10/21/2020

WHY SHOULD YOU CARE? ASSOCIATED DISEASE IN MICHIGAN

WITH AN EMPHASIS ON  Incidence –most common tick borne disease in US

LYME DISEASE  CDC est. 330,000 cases – more than Breast cancer and and HIV combined

 Great imitator – MS, Parkinson’s, Rheumatoid Arthritis, Attention Deficit Disorder, Chronic Fatigue Syndrome,

 Long term medical impact

 Economic and social impact – cost of testing, # tested, PTLD

 Our role as physicians: dx and treatment

 Satisfaction of giving someone their life back

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THE HIGH COST OF DISTRIBUTION: MICHIGAN LYME DISEASE RISK 2000 VS. 2020

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INCREASE DISTRIBUTION IN

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EARLY HISTORY RECENT HISTORY

 Europe:  1883 – atrophic rash Dr. A. Buchwald  Named ACA Acrodermatitis chronica atrophicans 1902  Arvid Afzelius 1909 ECM/Ixodes  (Garrin- Bujadoux) Bannwarth syndrome 1941  USA –  Polly Murray -1975 – 39 children, 12 adults  Allen C. Steere Investigated, published 1977  Wilhelm "Willy" Burgdorfer - 1982 isolated organism  Serology available 1983

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MY EXPERIENCE ORIGINAL CDC GUIDELINES FOR LYME 1995

 Clinical Description  A systemic, tick-borne disease with protean manifestations, including dermatologic, rheumatologic, neurologic, and cardiac abnormalities. The best clinical marker for the disease is the initial skin lesion, erythema migrans (EM), that occurs among 60%-80% of patients.  Clinical Criteria  Erythema migrans, OR  At least one late manifestation, as defined below, and laboratory confirmation of infection  Laboratory Criteria for Diagnosis  Isolation of from clinical specimen, OR  Demonstration of diagnostic levels of immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies to the spirochete in serum or cerebrospinal fluid (CSF), OR  Significant change in IgM or IgG antibody response to B. burgdorferi in paired acute- and convalescent-phase serum samples

 This surveillance case definition was developed for national reporting of Lyme disease; it is NOT appropriate for clinical diagnosis.

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ORIGINAL CDC PATIENT PRESENTATIONS UNDERSTANDING TICK ASSOCIATED DISEASE/REGIONAL TICK IDENTIFICATION

 Musculoskeletal system  Recurrent, brief attacks (weeks or months) of objective joint swelling in one or a few joints, sometimes followed by chronic arthritis in one or a few joints. Manifestations not considered as criteria for diagnosis include chronic progressive arthritis not preceded by brief attacks and chronic symmetrical polyarthritis. Additionally, arthralgia, myalgia, or fibromyalgia syndromes alone are not criteria for musculoskeletal involvement.  Nervous system  Any of the following, alone or in combination: Lymphocytic meningitis; cranial neuritis, particularly facial palsy (may be bilateral); radiculoneuropathy; or, rarely, encephalomyelitis. Encephalomyelitis must be confirmed by showing antibody production against B. burgdorferi in CSF, demonstrated by a higher titer of antibody in CSF than in serum. Headache, fatigue, paresthesia, or mild stiff neck alone are not criteria for neurologic involvement.  Cardiovascular system  Acute onset, high-grade (2nd or 3rd degree) atrioventricular conduction defects that resolve in days to weeks and are sometimes associated with myocarditis. Palpitations, bradycardia, bundle branch block, or myocarditis alone are not criteria for cardiovascular involvement.  Laboratory confirmation  As noted above, laboratory confirmation of infection with B. burgdorferi is established when a laboratory isolates the spirochete from tissue or body fluid, detects diagnostic levels of IgM or IgG antibodies to the spirochete in serum or CSF, or detects a significant change in antibody levels in paired acute- and convalescent-phase serum samples. States may determine the criteria for laboratory confirmation and diagnostic levels of antibody. Syphilis and other known causes of biologic false-positive serologic test results should be excluded when laboratory confirmation has been based on serologic testing alone.

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TICK LIFE CYCLE QUESTING

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TICK MOUTH PARTS BORRELIA SPECIES

North American European

 Borrelia burgdorferi (sensu stricto) - has been found in  Borrelia afzelii blacklegged (Ixodes scapularis) throughout North America  Borrelia garinii p

 Borrelia mayonii has been found in blacklegged ticks  Many others that don’t seem to be currently of (Ixodes scapularis) in Minnesota and Wisconsin. Borrelia mayonii is a new species and is the limited consequence for human disease and the only species besides B. burgdorferi known to cause Lyme disease in North America.  Borrelia miyamotoi transmitted by the blacklegged tick (Ixodes scapularis) and has a range similar to that of Lyme disease.

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OTHER TICK ASSOCIATED DISEASES LYME DISEASE ITSELF: PRESENTATIONS – THREE PHASES

  Alha Gal – is transmitted to humans by the lone star tick (Ambylomma Rocky Mountain spotted fever (RMSF) is transmitted by the American dog tick americanum), (Dermacentor variabilis), Rocky Mountain wood tick (Dermacentor andersoni), and the brown dog tick (Rhipicephalus sangunineus) in the U.S. The brown dog  Bourbon infection has been identified in a limited number patients in the tick and other tick species are associated with RMSF in Central and South Midwest and southern United States. At this time, we do not know if the virus America. might be found in other areas of the United States.  STARI (Southern tick-associated rash illness) is transmitted via the lone star  Colorado tick feveris caused by a virus from the Rocky Mountain wood tick tick (Ambylomma americanum), found in the southeastern and eastern U.S.  Early – ECM, fever, chills, headache, rash, fatigue, myalgia (Dermacentor andersoni). It occurs in the the Rocky Mountain states at elevations of 4,000 to 10,500 feet.  Tickborne (TBRF) is transmitted to humans through the bite of infected soft ticks –and Ornithoderis hermsi is the cause of most TBRF.  Disseminated – neuritis, paresthesia, carditis, eye, deafness, meningitis, muscle pain, arthritis/joint pain  Ehrlichiosis is transmitted to humans by the lone star tick (Ambylomma Reported in: Arizona, California, Colorado, Idaho, Kansas, Montana, Nevada, americanum), found primarily in the southcentral and eastern U.S. New Mexico, Ohio, Oklahoma, Oregon, Texas, Utah, Washington, and Wyoming. Associated with rustic cabins and vacation homes.  Late - Neuroborreliosis, arthritis Bell’s palsy or other cranial neuritis, encephalomyelitis, lymphocytic  Heartland virus cases have been identified in the Midwestern and southern United States. Studies suggest that Lone Star ticks can transmit the virus.  is transmitted by the dog tick (Dermacentor variabilis), the wood tick meningitis, radiculoneuropathy, 2nd/3rd degree atrioventricular block, psychiatric symptoms, CFS (myalgic Unknown if the virus is in other areas of the U.S. (Dermacentor andersoni), and the lone star tick (Amblyomma americanum). Tularemia occurs throughout the U.S. encephalomyelitis), Fibromyalgia, fatigue, neurocognitive  Powassan disease is transmitted by the blacklegged tick and the groundhog tick (Ixodes cookei). Reported primarily from northeastern states and Great  364D rickettsiosis ( phillipi, proposed) is transmitted to humans by Lakes region. the Pacific Coast tick (Dermacentor occidentalis ticks). This is a new disease that has been found in California.  Rickettsia parkeri rickettsiosis is transmitted to humans by the Gulf Coast tick (Amblyomma maculatum).

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FREQUENCY OF ECM APPEARANCE

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DIFFERENTIAL DX OF THE RASH– AT LEAST THINK ABOUT IT

Tinea Incognito Misdiagnosed as Erythema Rash Migrans  Stari ACA-ACRODERMATITIS  Ringworm CHRONICA ATROPHICANS  Cellulitis

 Other insect bites

 Granuloma annulari

 Nummular eczema

 Chemical irritants

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MIGRATORY LARGE JOINT ARTHRALGIAS CLINICAL PRESENTATIONS – THE GREAT IMITATOR

Includes:  Migratory arthralgia/arthritis

 Focal Neuropathy including cranial neuropathy, Uveitis, Optic neuritis  Post infectious arthritis  Cardiac arrhythmias  Strep  Neurological signs and symptoms including psychiatric, depression, psychosis, confusion, ADD, Memory loss, word loss  Chlamydia

 Neuromuscular problems – Parkinson’s, stiff man syndrome, gegenhalten, CFS,  Mycoplasma Fibromyalgia  Hepatitis C

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NEUROLOGICAL MANIFESTATIONS OF L.B. (FRONT. MED., 23 JULY 2020) FOCAL NEUROPATHY

Includes

 Vasculitis

 Coagulopathies

 Toxins

 Connective tissue disorders

 Structural anomalies

 Metabolic disorders

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LAB DIAGNOSIS EHRLICHIA STAIN

If it imitates everything, how do we diagnose?

 A. Special media– Barbour Stoenner Kelly

 B. PCR –blood, CSF, joint fluid

 C. Serology,

 Immunfloroassay IFA

 Immunoblot testing.  D. Urine antigen

 E. Gen laboratory is not helpful

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STATS

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CURRENT RECOMMENDATIONS 2019 SPECIFICITY V SENSITIVITY SPECIFICITY V SENSITIVITY- Current recommendations: serologic assays that utilize 1-2 EIA only rather than western Two-test methodology uses an ELISA sensitive immunoblot assay in a two-test format for the enzyme immunoassay (EIA) or  VS laboratory diagnosis of Lyme disease  STTT/MTTT range 38-58%, immunofluorescence assay as a first test,  Acute has sensitivity of 38-58% followed by a western immunoblot assay for Rash only – specimens yielding positive or equivocal Early disease -  Convalescent 27-89%  Noncutaneous manifestions 87-100% results Neurologic or cardiac disease –  Neuritis or Carditis 73-100 % sensitivity Post treatment Lyme disease - controversial  PERCENTAGE SPECIFICITY 98-100 %

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4918152/

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LAB TESTS THAT ARE NOT RECOMMENDED EXCLUSIONARY DIAGNOSIS

 Connective tissue diseases  Syphilis  Hep C, EBV, CMV  Toxoplasmosis  Mycoplasma, Chlamydia  Nutritional, Electrolyte Disorders  Chemical/Industrial Exposures – radiation toxicity?  Invasive fungal infections  Coagulopathies

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RADIOLOGIC TESTING, MRI ETC. EKG

 Lyme can infect all parts of the heart

 Cardiac death is rare.2

 Oct 7 2019https://doi.org/10.1148/rg.2019190020

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ALTERNATIVE SCHEDULE SOME CDC GUIDELINES FOR TREATMENT

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TREATMENT – WHAT I DO AND WHY

 What I do and why:

 Tick only –

 Rash only –

 Early disease-

 Neurologic and cardiac disease

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CONTROVERSIAL ASPECTS

 Duration of therapy

 Choice of therapy

 Ancillary therapies

 Persistence

 CDC Guidelines

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ALPHA GAL SYNDROME (AGS) (aka alpha-gal allergy, red meat allergy, or tick bite meat allergy) is serious, potentially life-threatening allergic reaction. INTERESTING ASSOCIATIONS –

 Alpha-gal (galactose-α-1,3-galactose) is a sugar molecule found in most mammals. AGS reactions can include: •Rash/Hives  Not normally found in fish, reptiles, birds, or people. •Nausea or vomiting  NEUROLOGIC ENTITIES: ALS, ALZHEIMERS, MS, PARKINSONS •Difficulty breathing  Found in products made from mammals (including •Drop in blood pressure  GEGENHALTEN some medications, cosmetics, vaccines, gelatin, •Dizziness or faintness  HEMATOLOGICAL DISORDERS, THROMBOCYTOPENIA and milk products). •Severe stomach pain •Symptoms commonly appear 3-6 hours after eating  PSYCHIATRIC DISEASES  Molecule found in the saliva of Lonestar tick and meat or exposure to products containing alpha-gal (for occasionally ixodes. example, gelatin-coated medications).  ALPHA GAL (NEXT SLIDE) •AGS reactions range from mild to severe or even life-  We have cases in Michigan. threatening. •People may not have an allergic reaction after every alpha-gal exposure.

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MORE CONTROVERSIAL ASPECTS ILADS V IDSA

 Institutional Guidelines for Diagnosis (including laboratories, IDSA, CDC, ILADS)

 Laboratory Issues including unapproved laboratories

 ELISA v. Western Blot

 Duration of Therapy for initial bite, late treatment – everyone agrees on the middle zone

 Biofilm and Cystic forms

 Conspiracy theories

 Vertical transmission

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KEY POINTS - SUMMARY ENDNOTES AND CITATIONS

 INCIDENCE  Tinnea Slide 1, July 6, 2000  REGIONAL NATURE OF TICKS N Engl J Med 2000; 343:69  B. BURGDOFERI SUBSETS DOI: 10.1056/NEJM200007063430116

 DEVELOPMENT OF RASH  Lyme Carditis Slide 2 References Bockenstedt LK. Lyme disease. In: Firestein GS, Budd RC, Gabriel SE, O’Dell JR, McInnes IB., eds. Kelley’s Textbook of Rheumatology, 9th ed. Philadelphia, PA: Elsevier; 2013:1815–1828. Google  3 PHASES Scholar  CLINICAL PRESENTATION – 4 PARAMETERS  https://www.cdc.gov/ticks/tickbornediseases/TickborneDiseases-P.pdf  TREATMENT  https://www.youtube.com/watch?v=Xzuwv3OkMBA – capture slides  FUTURE DIRECTIONS  https://www.cdc.gov/lyme/resources/LymeDiseaseCaseReportForm.pdf

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