Crystal deposition arthropathy

Crystal deposition arthropathy

• Pathology from accumulation of crystal formation or deposition in or

  around joints

  • Gout: monosodium urate

  • CPDD, also called pseudogout: calcium pyrophosphate

  • Tumoral calcinosis: calcium apatite

  • Calcium oxalate

• Gout (see Table 1.20)

  • Disorder of purine nucleic acid metabolism, causing hyperuricemia

  • Deposition of monosodium urate crystals in joints

  • Crystals activate inflammatory mediators

    • Inflammatory mediators are inhibited by colchicine.

    • Attacks precipitated by dehydration, excess alcohol or dietary purines, chemotherapy

  • Diagnosis

    • Recurrent acute joint pain

    • Men aged 40–60 years, postmenopausal women

    • Usually lower extremity, great toe (podagra)

    • Crystal deposition as tophi when chronic

      • Ear helix, eyelid, olecranon, Achilles tendon

    • Renal disease or stones—second most common site

  • Radiographic findings

    • Soft tissue swelling early: edema, tophi

    • Punched-out or rat bite periarticular erosions

    • Sclerotic overhanging borders

  • Synovial fluid findings

    • Concomitant septic arthritis must be ruled out

    • WBC count: wide range (5,000–80,000 cells/µL; average, 15,000–20,000 cells/µL), mostly PMNs

       

      Table 1.22

       

      Associations Between HLA Alleles and Susceptibility to Some Rheumatic Diseases

       

       

      Disease	HLA Marker	Frequency (%) in Patients (Whites)	Frequency (%) in Controls (Whites)	Relative Risk
      Ankylosing spondylitis	B27	90	9	87
      Reactive arthritis (Reiter syndrome)	B27	79	9	37
      Psoriatic arthritis	B27	48	9	10
      Inflammatory bowel disease with spondylitis	B27	52	9	10
      Adult rheumatoid arthritis	DR4	70	30	6
      Polyarticular juvenile rheumatoid arthritis	DR4	75	30	7
      Pauciarticular juvenile rheumatoid arthritis	DR8	30	5	5
      	DR5	50	20	4.5
      	DR2.1	55	20	4
      Systemic lupus erythematosus	DR2	46	22	3.5
      	DR3	50	25	3
      Sjögren syndrome	DR3	70	25	6

       

       

      Adapted from Nepom BS, Nepom GT: Immunogenetics and the rheumatic diseases. In McCarty DJ, Koopman WJ, editors: Arthritis and allied conditions: a textbook of rheumatology, ed 12, Philadelphia, 1993, Lea & Febiger.

       

       

      FIG. 1.37 Reactive arthritis (formerly Reiter syndrome).

      (A) Conjunctivitis. (B) Circinate balanitis (urethritis not shown). (C) Oligoarthritis (single knee effusion). (D) Fluffy calcaneal periostitis. (E) Dactylitis (sausage digit).

      From Miller MD et al: Review of orthopaedics, ed 6, Philadelphia, 2012, Saunders; and Wu IB, Schwartz RA: Reiter’s syndrome: the classic triad and more, J Am Acad Dermatol 59:113–121, 2008.

       

    • Yellow, needle-shaped crystals when parallel to compensator (Fig. 1.38A)

    • Strong negative birefringence

  • Treatment:

    • NSAIDs and colchicine (microtubule inhibitor that inhibits mitosis) for acute attack

    • Chronic/maintenance therapy

    • Weight loss, low-purine diet, limit of alcohol intake

    • Probenecid: uricosuric agent

    • Allopurinol: xanthine oxidase inhibitor

    • Febuxostat in renally impaired patients

• Pseudogout (see Table 1.20)

  • Deposition of calcium pyrophosphate dehydrate (CPPD) crystals in joints

  • Associated with lupus, renal dialysis, hemochromatosis,

    hyperparathyroidism, RA, Wilson disease

  • Chondrocalcinosis

  • Calcification within hyaline or fibrocartilage or menisci

  • Seen in pseudogout but also in other conditions

  • Genetic version: ANKH gene mutation

  • Increases extracellular pyrophosphate

  • Synovial fluid findings

    • WBC counts 5000–100,000 cells/µL (average, 24,000 cells/µL)

    • Rhomboid-shaped crystals in WBCs

    • Weakly positively (blue) birefringent when parallel (see Fig. 1.38B)

  • Radiographic findings: fine linear calcification in hyaline cartilage and more diffuse calcification of menisci and other fibrocartilage (triangular fibrocartilage complex, acetabular labrum)

  • Treatment with NSAIDs and, potentially, steroid injection

• Calcium hydroxyapatite crystal deposition disease

  • Apatite is primary crystal of normal bone.

  • Accumulates abnormally in areas of tissue damage or in hypercalcemic or hyperparathyroid states (chronic kidney disease [CKD])

  • Associated with

    • Acute attacks of bursitis/synovitis

    • Severe degenerative joint disease

    • Calcific tendinitis of rotator cuff and hip abductors

  • Destructive arthropathy can occur in the knee and shoulder.

    • Milwaukee shoulder: calcium phosphate deposition with cuff tear arthropathy

• Calcium oxalate deposition

  • Primary oxalosis—rare genetic defect of liver enzymes

    • Alanine glyoxylate aminotransferase (AGT)

    • Glyoxylate reductase (GR)

  • Nephrocalcinosis, renal failure, and death by age 20 years

  • Treatment: liver/kidney transplantation

  • Secondary oxalosis—more common

    • Metabolic abnormalities of chronic renal insufficiency

    • Associated with calcium oxalate arthritis/periarthritis and nephrolithiasis

  • Diagnosis: synovial fluid usually contains fewer than 2000 WBCs/µL.

    • Birefringent bipyramidal crystals (see Fig. 1.38C)

Hemophilic arthropathy ( Fig. 1.39)

• X-linked recessive defect of factor VIII (A) or IX (B); discussed further in Chapter 3, Pediatric Orthopaedics

• Decreased ROM and eventually ankylosis

• Pathophysiology

  • Recurrent bleeds and chronic synovitis

  • Synovial hypertrophy/hyperplasia

  • Iron-laden phagocytic type A synovial cells

  • Synovium destroys cartilage

• Radiographic findings

  • Flat condylar surface and widened notch in knee

  • Inferior patellar squaring

  • Talar flattening in ankle

• Treatment

  • Early: prevention of bleeds/factor replacement

  • Radiation ablation of synovium with yttrium (Y) 90 microspheres and phosphorus (P) 32 colloid

  • Late: arthroplasty

     

     

     

    FIG. 1.38 Synovial fluid crystals. (A) Gout: yellow uric acid parallel to compensator, most common in first metatarsophalangeal joint. (B) Calcium pyrophosphate (dihydrate crystal) deposition disease (CPDD) or pseudogout crystals: blue rhomboid crystals (arrow) most common in knees and wrists.

    (C) Calcium oxalate crystals (arrow) are pyramidal and almost exclusively seen in patients with renal damage and oxalosis. (D) Platelike cholesterol crystals are rare and can be found in inflammatory synovial fluid and in fluids drained from bursas of patients with rheumatoid arthritis, systemic lupus erythematosus, and seronegative spondyloarthropathy. (E) Calcium apatite crystals from tumoral calcinosis on histology slide from tissue.

    From McPherson RA, Pincus MR, editors: Henry’s clinical diagnosis and management by laboratory methods, ed 21, Philadelphia, 2007, Saunders Elsevier; Firestein GS et al, editors: Kelley’s textbook of rheumatology, ed 8, Philadelphia, 2008, Saunders; Courtney P, Doherty M: Joint aspiration and injection and synovial fluid analysis, Best Pract Res Clin Rheumatol 23:161–192, 2013; Martínez-Castillo A et al: Synovial fluid analysis, Rheumatol Clin 6:316–321, 2010; and Topaz O et al: A deleterious mutation in SAMD9 causes normophosphatemic familial tumoral calcinosis, Am J Hum Genet 79:759–764, 2006.