Pseudogout (Calcium Pyrophosphate Deposition Disease)

Definition & Pathophysiology

Associated Metabolic Conditions

• Hyperparathyroidism (↑ PTH → ↑ extracellular Ca²⁺)
• Hemochromatosis (iron deposition alters pyrophosphatase activity)
• Hypomagnesemia (Gitelman syndrome) — Mg²⁺ is a pyrophosphatase cofactor
• Hypophosphatasia (↓ alkaline phosphatase → ↑ inorganic pyrophosphate)
• Hypothyroidism, diabetes, prior joint trauma/surgery

Clinical Presentations

Acute Attack Features

• Most common joint: knee (followed by wrist, elbow, shoulder, ankle)
• Warm, swollen, acutely tender joint — similar to gout
• Patients tend to be older than typical gout patients
• Onset is less abrupt than gout; attacks can persist weeks to months
• ~50% of pseudo-OA patients experience superimposed acute attacks

Diagnosis

Synovial Fluid Analysis (Definitive)

• Crystal morphology: rhomboid-shaped, 0.5–5 μm
• Birefringence: weakly positively birefringent under compensated polarized light (blue when parallel to slow axis — contrast with gout's needle-shaped, negatively birefringent urate crystals)
• Leukocyte count during acute attack: 15,000–30,000 cells/mm³, neutrophil predominance
• ⚠️ Crystals and concurrent infection can coexist — always consider septic arthritis

Robbins Basic Pathology — Fig. 19.41: (A) CPPD deposits in cartilage as amorphous basophilic aggregates. (B) Rhomboid CPP crystals on smear.

Imaging

• Chondrocalcinosis on plain radiograph: linear calcifications in articular cartilage — supportive but not diagnostic; absent in >50% of cases
• Best views: wrists, knees, pubic symphysis
• Hook-like osteophytes at MCPs (unlike the erosions of RA)
• DECT can identify CPPD deposits (distinct from urate on dual-energy CT)

Metabolic Workup (especially in young patients or severe disease)

Crystal Comparison: Pseudogout vs. Gout

Treatment

Acute Attack

1. NSAIDs — first-line for most patients (short high-dose course); may be contraindicated in elderly or those with renal/GI comorbidities
2. Colchicine — effective via inhibition of PMN activity; narrow therapeutic window limits use in elderly
3. Corticosteroids — intra-articular injection (rapid relief after ruling out infection) or systemic oral course
4. Joint aspiration — both diagnostic and provides symptomatic relief

Chronic/Prophylactic

• Low-dose colchicine 0.6 mg twice daily for prevention of recurrent attacks
• NSAIDs for chronic pseudo-OA
• Methotrexate, IL-1 inhibitors, anti-TNF-α — show promise in small studies for refractory or periarticular disease
• Treat underlying metabolic disease (e.g., hyperparathyroidism, hypomagnesemia) — may improve arthritis in those subtypes, though benefit on crystal burden in hemochromatosis is uncertain

Key Points

• CPPD is primarily a disease of the elderly; consider underlying metabolic disease in young patients
• Definitive diagnosis requires synovial fluid crystal identification under polarized light
• Chondrocalcinosis on X-ray is supportive but neither sensitive nor specific
• ~50% of affected individuals develop significant joint damage over time
• No disease-modifying therapy exists; treatment is entirely symptomatic

Septic Arthritis

Definition & Overview

Pathogenesis & Routes of Infection

Microbiology

Risk Factors

Clinical Features

• Onset: Acute (faster than osteomyelitis); the joint becomes exquisitely painful over hours
• Monoarticular in >80% of cases
• Most common joint: Knee (>50%), hip (25%), shoulder (15%) in adults; lower extremity predominates in all age groups
• Fever in >80% of children, ~40% of adults; immunosuppressed patients may be afebrile
• Signs: Swelling, erythema, warmth, exquisite tenderness; joint held in flexion (position of comfort); pain markedly worsened with passive range of motion
• Children: May present with pseudoparalysis or refusal to bear weight
• Polyarticular (<10–20%): seen in RA, SLE, immunocompromised patients — these patients may appear deceptively well but can decompensate rapidly

Synovial Fluid Analysis — Cornerstone of Diagnosis

Harrison's Principles of Internal Medicine — Synovial fluid diagnostic algorithm

Diagnostic Workup

Laboratory

• Blood cultures × 2 — positive in up to 50%; obtain before starting antibiotics
• Serum WBC: leukocytosis in only ~50% of cases — insensitive
• ESR: elevated in ~90%; CRP: useful to track resolution
• Procalcitonin: shows promise but needs further validation
• In young patients/IVDU: urethra/cervix/pharynx/rectal cultures for gonococcal disease
• Metabolic workup if unusual organism suspected: iron studies, complement levels

Imaging

• Plain radiography: usually normal early; provides baseline; may show joint space widening or erosion
• Ultrasound: confirms effusion; guides arthrocentesis of deep joints (hip, sacroiliac)
• MRI with contrast: preferred modality for diagnostic uncertainty and assessment of concurrent osteomyelitis, soft tissue involvement, fibrocartilaginous joints
• CT: useful for sacroiliac or sternoclavicular joints
• Bone scintigraphy: detects infection earlier than other modalities (increased symmetric uptake)

Differential Diagnosis

Treatment

1. Antibiotics — Empirical (Start ASAP After Cultures)

Gram stain guides initial selection; modify when sensitivities return. Duration: 2–6 weeks (typically 4 weeks for S. aureus).

Targeted Therapy (Goldman-Cecil Table)

2. Joint Drainage

• Serial needle aspiration: standard initial approach for most joints; performed daily until clinical improvement
• Arthroscopic irrigation and debridement: preferred for hip (deep joint, difficult needle access); post-ACL reconstruction septic arthritis; failure to respond to needle aspiration
• Open surgical drainage: reserved for life-threatening complications (necrotizing fasciitis), failed arthroscopic management, or anatomically inaccessible joints
• Gonococcal arthritis rarely requires surgery

3. Adjunctive Measures

• Immobilization initially, then early mobilization to prevent contractures
• Dexamethasone (short course) in children may speed symptom resolution
• Treat underlying source (cellulitis, UTI, pneumonia, endocarditis)

Gonococcal Arthritis — Special Considerations

• Most common cause of infectious arthritis in sexually active adults <40 years
• Two presentations:
  1. Purulent monoarthritis (large or distal joints, elbows/knees)
  2. Triad: tenosynovitis + dermatitis (pustular/vesicular skin lesions) + polyarthralgias — associated with bacteremia
• Synovial fluid cultures often negative (positive in only 25–50%); culture pharynx, cervix/urethra, rectum, and blood — PCR of all sites increases yield
• Screen for coexisting STIs (syphilis, HIV, chlamydia, hepatitis B/C)
• Treatment: Ceftriaxone 1g IM/IV q24h until improvement, then oral step-down; consult current CDC guidelines for emerging resistance
• Prognosis: Good — rarely causes joint destruction compared to nongonococcal septic arthritis

Prognosis

• Loss of function occurs in 25–50% of patients even with adequate treatment
• Worse outcomes with: delayed diagnosis, MRSA, prosthetic joints, RA, immunosuppression
• Bacteremia from septic arthritis carries risk of seeding other sites — assess for endocarditis if S. aureus bacteremia is confirmed