Gicht und Calciumpyrophosphat-Dihydrat-Arthropathie („Pseudogicht“) – ein Update

2018 ◽  
Vol 143 (16) ◽  
pp. 1157-1166 ◽  
Author(s):  
Monika Reuss-Borst ◽  
Anne-Kathrin Tausche

AbstractThe metabolic diseases gout and calciumpyrophosphate deposition (CPPD) (formerly: chondrocalcinosis/pseudogout) are crystal arthropathies which are caused by crystals in synovial fluid and in the case of gout also in periarticular structures. Today, in particular gout is considered as an auto-inflammatory process since phagocytosis of monosodium urate crystals by monocytes/macrophages results in the activation of the innate immune system by activation of the NRLP3-Inflammasome and consecutive secretion of the key cytokine interleukin-1ß and other pro-inflammatory cytokines. The prevalence of both crystal arthropathies rises with increasing age of patients. Most often they present clinically as an acute monarthritis of different locations. Beside typical clinical presentation, performance of ultrasonography, conventional X-Ray of joints and under special circumstances dual-energy-computer tomography could be also helpful diagnostic tools. There are EULAR guidelines describing the diagnostic algorithm for making right diagnosis. The arthrocentesis with microscopic detection of crystals is established diagnostic gold standard. Whereas crystals of monosodium urate could be very clearly be seen as relatively large intra- and extracellular needles with a strong birefringence in polarized light microscopy the detection of CPPD-crystals is more difficult. Those crystals are much smaller, showing weaker birefringence and are sometimes only seen with ordinary light microscopy. As both crystal diseases are mediated by IL-1 driven processes, the therapeutic intervention first target the acute inflammation consisting in colchicine, NSAIDs and glucocorticoids. Secondarily, in gout there are well established causal therapies to lower effectively serum urate levels below the target of 6 mg/dL (360 µmol/l). Unfortunately, those causal therapeutic options are still lacking in CPPD.

2020 ◽  
Vol 47 (9) ◽  
pp. 1416-1423
Author(s):  
Sonia Pastor ◽  
José-Antonio Bernal ◽  
Rocío Caño ◽  
Silvia Gómez-Sabater ◽  
Fernando Borras ◽  
...  

Objective.Lack of access to polarized light microscopy is often cited as an argument to justify the clinical diagnosis of crystal-related arthritis. We assessed the influence of time since sampling and preservation methods on crystal identification in synovial fluid (SF) samples under polarized light microscopy.Methods.This was a prospective, longitudinal, observational factorial study, analyzing 30 SF samples: 12 with monosodium urate (MSU) crystals and 18 with calcium pyrophosphate (CPP) crystals. Each SF sample was divided into 4 subsamples (120 subsamples in total). Two were stored in each type of preserving agent, heparin or ethylenediamine tetraacetic acid (EDTA), at room temperature or at 4°C. Samples were analyzed the following day (T1), at 3 days (T2), and at 7 days (T3) by simple polarized light microscopy, and the presence of crystals was recorded.Results.The identification of crystals in the MSU group was similar between groups, with crystals observed in 11/12 (91.7%) room temperature samples and in 12/12 (100%) refrigerated samples at T3. Identification of CPP crystals tended to decrease in all conditions, especially when preserved with EDTA at room temperature [12/18 (66.7%) at T3], while less reduction was seen in refrigerated heparin-containing tubes.Conclusion.Preserving samples with heparin in refrigerated conditions allows delayed microscopic examination for crystals. Avoiding crystal-proven diagnosis because of the immediate unavailability of microscopy no longer appears justified.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 444.1-445
Author(s):  
J. A. Bernal ◽  
M. Andres ◽  
S. López Salguero ◽  
V. Jovani ◽  
P. Vela-Casasempere ◽  
...  

Background:Optical microscopy remains the gold standard for the diagnosis of crystal arthropathies. The complete protocol consists of three phases. In the first stage, microscopy with simple light provides information on the morphology of the crystal. The second stage, polarized light, allows detecting the intensity of the birefringence. Finally, with the first-order red compensator, the type of elongation is detected, positive for calcium pyrophosphate (CPP) crystals and negative for monosodium urate (MSU) crystals. Finally, with the obtained data, the presence and type of crystals is concluded.Objectives:Analyze the validity and agreement of each stage of microscopy regarding the conclusion, emphasizing ordinary light microscopy.Methods:Fifty consecutive samples of synovial fluid obtained in routine clinical practice were independently analyzed under the compensated polarized microscope by 5 observers blinded to clinical data (250 observations in total). Each observer recorded the presence and type of crystals at each stage and reached a conclusion after gathering all the information. To estimate the diagnostic yield of each microscope stage, sensitivity, specificity and positive and negative predictive values, as well as the accuracy (number of correct observations/number of total observations), were calculated; also, the total weighted kappa was used to assess the degree of agreement with the complete protocol.Results:Main results of the study are shown in Table 1. Regarding diagnostic yield, ordinary light microscopy showed excellent sensitivity, specificity and predictive values, similar to the results noted with simple and compensated polarized microscopy.Table 1.In parentheses, 95% confidence intervals.AccuracySensitivitySpecificityPositive predictive valueNegative predictive valueKappaOrdinary light96.8%(93.8-98.4)97.2%(93.1-98.9)96.2%(90.7-98.5)97.2%(93.1-98.9)96.2%(90.7-98.5)0.954(0.919-0.989)Simple polarized light92.0%(88.0-94.8)84.1%(76.8-89.5)100%(97.0-100)100%(96.5-100)86.1%(79.5-90.8)0.874(0.821-0.927)Compensated polarized light97.6 %(94.9-98.9)95.5%(89.8-98.0)99.3%(96.1-99.9)99.1%(94.8-99.8)96.5%(92.1-98.5)0.962(0.933-0.992)Diagnoses established by ordinary light microscopy matched conclusions (accuracy) in 242/250 (96.8%) observations. Discrepant cases were crystals missed under ordinary light in 4 cases (3 MSU, 1 CPP), and 4 samples with CPP crystals initially seen but later concluded their absence. Interestingly, lowest accuracy was seen with simple polarization; CPP crystals were not detected in 20 out of 93 observations with CPP (21.5%). The accuracy of compensated polarized light was similar to ordinary light. On 5 occasions no crystals were seen but finally they were present (1 MSU, 4 CPP); on the contrary, CPP was registered in one observation but the conclusion indicated no crystals.Regarding agreement with the complete protocol, the kappa with simple light is 0.954, similar to compensated polarized light (0.962), while simple polarized light showed the lowest agreement (0.874).Conclusion:Ordinary light microscopy is enough to correctly reach the majority of diagnoses, with a very high degree of agreement with the complete protocol. Results were comparable to using a compensated polarized microscopy. Thus, if a microscope with polarizer and first-order compensator was not available, using ordinary light would be enough on most occasions. Polarized light microscopy better identifies MSU crystals, but over 20% of CPP crystals were missed at this stage, reinforcing the value of the ordinary light microscopy.Acknowledgments:Thanks to Loreto Carmona for the help with the statistical aspects.Disclosure of Interests: :None declared


1989 ◽  
Vol 4 ◽  
pp. 101-119 ◽  
Author(s):  
Joseph G. Carter ◽  
Wallace W. Ambrose

Until the mid-1960's, procedures for studying shell microstruetures were laborious and, for many purposes, unsatisfactory. Depositional surfaces were observed with binocular microscopy, and shell material was embedded in various media, sectioned, mounted on a glass slide, and observed with ordinary light and polarized light microscopy. These procedures revealed the major microstructural organization of shell layers and their optical crystallographic properties, but they provided little information regarding what is now termed shell ultrastructure. Nevertheless, these techniques provided the basis for a number of important pioneering works on molluscan shell microstructure between 1921 and 1967.


Author(s):  
Walter C. McCrone

An excellent chapter on this subject by V.D. Fréchette appeared in a book edited by L.L. Hench and R.W. Gould in 1971 (1). That chapter with the references cited there provides a very complete coverage of the subject. I will add a more complete coverage of an important polarized light microscope (PLM) technique developed more recently (2). Dispersion staining is based on refractive index and its variation with wavelength (dispersion of index). A particle of, say almandite, a garnet, has refractive indices of nF = 1.789 nm, nD = 1.780 nm and nC = 1.775 nm. A Cargille refractive index liquid having nD = 1.780 nm will have nF = 1.810 and nC = 1.768 nm. Almandite grains will disappear in that liquid when observed with a beam of 589 nm light (D-line), but it will have a lower refractive index than that liquid with 486 nm light (F-line), and a higher index than that liquid with 656 nm light (C-line).


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 440.1-441
Author(s):  
M. L. Peral ◽  
I. Calabuig ◽  
A. Martín-Carratalá ◽  
M. Andrés ◽  
E. Pascual

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


Author(s):  
Maryam Bari ◽  
Alexei A. Bokov ◽  
Zuo-Guang Ye

Polarized light microscopy reveals twin domains and symmetry of the phases in CH3NH3PbBr3 crystal; domain structure remains unresponsive to electric field but changes under external stress, confirming ferroelasticity while ruling out ferroelectricity.


Metabolites ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 479
Author(s):  
Elizabeth L. Lieu ◽  
Neil Kelekar ◽  
Pratibha Bhalla ◽  
Jiyeon Kim

History suggests that tasteful properties of sugar have been domesticated as far back as 8000 BCE. With origins in New Guinea, the cultivation of sugar quickly spread over centuries of conquest and trade. The product, which quickly integrated into common foods and onto kitchen tables, is sucrose, which is made up of glucose and fructose dimers. While sugar is commonly associated with flavor, there is a myriad of biochemical properties that explain how sugars as biological molecules function in physiological contexts. Substantial research and reviews have been done on the role of glucose in disease. This review aims to describe the role of its isomers, fructose and mannose, in the context of inborn errors of metabolism and other metabolic diseases, such as cancer. While structurally similar, fructose and mannose give rise to very differing biochemical properties and understanding these differences will guide the development of more effective therapies for metabolic disease. We will discuss pathophysiology linked to perturbations in fructose and mannose metabolism, diagnostic tools, and treatment options of the diseases.


1994 ◽  
Vol 2 (4) ◽  
pp. 16-16
Author(s):  
Walter C. McCrone

Having been brought up on monocular microscopes I find the omnipresent binocular systems a luxury. To support this viewpoint I'd like to suggest some benefits you may not have considered.Because I'm used to monocular viewing I sometimes use two different oculars, say 10X and 25X, in order to scan quickly to find an area of interest and then to examine the detail with higher magnification. Occasionally I use both oculars simultaneously and “concentrate” on either image to the exclusion of the other. A better way is to set the interocular distance at the extreme setting most different from your own interocular distance. By moving your head about a centimeter either way you can use either ocular.


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