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Calcium pyrophosphate dihydrate crystal deposition in and around the atlantoaxial joint: association with type 2 odontoid fractures in nine patients.

PURPOSE: To investigate the histopathologic anatomy of calcium pyrophosphate dihydrate (CPPD) crystal deposition in and around the atlantoaxial joint and the association between CPPD crystal deposition and subchondral cysts, erosions, and fracture involving the odontoid process of the axis. MATERIALS AND METHODS: One adult cadaver demonstrating calcification in the retro-odontoid area at computed tomography (CT) was selected for further radiography, CT, and magnetic resonance (MR) imaging at the C1-2 level. Anatomic sectioning and histologic evaluations were performed in the specimen. For clinical study, radiographs (n = 5), CT scans (n = 8), and MR images (n = 6) in nine patients (mean age, 74.4 years) with odontoid process fractures and CPPD crystal deposits in and around the atlantoaxial joint were reviewed. RESULTS: In the cadaveric specimen, radiography and CT demonstrated calcifications in the transverse ligament; histologic evaluation confirmed that these calcifications were CPPD crystal deposits. In all nine patients, radiography (n = 5) and CT (n = 8) also showed calcification in areas adjacent to the odontoid process, which included the transverse ligament. T1- and T2-weighted MR imaging showed a retro-odontoid mass of low signal intensity that compressed the cervical cord in six patients. CT, MR imaging, or both demonstrated subchondral cysts, osseous erosions, or a type 2 odontoid fracture in all patients. CONCLUSION: CPPD crystal deposition disease involving the C1-C2 articulation can be a clinically important entity that may place affected patients at increased risk of pathologic fracture of the odontoid process.

Aged↗

Up-regulated expression of cartilage intermediate-layer protein and ANK in articular hyaline cartilage from patients with calcium pyrophosphate dihydrate crystal deposition disease.

OBJECTIVE: Excess accumulation of extracellular inorganic pyrophosphate (ePPi) in aged human cartilage is crucial in calcium pyrophosphate dihydrate (CPPD) crystal formation in cartilage matrix. Two sources of ePPi are ePPi-generating ectoenzymes (NTPPPH) and extracellular transport of intracellular PPi by ANK. This study was undertaken to evaluate the role of NTPPPH and ANK in ePPi elaboration, by investigating expression of NTPPPH enzymes (cartilage intermediate-layer protein [CILP] and plasma cell membrane glycoprotein 1 [PC-1]) and ANK in human chondrocytes from osteoarthritic (OA) articular cartilage containing CPPD crystals and without crystals. METHODS: Chondrocytes were harvested from knee cartilage at the time of arthroplasty (OA with CPPD crystals [CPPD], n = 8; OA without crystals [OA], n = 10). Normal adult human chondrocytes (n = 1) were used as a control. Chondrocytes were cultured with transforming growth factor beta1 (TGFbeta1), which stimulates ePPi elaboration, and/or insulin-like growth factor 1 (IGF-1), which inhibits ePPi elaboration. NTPPPH and ePPi were measured in the media at 48 hours. Media CILP, PC-1, and ANK were determined by dot-immunoblot analysis. Chondrocyte messenger RNA (mRNA) was extracted for reverse transcriptase-polymerase chain reaction to study expression of mRNA for CILP, PC-1, and ANK. NTPPPH and ANK mRNA and protein were also studied in fresh frozen cartilage. RESULTS: Basal ePPi elaboration and NTPPPH activity in conditioned media from CPPD chondrocytes were elevated compared with normal chondrocytes, and tended to be higher compared with OA chondrocytes. Basal expression of mRNA for CILP (chondrocytes) and ANK (cartilage) was higher in both CPPD chondrocytes and CPPD cartilage extract than in OA or normal samples. PC-1 mRNA was less abundant in CPPD chondrocytes and cartilage extract than in OA chondrocytes and extract, although the difference was not significant. CILP, PC-1, and ANK protein levels were similar in CPPD, OA, and normal chondrocytes or cartilage extracts. Both CILP and ANK mRNA expression and ePPi elaboration were stimulated by TGFbeta1 and inhibited by IGF-1 in chondrocytes from all sources. CONCLUSION: CILP and ANK mRNA expression correlates with chondrocyte ePPi accumulation around CPPD and OA chondrocytes, and all respond similarly to growth factor stimulation. These findings suggest that up-regulated CILP and ANK expression contributes to higher ePPi accumulation from CPPD crystal-forming cartilage.

Adult↗

Compressive cervical myelopathy due to calcium pyrophosphate dihydrate deposition disease: report of a case and review of the literature.

Calcium pyrophosphate dihydrate (CPPD) deposition disease is an inflammatory arthropathy that is defined by the deposition of CPPD crystals in articular and periarticular structures. The deposition of CPPD in hyaline cartilage and fibrocartilage leads to the chondrocalcinosis that is characteristic of the disease. It can occur independently or in association with any of a number of inflammatory or endocrine disorders. This form of crystal-induced arthritis tends to affect the peripheral joints, particularly the knees, ankles, shoulders, wrists, and second and third metacarpophalangeal joints, but involvement of the lumbar spine is not uncommon. Cervical spine disease due to CPPD deposition is, however, rare. We report a case of compressive cervical myelopathy due to CPPD deposition disease of the cervical spine in a woman with long-standing rheumatoid arthritis. We also, from a review of the English-language literature, describe the collective reported clinical experience with CPPD deposition disease of the cervical spine.

Aged↗

Case report 859: Massive calcium pyrophosphate dihydrate crystal deposition disease involving the wrist joint.

A case of massive calcium pyrophosphate dihydrate crystal deposition disease (MCPDD) is reported. A 41-year-old Japanese man presented with swelling, intermittent pain, and limitation of motion in the wrist. Radiological studies indicated amorphous calcification and bone erosion. MCPDD, although rare, should be included in the list of the differential diagnosis of periarticular calcific diseases.

Adult↗

Calcium pyrophosphate dihydrate deposition disease causing thoracic cord compression: case report.

OBJECTIVE AND IMPORTANCE: Calcium pyrophosphate dihydrate (CPPD) deposition disease is being increasingly recognized. Spinal involvement in CPPD deposition disease is rare. When involved, the cervical and lumbar regions are commonly affected. We report a rare case of CPPD deposition disease that caused thoracic cord compression. CLINICAL PRESENTATION: A 45-year-old woman presented with clinical features suggestive of thoracic cord compression. Radiographic findings were consistent with calcification of the ligamenta flava in the lower thoracic levels causing cord compression. Calcification of the ligamentum flavum is commonly attributed to CPPD deposition disease. Evaluation for conditions that might be associated with CPPD deposition disease proved to be negative. INTERVENTION: Laminectomy with removal of the calcified ligamenta flava was performed. Histopathological examination of the excised ligaments revealed evidence of CPPD crystals. Postoperatively, the patient's spasticity decreased and sensations improved, with no significant improvement in motor power. CONCLUSION: Calcification of the ligamenta flava due to CPPD deposition disease is a rare cause of thoracic cord compression. CPPD deposition disease should be entertained in the differential diagnosis of thoracic cord compression.

Chondrocalcinosis↗

Massive calcium pyrophosphate dihydrate crystal deposition disease: a cause of pain of the temporomandibular joint.

Calcium pyrophosphate dihydrate deposition (CPDD) disease is a disorder that occasionally affects the temporomandibular joint (TMJ) and temporal bone, causing pain (66.6% of cases), swelling (50%), trismus (36.8%), and hearing loss (22.2%). Diagnosis of CPDD is challenging because clinical symptoms and imaging features are not characteristic and may mimic a chondrosarcoma. When the diagnosis of CPDD of the TMJ is under consideration, conventional radiographs of the wrist or the knee may contribute to the final diagnosis. Imaging features of CPDD are discussed with a review of the literature.

Aged↗

The effect of inhibiting topoisomerase I and II on the anti-apoptotic response associated with pro-inflammatory crystals of calcium pyrophosphate dihydrate in human neutrophils.

OBJECTIVE AND DESIGN: To investigate the ability of various topoisomerase I and II inhibitors to reverse the pro-survival effects of calcium pyrophosphate dihydrate (CPPD) crystals on human neutrophils, thereby identifying potential agents that may promote the resolution of neutrophil accumulation typical of crystal associated inflammatory diseases. MATERIALS AND METHODS: Freshly isolated human neutrophils incubated in the presence of CPPD crystals, with or without the pro-apoptotic cytokine TNF-alpha, were pre-incubated in the presence or absence of the topoisomerase I inhibitors camptothecin, nogalamycin or beta-lapachone, or topoisomerase II inhibitors etoposide, doxorubicin or mitoxantrone. Neutrophil respiratory burst was assessed via chemiluminescence, and two quantitative methods were used for the determination of neutrophil apoptosis; cytoplasmic histone-associated-DNA fragmentation assessment, and endogenous caspase 3 substrate (Ac-DEVD-AMC) cleavage. RESULTS: Beta-lapachone and mitoxantrone effectively repressed CPPD crystal associated respiratory burst, whereas the other topoisomerase inhibitors had no inhibitory or stimulatory effect. Camptothecin and all of the topoisomerase II inhibitors induced neutrophil apoptosis, even in the presence of the CPPD crystals that normally repress TNF-alpha-induced and spontaneous apoptosis. CONCLUSIONS: These results suggest that although topoisomerase II antagonists are distinctively effective agents at reversing the pro-survival effects of crystals on neutrophils, camptothecin was unique as a topoisomerase I inhibitor in that it was significantly more effective as a pro-apoptosis inducer than the topoisomerase II poisons without affecting normal neutrophil activation responses.

Apoptosis↗

Roentgenographic aspects of calcium pyrophosphate dihydrate crystal deposition disease (pseudogout).

A comprehensive review of the roentgenographic features of calcium pyrophosphate crystal deposition disease (pseudogout) is presented. The roentgenographic techniques are reviewed. Those recommended as optimal are as follows: for small peripheral joints, industrial Type M film with contact exposure; for large central joints, direct radiographic magnification (3-4 X) with a microfocus tube. The classic appearances of articular chondrocalcinosis in fibrocartilage, hyaline cartilage, and capsular structures are discussed. Distinctive features of pyrophosphate arthropathy, including the distribution of involvement and the degree of destruction, are emphasized. Finally, the relationship among articular chondrocalcinosis, arthropathy, microscopic crystals, and symptoms is discussed.

Adult↗

Calcium pyrophosphate deposition disease mimicking polymyalgia rheumatica: a prospective followup study of predictive factors for this condition in patients presenting with polymyalgia symptoms.

OBJECTIVE: To assess the characteristics of calcium pyrophosphate deposition disease (CPDD) with proximal involvement mimicking polymyalgia rheumatica (PMR), and to identify the best predictive factors for the presence of a clinical pattern of CPDD in patients presenting with polymyalgia symptoms. METHODS: Patients diagnosed with either PMR or CPDD at the Rheumatology Division of Hospital Meixoeiro (Vigo, Spain) over a 7-year period (1997-2003) were prospectively followed for at least 12 months. RESULTS: The study group comprised 118 patients with PMR features and 112 patients with CPDD. Eighty-two of the 118 patients with PMR manifestations were diagnosed as having pure PMR, and 36 met the diagnostic criteria for both PMR and CPDD. Patients with CPDD mimicking PMR were older (P = 0.02) and had peripheral arthritis more frequently (P = 0.004) than those with pure PMR. Radiologic osteoarthritic changes in the hands and knees, including more advanced radiologic grade of knee osteoarthritis, and tendinous calcifications were more frequent in patients with PMR/CPDD (P < 0.001). The best predictive factors for the occurrence of this atypical pattern of CPDD in a patient presenting with PMR features were the age at diagnosis and the presence of tibiofemoral osteoarthritis, tendinous calcifications, and ankle arthritis. CONCLUSION: Involvement of proximal joints may be the clinical presentation of CPDD. CPDD should be included in the spectrum of diseases mimicking PMR. The presence of tibiofemoral osteoarthritis, tendinous calcifications, and ankle arthritis are clues that may alert the clinician to the presence of CPDD in an elderly patient presenting with PMR manifestations.

Aged↗

[New knowledge on the calcium pyrophosphate dihydrate (CPPD) crystal deposition disease in the cervical ligamentum flavum].

A case of 64-year-old Japanese woman with cervical radiculomyelopathy caused by the deposition of both calcium pyrophosphate dihydrate (CPPD) and hydroxyapatite crystals in the cervical ligamentum flavum is reported. The patient developed paresthesia in her both hands and gait disturbance in the previous six months. Neurological examination revealed generalized hyperreflexia and hypesthesia in the C7 region. Neuroradiologically, two nodular opacifications were shown in the C3-4 and C5-6 level. CT scan revealed linear and symmetrical calcifications in the C3-4 and nodular calcifications in the C5-6 level. En bloc laminectomy was performed and the patient was discharged from the hospital with improvements of neurological symptoms. Specimens of the spinal laminae and ligamenta flava were studied by light microscopy, scanning electron microscopy (SEM), energy dispersive X-ray microanalysis (X-MA) on SEM, and an X-ray diffraction study was carried out on the crystals. The results showed A. CPPD crystal depositions throughout the ligamenta flava together with a minimal thickening of the ligaments. The deposition was seen in the midzone of the ligaments forming a plate-like distribution and forming lines in the cut surface, the latter coincided well with the CT finding at the C3-4 level. B. The nodule (7 X 6 X 6 mm in size) at the C5-6 level was composed of two crystals, CPPD and hydroxyapatite, the latter being encased by the former. The thickness of the CPPD layer was quite thin varying from 10 to 100 mu. Myelographically, the spinal cord was most severely compressed by the C5-6 nodule. C. Because of the absence of family histories and predisposing factors, the case was considered one of primary or idiopathic CPPD crystal deposition disease. The origin of the deposition of mixed crystals was discussed and it appeared likely that the central part of CPPD crystal deposition had transformed to hydroxyapatite at the C5-6 level. In the literature a considerable number of cases have been reported under the title, "Calcification of the Ligamentum Flavum", and some of them have been shown to have hydroxyapatite deposition. Considering the great similarities in clinical, radiological and histological findings between the so-called "calcification of the lig. fl." and CPPD crystal deposition disease, the present case was the first to clearly indicate that these two conditions belong to a single category, i.e. CPPD crystal deposition disease.(ABSTRACT TRUNCATED AT 400 WORDS)

Calcium Pyrophosphate↗

Tumoral calcium pyrophosphate dihydrate deposition disease. Report of a case with a review of the literature.

In a 56-year-old female patient with a mass at the proximal end of the left third finger for 22 years, the lesion enlarged obviously during the last 4 years. Initial diagnosis was chondroma with malignant change, and disarticulation of the finger was performed. Pathological diagnosis was "secondary chondrosarcoma". Microscopically, the mass contained a large amount of amorphous basophilic phosphate deposits surrounded by fibrous capsule. The pyrophosphate deposits consisted of birefringent needle shaped or rhomboid crystals which can be identified by polarizing microscope. It can be distinguished as tumoral calcium pyrophosphate dihydrate deposition disease, differing from tophaceous pseudogout, tumoral calcinosis and chondrocalcinosis. Nine cases were collected from the literature and the clinical, radiological and pathological features were discussed.

Calcinosis↗

Vertebral involvement in calcium pyrophosphate dihydrate crystal deposition disease. Radiographic-pathological correlation.

The authors conducted a comprehensive radiographic and pathological investigation of more than 1,000 postmortem spinal specimens and documented many examples of calcium pyrophosphate dihydrate crystal deposition disease (CPPD/CDD) in a variety of vertebral structures, including not only the intervertebral disk but also the apophyseal and sacroiliac joints, posterior longitudinal ligament, interspinous and supraspinous ligaments, ligamentum flavum, interosseous sacroiliac ligament, transverse atlas ligament, and posterior median atlanto-axial joint. Such crystal accumulation supports previous reports of abnormal calcification and structural damage on radiographs of the axial skeleton in patients with CPPD/CDD and may explain not only the associated spinal symptoms and signs but also spinal stenosis, spondylolisthesis, and atlanto-axial subluxation.

Calcinosis↗

Calcium pyrophosphate crystal deposition disease and hyperparathyroidism: a controlled, prospective study.

A prospective, controlled study of patients with primary hyperparathyroidism has been carried out to establish the relation of this endocrinopathy to calcium pyrophosphate dihydrate crystal deposition disease. Eight of 26 patients with documented hyperparathyroidism were found to have chondrocalcinosis compared to four of 104 individuals in the control group (p less than 0.01). Two of these eight patients had confirmed pseudogout attacks shortly after parathyroidectomy. Four other patients, including two without chondrocalcinosis, gave a history of typical pseudogout. Patients with hyperparathyroidism and chondrocalcinosis were significantly older than those without the articular lesion (p = 0.006). We could not delineate specific metabolic abnormalities of hyperparathyroidism which contributed to the development of chondrocalcinosis.

Adult↗

Patterns of radiographic abnormalities associated with basic calcium phosphate and calcium pyrophosphate dihydrate crystal deposition in the knee.

Radiographs and synovial fluids from 66 knees representing 59 patients with symptomatic osteoarthritis were evaluated to determine the pattern of radiographic abnormalities associated with basic calcium phosphate (BCP), calcium pyrophosphate dihydrate (CPPD), or both crystals together. Crystals were found in 71% of fluids. In general, CPPD crystals correlated with patient age, while BCP crystals correlated with joint degeneration. Synovial fluid BCP and CPPD crystals were found together more often than either alone. Joint compartment narrowing and osteophytes in three compartments are often associated with BCP crystals.

Aged↗

Fever with acute arthritis in calcium pyrophosphate dihydrate deposition disease: a missed explanation for altered mental status in elderly patients?

Calcium pyrophosphate dihydrate (CPPD) deposition disease is a relatively common condition primarily affecting the elderly. Various clinical presentations ranging from an acute arthritis resembling gout (pseudogout) to fever of unknown origin have been reported. We describe four elderly patients with fever and altered mental status. Each patient underwent an extensive unrevealing work-up. An acute arthritis missed by the health-care team in their initial evaluation was later identified, leading to rheumatologic consultation and subsequent diagnosis of CPPD disease after joint aspiration and synovial fluid analysis. Defervescence and resolution of mental status changes occurred after improvement of the arthritis. Awareness that CPPD disease may present with systemic symptoms, including fever and altered mental status, may assure careful examination of joints and can prevent unnecessary testing and diagnostic delay.

Journal Article↗

Effect on dental caries of a stannous fluoride-calcium pyrophosphate dentrifice in an adult population: one-year results.

The first year of a two-year double-blind clinical trial of the anticaries effectiveness of a stannous fluoride-calcium pyrophosphate (SnF2-CPP) dentifrice as compared to a placebo control dentifrice involved 1,337 adult subjects, 18 to 78 years of age. Adult subjects were examined for dental caries at a baseline examination and after one year of ad lib dentifrice usage by an experienced clinical examiner using a visual-tactile examination and a radiographic evaluation. Results of the study after one year indicate a significant (P < 0.05) 33.3% difference in new caries formation with use of the SnF2-CPP dentifrice as compared to the placebo control based on the DMFS score.

Adolescent↗

Phagocytosis of sodium urate and calcium pyrophosphate crystals by leukocytes of gouty, pseudogouty and health donors.

The initial rates of oxygen consumption and of glucose oxidation via the hexose monophosphate shunt were measured during the phagocytosis of sodium urate and calcium pyrophosphate microcrystals. By applying the kinetics of an enzyme-catalyzed reaction, the affinity of the polymorphonuclear leukocytes for crystals, Km, and the maximum rate, Vmax, were determined. When the comparisons are made between the two kinds of crystals, the differences in Vmax are always significant (p less than 0.02). The lesser phlogistic properties of pyrophosphate crystals stem probably in part from different crystal-protein interactions. The influence of the donor is less marked. Part of the weakly depressed phagocytic activity observed with pseudogouty PMN may be attributed to antiinflammatory drugs.

Adult↗

The tophus in calcium pyrophosphate deposition disease.

A 61-year-old man had a tophus on the third finger of his right hand. There was no history of arthritis, no laboratory abnormality, and no chondrocalcinosis. Crystalline material from the tophus was identified as calcium pyrophosphate dihydrate by x-ray diffraction.

Calcium Pyrophosphate↗