremia - Present in 19-56% of cases
• Bilirubin levels – Increased in 8-9% of patients.
• Mild cerebrospinal fluid pleocytosis with monocyte predominance
• Azotemia - Develops in 12-14% of cases
• Prothrombin time and activated partial thromboplastin time - May be elevated

Anemia, an increased blood urea nitrogen (BUN) level, or abnormal liver function test results are found in 30% of patients. Late findings associated with advanced disease include signs of multiorgan failure, such as elevated BUN, creatinine, and creatinine kinase levels.

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. Serologic test results are negative prior to convalescence.

Blood culture

Isolation of R rickettsii from the blood is possible, but few laboratories perform this isolation because of biohazard concerns. This is an insensitive test because most Rickettsia is found in the vascular endothelial cells, not in the bloodstream.

Imaging studies

Obtain a chest radiograph in patients who appear significantly ill or have abnormal lung findings on physical examination. Chest radiographs that show an early pulmonary infiltrate should prompt consideration of a different diagnosis.

Computed tomography (CT) scanning or magnetic resonance imaging (MRI) are indicated for altered mental status or neurologic deficits and may reveal infarction, edema, and meningeal enhancement.

Lumbar puncture

Lumbar puncture usually is performed as part of the workup for suspected meningitis. Pleocytosis is found in 34-38% of cases. Usually 10-100 cells/µL with either lymphocytic or polymorphonuclear cell predominance are found. Increased protein is found in 30-35% of cases; the glucose level usually is normal.

Other tests

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.

Electrocardiography may be used to indicate whether myocardial or conduction abnormalities are present.

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Skin Biopsy

Direct immunofluorescent microscopy, if available, may be used for rapid histologic diagnosis of Rocky Mountain spotted fever (RMSF). Immunofluorescent or immunoperoxidase staining of R rickettsii in a biopsy skin or organ specimen is sensitive (73%) and specific (100%).^[16] However, because direct immunofluorescence has a 30% false-negative rate, patients should be treated even if the test is negative and the suspicion is high.

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.

Amplification of R rickettsii deoxyribonucleic acid (DNA) with polymerase chain reaction (PCR) assay has not been proven to be a sensitive diagnostic method except for later in the disease course, particularly in fatal cases. It has been successful when applied to biopsy skin samples during rickettsioses and also when applied 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.

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Approach Considerations

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 also require oxygen or intubation.^[15]

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.

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.^[17]

Transfer

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

Outpatient care

Clinically mild cases may be treated on an outpatient basis. However, RMSF can progress rapidly. Because roughly 10% of outpatients subsequently required admission, close follow-up is necessary if outpatient management is planned.

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.

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Prehospital and Emergency Department Care

In emergency prehospital care for Rocky Mountain spotted fever (RMSF), deliver supportive therapy, including airway support and intravenous (IV) fluids, as determined by the severity of the patient's condition. Emergency department care in RMSF includes early empiric therapy with doxycycline and hemodynamic support, as needed.

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Inpatient Care

Hospitalization was required in 72% of confirmed cases of Rocky Mountain spotted fever (RMSF) reported to the Centers for Disease Control and Prevention (CDC). Hospitalization, when required, usually occurs on the fourth day after symptom onset.

Admit moderately to severely ill patients to the hospital. Indications for admission may include altered mental status or other neurologic manifestations of RMSF, abdominal pain (may mimic an acute surgical abdomen), thrombocytopenia, or hypotension due to RMSF myocarditis. Admit severely ill patients to the intensive care unit (ICU).

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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 to relieve discomfort from periorbital edema and petechial conjunctivitis.

Patients with Rocky Mountain spotted fever (RMSF) usually do not present initially to an ophthalmologist. Usually, these patients are already under the care of an internist or infectious disease physician.

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Prevention

Protective measures against tick bites include the following:

• 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

When a tick is present, it should be promptly removed using gentle, steady traction with tweezers. Care should be taken not to crush the tick or to leave any mouthparts. Hands should be protected 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.

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Medication Summary

In adults with Rocky Mountain spotted fever (RMSF), the drug of choice is doxycycline for life-threatening RMSF. Chloramphenicol is an alternative, although doxycycline is preferable because tetracyclines have been shown to be associated with a higher survival rate than chloramphenicol.^[18] In vitro and in ovo R rickettsii are also susceptible to rifampin.

Doxycycline therapy also treats Lyme disease, ehrlichiosis, and relapsing fever—entities often clinically confused with RMSF.^[19] Oral formulations may be used for patients being treated at home or for hospitalized patients who can take oral medications.

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.^[20] Beta-lactam antibiotic coverage does not treat RMSF.

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Doxycycline (Adoxa, Oraxyl , Doryx, Vibramycin)

• Dosing, Interactions, etc.

Clinical Context:  Doxycycline is the drug of choice for Rocky Mountain spotted fever (RMSF). It inhibits protein synthesis and, consequently, bacterial growth by binding to 30S and possibly 50S ribosomal subunits of susceptible bacteria.

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Chloramphenicol

• Dosing, Interactions, etc.

Clinical Context:  Chloramphenicol is the alternative choice for RMSF in pregnant women and patients allergic to tetracyclines. It binds to 50S bacterial ribosomal subunits and inhibits bacterial growth by inhibiting protein synthesis.

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Class Summary

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

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Cyclopentolate 1% (AK-Pentolate, Cyclogyl, Cylate)

• Dosing, Interactions, etc.

Clinical Context:  Cyclopentolate is the drug of choice in corneal abrasions. It blocks the muscle of the ciliary body and the sphincter muscle of the iris from responding to cholinergic stimulation, thus causing mydriasis and cycloplegia. Cyclopentolate induces mydriasis in 30-60 minutes and cycloplegia in 25-75 minutes. These effects last up to 24 hours.

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Class Summary

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.

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Prednisolone ophthalmic (Omnipred, Pred Forte, Pred Mild)

• Dosing, Interactions, etc.

Clinical Context:  This agent decreases autoimmune reactions, possibly by suppressing key components of the immune system.

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Loteprednol etabonate (Lotemax, Alrex)

• Dosing, Interactions, etc.

Clinical Context:  Loteprednol etabonate decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reversing increased capillary permeability. It is a topical ester steroid drop with decreased risk of glaucoma. Loteprednol etabonate is available in 0.2% and 0.5% drops.

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Class Summary

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

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Diclofenac ophthalmic (Voltaren Ophthalmic)

• Dosing, Interactions, etc.

Clinical Context:  This agent inhibits prostaglandin synthesis by decreasing the activity of the enzyme cyclooxygenase, which in turn decreases formation of prostaglandin precursors. Diclofenac ophthalmic may facilitate outflow of aqueous humor and decreases vascular permeability.

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Ketorolac ophthalmic (Acular, Acuvail)

• Dosing, Interactions, etc.

Clinical Context:  Ketorolac ophthalmic is available in preserved bottles, as well as in preservative-free, single-dose-unit containers.

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Class Summary

These drugs have analgesic and anti-inflammatory activities. Their mechanism of action is not known, but they 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.

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