Raj Patel, MD

Raj Patel, MDRaj Patel, MD Page 1

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:18+ years clinical experienceActive member of Defeat Autism Now (DAN)Active member of International Lyme and Associated Diseases Society (ILADS)

Raj Patel, MDMedical Options for Wellness5050 El Camino Real, #110Los Altos, CA 94022

650-964-6700http://www.DrRajPatel.net

Raj Patel, M.D.

Lyme Disease

Overview Fastest growing vector borne infection

CDC estimated 24,000 cases in 2002 with the CDC itself admitting reported cases represent less than 10% of all cases.

Tick bites frequently transmit multiple infections:

BorreliaEhrlichia/AnaplasmaBabesia and other piroplasmsBartonella like organisms

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 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.

Lyme Disease

Classic Symptoms Associated with Ehrlichia / Anaplasma Myalgias

Sharp knife like headaches behind eyesLow WBC countElevated liver enzymes

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.

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.

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.

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, MycoplasmaFISH for Babesia Western-Blot not useful. Take 2-6 weeks to turn positive

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.

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.

Two Standards of Care

IDSA (Infectious Diseases Society of America)

“…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