Lyme disease is a form of tick–borne illness first recognized in the year 1975. The disease is more prevalent in North America and Europe [1].
Presentation
In the preliminary stages, Lyme disease manifests as skin rashes and flu like symptoms. When the individual is first bitten by ixodid tick, a small red bump may develop in the affected area. After few days, the red bump expands to a larger area resembling “bull’s eye pattern”. Such a kind of rash is known as erythema migrans [8]. Many individuals develop multiple lesions which is also a major characteristic of Lyme disease. In addition to rash, affected individuals would also experience fever, body ache, fatigue and headache.
In the later stages, as the disease progresses, individuals complain of joint pain and neurological problems set in. Neurological conditions such as Bell’s palsy, meningitis, weakness of one or both limbs and impaired muscular movements are some of the grave problems experienced.
Some of the less common signs and symptoms of Lyme disease include inflammation of the liver and eyes, development of cardiac problems and extreme fatigue.
Immune System
- Inguinal Lymphadenopathy
Six weeks after initial development of symptoms, the patient was voiding without difficulty, and her inguinal lymphadenopathy was regressing. [doi.org]
- Generalized Lymphadenopathy
Generalized lymphadenopathy is not a classic feature of Lyme disease, but a Borrelial lymphocytoma may develop at the site of antecedent tick bite. [doi.org]
Entire Body System
- Fever
Individuals affected with this disease often present with arthritis, fever, rashes, conjunctivitis and many other debilitating conditions. [symptoma.com]
Some synonyms in other countries include "tick typhus", "tobia fever" in Columbia, "São Paulo fever" or "febre maculosa" in Brazil and "fiebre manchada" in Mexico. [web.archive.org]
These bacteria range from tick-borne, relapsing fever-inducing strains detected in some soft ticks, such as B. mvumii, to those from bat ticks resembling B. turicatae. [ncbi.nlm.nih.gov]
Along with the rash, you might have a fever, headache, stiff neck, body and joint aches, fatigue and sometimes fever and swollen glands (lymph glands) which can last from a few days to a few weeks. [my.clevelandclinic.org]
- Pain
Some people have numbness or shooting pains in the back, legs, and arms. [merckmanuals.com]
Neuropathic pain is a relatively common outcome of Lyme disease. Pain management options for these patients have been limited to pharmaceutical treatments. [ncbi.nlm.nih.gov]
Irritable bladder (trouble starting, stopping) or interstitial cystitis Upset stomach (nausea or pain) or GERD (gastroesophageal reflux disease) Bone pain, joint pain or swelling, carpal tunnel syndrome Stiffness of joints, back, neck, tennis elbow Muscle [lymedisease.org.au]
[…] neck Jaw pain or stiffness Dental problems 10. [canlyme.com]
- Fatigue
Some of the less common signs and symptoms of Lyme disease include inflammation of the liver and eyes, development of cardiac problems and extreme fatigue. [symptoma.com]
Chronic fatigue states have been reported to occur following any number of infections, including Lyme disease. [doi.org]
The symptoms associated with Chronic Lyme disease include disabling fatigue, severe headaches, and diffuse muscle or joint pain. These symptoms often mimic fibromyalgia and chronic fatigue syndrome. [physio-pedia.com]
Symptoms in early stage Lyme disease (close to the time of the bite) commonly include: flu-like symptoms, headaches, fever, swollen lymph nodes, fatigue, muscle aches and joint pain. [lymedisease.org.au]
- Weakness
OBSERVATIONS: A 64-year-old man presented with a 1-month history of rapidly progressive weakness involving bulbar, upper limb and lower limb muscles. The physical examination showed widespread weakness, atrophy, fasciculation, and brisk reflexes. [ncbi.nlm.nih.gov]
- Chronic Fatigue Syndrome
The majority of these patients also had the chronic fatigue syndrome or fibromyalgia; the others usually had rheumatic or neurological diseases. [dx.doi.org]
"Then they are coming back with a test that is positive and saying, 'You doctors are all wrong and I don't have chronic fatigue syndrome, I have chronic Lyme disease.' [bbc.com]
We concluded that women with endometriosis are more likely to have chronic fatigue syndrome, systemic lupus erythematous, Sjögren's syndrome, rheumatoid arthritis, multiple sclerosis, and other autoimmune inflammatory and endocrine diseases. [ncbi.nlm.nih.gov]
The symptoms associated with Chronic Lyme disease include disabling fatigue, severe headaches, and diffuse muscle or joint pain. These symptoms often mimic fibromyalgia and chronic fatigue syndrome. [physio-pedia.com]
Respiratoric
- Dyspnea
The patient presented with dyspnea and pain behind the sternum, which had been occurring for several months, mainly during fast walking upstairs. The patient reported having no symptoms when he was motionless. [doi.org]
[…] within one to two months after infection (range of less than one week to seven months). 17 – 19 Lyme carditis is a less common complication of systemic disease, occurring in approximately 4 to 10 percent of patients. 19 It may present as chest pain, dyspnea [web.archive.org]
Hospitalization and continuous monitoring, with consideration for temporary pacing, are advisable for patients with any of the following: Associated symptoms (eg, syncope, dyspnea, or chest pain) Second-degree or third-degree AV block First-degree heart [emedicine.medscape.com]
Gastrointestinal
Cardiovascular
- Heart Block
For most neurologic abnormalities and for a type of abnormal heart rhythm (arrhythmia) called third-degree heart block (complete heart block), ceftriaxone or penicillin is given intravenously for 2 to 4 weeks. [merckmanuals.com]
If the infection goes untreated, you may develop multiple areas of rash, paralysis of facial muscles (Bell’s palsy), heart block (interruption of the electrical system of the heart) or areas of numbness or abnormal sensation (neuropathy). [my.clevelandclinic.org]
He initially presented in complete heart block. A transvenous pacemaker was placed in the emergency department, and he was started empirically on Ceftriaxone for Lyme disease. [ncbi.nlm.nih.gov]
- Tachycardia
The pathogenesis of postural orthostatic tachycardia syndrome (POTS) is poorly understood. However, it has been suggested that altered immune activity or denervation of the autonomic system following illness may be an important trigger. [ncbi.nlm.nih.gov]
Symptoms of cardiac involvement include bradycardia, tachycardia, irregular heartbeat, dizziness, syncope, and shortness of air. [1] Neurological disorders Neurological and mental health co-morbidities develop in approximately 5% of Lyme disease patients [physio-pedia.com]
Bonney, Junctional Tachycardia in a Child with Lyme Carditis, Pediatric Cardiology, 32, 5, (689), (2011). Michael P. Glotzbecker, Mininder S. Kocher, Robert P. Sundel, Benjamin J. Shore, Samantha A. Spencer and James R. [doi.org]
Ears
- Tinnitus
Ear-ringing (tinnitus). Tinnitus can be a nuisance, especially at bedtime when it seems to get louder as you’re trying to fall asleep. About 10 percent of people with Lyme experience this (15). Hearing loss. [healthline.com]
Other clues to Lyme disease have been identified, although these have not been consistently present in each patient: numbness and tingling, muscle twitching, photosensitivity, hyperacusis, tinnitus, lightheadedness, and depression. [web.archive.org]
Fifteen percent of patients on atovaquone-azithromycin reported adverse reactions, most commonly diarrhea and rash; clindamycin-quinine was associated with adverse reactions (tinnitus, diarrhea, and decreased hearing) for 72% of patients ( 103 ). [doi.org]
Eyes
- Blurred Vision
We report a case of a 27-year-old woman with blurred vision on her right eye. Because of the suspicion of optic neuritis (multiplex sclerosis) neurological examination was ordered. [ncbi.nlm.nih.gov]
People who have good vision and can blink normally don’t tend to like very viscous artificial tears. Some people use them at night, but you can even have blurred vision for an hour or so after you wake up in the morning,” he adds. [reviewofophthalmology.com]
- Diplopia
A 71-year-old woman with headache, malaise, fever, and diplopia. Initial coronal postcontrast T1 MR imaging ( A and B ) with enhancing bilateral third and fifth cranial nerves. [doi.org]
Musculoskeletal
- Arthritis
Autoimmune Arthritides, Rheumatoid Arthritis, Psoriatic Arthritis, or Peripheral Spondyloarthritis Following Lyme Disease: Arthritis; Rheumatology. Published online December 28, 2016. DOI: 10.1002/art.39866. ↑ 18.0 18.1 Burrascano JJ. [physio-pedia.com]
There is recent research that demonstrates an increased risk for autoimmune forms of arthritis, including psoriatic arthritis, rheumatoid arthritis, and peripheral spondyloarthropathy, as a result of chronic Lyme disease (or post-treatment Lyme disease [medicinenet.com]
It was subsequently identified as a new clinical entity originally called Lyme arthritis based on the observation that arthritis was a major clinical feature. [ncbi.nlm.nih.gov]
- Arthralgia
Only one patient in each group reported severe arthralgia. [doi.org]
This review addresses the clinical presentation of Lyme arthritis as a mono- or oligoarticular relapsing/remitting arthritis primarily affecting the large joints and describes presentations in which arthralgias rather than arthritis are seen. [ncbi.nlm.nih.gov]
no of cases Year 1 2 13 83% .001 Year 2 0 15 100% .001 Adverse events after vaccine, % of subjects Arthralgia 3.9 3.5 .34 Myalgias 3.2 1.8 Achiness 2.0 1.4 .01 Late arthralgia (>30 days after receipt of dose) 1.3 1.2 .54 Table 1. [dx.doi.org]
- Myalgia
Most patients with NAGU exhibit nonspecific symptoms such as myalgias and fever, suggesting an infectious agent, but the majority have no identifiable pathogen. [ncbi.nlm.nih.gov]
Fever, chills, myalgia and headache are common. Meningeal involvement may follow. Central nervous system and other complications may occur weeks or months after the onset of illness. Arthritis may develop up to 2 years after onset. [who.int]
Additionally, arthralgia, myalgia, or fibromyalgia syndromes alone are not criteria for musculoskeletal involvement. Nervous system. [web.archive.org]
- Joint Effusion
Radiographs may be useful to document joint effusion if there is any uncertainty and computed tomography or MRI of the brain may document enlargement of ventricles if there is increased intracranial pressure associated with Lyme meningitis. [clinicaladvisor.com]
effusions, and heart block). [web.archive.org]
Since joint effusions resolved in most patients during the course of antibiotic therapy, it was usually not possible to obtain samples of synovial fluid after treatment. [doi.org]
There is usually large joint effusion and swelling, but only mild or moderate pain.[29] Without treatment, swelling and pain typically resolve over time but periodically return.[29] Baker's cysts may form and rupture. [en.wikipedia.org]
- Back Pain
Magnetic resonance images of the thoracic, lumbar or sacral vertebrae were acquired in patients with back pain, low back pain and sacro-iliac joint pain. [dergipark.org.tr]
They include: fatigue trouble concentrating joint pain, particularly in the elbows, knees, and shoulders decreased short-term memory speech problems restlessness when trying to sleep muscle aches neck pain lower back pain irritability depression There [medicalnewstoday.com]
Meningoradiculitis due to borreliosis presenting as low back pain only. Neuroradiology 1998 ; 40 : 126 –27 ↵ Ljostad U, Okstad S, Topstad T, et al. Acute peripheral facial palsy in adults. J Neurol 2005 ; 252 : 672 –76 ↵ Lesser RL. [doi.org]
It may be progressive and can involve cognitive impairment, brain fog, migraines, balance issues, weakness in the legs, awkward gait, facial palsy, bladder problems, vertigo, and back pain. [en.wikipedia.org]
Skin
- Erythema
Erythema migrans often is asymptomatic but it may be pruritic or, rarely, painful, and can have central vesicles on occasion. Figure 1. Erythema migrans rash Figure 2. Erythema migrans rash. [clinicaladvisor.com]
In 1912, the Swedish dermatologist Arvid Afzelius described the rash, then called erythema chronicum migrans, which currently is referred to simply as erythema migrans (EM). [emedicine.medscape.com]
[…] episodes of erythema migrans. [doi.org]
Participants were most familiar with the classic target erythema migrans of Lyme disease but were unlikely to correctly identify the nonclassic erythema migrans. [ncbi.nlm.nih.gov]
- Skin Lesion
Table 3 Comparison of the characteristics of erythema migrans (EM)—like skin lesions. Table 3 Comparison of the characteristics of erythema migrans (EM)—like skin lesions. [doi.org]
Microbial or serological confirmation of borrelial infection is needed for all manifestations of the disease except for typical early skin lesions. [ncbi.nlm.nih.gov]
- Eczema
People with eczema also may be particularly susceptible to bacterial, viral, and fungal skin infections. [niaid.nih.gov]
[…] primary symptom is a red rash that: Can appear several days after infection, or not at all Can last up to several weeks Can be very small or grow very large (up to 12 inches across), and may resemble a "bulls-eye" Can mimic such skin problems as hives, eczema [hopkinsmedicine.org]
For single erythema migrans: Nummular eczema Ringworm Cellulitis Insect or spider bites Erythema granulare For multiple erythema migrans: Erythema multiforme Multiple insect bites For facial palsy: Idiopathic (Bell's palsy) Tumors (e.g., acoustic neuroma [clinicaladvisor.com]
Contact dermatitis or discoid eczema. [patient.info]
Variable Methicillin-resistant Staphylococcus aureus infection Erythematous lesions of variable size that may be associated with necrotic eschar Most commonly located on the extremities, but may involve the axilla, abdomen, chest, or back Nummular eczema [aafp.org]
- Erythema Annulare
Erythema multiforme. Granuloma annulare. Contact dermatitis or discoid eczema. [patient.info]
Different clinical manifestations of Lyme disease were known long time ago and were described as independent illnesses, or as syndromes of unclear etiology: chronic erythema migrans, erythema Afcelius, tick-borne erythema annulare, acrodermatitis, chronic [mdpi.com]
Neurologic
- Headache
Special attention should be paid to patients with headaches who have traveled to endemic areas. [ncbi.nlm.nih.gov]
Other symptoms include fever, headache, muscle and joint pain, chills, fatigue, and swollen lymph nodes. Contact your healthcare practitioner immediately if you develop symptoms. [iamat.org]
Other symptoms include joint pain, neurological problems, fever, fatigue, headache and muscle aches. Diagnosis Diagnosis of Lyme disease gets difficult as the symptoms often mimic other disease conditions. [symptoma.com]
"Classic" Erythema Migrans Rash Fever, chills, headache, fatigue, muscle and joint aches, and swollen lymph nodes may occur in the absence of rash Erythema migrans (EM) rash (see photos): Occurs in approximately 70 to 80 percent of infected persons Begins [cdc.gov]
- Confusion
Although incomplete presentations of neurologic involvement of Lyme disease may be confused with other entities, the typical constellation of neurologic symptoms represents a unique clinical picture. [ncbi.nlm.nih.gov]
- Neck Stiffness
Headache and mild neck stiffness, which fluctuated in intensity, and lymphocytic pleocytosis were the common findings. Half of the patients also had facial palsies, which were unilateral in 12 and bilateral in seven. [ncbi.nlm.nih.gov]
stiffness Additional EM rashes on other areas of the body Facial palsy (loss of muscle tone or droop on one or both sides of the face) Arthritis with severe joint pain and swelling, particularly the knees and other large joints. [cdc.gov]
stiffness during their acute illness (87% compared with 13%; odds ratio, 2.4 [CI, 1.0 to 5.5]; P = 0.045); however, the performance of the two groups on neurocognitive tests did not significantly differ. [doi.org]
Over the course of several weeks, there may be heart and nervous system issues, Bell’s palsy (loss of muscle tone on one or both sides of the face), severe headache, neck stiffness due to inflammation of the spinal cord (meningitis), pain and swelling [arthritis.org]
- Peripheral Neuropathy
neuropathy, and painful radiculoneuropathy. [ncbi.nlm.nih.gov]
neuropathy or partial paralysis Pressure in the head Numbness in body, tingling, pinpricks Poor balance, dizziness, difficulty walking Increased motion sickness Light-headedness, wooziness Psychological Well-being Mood swings, irritability, bi-polar [canlyme.com]
- Sleep Disturbance
Symptoms include severe headaches, meningitis, swollen joints, skin lesions, heart palpitations, dizziness, persistent fatigue, sleep disturbance, as well as loss of muscle tone in the face (Bell's palsy). [iamat.org]
Other symptoms—Less common symptoms include eye inflammation (redness and swelling), fatigue, sleep disturbance, stiff neck, fever, and body aches. Once the diagnosis has been made, Lyme disease is treated with antibiotics. [doi.org]
These symptoms can include muscle and joint pains, cognitive defects, sleep disturbance, or fatigue. The cause of these symptoms is not known, but there is no evidence that these symptoms are due to ongoing infection with B. burgdorferi. [web.archive.org]
The same study reported that 41 percent experienced sleep disturbances (15). Twenty-five percent of children with Lyme reported disturbed sleep (8). Summary: Sleep disturbances are common with Lyme, including night sweats and chills. [healthline.com]
Workup
Signs and symptoms of Lyme disease often mimic other disease conditions and therefore the disease is sometimes also referred to as “The great imitator”. The following are the diagnostic procedures employed to detect Lyme disease:
- ELISA test is carried out to detect the antibodies to the bacterium. However, this test can sometimes provide false positive results and is also not useful in the initial stages of the disease [9].
- Western blot test is done for confirming the presence of Lyme disease.
- The polymerase chain reaction (PCR) test involves testing of the bacterial DNA from the fluid that is obtained from the joint of the affected individual.
Microbiology
- Borrelia Burgdorferi
Lyme disease is caused by the bacterium Borrelia burgdorferi. It is transmitted to humans when they are bitten by ixodid ticks. [symptoma.com]
After being bitten by a tick that has transmitted Borrelia burgdorferi, 80 percent of humans will develop a rash and/or flu-like symptoms. [veterinarypartner.com]
In the United States, Lyme disease is caused by Borrelia burgdorferi, which is transmitted by the bite of the tick species Ixodes scapularis and Ixodes pacificus. Clinical manifestations most often involve the skin, joints, nervous system, and heart. [idsociety.org]
Gilmore, Invasion of human neuronal and glial cells by an infectious strain of Borrelia burgdorferi, Microbes and Infection, 8, 14-15, (2832), (2006). Geeta Ramesh and Mario T. [doi.org]
Blocks
- Third Degree Atrioventricular Block
block. 4, 12, 18, 19 A study of 105 patients with Lyme carditis reported that 49 percent had third-degree atrioventricular block, 28 percent had some form of second- or first-degree atrioventricular block, and 23 percent had no conduction abnormalities [aafp.org]
Differential Diagnoses Bell Palsy Chronic Fatigue Syndrome (CFS) Fibromyalgia Insect Bites Juvenile Idiopathic Arthritis Myocarditis Pediatric Contact Dermatitis Systemic Lupus Erythematosus (SLE) Third-Degree Atrioventricular Block (Complete Heart Block [emedicine.medscape.com]
atrioventricular block for 1,222 (0.8%) cases. [cdc.gov]
- First-Degree Atrioventricular Block
A 16-year-old girl with serologic evidence of Borrelia burgdorferi infection and transient first-degree atrioventricular block underwent cardiac magnetic resonance imaging, which demonstrated myocardial hyperemia, edema, and delayed gadolinium enhancement [ncbi.nlm.nih.gov]
block. 4, 12, 18, 19 A study of 105 patients with Lyme carditis reported that 49 percent had third-degree atrioventricular block, 28 percent had some form of second- or first-degree atrioventricular block, and 23 percent had no conduction abnormalities [aafp.org]
HLA Type
- HLA-DR2
Association of chronic Lyme arthritis with HLA-DR4 and HLA-DR2 alleles. N Engl J Med. 1990 Jul 26;323(4):219-23. Erratum in: N Engl J Med 1991 Jan 10;324(2):129. Steere AC, Klitz W, Drouin EE, Falk BA, Kwok WW, Nepom GT, Baxter-Lowe LA. [ghr.nlm.nih.gov]
Association of chronic Lyme arthritis with HLA-DR4 and HLA-DR2 alleles [published erratum appears in N Engl J Med 1991 10 Jan;324:129]. N Engl J Med 990; 323:219–223 10. [dx.doi.org]
Treatment
Lyme disease can be successfully treated when the disease has been diagnosed in the initial stages. Antibiotics are the only way by which the disease can be treated. These are administered either orally or through the intravenous route depending on the condition of the patient. For oral antibiotics, the course duration is as long as 14 – 21 days depending on the severity of the condition [10] [11]. When administered through the intravenous route, the course duration is about 14 – 28 days. However, some studies have postulated that antibiotics given for 10 – 14 days are equally effective.
Prognosis
The prognosis of Lyme disease is usually favorable as the condition can be successfully treated with prompt initiation of strong antibiotic regime. Failure to initiate early treatment can pave way for several unpleasant complications to set in [7].
Etiology
Lyme disease occurs due to tick bites that are infected by the bacteria known as Borrelia burgdorferi. The disease manifests itself in 2 stages namely the initial stage and the late or the chronic stage [3]. For an infection to occur, the bacterium must gain entry into the human body which is achieved through infected ixodid ticks. The ticks appear so small that it is almost impossible to spot them with naked eye. Once the bacterium gains entry, it spreads through the blood affecting various body organs and systems.
Epidemiology
Lyme disease commonly affects individuals of North America and Europe. In the year 2013, it was ranked as the 5th most common nationally identifiable disease. It has been estimated that each year in the United States, as high as 30,000 cases of the disease are reported. In the year 2011 alone, the disease struck about 33,097 individuals of the United States [4].
Pathophysiology
For an individual to develop Lyme disease, he or she should have been bitten by ixodid ticks infected by bacterium Borrelia burgdorferi. Once the bacterium gains entry into the body it spreads through the blood stream giving rise to unpleasant symptoms. For an infection to occur, the tick must be attached to the skin for about 25 – 36 hours [5]. It is therefore necessary to remove the tick as soon as possible in order to prevent transmission of the disease [6].
Prevention
Following certain simple steps can help you prevent from Lyme disease. In countries where Lyme disease is a common occurrence, individuals should avoid wandering in areas where ixodid (deer) ticks are common. These include bushy areas with long grass and wooded areas. Individual are advised to wear long pants when exploring such areas. It is also necessary to use insect repellents. When bitten by deer tick, it is necessary to remove the tick as soon as possible to prevent the infection. Individuals are also advised to check their pets for ticks. Whenever they notice tick bites, it should immediately be removed with the help of tweezers.
Summary
Lyme disease is caused by the bacterium Borrelia burgdorferi. It is transmitted to humans when they are bitten by ixodid ticks. Lyme disease greatly affects the body organs such as the joints, muscles, hearts, neurological system and gastrointestinal system [2]. Individuals affected with this disease often present with arthritis, fever, rashes, conjunctivitis and many other debilitating conditions. Lyme disease is treated with a strong antibiotic course that works towards elimination of the bacterium from the body. The disease can be successfully treated if treatment is initiated in the early stages.
Patient Information
Definition
Lyme disease is a kind of bacterial infection caused by infected ticks. The bacterium that causes the disease is called as Borrelia burgdorferi. It is the most common form of vector illness in the United States. It has been estimated that about 30,000 cases of Lyme disease are detected each year in the US.
Cause
Infected deer tick is the sole cause of Lyme disease. In this, the bacterium gains entry into the human system through the tick bite and spreads through the blood affecting other body organs and system.
Symptoms
Symptoms of Lyme disease include development of rash which is small and red colored in the initial stages. As the disease progresses, the rash extends in bull’s eye pattern. Other symptoms include joint pain, neurological problems, fever, fatigue, headache and muscle aches.
Diagnosis
Diagnosis of Lyme disease gets difficult as the symptoms often mimic other disease conditions. Many a time physical examination of the rash is enough to confirm the diagnosis. However additional tests such as ELISA test, Western blot test and polymerase chain reaction test may also be necessary to confirm the disease condition.
Treatment
A strong antibiotic course for 14 – 21 days would be enough to successfully treat the condition.
References
- Feder HM Jr. Lyme disease in children. Infect Dis Clin North Am. Jun 2008;22(2):315-26, vii.
- Steere AC. Lyme disease. N Engl J Med 2001; 345:115.
- Oschmann P, Dorndorf W, Hornig C, et al. Stages and syndromes of neuroborreliosis. J Neurol 1998; 245:262.
- Centers for Disease Control (CDC). Lyme disease--United States, 1987 and 1988. MMWR Morb Mortal Wkly Rep 1989; 38:668.
- Sood SK, Salzman MB, Johnson BJ, Happ CM, Feig K, Carmody L, et al. Duration of tick attachment as a predictor of the risk of Lyme disease in an area in which Lyme disease is endemic. J Infect Dis. Apr 1997;175(4):996-9.
- Kalish RA, Kaplan RF, Taylor E, et al. Evaluation of study patients with Lyme disease, 10-20-year follow-up. J Infect Dis 2001; 183:453.
- Seltzer EG, Gerber MA, Cartter ML, Freudigman K, Shapiro ED. Long-term outcomes of persons with Lyme disease. JAMA. Feb 2 2000;283(5):609-16
- Steere AC, Bartenhagen NH, Craft JE, et al. The early clinical manifestations of Lyme disease. Ann Intern Med 1983; 99:76.
- Ang CW, Notermans DW, Hommes M, Simoons-Smit AM, Herremans T. Large differences between test strategies for the detection of anti-Borrelia antibodies are revealed by comparing eight ELISAs and five immunoblots. Eur J Clin Microbiol Infect Dis. Aug 2011;30(8):1027-32.
- Steere AC, Angelis SM. Therapy for Lyme arthritis: strategies for the treatment of antibiotic-refractory arthritis. Arthritis Rheum. Oct 2006;54(10):3079-86Steere AC, Sikand VK. The presenting manifestations of Lyme disease and the outcomes of treatment. N Engl J Med. Jun 12 2003;348(24):2472-4.