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Does Your Child Have Autism or Lyme Disease? By Raj Patel, M.D.

Dr. Raj Patel provides an overview of chronic Lyme disease and its similarities and differences with autism. He also examines the controversy surrounding chronic Lyme disease and offers guidelines for handling tick bites and testing for Lyme disease in individuals with autism.

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Does Your Child Have Autism or Lyme Disease? By Raj Patel, M.D.

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  1. Does Your Child Have Autism or Lyme Disease? By Raj Patel, M.D. Raj Patel, M.D.

  2. Raj Patel, MD Education: MS-Rutgers University MD – Robert Wood Johnson Medical School Residency-Family Medicine Post Graduate studies in Autism Spectrum Disorders & Lyme Disease Research: Ampligen-CFIDS (Hemispherx Pharmaceutical) Clinical: 20+ years clinical experience Active member of Defeat Autism Now (DAN) Active member of International Lyme and Associated Diseases Society (ILADS) Active member of California Lyme Disease Association (CALDA) Raj Patel, MD Medical Options for Wellness 5050 El Camino Real, #110 Los Altos, CA 94022 650-964-6700 www.DrRajPatel.net Raj Patel, MD

  3. Goals Provide an overview of chronic Lyme disease (LD) Review the similarities and differences between Autism and LD Review the controversy in the medical community regarding chronic LD Handling Tick Bites Guidelines on testing for Lyme in ASD Does Your Child Have Autism or Lyme Disease? Raj Patel, M.D.

  4. Lyme Disease Overview Fastest growing vector borne infection With approximately 20,000 new cases reported each year, Lyme disease is the most common vector-borne disease in the United States. MMWR. CDC. June 15,2007/56(23);573-576. Tick bites frequently transmit multiple infections: Borrelia Ehrlichia/Anaplasma Babesia and other piroplasms Bartonella like organisms Raj Patel, M.D.

  5. Lyme Disease Overview Raj Patel, M.D.

  6. Reported Cases of Lyme Disease, 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 Raj Patel, M.D.

  7. Raj Patel, M.D.

  8. Lyme Disease Overview (con’t) Other possible coinfections to consider in differential diagnosis: Bacteria - Mycoplasma, Chlmydia, RMSF, Tularemia, Q-Fever Parasites - Filiariasis, Amebiasis, Giardiasis, … Viruses – EBV, CMV, HHV6, XMRV, Borna virus, Powassan virus, … Transmission: Ticks Mosquitos, Fleas, Rodents Transplacental Breast milk Sexual Raj Patel, M.D.

  9. Lyme Disease Lyme Disease Symptoms Symptom presentation typically mixed depending on mix of infections present Classic Symptoms Associated with Borrelia Starts gradually with flu-like symptoms Multi system involvement when disseminated Migratory arthralgias that evolve into arthritis Occipital headaches with neck stiffness Fatigue Four week cycle of symptom flare-ups EM rash (bulls-eye) Raj Patel, M.D.

  10. Lyme Disease Classic Symptoms Associated with Babesia Rapid onset of symptoms (cyclic high fevers, severe headaches, & sweats esp. at night) Air hunger Dull global headaches Prominent fatigue with exercise intolerance Symptoms cycle every 4-7 days Hypercoagulable states Raj Patel, M.D.

  11. Lyme Disease Classic Symptoms Associated with Ehrlichia / Anaplasma Myalgias Sharp knife like headaches behind eyes Low WBC count Elevated liver enzymes Raj Patel, M.D.

  12. Lyme Disease Classic Symptoms Associated with Bartonella like organisms CNS symptoms prominent (anxiety, agitation, insommnia, seizures, outbursts and anti-social behavior) Lymphadenopathy Soles tender esp. in morning Striae (hyperpigmented stretch marks) Elevated VEGF (vascular endothelial growth factor) useful marker to follow response to treatment. Raj Patel, M.D.

  13. Bartonella Rash Raj Patel, M.D.

  14. Bartonella Rash Raj Patel, M.D.

  15. Lyme Bulls Eye Rash Raj Patel, M.D.

  16. Lyme Bulls Eye Rash Raj Patel, M.D.

  17. Raj Patel, M.D.

  18. Signs/Symptoms of Autism Spectrum Disorders • DSM Related • Poor eye contact Sensory issues (light, touch, sound) • Echolalia Repetitive movements/behav. • Speech delay &/or loss of previously acquired language • Poor socialization/unaware of others’ feelings/does not respond to name • Non DSM Related: Abdominal bloating/Diarrhea/Constipation Hypotonia Difficulty with Abstract Reasoning Decreased attention/hyperactivity Insommnia Obscessive-compulsive behavior Food Intolerances Raj Patel, M.D.

  19. Signs/Symptoms of Autism Spectrum Disorders • DSM Related • Poor eye contact Sensory issues (light, touch, sound) • Echolalia Repetitive movements/behav. • Speech delay &/or loss of previously acquired language • Poor socialization/unaware of others’ feelings/does not respond to name • Non DSM Related: Abdominal bloating/Diarrhea/Constipation Hypotonia Difficulty with Abstract Reasoning Decreased attention/hyperactivity Insommnia Obscessive-compulsive behavior Food Intolerances Raj Patel, M.D.

  20. Common Laboratory Markers in ASD and Chronic Lyme Disease Mitochondrial Dysfunction - Urine organic acid testing Cerebral Inflammation and Hypoperfusion - Spect scans Generalised Inflammation/Viral Issues - Urinary neopterin/biopterin Chronic Low level Viral Titers - Blood testing IgG Mediated Food Sensitivities - Blood testing Methylation Cycle Impairments - Urine amino acid & blood testing Raj Patel, M.D.

  21. Diagnostic Testing in Chronic Lyme Disease “Lyme disease is a clinical diagnosis and tests should be used to support rather than supersede the physician’s judgment.” Evidence-based guidelines for the management of Lyme disease. Expert Rev. Anti-infect. Ther. 2(1), p.S5 (2004) Indirect Tests ELISA (enzyme-linked immunosorbent assay) – though used as a screening test, studies show poor sensitivity as low as 45%. Bakken, et al, 1997. Western Blot – test for antibodies against a wide range of borrelia proteins. Direct Tests PCR – detects Borrelia DNA in urine, blood, or tissue. Culture – grows the borrelia organism. Raj Patel, M.D.

  22. Lyme Western Blot Testing Raj Patel, M.D. Grier, T. Laboratory Tests. Lyme Times. Summer 2004:21-25

  23. Lyme Western Blot Testing in Chronic Lyme Disease Overview: Reasons for seronegativity-Test done too early Antibiotics given early Early use of steroids B. burgdorferi not present in blood (it may be in tissues as cell wall deficient form) Free antibody not available (maybe bound into immune complexes) Antibody levels fall late in disease Lyme WB should be used for screening. The College of American Pathologists (CAP) found that ELISA tests have poor sensitivity for screening purposes. (Bakken 1997) Raj Patel, M.D.

  24. Two Standards of Care IDSA (Infectious Diseases Society of America) Denies existence of chronic Lyme disease. Requires serological evidence for treatment (positive PCR or IgM on WB) Treatment restricted to 2-3 weeks of single antibiotic (typically Doxycycline 100mg BID) “…unproven and very improbable assumption that chronic B. burgdorferi infection can occur in the absence of antibodies against B. burgdorferi in serum.” “patients who remain seronegative, despite continuing symptoms for 6-8 weeks, are unlikely to have Lyme disease…” “To date there is no convincing biologic evidence for the existence of symptomatic chronic B. burgdorferi infection among patients after receipt of recommended treatment regimens for Lyme disease.” “Retreatment is not recommended unless relapse is shown by reliable objective measures.” Clinical Practice Guidelines by the Infectious Diseases Society of America. Clin Infect Dis 2006 Nov 1;43(9):1089-134. Epub 2006 Oct 2 Raj Patel, M.D.

  25. Two Standards of Care • ILADS (International Lyme and Associated Diseases Society) • “Since there is currently no definitive test for Lyme disease, laboratory results should not be used to exclude an individual from treatment. • Lyme disease is a clinical diagnosis and tests should be used to support rather than supersede the physician’s judgment. • The early use of antibiotics can prevent persistent, recurrent and refractory Lyme disease. • The duration of therapy should be guided by clinical response, rather than by an arbitrary (i.e., 30 days) treatment course. • The practice of stopping antibiotics to allow for delayed recovery is not recommended for persistent Lyme disease. In these cases, it is reasonable to continue treatment for several months after clinical and laboratory abnormalities have begun to resolve and symptoms have disappeared.” • Evidence Based Guidelines for the Management of Lyme Disease. The International Lyme and Associated Diseases Society. Expert Rev. Anti-infect. Ther.2(1), Suppl. (2004) Raj Patel, M.D.

  26. Medical Literature False Seronegativity in Lyme well documented …chronic lyme disease cannot be excluded by the absence of antibodies against B. burgdorferi.” Dattwyler RJ, Volkman DJ, Luft BJ, Halperin JJ, Thomas J, Golightly MG. Seronegative Lyme Disease. Dissociation of specific T- and B- lymphocyte responses to Borrelia burgdorferi. N Engl J Med. 1988 Dec 1;319(22):1441-6. “Greater than 70% of patients with chronic Lyme disease were seronegative by CDC criteria. Donta ST. Tetracycline therapy for chronic Lyme disease. Clin Infect Dis 1997 Jul;25 Suppl 1:S52-6. “Lyme borreliosis patients who have live spirochetes in body fluids have low or negative levels of borrelial antibodies in their sera.” Tylewska-Wierzbanowska S, Chmielewski T. Limitation of serological testing for Lyme borreliosis: evaluation of ELISA and western blot in comparison with PCR and culture methods. Wien Klm Wochenschr. 2002 Jul 31;114(13-14);601-5. “Seronegative patients in the study had higher rates of positive CSF PCR” Keller TL, Halperin JJ, Whitman M. PCR detection of Borrelia burgdorferi DNA in cerebrospinal fluid of Lyme neuroborreliosis patients. Neurology. 1992 Jan;42(1):32-42. Raj Patel, M.D.

  27. Medical Literature Persistent Infection Well Documented 74% Remained PCR Positive Despite Extended Antibiotic Therapy. Bayer ME, Zhang L, Bayer MH. Borrelia burgdorferi DNA in the urine of treated patients with chronic Lyme disease symptoms. A PCR study of 97 cases. Infection. 1996 Sep.24:5. 347-53. 30% Remained PCR Positive Despite Multiple Courses of “Adequate” Antibiotic Therapy. Nocton JJ, Dressler F, Rutledge BJ, Rys PN, Persing DH, Steere AC. Detection of Borre;lia burgdorferi DNA by polymerase chain reaction in synovial fluid from patients with Lyme arthritis. N Engl J Med 1994 Jan. 330:4, 229-34. 165 Lyme patients treated for at least 3 months -> 32 (19.4%) relapsed despite therapy -> 38% of relapsers were culture or PCR positive Oski J, Marjamaki M, Nikoskelainen J, et al. Borrelia burgdorferi detected by culture and PCR in clinical relapse of disseminated Lyme borreliosis. Ann Med. 1999 Jun;31(3):225-232. 64 year old female presents with bullous and ulcerating lichen sclerosis et atrophicus (LSA). Lyme serologies were repeatedly negative. Borrelia burgdorferi was isolated by live culture from enlarging LSA lesions even after 4 courses of Ceftriaxone. After 5th course of ceftriaxone, improvements seen in skin and negative cultures for B. burgdorferi. Breier F, Khanakah G, Stanek G, Kunz G, Aberer E, Schmidt B, Tappeiner G. Isolation and polymerase chain reaction typing of Borrelia afzelii from a skin lesion in a seronegative patient with generalized ulcerating bullous lichen sclerosis et atrophicus. Br J Dermatol. 2001 Feb:144(2):387-92. Raj Patel, M.D.

  28. What To Do If You Get A Tick Bite • See a doctor immediately. The sooner treatment is started the better the results are. • Go to www.lymediseaseassociation.org for a list of lyme literate MDs (LLMD). Otherwise, take a copy of the ILADS treatment guidelines with you for your doctor http://www.ilads.org/files/ILADS_Guidelines.pdf • Save the tick. Laboratories can test the tick for the presence of lyme and associated coinfections. • If a rash develops take photographs. It may help your doctor in making the diagnosis • Laboratories vary in terms of the depth of lyme testing provided. Dr. Patel prefers to use the following: • Igenex • www.Igenex.com • 1-800-832-3200 • Stony Brook Laboratories • http://www.path.sunysb.edu/labsvs/tickpics/TICKpic.htm • 1-631-444-3824 • Clongen Laboratories • www.Clongen.com • 1-301-916-0173 Raj Patel, M.D.

  29. Testing and Treatment After Tick Bite • Testing • PCR (blood and Serum) for Lyme, Ehrlichia, Bartonella, Babesia, Mycoplasma (can be done on individual &/or tick) • Culture (blood) • FISH for Babesia • Western-Blot not useful. Take 2-6 weeks to turn positive • ELISA not useful • Treatment: IDSA: Rx within 72 hours with Doxycycline 200 mg (4mg/kg) one time dose if age >8 years. No treatment recommended for < 8 years unless symptoms warrant it. ILADS: No specific Rx. Use clinical judgement based on geographical location, type of tick, if engorged, and method of removal. Burrascano Guidelines: Treat 28 days regardless of age. Raj Patel, M.D.

  30. Vector Life Cycle www.cdc.gov/ncidod/dvbid/lyme/ld_transmission.htm Raj Patel, M.D.

  31. Ticks: Year round threat with Spring and Summer being prime time Carried by deer as well as other animals to your yard Mice become carriers when infected ticks feed on them. Subsequently, when non-infected ticks feed they become infected Found in cool moist areas, around shrubs and woody areas, tall grass, and around the edge of yards Ticks prefer moist skin folds: Back of neck Inside part of elbows and knees Hairlines In and around ears Protecting Yourself Raj Patel, M.D.

  32. Minimize Exposure: Yard Prevention Yard prevention very important Keep lawn mowed, cut down brushy areas, & clear away leaves Trim trees to ensure adequate sunshine Creating a 3 ft. wide wood chip or gravel border and stone wall can reduce ticks by 50% Hiking Precautions Walk in middle of trails Wear light colored clothing Wear gloves, hat, long sleeves Use Deet type repellent on exposed skin Use Permethrin tick repellent on clothing Check yourself thoroughly afterwards After possible exposure take clothing and place in dryer at high heat for 15 minutes to kill ticks left behind Protecting Yourself Raj Patel, M.D.

  33. Keep your pets protected: Particularly susceptible, frequently bringing deer ticks into your house Use Frontline or K9 Advantix monthly for cats and dog Use Damminix tubes to reduce deer ticks by more than 90% (tubes filled with cottton treated with Permethrin) Protecting Yourself Raj Patel, M.D.

  34. ILADS (International Lyme and Associated Diseases Society) www.ilads.org Turn The Corner www.turnthecorner.org CALDA (California Lyme Disease Association) www.lymedisease.org “Coping with Lyme Disease, A Practical Guide to Dealing with Diagnosis and Treatment” by Denise Lang and Kenneth Liegner, MD “Prevention Tips” LymeTimes. Summer 2004, p.5-8. Other Useful Websites/Articles www.tickencounter.org www.ilads.org/lyme_disease/B_guidelines_12_17_08.pdf www.healthypets.com/ticks.html www.igenx.com www.drrajpatel.net/pages/lyme.php www.drrajpatel.net/pages/lyme/lyme-support-group.php Useful Resources Raj Patel, M.D.

  35. Indications for Lyme Testing in ASD History of characteristic Bulls eye rash Presence of Bartonella rash (striae) ASD symptoms improve on antibiotics History of tick bite in child History of tick bite in mom before or during pregnancy Presence of night sweats, impulsivity, or other characteristic symptom picture Resided in tick endemic area Lack of response to standard biomedical interventions Raj Patel, M.D.

  36. Thank you Raj Patel, M.D.

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