Infectious Arthritis
1. Bacterial
Septic arthritis
Causes
Spontaneous primary arthritis: probably via hematogenous spread than from a
cutaneous origin, occurring at an annual rate of 2–10/100.000. Half of the primary cases are
formally bacteremic during the initial acute phase. Among sexually active adults, Neisseria
gonorrheae remains a common pathogen, especially when associated with tenosynovitis.
After injury: 3 distinct origins differ in pathogenesis and microbiology.
i) bites: usually Gram (-)
ii) thorn accidents: Pantoea agglomerans
iii) trauma
Post-surgical (think also Cutibacterium acnes and coagulase (-) staphylococci)
Septic emboli (endocarditis, abscesses)
Pathogens
-Staphylococcus aureus and streptococci: most common in general. Do heart u/s to exclude
endocarditis!
-Neisseria gonorrheae: most common in young and sexually active, mostly women, around
menses. Associated with pustulosis + tenosynovitis + migratory arthritis. Only 50% positive
cultures. Use synovial fluid NNAT for diagnosis. 1-3% of gonorrhea patients get arthritis. Can also
cause aortic aneurism. May be from immune complexes.
-Gram (-) (9-17%): animal bites, UTI-patients
-anaerobes (1-3%)
-Brucella: esp. for axial disease (SIJ > spinal) and lower extremities
-Kingella kingae (a very rare Gram [-]): in infants or adult endocarditis
-Salmonella spp.: in severe sickle cell disease, also causes osteomyelitis and aortitis
-Coccidioides: central/south America, respiratory illness
-Borrelia: Lyme disease (erythema migrans, flu-like)
-Syphilis
-Cutibacterium acnes: usually present with chronic symptoms since the time of surgery and
patients often have no specific complaints. In patients with chronic symptoms for more than a
year, you should be thinking of indolent organisms, such as C. acnes or coagulase (-)
staphylococci. C. acnes typically takes 7 days to grow in culture.
Clinical
Usually acute monoarthritis, but in 20% can be oligoarthritis. Polyarticular is likely to occur in
patients with uncontrolled inflammatory arthritis or in patients with overwhelming sepsis or
endocarditis (septic emboli?). Chills and spiking fevers are unusual, unless there is concomitant
bacteremia. Chronic septic arthritis may lead to osteomyelitis. Chronic bacterial self-draining
arthritis mainly occurs in polyneuropathic (diabetic) foot infections with ulcers. A clinically
significant joint destruction usually occurs after 2-3 weeks.
Gonococcal: migratory polyarthralgia, extensor tenosynovitis, rash (60%: macules,
papules or pustules on the distal extremities; patients are often unaware of these lesions and
they may be easily overlooked on physical exam).
, Syphilis: polyarthritis + palmoplantar maculopapular rash (75–100%), generalized
lymphadenopathy (75%), fever (50%), sore throat, mucosal ulcers and condyloma lata. The
arthritis is symmetric and involves the knees and ankles more than small joints of the hands.
Tenosynovitis may be present.
Lab
- Gram stain is usually disappointing with <50% accuracy
- Culture is the gold standard, although it can too be negative due to prior antimicrobial
exposure or a low number of fastidious (= special nutritional requirements) organisms
(Haemophilus influenza, Neisseria gonorrhoeae, Brucella).
- PCR can be used, but it’s better kept for identification of specific bacteria like Kingella etc.
- Synovial fluid: usually >50.000cells/mm3 + high neutrophil count.
- Elevated inflammation markers are not proof of bacterial arthritis regardless of the cutoff,
even in the presence of fever.
- Procalcitonin: in localized arthritis without systemic signs, is often negative despite the
presence of localized pus.
Gonococcus: Gram stain of synovial fluid is positive in <25%, while cultures in 50%.
Because urethritis is often asymptomatic, all patients should have a urine specimen as well as
urethral/rectal/pharyngeal swabs sent for Gram stain, culture and NAAT testing. Urethral
smears and cultures are more useful in men (>90% sensitivity) than in women.
Syphilis: non-treponemal tests (RPR, VDRL, can have false positives) as screening,
followed by confirmatory treponemal antibody tests (positive for life, can’t differentiate acute
vs. chronic).
Treatment
-Drainage/lavage (esp. in difficult joints like hip).
-Antibiotics for 4-6 weeks (except Neisseria gonorrheae → 7-10 days).
Most treatments start IV. However, we also may treat selected cases (chronic septic
arthritis without systemic inflammation, such as in the diabetic foot) empirically with oral agents
from the start. Indeed, quinolones, TMP/SMX and basically all non-β-lactam antibiotics are
known for their good bioavailability in synovial tissues and/or adjacent bone. Rifampin is often
added to penetrate biofilms. IA antiseptic use is discouraged because of potential toxicity for the
cartilage. The synovial penetration of all IV antibiotics and most oral antimicrobials is sufficient
and significantly better than for bone infections.
We cover blindly for Staph. and Gram (-) [especially in case of bites].
Rocephin/Ciproxin/Tavanic (quinolones for Pseudomonas) + Voncon (for MRSA). In
posttraumatic septic arthritis, an empiric therapy covering Gram (-) would be more appropriate
than a simple Gram (+) coverage.
Gonococcus: treatment 7-10 days (Rocephin) + cover chlamydia (Azithromycin
1gr once or doxycycline 100mg x2 for 7 days) + treat partner.
Syphilis: benzathine penicillin G 2.4x106IU (IM), once.
Tuberculosis
Osteoarticular TB occurs in 1-3% of all forms of TB, 10% of extrapulmonary TB and is associated
with pulmonary TB in only 50%. Radiographically, TB infection extends slower than other
pyogenic arthritis.
, Spondylitis (Pott’s disease) (50% of cases of skeletal TB)
The most common form of articular TB. Hematogenous or lymphogenous (from pleura) spread
or tissue continuity. Localization: anterior superior or inferior end plate → wedge-shaped
vertebral destruction → kyphosis (gibbus spine [gibbus in Latin = hump]). In the early stages, the
disk is not affected (while in brucellosis there’s early disc involvement) and spread to the
adjacent vertebra occurs under the anterior longitudinal ligament. The disc is secondarily
affected. Thoracic spine is more frequently affected than lumbar (in contrast to other septic
spondylitis). The presence of cold abscesses (75% in TB vs. 0% in pyogenic spondylitis) is a
characteristic finding (cold means without overt inflammation). Also, well-defined
paravertebral/epidural soft tissue involvement (67% in TB vs. 11% in pyogenic spondylitis) favors
TB over pyogenic spondylitis. Fever in only 20-30%.
Peripheral arthritis (30%)
Usually monoarthritis of big joints: knee, hip, ankle. Rare: polyarticular, tenosynovitis. Culture of
tissue obtained from synovial biopsy is 90% sensitive in patients with TB arthritis. On the
contrary, acid-fast bacilli stain smears of synovial fluid are only 20% sensitive.
Osteomyelitis (5-20%)
usually a solitary cold abscess, presenting as a lytic lesion with a sclerotic rim accompanied by
mild erythema and pain and it is frequently mistakenly with malignancy. It occurs in both
children and adults in 2-3% of articular TB. Any bone can be affected, but the femur and tibia are
the most common followed by short bones (metacarpals, metatarsals, phalanges).
Reactive (Poncet’s disease)
is characterized by non-erosive, non-deforming polyarthritis, dactylitis or enthesitis associated
with extrapulmonary TB, with no evidence of direct joint involvement. Molecular mimicry is
thought to be the cause leading to Th1-response. A rise in ReA cases related to the intravesical
use of BCG to treat bladder cancer has been noted in recent years.
Dactylitis (spina vendosa)
Means “inflated” bone. In hands/feet, mainly in children, whose bones have active marrow and
are more prone to hematogenous spread. In Rx: cystic lytic lesion with thinned cortex, minimal
periosteal reaction.
Sacroiliitis
10% of osteoarticular TB, usually unilateral.
Aortic aneurysm: mimic of LVV
Non-tuberculous mycobacteria: tenosynovitis and bursitis occur more commonly in NTM.
Diagnosis
Synovial fluid: moderately elevated WBC (10.000-20.000 cells), with neutrophil predominance.
Synovial membrane biopsy exhibits caseating granulomas in up to 80%. Synovial fluid ADA.
Culture is an important tool and can be positive in 80%. Mantoux and Quantiferon cannot
differentiate latent infection from active. PCR from synovial fluid or synovial biopsy.
Treatment
1. Bacterial
Septic arthritis
Causes
Spontaneous primary arthritis: probably via hematogenous spread than from a
cutaneous origin, occurring at an annual rate of 2–10/100.000. Half of the primary cases are
formally bacteremic during the initial acute phase. Among sexually active adults, Neisseria
gonorrheae remains a common pathogen, especially when associated with tenosynovitis.
After injury: 3 distinct origins differ in pathogenesis and microbiology.
i) bites: usually Gram (-)
ii) thorn accidents: Pantoea agglomerans
iii) trauma
Post-surgical (think also Cutibacterium acnes and coagulase (-) staphylococci)
Septic emboli (endocarditis, abscesses)
Pathogens
-Staphylococcus aureus and streptococci: most common in general. Do heart u/s to exclude
endocarditis!
-Neisseria gonorrheae: most common in young and sexually active, mostly women, around
menses. Associated with pustulosis + tenosynovitis + migratory arthritis. Only 50% positive
cultures. Use synovial fluid NNAT for diagnosis. 1-3% of gonorrhea patients get arthritis. Can also
cause aortic aneurism. May be from immune complexes.
-Gram (-) (9-17%): animal bites, UTI-patients
-anaerobes (1-3%)
-Brucella: esp. for axial disease (SIJ > spinal) and lower extremities
-Kingella kingae (a very rare Gram [-]): in infants or adult endocarditis
-Salmonella spp.: in severe sickle cell disease, also causes osteomyelitis and aortitis
-Coccidioides: central/south America, respiratory illness
-Borrelia: Lyme disease (erythema migrans, flu-like)
-Syphilis
-Cutibacterium acnes: usually present with chronic symptoms since the time of surgery and
patients often have no specific complaints. In patients with chronic symptoms for more than a
year, you should be thinking of indolent organisms, such as C. acnes or coagulase (-)
staphylococci. C. acnes typically takes 7 days to grow in culture.
Clinical
Usually acute monoarthritis, but in 20% can be oligoarthritis. Polyarticular is likely to occur in
patients with uncontrolled inflammatory arthritis or in patients with overwhelming sepsis or
endocarditis (septic emboli?). Chills and spiking fevers are unusual, unless there is concomitant
bacteremia. Chronic septic arthritis may lead to osteomyelitis. Chronic bacterial self-draining
arthritis mainly occurs in polyneuropathic (diabetic) foot infections with ulcers. A clinically
significant joint destruction usually occurs after 2-3 weeks.
Gonococcal: migratory polyarthralgia, extensor tenosynovitis, rash (60%: macules,
papules or pustules on the distal extremities; patients are often unaware of these lesions and
they may be easily overlooked on physical exam).
, Syphilis: polyarthritis + palmoplantar maculopapular rash (75–100%), generalized
lymphadenopathy (75%), fever (50%), sore throat, mucosal ulcers and condyloma lata. The
arthritis is symmetric and involves the knees and ankles more than small joints of the hands.
Tenosynovitis may be present.
Lab
- Gram stain is usually disappointing with <50% accuracy
- Culture is the gold standard, although it can too be negative due to prior antimicrobial
exposure or a low number of fastidious (= special nutritional requirements) organisms
(Haemophilus influenza, Neisseria gonorrhoeae, Brucella).
- PCR can be used, but it’s better kept for identification of specific bacteria like Kingella etc.
- Synovial fluid: usually >50.000cells/mm3 + high neutrophil count.
- Elevated inflammation markers are not proof of bacterial arthritis regardless of the cutoff,
even in the presence of fever.
- Procalcitonin: in localized arthritis without systemic signs, is often negative despite the
presence of localized pus.
Gonococcus: Gram stain of synovial fluid is positive in <25%, while cultures in 50%.
Because urethritis is often asymptomatic, all patients should have a urine specimen as well as
urethral/rectal/pharyngeal swabs sent for Gram stain, culture and NAAT testing. Urethral
smears and cultures are more useful in men (>90% sensitivity) than in women.
Syphilis: non-treponemal tests (RPR, VDRL, can have false positives) as screening,
followed by confirmatory treponemal antibody tests (positive for life, can’t differentiate acute
vs. chronic).
Treatment
-Drainage/lavage (esp. in difficult joints like hip).
-Antibiotics for 4-6 weeks (except Neisseria gonorrheae → 7-10 days).
Most treatments start IV. However, we also may treat selected cases (chronic septic
arthritis without systemic inflammation, such as in the diabetic foot) empirically with oral agents
from the start. Indeed, quinolones, TMP/SMX and basically all non-β-lactam antibiotics are
known for their good bioavailability in synovial tissues and/or adjacent bone. Rifampin is often
added to penetrate biofilms. IA antiseptic use is discouraged because of potential toxicity for the
cartilage. The synovial penetration of all IV antibiotics and most oral antimicrobials is sufficient
and significantly better than for bone infections.
We cover blindly for Staph. and Gram (-) [especially in case of bites].
Rocephin/Ciproxin/Tavanic (quinolones for Pseudomonas) + Voncon (for MRSA). In
posttraumatic septic arthritis, an empiric therapy covering Gram (-) would be more appropriate
than a simple Gram (+) coverage.
Gonococcus: treatment 7-10 days (Rocephin) + cover chlamydia (Azithromycin
1gr once or doxycycline 100mg x2 for 7 days) + treat partner.
Syphilis: benzathine penicillin G 2.4x106IU (IM), once.
Tuberculosis
Osteoarticular TB occurs in 1-3% of all forms of TB, 10% of extrapulmonary TB and is associated
with pulmonary TB in only 50%. Radiographically, TB infection extends slower than other
pyogenic arthritis.
, Spondylitis (Pott’s disease) (50% of cases of skeletal TB)
The most common form of articular TB. Hematogenous or lymphogenous (from pleura) spread
or tissue continuity. Localization: anterior superior or inferior end plate → wedge-shaped
vertebral destruction → kyphosis (gibbus spine [gibbus in Latin = hump]). In the early stages, the
disk is not affected (while in brucellosis there’s early disc involvement) and spread to the
adjacent vertebra occurs under the anterior longitudinal ligament. The disc is secondarily
affected. Thoracic spine is more frequently affected than lumbar (in contrast to other septic
spondylitis). The presence of cold abscesses (75% in TB vs. 0% in pyogenic spondylitis) is a
characteristic finding (cold means without overt inflammation). Also, well-defined
paravertebral/epidural soft tissue involvement (67% in TB vs. 11% in pyogenic spondylitis) favors
TB over pyogenic spondylitis. Fever in only 20-30%.
Peripheral arthritis (30%)
Usually monoarthritis of big joints: knee, hip, ankle. Rare: polyarticular, tenosynovitis. Culture of
tissue obtained from synovial biopsy is 90% sensitive in patients with TB arthritis. On the
contrary, acid-fast bacilli stain smears of synovial fluid are only 20% sensitive.
Osteomyelitis (5-20%)
usually a solitary cold abscess, presenting as a lytic lesion with a sclerotic rim accompanied by
mild erythema and pain and it is frequently mistakenly with malignancy. It occurs in both
children and adults in 2-3% of articular TB. Any bone can be affected, but the femur and tibia are
the most common followed by short bones (metacarpals, metatarsals, phalanges).
Reactive (Poncet’s disease)
is characterized by non-erosive, non-deforming polyarthritis, dactylitis or enthesitis associated
with extrapulmonary TB, with no evidence of direct joint involvement. Molecular mimicry is
thought to be the cause leading to Th1-response. A rise in ReA cases related to the intravesical
use of BCG to treat bladder cancer has been noted in recent years.
Dactylitis (spina vendosa)
Means “inflated” bone. In hands/feet, mainly in children, whose bones have active marrow and
are more prone to hematogenous spread. In Rx: cystic lytic lesion with thinned cortex, minimal
periosteal reaction.
Sacroiliitis
10% of osteoarticular TB, usually unilateral.
Aortic aneurysm: mimic of LVV
Non-tuberculous mycobacteria: tenosynovitis and bursitis occur more commonly in NTM.
Diagnosis
Synovial fluid: moderately elevated WBC (10.000-20.000 cells), with neutrophil predominance.
Synovial membrane biopsy exhibits caseating granulomas in up to 80%. Synovial fluid ADA.
Culture is an important tool and can be positive in 80%. Mantoux and Quantiferon cannot
differentiate latent infection from active. PCR from synovial fluid or synovial biopsy.
Treatment
