Docstoc

Lyme_Disease

Document Sample
Lyme_Disease Powered By Docstoc
					Lyme Disease
 John O Meyerhoff, MD, Assistant Professor, Department of Internal Medicine, Johns Hopkins University
 School of Medicine; Clinical Scholar in Rheumatology, Department of Medicine, Sinai Hospital of
 Baltimore
 Nov 19, 2008

Introduction

Background
Lyme disease is due to infection with the spirochete Borrelia burgdorferi and the body's immune
response to the infection. In Europe, the rash (then called erythema chronicum migrans [ECM]) was
first described at the beginning of the 20th century. The neurologic manifestations and the association
with Ixodes ticks (also known as deer ticks; see Image 1) were recognized by the mid 1930s and were
known as tick-borne meningoencephalitis. In the United States, Lyme disease was not recognized until
the early 1970s, when an outbreak of pediatric arthritis occurred in the region around Lyme,
Connecticut. This was investigated by Allen Steere, MD, and others from Yale. The recognition that the
patients in the United States had ECM led to the recognition that Lyme arthritis was one manifestation
of the same tick-borne condition known in Europe.

After Willy Burgdorfer, MD, discovered a borrelial organism in Ixodes ticks, it was recovered from
patients with clinical Lyme disease, confirming it as the causative agent. This led to the development of
antibody tests for the disease. Different strains of Borrelia are recognized, which probably explains
why the clinical manifestations of Lyme disease are different in the United States and Europe.

Lyme disease has become common in the United States from Maryland to Maine and in Wisconsin
and Minnesota, with a smaller focus in northern California. A great deal of fear and concern exists
among residents and visitors to these areas. The development of vaccines against Lyme disease and
the subsequent advertising of one of the vaccines have led to further apprehension among the
populations of these areas. The emergence of Lyme disease is probably due to the explosion of deer
and tick populations with the reforestation of the northeastern United States and the subsequent
contact between ticks and humans as people move into deer habitats. B burgdorferi has been found in
tick specimens collected in the 1940s on eastern Long Island.

For additional information on Lyme disease, see Medscape’s Lyme Disease Resource Center.

Pathophysiology
B burgdorferi is a spirochete. It is transmitted from host to host by the Ixodes, or deer tick. The life
cycle of the Ixodes tick and B burgdorferi is important, as it relates to the epidemiology of Lyme
disease.

The Ixodes tick is born as a larval tick in the summer and feeds only once. Its preferred host is the
common field mouse, but other animals apparently suffice. The following spring, it becomes a nymph
and again feeds only once, with its preferred host again being the field mouse. In the fall, the nymph
becomes an adult and feeds a single time. Its preferred host is the white-tailed deer. Thus, unless the
tick feeds on an infected host before feeding on a person, infection cannot result from that tick bite.
Even if a tick feeds on an infected animal, it may not acquire the infection. Mice do not appear to
develop Lyme disease, but they do carry the bacteria. They may be considered infested rather than
infected.

Not all strains of mice continue to carry the bacteria after exposure to B burgdorferi. As mice mature,
they may be less able to sustain a B burgdorferi bacteremia. Even when they are exposed to the
bacteria, they do not remain carriers for extended periods. Other animals are even poorer hosts for B
burgdorferi.

Some studies suggest that uninfected ticks do not become infected unless they feed next to infected
ticks that have been feeding on the same animal. This suggests that, although B burgdorferi may
disseminate throughout the body of its host, not enough bacteria may be present in the distant sites to
pass on the infection.

A tick must be attached to a person for 2-3 days to result in infection. This is due to the life cycle of B
burgdorferi in ticks. In previously infected ticks, only small numbers of bacteria are present until the tick
feeds. Once feeding begins, the bacteria then multiply in the gut of the tick. The bacteria then migrate
to the salivary glands of the tick after 2-3 days. There, they are injected into the animal by the tick as it
ends its feeding. Until this multiplication occurs, ticks are rarely able to pass on the infection.

Humans are infected by ticks in the nymph stage 85% of the time (spring to summer) and the adult
stage 15% of the time (fall). Thus, for many reasons, only approximately 1% of all tick bites occurring
in an endemic area result in Lyme disease.

Once B burgdorferi is injected into the host, 1 of 3 events occurs, as follows:


           In the first event, patients may clear the infection without developing any manifestations, as
            demonstrated by patients who are asymptomatic but seropositive.
           In the second event, B burgdorferi spreads throughout the body and produces symptoms by
            direct invasion, particularly in the early stages of the disease. Because growing B burgdorferi
            is difficult, confirming that the organism is actually present in a specific organ that may be
            involved in Lyme disease is also difficult. The inflammatory response to B burgdorferi in the
            skin is probably the cause of erythema migrans.
           In the third event, B burgdorferi induces an immune response that may lead to symptoms in
            various organs, with little evidence of bacterial invasion. Studies of Lyme arthritis have shown
            that the arthritis is associated with certain immunological factors, including the production of
            proinflammatory cytokines and the formation of immune complexes, and also genetic factors,
            such as human leukocyte antigen (HLA)–DR4 and HLA-DR2.

The manifestations of Lyme disease are related to the particular strain of Borrelia involved. In the
United States, isolates from the East Coast are known as B burgdorferi sensu stricto. In Europe, B
burgdorferi garinii is associated with neurologic disease, while B burgdorferi afzelii is associated with a
dermatologic manifestation known as acrodermatitis chronica atrophicans.

Frequency
United States

At best, frequency data for Lyme disease are approximations, for the following reasons:


        Separating false-positive antibody tests from asymptomatic infection is impossible.
         Approximately 5-10% of patients in endemic areas have positive antibody results without a
         history of symptoms.
        Although Lyme disease is a reportable disease, not all cases are reported or discovered
         through laboratory records because early disease should be treated without antibody testing.
        In 1999, state health departments reported 13,306 cases of Lyme disease. This was 3500
         cases fewer than in 1998. Approximately 90.5% of cases were reported from the states
         between Maryland and Maine, 2.8% from Wisconsin and Minnesota, and 1.1% from California
         and Oregon. Wisconsin had an 82% drop in reported cases between 1998 and 1999.
        In 1997, Connecticut had the highest reported rate of Lyme disease in the United States at
         69.9 cases per 100,000 persons, with a 16.6-fold difference among the 8 counties in
         Connecticut. Maryland had only 9.6 cases per 100,000 persons but a 180-fold difference in
         rates by county. In both states, the lowest rates were reported from the most urban areas.
        Actual rates of Lyme disease may be 5 times higher than state health department rates.


International

Rates of Lyme disease in Europe may be similar to those in the United States. A rate of 69 cases per
100,000 persons was reported in southern Sweden, with peaks at ages 5-9 years and 60-69 years.

Race
Lyme disease is reported primarily in whites. In the United States in 1998, 76% of reported cases
involved whites, followed by other ethnic groups at 21%.

Sex
Reports from Europe indicate that, among children, the rate of Lyme disease is slightly higher in boys
than in girls, but, in the older age peak, the disease is more common in women than in men.

Age
The incidence of Lyme disease has two age-based peaks: at age 5-9 years and another at age 50-54
years. The incidence of Lyme disease is lowest in individuals aged 20-24 years.

Clinical

History
The manifestations of Lyme disease have been divided into 3 stages: localized, disseminated, and
persistent. The first 2 stages are part of the early infection, while persistent disease is considered late
infection. Unlike syphilis, stage 3 disease may occur within 1 year of infection, not many years later.
Certain manifestations of Lyme disease are more common in the United States, while others are more
common in Europe.
The primary symptoms of stage 1 are erythema migrans and some associated symptoms. The primary
symptoms of stage 2 include intermittent arthritis, cranial nerve palsies and radicular symptoms,
atrioventricular (AV) nodal block, and severe malaise and fatigue. The primary symptoms of stage 3
include prolonged arthritis; chronic encephalitis, myelitis, and parapareses; and symptoms consistent
with fibromyalgia.

The natural history of Lyme disease is as follows:


       Tick bite
             o      The Ixodes tick is small, and the bite is often innocuous enough that 30% of patients
                 in the United States do not remember being bitten.
             o In Europe, 64% do not remember being bitten.
       Erythema migrans
             o Erythema migrans (see Image 2) is an erythematous lesion that grows (hence the
                 name) over several days. It may be asymptomatic or it may itch or burn. It often
                 occurs at or near the site of the tick bite, which may be an area not normally
                 visualized by individuals, such as the axilla, groin, or popliteal areas. The rash may
                 not be observed until it is already full size.
             o Untreated, the rash persists for 2-3 weeks. Eighty percent of patients with Lyme
                 disease have only one episode of erythema migrans, while 20% may have recurrent
                 episodes. Multiple lesions may occur in 40% of patients with Lyme disease and are
                 not the result of multiple tick bites. The rash may be associated with
                 lymphadenopathy and symptoms such as fever and myalgias, which may be
                 described by the patient as flulike in nature.
             o Malaise and fatigue are the most common findings after the skin lesion in early
                 disease. They affect as many as 80% of patients with Lyme disease in the United
                 States but less than 35% in Europe.
             o Approximately one third of all patients with erythema migrans develop no further
                 manifestations of Lyme disease, while two thirds of patients develop further
                 symptoms listed below.
       Intermittent inflammatory arthritis
             o This often begins as a migratory polyarticular process involving bursae, tendons, and
                 joints, which evolves over 1-2 days into a monoarticular process involving the knee,
                 ankle, and wrist, in decreasing frequency. When asked about their symptoms after
                 they have resolved, patients with Lyme disease are less likely to remember those
                 symptoms that occurred prior to the monoarthritis. Polyarticular episodes may also
                 occur.
             o In two thirds of patients, the first episode occurs within 6 months of the erythema
                 migrans lesion. Untreated, the episodes last approximately a week. Two thirds of
                 patients have 3 recurrences approximately 2.5 months apart. The recurrences are
                 more likely to involve more than one joint than the initial event. With time, these
                 episodes become less frequent and severe and involve fewer joints. Even without
                 treatment, the recurrent episodes usually resolve over a 10-year period.
        o      Some patients may present with intermittent joint pain without inflammatory findings.
               This is more common in Europe, where arthritis was not recognized as a
               manifestation of Lyme disease until the early reports from the United States.
   Cranial nerve palsies
        o      This is the most common neurologic manifestation of Lyme disease in the United
               States and is probably the most common in Europe, particularly in children. More
               than half of children with neurologic symptoms have a facial palsy. It may be bilateral.
        o      The palsy lasts less than 2 months and may begin to resolve even in the first several
               days.
   Meningoradiculoneuritis (Bannwarth syndrome)
        o      This occurs much more frequently in Europe than in the United States.
        o      It is characterized by severe radicular pain (due to neuritis), with a prominent
               nocturnal component. The meningitis may be relatively mild.
   Carditis
        o      This usually manifests as fever and syncope due to AV block.
        o      The level of AV block varies and fluctuates so that the symptoms may be intermittent.
               The block rarely lasts longer than a week; a temporary pacemaker is rarely required.
   Meningitis
        o      This may occur along with other neurologic manifestations or by itself.
        o      Severity ranges from mild to severe and usually presents as headache, photophobia,
               and/or a stiff neck. The severity of the meningitis is less than that observed in
               patients with more typical bacterial meningitis.
   Chronic arthritis
        o      Approximately 10% of patients with intermittent arthritis develop a chronic arthritis
               that typically involves the knee.
        o      While it may last several years, it rarely develops into a destructive arthritis.
   Chronic neuropathy
        o      Chronic paresthesias and, less frequently, radicular pain without sensory or motor
               deficits may occur.
        o This is usually not associated with other chronic neurologic symptoms.
   Chronic meningoencephalitis
        o This appears to be more common in Europe than in the United States.
        o Abnormalities in mood, memory, and sleep may develop.
        o Symptoms may vary from mild to severe. More severe symptoms of ataxia, spastic
            paresis, and cognitive dysfunction may develop, possibly more often in patients who
            have had CNS involvement. Children who have had Lyme disease seem to be at low
            risk for the development of such findings.
   Fibromyalgia and chronic fatigue
        o Symptoms consistent with fibromyalgia and chronic fatigue syndrome develop in
            patients who have had clear-cut Lyme disease, even after adequate treatment.
        o A biological relationship does not seem to exist between these symptoms and Lyme
            disease, and it does not appear to be due to active infection.
   Other manifestations
               o     A bluish-red nodular lymphocytic infiltrate known as a lymphocytoma, typically
                     appearing on the earlobe or nipple, occurs in Europe but not the United States. It is
                     usually found as part of stage 2 disease.
               o     Atrophic areas can develop over the extensor surfaces of the extremities during late
                     disease and are known as acrodermatitis chronica atrophicans. This has not been
                     reported in the United States.

Physical

        Erythema migrans is an erythematous lesion. The entire lesion may be uniform in color or
         central clearing may be present (one third of US cases and two thirds of European cases).
         More proximal to the clearing may be additional erythema leading to a so-called "bull's eye"
         appearance. The center may be scaly or discolored. Single lesions average 16 cm in
         diameter.
        Lyme arthritis presents with the usual findings of an acute arthritis. These include warmth,
         erythema, and swelling and pain upon motion of the joints, but usually not as severe as in a
         septic joint. Effusions may be large and generally recur following aspiration, as is often seen
         in spondyloarthropathies.
        Lyme meningitis does not manifest as the usual signs of bacterial meningitis (boardlike
         rigidity, Kernig and Brudzinski signs).
        Chronic radicular paresthesias are usually not associated with motor or sensory deficits, and
         the physical examination results are normal.


Differential Diagnoses

Aseptic meningitis
Fibromyalgia
Reactive arthritis
Rheumatoid Arthritis
Systemic Lupus Erythematosus

Other Problems to Be Considered
AV nodal block
Encephalitis
Radiculopathy

Workup

Laboratory Studies

        Culture is the usual method for confirming bacterial infections. Although culturing B
         burgdorferi from skin biopsy specimens is possible, this is not practical in the usual clinical
         settings. While a recent article from an endemic area reported positive culture results in
         43.7% of patients with Lyme disease, this required culturing specifically for Lyme disease. In
         addition, all but 2 of the 213 patients met US Centers for Disease Control and Prevention
    (CDC) criteria for Lyme disease and warranted treatment, regardless of culture results.
    Culturing the organism from joint fluid is rarely effective. Polymerase chain reaction (PCR)
    testing of biologic specimens is not clinically useful because of the uncertainty about the
    relationship between a positive test result and live organisms in biologic fluids.
   The most widely used tests for Lyme disease are antibody detection tests. Unfortunately, no
    national standards have been set for the best antigen for the test, and the performance of
    clinical laboratories is difficult to determine given the absence of a criterion standard to
    evaluate for infection. In addition, given that many more tests (by at least a factor of 10) are
    ordered than the number of reported cases and the absence of antibody production in the
    earliest cases, there are many false-positive and false-negative test results due to
    inappropriate testing.
   The current recommendation from the CDC is for a 2-step testing process.
        o    The first step in patients with symptoms consistent with Lyme disease is to obtain an
             antibody titer. This can be either a total Lyme titer or separate immunoglobulin G
             (IgG) and immunoglobulin M (IgM) titers.
        o    The second step is to confirm positive titers with a Western blot. For IgM blots, if any
             2 of the following 3 bands are positive, the test is positive: 23 kd, 39 kd, and 41 kd.
             For IgG blots, any 5 of the following bands are considered a positive test result: 18,
             21, 28, 30, 39, 41, 45, 58, 66, and 93 kDa.
        o    In the absence of treatment, patients continue to produce IgM antibodies long after
             the initial infection. Thus, patients may have both IgM and IgG antibodies
             concurrently.
        o    While some authors recommend other bands and bypassing antibody titers, no other
             testing recommendations are available from other national organizations.
        o    In patients who have not been in endemic areas, the false-positive and false-negative
             rates of these tests reduce the likelihood that the predictive values of the results
             would be helpful.
   Antibody testing in patients with erythema migrans is not indicated because the rash may
    develop before the antibodies.
   In the United States, patients with extracutaneous involvement in the absence of treatment
    almost universally have positive titers. In Europe, negative serum titers have been reported in
    patients with neurologic Lyme disease that was confirmed by intrathecal antibody production.
   Synovial fluid usually is inflammatory, with cell counts ranging from 500-98,000/µL reported. In
    adult patients, the fluid should also be examined for crystals to rule out gout and pseudogout.
   Spinal fluid should be obtained in patients with neurologic symptoms whose diagnosis is not
    obvious (eg, patients without erythema migrans).
        o    Unlike most bacterial infections in the spinal fluid, Lyme disease produces a
             pleocytosis characterized by mononuclear cells.
        o    Spinal fluid levels of IgM and IgG antibodies to B burgdorferi should be measured,
             and an index of cerebrospinal fluid (CSF) to serum antibody (immunoglobulin-to-
             albumin ratio) should be calculated. This is particularly true in patients who have no
             other signs of Lyme disease.
        o    IgG and IgM antibodies may persist in CSF long after adequate treatment and in the
             absence of evidence of active neurologic disease.
       All of the currently available and recommended tests are antibody tests, which can only
        ascertain that a patient has been exposed to B burgdorferi but cannot be used to confirm
        infection. In the presence of typical clinical manifestations and laboratory results suggestive of
        current activity (elevated synovial and spinal fluid cell counts), they can be used to confirm the
        clinical diagnosis.

Other Tests

       ECGs show fluctuating levels of AV block in patients with syncopal or near-syncopal
        symptoms secondary to Lyme carditis. In patients with possible exposure but without
        symptoms of myocardial ischemia, such changes should prompt further investigation for Lyme
        disease.


Treatment

Medical Care
Lyme disease is treated primarily with outpatient antibiotics. Patients with carditis may need
hospitalization to prevent syncope during episodes of AV block. In these patients, prompt institution of
appropriate antibiotics is usually the only treatment needed.

The Infectious Diseases Society of America recently released clinical practice guidelines for the
assessment, treatment, and prevention of Lyme disease. The treatment guidelines are consistent with
the recommendations presented in this article.1

In 2003, Wormser et al suggested that patients with Lyme disease can be treated with only 10 days of
doxycycline. Patients with other manifestations who are treated with oral formulations should be
treated for 30 days because, with these manifestations, accurately pinpointing the date of infection is
not always possible. This regimen may also be effective for neurologic disease.

Treatment recommendations are as follows (see Medication for doses):


       Tick bite
             o      Until recently, no therapy was indicated for tick bites, even in endemic areas.
                    However, a 2001 article in the New England Journal of Medicine suggested that
                    treatment with a single dose of 200 mg of doxycycline within 72 hours of removing a
                    tick can prevent the development of Lyme disease.2
             o      This still should be limited to patients who have had possible tick exposure in
                    endemic areas.
       Skin manifestations: Institute an oral regimen for 30 days.
       Arthritis
             o      Institute an oral regimen for 30 days.
             o      Re-treat for 30 days with oral regimen or intravenous ceftriaxone for 14-30 days if the
                    first oral course is unsuccessful.
       Neuroborreliosis
              o    Facial palsies: Institute an oral regimen for 30 days. Although facial palsies may
                   resolve without treatment, antibiotic therapy may prevent further sequelae.
              o    Paresthesias/radiculopathy: Institute intravenous therapy for 14 days. Oral
                   doxycycline for 30 days may be as good as intravenous ceftriaxone for
                   neuroborreliosis.
              o    Encephalitis/encephalopathy: Institute intravenous therapy for 28 days.
        Fibromyalgia: The treatment of fibromyalgia and fibromyalgialike symptoms following Lyme
         disease has not been shown in any controlled trials to be responsive to antibiotic therapy. The
         latest trial, published in the New England Journal of Medicine, failed to show a benefit of
         treatment with 2 g of intravenous ceftriaxone daily for 30 days followed by oral doxycycline at
         200 mg/d for 60 days.3

Surgical Care

        Patients with chronic arthritis that does not respond to intravenous antibiotics may need a
         synovectomy to eradicate the inflammatory arthritis in the involved joint.
        Rarely, patients with carditis require a temporary pacemaker.

Consultations

        Consultation with a rheumatologist and neurologist may be indicated to ensure that other
         diseases are not the cause of unusual presenting symptoms in a patient with a positive Lyme
         titer.
        Consultation with a rheumatologist may be helpful in the evaluation and treatment of patients
         who present with fibromyalgia occurring after treated Lyme disease.

Activity

        Activity restrictions are not indicated in patients with Lyme disease who are feeling well.


Medication

The goals of pharmacotherapy with antibiotics are to reduce morbidity and to prevent complications.

Antibiotics
Antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of
the clinical setting.




Doxycycline (Bio-Tab, Doryx, Vibramycin)

Drug preferred for oral treatment in all patients except for pregnant and nursing women and children
<8 y. Inhibits protein synthesis and thus bacterial growth by binding to 30S and possibly 50S ribosomal
subunits of susceptible bacteria.
Dosing

Adult

100 mg PO bid

Pediatric

<8 years: Not recommended
>8 years: 100 mg PO bid

Interactions

Bioavailability decreases with antacids containing aluminum, calcium, magnesium, iron, or bismuth
subsalicylate

Contraindications

Documented hypersensitivity; pregnant or nursing women; young children

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Rarely, photosensitivity may occur with prolonged exposure to sunlight or tanning equipment;
tetracycline use during tooth development (last half of pregnancy up to 8 y) can cause permanent
discoloration of teeth; always take with food




Amoxicillin (Amoxil, Polymox, Trimox)

DOC for oral treatment for pregnant or nursing women and children <8 y. Interferes with synthesis of
cell wall mucopeptides during active multiplication, resulting in bactericidal activity against susceptible
bacteria.

Dosing

Adult

500-1000 mg PO q8h

Pediatric

250 mg or 20 mg/kg PO tid

Interactions

Reduces efficacy of oral contraceptives; simultaneous use with allopurinol may cause rashes
Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Adjust dose in severe renal impairment




Erythromycin (EES, E-Mycin, Ery-Tab)

Limit use to patients who cannot take drugs listed previously. Inhibits bacterial growth, possibly by
blocking dissociation of peptidyl t-RNA from ribosomes, causing RNA-dependent protein synthesis to
arrest.
In children, age, weight, and severity of infection determine proper dosage. When bid dosing is
desired, half the total daily dose may be taken q12h. For more severe infections, double dose.

Dosing

Adult

250-500 mg PO tid

Pediatric

30 mg/kg PO tid

Interactions

Coadministration may increase toxicity of theophylline, digoxin, carbamazepine, and cyclosporine; may
potentiate anticoagulant effects of warfarin; coadministration with lovastatin and simvastatin increases
risk of rhabdomyolysis

Contraindications

Documented hypersensitivity; hepatic impairment

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions
Caution in liver disease; estolate formulation may cause cholestatic jaundice in adults; adverse GI
effects are common (give doses pc); discontinue use if nausea, vomiting, malaise, abdominal colic, or
diarrhea occur




Ceftriaxone (Rocephin)

Third-generation cephalosporin. Arrests bacterial growth by binding to one or more penicillin-binding
proteins. Preferred for IV therapy.

Dosing

Adult

2 g IV qd

Pediatric

Administer as in adults

Interactions

Coadministration with ethacrynic acid, furosemide, and aminoglycosides may increase nephrotoxicity

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Adjust dose in renal impairment; caution in breastfeeding women and allergy to penicillin; diarrhea;
pseudobiliary lithiasis




Cefuroxime (Ceftin)

Second-generation cephalosporin. Only drug approved by FDA for use in Lyme disease. Approved for
adults.

Dosing

Adult
500 mg PO bid
Pediatric

Administer as in adults

Interactions

May increase hypoprothrombinemic effects of anticoagulants

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Administer half dose if creatinine clearance is 10-30 mL/min and quarter dose if <10 mL/min




Chloramphenicol (Chloromycetin)

May be effective for IV therapy in patients who are allergic to ceftriaxone; has not been tested in trials;
has serious adverse effects. Binds to 50 S bacterial-ribosomal subunits and inhibits bacterial growth by
inhibiting protein synthesis. Rarely used in the United States.

Dosing

Adult

500 mg IV qid

Pediatric

Not established

Interactions

Concurrently with barbiturates, serum levels may decrease while barbiturate levels may increase,
causing toxicity; manifestations of hypoglycemia may occur with sulfonylureas; rifampin may reduce
serum chloramphenicol levels, presumably through hepatic enzyme induction; may increase effects of
anticoagulants; may increase serum hydantoin levels, possibly resulting in toxicity (chloramphenicol
levels may be increased or decreased)

Contraindications

Documented hypersensitivity

Precautions
Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if
benefits outweigh risk to fetus

Precautions

Serious and fatal blood dyscrasias (aplastic anemia, hypoplastic anemia, thrombocytopenia,
granulocytopenia) can occur rarely (idiosyncratic effects); cytopenia, anemia, or findings attributable
(dose-related effects) to chloramphenicol; adjust dose in severe liver or kidney dysfunction; caution in
pregnancy at term or during labor because of potential toxic effects on fetus (gray syndrome)

Follow-up

Further Outpatient Care

       Patients with Lyme disease whose specific symptoms of Lyme disease (not symptoms of
        fibromyalgia or chronic fatigue) do not improve may need retreatment. Patients who continue
        to improve but plateau in their improvement may also need retreatment.
       Given the cost and convenience, a 30-day course of oral therapy may be indicated before
        repeating intravenous therapy.
       Repeat serologic testing is not indicated because IgM titers may persist with treatment, and
        changes in IgG titers do not reflect the efficacy of treatment.

Deterrence/Prevention

       Avoidance of ticks and areas associated with ticks
             o   Backyard patios, decks, and grassy areas that are mowed regularly are unlikely to
                 have ticks present. This may be because of the lack of cover for mice from owls and
                 other raptors that prey on mice. The ticks also need moisture, which these areas do
                 not provide.
             o   The areas around ornamental plantings and gardens are more hospitable for mice
                 and ticks. The highest concentration of ticks is found in wooded areas.
             o   Individuals should try to prevent ticks from getting onto skin and crawling to preferred
                 areas.
            o Long hair should be worn under a hat.
            o Wearing long-sleeved shirts and tucking long pants into socks is recommended.
       Inspection
            o Because the above recommendations are not always practical, particularly for
                 children and during the summer, and because ticks do not appear to transmit Lyme
                 disease until they have been attached for several days, close inspection for ticks
                 should be performed each time one has been outdoors.
            o The groin, axilla, and hairline should be inspected particularly well.
       Animals
          o    Because pets can develop Lyme disease and can carry ticks, making sure they are
               wearing tick collars seems prudent. Applying the suggestions concerning skin
               inspection may also be prudent after playing with outdoor pets.
          o    If ticks are found, they should be removed promptly. In animal studies, a preferred
               method of removing ticks is not clearly evident. Removal by holding on to the body of
               the tick does not increase the transmission rate.
     Repellants
          o The use of tick repellants may be appropriate for adults.
          o In children, increased absorption and resultant toxicity is a concern.
     Vaccination: The Lyme disease vaccine is no longer available because not enough patients
      were being vaccinated to justify keeping it on the market. As a result, the prevention methods
      mentioned above are even more important.

Prognosis

     Making definitive statements regarding the outcome of Lyme disease is difficult because of (1)
      the inability to separate false-positive titers from asymptomatic infection, (2) the necessity of
      depending on clinical acumen in diagnosing erythema migrans (because titers are often
      negative at that stage), (3) the lack of uniform treatment regimens, and (4) the absence of
      long-term follow-up in most patients.
          o    Lyme disease appears to rarely be a fatal disease, with only several fatal cases
               reported.
          o    Cranial nerve palsies usually resolve without treatment.
          o    Carditis does not seem to be associated with long-term cardiac sequelae.
          o    Even without treatment, the recurrent episodes of Lyme arthritis resolve over a 10-
               year period.
     Children who are appropriately treated seem to have a good prognosis for complete recovery.
     In adults, the long-term outcome is usually good. While several studies have suggested that
      subjective chronic musculoskeletal symptoms and difficulties with memory, concentration, and
      fatigue may be more common in adults and may be associated with an extended time to
      treatment (years vs months) and initial treatment with antibiotics other than doxycycline or
      amoxicillin, several studies suggest that these patients did not, in fact, have symptoms at a
      greater rate than age-matched controls.4, 5 Reports of chronic symptoms in patients with a
      reported diagnosis of Lyme disease may include patients who did not meet the case definition
      for Lyme disease, thus raising the question of whether these patients actually had Lyme
      disease.4

Patient Education

     For excellent patient education resources, visit eMedicine's Bites and Stings Center, Arthritis
      Center, and Muscle Disorders Center. Also, see eMedicine's patient education articles Lyme
      Disease, Ticks, Chronic Fatigue Syndrome, and Chronic Pain.


Miscellaneous
Special Concerns

      Pregnancy
          o   Pregnant women who develop Lyme disease should be treated, but not with
              doxycycline or another tetracycline.
          o   No evidence indicates an increase in congenital heart or neurologic disease in
              endemic areas. This suggests that if a pregnant woman is bitten by a tick, antibiotic
              treatment is not indicated.


Multimedia




Media file 1: Normal and engorged Ixodes ticks.
Media file 2: Erythema migrans, the characteristic rash of early Lyme disease.

References

   1.   Wormser GP, Dattwyler RJ, Shapiro ED, Halperin JJ, Steere AC, Klempner MS, et al. The
        clinical assessment, treatment, and prevention of lyme disease, human granulocytic
        anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society
        of America. Clin Infect Dis. Nov 1 2006;43(9):1089-134. [Medline]. [Full Text].

   2.   Nadelman RB, Nowakowski J, Fish D, et al. Prophylaxis with single-dose doxycycline for the
        prevention of Lyme disease after an Ixodes scapularis tick bite. N Engl J Med. Jul
        12 2001;345(2):79-84. [Medline].

   3.   Klempner MS, Hu LT, Evans J, et al. Two controlled trials of antibiotic treatment in patients
        with persistent symptoms and a history of Lyme disease. N Engl J Med. Jul
        12 2001;345(2):85-92. [Medline].

   4.   Seltzer EG, Gerber MA, Cartter ML, et al. Long-term outcomes of persons with Lyme
        disease. JAMA. Feb 2 2000;283(5):609-16. [Medline].

   5.   Shadick NA, Phillips CB, Sangha O, Logigian EL, Kaplan RF, Wright EA, et
        al. Musculoskeletal and neurologic outcomes in patients with previously treated Lyme
        disease. Ann Intern Med. Dec 21 1999;131(12):919-26. [Medline].

   6.   Adams WV, Rose CD, Eppes SC, Klein JD. Cognitive effects of Lyme disease in children: a 4
        year followup study. J Rheumatol. May 1999;26(5):1190-4. [Medline].
    7.   Kaplan RF, Trevino RP, Johnson GM, Levy L, Dornbush R, Hu LT, et al. Cognitive function in
         post-treatment Lyme disease: do additional antibiotics help?. Neurology. Jun
         24 2003;60(12):1916-22. [Medline].

    8.   Karlsson M, Hammers-Berggren S, Lindquist L, et al. Comparison of intravenous penicillin G
         and oral doxycycline for treatment of Lyme neuroborreliosis. Neurology. Jul 1994;44(7):1203-
         7. [Medline].

    9.   Krupp LB, Hyman LG, Grimson R, Coyle PK, Melville P, Ahnn S, et al. Study and treatment of
         post Lyme disease (STOP-LD): a randomized double masked clinical trial. Neurology. Jun
         24 2003;60(12):1923-30. [Medline].

    10. Ljøstad U, Skogvoll E, Eikeland R, Midgard R, Skarpaas T, Berg A, et al. Oral doxycycline
         versus intravenous ceftriaxone for European Lyme neuroborreliosis: a multicentre, non-
         inferiority, double-blind, randomised trial. Lancet Neurol. Aug 2008;7(8):690-5. [Medline].

    11. Logigian EL, Kaplan RF, Steere AC. Successful treatment of Lyme encephalopathy with
         intravenous ceftriaxone. J Infect Dis. Aug 1999;180(2):377-83. [Medline].

    12. Meyerhoff J. Lyme disease. Am J Med. Oct 1983;75:663-70. [Medline].

    13. Nadelman RB, Wormser GP. Lyme borreliosis. Lancet. Aug 15 1998;352:557-65. [Medline].

    14. Steere AC. Lyme disease. N Engl J Med. Aug 31 1989;321:586-96. [Medline].

    15. Wormser GP, McKenna D, Carlin J, et al. Brief communication: hematogenous dissemination
         in early Lyme disease. Ann Intern Med. May 3 2005;142(9):751-5. [Medline]. [Full Text].

    16. Wormser GP, Ramanathan R, Nowakowski J, et al. Duration of antibiotic therapy for early
         Lyme disease. A randomized, double-blind, placebo-controlled trial. Ann Intern Med. May
         6 2003;138(9):697-704. [Medline].




Contributor Information and Disclosures

Author

John O Meyerhoff, MD, Assistant Professor, Department of Internal Medicine, Johns Hopkins
University School of Medicine; Clinical Scholar in Rheumatology, Department of Medicine, Sinai
Hospital of Baltimore
John O Meyerhoff, MD is a member of the following medical societies: American College of Physicians
and American College of Rheumatology
Disclosure: Nothing to disclose

Medical Editor
Kristine M Lohr, MD, MS, Program Director, Professor, Department of Internal Medicine, Division of
Rheumatology and Women's Health, University of Kentucky School of Medicine
Kristine M Lohr, MD, MS is a member of the following medical societies: American College of
Physicians, American College of Rheumatology, and American Medical Women's Association
Disclosure: Nothing to disclose

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose

				
DOCUMENT INFO