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Gout and 'pseudogout'. When are arthritic symptoms caused by crystal deposition?

The proper diagnosis of gout and pseudogout (ie, calcium pyrophosphate dihydrate crystal deposition disease) leads to correct treatment. The two disorders can be easily confused and misdiagnosed in certain situations. Thus, in every case, synovial fluid aspiration and microscopic synovial fluid analysis under compensated polarized light should be done to confirm the suspicion of crystal-induced arthropathy. Underlying diseases should always be sought, because many are treatable.

Calcium Pyrophosphate↗

[Identification of crystals in synovial fluid: joint-specific identification rate and correlation with clinical preliminary diagnosis].

The diagnostic clarification of joint effusions of unknown origin is a challenge to every primary-care physician. Important diagnostic procedures are arthrocentesis and analysis of the aspirated synovial fluid. Synovial fluid analysis frequently allows differentiation between harmless effusions due to osteoarthritis and crystal induced inflammation, or the more devastating septic arthritis. 4475 synovial fluids were evaluated retrospectively to calculate the identification rate of crystals compatible with calcium pyrophosphate dihydrate (CPPD) and monosodium urate monohydrate (MSUM). 40.8% (1827) of synovial fluids were taken from females and 59.2% (2648) from males. The frequency of crystal identification varied considerably: 13.2% CPPD crystal identification in females, 10.9% in males; MSUM was identified in 1.5% of females, and in 10.9% of males. The spectrum of joint involvement was nearly identical in CPPD and MSUM positive synovial fluids. Exceptions were the higher frequency of CPPD identification in shoulder joints (CCPD:MSUM = 15.6:1), the higher frequency of MSUM identification in the ankle (MSUM:CPPD = 15.6:1) and the first metatarsophalangeal joints (MSUM:CPPD = 8:1). Clinical suspicion correlated well with crystal identification in MSUM positive samples (60%), but was poor in CPPD positive samples (36%). The poor correlation between clinical suspicion and crystal identification in CPPD positive synovial fluids is explicable by the less characteristic clinical presentation of pyrophosphate arthropathy in contrast to classical gout. A high percentage of crystal identification was found in joints or periarticular swellings in which aspiration is difficult and therefore rare (e.g. tendon sheaths, first metatarsophalangeal and first metacarpophalangeal joints), underlining the importance of synovial fluid aspiration despite the difficulty of arthrocentesis.

Adolescent↗

Synovial osteochondromatosis and pseudogout.

A middle aged male developed recurrent episodic inflammatory effusions of the right knee associated with radiographic findings consistent with osteochondromatosis. Calcium pyrophosphate dihydrate (CPPD) crystals were identified by polarized light and electron microscopy, although chondrocalcinosis was not demonstrated radiographically in this joint or any other locations. Analysis of noninflammatory fluid from the left knee demonstrated apatite crystals. The unique association of CPPD crystals and synovial osteochondromatosis without evidence of chondrocalcinosis and the relationship of these 2 entities is discussed.

Calcium Pyrophosphate↗

Contribution of digit joint aspiration to the diagnosis of rheumatic diseases.

OBJECTIVES: To assess the diagnostic usefulness of digit joint aspiration in patients with involvement of one or more digit joints. PATIENTS AND METHODS: All patients who underwent digit joint aspiration during a rheumatology outpatient visit between 1994 and 1998 were included. Fine needles (25 or 28 G) were used, and the aspirate was immediately examined under the microscope to determine the leukocyte count and to look for crystals under polarized light. RESULTS: Digit aspiration yielded a diagnosis of crystal deposition arthropathy in 20 (29%) of the 71 patients (gout, N = 14; calcium pyrophosphate dihydrate crystal deposition disease, N = 6). In 28 patients, the amount of fluid was too small to allow analysis. The leukocyte count indicated inflammatory disease in eight of the remaining 23 patients and mechanical disease in 15. CONCLUSION: Fine-needle aspiration of symptomatic digit joints provided the diagnosis in two-thirds of patients.

Adult↗

Inhibitors of articular calcium crystal formation.

The coexistence of calcium phosphate and calcium pyrophosphate crystals in osteoarthritis is a well-described phenomenon. In addition to deposition in articular cartilage, the crystals induce numerous changes to biochemical parameters in the surrounding fluid. This survey discusses crystal-inhibitor interactions whereby defining the molecular structure of crystals assists in an optimal inhibitor design. Crystal growth studies in the presence and absence of a test compound can generate data on crystal face changes. Together with knowledge of the inhibitors' molecular structure, computer modeling can portray crystal-inhibitor interactions. Few inhibitors have been tested in both in vitro and in vivo phases. One exception is phosphocitrate. This compound inhibits both the development of specific calcium crystals and crystal-induced intracellular changes. Animal studies confirm a strong action on pathologic calcification. The recently described phosphocitrate in a mixed calcium and sodium salt, yet to be tested in a guinea pig osteoarthritis model, appears to be an even more powerful inhibitor.

Animals↗

Studies into the mode of action of non-steroidal anti-inflammatory drugs using a model of facsimile synovium.

The effect of non-steroidal anti-inflammation produced in the 6-day old air pouch by carrageenan or calcium pyrophosphate crystals has been examined. The system is a very reproducible way of studying the cellular and vascular components of inflammation. Non-steroidal drugs have different profiles of activity when tested on the inflammation produced with the two irritants. In general, however, the tested compounds showed similar activity on individual models.

Air↗

[Scanning electron microscopy and microcrystals in articular diseases].

The value of scanning electron microscopy (SEM) in the study of crystals in articular diseases is underlined in several cases of examination of joint fluid, or crystal deposits in articular or periarticular tissues obtained by percutaneous or surgical treatment with chemical and crystallographic correlations. Apatite crystals. Two deposits of hydroxyapatite of the rotator cuff were studied by SEM, crystallographic techniques and chemical analysis. SEM study showed spherical aggregates of various size. Urate crystals. Three tophi were observed by SEM, with crystallographic techniques and chemical analysis. Their needle-shape and their great size (20 m) were characteristic. Calcium pyrophosphate crystals. In a case of typical clinical and radiological features, examination of joint fluid, with chemical correlation showed shorter and thicker crystals than those or urate. The precise identification of crystals is based on sophisticated crystallographic techniques such as X-ray diffraction, although SEM allows an accurate and quite simple morphologic study, most often sufficient.

Apatites↗

CPPD crystal deposition disease in patients with rheumatoid arthritis.

The aim of this study was to assess the frequency and the outcome of patients suffering from rheumatoid arthritis in which calcium pyrophosphate dihydrate (CPPD) crystal deposits were found to coexist in synovial fluid analysis. Such association was more frequent than previously believed with CPPD crystals found in 25.8% of 93 patients with rheumatoid arthritis. As a group, a trend toward a worse outcome was suggested by more frequent prostheses of the lower limb.

Adult↗

The relative caries-inhibiting effects of a stannous fluoride dentifrice in a silica gel base.

An unsupervised toothbrushing study involving 1,339 children from 5 to 13 years of age conducted for three years compared two stannous fluoride dentifrices, one in a calcium pyrophosphate base and the other in a silica gel base, with a nonfluoride control dentifrice. The test dentifrice, stannous fluoride in a silica gel base, reduced caries to a significant extent when compared with the nonfluoride control dentifrice.The percentage of reductions ranged from 15% to 25% for whole mouth and interproximal surface indexes. There was no significant difference between the two fluoride dentifrices.

Adolescent↗

[Influence of inflammation on keratinocytes of the palatal mucosa of guinea pigs].

The palatal mucosa of the guinea pig contained in the normal state a certain number of binucleated cells. Injections of substances inducing inflammation (carrageenan, calcium pyrophosphate dihydrate, monosodium urate) were made in order to produce an inflammatory reaction in the palatal mucosa of young male and adult guinea pigs. The percentage of binucleated epithelial cells was estimated at different time intervals after injections. For the three injected substances, a significant increase of the binucleated epithelial cells was noted in the palatal injected mucosa, when compared with a healthy mucosa or a mucosa having been injected with saline.

Animals↗

Promotion of neutrophil adherence to human osteoblasts by microcrystals and f-Met-Leu-Phe.

Human osteoblast-like cells (hOB) stimulated by monosodium urate monohydrate (MSUM) or calcium pyrophosphate dihydrate (CPPD) microcrystals produce the neutrophil chemoattractant IL-8. We investigated whether human neutrophils can adhere to hOB and respond to hOB preactivated by MSUM, CPPD, or by f-Met-Leu-Phe (fMLP). Confluent hOB were coincubated with human blood neutrophils in the presence of MSUM, CPPD or fMLP. MSUM, CPPD, and fMLP stimulated a significant adherence of neutrophils to hOB after a 1h incubation. This effect was not abrogated by pretreating the cells with an anti-CD18 mAb. MSUM stimulated more efficiently the adherence of neutrophils to non-preactivated hOB while CPPD were more efficient when hOB were preactivated. Crystal-free conditioned media from MSUM- or CPPD-stimulated hOB mobilized intracellular free calcium in human neutrophils. Thus, microcrystals were powerful promoters of neutrophil adherence to hOB via a CD18-independent mechanism. The bacterial peptide fMLP also stimulated the adherence of neutrophils to hOB. Functional neutrophil-hOB interactions could be important in bone pathophysiology of crystal- or infection-associated arthritis.

Calcium↗

Crystal deposition disease. Diagnosis by electron microscopy.

The diagnosis of gout and pseudogout has traditionally been established by the identification, in synovial fluid, of monosodium urate and calcium pyrophosphate dihydrate crystals with compensated polarizing light microscopy. In this paper the utility of electron microscopy in establishing these diagnosis in two cases, when the conventional means of synovial fluid analysis had failed to do so, is discussed. The application of ultrastructural analysis of synovial fluid increases diagnostic capability in the crystal deposition diseases, and it is recommended for those patients in whom the more usual studies have not established a diagnosis.

Aged↗

Cervical spine and crystal-associated diseases: imaging findings.

The cervical spine may be specifically involved in crystal-associated arthropathies. In this article, we focus on the three common crystals and diseases: hydroxyapatite crystal deposition disease, calcium pyrophosphate dihydrate (CPPD) deposition disease, and monosodium urate crystals (gout). The cervical involvement in crystal-associated diseases may provoke a misleading clinical presentation with acute neck pain, fever, or neurological symptoms. Imaging allows an accurate diagnosis in typical cases with calcific deposits and destructive lesions of the discs and joints. Most of the cases are related to CPPD or hydroxyapatite crystal deposition; gout is much less common.

Adult↗

What is new about crystals other than monosodium urate?

Recently, attention has focused on the effects of weather conditions and seasonal changes on the incidence of acute microcrystalline events. Acute gout attacks are more frequent during the spring, but seasonal variations in the incidence of acute pseudogout attacks are less clearly defined. Genetic analysis of two unrelated families with calcium pyrophosphate dihydrate (CPPD) crystal deposition disease showed linkage to the short arm of chromosome 5p. Several recent reports show CPPD crystal disease occurring in association with Gitelman syndrome, the hypocalciuric-hypomagnesemic variant of Bartter syndrome. Two signaling pathways, protein kinase C and adenyl cyclase, modulate generation of extracellular pyrophosphate by porcine cartilage chrondrocytes. These transduction mechanisms may provide potential targets for the treatment of CPPD crystal deposition disease. A controlled clinical trial showed ultrasound therapy to be beneficial in the treatment of symptomatic chronic calcific tendinitis of the shoulder. There is evidence that apatite crystals may contribute to cartilage damage in osteoarthritis and that therapeutic interventions to prevent the formation and biologic effects of the crystals may potentially retard the progression of the osteoarthritic process.

Acute Disease↗

Rhesus macaques as an experimental model for degenerative arthritis.

To understand the pathogenesis of degenerative arthritis, an experimental model of the disease in which systemic factors can be investigated is required. This study reviews the evidence that the spontaneous degenerative arthritis in free ranging rhesus macaques at the Caribbean Primate Research Center meets the criteria for such a model. Two forms of degenerative arthritis in rhesus macaques have been identified: osteoarthritis and calcium pyrophosphate dihydrate crystal deposition disease. These diseases resemble spontaneous human arthritis with respect to age, sex, joint histology and cartilage composition. The availability of large numbers of affected primates as well as the availability of age/sex matched controls free of disease are additional factors that make spontaneous degenerative arthritis in rhesus macaques a suitable experimental model for the study of the human disease.

Academies and Institutes↗

Synovial fluid analysis--another look at the mucin clot test.

We analyzed the relationship between the mucin clot test and the synovial fluid (SF) leukocyte count in osteoarthritis, rheumatoid arthritis (RA), gout, and calcium pyrophosphate dihydrate crystal deposition disease. Except for RA there was no statistically significant relationship between white count and a tight mucin determination within the disease categories. For low (2 X 10(9) cells/l or less) leukocyte counts, the crystal induced arthropathies had a significantly greater proportion showing a tight reaction than found in the osteoarthritic and rheumatoid fluids. We propose that mucin clot determinations may reflect synovial membrane activity rather than SF leukocyte counts.

Adult↗

Staphylococcal septic arthritis presenting as acute flare of pseudogout: clinical, pathological and arthroscopic findings with a review of the literature.

A patient with primary hyperparathyroidism and known pseudogout presented with an acute flare of the right knee. Gram stain was negative, and many intracellular calcium pyrophosphate dihydrate (CPPD) crystals were seen by both compensated polarized light and transmission electron microscopy. Cultures grew Staphylococcus aureus; the joint was probably seeded by an antecedent skin infection, with enzymatic "strip mining" precipitating acute pseudogout. The patient was refractory to therapy with oxacillin, naproxen, intravenous colchicine, and closed drainage. Arthroscopic debridement with insertion of drainage tubes led to rapid improvement, and offers an alternative to arthrotomy in septic knee arthritis unresponsive to closed drainage.

Aged↗

Cervical spine pseudogout with myelopathy and Charcot joints.

Myelopathy due to calcium pyrophosphate dihydrate (CPPD) crystals in the cervical spine is rare. Neuropathic-like joints are also uncommon manifestations of CPPD crystal disease. We describe a 79-year-old woman with multiple neuropathic joints containing CPPD crystals. She also had a large mass containing CPPD crystals impinging on the cervical spinal cord, causing a myelopathy. She appears to be the first patient with this combination of unusual clinical features with CPPD disease.

Aged↗