Lyme Disease


Article Author:
Gwenn Skar


Article Editor:
Kari Simonsen


Editors In Chief:
Chaddie Doerr


Managing Editors:
Avais Raja
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Khalid Alsayouri
Trevor Nezwek
Radia Jamil
Erin Hughes
Patrick Le
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Hassam Zulfiqar
Hussain Sajjad
Steve Bhimji
Muhammad Hashmi
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Sarosh Vaqar
Mark Pellegrini
James Hughes
Beata Beatty
Beenish Sohail
Nazia Sadiq
Hajira Basit
Phillip Hynes


Updated:
10/27/2018 12:31:42 PM

Introduction

Lyme disease or Lyme borreliosis is the most commonly transmitted tick-borne infection in the United States and among the most frequently diagnosed tick-borne infections worldwide. Lyme disease is divided into three stages: early localized, early disseminated, and late. The early localized disease is distinguished by the red ring-like expanding rash of Erythema migrans at the site of a recent tick bite. Other symptoms experienced at this stage may be flu-like symptoms, malaise, headache, fever, myalgia, and arthralgia. Most patients only experience the symptoms of early, localized disease. About 20% of patients develop the early disseminated disease, with the most common symptoms being multiple erythema migrans lesions. Other symptoms of the disseminated stage are flu-like symptoms, lymphadenopathy, arthralgia, myalgia, palsies of the cranial nerves (especially CN-VII), ophthalmic conditions, and lymphocytic meningitis. Additionally, cardiac manifestations such as conduction abnormalities, myocarditis, or pericarditis may occur. The most common manifestation of the late disease is arthritis that is usually pauciarticular and affects large joints, especially the knees.[1][2]

Etiology

In the United States, Lyme disease is caused by the bacterial spirochete Borrelia burgdorferi and is transmitted by the bite of an Ixodes genus tick, mostly commonly Ixodes scapularis. In Eurasia, the predominant causes are B. burgdorferiBorrelia afzelii, and Borrelia garinii.[3][4]

Epidemiology

Lyme disease is most commonly reported in the  Northeastern and upper Midwestern United States. The primary states with endemic Lyme disease are Connecticut, Delaware, Maine, Maryland, Massachusetts, Minnesota, New Hampshire, New Jersey, New York, Pennsylvania, Rhode Island, Vermont, Virginia, and Wisconsin. Sporadic cases have been reported in northern California, Oregon, and Washington.[5][6]

Pathophysiology

The most common and first presenting sign of Lyme disease is the erythema migrans rash, which is found in 70% to 80% of cases and appears at the site of the tick bite as an expanding, erythematous skin lesion, measuring 5 cm in diameter or larger. The lesion may present as homogeneous erythema or display a targetoid appearance. The appearance of the rash occurs one to two weeks after the initial tick bite. If untreated, disease progression may lead to other relatively common findings including early arthritis in up to 30% in some series; neurologic manifestations, 10% to 15%; or cardiac involvement, 1% to 2%.[7]

Histopathology

Erythema migrans histologic findings are nonspecific, usually showing a perivascular cellular infiltrate which consists of histiocytes, lymphocytes, and plasma cells. Rarely, mast cells and neutrophils are identified. A biopsy may show eosinophilic infiltrates which consist of a local reaction to the bite. Spirochetes may be identified using antibody-labeled or silver stains. Usually, a paucity of spirochetes is found in the tissues of those infected with Lyme disease.

Acrodermatitis Chronica Atrophicans

In acrodermatitis chronica atrophicans, an early biopsy may show a lymphocytic dermal infiltrate, often perivascular in location, with some vascular lymphedema and telangiectasia. Plasma cells may be seen in the cellular infiltrate. Late lesions may demonstrate epidermal thinning with loss of skin appendages. In the later stages, plasma cells may be the only feature to distinguish morphea from acrodermatitis chronica atrophicans.

Fibrotic nodules may show fibrosis of the deeper dermis and hyalinization of collagen bundles. B. burgdorferi can sometimes be cultivated from the lesions.

Borrelial Lymphocytoma

Histologic examination is performed in patients with suspected borrelial lymphocytoma when the history is not clear enough to support a diagnosis. Borrelial lymphocytoma biopsy shows a dense dermal lymphocytic infiltrate with lymphoid follicles and pseudoterminal centers. Lymphocytes with both B- and T-cell markers, occasional macrophages, plasma cells, and eosinophils are seen.

History and Physical

Localized Lyme disease is characterized by erythema migrans occurring 1 to 2 weeks after tick exposure in an endemic area. The differential diagnosis for early Lyme disease with erythema migrans includes other skin conditions such as tinea and nummular eczema. If not treated in the localized stage, patients may go on to develop early disseminated or late disease manifestations. Early neurologic Lyme disease manifestations include facial nerve (CN-VII) palsy, lymphocytic meningitis, or radiculopathy. Cardiac involvement includes myopericarditis and typically presents with heart block. Lyme arthritis is mono- or pauciarticular, generally involving large joints, most commonly the knee, and occurring months removed from the initial tick bite.

Evaluation

Serologic testing is insensitive during the first few weeks of infection, and patients presenting with erythema migrans rash and history of residing in or traveling to an endemic region may be treated based on clinical findings. In later stages of the disease, a 2-step approach is recommended for the serologic diagnosis of Lyme disease. The first step is to perform a quantitative screening test for serum antibodies to B. burgdorferi using a sensitive enzyme immunoassay (EIA) or immunofluorescent antibody assay (IFA). A Western blot should follow specimens with positive or equivocal results. Serologic diagnosis is sensitive (greater than 80%) for patients presenting with neurologic or cardiac manifestations.[8][9][10]

Treatment / Management

Specific treatment is dependent upon the age of the patient and stage of the disease. For patients older than 8 years of age with early, localized disease, doxycycline is recommended for 10 days. Patients under the age of 8 should receive amoxicillin or cefuroxime for 14 days to avoid the potential for tooth staining caused by tetracycline use in young children. Longer courses and parenteral antibiotics may be required for more severe manifestations such as arthritis, atrioventricular heart block, carditis, meningitis or encephalitis, although European data and newer studies demonstrate that oral treatment regimens or transitioning to oral therapy at hospital discharge may be appropriate for some patients.[11][12][13]

Differential Diagnosis

In patients with erythema migrans, a careful history and physical examination are all that is required to establish the diagnosis of Lyme disease. However, many patients with Lyme disease present with erythema migrans or extracutaneous symptoms where diagnosis becomes a challenge. In those cases, erythema migrans may never have occurred, may not have been recognized, or may not have been correctly diagnosed by the clinician.

Other problems include the following:

  • Acute memory disorders
  • Ankylosing spondylitis and rheumatoid arthritis
  • Atrioventricular nodal block
  • Cellulitis
  • Contact dermatitis
  • Gout and pseudogout
  • Granuloma annulare
  • Prion-related diseases

Staging

Stages of Lyme Disease

  1. Stage 1: Localized disease associated with erythema migrans and flu-like symptoms; Duration 1 to 30 days
  2. Stage 2: Early disseminated disease with malaise, pain, and flu-like symptoms; May affect the neurological, ocular, and musculoskeletal organs; Duration 3 to 10 weeks
  3. Stage 3: Late or chronic disease chiefly affects the joints, muscles, and nerves, May last months or years, Lyme arthritis is a hallmark of this stage.
  4. The occurrence of post-treatment Lyme syndrome is debatable.

Prognosis

For early cases, treatment is usually curative. However, treatment may be complicated due to late diagnosis, antibiotic treatment failure, and concomitant infection with other tick-borne diseases such as ehrlichiosis, babesiosis, and immune suppression.

Approximately 5% of patients will have lingering symptoms of fatigue, pain, or joint and muscle aches after treatment. These symptoms can last for 6 or more months. This is called post-treatment Lyme disease syndrome. Chronic Lyme disease is generally managed similarly to fibromyalgia or chronic fatigue syndrome.

Complications

Consultations

  • Infectious disease expert
  • Dermatologist
  • Neurologist

Pearls and Other Issues

Based on the geographic distribution of the shared vector Ixodes scapularis, co-infections with Lyme disease and human granulocytic anaplasmosis and/or babesiosis can occur. Co-infected patients may be more severely ill at presentation, have a persistent fever longer than 48 hours after initiating antibiotic therapy for Lyme disease, or present with anemia, leukopenia, and/or thrombocytopenia. When co-infection is suspected or confirmed, treatment with an appropriate antimicrobial regimen for each infection is necessary for resolution of illness.

Enhancing Healthcare Team Outcomes

The key to Lyme disease is prevention. All healthcare workers should provide patient education on measures to prevent tick bites while hiking or working outdoors. In areas where ticks are common, cleaning up of the environment by removing the underbrush and spraying an insecticide may reduce the tick burden in the area. The nurse should educate the patient on how to remove the tick from the skin and when to seek medical assistance. The pharmacist should educate the patient on medication compliance for those who have been confirmed to have acquired Lyme disease. Even though there is a Lyme vaccine the public should be educated that the effects of the vaccine are not consistent or long-lasting; hence one should not rely on the vaccine to prevent Lyme disease.[14][15] (Level V)

Outcomes

The prognosis for patients who are treated for Lyme disease is excellent with no residual deficits. However, a few individuals may develop a recurrent infection if an infected tick bites them. Individuals who receive late treatment may develop neurological and musculoskeletal symptoms. Lyme arthritis is not uncommon. Some patients may develop Lyme carditis that results in a heart block and requires temporary pacing of the heart. Despite the large numbers of people affected, Lyme disease is not fatal. There continues to be a debate about the existence of post-treatment Lyme disease, but so far, this diagnosis has been promoted by the lay public and media as there is no good evidence that such a condition exists.[16][17] (Level V)


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Attributed To: Contributed by James Gathany, Center for Disease Control and Prevention (CDC PHIL)

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Lyme Disease - Questions

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A patient in the Northeast U.S. has been hiking for the past 2 week. She presents with complaints of general malaise, fatigue and an enlarging rash. She remembers being bitten by a bug. Echocardiogram reveals frequent premature ventricular beats. The chest radiograph is unremarkable. What is the next step in management?



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A female from the Northeast is seen for general malaise and low-grade fever. She was out all weekend hiking and now feels extremely tired. On examination, erythema chronicum migrans is observed. What may the patient have acquired?

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A female presents with joint pain and stiffness for 2 weeks. She has had subjective fevers since a camping trip about a month ago. This was followed by mild diarrhea and a rash. The patient's son had a similar rash. The patient has no significant past medical history or family history. The physical exam shows a temperature of 36.5°C, as well as swelling of all 10 metacarpal phalangeal joints and proximal interphalangeal joints. The right knee has an effusion. Which of the following physical findings would not be helpful in narrowing the differential diagnosis?



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A 14-year-old male has had 6 weeks of joint pain. What physical finding would make Lyme disease more likely than juvenile idiopathic arthritis?



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What would most likely be found in the synovial fluid of a patient with Lyme disease?



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Which of the following is a true statement about the laboratory tests for Lyme disease?



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Which of the following is the most effective and safe treatment for Lyme disease?



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A patient is diagnosed with Lyme disease and started on doxycycline 100 mg PO BID for 4 weeks. After the first dose, the patient is worse with dizziness, shaking, and fever. What is the cause of the change in the patient's condition?



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Which of the following is the appropriate treatment for Lyme disease-induced complete heart block?



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An outdoorsman in Wisconsin is concerned about Lyme disease. What is the best method for primary prevention?



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A 34-year-old forest ranger, previously healthy, presents with dizziness, syncope, and increasing fatigue for 2 weeks. Vital signs show a temperature of 98 degrees Fahrenheit, blood pressure of 110/80 mm Hg, and a heart rate of 38 beats per minute with a regular pulse. No murmur is noted. Neurological exam reveals a Bell palsy. An EKG shows complete heart block. Which treatment is most appropriate for this patient?



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Early Borrelia burgdorferi infection is best treated with which of the following medications?



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Bilateral facial paralysis accompanied by fever, rash, and arthralgias is suggestive of which of the following types of infection?



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A jogger presents with erythema chronicum migrans. She may have which of the following conditions?

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A jogger presents to the ER complaining of a rash that appear like a bull eye. She denies any trauma but is unsure of any insect bites. The rash is about circular and erythematous with central clearance. Wood lamp is negative for a mycological examination. What is the most likely diagnosis?



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An 8-year-old girl develops monoarticular arthritis of the left knee 3 months after traveling with her family in Wisconsin. You suspect late disseminated disease manifesting as Lyme arthritis. Of the following, which is the most appropriate statement about the diagnosis of Lyme disease?



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A 5-year-old boy from New York comes to your office with a swollen, tender left knee and some limitation of motion. His mother remembers the child having been bitten by a tick a few months ago during the summer. You suspect Lyme disease, which is confirmed by serology. The mother was treated for Lyme disease 2 years ago with doxycycline and wonders if her child should also be treated with doxycycline. How should the patient's mother be advised?



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Which is not true of Lyme disease?



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With Lyme-induced reactive arthritis, which joint is commonly affected?



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An adult female presents with progressive confusion over weeks with memory loss. She has a slight fever at 100.4 F. Prior to cognitive changes, she had been complaining of arthralgias. History is otherwise unremarkable except for the fact she is an avid camper. What is her most likely diagnosis?



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A patient presents with fatigue, joint pain, and headache for four days. He was on a hiking trip in Maryland. During exam, there is the presence of an 8 cm erythematous patch with a small vesicle at the center. What should be done next?



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A 10-year-old girl develops fever to 102 degrees F (38.8 degrees C) and a swollen, tender left knee joint 4 weeks after returning to school in the fall. There is also pain and limitation of movement of the joint. She had visited relatives in Northern California in July about 3 months ago. Neither she nor her parents recall an illness when visiting in California. You suspect arthritis, a manifestation of late, disseminated Lyme disease. What is the diagnostic test of choice to confirm the diagnosis?



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What is the most appropriate antibiotic for treatment of Lyme arthritis in a 10-year old girl?



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What is the probable diagnosis in the case of an patient with a recent history of a rash with central clearing following a hiking trip 6 weeks ago who presents with facial nerve palsy?



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Which of the following about Lyme disease is FALSE?



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What is the probable diagnosis in a patient with a recent history of a rash with central clearing following a hiking trip 6 weeks ago presenting with facial nerve palsy?



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Which of the following organisms causes erythema migrans?



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Lyme disease in adults is treated with which medication?



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What clinical feature is seen in a patient with stage I Lyme disease?



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Erythema chronicum migrans is pathognomonic for what disease?



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How does Lyme disease generally present?



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Which of the following most commonly occurs in the northeastern United States?



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Which of the following medications is NOT used for treatment of Lyme disease?



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A 22 year old male presents with malaise, arthralgias and headache for two days. During exam you note the presence of a 10 cm erythematous patch with a small vesicle at the center. He has recently returned from a camping vacation in Connecticut. What should be done next?



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What is the most common clinical feature of neuroborreliosis?



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Which of the following is the rash associated with Lyme disease?



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A patient presents with a solitary erythema migrans lesion after vacationing on Martha's Vineyard. What is the next best step?



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Which cranial nerve does Lyme disease most commonly affect?



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Which of the following statements is true about Lyme disease and its clinical manifestations?



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A 12-year-old male from Wisconsin complains of left knee pain. His mother reports he had a tick bite more than a month ago. He then developed an erythematous, large, annular rash at the site. Select the incorrect statement about this condition.



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What infection is caused by Borrelia burgdorferi?



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With what is migratory erythema associated?



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With what is Lyme disease treated?



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A patient has been diagnosed with Lyme disease. Which of the following is the treatment of choice for this disease?



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What is the term for the regular occurrence of Lyme disease in the northeastern part of the United States?



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A 17-year-old male comes to the emergency department complaining of fatigue, dyspnea, chest pain, and syncope that occurs especially when he plays soccer. This has been going on for the past 2 weeks. He has no significant past medical history. He denies smoking, caffeine intake, tinnitus, vomiting, or coughing. He has been taking NSAIDs regularly for the past year due to headaches that he attributes to "being stressed out from my new job in Minnesota." On examination, BP: 120/81 mmHg, HR: 55 bpm, RR: 18/min, and O2: 99% on room air. Skin examination: no rashes, abdominal examination: mild epigastric tenderness but no organomegaly, chest examination: equal air entry bilaterally with no abnormal sounds. ECG shows P waves and QRS complexes that are independent of each other. Blood tests show antibodies to the organism in the picture. Which of the following is the most appropriate treatment for this patients case?

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  • Image 6632 Not availableImage 6632 Not available
    Image courtesy S Bhimji MD
Attributed To: Image courtesy S Bhimji MD



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A patient presents because she believes she is bitten by a tick a few days ago while hiking in the woods. She mentions swelling in her right ear and general malaise. On exam, she has a 1 x 2 cm bluish-red nodule located on the right ear lobe. What is the next best step in management for this patient?



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A 28-year old hiker was in the woods this past weekend. He now returns to the emergency department because he claims a tick bit him. He is worried that he may have acquired Lyme disease. There is nothing unusual on the physical exam except for a non-specific skin rash. According to the CDC, the first test of choice to make a diagnosis of Lyme disease is which one of the following?



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Which of the following is the initial diagnostic test for Lyme arthritis?



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A 7-year-old boy who presents with a pronounced limp secondary to pain in his leg. The pain is around his left knee, and on physical examination, he presents with a swollen left knee. Two weeks earlier he had a painful right ankle with limping. His mother reports he has had an elevated temperature in her opinion, but she has not measured it. He lives in a rural area which has a stream running through the back of the property. Prior to aggressive-invasive therapy, what infective process should the surgeon consider that may not need surgical intervention as the primary mode of treatment?



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A patient presents to an emergency department triage with a rash, fever, chills, headache, fatigue, and muscle and joint pain. An exam reveals a target or “bull’s-eye” rash on their thigh. Which of the following questions are appropriate to ask the patient? Select all that apply.



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Which of the following signs and symptoms are common in a patient with acute Lyme disease? Select all that apply.



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A patient who was hiking in the woods presents to the emergency room with a headache and low-grade fever. The patient admits to feeling tired for the past 2 days and shows the nurse the skin rash seen in the image below. What is true regarding this condition? Select all that apply.

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  • Image 1580 Not availableImage 1580 Not available
    Contributed by James Gathany, Center for Disease Control and Prevention (CDC PHIL)
Attributed To: Contributed by James Gathany, Center for Disease Control and Prevention (CDC PHIL)



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A 16-year-old woman presents to the outpatient clinic with complaints of left knee pain and swelling that started a month ago. She denies any trauma to the knee. She is sexually active but in a monogamous relationship. She denies travel outside the United States but mentions a camping trip to the northeastern U.S. 4 months ago. For the last few days, she has been using a cane to walk due to her knee pain. She was seen in the emergency room last week and was told to apply ice and use ibuprofen. She has no allergies. On examination, the knee feels boggy and swollen. The clinician suspects a bacterial infection and prescribes a month-long course of oral doxycycline. Then clinician also suspects that this patient may be co-infected with another bacteria. Which of the following would be the clinical presentation of infection with the other bacteria?

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  • Image 233 Not availableImage 233 Not available
    Contributed by DermNetNZ
Attributed To: Contributed by DermNetNZ



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A patient presents after having found a tick attached to his inner thigh today in the morning while taking a shower. Three days ago he went hiking to the forest in Maine and returned home the same day. There is no rash at the site of tick attachment on physical exam. One of his friends was hospitalized five years ago due to Lyme carditis and required a temporary pacemaker for five days. The patient worries that he could develop the same condition and is requesting treatment to avoid what happened to his friend. What should be recommended to the patient?



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Lyme Disease - References

References

Cervantes J, [Lyme disease in Perú. A clinical and epidemiological review]. Revista peruana de medicina experimental y salud publica. 2018 Apr-Jun     [PubMed]
Bransfield RC, Neuropsychiatric Lyme Borreliosis: An Overview with a Focus on a Specialty Psychiatrist's Clinical Practice. Healthcare (Basel, Switzerland). 2018 Aug 25     [PubMed]
Bernard Q,Thakur M,Smith AA,Kitsou C,Yang X,Pal U, Borrelia burgdorferi protein interactions critical for microbial persistence in mammals. Cellular microbiology. 2018 Jun 22     [PubMed]
Muhammad S,Simonelli RJ, Lyme Carditis: A Case Report and Review of Management. Hospital pharmacy. 2018 Jul     [PubMed]
Berry K,Bayham J,Meyer SR,Fenichel EP, The allocation of time and risk of Lyme: A case of ecosystem service income and substitution effects. Environmental     [PubMed]
Shapiro ED,Wormser GP, Lyme Disease in 2018: What Is New (and What Is Not). JAMA. 2018 Aug 21     [PubMed]
Norris SJ, Catching up with Lyme Disease Antigenic Variation Computationally. Trends in microbiology. 2018 Aug     [PubMed]
Yeung C,Baranchuk A, Systematic Approach to the Diagnosis and Treatment of Lyme Carditis and High-Degree Atrioventricular Block. Healthcare (Basel, Switzerland). 2018 Sep 22     [PubMed]
Paparone P,Paparone PW, Variable clinical presentations of babesiosis. The Nurse practitioner. 2018 Oct     [PubMed]
Trayes KP,Savage K,Studdiford JS, Annular Lesions: Diagnosis and Treatment. American family physician. 2018 Sep 1     [PubMed]
Antony S, Mosquito and Tick-borne Illnesses in the United States. Guidelines for the Recognition and empiric Treatment of Zoonotic Diseases in the Wilderness. Infectious disorders drug targets. 2018 Jun 26     [PubMed]
Synopsis: Lyme Disease in Canada - A Federal Framework. Canada communicable disease report = Releve des maladies transmissibles au Canada. 2017 Oct 5     [PubMed]
Patton SK,Phillips B, CE: Lyme Disease: Diagnosis, Treatment, and Prevention. The American journal of nursing. 2018 Apr     [PubMed]
Jacquet C,Goehringer F,Baux E,Conrad JA,Ganne Devonec MO,Schmutz JL,Mathey G,Tronel H,Moulinet T,Chary-Valckenaere I,May T,Rabaud C, Multidisciplinary management of patients presenting with Lyme disease suspicion. Medecine et maladies infectieuses. 2018 Sep 3     [PubMed]
Benelli G,Duggan MF, Management of arthropod vector data - Social and ecological dynamics facing the One Health perspective. Acta tropica. 2018 Jun     [PubMed]
Goodlet KJ,Fairman KA, Adverse Events Associated with Antibiotics and Intravenous Therapies for Post-Lyme Disease Syndrome in a Commercially Insured Sample. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2018 Apr 17     [PubMed]
van den Wijngaard CC,Hofhuis A,Wong A,Harms MG,de Wit GA,Lugnér AK,Suijkerbuijk AWM,Mangen MJ,van Pelt W, The cost of Lyme borreliosis. European journal of public health. 2017 Jun 1     [PubMed]

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