Pseudogout
- 3. CPPD DEPOSITION DISEASE • The deposition of CPPD crystals in articular tissues is most common in the elderly. • occurring in 10–15% of persons aged 65–75 years and 30–50% of those >85 years. • In most cases this process is asymptomatic, and the cause of CPPD deposition is uncertain.
- 4. • The increase in pyrophosphate production appears to be related to enhanced activity of adenosine triphosphate (ATP) pyrophosphohydrolase and 5’-nucleotidase, which catalyze the reaction of ATP to adenosine and pyrophosphate. • This pyrophosphate could combine with calcium to form CPPD crystals in matrix vesicles or on collagen fibers. • There are decreased levels of cartilage glycosaminoglycans that normally inhibit and regulate crystal nucleation
- 5. • Release of CPPD crystals into the joint space is followed by the phagocytosis of these crystals by monocyte-macrophages and neutrophils, which respond by releasing chemotactic and inflammatory substances. • A minority of patients with CPPD arthropathy have metabolic abnormalities or hereditary CPPD disease.
- 6. • These associations suggest that a variety of different metabolic products may enhance CPPD deposition either by directly altering cartilage or inhibiting inorganic pyrophos-phatases. • Included among these conditions are hyperparathyroidism, hemochromatosis, hypophosphatasia, and hypomagnesemia. • The presence of CPPD arthritis in individuals <50 years old should lead to consideration of these metabolic disorders and inherited forms of disease, including those identified in a variety of ethnic groups
- 7. • Genomic DNA studies have shown a possible location of genetic defects on chromosome 8q or on chromosome 5p in a region that expresses the gene of the membrane pyrophosphate channel (ANKH gene). • Mutations as noted above with CPPD arthritis can increase extracellular pyrophosphate and induce CPPD crystal formation. • Investigation of younger patients with CPPD deposition should include inquiry for evidence of familial aggregation and evaluation of serum calcium, phosphorus, alkaline phosphatase, magnesium, serum iron, and transferrin.
- 8. CLINICAL MANIFESTATIONS CPPD arthropathy may be : • asymptomatic, • acute, • subacute, • or chronic or cause acute synovitis superimposed on chronically involved joints. • Acute CPPD arthritis was originally termed pseudogout by McCarty and coworkers because of its striking similarity to gout.
- 10. Other clinical manifestations of CPPD deposition include 1. induction or enhancement of peculiar forms of osteoarthritis; 2. induction of severe destructive disease that may radiographically mimic neuropathic arthritis 3. Production of symmetric proliferative synovitis, clinically similar to rheumatoid arthritis and frequently seen in familial forms with early onset 4. intervertebral disk and ligament calcification with restriction of spine mobility, mimicking ankylosing spondylitis (also seen in hereditary forms) 5. rarely spinal stenosis (most commonly seen in the elderly)
- 11. • The knee is the joint most frequently affected in CPPD arthropathy. Other sites include the wrist, shoulder, ankle, elbow, and hands. Rarely, the temporomandibular • joint and ligamentum flavum of the spinal canal are involved.
- 12. • If radiographs reveal punctate and/or linear radiodense deposits in fibrocartilaginous joint menisci or articular hyaline cartilage (chondrocalcinosis). • Definitive diagnosis requires demonstration of typical crystals in synovial fluid or articular tissue
- 13. SHOULDER IN CPPD. THERE IS WELL DEFINED CHONDROCALCINOSIS OF THE HUMERAL ARTICULAR CARTILAGE Knee in CPPD. Note chondrocalcinosis of the meniscus and the articular cartilage in the lateral compartment.
- 14. Fig. Frontal radiograph of the wrist shows calcifications of the lunotriquetral ligament (arrowhead) and triangular fibrocartilage (red arrow). Joint space narrowing with sclerosis of the trapezioscaphoid and carpometacarpal joints (yellow arrows) are noted. Note absence of osteophytes. This patient presents with classic radiographic features of CPPD, which include: Chondrocalcinosis Degenerative change without apparent osteophytosis
- 15. • Acute attacks of CPPD arthritis may be precipitated by trauma. • Rapid diminution of serum calcium concentration, as may occur in severe medical illness or after surgery (especially parathyroidectomy), can also lead to pseudogout attacks.
- 16. • 50% of cases, episodes of CPPD-induced inflammation are associated with low-grade fever and, on occasion, temperatures as high as 40°C. • synovial fluid analysis with microbial cultures is essential to rule out the possibility of infection • The leukocyte count can range from several thousand cells to 100,000 cells/μL, the mean being about 24,000 cells/μL and the predominant cell being the neutrophil. • Polarized light microscopy usually reveals rhomboid, square, or rod-like crystals with weak positive birefringence inside tissue fragments and fibrin clots and in neutrophils . • CPPD crystals may coexist with MSU and apatite in some cases.
- 17. INTRACELLULAR AND EXTRACELLULAR CALCIUM PYROPHOSPHATE DIHYDRATE CRYSTALS
- 18. TREATMENT: CPPD DEPOSITION DISEASE acute attacks may last a few days to as long as a month 1. joint aspiration and NSAIDs or by intraarticular glucocorticoid injection may result in return to prior status in <10 days. 2. Frequent recurrent attacks of pseudogout, daily prophylactic treatment with low doses of colchicine may be helpful 3. Severe polyarticular attacks usually require short courses of glucocorticoids.
- 19. • There is no effective way to remove CPPD deposits from cartilage and synovium. • Uncontrolled studies suggest that the administration of antimalarial agents or even methotrexate may be helpful in controlling persistent synovitis. • Patients with progressive destructive large joint arthropathy may require joint replacement.