Tick Talk: What’s new in Lyme Disease

May 5th, 2017

Cristina Baker, M.D., M.P.H.

Dr. Baker indicated no potential conflict of interest to this presentation. She does not intend to discuss any unapproved/investigative use of a

commercial product/device.

Disclosures

• None

Objectives1. Outline approaches early vs late-stage disease

2. Discuss prophylaxis following tick bites

3. Review how to monitor after treatment

Distribution of the Blacklegged tick, Ixodes scapularis that transmits Lyme Disease

cdc.gov

Tick Identification

cdc.gov

Nymphs and females are most likely to bite. Most exposures occurs from May through the fall.

http://www.health.state.mn.us/lyme

Clinical Infectious Diseases 2006; 43:1089–134

Case study

• 14 yo girl presents with dizziness and arthralgias during high school fall soccer pre-season

• Traveled to Long Island, NY and northern MN over the summer• Developed a “rash” on upper back and fever/flu-like symptoms for several days

in July• Seen by pediatrician – diagnosed with “mono” in late August• 2 weeks later develops Bell’s palsy – thought to be related to “mono”• Develops headaches and photosensitivity• LP shows lymphocytic pleocytosis• 2-3 weeks later develops acute onset of chest pain with 2-3 degree heart block

and carditis• Develops radiculopathy, migrating monoarthritis of the hips and knees• Sent to several specialists without diagnosis

Case study

• Ultimately sees an Infectious Disease specialist at Park Nicollet

• Lyme Disease testing – Western blot IgG positive and CSF testing positive for Lyme Disease

• Treated with Ceftriaxone x 4 weeks

• Lingering symptoms of fatigue, neurologic symptoms (headaches, neuropathy) and migratory arthralgias for 1 year following treatment but then made a full recovery

Lyme Disease

Spread via Ixodes scapularis tick

Caused by spirochete, Borrelia burgdorferi

Symptoms

• Localized: Rash (erythema migrans) with or without constitutional symptoms

• Disseminated: multiple annular rashes, flu-like symptoms, lymphadenopathy

• Rheumatologic : arthralgias, mono or polyarthritis

• Cardiac: progressive heart block

• Neurologic: meningitis, radiculitis, Bells palsy

Lyme Disease Skin Manifestations

Erythema migrans

Manifestations - Early vs Late Stage

• Early - 3-30 days after bite– Testing usually negative– Erythema migrans/rash– Fever– Headache– Flu-like symptoms– Myalgia/Polyarthalgia

*Rash as only symptom occurs in 30%

• Early Disseminated -Weeks to months after bite– Testing usually positive– Multiple erythema migrans– Carditis (rare – 1-5%)

• AV block (1>2>3)• Myocarditis

– Neurologic• Cranial nerve palsy: CN VII

most common• Lymphocytic meningitis• Radiculitis, paresthesia and

rarely weakness

Manifestations - Early vs Late Stage

Late – months to > 1 yr

• Testing nearly always positive

– Late neurologic (rare)

• Encephalitis

• Encephalopathy

• Peripheral neuropathy (sensory)

– Late Lyme arthritis

• Joint swelling and pain usually knee

• Universally seropositive

• Usually monoarthritis but then may recur in same or different joint

Late cutaneous (seen more in Europe)

• Lymphocytoma

– Usually ear lobe

– Mistaken for cutaneous lymphoma

• Acrodermatitis chronica atrophicans

– Bluish to red discoloration affecting distal extremities (fingers/toes) with swelling developing over months to years

Lyme disease testing

• Labs: elevated CRP and ESR, mildly elevated LFTS

• Diagnosis:

– Testing on blood:

• Lyme ELISA and Western Blot (if ELISA positive or equivocal)

• Testing can be negative in the first few weeks of illness.

• Can do acute (may be negative 30-70%) then convalescent serology (4-6 weeks later)

– Testing on CSF

• Lyme IgM and IgG antibodies

• Borrelia burgdorferi PCR

• Cell count with lymphocytic pleocytosis

– Testing on joint fluid

• Borrelia burgdorferi PCR

Advice on testing

• Avoid serologic testing without objective symptoms

• Subjective symptoms alone are not an indication for Lyme testing

– Fatigue

– Neurocognitive symptoms

– Fibromyalgia-like pain

• KEY POINT: Lyme IgM Western blot should not be used to diagnosis any condition > 1 month duration due to high rate of false positives

• IgM Western blot is the most common reason for misdiagnosis and unnecessary treatment

New testing

• VlsE C6 ELISA

– May be positive earlier in acute infection (sensitivity 66% vs 35% for 2tier testing)

– Comparable sensitivity to IgM ELISA tests with improved specificity

– Not yet endorsed by the United States Centers for Disease Control and Prevention or guidelines from major organizations, and they have not gained widespread acceptance

– Not widely available

Question #1

• A 20-year-old female is evaluated for a skin eruption on her thigh. She lives in Wisconsin and is active outdoors. One week ago, she removed a tick on her thigh. Now she has developed diffuse myalgia, neck stiffness, and fatigue. She also noticed a red ring-like rash at the site of the previously attached tick.

• On physical examination, temperature is 100.5 F; other vital signs are normal. Exam is normal aside from a macular skin lesion with central clearing.

Question #2

• A 42-year-old man is evaluated in the emergency department for a 3-day history of dizziness and shortness of breath. He is training for a marathon. Despite rest and hydration, his symptoms have persisted.

• On physical examination, he appears well. Temp is normal, bp is 100/60 mm Hg, and pulse is 35/min.

• Labs: normal CBC, BMP and cardiac enzymes. EKG shows a second degree heart block

• Serologic testing for Borrelia burgdorferi is performed. Both the initial ELISA and a confirmatory Western blot assay are positive.

Lyme Disease Treatment

• Early infection (erythema migrans)

– Duration 14-21 days

• Doxycycline 100mg po bid

– Advantage of also covering Anaplasma, Ehrlichia, Rocky Mountain Spotted Fever

• Cefuroxime 500mg po bid

• Amoxicillin 500mg po tid

• Bell’s palsy

– Oral therapy as above

– Some use parenteral therapy if abnormal CSF

Lyme Disease Treatment

• Carditis/heart block– Oral regimen 14 days for those with asymptomatic 1 degree heart block– Ceftriaxone 2gm IV daily generally recommended along with

hospitalization for those with symptomatic 2nd or 3rd degree until heart block resolves

• Meningitis/radiculitis: – Ceftriaxone 2 grams IV q day for 28 days– European data suggests oral doxycycline is equivalent to IV ceftriaxone

• Arthritis– Doxycycline for 28 days

• Recurrent Arthritis– Repeat doxycycline for 28 days– Or consider Ceftriaxone 14-28 days– 10-15% will develop persistent arthritis despite multiple rounds of

antibiotics due to auto-immune, non-infectious inflammatory synovial process that is treated similarly to rheumatoid arthritis

Clinical Infectious Diseases 2006; 43:1089–134

NEJM 2001: 345: 79-84

Lyme Disease Prophylaxis

• Consider prophylaxis if:

– Ixodes tick engorged and on for over 36 hours

– Prophylaxis given within 72 hours of tick bite

• Ecological information states that percentage of ticks with B. burgdoferi is over 20% (New England, parts of mid Atlantic, parts of MN, Wisconsin)

• Doxycycline 200mg po once

• This RCT showed 87% efficacy in preventing Lyme disease

• Lyme vaccine no longer available

Tick Bite Prevention

- Wear long sleeve clothing

- Socks

- Insect repellant -DEET

- Shower after being outdoors

- Tick checks

Question #3

• A 72-year-old man is evaluated for fatigue and memory loss of 9 months' duration. The patient is a retired executive who is an avid outdoorsman and recalls many tick bites over the past several years. He lives in Florida now but has traveled extensively throughout the United States.

• The patient was seen in a walk-in clinic 1 week ago and had laboratory testing for Lyme disease. An enzyme-linked immunosorbent assay for Borrelia burgdorferiwas positive. A Western blot assay was negative for IgG antibodies and positive for IgM antibodies.

• On physical examination today, vital signs are normal. Remaining physical examination findings are unremarkable.

• An electrocardiogram is normal.

What to watch for after treatment

• Persistent symptoms of musculoskeletal pain, fatigue, headache, sleep disturbance, anxiety or depression

• Occurs within 6 month of Lyme diagnosis

• More common in adults than children

• 3 months: up to 25%

• 6 months: 10%

• 15 years: similar symptoms to general US population

Clinical Infectious Diseases 2006; 43:1089–134Infectious Dis Clin NA June 2008: 341-360

What to watch for after treatment

• If symptoms persist for > 6 months termed “post-treatment Lyme Disease Syndrome (PTLDS)”– Post-infectious disease fatigue syndrome– Rule out alternative explanations (sleep disorders, thyroid

problems, anemia)– Can try strategies that are used for patient with

fibromyalgia and chronic fatigue syndrome (CDC chronic fatigue toolkit)• Low impact, gradual increase exercise program• Cognitive behavioral therapy• Sleep hygiene• Pacing protocols

– Pharmacologic therapy • Antidepressants for pain or fatigue• Pain modifiers – Gabapentin, Pregabalin

Post-treatment Lyme Disease Syndrome

• No role for prolonged antibiotics• Most symptoms slowly resolve with time• No proven benefit

– Hyperbaric oxygen– IVIG– Vitamins– Nutritional management– Chelation therapy– Cholestyramine

• Avoid empiric treatment of babesiosis or bartonellawithout supportive lab testing

Controversy

Different viewpoints on Lyme Disease• Primary care providers need to be aware of the differing

viewpoints on testing and management of Lyme Disease

• If patients use the internet as a primary source of medical knowledge, they are likely to be overwhelmed by the information that is out there are varying viewpoints

• It is helpful when referring patients for Lyme Disease management to be clear on the different practice patterns of providers

– Providers that follow Infectious Disease Society of American Guidelines (IDSA) on testing and treatment

– Providers that are associated with International Lyme and Associated Disease Society (ILADS)

THANK YOU