Lyme Borreliosis, Erythema Migrans and Annular Skin Lesions
A 68 year old female presented to an urgent care center complaining of three weeks of intermittent low grade temperature accompanied by chills, diffuse myalgias, arthralgias and rash. The patient and her husband, a retired pathologist, noted that the rash started on her right thigh, was initially quarter-sized and bright red with an even distribution that lasted for about one week and then seemed to expand and ultimately fade with the red remaining only at the border.
The review of systems was negative, and the patient denied past medical history, took no medications, and had no known drug allergies. Her family history was noncontributory. She denied tobacco and illicit drug intake and endorsed rare alcohol use. The patient had no pets, had not recently changed detergents or purchased new clothing.
Upon further questioning, the patient recounted that she and her husband returned from visiting their grandchildren in Seattle, Washington, about three weeks ago. She stated that the family had a picnic in the local park one day prior to the couple embarking on a flight back to Florida. The patient did not recall any insect bites, including tick bites. As is their usual practice when flying, the patient and her husband took three days worth of amoxicillin to "ward off" any respiratory ailments they may have come into contact with during the flight home.
The patient has normal vital signs, and physical exam with the exception of her skin which had two salmon colored patches located on the left calf (3x2 inches) and right forearm (2x2.5 inches), as well as multiple annular, dime-sized target lesions under the right axilla breast.
Routine labs were normal. Chest x-ray showed no acute process. A Lyme IgM/IgG was equivocal.
The patient's dermatologic condition was determined to be erythema migrans and erythema multiforme. The extensive differential diagnoses for these conditions in adults is listed in Table 1 and Table 2 .
As the patient had partially treated the spirochete infection with three days of amoxicillin, she was instructed to complete a seven day regimen of amoxicillin, and her treatment regimen was augmented with doxycycline 100mg bid for 14 days. She was also to return in two weeks for repeat ELISA testing for confirmation. The repeat ELISA test was positive and confirmed with Western blot. Patient had a baseline EKG on her return to clinic that was normal. The patient reported resolution of her symptoms with the completion of the antibiotic course.
Lyme borreliosis (LB) or Lyme disease is caused by the spirochete, Borrelia burgdorferi, which is transmitted through the bite of an infected adult tick or nymph. Ixodes scapularis, also known as the deer tick, is the most common vector for Lyme disease in North America. At present, Lyme borreliosis is the most prevalent vector-borne disease in North America, with over 20,000 cases reported annually across 46 states and the District of Columbia. The first incidence described nearly 100 years ago by Swedish dermatologist Arvid Afzelius included key manifestations of an expanding ring-like lesion on a female patient (erythema migrans). The initial reports of Lyme disease were documented in epidemic form in Lyme, Connecticut, in the late 1970s where 59 cases appeared in a single year, and since 1982, more than 200,000 cases have been reported to the CDC.
Although Florida is a low-risk area, it is essential to have a high index of suspicion for Lyme disease when evaluating patients with erythema migrans and systemic complaints. In such patients, it is crucial to elicit a thorough travel history and exposure to the elements. Indeed, our patient initially denied recent travel as she did not consider travel within three weeks to be "recent." However, she was likely infected in another low risk locale, Washington State, while at the local state park.
Lyme disease usually manifests itself as a localized infection of the skin (erythema migrans), followed by multiple spirochete reactions on the skin and body parts such as the heart, joints and nervous system. See Figure 1. The disease is divided into three stages. The first stage, or acute illness, occurs at the site of the tick bite and results in the development of a skin lesion as the Borreliae multiply and spread into the dermis layer of the skin. The usual systemic symptoms of the first stage include headaches, fever, myalgia, and arthralgia. In the second, or the dissemination phase, the Borreliae spread hematogenously and cause secondary annular skin lesions, migratory arthritis, cardiac arrhythmias and meningitis. Our patient presented during the dissemination phase and had multiple annular skin lesions. To fight off the infection, the body develops antibodies to the spirochete.
(Enlarge Image)
Figure 1.
Erythema Migrans Figures 1 is used with the permission of the Division of Infectious Diseases and Tropical Medicine, College of Medicine, University of South Florida, Tampa.
Finally, the late chronic phase develops if the disease remains untreated and may occur in some cases, up to two to three years after the initial infection and demonstrate clinical signs such as destructive chronic arthritis, acrodermatitis chronica atrophicans and neuropathy.
In one double-blind, placebo-controlled study with 118 infected patients, erythema migrans, due to Lyme disease presented itself with a number of secondary signs and symptoms which included fever, headaches, myalgia, arthralgia and fatigue. Myalgia or arthralgia was present in 35% of the patients with Lyme disease. Our patient's presentation echoes the findings in this study.
Interestingly, the Borrelia burgdorferi species found in North America appears to generate an erythema migrans that is more erythematous, of briefer duration and which spreads more rapidly when compared to its European counterpart B. afzelii or B. garinii. In these organisms, the erythema migrans manifest slower, less intensely inflamed and have a longer duration. The difference in the appearance and duration of the erythema migrans allows for early detection in the North American spirochete, Borrelia burgdorferi, as compared to the European species. Although rare, Lyme carditis is another complication of the disease which results in first degree AV block.
Lyme disease is usually diagnosed by cultures taken from skin biopsies of erythema migrans, skin lesions in 70 to 80% of patients and from blood sample in 40 to 50% of the patients. Although elusive to culture from patients with Lyme arthritis, B. burgdorferi DNA can be detected by PCR in the joint fluid of most patients prior to antibiotic therapy. Even so, both the culture and PCR technique remain lowyield in detection in patients with acute or chronic neuroborreliosis. Furthermore, a two-tiered approach is used more commonly today consisting of ELISA and Western blot, using B. burgdorferi sonicates, which tend to have a high degree of sensitivity and specificity in detection of the disease. Indeed, our patient's diagnosis was firmly established with her second ELISA test, confirmed via Western blot.
When treated in its early stages, treatment of Lyme disease has an incredible success rate which prevents further complications from developing. It is usually treated by a two to three week course of antibiotics which include oral courses of doxycycline or amoxicillin. In patients whose disease has progressed, treatment entails a four week course of oral medication or a two to four week course of IV ceftriaxone if the patient does not respond to oral therapy. Our patient reported resolution of her symptoms with completion of the antibiotic course.
In addition to antibiotics, two vaccines have been developed to combat Lyme disease, particularly in endemic regions. These vaccines use recombinant B. burgdorferi lipidated outer-surface protein A (rOspA) as immunogen -- LYMErix and ImuLyme. LYMErix is administered through intramuscular injections in the deltoid muscle with a single dosage of 0.5ml at a time. Three doses are given to the patient with a time lapse of one month between the first two and a year lapse between the second and third injections. In a randomized controlled trial of LYMErix with 10,936 subjects it was noted that the vaccine efficacy in protecting against Lyme disease with the presence of erythema migrans or objective neurologic, musculoskeletal or cardiovascular manifestations of Lyme disease after two doses was 49% and 76% after three. Subjects enrolled in the study were tested for the development of OspA antibodies at months 2, 12, 13 and 20 and from the results it was concluded that a titer greater than 1,200 ELISA units/mL correlated with protection for the disease. The Lyme disease vaccine does not protect all recipients against infection with B. burgdorferi and offers no protection against other tick related disease. It is best if a person observes protective measures against ticks and seeks early diagnosis of the suspected tick borne infection.
A 68 year old female presented to an urgent care center complaining of three weeks of intermittent low grade temperature accompanied by chills, diffuse myalgias, arthralgias and rash. The patient and her husband, a retired pathologist, noted that the rash started on her right thigh, was initially quarter-sized and bright red with an even distribution that lasted for about one week and then seemed to expand and ultimately fade with the red remaining only at the border.
The review of systems was negative, and the patient denied past medical history, took no medications, and had no known drug allergies. Her family history was noncontributory. She denied tobacco and illicit drug intake and endorsed rare alcohol use. The patient had no pets, had not recently changed detergents or purchased new clothing.
Upon further questioning, the patient recounted that she and her husband returned from visiting their grandchildren in Seattle, Washington, about three weeks ago. She stated that the family had a picnic in the local park one day prior to the couple embarking on a flight back to Florida. The patient did not recall any insect bites, including tick bites. As is their usual practice when flying, the patient and her husband took three days worth of amoxicillin to "ward off" any respiratory ailments they may have come into contact with during the flight home.
The patient has normal vital signs, and physical exam with the exception of her skin which had two salmon colored patches located on the left calf (3x2 inches) and right forearm (2x2.5 inches), as well as multiple annular, dime-sized target lesions under the right axilla breast.
Routine labs were normal. Chest x-ray showed no acute process. A Lyme IgM/IgG was equivocal.
The patient's dermatologic condition was determined to be erythema migrans and erythema multiforme. The extensive differential diagnoses for these conditions in adults is listed in Table 1 and Table 2 .
As the patient had partially treated the spirochete infection with three days of amoxicillin, she was instructed to complete a seven day regimen of amoxicillin, and her treatment regimen was augmented with doxycycline 100mg bid for 14 days. She was also to return in two weeks for repeat ELISA testing for confirmation. The repeat ELISA test was positive and confirmed with Western blot. Patient had a baseline EKG on her return to clinic that was normal. The patient reported resolution of her symptoms with the completion of the antibiotic course.
Lyme borreliosis (LB) or Lyme disease is caused by the spirochete, Borrelia burgdorferi, which is transmitted through the bite of an infected adult tick or nymph. Ixodes scapularis, also known as the deer tick, is the most common vector for Lyme disease in North America. At present, Lyme borreliosis is the most prevalent vector-borne disease in North America, with over 20,000 cases reported annually across 46 states and the District of Columbia. The first incidence described nearly 100 years ago by Swedish dermatologist Arvid Afzelius included key manifestations of an expanding ring-like lesion on a female patient (erythema migrans). The initial reports of Lyme disease were documented in epidemic form in Lyme, Connecticut, in the late 1970s where 59 cases appeared in a single year, and since 1982, more than 200,000 cases have been reported to the CDC.
Although Florida is a low-risk area, it is essential to have a high index of suspicion for Lyme disease when evaluating patients with erythema migrans and systemic complaints. In such patients, it is crucial to elicit a thorough travel history and exposure to the elements. Indeed, our patient initially denied recent travel as she did not consider travel within three weeks to be "recent." However, she was likely infected in another low risk locale, Washington State, while at the local state park.
Lyme disease usually manifests itself as a localized infection of the skin (erythema migrans), followed by multiple spirochete reactions on the skin and body parts such as the heart, joints and nervous system. See Figure 1. The disease is divided into three stages. The first stage, or acute illness, occurs at the site of the tick bite and results in the development of a skin lesion as the Borreliae multiply and spread into the dermis layer of the skin. The usual systemic symptoms of the first stage include headaches, fever, myalgia, and arthralgia. In the second, or the dissemination phase, the Borreliae spread hematogenously and cause secondary annular skin lesions, migratory arthritis, cardiac arrhythmias and meningitis. Our patient presented during the dissemination phase and had multiple annular skin lesions. To fight off the infection, the body develops antibodies to the spirochete.
(Enlarge Image)
Figure 1.
Erythema Migrans Figures 1 is used with the permission of the Division of Infectious Diseases and Tropical Medicine, College of Medicine, University of South Florida, Tampa.
Finally, the late chronic phase develops if the disease remains untreated and may occur in some cases, up to two to three years after the initial infection and demonstrate clinical signs such as destructive chronic arthritis, acrodermatitis chronica atrophicans and neuropathy.
In one double-blind, placebo-controlled study with 118 infected patients, erythema migrans, due to Lyme disease presented itself with a number of secondary signs and symptoms which included fever, headaches, myalgia, arthralgia and fatigue. Myalgia or arthralgia was present in 35% of the patients with Lyme disease. Our patient's presentation echoes the findings in this study.
Interestingly, the Borrelia burgdorferi species found in North America appears to generate an erythema migrans that is more erythematous, of briefer duration and which spreads more rapidly when compared to its European counterpart B. afzelii or B. garinii. In these organisms, the erythema migrans manifest slower, less intensely inflamed and have a longer duration. The difference in the appearance and duration of the erythema migrans allows for early detection in the North American spirochete, Borrelia burgdorferi, as compared to the European species. Although rare, Lyme carditis is another complication of the disease which results in first degree AV block.
Lyme disease is usually diagnosed by cultures taken from skin biopsies of erythema migrans, skin lesions in 70 to 80% of patients and from blood sample in 40 to 50% of the patients. Although elusive to culture from patients with Lyme arthritis, B. burgdorferi DNA can be detected by PCR in the joint fluid of most patients prior to antibiotic therapy. Even so, both the culture and PCR technique remain lowyield in detection in patients with acute or chronic neuroborreliosis. Furthermore, a two-tiered approach is used more commonly today consisting of ELISA and Western blot, using B. burgdorferi sonicates, which tend to have a high degree of sensitivity and specificity in detection of the disease. Indeed, our patient's diagnosis was firmly established with her second ELISA test, confirmed via Western blot.
When treated in its early stages, treatment of Lyme disease has an incredible success rate which prevents further complications from developing. It is usually treated by a two to three week course of antibiotics which include oral courses of doxycycline or amoxicillin. In patients whose disease has progressed, treatment entails a four week course of oral medication or a two to four week course of IV ceftriaxone if the patient does not respond to oral therapy. Our patient reported resolution of her symptoms with completion of the antibiotic course.
In addition to antibiotics, two vaccines have been developed to combat Lyme disease, particularly in endemic regions. These vaccines use recombinant B. burgdorferi lipidated outer-surface protein A (rOspA) as immunogen -- LYMErix and ImuLyme. LYMErix is administered through intramuscular injections in the deltoid muscle with a single dosage of 0.5ml at a time. Three doses are given to the patient with a time lapse of one month between the first two and a year lapse between the second and third injections. In a randomized controlled trial of LYMErix with 10,936 subjects it was noted that the vaccine efficacy in protecting against Lyme disease with the presence of erythema migrans or objective neurologic, musculoskeletal or cardiovascular manifestations of Lyme disease after two doses was 49% and 76% after three. Subjects enrolled in the study were tested for the development of OspA antibodies at months 2, 12, 13 and 20 and from the results it was concluded that a titer greater than 1,200 ELISA units/mL correlated with protection for the disease. The Lyme disease vaccine does not protect all recipients against infection with B. burgdorferi and offers no protection against other tick related disease. It is best if a person observes protective measures against ticks and seeks early diagnosis of the suspected tick borne infection.
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