Borrelia Burgdorferi: A Clinical Chameleon

ABSTRACT: Lyme disease is a multisystem disease, with over 30,000 confirmed and probable cases reported in the United States. Cardiac involvement occurs in the early disseminated phase and commonly presents with atrioventricular nodal block. It is evident that Lyme disease is not isolated to North America alone, making it important for clinicians to have a low clinical suspicion in order to initiate appropriate treatment. 

Lyme disease is a spirochete infection transmitted through the bite of blacklegged ticks.  First identified in 1977, the disease is caused by the bacterium Borrelia burgdorferi in the United States, B afzelii in Europe, and B garinii in Asia.¹ 

Lyme disease became a reportable disease in 1982 and since then, the incidence of the disease has risen secondary to heightened awareness of Lyme disease by patients and physicians, increased use of laboratory testing for the disease, and better surveillance. There were 30,000 confirmed cases of Lyme disease in the United States in 2012, with most of the cases based mainly in the Northeast (Connecticut, Delaware, Maine, Maryland, Massachusetts, New Hampshire, New Jersey, New York, Pennsylvania, Rhode Island and Vermont) and Upper Midwest (Minnesota and Wisconsin).^2,3 This data highlights the varied, inconsistent, and often subtle presentations of Lyme disease, which emphasizes the need for clinicians to have a broad differential and low threshold for testing patients for Lyme disease. 

In December 2013, the CDC reported 3 cardiac deaths secondary to Lyme disease. Untreated Lyme disease can manifest from a wide range of symptoms from joint disease to complete heart blocks requiring temporary pacing. Cardiac and neurological involvement are linked to the highest mortality rates. 

Lyme disease is a growing disease that is often underdiagnosed, partially because it presents in several different clinical forms. Occasionally, the outcome of the disease could be fatal. From 1999 to 2003, there have been 114 deaths associated with Lyme disease.⁴ This article provides an overview of Lyme disease, from initial presentation to treatment options.  

Classification and Presentation

Lyme disease is observed in 3 stages: early localized infection (primary), early disseminated disease (secondary), and late disease (tertiary). Early localized infection presents within 1 month of exposure and is evidenced by a red macule at the tick bite site, which expands evolving a central clearing occasionally appearing as the classic target lesion. Erythema migrans is the dermatologic presentation in the early localized infection and is generally large (15 cm, on average). 

These lesions are generally painless but can sometimes have pruritis or burning. Estimates of about half of patients in the early localized stage experience constitutional symptoms that quickly resolve with appropriate therapy. A few days after erythema migrans is present, satellite lesions can be present indicating dissemination. Early disseminated disease occurs within weeks to several months after exposure, manifests in up to 50% of untreated patients. 

Cardiovascular, musculoskeletal, and nervous system involvement are the classic manifestations of early disseminated disease. Migratory polyarthritis usually evolves over 1 to 2 days to a single joint arthritis. Nervous system manifests as headache that comes and goes. Close to 10% of untreated patients with nervous system involvement can progress to severe problems such as meningitis, cranial nerve palsies (eg, Bell’s palsy), and peripheral neuritis. Bannworth’s syndrome includes the triad of meningitis, cranial nerve palsies, and neuritis. 

Cardiac involvement of Lyme disease may manifest as an atrioventricular (AV) block, myopericarditis, and left ventricular dysfunction. Studies have shown that carditis occurred in approximately 4% to 10% of untreated Lyme disease patients; the incidence increases if asymptomatic carditis is also included.² Spirochetes can directly invade the myocardium leading to a lymphocytic inflammatory response. This causes conduction defects—most commonly first-degree AV block, but can be as serious as second-degree and complete heart block. Myocarditis leading to heart failure is rare. 

Late disease typically develops months to years after exposure. The most common complaints involve the musculoskeletal system—such as migratory
arthralgias, joint swelling, and arthritis. Arthritis typically resolved after proper antibiotic therapy. Neurologic manifestations in late disease and may involve a chronic encephalopathy, peripheral neuropathy, mood, and sleep disorders. Other late disease manifestations include acrodermatitis chronica atrophicans, fibromyalgia-like syndrome, chronic fatigue, and failure to respond to antibiotics. 

Table 1-3 illustrate the presenting illness, physical examination, and laboratory findings in our patients and Figures 1-2 shows EKG changes found in our patients.

Diagnosis

Diagnosis of Lyme disease begins with proper history and physical exam, leading to clinical probability of having Lyme disease. This includes knowing probability of exposure, location to endemic areas, time of year, as well as evidence of erythema migrans on physical exam. The rash begins at the tick bite site and must enlarge to at least 2.5 inches in diameter to meet the case definition of Lyme disease and to distinguish it from a tick bite reaction.⁵ 

In the absence of this rash, there must be at least 1 objective sign of involvement of the musculoskeletal system (eg, joint swelling), nervous system (eg, meningitis and peripheral nerve abnormality), or cardiovascular system (eg, arrhythmia), in addition to a positive laboratory test result that supports B burgdorferi infection.^2,5 Many times patients will not know they experienced a tick bite. The CDC recommends a 2-step approach to laboratory diagnosis in patients with suspicions for Lyme disease. The Lyme disease enzyme-linked immunosorbent assay (ELISA) detects IgG and IgM antibodies against B burgdorferi. In early disease, only about 60% of patients will have a significant rise in their antibodies. Therefore, ELISA should be checked again in several weeks as IgM titers may not be significant for as many as 8 weeks after exposure. 

IgG titers generally remain positive for life. False positives can occur and are more common in patients with other infections, such as syphilis, malaria, endocarditis, and viral illnesses. Western blot is the second step recommended by the CDC to confirm any positive ELISA test looking for antibodies against specific peptide components of B burgdorferi. Antibiotic therapy can interfere and cause false negative results. Joint effusions generally result in an inflammatory type cell count. Culturing the organism is generally low yield. 

Cardiovascular Impact

Lyme disease can cause carditis and AV nodal heart block, myopericarditis, and chronic cardiomyopathy. 

Carditis

Lyme carditis is presentation of disseminated stage and patients during this stage might usually have either IgM or IgG antibodies present. Most cases of Lyme carditis occur between June and December, anywhere from 4 days to 7 months (median 21 days) after initial illness.² 

Carditis occurs in 4% to 10% of Lyme disease cases and usually begins 3 to 6 weeks after the initial illness.⁶ Temporary cardiac pacing is frequently needed by patients who have severe heart block with hemodynamic instability.⁶ 

Evidence suggests that, in most cases, the block is at the level of the AV node. The block generally resolves completely with antibiotic treatment. Complete heart block rarely persists more than 1 week and the long-term prognosis appears to be excellent. The degree of AV block can fluctuate rapidly from first degree AV block to complete AV block and back to first-degree AV block in a matter of minutes.² 

In a study conducted in North America and Europe of 105 patients with Lyme carditis, 49% had complete heart blocks, 16% had second degree heart blocks and 12% had first-degree heart blocks.⁷ Lyme carditis occurs when the bacteria causing the disease is disseminated in blood and establishes infection in the heart tissue.^2,8 

The Lyme bacterium can infect all parts of the heart, including the conduction system around the AV node, the outer or inner membranes of the heart, the cardiac muscle, and more rarely, cardiac blood vessels or heart valves.^2,5 Tissue damage results mostly from inflammation that occurs as the host immune cells respond to bacteria that enter the tissue. This inflammation leads to electrical conduction impairment that manifests as a heart block (Figures 1 and 2). Consideration and prompt recognition of this potentially lethal, but reversible cause of heart block is crucial in order to avoid inappropriate permanent pacemaker implantation.⁶

Myopericarditis

Lyme disease can also result in a self-limited myopericarditis, which sometimes causes a mild effusion.² Occasionally, patients will need pericardiocentesis for symptomatic treatment. The pericardical fluids obtained are usually positive for IgG, IgM, and B burgdoferi, which is identified by indirect immunofluorescence by a monoclonal antibody immuno-gold silver stain.⁷ Spirochetes were also found in synovial biopsies using a silver stain. Once treated with intravenous (IV) antibodies, the patients recover completely.⁹

Chronic Cardiopathy

B burgdoferi have also known to cause chronic dilated cardiopathy. Myocarditis associated with Lyme disease is a potential cause of chronic dilated cardiomyopathy (DCM). Stanek et al¹⁰ published the first report of B burgdorferi being cultured from the myocardium of a patient with DCM. Once a patient develops DCM, treatment with IV antobiotics (eg, ceftriaxone) does not improve cardiac function. 

In another study,¹¹ B burgdorferi was cultured from endomyocardial biopsy in 10 of 72 patients with DCM with no improvement in cardiac function after being treated with IV antibiotics. Numerous other studies have been failed to identify B burgdorferi in patients with DCM by either seroreactivity or endomyocardial biopsy. A retrospective study conducted by Palecek et al¹³ failed to detect specific B burgdorferi recombinant outer surface protein A (OspA) gene in myocardial tissue from 68 patients with end-stage DCM who had undergone heart transplantation. Recent studies with more sensitive qualitative polymerase chain reaction (PCR) and electron microscopy have detected B burgdorferi in the myocardium of patients with dilated cardiomyopathy and Lyme carditis.¹² 

Kubánek et al¹³ used quantitative PCR and electron microscopy to detect B burogedfori in 39 patients with <6 months onset of DCM; left ventricular function improved significantly with 3 weeks of IV ceftriaxone.¹³ Other studies have used qualitative and quantitative PCR to isolate the bacterial DNA, but the patients did not improve their left ventricular function.¹⁴ As there are studies that both support and contradict the effectiveness of treatment in patients with new onset of DCM, it would be prudent to treat immediately. Patients who fail to improve should be treated symptomatically. 

Treatment

Patients with erythema migrans, isolated neurological defictis, mild carditis (first-degree heart block), arthritis without neurological disease, and acrodermatitis chronica atrophicans should be treated with oral antibiotics.⁸ Severe heartblocks (PR interval >300 ms), second- or third-degree heart block, or neurological disease (eg, meningitis and recurrent arthritis) with failure to respond to oral therapy should be treated with IV antibiotics. 

Patients with severe symptoms (eg, syncope, dyspnea, and chest pain) and who have second- or third-degree heart blocks should be admitted to the hospital for closer monitoring with telemetry and IV antibiotics.¹⁴ Patients who are symptomatic (eg, syncope, dyspnea, or chest pain), have second- or third-degree AV block, or have first-degree AV block with a markedly prolonged PR interval (≥300 ms) require hospitalization for close monitoring with cardiac telemetry and IV antibiotics.⁸ Patients who are symptomatic with severe heart blocks will need temporary cardiac pacing for a few days.¹⁵

As per the Infectious Disease Society of America, routine use of antibiotics for prophylaxis is not recommended. A single dose of antibiotics should be administered when:¹⁷

1.The attached tick can be reliably identified as an adult or nymphal ixodes scapularis has been estimated to be attached for
≥36 hours.

2.Prophylaxis can be started within 72 hours of the time the tick was removed.

3.Ecologic information indicating the local rate of infection of these ticks with B burgdoferi to be ≥20%.

4.Doxicyline is not contraindicated (eg, pregnant women).

Prevention

Avoid wooded and bushy areas and clear any bushes and yards around the house. Dress appropriately with long sleeves and pants when walking through wooded or grassy areas, tuck pants into your socks, and wear a hat and gloves. Use repellents containing N,N-diethyl-meta-toluamide (DEET) between 20% to 30%, or permethrin.  Permethprim on clothing will last through several washings. Remember to carefully check children and pets for small ticks.  

Note: You cannot build immunity from Lyme disease from past infections.

Lyme disease is increasing in incidence secondary to increased awareness of the disease. Patients living in high endemic areas should be tested based on the physical examination and clinical history. Patients with tick bites should also be screened for other tick-borne disease (eg, anaplasmosis, babesiosis, B miyamotoi, tularemia, Powassan virus). 

Bensson Samuel, MD, PGDip, is the medical director of War Memorial Hospital in Sault Ste Marie, MI.

Jennifer Axelband, DO, is a critical care attending at St. Luke’s University Hospital and Health Network and an associate clinical professor at Temple University School of Medicine, both in Bethlehem, PA. 

Kevin Mckim, MD, is a graduate of Temple University School of Medicine in Bethlehem, PA, with future plans to train in pediatrics.

David Leh, MD, is a faculty member of the internal medicine residency program at St. Luke’s University Hospital in Bethlehem, PA, and an associate professor of medicine at Temple University School of Medicine, Philadelphia, PA.

References:

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16.  CDC. Tick removal. www.cdc.gov/ticks/removing_a_tick.html. Accessed June 26, 2015.
17. Agency for Healthcare Research and Quality. Guideline summary. www.guideline.gov/content.aspx?id=9537. Accessed June 29, 2015.