Academic literature on the topic 'Microcrystal arthritis'

A 46-year-old man with long-standing, poorly controlled diabetes is hospitalized for right knee monoarthritis after trauma. His clinical evaluation found joint deformity, synovitis in the right knee and absence of multiple toes due to a history of amputation. With the radiological evaluation that showed bone destruction and the synovial fluid analysis that ruled out infectious causes and microcrystal arthritis, the diagnosis of Charcot neuroarthropathy of the knee was made. Conservative management was indicated with the use of a felt insole for unloading and the use of a walker, the case being followed up to define behavior according to evolution. Despite being rare, it is important to consider Charcot neuroarthropathy in all diabetic patients with monoarthritis of the knee, in order to make an early diagnosis and avoid important complications and sequelae, always ruling out infectious causes and arthritis due to microcrystals.

The data accumulated to date suggests that it is extremely rare for a gout patient to have only his or her main disease and no accompanying pathology. One of the frequent situations is a combination with another microcrystal arthritis, a disease of calcium pyrophosphate crystals deposition. In addition, diseases of the kidneys (including chronic renal failure), cardiovascular system, gastrointestinal tract, as well as metabolic disorders directly associated with gout or indirectly related to taking medications necessary to control the disease, not only affect the quality and longevity of life of the patient, but also create difficulties for its curation. The prescription of drug therapy, both symptomatic and pathogenetic, in such cases involves an assessment of all the associated risks, and the choice of drugs, in addition to efficiency, should be based on their safety profile in relation to comorbid pathology. This article analyzes the main principles and approaches to the treatment of gout and the disease of calcium pyrophosphate crystals deposition in the presence of concomitant diseases (arterial hypertension, chronic kidney disease, chronic heart failure, obesity, dyslipidemia, etc.) on the example of a 50-year-old patient. The possibilities of combined symptomatic therapy including colchicine, non-steroidal anti-inflammatory drugs and glucocorticoids are shown. The necessity and tactics of choice of preventive prophylactic therapy for arthritis attacks and use of phebuxostat in the presence of contraindications for prescription or ineffectiveness of allopurinol are also discussed.

Background:Synovial fluid analysis using polarized microscopy is the gold standard for the diagnosis of crystal-related arthritis. In our experience, we have noted that, when calcium pyrophosphate (CPP) crystals are observed, they sometimes appear within intracellular vacuoles. However, this phenomenon is not seen in those samples containing monosodium urate (MSU) crystals. This finding has been scantly reported in the literature, but may be useful in clinical practice to ensure accurate crystal identification.Objectives:Our study aims to assess whether the presence of vacuoles contributes to identifying the type of crystal, and also to gauge the frequency of their presentation.Methods:We conducted an observational study in a rheumatology unit between February and June of 2019. Synovial fluids containing CPP or MSU crystals, obtained in daily clinical practice, were consecutively included for analysis. Two observers simultaneously analyzed the presence of vacuoles by ordinary light and phase contrast microscopy in less than 24 hours after their extraction, using a microscope equipped with two viewing stations. The primary study variable was to determine whether CPP and MSU crystals are seen inside intracellular vacuoles, and to calculate the frequency of this finding for each type of crystal, estimating their 95% confidence interval (95% CI) and comparing rates using Fisher’s exact test.Results:Twenty-one samples were obtained. Data is given in the Table. MSU crystals were present in 7 (33.3%) and CPP crystals in 14 (66.6%). Interestingly, none of the MSU samples showed crystal-containing vacuoles (95% CI 0-35.4%). On the contrary, cytoplasmic vacuoles containing crystals were present in all of the CPP samples (95% CI 78.5-100%). The findings were confirmed by phase-contrast microscopy. Differences were statistically significant (p<0.001).Table.SAMPLES ACCORDING TO TYPE OF MICROCRYSTAL(n=21)SAMPLES WITH VACUOLS(UNDER ORDINARY LIGHT)SAMPLES WITH VACUOLS(UNDER PHASE CONTRAST)CPP (14; 66.6%)14 (100%)(95%CI 78.5-100%)14 (100%)(95%CI 78.5-100%)MSU (7; 33.3%)0 (0%)(95%CI 0-35.4%)0 (0%)(95%CI 0-35.4%)Conclusion:The presence of vacuoles may be a useful and easy way to differentiate MSU and CPP crystals when performing synovial fluid microscopy in clinical practice, since it appears to be a distinctive feature in CPP crystal fluids.References:[1]Kohn NN, Hughes RE, McCarty DJ Jr, Faires JS. The significance of calcium phosphate crystals in the synovial fluid of arthritic patients: the «pseudogout syndrome». II. Identification of crystals. Ann InternMed. 1962 May;56:738-45.[2]Pascual E, Sivera F, Andrés M. Synovial Fluid Analysis for Crystals. CurrOpRheumatol 2011;23:161-169.[3]McCarty DJ, Koopman WJ. Arthritis and allied conditions: A textbook of rheumatology, volumen 1. Lea &amp;Febiger. 1993.[4]Pascual E, Sivera F. Synovial fluid crystal Analysis. En Gout and other crystal arthropathies. Terkeltaub R ed. Elsevier; 2012: p.20-34.[5]Hwang HS, Yang CM, Park SJ, Kim HA. Monosodium Urate Crystal-Induced Chondrocyte Death via Autophagic Process. Int J Mol Sci. 2015 Dec 8;16(12):29265-77.Image 1. Microscopy with ordinary light. Cells with cytoplasmic vacuoles are observed, as well as abundant intra and extracellular CPP crystals.Image 2. Microscopy with phase contrast technique. Cells with intracellular vacuoles are observed inside which have microcrystals with parallelepiped morphology, compatible with CPP.Disclosure of Interests: :None declared

Acute gouty arthritis represents an inflammatory response to microcrystals of monosodium urate that precipitate in joint tissues from supersaturated body fluids or are shed from preexisting articular deposits [1]. Gout is a metabolic disease characterized by recurrent episodes of arthritis associated with the presence of monosodium urate crystals in the tissue or synovial fluid during the attack.These forms of crystal-induced arthritis usually affect peripheral joints, including knee, ankle, wrist, and metacarpophalangeal and metatarsophalangeal joints. All of them may be associated with other inflammatory, endocrine diseases [2]. The present study was done to highlight the relationship between increased levels of uric acid and specific laboratory tests in order to possible forecast development of further disease in patients with gouty arthrithis.The present study was done on 34 patients hospitalized in Felix Hospital of Rehabilitation in 2015-2016, with age between 44 and 74, having the main diagnosis of gouty arthritis.We studied the following laboratory tests:urea and other related analysis, like uric acid, creatinine, cholesterol, glutamate pyruvate transaminase and glutamate oxalate transaminase.

Abstract The formation and deposition of monosodium urate (MSU) microcrystals in articular and periarticular tissues is the causative agent of acute or chronic inflammatory responses known as gouty arthritis. Mononuclear phagocyte activation is involved in early triggering events of gout attacks. Because stimulated mononuclear phagocytes can constitute an important source of the inducible isoform of cyclooxygenase (COX-2), we evaluated the effects that proinflammatory microcrystals might have on COX-2 protein expression in crystal-stimulated monocytes. We found that MSU crystals, but not calcium pyrophosphate dihydrate (CPPD) crystals, induced COX-2, which correlated with the synthesis of prostaglandin E2 (PGE2) and thromboxane A2(TXA2). Crystal-induced de novo synthesis of COX-2 was dependent on transcriptional and translational events. Inhibition of tyrosine phosphorylation, by herbimycin A, blocked crystal-induced COX-2. Similarly, an inhibitor of the p38 mitogen-activated protein kinase, SB 203580, inhibited the stimulation of COX-2. Colchicine inhibited crystal-induced COX-2. In all cases, prostanoid synthesis was concomitantly inhibited. Taken together, these results implicate COX-2 in the development of MSU-induced inflammation.

The formation and deposition of monosodium urate (MSU) microcrystals in articular and periarticular tissues is the causative agent of acute or chronic inflammatory responses known as gouty arthritis. Mononuclear phagocyte activation is involved in early triggering events of gout attacks. Because stimulated mononuclear phagocytes can constitute an important source of the inducible isoform of cyclooxygenase (COX-2), we evaluated the effects that proinflammatory microcrystals might have on COX-2 protein expression in crystal-stimulated monocytes. We found that MSU crystals, but not calcium pyrophosphate dihydrate (CPPD) crystals, induced COX-2, which correlated with the synthesis of prostaglandin E2 (PGE2) and thromboxane A2(TXA2). Crystal-induced de novo synthesis of COX-2 was dependent on transcriptional and translational events. Inhibition of tyrosine phosphorylation, by herbimycin A, blocked crystal-induced COX-2. Similarly, an inhibitor of the p38 mitogen-activated protein kinase, SB 203580, inhibited the stimulation of COX-2. Colchicine inhibited crystal-induced COX-2. In all cases, prostanoid synthesis was concomitantly inhibited. Taken together, these results implicate COX-2 in the development of MSU-induced inflammation.

Introduction. Patients with rheumatoid arthritis (RA) are twice as likely to have osteoporosis (OP) compared to the general population. The strength of bones depends on mineral substances, mainly represented by calcium phosphate microcrystals. The chief role in the regulation of calcium-phosphorus metabolism is played by vitamin D and parathormone (PTH). The aim of the study. To investigate markers of calcium-phosphorus metabolism in patients with rheumatoid arthritis accompanied by bone mineral density (BMD) disorders and to find out their diagnostic value. Materials and methods. 76 patients with RA (64 premenopausal women and 12 mature men) were included in the study. All patients with RA were subjected to ultrasound bone densitometry and according to its results, patients were divided into three groups: patients with RA and osteopenia, patients with RA and OP; RA patients without BMD disorders. The control group included 22 healthy individuals of both genders without BMD abnormalities. To evaluate calcium-phosphorus metabolism, ionized calcium, total calcium, phosphorus, PTH, and vitamin D in blood serum, and levels of calcium and phosphorus in urine were detected. Results. It was revealed that concentration of total calcium in blood serum of patients with RA is lower compared to healthy individuals, while the same index in urine of patients with RA accompanied by osteopenia, OP or without BMD disorders is higher compared to healthy people. The concentration of vitamin D is significantly lower in patients with RA and OP compared to patients with RA with osteopenia, without BMD disorders, or healthy individuals. The concentration of PTH is higher in healthy individuals compared to patients with RA without BMD abnormalities or with osteopenia. Conclusions. In patients with rheumatoid arthritis with osteopenia or osteoporosis, significantly more often than in patients with rheumatoid arthritis without a violation of bone mineral density, ionized and total calcium, phosphorus in serum and urine, as well as vitamin D indices have deviations from the reference values and are of diagnostic significance.

Background: The purinergic P2X7 receptor (P2X7R) is a nucleotide-gated ionotropic channel chiefly involved in the inflammatory response triggered by release of ATP from damaged cells. It is largely expressed in inflammatory cells and plays a key role in promoting the release of pro-inflammatory cytokines such as IL-1β. Increasing evidence suggest that it is also expressed in fibroblasts and may play a pivotal role in the development of tissue fibrosis in different body districts. Therefore, we hypothesized a possible P2X7R involvement in the pathogenesis of two different diseases, Systemic sclerosis (SSc; scleroderma) and Chronic Heart Failure (CHF), that include the development of tissue fibrosis among their hallmarks. SSc is a connective tissue disease characterized by generalized fibrosis of the skin and internal organs, for which no effective treatments are currently available. CHF is a complex multistep disorder representing the final result of a number of cardiovascular diseases characterized by cardiac remodelling. Objective and methods: The aims of this study are to investigate the expression and the function of P2X7R in cultured human dermal fibroblasts from SSc patients in comparison with healthy dermal fibroblasts as control or in cardiac fibroblasts from CHF patients in comparison with human atrial fibroblast cell line as control, and also to analyze putative underlying mechanistic pathways involved in the fibrotic process. SSc fibroblasts were isolated from the skin biopsies of SSc patients and healthy volunteers; while CHF fibroblasts were isolated from human atrial fragments obtained from patients undergoing cardiac surgical intervention and the cell line Normal Human Cardiac Fibroblasts-Atrium (NHCF-A) was used as control. In these cells, P2X7R expression were evaluated by flow cytometry and RT q-PCR. P2X7R function and the ensuing effects were assessed by measuring: -cytosolic Ca2+ entry, by single cell fluorescence microscopy; -collagen production, by EIA assay; -α-SMA expression, by immunofluorescence; -fibroblasts migration, by using a wound healing scratch assay. Intracellular pathways potentially involved in fibrogenic process were investigated by measuring: -the effect of P2X7R and/or ERK1/2 inhibitors in different experiments; -the expression of ERK 1/2 by Western Blot analysis; -pro-inflammatory cytokines/growth factor release by ELISA. Results: P2X7R was overexpressed in SSc fibroblasts, compared to control fibroblast, and its stimulation correspond to a markedly higher Ca2+ permeability and collagen production. Moreover, increased α-SMA expression/organization and cell migration were observed in lipopolysaccharides (LPS)-primed SSc fibroblasts after P2X7R stimulation with respect to control fibroblasts. P2X7R-stimulation with LPS plus 2,3-O-(4-benzoylbenzoyl)-ATP (BzATP) induced IL-6 release in SSc fibroblasts, however IL-6 stimulation did not affected collagen production. Instead, collagen secretion was completely abrogated by P2X7R-inhibition with periodate-oxidized ATP (oATP) or by ERK 1/2-inhibition with FR-180204. Cardiac fibroblasts from CHF patients showed, with respect to control cardiac fibroblasts, a higher surface expression of P2X7R and an enhanced receptor function in terms of Ca2+ influx and collagen production. Unlike from SSc fibroblasts, P2X7R activation did not induce cytokine changes. Moreover, TNF-α induced a further increase of P2X7R expression. Finally, phosphorylated-ERK was more expressed in CHF fibroblasts compared to control cell and strictly correlated with the collagen production. Conclusions: In conclusions, our data provide evidence that both in dermal fibroblasts from SSc patients and in cardiac fibroblasts from CHF patients the expression and the function of the purinergic P2X7R are increased compared to healthy controls and are related to an increased collagen secretion. All together these results suggest a causative role of the P2X7R in the pathophysiology of the SSc and CHF and suggest P2X7R as a new attractive target for pharmacological modulation under these pathological conditions.
Background: A novel neutrophils defense mechanism discovered in recent years consists in the extracellular release of network consisting of DNA associated with histones and neutrophils granule enzymes in the form of Neutrophil Extracellular Traps (NETs). Although NETs were originally recognized as a host defence mechanism in which neutrophils release their nuclear and granular contents to kill pathogens, today it is know that NETs are also involved in the pathogenesis of autoimmune and inflammatory diseases, including microcrystalline arthropathies such as gout and pseudogout. Objective and Methods: The aim of this study is to characterize NETs formation in synovial fluid of patients affected by microcrystal arthritis (gout and pseudogout caused, respectively, by MSU or CPPD crystals) compared to that of arthritis not induced by microcrystals (rheumatoid arthritis, psoriatic arthritis). Our first step was to separate neutrophils from other cells present in synovial fluid of gout, pseudogout and non-microcrystal arthritis samples obtained through arthrocentesis. In order to pursue our goal in these samples we evaluated: -the presence of NETs using an immunofluorescence technique; -the amount of NETs released through a fluorimetric assay measuring extracellular DNA; -the levels of pro-inflammatory cytokines and Neutrophil Elastase (NE) by ELISA test. The potential involvement of RIPK3-MLKL-activated necroptotic pathway in NETs formation were also investigated through the analysis of phosphorylated (p)-MLKL, measured by Western Blot technique. In vitro experiments were also performed to evaluate how neutrophils separated from peripheral blood of healthy donors undergo NETs formation when incubated with MSU or CPPD crystals. Results: The experiments performed in this study showed: -microscope images of NETs structures released by neutrophils obtained from synovial fluid of both microcrystal-induced arthritis and non-microcrystal arthritis; -fluorimetric measurement of NETs released directly correlated to microcrystals concentration present in the synovial fluid; -elevated level of IL-6 in both microcrystal and non-microcrystal arthritis; higher IL-1β, IL-8 and IL-10 concentrations in samples from microcrystal-induced arthritis containing a huge amounts of NETs, respect to microcrystal arthritis samples containing low amounts of NETs and non-microcrystal arthritis; -phosphorylation of MLKL, as an index of necroptotic pathway activation in both microcrystal e non-microcrystal arthritis. In vitro experiments confirmed ex vivo data: -increasing concentrations of MSU and CPPD crystals induce NETs release and necroptosis activation in a dose-dependent manner. Conclusions: In conclusions our data provide evidence of NETs formation in synovial fluid of patients affected by gout, pseudogout and non-microcrystal arthritis. Interestingly, NETs formation appears higher in microcrystal arthritis samples and directly correlates with microcrystals (MSU or CPPD) present in synovial fluid of gout and pseudogout patients. Moreover, activation of RIPK3-MLKL necroptotic pathway seems to be involved in NETs production in all these diseases. Therefore, our study pointed out the importance of RIPK3-MLKL activation in NETs release suggesting this pathway as a potential target to regulate NETs cascade in microcrystal and non-microcrystal arthritis.