Brian S. Murphy, MD, MPH November 5, 2008 40th Annual Family Medicine Review Discuss the reservoirs and vectors of the causative organisms of Lyme disease and other tick-borne diseases Discuss the distribution and epidemiological risk factors of Lyme disease and other tick-borne diseases Discuss the diagnosis, management and treatment of Lyme disease and other tick-borne diseases 1
30 y/o woman presents with fever, headache, myalgias and a new rash on her left flank that had begun 7 days earlier Recently returned to Kentucky from opening her summer home on an island off the northeastern coast of the United States The patient was uncomfortable but did not appear toxic. Fever to 102 F and there was a large annular rash on her left flank Most common tick-borne disease in US Earliest stage is the skin lesion Erythema migrans (EM) Appears as an expanding erythematous papule or macule with central clearing at the site of a deer tick bite Most patients with early EM respond well to short courses of oral antibiotics Late stages are based on clinical and epidemiological evidence of disease and supported by serologic testing Affects skin, heart, joints and nervous system 2
B. burgdorferi transmitted through the skin of the host via a Ixodes scapularis tick Incubation several days to week The organism migrates outward producing the characteristic skin rash EM In some, may spread to lymph nodes (regionally) or hematologically ll to other organs Discovered by Willy Burgdorfer Has been cultured from blood, skin, synovial fluid and CSF But with the exception of skin biopsy specimens, it is difficult to culture from sites of infection Different separate genospecies are important in various locations B. burgdorferi sensu stricto include the US strains 3
Numbers have increased steadily since 1982 when a national surveillance was initiated 2001-49 states reported 17,029 cases of Lyme disease to CDC 4
Most distinct clinical marker for Lyme disease Primary lesion > 5 cm Secondary lesions (in ~20% of cases) may be smaller EM lesions minimally symptomatic In US, about 70% have viral-like sx (lower in Europe) DDx TB hypersentivity reaction Dx based on appearance 5
Mixed,,predominatly mononuclear cellular infiltrate with monocytes/macrophages and also T and B cells Believed that this combined effect of local spirochetal infection with an intense immunoogic reaction to the organism is responsible for disease expression Culture of B. burgdoreri from EM Test is not readily available for routine patient care Serological tests are typically negative Specific IgM develop 2-6 weeks after onset of EM IgG appear ~6 weeks after disease (may take years) Highest titers occur during arthritis Patients receiving abx for EM may never have measurable Ab response Flu-like illness in summer with a h/o tick bite in an endemic area 6
IgG response almost always positive in patients with cardiac, neurologic or arthritic manifestations Cross-reactivity to other organisms can occur ACP Guidelines Only test patients with clear clinical symptoms of Lyme Disease Use a 2-step protocol in which either positive or indeterminate ELISAs are followed by WB Withholding Lyme Disease antibiotic therapy for patients with only vague symptoms such as malaise Providing empiric abx for a patient who presents with a rash resembling EM if they have visited a high-risk area 7
Doxycyline y 100 mg BID x 10-21 days -OR- Amoxicillin 500 mg TID x 10-21 days -OR- Cefuroxime 500 mg TID x 21 days -OR- Azithromycin 500 mg daily x 10 days 8
Cranial neuropathy, radiculopathy, mononeuropathy multiplex 7 th N. palsy most common Bilateral Lyme Disease Unilateral Maybe Lyme Disease Lymphocytic meningitis Encephalopathy Imprecisely defined; objective MILD cognitive dysfunction; CSF may be WNL or only slightly abnormal Peripheral neuropathy Mild diffuse axonal neuropathy associated with limb paresthesias or radicular pain; nerve bx shows perivascular collections of lymphs; CSF usually WNL Encepahlomyelitis Monophasic, slowly progressive. Involves white matter. CSF+ for lymphocytic pleocytosis and intrathecal Ab 9
Facial palsy Oral abx as recommended for early disease Other manifestations Ceftiaxone 2 g/day IV x 14-28 days PCN G 20 million units IV daily x 28 days -OR- -OR- Chloramphenicol 1 g QID x 28 days Dominant feature of late-stage Lyme Disease Occurs up to 60% of untreated patients Migratory arthritis 50% intermittent attacks Large joints most commonly involved Synovial fluid typically shows about 25,000 cells/mm 3 with a PMN predominance Range (500 - >100,000 cells/mm 3 ) 10
In certain genetically predisposed p patients, joint inflammation will persist although Bb DNA can no longer be detected R x options include NSAIDS DMARDS Intra-articular steroids Synovectomy Doxycycline y 100 mg BID x 30-60 days -OR- Amoxicillin 500 mg QID x 30-60 days -OR- PCN G 20 million U/day x 14-28 days -OR- Ceftriaxone 2 g/day x 14-28 days -OR- Cefuroxime 500 mg BID x 30-60 days 11
Ocular lesions in every yportion Conjunctivitis, photophobia and neuroophthalmologic manifestations due to CN palsies Carditis Occurs in ~10% after 4-6 weeks Conduction system involvement: 3 rd degree AV block Does not affect heart valves Rapidly reversible with abx 24 hours 0/58 48 hours 4/50 (8%) 72 hours 36/52 (69%) Des Vignes et al. JID 2001; 183:773-8. 12
Author No. Antibiotic/ duration Incidence of EM Efficacy rate of abx Antibiotic Placebo Costello 58 PCN/ 10 d 0.0% 3% 100% Shapiro 385 Amox/ 10 d 0.0% 0% 1.2% 100% Agre 179 Nadelman 482 PCN or Tet/ 10 d Doxy/ 1 dose 0.0% 1.1% 100% 0.4% 3.2% 87% Nonspecific symptoms Positive CSF cx may persist after 0/128 appropriate treatment of Positive CSF PCR Lyme disease 0/128 H/A, fatigue, arthralgias, + Blood PCR baseline cognitive c/o 0/129 No evidence that these + Blood PCR during R x subjective c/o represent 0/458 ongoing active infection Klempner. NEJM, 2001. Klempner. Vect Borne Zoonotic Dis. 2002. 13
Previously treated Lyme disease but persistent MS pain, cognitive symptoms and fatigue B. burgdorfer Ab + B. burgdorfer Ab + 30 days ceftriaxone (2gm/d) then 60 days doxy (200mg/d) Placebo 30 days ceftriaxone (2gm/d) then 60 days doxy (200mg/d) Placebo Klempner. NEJM, 2001. The studies were discontinued as data indicated that a significant difference in treatment efficacy between the groups would be observed Severe impairment in the patients' health-related quality of life with therapy Klempner. NEJM, 2001. 14
Other suggested modes of transmission Person-to-Person No evidence During Pregnancy & While Breastfeeding Lyme disease acquired during pregnancy may lead to infection of the placenta and possible stillbirth; however, no negative effects on the fetus have been found when the mother receives appropriate antibiotic treatment There are no reports of Lyme Disease transmission from breast milk From Blood Although no cases of Lyme Disease have been linked to blood transfusion From Pets Dogs and cats can get Lyme Disease. There is no evidence that they spread the disease directly to their owners. Other Transmission There is no credible evidence that Lyme disease can be transmitted through air, food, water or from the bites of mosquitoes, flies, fleas or lice. Labs were checked and ELISA for Lyme y Disease was negative Biopsy of rash revealed no organisms Is there anything else to consider? 15
Can transmit several tick-borne diseases Lyme Disease Anaplasmosis Babesiosis The smaller nymphal stage ticks which most commonly bite humans 16
Nymph stage appears to be responsible for most Lyme Disease cases Adult prefers to feed on white-tailed deer Tick Deer Tick Reservoir (Adult) White-tailed Deer Brown Dog Tick Lone Star Tick Dog, deer, lower animals White-tailed tailed Deer American Dog Tick Dog, deer, lower animals 17
Linked to transmission of Ehrlichiosis and Southern tickassociated rash illness (STARI) Saliva is irritating and can cause an allergic reaction at the site of the bite Can transmit many diseases including Rocky Mountain spotted fever and tularemia 18
STARI Lyme Disease A. americanum Ixodes species Recall of tick bite Recall of tick bite (86%) (20%) Symptomatic (20%) Symptomatic (75%) Single EM (95%) Single EM (75%) Central clearing (75%) Central clearing (20%) What is the etiology? Is it caused by an infectious agent? Are there several different causes? Are there extracutaneous manifestations? What is the optimal treatment? t t? 19
Babesia microti and divergens Incubation period: 1-4 weeks Malaria-like illness Obligate RBC intracellular parasite Mild to fatal Fulminant to fatal infection in asplenics Fever, chills, myalgias, headaches Signs: splenomegaly, relative bradycardia Laboratory features A i l h i th b t i Anemia, lymphopenia, thrombocytopenia, atypical lymphocytes, elevated LDH, elevated bilirubin 20
Ring forms common Intracellular RBC Maltese Cross Babesia IFA >1:256 (cross-reacts with Plasmodia) PCR Clindamycin/quinine Clindamycin/atovaquone Monotherapy is ineffective Exchange transfusion in critically ill (asplenics) 21
Ehrlichia caffenensis (human monocytic ehrlichiosis; HME) Anaplasma phagocytophilium (formerly E. equi, E. phagocytophila (human granuloctyic ehrlichiosis; HGE) HGE HME Gram negative intracellular WBC g pathogen Incubation period 1-3 weeks Spotless RMSF F/C Mental confusion Headache Myalgias N/V Cough 22
Leukopenia Atypical lymphocytosis Relative lymphopenia Eosinopenia Thrombocytopenia Mildly increased transaminases Presence of these argues AGAINST ehrlichiosis: anemia and renal involvement Serology Cross-reactive with Brucella, Borrelia, Rickettsia Microbiology Morulae in cytoplasm of granulocytes (HGE) or monocyts (HME) Morulae present in HGE>>HME 23
Treatment Preferred: Doxycycline Alternative: Chloramphenicol Complications Thrombocytopenia Rhabdomyolysis ARDS Myocarditis Pancytopenia (HGE) Death: HME>>HGE Doxycycline photosensitivity, nausea, y y p y,, vomiting, diarrhea, toxicity in pregnant women & children Amoxicillin ineffective vs. Rickettsia Cefuroxime ineffective vs. Rickettsia and more expensive Macrolides less effective 24