Diagnosing Lyme Disease: Insights and Challenges

Show Notes

Episode Produced by Audrey Bree Tse, MD

Background

• Most common tick-born illness in North America
• Endemic in Northeast, Upper Midwest, northwest California
• 80% to 90% in summer months

Pathophysiology

• Ixodes tick (deer tick) has a 3-stage life cycle (larvae, nymph, adult) & takes 1 blood meal per stage
• Deer tick feeds on an infected wild animal (infected with spirochete Borrelia burgodrferi) then bites humans
• On humans, they typically move until they encounter resistance (e.g. hairline, waistband, elastic, skin fold).  It takes 24-48 hrs for B. Burgdorferi to move from the tick to the host
• Pathogenesis: organism induced local inflammation, cytokine release, autoimmunity
• No person to person transmission

Clinical Presentation

Stage 1: Early

• Symptom onset few days to a month after tick bite
• Erythema migrans rash: bulls eye rash seen in more than 90% of patients with Lyme disease (Irregular expanding annular lesion(s))
• Regional adenopathy, intermittent fevers, headache, myalgias, arthralgia, fatigue, malaise

Stage 2: disseminated/ secondary

• Days to weeks after tick bite
• Intermittent fluctuating sx that eventually resolve
• Triad of aseptic meningitis, cranial neuritis, and radiculoneuritis: bell palsy most common
• Cardiac symptoms: tachycardia, bradycardia, AV block, myopericarditis

Stage 3: tertiary/ late

• Symptoms occur >1 year after tick bite
• Acrodermatitis chronic atrophicans: Atrophic lesions on extensor surfaces of extremities (resembles scleroderma)
• Monoarthritis, oligoarthritis (knee > shoulder > elbow)
• GI: Hepatitis, RUQ pain
• Ocular: keratitis, uveitis, iritis, optic neuritis
• Neurological: Chronic axonal polyneuropathy or encephalopathy

Chronic Lyme disease (versus well-accepted Lyme disease sequelae):

• Continuation of symptoms after antibiotics
• Current recommendation for management is supportive care only

Pediatric considerations:

• More likely to be febrile than adults
• Facial palsy accompanied by aseptic meningitis in 1/3
• Untreated kids can develop keratitis
• Excellent prognosis if appropriately treated

History

• Travel, camping, woods, playing under leaves or in wood piles
• Living in endemic area (Northeastern area: Maine to Virginia; upper Midwestern: Wisconsin, Minnesota; Northwest California)
• Endemic in Northern Europe and Eastern Asia as well
• History of tick bite (- 30-50% of patients recall tick bite)
• Flu like illness in summer
• Rash: https://www.cdc.gov/lyme/signs_symptoms/rashes.html
• Joint complaints
• Cardiac complaints
• Neurologic complaints
• Careful search for tick

Diagnosis

Labs

• CBC (leukocytosis, anemia, thrombocytopenia)
• ESR: most common lab abnormality (>30 mm/hr)
• Chem 7
• LFTs: commonly elevated especially GGT
• Cultures not typically indicated
• LP when meningeal signs (CSF: pleocytosis, elevated protein, CSF spirochete ABs).  LP function is more to rule out other etiologies of meningitis rather than diagnose Lyme meningitis given that lyme PCR and lyme Ab index are not very accurate.

Serological Testing

• Serological testing is not always warranted because of the very high incidence of false positive results
• Serologies are not useful in acute phase (<30 days of infection) because they are negative; it takes several weeks to develop enough antibodies for either test below (ELISA or Western Blot)
• Acute Lyme is a clinical diagnosis and does not need laboratory testing, especially in endemic areas such as NY
• If pretest probability is high (symptoms consistent with Lyme + epidemiological background), say patients with CN palsy, meningitis, carditis, or migratory large joint arthritis, then serologies can be very helpful
• Do not test if patients in endemic areas with potential tick exposure present with EM — just treat with antibiotics
• Do not test if patients in endemic areas present with no history of tick exposure or only nonspecific symptoms
• Test if you have high suspicion of lyme without EM
• PCR is highly specific and sensitive but not available for routine use.  There are two tests you need to use together:

1) ELISA: this detects antibodies to lyme bacteria (borrelia burgdorferi)  in your blood, BUT it can’t distinguish between borrelia and similar bacteria (even sometimes normal flora that lives in you).  In addition, IgM response takes 1-2 weeks while IgG response takes 2-4 weeks.

If ELISA is positive or equivocal, then you move onto the:

2) Western blot test: this looks for antibodies not to the whole organism, but to the basic building blocks of the lyme bacteria — the individual proteins, BUT many types of bacteria use the same building blocks. So the CDC says that the Western Blot test must detect IgG antibodies to 5 out of the 10 proteins.

See figure 2: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4918152/

• Two-tiered testing has sensitivity between 70-100% and specificity ~95% in late stages
• Interpretation of Lyme serologies should be done by an ID specialist because they can be confusing and can lead to wrong conclusions if unfamiliar with them
• NYC is an endemic region where 5% of the population can have a positive without symptoms!
• If somebody who HAD Lyme disease but successfully treated it with doxycycline tested themselves years later, they could still have the antibodies and therefore it would look like they still had Lyme disease (despite being cured)
• Positive serology or previous Lyme disease not ensure protective immunity

Other tests:

• Arthrocentesis for acute arthritis: elevated cryoglobulin
• XRs: may show soft tissue, cartilaginous, osseous changes
• ECG

Differential Diagnosis

• Tick-borne diseases: Rocky Mountain Spotted fever, tularemia, relapsing fever, Colorado tick fever, tick-bite paralysis, babesiosis, anaplasmosis, powassan virus
  • Remember that doxycycline covers anaplasmosis and lyme but not babesiosis, which requires Atovaquone
• Rheumatic fever (usually presents with erythema marginatum rash, valvular involvement rather than heart block, TM joint arthritis)
• Viral meningitis
• Septic arthritis
• Syphilis
• Parvovirus B19
• Infectious endocarditis
• Juvenile rheumatoid arthritis
• Reiter syndrome
• Brown recluse spider bite
• Fibromyalgia
• Chronic fatigue syndrome

Treatment

• Remove tick: disinfect site then with blunt instrument, grasp tick proximal to skin and pull upward with gentle constant traction.  Mouthparts will release after about a minute. If residual mouthparts are left in skin, leave them alone to avoid infection (they will extrude from skin naturally over time).  Since ticks that have not attached or are moving on the skin cannot transmit Lyme, they can just be brushed off.
• NS IVF bolus, supportive care
• Cardiac monitoring, temporary pacemaker for heart block
• Beware Jarisch Herxheimer reaction: worsening of sx a few hours after treatment initiated
• Aspirin for cardiac involvement, NSAIDs for arthralgias/ arthritis

Prophylaxis:

• Per the IDSA, give a single dose of 200 mg PO doxycycline to patients who meet all of the following criteria:
  • Deer tick has been attached for 36 hours or more  (the rationale for time of attachment relates to the fact that the spirochetes live in the tick’s gut so they need a long time to multiply and travel to the salivary glands (event that’s triggered by a blood meal) and later overcome the salivary gland  (which only a few do) and finally reach the patient’ skin
  • Prophylaxis can be provided within 72 hours of tick removal
  • Local rate of B. Burgdorferi infection in ticks exceeds 20% (in the northeast USA, the prevalence of infected ticks is between 15-20%)
  • Doxycycline can be used (children >8 years old, non-pregnant females)
• A 2001 study examined doxycycline vs placebo prophylaxis.  A single dose of 200 mg of oral doxycycline or placebo was given to persons presenting within 72 hours of removal of an I scapularis tick. One of 235 persons in the doxycycline group developed erythema migrans (EM) versus 8 of 247 in the placebo group, for treatment efficacy of 87% (95% CI, 25%–98%; P<0.04) (9).
• Reasonable alternative strategy: monitor for EM or other signs of infection then initiate treatment if they develop Lyme disease (excellent outcomes in patients treated during early EM stage of disease)

Antibiotics:

• Antibiotics can speed resolution of arthritis and cardiac conduction delays, but not necessarily facial palsy
• Doxycycline has the best bioavailability and CNS penetration
• Always check with your ID colleagues to determine appropriate duration of treatment in more serious cases of Lyme disease
• Stage 1:
  • Amoxicillin (500 mg PO TID) or cefuroxime (500 mg PO BID) or doxycycline (100 mg PO BID; > 8 years old & not pregnant) x 21 days; azithromycin (500 mg PO qday x 14-21 days)
  • IV therapy in pregnant patients

• Stage 2:
  • PO antibiotics for isolated Bell palsy and mild involvement
  • Amoxicillin with probenecid (500 mg PO TID) x 30 days or doxycycline (100 mg PO BID; > 8 years old & not pregnant) x 10-21 days
  • IV ceftriaxone (2 g IV qday) x 14-21 days, or penicillin G (20-24 million units IV q4-6h x 14-28 days) for meningitis, carditis, severe arthritis

• Stage 3:
  • Penicillin G (20-24 million units IV q4-6h) x 14-21 days or ceftriaxone (2 g IV qday x 14-28 days)

Dispotition

• Admit unstable or sick patients, those with meningoencephalitis, & carditis (telemetry/ ICU admission)
• DC patients treated with PO therapy
• Future prevention strategies: wear long pants & shirts, light-colored clothing (easier to spot crawling ticks), tuck pants into socks, DEET spray, clothing impregnated with permethrin

References

Baker C et al, Lyme Disease Review Panel of the Infectious Diseases Society of America (IDSA).  Final report of the lyme disease review panel of the infectious diseases society of America (IDSA). 2006.  https://www.idsociety.org/globalassets/idsa/topics-of-interest/lyme/idsalymediseasefinalreport.pdf

(22 July 2019, date last accessed)

Centers for Disease Control and Prevention.  CDC — Lyme. 2019. https://www.cdc.gov/lyme/index.html (22 July 2019, date last accessed)

Hilton E, DeVoti J,, Benach JL, Halluska ML, White DJ, Paxton H, Dumler JS.  Seroprevalence and seroconversion for tick-borne diseases in a high-risk population in the northeast United States.  Am J Med. 1999 Apr;106(4):404-9.

Hu LT.  Lyme Disease.  Ann Intern Med.  2016;164:ITC65-ITC80.  Doi: 10.7326/AITC201605030

Lee, M.  Lyme Disease.  Rosen and Barkin’s 5-Minute Emergency Medicine Consult.  2015; 664-665.

Nadelman RB, Nowakowski J, Fish D et al., Tick Bite Study Group.  Prophylaxis with single-dose doxycycline for the prevention of Lyme disease after an Ixodes scapularis tick bite.  N Engl J Med.  2001;345:79-84.

Sanders, L.  (2009). Every patient tells a story: Medical mysteries and the art of diagnosis.

A special thanks to our Infectious Diseases Editor:

Angelica Cifuentes Kottkamp, MD

Infectious Diseases & Immunology

NYU School of Medicine