Lyme Disease Presentation and Treatment in the Pediatric Population A. Hope Tobey Assistant Professor of Pediatrics VCOM VOMA 2010 Objectives • Review regional trends in Lyme disease prevalence. • Become familiar with common presentations of Lyme disease in children. • Discuss age appropriate treatment. • LYME DISEASE was recognized in Sweden as long ago as 1908. • It was first identified in the United States in 1975, after a mysterious outbreak of arthritis among the residents of Lyme, Connecticut. • In 1978 It was realized Lyme was a tick borne illness. • In 1982 B. burgdorferi was identified. • Since that time incidence has increased dramatically. Number of reported Lyme disease cases, by year - United States, 1995-2009 National Surveillance case definition revised in 2008 to include probable cases; details at http://www.cdc.gov/ncphi/disss/nndss/casedef/lyme_disease_2008.htm 0 Year 2008 2009 2006 2007 2005 2004 2003 2002 2000 2001 1999 1998 1997 1995 1996 1993 1994 1992 1991 1990 1989 Lyme Disease Cases per 100,000 Population Lyme Disease Cases in Virginia, 1989 - 2009 14 12 10 8 6 4 2 Reported Cases of Lyme Disease in Virginia, 2009 (n=908) So How is VA doing in 2010? • “As of mid September, we will have counted about 700 Lyme disease cases and this will probably put Virginia somewhere over 1000 cases when the counting for 2010 is complete.” David N. Gaines, Ph.D. State Public Health Entomologist Virginia Department of Health Average Annual Incidence of Reported Cases of Lyme Disease by Age Group and Sex , United States, 19922004. Reported Cases of Lyme Disease by Month of Illness Onset United States, 1992-2004 Which tick is our vector ? A B C D • Vector: Ixodes scapularis (or Ixodes pacificus) • Spirochete: Borrelia burgdorferi • Co-Infection: babesiosis and ehrlichiosis. • The larval and nymphal stages of the tick are less then 2mm (no bigger than a pinhead) • The risk of exposure to ticks is greatest in the woods and garden fringe areas of properties, but ticks may also be carried by animals into lawns and gardens. • Ticks wait for host animals from the tips of grasses and shrubs and transfer to animals or persons who brush against vegetation. Adult Nymph Female • They usually attach themselves in areas that are more hidden or hairy, such as the groin, armpits and scalp. Adult Larva Male • Most Children do not know they have been bitten by a tick. • Due to the small size the tick often goes unnoticed. Transmission • Borrelia burgdorferi lives in the tick midgut. • Upon attachment it is initially immobile. • The tick must have ingested blood for B. burgdorferi to be mobile. • Once it becomes mobile, it is excreted through the saliva of the tick into the host. 10 • Ticks need at least 24-36hrs to transmit Lyme • Incubation period from bite to infection 1-55 days average 11 days. Does this patient have Lyme disease? Does this patient have Lyme disease? Does this patient have Lyme disease? Does this patient have Lyme disease? Does this patient have Lyme disease? Reported Clinical Findings Among Lyme Disease Patients, 1992-2004 Clinical Manifestations • Stage 1 (early localized) – erythema migrans, fever, vomiting, malaise, neck stiffness, myalgia, arthralgia. (3-30 days) • Stage 2 (early disseminated) – multiple erythema migrans, facial nerve palsy, meningitis, conjunctivitis, carditis, arthralgia, myalgia, headache, fatigue. (1-4 months) • Stage 3 (late disease) – recurrent arthritis, peripheral neuropathy, cognitive disorders (months – years) ALWAYS Be Suspicious • Children with early localized disease often prevent with a fever and mild illness that is misdiagnosed as a viral illness. • Children may initially present with early disseminated disease and complain only of fatigue, myalgias and arthralgias. • Children may initially present with arthritis and already have Late disseminated disease. Facial Nerve Palsy • Lyme is the most common cause of acquired facial nerve palsy among children in endemic areas. 1 • Positive Predictors : Fever, Headache, Peak Lyme season, no previous herpetic lesions. 1 • In children with FN palsy serology and emperic antibiotics should be strongly considered • Recovery is very good and similar to idiopathic facial nerve palsy or bell’s palsy 6 Meningitis • Occurs in 2-12% of kids with Lyme disease. 2 • CSF will show an aseptic meningitis • Positive predictors: Headache >7 days at diagnosis, Predominance of lymphocytes and monocytes in CSF (>70%) and presence of cranial nerve palsy (CN7). 2,3 Carditis • In children with early disseminated Lyme disease 16% had carditis 11 • Children >10 years of age, those with arthralgias, and those with cardiopulmonary symptoms were more likely to have carditis. 11 • The spectrum of presentation for children with Lyme carditis is broad, ranging from asymptomatic, first-degree heart block to complete block or myocarditis. • 89% of children have complete resolution of cardiac dysfunction and arrhythmias. 11 Arthritis • 6% of new diagnosis Lyme disease presents with arthritis 5 • Typically presents as oligoarthritis of the large joints, classically the knee. • ESR, CRP and serum WBC are often elevated. • Synovial WBC count is widely variable. • Lack of fever and Knee involvement may be predictive 4 • Children rarely progress to chronic arthritis and long term prognosis is excellent5 Diagnosis • Early Localized Disease – Clinical diagnosis is best. – Antibodies to B burgdorferi are not detectable in the first few weeks post infection. Patients treated early may never develop antibodies. • Early or Late Disseminated Disease – Diagnosis should be based on clinical findings and serologic testing. – Antibodies are present in most patients with Early and all patients with late Disseminated disease. Once a pt develops antibodies they will persist for years if not life. What Test Should We Order? • A 2 step approach to testing is recommended. – Serum antibodies by EIA or IFA – Western immunoblot. • Patients with suspected Lyme meningitis should have CSF PCR sent. Western Blot • For early disseminated you need to look at both IgM and IgG for late only IgG is necessary. • Positive test - 5 or more IgG bands positive or - 2 or more IgM bands are positive Treatment • Early Localized >8yo = Doxycycline 100 mg PO BID x 14-21 < 8yo = Amoxicillin 50mg/kg/day BID x 14-21 (Max Dose 1g/ day) PCN All = Cefuroxime 30mg/kg/day BID x 14-21 (Max dose 1g/day) Treatment • Early and Late Disseminated - Multiple EM = Same PO as early local but x 21 d - Isolated facial palsy = Same PO as early local but x 21 -28d - Arthritis = Same PO as early local but x 28 d Treatment • Persistent or recurrent arthritis, carditis, meningitis, encephalitis: - Ceftriaxone 75-100 mg/kg IV or IM Qday x 1428d (Max 2g/day) OR - Penicillin 300,000 U/Kg/Day IV Q4hr x 14-28d (Max 20 Million U/day) Chemoprophylaxis? • Is not currently recommended. Even in highly endemic areas. 9 • Doxycycline 200mg po x 1dose in children >12y (4.4 mg/kg if < 45kg) Prevention • Avoid Tick habitat • Wear light colored clothing that covers arms and legs. • Tuck pant legs into boots • Insect repellants such as DEET • Checking clothes and body after possible tick exposure. • Tick repellants and daily tick checks for pets. • 1998 Vaccine licensed for patients age 15y-70y. Early 2002 it was removed from the market due to side effects and questionable efficacy Tick Removal • Do NOT use: - A match - Vaseline - Nail polish remover - Alcohol - Gasoline Tick Removal Special Populations - Pregnant or Breastfeeding • Lyme can be transmitted to the fetus and may result in stillbirth. • No harm has been shown to occur to a fetus of a properly treated mother. • Lyme can NOT be transmitted by human milk. Special Populations – Blood Donation • People being treated for Lyme disease should not donate blood as Lyme can live in stored blood and result in Lyme disease in the recipient Special Population - Hunters • You will not get Lyme disease from eating venison or squirrel meat • Hunting and dressing deer or squirrels may bring you into close contact with infected ticks and at higher risk for tick bites. Long Term Cognitive Complications? • Research has shown no differences between LD and control groups performance on neuropsychologic testing. 6 • There was also no difference in testing results between groups of patients LD who received different antibiotic regiments or who started treatment at different stages. 6 • No predisease versus postdisease difference in academic performance was found. 6 • No perceived long-term deterioration in cognitive, social, or personality areas was reported by parents. 6 • Children with CN7 palsy also have shown no difference in cognitive outcome compared to children who did not have LD. 7 • Conclusion. Children appropriately treated for LD have an excellent prognosis for unimpaired cognitive functioning. 6,7 Resources • CDC http://www.cdc.gov/ncidod/dvbid/lyme/index.h tm • Committee on Infectious Diseases 2009 Red Book 28th ed. American Academy of Pediatrics • VA Dept Health http://www.vdh.virginia.gov/epidemiology • American Lyme Disease Foundation www.aldf.com References • • • • • • • • • • • Lise E. Nigrovic, Amy D. Thompson, Andrew M. Fine, and Amir Kimia Clinical Predictors of Lyme Disease Among Children With a Peripheral Facial Palsy at an Emergency Department in a Lyme Disease–Endemic Area Pediatrics, Nov 2008; 122: e1080 - e1085. (1) Aris C. Garro, Maia Rutman, Kari Simonsen, Jenifer L. Jaeger, Kimberle Chapin, and Gregory Lockhart Prospective Validation of a Clinical Prediction Model for Lyme Meningitis in Children Pediatrics, May 2009; 123: e829 e834. (2) Robert A. Avery, Gary Frank, Joseph J. Glutting, and Stephen C. Eppes Prediction of Lyme Meningitis in Children From a Lyme Disease–Endemic Region: A Logistic-Regression Model Using History, Physical, and Laboratory Findings Pediatrics, Jan 2006; 117: e1 - e7. (3) Amy Thompson, Rebekah Mannix, and Richard Bachur Acute Pediatric Monoarticular Arthritis: Distinguishing Lyme Arthritis From Other Etiologies Pediatrics, Mar 2009; 123: 959 - 965. (4) Michael A. Gerber, Lawrence S. Zemel, and Eugene D. Shapiro Lyme Arthritis in Children: Clinical Epidemiology and Long-term Outcomes Pediatrics, Oct 1998; 102: 905 - 908. (5) Marietta Vázquez, Sara S. Sparrow, and Eugene D. Shapiro Long-Term Neuropsychologic and Health Outcomes of Children With Facial Nerve Palsy Attributable to Lyme Disease Pediatrics, Aug 2003; 112: e93 - e97. (6) Wayne V. Adams, Carlos D. Rose, Stephen C. Eppes, and Joel D. Klein Cognitive Effects of Lyme Disease in Children Pediatrics, Aug 1994; 94: 185 - 189. (7) Henry M. Feder, Jr, Michael A. Gerber, Peter J. Krause, Eugene D. Shapiro, and Raymond Ryan Early Lyme Disease: A Flu-Like Illness Without Erythema Migrans Pediatrics, Feb 1993; 91: 456 - 459. (8) Committee on Infectious Diseases Treatment of Lyme Borreliosis Pediatrics, Jul 1991; 88: 176 - 179. (9) http://www.sciencedaily.com/releases/2009/11/091116180134.htm (10) John M. Costello, Mark E. Alexander, Karla M. Greco, Antonio R. Perez-Atayde, and Peter C. Laussen Lyme Carditis in Children: Presentation, Predictive Factors, and Clinical Course Pediatrics, May 2009; 123: e835 - e841 (11) Additional References • • • • • • • • • • Holly Rothermel, Thomas R. Hedges III, and Allen C. Steere Optic Neuropathy in Children With Lyme Disease Pediatrics, Aug 2001; 108: 477 - 481. J. H. Oliver, Et al Isolation and transmission of the Lyme disease spirochete from the southeastern United States Proc. Natl. Acad. Sci. USA Vol. 90, pp. 7371-7375, August 1993 Committee on Infectious Diseases Prevention of Lyme Disease Pediatrics, Jan 2000; 105: 142 - 147. Carlos D. Rose, Paul T. Fawcett, Bernhard H. Singsen, Sharon B. Dubbs, and Robert A. Doughty Use of Western Blot and Enzyme-Linked Immunosorbent Assays to Assist in the Diagnosis of Lyme Disease Pediatrics 1991;88;465-470 Henry M. Feder and Jr, MD Lyme Disease Vaccine: Good for Dogs, Adults, and Children? Pediatrics, Jun 2000; 105: 1333 - 1334. James M. Moses, Robyn S. Riseberg, and Jonathan M. Mansbach Lyme Disease Presenting With Persistent Headache Pediatrics, Dec 2003; 112: e477 - e479. Stephen C. Eppes and Judith A. Childs Comparative Study of Cefuroxime Axetil Versus Amoxicillin in Children With Early Lyme Disease Pediatrics, Jun 2002; 109: 1173 - 1177. Thomas Murray and Henry M. Feder, Jr Management of Tick Bites and Early Lyme Disease: A Survey of Connecticut Physicians Pediatrics, Dec 2001; 108: 1367 - 1370. Vijay K. Sikand, Neal Halsey, Peter J. Krause, Sunil K. Sood, Richard Geller, Christian Van Hoecke, Charles Buscarino, Dennis Parenti, and for the Pediatric Lyme Vaccine Study Group Safety and Immunogenicity of a Recombinant Borrelia burgdorferi Outer Surface Protein A Vaccine Against Lyme Disease in Healthy Children and Adolescents: A Randomized Controlled Trial Pediatrics, Jul 2001; 108: 123 - 128. http://ento.psu.edu/extension/urban/lyme-disease
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