Sitting around the table with my medical students discussing our recently diagnosed child with Lyme disease, our discussion focused on the need for early diagnosis. While this particular patient was caught fairly early in her disease based on symptoms, the diagnosis remains elusive for many. Blood tests do not detect early stages of the disease and patients often disregard early symptoms as being insignificant. Yet, practicing medicine in an area where Lyme is present and prevalent (NJ), we each had a case to share of the horrific late stages of the disease, including a young man with Lyme encephalitits and another middle aged man with Lyme carditis and a heart rate of 29.
Lyme disease is a vector-borne illness cause by the spirochete Borrelia burgdorferi transmitted primarily in the US by Ixodes scapularis, commonly known as the deer tick. It was first recognized in Scandinavia in the early 1900’s but did not become well-known until a group of school children from the same street in Lyme, Connecticut were diagnosed with juvenile rheumatoid arthritis in the mid-1970’s. Further investigation led to the bacterial etiology in 1976. Since that time, it has grown in its incidence and geographic range.
The spirochetes of Borrelia are unique bacteria possessing an unusual genome, which is made up of one linear chromosome with a one mega base size and several circular and linear plasmids. The chromosome size is relatively small compared to other bacteria. The genetic map of Borrelia burgdorfi was published in 1997. The chromosome possess 842 functional genes and one pseudogene. This organism lacks enzymes necessary for biosynthesis of aminoacids, fatty acids, nucleotides, and cofactors, which explains the need for a complex medium containing all these for the growth of the Lyme spirochetes.
Biologically, B. burgdorfi is a gram-negative organism which grows best in a microareophilic atmosphere. It divides every 8-12 hours during log-phase growth. It resembles other organisms in the Borrelia genuse and possesses 7-11 periplasmic flagella, which are made up of flagellin.
According to the CDC, Lyme Disease is now the fastest growing vector transmitted disease in the US infecting approximately 300,000 Americans annually. Since national surveillance began in 1982, its incidence increased 25-fold. Furthermore, new Lyme Disease cases in the US are being detected at a rate of 25,000 cases per month, 5,770 per month, 822 per day, or 3 per hour. What is especially concerning is the fact that there is no reliable test to detect Lyme Disease and currently only 50% of patients recall a tick bite or a typical rash. The ELISA screening test is only 30% reliable and 40% of infected patients go on to suffer long-term medical problems for which there is no good treatment. The evidence is lacking that short courses of antibiotics eliminate the Lyme spirochete and there is a 40% relapse rate.
Lyme disease cases have been reported in 49 states, excluding in Hawaii. However, most cases, approximately 96%, occur in 14 states. The New England states have the most number of cases followed by the Mid-Atlantic and Mid-west states. It tends to occur more in wooded or rural areas.
White-tailed deer are the principle host for the tick, although they themselves do not become infected. The white-footed mouse is the reservoir and if a tick bites one that is infected, it becomes infected as well. Humans develop Lyme disease after being infected by an infected tick. The tick is an obligate feeder, meaning that it needs to attach to a host to be able to feed. It often waits in the grass until a large host happens by. It then bites the host and attaches itself. The pathogen takes 72 hours to transmit so removal of the tick as soon as possible is imperative. It should be removed in one piece.
What are the signs and symptoms?
3-30 days after the tick bite:
- Erythema migrans (EM) rash: this begins usually within 7 days of a tick bite and gradually expands over days, reaching a size of up to 12 inches. Approximately 70-80% of patients will develop this rash. It clears as it enlarges, forming the typical “bull’s eye” appearance. It can appear on any area of the body.
- Enlarged lymph nodes
Days to months after the tick bite (later manifestations):
- Severe headache and neck stiffness
- Other rashes
- Arthritis, particularly the knees and large joints
- Facial palsy
- Pains in tendons, muscles, joints, bones
- Palpitations or irregular heart rhythm (Lyme carditis)
- Brain or spinal cord inflammation
- Nerve pain
- Short-term memory loss
Lyme disease is often difficult to diagnose and can be misdiagnosed as other disorders, such as fibromyalgia or other immunologic disorders. Additionally, the ticks that spread Lyme disease can transmit other diseases complicating the diagnosis as well. The ELISA (enzyme-linked immunoabsorbent assay) test is the one used most frequently to detect Lyme disease. The ELISA detects antibodies to B. burgdorferi but it sometimes produces false positives so is does not provide a conclusive diagnosis. Also, it is not very reliable very early in the disease. If a patient has a typical rash and lives in a Lyme prevalent area, they should be treated. When the ELISA test is positive, the Western blot test is done as confirmation. The Western blot detects antibodies to several proteins of B. burgdorferi.
In the first few weeks of Lyme disease, serologic tests are not very sensitive. If a patient lives in an endemic area and develops a typical rash with a recent tick exposure, tests should not be performed and treatment started instead. Symptoms typically improved within a few days of initiation of antibiotics. If a patient does not recall a tick bite or typical symptoms, laboratory testing should be considered. If a patient also has leukopenia or thrombocytopenia, co-infection with Ehrlichia or Babesia may be present. In 40% of patients infected with Lyme disease, at least one liver function test is elevated. Biopsy of skin lesions can sometimes be helpful in establishing the diagnosis. Microscopic hematuria and proteinuria have also been noted. Joint aspiration is not needed to diagnose Lyme arthritis but may be useful to eliminate other diagnoses, such as septic arthritis, gout or pseudogout. In Lyme meningitis, CSF can show a mild pleocytosis with a predominance of lymphocytes and Lyme antibody is considered positive when it exceeds that in the serum.
If Lyme disease is diagnosed and treated early enough, patients usually recover quickly and completely. Antibiotics used for treatment include Amoxicillin, Doxycycline, or Cefuroxime. However, the best treatment is prevention and taking precautions include protective clothing, tick repellant, daily checks for ticks on the body, and prompt removal if any are discovered. Prophylaxis treatment can also be effective including single doses of Doxycycline at 200 mg per dose in adults and 4 mg/kg up to a maximum of 200 mg in children 8 years of age and older. Amoxicillin should only be used in case where doxycycline is contraindicated, such as in pregnant patients and children under the age of 8. For patients with Lyme meningitis or other late neurologic sequale, Ceftriaxone can be given at a dose of 2 grams a day IV for 14 days. Similarily, ceftriaxone may also be used in children. In patients with Lyme carditis, they may need to be hospitalized if they experience syncope, dyspnea, chest pain or 2nd or 3rd degree A-V block. In patients who continue to experience joint pain or swelling after standard therapy, retreatment with 4 weeks or oral antibiotics or IV ceftriaxone is advised.
Chronic Lyme disease (CLD) remains a controversial area. These patients present with atypical symptoms and are often seronegative. These symptoms include chronic fatigue, chronic pain, neurocognitive symptoms, behavioral abnormalities, and rheumatologic complaints. Perhaps, the biggest debate is whether these patients should be treated with prolonged courses of antibiotics. CDL, in fact, has no clinical definition or typical presentation. Clinical trials are difficult to conduct since the treatment population is so broad and ill-defined. And many of patients considered to suffer CLD are often found to have rheumatological or neurological disorders. There is very scant microbiologic evidence that supports the persistence of this infection. Despite the confusion, many patients suffer greatly. Clearly, more research is needed.
In 1998, LYMERix vaccine was produced by SmithKline Beecham. It was a 3-dose series that was unique in that it produced antibodies that attacked the bacteria in the gut of the tick as it fed on the human host. Its efficacy was about 78% after all 3 doses but this immunity waned after time. It was removed from the market in 2002 due to lack of consumer demand. There is currently no Lyme vaccine being developed and no companies have any plans to develop one in the near future. However, giving the rising incidence of this disease, a vaccine would likely benefit many.
Lyme disease is often a misunderstood and misdiagnosed disease. Researchers still have not unlocked the keys to the long term suffering some experience with this disease. While we do have effective treatments available, they will not work unless we are more diligent in diagnosing it, especially in the absence of a known tick exposure or typical EM rash.
About the Author
Linda Girgis MD, FAAFP is a family physician practicing in South River, New Jersey. She was voted one of the top 5 healthcare bloggers in 2016. Follow her on twitter @DrLindaMD.