Practice Guidelines

Guidelines for the Diagnosis and Treatment of Tick-Borne Rickettsial Diseases

AMBER HUNTZINGER

Although antimicrobial therapy is widely available, tick-borne rickettsial diseases cause severe morbidity and mortality in otherwise healthy Americans. The diseases most common in the United States include Rocky Mountain spotted fever (RMSF), human monocytic ehrlichiosis (HME), human granulocytic anaplasmosis (HGA), and Ehrlichia ewingii infection. The most difficult challenge is making diagnoses early, when antibiotics are most effective.

Epidemiology

Tick-borne rickettsial diseases are caused by pathogens acquired from hard-bodied ticks. The epidemiology of these diseases is related to seasonal and geographic factors. The diseases are most common during the warmer months of spring and summer, when ticks are most likely to feed on humans; however, these diseases may occur any time of year. RMSF and HME are most common in southeastern and south central states, although RMSF is widespread throughout the United States. HGA is most common in New England, north central states, and certain areas on the West Coast. Although the etiology of E. ewingii infection is unclear, it has been reported in south Atlantic and south central states and in isolated areas of New England. Table 1 lists the features of tick-borne rickettsial diseases.

Table 1. Features of Common Tick-Borne Diseases in the United States
Disease (causative agent)	Primary vector(s)	Approximate distribution	Incubation period (days)	Common initial signs and symptoms	Common laboratory abnormalities	Rash	Fatality rate (%)
Rocky Mountain spotted fever (Rickettsia rickettsii)	American dog tick (Dermacentor variabilis), Rocky Mountain wood tick (Dermacentor andersoni), brown dog tick (Rhipicephalus sanguineus) in Arizona	Widespread in the United States, especially in south Atlantic and south central states	Two to 14	Fever, nausea, vomiting, myalgia, anorexia, headache	Thrombocytopenia, mild hyponatremia, mildly elevated hepatic transaminase levels	Maculopapular rash appears approximately two to four days after fever onset in 50 to 80 percent of adults and in more than 90 percent of children; may involve the palms and soles	5 to 10
Human monocytic ehrlichiosis (Ehrlichia chaffeensis)	Lone star tick (Amblyomma americanum)	Southern, south central, mid-Atlantic, and northern states; isolated areas of New England	Five to 14	Fever, headache, malaise, myalgia	Leukopenia, thrombocytopenia, elevated serum transaminase levels	Rash appears in less than 30 percent of adults and in about 60 percent of children	2 to 3
Human granulocytic anaplasmosis (Anaplasma phagocytophilum)	Black-legged tick (Ixodes scapularis and Ixodes pacificus) in the United States	North central and Pacific states; New England	Five to 21	Fever, headache, malaise, nausea, vomiting	Leukopenia, thrombocytopenia, elevated serum transaminase levels	Rare	Less than 1
Ehrlichia ewingii infection	Lone star tick	South Atlantic and south central states; isolated areas of New England	Five to 14	Fever, headache, myalgia, nausea, vomiting	Leukopenia, thrombocytopenia, elevated serum transaminase levels	Rare	None documented
NOTE: Treatment for these diseases is the same: adults should receive 100 mg of doxycycline (Vibramycin) orally or intravenously twice a day, and children who weigh less than 100 lb (45.4 kg) should receive 2.2 mg per kg of doxycycline orally or intravenously twice a day. Adapted from Chapman AS, Bakken JS, Folk SM, Paddock CD, Bloch KC, Krusell A, 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 Recomm Rep 2006;55(RR-4):3.

Diagnosis

Early diagnosis is difficult because early signs and symptoms usually are nonspecific or mimic benign viral illnesses. However, some clinical clues can help physicians detect early tick-borne rickettsial disease and differentiate it from similar illnesses.

clinical history

A thorough clinical history should include questions about tick bites, recent exposure to tick habitats, recent travel, and similar illness in close contacts and pets. The history can help physicians determine a likely diagnosis, although the absence of these features does not rule out tick-borne illness.

Outdoor recreational or occupational activities can increase the risk of tick-borne rickettsial diseases, particularly from April to September and if the activity takes place near high vegetation (e.g., camping, hiking, gardening). Persons in frequent contact with animals and those who have pets with a history of tick bites also are at increased risk. Patients may not report a specific personal history of tick bite because most do not realize they have been bitten; bite marks may be difficult to detect or distinguish from other bites (e.g., spider or chigger bites). Persons who live in endemic areas (e.g., south Atlantic, north central, south central, and New England states) are at risk even in their own backyards and neighborhoods.

It is important to ask patients if they have recently traveled to endemic areas. Patients who have traveled to international destinations such as the southern Mediterranean, Central and South America, Africa, Asia, and the Middle East may have acquired a tick-borne rickettsial disease not seen in the United States, especially if the patient visited rural or outdoor areas.

Tick-borne pathogens can cause clusters of illness among persons who have spent time in the same location. Therefore, patients should be questioned about similar illness in family members, coworkers, and community members.

signs and symptoms

Most tick-borne rickettsial diseases cause sudden fever, chills, and headache (possibly severe). These symptoms commonly are associated with malaise and myalgia. Nausea, vomiting, and anorexia are common in early illness, especially with RMSF and HME. Children with RMSF or HME may have abdominal pain, altered mental status, and conjunctival infection. Rare symptoms include severe abdominal pain and meningoencephalitis. Rash is common with RMSF, but it is less common with HME and rare with HGA or E. ewingii infection. Clinically, tick-borne rickettsial diseases are difficult to differentiate from other diseases.

The rash associated with RMSF usually appears two to four days after onset of fever, and typically presents as small, blanching, pink macules on the ankles, wrists, or forearms that evolve into maculopapules. It can spread throughout the body, including to the palms and soles, but the face usually is not affected. One half of patients develop petechiae, often with severe illness. The progression of the rash is variable and may be difficult to discern. Other causes of fever and maculopapular or petechial rash include murine typhus, monocytotropic ehrlichiosis, group A streptococcal pharyngitis, erythema infectiosum (fifth disease), roseola, and enteroviral infection. The rash's dermatologic classification, distribution, pattern, and timing of onset can help rule out other exanthemata.

laboratory findings

Patients with suspected tick-borne rickettsial disease should receive a complete blood count, comprehensive metabolic panel, and peripheral blood smear. Thrombocytopenia and hyponatremia suggest RMSF; and leukopenia, thrombocytopenia, and modest elevations of liver transaminase levels suggest HME and HGA. Blood tests may help detect HGA and E. ewingii infections. However, the absence of these results does not necessarily rule out tick-borne rickettsial disease.

Treatment

Assessing a patient's symptoms and signs, clinical history, and laboratory test results can help guide decisions regarding the treatment of tick-borne rickettsial disease, although treatment should not be delayed while awaiting laboratory confirmation.

Outpatient monitoring for 24 to 48 hours may be considered for patients in the early course of illness who have a nonspecific history and physician examination and normal laboratory test results. If tick-borne rickettsial disease is suspected, antibiotic treatment should be initiated. Prophylactic antibiotic therapy is not indicated for patients without recent tick bites or who are not ill.

Doxycycline (Vibramycin) is the antibiotic of choice for adults and children. Doxycycline is contraindicated in pregnant women, although it may be considered in life-threatening situations when clinical suspicion of tick-borne illness is high. The recommended dosage of doxycycline is 100 mg orally or intravenously twice a day for adults, and 2.2 mg per kg orally or intravenously twice a day for children who weigh less than 100 lb (45.4 kg). Although the optimal duration of therapy has not been established, a five- to seven-day course is recommended for RMSF and HME after the fever subsides. A 10- to 14-day course is recommended for HGA. Chloramphenicol (Chloromycetin) may be used as an alternative to doxycycline; however, this drug may cause side effects, and monitoring of blood indices may be needed.

Early symptoms of invasive meningococcal infection overlap with those of tick-borne rickettsial disease. Therefore, if meningococcal infection cannot be ruled out, physicians should add a parenteral penicillin or cephalosporin that is active against Neisseria meningitidis to doxycycline therapy.

Practice Guideline Briefs

AAN Guidelines on Reporting Medical Conditions That May Affect Driving Competency

Driving laws for persons with medical conditions that affect cognition, consciousness, vision, or motor skills vary from state to state. Physicians are expected to report a patient's driving-related condition to authorities if the condition might pose a safety risk, especially when the patient does not comply with requests to be tested or stop driving. Requiring mandatory reporting, however, may negatively affect the patient-physician relationship. Reporting also may not result in safety benefits to the public or the patient, who may consequently withhold important medical information.

Poorly designed reporting laws may also expose physicians to liability for a patient's driving outcomes, even when a physician has followed all applicable laws. Most states have full legal immunity for physicians who follow applicable laws in good faith. However, physicians in some states (e.g., Arkansas, Georgia) may be sued for reporting a patient with questionable driving abilities, resulting in a suggested violation of patient-physician privilege. In other states (e.g., Michigan, Montana), a physician who does not report a patient who appears to be a sound driver is at risk of being sued if that patient later causes an accident.

The American Academy of Neurology (AAN) encourages physicians to review applicable driving laws with their patients and to discuss and document their medical recommendations with their patients. The AAN also supports optional reporting of persons with medical conditions that may affect their ability to drive safety, especially for cases in which public safety has already been compromised or when the person clearly no longer has the skills to drive safely.

Physician immunity policies should be clarified so that physicians are granted immunity for reporting or not reporting a patient's condition when such action is taken in good faith, when the patient is reasonably informed of his or her driving risks, and when such actions are documented by the physician in good faith.

CARRIE ARMSTRONG

Preventing Premature Discontinuation of Thienopyridine Therapy

In combination with aspirin, thienopyridine therapy (primarily clopidogrel [Plavix] in the United States) may reduce the incidence of early major adverse cardiac events in patients who have undergone placement of a bare-metal stent compared with aspirin therapy alone or in combination with warfarin (Coumadin). Using thienopyridines with aspirin for up to one year after non-ST segment elevation acute coronary syndromes can decrease the incidence of ischemic cardiovascular events. Thienopyridines also are recommended by the American Heart Association (AHA) and the American College of Cardiology (ACC) for patients who are undergoing percutaneous coronary intervention. However, antiplatelet therapy is sometimes prematurely discontinued in the first year of treatment either by the patient or a health care professional. Prematurely discontinuing this therapy increases the risk of stent thrombosis, which often leads to acute myocardial infarction or death.

Current recommendations for the prevention of stent thrombosis after coronary stent implantation state that, at a minimum, patients should be treated with 75 mg of clopidogrel and 325 mg of aspirin for one month after bare-metal stent implantation; three months after sirolimus drug-eluting stent implantation; and six months after paclitaxel drug-eluting stent implantation (ideally, up to 12 months if they are not at high risk for bleeding). The AHA, ACC, the Society for Cardiovascular Angiography and Interventions, the American College of Physicians, the American College of Surgeons, and the American Dental Association have released a science advisory on the importance of antiplatelet therapy in patients with coronary artery stents. The advisory was published in the February 13, 2007, issue of Circulation.

Factors that may contribute to premature cessation of thienopyridine therapy include drug costs, instructions from a physician or dentist to discontinue therapy before a procedure, and inadequate patient education about the importance of continuing therapy. To help eliminate premature cessation of therapy, physicians should discuss the need for dual antiplatelet therapy with their patients before implanting a stent. Physicians should also strongly consider whether to avoid a drug-eluting stent in patients who are not expected to comply with 12 months of thienopyridine therapy.

Implanting a bare-metal stent or performing balloon angioplasty with provisional stent implantation instead of using a drug-eluting stent should also be considered for patients undergoing preparation for percutaneous coronary intervention who are likely to require invasive or surgical procedures in the next year.

Physicians should ensure that their patients understand the reasons they have been prescribed thienopyridines, and patients should be aware of the significant risks of prematurely discontinuing the therapy. Additionally, health care professionals who perform surgical or invasive procedures must be informed of the potential risks of premature discontinuation of thienopyridine therapy. Consequently, elective procedures with a significant risk of perioperative or postoperative bleeding should be deferred until after the patient has completed thienopyridine therapy.

For patients treated with a drug-eluting stent who are undergoing procedures for which thienopyridine therapy must be discontinued, aspirin therapy should be continued if possible. However, patients should restart thienopyridine therapy as soon as possible after the procedure because of the risk of late-stent thrombosis.

SHERRI DAMLO

Answers to This Issue's Clinical Quiz Q1. B Q2. D Q3. A Q4. A Q5. B Q6. E Q7. C Q8. A, B, D Q9. A, B Q10. A, B, C, D Q11. A, B, C, D

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