Borrelia burgdorferi - Lyme Disease

1,736 views

Published on

0 Comments
0 Likes
Statistics
Notes
  • Be the first to comment

  • Be the first to like this

No Downloads
Views
Total views
1,736
On SlideShare
0
From Embeds
0
Number of Embeds
1
Actions
Shares
0
Downloads
11
Comments
0
Likes
0
Embeds 0
No embeds

No notes for slide

Borrelia burgdorferi - Lyme Disease

  1. 1. The Physician's Guide to Laboratory Test Selection and Interpretation Borrelia burgdorferi - Lyme Disease Clinical Background Lyme disease is the most common vector-borne disease in the U.S. Epidemiology • Incidence – 20-100/100,000 in U.S. • Age – bimodal peaks • Pediatric – 5-14 years • Elderly – >60 years • Sex – M:F, equal • M<F with acrodermatitis chronica atrophicans • Transmission – infected Ixodes tick bite Organism • Borrelia burgdorferi is a member of the Spirochaetales family, which also includes Treponema and Leptospira Risk Factors • Exposure in regions where deer population is high during the spring or summer • Northeast or Midwest geographic location • 12 U.S. states account for 95% of reported cases Clinical Presentation • Clinical case epidemiologic surveillance criteria for defining Lyme disease (Centers for Disease Control) • Erythema migrans (EM) ≥5 cm in diameter or laboratory confirmation of infection plus ≥1 late manifestation • Musculoskeletal manifestation – recurrent, brief attacks of objective swelling in 1 or more joints • Neurological manifestations (all or part of a triad) • Lymphocytic meningitis – cerebrospinal fluid (CSF) pleocytosis with higher number of monocytes • Cranial neuritis • Radiculoneuritis (termed Garin-Bujadoux-Bannwarth syndrome) • Encephalomyelitis – requires demonstration of CSF antibody production • Cardiovascular manifestations – acute second- or third-degree arteriovenous heart block • Lyme disease stages • Stage 1 – early localized • Occurs within hours to several weeks after infection • Characterized by EM or lymphocytoma (rare in U.S.) • Manifestations • Regional adenopathy, minor constitutional symptoms • Stage 2 – early disseminated • Occurs weeks to months following the tick bite • Characterized by neurologic (15% of patients) and cardiac (8% of patients) involvement • Manifestations • Fever • Myalgias • Multiple EM lesions • Meningitis ARUP LABORATORIES | 500 Chipeta Way | Salt Lake City, Utah 84108-1221 | (800) 522-2787 | www.arupconsult.com | www.aruplab.com © 2006–2010 ARUP Laboratories. All Rights Reserved. Borrelia burgdorferi - Lyme Disease - p. 1 of 10
  2. 2. The Physician's Guide to Laboratory Test Selection and Interpretation • Bells palsy • Guillain-Barré-like syndrome • Cardiac conduction abnormalities • Arthritis • Stage 3 – late disseminated • Occurs within a few weeks to 2 years following infection • Symptoms are more severe than early disseminated-stage disease • Characterized by arthritis or central nervous system (CNS) involvement • Occurs in 60% of individuals not effectively treated early in infection • Tends to be intermittent, lasting from several days to weeks • Manifestations • Memory loss • Fatigue • Neuropathy (often polyneuropathy) • Initial symptoms usually appear in late spring/early summer, when ticks are active • Late manifestations occur anytime Treatment • Lyme disease is easily treated if diagnosed early • Treatment prevents progression to chronic stage (stages 2 or 3) • Severe, long-term effects occur in <10% of untreated patients • If known tick bite and EM present, proceed with treatment; testing is not necessary • Prophylactic antibiotic therapy for tick bites not recommended, even in endemic regions Prevention • Avoid exposure to ticks • If exposure is unavoidable, use protective clothing and tick repellant (DEET); check for and remove ticks Diagnosis Lyme Disease Indications for Testing • Patient at risk for Lyme disease with clinical symptoms • No testing necessary if patient presents with tick bite and erythema migrans Laboratory Testing • Current CDC recommendations for serologic diagnosis of Lyme disease • Screen with a polyvalent ELISA test or C6 peptide antibodies • Confirm equivocal and positive results with Western Blot • <8 weeks after onset of disease – IgG-, IgM+ • >8 weeks after onset of disease – IgG+ • If testing is initially negative, consider other diseases; test convalescent sample • Serological testing • False-positive results from serologic tests may result from • Other spirochetal disease (syphilis, periodontitis) • Autoimmune diseases (systemic lupus erythematosus, rheumatoid arthritis) • Other infections (subacute bacterial endocarditis, HIV, acute Epstein-Barr virus [EBV]) • Co- and triple-infections by parasites that cause babesiosis and granulocytic anaplasmosis (formerly known as human granulocytic ehrlichiosis) may occur (particularly in endemic areas) ARUP LABORATORIES | 500 Chipeta Way | Salt Lake City, Utah 84108-1221 | (800) 522-2787 | www.arupconsult.com | www.aruplab.com © 2006–2010 ARUP Laboratories. All Rights Reserved. Borrelia burgdorferi - Lyme Disease - p. 2 of 10
  3. 3. The Physician's Guide to Laboratory Test Selection and Interpretation • Serologic testing specific for these agents is recommended • Babesia microti IgG, IgM antibodies • Anaplasma phagocytophilum IgG, IgM antibodies • Ehrlichia chaffeensis IgG, IgM antibodies Neurologic Disease Evaluation Indications for Testing • Meningoradiculitis, meningitis, cranial nerve deficits Criteria for Diagnosis • Possible neuroborreliosis • Typical clinical features (eg, meningitis, meningoradiculitis, cranial nerve deficits) • B. burgdorferi-specific IgG and/or IgM serum antibodies • CSF findings not available/lumbar puncture not performed • Probable neuroborreliosis • Criteria of possible neuroborreliosis plus • Inflammatory CSF changes (lymphocytic pleocytosis, elevated protein content, intrathecal IgG antibody production) • Exclusion of other causes • Proven (definite) neuroborreliosis • Criteria of probable neuroborreliosis plus • Intrathecal B. Burgdorferi-specific antibody production (positive culture or PCR) Laboratory Testing • Lumbar fluid analysis • Cell count – lymphocytic pleocytosis is typical (>8 wbc/mm3) • Total protein, glucose, culture with gram stain (all CSF) • IgG and IgM antibody testing • Acute disease • Borrelia burgdorferi C6 peptide antibodies • Borrelia burgdorferi total antibodies • Borrelia burgdorferi IgG, IgM antibodies • Borrelia species DNA detection • Chronic disease • Borrelia burgdorferi IgG antibody • Borrelia species DNA detection Differential Diagnosis • Neurologic • HIV • Acute meningitis • Acute encephalitis • Multiple sclerosis • Demyelinating disorder • Guillain-Barré syndrome • Treponema pallidum (syphilis) • Arboviral disease • EBV ARUP LABORATORIES | 500 Chipeta Way | Salt Lake City, Utah 84108-1221 | (800) 522-2787 | www.arupconsult.com | www.aruplab.com © 2006–2010 ARUP Laboratories. All Rights Reserved. Borrelia burgdorferi - Lyme Disease - p. 3 of 10
  4. 4. The Physician's Guide to Laboratory Test Selection and Interpretation • Musculoskeletal • Neisseria gonorrhea • Parvovirus • Septic arthritis • Connective tissue diseases (eg, SLE) • Rheumatoid arthritis • Fibromyalgia • Rheumatic fever • Reactive arthritis trachomatis • Crystalline arthritis • Acute febrile illness • Ehrlichia chaffeensis • Rickettsia rickettsii • Babesia microti • Francisella tularensis • Malaria • Colorado tick fever • Arbovirus • EBV • Heart block • Endocarditis • Sick sinus syndrome • Connective tissue disease • Anaplasma phagocytophilum Lab Tests Indications for Laboratory Testing Tests generally appear in the order most useful for common clinical situations. For test-specific information, refer to the test number in the ARUP Laboratory Test Directory on the ARUP Web site at www.aruplab.com. Test Name and Number Recommended Use Limitations Follow Up Borrelia burgdorferi Screen for Lyme disease <8 weeks No objective tests for Antibodies, Total by ELISA after onset of disease Lyme borreliosis are with Reflex to IgG & IgM If known tick bite and erythema 100% sensitive and by Western Blot (Early migrans present, proceed with 100% specific Disease) treatment – no testing necessary Diagnosis depends 0050267 on clinical features, Method: combined with Enzyme-Linked available laboratory Immunosorbent tests Assay/Western Blot ARUP LABORATORIES | 500 Chipeta Way | Salt Lake City, Utah 84108-1221 | (800) 522-2787 | www.arupconsult.com | www.aruplab.com © 2006–2010 ARUP Laboratories. All Rights Reserved. Borrelia burgdorferi - Lyme Disease - p. 4 of 10
  5. 5. The Physician's Guide to Laboratory Test Selection and Interpretation Borrelia burgdorferi C6 Screen for Lyme disease <8 weeks No objective tests for Peptide Antibodies, Total after onset of disease Lyme borreliosis are by ELISA with Reflex to If known tick bite and erythema 100% sensitive and IgG & IgM by Western Blot migrans present, proceed with 100% specific 0051043 treatment – no testing necessary Diagnosis depends Method: on clinical features Enzyme-Linked combined with Immunosorbent available laboratory Assay/Western Blot tests Borrelia burgdorferi Confirm an equivocal or positive No objective tests for Retesting in 10-14 days Antibodies, IgG & IgM by antibody test performed <8 weeks Lyme borreliosis are may be helpful when Western Blot after appearance of erythema 100% sensitive and serology test results 0050254 migrans 100% specific are equivocal Method: If known tick bite and erythema Diagnosis depends Western Blot migrans present, proceed with on clinical features treatment – no testing necessary combined with available laboratory tests Borrelia burgdorferi Confirm an equivocal or positive No objective tests for Antibody, IgG by Western antibody test performed >8 weeks Lyme borreliosis are Blot after appearance of erythema 100% sensitive and 0050255 migrans 100% specific Method: If known tick bite and erythema Diagnosis depends Western Blot migrans present, proceed with on clinical features treatment – no testing necessary combined with available laboratory tests Borrelia species DNA Diagnose Lyme disease in patient Negative result does Detection by PCR (Lyme with negative serologic results but not rule out presence Disease) disease still strongly suspected or of PCR inhibitors or 0055570 with immune deficiency B. burgdorferi DNA If known tick bite and erythema concentrations below Method: migrans present, proceed with detection level of assay Polymerase Chain Reaction treatment – no testing necessary No objective tests for Lyme borreliosis are 100% sensitive and 100% specific Diagnosis depends on clinical features, combined with available laboratory tests Cell Count, CSF Aids in differentiating Lyme disease 0095018 from other forms of meningitis Method: Cell Count/Differential ARUP LABORATORIES | 500 Chipeta Way | Salt Lake City, Utah 84108-1221 | (800) 522-2787 | www.arupconsult.com | www.aruplab.com © 2006–2010 ARUP Laboratories. All Rights Reserved. Borrelia burgdorferi - Lyme Disease - p. 5 of 10
  6. 6. The Physician's Guide to Laboratory Test Selection and Interpretation Protein, Total, CSF Aids in differentiating Lyme disease 0020514 from other forms of meningitis Method: Reflectance Spectrophotometry Glucose, CSF Aids in differentiating Lyme disease 0020515 from other forms of meningitis Method: Enzymatic CSF Bacterial Culture Aids in differentiating Lyme disease (Includes Gram Stain from other forms of meningitis 0060101) 0060106 Method: Standard reference procedures for bacterial stain, aerobic culture, and identification Borrelia burgdorferi Adjunct test for neuroborreliosis No objective tests for Detection of antibodies Antibody, IgG by Western in patient with neurological Lyme borreliosis are to B. burgdorferi in Blot (CSF) symptoms >8 weeks after onset of 100% sensitive and CSF may indicate CNS 0055259 disease 100% specific infection Method: Diagnosis depends Consider possible Western Blot on clinical features contamination by blood combined with or transfer of serum available laboratory antibodies across tests blood-brain barrier Borrelia burgdorferi C6 Adjunct test for neuroborreliosis in No objective tests for Detection of antibodies Peptide Antibodies, Total patient with neurologic symptoms <8 Lyme borreliosis are of B. burgdorferi in by ELISA (CSF) weeks from onset of disease 100% sensitive and CSF may indicate CNS 0051046 100% specific infection Method: Diagnosis depends Consider possible Enzyme-Linked on clinical features contamination by blood Immunosorbent Assay combined with or transfer of serum available laboratory antibodies across tests blood-brain barrier For equivocal results, repeat testing in 10-14 days may be helpful ARUP LABORATORIES | 500 Chipeta Way | Salt Lake City, Utah 84108-1221 | (800) 522-2787 | www.arupconsult.com | www.aruplab.com © 2006–2010 ARUP Laboratories. All Rights Reserved. Borrelia burgdorferi - Lyme Disease - p. 6 of 10
  7. 7. The Physician's Guide to Laboratory Test Selection and Interpretation Borrelia burgdorferi Screening test (confirmed by No objective tests for Detection of antibodies Antibodies, Total by ELISA Western Blot) for neuroborreliosis in Lyme borreliosis are to B. burgdorferi in (CSF) patient with neurologic symptoms <8 100% sensitive and CSF may indicate CNS 0099483 weeks from onset of disease 100% specific infection Method: Diagnosis depends Consider possible Enzyme-Linked on clinical features contamination by blood Immunosorbent Assay combined with or transfer of serum available laboratory antibodies across tests blood-brain barrier Retesting in 10-14 days may be helpful when serology test results are equivocal Borrelia burgdorferi Confirm positive test for CSF No objective tests for Detection of antibodies Antibodies, IgG & IgM by antibodies Lyme borreliosis are to B. burgdorferi in Western Blot (CSF) 100% sensitive and CSF may indicate CNS 0055260 100% specific infection Method: Diagnosis depends Consider possible Western Blot on clinical features contamination by blood combined with or transfer of serum available laboratory antibodies across the tests blood-brain barrier Babesia microti Consider for those who test negative Antibodies, IgG & IgM by for Lyme disease antibodies but IFA who live in endemic areas and have 0093048 compatible symptoms Method: Indirect Fluorescent Antibody Anaplasma Consider for those who test negative phagocytophilum (HGA) for Lyme disease antibodies but Antibodies, IgG & IgM who live in endemic areas and have 0097303 compatible symptoms Method: Indirect Fluorescent Antibody ARUP LABORATORIES | 500 Chipeta Way | Salt Lake City, Utah 84108-1221 | (800) 522-2787 | www.arupconsult.com | www.aruplab.com © 2006–2010 ARUP Laboratories. All Rights Reserved. Borrelia burgdorferi - Lyme Disease - p. 7 of 10
  8. 8. The Physician's Guide to Laboratory Test Selection and Interpretation Ehrlichia and Anaplasma Consider for those who test negative species by Real-Time PCR for Lyme disease antibodies but 2003078 who live in endemic areas and have compatible symptoms Method: Real-Time Polymerase Chain Reaction /DNA Probe Hybridization Additional Tests Available Test Name and Number Comments Borrelia burgdorferi C6 Peptide Antibodies, Total by ELISA 0051044 Method: Enzyme-Linked Immunosorbent Assay Borrelia burgdorferi Antibody, IgM by Western Blot 0050253 Method: Western Blot Borrelia burgdorferi Total Antibodies, IgG and/or IgM by ELISA with Reflex to IgG by Western Blot (Late Disease) 0050268 Method: Enzyme-Linked Immunosorbent Assay/Western Blot Borrelia burgdorferi Antibody, IgM by Western Blot (CSF) 0055258 Method: Western Blot Borrelia hermsii Antibody Panel, IFA 0093170 Method: Immunofluorescence Assay Lyme Antigen, Urine 0050219 Method: Lyme Dot-Blot Assay ARUP LABORATORIES | 500 Chipeta Way | Salt Lake City, Utah 84108-1221 | (800) 522-2787 | www.arupconsult.com | www.aruplab.com © 2006–2010 ARUP Laboratories. All Rights Reserved. Borrelia burgdorferi - Lyme Disease - p. 8 of 10
  9. 9. The Physician's Guide to Laboratory Test Selection and Interpretation Borrelia burgdorferi Antibodies, Total by ELISA Alternative first-line screening test for Lyme disease 0050216 If known tick bite and erythema migrans present, Method: proceed with treatment – no testing necessary Enzyme-Linked Immunosorbent Assay Up to 40% of patients with early disease are seronegative by ELISA at time they present with erythema migrans Serologic diagnosis often not established until advanced stage of disease No objective tests for Lyme borreliosis are 100% sensitive and 100% specific Diagnosis depends on clinical features combined with available laboratory tests Retesting in 10-14 days may be helpful when serology test results are equivocal Borrelia burgdorferi C6 Peptide Antibodies, Total by ELISA Screen for Lyme disease >8 weeks after onset of with Reflex to IgG by Western Blot disease 0051045 If known tick bite and erythema migrans present, Method: proceed with treatment – no testing necessary Enzyme-Linked Immunosorbent Assay/Western Blot No objective tests for Lyme borreliosis are 100% sensitive and 100% specific Diagnosis depends on clinical features combined with available laboratory tests Ehrlichia chaffeensis Antibodies, IgG & IgM by IFA Consider for those who test negative for Lyme 0051002 disease antibodies but who live in endemic areas and have compatible symptoms Method: Indirect Fluorescent Antibody Guidelines Halperin JJ, Shapiro ED, Logigian E, Belman AL, Dotevall L, Wormser GP, Krupp L, Gronseth G, Bever CT Jr. Practice parameter: treatment of nervous system Lyme disease (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology.Neurology. 2007; 69 (1) :91-102. Wormser GP, Dattwyler RJ, Shapiro ED, Halperin JJ, Steere AC, Klempner MS, Krause PJ, Bakken JS, Strle F, Stanek G, Bockenstedt L, Fish D, Dumler JS, Nadelman RB. The clinical assessment, treatment, and prevention of lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America.Clin Infect Dis. 2006; 43 (9) :1089-1134. General References Aberer E. What should one do in case of a tick bite?.Curr Probl Dermatol. 2009; 37 :155-166. Aguero-Rosenfeld ME. Lyme disease: laboratory issues.Infect Dis Clin North Am. 2008; 22 (2) :301-13, vii. Bratton RL, Whiteside JW, Hovan MJ, Engle RL, Edwards FD. Diagnosis and treatment of Lyme disease.Mayo Clin Proc. 2008; 83 (5) :566-571. Dandache P, Nadelman RB. Erythema migrans.Infect Dis Clin North Am. 2008; 22 (2) :235-60, vi. Feder HM Jr. Lyme disease in children.Infect Dis Clin North Am. 2008; 22 (2) :315-26, vii. Hoppa E, Bachur R. Lyme disease update.Curr Opin Pediatr. 2007; 19 (3) :275-280. ARUP LABORATORIES | 500 Chipeta Way | Salt Lake City, Utah 84108-1221 | (800) 522-2787 | www.arupconsult.com | www.aruplab.com © 2006–2010 ARUP Laboratories. All Rights Reserved. Borrelia burgdorferi - Lyme Disease - p. 9 of 10
  10. 10. The Physician's Guide to Laboratory Test Selection and Interpretation Hytonen J, Hartiala P, Oksi J, Viljanen MK. Borreliosis: recent research, diagnosis, and management.Scand J Rheumatol. 2008; 37 (3) :161-172. Marques A. Chronic Lyme disease: a review.Infect Dis Clin North Am. 2008; 22 (2) :341-viii. Puius YA, Kalish RA. Lyme arthritis: pathogenesis, clinical presentation, and management.Infect Dis Clin North Am. 2008; 22 (2) :289-vii. Rupprecht TA, Pfister HW. What are the indications for lumbar puncture in patients with Lyme disease?.Curr Probl Dermatol. 2009; 37 :200-206. Shapiro ED. Lyme disease.Adv Exp Med Biol. 2008; 609 :185-195. Wilske B, Fingerle V, Schulte-Spechtel U. Microbiological and serological diagnosis of Lyme borreliosis.FEMS Immunol Med Microbiol. 2007; 49 (1) :13-21. Reviewed by Hillyard, David R., MD. Medical Director, Molecular Infectious Diseases at ARUP Laboratories; Professor of Pathology, University of Utah Litwin, Christine, MD. Medical Director, Immunology at ARUP; Professor of Pathology (Clinical), University of Utah Diagnostic Algorithm(s) PDF algorithm(s) available at www.arupconsult.com. Lyme Disease Testing Algorithm Related Content Arboviruses Babesia microti Dengue Fever Virus Ehrlichiosis and Colorado Tick Fever Encephalitis, Infectious Francisella tularensis - Tularemia Meningitis, Acute Multiple Sclerosis Parvovirus B19 Plasmodium Species - Malaria Rickettsia rickettsii - Rocky Mountain Spotted Fever Comprehensive Review: June 2010 Last Update: June 2010 ARUP LABORATORIES | 500 Chipeta Way | Salt Lake City, Utah 84108-1221 | (800) 522-2787 | www.arupconsult.com | www.aruplab.com © 2006–2010 ARUP Laboratories. All Rights Reserved. Borrelia burgdorferi - Lyme Disease - p. 10 of 10

×