Current Status of Lyme Disease and Co-Infections Sam T Donta MD Infectious Diseases Professor of...
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Transcript of Current Status of Lyme Disease and Co-Infections Sam T Donta MD Infectious Diseases Professor of...
Current Status of Lyme Disease and Co-Infections
Sam T Donta MD
Infectious Diseases
Professor of Medicine (ret)
Introduction/Overview
Diagnosis of Lyme Disease Clinical Aspects
Stages of Lyme Disease Differential Diagnosis of Lyme Disease
Laboratory Diagnosis Routine Bloodwork Lyme Serologic Testing
Adjunctive Studies MRI Brain SPECT scan
Treatment of Lyme Disease
Stages of Lyme Disease Early Lyme Disease Early Disseminated Lyme Disease Late or Chronic Lyme Disease
Early Lyme Disease Tick Bite Rash
Typical Erythema Migrans (EM) Atypical Rash(es)
Diagnosis Clinical Serology
Treatment of Tick Bite Empiric vs waiting for tick results
Double dose doxycycline? 2-3 weeks of doxycycline or amoxicillin?
What to do if tick bite, but no tick Wait to see if symptoms develop? Any value to serologic testing? Double dose doxycycline? 2-3 weeks of doxycycline or amoxicillin?
Early Disseminated Lyme Disease
Clinical Rash “Flu-like” Symptoms
Diagnosis Clinical Serology
Late Lyme Disease Early/Late LD Symptoms/Signs
Bell’s Palsy Meningitis Carditis
Arthritis-Oligoarthritis Encephalopathy Diagnosis
Chronic Lyme Disease Clinical
Major Criteria Fatigue MusculoSkeletal Neurocognitive
Minor Criteria
“Minor” Symptoms & Signs Headaches Eye Symptoms Ear Symptoms Jaw/Tooth Pain Bell’s Palsy Dysequilibrium Dyspnea
Chest/Rib Pains Palpitations Paresthesias Tremors GI Symptoms GU Symptoms Fevers/Sweats
Spectrum of Lyme Disease Generalized Symptoms Neurologic Symtoms/Manifestations Rheumatologic Symptoms/Signs
Chronic Fatigue Syndrome
Definition: New Onset Severe, Unexplained Fatigue >6mo
Other Symptoms (4 of 8) Memory or Concentration Sore Throat Tender Lymph Nodes Muscle Pain Multijoint Pain New Pattern Headache Unrefreshed Sleep Postexertional Malaise>24hrs
Fibromyalgia
Definition: Pain in fibrous tissues & muscles Specific Symptoms:
Pain (widespread)-myalgias, stiffness Fatigue Sleep Disorder Mental Concentration problems Mood Changes Headaches Abdominal Pain/Diarrhea Paresthesias (Numbness, Tingling, Itching Dizziness Facial Rashes Urinary Urgency Fluid Retention
Gulf War Veterans’ Illness
Definition: New Onset Fatigue, Musculoskeletal, and/or Neurocognitive symptoms (2/3) arising after deployment to the Persian Gulf, and persisting >6mo
Specific Symptoms Headaches Sleep Disorder Paresthesias Fatigue Abdominal Pain Sore Throat Arthralgias Diarrhea Cough Myalgias Weight Gain Chest Pain Memory Shortness of Breath Sweats, fevers Concentration Decreased Libido Lymph Nodes Irritability Depression Rashes, sores
Chronic Lyme and Lyme-like Illnesses
Symptom Lyme CFS Fibro GWI Fatigue + + + + Myalgias + + + + Arthralgias + + + + Memory + + + + Confusion + + + + Mood Changes + + + + Headache + + + + Paresthesias + ? + + Sore Throat + + ? + Lymph Nodes + + ? + Sleep Disorder + + + + Abd pain/Diarrhea + ? ? + Urinary Frequency + ? ? ? Fevers/Sweats + + ? + Palpitations + ? ? + Rashes/Sores + ? ? + Weight Gain + + ? +
Etiology of Chronic or “Post-Treatment” Lyme Disease
Persisting Infection Autoimmunity Post-infectious sequelae
Pathogenesis of Symptoms Infection
Where do bacteria go? Do they persist? How do you know if they’re gone?
Mechanisms Neurotoxicity? Borrelia/Host Interaction?
Auto-Immunity Cross-reaction between bacteria and neural
gangliosides? Need for continuing infection?
Damage Other ?, Disease Tolerance
Laboratory Issues
Serologic Tests EIA, ELISA Western Blot
IgM vs IgG in early vs chronic disease-?dysregulation of IgM vs IgG response
Numbers of bands vs specificity of bands Specific bands: 23,31,34,39,83/93
Lymphocyte Stimulation PCR-DNA Culture Spinal Fluid
Serologic Testing CDC Criteria
Surveillance vs Clinical Diagnosis Two-step testing
EIA/ELISA Western Blot-IgM, IgG
Imaging Studies
MRI 15% T2 Signals
Brain SPECT Scan 75% perfusion defects
Brain SPECT Scans in Patients with Chronic Lyme Disease
0
5
10
15
20
25
30
35
40
45
50
TEMPORAL FRONTAL PARIETAL OCCIPITAL PERIVENTRIC OTHER
MILD
MODERATE
SEVERE
Issues Regarding Treatment of Chronic Lyme Disease
In vitro antibiotic sensitivities Antibiotic treatment studies
Beta-lactam antibiotics Tetracyclines Macrolides Others
Klempner/Steere Treatment Trial of Chronic Lyme Disease
Assumptions Equivalence of Doxycycline and
Ceftriaxone Duration of Treatment
Conclusions No analysis of Other Treatment Options ?No need for further Treatment Trials
Doxycycline v Tetracycline
Dose differences 200mg/d v 1500mg/d
Protein Binding differences 90+ protein bound v 40% protein bound
Ceftriaxone Questions Duration of Treatment
1 months v 3-6 months Mechanism of Action
Reconciling in vitro v in vivo observations Antibiotic v Glutamate Receptor
Upregulation
Macrolide Antibiotics inTreatment of Lyme Disease
In vitro activities Resolving lack of in vivo efficacy
Macrolide MICs of B.burgdorferi
Cell Trafficking
Maurin M, Benoliel AM, Bongrand P, and Raoult D. Phagolysosomal alkalinization and the bactericidal effect of antibiotics: the Coxiella burnetii paradigm. J Infect Dis 1992, 166:1097-102.
Inhibition of Acidification
Macrolide Therapy of Chronic Lyme Disease
OUTCOME AT 2 AND 3 MONTHS
0
1 0
2 0
3 0
4 0
5 0
6 0
7 0
8 0
9 0
1 0 0
2 m o 3 m o
< 2 5 %
2 5 - 5 0 %
5 0 - 7 5 %
> 7 5 %
Prior Symptom Duration vs Outcome of Rx
CURE IMPROVEMENT FAILUREPRIOR Sx DURATION
<1 YR 33 (28%) 78 (67%) 6 ( 5%)
1-3 YR 9 (15%) 45 (75%) 6 (10%)
>3 YR 7 (11%) 43 (70%) 11 (18%)
Gender vs OutcomeCURE IMPROVEMENT FAILURE
MALE 27 (32%) 51 (61%) 6 ( 7%)
FEMALE 22 (14%) 115 (75%) 17 (11%)
Other Treatment Issues Vitamin Supplements
B Vitamins Vitamin C
Mineral Supplements Hyperbaric Oxygen Heat
Questions/Future Directions Is there persistent/latent infection?
Where are the bacteria in chronic disease? Where were the bacteria before treatment? Evidence points to intracellular reservoir
Identification of Lyme-specific products for diagnosis and monitoring treatment
Development of New Vaccines Controlled Clinical Treatment Trials
Validation or refutation of other treatment regimens Importance of duration of treatment
Ixodes Tick Co-Infections
Babesiosis Clinical Aspects Laboratory Diagnosis
Ehrlichia/Anaplasma Clinical Aspects Laboratory Diagnosis
Bartonella Clinical Aspects Laboratory Diagnosis