• pyogenic
• tuberculous
• septic arthritis
• skeletal syphilis 

• S. aureus = 80-90%; bone in kids via hematogenous spread; extension from contiguous site or direct implantation in adults
• E.coli during UTIs or IV drug use
• Salmonella if have sickle cell disease (encapsulated)
• in adults see occurrence in vertebrae, rarely in long bones EXCEPT Brodie Abscess with staph in metaphysial area of long bone in adults 
• Sclerosing osteomyelitis of Garre: in jaw, new bone forms

• Active visceral disease-->blood borne-->pulmonary infection-->direct extension from lungs to rib-->to adjacent vertebrae
• Pott disease = infxn through intervertebral discs into soft tissue and form abscess
• May infect knees and hips; difficult to congrol
• May have compression fractures that produce sclerotic and kyphotic deformities, neuro deficits 

Septic Arthritis: 

• S. Aureus in kids, adults with abnormal joints; in large joints; Neisseria gonorrhoeae in sex active pts. 
• cytokine inflammation-->bone necrosis -->spreads through haversian canals to periosteum--> sub-periosteal abscess in kids-->limit blood supply--> more necrosis -->weed later, cytokines stimulate osteoclastic bone resorption, ingrowth of fibrous tissue, deposition of reactive bone
• sequestrum=dead bone piece; involucrum=newly made bone around infected bone; rupture periosteum get soft tissue abscess and draining sinus
• radiographic: lytic focus surrounded by sclerosis 

• Syphilis = treponema pallidum
• Yaws = Treponema perenue
• Congenital = spirochetes in active endochondral ossification and periosteum
• Acquired = being age 2-5y.o.
• Saber shin=massive reactive periosteal bone deposition on tibia 

• Reactive arthritis with: arthritis, nongonococcal urethritis or cervictus, and conjunctivitis 
• autoimmune rxn initiated by prior GI infection
• asymmetric joint, low back, ankles, knees, feet stiffness
• synovitis of digital tendon sheath-->sausage finger/toe and ossification of tendoligamentous insertion--> calcaneal spurs and bone outgrowths
• have extra-articular involvement (conjunctivitis, cardiac conduction abnormalities)

• Reiter's syndrome
• Enteritis-associated arthritis
• Psoriatic arthritis
• Septic arthritis 
• Infectious arthritis
  • bacterial
  • tuberculous
  • lyme 

• GI infection by Yersinia, Salmonella, Shigella, or Campylobacter with lipopolysaccharide -->immune rxn
• get arthritis for about a year in knees and ankles; can involve wrists, fingers, toes 

• chronic inflammatory arthropathy affecting peripheral and axial joints and entheses (where tendon or ligament inserts into bone)
• associated with psoriasis
• distal interphalangeal joints of hands, feet first affect asymmetrically
• rare to have extra-articular manifestations  

• bacteremia-->joint seeded
• gonoccocus, stap, strep, h. influenza, gram 1 bacilli
• H. influenza in kids under 2y.o.
• S. aureus in older kids, adults
• gonoccus: late adolescence, young adults; females 
• painful, swollen, infected joint, elevated sed rate 
• non-gonoccocal infections affect 1 joint 

• chronic, progressivce, monoarticular disease (one joint)
• all age groups, mainly adults
• complication: adjoining osteomyelitis or hematogenous dissemination from visceral infection
• insidious, gradual progressive pain
• confluent granulomas w/ central necrosis and pannus (hangs over) over articular cartilage
• weight bearing joints highly affected 

• borrelia burgdorferi spirochete infxn; transmitted by ixodes ricinus tick 
• remitting and migratory over large joints 
• synovium=chronic papillary synovitis w/ synoviocyte hyperplasia, fibrin deposition, mononuclear CD4 infiltrates and onion-skin thickening of arterial walls 
• may have molecular mimicry via HLA-DR
• joints have synovial pannus-->destruction of articular cartilage 

• borrelia burgdorferi (lyme disease)
• clostridium tetani
• clostridium botulinum 

• causes lyme disease
• weak staining gram- spirochetes; stain with giemsa, wright or silver-impregnation; can't see w/ LM
• twisting motility; linear chromosome w/ circular plasmids
• microaerophilic, require N-acetylglucosamine, long chain saturated and unsaturated FAs, AAs
• culture usually unsuccessful; dx with symptoms (relapsing fever, lyme serology) 

• leading vector-borne disease in US
• vector=hard tick; reservoir=white footed mouse and white tailed deer 
  • Ixodes scapularis vector in eastern, midwest US
  • Ixodes pacificus in western US
• tick larvae feeds on mouse reservoir-->larva molts to nymph in late spring-->tick feeds on human-->nymph matures to adult and feeds on deer (natural host)
• see pts infected in May-August 

• OspA, OspB, lipoprotein 6.6 expressed in midgut of unfed tick-->bite human and OspA repressed-->spirochete moves to tick salivary glands-->OspC expression up-regulated (essential to transmit to humans)
• adhere to proteoglycans on host cells via borrelial GAG receptor -->migrate out (erythema migrans)--> disseminate via lymphatics, blood
• Low levels in skin (erythema migrans); antibodies for complement-mediated clearance of borreliae 

• MSK, nervous, or cardiac involvement and lab confirmation of infxn + Erythema migrans (macule then papule then 5-50cm, flat red border and central clearing)
• 3-30 day incubation; hematogenous spread if untreated & 60% get knee arthritis; 10-20% get facial nerve palsy
• arthritis lasts if leave untreated 

• no LM; use serology, IFA, ELISA
• diagnostic levels of anti-IgG or anti-spirochete IgM
  • IgM appearing 2-4 weeks after onset, peaking at 6-8 weeks & decline to normal in 4-6 months 
  • IgG peaks at 4-6mo, persists in addition to anti-OspA/B
  • Abs in CSF if have neuroborreliosis 
• Early Dx: doxycycline orally
• Late Dx: ceftriaxone IV (3rd gen cephalosporin;inhibit cell wall synthesis by inhibiting transpeptidase rxn)

• large motile, spore-forming Gram+ rod
• strict anaerobe, can't reduce sulfate to sulfite
• produce round, terminal spores (look like drumsticks)
• common O (somatic) antigen
• difficult to grow, O2 is toxic
• appears as film over agar
• can't ferment carbs; is proteolytic
• live as saprophytes

• Ubiquitous (soils, colonize GI tract) 
• exposure common, disease is not except in developing countries 

• No immunity induced(vaccine-induced immunity in US)
• 2 toxins: Tetanospasmin and Tetanolysin
  • Tetanospasmin: plasmid-encoded heat labile AB neurotoxin that's nonconjugative. Produced during stationary growth phase-->released when bacteria is lysed-->binds specific sialic acid receptors (polysialogangliosides) on surface of motor neurons & toxin transmitted to soma in spinal cord via endosome-->the light chain of the toxin is a zinc endopeptidase that cleaves synaptobrevin-->inhibit release of GABA, glycine-->spastic paralysis and is irreversible (need to make new axon terminals)
  • Tetanolysin: heat labile hemolysin
• Tetanospasmin=degrades synaptobrevin, a protein required for docking NT vesicles on presynaptic membrane
• spores allow it to survive oxygen exposure; germination enhanced by:
  • necrotic tissue, calcium salts, associated pyogenic infections help keep low O2

• muscle spasms, ANS involvement
• days-to-weeks incubation, related to distance from wound site to CNS)
• Generalized Tetanus: masseter muscle (lockjaw), drooling, sweating, irritability, back spasms (opisthotonos)
  • Risus sardonicus: sardonic smile from sustained contraction
• Localized tetanus, Cephalic tetanus (head, poor Px), Neonatal tetanus (infection of umbilical stump, 90% mortality)

• Dx from clinical presentation, not testing
• microscopy, culture are insensitive; no tetanus toxin or Abs detectable
• Tetanus vaccine
• Rx with debridement and Ab Rx (metronidazole) if no booster w/in last 15years
  • hydroxyl-amine on nitro group-->degrade DNA in anaerobic organisms like clostridium tetani 
• need muscle relaxants, sedation, assisted ventilation 

• large, fastidious, spore-forming gram+ anaerobic rod 
• live as saprophytes (get nutrients from decaying matter)
• 7 distinct botulism toxins: A-G
  • human disease with toxins A, B, E, F

• Found in soil worldwide, few in US
• Type A: neutral, alkaline soil west of Mississippi
• Type B: eastern part of country in rich, organic soil
• Type E: in wet soil 
• 4 forms: 
  1. classic/foodborne: home canned items (type A,B) or preserved fish (type E)
  2. infant: common, consumption of spore infected foods, soil, dust
  3. wound: rare
  4. inhalation: bioterrorism, rapid onset

• Toxin A=zinc endopeptidase that protects neurotoxin from Gi acidity-->C-terminus binds sialic acid residues on muscle -->stimulate endocytosis-->toxin stays at neuromuscular junction-->cleave SNARE proteins (synaptobrevin)-->inactivates proteins that regulate release of ACh
  • Toxin remains bound, requires regeneration of nerve terminals
  • MOST TOXIC SUBSTANCE KNOWN
• flaccid paralysis 

• Type 1: weak and dizzy 1-3 days out; blurred vision w/ fixed dilated pupils, dry mouth (anticholinergic), DUMBELSS but NO FEVER, bilateral descending weakness of peripheral muscles
  • Death due to respiratory paralysis
• Type 2: neurotoxin produced in vivo by C. botulinum colonizing GI tract due to absence of competitive bowel microbes; see in up to 1y.o. 
  • constipation, weak cry, failure to thrive, mortality rate low but may be misdiagnosed as SIDS
• Type 3: contaminated wounds, longer incubation than foodborne (type I) and GI symptoms are less common but have DUMBELSS 

• diagnose Type I (foodborne) when confirm toxin activity (pt serum, feces, gastric fluid)
  • mouse bioassay
• diagnose type II (infant) in feces, serum, or cultured from feces (floppy-baby syndrome) 
• diagnose type III (wound) if in pt serum or wound or culture
• Metronidazole and Penicillin G Treatment, adequate ventilation, gastric lavage, antitoxin (A,B,E)
  • Abs don't form readily
  • kids shouldn't eat honey
  • acidic pH or 4 degrees or colder-->prevent germination of spores
  • 60-100 degrees C for 10min destroys toxin