Synovial xanthomatosis: are there clues to mechanisms for this rare disease?

We report a 64-year-old man with arthritis and nodules to describe that this picture can be caused by normo-lipidemic xanthomas. Light and electron microscopy (EM) plus polymerase chain reaction (PCR) studies were performed for diagnosis and investigation. These showed features typical of xanthomas plus PCR and EM evidence of possible infection with Chlamydia pneumoniae as a pathogenetic mechanism deserving consideration. With such rare diseases, any clues to possible mechanisms seem important to record and thus to encourage future investigations. This uncommon cause of arthritis and nodules had been confused with rheumatoid arthritis by others in this case.

Clinical diagnostic criteria for gout: comparison with the gold standard of synovial fluid crystal analysis.

BACKGROUND: Several classification or diagnostic criteria sets for gout have been proposed but none validated. OBJECTIVE: This small pilot study considered urate crystal identification as the gold standard for diagnosis and compared the clinical aspects of 3 proposed criteria sets with that standard. METHODS: Eighty-two subjects who had synovial fluid analyses in a VA medical center were studied. ARA (ACR), Rome, and New York clinical criteria sets and individual criteria were recorded in the 30 patients who had urate crystals versus the remainder with no urate crystals. RESULTS: Presence of 2 of 3 Rome clinical criteria had the highest positive predictive value at 76.9%. None of the 3 studied criteria sets were more than 70% sensitive or 88.5% specific. The clinical features of the ARA (ACR) preliminary classification criteria had 70% sensitivity and 78.8% specificity. CONCLUSIONS: The various proposed clinical criteria can provide support for a diagnosis or exclusion of gout, but unless improved criteria can be developed crystal identification should remain the gold standard.

Elimination of rheumatoid synovium in situ using a Fas ligand 'gene scalpel'.

Surgical synovectomy to remove the inflammatory synovium can temporarily ameliorate rheumatoid inflammation and delay the progress of joint destruction. An efficient medically induced programmed cell death (apoptosis) in the rheumatoid synovium might play a role similar to synovectomy but without surgical tissue damage. Gene transfer of Fas ligand (FasL) has increased the frequency of apoptotic cells in mouse and rabbit arthritic synovium. In this study, we investigated whether repeated FasL gene transfer could remove human inflammatory synovial tissue in situ and function as a molecular synovectomy. Briefly, specimens of human synovium from joint replacement surgeries and synovectomies of rheumatoid arthritis (RA) patients were grafted subcutaneously into male C.B-17 severe combined immunodeficiency (SCID) mice. Injections of a recombinant FasL adenovirus (Ad-FasL) into the grafted synovial tissue at the dosage of 10(11) particles per mouse were performed every two weeks. Three days after the fifth virus injection, the mice were euthanized by CO2 inhalation and the human synovial tissues were collected, weighed and further examined. Compared to the control adenovirus-LacZ (Ad-LacZ) and phosphate buffered saline (PBS) injected RA synovium, the Ad-FasL injected RA synovium was dramatically reduced in size and weight (P < 0.005). The number of both synoviocytes & mononuclear cells was significantly reduced. Interestingly, an approximate 15-fold increased frequency of apoptotic cells was observed in RA synovium three days after Ad-FasL injection, compared with control tissues. In summary, our in vivo investigation of gene transfer to human synovium in SCID mice suggests that repeated intra-articular gene transfer of an apoptosis inducer, such as FasL, may function as a 'gene scalpel' for molecular synovectomy to arrest inflammatory synovium at an early stage of RA.

Prophylactic effect of highly selective COX-2 inhibition in acute monosodium urate crystal induced inflammation in the rat subcutaneous air pouch.

OBJECTIVE: To examine the ability of rofecoxib prophylaxis to blunt the effect of monosodium urate (MSU) crystal inflammation induced in the rat subcutaneous air pouch. METHODS: Eight rats were used in each of 4 groups. On day one, air was injected subcutaneously to create the pouches and gavage feedings were started with placebo or 2 different doses of rofecoxib. Six days later MSU crystals or saline were injected into the pouches. Twenty-four hours later, rats were examined, sacrificed, and pouch fluid studied. RESULTS: Rofecoxib 15 or 30 mg/kg given for 6 days before MSU crystal injection into rat air pouches significantly suppressed the inflammation following injection of 10 mg crystals (p = 0.001) and tended to suppress the milder inflammation induced by 5 mg MSU. Greater effects on phagocytosis were seen with 30 mg/kg rofecoxib. Tumor necrosis factor-alpha levels in pouch fluid measured by ELISA were not suppressed by the rofecoxib. CONCLUSION: Prophylactic use of this cyclooxygenase 2 (COX-2) selective inhibitor in this pilot study suppressed acute MSU crystal induced inflammation. Effects on cytokines need further investigation. COX-2 inhibitors deserve consideration for prophylactic use in interim gout.

Update on identification of pathogenic crystals in joint fluid.

Crystal identification in joint fluid has been an essential part of diagnosis of joint disease. Recent advances have included progress in crystal identification on stained slides, attention to aspiration techniques, and arthrocenteses of asymptomatic joints. Challenges remain to increase use and optimize techniques.

Are there distinctive inflammatory flares after hylan g-f 20 intraarticular injections?

OBJECTIVE: This survey was designed to examine features of a group of patients with acute painful joint effusions following hylan G-F 20 (Synvisc) knee injections. METHODS: Eight patients with painful local reactions after intraarticular hylan G-F 20 injections for knee osteoarthritis were evaluated clinically, with detailed synovial fluid analysis, and followed for outcome. RESULTS: Leukocyte counts ranged from 3150 to 103,000/mm3. Crystals were seen in one patient. Inflammatory knee effusions occurred from 1 to 48 h after injections, but never with first injections. Synovial fluid volumes were 30 to 71 mm(3). Three patients had shiny clumps (not further characterized) that were noted in leukocytes on Wright stained smears. Most patients were treated with aspiration and depot steroids. Five of the 8 patients had moderate or greater improvement at 6 months. CONCLUSION: The majority of the occasional dramatic episodes of inflammation after hylan G-F 20 injection do not seem to be related to crystals. No detrimental lasting results were noted. The absence of post-hylan flares following the first intraarticular injection in this small series suggests that sensitization to or accumulation of hylan G-F 20 or its breakdown products may play an etiologic role in these flares.