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The high prevalence of pathologic calcium crystals in pre-operative knees.

OBJECTIVE: Calcium pyrophosphate dihydrate (CPPD) and basic calcium phosphate (BCP) crystals are important in the pathogenesis of osteoarthritis (OA) but are under recognized even in end stage disease. We determined the prevalence of these calcium crystals in synovial fluid (SF) of persons undergoing total knee arthroplasty for degenerative arthritis. METHODS: SF samples were obtained from 53 knee joints undergoing total arthroplasty for a pre-operative diagnosis of OA. SF were analyzed via compensated light microscopy for CPPD crystals and a semiquantitative radiometric assay for BCP crystals. Fifty pre-operative radiographs were analyzed and graded according to the scale of Kellgren and Lawrence. RESULTS: Patients had an average age of 70 years at the time of surgery. CPPD and/or BCP crystals were identified in 60% of SF. Overall radiographic scores correlated with mean concentrations of BCP crystals. Higher mean radiographic scores correlated with the presence of calcium-containing crystals of either type in SF Radiographic chondrocalcinosis was identified in only 31% of those with SF CPPD. CONCLUSIONS: Pathologic calcium crystals were present in a majority of SF at the time of total knee arthroplasty. Intraoperative SF analysis could conveniently identify pathologic calcium crystals providing information that may be relevant to the future care of the patient's replaced joint and that of other joints. This information could also potentially aid in predicting the likelihood of the need for contralateral total knee arthroplasty.

Aged↗

"Pseudoseptic" pseudogout associated with hypomagnesemia in liver transplant patients.

Hypomagnesemia has been associated with deposition of calcium pyrophosphate dihydrate crystals in articular structures, causing pseudogout, also known as calcic gout. Occasionally, pseudogout may mimic septic arthritis; this "pseudoseptic" attack may be of especial concern in the immunocompromised host, such as transplant recipient patients, who may be indeed at risk of developing septic arthritis. We report the cases of two patients in whom pseudogout developed after liver transplantation. Synovial fluid appearance and leukocyte counting in synovial fluid mimicked septic arthritis, but calcium pyrophosphate dihydrate crystals were observed. Magnesium depletion before transplantation and further tacrolimus-induced renal magnesium leakage were probably working in these patients.

Arthritis, Infectious↗

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.

Arthritis↗

Radiographic patterns and associations of osteoarthritis of the knee in patients referred to hospital.

OBJECTIVES: To investigate differing patterns and associations of osteoarthritis of the knee in patients referred to hospital. METHODS: Two hundred and fifty two consecutive patients (161 women, 91 men; mean age 70 years, range 34-91 years) referred to hospital with osteoarthritis of the knee underwent clinical, radiographic, and synovial fluid screening. RESULTS: Radiographic changes of osteoarthritis of the knee (definite narrowing with or without osteoarthritic features) were bilateral in 85% of patients. Of 470 knees affected, 277 (59%) were affected in two compartments and 28 (6%) in three compartments. Unilateral and isolated medial tibiofemoral osteoarthritis were more common in men. Calcium pyrophosphate crystal deposition was common (synovial fluid identification in 132 (28%) knees; knee chondrocalcinosis in 76 (30%) patients) and associated with disability, bilateral, multicompartmental and severe radiographic osteoarthritis, marked osteophytosis, attrition, and cysts. Multiple clinical nodes (58 (23%) patients) and radiographic polyarticular interphalangeal osteoarthritis (66 (26%) patients) were associated with a higher frequency of inactivity pain, disability, multicompartmental and severe radiographic change. Forestier's disease predominated in men but showed no other associations. CONCLUSIONS: In a group of patients referred to hospital osteoarthritis of the knee is usually bilateral and affects more than one compartment. Severe and multicompartmental radiographic changes are associated with calcium pyrophosphate crystal deposition, nodal change, and polyarticular interphalangeal osteoarthritis.

Adult↗

The significance of enthesopathy as a skeletal phenomenon.

Enthesophytes and enthesopathy, while easy to define, represent a phenomenon of unclear clinical significance. As the high frequency in skeletal populations suggests that enthesopathy may not be disease-specific, the nature of the reaction was assessed in 872 individuals from a representative skeletal population, subdivided into groups characterized by the presence or absence of rheumatoid arthritis, spondyloarthropathy, calcium pyrophosphate deposition disease and diffuse idiopathic skeletal hyperostosis (DISH). Achilles, plantar fascia, patellar and iliac crest entheses were examined for evidence of calcific overgrowth or "erosions." Enthesophytes were found to be a phenomenon of aging in individuals, and unrelated to the presence of inflammatory arthritis or DISH. The frequency increased with age, independent of sex or the site examined, plateauing in frequency after age 60. Enthesophytes in individuals under age 60 were usually unrelated to any underlying disorder. The absence of effect of underlying forms of arthritis on the frequency of enthesophytes at the patellar, Achilles and plantar sites suggests that mechanical factors outweigh the "enthesis calcifying" impact of such disorders as spondyloarthropathy, calcium pyrophosphate deposition disease and DISH. Individuals with rheumatoid arthritis, however, manifested a less severe iliac crest enthesial reaction, in keeping with the minimal reactive new bone formation characteristic of its erosions. Analysis of Achilles, plantar, and patellar enthesial reactions as a function of underlying inflammatory arthritis or DISH also revealed no significant variation with the underlying process. Cortical discontinuity at enthesial sites was a relatively infrequent phenomenon. While calcaneal discontinuities were originally thought to be erosive in nature, these observations suggest the possibility of tendon avulsion injuries.

Adult↗

[Two patients with pseudogout manifested by severe neck pain].

We reported 2 patients with pseudogout manifested by severe posterior neck pain. Patient 1 was a 78-year-old woman. She had experienced attacks of posterior neck pain several times for 4 years. On July 3, 2001, she developed severe pain in the posterior neck and left acromioclavicular joint, and was admitted to our hospital. On examination, her body temperature was 38.1 degrees C, ESR 140 mm/hr and CRP 14.7 mg/dl. Linear calcifications in meniscus of the right knee and left acromioclavicular joint were observed in roentgenograms. The CT of the cervical spines revealed multiple nodular calcifications in the ligamenta flava at the level of C3-C7. She was treated with NSAIDs, and her symptoms and inflammatory reactions rapidly subsided. Patient 2 was was a 76-year-old man. His clinical courses and laboratory findings were very similar to those of patient 1. Both patients presented here were older than 70, and shared such common clinical findings as back neck pain, fever, elevations of serum ESR and CRP level, and effiveness of NSAIDs. We could not detect any findings that could explain the neck pain and fever in cervical spinal roentgenograms and MRIs. Cerebrospinal fluid examinations showed no abnormalities. We diagnosed them as having cervical arthritis caused by calcium pyrophosphate dihydrate deposition (pseudogout) based on the cervical CT examinations, which showed multiple nodular calcifications in the ligamenta flava. Calcium pyrophosphate dihydrate deposition on cervical spine is very rare, and only 50 patients with this condition have been reported to date. In the literatures, the mean age of patients with cervical spine pseudogout is old (72.3 years old) and 84% of them are females. The ligamenta flava at the level of C3-C6 and transverse ligament of the atlas are most commonly involved. Pseudogout of the cervical spine should be considered as a differential diagnosis when we examine the elderly patients with back neck pain. Cervical spinal CT is the most sensitive and useful examination to diagnose this disease.

Aged↗

Metabolism of extracellular pyrophosphate.

Accumulation of excess inorganic pyrophosphate in cartilage matrix leads to calcium pyrophosphate dihydrate crystal deposits. Recent animal and human studies now support a role for physiologic extracellular pyrophosphate levels in preventing ectopic apatite calcification in joints and extracellular tissues. Extracellular pyrophosphate is likely generated by ectoenzymes and/or is a consequence of transport of intracellular pyrophosphate to the extracellular space. Generation of pyrophosphate by chondrocytes is modulated by aging, several soluble growth factors and cytokines, and transglutaminase. The transduction mechanisms involved in regulating pyrophosphate metabolism include protein kinase C and adenylyl cyclase. It appears that regulation of extracellular pyrophosphate levels within a narrow range is complex and necessary for appropriate mineral homeostasis in articular and nonarticular tissues.

Animals↗

Bilateral shoulder arthroplasty in a patient with pseudogout: a case report.

Pseudogout or calcium pyrophosphate dihydrate deposition disease (CPPD) can be a significant cause of morbidity among many patients. The pathophysiology involves the accumulation of calcium pyrophosphate dihydrate crystals and can be confused with degenerative osteoarthritis. Treatment is usually with NSAIDs. There has been little documentation relating CPPD to joint replacement surgery. We present a case report of a patient who underwent staged, bilateral total shoulder arthroplasty and was found to have pseudogout.

Aged↗

[Arthropathies of the limbs in dialyzed renal failure patients].

During the last few years, articular symptoms have been reported in chronic renal failure patients on maintenance haemodialysis. A prospective study of arthropathies of the limbs was conducted in 73 such patients: 20 had experienced periarthritis, 32 had tendinous calcifications (3 or more in 16 cases), 29 had destructive arthropathies (especially of the hands) and 10 had calcium pyrophosphate dihydrate deposition. The periarthritis attacks were associated with the presence of tendinous calcifications. The destructive arthropathies could be due to calcium apatite microcrystal deposition, but the study provided no direct evidence of this mechanism. However, the pattern of erosive lesions, their location and their possible association with tendinous calcifications in the same joint were suggestive of calcium apatite deposition. Calcium pyrophosphate deposition, which affected the oldest patients, did not seem to be due to chronic renal failure treated with dialysis. The most important arthropathies were found in patients who had been haemodialysed for a long time, although the correlation was not statistically significant. The dialysis pattern did not seem to influence the articular disorders. There were more cases of calcification and periarthritis among patients whose phosphocalcium product (in mg) exceeded 6000, but the difference with other patients was not statistically significant. Periarthritis and arthropathies are truly disabling for these patients.

Calcinosis↗

Studies on in vitro colony formation by mouse bone marrow cells using different inflammatory pleural exudates. Relation to colony stimulating factor (CSF).

An inflammatory exudate obtained in Swiss mice 3 hours after intrapleural injection of dextran was able to increase the number of cultivated peritoneal macrophages in S phase. This exudate was also able to stimulate the formation of colonies from mice bone marrow progenitors of macrophages and granulocytes in methylcellulose culture. The stimulating activity of this acute inflammatory exudate was compared with that of colony stimulating factor (GM.CSF). The qualitative and quantitative results showed that the biological activity of the mitogenic factor of this inflammatory exudate, inflammatory mitogenic factor (IMF) was very close to GM.CSF at optimal concentration, but when used at the same concentration, the exudate was less active than GM.CSF. A stimulating activity was also found with another inflammatory pleural exudate induced by calcium pyrophosphate. The comparative kinetics of the action of the two exudates on CFUc appeared alike but the rise was earlier with calcium pyrophosphate. These results suggest the release of a growth factor for monocyte-macrophage in different acute inflammatory exudates.

Animals↗

[Role of radiology in the diagnosis of joint chondrocalcinosis. Calcium pseudogout].

Chondrocalcinosis is a really frequent clinicopathologic entity, which is caused by the penetration of calcium pyrophosphate dihydrate microcrystals into the structures of the joint, including hyaline cartilages and fibrocartilages--hense its name--as well as the synovial fluid and membrane. Calcium gout, which preferentially appears in the knees, is the most spectacular and characteristic symptom of chondrocalcinosis, expressing a crisis of acute microcrystal synovitis, of which it has all the usual clinical features, and thus simulating uratic gout. The positive diagnosis is based on: a) the radiologic demonstration of articular calcifications in the lining cartilages, forming a continuous or fragmented opaque border on the subchondral bone, from which it is separated by a light space, and/or in the fibrocartilaginous structures (most often the menisci, the symphysis pubis, the disk of the inferior radioulnar joint) where they appear as small, irregular clusters with blurred or cloudy margins. The knee is the most frequent site of calcium impregnation images, both in hyaline cartilages and in fibrocartilages. b) the presence of calcium pyrophosphate microcrystals in the synovial fluid; their nature is usually demonstrated convincingly enough with a conventional light microscope; c) needle biopsy findings of microcrystalline clusters embedded in the synovial membrane, that can be easily identified with routine staining. In practice, demonstrating radiologic signs, when these are characteristic and can be detected in their preferred sites, allows recognizing diffuse chondrocalcinosis in satisfactory safety conditions after a calcium gout crisis, as well as in the presence of the many atypical or misleading symptomatic aspects of this microcystal arthropathy, that will be the subject of a further paper.

Calcium↗

Calcium crystal-associated arthritides.

Articular calcium-containing crystals cause calcium pyrophosphate dihydrate (CPPD) deposition disease, basic calcium phosphate (BCP)-associated syndromes, and calcium oxalate arthritis. During the past year, important contributions have been made to our understanding of CPPD- and BCP-related syndromes. Clinical studies of CPPD deposition disease underscore the importance of extra-articular and spinal CPPD deposits, and question the association between hypothyroidism and chondrocalcinosis. Laboratory reports add key information to our current paradigms of CPPD crystal formation and CPPD-induced inflammation. Several interesting new therapeutic interventions may arise from this work. A case collection of BCP-related syndromes emphasizes the need for considering this diagnosis in young healthy patients with acute arthritis or periarthritis.

Adrenal Cortex Hormones↗

Crystal-induced arthritis.

The identification of monosodium urate crystals in joint effusions of patients with gouty arthritis established that crystals can cause arthritis. Other crystals causing arthritis have also been identified, including calcium, pyrophosphate dihydrate (chondrocalcinosis, pseudo-gout), calcium hydroxapatite crystals (calcific periarthritis, acute arthritis) and depot corticosteroid crystals (which occasionally cause arthritis when injected intra-articularly.) Crystal-induced arthritis is characterized by acute articular inflammation although rarely causing joint destruction or permanent disability. It is important for clinicians because it can mimic more serious joint diseases like septic arthritis or even rheumatoid arthritis. It can be diagnosed with precision and in some types as in gout can be treated effectively. Also, it constitutes one of the best understood articular inflammatory processes and often is the first clinical clue for the presence of curable metabolic or endocrine diseases.

Adrenal Cortex Hormones↗

Tophaceous pyrophosphate deposition with extensor tendon rupture.

Tophaceous deposition of calcium pyrophosphate dihydrate (CPPD) crystals is considered unusual as is deposition within tendon sheaths. Associated tendon rupture is described but is rare. We report a lady with tophaceous CPPD deposition at the wrist, a previously unreported site. Contrary to previous cases, this occurred in the setting of symptomatic, polyarticular, pyrophosphate arthropathy. An additional point of interest was development of associated extensor tendon rupture with features favouring a non-inflammatory mechanism of tendon damage.

Aged↗

Comparison of keratan sulphate concentrations and the size distribution of proteoglycans in the synovial fluid of patients with osteoarthritis and pyrophosphate arthropathy.

In order to evaluate the effect of calcium pyrophosphate dihydrate (CPPD) deposition on articular cartilage catabolism, the proteoglycans released into normal synovial fluid were compared with those in synovial fluid obtained from patients with osteoarthritis (OA), chronic pyrophosphate arthropathy (CPA) and acute pyrophosphate arthropathy (APA). Keratan sulphate (KS) was measured by the modified 1,9-dimethylmethylene blue (DMB) assay in synovial fluids treated with chondroitin ABC lyase. This enzyme was found to eliminate all of the sulphated glycosaminoglycans in synovial fluid except KS. In OA, CPA and APA the concentrations of KS were found to be significantly higher than in normal synovial fluid (NSF) (P less than 0.01). Similar KS concentrations were observed in CPA and APA. In CPA they were significantly higher than in OA (P less than 0.02). The size distribution of proteoglycan fragments varied between different patients with the same disease, but only minor differences were observed in patients with OA and CPA who were matched for age, sex and disease severity. Furthermore, the size distribution of proteoglycan fragments in the acute and chronic phases of pyrophosphate arthritis was similar. Thus although in pyrophosphate arthritis the rate at which proteoglycans are released from the cartilage may be greater than in OA or normal joints, the fundamental processes governing the release of these macromolecules may be the same.

Adult↗

Upper limb pyrophosphate tenosynovitis outside the carpal tunnel.

Three cases of calcium pyrophosphate dihydrate (CPPD) crystal deposits in tendon sheaths outside the carpal tunnel are reported. Crystals were shown by x ray diffraction analysis in one case and by compensated light microscopy in the other two. Surgical excision of the tendon synovial sheath had to be done in two cases (one case with CPPD crystal deposits).

Aged↗

[Clinical manifestations of joint chondrocalcinosis].

Articular chondrocalcinosis is identified by radiological opacity of articular cartilage and fibrocartilage with calcium intensity. This disease is often asymptomatic. The most significant clinical pattern is an acute arthritis, caused by microcrystals of calcium pyrophosphate dihydrate, the so-called pseudo-gout syndrome. Chronic pyrophosphate arthropathy can blend mechanical illness and inflammatory flares. When the X-rays are normal or display ordinary osteoarthritis, arthrocentesis makes the diagnosis thanks to the identification of calcium pyrophosphate crystals by polarizing microscope. Large joints are usually involved but the disease can impair the spine, small joints, tendon sheaths or synovial bursae. Though unpredictable the evolution can be worse than that of common osteoarthritis and strike joints that are usually spared by primary arthrosis. One can even see articular destruction. Thus certain patients may resemble rheumatoid arthritis, others a Charcot joint. The disease does not exist in children. Its outcome before the age of fifty implies the search for familial occurrence or a secondary form (hyperparathyroidism, hypophosphatasia, hemochromatosis, hypomagnesemia). The sporadic, primary chondrocalcinosis is very frequent in old age.

Acute Disease↗

[Chondrocalcinosis of the intervertebral disks].

Intervertebral discs removed in cases of disc herniation were investigated by polarized light microscopy. In about 4% of all cases crystalline deposits were detected. The crystals were characterized by different staining methods, scanning electron microscopy and X-ray diffraction. From the results it is concluded that the crystalline deposits are usually composed of calcium pyrophosphate dihydrate. With regard to the age of the patients it became obvious that there was an increased frequency of crystalline deposits with increasing age. Therefore it is assumed that calcium pyrophosphate deposits in intervertebral discs are an agerelated phenomenon as is known from chondrocalcinosis of other joints.

Aging↗