Re-posting for more people to see. You can find his papers on the web with a google search or on lyme sites. Especially important is his Diagnostic Hints and Treatment Guidelines for Lyme and Other Tick Borne Illnesses. ;-} Dr. Burrascano is considered the foremost doctor in U.S. on Lyme and has been treating Lyme patients for 30 years. TREATING CHRONIC LYME DISEASE J. J. Burrascano, MD April 24, 2004 Board Member of International Lyme and Associated Diseases Society East End Medical Associates, P.C. East Hampton, New York 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 - Treatment must be more aggressive and of longer duration DEFINITION OF CHRONIC LYME . Ill for more than one year, regardless of whether treatment has been given . Disease changes character . Involves immune suppression . Less likely to be sero-positive for Lyme . More likely to be co-infected . More difficult to treat CHRONIC LYME DISEASE Why are patients more ill? . Higher spirochete Load . Development of alternate forms . Immune suppression and evasion . Protective niches . Co-infections SPIROCHETE LOAD . Low Spirochete Load- - Inapparent infection . Increased Spirochete Load- - Symptoms - Seropositive ALTERNATE MORPHOLOGIC FORMS . Spirochete form- has a cell wall - Penicillins, cephalosporins, Primaxin, Vanco . L-form (spiroplast)- no cell wall - Tetracyclines, Erythromycins . Cyst? - Flagyl (metronidazole), tinidazole - Rifampin IMMUNE SUPPRESSION BY Borrelia burgdorferi . Bb demonstrated to invade and kill cells of the immune system . Bb demonstrated to inhibit those immune cells not killed . 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 . Is a clinical diagnosis- look for multisystem involvement . 17% recall a bite; 36% recall a rash . 55% with chronic Lyme are sero-negative . Spinal tap- Only 7% have + CSF antibodies! . ELISAs are of little value- do Western Blots . PCRs- 30 % sensitivity at best- requires multiple samples, multiple sources CD-57 COUNT (Natural Killer Cells) . Low counts seen in active Lyme . Reflects degree of infection . Can be a screening test . Can be used to track treatment response . Can predict relapse . Commercially available and covered by insurance! WESTERN BLOT IN LYME . Reflects antibody response to specific Bb antigens- they are reported as numbers called "bands" . Some bands are seen in many different bacteria- "nonspecific bands" . Some bands are specific to spirochetes . Some bands are specific to Bb . Positive blot contains bands specific for Lyme . Specific: 18, 21-24, 31, 34, 37, 39, 83 & 93 . Spirochetes in general: 41 . Nonspecific: All others! . The more specific bands that are present, the more sure the diagnosis NOW THE BAD NEWS! PITFALLS OF THE WESTERN BLOT . Very difficult to produce and interpret a western blot . Bands do not easily line up . Appearance affected by subtle changes in temperature and chemistry of the test system . The specific strain of Bb used to produce the antigens may not match the strain the patient has! HOW DO YOU MAKE THE DIAGNOSIS? . Lyme is a clinical diagnosis . Even the best Lyme tests are only an adjunct . Use the ILADS point system POINT SYSTEM . Tick exposure in an endemic region 1 . History consistent with Lyme 2 . Systemic signs & symptoms consistent with Bb infection (other potential diagnoses excluded): . Single system, e.g., monoarthritis 1 . Two or more systems 2 . Erythema migrans, physician confirmed 7 . ACA, biopsy confirmed 7 . Seropositivity 3 . Seroconversion on paired sera 4 . Tissue microscopy, silver stain 3 . Tissue microscopy, monoclonal IFA 4 . Culture positivity 4 . B. burgdorferi antigen recovery 4 . B. burgdorferi DNA/RNA recovery 4 POINT SYSTEM DIAGNOSIS . Lyme Borreliosis Highly Likely - 7 or above . Lyme Borreliosis Possible - 5-6 . Lyme Borreliosis Unlikely - 4 or below LYME DISEASE TREATMENT ESSENTIALS . Pharmacology . Appropriate route of administration . Appropriate duration of therapy . Supportive measures . Search for co-infections LYME DISEASE TREATMENT Pharmacology . Kinetics of killing B. burgdorferi - Pulse therapy; cell wall agents vs. doxycycline . Critical to achieve therapeutic drug levels . Tissue penetration of the antibiotic . Intracellular site of action . Alternate forms of B. burgdorferi - Cell wall agents vs. other mechanisms . Antibiotic combinations ROUTE OF ADMINISTRATION Repeated Antibiotic Treatment in Chronic Lyme Disease (Fallon, JSTBD, 1999) . No response to placebo . Slight benefit from oral antibiotics . Intramuscular benzathine penicillin more effective than oral antibiotics . Intravenous therapy most effective INDICATIONS FOR INTRAVENOUS THERAPY . Abnormal spinal fluid (WBC, Protein) . Synovitis with high ESR . Illness for more than one year . Age over 60 . Prior use of steroids . Failure or intolerance of oral therapy ANTIBIOTIC CHOICES: Oral antibiotics . Amoxicillin + probenecid, Augmentin XR . Doxycycline, minocycline and tetracycline . Cefuroxime (Ceftin) . Clarithromycin (Biaxin) . Azithromycin . Metronidazole (Flagyl) . Rifampin INTRAVENOUS THERAPY . Ceftriaxone (Rocephin) still used the most - Current recommendation: 2 grams twice a day, 4 days in a row each week . more effective . safer, and better lifestyle . can use peripheral IV line - May also prescribe Actigall to prevent gallstones (Bb in gallbladder!) INTRAVENOUS THERAPY Other Options . Cefotaxime (Claforan) . Doxycycline . Azithromycin (Zithromax) . Vancomycin . Imipenem (Primaxin) BICILLIN-LA . Injection of long acting penicillin- "Benzathine Penicillin" . Efficacy is close to that of IV's! . 1.2 million U- 3 or 4 doses per week . No GI side effects and minimal yeast . Excellent foundation for combination Rx . Given for 6 to 12 months TREATMENT DURATION . Early infection - Four to six weeks to bracket an entire B. burgdorferi generation cycle . Late Infection - Open ended therapy that must continue until signs of active infection have cleared - IV for 3 to 6+ months, then oral or IM maintenance therapy if tolerated and effective - May need to continue treatment for months to years KEY POINTS- I . In chronic Lyme Disease, infection may persist despite prior antibiotic therapy . Repeated or prolonged antibiotic therapy may be necessary- follow 4-week cycles . Illogical to follow serologies . PCR positivity and low CD-57 counts imply persisting, active infection . Search for co-infections (clinical diagnosis!) KEY POINTS- II . Treat co-infections . Do not use too low a dose . Target all morphologic forms of Borrelia . Appropriate route of administration . Appropriate duration of therapy . Supportive measures CO-INFECTIONS IN LYME . Nearly universal in chronic Lyme . Symptoms more vague, and overlap . Diagnostic tests LESS reliable . Co-infected patients more ill . Co-infected patients more difficult to treat CO-INFECTIONS IN LYME . Bartonella . Babesia . Ehrlichia . Mycoplasma . Viruses . ?Others CO-INFECTIONS IN LYME WHAT IS THE MOST COMMON TICKBORNE INFECTION IN THE NORTHEAST? Bartonella . 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! (serologies and PCR) . Levofloxacin (Levaquin) is drug of choiceconsider adding proton pump inhibitor PIROPLASMS (Babesia species) . Many different species found in ticks (13+) . Not able to test for all varieties . WA-1 more difficult to treat than B. microti . Diagnostic tests insensitive . Chronic persistent infection documented . Infection is immunosuppressive Babesia Testing . PCR and Serology . Fluorescent In-situ Hybridization Assay - Fluorescent-linked RNA probe - Increases sensitivity 100-fold over conventional Giemsa-stained smears . Enhanced smears- - Buffy coat - Prolonged scanning - Digital photography BABESIA SMEAR Conventional blood smear Fluorescent In-situ Hybridization Assay Babesia FISH Treating Babesiosis . Is a parasite, so is not treated with antibiotics . Can be treated while on Lyme medications . Clindamycin + quinine rarely used . Atovaquone (Mepron) plus azithromycin for 4 to 6 months . Malarone . Added sulfur . Added metronidazole (Flagyl) . Artemesia Ehrlichia . Can cause acute and chronic presentations . Acute- sudden high fever, severe headaches, very painful muscles, low WBC counts, elevated liver enzymes . Chronic- same, but not as severe . Test with serology, PCR or smear . Treat with doxycycline or rifampin 40 J. J. Burrascano, MD April 24, 2004 Mycoplasma . "Chronic fatigue" germ . Not clear its origin or source . More often seen in the immunosuppressed . Test with PCR . Treat with doxycycline and add fluoroquinolone . Erythromycins & rifampin, with added hydroxychloroquine OK but less effective Other Co-infections . Especially in the immunosuppressed . Chlamydiae . Viruses - HHV-6, CMV, other herpes . Yeasts . Others DANGEROUS MIX! . Co-infections missed in Lyme patients . Co-infected patients more ill . Babesiosis and Ehrlichiosis can be fatal! . Lyme treatments do not treat Babesia or Bartonella . One reason for "treatment-resistant" Lyme . "Silent infections" may be transmitted by transfusions ASSOCIATED CONDITIONS Neurally Mediated Hypotension . Dehydration, autonomic neuropathy, pituitary insufficiency . Paradoxical response to adrenaline - profound fatigue - adrenaline rushes and palpitations - unavoidable need to lie down . Diagnose with tilt table test performed by a cardiologist, and pituitary function tests ASSOCIATED CONDITIONS Hormonal Dysfunction . Significant disturbance of the hypothalamic-pituitary axis . Extremely difficult to diagnose . When corrected, are tremendous benefits! . A major key to the debility in chronic Lyme ASSOCIATED CONDITIONS Hormonal Dysfunction . Chronic lack of stamina . Loss of libido . Intolerance of stress including Herxheimers! . Unexplained weight gain . Hypersensitivity to the environment . Persistent encephalopathy despite Lyme treatment ASSOCIATED CONDITIONS Borrelia Neurotoxin . Effects - Neurologic dysfunction - Cytokine activation - Hormone receptor blockade . Testing for neurotoxin: - Visual contrast sensitivity test - Measure cytokine levels - Test for insulin resistance . Treat with bile acid sequestrants ASSOCIATED CONDITIONS Cerebral Vasculitis . Contributes to encephalopathy . Vascular headaches . Seen on SPECT brain scans SPECT BRAIN SCANS . Reflects blood flow and health of the nerve cells . Pre and post-Diamox scans . Proves the symptoms are real! . Useful in differentiating Lyme Disease from a psychogenic illness . Can be done serially to reflect clinical changes SUPPORTIVE THERAPY . NUTRITIONAL SUPPORT - Blend of multivitamins, B-complex, CoEnzyme Q-10, and magnesium - Essential fatty acids - Low glycemic index, high fiber diet - Absolutely no alcohol . MANAGE YEAST OVERGROWTH - Oral hygiene, acidophilus/yogurt - Low carbohydrate diet METHYLCOBALAMIN . Prescription drug derived from vitamin B12 - Aids in healing the central and peripheral nervous system - Documented benefit in strength, energy and cognition - Helps restore normal day-night cycle - Improves T-cell immune responsiveness . Must be injected daily for 3 to 6 months . Available only as a "compounded drug" . Excellent safety profile . ENFORCED REST; NO CAFFEINE - Must try to prevent afternoon energy sags - Proper sleep is essential . REHAB AND EXERCISE PROGRAM - Required for a full recovery - Intermittent program one to three days per week - Toning, stretching, posture, balance - Aerobics are not allowed until nearly fully recovered ALTERNATIVE THERAPIES THREE CATEGORIES: . Known to be helpful . Possibly helpful . No proven benefit ALTERNATIVE THERAPIES: KNOWN TO BE HELPFUL . Vitamins - Multi + Co-Q 10 + B complex + EFAs + Mg . Hyperbaric oxygen therapy - Monochamber preferred; three 30-day dives, one month apart . Eastern medicinals . Exercise program ALTERNATIVE THERAPIES: POSSIBLY HELPFUL . Immune modulation - Reishi spore extract, transfer factor - IVIG only if deficient . Vitamin C . Acupuncture ALTERNATIVE THERAPIES: NO PROVEN BENEFIT . Colloidal silver . Heat therapy - Sauna, infrared, hot tubs . Rife machines YOUR DUTY AS A LYME PATIENT . Political awareness and activity - Join support groups and be pro-active - Be willing to participate in events - Support the major Lyme organizations- ILADS, LDA, LDF . Fundraising!!! . Aggressively spread the truth especially to the media . Never give up, and never go away until our goals are met!