What we Know and Don ’t Know
About Lyme Disease
Sam T Donta MD
Infectious Diseases
Professor of Medicine (ret)

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A mysterious illness in children
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An unusual rash following a tick bite
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Swollen joint(s), other symptoms
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Initial considerations
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Form of juvenile rheumatoid arthritis
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Discovery of the cause
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Dr Burgdorfer, Dr Barber

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Transmission of Lyme Disease
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From Ixodes to target hosts
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Any other form of transmission?
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Pathogenesis of Lyme Disease
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Course of infection
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Cause of symptoms/signs

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Generalized Symptoms
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Neurologic Symptoms/Manifestations
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Rheumatologic Symptoms/Signs

Diagnosis of Lyme Disease
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Early vs Late vs Chronic Illness
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Clinical Issues
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Laboratory Issues
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Imaging Studies
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Treatment Trial as Diagnostic Tool

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Tick Bite
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Rash
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Typical Erythema Migrans (EM)
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Atypical Rash(es)
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Diagnosis
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Clinical
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Serology

Early Disseminated Lyme Disease
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Clinical
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Rash
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“ Flu-like ” Symptoms
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Diagnosis
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Clinical
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Serology

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Early/Late LD Symptoms/Signs
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Bell ’ s Palsy
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Meningitis
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Carditis
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Arthritis-Oligoarthritis
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Encephalopathy
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Diagnosis

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Major Criteria
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Fatigue
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MusculoSkeletal
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Neurocognitive
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Cognitive-Memory, Concentration
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Mood
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Minor Criteria

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Headaches
Eye Symptoms
Ear Symptoms
Jaw/Tooth Pain
Bell ’ s Palsy
Dysequilibrium
Dyspnea
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Chest/Rib Pains
Palpitations
Paresthesias
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Tremors
GI Symptoms
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GU Symptoms
Fevers/Sweats

Chronic Fatigue Syndrome
(Systemic Exertion Intolerance Disease)
Definition: New Onset Severe, Unexplained Fatigue >6mo
Other Symptoms (4 of 8)
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Memory or Concentration
Sore Throat
Tender Lymph Nodes
Muscle Pain
Multijoint Pain
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New Pattern Headache
Unrefreshed Sleep
Postexertional Malaise>24hrs

Definition: Pain in fibrous tissues & muscles
Specific Symptoms:
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Pain (widespread)-myalgias, stiffness
Fatigue
Sleep Disorder
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Mental Concentration problems
Mood Changes
Headaches
Abdominal Pain/Diarrhea
Paresthesias (Numbness, Tingling, Itching
Dizziness
Facial Rashes
Urinary Urgency
Fluid Retention

Definition: New Onset Fatigue, Musculoskeletal, and/or Neurocognitive symptoms (2/3) arising after deployment to the Persian Gulf, and persisting >6mo
Headaches
Specific Symptoms
Sleep Disorder Paresthesias
Fatigue
Arthralgias
Myalgias
Abdominal Pain
Diarrhea
Weight Gain
Sore Throat
Cough
Chest Pain
Memory
Concentration
Irritability
Shortness of Breath
Decreased Libido
Depression
Sweats, fevers
Lymph Nodes
Rashes, sores

Chronic Lyme and Lyme-like Illnesses
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Symptom
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
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Lyme
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CFS
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Fibro
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GWI
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Serologic Tests
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EIA, ELISA
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Western Blot
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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

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CDC Criteria
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Surveillance vs Clinical Diagnosis
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Two-step testing
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EIA/ELISA
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Western Blot-IgM, IgG

Western Blot vs EIA in
Chronic Lyme Disease
M+G+ M+G- M-G+ M-G-
EIA
POSITIVE 28 (57%) 7 (14%) 11 (22%) 3 (6%)
NEGATIVE 28 (20%) 49 (35%) 18 (12%) 47(33%)

SYMPTOMATIC ASYMPTOMATIC
IgG
IgM
4/64 ( 6%) 17/32 (53%)
23/64 (36%)
IgG+IgM 37/64 (58%)
3/32 ( 9%)
5/32 (16%)
None 7/32 (22%)

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MRI
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15% T2 Signals
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Brain SPECT Scan
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75% perfusion defects

Brain SPECT Scans in Patients with Chronic Lyme Disease

Brain SPECT scan pre- and post-antibiotic treatment

Pathogenesis of Symptoms
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Infection
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Where do bacteria go? Do they persist?
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Antibiotic Tolerance?
How do you know if they ’ re gone?
Mechanisms
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Neurotoxicity?
Borrelia/Host Interaction?
Auto-Immunity
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Cross-reaction between bacteria and neural gangliosides?
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Need for continuing infection?
Damage

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Symptom-based Treatments
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Helpful but not curative
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Antibiotic Treatments
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Efficacy of different antibiotics
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Need for Intracellular penetration?
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Is Blood-Brain Barrier an issue?
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Non-antibiotic effects?
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Gender response differences

Issues Regarding AntibioticTreatment of
Chronic Lyme Disease
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In vitro antibiotic sensitivities
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Antibiotic treatment studies
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Beta-lactam antibiotics
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Tetracyclines
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Macrolides
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Others

Klempner/Steere Treatment Trial of
Chronic Lyme Disease
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Assumptions
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Equivalence of Doxycycline and
Ceftriaxone
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Duration of Treatment
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Conclusions
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No analysis of Other Treatment Options
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?No need for further Treatment Trials

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Dose differences
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200mg/d v 1500mg/d
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Protein Binding differences
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90+ protein bound v 40% protein bound

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Duration of Treatment
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1 months v 3-6 months
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Mechanism of Action
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Reconciling in vitro v in vivo observations
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Antibiotic v Glutamate Receptor
Upregulation

Macrolide Antibiotics in
Treatment of Lyme Disease
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In vitro activities
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Resolving lack of in vivo efficacy

B.burgdorferi

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.

Prior Symptom Duration vs
Outcome of Rx
CURE IMPROVEMENT
PRIOR Sx
DURATION
<1 YR
1-3 YR
>3 YR
33 (28%)
9 (15%)
7 (11%)
78 (67%)
45 (75%)
43 (70%)
FAILURE
6 ( 5%)
6 (10%)
11 (18%)

CURE IMPROVEMENT FAILURE
MALE 27 (32%) 51 (61%) 6 ( 7%)
FEMALE 22 (14%) 115 (75%) 17 (11%)

Treatment of Early Lyme Disease
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Early Lyme Disease
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Doxycycline-100mg bid, or
Amoxicillin-500mg bid, or
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Cefuroxime-500mg bid for 3-4 wks
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Continue treatment if still symptoms until symptoms resolve

Treatment of Chronic Lyme Disease
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Chronic Lyme Disease
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Tetracycline-1500mg/day for 3+ months, or
Macrolide Antibiotic
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Clarithromycin-500mg bid, or
Erythromycin-500mg bid, or
Azithromycin-500-600mg qd
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Hydroxychloroqine (Plaquenil)-200mg bid for 3+ months
 Continue treatment if still symptoms until symptoms resolved
(and have not reappeared for at least 1 month). May need to alternate above 2 regimens every 6 months for 18-24 months in illness> 1-2 yrs

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Vitamin Supplements
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B Vitamins
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Vitamin C
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Mineral Supplements
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Hyperbaric Oxygen
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Heat

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Identification of Lyme-specific Products for Diagnosis and Monitoring Treatment
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Controlled Clinical Treatment Trials
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Development of Vaccines