COMPREHENSIVE LYME DISEASE OVERVIEW: GOOD BULLET POINTS

                          Lyme rashes can present in many different shapes, sizes and colors. See side bar for more rash pictures. The following summary from http://www.holtorfmed.com/lyme-disease.html  is a good overview of Lyme disease, its coinfections, the spirochete's characteristics , and how to test and treat. It is a bullet point presentation and may be good to print out and take to your doctor if he is not an expert in Lyme disease. Doctors have not been properly educated when it comes to Lyme disease and its coinfections. One word of advice from someone who has "been there". If you do bring Lyme info to your doc , try to be very tactful and know your stuff before you go. For some reason Lyme disease is a very touchy subject and doctors often react very oddly when confronted with a patient who thinks he may have Lyme disease. Testing is not accurate so diagnosis must be made based on patient history and symptoms.

(A Culmination of the Literature) Kent Holtorf, M.D.


CHARACTERISTICS of BORRELIA BURGDORFERI

Over 1500 gene sequences
At least 132 functioning genes (in contrast, T. pallidum has 22 functioning genes)
21 plasmids (three times more than any known bacteria)

IMMUNE EVASION (‘STEALTH’ PATHOLOGY)
Immune suppression
Phase & antigenic Variation
Physical seclusion
Secreted factors

TYPES OF LYME DISEASE
Early Lyme Disease (“Stage I”)
At or before the onset of symptoms
Can be cured if treated properly

Disseminated Lyme (“Stage II”)
Multiple major body systems affected
More difficult to treat

Chronic Lyme Disease (“Stage III”)
Ill for one or more years
Serologic tests less reliable (seronegative)
Treatment must be more aggressive and of longer duration

CHRONIC LYME
Disease changes character
Involves immune suppression
Less likely to be sero-positive for Lyme
Development of alternate forms of Borrelia
More likely to be co-infected
Immune suppression and evasion
More difficult to treat
Protective niches

ALTERNATE MORPHOLOGIC FORMS
Spirochete form- has a cell wall
L-form (spiroplast)- no cell wall
Cystic form

IMMUNE SUPPRESSION BY Borrelia burgdorferi
Bb demonstrated to invade, inhibit and kill cells of the immune system
The longer the infection is present, the greater the effect
The more spirochetes that are present, the greater the effect

PROTECTIVE NICHES
Within cells
Within ligaments and tendons
Central nervous system
Eye

DIAGNOSING LYME
It is a clinical diagnosis supported by appropriate testing (likelihood of a false negative must be understood)
Look for multi-system involvement
17% recall a bite; 36% recall a rash
55% with chronic Lyme are sero-negative
PCRs- 30% sensitivity at best- requires multiple samples, multiple sources

NATURAL KILLER CELL ACTIVITY AND NUMBER
Low counts seen in active Lyme
Reflects degree of infection
Can be used as a screening test
Can be used to track treatment response
Can predict relapse

ELISA ANTIBODY TESTING
Over 75% of patients with chronic Lyme are negative by ELISA

WESTERN BLOT
Reflects antibody response to specific Bb antigens
Different sensitivities and specificities of the bands
Some bands are potentially seen in different bacteria- “nonspecific bands”
Some bands are specific to spirochetes
Some bands are specific to Bb
Specific: 18, 23-25, 28, 31, 34, 37, 39, 58, 83 & 93
Spirochetes in general: 41 (flagellum)
First immune response if present is usually 41 and 23 KD bands
Response to the 31 KD proteins is not usually seen for a year after initial infection

CDC IGG WB CRITERIA
IGG WB 5 of the 10 bands (18, 23, 28, 30, 39, 41, 45, 58, 66)
Criteria based on Early Lyme
IGENEX adds 3 specific bands (31, 83 and 34) and 3 non-specific bands (22, 37, 73)

CDC IGM WB CRITERIA
IGM WB 2 of the 3 bands 23, 39, 41
IGENEX adds 3 specific bands (31, 34 and 83) and 3 non-specific bands (22, 37, 73)

REVISED CRITERIA WITH QUEST WB
IGG WB: 2 specific band criteria have demonstrated improved sensitivity and maintained specificity

Can diagnose Lyme if any one band (IgG or IgM) of 18, 23, 28, 39 or 58 kDa or if any 2 or more of the following bands are present: 30, 45, 41 and 93

If negative or require further confirmation, can obtain IGENEX WB (adds specific bands of 31, 34 an 83, which are typically seen in chronic disease)

Positive if any one band of 18, 23, 28, 31, 34, 39, 58 or 83

If positive for Borellia on any test, test for neurotoxins.

Consider testing for co-infections (discussed below)

Check for coagulation defect

LYME DISEASE TREATMENT
Use an integrative treatment for optimal results. Treating with just antibiotics has poor likelihood for success with chronic Lyme.

Extended duration often needed for chronic lyme.

Use clinical endpoints.

Watch for Herxheimer reactions (may occur in 3-4 week cycles)

Directed neutraceutical can be beneficial

Immune Modulators

Antibiotics

Oral

Intramuscular

Intravenous

Often need antibiotic combinations with lysomotropics in addition to integrative approach to address different forms (spirochete, L-form, cystic)

Intravenous Antimicrobial IV’s (Viral Plus, etc) or IV Immunoglobulin

Adjunctive medications (Lysosomotropics) to increase antibiotic effectiveness

NUTRACEUTICAL
Samento or improved version Keline

Cumanda improved version Eklipse

Consider combination of Eklipse, artemesinin I and Keline as a basis

Fibrinolytic enzymes and heparin if coagulation defect present (present in approximatley 80% of cases)

Give probiotics and natural antifungals when using prolonged antibiotics

IMMUNMODULATION
Essential to improve immune function

Leukostim

Proboost

Maitaki Mushroom

Transfer Factor-Lyme specific

Low Dose Naltrexone 3.5 mg qhs

Delta-Immune

Neupogen (filgrastim) (Enhanced eradication of Bb demonstrated in mice) 5 mcg/kg SQ

Benicar (Marshal Protocol)

ORAL ANTIBIOTICS
Tetracyclines-Doxycycline, Minocycline 100 mg II tabs bid or Tetracycline 500 mg II tabs tid-qid

Good Tissue penetration

Covers Borrelia and Ehrlichia

Anti-inflamatory properties

Photosensitivity, GI upset frequent

Penicillins such as Augmentin 875 mg PO bid-tid or Amoxicillin 875 II tabs bid-tid

Monitor LFT’s with Augmenti

Addition of Probenecid 500 mg/qd-tid

Cannot exceed 3 tabs Augmentin per day due to clavulanate, thus can give with Amoxicillin

Macrolides such as Zithromax 500-600 mg, Biaxin 1000-2000 mg/day or Ketek 800 mg/da

Combination therapy often needed (ie plus cephalosporin or Flagyl)

Well tolerated

Improved tissue penetration with hydroxycholoroquine or amantadine

Cephlosporins (3rd generation) Omnicef 300 mg one po tid or (2nd generation) Ceftin 500 mg II tabs bid

Flagyl 250-500 qd-tid or tinidizole (better tolerated) 500 mg bid for 2 weeks every 1-3 months

Kills spore forms of Borrelia

May decrease effect of tetracyclines

Antabuse reaction with alcohol

Potentially neurotoxic

Adults only

Rifampin 300 mg bid

IM ANTIBIOTICS
Benzathine Pennicillin 1.2-2.4 Million Units 1-2 times per week

Excellent foundation for combination treatment

No GI Side effects

Efficacy may be close to IV

IV ANTIBIOTICS
Consider if illness for greater than year

Failure or intolerance of oral therapy

Consider starting with IV antibiotics for 1- 3 months (until clearly improved) then oral/IM maintenance

May require extended duration with long term disease and immune supression

Ceftriaxone (Rocephin) most commonly used (dose 2 grams qd 4 x/week)

Risk of billiary slugging-use Actigall

Monitor LFT’s

Cefotaxime (Claforan)

Requires twice daily dosing 2 grams bid. Can give as continuous infusion of up to 8 grams/day

Monitor LFT’s

Doxycycline 400 mg qd (slow infusion)

Requires central line

Do not use in pregnancy or children

Azithromycin 500 mg qd

Requires central line

Limited experience

Unasyn (ampicillin-sulbactum) 3 grams IV tid

Timentim (4th generation penicillin and clavulanate) 3.1 grams IV q 6 hours

Primaxin 500-1000 mg IV bid-tid

CO-INFECTIONS IN LYME
Very common and nearly universal in chronic Lyme

Diagnostic tests even less reliable

Co-infected patients more ill

Co-infected patients more difficult to treat

POSSILBE CO-INFECTIONS
Babesia

Bartonella


Ehrlichia


Mycoplasma


Viruses such as EBV, CMV, HHV6, HHV7


Others

TESTING
Antibody testing has a high rate of false-negative

Consider treatment if poor response despite negative test results

BABESIA
Is a parasite (one study showed 66% of chronic Lyme have Babesia co-infection)

Many different species found in ticks (13+)

Not able to test for all varieties

Diagnostic tests insensitive

Chronic persistent infection documented

Infection is immunosuppressive

TREATING BABESIOSIS
Can be treated while on Lyme medications

Lariam 250 mg (5 caps loading dose) then 1 po week for 5 weeks with Artemisinin

Atovaquone (Mepron) 750 mg qd-bid plus azithromycin 500-600 mg for 4 to 6 months

Consider Flagyl or tinidiazole

Artemesinin demonstrated to be beneficial (2-3 tabs bid)

BARTONELLA                                                                                      BARTONELLA RASH
More ticks in NE contain Bartonella than contain Lyme

                                                                                 

Clinically seems to be a different species than “cat scratch disease”

Gastritis and rashes, CNS, seizures, tender skin nodules and sore soles

Tests are insensitive

TREATING BARTONELLA
Levaquin 750 mg qd

Cipro 750 bid

Doxy 100 mg II po bid

Zithromax 500-600 mg qd

EHRLICHIA
Flu-like symptoms of severe headaches, very painful muscles, low WBC counts or elevated liver enzymes

Testing insensitive

TREATMENT OF EHRLICHIA
Doxy 200 mg bid

Rifampin 300 mg bid

ADJUNCTIAL MEDICATIONS TO INCREASE ANTIBIOTIC EFFECTIVNESS
(Lysosomotropics) Will increase the effectiveness of antibiotics and improve success

Porbenecid 500 mg qd-tid. Decreases B-lactam excretion and used to achieve higher serum levels.

Will also decrease excretion on NSAIDS, benzodiazepines and other medications

Hydoxychloroquine (200 mg qd-bid)-decreases formation of cystic forms and increases penetration of antibiotics into cysts

Amantadine 100 mg qd-tid. Increases penetration into cells and cysts, immune boosting and is antiviral

For a recommended list of books on Lyme disease go to
http://astore.amazon.com/thelymdissenb-20?_encoding=UTF8&node=2