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, the most common tick-borne 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 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 is underreported in Texas as many cases are misdiagnosed due to health care provider unfamiliarity with the clinical presentation. 1-4 Lyme 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 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 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 transmission risk. The nymph stage is the main source for Lyme 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, 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 1
3, 6, 8, 9 larvae stage is rarely infected with B. burgdorferi and is least likely to transmit. Evidence does not support person-to-person transmission of Lyme or acquisition of the 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 bacteria can survive in blood stored for transfusion, patients receiving antibiotic therapy for Lyme as well as those receiving incomplete treatment should not donate blood. Only those individuals who have successfully completed antimicrobial therapy for Lyme can be considered candidates for potential blood donation. 6 Symptoms of Lyme 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, early disseminated stage, and late Lyme. Features of each stage, however, can overlap and patients can present in a later stage of Lyme without previous signs and symptoms indicative of earlier.7-10 If left untreated, Lyme may circulate through the lymphatic system or blood and exhibit signs and symptoms throughout the body (i.e., early disseminated, late ). 9 Table 1. Clinical Manifestations and Stages of Lyme Disease 7-10 Stage Clinical Manifestations 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 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; peripheral neuropathy (weeksseveral *Dermatologic symptoms: additional erythema migrans lesions in other parts of *Cardiac symptoms: atrioventricular block; carditis months after body; borreliosis lymphocytoma *(rare) bite) *Ocular symptoms (rare): conjunctivitis; keratitis; retinal vasculitis; choroiditis; neuropathy Late Lyme (monthsseveral years after bite) *Lyme arthritis: recurrent, persistent, occurring in a few large joints (especially knee); occurs in ~60% of untreated patients in late stage *Neurologic symptoms (differ from those seen in early disseminated stage): Lyme encephalopathy (characterized by mild cognitive disturbances), chronic polyneuropathy migrans; occurs more commonly in children than adults *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 Treatment with effective antibiotics in the early stages of Lyme reduces the associated signs and symptoms and diminishes the risk of developing late manifestations. Oral doxycycline, amoxicillin, and cefuroxime are equally effective in managing early, 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 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 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 8, 9, 11-13 14 days. Subjective flu-like symptoms can take weeks to months to dissipate. Patients with early disseminated Lyme and neurologic manifestations as well as those 2
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 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 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 -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. This is termed post-lyme syndrome and usually involves re-evaluation for potential additional contributing problems. Table 2 summarizes Lyme antibiotic doses and treatment duration. Table 2. Antibiotic Dosing and Treatment Duration for Lyme Disease Disease Stage Adult Dose/Duration Pediatric Dose/Duration Early localized Early disseminated First-line agents: First-line agents: Doxycycline + 100 mg twice Doxycycline + 4 mg/mg (maximum dose 100 mg) daily orally for 10-21 days twice daily orally for 10-21 days Amoxicillin 500 mg three time Amoxicillin 50 mg/kg/day orally in three divided daily orally for 14-21 days doses for 14-21 days (maximum single dose: 500 Cefuroxime 500 mg twice daily mg) orally for 14-21 days Cefuroxime 30 mg/kg/day orally in two divided Alternative: doses for 14-21 days (maximum single dose: 500 Azithromycin 500 mg once mg) daily orally for 7-10 days Alternative: Clarithromycin 500 mg twice Azithromycin 10 mg/kg once daily orally for 7-10 daily orally for 14-21 days (if days (maximum single dose: 500 mg) patient not pregnant) Clarithromycin 7.5 mg/kg twice daily orally for 14-21 Erythromycin 500 mg four days (maximum single dose: 500 mg) (if patient not times daily orally for 14-21 pregnant) days (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 2 g intravenous Ceftriaxone 50-75 mg/kg/day IV (maximum dose: 2 (IV) once daily for 28 days g) for 28 days (range, 10-28 days) (range, 10-28 days) Alternatives: Alternatives: Cefotaxime 150-200 mg/kg/day in three divided Cefotaxime 2 g IV every 8 doses IV (maximum daily dose: 6 g) for 14-28 days hours for 14-28 days Penicillin G 200,000-400,000 units/kg/day, divided Penicillin G 18-24 million units every 4 hours (maximum: 18-24 million units/day), daily IV, divided every 4 hours, for 28 days (range, 14-28 days) for 28 days (range, 14-28 days) 3
Late Lyme Arthritis (no neurologic Arthritis (no neurologic ): ): Doxycycline + 4 mg/mg (maximum dose 100 mg) Doxycycline + 100 mg twice twice daily orally for 28 days daily orally for 28 days Amoxicillin 50 mg/kg/day orally in three divided Amoxicillin 500 mg three time doses for 28 days (maximum single dose: 500 mg) daily orally for 28 days Arthritis (with neurologic ): Arthritis (with neurologic Ceftriaxone 50-75 mg/kg/day IV (maximum dose: 2 ): g) for 28 days (may also give cefotaxime 150-200 Ceftriaxone 2 g IV once daily mg/kg/day in three divided doses IV (maximum daily for 28 days (may also give dose: 6 g) for 14-28 days OR cefotaxime 2 g IV every 8 penicillin G 200,000-400,000 units/kg/day, divided hours for 14-28 days or every 4 hours (maximum: 18-24 million units/day), penicillin G 18-24 million units for 14-28 days daily IV, divided every 4 hours, for 14-28 days) +not for use in women who are pregnant or lactating or in children < 8 years of age Lyme is a preventable 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. 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. In those patients who cannot tolerate doxycycline, observation for signs/symptoms of B. burgdorferi infection is 8, 9, 14, 15 recommended. A vaccine against Lyme is no longer available. Concerns about Lyme 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 : Lyme 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 s. Available at: http://www.dshs.state.tx.us/idcu/health/zoonosis//2010/. Accessed August 21, 2103. 3. Beard CB. Epidemiology of Lyme. In: UpToDate, Basow, DS (Ed), UpToDate, Waltham, MA, 2013. 4. Texas Lyme Disease Association. Lyme in Texas. Available at: http://www.txlda.com/lyme_texas.php. Accessed August 21, 2013. 5. Texas Department of State Health Services. Lyme : description. Available at: http://www.dshs.state.tx.us/idcu//lyme/description/. Accessed August 22, 2013. 6. Centers for Disease Control and Prevention. Lyme transmission. Available at: http://www.cdc.gov/lyme/transmission/index.html. Accessed August 22, 2013. 7. Hu L. Clinical manifestations of Lyme 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. 4
9. Wright WF, Riedel DJ, Talwani R, Gilliam BL. Diagnosis and management of Lyme. Am Fam Physician. 2012;85(11):1086-93. 10. Centers for Disease Control and Prevention. Lyme : signs and symptoms of Lyme. Available at: http://www.cdc.gov/lyme/signs_symptoms/index.html. Accessed August 23, 2013. 11. Centers for Disease Control and Prevention. Lyme : treatment. Available at: http://www.cdc.gov/lyme/treatment/. Accessed August 28, 2013. 12. Hu L. Treatment of Lyme. 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, 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. In: UpToDate, Basow, DS (Ed), UpToDate, Waltham, MA, 2013. 15. Centers for Disease Control and Prevention. Lyme : preventing tick bites. Available at: http://www.cdc.gov/lyme/prev/index.html. Accessed August 28, 2013. Forward this email This email was sent to paul.davis@tshp.org by paul.davis@tshp.org Update Profile/Email Address Instant removal with SafeUnsubscribe Privacy Policy. TSHP 3000 Joe DiMaggio #30A Round Rock TX 78665 5