Musculoskeletal

Question 1

Borrelia sp.

Answer 1

Responsible for both Lyme disease and relapsing fever

Two types of relapsing fever

1) louse-born
2) Endemic (spread by soft ticks)

Question 2

Borrelia Physiology and Structure

Answer 2

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

Question 3

Epidemic relapsing fever

Answer 3

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

Question 4

Endemic Relapsing Fever

Answer 4

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

Question 5

Lyme Disease

Answer 5

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

Question 6

Treatment for Borrelia infections

Answer 6

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

Question 7

Borrelia Pathogenesis

Answer 7

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

Question 8

Lyme Disease Clinical Presentation

Answer 8

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.

Question 9

Relapsing Fever Clinical Presentation

Answer 9

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

Question 10

Serology of Borrelia burgdorferi

Answer 10

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)

Question 11

Clostridium sp.

Answer 11

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

Question 12

Clostridium tetani

Answer 12

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

Question 13

C. tetani virulence

Answer 13

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

Question 14

Generalized Tetanus Clinical Presentation

Answer 14

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

Question 15

Tetanus Variants Clinical Presentation

Answer 15

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.

Question 16

Tetanus Treatment

Answer 16

Cleaning/debridement of wound,

Use of metronidazole

Passive immunization with tetanus immunoglobin

Vaccination with tetanus toxoid

Penicillin inhibits GABA, should not be used

Question 17

Clostridum botulinum

Answer 17

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.

Question 18

C. botulinum Virulence

Answer 18

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

Question 19

Foodborne Botulism

Answer 19

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

Question 20

Infant Botulism

Answer 20

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

Question 21

Wound Botulism

Answer 21

Disease is very rare

Identical to foodborne, but with a longer (4 days or more) incubation period

GI tract symptoms are less prominent

Question 22

Inhalation Botulism

Answer 22

A potential weapen of bioterrorism.

The toxin can be aerosolized as a biologic weapon.

This would lead to a rapid onset and high mortality

Question 23

Pyogenic Osteomyelitis

Answer 23

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

Question 24

Tuberculous Osteomyelitis

Answer 24

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.

Question 25

Skeletal Syphilis

Answer 25

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)

Question 26

Sporotrichosis

Answer 26

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

Question 27

Chromoblastomycosis

Answer 27

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

Question 28

Mycetoma

Answer 28

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

Question 29

Subcutaneous Zygomycosis

Answer 29

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

Question 30

Subcutaneous Hyphomycosis

Answer 30

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

Question 31

Lobomycosis

Answer 31

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

Question 32

Trichinella spiralis

Answer 32

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

Question 33

Wuchereria bancrofti and Brugia malayi

Answer 33

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

Question 34

Onchocerca Volvulis

Answer 34

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