Sections View Full Chapter Figures Tables Videos Annotate Full Chapter Figures Tables Videos Supplementary Content + Download Section PDF Listen ++ For further information, see CMDT Part 34-11: Lyme Disease (Lyme Borreliosis) + Key Features Download Section PDF Listen +++ +++ Essentials of Diagnosis ++ Erythema migrans, a flat or slightly raised red lesion that expands with central clearing Headache or stiff neck Arthralgias, arthritis, and myalgias; arthritis is often chronic and recurrent Wide geographic distribution, with most cases in the northeast, mid-Atlantic, upper midwest, and Pacific coastal regions of the United States +++ General Considerations ++ Causative spirochete varies by geography In the United States, it is Borrelia burgdorferi senu strictu In Europe and Asia, it is Borrelia garinii and Borrelia afzelli Incidence of disease is significantly higher when tick attachment is for longer than 72 h The percentage of ticks infected varies on a regional basis. In the northeast and midwest, 15–65%, in the west, < 5% Congenital infection has been documented Ixodes scapularis is capable of transmitting other infections in addition to Lyme disease, including babesiosis and human granulocytic anaplasmosis (formerly human granulocytic ehrlichiosis) Coinfection with two or even all three of these organisms can occur, causing a clinical picture that is not "classic" for any of these diseases Coinfection should be considered and excluded in patients who have Persistent high fevers 48 hours after starting appropriate therapy for Lyme disease Persistent symptoms despite resolution of rash Anemia, leukopenia, or thrombocytopenia +++ Demographics ++ Most cases are reported from the mid-Atlantic, northeastern, and north central regions of the country True incidence is unknown and overreporting continues to be a problem for following reasons: Serologic tests are not standardized Clinical manifestations are nonspecific Serology tests are insensitive in early disease Most infections occur in the spring and summer + Clinical Findings Download Section PDF Listen +++ +++ Symptoms and Signs ++ Stage 1, early localized infection Erythema migrans A flat or slightly raised red lesion at the bite site ~1 week after the tick bite (range, 3–30 days; median, 7–10 days) Common in areas of tight clothing such as the groin, thigh, or axilla The lesion expands over several days Classic lesion progresses with central clearing ("bulls-eye" lesion); often there is a more homogeneous appearance or even central intensification Concomitant viral-like illness develops in most patients and is characterized by Myalgias, arthralgias Headache, fatigue Fever may or may not be present Stage 2, early disseminated infection (weeks to months later) Bacteremia (in up to 50–60% of patients with erythema migrans) Secondary skin lesions Develop within days to weeks of original infection in about 50% of patients Lesions similar to primary lesion but smaller Skin involvement can be manifested as a cutaneous hypopigmented lesion called a borrelial lymphocytoma (rare) Malaise, fatigue, fever, headache, neck pain generalized achiness common with skin lesions Myopericarditis, with atrial or ventricular arrhythmias and heart block (4–10%) Neurologic manifestations (10–15%) Aseptic meningitis with mild headache and neck stiffness Cranial nerve VII neuropathy (eg, facial palsy) Sensory or motor radiculopathy and mononeuritis multiplex occur less frequently Conjunctivitis, keratitis Panophthalmitis (rare) Stage 3, late persistent infection (months to years later) Musculoskeletal manifestations (up to 60%) Monarticular or oligoarticular arthritis of knee or other large weight-bearing joints Chronic arthritis develops in about 10% of patients Neurologic manifestations (rare) Subacute encephalopathy (memory loss, mood changes, and sleep disturbance) Intermittent paresthesias, often in stocking glove distribution, or radicular pain Severe encephalomyelitis, seen more in Europe, presents with cognitive dysfunction, spastic paraparesis, ataxia, and bladder dysfunction Acrodermatitis chronicum atrophicans Cutaneous manifestation Usually bluish-red discoloration of distal extremity with associated swelling Lesions atrophic and sclerotic, resemble localized scleroderma Great overlap between stages: skin, CNS, and musculoskeletal systems can be involved early or late +++ Differential Diagnosis ++ Babesiosis, ehrlichiosis A americanum (Lone Star tick) bite-related illness Southern tick–associated rash illness (STARI) Urticaria, reaction to arthropod bite, cellulitis, erythema multiforme, granuloma annulare Rocky Mountain spotted fever Primary HIV infection Parvovirus B19 infection Rheumatic fever, Still disease, gonococcal arthritis, sarcoidosis, systemic lupus erythematosus Viral meningitis, facial palsy + Diagnosis Download Section PDF Listen +++ +++ Laboratory Tests ++ Elevated sedimentation rate of > 20 mm/h (50% of cases) Mildly abnormal liver biochemical tests (30% of cases) Mild anemia, leukocytosis, and microscopic hematuria in 10% or less Detection of specific antibodies to B burgdorferi in serum by ELISA (more sensitive and specific) A two-test approach is recommended, with all specimens positive or equivocal by ELISA or indirect immunofluorescence assay (IFA) followed by Western immunoblot assay that can detect both IgM and IgG antibodies Polymerase chain reaction (PCR) test Very specific for detecting Borrelia DNA However, sensitivity is variable and depends on which body fluid is tested and which stage of disease Testing should not be done on blood or urine but has been succesfully performed on synovial fluid and cerebrospinal fluid (CSF) Up to 85% of synovial fluid samples are PCR positive in active arthritis CSF samples in late nervous system Lyme disease May show evidence of inflammation (pleocytosis or elevated protein, or both), and localized antibody production, ie, a ratio of CSF to serum antibody of > 1.0 in patients with encephalopathy PCR test on CSF has low sensitivity and is not recommended for routine diagnosis 38% of CSF samples are PCR positive in acute nervous system Lyme disease, but only 25% are positive in chronic nervous system Lyme disease Elevated levels of the chemokine CXCL13 have been associated with CNS Lyme disease, but they can also occur in other infections such as neurosyphilis Lyme urinary antigen test, lymphocyte stimulation test, PCR tests on blood and urine Have not been approved or standardized Should not be used to support the diagnosis of Lyme disease +++ Diagnostic Procedures ++ A person who has been exposed to a potential tick habitat (within the 30 days just prior to developing erythema migrans) with the following fulfills the diagnostic criteria for Lyme disease Erythema migrans diagnosed by a physician At least one late manifestation of the disease Laboratory confirmation Cultures for B burgdorferi can be performed but are not routine Aspiration of erythema migrans lesions is positive in up to 30% of cases 2-mm punch biopsy is positive in 50–70% Blood cultures positive in up to 50% CSF rarely culture positive Peripheral neuropathy may be detected by electromyography + Treatment Download Section PDF Listen +++ +++ Medications ++ See Table 34–4 Erythema migrans Doxycycline, 100 mg orally twice daily for 2–3 weeks, or Amoxicillin, 500 mg orally three times daily for 2–3 weeks, or Cefuroxime axetil, 500 mg orally twice daily for 2–3 weeks Facial palsy Doxycycline, 100 mg orally twice daily for 2–3 weeks, or Amoxicillin, 500 mg orally three times daily for 2–3 weeks Cefuroxime axetil, 500 mg orally twice daily for 2–3 weeks Other CNS disease Ceftriaxone, 2 g intravenously once daily for 2–4 weeks, or Penicillin G, 18–24 million units daily intravenously in six divided doses for 2–4 weeks, or Cefotaxime, 2 g intravenously every 8 hours for 2–4 weeks First-degree block (PR < 0.3 s) Doxycycline, 100 mg orally twice daily for 3–4 weeks, or Amoxicillin, 500 mg orally three times daily for 3–4 weeks High-degree atrioventricular block Ceftriaxone, 2 g intravenously once daily for 2–4 weeks, or Penicillin G, 18–24 million units daily intravenously in six divided doses for 2–4 weeks Arthritis Oral: doxycycline, 100 mg twice daily for 4 weeks; or amoxicillin, 500 mg three times daily for 4 weeks; if this fails (persistent or recurrent joint swelling), re-treat with oral agent for 8 weeks or switch to intravenous agent for 2–4 weeks Parenteral: ceftriaxone, 2 g intravenously once daily for 2–4 weeks; cefotaxime, 2 g intravenously every 8 hours for 2–4 weeks; or penicillin G, 18–24 million units daily intravenously in six divided doses for 2–4 weeks Acrodermatitis chronicum atrophicans Doxycycline, 100 mg orally twice daily for 3–4 weeks, or Amoxicillin, 500 mg orally three times daily for 4 weeks ++Table Graphic Jump LocationTable 34–4.Treatment of Lyme disease.View Table||Download (.pdf) Table 34–4. Treatment of Lyme disease. Manifestations Medication and Dosage Tick bite No treatment in most circumstances (see text); observe Erythema migrans1 Doxycycline, 100 mg orally twice daily for 10–14 days, or amoxicillin, 500 mg orally three times daily for 2–3 weeks, or cefuroxime axetil, 500 mg orally twice daily for 2–3 weeks Neurologic disease Facial palsy (without meningitis) Doxycycline, amoxicillin, or cefuroxime axetil as above for 2–3 weeks Other central nervous system disease Ceftriaxone, 2 g intravenously once daily, or penicillin G, 18–24 million units daily intravenously in six divided doses, or cefotaxime, 2 g intravenously every 8 hours—all for 2–4 weeks Cardiac disease Atrioventricular block and myopericarditis2 An oral or parenteral (if more severe disease) regimen as described above can be used Arthritis Oral dosage Doxycycline, amoxicillin, or cefuroxime axetil as above for 28 days (see text) Parenteral dosage Ceftriaxone, cefotaxime, or penicillin G as above for 2–4 weeks Acrodermatitis chronicum atrophicans Doxycycline, amoxicillin, or cefuroxime axetil as above for 3 weeks “Chronic Lyme disease” or “post-Lyme disease syndrome” Symptomatic therapy; prolonged antibiotics are not recommended 1Patients who cannot tolerate tetracyclines or beta-lactams can be treated with azithromycin 500 mg orally daily for 10 days.2Symptomatic patients, those with second- or third-degree block, and those with first-degree block with a PR interval ≥ 300 milliseconds should be hospitalized for observation. +++ Therapeutic Procedures ++ Tick bite: no treatment in most circumstances; observe If acute arthritis, need aspiration to rule out pyogenic arthritis If neurologic symptoms, need lumbar puncture because drug and duration of therapy are unique for nervous system Lyme disease If suspect peripheral neuropathy, perform nerve conduction studies + Outcome Download Section PDF Listen +++ +++ Follow-Up ++ Routine follow-up Complete recovery in 4–6 weeks after therapy of early disease Fatigue, arthralgias, myalgias may persist for weeks or months but do not require antimicrobial therapy After treatment of arthritis, arthralgias may persist and be severe; if not resolved after 3 months, re-treat with antibiotics; if arthralgias still persist treat symptomatically +++ Complications ++ Rarely, residual facial nerve palsy, synovitis or heart block requiring a pacemaker +++ Prevention ++ Avoiding tick-infested areas, covering exposed skin, using repellents, and inspecting for ticks after exposure Prophylactic antibiotics (eg, single 200 mg dose of doxycycline) is recommended in certain high-risk situations if all of the following criteria are met A tick identified as an adult or nymphal Ixodes scapularis has been attached for ≥ 36 h Prophylaxis can be started within 72 h of tick removal More than 20% of ticks in the area are known to be infected with B burgdorferi There is no contraindication to the use of doxycycline (not pregnant, age > 8 years, not allergic) +++ Prognosis ++ With appropriate therapy, symptoms usually resolve within 4 weeks The long-term outcome of adult patients with Lyme disease is generally favorable Long-term sequelae are uncommon +++ When to Refer ++ Consultation with an infectious diseases specialist with experience in treating Lyme disease can be helpful in atypical or prolonged cases +++ When to Admit ++ Admission for parenteral antibiotics is indicated for any patient with Symptomatic CNS or cardiac disease Second- or third-degree atrioventricular block First-degree block with a PR interval ≥ 300 milliseconds + References Download Section PDF Listen +++ + +Berende A et al. Randomized trial of longer-term therapy for symptoms attributed to Lyme disease. N Engl J Med. 2016 Mar 31;374(13):1209–20. [PubMed: 27028911] + +Cardenas-de la Garza JA et al. Clinical spectrum of Lyme disease. Eur J Clin Microbiol Infect Dis. 2019 Feb;38(2):201–8. [PubMed: 30456435] + +Eldin C et al. Review of European and American guidelines for the diagnosis of Lyme borreliosis. Med Mal Infect. 2019 Mar;49(2):121–32. [PubMed: 30528068] + +Eldin C et al. Values of diagnostic tests for the various species of spirochetes. Med Mal Infect. 2019 Mar;49(2):102–11. [PubMed: 30765286]