General Examination.: The physical examination searches for evidence of both local and systemic manifestations of rheumatic diseases (Table 116-2).

Joints.: Joints are examined for warmth (the dorsum of the hand can detect a difference of 0.5° C), effusion, synovial thickening, deformity, range of motion, pain on actively loaded motion, and tenderness (generalized or localized, articular or periarticular).

Spine.: The spine evaluation is best performed with the patient standing; the vertebral column is assessed for abnormal curvature or asymmetry. Although supporting evidence is scant, Schober’s maneuver is used to assess for the limitation of the lumbar spine motion that occurs in ankylosing spondylitis.⁷

Upper Extremities.: Localized tenderness and pain associated with active movement are more likely to be periarticular in origin. A shoulder affected by chronic arthritis or bursitis will have atrophy of the deltoid muscle. Generalized tenderness and pain, both at rest and with active and passive motion, suggest joint involvement.

Early signs of joint inflammation in the elbow are limitation of extension and an increase in the normal angle at which the patient holds the elbow at the side.

The hand and wrist provide many clues to the presence of long-standing rheumatic diseases: MP and PIP joints are affected in RA; and the first carpometacarpal, PIP, and DIP joints are affected in OA. The fingers may be swollen or sausage-like in appearance, an indication of psoriasis or reactive arthritis. Subluxation at the MP joints, ulnar deviation, and swan-neck deformities occur in RA. The nails may have pitting characteristic of psoriatic arthritis.

Assessment of the wrist is difficult because it may not be obviously swollen. Discomfort and decreased range of motion, particularly on extension, may indicate synovial involvement.

Lower Extremities.: Inflammation affecting the hip joint can be manifested as pain in the anterior thigh, knee, or groin. A hip joint effusion will cause the patient to hold the hip partially flexed. An externally rotated and abducted leg in a neonate strongly suggests infection.⁸ Range of motion of the hip is most easily tested by flexing the hip, bending the knee at a right angle, and rotating the heel medially and laterally to test for external and internal rotation, respectively.

An effusion of the knee joint is relatively easy to detect when it appears as a ballotable fullness medially and laterally. Fullness of the popliteal fossa may indicate Baker’s cyst. Passive range of motion may elicit crepitus (suggestive of degenerative joint disease) or clicking (suggesting a meniscal tear). Tibiotalar joint effusions produce swelling under the medial malleolus and make it difficult to palpate the extensor hallucis longus tendon. Tenderness, warmth, and swelling of the great toe MTP joint occur in cases of gout but can also occur with OA and RA. Sausage-like swellings of the toes are seen in reactive arthritis.

General Appearance.: Bedside inspection of synovial fluid for color, clarity, and viscosity can provide diagnostic clues. Normal synovial fluid is clear and colorless, with a viscosity that permits stretching of a “string” of fluid between the thumb and forefinger. Inflamed fluid is more opaque from an elevated WBC count, with a viscosity more like water because of enzymatic breakdown of glycosaminoglycans. Hemarthrosis is manifested after acute trauma or in the presence of coagulopathy, particularly with hemophilia. Lipohemarthrosis indicates ligamentous injury or an intra-articular fracture, and brownish synovial fluid may suggest the rare diagnosis of pigmented villonodular synovitis.

Synovial Fluid Studies.: Routine laboratory analysis includes a cell count with differential, Gram’s stain, and crystal analysis; synovial glucose and protein concentrations are of little diagnostic assistance.¹⁶ A positive Gram’s stain is diagnostic, but a negative result for bacteria does not rule out septic arthritis; culture specimens should also be obtained. Blood culture bottles are more sensitive than other media at identification of pathogens.^17,18

Synovial White Blood Cell Count.: Synovial WBC (sWBC) counts are often used to differentiate classes of synovial fluid; unfortunately, significant overlap exists between inflammatory and septic causes of acute arthritis.¹⁷ A very high fluid sWBC count or polymorphonuclear (PMN) cell pleocytosis indicates infection, but a more modest sWBC count or differential does not exclude it. The likelihood ratio (LR) for septic arthritis increases as the joint WBC count rises. According to one review, sWBC count of less than 25,000/mm³ = LR of 0.32; sWBC count of more than 25,000/mm³ = LR of 2.9; sWBC count of more than 50,000/mm³ = LR of 7.7; and sWBC count of more than 100,000/mm³ = LR of 28.0.⁹ However, low sWBC counts do occur early in infectious arthritis and in partially treated infections; high sWBC counts (>50,000/mm³) can occur in RA, gout, and pseudogout. Most of the cells in both septic and severe inflammatory arthritis are PMN cells.

In summary, cell counts cannot be used to absolutely rule out a septic cause. When in doubt, bacterial cultures sent in blood culture bottles are recommended.

Crystal Analysis.: Although there is some variation in study findings, overall there is an acceptable inter-rater reliability in identifying monosodium urate and calcium pyrophosphate dihydrate crystals in acute arthritis.¹⁹ Crystal analysis is best performed by polarizing microscopy of a fresh drop of synovial fluid placed on a slide with cover slip (Fig. 116-2). Monosodium urate crystals are needle shaped and strongly negatively birefringent (yellow when parallel to the compensator and blue when perpendicular), ranging in size from 2 to 10 µm. Calcium pyrophosphate crystals, in contrast, are polymorphic, rhomboid, and positively (although weakly) birefringent. Lipid appears as a spherule with a Maltese cross, and hydroxyapatite is difficult to recognize.

Epidemiology.: In two prospective series of patients presenting to the ED with monarticular arthritis prompting arthrocentesis, 8 to 27% of patients had bacterial joint infections.16,21 The incidence of septic arthritis in the general population is approximately 2 to 10 cases per 100,000 per year, with an age distribution curve for septic arthritis revealing bimodal peaks for young children and adults older than 55 years.²² Additional risk factors include low socioeconomic status, injection drug abuse (in which joint infections typically involve the axial skeleton but can involve extremities), alcoholism, diabetes, skin infections, advanced human immunodeficiency virus (HIV) infection or other immunocompromised states, chronic arthritis (particularly rheumatoid, crystalline, and degenerative OA), and following intra-articular corticosteroid injections or prosthetic implants.

Pathophysiology.: Any diarthrotic joint, whether it is native, chronically diseased, or prosthetic, can develop septic arthritis. Bacterial pathogens infect the joint space most commonly by hematogenous spread, but direct inoculation and contiguous spread from bone or soft tissue infections also occur. Once in the joint, bacteria proliferate essentially unchecked in the highly vascular synovium, which has no limiting basement membrane. Bacterial components and toxins, as well as the inflammatory cascade they induce, trigger synovial proliferation with neovascularization and subsequent enzymatic, cellular, and cytokine degradation of articular cartilage. Septic arthritis, unless it is rapidly recognized and treated, results in serious disabling morbidity, with mortality ranging from 7 to 15% or higher.¹⁷

Septic arthritis can occur simultaneously with other forms of arthritis, especially RA and gout.²⁰ The diagnosis of infectious arthritis in a patient with known crystal arthritis can be challenging because acute flare-ups of gout or pseudogout can cause fever, and crystals can emerge from an infected joint. For this reason, Gram’s stain and culture should be considered in select cases.

Microbiology.: The microbiology of nongonococcal arthritis has remained fairly constant over time, except for the notable decline of Haemophilus and pneumococcal species in the postimmunization era.²² Acute nongonococcal septic arthritis in adults is caused most often by gram-positive organisms (75-90%), followed by gram-negative bacilli (10-20%) and then anaerobes, mycobacteria, and fungal and other unusual organisms.²³ Overall, Staphylococcus aureus is still the most common cause of septic arthritis, with the rapid emergence of methicillin-resistant strains.²⁴ Neisseria gonorrhoeae accounts for only 20% of cases of monarticular septic arthritis and more commonly is manifested with polyarthritis; it is discussed separately. Select populations have higher propensities for specific infecting organisms (Table 116-5).

Clinical Features.: Patients with septic arthritis present with fever, joint pain, and effusion, typically in a single large joint (the knee is most common). Moderate fever occurs in 50% of cases¹⁷ but may be less common in the presence of advancing age or immunosuppressive states.¹⁷ Rigors and chills are reported in only 20% of patients. Polyarticular presentation occurs in 20% of cases, particularly in patients with RA or chronic joint disease, meningococcal infections, or overwhelming sepsis.¹⁷ Other physical signs, such as edema, tenderness, and decreased range of motion, have not been adequately evaluated for their prognostic value.

Diagnostic Strategies.: Laboratory evaluation typically includes complete blood cell count, ESR, and CRP level, although in one study a WBC count above 10,000/µL and an ESR above 30 mm/hr only minimally increased the likelihood of septic arthritis.²⁸ Furthermore, systematic reviews show insufficient evidence for a normal CRP level, ESR, WBC count, or procalcitonin level to rule out septic arthritis.^29,30 Serum blood cultures reveal the causative organism approximately 25 to 50% of the time.^31,32

Radiographs demonstrate only soft tissue swelling if it is present; the bone changes of septic arthritis are long-term findings and are not usually present on the initial examination. Radiographs are recommended to assess for osteomyelitis or as a baseline for future comparisons.

The only definitive diagnostic test for septic arthritis is synovial fluid analysis. The fluid WBC count is directly proportional to the probability of a septic joint. Polymorphonucleocyte concentrations above 90% are also associated with an increased likelihood for septic arthritis. Synovial lactate levels greater than 5.6 mmol/L have an LR+ of 2.4 to infinity; smaller values make septic arthritis unlikely.³³ Synovial lactate dehydrogenase (LDH) levels above 250 U/L are sensitive for septic arthritis, according to one study,¹⁶ whereas LDH levels below this seem to exclude septic arthritis. Low synovial glucose and high protein concentrations are neither sensitive nor specific for septic arthritis.³² Gram’s stain will show bacteria in 50 to 80% of infected joints.¹⁷ Synovial fluid cultures for both aerobic and anaerobic organisms should be performed.

Management.: The key to successful treatment of nongonococcal septic arthritis is early diagnosis. Substantial delays in diagnosis directly worsen prognosis. Empirical antibiotic therapy is based on Gram’s stain or the presumptive consideration of likely organisms. Once the diagnosis is made, hospital admission is indicated for administration of intravenous antibiotics and needle, arthroscopic, or open drainage of the affected joint.³⁴ Whereas the utility of performing or omitting joint drainage has not been prospectively studied, retrospective reviews suggest good cure rates with drainage, with outcomes dependent on initial severity.³⁵ More severe cases require frequent, potentially daily joint aspirations.

There are no randomized controlled trials of antibiotic regimens in septic arthritis. Antibiotic selection is initially based on Gram’s stain results and then adjusted on the basis of final culture results and sensitivities. For gram-positive organisms, the initial drug of choice is vancomycin 30 mg/kg daily in two divided doses as MRSA is frequently causative.²⁴ For gram-negative bacilli, use a third-generation cephalosporin, such as ceftriaxone 2 g IV once daily, cefotaxime 2 g IV three times a day, or ceftazidime with gentamicin (especially if Pseudomonas infection is suspected). Although no trials of antibiotic duration have been reported, antibiotic therapy is generally continued parenterally for 2 to 4 weeks, depending on the response, and followed with 2 to 6 weeks of oral antibiotic therapy.

The failure to respond to therapy within a few days of hospitalization, the presence of osteomyelitis, the involvement of the hips or shoulders, or the involvement of any prostheses usually mandates open arthrotomy for drainage. Parenteral opioid analgesics and immobilization are recommended for pain and discomfort.

Principles of Disease.: Gonococcal arthritis was considered the most common infective arthritis in the United States in the 1970s and 1980s and remains the most common form of joint infection in the sexually active population. In recent years, the incidence has decreased, most likely because of a general decline of N. gonorrhoeae prevalence, particularly of the more virulent strains.³⁶ Host risk factors for dissemination of gonococcal infection to joints include pregnancy, menstruation, and complement deficiency. There is a 4 : 1 female predominance, possibly explained by mucosal infections more often being asymptomatic in women.

Gonococcal arthritis represents a clinical and pathologic course distinctly different from that of other bacterial infections and is less likely to create long-term joint disease.²⁵

Clinical Features.: Systemic gonococcal infection complicates 0.5 to 3% of mucosal infections and is manifested with two somewhat overlapping musculoskeletal syndromes. The first is a localized septic arthritis, more commonly oligoarthritis than monarthritis, predominantly in the wrist, knee, or ankle. The effusions may be modest. True disseminated gonococcal infection (sometimes termed arthritis-dermatitis syndrome) is manifested with bacteremia, diffuse migratory arthralgias, characteristic skin lesions, and tenosynovitis (Fig. 116-4). A similar syndrome has recently been recognized as a result of Neisseria meningitidis infection.³⁷

Management.: Microbiologic diagnosis is a problem because both synovial and blood cultures are positive for gonococcus in no more than 10 to 50% of cases.²⁵ The diagnostic yield is higher when specimens are plated on Thayer-Martin medium and even greater with the use of polymerase chain reaction. Synovial fluid often yields a positive Gram’s stain result, and the synovial WBC count tends to be lower than in nongonococcal arthritis (40,000-60,000 cells/mm³). Cervical, urethral, rectal, and pharyngeal cultures are positive in up to 75% of cases, so all mucosal orifices of the patient (and partner, if possible) should be cultured appropriately.³⁶ In disseminated gonococcal infection, the skin lesions often contain the gram-negative diplococcus.

The current Centers for Disease Control and Prevention (CDC) guidelines recommend hospitalization, especially if etiology or compliance is uncertain, and treatment with intramuscular or intravenous ceftriaxone 1 g every 24 hours or intravenous ceftizoxime or cefotaxime 1 g three times daily, with transition to oral cefixime 400 mg twice daily for at least a week.³⁸ Partners should be evaluated. Presumptive treatment of Chlamydia is also advised.

Repeated therapeutic arthrocentesis need not be as aggressively used in this form of septic arthritis. With prompt antibiotic therapy, residual joint problems are uncommon.