Raj Patel, M.D.

Does Your Child Have Autism or Lyme Disease?

By

Raj Patel, M.D.

Raj Patel, MDRaj Patel, MD

Raj Patel, MDRaj Patel, MD

Education:MS-Rutgers UniversityMD – Robert Wood Johnson Medical SchoolResidency-Family MedicinePost Graduate studies in Autism Spectrum Disorders & Lyme Disease

Research:Ampligen-CFIDS (Hemispherx Pharmaceutical)

Clinical:20+ years clinical experienceActive 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, MDMedical Options for Wellness5050 El Camino Real, #110Los Altos, CA 94022

650-964-6700www.DrRajPatel.net

Raj Patel, M.D.

Does Your Child Have Autism or Lyme Does Your Child Have Autism or Lyme Disease?Disease?

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

Raj Patel, M.D.

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:BorreliaEhrlichia/AnaplasmaBabesia and other piroplasmsBartonella like organisms

Raj Patel, M.D.

Lyme Disease

Overview

Raj Patel, M.D.

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.

Raj Patel, M.D.

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.

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 disseminatedMigratory arthralgias that evolve into arthritisOccipital headaches with neck stiffnessFatigueFour week cycle of symptom flare-upsEM rash (bulls-eye)

Raj Patel, M.D.

Lyme Disease

Classic Symptoms Associated with Babesia Rapid onset of symptoms (cyclic high fevers, severe headaches, & sweats

esp. at night)Air hungerDull global headachesProminent fatigue with exercise intoleranceSymptoms cycle every 4-7 daysHypercoagulable states

Raj Patel, M.D.

Lyme Disease

Classic Symptoms Associated with Ehrlichia / Anaplasma Myalgias

Sharp knife like headaches behind eyesLow WBC countElevated liver enzymes

Raj Patel, M.D.

Lyme Disease

Classic Symptoms Associated with Bartonella like organisms CNS symptoms prominent (anxiety, agitation, insommnia, seizures, outbursts

and anti-social behavior)LymphadenopathySoles tender esp. in morningStriae (hyperpigmented stretch marks)Elevated VEGF (vascular endothelial growth factor) useful marker to follow

response to treatment.

Raj Patel, M.D.

Bartonella Rash

Raj Patel, M.D.

Bartonella Rash

Raj Patel, M.D.

Lyme Bulls Eye Rash

Raj Patel, M.D.

Lyme Bulls Eye Rash

Raj Patel, M.D.

Raj Patel, M.D.

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 languagePoor socialization/unaware of others’ feelings/does not respond to name

Non DSM Related:

Abdominal bloating/Diarrhea/Constipation Hypotonia Difficulty with Abstract Reasoning

Decreased attention/hyperactivityInsommniaObscessive-compulsive behaviorFood Intolerances

Raj Patel, M.D.

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 languagePoor socialization/unaware of others’ feelings/does not respond to name

Non DSM Related:

Abdominal bloating/Diarrhea/Constipation Hypotonia Difficulty with Abstract Reasoning

Decreased attention/hyperactivityInsommniaObscessive-compulsive behaviorFood Intolerances

Raj Patel, M.D.

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.

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 TestsPCR – detects Borrelia DNA in urine, blood, or tissue.

Culture – grows the borrelia organism.

Raj Patel, M.D.

Lyme Western Blot Testing

Grier, T. Laboratory Tests. Lyme Times. Summer 2004:21-25

Raj Patel, M.D.

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.

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.

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.

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.

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 positiveOski 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.

What To Do If You Get A Tick Bite

1. See a doctor immediately. The sooner treatment is started the better the results are.

2. 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

3. Save the tick. Laboratories can test the tick for the presence of lyme and associated coinfections.

4. If a rash develops take photographs. It may help your doctor in making the diagnosis

5. Laboratories vary in terms of the depth of lyme testing provided. Dr. Patel prefers to use the following:

Igenex www.Igenex.com 1-800-832-3200Stony Brook Laboratorieshttp://www.path.sunysb.edu/labsvs/tickpics/TICKpic.htm 1-631-444-3824Clongen Laboratories www.Clongen.com 1-301-916-0173

Raj Patel, M.D.

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 positiveELISA 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.

Vector Life Cycle

www.cdc.gov/ncidod/dvbid/lyme/ld_transmission.htm

Raj Patel, M.D.

Protecting YourselfProtecting Yourself

Ticks:

Year round threat with Spring and Summer being prime timeCarried by deer as well as other animals to your yardMice 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 neckInside part of elbows and kneesHairlinesIn and around ears

Raj Patel, M.D.

Protecting YourselfProtecting Yourself

Minimize Exposure:

Yard PreventionYard prevention very importantKeep lawn mowed, cut down brushy areas, & clear away leavesTrim trees to ensure adequate sunshine Creating a 3 ft. wide wood chip or gravel border and stone wall

can reduce ticks by 50%

Hiking PrecautionsWalk in middle of trails Wear light colored clothingWear gloves, hat, long sleevesUse Deet type repellent on exposed skinUse Permethrin tick repellent on clothingCheck yourself thoroughly afterwardsAfter possible exposure take clothing and

place in dryer at high heat for 15 minutes to kill ticks left behind

Raj Patel, M.D.

Protecting YourselfProtecting Yourself

Keep your pets protected:

Particularly susceptible, frequently bringing deer ticks into your house

Use Frontline or K9 Advantix monthly for cats and dogUse Damminix tubes to reduce deer ticks by more than 90%

(tubes filled with cottton treated with Permethrin)

Raj Patel, M.D.

Useful ResourcesUseful Resources

ILADS (International Lyme and Associated Diseases Society)

www.ilads.orgTurn The Corner

www.turnthecorner.orgCALDA (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/Articleswww.tickencounter.orgwww.ilads.org/lyme_disease/B_guidelines_12_17_08.pdfwww.healthypets.com/ticks.htmlwww.igenx.comwww.drrajpatel.net/pages/lyme.phpwww.drrajpatel.net/pages/lyme/lyme-support-group.php

Raj Patel, M.D.

Indications for Lyme Testing in ASD

History of characteristic Bulls eye rashPresence of Bartonella rash (striae)ASD symptoms improve on antibioticsHistory of tick bite in childHistory of tick bite in mom before or during pregnancyPresence of night sweats, impulsivity, or other characteristic symptom picture Resided in tick endemic areaLack of response to standard biomedical interventions

Raj Patel, M.D.

Thank you