Musculoskeletal Infections and Crystal- Induced Arthropathies Arthur Weinstein, MD James D. Katz, MD Contents Contents Musculoskeletal Infections Crystal-Induced Arthropathies 1. Introduction: 1. Introduction: Musculoskeletal Infections Crystal-Induced Arthropathies 2. Acute Bacterial Arthritis 2. Overview of Implicated Crystals 3. Prosthetic Joint Infections 3. Clinical Syndromes 4. Infections in Children 4. References and Geriatric Patients 5. Questions 5. Septic Arthritis with Other Conditions 6. Lyme Disease 7. Acute Bacterial Infections of Other Musculoskeletal Structures 8. Osteoarticular Tuberculosis 9. Fungal Arthritis 10. Viral Arthritis 11. Poststreptococcal Reactive Arthritis and Rheumatic Fever 12. References MUSCULOSKELETAL INFECTIONS AND CRYSTAL-INDUCED ARTHROPATHIES Musculoskeletal Infections Arthur Weinstein, MD, FACP, FACR Contents 1. Introduction: Musculoskeletal Infections 2. Acute Bacterial Arthritis 3. Prosthetic Joint Infections 4. Infections in Children and Geriatric Patients 5. Septic Arthritis with Other Conditions 6. Lyme Disease 7. Acute Bacterial Infections of Other Musculoskeletal Structures 8. Osteoarticular Tuberculosis 9. Fungal Arthritis 10. Viral Arthritis 11. Poststreptococcal Reactive Arthritis and Rheumatic Fever 12. References MUSCULOSKELETAL INFECTIONS AND CRYSTAL-INDUCED ARTHROPATHIES 1 1. Introduction: 2. Acute Bacterial Arthritis Musculoskeletal Infections Classification Infection may occur in bone, joints, bursae, muscle, or tendon sheaths, although osteomyelitis, infec - tious arthritis, and bursitis are by far the most com - Despite improved antimicrobial therapy, acute bac - mon musculoskeletal infections. Varieties of terial arthritis (septic arthritis) remains a medical microorganisms including bacteria, viruses, fungi, emergency and the cause of significant morbidity 1,2 and parasites may infect joints and other muscu - and mortality. Acute bacterial arthritis is usually loskeletal tissues. Acute bacterial infections most classified by the type of infecting organism (Table often present as a monoarthritis but trauma and 1). Bacteria commonly infect the synovium through crystal arthritis are much more common causes of hematogenous spread from a distant site or occasion - acute monoarticular pain and swelling. Most mus - ally directly from penetrating trauma, iatrogenic culoskeletal infections result from hematogenous joint needling, or an adjacent osteomyelitic focus. spread of the organism to the site. Staphylococcus Table 1 aureus (S aureus ) is the most common cause of musculoskeletal infection. Positive culture in syn - Septic Arthritis: The Infecting Bacteria ovial fluid remains the gold standard for the diagno - sis of septic arthritis. Other causes of infectious arthritis often require alternative methods for diag - Gram-positive Cocci nosis including blood and fluid cultures (dissemi - nated gonococcal disease), antibody titers (Lyme Staphylococci: aureus, epidermidis arthritis, viral arthritis), synovial biopsy and culture Streptococci: pyogenes (beta-hemolytic group A), (chronic bacterial and fungal arthritis). The diagno - other beta-hemolytic groups (esp. B, sis of infectious arthritis using the polymerase chain G), pneumoniae, viridans group reaction (PCR) to detect bacterial DNA in synovial fluids has not yet reached its potential of routine Gram-negative Cocci clinical use. Neisseria gonorrhoeae Neisseria meningitidis Other: Moraxella, Kingella, Branhamella Gram-positive Bacilli Corynebacterium pyogenes Listeria monocytogenes Gram-negative Bacilli Brucella species Campylobacter species Chryseobacterium meningosepticum Escherichia coli Haemophilus influenzae Kingella kingae Klebsiella pneumoniae Pasteurella multocida Proteus mirabilis Pseudomonas aeruginosa (continued next page) 2 EDUCATIONAL REVIEW MANUAL IN INTERNAL MEDICINE. VOLUME I: RHEUMATOLOGY Table 1 (continued) Table 2 Septic Arthritis: The Infecting Bacteria Pathogenesis of Arthritis Associated with Infection Salmonella species Serratia marcescens Direct Synovial Infection Anaerobes Hematogenous from a distant focus Penetrating trauma Bacteroides fragilis Adjacent infection: osteomyelitis, soft tissue abscess Clostridium species Iatrogenic: postsurgery, post joint needling Fusobacterium necrophorum Peptococcus and Peptostreptococcus species Propionibacterium acnes Immune Complex Formation Spirochetes Hepatitis B Disseminated gonococcal infection Borrelia burgdorferi Bacterial endocarditis Treponema pallidum ? Postinfectious synovitis Mycoplasma Molecular Mimicry Mycoplasma hominis Chronic Lyme arthritis Mycoplasma pneumoniae ? Rheumatic fever Ureaplasma urealyticum Unknown Mechanisms Reactive arthritis HIV Microorganisms may also lead to arthritis by indi - Predispositions to septic arthritis include older age rect means, such as immune complex formation, (>80 years), serious chronic illness such as diabetes molecular mimicry, or unknown mechanisms mellitus, cancer and chronic renal failure, rheuma - (Table 2). toid arthritis, the presence of a prosthetic joint, intravenous drug use, skin infection and an immunosuppressed state (Table 3). Males and females are equally affected. Polyarticular septic arthritis is not rare, occurring in approximately 15% of cases of septic arthritis, depending on the popu - lation studied, with rheumatoid arthritis an impor - 3 tant predisposing factor. Polymicrobial infections occasionally occur with penetrating trauma and in patients with joint prostheses. MUSCULOSKELETAL INFECTIONS AND CRYSTAL-INDUCED ARTHROPATHIES 3 Table 3 Table 4 Septic Arthritis: Predisposing Factors Common Causes of Nongonococcal Acute Bacterial Arthritis Old age Staphylococcal aureus 60% Comorbidities: cancer, diabetes, chronic renal failure, chronic liver disease, rheumatoid arthritis ␤-hemolytic streptococci 15% Pre-existing joint disease: rheumatoid arthritis, crystal disease, hemophiliac arthropathy Gram negative bacilli 15% Prosthetic joint Streptococcus pneumoniae 5% Intravenous drug use Congenital: hypogammaglobulinemia, complement Other and polymicrobial 5% deficiency Concomitant infection, eg, skin Acquired: AIDS, immunosuppressant medication Pathogenesis Immunosuppression When bacteria arrive by the bloodstream, they deposit in the synovial membrane where they are able to incite an inflammatory reaction by a number of mechanisms involving the release of bacterial Nongonococcal Septic Arthritis products: lipopolysaccharide endotoxins from Gram negative organisms; exotoxins from Gram positive organisms; and cell wall fragments or bac - The most common bacterial causes of acute non - terial antigens resulting in immune complex forma - gonococcal septic arthritis are shown in Table 4. tion. The resultant cellular and humoral proinflam - While S aureus is the most common cause of septic matory events, which have been elucidated in ani - arthritis, it generally occurs in joints that were mal models of septic arthritis, include synovial pro - abnormal due to arthritis, trauma, prosthesis, and/or liferation with phagocytosis of bacteria, early infil - surgery prior to infection, whereas N gonorrhoeae tration of CD4+ T cells, and the release of cytokines ␤ is more likely to infect previously intact joints and such as interleukin-1 and tumor necrosis factor- . otherwise healthy individuals. S aureus causes the These in turn stimulate the release of metallopro - majority of joint infections in the elderly and in teinases, collagen, and stromelysin from synovial patients with rheumatoid arthritis. cells and chondrocytes, leading to early cartilage loss as a result of proteoglycan breakdown. Cytokine upregulation of adhesion molecules (eg, ICAM-1) results in infiltration of neutrophils with subsynovial micro-abscess formation. The bacteria and inflammatory reaction spill into the joint cavity where bacterial products activate the complement system and phagocytosing neutrophils release lyso - somal enzymes; this further enhances the inflamma - tory reaction and contributes to tissue damage. With ongoing untreated infection, the synovial inflamma - tion is driven forward by these cellular and humoral processes resulting in pannus formation with further erosion of cartilage and bone. The inhibition of these infection-induced inflammatory processes in 4 EDUCATIONAL REVIEW MANUAL IN INTERNAL MEDICINE. VOLUME I: RHEUMATOLOGY experimental S aureus arthritis by the concomitant below. The frequency of involvement of specific use of nonsteroidal anti-inflammatory drugs or cor - joints is given in Figure 1. The differential diagnosis ticosteroids with antibiotics has been shown in ani - of septic arthritis includes crystal disease, trauma, mal models to lessen cartilage damage and reduce and acute inflammatory monoarthritis or 4,5 postinfection synovitis. A recent controlled study oligoarthritis, including Reiter’s syndrome and of septic arthritis in children showed that a short juvenile rheumatoid arthritis. course of intravenous dexamethasone given along with antibiotics resulted in significantly reduced These atypical scenarios will be discussed below. short-term and long-term residual articular dysfunc - The frequency of involvement of specific joints is 6 tion. An immune-mediated postinfection synovitis given in Figure 1. The differential diagnosis includes that is probably related to the stimulatory effects of crystal disease, trauma, and acute inflammatory the intra-articular bacterial products and the release monoarthritis or oligoarthritis, including Reiter’s of neoantigens from cartilage may persist after erad - syndrome