Paul Davis

From: Sent: To: Subject: TSHP <paul.davis@tshp.org> Tuesday, September 03, 2013 4:00 AM paul.davis@tshp.org 9-3-13 Drug & Disease Info Alert - Lyme Disease in Texas

DRUG & DISEASE INFORMATION ALERT

September 3, 2013

Lyme Disease - In Texas?

Jennifer K Seltzer, PharmD Lyme disease, the most common tick-borne disease in the United States, has become increasingly prevalent in Texas in recent years. While over 20,000 cases are reported yearly in the U.S. and the disease predominantly occurs in the northeast, 216 cases were documented by the Texas Department of State Health Services in 2010-11. It is speculated that Lyme disease is underreported in Texas as many cases are misdiagnosed due to health care provider unfamiliarity with the clinical presentation.1-4 Lyme disease is caused by the spirochete bacterium Borrelia burgdorferi and was first identified clinically in 1977 as Lyme arthritis through studying a group of Connecticut children with presumed juvenile rheumatoid arthritis. The majority of people are infected through the bite of the blacklegged tick, or deer tick (Ixodes scapularis), which is common in the northeastern, mid-Atlantic, and northcentral U.S. states, but is also endemic to Texas. 1, 3, 5 While ticks can attach to any part of the human body, they normally locate in hard-to-see areas such as the groin, armpits, popliteal fossa (behind the knee), the belt line or the scalp.6, 7 The blacklegged tick has a life cycle from 2 to 6 years, which is comprised of four life stages: egg, larvae, nymph, and adult. Larvae, nymphs and adult females need a blood meal from a vertebrate host for survival, and require a new host for each stage of their life cycle. The male tick rarely feeds and never engorges. In the feeding process, ticks insert a feeding tube into the host and also secrete a cement-like substance that helps keep the organism firmly attached during the meal. These creatures can also secrete saliva with some anesthetic properties so the host is not aware of the feeding process. Ticks feed slowly over a period of approximately two days, allowing the ingested Lyme disease spirochetes to multiply and move to the tick's salivary glands. It typically takes a feeding period of over 36 hours for the tick to successfully transmit B. burgdorferi to the host. Infected ticks become engorged and subsequently transmit Lyme disease through their saliva during this feeding process. How long the tick is attached and whether the tick is engorged are key factors in determining Lyme disease transmission risk. The nymph stage is the main source for Lyme disease transmission as they are less than 2 mm in size and are difficult to see. This stage feeds typically during the spring and summer months when people spend the most time outdoors. Adult ticks can also transmit disease, but they feed during cooler months of the year, are larger, and more likely to be seen and removed before the Lyme spirochetes are transmitted. The
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larvae stage is rarely infected with B. burgdorferi and is least likely to transmit disease. 3, 6, 8, 9 Evidence does not support person-to-person transmission of Lyme disease or acquisition of the disease through direct contact with pets, mosquito bites, breast feeding, or ingesting venison or squirrel meat. Pregnant patients infected with B. burgdorferi have risks of infected placenta and stillbirth, but fetal risk is minimal if the mother successfully completes antibiotic therapy. Because the Lyme disease bacteria can survive in blood stored for transfusion, patients receiving antibiotic therapy for Lyme disease as well as those receiving incomplete treatment should not donate blood. Only those individuals who have successfully completed antimicrobial therapy for Lyme disease can be considered candidates for potential blood donation.6 Symptoms of Lyme disease are typically observed within several weeks of the blacklegged tick bite (range, 3 to 30 days). Clinical manifestations, summarized in Table 1, are categorized into three stages: early localized disease, early disseminated stage, and late Lyme disease. Features of each stage, however, can overlap and patients can present in a later stage of Lyme disease without previous signs and symptoms indicative of earlier disease.7-10 If left untreated, Lyme disease may circulate through the lymphatic system or blood and exhibit signs and symptoms throughout the body (i.e., early disseminated disease, late disease).9

Table 1. Clinical Manifestations and Stages of Lyme Disease7-10 Stage Clinical Manifestations
*painl
ess, bluishred nodule that develo ps on earlob e, nipple or scrotu m that resolv es sponta neousl y but lasts longer than erythe ma

Early *Slow, expanding rash at tick bite site known as erythema migrans-may clear localized centrally as it enlarges, resembling a bull's eye; may occur on any area of body disease but rarely causes pain or itching; occurs in ~80% of patients (3-30 days *Symptoms resembling viral illness (e.g., fatigue, anorexia, headache, chills, after bite) fever, lymphadenopathy, arthralgias, myalgias) Early *Neurologic symptoms: lymphocytic meningitis, unilateral or bilateral cranial disseminated nerve palsies, especially of facial nerve (e.g., Bell's palsy); radiculopathy; disease peripheral neuropathy (weeks*Cardiac symptoms: atrioventricular block; carditis several *Dermatologic symptoms: additional erythema migrans lesions in other parts of months after body; borreliosis lymphocytoma *(rare) bite) *Ocular symptoms (rare): conjunctivitis; keratitis; retinal vasculitis; choroiditis; neuropathy Late Lyme *Lyme arthritis: recurrent, persistent, occurring in a few large joints (especially disease knee); occurs in ~60% of untreated patients in late stage (months*Neurologic symptoms (differ from those seen in early disseminated stage): several Lyme encephalopathy (characterized by mild cognitive disturbances), chronic years after polyneuropathy bite)
migrans; occurs more commonly in children than adults

Treatment with effective antibiotics in the early stages of Lyme disease reduces the associated signs and symptoms and diminishes the risk of developing late disease manifestations. Oral doxycycline, amoxicillin, and cefuroxime are equally effective in managing early disease, although doxycycline may be a preferred agent because it also can treat a potential co-infection (Anaplasma phagocytophilum causes human granulocytic anaplasmosis) and has optimal penetration into the central nervous system compared to the other effective antimicrobials. However, doxycycline causes photosensitivity, should not be used in pregnant or lactating women, and is not recommended for use in children younger than 8 years of age. Macrolides are considered second-line therapy for Lyme disease and should be reserved for those patients intolerant to doxycycline, amoxicillin and cefuroxime as clinical trials have shown this drug class to be less affective against B. burgdorferi. First generation cephalosporins are not effective in Lyme disease and should not be used. Erythema migrans lesions may increase in size and intensity within 24 hours of treatment initiation but usually resolve within 7 to 14 days. Subjective flu-like symptoms can take weeks to months to dissipate.8, 9, 11-13 | Patients with early disseminated Lyme disease and neurologic manifestations as well as those
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patients with cardiac sequelae requiring hospitalization should be managed with parenteral therapy. Ceftriaxone is the drug of choice due to its superior activity against B. burgdorferi, ability to cross the blood brain barrier, and extended half-life. Other options, however, include cefotaxime and penicillin G. Patients with cardiac symptoms not requiring hospitalization and those patients who manifest only with facial nerve palsies can be managed with oral antibiotic therapy. Late disease arthritis and neurologic symptoms are managed with the same oral antibiotics used to treat the early stage of the infection. Patients who do not adequately respond to an initial course of antibiotic therapy may be re-treated with a second oral antibiotic course. Parenteral antibiotic therapy is reserved for those patients with late Lyme disease who exhibit neurologic as well as arthritic symptoms. Those patients with residual arthritic symptoms following IV therapy and negative synovial fluid samples may benefit from nonsteroidal anti-inflammatory drugs, intra-articular glucocorticoid injections or disease-modifying antirheumatic drugs. In some individuals, nonspecific symptoms such as fatigue, musculoskeletal pain, and concentration/memory issues persist for months after treatment is completed, especially in patients with late Lyme disease. This is termed post-Lyme disease syndrome and usually involves re-evaluation for potential additional contributing problems. Table 2 summarizes Lyme disease antibiotic doses and treatment duration.

Table 2. Antibiotic Dosing and Treatment Duration for Lyme Disease

Disease Stage Early localized disease Adult Dose/Duration First-line agents: Doxycycline+ 100 mg twice daily orally for 10-21 days Amoxicillin 500 mg three time daily orally for 14-21 days Cefuroxime 500 mg twice daily orally for 14-21 days Alternative: Azithromycin 500 mg once daily orally for 7-10 days Clarithromycin 500 mg twice daily orally for 14-21 days (if patient not pregnant) Erythromycin 500 mg four times daily orally for 14-21 days (if patient not pregnant) Pediatric Dose/Duration First-line agents: Doxycycline+ 4 mg/mg (maximum dose 100 mg) twice daily orally for 10-21 days Amoxicillin 50 mg/kg/day orally in three divided doses for 14-21 days (maximum single dose: 500 mg) Cefuroxime 30 mg/kg/day orally in two divided doses for 14-21 days (maximum single dose: 500 mg) Alternative: Azithromycin 10 mg/kg once daily orally for 7-10 days (maximum single dose: 500 mg) Clarithromycin 7.5 mg/kg twice daily orally for 14-21 days (maximum single dose: 500 mg) (if patient not pregnant) Erythromycin 12.5 mg/kg four times daily orally for 14-21 days (maximum single dose: 500 mg (if patient not pregnant) Ceftriaxone 50-75 mg/kg/day IV (maximum dose: 2 g) for 28 days (range, 10-28 days) Alternatives: Cefotaxime 150 -200 mg/kg/day in three divided doses IV (maximum daily dose: 6 g) for 14-28 days Penicillin G 200,000-400,000 units/kg/day, divided every 4 hours (maximum: 18-24 million units/day), for 28 days (range, 14-28 days)

Early disseminated disease

Ceftriaxone 2 g intravenous (IV) once daily for 28 days (range, 10-28 days) Alternatives: Cefotaxime 2 g IV every 8 hours for 14-28 days Penicillin G 18-24 million units daily IV, divided every 4 hours, for 28 days (range, 14-28 days)

Late Lyme disease

Arthritis (no neurologic disease): Doxycycline+ 100 mg twice daily orally for 28 days Amoxicillin 500 mg three time daily orally for 28 days Arthritis (with neurologic disease): Ceftriaxone 2 g IV once daily for 28 days (may also give cefotaxime 2 g IV every 8 hours for 14-28 days or penicillin G 18-24 million units daily IV, divided every 4 hours, for 14-28 days)

Arthritis (no neurologic disease): Doxycycline+ 4 mg/mg (maximum dose 100 mg) twice daily orally for 28 days Amoxicillin 50 mg/kg/day orally in three divided doses for 28 days (maximum single dose: 500 mg) Arthritis (with neurologic disease): Ceftriaxone 50-75 mg/kg/day IV (maximum dose: 2 g) for 28 days (may also give cefotaxime 150 -200 mg/kg/day in three divided doses IV (maximum daily dose: 6 g) for 14-28 days OR penicillin G 200,000-400,000 units/kg/day, divided every 4 hours (maximum: 18-24 million units/day), for 14-28 days

+not for use in women who are pregnant or lactating or in children < 8 years of age Lyme disease is a preventable disease and can be minimized by avoiding direct contact with ticks and tick-infested environments. Bare skin and clothing should be covered with tick repellants such as N, N-diethyl-m-toluamide (DEET) or permethrin when participating in outdoor activities, especially in endemic areas. Environmental modifications (e.g., lawn mowing, removing leaf litter, laying wood chips in areas adjacent to forests, installing fencing to exclude deer) can be employed in tick-laden areas to reduce tick burden. Bathing within 2 hours and performing tick checks within 36 hours of coming indoors can aid in identifying potential tick attachments. If a tick is discovered, the arthropod should be grasped with tweezers as close to the mouthparts as possible and gently pulled off without squeezing. The person should then be observed for up to 30 days for signs and symptoms of Lyme disease. A single dose of doxycycline 200 mg in adults or 4 mg/kg (up to a maximum dose of 200 mg) in children is recommended as prophylaxis in those situations where a tick is presumed to have been attached for over 36 hours to minimize development of Lyme disease. In those patients who cannot tolerate doxycycline, observation for signs/symptoms of B. burgdorferi infection is recommended. A vaccine against Lyme disease is no longer available.8, 9, 14, 15 Concerns about Lyme disease have now extended to Texas. Strategies to protect against tick bites should be implemented by residents exposed to blacklegged ticks to minimize B. burgdorferi infections. References

1. Centers for Disease Control and Prevention. Lyme disease: Lyme disease data. Available at: http://www.cdc.gov/lyme/stats/index.html. Accessed August 21, 2013. 2. Texas Department of State Health Services. Human case data 2010-2019: zoonotic diseases. Available at: http://www.dshs.state.tx.us/idcu/health/zoonosis/disease/2010/. Accessed August 21, 2103. 3. Beard CB. Epidemiology of Lyme disease. In: UpToDate, Basow, DS (Ed), UpToDate, Waltham, MA, 2013. 4. Texas Lyme Disease Association. Lyme disease in Texas. Available at: http://www.txlda.com/lyme_texas.php. Accessed August 21, 2013. 5. Texas Department of State Health Services. Lyme disease: description. Available at: http://www.dshs.state.tx.us/idcu/disease/lyme/description/. Accessed August 22, 2013. 6. Centers for Disease Control and Prevention. Lyme disease transmission. Available at: http://www.cdc.gov/lyme/transmission/index.html. Accessed August 22, 2013. 7. Hu L. Clinical manifestations of Lyme disease in adults. In: UpToDate, Basow, DS (Ed), UpToDate, Waltham, MA, 2013. 8. Stanek G, Wormser GP, Gray J, Strle F. Lyme borreliosis. Lancet. 2012;379:461-73.
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9. Wright WF, Riedel DJ, Talwani R, Gilliam BL. Diagnosis and management of Lyme disease. Am Fam Physician. 2012;85(11):1086-93. 10. Centers for Disease Control and Prevention. Lyme disease: signs and symptoms of Lyme disease. Available at: http://www.cdc.gov/lyme/signs_symptoms/index.html. Accessed August 23, 2013. 11. Centers for Disease Control and Prevention. Lyme disease: treatment. Available at: http://www.cdc.gov/lyme/Treatment/. Accessed August 28, 2013. 12. Hu L. Treatment of Lyme disease. In: UpToDate, Basow, DS (Ed), UpToDate, Waltham, MA, 2013. 13. Wormser GP, Dattwyler RJ, Shapiro ED, et al. The clinical assessment, treatment, and prevention of Lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis. 2006;43(9):1089-134. 14. Hu L. Evaluation of a tick bite for possible Lyme disease. In: UpToDate, Basow, DS (Ed), UpToDate, Waltham, MA, 2013. 15. Centers for Disease Control and Prevention. Lyme disease: preventing tick bites. Available at: http://www.cdc.gov/lyme/prev/index.html. Accessed August 28, 2013.

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