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.
Skeletal Syphilis
Caused by syphilis and yaws (Treponema pertenue)
Bone involvement is infrequent because treatment is carried out earlier
Congenital syphilis: bone lesions are well developed at birth.
Has characteristic saber shin (reactive periosteal bone deposition)
Sporotrichosis
Caused by Sporothrix schenckii, a dimorphic fungus that is ubiquitous in soil
Infection characterized by nodular and ulcerative lesions that develop along lymphatics that drain site of inoculation
oval conidia that look like a “daisy petal”
yeast form is cigar shaped (rare in tissue)
Associated with gardening, warmer climates
Culture to diagnose, treat with potassium iodide
Chromoblastomycosis
Characterized by development of slow-growing verrucous nodules or plaques.
Most common in the tropics, caused by Fonsecaea, Cladosporium, Exophiala (annelids), Cladophialophora, Rhinocladiella, and Phialophora
Dematiaceous molds that form muriform cellls (sclerotic bodies, Medlar bodies) in tissue (look like chestnuts)
Indolent and resistant to treatment. Grow like cauliflower
Treat with itraconazole and terbinafine, but refractory to treatment. May be shrunk with heat or cryotherapy
Mycetoma
Caused by true fungi (not actinomycetes)
Seen in tropics.
Defines as a localized, chronic, granulomatous infections process involving cutaneous and subcutaneous tissues and abscesses of fungal hyphae called granules or grains.
Grains extrude through skin, can be pigmented or not
Exposure is through traumatic implantation
Amputation is only definite treatment
Subcutaneous Zygomycosis
AKA entomopthoromycosis, cuases by Conidiobolus coronatus and Basidiobolus ranarum.
- C. coronatus:* nose of adults, firm painless swelling of lips
- B. ranarum*: Body of children, thick rubbery movable masses
Hyphae often fragmented and surrounded by eosinophilic “Splendore-Hoeppli material.”
Seen in Africa and India, both present in leaf and plant debris, hit more males than females
Can be treated with potassium iodide or itraconazole
Subcutaneous Hyphomycosis
Phaeohyphomycosis is a term used to descripe an array of fungal infections caused by pigmented fungi which are present in irregular hyphae form.
All grow as black molds. Fontana-Masson melanin stain confirms dematiaceous nature
Found in decaying vegetation
Forms a cyst that is removable by surgery
Lobomycosis
Chronic fungal infection of the skin caused by Lacazia loboi.
It’s an ascomycete found in the tropics, infecting humans and dolphins (but can be experimentally used to infect armadillos and hamsters)
Never been cultured in vitro.
Thick, double refractile cell wall, grows in budding chains
Forms nodular keloid-like lesion
Surgical excision is optimal therapy
Trichinella spiralis
Causes trichinosis. Adult form lives in intestines, releases eggs that hatch into larvae, larval form invades muscle
Catch from PORK.
Preferential to extraocular muscles, tongue, deltoid, pectoral, and intercostals. Form calcified cysts
One of the few parastic diseases still in the US
Symptoms based on larval load. (more than 100 per gram of tissue is symptomatic)
No good antiparasitic agents for tissue larvae
Zoonitc disease, humans dead end hosts
Wuchereria bancrofti and Brugia malayi
Humans infected by mosquito bite lead to Bancroft and Malayan filariasis.
The presence of microfilariae in blood is diagnostic for human disease and can infect feeding mosquitoes
- W. bancrofti* infections occur in tropical areas
- B. malayi* is found primarily in eastern Asian countries
Lymph nodes enlarge and can cause elephantiasis, chronic disfigurement, et c.
Can have nocturnal or subperiodic periodicity in production of microfilariae.
Treat with diethylcarbamazine or ivermectin/albendazole
Onchocerca Volvulis
African river blindess, vectored by blackfly. Causes blindness in 5% of infected people
Causes “hanging groin” a form of elephantiasis
Diagnosis is made from microscopically observing a “skin snip” off the infrascapular or gluteal region
Treat with surgical removal of nodules and ivermectin
Not found in bloodstream
