Is it Lyme Disease?

 

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Case Study

Abby, a 39-year-old writer, has been experiencing common flu-like symptoms of fever, fatigue, and muscle pain for over a week now. She complains of an ongoing lymphadenopathy and she feels as though her knees are 100 years old.

Her clinician takes a thorough history and discovers that three weeks ago she had taken a trip to upstate New York, where she hiked a great deal of the time. While Abby doesn’t have the usual erythema migrans associated with Lyme disease, her clinician still suspects that she came in contact with a deer tick that attached itself to her during her trip. He orders an antibody test and the results come back negative for the Borrelia burgdorferi spirochete; however, he still suspects Lyme disease because of her travel history, symptoms, and the possibility that not enough time has passed for antibodies to develop.

Lyme borreliosis (LB; Lyme disease) is the most common vector-borne illness in North America. Caused by the spirochete, Borrelia burgdorferi, the disease is transmitted through the bite of an infected tick. According to the Centers for Disease Control and Prevention (CDC), in 2009 there were 29,959 cases of Lyme disease and 8,509 probable cases, a 3.5% increase in confirmed cases compared with 2008 (Figure 1).[1] In 2010, there were 22,572 confirmed cases and 7,597 probable cases, the first drop since 2006. Lyme disease has become common in the United States with moderate-to-high risk areas from Maryland to Maine, in Wisconsin and Minnesota, and the coast of northeast/west California; in 2010, 94% of the cases were reported from these areas. A few cases have also been reported in a much wider low-risk area (Figure 2).[1]



The effects of Lyme disease were known in Europe as tick-borne meningoencephalitis. It was not recognized in the United States until the 1970s when the town of Lyme, Connecticut, experienced an outbreak of childhood arthritis. Yale epidemiologists noticed the characteristic bull’s eye rash and made the connection with the tick-borne condition known in Europe.[2] The rash, known as erythema migrans (EM), is an early sign of Lyme disease, occurs at the site of the tick bite, and affects about 70% to 80% of infected people.[3] Two-thirds of those who develop EM go on to develop further symptoms.[4]

The disease is divided into three stages: each stage having its own distinct symptoms.

Common Symptoms[5,6]

Stage 1 Early Localized (3- to 30-day onset after tick bite)—the infection has not spread throughout the body yet.

      • Erythema migrans
      • Flu-like symptoms (fever, headache, malaise, myalgia, fatigue, muscle/joint aches, or regional lymphodenopathy)

Stage 2 Early Disseminated (days to weeks onset after tick bite)—the bacteria have begun to spread throughout the body into the bloodstream.

      • Multiple erythema migrans lesions
      • Cranial nerve palsies
      • Severe headaches and neck stiffness (meningitis)
      • Flu-like symptoms may also still be present
      • Musculoskeletal pain (mild arthralgia, myalgia, or mild oligoarthritis)
      • Cardiovascular complications (abnormal heartbeat, palpitations)
      • Rare manifestation: carditis, Bannwarth’s syndrome, plexus neuritis

Some organizations have condensed Stage 1 and 2 into one stage)

Stage 3 Late Disseminated (months to years after tick bite)—the bacteria have spread throughout the body.

      • Arthritis (monoarticular or oligoarticular), particularly affecting the large joints
      • Severe, sometimes intermittent, joint pain and swelling
      • Rare manifestations: encephalitis, encephalopathy, and polyneuropathy, uveitis, keratitis

Chronic Lyme Disease

The term “chronic Lyme disease” has become a catch-all phrase for a variety of patients: patients with symptoms of late Lyme disease (Stage 3) who have not taken antibiotics, patients who have post-Lyme disease syndrome, and patients who have an array of symptoms of unknown cause or without any evidence of an association with B. burgdorferi infection.

There is an ongoing controversy within the medical community as to whether chronic Lyme disease is an actual diagnosis. One group, which includes the International Lyme and Associated Diseases Society, states some patients do not notice tick bites, the disease spreads, testing is inaccurate, and the disease is not recognized until it becomes chronic; patients then need to be treated long term with antibiotics, steroids, and/or other immunosuppressive medications.[7,8] The other group, which includes the Infectious Diseases Society of America (IDSA), reports there is no evidence of its existence and that long-term antibiotics can be more harmful—or even fatal—to the patient.[9,10]

Co-Infections and Other Diseases

Another complication to diagnosing Lyme disease is the co-infections commonly associated with the disease. Many of these co-infections are also tick-transmitted: neuroborreliosis, babesiosis, or ehrlichiosis anaplasmosis. Neuroborreliosis is an infectious disease of the central nervous system. Babesiosis generally increases the severity and array of symptoms, and ehrlichiosis is a rickettsial infection that may cause hemolytic anemia.

There are published studies and case reports that associate Lyme disease with other diseases such as non-Hodgkin lymphoma,[11] autism,[12] and Alzheimer’s disease.[13]

Laboratory Testing

A variety of laboratory tests are available to confirm a diagnosis of Lyme disease, although many are not approved by the Food and Drug Administration (FDA). The National Institute of Health (NIH) recommends using only FDA-approved testing and actively supports research on diagnostic testing for Lyme disease.

The CDC recommends a 2-step blood test process. The first test is a screening test using EIA (enzyme immunoassay; aka ELISA); this detects antibodies, but not the B. burgdorferi itself. If the EIA is positive or indeterminate, then an immunoblot test, also called “Western blot,” should be used to confirm the results. The Western blot assay will typically show positive results only if the patient is infected. A negative result suggests the EIA was a false-positive. The Western blot should not be used unless the EIA has been done first (Figure 3).[14]

The EIA and Western blot have several limitations: low sensitivity during early stages of infection, significant time/expense, subjective interpretation of positive bands, and an inability to determine active infection from prior infection. In 2010, the NIH revealed they had developed a more sensitive and cost-effective test that may resolve these issues, the VOVO LIPS test. The luciferase immunoprecipitation system (LIPS) is designed to detect the B. burgdorferi protein in blood samples. Using the LIPS test along with the synthetic protein VOVO, researchers reported a 98% to 100% diagnostic rate.

So if the VOVO LIPS is more efficient, cost effective, and has a more accurate method of infection detection without the cumbersome dilutions/calculations of the EIA/Western Blot, where is it? Why is it not replacing the EIA/Western Blot? To adopt the new testing system, the major laboratories running Lyme disease tests would incur considerable expense. It appears the advantages do not outweigh the time, effort, and money required to alter current practice. Perhaps as the newer test becomes more widely accepted, the laboratories will begin including the peptide-based assays.[15,16]

The B. burgdorferi spirochete is difficult to detect, due to its various individual antigens and its ability to change its surface proteins. Therefore, it is recommended that clinicians not rely solely on the results of serologic testing in making the diagnosis of Lyme disease. A diagnosis should be based on the patient’s symptoms and the probability of exposure. In fact, testing is not recommended if the patient’s history and symptoms are suggestive of Lyme disease—in this case, the clinician should proceed with antibiotic therapy.[17]

Treatment

Antibiotics are the indicated treatment for both adults and children. These usually include doxycycline for adults and children older than 8 years, or amoxicillin or cefuroxime for adults, younger children, and pregnant or breastfeeding women. These drugs often clear the infection and prevent complications. A 3- to 4-week course of antibiotics is usually recommended.[18] Children who receive treatment usually do well. The long-term prognosis for adults is more difficult to assess due to difficulties of diagnosis, lack of uniform treatment regimens, and absence of long-term follow-up of most patients.[3] Approximately 10% to 20% of patients may report still having symptoms, such as persistent pain, fatigue, unexplained numbness, or impaired cognitive function. There is strong controversy over the benefit of long-term antibiotic treatments; however, various studies repeatedly show no meaningful or lasting benefit of prolonged courses of treatment.[19-22]

A recombinant vaccine against Lyme disease, based on the outer surface protein A (OspA) of B. burgdorferi, was developed by Smith Kline Beecham Biologicals. In clinical trials involving more than 10,000 people, the vaccine, called LYMErix, was found to confer protective immunity to Borrelia in 76% of adults and 100% of children with only mild or moderate and transient adverse effects. LYMErix was approved by the US Food and Drug Administration (FDA) on December 21, 1998.

Following approval of the vaccine, its entry in clinical practice was slow for a variety of reasons including its cost, which was often not reimbursed by insurance companies. Subsequently, hundreds of vaccine recipients reported that they had developed autoimmune side effects. Despite testimony of FDA and the CDC that there was no connection between the vaccine and the autoimmune complaints, sales plummeted and LYMErix was withdrawn from the US market by February 2002.

The NIH continues to support research efforts on a human vaccine against Lyme disease. Some of the projects they are working on include the development of a new, second-generation vaccine fur humans, and early-stage discovery and characterization of novel vaccine targets.[23]

Case Study

Based on her symptoms and activity suggesting Lyme disease, Abby was treated with doxycycline 100 mg twice daily for 14 days. She reports still feeling tired and achy, but was reassured that this is a normal part of the recovery process. After 6 months, she reports that the lingering malaise and muscle pain have dissipated and that she is feeling well again. She is reminded to protect herself against tick bites.

Preventive Treatment

  • Wear light-colored clothing and long sleeves.
  • Tuck trouser legs into socks and shirt into trousers.
  • Wear shoes or boots rather than open sandals.
  • Check yourself after sitting on grass or logs, brushing past branches or leaning against tree trunks.
  • Use a light-colored picnic blanket to easily spot ticks and other insects.
  • Inspect outdoor pets regularly for ticks and keep them off furniture.
  • Arrange with travel companions to check each other for signs of ticks (or use a mirror to check the parts you can’t see).
  • Use insect repellants effective against ticks.
  • Check clothing and shoes before entering the car or home

In 2006, the IDSA released updated guidelines for the diagnosis and treatment of Lyme disease. The Attorney General of Connecticut launched an investigation into practices and conflicts of interest of the IDSA members who developed the guidelines. The guidelines were re-evaluated by a Review Panel in 2010 and they found in favor of the IDSA on all counts. The guidelines are for healthcare providers who care for patients with tick-borne infections or may be at risk for them. You can find tables listing doses and durations of therapy, recommendations for prevention and treatment of Lyme disease, as well as treatments that should be avoided.

Updated on May 29, 2012
Published on August 3, 2010

 

Resources

For you
Tickborne Diseases in Massachusetts
: A Physician’s Manual (a great resource for all physicians dealing with tickborne diseases)

Tick Management Handbook (a guide for public health officials and homeowners)

For your patients
Avoid Mosquito and Tick Bites
(a handout you can give to your patients)

Tick Fact Card

Protect Yourself from Tick-borne Diseases

 

References

  1. Lyme disease data. Centers for Disease Control and Prevention Website. http://www.cdc.gov/lyme/stats/index.html. Updated April 12, 2012. Accessed May 14, 2012.
  2. A history of Lyme disease, symptoms, diagnosis, and treatment. National Institute of Allergy and Infectious Diseases Website. http://www.niaid.nih.gov/topics/lymedisease/understanding/Pages/intro.aspx. Updated March 29, 2011. Accessed May 14, 2012.
  3. Steere AC, Sikand VK. The presenting manifestations of Lyme disease and the outcomes of treatment. N Engl J Med. 2003;348(24):2472-2474.
  4. Kruger D. On target with Lyme disease: understanding vector-borne infections. JAAPA. 2010;23(5):22-26.
  5. Hansen GT, Bonham SC. Lyme disease: finding the balance of diagnostic testing and clinical disease features. Clin Lab News. 2010;36(1):8-10.
  6. Signs and symptoms of Lyme disease. Centers for Disease Control and Prevention Website. http://www.cdc.gov/lyme/signs_symptoms/index.html. Updated November 15, 2011. Accessed May 22, 2012.
  7. International Lyme and Associated Diseases Society. Diagnostic Hints and Treatment Guidelines for Lyme and Other Tick Borne Illnesses. 16th ed. 2008.
  8. Fallon BA, Keilp JG, Corbera KM, et al. A randomized, placebo-controlled trial of repeated IV antibiotic therapy for Lyme encephalopathy. Neurology. 2008;70:996-1003.
  9. Frequently asked questions about Lyme disease. Infectious Diseases Society of America Web site. http://www.idsociety.org/lymediseasefacts.htm. Accessed July 24, 2010.
  10. Klempner MS, Hu LT, Evans J, et al. Two controlled trials of antibiotic treatment in patients with persistent symptoms and a history of Lyme disease. N Engl J Med. 2001;345(2):85-92.
  11. Schöllkopf C, Melbye M, Munksgaard L, et al. Borrelia infection and risk of non-Hodgkin lymphoma. Blood. 2008;111(12):5524-5529.
  12. Bransfield RC, Wulfman JS, Harvey WT, Usman AL. The association between tick-borne infections, Lyme borreliosis, and autism spectrum disorders. Med Hypotheses. 2008:70(5):967-974.
  13. Miklossy J, Khalili K, Gern L, et al. Borrelia burgdorferi persists in the brain in chronic lyme nueroborreliosis and may be associated with Alzheimer disease. J Alzheimers Dis. 2004;6(6):639-649.
  14. Lyme disease: laboratory testing. Centers of Disease Control and Prevention Website. http://www.cdc.gov/lyme/diagnosistreatment/LabTest/. Updated November 15, 2011. Accessed May 24, 2012.
  15. Matthews L. Lyme disease test—the promise of VOVO LIPS. Lyme Disease Guide Organization Website. http://lymediseaseguide.org/lyme-disease-test-the-promise-of-vovo-lips. Published March 15, 2012. Accessed May 24, 2012.
  16. Burbelo PD, Issa AT, Ching KH, et al. Rapid, simple, quantitative, and highly sensitive antibody detection for Lyme disease. Clin Vaccine Immunol. 2010;17(6):904-909.
  17. Wormser GP, Dattwyler RJ, Shapiro ED, et al. 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.
  18. Lyme disease. National Institute of Allergy and Infectious Diseases Website. http://www.niaid.nih.gov/topics/lymedisease/research/Pages/antibiotic.aspx. Updated April 19, 2011. Accessed May 24, 2012.
  19. Fallon BA, Keilp JG, Corbera MK, et al. A randomized, placebo-controlled trial of repeated IV antibiotic therapy for Lyme encephalopathy. Neurology. 2008;70:992-1003.
  20. Klempner MS. Controlled trials of antibiotic treatment in patients with post-treatment chronic Lyme disease. Vector-borne Zoonotic Diseases. 2002;2:255-263.
  21. Krupp LB, Hyman LG, Grimson R, et al. Study and treatment of post Lyme disease (STOP-LD); a randomized double masked clinical trial. Neurology. 2003;60:1923-1930.
  22. Oksi J, Nikoskelainen J, Hiekkanen H, Lauhio A, et al. Duration of antibiotic treatment in disseminated Lyme borreliosis: a double-blind, randomized, placebo-controlled, multicenter clinical study. Eur J Clin Microbiol Infect Dis. 2007;26:571-581.
  23. Lyme disease: Vaccines. National Institute of Allergy and Infectious Diseases Website. http://www.niaid.nih.gov/topics/lymeDisease/research/Pages/vaccine.aspx#. Updated May 9, 2011. Accessed May 25, 2012.