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Published by Darko Svetozarevski, 2019-07-10 18:16:27

Amsterdam NL

Amsterdam NL

Introduction To Lyme & Chronic
Disease

Amsterdam NL

June 19th 2019

Dr. Richard Horowitz,
Medical Director HVHAC, Hyde Park, N.Y.

Board Certified Internal Medicine
Member, HHS Tick-Borne Disease Working Group 2017-2019
Co-chair, HHS Other Tick-Borne Diseases and Co-infections 2017-2019

Important HHS Lyme Web sites:

◼ www.hhs.gov/tickbornediseaseworkinggroup

◼ 2018 Report to HHS Secretary and Congress
◼ Subcommittee reports: Access to Care & Support to

Patients;
◼ Vector Surveillance +Prevention
◼ Testing & Diagnostics
◼ Pathogenesis, Transmission &
◼ Treatment
◼ Vaccine & Therapeutics
◼ Other Tick-borne Diseases & Co-inf’s (Co-chair)

◼ https://www.hhs.gov/ash/advisory-committees/tickbornedisease/reports/index.html

Disclaimer/Conflicts of Interest

◼ Conflicts of Interest:
◼ St Martin’s Press: royalties for two books: “Why

Can’t I Get Better?” and “How Can I Get Better?”
◼ Xymogen Board of Advisors, stock, honorariums
◼ Grants: Bay Area Lyme Foundation, MSIDS

Research Foundation
◼ Disclaimer: The views expressed in this

presentation do not represent the views of the
Tick Borne Disease Working Group, HHS or the
United States

Why Do Patients Stay Sick?

◼ HVHAC: 13,000 Lyme patients over 30 years

◼ Koch’s postulate: one cause for one disease

◼ What if there were multiple overlapping causes of
inflammation affecting Lyme symptoms?

◼ MSIDS model: Up to 16 reasons why patients stay
ill (Horowitz, 2008): Paradigm Shift for Chr. Disease

◼ The 3 “I”s: Infection(s)

Inflammation

Immune Dysfunction

◼ Horowitz, R.I. Clinical Roundup: Selected Treatment Options for Lyme disease: Multiple Causative
Factors in Chronic Disease. Alt and Compl Therapies. DOI:10. 1089/act.2012.18407. Mary Ann Liebert,
Inc. Vol 18, No.4 Aug 2012.

Why Shift The Paradigm for Chronic
Disease? High US Disability Rates

◼ Chronic tick-borne diseases can be both emotionally and
financially devastating to individuals and families and to
their productivity

◼ In 2012, approximately half of all adults (49.8%, 117
million) in the US had at least 1 of 10 selected chronic
conditions, 24.3% had 1 chronic condition, 13.8% had 2
conditions, and 11.7% had 3 or more conditions.

◼ The American Community Survey (ACS) estimates the
overall rate of people with disabilities in the US population
in 2016 was 12.8% (pain/cognitive difficulties: ? Seronegative LD)

◼ Ward BW, Schiller JS, Goodman RA. Multiple Chronic Conditions Among US Adults: A 2012 Update. Prev
Chronic Dis 2014;11:130389. doi: http://dx.doi.org/10.5888/pcd11.130389

◼ https://disabilitycompendium.org/sites/default/files/user-uploads/AnnualReport_2017_FINAL.pdf

RIVM Foresight: A Healthier Netherlands
With More Chronically Ill People

◼ The Netherlands will have around 7 million
people with a chronic disease in 2030, increasing
from 32% to about 40% of the population

◼ The RIVM National Institute for Public Health and
the Environment foresees an increase from 5.3
million in 2011 to 7 million in 2030. The number
of people with two or more disorders will also
increase. The number of people with an illness
has risen over the past decade

◼ https://www.rivm.nl/nieuws/toekomstverkenning-rivm-gezonder-nederland-met-meer-chronisch-
zieken

Rising Numbers of Individuals With Chronic
Disease in NL 2007- 2017: % Change

http://www.healthdata.org/netherlands

◼ What causes the most deaths? Largest ∆: Alzheimer's ↑ 43.1%
◼ What causes the most premature deaths: largest % change

2007-2017: Alzheimer's disease: ↑36.5% (2017 population 17.0M)

◼ What health problems cause the most disability? 7/11 ?LD

◼ 1st: Low back pain (-3%)
◼ 2nd: Headache disorders increased by 2.6%
◼ 4th: Neck pain increased by 6.0%
◼ 5th: Depressive disorders increased by 4.9%
◼ 6th: Anxiety disorders increased by 5.8%
◼ 8th: Falls increased by 35.1%
◼ 11th: Other musculoskeletal disorders increased by 1.4%

Lyme as the “Great Imitator”

◼ Treating chronic diseases accounts for 86% of US health
care costs, & chronic diseases are on the rise

◼ The prevalence of autism in the US has risen from 1/150
cases in 2000 to 1 in 68 in 2012. Every 67 seconds someone
in the US is diagnosed with Alzheimer’s disease & 46.5
million Americans have preclinical AD. Autoimmune
diseases like rheumatoid arthritis and multiple sclerosis
(MS) affect over 23 million Americans. Chronic Fatigue
Syndrome/Myalgic Encephalomyelitis and Fibromyalgia
together affect 5% of the US population

◼ Lyme has been associated w/ each of these diseases

◼ Bu X- L, et al. A study on the association between infectious burden and Alzheimer’s disease. Eur J
Neurol. 2015 Dec;22(12):1519–25. doi: 10.1111/ene.12477. Epub 2014 Jun 9.

◼ https://www.nbcnews.com/health/health-news/new-estimate-says-46-million-americans-headed-
alzheimer-s-n827456

Teaching Objectives

◼ Learn the basic clinical manifestations of LD

◼ Understand the difference between Lyme disease
& other borrelia species, & how it may affect tests

◼ Review the most common tick-borne co-infections

◼ Determine different methods of transmission and
how we can reduce our risk

◼ Learn the role of laboratory testing & a detailed
history in differential diagnostics for chronic dis.

◼ Understand the 3 I’s and the basics of the MSIDS
model: why individuals remain ill after treatment

© 2019 Richard I. Horowitz, M.D.

Who doesn’t have Lyme in
Connecticut?

Why Do We Get Sick?

◼ 1. Environment: Numbers of cases are increasing

in part because of changes in predators for small
mammals like the white footed mouse (↓ foxes),
and building homes in parcels near wooded areas

◼ 2. Effects of Climate change: ticks are emerging

3 weeks earlier, & new species are appearing

◼ 3. Ticks: types of ticks with different infections are

spreading across states and countries due to
migratory birds (ex: Lone Star tick, Asian Bush tick)

◼ Levi T, et al. 2015 Accelerated phenology of blacklegged ticks under climate warming. Phil. Trans. R. Soc.
B 370: 20130556; Scott JD. et al. Prevalence of the Lyme Disease Spirochete, Borrelia burgdorferi, in
Blacklegged Ticks, Ixodes scapularis at Hamilton-Wentworth, Ontario. I Int J Med Sci. 2016 Apr
10;13(5):316-24.; Longhorned Tick in CT, WCSU, Sept 2018

Why Do We Get Sick?

◼ 4. Modes of Tick-borne Transmission are
Increasing: B. miyamotoi is the first species with

transovarial transmission (6-73%) + larval transmission→ ↑
human infection

◼ 5. Modes of Human Transmission are
Increasing: Blood transfusion (↑ #’s, types of inf’s),

solid organ transplantation, maternal/fetal transmission
(for borrelia and co-infections), sexual transmission?

◼ 6. Infections: ↑ numbers of species of borrelia and co-

inf’s are being found in ticks (bacteria, parasites,viruses)

◼ Krause,P. et al. Borrelia miyamotoi: The Newest Infection Brought to Us by Deer Ticks. Ann Intern Med.
2015;163(2):141-142;

Why Do We Get Sick?

◼ 7. Diagnostics: tests lack adequate sensitivity for early

and late infection. Leads to improper diagnoses (CFS/ME,
FM, A.I. dx & Neuropsychiatric disease w/dementia)

◼ 8. Persistence: Borrelia can persist despite seemingly

“adequate” antibiotics. “Persisters” have also been
reported with Babesia, & multiple IC bacteria: Bartonella,
Mycoplasma, Tularemia & Brucella→ chronic disease

◼ 9. Health Care Politics: denies problems w/

diagnostics & persistence→↑ health care costs + disability

◼ Lee SH, et al. DNA sequencing diagnosis of off-season spirochetemia with low bacterial density in
Borrelia burgdorferi and Borrelia miyamotoi infections. Int J Mol Sci. 2014 Jun 25;15(7):11364-86

◼ Abraham A, et al. Establishment of a continuous in vitro culture of Babesia duncani in human
erythrocytes reveals unusually high tolerance to recommended therapies. J Biol Chem. 2018 Dec
28;293(52):19974-19981.

Cost of Lyme in the Netherlands:
20 Million Euros/year

◼ Lyme disease costs EUR 20 million annually NL

◼ Includes: health care costs, employee
absenteeism & costs that patients pay themselves

◼ Serious infections and persistent symptoms after
treatment of Lyme are responsible for the largest
share of these costs

◼ Prevention of tick bites is important!

◼ www.rivm.nl/tekenbeet and www.tekenradar.nl

◼ http://www.rivm.nl/en/Documents_and_publications/Common_and_Present/Newsmessages/2017
/Lyme_disease_costs_EUR_20_million_annually

Disability for LB in NL: 3 X ↑ in 15 yrs
7.58 to 16.93 DALY’s

Rising Incidence of Lyme Disease: US

◼ 1.3% of U.S. respondents (2009) and 0.9% in 2012

◼ Conclusion: with a population of >300 million, a very large
number have been diagnosed with LD (0.3% pop, 2012)

◼ CDC revised figures in 2015: from 30,000 to over
300,000/year (400k+), 320% ↑ in counties in 20 years

◼ A record high of 59,349 cases of tickborne diseases were
reported in 2017 in the US: 22% ↑ in TBD: November 2018

◼ Quest labs: 2018 Health Trends: Rates of positive LD test
results are ↑ dramatically: 6.7% in 2014 to 11.2% in 2017

◼ CDC Abstract--ICLB 2013, Hook et al. Self-reported Lyme disease diagnosis, treatment, and recovery:
Results from 2009-2012 nationwide surveys. Geographic Distribution and Expansion of Human Lyme
Disease, United States, Kiersten J. Kugeler et al, E.I.D., August 2015;

◼ https://www.hhs.gov/sites/default/files/tbdwg-report-to-congress-2018.pdf
◼ Health Trends™ Lyme Disease, July 2018. www.QuestDiagnostics.com

WHO: Number of Lyme Cases in
Europe Keeps Rising (2014)

↑ Incidence of Lyme Borreliosis in
Europe: W.H.O.

◼ Lyme Borreliosis (LB) is the most common tick-
borne disease in Europe. The number of cases in
Europe has increased steadily, with more than
360,000 cases reported over the last two decades

◼ Between 1990 and 2010, the highest average
incidence rates among the reporting countries were
found in Belarus, Belgium, Croatia, Norway, the
Russian Federation and Serbia (Central Europe has
the highest incidence)

◼ Lyme Borreliosis (Lyme disease). In: International travel and health [website]. Geneva: World Health
Organization; 2014 (http://www.who.int/ith/diseases/lyme/en/).

Increasing LB in Western Europe

◼ Results: Countries in Western Europe have a large
variance in the incidence rates for LB: the highest
incidence = southern Sweden, the lowest = Italy

◼ The unweighted mean for the data showed an
incidence of 56.3 per 100,000 persons/year,
equating to approximately 232,125 cases in 1 year
throughout the region

◼ Conclusions: LB is the most common zoonotic
infection in Western Europe approaching endemic
proportions in many European countries.

◼ Sykes, R. An Estimate of Lyme Borreliosis Incidence in Western Europe, Res Medica 2014, 22(1): pp. 76-
87.

PTLDS Belgium: Appx 10,000/year
Get an EM Rash: 2017

van den Wijngaard CC, et al. Surveillance perspective
on Lyme borreliosis across the European Union and

European Economic Area

Euro Surveill. 2017;22(27):pii=30569.

Underestimating Lyme Disease Risk &
the Spread of Borreliosis

◼ “The lack of a gold standard for diagnosis makes

producing accurate statistics difficult. Some
pathogenic strains belonging to the B. burgdorferi
sensu lato complex have a worldwide distribution,
yet they are rarely considered or tested for”

◼ Perronne C (2014) Lyme and associated tick-borne diseases: Global challenges of Lyme disease. Front.
Cell. Infect. Microbiol. 4:74

◼ Stanek G, Reiter M. The expanding Lyme Borrelia complex – clinical significance of genomic species? Clin
Microbiol Infect (2011) 17: 487-93.

The Rising Incidence of Borrelia infections:
>16 New Species (1990-2017)

◼ USA: B. burgdorferi sensu lato, Borrelia sensu stricto (B31)
(297), Borrelia kurtenbachii, B. mayonii, B. californiensis

◼ Europe: Borrelia afzelii (ACA) + Borrelia garinii
(neuroborreliosis) + B. spielmani (early skin disease), + B.
valaisana, B. lusitanea, B. bavariensis

◼ Asia: B. japonica, B. turdi, B. tanukii, B.yangtze

◼ North America: Borrelia andersonii

◼ Southern U.S. : B. americanum, B. carolinensis

◼ Pacific U.S.: B. bissettii & Borrelia lanei were recently
implicated as human pathogens in California

Girard YA, Fedorova N, Lane RS. Genetic diversity of Borrelia burgdorferi and detection of B. bissettii-like
DNA in serum of north-coastal California residents. J Clin Microbiol. 2011;49:945–54. Margos et al.
International Journal of Systematic and Evolutionary Microbiology, 08 Sept 2017

Different Borrelia Species Cause Dx

◼ The genus Borrelia has two primary genera: the Lyme
disease group and Relapsing fever group

◼ Lyme disease: B. sensu stricto is the main N. American
strain; Borrelia sensu lato comprises all species known to
cause disease. This includes:

◼ B. burgdorferi (US), B. afzelii (ACA), B. garinii
(neuroborrelosis), B. bisetti (Calif), B. mayonii (Midwest)
B. bavariensis, B. valaisiana, B. spielmanii, B. lusitaniae
(Europe), B. chilensis (Chile), B. finlandensis (Finland)

◼ Relapsing fever group: B. hermsii, B. parkerii, B. turicate,
B. dutonii, B. crocidurae, B. recurrentis…B. miyamotoi

(Ixodes Ricinus complex) Barbour, A. et al. Int J Syst Evol Microbiol 2017; 67: 2058-2067

Transmission Time After A Tick Bite

◼ Lyme disease: 24-72 hrs? (Prob. of transmission ↑ if multiple ticks

attached. Re-attachment of previously partially fed infected ticks may lead to

more rapid transmission; ↑ nymphs); in animal models, transmission
can occur in < 16 hours; A European study documented 6
cases in <6 hours. Spirochetes in the tick salivary glands
prior to feeding could ↑ transmission Cook, M. Int J Gen Med. 2015; 8: 1-8

◼ Powassan virus: within 15 minutes of tick attachment

(Ebel GD, et al. Am J Trop Med Hyg. 2004;71(3):268–271)

◼ Rickettsia rickettsii can occur in as little as 10 minutes

with fed Ambl. ticks (Saraiva DG, et al. Emerg Infect Dis. 2014;20(9):1504–1510).

◼ Relapsing fever bacteria (Borrelia hermsii) < 5 minutes

◼ Pathogen transmission in relation to duration of attachment by Ixodes scapularis ticks. Eisen, L. 2018

Ixodes Ricinus Midgut/Salivary Glands:

Borrelia spp. (B. lusitaniae, B. afzelii, B. garinii,
B. spielmanii) Anaplasma, R. Helvetica/felis

Different ticks: Ixodes scapularis (NE), I.
pacificus (Calif), I. Ricinus (Europe)
Lone star, Ambylomma americanum

TEARS: (Tularemia, Ehrlichiosis, Alpha Gal, RMSF, STARI, virus)
? Transmit Filariasis (Rasgon, L., Ticks and Tick-borne Diseases, Volume 7, Issue 2, March

2016)

ASIAN
LONGHORNED TICK

• Haemaphysalis
longicornis: vector of
various pathogens
infectious to humans:
SFTS, Alpha Gal allergy

• Viruses transmitted
transstadially and
transovarially

• Asexual reproduction

• Tufts, D. et al. Distribution, Host-Seeking
Phenology, and Host and Habitat
Associations of Haemaphysalis longicornis
Ticks, Staten Island, New York, USA. EID
journal Volume 25 Number 4—April 2019

Ticks: Larvae, Nymphs, Adults, Engorged
Female adult tick (swollen grey tick near

pencil head)

Maternal Transmission of TBD’s

◼ Transplacental infection of the human fetus has
been recognized for syphilis & leptospirosis (other
spirochetal org’s) as well as relapsing fever
borreliosis (RF), Lyme Disease and Babesiosis

◼ Molecular evidence of perinatal transmission of
Bartonella vin. subsp. Berkhoffii and B. henselae
to a child. Breitschwerdt et al. Journal of Clin Microbiol. April 14, 2010

◼ Rocky Mountain spotted fever in pregnancy:
Differential diagnosis and treatment.

◼ Herbert, WN, et al. South Med J 1982
◼ Human Fetal Borreliosis, Toxemia of Pregnancy, and Fetal Death. Zbl. Bakt. Hyg. A 263, 189-200 (1986).

MacDonald, A.; Lyme Disease During Pregnancy. H. Silver. Inf Dis Clinics of N. Amer. Vol 11, No 1, Mar
1997; Lyme Disease and Pregnancy. Horowitz et al. 16th Intl Scientific Conference on Lyme Disease.
May 2003.

Tick-Borne Infections Are in the Blood
Supply: ↑ Transfusion Risk

:◼ Babesia The Risk of Acquiring Lyme dx or Babesiosis from a blood transfusion.

Gubernot DM, et al. Clin Infect Dis. 2009;48:25-30. MMWR Summary of Notifiable Diseases 2013.

Centers for Disease Control & Prevention, 63(32): 702-715. August 14, 2014. Recent report:
4/1000 samples + Babesia (B. microti, B. duncani)

◼ Anaplasma/Ehrlichia ewingii: Annen, K. et al. Two cases of Transfusion-

Transmitted Anaplasma phagocytophilum. American Journal of Clinical Pathology. 2012
Apr;137(4):562-5);

Bartonella:◼ Pitassi, et al. Bartonella spp. bacteremia in blood donors from Campinas, Brazil.

PLoS Negl Trop Dis. 2015 Jan 15;9(1)

◼ Relapsing fever/B. miyamotoi: Can survive in human blood

◼ Distribution and survival of Borrelia miyamotoi in human blood components. Thorp AM, Tonnetti L.
Transfusion, online first, 2015 Dec 21.

◼ RMSF: Rickettsia rickettsii

◼ Viruses: TBEV, Colorado tick fever virus (Leiby, FDA, 2018)

? Sexual Transmission of TBD’s

◼ Studies implicate sexual transmission of LD
◼ Spirochetes were observed in cultures of genital

secretions from 11 of 13 subjects diagnosed w/ LD.
◼ PCR sequencing indicated that 2 couples had

identical strains of Bb sensu stricto in their semen
and vaginal secretions, while the 3rd couple had
identical strains of B. hermsii

◼ Middelveen MJ, et al. Culture and identification of Borrelia spirochetes in human vaginal and seminal
secretions F1000Research 2014, 3:309 ; Stricker RB, et al: Clinical and immunologic evidence for
transmission of Lyme disease through intimate human contact. J Investig Med. 2004; 52: S151.

Lyme and Co-infections

◼ Lyme disease can present as an acute or chronic
illness. The rash of LD (Erythema migrans) is only
present in approximately 50% of cases (?10- 20%)

◼ Acute: Flu like symptoms with fevers, fatigue,
swollen glands, sore throat, nausea and vomiting,
headaches, stiff neck, photophobia. May include
Bell’s palsy & other neurological symptoms

◼ Chronic: Symptoms of Chronic LD (PTLDS, Lyme-
MSIDS…), is often associated with co-infections

◼ Aucott J, et al. Diagnostic challenges of early Lyme disease: lessons from a community case series. BMC
Infect Dis 2009;9:79; Horowitz, R.I.; Freeman, P.R. Precision Medicine: retrospective chart review and
data analysis of 200 patients on dapsone combination therapy for chronic Lyme disease/post-
treatment Lyme disease syndrome: part 1. International Journal of General Medicine 2019:12 101–119

Check For Tick-Borne Co-Infections

◼ Borrelia (multiple species): sensu lato spp., RF (hermsii, BMD)
◼ Neorickettsia, Ehrlichia, Anaplasma

◼ Parasites: Babesia (microti, WA-1/duncani, divergens, EU-
1), others: FL1953, filarial (? transmitted)

◼ Bartonella (multiple species): > 20 pathogenic
◼ Mycoplasma (multiple species): M. fermentans

◼ Rickettsial infections: RMSF, Typhus, Q-fever, R. helvetica

◼ Tularemia, Brucella (most of the above inf’s = IC)

◼ Viruses: DTV/Powassan virus, TBEV, Heartland/Bourbon

◼ Swanson SJ, et al. Coinfections acquired from ixodes ticks. Clin Microbiol Rev 2006; 19(4):708-27
◼ Bartonella spp. - a chance to establish One Health concepts in veterinary and human medicine. Regier et

al. Parasites & Vectors (2016) 9:261

Prevention Is Essential!

◼ Acaricides: Use permethrin sprays on clothes, or
permethrin treated clothing. DEET: 20%-30% (25 %
DEET works for 6 hours) also kills ticks

◼ Repellants: Avon SSS (IR 3535) or Picaridin on skin

◼ Natural sprays: eucalyptus oils..

◼ Avoid strong-smelling perfumes and lotions

◼ If bit: proper tick removal is important. Local AB?

◼ Single dose doxycycline? not proven to work

◼ Knauer J, et al. Evaluation of the preventive capacities of a topically applied azithromycin formulation
against Lyme borreliosis in a murine model. Journal of Antimicrobial Chemotherapy online, Sept. 15,
2011. Nadelman RB, et al.

◼ Prophylaxis with single-dose doxycycline for the prevention of Lyme disease after an Ixodes scapularis
tick bite. N Engl J Med 2001;345(2):79-84







Disseminated EM rashes: Treat > 30 days

IMAGES IN CLINICAL MEDICINE
DISSEMINATED LYME DISEASE
NORA REGELIN, M.D., AND ERNESTO MONTARULI, M.D.
N ENGL J MED 2015; 372:2136MAY 28, 2015

ACA: Acrodermatitis Chronicans
Atrophicans (B. Afzelii)



Optic Neuritis

Cardiac Problems: 3rd Degree
Heart Block secondary to LD

Check Baseline EKG, & QT intervals

Symptoms of Disseminated LD

An EM rash with one or multiple symptoms:

◼ Neck stiffness with headaches, light and sound sensitivity
◼ Memory and concentration problems
◼ Vertigo, dizziness, difficulty walking: infection in the CNS

(Central Nervous System)
◼ Tingling, numbness, burning sensations hands and feet

(infection in PNS, Peripheral Nervous System), or face/scalp
(CNS)
◼ Fevers, sweats, chills (? Babesia): see Questions 1+22 HMQ
◼ Multiple EM rashes imply dissemination. Treat until well.

◼ Marques, A. et al. Early Disseminated Lyme Disease Causing False-Positive Serology for Primary Epstein-
Barr Virus Infection: Report of 2 Cases. Clin Infect Dis, Volume 65, Issue 2, 15 July 2017, Pages 336–337

Lyme disease: The Grand Imitator

◼ Chronic Fatigue Syndrome

◼ Fibromyalgia (fatigue, pain, insomnia..)

◼ Auto-immune diseases: Lupus (SLE), Rheumatoid
arthritis (RA), Multiple Sclerosis

◼ Neurological problems: memory and concentration
problems, headaches, resistant pain syndromes,
dementia…

◼ Psychiatric issues: depression and anxiety, OCD,
psychotic reactions and schizophrenia, Tourettes..

◼ Pachner AR. Neurologic manifestations of Lyme disease, the new “great imitator.” Rev Infect Dis.
1989;11 Suppl 6: S1482–1486.

What is the Common Denominator?

◼ CFS, FM, AI disorders, Neuropsychiatric disorders
and Lyme-MSIDS all share certain common clinical
features: fatigue, widespread joint and muscle pain,
memory/concentration problems, sleep and mood
disorders, +/- dysautonomia

◼ Due to an underlying inflammatory process and
cytokine production: often assoc. with the “3 I’s”

◼ The “Sickness Syndrome” is due to ↑ production of TNF-
alpha, IL-1, IL-6 & other inflammatory
cytokines/chemokines. How can we tell if its Lyme?

◼ Glassford, J. The Neuroinflammatory Etiopathology of Myalgic Encephalomyelitis/Chronic Fatigue
Syndrome (ME/CFS). Front. Physiol., 17 February 2017

Six Signs That Your Aches and Pains
May be Due to Lyme Disease

◼ 1. You have more than one symptom: Lyme

disease is a multisystemic illness. Classic constellation of
symptoms: fatigue, pain, insomnia, cognitive problems,
depression..

◼ 2. Symptoms c + g with good & bad days

◼ 3. Your pain migrates around your body

(migratory joint, muscle & nerve pains that come and go
and migrate are classic for Lyme!)

◼ Rebman A., et al. The Clinical, Symptom, and Quality-of-Life Characterization of a Well-Defined Group of
Patients with Posttreatment Lyme Disease Syndrome. Front. Med. 4:224. 14 Dec 2017

Six Signs that Your Aches and Pains
may be due to Lyme Disease

◼ 4. Women: symptoms tend to worsen right
before, during, and after the menstrual cycle

(hormonal changes affect symptoms)

◼ 5. Symptoms worsen or improve after
antibiotic therapy (for Lyme or an unrelated infection

like a urinary tract infection). Worsening of symptoms: ?
Herxheimer reaction (JH reaction), killing off of spirochetes
with inflammatory cytokine release: TNF-alpha, IL-1, IL-6, 8

◼ Kaplanski G, Granel B, Vaz T, Durand JM (July 1998). "Jarisch–Herxheimer reaction complicating the
treatment of chronic Q fever endocarditis: elevated TNFalpha and IL-6 serum levels". J. Infect. 37 (1):
83–4.

Six Signs that Your Aches and Pains
may be due to Lyme Disease

◼ 6. You have positive blood tests for Lyme and
associated tick-borne diseases

◼ The tests are not reliable (ELISA, Western blot)

◼ Different strains of Borrelia: →Borrelia burgdorferi ss, B.

mayonii. B. bisettii (USA, Europe, North Africa), Borrelia afzelii
(Europe, Asia) Borrelia garinii (Europe, Asia, North Africa), Borrelia
valaisiana, Borrelia lusitaniae (Portugal, Italy, North Africa):
vasculitis, Borrelia spielmanii (Holland, Germany, Hungary, Slovenia)

◼ 5 bands on the Western Blot are specific for Bb:

◼ 23 (Osp C), 31 (Osp A), 34 (Osp B), 39, 83-93

◼ Ma et al: Serodiagnosis of Lyme Borreliosis by Western Immunoblot. Jnl of Clin Microbiology, Feb. 1992,
p. 370-376; Horowitz, R.I., Freeman PR. International Journal of General Medicine 2019:12 101–119

Syndromic Surveillance

◼ HOW CAN WE ESTABLISH THE PROPER
DIAGNOSIS?

1) DO A COMPREHENSIVE HISTORY AND PHYSICAL
2) SCREEN FOR LYME AND ASSOCIATED TBD’S
3) PERFORM A BROAD DIFFERENTIAL DIAGNOSIS
(PAGES 50-64, HCIGB)

Why Can’t I Get Better? Solving the Mystery of Lyme and Chronic Disease. Dr Richard I. Horowitz. St
Martin’s Press, NYC. November 2013
How Can I Get Better? An Action Plan for Treating Resistant Lyme & Chronic Disease. Dr Richard I.
Horowitz. St Martin’s Press, NYC. February 2017
Citera M, Freeman PR, Horowitz RI. International Journal of General Medicine 2017:10 249–273.


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