Lyme Disease and Co-Infections
Lyme Disease Basics
Lyme disease, a multisystemic illness caused by
the spirochete Borrelia burgdorferi (Bb), is the
most common vector-borne illness in the US.
Approximately 20,000 new cases are reported to
the CDC each year and the CDC acknowledges
that 90% of cases go unreported.[Adler, J. (2004).
Lyme: battles with illness, emotions, insurance.
(NJ) Herald News.] Infected black-legged ticks
transmit Bb to humans via a bite. These ticks are
quite small and easily overlooked; most patients
do not recall being bitten prior to becoming ill.
Lyme disease has both early and late disease
manifestations. Patients may exhibit one or both
of these stages; many patients initially present
with late Lyme disease. Any organ system can be
involved, but Bb commonly strikes skin, joint,
heart and nervous tissue, including the brain.
Early Lyme disease begins 3-30 days after a tick bite and is readily identified by an erythema migrans (EM) rash. EMs vary in appearance. The
most common rash is a homogeneously colored
oval lesion. The classic “bull’s eye” accounts for
less than 20% of all EM cases; [Smith R et al,
Ann Intern Med. 2002;136:421-428, Tibbles C,
JAMA 2007; 297:2617-27.] 30% of patients
never have a rash.[MMWR 56(23); 573-576]
Flu-like symptoms such as fever, fatigue, headache, myalgias, arthralgias and neck stiffness may accompany an EM or be the only evidence of early Lyme disease.[Steere A et al, Am J Med. 2003; 114(1):58-62]
Late Lyme disease develops weeks - years later and is the result of disseminated infection. Early disseminated Lyme disease may cause multiple EM rashes, Bell’s palsy or other cranial neuropathies, meningitis, meningoradiculitis, carditis, lymphadenopathy and arthralgia; constitutional symptoms may be present. In endemic areas, Lyme disease is implicated in 50% of all cases of Bell’s palsy in children.[Cook SP et al, Am J Otolaryngol 1997; 18(5):320-3]
In the US, arthritis and disorders of the nervous system are seen in late disseminated Lyme disease. Arthritis can affect any joint; knees are the most common site. Up to 60% of untreated patients will experience arthritis.
Neurologic conditions include peripheral sensory neuropathies, motor neuropathies, cranial neuropathies, autonomic dysfunction, movement disorders, neuropsychiatric illnesses and encephalopathy. Neuroborreliosis is the term used when Lyme infects the brain. 15 – 40% of Lyme disease patients have neurologic disorders due to the infection. [Caliendo et al, Psychosomatics
1995; 36:69-74] Late disease can be severe
with marked morbidity and poor treatment outcomes.
|International Lyme and
Associated Diseases Society
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The symptoms of Lyme disease are widespread and
variable; relapsing/remitting patterns are common.
The validity of individual symptoms has been documented in numerous reports and studies on Lyme disease.
Frequently reported symptoms include:
Extreme fatigue, often interfering with activities
Headaches of all types
Recurrent fevers, chills, night sweats
Myalgias and arthralgias; either may be migratory
Muscle fasciculations and weakness
Paresthesias and neuropathic pain syndromes
Cranial nerve dysfunction
Neuropsychiatric problems – irritability, depression, anxiety, panic attacks, new onset ADHD, mood swings similar to bipolar disease, rage attacks, OCD
Cognitive losses: memory impairment, difficulty
multi-tasking, slowed mental processing, speech and language problems, poor concentration, loss of math skills, impaired visual/spatial processing
Children may have behavioral changes, declining
school performance, headache, fatigue,forgetfulness, complex partial seizures, depression and be misdiagnosed with primary ADHD.
Although Lyme disease symptoms overlap with symptoms of other conditions such as fibromyalgia, chronic fatigue syndrome, MS, early ALS, RA, lupus and psychiatric disorders, patients with Lyme disease often have symptom patterns which are atypical for these other illnesses. Making sense of the multitude of reported symptoms can be challenging; but bear in mind that symptoms which appear unrelated may be linked via an underlying autonomic neuropathy or encephalopathy.
Ticks also carry Babesia, Anaplasma, Ehrlichia, Bartonella, Mycoplasma and other pathogens. The presence of these organisms complicates the diagnosis, testing and treatment of Lyme disease patients. In animal models, co-infections alter the immune response, pathogen load and disease severity.[Thomas V. Infect.
Immun. 2001;69:3359–3371.] In humans, coinfections
increase morbidity and delay recove
Physical Exam in Lyme Disease
Lyme disease patients may have exam findings
when carefully assessed but findings may be few or
absent in some cases. In addition to a general exam,
detailed neurologic, dermatologic and rheumatologic exams should be performed.
Serologic Testing in Lyme Disease
Borrelia burgdorferi is very difficult to culture, thus
serologic tests are used to detect the presence of
antibodies to Bb. In 1995 the CDC, in an move to
standardize testing procedures and Western blot
interpretations, published guidelines for laboratory
testing in Lyme disease.[MMWR 1995; 44:590-1]
The CDC recommended a two-tier testing algorithm.
Step 1 is an ELISA or IFA; positive or
equivocal results advance to step 2, IgM and IgG
Western blotting. Samples negative in step 1 are not
tested further. The purpose of standardization
was to establish parameters for laboratory confirmation
of Lyme disease surveillance cases, not
clinical diagnosis.[Mead P. CT Dept of Public
Health Hearing Jan 29, 2004]
Two-tier testing doesn’t work
The step 1 tests are insufficiently sensitive to be
used as “screening” tests. [Trevejo R, JID 1999;
179:931–8.] Western blots, increase specificity but,
following a step 1 test, further decrease overall sensitivity.
The bands included in the Western blot
interpretation schemes were chosen on a statistical,
rather than a clinical, basis.[Dressler F. JID 1993;
167:392-400.] Recently, the C6 peptide ELISA
alone was proposed as an alternative to the two-tier
approach. Unfortunately, the C6 ELISA also lacks
adequate sensitivity for clinical use.[Bacon R. J
Infect Dis 2003; 187:1187- 99.]
Lyme disease, like many other diseases, is a clinical diagnosis; with testing playing a supportive role.