INFECTIOUS ARTHRITIS:

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 synovialfluid (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 mono-arthritis 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 polyarthralgiaswithout 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) • “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 • Joint Drainage • for “purulent arthritis” • repeated needle aspirations or arthroscopically if continued effusions, leukocytosis, fever, severe pain • Step-Down to oral treatment • 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) • ModifiedJones 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) • ModifiedJones 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

INFECTIOUS ARTHRITIS: