LYME DISEASE

Epidemiology

Clinical Manifestations

Differential Diagnosis

Diagnosis

Treatment

Prevention

EPIDEMIOLOGY

Caused by spirochete Borrelia burgdorferi

Transmitted by Ixodes ticks

Nymph-stage ticks feed on humans May through July - transmit spirochete

Endemic areas

Northeastern coastal states

Wisconsin & Minnesota

Coast of Oregon & northern California

Slide 3

Slide 4

EPIDEMIOLOGY (cont)

> 2 of dear ticks carry spirochete

Rising frequency attributed to enlarging deer population & concurrent suburbanization

High risk areas - wooded or brushy, unkempt grassy areas & fringe of these areas

Lower risk on lawns that are mowed

MAJOR RISK FACTORS

Geographical

Northeast, north-central (Wisconsin, Minnesota) coastal regions of California & Oregon

Occupational

Landscaper, forester, outdoor

Recreational

hiking, camping, fishing, hunting

CLINICAL MANIFESTATIONS

Stage 1 - Acute, localized disease

Stage 2 - Subacute, disseminated disease

Stage 3 - Chronic or late persistent infection

ACUTE INFECTION

Tick must have been feeding for at least 24-48 hrs

Erythema migrans develops 1 to 4 weeks after bite

Without treatment rash clears within 3 to 4 weeks

About 50% of pts will also c/o flulike illness - fever, H/A, chills, myalgia

DISSEMINATED DISEASE

May develop in wks to mos in untreated pts

Symptoms usually involve skin, CNS, musculoskeletal system, & cardiac

Dermatological manifestations

new skin lesions, smaller and less migratory than initial

Erythema and urticaria have been noted

DISSEMINATED (cont)

Neurologic complications

Occurs wks to mos later in about 15% to 20% of untreated

Symptoms

Lyme meningitis

mild encephalopathy

unilateral or bilateral Bell’s palsy

peripheral neuritis

Slide 11

DISSEMINATED (cont)

Musculoskeletal symptoms

Symptoms evolve into frank arthritis in up to 60% of untreated pts

Onset averages 6 mos from initial infection

Symptoms

migratory joint, muscle, & tendon pain

knee most common site

no more than 3 joints involved during course

lasts several days to few weeks then joint returns to normal

DISSEMINATED (cont)

Cardiac involvement

Noted in about 5% to 10% beginning several wks after infection

Transient heart block may be consequence

Range from asymptomatic to first-degree heart block to complete

Cardiac phase lasts from 3 to 6 wks

CHRONIC - LATE PERSISTENT

Follows latent period of several mos to a yr after initial infection

60% to 80% will have musculoskeletal complaints

Most common; arthritis of knee - may also occur in ankle, elbow, hip, shoulder

CHRONIC (cont)

Neurologic impairment

distal paresthesias

radicular pain

memory loss

fatigue

NATURAL HISTORY

Without treatment will see disseminated disease in about 80% of pts

Oligoarthritis - 60% to 80%

Chronic neurologic & persistent joint symptoms - 5% to 10%

Slide 17

CONCURRENT INFECTIONS

Human babesiosis

fever, chills, sweats, arthralgias, headache, lassitude

pts with both appear to have more severe Lyme disease

Ehrlichiosis

described as “rashless Lyme disease”

high fever & chills & may become prostrate in day or two

DIFFERENTIAL DIAGNOSIS

Acute & early disseminated stages

Rocky Mountain spotted fever

human babiosis

summertime viral illnesses

viral encephalitis

bacterial meningitis

DIFFERENTIAL (cont)

Late disseminated & chronic stages

gout

pseudogout

Reiter’s syndrome, psoriatic arthritis, ankylosing spondylitis

rheumatoid arthritis

depression

fibromyalgia

chronic fatigue syndrome

DIAGNOSIS

Clues to early disease

EPIDEMIOLOGIC

travel or residence in endemic area within past month

h/o tick bite (especially within past 2 weeks)

late spring or early summer (June, July, August)

EARLY DISEASE (cont)

RASH

expanding lesion over days (rather than hours or stable over months)

central clearing or target appearance

minimal pruritis or tenderness

central papular erythema, pigmentation, or scaling at sit of tick bite

lack of scaling

location at sites unusual for bacterial cellulitis (usually axillae, popliteal fossae, groin, waist

Slide 23

Slide 24

EARLY DISEASE (cont)

ASSOCIATED SYMPTOMS

fatigue

myalgia/arthralgia

headache

fever and/or chills

stiff neck

respiratory & GI complaints are infrequent

EARLY DISEASE (cont)

PHYSICAL EXAM

Regional lymphadenopathy

Multiple erythema migrans lesion

Fever

DISSEMINATED DISEASE

Clinical presentation can make diagnosis

epidemiological inquiry

review of key historic features

physical findings

serum for antibody testing

spinal tap

LATE DISEASE

Careful attention to musculoskeletal & neurologic symptoms

Differentiating Lyme from fibromyalgia & CFS

oligoarticular musculoskeletal complaints that include signs of joint inflammation

limited & specific neuro deficits

abnormalities of CFS

absence of disturbed sleep, chronic H/A, depression, tender points

ANTIBODY TESTING

Testing with ELISA is not required to confirm diagnosis

Pts with objective clinical signs have high pretest probability of disease

Tests are not sensitive in very early disease

Should not use is pt without subjective symptoms of Lyme

TESTING(cont)

A + test in person with low probability of disease risks false + rather than true +

Test when pts fall between these two extremes

pt with lesion or symptoms without known endemic exposure (new area)

pretest probability now has high sensitivity & specificity

TESTING (cont)

For a positive or equivocal ELISA or IFA CDC recommends Western blot

Testing cannot determine cure as pt remains antibody +

PCR is being developed - still considered investigational

TREATMENT

Early Lyme disease

doxycycline, 100 mg BID for 21 to 18 days

amoxicillin, 500 mg TID for 21 to 28 days

cefuroxime, 500 mg BID for 21 days

PREVENTION

Wear light-colored clothes - easier to spot tick

Wear long pants, long sleeves

Use tick repellent, such as permethrin, on clothes

Use DEET on skin

Check for ticks after being outside

Remove ticks immediately by head

VACCINATION

NO LONGER AVAILABLE

WEST NILE VIRUS

Summer 1999 - first detected in NYC & Western hemisphere

59 hospitalized - epicenter Queens - 7 died

Summer 2000 - epicenter Staten Island - 19 hospitalized - 2 died

For 2002 - 39 states, 3737 confirmed cases, 214 deaths

INFECTIOUS AGENT

Member of family Filaviviridae

Belongs to Japanese encephalitis complex

Before 1999 outbreaks seen only in Africa, Asia, Middle East, rarely Europe

Reservoir & Mode of transmission

wild birds primary reservoir & Culex spp. major mosquito vector

INCUBATION PERIOD/SYMPTOMS

Incubation usually 6 days (range 3-15)

Symptoms

milder: fever, headache, myalgias, arthralgias, lymphadenopathy, maculopapular or roseolar rash affecting trunk & extremities

occasionally reported: pancreatitis, hepatitis, myocarditis

CNS involvement rare & usually in elderly

TREATMENT

No known effective antiviral therapy or vaccine

Intensive supportive in more severe cases

DIFFERENTIAL DIAGNOSIS

Enteroviruses

Herpes simplex virus

Varicella

TESTING

Lab conformation based on following criteria:

isolating West Nile virus from or demonstrating viral antigen or genomic sequences in tissue, blood, CSF, or other body fluid

demonstrating IgM antibody to West Nile virus in CSF by ELISA

demonstrating 4-fold serial change in plaque reduction neutralization test (PRNT) antibody to West Nile virus in paired, acute & convalescent serum samples

demonstrating both West Nile virus-specific IgM & IgG antibody in single serum specimen using ELISA & PRNT

"Must report suspected cases of..."

Must report suspected cases of West Nile to the NYC Department of Health

During business hours call Communicable Disease Program (212) 788-9830

At all other times call Poison Control Center - (212) 764-7667

INFECTIOUS MONONUCLEOSIS

Infectious mononucleosis - designates the clinical syndrome of prolonged fever, pharyngitis, lymphadenopathy

Epstein-Barr virus-associated infectious mononucleosis (EBV-IM)

non Epstein-Barr virus-associated infectious mononucleosis (non-EBV-IM)

approximately 10-20% have

EPIDEMIOLOGY

>90% of adults have serologic evidence of prior EBV infection

Mean age of infection varies

In US 50% of 5-year-old children & 50-70% of first-year college students have evidence of prior infection

Infection in children most prevalent amongst lower socioeconomic

15-19 - peak rate of EBV-IM

"Chance of acute EBV infection..."

Chance of acute EBV infection leading to IM with age

Good sanitation & uncrowded living conditions risk of EBV-IM

OTHER CAUSES OF IM

CMV

Human herpesvirus 6

HIV

Adenovirus

Toxo

Corynebacterium diptheriae

Hep A

Rubella

Coxiella burnetii

CLINICAL MANIFESTIONS

Classic triad - fever, pharyngitis, lymphadenopathy

Prodrome- malaise, anorexia, fatigue, headache, fever

Symptoms usually peak 7 days after onset & ¯ over next 1-3 wks

Splenic enlargement - 41-100%

"Less common clinical features"

Less common clinical features

upper airway compromise

abdominal pain

rash (ampicillin risk of)

hepatomegaly

jaundice

eyelid edema

DIAGNOSTIC TESTING

Serologic test for heterophil antibodies

Percentage with antibodies higher > 4yrs old

% of persons who are + at 1 week varies with test (1 study - 69% + at 1 wk; 80% + by 3 wks)

False +s rare

"If heterophil antibody continues neg..."

If heterophil antibody continues neg & still suspect;

serum for viral capsis antigen (VCA) IgG & IgM & for EBV nuclear antigen (EBNA) IgG

VCA antibodies + in many at onset

LABORATORY ABNORMALITIES

Total leukocyte count

usually > 50% of total leukocytes consist of lymphocytes

possible mild thrombocytopenia

LFTs - 2-3-fold

abnormalities on UA

IM IN OLDER ADULTS

3-10% of persons >40 are susceptible

Presenting S & S different

Fever present but few have pharyngitis & lymphadenopathy

Jaundice in >20%

R/O; hepatobiliary disease, neoplasms, collagen vascular diseases, bacterial infections

MANAGEMENT

Supportive

NSAIDs or tylenol - no ASA

Bedrest during febrile stage

If have splenomegaly avoid vigorous activity for 3-4 wks

No evidence that steroids or antivirals are of benefit

CHRONIC FATIGUE SYNDROME

Has been called: chronic EBV syndrome, postviral fatigue syndrome, “yuppie flu”

1988 CDC convened researchers & clinicians to define & classify CFS

1994 international group proposed guidelines for CFS

CDC reported prevalence of 4-11 cases/100,000 population

In US most cases occur in young to middle-aged white women

ETIOLOGY

No cause identified

Postulated

infective

neuromuscular

immunologic

neurologic

psychiatric

DIAGNOSTIC CRITERIA (PER CDC)

Fatigue criteria

Must not be lifelong

Must be persistent, relapsing & unexplained

Must not be result of ongoing exertion & cannot be relieved by rest

"Symptom Criteria"

Symptom Criteria

Sore throat

Short-term memory or concentration impairment

Tender cervical or axillary lymph nodes

Headaches of a new type, pattern, or severity

Unrefreshing sleep

Postexertional malaise lasting > 24 hrs

Multijoint pain without joint swelling or inflammation

Muscle pain

"Exclusion Criteria"

Exclusion Criteria

Past or current diagnosis of major depression with psychotic or melancholic features, bipolar disorder, schizophrenia, delusional disorders, dementia, bulimia nervosa, anorexia nervosa

Active medical conditions

Previously diagnosed conditions with unclear resolution (malignancies, hepatitis B or C)

Alcohol or substance abuse within 2 yrs of onset of fatigue

Severe obesity (BMI ³ 45)

"Detailed medical history"

Detailed medical history

Complete physical

Labs

CBC

ESR

TSH

UA

Serum chem for electrolytes, BUN, cr, glucose, calcium, phosphorus, alk phos, total protein, albumen, globulin, LFTs

MANAGEMENT

Goal: Restore pts occupational & social functioning & prevent further disability.

Guidelines

Establish diagnosis

Prevent further disability

If indicated, start medication ASAP

Warn about unproven therapies

Initiate psychological intervention

PHARMACOTHERAPY

Antivirals

Immunomodulators

Psychotropic agents

Pain medications

Antiallergy medications

Acetylcholinesterase inhibitors

Agents used in alternative medicine

NONPHARMACOLOGIC TREATMENT

Exercise

Cognitive behavior therapy

Self-help groups

Work as therapeutic modality

DIFFERENTIAL

Fibromyalgia

Endocrine

Chronic viral infections

Malignancy

Sleep disorders causing fatigue

Connective tissue diseases

Body weight changes

Side effects of medications

Other illnesses

PSYCHIATRIC CONDITIONS EXCLUDING CFS DIAGNOSIS

Major depressive episodes

Anxiety disorders

Delusional disorders

Bipolar disorder

Schizophrenia

Eating disorders

Dementias

Sleep disorders

Substance use disorders

HERPES ZOSTER

Represents reactivation of varicell-zoster virus

Latently resides in a dorsal root or cranial nervie ganglia

Multiple erythematous plaques with clustered vesicles

Vesicles begin to dry & crust in 7-10 days, clear within 2-3 wks, new may continue to appear for up to 1 wk

COMMON DISTRIBUTION

Thoracic dermatome 50%

Cervical dermatome 20%

Trigeminal dermatome 15%

Lumbosacral dermatome 10%

PRESENTATION/DIAGNOSIS

Prodrome

Vesicular rash

Diagnosis - presentation

Slide 67

Slide 68

POTENTIAL COMPLICATIONS

Trigeminal dermatome

may affect second branch associated with involvement of eye

keratitis, uveitis, secondary glaucoma, iridocyclitis

Ramsay-Hunt syndrome

affects facial & auditory nerves

facial palsy with cutaneous zoster of external ear or TM, with associated tinnitus, vertigo, &/or hearing loss

TREATMENT

Early treatment

within 48-72 hrs

Acyclovir (Zovirax)

800mg 3x/day

Valacyclovir (Valtrex)

1,000mg 3x/day

Famciclovir (Famvir)

500mg 3x/day

POSTHERPETIC NEURALGIA

Famvir and Valtrex ¯ incidence

Capsaicin cream (Zostrix 0.025% & Zostrix HP 0.075%) 4x/day

Amitriptyline

Gabapentin

Often remits spontaneously after 6 months

Pain referral


	Epidemiology
	Clinical Manifestations
	Differential Diagnosis
	Diagnosis
	Treatment
	Prevention


	Caused by spirochete Borrelia burgdorferi
	Transmitted by Ixodes ticks
	Nymph-stage ticks feed on humans May through July - transmit spirochete
	Endemic areas
		Northeastern coastal states
		Wisconsin & Minnesota
		Coast of Oregon & northern California


	> 2 of dear ticks carry spirochete
	Rising frequency attributed to enlarging deer population & concurrent suburbanization
	High risk areas - wooded or brushy, unkempt grassy areas & fringe of these areas
	Lower risk on lawns that are mowed


	Geographical
		Northeast, north-central (Wisconsin, Minnesota) coastal regions of California & Oregon
	Occupational
		Landscaper, forester, outdoor
	Recreational
		hiking, camping, fishing, hunting



	Stage 1 - Acute, localized disease

	Stage 2 - Subacute, disseminated disease

	Stage 3 - Chronic or late persistent infection


	Tick must have been feeding for at least 24-48 hrs
	Erythema migrans develops 1 to 4 weeks after bite
	Without treatment rash clears within 3 to 4 weeks
	About 50% of pts will also c/o flulike illness - fever, H/A, chills, myalgia


	May develop in wks to mos in untreated pts
	Symptoms usually involve skin, CNS, musculoskeletal system, & cardiac
	Dermatological manifestations
		new skin lesions, smaller and less migratory than initial
		Erythema and urticaria have been noted


	Neurologic complications
	Occurs wks to mos later in about 15% to 20% of untreated
	Symptoms
		Lyme meningitis
		mild encephalopathy
		unilateral or bilateral Bell’s palsy
		peripheral neuritis


	Musculoskeletal symptoms
	Symptoms evolve into frank arthritis in up to 60% of untreated pts
	Onset averages 6 mos from initial infection
	Symptoms
		migratory joint, muscle, & tendon pain
		knee most common site
		no more than 3 joints involved during course
		lasts several days to few weeks then joint returns to normal


	Cardiac involvement
	Noted in about 5% to 10% beginning several wks after infection
	Transient heart block may be consequence
	Range from asymptomatic to first-degree heart block to complete
	Cardiac phase lasts from 3 to 6 wks



	Follows latent period of several mos to a yr after initial infection
	60% to 80% will have musculoskeletal complaints
	Most common; arthritis of knee - may also occur in ankle, elbow, hip, shoulder



	Neurologic impairment
		distal paresthesias
		radicular pain
		memory loss
		fatigue



	Without treatment will see disseminated disease in about 80% of pts
	Oligoarthritis - 60% to 80%
	Chronic neurologic & persistent joint symptoms - 5% to 10%


	Human babesiosis
		fever, chills, sweats, arthralgias, headache, lassitude
		pts with both appear to have more severe Lyme disease
	Ehrlichiosis
		described as “rashless Lyme disease”
		high fever & chills & may become prostrate in day or two



	Acute & early disseminated stages
		Rocky Mountain spotted fever
		human babiosis
		summertime viral illnesses
		viral encephalitis
		bacterial meningitis


	Late disseminated & chronic stages
		gout
		pseudogout
		Reiter’s syndrome, psoriatic arthritis, ankylosing spondylitis
		rheumatoid arthritis
		depression
		fibromyalgia
		chronic fatigue syndrome



Clues to early disease
	EPIDEMIOLOGIC
		travel or residence in endemic area within past month
		h/o tick bite (especially within past 2 weeks)
		late spring or early summer (June, July, August)


		RASH
			expanding lesion over days (rather than hours or stable over months)
			central clearing or target appearance
			minimal pruritis or tenderness
			central papular erythema, pigmentation, or scaling at sit of tick bite
			lack of scaling
			location at sites unusual for bacterial cellulitis (usually axillae, popliteal fossae, groin, waist



		ASSOCIATED SYMPTOMS
			fatigue
			myalgia/arthralgia
			headache
			fever and/or chills
			stiff neck
			respiratory & GI complaints are infrequent



		PHYSICAL EXAM

			Regional lymphadenopathy

			Multiple erythema migrans lesion

			Fever



	Clinical presentation can make diagnosis
		epidemiological inquiry
		review of key historic features
		physical findings
		serum for antibody testing
		spinal tap


	Careful attention to musculoskeletal & neurologic symptoms
	Differentiating Lyme from fibromyalgia & CFS
		oligoarticular musculoskeletal complaints that include signs of joint inflammation
		limited & specific neuro deficits
		abnormalities of CFS
		absence of disturbed sleep, chronic H/A, depression, tender points


	Testing with ELISA is not required to confirm diagnosis
	Pts with objective clinical signs have high pretest probability of disease
	Tests are not sensitive in very early disease
	Should not use is pt without subjective symptoms of Lyme


	A + test in person with low probability of disease risks false + rather than true +
	Test when pts fall between these two extremes
		pt with lesion or symptoms without known endemic exposure (new area)
		pretest probability now has high sensitivity & specificity



	For a positive or equivocal ELISA or IFA CDC recommends Western blot
	Testing cannot determine cure as pt remains antibody +
	PCR is being developed - still considered investigational



	Early Lyme disease
		doxycycline, 100 mg BID for 21 to 18 days
		amoxicillin, 500 mg TID for 21 to 28 days
		cefuroxime, 500 mg BID for 21 days


	Wear light-colored clothes - easier to spot tick
	Wear long pants, long sleeves
	Use tick repellent, such as permethrin, on clothes
	Use DEET on skin
	Check for ticks after being outside
	Remove ticks immediately by head


	Summer 1999 - first detected in NYC & Western hemisphere
	59 hospitalized - epicenter Queens - 7 died
	Summer 2000 - epicenter Staten Island - 19 hospitalized - 2 died
	For 2002 - 39 states, 3737 confirmed cases, 214 deaths


	Member of family Filaviviridae
	Belongs to Japanese encephalitis complex
	Before 1999 outbreaks seen only in Africa, Asia, Middle East, rarely Europe
	Reservoir & Mode of transmission
		wild birds primary reservoir & Culex spp. major mosquito vector


	Incubation usually 6 days (range 3-15)
	Symptoms
		milder: fever, headache, myalgias, arthralgias, lymphadenopathy, maculopapular or roseolar rash affecting trunk & extremities
		occasionally reported: pancreatitis, hepatitis, myocarditis
		CNS involvement rare & usually in elderly