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8/7/2019 Lyme Disease Black and White

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LYME DISEASE

Rheumatology Lecture Series

San Joaquin General Hospital


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a Can of Worms ?

or,

Do we just need to rationally approach this uncommon but potentially

devastating disease?

LYME DISEASE


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LYMEDISEASEBORRELIA SPECIES

SCANNING ELECTRON MICROSCOPY


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bitten them in search of blood which sustains them, and coincidentally

inoculated them with a species ofBorrelia, native to the region, which is

capable of inducing a potentially severe illness which affects the individual

in three phases if the acute event is not recognized and treated

LYMEDISEASE

THE REALITY IS THAT A TICK ON A LEAF MAY HAVE CRAWLED INTO SOMEONES

CLOTHING VIA A SLEEVE, PANT OR SHORTS CUFF


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LYME DISEASEHISTORICALPERSPECTIVE

First awareness in U.S. of the constellation of symptoms thatmay follow a tick bite in Lyme and Old Lyme, Connecticut in 1975after mothers reported to the state health department aneighborhood clustering of 50 cases of what was initially thought

to be JRA in their children Europe

1873- a German physician, Herxheimer, described a rashcalled acrodermatitis chronica atrophicans

1910- erythema migrans first attributed to a tick bite

1941- Bannworth reported an illness characterized bymeningitis, radiculitis and rheumatism

1946- successful treatment = penicillin


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LYME DISEASEDEFINITION

Cause = infection with the tick-borne spirochete Borrelia burgdorferi

(discovered in 1982)

Similar to syphilis, another spirochete vector transmitted disease, it is a

multi-system disease that occurs in stages that can mimic other diseases

Organ systems involved: skin (erythema migrans, EM, or erythema

chronicum migrans, ECM, occurring at the site of the tick bite or, fromdissemination); if the rash is not treated with antibiotics, there is a 1-5%

chance of developing cardiac manifestations, a 15% chance of

developing neurologic manifestations, and a 60% chance of developing

arthritis (50% migratory polyarthritis, 10% chronic monoarthritis)


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LYMEDISEASESYMPTOMS AND SIGNS- STAGE 1- LOCALIZED

Erythema migrans, the expanding (up to 20 cm) rash with variablecentral clearing, a dark red border and often a bullseye appearance

occurs in 70-80% of Lyme disease patients (only 50% of patients even

recall a tick bite). The rash most commonly occurs in a warm moist

area- axilla, groin, belt-line, popliteal area because the ticks prefer tofeed in a warm, moist area. EM occurs after the incubation period for

Borellia- 7-10 days after the tick bite. The rash clears after days to

weeks.

Regional lymphadenopathy may occur (25%) , leading to confusionwith tularemia.

Flu-like symptoms, headache, fatigue, arthralgias, myalgias, fever

(15%) may occur.


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LYME DISEASESYMPTOMS AND SIGNS- STAGE 2- DISSEMINATED

Begins days to months after EM and is due to hematogenous spread.

Characteristically, the central nervous system is involved.

Meningitis

Headache

Cranial neuritis, especially Bells palsy

Motor or sensory radiculoneuritis

Mononeuritis multiplex

Cardiac manifestations- varying degrees of AV block, usually

temporary, and myo- or pancarditis

Secondary skin lesions are common

Arthralgias, bursitis and tendon involvement are common and transient.

Frank arthritis is usually not prevalent until the third stage.


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LYME DISEASESYMPTOMSANDSIGNS- STAGE 3

Probably represents persistent infection

Episodic attacks of asymmetric oligoarticular arthritis in the large

joints, particularly the knee. With time, the arthritis becomes more

persistent and chronic, leading to attacks which last months ratherthan weeks.

Fatigue commonly accompanies the arthritis episodes but fever and

other systemic symptoms do not.

Chronic nervous system involvement (5%) usually is in the form ofencephalopathy affecting memory, mood and sleep and/or

peripheral sensory neuropathy


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MAJORMANIFESTATIONSOFLYME DISEASE(STEERE AC. LYME DISEASE. NEJM 1989; 321:589)

Stage 1

Localized

Stage 2

Disseminated

Stage 3

Chronic

Skin Erythema migrans Secondary annular

lesions

Acrodermatitis chronica

atrophicans

Musculoskeletal Myalgias Migratory pain in

joints, bone, muscle;

brief arthritis attacks

Prolonged arthritis attacks,

chronic arthritis

Neurologic Headache Meningitis, Bells

palsy, cranial neuritis,

radiculoneuritis

Encephalopathy,

polyneuropathy,

leukoencephalitis

Cardiac AV block,myopericarditis,

pancarditis

Constitutional Flu-like symptoms Malaise, fatigue Fatigue

Lymphatic Regional

lymphadenopathy

Regional/generalized

lymphadenopathy

System Early Late


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LYME DISEASEERYTHEMA MIGRANS


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LYMEDISEASEERYTHEMA MIGRANS


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LYMEDISEASESTAGE 2 DISSEMINATED SECONDARY ANNULAR ERYTHEMA MIGRANS


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LYMEDISEASEACRODERMATITIS CHRONICA ATROPHICANS

LATE, STAGE 3 CHRONIC SKIN MANIFESTATION


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LYMEDISEASESKIN BIOPSYUPPER DERMAL PERIVASCULAR MONONUCLEAR INFILTRATES

(NONSPECIFIC & NONDIAGNOSTIC)


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LYMEDISEASEARTHRITIS LEFT > RIGHT KNEE


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LYMEDISEASENEUROBORRELIOSISUS FOREST WORKER WITH HISTORY OF PREVIOUSLY TREATED LYME DISEASE

AND MORE RECENT TICK BITES FOR WHICH HE WAS NOT TREATED


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LYMEDISEASECHRONIC NEUROBORRELIOSISEUROPEAN PATIENT FROM GERMANY


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LYMEDISEASEENCEPHALITIS

WHITE MATTER CHANGES- MRI


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LYMEDISEASEOPHTHALMOLOGIC

Conjunctivitis

Iritis

Choroiditis


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LYME DISEASE

Lyme disease is the most common vector-borne disease in the U.S.and the second most common in the world (malaria is #1)

Of the three pathogenic species of Borrelia, only one, B. Burgdorferi,occurs in North America, while all three species occur in Europe

The arthropod vector first identified, Ixodes scapularis (previouslycalled I. dammini) occurs in the northeast and midwest U.S. Up to50% of ticks are infected in endemic areas. On the West Coast,Ixodes pacificus is the vector and its most common host is the lizard

(which is not a very good reservoir for Borrelia)

Other Ixodid species are vectors in other parts of the world: I. ricinusin Europe, I. persculatis in Russia and Asia. Small and large mammalsare the generally preferred hosts

LYME DISEASE


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LYMEDISEASEBORRELIA BURGDORFERI, A SPIROCHETEDARKFIELD MICROSCOPY, 400 X

LYME DISEASE


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LYMEDISEASEMULTIPLE BORRELIA SPIROCHETES-

SCANNING ELECTRON MICROSCOPY, 7-10,000 X

LYME DISEASE


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LYMEDISEASEDORSAL AND VENTRAL ASPECTS IXODES TICK

LYME DISEASE


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LYME DISEASENORMALAND ENGORGED IXODES TICKS


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LYMEDISEASELIFE CYCLE OF IXODES


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LYME DISEASE


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LYMEDISEASELIFE CYCLE OF THE TICK (IXODES)

In spring, eggs which were laid in the leaf clutter of the forest floorhatch into larvae

During the summer, the larvae feed on asymptomatic reservoir mice,squirrels, racoons, rabbits, chipmunks, shrews and opposums.

If the host is infected with Borellia, this is when they acquire thespirochete

In the fall the larvae mature into nymphs which then hibernate overwinter

In spring and summer the nymphs become active again, preferring tofeed on mice.

It is during the nymphal stage that the tick is most likely to infecthumans

At the end of the life cycle the female tick lays eggs and dies

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LYMEDISEASELIFE CYCLE OF THE TICK (IXODES)

The adult female tick attaches to a deer in the region of the shoulder(I. Scapularis) and feeds on blood such that eggs may be produced.The eggs are not infected with Borellia even if the female tick is. Thedeer does not remain infected with Borellia.

Hosts

Dogs, cats, cattle, horses and other domestic animals may alsoexhibit a variety of signs, including fever and lameness. (In

endemic areas, Lyme disease is a common cause of lameness indogs.)

Wild animals such as deer, racoons, and mice show no signs andapparently suffer no ill effects from the disease.


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LYMEDISEASEEPIDEMIOLOGY- CALIFORNIA

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LYMEDISEASEEPIDEMIOLOGY

Most prevalent: April - November

Peak incidence: late Spring and early Summer months- June and July

Reported in all 48 contiguous states, but most common in threeregions:

Northeast coast between Massachusetts and Maryland

Midwest in Wisconsin and Minnesota

Western coast of northern California and Oregon

The disease also occurs in Europe, Scandinavia, China, Japan, othercountries in Asia, and Australia

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LYMEDISEASEDIAGNOSIS

Erythema migrans is diagnostic for Lyme disease but does notoccur in 30% of infected individuals

Usual symptoms of early disease, fever, fatigue, headache,myalgias and arthralgias are too nonspecific to be diagnostic

Although Borreliaburgdorferihas been isolated from blood, skinand CSF, this is a low yield procedure and is not recommended

Serologic tests are used most commonly for diagnosis of Lymedisease

Unfortunately, most currently available tests are unable to detectearly antibody responses to Bb, which may take up to two monthsto develop Thus the diagnosis of early Lyme disease in a patientwithout erythema migrans can be difficult

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LYMEDISEASEDIAGNOSIS (CONTD)

With serologic tests, false positive results may occur due to cross-reacting antibodies against other bacteria, especially T.pallidum andother spirochetes, ie. Ehrlichia, T. denticola. Also, patients withconnective tissue disorders or certain acute viral infections (EBV, CMV,parvovirus) may demonstrate false positive serologic results

If patients are carefully screened for symptoms compatible with Lymedisease and epidemiologic factors are considered, positive predictivevalue of serologic tests is quite acceptable

Interlaboratory differences in substrate antigens, in antigen preparation

and interpretive criteria compound problems of validity To improve sensitivity and specificity of serodiagnosis of Lyme disease

1) Perform a sensitive screening test: IF or ELISA

2) Equivocal and positive test results should be further analyzed by

Western blot technique

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LYMEDISEASEDIAGNOSIS (CONTD)

4 weeks from symptom onset, check both IgM and IgG

> 4 weeks from symptom onset, check only IgG

If first test is negative and symptoms of early Lyme

disease are present, test again after 2-4 additional weeks

LYME DISEASE


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LYMEDISEASEDIAGNOSIS- WESTERN BLOT


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LYMEDISEASEDIAGNOSIS- WESTERN BLOT

Duration of disease Isotype tested Bands to be considered

First few weeks of infection IgM 2 of the following 8: 18, 21, 28, 37,

41, 58, 93or

2 of 3: ospC (23, 39, 41

After first weeks of infection IgG 5 of the following 10: 18, 21, 28, 30,39, 41, 45, 58, 66, 93

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LYMEDISEASETREATMENT

Early localized disease (1 day 1 month after the tick

bite; mean, 7-10 days)

Doxycycline 10 - 21 days (not in children or

pregnant women)

Amoxicillin, cefuroxime- 14 - 21 days

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Early disseminated disease (days-10 months after tick bite)

Neurologic or cardiac features- ceftriaxone, cefotaxime IV 2 4weeks

Heart block

Resolves in most people within several weeks May require a temporary pacemaker

Facial palsy

LP normal- oral doxycycline CSF suggestive of Lyme disease- IV as above

Meningitis

IV ceftriaxone or cefotaxime, 10 28, (usually 14) days

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LYME DISEASETREATMENT

Late Lyme disease (months-years after tick bite)

Arthritis- PO 28 days, IV recommended only if the arthritis does notimprove after oral therapy (In some adults and children, arthritispersists after antibiotic therapy) For lingering arthritis, suggesthydroxychloroquine and/or synovectomy

Neurologic condition- IV ceftriaxone or cefotaxime, 2 4 weeks

No treatment required

Post-Lyme disease Syndrome- headache, fatigue, arthralgias-additional antibiotics- no benefit

Chronic Lyme disease- pain, fatigue, difficulty thinking clearly- noevidence for active infection

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Pearls

1) After being infected and treated for early Lyme disease, it is

possible to become infected with Lyme disease again

2) Late Lyme disease- there, as yet, has never been a case of

re-infection in someone who has been treated for this stage ofdisease

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