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Lyme disease

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Caused by tick-borne bacterium Borrelia burgdorferi.

A zoonosis, transmitted by certain ixodid ticks.

Called a great imitator-its symptoms resemble those of more than 350 unrelated medical conditions.

The most common vector-borne disease in North America.

Most common tickborne disease in the US.

Estimated seroprevalence of 14.5% with the highest prevalence in the temperate regions of central and western Europe and east Asia.

Most patients are not aware of the tick bite, since most tick bites go undetected.

Caused by borrelia burgdorferi in US, B afzelii in Europe and B. garinii in Asia.

Worldwide, age involves four dominant tick species, although generally only one tick species is important in any given region.

Wide ranging reservoir hosts, including mammals, such as mice and squirrels, lizards, and birds are part of ecological complexities, but humans play no role in ongoing transmission.

The lifecycle and prevalence of tick vectors, primarily Ixodes sccapularis, and I pacificus ticks in North America, and and I persulcatis in  Europe, are  strongly influenced by the abundance of reservoir hosts, and by ambient air temperature.

Deer ticks transmit disease,causing bacteria in Borrelia burgdorferi with their bites.

These ticks thrive in regions with high humidity and temperatures higher than 45°F.

Shorter winters are also increasing the number of ticks and their activity and causing more people to be exposed to the disease.

Incubation period of 7-21 days.

The CDC has reported the number of cases has almost doubled to 30,000 per year and evidence exists that only about one in 10 cases is reported.

Lyme disease is increasing in the US as the environmental niche of the deer tick and deer population expands.

Without early treatment, infection can cause debilitating multi system to cry disease

Estimated number of cases treated is nearly 476,000 annually.

Reportable disease since 1982.

The disease is one of geography with nearly 95% of cases occurring in 12 states, and even within those states, the incidence is very focal.

The disease process is seasonal with increased cases diagnosed during the summer.

Incidence highest among children from 5-14 years and adults from 40-50 years of age.

Ticks ingest the nymphal stage of the spirochete from an infected animal and transfer the disease to humans.

Patients with symptomatic infection manifest with skin rash, arthritis and neurologic deficits.

Some patients have chronic inflammation of the skin with a dense lymphocytic infiltration which is followed by atrophy and is known and is acrodermatitis chronica atrophicans.

Classic feature is erythema migrans with typical findings of a beltline, axilla, or inguinal rash with painless areas of erythema and central clearing.

Classic bull’s eye or target lesion is not the most common skin manifestation.

Erythema migrans is usually asymptomatic, but may be pruritic or painful.

20% of patients do not develop erythema migrans (Steere AC).

Erythema migrans is an annular, erythematous skin lesion that is greater than 5 cm in diameter with central erythema that occurs in 80% of patients with Lyme disease.

Transmitted by the bite of Ixodes scapularis tick and is the most common vector-borne disease in the U.S.

Lyme disease can also be transmitted by the bite of an infected Weston black-legged tick, Ixodes pacificus which accounts for Lyme disease occurring in California, Oregon and Washington.

Average 12,000 cases annually in the U.S. with most cases in New England and Middle Atlantic states.

Overall incidence in the U.S. is 7 cases per 100,000 population, but in endemic areas may reach as high as 134 cases per 1000,000 population.

CDC suggests there about 476,000 cases diagnosed each year in United States, and this new estimate is 10 times greater than the number of cases of infection actually reported to the CDC annually.

In 2011 13 states: Connecticut, Delaware, Maine, Maryland, Massachusetts, Minnesota, New Hampshire, New Jersey, New York, Pennsylvania, Vermont, Virginia, and Wisconsin comprise 96% of cases reported.

Presently about 36,000 cases of Lyme disease reported to CDC annually, primarily from upper Midwest and Northeast.

The increased frequency and geographic focalization is explained by an increase in the deer population, with greater human exposure to those environments.

Patients with erythema migrants, will most likely present in warm weather, while patients with late manifestations of disease,such as arthritis, present at any time.

Erythema migrans is often accompanied by systemic symptoms such as fever, headache, malaise, myalgias, and arthralgias.

Approximately 90% of patients diagnosed as having Lyme disease have erythema migrans, some, however, will present with nonspecific febrile illness without rash.

Patients with flulike illness during the summer time, in the right epidemiological context, should be examined for the presence of a erythema migrans lesion.

As the deer population increases so does the tick population, with more tics and more tick bites.

A disease of exposure.

No available vaccine exists.

1-3% of individuals who recognize a tick bite become infected with B burgdorferi.

Only 25% of patients recall a tick bite.

Commonly misdiagnosed.

Chronic Lyme disease has not yet been defined as a clinical entity.

Patients with erythema migrans are often seronegative.

Diagnosis of erythema migrans is made by history and physical exam interpreted within epidemiological context.

Early Lyme disease is diagnosed clinically based on the characteristic skin lesion, erythema migrans, because standard antibody testing is too insensitive, with positive rates of just 20 to 40%.

The standard laboratory approach involves a screening ELISA followed by confirmatory western blot test, but the sensitivity and specificity of the current two tier diagnostic algorithm are reduced in patients who present in the first month of illness.

Serological testing in early disease is not necessary or indicated.

Serological testing is usually positive in early disseminated disease, but may require at least 5 to 6 weeks before it is positive.

Many patients will be seronegative early in the illness.

Seropositivity rates in Lyme disease in endemic areas in the US may exceed 5%.

Routine serologic testing for Lyme disease is not recommended for a patient with cognitive decline, dementia or another nonspecific white matter abnormalities seen on MRI, patient with psychiatric disorders, children with developmental or behavioral disorders in patients with chronic cardiomyopathy.

A positive lyme disease serology refers to a positive first step polyvalent enzyme immunoassay and a positive second step immunoblot ( immunoglobulin IgM). and or immunoglobulin G.

An IgM Immunoblot is positive if two of three bands are present.

After 4-6 weeks of untreated Lyme disease, the IgG immunoblot should be positive.

An IgG immunoblot is positive if five of 10 particular bands are present.

Patient infected by B burfdorferi for many weeks or months almost invariably seropositive by 2 tier tests.

Many patients remain serpositive for many months or years after infection has been cured.

Low CD57 levels is an indicator of the disease.

Approximately 10-15% of patients have nervous system involvement-Lyme neuroborreliosis.
Rarely nervous system involvement is characterized by painful radiculopathy, with motor weakness, cranial nerve palsies, and lymphocytic Pleocytosis  and elevated CSF protein with normal glucose levels.

Dermatologic findings can be highly suggestive of Lyme disease, but incomplete skin exams contribute to delayed diagnosis.

Treatment with intravenous or oral antibiotics for 90 days does not improve symptoms more than placebo.

Culture is not a routinely recommended diagnostic test due to its low test sensitivity.

PCR testing for detection of nucleic acids is insensitive in the CSF.
PCR sensitivity rates on synovial fluid for Lyme arthritis ranges from 71 to 100%.
Standard 2 tier serologic testing of IgM  and IgG immunoblot is the primary diagnostic testing strategy.
Treatment is recommended without pursuit of serological testing for patients who present with erythema migrans.

Antibodies against B. BurgdorferI C6, recombinant peptide from its surface antigen is more sensitive in the early course of disease.

Doxycycline, amoxicillin, or cefuroxime axetil drugs of choice.

Early disease responds well to oral antibiotics with amoxicillin and doxycycline being the drugs of choice with a recommended duration of treatment being two to three weeks.

Amoxicillin is recommended for children younger than eight years of age and pregnant women.

Azithromycin is an alternative for allergic patients who cannot take doxycycline but macrolide antibiotics are less effective than other agents.

Early treatment is highly effective.

Parenteral antibiotics may be required in more severe infections.

Patients who have well-documented disease who have residual nonspecific symptoms after treatmen do not benefit from additional treatment even with extended courses of intravenous antibiotics.

Trials to suggest 10 days of doxycycline rather than longer treatment courses is now recommended for treatment in patients with Erothema migraines.

Co-infection by babesiosis or anaplasmosis may occur.

Patients with coinfections are more ill, have higher fever, pancytopenia and elevated liver functions.

Duration of attachment of ticks associated with a risk of 25 % if greater than 72 hours and zero if the tick has fed for less than 72 hours.

A single dose of 200 mg of doxycycline given within 72 hours after an I. scapularis tick bite can prevent the development of Lyme disease.

Erythema migrans is a clinical diagnosis based on a characteristic rash in patients where Lyme disease is endemic.

Erythema migrans rash treatment recommended is doxycycline 100 mg orally bid for 14 days.

Lyme meningoridiculitis is related with subacute symptoms over several weeks with radicular pain, motor weakness, sleep disturbances, erythema migrans, headache, fatigue, paresthesias, and facial palsy.

Almost all patients report radicular pain, usually at the site of existing or previous rash, and typically involves several adjacent nerve roots.
Cranial neuropathies that affect the facial nerve and less commonly the trigeminal nerve may occur.

The presence of Bell’s palsy without meningitis is it recommended to treat with doxycycline 100 mg orally bid for 14 days.

For manifestations of neurologic processes of meningitis or encephalitis ceftriaxone 2 gm IV recommended for 14 days.

Fewer than 1% of patients Lyme disease present with cardiac involvement.

Patients with Lyme carditis tend to be younger and male, and the conduction system is predominantly affected, but myocardial and pericardial disease may occur.

Patients may have insignificant first-degree AV block to complete heart block but generally pacing is not required.

Myocardial disease is generally mild and self-limited

In the presence of cardiac disease or arthritis doxycycline 100 mg orally bid for 14 days or ceftriaxone 2 gm IV for 14 days are recommended.

Symptoms of acute neuroborreliosis develop in about 15% of untreated patients and typically improve or resolve within weeks to months.

Lyme neuroborreliosis Is highly treatable with approximately 95% of patients having symptomatic improvement with 10-28 day course of appropriate antibacterial agent.

Lyme neuroborreliosis can be successfully treated with parenteral penicillin, ceftriaxone, and doxycycline.

Three cardinal features of neurologic involvement are lymphocytic meningitis, cranial nerve neuropathies, with the seventh nerve the most commonly involved, often with bilateralism, and painful radiculitis.

Peripheral neuropathies can occur with radiculopathy, plexopathy, or diffuse polyneuropathy, often mimicking an acute inflammatory demyelinating polyradiculopathy.

Nerve root enhancement, focal brain or spinal cord involvement may be demonstrated by MRI scanning.

CSF analysis may reveal lymphocytic pleocytosis with up to several hundred cells, normal to slightly increased protein and the glucose level may slightly decreases or normal.

Mice rather than deer are most responsible for the transmission of Lyme disease.

Months after onset of illness about 60% of untreated patients have intermittent joint swelling and pain, especially in the knee.

Acrodermatitis chronica atrophicans can induce cutaneous B cell lymphomas of the skin.

B cell lymphomas of the skin induced by chronic Borrelia infections of the skin may regress upon treatment of the infection.

No deaths have been linked to the infection.

Two-step approach to diagnosis involving enzyme-linked immunosorbent assay (ELISA) followed by confirmatory Western Blot analysis.

Risk of disease after a deer-tick bite is 3.2 percent.

Deer ticks have three-cycles-larva, nymph and adult.

Lyme disease develops only after bites by nymphal ticks.

Early localized disease after tick bite characterized by erythema chronicum migrans and occurs in 60-80% of cases.

Deer ticks much smaller than dog ticks, 1-2 mm vs. 5-6 mm.

Deer ticks typically found on long grass blades where they can attach to deer or humans.

Rash is the most common presentation and is related to the life cycle of the Ixodes tick with timing related to late spring, summer or early fall.

Facial palsy relatively common presentation, allthough three of four facial palsies are unrelated to Lyme disease.

Multiple cranial neuropathy may be a presenting manifestation.

Clinical trials show that prolonged antibiotic therapy has no benefit in relieving post treatment Lyme disease symptoms, condition called chronic Lyme disease.
There is no evidence of active infection of these patients by culture or molecular methods.
Post treatment Lyme disease symptoms are most likely caused by persistently active biological remnants of B. burgdorferi cells and not due to a persistent infection that is refractory to anabiotic therapy.

There is no evidence by culture or molecular methods to indicate a post treatment Lyme disease symptoms are caused by persistent infection, and that extended antibiotic therapy is beneficial.

Prevention largely depends on preventing I.sccapularis bites and useful measures include covering up the skin as much as possible, using tick repellent on exposed skin, permethrin apply to clothing and regular chip chicks over the entire skin surface after outdoor activities.

Personal protective measures such as protective clothing and tick repellents are recommended to prevent infection and transmission.

The prompt removal of attached ticks can prevent infection: at least 36 hours of tick attachment is needed for transmission of Borrelia burgdorferi.

A single dose of oral doxycycline to prevent Lyme disease may be considered within 72 hours of tick removal for tick bites deemed high risk.

Erythema migraine treatment is recommended to be 10 days of doxycycline.

A 28 day course of oral doxycycline, amoxicillin, cefuroxime is recommended for treatment of Lyme arthritis:90% patients have resolution of arthritis within 1 to 3 months.

Similar agents are equally effective for Lyme neuroberylliosis.

Posttreatment Lyme disease (PTLD) is increasing from several hundred thousand to several million people.

About 10 to 20% of individuals infected with Lyme disease will experience posttreatment, Lyme disease syndrome.

Posttreatment Lyme disease manifests with fatigue, joint pain, memory loss, difficulty focusing, which can last months to years and even decades.

Hypothetically, PTLD syndrome may persist after antibiotic treatment as parts of the organism may endure in the persons body activating an immune response, or antibodies may form causing damage to the brain or other organs.

 

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