1. Complexity and Controversy
The Lyme Enigma
Complexity and Controversy

2. Lyme Life Cycle
Lyme disease is caused by a tick-borne spirochete, Borrelia burgdorferi.
Humans are an incidental host
The lifecycle of the spirochete is predominantly between mice, deer and the deer tick. In CA ixodes pacificus is the vector and in the east coast it is ixodes scapularis
The nymph deer tick is the most likely to transmit Lyme, and they are generally feeding in the spring and summer, adults feed in the fall

3. A closer look
Borrelia burgdorferi is found in NA. But also B miyamotoi
Borrelia garinii and afzelii are found in Europe. Or American patients returned from Europe.
Ticks are not the only way to get Lyme: sexual and placental transmission

4. Early signs and symptoms of Lyme
Erythema Migrans onset 7-14 days after bite
Sore throat, myalgias, arthralgias, fever, chills, and headache within days to 2 weeks after infection
If symptoms are severe and high fever is present consider co-infection with human granulocytic anaplasmosis(HGA) and Babesia.
Babesia microti/duncani in the East and babesia duncani in CA

5. Early disseminated Lyme
Arthralgias,
Neurologic symptoms, headaches, cranial neuropathy, diffuse or focal mononeuropathy multiplex, lymphocytic meningitis, plexopathy,
Radiculoneuropathy (Bannwarth syndrome)
Cardiac symptoms syncope, dyspnea, chest pain, palpitations, A-V block
Skin involvement-secondary erythema migrans, acrodermatitis chronicum atrophicans

6. Late Lyme disease
Occurs months to years after infection and often a period of latency
Joint and neurologic symptoms most common
Sub acute encephalopathies, axonal neuropathies and peripheral neuropathy
Bannwarth syndrome
Neuropsychiatric symptoms

7. Diagnosis
antibodies,
antigen,
PCR,
T-cell response,
culture

8. Direct testing
PCR
Lyme antigen
Coyle’s research

9. Antibodies Initial lag time to seroconversion Conversion of IgM to IgG
sensitivity of ELISA
sensitivity of WB
WB comparison
C6LPE
afzelii and garinii
Coyle’s research

10. T-cell response
aka iSpot

11. long incubation, preferred media, preferred surfaces
Lyme culture
fussy bug:
long incubation, preferred media, preferred surfaces

12. Associated Lab Findings
low CD57, low WBC
possibly low IgG3 or slightly elevated ANA
normal ESR, CRP
first-degree heart block

13. Babesia, Bartonella, Ehrlichia, Anaplasmosis...
Co-infections
Babesia, Bartonella, Ehrlichia, Anaplasmosis...

14. Treatments
antibiotics,
herbs,
oxidative therapies,
silver

15. IDSA Treatment of early Lyme disease without significant neurological or cardiac symptoms
Doxycycline 200mg bid
Amoxicillin 500mg tid
Cefuroxime 500mg bid
All the above are given for days

16. ILADS treatment of Erythema Migrans without other symptoms
Doxycycline 100mg qid or 200mg bid with food
Cefuroxime 1g bid
Amoxicillin 1g tid with probenicid 500mg tid if pregnant dose Amoxicillin q6h
Treat for 21 days
If pregnant treat for 6 weeks and test for Babesia, HGA, and Bartonella

17. IDSA treatment of Lyme carditis
Ceftriaxone 2gm qd for days
Doxycycline mg po bid for days
For AV block or myopericarditis use either of above regimes with appropriate inpatient monitoring. With resolution of heart block patient may be discharged home on po meds

18. ILADS Early disseminated Lyme
Milder symptoms present for less than one year with multiple Erythems Migrans lesions, constitutional symptoms, and lymphadenopathy,
Treat with oral therapy until no active disease for 4 weeks (4–6 months typical) using same antibiotic doses as outlined for Erythema Migrans 
Pregnancy: As in Erythema Migrans, but duration as above. Treat throughout pregnancy, and do not breast feed. 

19. IDSA treatment of late Lyme disease arthritis
Doxycycline 100mg bid
Amoxicillin 500mg tid
Cefuroxime 500mg bid
Treat for 28 days
If persistent or recurrent joint swelling retreat with another 28 days of above antibiotics or 2-4 weeks of IV ceftriaxone
Then supportive therapy B-3

20. IDSA late neurologic Lyme disease
This includes encephalopathy's and radiculopathies, Bannwarth syndrome
Treat with ceftriaxone 2 gm qd for 2-4 weeks
“Response to treatment is usually slow and may be incomplete”
“Re-treatment is not recommended unless relapse is shown by reliable objective measures”

21. ILADS Late Disseminated/ Chronic Lyme
Symptoms present greater than one year, more severely ill patients, and those with prior significant steroid therapy or any other cause of impaired immunity: 
Treat adults and pregnant woman with 10 or more weeks of IV therapy , then oral or IM till asymptomatic for 6-8 weeks Children: IV therapy for 6 or more weeks, then oral or IM follow up as above. 
Ceftriaxone Risk of biliary sludging can be minimized with intermittent breaks in therapy (ie: infuse five or less days in a row per week).  Adults and pregnancy: 2g q12h, four days in a row each week.  Children: 75 mg/kg/day up to 2g/day  Cefotaxime Comparable efficacy to ceftriaxone; no biliary complications.  Adults and pregnancy: 2g q8h; may dose as high as 12g daily. Suggest a continuous infusion.  Children: 90 to 180 mg/kg/day dosed q6h (preferred) or q8h, not to exceed 12 g daily.  *Doxycycline Requires central line as is caustic. Surprisingly effective, probably because higher overall, and spiked blood levels when given parenterally.  Always measure blood levels.  Adults: 400 mg q24h and adjust based on levels.  Cannot be used in pregnancy or in younger children.  Azithromycin Requires central line as is caustic.  Dose: 500 to 1000 mg daily in adolescents and adults.  Penicillin G IV penicillin G is minimally effective and not recommended.  Benzathine penicillin Surprisingly effective IM alternative to oral therapy.  May need to begin at lower doses as strong, prolonged (6 or more week) Herxheimer-like reactions have been observed.  Adults: 1.2 million U three times per week (higher doses with large body habitus)  Adolescents: 300,000 to 2.4 million U weekly.  May be used in pregnancy.  Poorly studied but anecdotally effective  Vancomycin Observed to be one of the best drugs in treating Lyme, but potential toxicity limits its use. It is a perfect candidate for pulse therapy to minimize these concerns.  Use standard doses and confirm levels.  Imipenim and Unisyn Similar in efficacy to cefotaxime, but often works when cephalosporins have failed.  Must be given q6 to q8 hours.  Cefuroxime Useful but not demonstrably better than ceftriaxone or cefotaxime.  Ampicillin IV More effective than penicillin G. Must be given q6 hours.  Ceftriaxone Risk of biliary sludging can be minimized with intermittent breaks in therapy (ie: infuse five or less days in a row per week).  Adults and pregnancy: 2g q12h, four days in a row each week.  Children: 75 mg/kg/day up to 2g/day  Cefotaxime Comparable efficacy to ceftriaxone; no biliary complications.  Adults and pregnancy: 2g q8h; may dose as high as 12g daily. Suggest a continuous infusion.  Children: 90 to 180 mg/kg/day dosed q6h (preferred) or q8h, not to exceed 12 g daily.  *Doxycycline Requires central line as is caustic. Surprisingly effective, probably because higher overall, and spiked blood levels when given parenterally.  Always measure blood levels.  Adults: 400 mg q24h and adjust based on levels.  Cannot be used in pregnancy or in younger children.  Azithromycin Requires central line as is caustic.  Dose: 500 to 1000 mg daily in adolescents and adults.  Penicillin G IV penicillin G is minimally effective and not recommended.  Benzathine penicillin Surprisingly effective IM alternative to oral therapy.  May need to begin at lower doses as strong, prolonged (6 or more week) Herxheimer-like reactions have been observed.  Adults: 1.2 million U three times per week (higher doses with large body habitus)  Adolescents: 300,000 to 2.4 million U weekly.  May be used in pregnancy.  Poorly studied but anecdotally effective  Vancomycin Observed to be one of the best drugs in treating Lyme, but potential toxicity limits its use. It is a perfect candidate for pulse therapy to minimize these concerns.  Use standard doses and confirm levels.  Imipenim and Unisyn Similar in efficacy to cefotaxime, but often works when cephalosporins have failed.  Must be given q6 to q8 hours.  Cefuroxime Useful but not demonstrably better than ceftriaxone or cefotaxime.  Ampicillin IV More effective than penicillin G. Must be given q6 hours.  Ceftriaxone Risk of biliary sludging can be minimized with intermittent breaks in therapy (ie: infuse five or less days in a row per week).  Adults and pregnancy: 2g q12h, four days in a row each week.  Children: 75 mg/kg/day up to 2g/day  Cefotaxime Comparable efficacy to ceftriaxone; no biliary complications.  Adults and pregnancy: 2g q8h; may dose as high as 12g daily. Suggest a continuous infusion.  Children: 90 to 180 mg/kg/day dosed q6h (preferred) or q8h, not to exceed 12 g daily.  *Doxycycline Requires central line as is caustic. Surprisingly effective, probably because higher overall, and spiked blood levels when given parenterally.  Always measure blood levels.  Adults: 400 mg q24h and adjust based on levels.  Cannot be used in pregnancy or in younger children.  Azithromycin Requires central line as is caustic.  Dose: 500 to 1000 mg daily in adolescents and adults.  Penicillin G IV penicillin G is minimally effective and not recommended.  Benzathine penicillin Surprisingly effective IM alternative to oral therapy.  May need to begin at lower doses as strong, prolonged (6 or more week) Herxheimer-like reactions have been observed.  Adults: 1.2 million U three times per week (higher doses with large body habitus)  Adolescents: 300,000 to 2.4 million U weekly.  May be used in pregnancy.  Poorly studied but anecdotally effective  Vancomycin Observed to be one of the best drugs in treating Lyme, but potential toxicity limits its use. It is a perfect candidate for pulse therapy to minimize these concerns.  Use standard doses and confirm levels.  Imipenim and Unisyn Similar in efficacy to cefotaxime, but often works when cephalosporins have failed.  Must be given q6 to q8 hours.  Cefuroxime Useful but not demonstrably better than ceftriaxone or cefotaxime.  Ampicillin IV More effective than penicillin G. Must be given q6 hours.  Ceftriaxone Risk of biliary sludging can be minimized with intermittent breaks in therapy (ie: infuse five or less days in a row per week).  Adults and pregnancy: 2g q12h, four days in a row each week.  Children: 75 mg/kg/day up to 2g/day  Cefotaxime Comparable efficacy to ceftriaxone; no biliary complications.  Adults and pregnancy: 2g q8h; may dose as high as 12g daily. Suggest a continuous infusion.  Children: 90 to 180 mg/kg/day dosed q6h (preferred) or q8h, not to exceed 12 g daily.  *Doxycycline Requires central line as is caustic. Surprisingly effective, probably because higher overall, and spiked blood levels when given parenterally.  Always measure blood levels.  Adults: 400 mg q24h and adjust based on levels.  Cannot be used in pregnancy or in younger children.  Azithromycin Requires central line as is caustic.  Dose: 500 to 1000 mg daily in adolescents and adults.  Penicillin G IV penicillin G is minimally effective and not recommended.  Benzathine penicillin Surprisingly effective IM alternative to oral therapy.  May need to begin at lower doses as strong, prolonged (6 or more week) Herxheimer-like reactions have been observed.  Adults: 1.2 million U three times per week (higher doses with large body habitus)  Adolescents: 300,000 to 2.4 million U weekly.  May be used in pregnancy.  Poorly studied but anecdotally effective  Vancomycin Observed to be one of the best drugs in treating Lyme, but potential toxicity limits its use. It is a perfect candidate for pulse therapy to minimize these concerns.  Use standard doses and confirm levels.  Imipenim and Unisyn Similar in efficacy to cefotaxime, but often works when cephalosporins have failed.  Must be given q6 to q8 hours.  Cefuroxime Useful but not demonstrably better than ceftriaxone or cefotaxime.  Ampicillin IV More effective than penicillin G. Must be given q6 hours. 

22. IDSA treatment of late Lyme disease arthritis
Doxycycline 100mg bid
Amoxicillin 500mg tid
Cefuroxime 500mg bid
Treat for 28 days
If persistent or recurrent joint swelling retreat with another 28 days of above antibiotics or 2-4 weeks of IV ceftriaxone
Then supportive therapy B-3

23. IDSA late neurologic Lyme disease
This includes encephalopathy's and radiculopathies, Bannwarth syndrome
Treat with ceftriaxone 2 gm qd for 2-4 weeks
“Response to treatment is usually slow and may be incomplete”
“Re-treatment is not recommended unless relapse is shown by reliable objective measures”

24. IDSA Post Lyme disease syndrome proposed definition
Onset of the following symptoms within 6 months of a documented case of Lyme that has been treated by IDSA guidelines
Fatigue
Widespread musculoskeletal pain
Complaints of cognitive difficulties
Exclusion of any diagnosable disease

25. Why antibiotic treatments don’t work
three forms of lyme (spirochete, L-form, cyst)
biofilm
tissue sequestration
patient’s intolerance to treatment: toxicity, gastritis, mycosis, mitochondrial fatigue
co-infections
evolution of bacteria, i.e. resistance
targeted vs comprehensive treatment strategy 25

26. Why treatments don’t work
Immune evasion
Using proteins that look like ours (ID badges), avoid recognition and therefore destruction by complement pathway.
Mutate surface proteins. Encysting.
Using proteins that look like ours (feeding misinformation), activate the immune system non-productively

27. Immune Evasion Modulation of it’s surface antigens, OspA and OspC
Evades complement pathway: OspC, CD59-like complement inhibiting protein
OspA potent neutrophil stimulator and inducer of IL-1b, TNF-a, and IL-6
Induces IL-10 initially to downregulate immune response
Delayed conversion of IgM to IgG

28. Comprehensive Support
anti-inflammatory: diet, herbs, proteolytic enzymes
lymphatics: walking, skin brushing, massage
gastro-intestinal: probiotics, regularity
liver support: phase I and II
brain/nerves: B12, herbals
methylation, glutathione
emotional/spiritual