Tips on the Management of
Lyme Disease
by
Raj Patel, M.D. &
Susan McCamish, Herbalist.
Raj Patel, MD
Page 1
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) 1998-2011
Active member of International Lyme and Associated Diseases Society
(ILADS)
Raj Patel, MD
Medical Options for Wellness
570 Price Avenue, #200
Redwood City, CA 94063
650-474-2130
http://www.DrRajPatel.net
Raj Patel, MD
Page 2
DISCLAIMER
This presentation contains treatment tips for
Lyme disease. It is not intended to serve as medical
advice. Please discuss potential treatment options
with your health care provider.
I have no financial arrangements with the various
nutritional companies whose products are
mentioned in this presentation beyond the resale of
these products in my office.
Raj Patel, M.D.
Tips on the Management of Lyme Disease
Overview: Jarisch-Herxheimer Reaction
Definition
Prevalence
Mechanism
Symptoms
Laboratory Markers
Prevention/Treatment
Variable Immune Response
Treatment Protocols
Foundation
Assess & Support Key Organs
Evaluate, Prioritize, & Treat Microbes
Raj Patel, M.D.
Jarisch-Herxheimer
Reaction
Raj Patel, M.D.
Jarisch-Herxheimer Reaction (JHR)
Definition:
Syndrome brought on by the lysis of certain organisms in the body.
Symptoms may include fevers/chills, tachycardia, myalgias, headaches and
hypotension among others.
Jarisch-Herxheimer reaction. Br Med J 1967;1:384.
Vaughan C, Cronin CC, Walsh EK, Whelton M. The Jarisch-Herxheimer
reaction in leptospirosis. Postgrad Med J 1994;70:118-121
Morrison, DC, et.al.: The effects of bacterial endotoxins on host mediation
systems. Amer Jrnl Path 93: 526, 1978.
Raj Patel, M.D.
Jarisch-Herxheimer Reaction (JHR)
Prevalence:
JHR originally reported in association with syphilis treatment. More
recently also found with other spirochetal organisms including borrelia.
Reported in non spirochetal infections such as Brucellosis, Anthrax and
Leprosy. Estimates range 50 – 75% in Lyme and tick borne diseases.
Study on tick borne relapsing fever in US and Canada, JHR reported in
only 54.1% of 61 cases.
Strominger MB1, et al. J. Neuroophthalmol. 1994 Jun;14(2):77-80.
Coxon RE1, et al. The effect of antibody against TNF alpha on cytokine response in Jarisch-Herxheimer reactions of louse-borne relapsing fever.
QJM. 1997 Mar;90(3):213-21.
Primary author unknown: The Herxheimer Effect, Supplement to the Art of Getting Well. The Arthritis Trust of America: 370, 1991.
Dworkin MS1, et al. Tick-borne relapsing fever in the northwestern United States and southwestern Canada. (Clin Infect Dis.
1998 Jan;26(1):122-31.
Raj Patel, M.D.
Jarisch-Herxheimer Reaction (JHR)
Mechanism:
Studies suggest the release of endotoxin like material triggering
production of cytokines resulting in symptoms of JHR.
There is a 3-20 fold release of endotoxins as a result of antibiotic action
on gram negative bacteria, both in vivo and in vitro.
Pound MW1, et al. Proposed mechanisms and preventative options of Jarisch-Herxheimer reactions. J Clin Pharm Ther. 2005
Jun;30(3):291-5.
Clin Infect Dis. 1992 Nov;15(5):840-54. Antibiotic-induced release of endotoxins: a reappraisal. Hurley JC.
Raj Patel, M.D.
Jarisch-Herxheimer Reaction (JHR)
Symptoms:
Vary widely. May include the following:
Low grade fevers
Encephalopathy
Arthralgias
Myalgias
Headaches
Non convulsive seizures
Hepatoxicity
Bells Palsy
Worsening radiculomyelitis
Decrease visual acuity
Strominger MB1, et al. Transient worsening of optic neuropathy as a sequel of the Jarisch-Herxheimer reaction in the treatment of Lyme disease. J
Neuroophthalmol. 1994 Jun;14(2):77-80.
Negussie Y1, et al. Detection of plasma tumor necrosis factor, interleukins 6, and8 during the Jarisch-Herxheimer Reaction of relapsing fever. J Exp Med.
1992 May 1;175(5):1207-12.
Berger EM1, et al. Unilateral facial paralysis after treatment of secondary syphilis. J Drugs Dermatol. 2008 Jun;7(6):583-5.
Kojan S1, et al. Nonconvulsive status epilepticus resulting from Jarisch-Herxheimer reaction in a patient with neurosyphilis. Clin Electroencephalogr. 2000
Jul;31(3):138-40.
Rishi P1, et al. Inhibition of endotoxin-induced hepatotoxicity by melatonininr ats. Int J Biomed Sci. 2008 Jun;4(2):103-12.
Raj Patel, M.D.
Jarisch-Herxheimer Reaction (JHR)
Lab Abnormalities:
Study on patients with louse borne relapsing fever (borrelia recurrentis)
elevations in TNF, IL-6 and IL-8 at baseline with levels rising 7, 6 & 4
fold respectively with treatment.
82% of patients in study experienced JHR symptoms. (18% did not?)
CSF analysis in neurosyphilis patients during JHR found marked
elevations in IL-8 with more moderate increases in IL-10 and IL-15
J Exp Med. 1992 May 1;175(5):1207-12.
Negussie Y1, Remick DG, DeForge LE, Kunkel SL, Eynon A, Griffin GE.
JAMA Neurol. 2013 Aug;70(8):1060-4. doi: 10.1001/jamaneurol.2013.2120.
Davis LE1, Oyer R, Beckham JD, Tyler KL.
Raj Patel, M.D.
Jarisch-Herxheimer Reaction (JHR)
Prevention/Treatment:
Several studies have shown inhibition of JHR after penicillin treatment using
TNF antibodies.
However, the potential toxicity of clinically available TNF inhibitors like
Etanercept (Enbril) make this impractical.
QJM. 1997 Mar; 90(3):213-21.
The effect of antibody against TNF alpha on cytokine response in Jarisch-Herxheimer reactions of louse-borne relapsing fever.
Coxon RE1, Fekade D, Knox K, Hussein K, Melka A, Daniel A, Griffin GG, Warrell DA.
N Engl J Med. 1996 Aug 1; 335(5):311-5.
Prevention of Jarisch-Herxheimer reactions by treatment with antibodies against tumor necrosis factor alpha.
Fekade D1, Knox K, Hussein K, Melka A, Lalloo DG, Coxon RE, Warrell DA.
Raj Patel, M.D.
Jarisch-Herxheimer Reaction (JHR)
Prevention/Treatment:
(continued)
Steroids have been used with some benefit in reducing JHR.
Bacterial endotoxin induced hepatotoxicity (↑ALT/AST) was found to be
significantly attenuated by melatonin administered pre and post endotoxin
challenge in rats. Corresponding depletions in antioxidants were also found to
be attenuated by melatonin.
S. Ma Y, Weis JJ ((1993)
Outer surface lipoproteins OspA and OSP B posess B-cell mitogenic and cytokine-stimulatory properties. Infect Immun. 61:3843-3853.
Rev Neurol. 2000 Dec 1-15;31(11):1066-70. HLA and multiple sclerosis. Studies of a Spanish population.
Pound MW, May DB. Proposed mechanisms and preventative options of Jarisch-Herxheimer reactions. J Clin Pharm Ther 2005;30:291-295
Int J Biomed Sci. 2008 Jun;4(2):103-12.Inhibition of endotoxin-induced hepatotoxicity by melatonin in rats.
Rishi P1, Bharrhan S, Bhalla MP, Koul A, Chopra K.
Raj Patel, M.D.
Jarisch-Herxheimer Reaction (JHR)
Variable Immune Response:
JHR is not consistently seen with studies showing 18-45% of cases with
spirochetal infections do not experience JHR to antimicrobials.
Inflammatory immune responses can be debilitating and vary dramatically
having significant clinical implications on individual case management and
the long term potential for a successful outcome.
J Exp Med. 1992 May 1;175(5):1207-12.
Detection of plasma tumor necrosis factor, interleukins 6, and8 during the Jarisch-Herxheimer Reaction of relapsing fever.
Negussie Y1, Remick DG, DeForge LE, Kunkel SL, Eynon A, Griffin GE.
Clin Infect Dis. 1998 Jan;26(1):122-31. Tick-borne relapsing fever in thenorthwestern United States and southwestern Canada.
Dworkin MS1, Anderson DE Jr, Schwan TG, Shoemaker PC, Banerjee SN, Kassen BO, Burgdorfer W.
Raj Patel, M.D.
Jarisch-Herxheimer Reaction (JHR)
Variable Immune Response:
HLA DR genes:
Extensive documentation in the literature linking to various illnesses including
celiac, ADHD, Rheumatoid Arthritis and MS among others.
HLA DRB/DQ genes:
Shoemaker identified specific combinations of subsets of these genes
associated with a defect in antigen presentation (specifically borrelial
antigens) by dendritic cells to native T cells. These cases were identified as
“Lyme Susceptible” correlated with high C4a responses.
Raj Patel, M.D.
Jarisch-Herxheimer Reaction (JHR)
Variable Immune Response:
Shoemaker in his private practice finds approximately 22% of cases are
“Lyme susceptible.”
Informal study in my office of 64 randomly chosen Lyme disease cases.
55 (86%) were found to have at least one allele that was either “Lyme
susceptible” or “Multisusceptible”.
Raj Patel, M.D.
Jarisch-Herxheimer Reaction (JHR)
Variable Immune Response:
Personal observation: Individuals not carrying a “Lyme susceptible” or
“Multisusceptible” allele tend to recover faster from Lyme Disease, have
minimal JHR symptoms, & need much shorter duration of antimicrobial
treatment.
This variable immune response may shed light on the ongoing controversy in
the medical community regarding length of treatment required to completely
recover from borrelia infection.
Obviously further studies are needed to clarify the true incidence of Lyme
susceptible HLA DR/DQ genes in the general population and the variable
inflammatory response to treatment.
Raj Patel, M.D.
Jarisch-Herxheimer Reaction (JHR)
Variable Immune Response:
Soloski’s group published a paper on cytokine immune response in acute
Lyme disease versus controls.
Wide range of immune mediators and acute phase markers were studied.
The study revealed 2 distinct response groups.
Soloski, Mark et al. Serum Inflammatory Mediators as Markers of Human Lyme Disease Activity. PLOS.org April 2014, Vol. 9, Issue 4.
Raj Patel, M.D.
Raj Patel, MD
Page 18
Jarisch-Herxheimer Reaction (JHR)
Variable Immune Response:
Summary:
The high mediator group displayed:
- more severe symptoms
- higher Ab levels
- higher rates of sero-conversion post treatment
- higher incidence of liver enzyme elevations
- lower lymphocyte levels at baseline
The low mediator group failed to mount a vigorous immune response leading
to speculations to why Lyme symptoms persist in some individuals post
treatment.
Raj Patel, M.D.
Raj Patel, MD
Page 20
Jarisch-Herxheimer Reaction (JHR)
Take Home Message:

LD cases vary widely in their baseline immune status, levels of
inflammation, and response to antimicrobial therapy.

Treat each patient individually in terms of the length of treatment,
providing appropriate drainage, anti inflammatory and immune support
as needed.
Raj Patel, M.D.
Treatment Protocols
Raj Patel, M.D.
Treatment Protocols
Goals:
Treat each case individually.
Provide appropriate support to minimize needless pain and
discomfort during treatment. Thus allowing the treatment to
progress in an efficient and consistent manner.
Outline:
Foundation
Assess and support key organs.
Evaluate, prioritize, & treat microbial load.
Raj Patel, M.D.
Treatment Protocols
A. Foundation:
1.
Diet
GFCFSF (Gluten Free, Casein Free, Sugar Free)
SCD/Paleo
Antinflammatory Diet
Benefits: Manages gut inflammation
Reduces gut dysbiosis
Prolongs the effectiveness of the treatment
Eliminate alcohol and reduce caffeine.
Benefits: Reduces hepatic stress.
Raj Patel, M.D.
Raj Patel, MD
Page 25
Treatment Protocols
A. Foundation: (continued)
2. Sleep
Ensure adequate, restful sleep (8-10 hours)
Sleep Aids (non Rx):
Melatonin
Theanine
Phosphatidylserine
Benadryl
Valerian, Kava Kava
Sleep Aids (Rx): Benzodiazepines (Halcion, Restoril, Ativan)
Tricyclics (Trazadone, Amitriptyline,Nortriptyline)
GABA meds (Ambien,Lunesta,Sonata)
Anti Seizure (Lyrica,Gabapentin)
Raj Patel, M.D.
Treatment Protocols
A. Foundation: (continued)
3. Exercise:
Gentle as tolerated, daily
Helps mobilize lymph/toxins
- improves oxygenation and
mitochondrial function
Ramp up as recovery progresses
Adequate fluid intake (8-10 glasses/day)
Raj Patel, M.D.
Treatment Protocols
A. Foundation: (continued)
4. Safe Environment:
Mold/Water Damage: ERMI
C4a
HLA DRB/DQ
Urine Mycotoxin
EMFs:
Raj Patel, M.D.
Cordless phones
Wireless routers
Treatment Protocols
B. Assess and Support Key Organs
1. Liver/Gallbladder:
a. Clues – Elevated LFT (elevated total bilirubin indicate GB stress)
History (f.f. intol., light greasy stools, ETOH /drug abuse)
Food intolerances
Waking up between 11-1 am (GB) or 1-3 am (Liver)
Caffeine intolerance (Phase 1)
b. Support – Nutritional support of Phase I or Phase II
Silymarin (liver) / bupleureum (GB)
Liver Life
Glutathione
ApoHepat/Mundipur
Cholestyramine
Consider GB flush / Coffee enemas
Raj Patel, M.D.
Treatment Protocols
B. Assess and Support Key Organs
2. GI:
a. Clues – Food intolerance (low BS symptoms between meals)
Physical exam (periumbilical discomfort on palpatation)
Diarrhea &/or Constipation
Borrelia & Viruses (HHV6)
b. Support – Digestive enzymes
Probiotics
Antifungals
Eliminate refined carbohydrates
Reduce complex carbohydrates
Consider anti inflammatory diet
Binders (CSM, charcoal, clay, bamboo)
Treat constipation
Raj Patel, M.D.
Treatment Protocols
B. Assess and Support Key Organs
3. Immune System/Inflammation:
a. Clues – Low total IgG/NK cells
Elevated C4a
Elevated CRP/ESR/TNF
Autoimmune markers
Joint tenderness on PE
b. Support – Immune globulins/TF/AHCC/Probiotics/Colostrum
CSM (r/o WBD)
Low dose antivirals
Homeopathics (Inflammayer, Mundipur, A-Inflam)
Herbal (Chinese Skullcap, Cyflacalm)
NSAIDS?
Raj Patel, M.D.
Treatment Protocols
B. Assess and Support Key Organs
4. Kidney:
a. Clues –
Elevated or high normal Creat.
Proteinuria/ ↓GFR
Back/Flank pain
b. Support – Ensure adequate fluid intake and regular exercise
Homeopathics (K-Drain, Renelix)
Herbal (Dandelion, Parsley)
Raj Patel, M.D.
Treatment Protocols
B. Assess and Support Key Organs
5. Endocrine (Adrenals & Thyroid):
a. Clues – Check blood for TSH, Free T3, Free T4, Reverse T3
Hypothyroid symptoms
Saliva cortisol (24 Hour)
Symptoms of POTS
Inability to tolerate stress
b. Support – Adequate T4/T3 supplementation
Consider Iodine and other nutrient deficiencies
Adrenal Support
REST
Raj Patel, M.D.
Treatment Protocols
B. Assess and Support Key Organs
6. Lymph/ECM
a. Clues – Rings get tight on fingers
Feeling stiff/sore in morning or after sitting for 1-2 hours
Lack of daily exercise/Sedentary lifestyle
Almost universally support needed
b. Support – Ensure 60-80 oz. of fluid per day
Avoid caffeine (diuretic)
Regular exercise (20-30 minute walk BID ideal)
Homeopathics (Itires, L-Drain, Lymphtone II, etc.)
Skin brushing, Lymphatic massage.
Raj Patel, M.D.
Treatment Protocols
C. Evaluate, Prioritize & Treat Microbial Load
1. Evaluation:
Parasites - Stool testing (Genova, DD, DiagnosTechs, &
ParaWellnessResearch.)
History of extensive foreign travel
Symptoms of rectal itching/teeth grinding at night
Elevated eosinophil count
Consider AK or EST
Babesia - Titers, FISH, malaria smear.
Symptoms of air hunger, night sweats, severe fatigue, dull
global HA, hypercoagulable states
Raj Patel, M.D.
Treatment Protocols
C. Evaluate, Prioritize & Treat Microbial Load
1. Assessment:
Bartonella - Titers (for henselae and quintana) & FISH.
(IgenX, Galaxy Diagnostics, Frye labs)
Symptoms of anxiety, pseudoseizures, sore soles,
irritability, hyperpigmented striae, lymphadenopathy
Ehrlichia/Anaplasma - Titers, low WBC count, low platelets, elevated
LFTs.
Symptoms of knifelike headaches
Borrelia - Titers (burgdorferi and hermsii), PCR, culture
Symptoms of migratory arthralgias /arthritis, occipital HA,
EM rash, multi-system involvement, 4 week cycle
Raj Patel, M.D.
Treatment Protocols
C. Evaluate, Prioritize & Treat Microbial Load
1. Assessment:
Stealth Pathogens (Chlamydia pneum. & trach., Mycoplasma pneum.)
- Titers & PCR
Viruses
- Titers, EBV/CMV/Parvo/HHV6, ↑Lymphocytosis,
↑adenosine, ↓SAM
Raj Patel, M.D.
Treatment Protocols
C. Evaluate, Prioritize & Treat Microbial Load
2. Prioritize:
Parasites
Babesia/Bartonella
Ehrlichia/Anaplasma
Borrelia
Stealth Pathogens
Viruses
Raj Patel, M.D.
Treatment Protocols
C. Evaluate, Prioritize & Treat Microbial Load
3. Treatment:
I. Parasites
Protozoans- Flagyl, Tindamax, Yodoxin, Alinia
Consider MC-PZ
Helminths & Nematodes – Albendazole/Praziquantel x 2 wks
+ Ivermectin/Mebendazole on days 12-14.
2 – 3 cycles typically necessary
Also Alinia, Humatin, Pyrantel effective.
Consider Parazomin, AromaTab, Paratrex, & DE
Raj Patel, M.D.
Treatment Protocols
C. Evaluate, Prioritize & Treat Microbial Load
2. Treatment:
II. Babesia
Mepron/Macrolide/Artemesinin
Septra/Macrolide
Lariam/Plaquenil
CoArtem + Artemesinin
Consider Bab1 & Bab 2, CryptoPlus, A-Bab, Enula,
Artemesinin
Raj Patel, M.D.
Treatment Protocols
C. Evaluate, Prioritize & Treat Microbial Load
2. Treatment:
III. Bartonella
Quinolones +/- Rifampin
Bactrim + Zithromax +/- Rifampin
Doxy + Rifampin
Bar 1&2, Houttuynia, A-Bart
Raj Patel, M.D.
Treatment Protocols
C. Evaluate, Prioritize & Treat Microbial Load
2. Treatment:
IV. Ehrlichia/Anaplasma
Doxy + Macrolide
Doxy + Rifampin
Doxy + Quinolone
Bb1&2, AL Complex
Raj Patel, M.D.
Treatment Protocols
C. Evaluate, Prioritize & Treat Microbial Load
2. Treatment:
V. Borrelia
Doxy + Macrolide + Plaquenil
PCN/Ceph + Macrolide + Plaquenil
Septra + Macrolide + Plaquenil
Consider Bb1&2, A-L Complex, Samento & Banderol
Raj Patel, M.D.
Treatment Protocols
C. Evaluate, Prioritize & Treat Microbial Load
2. Treatment:
VI. Chlamydia
Doxy + Macrolide +/- Rifampin
Doxy + Quinolone
Consider Bar 2, A-Cpn
Raj Patel, M.D.
Treatment Protocols
C. Evaluate, Prioritize & Treat Microbial Load
2. Treatment:
VII. Mycoplasma
Rifampin + Macrolide
Doxy + Quinolone
Bactrim + Macrolide
Consider A-Myco, ENL-MC
Raj Patel, M.D.
Treatment Protocols
C. Evaluate, Prioritize & Treat Microbial Load
2. Treatment:
VIII. Viruses
Famvir / Valtrex / Valcyte
Consider IMNV & IMNV2, AEBH6, Viralox or IRM.
Supplement Glutathione & Vit. D as needed.
Remember binders and detox support.
Consider GcMAF (for elevated Nagalase)
Raj Patel, M.D.
Take Home Message
1. Manage Inflammation (diet, genetics, infections)
2. Support elimination of biotoxins
3. Treat underlying infections at a rate that does not overwhelm
#1 & 2
4. Look for unrecognized sources of inflammation (mold!)
5. Be on the lookout for underlying emotional/lifestyle issues that
may jeopardize healing
Raj Patel, M.D.
THANK YOU
Raj Patel, MD
Page 48