Late symptoms are typically manifested by musculoskeletal, cardiovascular, or nervous system signs and symptoms. Chronic, intermittent arthritis affecting one or a few large joints is a common manifestation of late, chronic infection and may occur weeks to years after acute infection. The knee is commonly involved. Progressive arthritis or symmetric polyarthritis is not typical and should prompt consideration or another diagnosis. Nonspecific findings include arthralgias or myalgias.
Carditis is usually manifested by acute second- or third-degree atrioventricular conduction defects that typically resolve in days to weeks. Myocarditis may accompany the conduction abnormalities. Nonspecific findings may be seen, including bradycardia or palpitations.
A variety of nervous system abnormalities may be seen, including acute meningitis, cranial neuritis (facial nerve palsy), radiculopathy, or encephalomyelitis. The triad of aseptic fluctuating meningoencephalitis, Bell palsy, and peripheral neuropathy is very suggestive of Lyme disease. Nonspecific findings may be seen, including fatigue, headache, or paresthesias.
Laboratory Findings
Culture
: Not widely available and usually positive only early during the acute infection.
Serology
: Not helpful or necessary at the early, acute stage; tests are only 40–60% sensitive, and diagnosis is not ruled out by a negative test. Testing should be ordered only to support clinical diagnosis, not for screening persons with nonspecific symptoms because of their intrinsic poor sensitivity and specificity. Vaccination produces seropositivity. See Chapter
17
, Infectious Disease Assays for details of serologic testing for
B. burgdorferi
infection.
A negative EIA or IFA result usually excludes Lyme disease, but testing paired acute- and convalescent-phase serum samples may be needed for patients with a high index of suspicion and negative results of initial testing. Patients with disseminated or chronic Lyme disease are usually strongly positive for specific anti-
B. burgdorferi
IgG.
Specific IgM antibodies usually appear 2–4 weeks after EM and peak after 3–6 weeks of illness. IgM usually declines to undetectable levels after 4–6 months. In some patients, IgM remains elevated for many months or reappears late in illness, indicating continued infection. A negative test within 2 weeks of onset of symptoms does not rule out infection.
Specific IgG titers rise more slowly, usually appearing 4–8 weeks after rash. IgG titers peak after 4–6 months and may remain high for months or years, even with successful antibiotic therapy. A single increased IgG titer may be due to previous infection or vaccination and must be interpreted in the context of clinical symptoms. An IgG titer ≥1:800 usually indicates active infection; a titer of 1:200 to 1:400 is indeterminate. Titers <1:100 are considered negative.
Paired acute and convalescent sera at 4- to 6-week intervals may demonstrate a significant rise in titer, indicating active infection. Testing of paired serum samples may be needed to confirm infection in patients with compatible symptoms, but without a known tick bite or rash, who have been in endemic area.
RF may cause false-positive result for IgM. False-positive IgG in high titers may be caused by antibodies from spirochetal diseases (syphilis, relapsing fever, yaws, pinta); low titers may be found in infectious mononucleosis, hepatitis B, autoimmune diseases (e.g., SLE, RA), periodontal disease, ehrlichiosis, rickettsiosis, other bacteria (e.g.,
H. pylori
). Five percent to fifteen percent of persons in endemic areas may be seropositive without any signs or symptoms of active infection.
Western blot assays
: Used to confirm initial serologic testing with EIA or IFA. IgG WB assays may not become positive until after many months of illness; negative WB should be repeated in 2–4 weeks if Lyme disease is strongly suspected.
Molecular tests
: PCR plays a limited role in the diagnosis of Lyme disease and is not recommended in seronegative patients. PCR may be positive for CSF in acute lymphocytic meningitis (not encephalomyelitis or other neurologic syndrome) or for synovial fluid of joints with active disease. PCR is not reliable for other types of specimens.
Synovial fluid of affected joints
: Shows mild to moderate increased WBCs, typically with granulocyte predominance.
CSF findings
: Patients with Lyme encephalomyelitis show lymphocytic pleocytosis, slightly increased protein and globulin, and normal glucose. Oligoclonal bands may be demonstrated. Intrathecal antibody production may be demonstrated by higher titer in CSF than in serum. Almost all of these patients will have positive serum serologic tests.
Core laboratory
: Findings related to dysfunction of infected organs may be seen. Nonspecific laboratory findings include increase of ESR, lymphopenia, cryoglobulinemia, and increase of hepatic enzymes. Treponemal tests for syphilis may be positive, but nontreponemal tests should be nonreactive.
