Organisms may enter a joint from several routes. The most frequent modes are haematogenous spread, spread from an infected local focus, e.g. osteomyelitis or cellulitis, and direct penetrating injury (Nade 2003).

The most common causative organisms are staphylococcal and streptococcal species with Staphylococcus aureus being the most common (Gupta et al 2001, Kaandorp et al 1997a, Weston et al 1999). Methicillin-resistant staphylococcus aureus (MRSA) septic arthritis is becoming increasingly prevalent (Nixon et al 2007). Gram-negative organisms are less frequently implicated: Haemophilus influenzae is most frequently seen in children. Less frequently encountered organisms include enterobacteria, Pseudomonas aeruginosa and Mycobacterium tuberculosis.

Risk factors for septic arthritis include underlying joint disease (especially rheumatoid arthritis), prosthetic joints, low socioeconomic class, intravenous drug abuse, alcoholism, diabetes mellitus, previous intra-articular injection and cutaneous ulceration (Mathews et al 2007).

The classical presentation of septic arthritis is with a short history of a painful, hot, swollen, tender single joint with reduced range of movement (Mathews et al 2007). The most frequently affected joint is the knee. However, involvement is polyarticular in 22% of cases. Fever may be present but is absent in approximately 50% of cases.

The diagnosis of septic arthritis relies upon prompt aspiration of the affected joint prior to commencing antibiotic therapy (Coakley et al 2006). Gram stain, culture and crystal examination of synovial fluid should be performed. A possible infected prosthetic joint requires referral to an orthopaedic surgeon for aspiration in theatre. Blood cultures should always be taken and may identify a causative organism in 33% of cases (Weston et al 1999). Inflammatory markers such as white cell count, erythrocyte sedimentation rate and C-reactive protein should be measured but may not be raised in a significant number of cases (Gupta et al 2001, Weston et al 1999). The important differential diagnoses of septic arthritis include crystal arthropathies, e.g. gout and pseudogout, haemarthrosis, reactive arthritis and a monoarticular presentation of an inflammatory arthritis (Box 23.1).

As soon as the joint has been aspirated, intravenous antibiotics should be commenced. The choice of antibiotics will usually be guided by local microbiologists and should be modified in light of the results of Gram stain and culture. Conventionally, the duration of intravenous antibiotic therapy is 2 weeks followed by 4 weeks of oral therapy (Coakley et al 2006). Regular aspiration to dryness should be performed and arthroscopic aspiration may be required.

Septic arthritis is associated with considerable mortality and morbidity (Gupta et al 2001, Kaandorp et al 1997b, Weston et al 1999). The mortality of septic arthritis is approximately 11%. Adverse functional outcome is seen in 21–24% of cases. Factors predicting poor outcome include older age, pre-existing joint disease and the presence of synthetic material within the joint (Mathews et al 2007).

The primary risk factor for the development of gout is an elevated serum urate (uric acid) level (SUA) or hyperuricaemia. Uric acid is the end-product of purine metabolism in humans. Hyperuricaemia arises from overproduction or renal under-excretion of uric acid, or a combination of both. As hyperuricaemia develops, and body tissues become super-saturated with urate, the formation of MSU crystals leads to clinical gout.

Several independent risk factors for the development of gout are recognised (Table 23.1). Primary gout occurs almost exclusively in men and displays a familial tendency: several genetic factors have been identified (Cheng et al 2004, Huang et al 2006, Taniguchi et al 2005, Wang et al 2004). Further independent risk factors include hypertension, obesity and lifestyle factors (excess alcohol consumption, especially beer, and a diet rich in animal purines, for example red meat and seafood) (Choi et al 2004a, 2004b, 2005, Mikuls et al 2005). Gout associates with other features of the metabolic syndrome including hyperlipidaemia, insulin resistance and cardiovascular disease (Abbott et al 1988, Mikuls et al 2005). Diuretic therapy and renal failure are risk factors for secondary gout (Choi et al 2005, Mikuls et al 2005). Osteoarthritis (OA) predisposes to local MSU crystal deposition (Roddy et al 2007).

Clinical gout is sub-divided into acute gouty arthritis, interval (intercritical) gout and chronic tophaceous gout. Acute gouty arthritis typically manifests as acute mono-arthritis characterised by severe pain with associated redness, warmth, swelling and tenderness. The first metatarsophalangeal (MTP) joint is affected most frequently followed by the mid-foot, ankle, knee, finger interphalangeal joints, wrist and elbow. Attacks occur rapidly, often overnight, peaking within 24 hours, before resolving completely over a 2–3 week period. A variable period elapses before the next attack occurs (interval gout). With time, attacks become more frequent, more severe and are more often pauci- or polyarticular leading to chronic tophaceous gout characterised by chronic arthropathy and chalky-white subcutaneous deposits of MSU crystals (tophi). Typical sites for tophi include the toes (Fig. 23.1A), Achilles’ tendons, fingers, elbows (Fig. 23.1B) and, less commonly, the helix of the ear.

Figure 23.1 Tophaceous deposits of subcutaneous monosodium urate crystals on (A) the right 2^nd toe (white arrow) and (B) elbow.

Definitive diagnosis of gout requires compensated polarised light microscopy of aspirated synovial fluid or tophaceous material to demonstrate MSU crystals which appear needle-shaped with strong negative birefringence. The differential diagnosis includes septic arthritis, pseudogout, reactive arthritis and palindromic rheumatism (Box 23.1). Crystal arthropathies and septic arthritis can be readily differentiated by crystal examination, Gram stain and culture of synovial fluid.

Measurement of serum urate level (SUA) is an important investigation both to confirm hyperuricaemia and monitor response to treatment. However, the SUA level must be interpreted with caution. Many hyperuricaemic individuals do not develop gout (Campion et al 1987) and SUA is frequently lowered during an attack of acute gout (Schlesinger et al 1997).

Gout is potentially curable. The aim of long-term management is lowering of SUA to facilitate crystal dissolution (Zhang et al 2006).

CPPD deposition is most commonly idiopathic being more common in females and with increasing age. In the context of chronic pyrophosphate arthropathy, it associates with OA (Dieppe et al 1982, Zhang et al 2004). CPPD deposition may also occur as a consequence of metabolic disease; most importantly, haemochromatosis, hyperparathyroidism, hypomagnesaemia and hypophosphatasia (Jones et al 1992). Familial CPPD deposition is uncommon although genetic mutations associating with chondrocalcinosis have been identified (Pendleton et al 2002, Williams et al 2003).

Pseudogout is a common cause of acute monoarthritis in the elderly. As occurs with gout, the joint appears swollen, tender, red and warm. Onset is rapid, peaking within 24 hours, with resolution occurring within 2–3 weeks. The most commonly affected site is the knee followed by the wrist, ankle and shoulder. Systemic upset is common.

Chronic pyrophosphate arthopathy presents with features of OA (chronic pain and stiffness, crepitus, bony swelling and restricted movement) with or without superimposed attacks of acute synovitis. The knee is again the most frequently affected site. Chondrocalcinosis is a common asymptomatic incidental radiographic finding in the elderly.

CPPD crystals can be identified by compensated polarised light microscopy of aspirated synovial fluid as rhomboid or rod-shaped crystals with weak positive birefringence. Plain radiographs may show chondrocalcinosis or the structural changes of OA. Chondrocalcinosis mainly affects fibrocartilage and is most commonly seen at the knee (Fig. 23.2), wrist and symphysis pubis. Screening for haemochromatosis, hyperparathyroidism, hypomagnesaemia and hypophosphatasia is indicated under the age of 55 years and when radiographic chondrocalcinosis is particularly striking and widespread (Wright & Doherty 1997).

Figure 23.2 X-ray of the knee showing tibiofemoral chondrocalcinosis (black arrow), medial compartment loss of joint space and medial osteophytes (white arrows) – pyrophosphate arthropathy.