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Chondrocalcinosis of the temporomandibular joint. A parotid pseudotumor.

Chondrocalcinosis, ie, calcium pyrophosphate dehydrate (CPPD) crystal deposition disease, has a spectrum of clinical manifestations ranging from an absence of symptoms to a severely destructive arthropathy. We recently treated a patient with CPPD deposition adjacent to the temporomandibular joint, which simulated a parotid tumor. The CPPD crystals are weakly positively birefringent under a polarizing microscope. Most frequently they are found roentgenographically as asymptomatic deposits in fibrocartilaginous structures, especially the knee meniscus. A less frequent manifestation is "pseudogout" acute arthritis. Rarely, joint destruction is found.

Calcium Pyrophosphate↗

Chondrocalcinosis of the temporomandibular joint: an external ear canal pseudotumor.

An unusual case of calcium pyrophosphate arthropathy (pseudogout) involving the temporomandibular joint of a 53-year-old woman presented clinically as an ear canal tumor. Further evaluation and surgical exploration disclosed chondrocalcinosis of the temporomandibular joint with involvement of the bones at the left base of the skull. This case report emphasizes the importance of recognizing the lesion by frozen-section examination because excellent results can be obtained by intraoperative curettage of the calcareous deposits and local irrigation with saline solution.

Calcium Pyrophosphate↗

Crystals, inflammation, and osteoarthritis.

Calcium pyrophosphate and apatite crystals are common in osteoarthritic knee effusions. One or the other crystal was found in 60 percent or more of cases. These crystals offer the potential for mechanical effects in cartilage but are also often phagocytized by synovial cells. A low-grade inflammation with release of proteases and other mediators of inflammation may be an important factor in the pain and joint damage of osteoarthritis. Crystal-associated changes may merit specific attention in any future approach to therapy.

Apatites↗

Crystal-induced inflammation, enzyme release and the effects of drugs in the rat pleural space.

The pleural space of the rat has been used to study the acute inflammatory response to crystals of monosodium urate monohydrate, calcium pyrophosphate dihydrate and hydroxyapatite. Each crystal caused a brisk inflammatory response accompanied by crystal phagocytosis and release of lysosomal enzymes. These responses were modified by the anti-inflammatory drugs indomethacin, dexamethasone, colchicine and cyclophosphamide. The results of these experiments suggesting that the resting cell population of the pleural space contributed to the response, and that lysosomal enzyme release may play only a minor role in the mediation of increased vascular permeability.

Acid Phosphatase↗

[Osteoarthritis with rice bodies rich in calcium microcrystals. 4 cases with ultrastructural study].

Rice bodies are often found in inflammatory joint fluid specimens, especially from rheumatoid arthritis patients, but have rarely been reported in osteoarthritis. We found rice bodies in knee joint fluid specimens from four of 88 patients with osteoarthritis. There were three males and one female. Age ranged from 61 to 86 years. Three patients had slowly progressive knee osteoarthritis and one had rapidly destructive disease. Abundant, recurrent effusions occurred in all four patients despite one to five local corticosteroid injections per patient and radiation synovectomy in two patients. The joint fluid specimens contained 120 to 320 cells/mm3 and large numbers of rice bodies that stained with alizarin red S. Transmission electron microscopy studies showed that the rice bodies were composed of fibrin and contained numerous intra- and extra-cellular calcium crystals composed of apatite alone in two cases and of a combination of apatite and calcium pyrophosphate dihydrate in the two others. Collagen fibers and fragments of bone and cartilage were present in a few rice bodies. Phagocytic cells, type C synoviocytes, chondrocytes and a few inflammatory cells were also seen. These rice bodies composed mainly of fibrin and apatite may have played a role in the pathogenesis of the recurrent joint effusions in our patients.

Aged↗

Synovial inflammation, crystals, and osteoarthritis.

Inflammation is now generally accepted as a component in the course of most patients with symptomatic osteoarthritis (OA), although the stage at which it occurs and how it affects the course has not been resolved. When joint effusions are present in OA they almost always contain more leukocytes than normal synovial fluid, although often still falling into what was considered a noninflammatory range. Multiple factors can contribute to this low grade inflammation, with crystals being only one of many such factors needing consideration. Crystals of calcium pyrophosphate dihydrate (CPPD) and apatite are more frequent in more severe radiographic OA, but whether these are a result, a contributing factor, or both is not known. Experimental studies and the few clinical observations do not show that either CPPD or apatite consistently cause either inflammation or more rapid destruction in OA. These attempts at correlations are plagued with technical questions about what crystal numbers may be meaningful, and about techniques for crystal identification. Continued efforts are indicated to identify a treatable component of OA.

Apatites↗

Myeloradiculopathy secondary to pseudogout in the cervical ligamentum flavum: case report.

A case of cervical myeloradiculopathy secondary to deposits of calcium pyrophosphate dihydrate (Ca2P2O7 2H2O) (CPPD) crystals in the degenerating ligamentum flavum, with marked granulomatous inflammation, is presented. This uncommon clinical presentation of pseudogout (CPPD deposition disease) was confirmed after surgical removal of a compressive cervical ligamentum flavum. The diagnosis of CPPD crystal deposition was determined by polarized light microscopy and energy-dispersive x-ray microanalysis in frozen sections of the biopsy specimen. A review of seven previously reported cases along with the present case failed to reveal trauma as a causative factor.

Aged↗

Alizarin red S staining of synovial fluid in inflammatory joint disorders.

In 153 patients with mainly inflammatory joint disorders alizarin red S staining was used to detect calcium-containing crystals in synovial fluid (SF). The reproducibility of the results of this staining technique in 207 SF samples proved to be fairly good (65% concordant results after two observations). Electron-microscope studies confirmed the presence of apatite or calcium pyrophosphate dihydrate (CPPD) crystals in 92% of the alizarin red S positive samples, and in 27% of the weakly positive samples. Based on these figures it can be estimated that approximately 16% of SF samples obtained from patients with inflammatory joint disorders contain apatite and/or CPPD crystals. In contrast with other studies, mainly involving patients with degenerative joint disorders, no correlation was found between alizarin red S staining results and either radiological joint destruction (n = 130) or age.

Anthraquinones↗

Evaluating CPPD crystal deposition, an important disease of aging.

Calcium pyrophosphate dihydrate deposition disease is a spectrum of disease including asymptomatic chondrocalcinosis, pseudogout, and chronic arthropathy. Its frequency increases with advancing age and is found very commonly in the aged. Underlying metabolic illnesses are occasionally identifiable. Differentiation from other causes of arthritis that it may mimic is often important and possible on clinical grounds, radiographic examination, and synovial fluid analysis. Prognosis is variable and treatment may include analgesics, nonsteroidal anti-inflammatory drugs, colchicine, and intra-articular corticosteroids.

Aged↗

Proteoglycan components of the intervertebral disc and cartilage endplate: an immunolocalization study of animal and human tissues.

Monoclonal antibodies have been used to study the presence and distribution of various components of the proteoglycan molecule in the intervertebral disc and cartilage endplate. Link protein, hyaluronic acid binding region, keratan sulphate and chondroitin 4- and 6-sulphate have been investigated in tissues from humans and other mammals. Exposure of the carbohydrate and protein epitopes was enhanced by chondroitinase and trypsin pretreatment respectively. The degree of immunoreactivity varied with location, being greater in the nucleus pulposus than the annulus fibrosus with least reactivity in the cartilage endplate. In addition, there was increased staining in the pericellular domains, particularly in adult tissues. Areas of ectopic calcification exhibited very different immunoreactivity, depending on the type of calcium salt present. Calcium hydroxyapatite deposits showed greater staining for 8A4 (link protein), while calcium pyrophosphate deposits demonstrated greater staining for 3B3(-), 7D4(-) and 3D5 than the surrounding non-calcified matrix. Staining for chondroitin sulphate isomer epitopes 3B3(-) and 7D4(-), indicative of modified chondroitin sulphate chains, was greater in human tissues of degenerate than non-degenerate appearance. This suggests that expression of these epitopes may be an indicator of disease and subsequent reparative procedures in intervertebral disc and cartilage endplate, similar to that seen in articular cartilage degeneration.

Adolescent↗

Crystal-neutrophil interactions lead to interleukin-1 synthesis.

Normal human blood neutrophils were studied for their capacity to synthesize and release interleukin-1 (IL-1) species after phagocytosis of triclinic monosodium urate (MSU) and calcium pyrophosphate dihydrate crystals (CPPD). MSU crystals were more potent inducers of IL-1 generation than CPPD or unopsonized zymosan. Microcrystal-stimulated neutrophils characteristically secreted most of the newly synthesized IL-1. Colchicine partly inhibited the secretion of IL-1 by neutrophils during phagocytosis of solid particles. However, colchicine selectively inhibited IL-1 synthesis induced by microcrystals. These results suggest that neutrophil-derived IL-1 may contribute to the pathogenesis of crystal-induced arthritis.

Calcium Pyrophosphate↗

Image alterations in the teaching microscope. A source of error in synovial fluid crystal identification.

An erroneous identification of sodium urate and calcium pyrophosphate crystals in synovial fluid may occur when utilizing compensated polarized microscopy with a dual-viewing-head teaching microscope. This is due to alteration of the observed image orientation with respect to the actual orientation of the crystal in space. By viewing a simple geometric figure through each microscope head, two basic types of image alterations are identified: a 180-degree rotation and a mirror-image transformation. Combinations of these two may also occur. This problem is clarified and illustrated and suggestions are offered to avoid erroneous crystal identification.

Calcium Pyrophosphate↗

Tophaceous pseudogout: a pitfall in the diagnosis of chondrosarcoma.

Tumoral calcium pyrophosphate dihydrate deposition disease (TCPPD, tumoral or tophaceous pseudogout) is a rare nonneoplastic entity which mimics soft-tissue or skeletal malignancy. We present here the fine-needle aspiration cytology findings of a unique case of TCPPD in a 76-yr-old woman, with a large paraischial soft-tissue mass diagnosed as a malignant neoplasm. The difficulty in diagnosing such lesions by fine-needle aspirates is discussed and reviewed in the context of known cases from the literature.

Aged↗

Interleukin 1 (IL 1) as a mediator of crystal arthritis. Stimulation of T cell and synovial fibroblast mitogenesis by urate crystal-induced IL 1.

We reported before that monosodium urate (MSU) crystals were potent stimulators of endogenous pyrogen (EP) production from human and rabbit mononuclear phagocytes, and proposed that this property of MSU crystals may be important in the pathogenesis of gout. EP activity is now attributed to interleukin 1 (IL 1) peptides but IL 1 is not the only pyrogenic monocyte-derived cytokine, since both interferon-alpha (alpha-IFN) and tumor necrosis factor (TNF) are also pyrogenic in rabbits. Using a T cell comitogenic assay based on a murine helper T cell clone that does not respond to IFN or TNF, we now report the release of IL 1 activity from human blood monocytes and synovial fluid mononuclear cells (MNC), following stimulation with MSU crystals. MSU-induced supernatants with IL 1 activity were neutralized with rabbit antiserum to human IL 1 and also stimulated the growth ([3H]thymidine incorporation) of long-term fibroblast-like cell lines derived from human synovial rheumatoid exudate. Two other crystals associated with articular inflammation were tested: hydroxyapatite was a much less potent stimulus compared with MSU crystals, and calcium pyrophosphate dihydrate did not stimulate IL 1 release from human monocytes or synovial fluid MNC. As a model for the inflammatory consequences of acute and chronic overproduction of IL 1, gout is the only sterile inflammatory disease where the local and systemic pathology is compatible with such overproduction; raised IL 1 levels have been found at the site of inflammation, and a necessary etiologic agent, crystalline urate, has been shown unequivocally to be a direct activator of mononuclear IL 1 release.

Adsorption↗

Calcium phosphate microcrystal deposition in the human intervertebral disc.

A variety of crystals have been identified in both normal and pathological connective tissues. Calcium phosphate 'cuboidal' microcrystal deposition has been found, using transmission electron microscopy (TEM), in femoral articular cartilage, where they are distributed as a band 5-50 microm beneath the articular surface. These cuboid microcrystals have been identified as magnesium whitlockite. Our objective was to investigate their presence in the human intervertebral disc. In this study, two degenerate and 15 scoliotic discs were examined using light microscopy and TEM techniques to determine the presence of calcium phosphate crystals. Calcium pyrophosphate dihydrate (CPPD) deposition was identified in one degenerate disc specimen. Using TEM and electron probe analysis, cuboid microcrystals were identified in the annulus fibrosus and nucleus pulposus of both degenerate specimens, but not in the discs from young scoliotic patients. Cuboid microcrystal deposition was found predominantly around cells, which were mainly necrotic, with some association with extracellular lipidic/membranous debris. This is the first TEM report of whitlockite in the intervertebral disc. In one specimen coexistence of cuboid and CPPD crystal deposition was found.

Adult↗

Crystal shedding in septic arthritis: case reports and in vivo evidence in an animal model.

Two cases of coexisting septic and crystalline joint disease are reported. In one patient polyarticular septic arthritis occurred simultaneously with gout and pseudogout. In a second patient septic arthritis preceded the appearance of calcium pyrophosphate dihydrate (CPPD) crystals in the joint fluid, supporting an earlier postulate that lysosomal enzymes released during sepsis lead to shedding of crystals from cartilage and synovium into the joint space. This sequence was demonstrated in a rat air pouch model of synovium, in which CPPD crystals embedded in facsimile synovial tissue were released after injection of pyogenic bacteria. Coexisting septic arthritis should always be considered when crystals are identified in inflamed joints, particularly in elderly patients with concurrent infections.

Aged↗

Transmission electron microscopic studies on articular calcium crystals and associated protein coatings.

Calcium pyrophosphate (CPPD) and apatite crystals are associated with several types of arthritis. Using transmission electron microscopy both the tiny apatite-like crystals and larger CPPD can be seen to be associated with granular materials. With the ferritin bridge technique immunoglobulins and complement are seen in the material with the apatite but not the CPPD. Immunoprotein is seen both intracellularly and extracellularly. Further study of these coatings is needed to ascertain if they have consistent patterns on all crystals and how they affect the ability of the crystals to induce inflammation.

Calcinosis↗

Alizarin red S staining as a screening test to detect calcium compounds in synovial fluid.

A simple, rapid screening method using alizarin red S stain and ordinary light microscopy to detect microcrystalline or noncrystalline calcium phosphate salts was used on wet drop preparations of synovial fluids. This proved to be helpful in detecting apatite crystal clumps and small calcium pyrophosphate dihydrate (CPPD) crystals missed by polarized light. The staining was positive in 100% of synovial fluids from patients later proven to have apatite and/or CPPD deposition diseases. Apatite and CPPD crystals were commonly found together in the same fluids. In addition, some synovial fluids from patients with osteoarthritis, renal failure dialysis, rheumatoid arthritis, and gout also exhibited positive staining. The correlation of positive alizarin red S staining with radiologic evidence of osteoarthritis suggests that apatite crystals might be related to articular cartilage degeneration in different rheumatic diseases.

Anthraquinones↗