NO DISCLOSURES Convention and Controversies Richard A. Jacobs, M.D., - PDF document

1/20/2017 Lyme Disease NO DISCLOSURES Convention and Controversies Richard A. Jacobs, M.D., PhD. Willie Burgdorfer, Ph.D. (1925 ‐ 2014) RM Lab in Hamilton, MT Polly Murray who first reported an outbreak of arthritis in 12 children from Old Lyme, CT in 1975—the first description of what would become to be known as Lyme disease. Author of “The Widening Circle: A Lyme disease Pioneer Tells Her Story” 1

1/20/2017 Dr. Allen Steere, who at the time Outline was a Rheumatology Fellow at Yale University, was sent to investigate the • Clinical manifestations outbreak of arthritis. • Diagnosis In 1977 published a paper on Lyme Arthritis. (Arthritis and • Therapy Rheumatism 1977;20:7) • Prevention • Controversies Case Case • Serologies • A 35 yo woman is being evaluated for a 6 month h/o – CDC recommends 2 ‐ stage testing fatigue, arthalgias without arthritis and memory loss manifest as word ‐ finding difficulties and • Screening ELISA—very sensitive but not specific forgetfulness. The work ‐ up has been thorough but – If negative—>no further testing frustrating for both the provider and the patient because answers have not been forthcoming. Finally, – If positive—>confirmatory test after an exhaustive internet search, she requests that • Confirmatory Western Blot Lyme disease serologies be performed. The provider – IgM reluctantly agrees. – IgG 2

1/20/2017 Case Questions • Serologies return: – ELISA screening test is equivocal • How do you interpret the serologies? – Confirmatory Western Blot is IgM (+) • Does she have Lyme disease? and IgG ( ‐ ) Definition “Tick Biology 101” Lyme disease is a bacterial infection caused almost exclusively by the spirochete Borrelia burgdorferi in the US and Borrelia burgdorferi, afzelii, and garinii in Europe and is transmitted to humans by the bite of infected Ixodes ricinus complex deer tick. The clinical manifestations can be complex but affect primarily the skin, joints, nervous system and heart 3

1/20/2017 “Tick Biology 101” “Tick Biology 101” (continued) • Hard ticks (over 700 species) • Three stages: – Ixodes ricinus complex – Larval—feeds from August to September on – Different geographic distributions white ‐ footed mouse • Northeastern and upper midwestern states – Nymphal ★★ ‐‐ feeds from May through July on – Ixodes scapularis (also called Ixodes dammini ) white ‐ footed mouse • Western states— Ixodes pacificus – Adult—feeds on larger mammals, especially deer • Europe— Ixodes ricinus in the spring and fall • Asia— Ixodes persulcatus ★★ Nymph primarily responsible for disease transmission • Soft ticks (over 150 species) Most clinical cases occur in the summer months Tick Biology (continued) Tick Biology (continued) 4

1/20/2017 Tick Biology (continued) Engorged Tick Clinical Manifestations Early Localized Disease • Early Localized Disease • Erythema Migrans – Usually occurs 7 ‐ 10 days after the bite – Seen in 70% ‐ 80% of cases – Range 3 ‐ 30 days – Begins 7 ‐ 10 days after the bite (3 ‐ 30 day range) • Early Disseminated Disease – Starts at the site of the the tick bite – Slowly expanding (over several days to weeks), flat – Weeks to months after the bite or slightly raised, erythematous rash that is often • Late Disease described by patients as burning, itching or painful – Months to years after exposure – Clears spontaneously over weeks 5

1/20/2017 Central Clearing Bulls Eye Rash 6

1/20/2017 Early Localized Disease Early Localized Disease • Erythema Migrans • Erythema Migrans – Usually with – Usually accompanied with • Nonspecific systemic symptoms • Nonspecific systemic symptoms – Fatigue – Fatigue – Anorexia “SUMMER FLU” – Anorexia – HA – HA – Myalgias – Myalgias – Fever – Fever • About 40% of patients have spirochetemia Early Disseminated Disease Early Disseminated Cutaneous Disease (weeks to months) • Cutaneous Manifestations – EM at sites other than the original bite • Neurologic (15% of UNTREATED patients) – Lymphocytic meningitis – Cranial nerve palsies (especially the facial nerve) – Radiculoneuritis • Heart (5% of UNTREATED patients) – Atrioventricular block – Myocarditis (rarely) 7

1/20/2017 Early Disseminated Cutaneous Disease Early Disseminated Cutaneous Disease Early Disseminated Disease Late Disease (weeks to months) (months to years) – Arthritis (60% of UNTREATED patients) • Cutaneous Manifestations • Large weight bearing joints – EM at sites other than the original bite • Often recurrent (70%) • Neurologic (15% of UNTREATED patients) – Neurologic • Polyneuropathy – Lymphocytic meningitis • Encephalomyelits – Cranial nerve palsies (especially the facial nerve) – True infection of the neuroaxis – Very rare < 1/10 6 – Radiculoneuritis – More common with B. garinii • Heart (5% of UNTREATED patients) • Encephalopathy (forgetfulness/cognitive impairment) – Common symptoms in individuals with inflammatory diseases – Atrioventricular block – Common background symptoms in general population – Myocarditis (rarely) – THESE SYMPTOMS ARE NOT MANIFESTATIONS OF CNS LYME 8

1/20/2017 Late Disease (months to years) – Arthritis (60% of UNTREATED patients) • Large weight bearing joints • Often recurrent (70%) – Neurologic • Polyneuropathy • Encephalomyelits – True infection of the neuroaxis – Very rare < 1/10 6 – More common with B. garinii • Encephalopathy (forgetfulness/cognitive impairment) – Common symptoms in individuals with inflammatory diseases – Common background symptoms in general population – THESE SYMPTOMS ARE NOT MANIFESTATIONS OF CNS LYME Diagnosis Diagnosis • Early Disease • Late Stages – Because of slow rise in antibody titers (IgM 1 ‐ 2 – CDC recommends 2 ‐ stage serologic testing weeks; IgG 2 ‐ 6 weeks), diagnosis is made clinically • Screening ELISA—very sensitive but not specific (syphilis, gingivitis, LYMErix, etc) – If repeat titers after 6 weeks almost all positive – If negative—>no further testing – If positive/equivocal—>confirmatory test • Confirmatory Western Blot 9

1/20/2017 Diagnosis of Late Manifestations New Approaches to Serodiagnosis (Steere AC et al. Clin Infect Dis 2008:47:188) • V1sE C6 ELISA (C6 test)—measures antibodies to a protein ‐ like sequence expressed in the • Sensitivity of 2 ‐ tier testing in late Lyme disease sixth invariant region is 100% and specificity is 99% – More sensitive in early disease than 2 ‐ stage • “Therefore, current thinking is that all patients testing with objective neurologic, cardiac, or joint – Equal sensitivity and specificity in late stage abnormalities associated with Lyme disease disease have serologic response (a + IgG western blot – More sensitive for European strains titer) to B. burgdorferi” Commonly Asked Questions Clues to Diagnosis • What is the explanation of an isolated positive • EM occurs 3 ‐ 30 days after bite ‐‐ most commonly in 7 ‐ Western Blot IgM? 10 days – FALSE POSITIVE – Early reactions that fade are due to the tick bite • Can you get Lyme disease more than once? and are not EM – Almost always re ‐ infection • Ticks must feed 24 ‐ 36 hours to transmit organism – NOT relapse • Know prevalence in your area • Does Lyme disease in pregnancy affect the fetus? – East Coast 60 ‐ 70% infected – Does not predispose to congenital anomalies or fetal – West Coast < 5% infected demise 10

1/20/2017 Clues to Diagnosis • EM occurs 3 ‐ 30 days after bite ‐‐ most commonly in 7 ‐ 10 days – Early reactions that fade are due to the tick bite and are not EM • Ticks must feed 24 ‐ 36 hours to transmit organism • Know prevalence in your area – East Coast 60 ‐ 70% infected – West Coast < 5% infected 11

1/20/2017 Prevention • Light colored protective clothing with shirt tucked into pants and pants tucked into socks • DEET • Permethrin spray for clothes • Tick checks with prompt removal • Antibiotic prophylaxis—200 mg doxycycline – Ixodes tick; fed for 36 hours; tick infection rate >20%; antibiotics given within 72 hours of tick removal 12

1/20/2017 Prevention Proper Tick Removal • Light colored protective clothing with shirt tucked into pants and pants tucked into socks • DEET • Permethrin spray for clothes • Tick checks with prompt removal • Antibiotic prophylaxis—200 mg doxycycline – Ixodes tick; fed for 36 hours; tick infection rate >20%; antibiotics given within 72 hours of tick removal New Lyme ‐ disease Borrelia spp Back to the Case Identified • A 35 yo woman is being evaluated for a 6 month • Borrelia mayonii h/o fatigue, arthalgias without arthritis and – Found in the upper midwestern states memory loss manifest as word ‐ finding difficulties – Transmitted by Ixodes scapularis tick and forgetfulness. • Only six patients identified • Lab tests – More nausea and vomiting – ELISA –equivocal – Higher temperatures – WB—positive IgM and negative IgG – Diffuse rash • NOTE—EXPLANATION OF AN ISOLATED (+) – High grade spirochetemia Western Blot IgM IS THAT IT IS A FALSE (+) • Detected by current 2 ‐ tier testing and C6 test • IN LATE STAGES OF DISEASE ALMOST ALL HAVE A • Responds to standard Lyme disease therapy (+) IgG ANTIBODY TITER Lancet Infect Dis, Feb 5, 2016 13