Calcium Pyrophosphate Dihydrate Deposition Research Articles

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.

A case of pseudogout without radiographic evidence of chondrocalcinosis.

Articular chondrocalcinosis with both arthritis and abnormal calcium deposition in hyaline and fibrocartilage was first described as a clinical entity in 1958 by Zitnan and Sitaj (9). Subsquently McCarty et al. (3) identified calcium pyrophosphate dihydrate (CPPD) crystals from both synovial fluid and cartilaginous tissues using compensated polarized light microscopy, x-ray diffraction and infrared spectrophotometry in patients with articular chondrocalcinosis and termed CPPD deposition disease or pseudogout. Although a considerable variation of clinical features has been described (1, 4), pseudogout without radiographic evidence of chondrocalcinosis seems to be very rare and also difficult to determine a correct diagnosis. In this paper, a case of pseudogout without radiographic evidence in either involved or distant joints is presented.

Pyrophosphate arthropathy: a clinical and radiological study of 105 cases.

105 consecutive patients who presented to a rheumatologist because of joint disease and who also had evidence of deposition of calcium pyrophosphate dihydrate (CPD) were studied clinically and radiologically. There were 76 women (mean age 73) and 29 men (mean age 62). Of only 18 patients below the age of 60 at presentation 12 were men. The majority of the younger male group suffered from acute attacks of synovitis, and had no clinical or radiological evidence of joint damage. In contrast the older female group had widespread destructive changes. Associated joint disease included generalised osteoarthritis (45), rheumatoid arthritis (8), joint hypermobility (13), previous knee surgery (8), and gout 92). Sixteen patients had received long-term steroid therapy. Severe destructive joint changes were seen in 16 patients. The radiological features in those with rheumatoid arthritis by ARA criteria were atypical. The relationship between CPD deposition and arthritis is discussed in the light of these findings.

Radiologic evaluation of the arthritis foot.

The presence or absence of erosions, periosteal new bone, and osteoporosis, as well as differences in their character and distribution, serve as radiologic clues to the differential diagnosis of the various arthritides that affect the foot. In this article we have emphasized these differences as they pertain to the following conditions: rheumatoid arthritis of adult onset, psoriatic arthritis, Reiter disease, ankylosing spondylitis, rheumatoid arthritis of childhood onset, osteoarthritis, gout, systemic lupus erythematosus, progressive systemic slcerosis, calcium pyrophosphate dihydrate deposition disease, and neuropathic joint disease.

Crystal arthropathies in osteo-arthritis--clinical aspects and laboratory techniques for crystal identification.

Crystal arthropathies are frequent findings in patients with radiographical osteo-arthritis (OA). The associations between cartilage degeneration and crystal deposition of hydroxy-apatite or calcium pyrophosphate dihydrate are not yet understood. However, from the clinical point of view it is important to differentiate synovitis caused by micro-crystals from other symptoms in OA since symptomatic relief is readily obtained with the use of antiphlogistic drugs. Methods to screen synovial fluids for crystals should be introduced in routine clinical practice.

Sacroiliac joint abnormalities in calcium pyrophosphate crystal deposition disease

Three cases of generalized calcium pyrophosphate dihydrate deposition disease and roentgenographic sacroiliac abnormalities (chondrocalcinosis, inflammatory change and degenerative change) are described.

Chairman's remarks

We report a series of 3 cases of tophaceous pseudogout of the temporomandibular joint (TMJ).Three patients, two men and one woman, ranging in age between 60 and 75 years, presented with unilateral painful swelling of the TMJ area associated with limitation of mouth opening.Radiographic and computed tomographic images showed opaque masses in the supracondylar region of the TMJ. The preoperative clinical impression was a “neoplastic lesion” in the 3 cases. Microscopic examination revealed numerous deeply basophilic masses of calcified deposits, exhibiting birefringence under polarized light and morphologically consistent with calcium pyrophosphate dihydrate deposition, referred to in these cases as “tophaceous pseudogout.”Tophaceous pseudogout is a rare benign arthropathy that presents with clinical and radiographic features mimicking neoplastic conditions of the TMJ. Therefore, it is recommended that tophaceous pseudogout be considered in the differential diagnosis when a TMJ is involved with “neoplasm-like” lesions clinically and radiographically.

Crystal-associated arthropathies: what's new in old joints.

Degenerative arthritis in the aged includes two major disease categories--osteoarthritis and the crystal-associated arthropathics. The crystals chiefly involved are monosodium urate (gout) and calcium pyrophosphate dihydrate (CPPD), although several others (e.g., cholesterol, brushite and apatite) have been implicated. This report illustrates how the newer diagnostic techniques such as polarized-light microscopy, analytical electron microscopy and x-ray microdiffraction have augmented knowledge concerning diseases associated with articular crystal deposition. For example, diffraction techniques are required for accurate identification of the apatite crystals found in synovial fluid effusions and in the matrix vesicles of degenerate cartilage. According to ultrastructural studies, monosodium urate crystals found in tophi, joint surfaces and effusions show a distinct morphology. Present in inactive joints, the crystal surfaces are bare; in acute gout, the crystals are covered with mucin, confirming the observation that protein binding to crystals is necessary for inflammation to proceed. CPPD disease is by far the most common crystal-associated arthropathy affeting the aged. The incidence of CPPD deposits in articular tissues increases with age but, in contrast to gout, affects both men and women. The pathogenesis of CPPD disease is a mystery, but factors under investigation include matrix abnormalities, ionic imbalances, and enzyme disorders.

Quantification of human plasma inorganic pyrophosphate

The methodologic variables of the UDPG pyrophosphorylase method for analysis of inorganic pyrophosphate (PPi) levels in biologic fluids are described. Use of a tourniquet in collection of blood specimens elevated plasma PPi levels from 35% to 55% above control values and may explain the differences in published normal values. The sodium pyrophosphate decahydrate used to prepare the standard solution lost 8 waters of hydration after dessication, which could result in the calculation of spuriously elevated PPi levels. Normal plasma PPi concentration was 2.18 muM with a range (95% confidence limits) of 0.58-3.78 muM. Comparison of plasma PPi in normal subjects, patients with primary osteoarthritis, and patients with calcium pyrophosphate dihydrate deposition disease revealed no significant intergroup differences.

Acute Pseudogout in Chronic Renal Failure

Acute pseudogout (calcium pyrophosphate dihydrate deposition disease [CPPD disease]) developed in two patients with chronic renal failure. The disease had atypical features. The calcification of the involved joints was more diffuse than the usual linear stippled calcification. The first patient, age 39, was young to have pseudogout. The second patient had pseudogout and chondrocalcinosis limited to the elbow. Review of wrist roentgenograms of 82 patients (mean age, 49.0 years), undergoing hemodialysis for chronic renal failure revealed three patients (a 3.7% incidence) with chondrocalcinosis. The incidence increased to three of 19 (15.8%) in the patients over the age of 60. Although considered uncommon, pseudogout may cause acute arthritis in chronic renal failure more often than previously suspected. Joint aspiration and identification of CPPD cystals with compensated polarized light microscopy will establish the diagnosis of pseudogout.

Subchondral cysts (geodes) in arthritic disorders: pathologic and radiographic appearance of the hip joint

A comprehensive study of femoral heads of patients and cadavers with osteoarthritis, rheumatoid arthritis, osteonecrosis, and calcium pyrophosphate dihydrate deposition disease allows insight into the radiographic and pathologic appearance of subchondral radiolucencies in these disorders. The term geode, rather than cyst or pseudocyst, may be a more appropriate decription of these lesions. In osteoarthritis, goedes occur on the pressure segment of the femoral head in association with loss of articular space; in rheumatoid arthritis, they are initially noted at the chondro-osseous junction and subsequently involve the entire femoral head. In osteonecrosis, geodes appear in the necrotic segment of the femoral head. In calcium pyrophosphate deposition disease, geodes resemble those in osteoarthritis but are larger, more numerous, and more widespread.

Chondrocalcinosis and haemophilia

Chondrocalcinosis has been found in a wide variety of diseases. Cartilage calcification is commonly noted in patients with haemochromatosis, but it has not been previously reported in haemophilia, although increased levels of iron are present in the joints in both these conditions. The radiographic demonstration of chondrocalcinosis in patients with advanced joint changes due to haemophilia is precluded by the extensive joint narrowing and cartilage damage associated with the repeated haemarthroses. Cartilage calcification in less severely damaged joints of three patients with Factor VII, AHG-deficient haemophilia is described. Inhibition of pyrophosphatase activity by divalent cations as a cause of calcium pyrophosphate dihydrate (CPPD) deposition in cartilage is reviewed. The biomechanics of articular cartilage and the effects of divalent cations on normal cartilage elasticity are discussed. The possibility that both the development of the degenerative joint changes and the associated chondrocalcinosis may occur simultaneously due to the presence of abnormal divalent cations is suggested.

Clinical, Radiographic and Pathologic Abnormalities in Calcium Pyrophosphate Dihydrate Deposition Disease (CPPD): Pseudogout

Clinical, radiographic and pathologic abnormalities in calcium pyrophosphate dihydrate deposition disease (CPPD) (pseudogout) are outlined in an investigation of 85 patients with definite or probable disease and available cadaveric and human surgical material. Pyrophosphate arthropathy produced distinctive roentgenographic abnormalities with were most frequent in the knee, wrist and metacarpophalangeal joints. Although the alterations superficially resembled osteoarthritis, they were frequently more severe and progressive with extensive fragmentation of bone, causing intra-articular osseous bodies. Pyrophosphate arthropathy occurred in unusual locations, such as the radiocarpal compartment of the wrist, elbow, and patellofemoral compartment of the knee. These characteristics allow the radiologist to suggest a probable diagnosis of CPPD even in the absence of articular calcification.

Wrist arthropathy in calcium pyrophosphate dihydrate deposition disease

Calcium pyrophosphate dihydrate deposition disease is associated with chondrocalcinosis and a characteristic radiographic abnormality. In the wrist this abnormality consists of radiocarpal joint narrowing, sclerosis, and subchondral cystic degeneration of the carpal bones. These changes sometimes occur in the absence of chondrocalcinosis. Two investigate the significance of this occurrence, 18 patients with the radiographic abnormality of radiocarpal joint narrowing, sclerosis, and subchondral cystic degeneration were examined. Six had neither local wrist nor distant chondrocalcinosis. Five of the latter had wrist arthrocentesis and 4 had calcium pyrophosphate dihydrate crystals. Calcium pyrophosphate dihydrate deposition disease can occur in the absence of chondrocalcinosis and the diagnosis is strongly suggested by a characteristic radiographic picture.

Crystal deposition joint disease.

Inflammation of joints may be associated with leukocytic phagocytosis of either monosodium urate (MSU) or calcium pyrophosphate dihydrate (CPPD) microcrys­ tals, and a previous review in this series summarized the mechanisms involved in induced inflammation (I). The broader generic term deposition disease was coined to embrace both classic gout (MSU crystal deposition) and pseudogout or chondrocalcinosis (CPPD crystal deposition) (2). With the recogni­ tion of the crystals as a sine qua non, the definition of these conditions was changed from being nonspecific and clinical to specific and crystallographic. Such crystal deposits probably represent final common pathways in either urate or pyrophosphate metabolism. In the case of gout and MSU crystals, a number of primary and secondary biochemical abnormalities leading to hyperuricemia are known and still others are being sought. It is likely that CPPD deposition is also a result of one or more biochemical perturbations. Systemic hyperuricemia resulting from increased synthesis of urate in the liver or decreased excretion by the kidney, or an elevated joint fluid inorganic pyrophosphate (PPj) level are viewed as necessary but not sufficient causes for formation of MSU or CPPD crystals respectively. This review will focus chiefly on PPj metabolism and pseudo gout as several good reviews of uric acid metabolism have appeared recently (3, 4). No attempt will be made at an exhaustive review of the clinical features of pseudogout. The reader is again referred to recent reviews on this subject (5, 6).

Hypophosphatasia associated with calcium pyrophosphate dihydrate deposits in cartilage. Report of a case.

AbstractA 51‐year‐old woman with hypophosphatasia had diffuse bone pain and widespread calcification in articular cartilage. Attacks of monarthritis had occurred for 27 years. Analysis of cartilage from the pubic symphysis revealed calcium pyrophosphate crystals.

Chondrocalcinosis of the knee with gout and rheumatoid arthritis.

X-RAY demonstration of multiple articular chondrocalcinosis has been advanced as a useful preliminary diagnostic sign for pseudogout, a disease marked by deposition of calcium pyrophosphate dihydrate (CPPD) crystals.1 When present, chondrocalcinosis is usually most evident in the knee joint, where in turn the menisci usually are most obviously involved. A recent uncontrolled study by Dodds and Steinbach2 reported meniscal calcification in 10 of 31 patients with gout, 6 of whom had involvement of all 4 menisci. Although these authors noted that the calcium deposits were not as heavy as those in reported cases of pseudogout, their findings have cast some . . .