Gram Negative Spiral
Lymes disease, all are true, except
|A||Borrelia burgdorferi replicates locally and invades locally|
|B||Infection progresses inspite of good humoral immunity|
|C||Polymorphonuclear leukocytosis in CSF suggest meningeal involvement|
|D||IgA intrathecally confirms meningitis|
Polymorphonuclear leukocytosis in CSF suggest meningeal involvement
a. Lyme’s disease or Lyme borreliosis is caused by the spirochete Borrelia burgdorferi sensu stricto, B. garinii and B.afzelii, transmitted to humans by the bite of an infected tick (nymphal stage). It is the most common vector borne disease in the northern hemisphere and its distribution matches the distribution of the Ixodid ticks.
b. The cycle is maintained in nature by a number of small rodents especially white-footed mouse, which act as asymptomatic reservoirs.
c. Although deer are not directly involved in transmission, they are important for survival of ticks.
d. The tick needs to be attached for at least 24 hrs to transmit disease.
e. After injection into human skin, the borreliae multiply locally and migrate outwards, producing the primary lesion and may spread hematogenously. Spread through the skin and other tissue matrices is aided by binding to certain host integrins, glycosaminoglycans and extracellular matrix proteins.
f. Due to its protean manifestations Lyme’s disease is called `the new great imitator’. As in syphilis, the manifestations can be cataloged into 3 stages:
a. Stage I is the stage in which the tick bite elicits the classic lesion, erythema chronicum migrans (EM). This is seen after an incubation period of 3-32 days, during which the spirochete multiplies locally and then spreads peripherally. The lesion is red, and may be warm, but is generally painless. Classically, the innermost portion remains dark red and becomes indurated; the outer edge remains red; and the portion in between clears, giving the appearance of a bull’s eye. Regional lymphadenopathy, malaise and fatigue may accompany the EM lesion.
b. Stage II is the stage of disseminated disease due to hematogenous dissemination. Within several days to weeks of EM, patients develop multiple secondary annular skin lesions which resemble the EM lesion along with generalized lymphadenopathy and intermittent migrating arthralgias and myalgias. About 15-20% of untreated patients develop meningitis, encephalitis, cranial neuritis, motor and sensory radiculoneuritis, cerebellar ataxia- alone or in combinations.
c. Patients with meningitis show a lymphocytic pleocytosis of about 100 cells/cumm with an elevated protein and normal glucose level in the CSF. Specific IgG, IgM or IgA antibodies are produced intrathecally.
d. About 5% of patients show fluctuating degrees of atrio-ventricular blocks and acute myopericarditis.
e. Conjunctivitis is the most common eye abnormality, though deeper tissues of eye may be involved.
f. Stage III starts months after the onset, manifesting most commonly as intermittent attacks of joint swelling and pain, primarily in large joints, especially knee. Attacks of arthritis last from few weeks to months separated by periods of complete remission. Joint fluid contains primarily PMN’s. About 10% of untreated develop chronic arthritis (1 yr or more of continuous inflammation). However, even untreated, arthritis resolves completely in several yrs.
g. 5% of patients develop chronic axonal polyneuropathy (radicular pain or paresthesia) and chronic encephalomyelitis (spastic paraparesis, ataxia, cognitive impairment or cranial neuropathy). There are no inflammatory changes in the CSF but intrathecal antibody production to the spirochete can often be demonstrated.
h. Acrodermatitis chronic atrophicans are red, violaceous lesions which may last for several yrs.
i. During disseminated infection, antibodies are produced against many components of the organism especially plasmid-coded outer-surface proteins (Osp) A through F. Despite an active immune response, the organism can survive for several years in joints, skin or nervous system.
j. Diagnosis- mainly clinical if characteristic EM lesion is present. B.burgdorferi can be cultured in a cell free liquid medium - Barbour-Stoenner-Kelly (BSK II) medium from early lesions. Demonstration of spirochetes by silver stains and by amplification techniques in skin lesions, peripheral blood and joint fluid can also be used.
k. The diagnostic method of choice is serologic analysis. An enzyme immunoassay or immunofluorescence assay is used as the initial test. Positive results should be confirmed with immunoblot assay for IgM and IgG. Serodiagnosis is insensitive during first one or two weeks of infection. IgM is the first antibody to appear. After one month, almost all patients with active infection have positive IgG antibody. Acute neuroborreliosis can be demonstrated by intra-thecal production of IgM, IgG and IgA antibodies but this test is less often positive in chronic neuroborreliosis.
l. After antibiotic treatment antibody titers decline slowly and IgG and even IgM may persist for many yrs.