Mixed tophi – Co-occurrence of sodium urate and calcium pyrophosphate dihydrate

Background Although clinical findings, laboratory serum markers, and radiographic images are also used, the purported gold standard or standard reference test for the diagnosis of gout is microscopic analysis of aspirated joint fluid. This observational investigation sought to identify the level of agreement with the microscopic analysis of joint fluid aspirate for the diagnosis of gout in the lower extremity between two departments in a single health-care center. Methods A retrospective medical record review identified consecutive patients seen for suspected gout who underwent diagnostic joint aspiration. Patients were included if a lower-extremity joint synovial fluid sample was obtained and were excluded if they were not independently evaluated by both the departments of rheumatology and pathology. We categorized the documented joint fluid findings into four groups: no crystals, sodium urate crystals, calcium pyrophosphate dihydrate crystals, or both sodium urate and calcium pyrophosphate dihydrate crystals. We defined a “clinically significant disagreement” as one department observing any type of crystals and the other department observing no crystals. Results We observed a clinically significant disagreement rate of 23.26% (intraclass correlation coefficient = 0.496). The department of rheumatology was more likely to observe the presence of crystals in a sample compared with the department of pathology (88.37% versus 65.12%; P = .02). Conclusions These results provide evidence that microscopic analysis of joint fluid aspirate might lack the accuracy and reliability needed to be considered a gold standard diagnostic test for gout in the lower extremity.

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DIFFERENTIAL MEMBRANOLYTIC EFFECTS OF MICROCRYSTALLINE SODIUM URATE AND CALCIUM PYROPHOSPHATE DIHYDRATE

Journal of Experimental Medicine ◽

10.1084/jem.133.1.100 ◽

1971 ◽

Vol 133 (1) ◽

pp. 100-112 ◽

Cited By ~ 72

Author(s):

Walter R. Wallingford ◽

Daniel J. McCarty

Keyword(s):

Synovial Fluid ◽

Time Course ◽

Calcium Pyrophosphate ◽

Erythrocyte Membranes ◽

Calcium Pyrophosphate Dihydrate ◽

Hydrogen Acceptor ◽

Erythrocyte Hemolysis ◽

Reaction Curve ◽

Pyrophosphate Dihydrate ◽

Sodium Urate

Microcrystals of sodium urate produced direct lysis of erythrocyte membranes, as had been described previously for silica. Calcium pyrophosphate crystals induced modest erythrocyte hemolysis, also, and time-course experiments showed a markedly different reaction curve from those produced by silica and urate. Polyvinylpyridine-N-oxide, a strong hydrogen acceptor, was bound from solution to urate and silica, but not to calcium pyrophosphate crystals; this compound effectively blocked urate and silica, but not calcium pyrophosphate or control hemolysis. Dextran and heparin inhibited urate-but not silica-induced hemolysis. If erythrocyte and lysosome membranes react similarly to these particles, then the absence of phagosomes in gouty synovial fluid leukocytes, and the presence of these structures in pseudogout, may be explained.

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Calcium pyrophosphate dihydrate crystal deposition disease

Archives of Internal Medicine ◽

10.1001/archinte.123.6.636 ◽

1969 ◽

Vol 123 (6) ◽

pp. 636-644 ◽

Cited By ~ 7

Author(s):

M. Skinner

Keyword(s):

Calcium Pyrophosphate ◽

Calcium Pyrophosphate Dihydrate ◽

Crystal Deposition ◽

Crystal Deposition Disease ◽

Deposition Disease ◽

Pyrophosphate Dihydrate

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Tumoral calcium pyrophosphate dihydrate deposition disease with bone destruction in the shoulder

Acta Radiologica ◽

10.3109/02841859809172192 ◽

1998 ◽

Vol 39 (3) ◽

pp. 269-272

Author(s):

H. Mizutani ◽

S. Ohba ◽

M. Mizutani ◽

S. Sasaki ◽

K. Ando ◽

...

Keyword(s):

Bone Destruction ◽

Calcium Pyrophosphate ◽

Calcium Pyrophosphate Dihydrate ◽

Deposition Disease ◽

Pyrophosphate Dihydrate

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Newly developed pseudogout arthritis after therapy with MAGE-A4 directed TCR T cells responded to treatment with tocilizumab

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2021-002716 ◽

2021 ◽

Vol 9 (7) ◽

pp. e002716

Author(s):

Sang T. Kim ◽

Jean Tayar ◽

Siqing Fu ◽

Danxia Ke ◽

Elliot Norry ◽

...

Keyword(s):

T Cells ◽

Synovial Fluid ◽

Th17 Cells ◽

Effector Cell ◽

Calcium Pyrophosphate ◽

Calcium Pyrophosphate Dihydrate ◽

Immune Effector Cell ◽

Cell Therapies ◽

Immune Effector ◽

Pyrophosphate Dihydrate

With durable cancer responses, genetically modified cell therapies are being implemented in various cancers. However, these immune effector cell therapies can cause toxicities, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Pseudogout arthritis is an inflammatory arthritis induced by deposition of calcium pyrophosphate dihydrate crystals. Here, we report a case of pseudogout arthritis in a patient treated with MAGE-A4 directed T cell receptor T cells, for fallopian tube cancer. The patient developed CRS and ICANS 7 days after infusion of the T cells. Concurrently, the patient newly developed sudden onset of left knee arthritis. Synovial fluid analyses revealed the presence of calcium pyrophosphate dihydrate crystal. Notably, the pseudogout arthritis was resolved with tocilizumab, which was administered for the treatment of CRS and ICANS. Immunoprofiling of the synovial fluid showed that the proportion of inflammatory interleukin 17 (IL-17)-producing CD4+ T (Th17) cells and amount of IL-6 were notably increased, suggesting a potential role of Th17 cells in pseudogout arthritis after T-cell therapy. To the best of our knowledge, this is the first reported case of pseudogout arthritis after cell therapy. Clinicians, especially hematologists, oncologists and rheumatologists, should be aware that pseudogout arthritis can be associated with CRS/ICANS.

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Calcium Pyrophosphate Dihydrate Crystals Increase the Granulocyte/Monocyte Progenitor (GMP) and Enhance Granulocyte and Monocyte Differentiation In Vivo

International Journal of Molecular Sciences ◽

10.3390/ijms22010262 ◽

2020 ◽

Vol 22 (1) ◽

pp. 262

Author(s):

Nobuyuki Onai ◽

Chie Ogasawara

Keyword(s):

Cell Differentiation ◽

Peripheral Blood ◽

Calcium Pyrophosphate ◽

Hematopoietic Progenitor Cell ◽

Calcium Pyrophosphate Dihydrate ◽

Dependent Manner ◽

Concentration Dependent Manner ◽

Hematopoietic Stem ◽

Cppd Crystal ◽

Pyrophosphate Dihydrate

Calcium pyrophosphate dihydrate (CPPD) crystals are formed locally within the joints, leading to pseudogout. Although the mobilization of local granulocytes can be observed in joints where pseudogout has manifested, the mechanism of this activity remains poorly understood. In this study, CPPD crystals were administered to mice, and the dynamics of splenic and peripheral blood myeloid cells were analyzed. As a result, levels of both granulocytes and monocytes were found to increase following CPPD crystal administration in a concentration-dependent manner, with a concomitant decrease in lymphocytes in the peripheral blood. In contrast, the levels of other cells, such as dendritic cell subsets, T-cells, and B-cells, remained unchanged in the spleen, following CPPD crystal administration. Furthermore, an increase in granulocytes/monocyte progenitors (GMPs) and a decrease in megakaryocyte/erythrocyte progenitors (MEPs) were also observed in the bone marrow. In addition, CPPD administration induced production of IL-1β, which acts on hematopoietic stem cells and hematopoietic progenitors and promotes myeloid cell differentiation and expansion. These results suggest that CPPD crystals act as a “danger signal” to induce IL-1β production, resulting in changes in course of hematopoietic progenitor cell differentiation and in increased granulocyte/monocyte levels, and contributing to the development of gout.

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