Musculoskeletal Flashcards
Borrelia sp.
Responsible for both Lyme disease and relapsing fever
Two types of relapsing fever
1) louse-born
2) Endemic (spread by soft ticks)
Borrelia Physiology and Structure
weakly staining gram-negative spirochetes (better seen with aniline dyes)
Easily seen in blood smears of relapsing fever, not Lyme disease
Microscopy is used to diagnose relapsing fever, not useful in Lyme disease due to low numbers of organisms
Serology is used to diagnose Lyme disease (IFA and EIA), not useful in relapsing fever due to antigenic variation.
Culture is not practical
Epidemic relapsing fever
Caused by Borrelia recurrentis
transmitted person-to-person (humans are only reservoirs) by human body louse
Often in unsanitary conditions
Occurs in Ethiopia, Rwanda, and the Andean foothills
A single relapse is most common/characterisitic
Clinical prognosis is normally worse than the Endemic version
Endemic Relapsing Fever
Many Borrelia species responsible
Transmitted from rodents to humans (rodents are reservoirs) by soft ticks
Worldwide distribution and Western US
A zoonotic disease (as opposed to epidemic relapsing fever)
Transovarian spread (vertical transmission)
Up to 10 relapses occur
Lyme Disease
Caused by Borrelia burgdorferi in US and Europe, Borrelia garinii and afzelii in Europe and Asia
Transmitted by hard ticks from mice to humans with white-footed mice and white-tailed deer as a reservoir.
Worldwide distribution
Most common in late spring and early summer
Leading vector-borne disease in the US
Treatment for Borrelia infections
For relapsing fever, treatment is with tetracycline or erythromycin
For Lyme disease, treatment is with amoxicilllin, doxycycline, cefuroxime; late manifestations with penicillin or ceftriaxone
Minimizing exposure is best option
A Jarisch-Herxheimer reaction is a shocklike profile with rigors, leukopenia, and an increase in temperature with a decrease in blood pressure that can occur due to rapid killing of borrelia and release of toxic products
No vaccines are currently in use
Borrelia Pathogenesis
Begins with expression of outer surface protein A (OspA) that binds to vector’s gut
Down-regulates OspA to migrate to infect, then upregulates OspC to get into mammal
Might cause Lyme disease through immunologic cross-reactivity
Relapsing fever is brought about by antigenic variation
Lyme Disease Clinical Presentation
Often begins with a rash at bite site 3 to 30 days following the bite
Lesion is normally flat, red, with central clearing, but central necrosis is also observed
Hematogenous dissemination leads to severe fatigue, headache, fever, malaise, arthritis and arthralgia, myalgia, erythematous skin leasions, cardiac dysfunction, and neurologic signs (facial nerve palsy)
Late manifestations include arthritis, chronic skin involvement called acrodermatitis chronica atrophicans.
Relapsing Fever Clinical Presentation
After a 1-week incubation period, shanking chills, fever, muscle aches, and headache, along with potential hepatomegaly and splenomegaly.
Fever regresses for a week, then resumes
Serology of Borrelia burgdorferi
Difficult due to delay in IgM response of 2-4 weeks following rash.
Cross reactions can occur with syphilis.
Confirmed with Western blots
Should only be used in absence of extreme suspicion of Lyme disease (absence b/c you don’t want to wait this long before treating Lyme disease)
Clostridium sp.
Defines by four properties: presence of endospores, strict anaerobic metabolism, inability to reduce sulfate to sulfite, and gram-positive cell wall structure
Not all requirements are met in all species
ubiquitous in soil, water, and sewage
Produces numerous histolytic toxins, enterotoxins, and neurotoxins
Clostridium tetani
Large, motile, spore-forming, gram positive rod
Produces round, terminal spores making it look like a drumstick.
Diagnosis based on clinical presentation, not lab tests
(microscopy, culture insensitive, negative serology)
Culture difficult due to oxygen sensitivity
Not invasive. Stays at site of infection but releases toxins that travel to CNS (spinal cord)
Death ensures from respiratory failure
C. tetani virulence
Primary virulence factor is plasmid encoded tetanospasmin, a heat-labile neurotoxin that blocks release of neurotransmitters (GABA, glycine) from inhibitory synapses leading to spastic paralysis
Consists of a light and heavy chain (A-B toxin). The heavy chain allows access to cell, and the light chain is a zinc endopeptidase
Disease does not induce immunity
Risk is greatest for people with inadequate vaccine-induced immunity
Also produces an oxygen-labile hemolysin called tetanolysin.
DEGRADES SYNAPTOBREVIN
Generalized Tetanus Clinical Presentation
Incubation ranges from a few days to weeks
Generalized tetanus is most common form, involving masseter muscles leading to “risus sardonicus” facial expression
Also leads to sweating, drooling, irritability, and persistent back spasms (opisthotonos)
ANS can be involved in more severe disease
Tetanus Variants Clinical Presentation
Localized tetanus stays in the musculature at initial site of infection
Cephalic tetanus is limited to the head, with a very poor prognosis
Neonatal tetanus is associated with initial infection of umbilical stump. This is a disease of developing countries
Highest mortality is in newborns and patients with a rapid onset following infection.
Tetanus Treatment
Cleaning/debridement of wound,
Use of metronidazole
Passive immunization with tetanus immunoglobin
Vaccination with tetanus toxoid
Penicillin inhibits GABA, should not be used
Clostridum botulinum
Large, fastidious, spore-forming, anaerobic rods.
Characterized in four groups that are probably separate species
A, B, E, and F toxin are associated with human disease
Presence of toxin in feces is diagnostic, can also heat samples to kill all non-sporeformers then allow botulinum to germinate
Found in feces, not in serum
Patients need ventilatory support, elimination of organism from GI tract, and trivalent botulinum antitoxin.
C. botulinum Virulence
Has A-B toxin consisting of a small A-subunit that is a zinc-endopeptidase and a large, nontoxic B-subunit.
Targets and cleaves SNAREs (synaptobrevin, syntazin, and SNAP 25.)
Complexed with non-toxic proteins to protect from digestive tract.
Botulinum neurotoxin is taken up by neurons and remains at neuromuscular junction.
Causes flaccid paralysis
Foodborne Botulism
Fewer than 30 cases seen annually (most with home-canned foods)
Typically become weak and dizzy 1-3 days after eating the food.
Effects are anticholinergic, including dry mouth and dilated pupils.
Descending weakness of peripheral muscles develops, death is due to respiratory paralysis.
Mortality has decreased due to better management of respiratory paralysis
Infant Botulism
Fewer than 100 cases annually (still most common form in US)
Associated with consumption of honey, milk poder contaminated with botulinum spores
Organism can thrive due to lack of competitive flora in infant bowels
Mortality is low
Associated with strains that produce E and F toxins
May be a cause of Sudden Infant Death Syndrome
Wound Botulism
Disease is very rare
Identical to foodborne, but with a longer (4 days or more) incubation period
GI tract symptoms are less prominent
Inhalation Botulism
A potential weapen of bioterrorism.
The toxin can be aerosolized as a biologic weapon.
This would lead to a rapid onset and high mortality
Pyogenic Osteomyelitis
Almost always caused by bacteria
Organisms reach bone through hematogenous spread, extension from a contiguous site, or direct implantation.
S. aureus is responsible for 80-90% of cases
E. coli, Pseudomonas, and Klebsiella are isolated from patients with genitourinary infections or are IV drug users
H. influenzae is common in neonates
Salmonella is common with sickle cell
A “Brodie abscess” is a sequestered focus of staph osteomyelitis that arises in the metaphyseal area of a long bone and occurs in adults.
Staph can also cause “septic arthritis” in young children and adults
Tuberculous Osteomyelitis
Caused by tuberculosis, found in immigrants and immunocompromised
Around 1 to 3% of patients with tuberculosis have osseous infection
Can spread via direct extension to rib.
Spine followed by knees and hips are most common sites of skeletal involvement. More destructive and difficult to control than pyogenic osteomyelitis
Patients present with pain on motion, localized tenderness, chills, weight loss.
