NON-GONOCOCCALSEPTIC ARTHRITIS

Outline

Introduction Risk Factors Pathogenesis Microbiology Clinical Features Treatment Prognosis Special Cases

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Introduction

Infectious arthritides Non-gonococcal septic arthritis Gonococcal arthritis Lyme disease Viral arthritis Fungal arthritis Osteomyelitis

Bacterial joint infection are serious Most rapidly destructive form of acute arthritis Significant mortality (10-15%) and morbidity (25-50%) Irreversible loss of function in up to 50% of patients

Hochberg et al. Chapter 96. Copyright ©2008 Elsevier Inc.

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Septic Arthritis

Incidence 2-6/100,000 in general population 30-60/100,000 in patients with RA and/or joint prostheses

Despite advances over last 25 years, fatality rate unchanged Although decreased number of prosthetic joint infections,

prosthetic joints remain most common cause of joint infections

Most important prognostic indicator Speed of diagnosis and treatment

General rule If treated within 7 days, patients generally do well

Hochberg et al. Chapter 104. Copyright ©2010- Elsevier Inc.

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Risk Factors for Septic Arthritis Recent joint surgery (+LR 6.9, 95% CI 3.8-12.0) Age > 80 years (+ LR 3.5, 95% CI 1.8-7.0) Prosthetic joint (+LR 3.1, 95% CI 2.0-4.9) Skin infection (+LR 2.8, 95% CI 1.7-4.5) Diabetes mellitus (+LR 2.7, 95% CI 1.0-6.9) Preexisting RA (+LR 2.5, 95% CI 2.0-3.1) TNF-I (?) Others Impaired immune system (cirrhosis, malignancy) Renal failure and hemodialysis Hemophilia Indwelling catheters IVDA & alcoholism

Margaretten ME, et al. JAMA 2007; 297(13):1478-1488.

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Pathogenesis

70%

20%

Arthrocentesis or Arthroscopy

Hochberg et al. Figure 96.1. Copyright ©2008 Elsevier Inc.Gilliland, WR. Rheumatology Secrets, 2nd ed, ed. West 2002. Hanley & Belfus: Philadelpha, pp. 281-289.

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Pathogenesis

Bacteria enter joint, deposit on synovial membrane Produce inflammatory response

Synovial tissue proliferates, becomes tender, blood flow increases Exudation of bacteria, cells, and proteins into SF

No limiting basement membrane Within 5-7 days

Joint becomes swollen Elastase, collagenase liberated from PMNs, synovial cells

degrade cartilage Infection, inflammation can spread to subchondral bone Pressure necrosis from large effusions result in further cartilage

and bone loss

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Pathogenesis

Bacterial DNA and toxins may have deleterious effect Staphylococcal toxic shock syndrome toxin (TSST)-1 Staphylococcal enterotoxins

Adhesins on bacteria probably important (MSCRAMMs) Important virulence factor Mediate adherence of bacteria to intraarticular proteins

Fibronectin, laminin, elastin, collagen, hyaluronic acid, and to prosthetic joint materials

Likely why S. aureus causes most septic arthritis

Hochberg et al. Chapter 96. Copyright ©2008 Elsevier Inc.

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Pathogenesis10

Microbiology

Gram-positive cocci (75-80%) S. aureus most common in native and prosthetic joints

Most common etiologic agent in 40-70% of cases Increasing incidence of CA-MRSA

Streptococci S. epidermidis common in prosthetic joints, rare in native joints

Gram-negative bacilli (10-20%) Elderly who are predisposed to systemic GNR infections Immunocompromised (e.g. SLE patients)

Anaerobes (1%) Occur in prosthetic joints, rare in native joints

Gilliland, WR. Rheumatology Secrets, 2nd ed, ed. West 2002. Hanley & Belfus: Philadelpha, pp. 281-289.Hochberg et al. Chapter 96. Copyright ©2008 Elsevier Inc.

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Microbiology of Septic Arthritis

Organism Clinical Clues

Staphylococcus aureus Healthy adults, skin breakdown, previously damaged joint (e.g. RA), prosthetic joint

Streptococcal species Healthy adults, splenic dysfunction/asplenia

Neisseria gonorrhea Healthy adults (particularly young, sexually active), F >> M’s, associated tenosynovitis, vesicular pustules, late complement deficiency, negative SF culture and gram stain

Aerobic gram negative bacteria Immunocompromised hosts, GI infection

Anaerobic gram negative bacteria Immunocompromised hosts, GI infection

Mycobacterial species Immunocompromised host, recent travel to or residence in an endemic area

Fungal species (sporotrichosis, cryptococcus, blastomycosis)

Immunocompromised host

Spirochete (Borellia burgdorferi) Exposure to ticks, antecedent rash, knee joint involvement

Mycoplasma hominis Immunocompromised hosts with prior GI tract manipulation

UpToDate®

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Joint Distribution

Monoarticular (80-90%) Predilection for single large joint, typically the knee or hip (60%) LE >> UE (particularly the knee) Always consider septic arthritis in DDx of an acute monoarthritis

Polyarticular (10-20%) More common in those with preexisting arthritis S. aureus is the major pathogen May portend a less favorable outcome

>50% mortality rate in RA patients Aspirate >1 joint when suspected

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Clinical Features of Septic Arthritis

Joint capsule Tumor (78%), Rubor, Calor

Severe pain (Dolor) (85%) Typically abrupt onset

Fever (57%) Sweats (27%) Rigors (19%)

Inflammatory SF Leukocytosis (45%) Elevated CRP/ESR (87%)

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Margaretten, ME, et al. JAMA 2007; 297(13):1478-1488.

Diagnosis (no gold standard) Traditional ‘index of suspicion’

Positive Gram stain OR

Positive cultureOR

Positive synovial biopsy or PCROR

Typical clinical syndrome with response to Rx

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Arthrocentesis –Cornerstone of Diagnosis

Cell Count Progressively higher SF WBC increases likelihood

< 25,000/μL (+LR 0.32, 95% CI 0.23-0.43) ≥ 25,000/μL (+LR 2.9, 95% CI 2.5-3.4) > 50,000/μL (+LR 7.7, 95% CI 5.7-11.0) > 100,000/μL (+LR 28.0, 95% CI, 12.0-66.0)

Wide range depending on timing, abx pre-treatment, etc. Typically a preponderance of PMNs

≥ 90% (+LR 3.4, 95% CI, 2.8-4.2) <90% (+LR 0.34, 95% CI, 0.25-0.47)

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Margaretten, ME, et al. JAMA 2007; 297(13):1478-1488.

Arthrocentesis –Cornerstone of Diagnosis

Gram stain (+ in 50-80%) Wet prep examination for crystals Culture (+ in majority of NG septic arthritis)

False (-) due to fastidious organisms or recent antibiotics Blood culture bottles reduces the false (-) results

Inoculation of bottles should be done in the lab, not at bedside Synovial glucose, protein, and LDH not helpful

Blood cx’s may id causative agent when SF cx unrewarding

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Matthews, CJ et al. Ann Rheum Dis 2007; 66:440-445.UpToDate®

UpToDate®

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Pseudoseptic Arthritis

First described in 1985 by Call et al. Acute arthritis (mono-/oligo-) superimposed on

chronic rheumatic disease with associated fever, inflammatory SF, and (-) culture

RA Gout Apatite-related arthropathy PsA Dialysis-related amyloidosis Plant thorn synovitis PVNS Neuropathic arthropathy

JIA Pseudogout ReA SLE Sickle cell disease Transient osteoporosis synovitis of the hip Metastatic carcinoma Hemarthrosis

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Imaging Adjuncts to Diagnosis

Plain films Presence of radiographic changes indicates that infection has

been present for 2-3 weeks or more Sonography

Useful for diagnosis of effusions, ST fluid collections Not useful for evaluating the presence of osseous infection

CT Detect early osseous erosion, sequestrum, foreign body,

gas formation Less sensitive than MRI/scintigraphy for detection of bone

infection

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Scintigraphy

Useful in identifying multifocal involvement

Hochberg et al. Chapter 96. Copyright ©2008 Elsevier Inc.

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MRI with Gadolinium

Synovial enhancement in 98% Due to increased vascularity Associated with perisynovial edema (84%), synovial thickening (22%)

Joint effusions common (70%) 91% of large joints, 54% of small joints Absence of effusions in not an absolute (-) predictor

Abnormal bone marrow signal has highest association with concomitant osteomyelitis Especially if diffuse and on T1-weighted images But also had a high false (-) rate

Karchevsky M, et al. AJR 2004; 182:119-122.

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Radiologic and Pathologic Changes(A-B-C-D-E-S)

Radiographic Sign Pathologic Correlate

A Bony ankylosis Fibrous or bony ankylosis (end-stage)

B Osteoporosis Increased blood flow, inflammatory cytokines

C Joint space loss Pannus with cartilage destruction

D Joint deformity End stage of arthritic destruction

E Erosions Pannus with bony destruction

S Joint effusion (the first sign), soft-tissue swelling

Edema of synovium with fluid production

Gilliland, WR. Rheumatology Secrets, 2nd ed, ed. West 2002. Hanley & Belfus: Philadelpha, pp. 281-289.

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Therapy for Septic Arthritis

Prompt treatment ! Start antibiotic(s) immediately after samples collected Use Gram stain and clinical scenario to make choice Broad coverage in debilitated elderly if Gm stain inconclusive

Once organism identified and sensitivities known Continue with

Most efficacious agent With best safety profile And lowest cost

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Therapy (no RCTs)Gram Stain Results Antibiotic

Gram-positive Cocci Vancomycin (30 mg/kg daily IV in 2 divided doses not to exceed 2 gm per day unless serum levels monitored)

Gram-negative Bacilli

If cephalosporin allergy

If suspect Pseudomonas

3rd generation cephalosporin Ceftazidime 1-2 gm IV q8h OR Cetriaxone 2 gm IV q24h OR Cefotaxime 2 gm IV q8h

Ciprofloxacin 400 mg IV q12h OR 500-750 mg PO q12h

Add Gentimicin 3-5 mg/kg/day in 2-3 divided doses

Negative Gram Stain

Immunocompetent

Immunocompromised or traumatic arthritis

Vancomycin

Vancomycin plus 3rd generation cephalosporin

UpToDate®2008.

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Therapy (no RCTs)SF Gram-Stain Findings Initial Antibiotic Regimen

Gram-positive

Gram-positive cocci in clusters (presumptive Staphylococcus)

Gram-positive cocci in chains (presumptive Streptococcus)

Nafcillin or oxacillin(add aminoglycoside if IVDA)

Nafcillin or oxacillin

Gram-negative

Gram-negative bacilli

Gram-negative diplococci (presumptive gonococcus)‡

Nafcillin or oxacillin/aminoglycoside†

Ceftriaxone or cefotaxime

†All with prosthetic joints, IV’s, or recent hospitalization are at risk for MRSA infection and should receive Vanc until cx results available, regardless of Gram-stain results.

‡In the absence of definitive Gram-stain results, a reasonable empiric regimen for the adult with possible septic arthritis is the combination of naf-/oxacillin with a cephalosporin (3 rd- or 4th-generation). An AMG should be added in IVDA. Vanc should be substituted for nafcillin/oxacillin if MRSA is a possibility.

Ho, G Jr. Septic Arthritis. Primer on the Rheumatic Diseases, 3rd ed, ed. Klippel. Springer: NY, 2008. Pages 271-276.

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How Long to Treat? It Depends…

Clinical Scenario Duration of Treatment

Uncomplicated native joint infections 2-4 weeks IV, then 2-3 weeks PO

Difficult to treat pathogens 3-4 weeks IV

Serious infection in compromised host 4-6 weeks IV

Bacteremia with secondary arthritis 4 weeks IV

Prosthetic joint infections Protracted course

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Therapy (no RCTs)

Drainage of purulent material Goals:

Relieve pain Eradicate infection Hasten recovery of lost function

Can be done surgically or via closed needle aspiration Controversy over which should be employed Only one paper compares the two

Retrospective analysis with small number of cases Results suggested needle aspiration appeared, in general, to be

preferable as the initial mode of treatment, but results did not have statistical significance

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Matthews, CJ et. Ann Rheum Dis 2007; 66:440-445.

Therapy (no RCTs)

Overall recommendation is to involve Orthopedics To help facilitate best choice of drainage procedure Arthroscopy often preferred for knee and shoulder Initial open drainage may be necessary for hip

Immobilization of affected joint initially

PT/OT as soon as patient can tolerate

Effective analgesic medication

NSAIDs for post-infectious synovitis

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When is Surgical Drainage Necessary?

Infected hip joints, probably shoulder joints Vertebral osteomyelitis with cord compression Needle aspiration technically difficult Inability to remove purulent fluid by needle drainage Sterilization of the joint fluid is delayed (>7 d) Joint already damaged by preexisting arthritis Associated osteomyelitis requiring surgical debridement Arthritis associated with foreign body

Gilliland, WR. Rheumatology Secrets, 2nd ed, ed. West 2002. Hanley & Belfus: Philadelpha, pp. 281-289.

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UpToDate®

Diagnostic approach to suspected bacterial arthritis

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Prognosis

Morbidity 30%, Mortality 10-15%* Factors portending poor outcome

Young age, old age Virulent microorganisms Delay in diagnosis/treatment Presence of underlying joint disease (e.g. RA) or prosthetic joint Infection of particular joints (shoulder, hip) Polyarticular* Positive blood cultures* Comorbid conditions (RA, IS, renal or cardiac disease)*

Carola, J et al. Arthritis Rheum 1997; 40(5): 884-892.Ho, G Jr. J Rheum 1993; 20: 2001-2003.

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Why Worse Prognosis in RA?

Previously damaged joints Immunosuppression Steroids may blunt symptoms

May be mistaken for a “flare” of RA Gram positive organisms (75-90% of infections)

Mortality 25% Only 50% surviving attain pre-infection level of function

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Prosthetic Joint Infections

Infection rate Knee 0.8-1.9% Hip 0.3-1.7%

Extremely costly Clinical Features

Depend on timing Early (< 3 months) Intermediate (3-24 months) Late (>24 months)

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Prosthetic Joint Infections35

Del Pozo JL, N Engl J Med 2009; 361(8):787-794

Risk Factors for Prosthetic Joint InfectionsEarly Infection Late Infection Signs of Infection

Prolonged duration of surgery Type of prosthesis Slow recovery

Number of OR personnel RA Wound infection

Inexperienced primary surgeon

Nonarticular infections UTI

Advanced age Duration of implant(?) Failed fracture

RA Loosening of implant (?) Increased pain

Periop nonarticular infections Decreased ROM Diabetes

• Revision arthroplasty has a 5-10x increased risk!

From UpToDate®. Adapted from Wymenga, et al., Acta Orthop Scand 1992; 63:665,and from Blackburn, WD Jr, Alarcon, GS, Arthritis Rheum 1991; 34:110.

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Pathogenesis of Prosthetic Joint Infections Wound contamination Hematogenous seeding Microbiology

Early infections typically due to S. epidermidis Late infections (hematogenous) due to S. aureus > others

Mucoid biofilm Coalesced glycocalyx forms on prosthetic joint Protective environment from host defenses, antimicrobials

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Diagnosis

Joint fluid analysis is key Leukocytosis (<10%) Fever (<50%) Elevated ESR/CRP Cultures or tissue biopsy Radiographs Scintigraphy

Gallium or technetium scans DDx includes aseptic joint loosening

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Treatment of Infected Prosthetic Joints

Surgical removal of hardware > 90% of prosthesis have to be removed

Arthrodesis Antibiotics

5-6 weeks of IV antibiotics Rifampin used in conjunction with other antibiotics

Delayed implantation with antibiotic impregnated cement Reinfection rate 10% at 3 yrs, 26% at 10 yrs Mortality 5-20%

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Prevention of Septic Arthritis

Antibiotic prophylaxis for dental procedures in patients who have undergone total joint replacements Within 2 years of implant Immunocompromised patients Patients with certain comorbidities

Controversial with no supporting studies; only consensus statements (2003)

Risk of late infection low 10-100 cases per 100,000 patients per year Counsel your patients

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Prevention of Septic Arthritis

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J Am Dent Assoc 2003; 134(7):895-899

Prevention of Septic Arthritis

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J Am Dent Assoc 2003; 134(7):895-899

Summary

Septic arthritis is the most potentially dangerous and destructive forms of arthritis

Risk factors include age > 80, DM, RA, prosthetic joints, recent joint surgery, and skin infection

Most common etiologic microorganism is S. aureus Don’t forget CA-MRSA, HA-MRSA!

Cornerstone of diagnosis is arthrocentesis Key to better prognosis is to treat ASAP Significant morbidity and mortality

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From UpToDate®. Adapted from Wymenga, et al., Acta Orthop Scand 1992; 63:665,and from Blackburn, WD Jr, Alarcon, GS, Arthritis Rheum 1991; 34:110.

Special Cases45

Septic Arthritis in Children

>90% monoarticular Knee and hip in 2/3 of cases Children <2 years old more susceptible

Signs of joint disease in neonate/infant minimal/absent S. aureus > Grp B strep, Gram negatives

Decline in H. flu septic arthritis in kids < 5 Septic arthritis often secondary to adjacent osteomyelitis

Metaphyseal and epiphyseal blood vessels communicate Some long bone metaphyses are within joint capsule

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Septic Arthritis in Children

Age very helpful in determining likely organism

Age Microorganism

Neonates Staphylococcus aureus (hospital-acquired)Streptococci (community-acquired)Gram-negative bacilli

Age < 2 years Haemophilus influenzae (less common with immunizations)Staphylococcus aureus

Age 2-15 years Staphylococcus aureusStreptococcus pyogenes

Gilliland, WR. Rheumatology Secrets, 2nd ed, ed. West 2002. Hanley & Belfus: Philadelpha, pp. 281-289

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Septic Arthritis (SA) in Children

AVN of femoral head can complicate SA of the hip Outcome more favorable than in adults Long-term sequelae occur in 25% of cases

Leg length discreptancy Limitation of joint mobility Secondary degenerative joint disease

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IVDA and Septic Arthritis

Clinical signs and symptoms may be subtle Common sites – axial skeleton

Sternoclavicular joint Sternomanubrial joint Lumbar vertebrae SI joint, symphysis pubis

Organisms Staphylococcus aureus Staphylococcal epidermidis GNRs (Pseudomonas, Serratia) Candida spp.

Good prognosis if given proper therapy unless HIV +

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More Special Populations

Underlying Disorder Microorganisms

Alcoholism/cirrhosis Gram negative bacilli, Streptococcus pneumoniae

Malignancies Gram negative bacilli

Diabetes mellitus Gram negative bacilli, Gram-positive cocci

Dog/cat bites Pasteurella multocida

Hemoglobinopathies Streptococcus pneumoniae, Salmonella spp

Raw milk/dairy products Brucella spp

SLE Encapsulated organisms (Neisseria, Salmonella, Proteus)

Gilliland, WR. Rheumatology Secrets, 2nd ed, ed. West 2002. Hanley & Belfus: Philadelpha, pp. 281-289

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Septic Bursitis

UpToDate® (above)Hochberg. Figure 96.4. (left)

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Septic Bursitis

Superficial bursae more susceptible to infection Olecranon bursa, prepatellar bursa (“housemaid’s knee”)

Etiology is direct extension of superficial infection Extensive cellulitis surrounding bursa (>50%) Look for skin lesions which are portal of entry Can also see distal edema of affected limb

Cause typically due to trauma to superficial bursae Carpet laying, mining, plumbing, roofing, gardening,

wrestling, gymnastics, hemodialysis

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Septic Bursitis Management

Aspirate effusion/fluctuance Fluid usually inflammatory

WBC elevated but not as much as septic joints Use large bore needle if fluid thick Gram stain usually positive for gram positive cocci

Start bactericidal anti-staphylococcal agent S. aureus responsible for >80% of cases

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Septic Bursitis Management

Mild infection Oral agent Outpatient follow-up and adequate drainage

Severe infection Admission and serial aspirations Parental antibiotics Oral abx after control of infection for additonal 1-3 wks

Surgical drainage or bursectomy rarely necessary Prognosis excellent

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Mycobacterium Infections

Tuberculosis Osteoarticular involvement in 1-5% Infection via hematogenous spread Types of articular infections

Spinal tuberculosis Peripheral joints Reactive

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Pott’s Disease

Tuberculous spondylitis Most common form of osteoarticular infection Thoracic > lumbar > cervical > sacral Collapse of anterior vertebral body

Gibbus deformity May extend

Adjoining discs, vertebrae, distant sites Paravertebral or psoas abscesses

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Above: Gibbus deformityLeft: Paravertebral abscess

Tuberculosis Joint Infections

Peripheral arthritis Monoarticular (hips, knees) Insidious, limited inflammation Phemister’s triad

Juxta-articular osteopenia Marginal erosions Gradual narrowing of joint space

SF WBC increased AFB smears (20% +) Cultures (80% +) Diagnosis best made by

synovium biopsy

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Mycobacterium Infections

Reactive Arthritis AKA Poncet’s disease Polyarticular arthritis in

setting of active TB Hands and feet SF, synovium sterile Resolves with TB

treatment

Others BCG vaccine

May cause a reactive arthritis as well

Atypical mycobacteria M. marinum M. kansasii M. avium complex

M. leprae

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Fungal Infections

Candida Rare C. albicans

Coccidiomycosis Primary Disseminated Polyarticular Migratory Chronic knee

monoarthritis

Sporotrichosis Blastomycosis Cryptococcosis Histoplasmosis Actinomyces Aspergillus

May mimic Pott’s dz Parasites

Giardia, entamoeba, trichomona, toxoplasma

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Questions?61