Lyme Disease : In the “ Lime Light ” for Over 25 Years

Lyme disease has been a topic of debate practically since its discovery in the 1970’s. The hot topic is whether or not long-term antibiotics should be used for Lyme disease patients with persistent symptoms. The source of such a long-running debate stems from the difference in opinions over the cause of long-term, persistent symptoms after treatment in some patients. Toward its end, Medicine has finally begun to embrace the existence of Chronic Lyme Disease, but changes still need to be made in the future. DOI: 10.14302/issn.2640-690X.jfm-18-2067 Corresponding author: Kenisha J Evans, Wayne State University School of Medicine Address: 540 E. Canfield St. Detroit, MI 48201, Email: keevan@med.wayne.edu


Introduction
Lyme disease, also known as Lyme Borreliosis, is caused by Borrelia burgodoreri sensu lato, a spirochete that is transmitted by ticks of the Ixodes ricinus complex [1,2]. This disease was first discovered in Lyme, Connecticut, a small town in eastern Connecticut.
Beginning in 1972, a cluster of children had developed what appeared to be juvenile rheumatoid arthritis.
Investigators discovered most of these children lived or played in wooded areas with the peak incidence of new cases coincide with tick season, summer and early fall.
Additionally, many of the children reported having an unique characteristic annular rash prior to the onset of arthritic symptoms and some even recalled having a tick bite at the same location that the rash had developed3.
Although the exact cause still had not been identified, the investigators termed these constellation of symptoms, Lyme disease [3].
It was not until 1977, Allen Steere, a rheumatologist at Yale, affirmed Lyme disease as its own entity [4]. In a prospective study Dr. Steere and a team of researchers evaluated 48 patients with erythema chronicum migran as its initial marker for the subsequent development of Lyme arthritis. They discovered serum cryoprecipitates associated with the disease clinical activity involving skin and joints [5]. The term erythema chronicum migrans had originally been used by European researchers in the early 1900's, in their evaluation of a similar pattern annular skin rash.
Nevertheless, in 1981, it was Willy Burgdorfer and his colleague, Alan Barbour, who were studying spirochetes (spiral-shaped bacteria) from deer ticks, who discovered the same spirochete that caused both erythema migrans and Lyme disease.
Since that time, to present date, much research has been done and a lot has been discovered about Lyme disease. However, there is a large part that is still unknown, which has caused confusion and controversy regarding the diagnosis and treatment of this disease.

Epidemiology
According to Infectious Diseases Society of America (IDSA), Lyme disease is the most commonly  [6]. However there is a relatively lower incidence observed in Northwest regions due to difference in feeding habits of the primary tick vectors. These vectors maintain an enzootic transmission but rarely feed on human [7]. (Figure 1).

Reported Cases, 2015
"Though Lyme disease cases have been reported in nearly every state, cases are reported from the infected person's county of residence, not the place where they were infected" [6].
The national incidence rate was 7.9 cases per 100,000 persons in 2015, and "96% of confirmed Lyme disease cases were reported in 14 states" [6]:  Lyme disease of 100-300 cases per 100, 000 persons in US and German [8]. The review also states that the prevalence of Lyme Disease cases has increased substantially in the past two decades [8].
Nevertheless, there are many factors that contribute to this epidemiologic transmission dynamics of Borrelia burgodoreri sensu lato. These factors include conditions that favor tick survival, the density and infection rate of local vectors, the abundance and infectivity of reservoir hosts, and the likelihood and duration of human exposure to tick vectors [3].

Tick Bite Without Symptoms
People who are exposed to endemic areas will sometimes notice a tick on their skin. It is important to properly remove the tick as promptly as possible.
According to the CDC, it takes up to 36 to 48 hours to transmit the bacterium [6]. It is recommended to remove the tick by using fine-tipped tweezers to grab the tick at the skin surface and steadily pull upward. If any mouth parts remain, remove them with tweezers.
Thoroughly clean the area with rubbing alcohol, iodine scrub, or soap and water. Dispose of the tick by submerging it in alcohol or flushing it down the toilet [6].

Stage 1: Early Localized Infection
The person may also experience flu-like symptoms such as fever, chills, headache, stiff neck, fatigue, and body aches and pains within days to weeks [9]. (Figure 2).
After injecting into human skin, the spirochete may migrate outward producing an annular or spread hematogenously or through the lymphatics to other organs. An infection begins with the characteristic expanding erythema migrans (EM) as previously described by the Europeans in the early 1900's.
Erythema migrans initially develops as a small red spot macule or papule isolated to the site of the tick bite but enlarges within one to two weeks. During this incubation   (Table 3).

Diagnosis
When the hallmark, bull's eye rash or erythema migrans is present during the early stage, the diagnosis is clinically based on history and physical exam and no blood test is required. When there is no erythema migrans rash, the diagnosis is still made clinically and a blood test can help confirm the diagnosis.
The CDC recommends a two-step process when testing blood [6]. These blood tests are most reliable about 2 weeks post-innoculation, as the body has had time to make antibodies. The following diagram shows the steps as laid out by the CDC [6]: (Figure 3).
The first test, an enzyme immunoassay, has high sensitivity, meaning however, there could be false positives and therefore must be confirmed by the

Prognosis
When treated early, Lyme disease is easily and rapidly cleared, preventing later stages of disease.
However, these later stages of Lyme disease also respond well to treatment if therapy is commenced soon after the appearance of symptoms [1,2].
Although there continues to be percentage of patients infected with Borrelia burgodoreri who develop chronic Lyme Disease, most patients recover fully from this infection [1,2]. It is critical to identify chronic lyme disease patient as their conditions may be intermittent but debilitating.

Conclusion
No matter what side of the fence you stand,

Post-Lyme Treatment Syndrome or Chronic Lyme
Disease, one thing is abundantly clear, more research still needs to be done! Though the course has been long and rocky, science and medicine have already taken a step in the right direction when it comes to diagnosing and treating patients with Lyme Disease. Over the next ten years, there should be advancements both academically and pharmacologically that will hopefully take Lyme disease out of the lime light and give much needed relief to those with Chronic Lyme Disease.