Raymond H Flores, MD FACR Associate Professor of Medicine Division of Rheumatology & Clinical Immunology

 Background  Etiology  Epidemiology  Clinical Manifestations  Treatment  Prevention  Frequently Asked Questions

 Systemic infection caused by spirochete Borrelia Burgdorferi and immune response to the infection  First cases described skin rash in individuals in 1883 Europe (acrodermatitis chronica atrophicans)  Later cases (1930s) described neurologic symptoms and skin rash following bite by deer ticks (tick-borne meningoencephalitis)

 Lyme disease recognized in US only recently (1970s)  Heavy cluster of cases of pediatric arthritis noted around Lyme, Connecticut  Investigators from Yale examined the outbreak and ultimately discovered the causative agent, its spread to humans, its clinical manifestations and response to antibiotics, and its similarities to the skin rash seen in Europe

 Willy Burgdorfer, MD discovered the spirochete Borrelia in Ixodes scapularis (deer) ticks responsible for disease transmission (Borrelia burgdorferi)  The bacterium is inoculated into the skin by the tick bite  There are several different strains of the organism, which explains why the disease is somewhat different in Europe and the US

 Endemic in North America, Europe and Asia  Vector is deer tick (Ixodes scapularis) responsible for cases in Northeast, Central US and Canada (approx. 95% of cases)  Approximately 20,000 new cases per year reported to CDC and rising  Rising rates reflects increased recognition, expansion of deer herds, increasing tick populations and urban expansion

 Transmission by Ixodes scapularis; I. pacificus on west coast  Four stages of development  Nymphs and adults require blood meals, usually in spring and summer  Acquire B. burgdorferi by feeding on infected host (deer and white footed mouse)  Nymph-stage ticks feed on humans from May through November

 Ticks transmit infection via bite and expelling infected saliva  Spirochete can be overwhelmed by host defenses or spread locally or into circulation causing human disease

 Risk factors for infection include: - geography: i.e., Northeast, including Maryland - wooded, high-grass locations - occupations: landscaper, forester, etc - recreational activities: camper, hiker, hunter

 Once organism introduced into host, individuals may clear the infection without any symptoms, although they may become seropositive  However, active infection by the organism may cause involvement of the skin, heart, central nervous system, joints and eyes  Stages of active infection include Early Localized Disease, Early Disseminated Disease and Late Disease

 Occurs within days of tick bite  Erythema chronicum migrans (ECM) or so- called “bulls-eye” rash  Symptoms of viral illness- fevers, headache, stiff neck, malaise, lymphadenopathy, arthralgias, and myalgias

 Occurs 1-3 months after tick bite  Cardiac involvement occurs in 10% (untreated) - pericarditis - myocarditis - conduction defects  Neurologic involvement in 10% (untreated) - meningitis - cranial nerve palsies (especially 7 th nerve, Bell’s palsy)

 Usually > 3-4 months after bite  Neurologic manifestations (untreated) - encephalopathy - peripheral neuropathy  Inflammatory arthritis, which may occur in up to 2/3 of untreated patients - typically monarthritis or 2-3 joints - almost always the knee is involved

 IgM antibodies appear in 2-4 weeks, peak at 4 weeks, often disappear at 6 weeks  IgG antibodies appear in 3-8 weeks, may persist indefinitely, dramatically high in Lyme arthritis  Use enzyme immunoassay (EIA) as initial screen; can see false (-) if too soon after bite, but can have a high level of false positives  If EIA (+), perform Western Blot, which is excellent test

 In first few days after rash, Lyme titers likely to be negative  When patients present with disseminated or late infection, the tests are almost always positive  If the clinical picture is not clear, testing a convalescent titer 2-4 weeks later may be very valuable (especially if the patient has not been treated)

 Oral antibiotics (doxycycline, amoxicillin) 2-4 weeks - skin rash - flu-like symptoms - arthritis - heart block (1 st degree)  IV antibiotics (ceftriaxone, PCN) usually at least 4 weeks - neurologic disease - advanced heart block *based on CDC recommendations

 Best treatment is prevention  When walking in woods, avoid bushy grassy areas  Wear long pants and long-sleeved shirts  Use insect repellant containing DEET on exposed skin  After being in wooded areas, examine skin carefully for ticks, including the scalp, armpits and groin

 If tick has attached, can remove carefully with tweezers as close to skin as possible and steady pressure  Clean area with alcohol or soap and water

 Check pets, especially dogs, as they can carry ticks and can develop Lyme disease, as well  The Lyme vaccine (LYMErix) was taken off the market in 2002 due to poor demand, side effects and disappointing prevention rates that were not long-lasting

 If you don’t see an ECM rash, does this mean you can’t have Lyme? NO. It’s estimated that 50% of individuals with Lyme who have been bitten by a tick do not see a rash, because it is in an area difficult to see by the individual or hidden in the scalp. Have a family member help you search for ticks. Also, the rash may not look classic, i.e. “bulls-eye”

 Is there anything I can do to prevent Lyme if I’ve been bitten by a tick? If the tick has been attached for less than 24 hours, and is not engorged, you can remove the tick and do nothing else. If it is engorged and been attached greater than hours, consider a single dose of 200mg doxycycline. This was found to be very protective in a recent prospective study.

 What is post-Lyme Syndrome? Onset within six months of proven treated Lyme infection of persistent fatigue, widespread musculoskeletal pain and/or cognitive difficulties lasting for at least 6 months. Usually severe, reducing occupational and social activities.

 Must exclude active Lyme disease from similar ailments such as arthritis or neurologic disease. Must exclude Fibromyalgia or Chronic Fatigue Syndrome or other medical condition that could explain symptoms.  Treatment is symptomatic. Randomized, controlled prospective study has shown that patients treated with long-term IV antibiotics do no better than those treated with placebo.

 If treatment with doxycycline does not result in a rapid response in early Lyme (i.e. clearing of ECM rash, fever, malaise, etc), what could be going on? Co-infections with other tick-borne illnesses do occur in < 5% of cases of Lyme. Human Babesiosis can cause fevers, sweats, chills, joint pain, headache and worsen symptoms. Erlichiosis can cause more severe symptoms as well. Erlichiosis will eventually respond to doxycycline, although babesiosis will require anti-parasitic treatment.

 Should I repeat Lyme serologies to confirm adequate treatment of the illness? NO. Up to a third of patients who have been treated adequately for Lyme with antibiotics still have positive blood tests up to years post-infection. Don’t follow serologies.