Transcript Biofilms, Methylation & Heavy Metal Detoxification in

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:
18+ years clinical experience
Active member of Defeat Autism Now (DAN)
Active member of International Lyme and Associated Diseases Society (ILADS)
Raj Patel, MD
Medical Options for Wellness
5050 El Camino Real, #110
Los Altos, CA 94022
650-964-6700
http://www.DrRajPatel.net
Raj Patel, MD
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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:
Borrelia
Ehrlichia/Anaplasma
Babesia and other piroplasms
Bartonella 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 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.
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.
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.
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.
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 language
Poor socialization/unaware of others’ feelings/does not respond to name
Non DSM Related:
Abdominal bloating/Diarrhea/Constipation
Difficulty with Abstract Reasoning
Insommnia
Obscessive-compulsive behavior
Food Intolerances
Raj Patel, M.D.
Hypotonia
Decreased attention/hyperactivity
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
Raj Patel, M.D.
Grier, T. Laboratory Tests. Lyme Times. Summer 2004:21-25
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
1-800-832-3200
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.
Testing and Treatment After Tick Bite
Testing
PCR (blood and Serum) for Lyme, Ehrlichia, Bartonella, Babesia,
Mycoplasma
FISH 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)
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“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 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.
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
Raj Patel, M.D.