Guest guest Posted May 17, 2000 Report Share Posted May 17, 2000 Dear Group: In my attempts to pursue " correct " treatment, I may be getting a bit neurotic. Each time I add/delete medication, is it best to try to cycle it in before, during or after a scheduled Herxheimer? I have had very timely Herxheimers with the Babesia treatment of Mepron and Zithromax (less duration and severity, a perfect straight line decline). My concern would be that I do not want to be creating multiple 28 day cycles. Is there a recommended way to manage the introduction of new meds? Thank you. Sincerely, Annie Note: I've included part of this to print -- much more is on the web site. Bonnie H. Click Here: <A HREF= " http://dwp.bigplanet.com/eojlyme/data/folders/Lyme%20Treatment%20Guideli nes/Lyme%20Guidelines%20May%202000.htm " >MANAGING LYME DISEASE</A> http://dwp.bigplanet.com/eojlyme/data/folders/Lyme%20Treatment%20Guidelines/Ly me%20Guidelines%20May%202000.htm ADVANCED TOPICS IN LYME DISEASE DIAGNOSTIC HINTS AND TREATMENT GUIDELINES FOR LYME AND OTHER TICK BORNE ILLNESSES JOSEPH J. BURRASCANO JR., M.D. Thirteenth Edition Copyright May, 2000 TABLE OF CONTENTS INTRODUCTION 3 BACKGROUND INFORMATION 4 DIAGNOSTIC HINTS PIROPLASMOSIS (Babesiosis) 5 EHRLICHIOSIS 5 LYME BORRELIOSIS ERYTHEMA MIGRANS 5 DIAGNOSING LATE DISEASE 6 DIAGNOSTIC CRITERIA 7 SYMPTOM CHECKLIST 8 LYME DISEASE TREATMENT GUIDELINES PIROPLASMOSIS (Babesiosis). 9 EHRLICHIOSIS. 9 LYME BORRELIOSIS 9 GENERAL INFORMATION 9 COURSE DURING THERAPY 10 TREATMENT INFORMATION 11 ANTIBIOTICS 11 MONITORING OF THERAPY 12 ANTIBIOTIC CHOICES 12 TREATMENT CATEGORIES PROPHYLAXIS 13 FOR KNOWN TICK BITES 13 EARLY LOCALIZED DISEASE 13 DISSEMINATED DISEASE 13 1. early 13 2. late 14 ALTERNATE SCHEDULING OF ANTIBIOTIC TREATMENTS 14 ADVANCED TOPICS 14 1. Cystic form 14 2. Borrelia Neurotoxin 15 REFRACTORY DISEASE 15 1. responsive to antibiotic therapy 15 2. non-responsive to antibiotic therapy 16 ADJUNCTIVE THERAPY 16 SAFETY 16 NUTRITIONAL SUPPLEMENTS IN CHRONIC LYME DISEASE 17 LYME DISEASE REHABILITATION 18 REHAB THERAPY PRESCRIPTION 19 MANAGING YEAST INFECTIONS 20 PATIENT INSTRUCTIONS ON TICK BITE PREVENTION AND TICK REMOVAL 21 APPENDIX Rationale for treating tick bites 22 Rationale for treatment recommendations 23 SUGGESTED READING 25 INTRODUCTION The pace of new discoveries in Lyme has accelerated, with many important clinical implications. I will attempt to familiarize you with the latest information. Because this is a rapidly evolving field, keep up your efforts at continuing education and communication with other experienced clinicians. This is an exciting time indeed! Much new information is included in this edition of the Guidelines, including new sections. Nearly every page has been revised. To me, " Lyme Disease " is not simply an infection with Borrelia burgdorferi, but a complex illness potentially consisting of multiple tick-derived co-infections. In later stages, it also includes collateral conditions that result from being ill with multiple pathogens, each of which can have profound impact on the person's overall health. Together, damage to virtually all bodily systems can result. In addition, it is possible to see latent infections reactivate, especially viruses of the Herpes type. We also have new information that B. burgdorferi exists in at least three different forms: bacterial (the well known, cell wall-containing spirochete), spheroplast or l-form, and the newly discovered cystic form. The importance is that only the spirochete form can be killed by beta lactam antibiotics. Spheroplasts seem to be susceptible to tetracyclines and erythromycins, yet the cyst so far has been proven to be susceptible only to metronidzole. It is clear that in the great majority of patients, chronic Lyme is a disease affecting predominantly the nervous system. Thus the value of careful evaluation that often includes neuropsychiatric testing, SPECT and MRI brain scans, CSF analysis when appropriate, regular input from Lyme-aware neurologists, pain clinics, and occasionally specialists in psychopharmacology. Two different researchers have provided recent evidence that B. burgdorferi, like many other pathogenic bacteria, can produce neurotoxins. Early clinical trials aimed at removing these toxins have proven quite promising! I will discuss this in more detail in a later section. More evidence has accumulated indicating the severe detrimental effects of immunosuppressants including steroids in the patient with active B. burgdorferi infection. Never give steroids to any patient who may even remotely be suffering from Lyme, or serious, permanent damage may result, especially if given for anything greater than a short course. The concept of a " therapeutic alliance " between the caregiver and patient must again be emphasized. This means that the patient has to work with and become part of the medical team, and must take responsibility for complying with the recommendations given, maintaining the best possible health status, reporting promptly any problems or new symptoms, and especially in realizing that despite all our best efforts, success in diagnosis and treatment is never assured. The medical team must make great efforts to listen carefully to the patient and not be too quick to dismiss seemingly bizarre or illogical complaints. I once again extend my best wishes to the many patients and caregivers who deal with Lyme, and a sincere thank you to my colleagues whose endless contributions have helped me shape my approach to tick borne illnesses. I hope that my new edition proves to be useful. Happy reading! BACKGROUND INFORMATION CO-INFECTION A huge body of research and clinical experience has demonstrated the nearly universal phenomenon in Lyme patients of co-infection with multiple tick-borne pathogens. As many have heard me say, coinfection is not surprising, for ticks are arachnids that literally live in dirt and drink the blood of wild animals. To think that a significant tick bite transmits only one infection is narrow minded indeed. Studies have shown that concurrent Borrelial and Ehrlichial and/or Babesial infections result in a change in their individual clinical presentations, with different symptoms, atypical signs, decreased reliability of standard diagnostic tests, and most importantly, the creation of chronic, persistent forms of each of these infections. As time goes by, I am convinced that more pathogens will be found. Therefore, Lyme, as we had come to know it, probably represents a mixed infection. I will leave to the reader the implications of how this may explain the discrepancy between laboratory study of pure Borrelia infections, and what front line physicians have been seeing for years in real patients. The evaluation of a Lyme patient must begin with testing for all currently known tick borne pathogens. Serological studies for Borrelia, Babesia and Ehrlichia should be combined where appropriate with direct antigen assays. Antigen detection tests (antigen capture and PCR) are especially helpful in evaluating the seronegative patient and those still ill or relapsing after therapy. Unfortunately, over a dozen protozoans other than Babesia microti can be found in ticks, yet commercial tests for only B. microti are available at this time, so as in Borrelia, clinical assessment is the primary diagnostic tool. In Ehrlichiosis, test for both the monocytic and granulocytic forms. Many presently uncharacterized Ehrlichia-like organisms can be found in ticks and may not be picked up by currently available assays, so in this illness too, serologies are only an adjunct in making the diagnosis. Babesia are parasites, and I suggest that if a coinfection is found involving this organism, treat this first, so that subsequent therapy for Borrelia and Ehrlichia will be more effective. GENERAL MEASURES Experience has shown that collateral conditions exist in those who have been ill a long time. Test B12 levels, and be prepared to aggressively treat with parenteral formulations of the B-vitamins: 100mg each of B1 and B6 and 1000 mcg of B12 IM at least weekly in the more ill patient. Magnesium deficiency is very often present and quite severe. Hyperreflexia, muscle twitches, myocardial irritability, and recurrent tight muscle spasms are clues to this deficiency. Magnesium is predominantly an intracellular ion, so blood level testing is of little value. Oral preparations are acceptable for maintenance, but most need additional, parenteral dosing: 1 gram IV or IM at least once a week until neuromuscular irritability has cleared. Activation of the inflammatory cascade has been implicated in blockade of cellular receptors. One example of this is insulin resistance, which may partly account for the dyslipidemia and weight gain that is noted in 80% of chronic Lyme patients. Clinical hypothyroidism can result from receptor blockade and thus hypothyroidism can exist despite normal serum hormone levels. Also, because the Lyme syndrome has been associated with faulty activation of T4, measure free T3 levels by RIA, and basal A.M. body temperatures. If hypothyroidism is found, you will need to treat with T3 preparations. SPECT scanning of the brain, if done by knowledgeable radiologists using high-resolution equipment, will show characteristic abnormalities in Lyme encephalopathy. This not only helps with the differential diagnosis, but if done before and after acetazolamide, it will guide in the use of vasodilators, which may clear some cognitive symptoms. Therapy can also include serotonin agonists, pentoxiphylline and even Ginkgo biloba. Therapeutic trials may be needed. Tilt table testing is another powerful tool which, just as in CFIDS, may demonstrate neurally mediated hypotension (NMH). If NMH is present, treatment can dramatically lessen fatigue, palpitations and wooziness, and increase stamina. This test should be done by a cardiologist and include Isuprel challenge. This will demonstrate not only if NMH is present, but also the relative contributions of hypovolemia and sympathetic dysfunction. Therapy is based on blood volume expansion (increased sodium and fluid intake and possibly Florinef plus potassium). If not sufficient, beta blockade may be added based on response to the Isuprel challenge. DIAGNOSTIC HINTS Lyme is diagnosed clinically, as no currently available test, no matter the source or type, is definitive in ruling in or ruling out infection with these pathogens, or whether these infections are responsible for the patient's symptoms. The entire clinical picture must be taken into account, including a search for concurrent conditions and alternate diagnoses, and other reasons for some of the presenting complaints. Often, much of the diagnostic process in late, disseminated Lyme involves ruling out other illnesses and defining the extent of damage that might require separate evaluation and treatment. Consideration should be given to tick exposure, rashes (even atypical ones), evolution of typical symptoms in a previously asymptomatic individual, and results of tests for tick borne pathogens. Another very important factor is response to treatment- presence or absence of Jarisch Herxheimer-like reactions, the classic four week cycle of waxing and waning of symptoms, and improvement with therapy. PIROPLASMOSIS (Babesiosis) Classic teachings state that acute infections are usually only seen in those with some form of immune compromise. Flu-like symptoms rapidly evolve to include shaking chills, high fevers, hemolysis and pancytopenia. Fatalities have been reported. Visualizing Babesial forms on peripheral smears can make the diagnosis in this situation. In those with intact immune systems, a mild flu-like illness appears one to two weeks after exposure and clears without treatment over six to eight weeks. In either case, it is imperative to also test for Borrelia and Ehrlichia. However, when coinfection exists, this acute presentation is much less common, and it is rare to see parasite forms on smear. Suggestions of coinfection include severe headaches, dyspnea, dry cough, dizziness, and encephalopathy out of proportion to the other Borrelial symptoms. Testing is not at all definitive, yet should include CBC, Babesia smear (very low yield), serologies (IgG and IgM) and if necessary, PCR of peripheral blood. Newer direct assays are currently being researched, as this is an active area of investigation. Always consider coinfection in your current Lyme patients who are not responding fully and be prepared to treat cased on clinical presentation even with negative tests. EHRLICHIOSIS While it is true that this illness can have a fulminant presentation, I am convinced that milder forms do exist especially when other tick-borne organisms were transmitted. When present in a Lyme patient, persistent leucopenia is an important clue. Thrombocytopenia is much less common, but likewise should not be ignored. Headaches, myalgias, and ongoing fatigue seem to relate to this illness, but are extremely difficult to separate from symptoms caused by Bb. At this time, we have to rely on serologies for laboratory diagnosis, as currently available PCR assays are of unknown sensitivity and specificity, and direct visualization of leucocytes is of low yield. As there may be a variety of pathogenic Ehrlichia-like organisms that will not be picked up by current testing technology, clinical diagnosis remains the primary diagnostic tool. Again, consider this diagnosis in a Lyme Borreliosis (LB) patient not responding well to therapy. LYME BORRELIOSIS ERYTHEMA MIGRANS Erythema migrans (EM) is diagnostic of Bb infection, but is present in fewer than half. Even if present, it may go unnoticed by the patient. It is an erythematous, centrifugally expanding lesion that is raised and warm. Sometimes there is mild stinging or pruritus. The EM rash will begin four days to several weeks after the bite, and may be associated with constitutional symptoms. Multiple lesions are present less than 10% of the time, but do represent disseminated disease. Some lesions have an atypical appearance and skin biopsy specimens may be helpful. When an ulcerated or vesicular center is seen, this may represent a mixed infection, involving other organisms besides B. burgdorferi. After a tick bite, serologic tests (ELISA. IFA, western blots, etc.) are not expected to become positive until several weeks have passed. Therefore, if EM is present, treatment must begin immediately, and one should not wait for results of Borrelia tests. You should not miss the chance to treat early disease, for this is when the success rate is the highest. Indeed, many knowledgeable clinicians will not even order a Borrelia test in this circumstance. DIAGNOSING LATE DISEASE When reactive, serologies indicate exposure only and do not directly indicate whether the spirochete is now currently present. Because Bb serologies often give inconsistent results, test at more than one laboratory using if possible different methods. I recommend ordering IgM and IgG western blots. Be aware that in late disease there may be repeatedly peaking IgM's and therefore a reactive IgM may not differentiate early from late disease, but it does suggest an active infection. When late cases of LB are seronegative, 36% will transiently become seropositive at the completion of successful therapy. Western blots are reported by showing which bands are reactive. 41KD bands appear the earliest but can cross react with other spirochetes. The 18KD, 23-25KD (Osp C), 31KD (Osp A), 34KD (Osp , 37KD, 39KD, 83KD and the 93KD bands are the most specific but appear later or may not appear at all. You need to see at least the 41KD and one of the specific bands. 55KD, 60KD, 66KD, and 73KD are nonspecific and nondiagnostic. Antigen detection tests including PCR are now available, and although they are very specific, sensitivity remains poor, possibly less than 30%. This is because Bb causes a deep tissue infection and is only transiently found in body humors. Therefore, multiple specimens must be collected to increase yield; a negative result does not rule out infection, but a positive one is significant. The patient must be antibiotic free for at least six weeks before testing to obtain the highest yield. Antigen capture can be done on urine, CSF, and synovial fluid. PCR can be done on blood (buffy coat is best), urine, CSF, any other body fluid including breast milk, and on tissue biopsy specimens. I strongly urge you to biopsy all unexplained skin lesions/rashes and perform PCR and careful histology. You will need to alert the pathologist to look for spirochetes. Spinal taps are not routinely recommended, as a negative tap does not rule out Lyme. Antibodies to Bb can be detected in the CSF in just 20% of patients with late disease. Therefore, spinal taps are only performed on patients with pronounced neurological manifestations, if they are seronegative, or are still significantly symptomatic after completion of treatment. When done, the goal is to rule out other conditions, and to determine if Bb antigens are present. It is especially important to look for elevated protein and mononuclear cells, which would dictate the need for more aggressive therapy, as well as the opening pressure, which can be elevated and add to headaches, especially in children. DIAGNOSTIC CHECKLIST To aid the clinician, a workable set of diagnostic criteria were developed with the input of dozens of front line physicians. The resultant document has proven to be extremely useful not only to the clinician, but it also can help clarify the diagnosis for third party payers and utilization review committees. It is important to note that the CDC's published reporting criteria are for surveillance only, not for diagnosis LYME BORRELIOSIS DIAGNOSTIC CRITERIA RELATIVE VALUE Tick exposure in an endemic region 1 Historical facts and evolution of symptoms 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, e.g., monoarthritis and facial palsy 2 Erythema migrans, physician confirmed 7 Acrodermatitis Chronica Atrophicans, biopsy confirmed 7 Seropositivity 3 Seroconversion on paired sera 4 Tissue microscopy, silver stain 3 Tissue microscopy, monoclonal immunofluorescence 4 Culture positivity 4 B. burgdorferi antigen recovery 4 B. burgdorferi DNA/RNA recovery 4 DIAGNOSIS Lyme Borreliosis Highly Likely........ 7 or above Lyme Borreliosis Possible...... 5-6 Lyme Borreliosis Unlikely....... 4 or below I suggest that when using these criteria, you state Lyme Borreliosis is " unlikely " , " possible " , or " highly likely " based upon the following criteria " - then list the criteria. SYMPTOM CHECK LIST This is not meant to be used as a diagnostic scheme, but is provided to streamline the office interview. Note the format- complaints referable to specific organ systems are clustered to better display multisystem involvement. NAME_______________________________________DATE__________________ RISK PROFILE (PLEASE CHECK) Tick infested area__ Frequent outdoor activities__ Hiking__ Fishing__ Camping__ Gardening__ Hunting__ Ticks noted on pets__ Do you remember being bitten by a tick?............. No__ Yes__ when________ Do you remember having the " bull's eye rash " ? ..No__ Yes__ Any other rash?.................................................... No__ Yes__ Have you had any of the following? CIRCLE ALL YES ANSWERS 1.Unexplained fevers, sweats, chills, or flushing 2.Unexplained weight change- (loss or gain) 3.Fatigue, tiredness, poor stamina 4.Unexplained hair loss 5.Swollen glands: list areas_________________________________________ 6.Sore throat 7.Testicular pain/pelvic pain 8.Unexplained menstrual irregularity 9.Unexplained milk production; breast pain 10.Irritable bladder or bladder dysfunction 11.Sexual dysfunction or loss of libido 12.Upset stomach 13.Change in bowel function- (constipation, diarrhea) 14.Chest pain or rib soreness 15.Shortness of breath, cough 16.Heart palpitations, pulse skips, heart block 17.Any history of a heart murmur or valve prolapse? 18.Joint pain or swelling: list joints_________________________________________________ 19.Stiffness of the joints, neck, or back 20.Muscle pain or cramps 21.Twitching of the face or other muscles 22.Headache 23.Neck creaks and cracks, neck stiffness, neck pain 24.Tingling, numbness, burning or stabbing sensations, shooting pains 25.Facial paralysis (Bell's Palsy) 26.Eyes/Vision: double, blurry, increased floaters, light sensitivity 27.Ears/Hearing: buzzing, ringing, ear pain, sound sensitivity 28.Increased motion sickness, vertigo, poor balance 29.Lightheadedness, wooziness 30.Tremor 31.Confusion, difficulty in thinking 32.Difficulty with concentration, reading 33.Forgetfulness, poor short term memory 34.Disorientation: getting lost, going to wrong places 35.Difficulty with speech or writing; word block 36.Mood swings, irritability, depression 37.Disturbed sleep-too much, too little, fractionated, early awakening 38.Exaggerated symptoms or worse hangover from alcohol LYME DISEASE TREATMENT GUIDELINES PIROPLASMOSIS (BABESIOSIS) Piroplasms are not bacteria, they are protozoans. Therefore, they will not be eradicated by any of the currently used Lyme treatment regimens. Therein lies the significance of coinfections- if a Lyme patient has been extensively treated yet is still ill, suspect a piroplasm. Just as in Lyme Borreliosis, the longer one has been infected, the longer the course of therapy must be. Similarly, clinical assessment is the only guide to treatment endpoint. Treatment choices are limited. Pentamidine is a treatment given as daily IM shots- very painful, and they cause sterile abscesses and permanent fibrous scars on the buttocks. More importantly, response is poor, and the patient risks development of glucose intolerance. Clearly, not a first choice. Clindamycin, 600 mg qid plus Quinine, 650 mg qid has been the published standard but the suggested two week course is nearly impossible to tolerate (hearing loss, rash, fever, headache) and treatment failures have been reported. Gentamicin has been used in treating livestock infected with piroplasms. There are only anecdotal reports of efficacy in Humans, where a 14-day course at standard doses has proven effective in early disease. Experience with this antibiotic in late disease is limited, and the optimal regimen has not been well worked out. The main side effect is potential hearing loss from the gentamicin, and the need for IM or IV doses. Mepron (atovaquone), 750 mg bid, has demonstrated efficacy, but should be given concurrently with azithromycin, 250 to 600 mg daily, or resistance may develop. Efficacy is by far the best with this combination, but surprisingly, Herxheimer-like reactions are almost always seen at the fourth day, and at the fourth week of therapy. Does this represent a newly described phenomenon in treating Piroplasms, or does this combination have heretofore unrecognized efficacy in killing Bb? Although I do not have the answer, I suspect the latter simply based on the familiar (in Bb) four-week cycle. In late, longstanding cases, one month of treatment is the minimum, and four or more months are often needed. Problems during therapy include diarrhea, mild nausea, the expense of Mepron ($600.00 per bottle- enough for one month of treatment), and rarely, a temporary yellowish discoloration of the vision. Regular blood counts and liver panels are recommended during any prolonged course of therapy. Patients who are not cured with this regimen can be retreated but with higher doses, as this has proven effective in many of my patients. EHRLICHIOSIS Treatment recommendations at this time are still preliminary, mainly due to the lack of direct detection methods needed to guide us in developing a solid clinical feel. The mainstay of treatment is doxycycline, either orally or IV, given for at least two weeks for an early infection, or at least four weeks in a longstanding one. Interestingly, the unexpected efficacy of IV doxycycline in treating Lyme cases which had previously responded poorly to cell wall agents, may in fact reflect concurrent therapy of coinfection of Bb with Ehrlichial species. The new concern for Ehrlichia is the main reason that doxycycline is now the first choice in treating tick bites and early Lyme, before serologies can become positive. Quote Link to comment Share on other sites More sharing options...
Guest guest Posted May 17, 2000 Report Share Posted May 17, 2000 Dear Everyone: Quick background: I have Lyme, Babesiosis ( and Ehrlichiosis (E). Two other family members have blood positive Lyme. My B and E were only detected via a Bone Marrow Biopsy (BMB). I really pushed my loved ones to get a BMB, in spite of much resistance. Lo and behold, the results are positive for B. Even with daily Rocephin, treatment was not progressing as hoped or expected. It all makes sense now! It is my understanding that B has to be eradicated to make the Lyme treatment be successful. By the way, BMBs are not as painful as people claim, a few second and it is all over. Done by someone who has done several, makes a big difference. Please, if treatment for Lyme appears to be hampered, please go the last yard and rule out the co-infections. My family are now true believers. I suspected this for a while, yet couldn't get resolution for this concern. The good news is that the Lyme treatment was not a waste, but the process is just that much more challenging. I am mildly taken aback, but we're better off knowing than not! Sincerely, Annie Dear Group: In my attempts to pursue " correct " treatment, I may be getting a bit neurotic. Each time I add/delete medication, is it best to try to cycle it in before, during or after a scheduled Herxheimer? I have had very timely Herxheimers with the Babesia treatment of Mepron and Zithromax (less duration and severity, a perfect straight line decline). My concern would be that I do not want to be creating multiple 28 day cycles. Is there a recommended way to manage the introduction of new meds? Thank you. Sincerely, Annie Note: I've included part of this to print -- much more is on the web site. Bonnie H. Click Here: <A HREF= " http://dwp.bigplanet.com/eojlyme/data/folders/Lyme%20Treatment%20Guideli nes/Lyme%20Guidelines%20May%202000.htm " >MANAGING LYME DISEASE</A> http://dwp.bigplanet.com/eojlyme/data/folders/Lyme%20Treatment%20Guidelines/Ly me%20Guidelines%20May%202000.htm ADVANCED TOPICS IN LYME DISEASE DIAGNOSTIC HINTS AND TREATMENT GUIDELINES FOR LYME AND OTHER TICK BORNE ILLNESSES JOSEPH J. BURRASCANO JR., M.D. Thirteenth Edition Copyright May, 2000 TABLE OF CONTENTS INTRODUCTION 3 BACKGROUND INFORMATION 4 DIAGNOSTIC HINTS PIROPLASMOSIS (Babesiosis) 5 EHRLICHIOSIS 5 LYME BORRELIOSIS ERYTHEMA MIGRANS 5 DIAGNOSING LATE DISEASE 6 DIAGNOSTIC CRITERIA 7 SYMPTOM CHECKLIST 8 LYME DISEASE TREATMENT GUIDELINES PIROPLASMOSIS (Babesiosis). 9 EHRLICHIOSIS. 9 LYME BORRELIOSIS 9 GENERAL INFORMATION 9 COURSE DURING THERAPY 10 TREATMENT INFORMATION 11 ANTIBIOTICS 11 MONITORING OF THERAPY 12 ANTIBIOTIC CHOICES 12 TREATMENT CATEGORIES PROPHYLAXIS 13 FOR KNOWN TICK BITES 13 EARLY LOCALIZED DISEASE 13 DISSEMINATED DISEASE 13 1. early 13 2. late 14 ALTERNATE SCHEDULING OF ANTIBIOTIC TREATMENTS 14 ADVANCED TOPICS 14 1. Cystic form 14 2. Borrelia Neurotoxin 15 REFRACTORY DISEASE 15 1. responsive to antibiotic therapy 15 2. non-responsive to antibiotic therapy 16 ADJUNCTIVE THERAPY 16 SAFETY 16 NUTRITIONAL SUPPLEMENTS IN CHRONIC LYME DISEASE 17 LYME DISEASE REHABILITATION 18 REHAB THERAPY PRESCRIPTION 19 MANAGING YEAST INFECTIONS 20 PATIENT INSTRUCTIONS ON TICK BITE PREVENTION AND TICK REMOVAL 21 APPENDIX Rationale for treating tick bites 22 Rationale for treatment recommendations 23 SUGGESTED READING 25 INTRODUCTION The pace of new discoveries in Lyme has accelerated, with many important clinical implications. I will attempt to familiarize you with the latest information. Because this is a rapidly evolving field, keep up your efforts at continuing education and communication with other experienced clinicians. This is an exciting time indeed! Much new information is included in this edition of the Guidelines, including new sections. Nearly every page has been revised. To me, " Lyme Disease " is not simply an infection with Borrelia burgdorferi, but a complex illness potentially consisting of multiple tick-derived co-infections. In later stages, it also includes collateral conditions that result from being ill with multiple pathogens, each of which can have profound impact on the person's overall health. Together, damage to virtually all bodily systems can result. In addition, it is possible to see latent infections reactivate, especially viruses of the Herpes type. We also have new information that B. burgdorferi exists in at least three different forms: bacterial (the well known, cell wall-containing spirochete), spheroplast or l-form, and the newly discovered cystic form. The importance is that only the spirochete form can be killed by beta lactam antibiotics. Spheroplasts seem to be susceptible to tetracyclines and erythromycins, yet the cyst so far has been proven to be susceptible only to metronidzole. It is clear that in the great majority of patients, chronic Lyme is a disease affecting predominantly the nervous system. Thus the value of careful evaluation that often includes neuropsychiatric testing, SPECT and MRI brain scans, CSF analysis when appropriate, regular input from Lyme-aware neurologists, pain clinics, and occasionally specialists in psychopharmacology. Two different researchers have provided recent evidence that B. burgdorferi, like many other pathogenic bacteria, can produce neurotoxins. Early clinical trials aimed at removing these toxins have proven quite promising! I will discuss this in more detail in a later section. More evidence has accumulated indicating the severe detrimental effects of immunosuppressants including steroids in the patient with active B. burgdorferi infection. Never give steroids to any patient who may even remotely be suffering from Lyme, or serious, permanent damage may result, especially if given for anything greater than a short course. The concept of a " therapeutic alliance " between the caregiver and patient must again be emphasized. This means that the patient has to work with and become part of the medical team, and must take responsibility for complying with the recommendations given, maintaining the best possible health status, reporting promptly any problems or new symptoms, and especially in realizing that despite all our best efforts, success in diagnosis and treatment is never assured. The medical team must make great efforts to listen carefully to the patient and not be too quick to dismiss seemingly bizarre or illogical complaints. I once again extend my best wishes to the many patients and caregivers who deal with Lyme, and a sincere thank you to my colleagues whose endless contributions have helped me shape my approach to tick borne illnesses. I hope that my new edition proves to be useful. Happy reading! BACKGROUND INFORMATION CO-INFECTION A huge body of research and clinical experience has demonstrated the nearly universal phenomenon in Lyme patients of co-infection with multiple tick-borne pathogens. As many have heard me say, coinfection is not surprising, for ticks are arachnids that literally live in dirt and drink the blood of wild animals. To think that a significant tick bite transmits only one infection is narrow minded indeed. Studies have shown that concurrent Borrelial and Ehrlichial and/or Babesial infections result in a change in their individual clinical presentations, with different symptoms, atypical signs, decreased reliability of standard diagnostic tests, and most importantly, the creation of chronic, persistent forms of each of these infections. As time goes by, I am convinced that more pathogens will be found. Therefore, Lyme, as we had come to know it, probably represents a mixed infection. I will leave to the reader the implications of how this may explain the discrepancy between laboratory study of pure Borrelia infections, and what front line physicians have been seeing for years in real patients. The evaluation of a Lyme patient must begin with testing for all currently known tick borne pathogens. Serological studies for Borrelia, Babesia and Ehrlichia should be combined where appropriate with direct antigen assays. Antigen detection tests (antigen capture and PCR) are especially helpful in evaluating the seronegative patient and those still ill or relapsing after therapy. Unfortunately, over a dozen protozoans other than Babesia microti can be found in ticks, yet commercial tests for only B. microti are available at this time, so as in Borrelia, clinical assessment is the primary diagnostic tool. In Ehrlichiosis, test for both the monocytic and granulocytic forms. Many presently uncharacterized Ehrlichia-like organisms can be found in ticks and may not be picked up by currently available assays, so in this illness too, serologies are only an adjunct in making the diagnosis. Babesia are parasites, and I suggest that if a coinfection is found involving this organism, treat this first, so that subsequent therapy for Borrelia and Ehrlichia will be more effective. GENERAL MEASURES Experience has shown that collateral conditions exist in those who have been ill a long time. Test B12 levels, and be prepared to aggressively treat with parenteral formulations of the B-vitamins: 100mg each of B1 and B6 and 1000 mcg of B12 IM at least weekly in the more ill patient. Magnesium deficiency is very often present and quite severe. Hyperreflexia, muscle twitches, myocardial irritability, and recurrent tight muscle spasms are clues to this deficiency. Magnesium is predominantly an intracellular ion, so blood level testing is of little value. Oral preparations are acceptable for maintenance, but most need additional, parenteral dosing: 1 gram IV or IM at least once a week until neuromuscular irritability has cleared. Activation of the inflammatory cascade has been implicated in blockade of cellular receptors. One example of this is insulin resistance, which may partly account for the dyslipidemia and weight gain that is noted in 80% of chronic Lyme patients. Clinical hypothyroidism can result from receptor blockade and thus hypothyroidism can exist despite normal serum hormone levels. Also, because the Lyme syndrome has been associated with faulty activation of T4, measure free T3 levels by RIA, and basal A.M. body temperatures. If hypothyroidism is found, you will need to treat with T3 preparations. SPECT scanning of the brain, if done by knowledgeable radiologists using high-resolution equipment, will show characteristic abnormalities in Lyme encephalopathy. This not only helps with the differential diagnosis, but if done before and after acetazolamide, it will guide in the use of vasodilators, which may clear some cognitive symptoms. Therapy can also include serotonin agonists, pentoxiphylline and even Ginkgo biloba. Therapeutic trials may be needed. Tilt table testing is another powerful tool which, just as in CFIDS, may demonstrate neurally mediated hypotension (NMH). If NMH is present, treatment can dramatically lessen fatigue, palpitations and wooziness, and increase stamina. This test should be done by a cardiologist and include Isuprel challenge. This will demonstrate not only if NMH is present, but also the relative contributions of hypovolemia and sympathetic dysfunction. Therapy is based on blood volume expansion (increased sodium and fluid intake and possibly Florinef plus potassium). If not sufficient, beta blockade may be added based on response to the Isuprel challenge. DIAGNOSTIC HINTS Lyme is diagnosed clinically, as no currently available test, no matter the source or type, is definitive in ruling in or ruling out infection with these pathogens, or whether these infections are responsible for the patient's symptoms. The entire clinical picture must be taken into account, including a search for concurrent conditions and alternate diagnoses, and other reasons for some of the presenting complaints. Often, much of the diagnostic process in late, disseminated Lyme involves ruling out other illnesses and defining the extent of damage that might require separate evaluation and treatment. Consideration should be given to tick exposure, rashes (even atypical ones), evolution of typical symptoms in a previously asymptomatic individual, and results of tests for tick borne pathogens. Another very important factor is response to treatment- presence or absence of Jarisch Herxheimer-like reactions, the classic four week cycle of waxing and waning of symptoms, and improvement with therapy. PIROPLASMOSIS (Babesiosis) Classic teachings state that acute infections are usually only seen in those with some form of immune compromise. Flu-like symptoms rapidly evolve to include shaking chills, high fevers, hemolysis and pancytopenia. Fatalities have been reported. Visualizing Babesial forms on peripheral smears can make the diagnosis in this situation. In those with intact immune systems, a mild flu-like illness appears one to two weeks after exposure and clears without treatment over six to eight weeks. In either case, it is imperative to also test for Borrelia and Ehrlichia. However, when coinfection exists, this acute presentation is much less common, and it is rare to see parasite forms on smear. Suggestions of coinfection include severe headaches, dyspnea, dry cough, dizziness, and encephalopathy out of proportion to the other Borrelial symptoms. Testing is not at all definitive, yet should include CBC, Babesia smear (very low yield), serologies (IgG and IgM) and if necessary, PCR of peripheral blood. Newer direct assays are currently being researched, as this is an active area of investigation. Always consider coinfection in your current Lyme patients who are not responding fully and be prepared to treat cased on clinical presentation even with negative tests. EHRLICHIOSIS While it is true that this illness can have a fulminant presentation, I am convinced that milder forms do exist especially when other tick-borne organisms were transmitted. When present in a Lyme patient, persistent leucopenia is an important clue. Thrombocytopenia is much less common, but likewise should not be ignored. Headaches, myalgias, and ongoing fatigue seem to relate to this illness, but are extremely difficult to separate from symptoms caused by Bb. At this time, we have to rely on serologies for laboratory diagnosis, as currently available PCR assays are of unknown sensitivity and specificity, and direct visualization of leucocytes is of low yield. As there may be a variety of pathogenic Ehrlichia-like organisms that will not be picked up by current testing technology, clinical diagnosis remains the primary diagnostic tool. Again, consider this diagnosis in a Lyme Borreliosis (LB) patient not responding well to therapy. LYME BORRELIOSIS ERYTHEMA MIGRANS Erythema migrans (EM) is diagnostic of Bb infection, but is present in fewer than half. Even if present, it may go unnoticed by the patient. It is an erythematous, centrifugally expanding lesion that is raised and warm. Sometimes there is mild stinging or pruritus. The EM rash will begin four days to several weeks after the bite, and may be associated with constitutional symptoms. Multiple lesions are present less than 10% of the time, but do represent disseminated disease. Some lesions have an atypical appearance and skin biopsy specimens may be helpful. When an ulcerated or vesicular center is seen, this may represent a mixed infection, involving other organisms besides B. burgdorferi. After a tick bite, serologic tests (ELISA. IFA, western blots, etc.) are not expected to become positive until several weeks have passed. Therefore, if EM is present, treatment must begin immediately, and one should not wait for results of Borrelia tests. You should not miss the chance to treat early disease, for this is when the success rate is the highest. Indeed, many knowledgeable clinicians will not even order a Borrelia test in this circumstance. DIAGNOSING LATE DISEASE When reactive, serologies indicate exposure only and do not directly indicate whether the spirochete is now currently present. Because Bb serologies often give inconsistent results, test at more than one laboratory using if possible different methods. I recommend ordering IgM and IgG western blots. Be aware that in late disease there may be repeatedly peaking IgM's and therefore a reactive IgM may not differentiate early from late disease, but it does suggest an active infection. When late cases of LB are seronegative, 36% will transiently become seropositive at the completion of successful therapy. Western blots are reported by showing which bands are reactive. 41KD bands appear the earliest but can cross react with other spirochetes. The 18KD, 23-25KD (Osp C), 31KD (Osp A), 34KD (Osp , 37KD, 39KD, 83KD and the 93KD bands are the most specific but appear later or may not appear at all. You need to see at least the 41KD and one of the specific bands. 55KD, 60KD, 66KD, and 73KD are nonspecific and nondiagnostic. Antigen detection tests including PCR are now available, and although they are very specific, sensitivity remains poor, possibly less than 30%. This is because Bb causes a deep tissue infection and is only transiently found in body humors. Therefore, multiple specimens must be collected to increase yield; a negative result does not rule out infection, but a positive one is significant. The patient must be antibiotic free for at least six weeks before testing to obtain the highest yield. Antigen capture can be done on urine, CSF, and synovial fluid. PCR can be done on blood (buffy coat is best), urine, CSF, any other body fluid including breast milk, and on tissue biopsy specimens. I strongly urge you to biopsy all unexplained skin lesions/rashes and perform PCR and careful histology. You will need to alert the pathologist to look for spirochetes. Spinal taps are not routinely recommended, as a negative tap does not rule out Lyme. Antibodies to Bb can be detected in the CSF in just 20% of patients with late disease. Therefore, spinal taps are only performed on patients with pronounced neurological manifestations, if they are seronegative, or are still significantly symptomatic after completion of treatment. When done, the goal is to rule out other conditions, and to determine if Bb antigens are present. It is especially important to look for elevated protein and mononuclear cells, which would dictate the need for more aggressive therapy, as well as the opening pressure, which can be elevated and add to headaches, especially in children. DIAGNOSTIC CHECKLIST To aid the clinician, a workable set of diagnostic criteria were developed with the input of dozens of front line physicians. The resultant document has proven to be extremely useful not only to the clinician, but it also can help clarify the diagnosis for third party payers and utilization review committees. It is important to note that the CDC's published reporting criteria are for surveillance only, not for diagnosis LYME BORRELIOSIS DIAGNOSTIC CRITERIA RELATIVE VALUE Tick exposure in an endemic region 1 Historical facts and evolution of symptoms 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, e.g., monoarthritis and facial palsy 2 Erythema migrans, physician confirmed 7 Acrodermatitis Chronica Atrophicans, biopsy confirmed 7 Seropositivity 3 Seroconversion on paired sera 4 Tissue microscopy, silver stain 3 Tissue microscopy, monoclonal immunofluorescence 4 Culture positivity 4 B. burgdorferi antigen recovery 4 B. burgdorferi DNA/RNA recovery 4 DIAGNOSIS Lyme Borreliosis Highly Likely........ 7 or above Lyme Borreliosis Possible...... 5-6 Lyme Borreliosis Unlikely....... 4 or below I suggest that when using these criteria, you state Lyme Borreliosis is " unlikely " , " possible " , or " highly likely " based upon the following criteria " - then list the criteria. SYMPTOM CHECK LIST This is not meant to be used as a diagnostic scheme, but is provided to streamline the office interview. Note the format- complaints referable to specific organ systems are clustered to better display multisystem involvement. NAME_______________________________________DATE__________________ RISK PROFILE (PLEASE CHECK) Tick infested area__ Frequent outdoor activities__ Hiking__ Fishing__ Camping__ Gardening__ Hunting__ Ticks noted on pets__ Do you remember being bitten by a tick?............. No__ Yes__ when________ Do you remember having the " bull's eye rash " ? ..No__ Yes__ Any other rash?.................................................... No__ Yes__ Have you had any of the following? CIRCLE ALL YES ANSWERS 1.Unexplained fevers, sweats, chills, or flushing 2.Unexplained weight change- (loss or gain) 3.Fatigue, tiredness, poor stamina 4.Unexplained hair loss 5.Swollen glands: list areas_________________________________________ 6.Sore throat 7.Testicular pain/pelvic pain 8.Unexplained menstrual irregularity 9.Unexplained milk production; breast pain 10.Irritable bladder or bladder dysfunction 11.Sexual dysfunction or loss of libido 12.Upset stomach 13.Change in bowel function- (constipation, diarrhea) 14.Chest pain or rib soreness 15.Shortness of breath, cough 16.Heart palpitations, pulse skips, heart block 17.Any history of a heart murmur or valve prolapse? 18.Joint pain or swelling: list joints_________________________________________________ 19.Stiffness of the joints, neck, or back 20.Muscle pain or cramps 21.Twitching of the face or other muscles 22.Headache 23.Neck creaks and cracks, neck stiffness, neck pain 24.Tingling, numbness, burning or stabbing sensations, shooting pains 25.Facial paralysis (Bell's Palsy) 26.Eyes/Vision: double, blurry, increased floaters, light sensitivity 27.Ears/Hearing: buzzing, ringing, ear pain, sound sensitivity 28.Increased motion sickness, vertigo, poor balance 29.Lightheadedness, wooziness 30.Tremor 31.Confusion, difficulty in thinking 32.Difficulty with concentration, reading 33.Forgetfulness, poor short term memory 34.Disorientation: getting lost, going to wrong places 35.Difficulty with speech or writing; word block 36.Mood swings, irritability, depression 37.Disturbed sleep-too much, too little, fractionated, early awakening 38.Exaggerated symptoms or worse hangover from alcohol LYME DISEASE TREATMENT GUIDELINES PIROPLASMOSIS (BABESIOSIS) Piroplasms are not bacteria, they are protozoans. Therefore, they will not be eradicated by any of the currently used Lyme treatment regimens. Therein lies the significance of coinfections- if a Lyme patient has been extensively treated yet is still ill, suspect a piroplasm. Just as in Lyme Borreliosis, the longer one has been infected, the longer the course of therapy must be. Similarly, clinical assessment is the only guide to treatment endpoint. Treatment choices are limited. Pentamidine is a treatment given as daily IM shots- very painful, and they cause sterile abscesses and permanent fibrous scars on the buttocks. More importantly, response is poor, and the patient risks development of glucose intolerance. Clearly, not a first choice. Clindamycin, 600 mg qid plus Quinine, 650 mg qid has been the published standard but the suggested two week course is nearly impossible to tolerate (hearing loss, rash, fever, headache) and treatment failures have been reported. Gentamicin has been used in treating livestock infected with piroplasms. There are only anecdotal reports of efficacy in Humans, where a 14-day course at standard doses has proven effective in early disease. Experience with this antibiotic in late disease is limited, and the optimal regimen has not been well worked out. The main side effect is potential hearing loss from the gentamicin, and the need for IM or IV doses. Mepron (atovaquone), 750 mg bid, has demonstrated efficacy, but should be given concurrently with azithromycin, 250 to 600 mg daily, or resistance may develop. Efficacy is by far the best with this combination, but surprisingly, Herxheimer-like reactions are almost always seen at the fourth day, and at the fourth week of therapy. Does this represent a newly described phenomenon in treating Piroplasms, or does this combination have heretofore unrecognized efficacy in killing Bb? Although I do not have the answer, I suspect the latter simply based on the familiar (in Bb) four-week cycle. In late, longstanding cases, one month of treatment is the minimum, and four or more months are often needed. Problems during therapy include diarrhea, mild nausea, the expense of Mepron ($600.00 per bottle- enough for one month of treatment), and rarely, a temporary yellowish discoloration of the vision. Regular blood counts and liver panels are recommended during any prolonged course of therapy. Patients who are not cured with this regimen can be retreated but with higher doses, as this has proven effective in many of my patients. EHRLICHIOSIS Treatment recommendations at this time are still preliminary, mainly due to the lack of direct detection methods needed to guide us in developing a solid clinical feel. The mainstay of treatment is doxycycline, either orally or IV, given for at least two weeks for an early infection, or at least four weeks in a longstanding one. Interestingly, the unexpected efficacy of IV doxycycline in treating Lyme cases which had previously responded poorly to cell wall agents, may in fact reflect concurrent therapy of coinfection of Bb with Ehrlichial species. The new concern for Ehrlichia is the main reason that doxycycline is now the first choice in treating tick bites and early Lyme, before serologies can become positive. Quote Link to comment Share on other sites More sharing options...
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