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INFECTIOUS ARTHRITIS: Overview - Part I Synovial Fluid Analysis Bacterial (Nongonococcal Arthritis) Disseminated Gonococcal Infection (DGI) Acute Rheumatic Fever Prosthetic Joint Infections Overview - Part II Viruses that cause arthritic symptoms Mycobacterial Arthritis Fungal Arthritis Parasites Spirochete (Lyme/Syphillis) Arthritis Synovial Fluid Analysis Normal Joint Fluid highly viscous clear essentially acellular (WBC < 200) protein concentration approximately one-third of plasma glucose concentration similar to that of plasma Synovial Fluid Analysis Non-inflammatory Joint Fluid (Type I) osteoarthritis, trauma, osteochondritis dissecans, neuropathic arthropathy, subsiding or early inflammation, hypertophic osteoarthropathy, pigmented villonodular synovitis also, scleroderma, SLE, and rheumatic fever which can cause inflammatory effusions as well highly viscous 200-2000 WBCs/mm3 yellow Synovial Fluid Analysis Inflammatory Joint Fluid (Type II) rheumatoid arthritis, crystal-induced synovitis, seronegative spondyloarthropathies, rheumatic fever, SLE, hypertrophic osteoarthropathy, and scleroderma low viscosity yellow to opalescent 2000 to 10K WBCs/mm3 (> 50% PMNs) increased total protein, decreased glucose Synovial Fluid Analysis Septic Joint Fluid (Type III) bacteria, mycobacteria, or fungus variable viscosity, yellow to green 50 - 150K WBCs/mm3 (> 75% PMNs) lower cell counts in some immunocompromised patients, mycobacteria infections, some Neisserial and several gram + organisms increased total protein, decreased glucose, however of limited diagnostic value Synovial Fluid Analysis Hemorrhagic Joint Fluid hemorrhagic diathesis, trauma with or without fracture, neuropathic arthropathy, PVNS, benign neoplasms Bacterial (Nongonococcal) Arthritis Most dangerous/destructive form of acute arthritis Predisposing Factors Most cases result from hematogenous spread IV drug use, indwelling catheters, and an underlying immunocompromised state (i.e., HIV, organ transplant pts, diabetes, neonates, and elderly) May be the presenting sign of infective endocarditis (consider in IV drug abusers, or septic arthritis due to Staph aureus, enterococci, or streptococci without obvious predisposing cause) Bacterial (Nongonococcal) Arthritis HIV: does not occur more often, however, in advanced HIV, more atypical infections like mycobacteria and fungal disease in addition to staph aureus. Underlying arthritis: bacteremia is more likely to localize in a joint with preexisting arthritis, particularly if associated with synovitis Especially rheumatoid arthritis, but also increased risk with gout, pseudogout, osteoarthritis, and Charcot’s arthropathy RA: prior intra-articular steroid injections and maintenance immunosuppressive medications Bacterial (Nongonococcal) Arthritis Other direct trauma or inoculation/skin infection prosthetic joints recent joint surgery sternoclavicular arthritis as a rare complication of subclavian vein catheterization hip arthritis from venipuncture or ruptured colonic diverticular disease hemoglobinopathy Bacterial (Nongonococcal) Arthritis Pathogenesis Bacteria deposit in synovial membrane >>> acute inflammatory response which spills over to synovial fluid >>> marked hyperplasia of the lining cells within 2-7 days with release of cytokines and proteases >>> cartilage degradation and cartilage synthesis inhibition >>> sometimes pressure necrosis from large effusion resulting in further cartilage and bone loss Bacterial (Nongonococcal) Arthritis Microbiology Most monomicrobial infections (staph/strep > gram negatives) polymicrobial rare (penetrating trauma, acute diverticulitis) Staph aureus: most common in adults (80% of joint infections in RA) Gram negative bacilli: IV drug abusers, neonates, elderly, major immune deficiency (also get staph) IV drug abusers have a predilection to develop bacterial arthritis in axial joints H. influenza, once common, now rare (vaccine) Strep pneumo small % but significant Bacterial (Nongonococcal) Arthritis Clinical Manifestations Mono-articular arthritis (differentiate clinically from bursitis) knee > 50% of cases, also wrists, ankles, hips 20% oligo (2-4): more common in RA, other systemic connective tissue disease, and overwhelming sepsis most pts febrile, although chills and spiking fevers unusual and elderly pts may be afebrile sometimes evidence of associated skin, urinary tract, or respiratory infection Bacterial (Nongonococcal) Arthritis Diagnosis Identification of bacteria in the synovial fluid (gram stain, culture) and leukocyte count/differential Closed needle aspiration vs. CT/Ultrasound/ Fluoroscopic guidance vs. sometimes surgical arthrotomy (hip/sacroiliac joints) Synovial Fluid: positive culture in majority of cases (can be negative if recent antibiotics or fastiduous organism such as some streptococci or mycoplasma) Gram stain: positive in most cases (75% staph aureus, 50% gram negatives, 25 % gonnococcal) Bacterial (Nongonococcal) Arthritis Diagnosis Blood cultures: positive in 50% of cases, should get in every pt suspected of having bacterial arthritis Other labs: increased WBC count and elevated ESR (common, not specific) Radiographs: usually normal at presentation, but should be obtained to rule out rare associated osteomyelitis or concurrent joint disease and for baseline Bacterial (Nongonococcal) Arthritis - Diagnosis Bacterial (Nongonococcal) Arthritis - Therapy Appropriate antimicrobials and adequate joint drainage Antibiotic Therapy Gram stain with gram positive cocci: vancomyicn (30 mg/kg IV bid) Switch to beta-lactam therapy if susceptible Gram stain negative Immunocompetent: vancomycin Immunocompromised or traumatic: vancomycin plus 3rd generation cephalosporin Bacterial (Nongonococcal) Arthritis - Therapy Gram stain with gram negative bacilli: 3rd generation cephalosporin Add aminoglycoside if pseudomonas aeruginosa suspected (IV drug abusers) Modify based on culture results Duration Generally 14 days parenteral, then 14 days oral If susceptible to fluoroquinolone, may shorten IV to 4-7 days followed by 14-21 days oral 3-4 weeks for pseudomonas or enterbacter species Consider 4 week course of parenteral if documented bacteremia (staph) Bacterial (Nongonococcal) Arthritis - Therapy Joint Drainage: Arthroscopy vs. Closed needle aspiration Arthroscopy often preferred in knee or shoulder infections because of easier irrigation and better visualization of the joint Initial open surgical drainage is usually necessary in hip Serial synovial fluid analysis should demonstrate that the fluid has become sterile and total leukocyte count is decreasing Rapid mobilization to prevent contractures and optimal nutrition to the articular cartilage Bacterial (Nongonococcal) Arthritis Adverse Prognostic Factors Prior joint damage Virulence of the infecting organism Older age Infected joint containing synthetic material DELAYED TREATMENT!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! Mortality Related To Advanced age Coexistent renal or cardiac disease Immunosuppression Disseminated Gonococcal Infection (DGI) Occurs in 1-3% of patients infected with Neisseria Gonorrhoeae Most are less than 40 years of age Majority of pts have arthritis or arthralgia Common cause of acute nontraumatic monoarthritis or oligoarthritis in young, healthy pts Unique clinical features vs. other infectious arthritis Disseminated Gonococcal Infection (DGI) Pathophysiology and Predisposing Factors Host Factors female > male 3:1 Men who have sex with men asymptomatic mucosal infection recent menstruation pregnancy or the immediate post-partum state congenital or acquired complement deficiencies (C5, C6, C7, or C8) systemic lupus erythematosis Disseminated Gonococcal Infection (DGI) Microbial Factors (associated strains) low molecular weight protein 1A (serotype 1A) require arginine, hypoxanthine, uracil for growth usually highly sensitive to penicillin, however some penicillinase producing fail to express outer membrane Protein II (transparent) Immune Factors Frequent absence of positive blood, skin, and synovial fluid cultures/subgroup with negative PCR gonococcal cell-wall components, antibody, complement, and immune complexes in skin lesions Disseminated Gonococcal Infection (DGI) Clinical Manifestations (usually one of two classic syndromes) 1. A triad of tenosynovitis, dermatitis, and polyarthralgias without purulent arthritis fevers, chills, generalized malaise tenosynovitis: wrists, fingers, ankles, and toes skin usually pustular or vesiculopustular can have hemorrhagic macules, papule, nodules transient, commonly only 2-10 in number, and even without treatment, only last 3-4 days Disseminated Gonococcal Infection (DGI) 2. Purulent arthritis without associated skin lesions most patients afebrile knees, wrists, and ankles most common polyarthritis, when present, usually asymmetric separation is not always absolute 1 may evolve to 2 rare manifestations endocarditis, meningitis, osteomyelitis Disseminated Gonococcal Infection (DGI) Laboratory Studies mean synovial fluid count: 50K WBCs/mm3, however < 10K may be observed synovial fluid cultures (positive less than 50%) urethral/cervical, rectal cultures, increase yield to 80% draw at least 2 sets of blood cultures if DGI suspected positive in less than 1/3 of DGI patients, usually in those with the triad form look for staph aureus and Neisseria meningitidis skin or tenosynovial fluid cultures usually sterile check HIV, hepatitis, and syphilis serologies Disseminated Gonococcal Infection (DGI) Initial Treatment (parenteral) Oral if refuses hospitalization or mild dz but give one dose parenteral at least ceftriaxone 1 g IV or IM q 24 hours cefotaxime 1 g IV every 8 hours spectinomycin 2 gm IM every 12 hours (PCN allergic) Not available in the U.S. Quinilones (resistance, CDC no longer recommends) Duration (no controlled clinical trials) minimum of 3 days or until clinical symptoms are gone “triad patients” usually cured after 3 days of therapy Disseminated Gonococcal Infection (DGI) Joint Drainage for “purulent arthritis” repeated needle aspirations or arthroscopically if continued effusions, leukocytosis, fever, severe pain Step-Down to oral treatment “purulent arthritis” up to 7-14 days CDC Guidelines: minimum treatment course of 7 days with a switch to oral 24 -48 hours after improvement cefixime (400 bid), cipro (500 bid) amoxicillin (500 qid) or doxycycline (100 bid) if sens. Treat partners if needed also the possibility of concurrent chlamydia Acute Rheumatic Fever (ARF) “migratory arthritis is generally considered the classic feature of rheumatic fever. While it is common, especially in the young adult patient, no one symptom offers greater diagnostic difficulty, whether the joint changes are objective or mere subjective complaints” Jones Acute Rheumatic Fever (ARF) Delayed non-supporative sequela of a pharyngeal infection with Group A streptococcus Pharyngitis usually occurs two to four weeks before the onset of ARF symptoms Clinical illness is self-limited, but damage to heart valves may be chronic and progressive Acute Rheumatic Fever (ARF) Pathogenesis Acute attack precipitated by infection of pharyngeal tissue by group A streptococci in genetically predisposed individuals Certain HLA-DR antigens (DRB1*16 allele) Organ inflammation is mediated by an aberrant immune response to certain streptococcal cellular antigens >> formation of cross-reacting antibodies or a cell-mediated immune response that recognizes and reacts with related antigens present in the tissue of affected organs Acute Rheumatic Fever (ARF) Clinical Manifestations occurs most frequently in children 4-9 years of age onset is acute febrile illness manifested in one of several ways (major criteria) or combination: migratory arthritis (large joint predominant) carditis and valvulitis central nervous system involvement (Sydenham chorea) rash subcutaneous nodules Acute Rheumatic Fever (ARF) Arthritis classically affect several joints in quick succession, each for a short time = MIGRATORY knees, ankles, elbows, and wrists most common leg joints typically first; sterile inflammatory joint fluid more common/severe in teenagers/young adults usually the earliest symptomatic manifestation joint pain often more prominent than objective signs (“pseudoparalysis”)and almost always transient 6-16 joints (each joint usually no longer than 1 week) usually very responsive to salicylates or nsaids Acute Rheumatic Fever (ARF) Carditis pancarditis (peri, epi, myo, and endocardium) mitral regurgitation is most common murmur isolated aortic regurgitation and hemodynamically significant stenotic lesions of the aortic/mitral valves unusual at presentation (mitral stenosis = sequele) severe valvular damage and myocardial dysfunction from myocarditis can lead to CHF Lab: EKG: all degrees of heart block Cardiomegaly on CXR Echocardiography: nearly all pts have signs of acute carditis Acute Rheumatic Fever (ARF) Sydenham’s Chorea abrupt, purposeless, nonrhythmic involuntary movements, asymmetrical, sometimes unilateral muscular weakness emotional disturbances no sensory loss or involvement of the pyramidal tract diffuse hypotonia may be present may have a longer latent period vs. other rheumatic manifestations, up to 8 months some patients may have no other symptoms Acute Rheumatic Fever (ARF) Subcutaneous Nodules firm and painless overlying skin noninflamed and movable few millimeters to two centimeters in diameter over bony surface or near tendons single lesion to a few dozen, mean 3-4, symmetric one or more weeks, rarely greater than one month smaller and more short-lived than RA nodules usually only in patients with carditis Acute Rheumatic Fever (ARF) Erythema Marginatum evanescent, non-pruritic rash, pink or faintly red trunk, sometimes proximal limbs, not face lesions extend centrifugally while skin in center returns to normal early in disease persists or recurs when all other manifestations have disappeared occurs only in patients with carditis Acute Rheumatic Fever (ARF) Modified Jones Criteria, 1992 Major manifestations: carditis, polyarthritis, Sydenham chorea, erythema marginatum, subcutaneous nodules Minor manifesations: Clinical: fever, arthralgia Laboratory: elevated acute phase reactants (ESR,CRP), prolonged PR interval Supporting evidence of antecedent Group A streptococcal infection Elevated or rising streptococcal antibody titers (ASO, DNAase, hyaluronidase, streptokinase) Positive throat culture or rapid streptococccal antigen test High probability of ARF if 2 Major, or one major and two minor with evidence of Group A streptococcal infection Acute Rheumatic Fever (ARF) Modified Jones Criteria, 1992 3 settings where diagnosis can be made without strict adherence to criteria Chorea as the only manifestation Indolent carditis as the only manifestationi in patients who come to medical attention months after the acute infection Recurrent rheumatic fever in patients with h/o rheumatic fever or rheumatic heart disease Acute Rheumatic Fever (ARF) 2002 AHA Update Concluded that there were insufficient data to support a revision of 1992 criteria If pre-existing rheuamtic heart disease, use caution in interpreting a single clinical finding as a sign of recurrence of rheumtic fever Strict adherence in areas of high prevalence may result in underdiagnosis Agreed that echocardiography in diagnosis of acute rheuamtic fever was controversial in patients without cardiac findings on physical exam Acute Rheumatic Fever (ARF) Treatment Symptomatic Relief Eradication of Group A beta-hemolytic streptococcus Prophylaxis against future infection to prevent recurrent cardiac disease Acute Rheumatic Fever (ARF) Symptomatic Relief Anti-inflammatory agents, most commonly aspirin, usually provide dramatic improvement of arthritis and fever (80-100 mg in children, 4 – 8 g/day in adults, serum conc. 20-30 mg/dl) Rash usually temporary and does not need treatment Carditis (severe disease = significant cardiomegaly, CHF, or third-degree heart block) Conventional therapy for heart failure Steroids 2 mg/kg/day 1-2 weeks, then taper over 1-2 weeks, however studies of benefit conflicting Acute Rheumatic Fever (ARF) Antibiotic Therapy Penicillin oral for 10 days or one time IM at time of diagnosis regardless of presence or absence of phayrngitis PCN allergic: oral erthryomycin or cephalosporin Throats of all family contacts should be cultured and treat with PCN if positive for B-hemolytic strep Acute Rheumatic Fever (ARF) Antibiotic Prophylaxis Goal: to prevent recurrence of ARF Oral: PCN VK 250 mg twice per day; alternative sulfadiazine 500-1000 mg per day, or e-mycin 250 mg bid Parenteral: benzathine PCN G 0.6-1.2 million units IM every 4 weeks (every 3 weeks may be more effective) Duration: unclear Until pt is a young adult (18-20 years), usually 10 years from acute attack with no recurrence Indefinite if documented evidence of rheumatic heart disease or continued exposure to B-hemolytic group A strep population Prosthetic Joint Infections Epidemiology Rate 0.5-1.0% for hip replacements and 0.5-2% knee Re-infection remains major problem in patients undergoing replacement arthroplasty Risk Factors (early infection) RA or other systemic illness, perioperative or nonarticular infections, prior infection of the joint or adjacent bone, prior surgery on joint, prolonged duration of surgery, higher number of O.R. personnel, postoperative bleeding or hematoma formation, advanced age Prosthetic Joint Infections Pathogenesis Early-Onset Infections Late-Onset Infections Within first 2 months after surgery Contamination of operative wound by bacteria on the skin of the patient or airborne in the operating room > 75% due to staph species or other gram positives Hematogenous seeding at the surface of bioprosthetic materials and damaged joint tissues Postoperative wound dehiscence may develop infection of prosthesis by contiguous spread of organisms such as gram negative rods Prosthetic Joint Infections Pathogenesis The Role of Biofilms Adherent bacteria to prosthetic joint multiply and elaborate exopolysaccharides, also known as glycocalyx Microcolonies of bacteria encased in glycocalyx coalesce to form a biofilm Bacteria deep within biofilm are metabolically inactive or in various stages of dormancy and protected from host defenses; typically highly resistant to antimicrobial agents (time-related) Delay of infection, treatment failure,clinical relapses Prosthetic Joint Infections Microbiology Early infection: majority coagulase negative staph, however staph aureus still important Late Infection: staph aureus most common Clinical Manifestations Early infection: pain; erythema, induration, and edema at the primary incision; wound drainage; fever common Late infection: prolonged indolent course, primarily joint pain, rarely fever, leukocytosis, or symptoms of infection at another site Prosthetic Joint Infections Diagnosis Acute-phase reactants: usually elevated, non-specific Radiographs loosening of prosthesis in late-onset infections only and is nonspecific as aseptic loosening can be due to mechanical causes Periosteal new bone formation highly suggestive but infrequently present Bone scan: nonspecific in early infections, and can be positive in a small number of patients with aseptic loosening Prosthetic Joint Infections Joint Fluid Analysis usually diagnostic in early-onset infections Biopsy of Joint Tissue or Periarticular Bone Intraoperative frozen section histology Sometimes required to diagnose late-onset infection Several sections should be sent routinely during elective revision arthroplasty even if infection is not suspected Prosthetic Joint Infections Treatment Early-onset: surgical debridement with long course of IV antibx curative between 25 and 33% Late-onset: vast majority need removal of prosthesis, particularly if it is loose Replacement Arthroplasty: one vs two stage Arthrodesis Suppressive Medical Therapy A small number ultimately require amputation Prosthetic Joint Infections Prevention Preoperative antibiotics: cephazolin or cefuroxime vs. vancomycin Screen for occult or minor infections Treat wound infection or skin necrosis early Unclear benefit: laminar flow in O.R., body-exhaust surgical suits, antibiotic-impregnated cements NO EVIDENCE TO SUPPORT ANTIBIOTIC PROPHYLAXIS PRIOR TO DENTAL OR UROLOGIC PROCEDURES QUESTIONS?