Dialysis arthropathy: identification and evaluation of a subset of patients with unexplained inflammatory effusions.

OBJECTIVE: Rheumatic disorders have been reported in patients with chronic renal failure treated with hemodialysis. We identified and evaluated 9 patients undergoing hemodialysis with inflammatory joint effusions not explained by known causes such as gout and bacterial infection. METHODS: Forty-nine consecutive synovial fluid (SF) analyses on 41 dialysis patients were reviewed. Nine with unexplained inflammatory arthritis were studied in detail. SF analysis included polarized light examination, alizarin red S stain, Congo red stain, cultures, transmission electron microscopy, and electron probe elemental analysis. RESULTS: SF leukocyte counts ranged from 4550 to 36,000/mm3 with 44-98% neutrophils. No infections were identifiable in these patients. Findings evaluated as possible factors in the joint inflammation included apatite crystals, iron, lipids, amyloid, and difficult to diagnose nonbacterial infections such as hepatitis C. CONCLUSION: Some highly inflammatory joint effusions in patients undergoing chronic hemodialysis are not due to pyogenic infections and may be attributable to other factors.

Idiopathic destructive arthropathies: clinical, light, and electron microscopic studies.

Rapidly destructive arthritis with relatively noninflammatory joint fluids has been described at shoulders as well as at other large joints under a variety of names in older persons. Because this syndrome frequently is not recognized, we have reviewed our experience with such cases. After excluding patients with known causes such as avascular necrosis, Paget's disease, neuropathic arthropathy, endocrine disorders, radiographic evidence of chondrocalcinosis, and hemodialysis, we have seen 20 such patients who are described in this report. All were over age 67, and 16 were women. Seventeen patients had shoulders involved; 6 had destructive arthritis at the knees. Many other patients had multiple sites affected. Six patients also had erosive osteoarthritis of small joints.All patients had diffuse cartilage loss and juxta-articular bone destruction. Patients had been symptomatic a mean of 3.5 years at the time of the study. Bony sclerosis on x-ray was more common than reported in previous series. Joint effusions were bloody or clear. All fluids had strongly positive alizarin red S positive chunks; apatites were confirmed in all 7 studied by electron microscopy. Nine had calcium pyrophosphate dihydrate crystals. The latter were somewhat more commonly associated with bony sclerosis, but crystal types did not explain all differences seen in x-ray patterns.Destructive arthropathy of the elderly involves many large joints in addition to the shoulders, and some patients also have erosive osteoarthritis of fingers. Although calcium pyrophosphate dihydrate crystals were present in many patients along with apatites, the role of crystals is not clear. Radiographic patterns may be more diverse than previously suggested by some researchers, so that the spectrum of idiopathic destructive arthritis reported may depend on selection criteria. It is important to be aware of this noninfectious cause of severe joint destruction at a variety of joints.

Calcium pyrophosphate dihydrate crystal deposition in synovium. Relationship to collagen fibers and chondrometaplasia.

OBJECTIVE: Reasons for apparent primary deposition of calcium pyrophosphate dihydrate (CPPD) crystals in some synovial membranes have not been systematically examined. We undertook the present study to investigate for and compare possible cellular and matrix factors related to the presence of these crystals in synovium and cartilage. METHODS: Ten synovial membrane specimens and 6 cartilage specimens were obtained at the time of joint surgery from 10 patients with CPPD crystal deposition disease, for light microscopic (LM) and electron microscopic (EM) studies. RESULTS: In all synovial and cartilage specimens, we found many of the small CPPD crystals aligned on or in parallel to collagen fibers, as seen by EM. In 9 of the 10 crystal-containing synovia, we found foci of chondrometaplasia adjacent to CPPD, by LM. In 7 of the synovia, including the one without LM evidence of chondrometaplasia, we observed the presence of chondrocyte-like cells by EM. We did not note any predictable relationship between the crystals and matrix vesicles, either in synovium or in cartilage. CONCLUSION: Our EM findings provide evidence of the relationship of small CPPD-like crystals, presumably early forms, to collagen fibers both in synovium and in cartilage. By LM and EM, we also demonstrate evidence of a close association between chondrometaplasia and CPPD deposits in synovium. We suggest that chondrometaplasia might be responsible for synovial CPPD formation in predisposed patients. Both the collagen fibers and chondrocyte-like cells seem to be involved in the primary formation of CPPD deposits in the synovium as well as in the cartilage.

Pseudoseptic arthritis: an unusual presentation of neuropathic arthropathy.

A 49 year old black man with scoliosis presented with bilateral shoulder swelling eventually shown to be due to neuropathic arthropathy related to underlying syringomyelia. The synovial fluid was highly inflammatory, but cultures from synovial fluid and synovial tissue were all sterile. Profuse fat droplets were noted and considered as a possible cause of the inflammation. This is an unusual presentation of neuropathic arthropathy in a patient who was also harbouring an adenocarcinoma that was undetected until later.

Supravital staining of cells in noninflammatory synovial fluids: analysis of the effect of crystals on cell populations.

Leukocyte differential counts are rarely performed on synovial fluids (SF) with low leukocyte (WBC) counts as they have been difficult to do with standard Wright stains. We performed SF analysis including supravital (SV) stains for differential counts on 100 consecutive relatively noninflammatory synovial fluids defined as any SF with less than 2,000 cells/mm3. SV stains gave clear cellular morphology. Monocytes were the most prominent cells in all noninflammatory synovial fluids. Thirty-eight fluids were found to have crystals (monosodium urate (MSU) in 15, calcium pyrophosphate dihydrate (CPPD) in 5, CPPD plus apatite-like crystals in 9, apatite-like clumps alone in 8 and lipid liquid in 1). WBC counts, percentages of polymorphonuclear (PMN) and absolute PMN counts were greatest in fluids with MSU or CPPD crystals. Fluids with apatite-like clumps alone tended to have the lowest WBC counts. The presence of WBC over 500 cells/mm3, over 20% PMN and absolute PMN counts over 250 cells/mm3 should encourage a careful search for crystals, especially MSU, in noninflammatory synovial fluids.

Light and electron microscopic studies on the synovial membrane in Reiter's syndrome. Immunocytochemical identification of chlamydial antigen in patients with early disease.

Studies by light microscopy on synovium obtained from 11 patients with Reiter's syndrome during the first month of an episode showed proliferation of synovial lining cells, polymorphonuclear neutrophils among the synovial lining cells, increased surface fibrin, and vascular congestion. Biopsy specimens taken later showed vascular congestion and still proliferated synovial lining cells, fewer polymorphonuclear neutrophils in some, and a tendency toward increased infiltration with lymphocytes and plasma cells. Electron microscopy of samples from 8 patients during the first month of disease activity showed occlusion of vessels by platelets in 4, and fibrin or dense granular material in the vessel walls in 4. Five of the patients with arthritis of less than 4 weeks duration had unidentified intracellular and extracellular particles; some of these were highly suggestive of Chlamydia. No such particles were noted in samples from patients with more chronic cases. Using an antibody to Chlamydia trachomatis and the peroxidase-antiperoxidase technique, immunocytochemistry showed reaction product in synovial macrophages in 2 patients with arthritis of less than 4 weeks duration, but not in the 1 patient studied who had more chronic disease. These studies provide support for dramatic synovial vascular injury consistent with that caused by endotoxin and the presence of chlamydial antigen in synovial macrophages, at least in the early phases of synovitis.

Arthropathy and cutaneous calcinosis in hemodialysis oxalosis.

Recently, calcium oxalate crystals have been identified in the synovial fluid of patients with arthritis and end-stage renal failure. We describe 4 patients who, during the course of long-term hemodialysis, developed calcium oxalate crystal deposits in the synovium and skin. Clinical manifestations included podagra, tenosynovitis, olecranon bursitis, and acute and chronic synovitis of the large joints that were associated with chondrocalcinosis or subchondral bone erosions. Diffuse involvement of the hand, with chondrocalcinosis of the finger joints, miliary calcified deposits in the skin, and artery calcifications, was observed in 3 patients. The fourth patient had erosive arthropathy. Oxalosis secondary to end-stage renal failure in patients treated with long-term hemodialysis can present with articular manifestations that resemble those of gout, pseudogout, and apatite deposition disease. Other characteristic features of the synovitis associated with oxalosis secondary to end-stage renal disease were: predominant involvement of the hand, mild inflammatory changes in the synovial fluid and synovium, and poor response to administration of nonsteroidal antiinflammatory agents.

Gold pneumonitis. A case report with electronmicroscopy and electron probe analysis.

A case of classical RA developed severe interstitial pulmonary disease and respiratory failure while on chrysotherapy. A high concentration of gold was found in lung tissue. Electron microscopic and electron probe examinations confirmed the presence of gold in the interstitial and intra-alveolar macrophages. The clinical course and possible pathogenic mechanism were discussed.

Reproducibility of synovial fluid analyses. A study among four laboratories.

Aliquots from 30 synovial fluids were submitted to 4 laboratories for comparison of leukocyte counts and differential cell counts, and to 3 laboratories for a search for and identification of crystals. Leukocyte counts showed only fair correlation (coefficients of 0.76-0.80) with the reference laboratory. In synovial fluid from 4 patients, there was sufficient difference in leukocyte counts to cause the fluids to be erroneously classified as either "inflammatory" or "noninflammatory". In 12 of 24 fluid specimens examined, percentages of neutrophils fell outside the 95% confidence limits of the value determined by the reference laboratory. In 7 of the 11 patients with crystals reported, discrepancies were found between the reports from 1 or more laboratories. More attention to quality control of synovial fluid analyses is important.

Transmission electron microscopic identification of silicon-containing particles in synovial fluid: potential confusion with calcium pyrophosphate dihydrate and apatite crystals.

Silicon-containing particles were identified by transmission electron microscopy (TEM) in thin sections of two synovial fluids, which also contained calcium pyrophosphate dihydrate (CPPD) crystals, aspirated during acute attacks of pseudogout. Such particles, which are interpreted as probably being artefacts from glassware, were electron dense and similar in appearance to some CPPD or hydroxyapatite crystals.