Learning objectives
• Definition
• Causes and risk factors
• Sighs and symptoms
• Pathophysiology
• Diagnosis
• Treatment
• Complication
• prevention
Case summary
For several weeks a 41 year old male has felt as if he is slightly drunk all the time. He
can’t walk properly anymore and feels as if he is in daze. At first he thought it might be
exhaustion but as it is not improving he wants to know what is wrong and what the
prognosis is .
Lyme disease
• Is an infectious disease
• Caused by spiral- shaped bacteria called Borrelia burgdorferi that carried by
infected Ixodes tick.
• A tick become infected by feeding on animals that carries the borrelia.
( white footed mouse, white tailed deer or black birds)
Epidemiology
Europe (In central Europe, particularly in Slovenia and Austria. Incidence in southern Europe, such as Italy and
Portugal, is much lower.)
• North America
• Canada
• Mexico ( A 2007 study suggests Borrelia infections are endemic to Mexico)
• United States (Lyme disease has been reported in all states except Montana)
• South America (Reported widely in Brazil, Colombia and Bolivia)
Risk factors
• Travelling to a city where the Lyme disease is common
• Having exposed skin.
• Spending time in wooded or grassy areas.
• Not removing ticks promptly or properly.
Signs And Symptoms
The clinical manifestation depends on the stage of disease:
1- Early Localized :
• Onset: within one month after bite
• Presentation:
Erythema Migraines:
• The redness of the rash expand forming a rash in a bull’s
eye pattern.
• Rash usually feels warm to the touch but is not itchy or
painful.
• The size of the rash can range from between 2cm-30cm.
Flu-like symptoms : Fever, chills, fatigue, body aches and a
headache .
Signs And Symptoms
2- Early disseminated stage :
• Onset : Within one to 4 months after the onset of local infection.
• Presentation:
1- Neurological symptoms:• Meningitis: ( severe headeches and neck stiffness)
• Radiculoneuritis: Infection of the nerve roots (shooting pains ,
numbness or tingling).
• Bell’s palsy.
2- Joint Problems:• Arthritis.
Signs And Symptoms
2- Early disseminated stage :
Heart problems:• In rare cases, untreated Lyme disease may lead to
inflammation of the heart (myocarditis).
• That causes :
• Light-headedness.
• fainting.
• shortness of breath.
• palpitations.
• chest pain.
Signs And Symptoms
3- late persistent stage:
• Onset: More Than 4 Months.
• Presentation:
Chronic neurologic symptoms occur in up to 5% of untreated
patients.
cognitive problems, such as difficulties with concentration and
short-term memory.
chronic arthritis
Stages of Lyme
disease
1- Early Localized
Within One Month
2- Early Disseminated
From One To 4 Months
3- Late Chronic
More Than 4 Months
Quiz
• 47 years old woman presented to hospital with rash that has
bull’s eye pattern, headache, fatigue and fever.
• Doctors diagnosed her with Lyme Disease.
• Q: in which stage of disease her symptoms is in ?
First stage ( early localized stage)
A tick becomes infected by
feeding on an animal that
carries the bacteria
Infected ticks then inject B. burgdorferi into the
human’s skin by attached to the skin for
approximately 24-48 hours
Tick saliva, which accompanies the spirochete into
the skin during the feeding process, contains
substances that disrupt the immune response at the
site of the bite
The spirochetes multiply and migrate outward within the
dermisDays to weeks following the tick bite, the spirochetes
spread via the bloodstream to different organs
Erythema Migraines in different
part of the body
Borrelia burgdorferi may
induce astrocytes to
undergo astrogliosis
(proliferation followed by
apoptosis), which may
contribute to
neurodysfunction.
Lyme cordites: cause
impairment of the
conduction
( atrioventricular block )
Lyme arthritis:
inflammation of the tissue
that lines the joints.
The spirochetes may also
induce host cells to
secrete products toxic to
nerve cells, including
quinolinic acid and the
cytokines IL-6 and TNF-
alpha, which can produce
fatigue and malaise.
Diagnosis History taking :
History of tick bite.
Epidemiologic context is extremely important. The clinician
should determine where the patient lives, works, and
vacations, and should ask about specific activities in which the
patient participates.
The season is important, especially with early disease. Most
cases of erythema migrans occur from late spring through
early fall.
Previous manifestations of Lyme disease from many years in
Physical Examination
Erythema migrans (EM) is thecharacteristic rash of Lyme disease.
Classic EM is a flat to slightly raisederythematous lesion that appears at thesite of the tick bite after 1-33 days bite(average, 7-10 days).
Without therapy, erythema migranstypically fades within 3-4 weeks.
1- Dermatological Finding
Less than 1% of patients with stage 2 Lyme
disease, develop Borrelia lymphocytoma
Described as a small, bluish-red nodule or
plaque.
The earlobe and scrotum are the typical
location in children,
whereas the nipple is the more common
location in adults.
2-Borrelial lymphocytoma
Muscle tenderness can result from myositis.
Tenderness of tendons and periarticular
structures may be present.
Frank arthritis can occur after weeks,
months, or years and may lead to erythema,
edema and tenderness of the affected joints.
Usually, this is a monoarthritis or
oligoarthritis involving large joints, especially
the knee.
3- Musculoskeletal findings
5-10% of untreated patients with Lyme
disease have signs of cranial
neuropathies.
Up to 60% of patients with early
neuroborreliosis develop cranial neuritis.
7th nerve palsy is by far the most
common.
4- Neurologic
involvement
Stretch reflex is a muscle contraction in
response to stretching within the muscle.
Absent ( lower motor neuron lesion)
Muscle stretch reflexes
Elicited when the sole of the foot is
stimulated with a blunt instrument.
Positive babinski sign (upper motor
neuron lesion)
Plantar reflex
Gait test ( unsteady )
Speech changes
Finger to nose test (intention tremor and
hypermetria)
Cerebellum dysfunction tests:
Sign of a disturbance of proprioception,
either from neuropathy or posterior
column disease.
In the dark or with eyes closed they have
problems. (positive)
Romberg’s test
Ophthalmic manifestations vary by disease
stage.
In stage 1 Lyme disease, the ocular
manifestations are conjunctivitis and
photophobia.
In stage 2 Lyme disease,
Fundoscopy : papilledema, optic atrophy
might occur.
Eye movement: Cranial nerve palsies
might occur.
6- Ophthalmic involvement
Laboratory Tests
To identify antibodies to help confirm the diagnosis.
These tests are most reliable a few weeks after an infection, after your body has time to develop
antibodies.
Investigation
Serological Laboratory tests
Has been demonstrated to be useful in detecting the antibody response to B. burgdorferi.
A Western blot (WB) assay is detects antibodies to several proteins
of B. burgdorferi and used to confirm positive Lyme ELISA results
due to the presence of IgG- or IgM-class antibodies.
ELISA
(enzyme-
linked
immunosorbe
nt assay )
Western
immunoblot
(WB)
Cont.
Positive results Negative results
Should be supplemented by re-
testing the corresponding serum
samples on a standardized
Western Blot test to confirm
the result .
No antibody to B.
burgdorferi detected.
This result does not
exclude the possibility of B.
burgdorferi infection
A second sample should
be drawn 2 – 4 weeks later
and re-tested.
If the sensitive screening test results
were :
PCR test PCR (Polymerase Chain Reaction) test amplifies
the DNA of the spirochete and will usually
indicate its presence.
It is used for people who may have chronic Lyme
arthritis or used to detect persistent infection in
CSF of people with nervous system symptoms.
This test does produce many false negatives
This is because Lyme bacteria are sparse and
may not be in the sample tested.
Blood test Blood tests measure antibodies made in response to the infection.
These tests may be falsely negative in patients with early disease,
but they are quite reliable for diagnosing later stages of disease.
Culture
Culture of the organism is the gold standard for the evaluation of all infections.
Borrelia burgdorferi is a slow growing organism, so culture may take weeks.
More problematic is that culture is rarely positive once the infection has disseminated beyond the stage of erythema migrans.
Because of the low yield of this test in cases of late stage or disseminated Lyme disease, culture is rarely used
Spinal Fluid analysis
Patients with neurologic symptoms suggestive of central nervous system involvement should have a lumbar puncture.
When the CSF is examined, the fluid is sent for routine studies such as cell count, and proteinand glucose levels.
In addition, the CSF should be sent for Borreliaburgdorferi (Bb) PCR assay and intrathecalindex (The index refers to the ratio of Bb antibodies in the CSF )
When the index is positive, that indicates that there is a production of antibodies against Bb in the CSF – a finding strongly suggestive of central nervous system invasion by the agent of Lyme disease.
MRI.
Imaging test that uses powerful
magnets and radio waves to create
pictures of the brain and
surrounding nerve tissues.
Unlike SPECT and PET images
which assess brain function, MRI
captures the physical structure
of the brain.
Inflammatory abnormalities in the
brain are also assessed with MRI
scans.
Complications
Stage 3 or late disseminated Lyme disease can cause:
long-term joint inflammation (Lyme arthritis) and heart rhythm
problems.
Brain and nervous system problems might include:
Decreased
concentration
Memory
disorders
Numbness
Sleep
disorders
Vision
problems
Treatment :
Antibiotics are the primary treatment for Lyme disease, and
almost all patients recover after antibiotic treatment.
The recommended treatment for Lyme disease varies
depending upon the stage of disease and the types of
symptoms.
The rate of recovery may also vary depending upon the
specific symptoms and recovery may take weeks to months
after finishing antibiotic treatment.
Prophylactic after Tick bite
Routine use of antimicrobial prophylaxis or serologic testing is not
recommended.
A single dose of doxycycline may be offered to adult patients
(200 mg dose) and to children ⩾8 years of age (4 mg/kg up to a
maximum dose of 200 mg) only considered if:
Identifiable tick
Treatment can be started 72 hours after tick removal
Doxycycline is not contraindicated
Early treatment is a 14 to 21 day
course of oral antibiotics.
Medications:
doxycycline.
cefuroxime
amoxicillin.
Early Stage:
+ Side Effects Pediatric dose Adult dose MedicationStage
nausea,
vomiting,
diarrhoea and
rashes
50 mg/kg per day
in three divided
doses
500 mg three
times daily
amoxicillinEarly Stage
anorexia, dry
mouth, flushing,
anxiety and
tinnitus.
2 mg/kg twice
daily for children
≥8 years of age.
100 mg twice
daily
doxycycline
Diarrhoea,
nausea,
vomiting,
abdominal
discomfort,
headache, fever,
rashes
30 mg/kg per day. 500 mg twice
daily
Cefuroxime
Intravenous antibiotics for a period
of 10 to 28 days.
Late Stage:
Side EffectsPediatric dose Adult dose MedicationStage
Same as
Cefuroxime
50 to
75 mg/kg intraven
ously once daily
2 g intravenously
once daily
Ceftriaxonelate
stage
Same as
Cefuroxime
150 to
200 mg/kg intrave
nously per day
divided in three
doses,
2 g intravenously
every eight hours
Cefotaxime
fever, chills,
malaise,
headache,
tachycardia, hy
perventilation
200,000 to
400,000 units/kg p
er day divided into
6 daily doses.
18 to 24 million
units per day
intravenously
divided into 6
daily doses
Penicillin G
Prognosis
If diagnosed in the early stages
Lyme disease usually recover rapidly and completely with antibiotics.
If diagnosed in the late stages
Approximately 10-20% of who were diagnosed later, may have
persistent or recurrent symptoms and are considered to have Post-
treatment Lyme disease syndrome (PTLDS). The cause of this
syndrome is unknown.
Prevention
Avoid areas where deer
ticks live, especially
wooded, bushy areas with
long grass
Use insect
repellents
Wear long pants
,long sleeves and
enclosed shoes
Prevention
Bathe as soon as possible after
going indoors to wash off and
more easily find ticks that may be
on you.
Do a final, full-body tick
check at the end of the
day
Summary
Definition
Causes and risk factors
Signs and symptoms
Pathophysiology
Diagnosis
Treatment
Complication
prevention
Referencehttp://www.nlm.nih.gov/medlineplus/ency/article/001319.htmhttp://www.mayoclinic.org/diseases-conditions/lyme-disease/basics/definition/con-20019701http://www.lymedisease.org/lyme101/lyme_disease/lyme_disease.htmlhttp://www.medicinenet.com/lyme_disease/article.htm
http://www.mayoclinic.org/diseases-conditions/lyme-disease/basics/risk-factors/con-20019701http://ldnr.us/lyme_disease_pathophysiology.htmlhttp://www.merckmanuals.com/professional/infectious_diseases/spirochetes/lyme_disease.html
http://emedicine.medscape.com/article/330178-clinicalhttp://www.uptodate.com/contents/treatment-of-lyme-diseasehttp://www.uptodate.com/contents/evaluation-of-a-tick-bite-for-possible-lyme-disease?source=see_link&anchor=H7#H7http://www.uptodate.com/contents/lyme-disease-treatment-beyond-the-basicshttp://www.lymedisease.org/lyme101/lyme_disease/lyme_treatment.htmlhttp://cid.oxfordjournals.org/content/43/9/1089.fullhttp://ldnr.us/lyme_disease_pathophysiology.html
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