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Home , Contracture, Crystal arthropathy, Polyarthritis

Calcium-Containing Crystal- Associated in the Elderly

Pranav Oza, MD; and Anthony M. Reginato, PhD, MD

Challenges still remain in the diagnosis, crystal identification, and treatment of pseudogout due to coexisting comorbid conditions and polypharmacy commonly found in veterans.

alcium pyrophosphate (CPP) sive to this disease, as it can be seen as intermittent flares and often is as- crystals may deposit in both in other crystal diseases (oxalosis, ymptomatic between flares. Trauma, articular tissues (predomi- basic calcium phosphate [BCP]) and surgery, or severe medical illness fre- nantly hyaline cartilage and can appear as casual finding or coex- quently provokes attacks of mono- C 2 fibrocartilage) and periarticular soft ist with OA. sodium urate (MSU) as well as acute tissues.1,2 Calcium pyrophosphate CPP . Systemic findings, such deposition disease (CPPD) may be CLINICAL MANIFESTATIONS as fever; leukocytosis with a left shift asymptomatic or be associated with In clinical practice, CPPD may pres- in the differential count; inflamma- a spectrum of clinical syndromes, in- ent with several phenotypic forms. In tory markers, such as elevated sedi- cluding both acute and chronic in- asymptomatic CPPD, CC is a common mentation rate (ESR); or C-reactive flammatory arthritis.2 radiographic finding without clinical protein, also can occur, resembling The European League Against symptoms. Acute CPP arthritis always pyogenic arthritis, osteomyelitis, (EULAR) recently sug- should be suspected in any patient and/or systemic sepsis in the elderly gested changes in CPPD terminol- aged > 65 years presenting with acute patient. ogy.2 According to the new EULAR monoarticular or oligoarticular, migra- Diagnosis must be confirmed classification, pseudogout, or CPPD, tory or additive, symmetrical, or poly- with aspiration, Gram stain and has been reclassified based on new articular arthritis.3 Acute CCP arthritis cultures of the synovial fluid, and key terms that include several of the is characterized by self-limited acute or evaluation for the presence of CPP previously described disease pheno- subacute attacks of arthritis involving crystals under polarized light micros- types: asymptomatic CPPD; acute 1 or several extremity (, copy.2 The diagnosis can be difficult CPP crystal arthritis (previously wrists, ankles; rarely affects large toe). to confirm secondary to the weakly known as pseudogout); osteoarthri- Typically, the acute attacks last 7 to birefringent nature of CPP crystals.4 tis (OA) with CPPD (previously, 10 days. Several unusual sites (eg, the Coexistence of MSU and CPP crys- pseudo-OA); and the chronic CCP joints, trochanteric bursa, and tals in a single inflammatory effusion crystal inflammatory arthritis (previ- deep spinal joints) also may be af- is neither uncommon nor unex- ously, pseudorheumatoid arthritis). fected. However, differences in pattern plained given increased frequencies In similar fashion, of involvement are insufficient of both hyperuricemia/ and CC (CC) refers to calcification of the fi- to permit definitive diagnosis without among elderly patients.5 brocartilage and/or hyaline cartilage demonstration of the specific crystal Chronic CPP crystal inflammatory identified by imaging or histologic type in the inflammatory joint fluid. arthritis may present as a chronic, analysis. Although CC is most com- Pseudogout attacks closely resem- symmetrical, bilateral, and deform- monly seen in CPPD, it is not exclu- ble gouty arthritis; CPPD presents ing . It frequently affects the wrists and metacarpophalangeal Dr. Oza is a hospitalist in the Department of Internal Medicine, and Dr. Reginato is the director of the joints and tendon sheaths. Chronic Fellowship Program and acting chief in the Division of Rheumatology, both at the Provi- dence VAMC in Rhode Island. Dr. Reginato also is an associate professor in medicine at The Warren Alp- CPP may resemble rheumatoid ar- ert School of Medicine at Brown University in Providence. thritis (RA) and produce wrist

14 • FEDERAL PRACTITIONER • APRIL 2016 www.fedprac.com , which may manifest as stood and does not carpal tunnel syndrome and/or cubi- have good treat- tal tunnel syndrome. Calcium pyro- ment alternatives. phosphate deposition disease should Calcium pyrophos- be on the differential diagnosis in phate crystals often the elderly patient presenting with a are associated with clinical picture that resembles “sero- manifestations of negative” RA, with morning stiffness, OA.1,2 Indeed, up synovial thickening, localized edema, to 20% of OA joints and restricted motion due to active have been found to or flexion be positive for CPP of the hands/wrist. It may present crystals in various with prominent systemic features, studies. Given the such as leukocytosis, fevers, mental extensive evidence confusion, and inflammatory oligo- supporting treat- arthritis or polyarthritis. The diag- ment of OA, usually nosis of CPPD still may be possible they are treated in a even though the rheumatoid factor similar fashion with (RF) is positive, given the increasing good results. Occa- likelihood of elevated RF in the older sionally, these will population. In this setting, aspiration have unusual mani- of joint fluid and radiography will as- festations for typical sist in clarification of the diagnosis. OA, such as involve- Furthermore, CPPD typically does ment of wrists and not cause the type of erosive disease metacarpophalangeal joints; however, pression syndromes or symptoms of that is often seen in RA. the presentation is often indolent either acute nerve compression or Calcium pyrophosphate deposi- like OA. chronic spinal stenosis.8,9 Calcium tion disease also can mimic poly- Calcium pyrophosphate crystal pyrophosphate crystal deposition rheumatica (PMR). A direct deposition involving the spine has also can occur in other soft tissues, comparison of a cohort of patients been associated with a number of such as bursae, ligaments, and ten- with pseudo-PMR (PMR/CPPD) with clinical manifestations. Spine stiff- dons and may be sufficient to cause actual PMR patients found that in- ness, sometimes associated with bony local nerve compression, such as car- creased age at diagnosis, presence of , can resemble ankylosing pal or cubital tunnel syndrome. , tendinous cal- spondylitis or diffuse idiopathic skel- cifications, and ankle arthritis car- etal hyperostosis. Such symptoms Epidemiology ried the highest predictive value in are seen more commonly in famil- Radiographic surveys of the knees, patients with CPPD presenting with ial CPPD rather than in the elderly. hands, wrists, and pelvis and epide- PMR-like symptoms.6 However, the However, crystal deposition in the miologic studies have demonstrated PMR/CPPD variant can be difficult to ligamentum flavum at the cervi- an age-related increase in the preva- distinguish, because both conditions cal spine levels has been associated lence of CPPD: 15% prevalence in can have elevated systemic inflam- with a condition called crowned dens patients aged 65 to 74 years, 36% matory markers, and both are steroid syndrome.7 Although mostly asymp- prevalence in patients aged 75 to responsive. tomatic, it may be present with acute 84 years, and 50% prevalence in pa- Calcium pyrophosphate deposi- neck , fever, and an increased tients aged > 84 years.10 In a recent tion disease involving a single joint ESR, sometimes mimicking PMR radiographic study, 40% of patients can rarely lead to extensive destruc- or giant cell arteritis or neurologic with CPPD did not present with CC tion—as with neuropathic joints in symptoms. Similarly, CPP crystal de- of the knee, and the study’s authors the absence of any neurologic defi- position in the posterior longitudi- recommended additional radiographs cits—and is extremely debilitating. nal ligament at the lower levels of the of pelvis, wrists, or hands for accu- This presentation is not well under- spine may lead to spinal cord com- rate diagnosis of radiographic CC.11

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Table. Comparative Treatment Optionsa Gout1,2 CPPD3 Basic Calcium Phosphate Local/intra-articular treatment Intra-articular Intra-articular corticosteroid Periarticular corticosteroid injection corticosteroid injection injection Calcification aspiration/needling Shockwave therapy Treatment of acute flare Colchicine Effective Effective (no loading dose) Limited data Nonsteroidal anti-inflammatory drugs Effective Effective Effective Corticosteroids (systemic) Effective Effective (polyarticular) Limited data Others ACTH, IL-1 inhibitors

Preventive treatments Treating associated metabolic conditions Hyperuricemia Magnesium, iron chelators None Inhibit crystal formation Xanthine oxidase Probenecid,b None inhibitors, uricosuric, phosphocitratec recombinant uricase Prevent inflammasome activation Colchicine Colchicine (emerging role) Colchicine (emerging role) Other Methotrexate, None hydroxychloroquined Anti IL-1 treatment Available Possible Possible (anakinra, canakinumab, IL-1 trap)

Abbreviations: ACTH, adrenocorticotropic hormone; CPPD, calcium pyrophosphate deposition disease. aBased on guidelines from the American College of Radiology 2012,1 European League Against Rheumatism (2006 and 2011).2,3 No guidelines available for basic calcium phosphate at time of publication. bProbenecid is a transmembrane-transport inhibitor that reduces the production of extracellular pyrophosphate in vitro but to date has never been demonstrated to decrease CPPD crystal deposition in humans.31 cNo evidence based on human trials for phosphocitrate (mouse model of murine progressive ankylosis). dVery limited data on methotrexate and hydroxychloroquine used for the prevention of CPPD flares.

Diagnosis trasound, provides the capacity to CPPD.16 Asymptomatic CPPD needs Accurate diagnosis should be visualize crystal deposits within the no treatment. In other CPPD phe- achieved on the basis of the clinical joint structures, the hyaline carti- notypes, the goals are to attempt picture and demonstration of CPP lage, and/or fibrocartilage (Figure prompt resolution of the acute sy- crystals in synovial fluid or tissue 2B and 2C).14 The presence of hy- novitis, reduction in chronic dam- by compensated polarized light mi- perechoic bands within the inter- age, and management of associated croscopy (Figures 1A and 1B).2 The mediate layer hyaline cartilage and conditions. In acute attacks, treat- sensitivity and specificity for CPP hyperechoic spots in fibrocartilage ment modalities used in gout are crystal detection has been shown to are consistent with CPP crystal often required; however, data for be 95.9% and 86.5%, respectively.12 deposits.2,14 The use of computed CPPD treatment are limited (Table). However, the CPP crystal is more tomography is the gold standard im- Treatment relies on the use of col- readily identified by a rheumatolo- aging modality for the identification chicine and nonsteroidal anti-in- gist rather than in a standard hospital of CPPD of the spine.15 There is not flammatory drugs (NSAIDs), but laboratory, which misses 30% of CPP enough evidence to support the use toxicity and comorbidities in the el- crystals.13 of magnetic resonance imaging in derly limit the usage of these drugs. Findings of CC on radiograph CPPD, but it may play a role in rare Given increased renal impairment, strengthens a CPPD diagnosis, complications.2 the loading dose of colchicine is not but its absence does not rule it recommended.16 Colchicine has re- out (Figure 2A).2 More recently, Treatment cently been shown to completely the use of new imaging modali- The EULAR recently defined new block crystal-induced maturation ties, such as musculoskeletal ul- guidelines for the management of of IL-1β in vitro, indicating that the

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drug acts upstream of inflam- masome activation.17 This is in addition to the well- known role of colchicine in inhibition of micro-tubule formation, which likely leads to prevention of cell migra- tion, phagocytosis, and acti- vation of inflammasome.18-20 A Intra-articular injection of B C corticosteroid is an efficient Figure 1. Compensated polarized light microscopy demonstrating calcium pyrophosphate crystal (A and well-tolerated treatment and B) and alizarin red S stain of basic calcium phosphate crystals (C). Arrow shows the direction of polar- alternative for monoarticu- izer. Perpendicular-yellow crystal (A) and parallel-blue crystal (B). lar CPP flares. Oral or par- enteral corticosteroids are frequently sociated diseases, such as hyper- tection and management of hypo- used for polyarticular flares in par- parathyroidism, hemochromatosis, magnesemia are recommended, ticular for those patients in which hypomagnesemia, and hypophos- because it occurs in patients who NSAIDs and colchicine are contra- phatemia, as well as avoidance of ta- have well-defined conditions and indicated.16 Parenteral adrenocorti- crolimus, which facilitates or causes situations: Gitelman syndrome, cotropic hormone has been used in CC.16 Correction of the underlying thiazide and loop diuretics use, patients with congestive heart failure, metabolic disorder, especially when tacrolimus use, familial forms of renal insufficiency, gastrointestinal undertaken early, may reduce the renal magnesium wasting or use of bleeding, or resistance to NSAIDs.21 severity of CPPD. However, there is proton pump inhibitors, short bowel For prophylaxis of acute CPP crys- little evidence to suggest that treat- syndrome, and intestinal failure in tal arthritis, a low dose of oral ment of associated disease results in patients receiving home parenteral NSAIDs, oral colchicine, or predni- resolution of CPPD—most famously, nutrition. Long-term administration sone may be used with good results.16 although therapeutic phlebotomy of magnesium in some patients with In chronic CPP arthritis, continu- does not help in hemochromato- chronic hypomagnesemia decreased ous use of colchicine, NSAIDs, or sis for prevention of crystal disease, meniscal calcification.27-29 low-dose prednisone is often ap- chelating agents do seem to be mod- propriate. If these interventions are erately effective.26 Only oral admin- Dietary Calcium ineffective or contraindicated, using istration of magnesium has shown Epidemiologic studies showed a hydroxychloroquine (HCQ) and a reduction in meniscal CC in a pa- lower incidence of CC in Chinese methotrexate (MTX) have been suc- tient with CPPD .27 In subjects. The authors of the study cessfully used to control chronic CPP addition, this was in the setting of speculate that this lower prevalence crystal inflammation.22,23 Recent tri- familial hypomagnesemia associated of CPPD could result from high lev- als have raised questions about MTX, CPPD. However, unlike uricosuric els of calcium found in the drinking and further trials on HCQ usage are agents for gout, no pharmacologic water in Beijing, which may affect underway.24 Biologic agents target- treatments can prevent CPPD crys- parathyroid hormone secretion.30 ing IL-1 are not currently approved tal formation and deposition in Further studies are needed to con- for the treatment of CPPD, but there tissues. firm this hypothesis, as it could be are suggestions that it may be effec- a cheaper approach to pseudogout tive in refractory cases and induce THERAPEUTIC AGENTS prevention. rapid stable remissions after 3 days of Magnesium therapy.25 Magnesium is a cofactor for the ac- Probenecid In contrast to gout, there is no tivity of pyrophosphatases that con- Probenecid is an in vitro inhibitor specific target therapy for lowering verts inorganic pyrophosphates of the transmembrane PPi trans- CPP crystal load in the elderly. Cru- (PPis) into orthophosphates. In ad- porter thought to possibly prevent cial in the management of CPPD dition, magnesium can increase the extracellular PPi elaboration. How- in the elderly is the search for as- solubility of CPP crystals. Early de- ever, this observation has not been

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behind this link is not completely understood, but bisphosphonates are structurally similar to PPi. Pseudogout attacks also have been described in neutropenic patients un- dergoing treatment with granulocyte-colony stimu- lating factor.38 In addition to phar- Figure 2. Radiographic (A) and maceutical exacerbation ultrasound image of the knee showing of pseudogout, surgical chondrocalcinosis (CC) and musculoskeletal procedures and trauma ultrasound of the hyaline cartilage (B) can precipitate attacks. and meniscal fibrocartilage (C) with Joint lavage has been de- hyperechogenicity signal consistent with scribed to increase the in- CC due to calcium pyrophosphate 39 crystals. The presence of calcium cidence of pseudogout. pyrophosphate crystals appears as It was hypothesized that hyperechoic enhancement in the joint lavage with fluid in- intermediate layer of the articular cartilage duced “crystal shedding” (arrows) with characteristic features of from CPPD crystals im- calcium pyrophosphate deposition disease. bedded in the joint tissue. Patients who underwent meniscectomy of the knee confirmed by either case reports or PRECIPITATORS OF ACUTE 20 years ago had a 20% incidence clinical trials.31 PSEUDOGOUT of CC in the knee that was operated Diuretics are known to exacerbate compared with 4% CC in the contra- Phosphocitrate gout, but they also can exacerbate lateral nonoperated knee.40 Overall, Phosphocitrate acts directly on pre- pseudogout. A recent case-control the surgery most linked with a pseu- venting crystal deposition in tissues study nested within a United King- dogout attack, however, is parathy- in CPPD as well as BCP based on in dom general practice database found roidectomy.41 vitro evidence and mouse models.32,33 that loop diuretics rather than hydro- chlorothiazide was associated with BASIC CALCIUM PHOSPHATE Hyaluronan increased risk of CPPD mediated pri- CRYSTALS An amelioration of pain and in- marily by magnesium reabsorption in Basic calcium phosphate crystals are creased range of motion were ob- the loop of Henle.28 Chronic kidney common but rarely diagnosed due served in radiographic CC with OA.34 disease associated with secondary and to the cumbersome and expensive However, it is associated with in- tertiary increases methods required to identify these creased acute CPP arthritis.35 calcium or PPi concentration, which crystals.42 Basic calcium phosphate leads to CPP-crystal deposition. crystals are difficult to identify by Radiosynovectomy In addition, multiple case reports light microscopy, as they congre- In a double-blind study of 15 patients have described acute pseudogout gate into clumps that can appear as with symmetrical CPPD arthropathy, caused by bisphosphonate admin- a stack of “shiny coins.” Multiple the knee that underwent intra-articular istration for osteoporosis or Paget techniques, including X-ray diffrac- injection of yttrium-90 (5 mCi) plus disease—more likely in the elderly tion and electron microscopy with steroid had less pain, stiffness, joint population. Intravenous pamidro- energy dispersive analysis, have been line tenderness, and effusion compared nate, oral etidronate, and alendronate shown to be specific for BCP crystal with the contralateral control knee in- therapy have all been described in identification; however, the expense jected with saline and steroids.36 the elderly.37 The overall mechanism and technical knowledge required to

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conduct these techniques is prohibi- also is effective and has occasion- crystal-associated arthropathies and tive. Similarly, BCP crystals can be ally been shown to reduce the size the coexisting osteoarthritis is great, identified with alizarin red S stain, of the calcium deposit as well, often and focused identification of the performed in specialized centers, in combination with IV drugs like disease process with tailored treat- but has high degree of false positive ethylenediaminetetraacetic acid.51-53 ment can achieve the goal of de- (Figure 1C).43 Acute calcific periarthritis creasing symptoms and improving Basic calcium phosphate and of the hand presents similar to quality of life. l CPPD crystals may coexist in sy- gout or pseudogout, affecting the novial fluid. Similar to CPPD, BCP wrist, usually in postmenopausal Acknowledgements crystal disease is often concurrent women.54 Basic calcium phosphate This work was supported by grant with OA and can cause calcification crystals are aspirated from the joint, P20GM104937 (A.M.R.). of articular cartilage. Basic calcium and periarticular crystals may be phosphate is more common than subtle. Local steroid injections are Author disclosures CPP crystals with occurrence of beneficial. The authors report no actual or poten- 30% to 50% in OA synovial fluid.42 Milwaukee syndrome is tial conflicts of interest with regard to Additionally, BCP crystal disease an arthropathy associated with BCP this article. has been linked to increased sever- crystals in the joint fluid and results ity of OA. Basic calcium phosphate in extensive destruction of shoulder Disclaimer crystals in knee joints were found to articular cartilage and surrounding The opinions expressed herein are have radiographically more severe tissues. It is commonly bilateral and those of the authors and do not nec- arthritis with larger effusions.44,45 occurs in elderly women more often essarily reflect those of Federal Similarly, BCP crystals in OA sy- than it does in men.55 Aspiration of Practitioner, Frontline Medical Com- novial fluid correlated with higher the shoulder joint typically reveals a munications Inc., the U.S. Govern- Kellgreen-Lawrence grade scores by serosanginous fluid. Fluid samples ment, or any of its agencies. This radiography.42,46 can be assessed for hydroxyapatite article may discuss unlabeled or in- It is currently believed that BCP crystals by staining with alizarin red vestigational use of certain drugs. crystals are continuously formed in the dye, which produces a characteristic Please review the complete prescrib- extracellular matrix, and their deposi- “halo” or orange-red stain by light ing information for specific drugs or tion is actively prevented by PPi pres- microscopy.43 Surgical treatment of drug combinations—including indi- ent in the matrix.47 Elevated PPi levels, Milwaukee shoulder syndrome is cations, contraindications, warnings, on the other hand, favor the formation difficult due to increased age of the and adverse effects—before admin- of CPP crystals.48 The clinical upshot population affected and the severity istering pharmacologic therapy to seems to be that although CPP crystals of the shoulder destruction. Usually patients. are almost universally intra-articular a conservative approach of analge- and released by chondrocytes, BCD sics, recurrent shoulder aspirations, REFERENCES crystals and deposits are more fre- and steroid injections is the best 1. Guerne PA, Terkeltaub R. Clinical Features, Diag- nosis, and Treatment of CPPD Crystal Arthropa- quently present in soft tissues. treatment option. thy. In: Terkeltaub R, ed. Gout and Other Crystal Arthropathies. Philadelphia, PA: Saunders/Elsevier; 2012:249-265. Acute CONCLUSIONS 2. Zhang W, Doherty M, Bardin T, et al. European Typically, this type of tendinitis Calcium-containing crystal- League Against Rheumatism recommendations for calcium pyrophosphate deposition. Part I: termi- involves the shoulder joint and is associated arthropathies are a com- nology and diagnosis. Ann Rheum Dis. 2011;70(4): extra-articular. Common treatments plex array of entities that target the 563-570. 3. McCarty DJ. Calcium pyrophosphate dihydrate help, including NSAIDs, intra- veteran elderly population with crystal deposition disease—1975. Arthritis Rheum. articular steroids, ice, and rest. In increasing frequency. Challenges 1976;19(S3):275-285. 4. Ivorra J, Rosas J, Pascual E. Most calcium pyro- addition, high-energy extracorpo- still remain in the diagnosis, crys- phosphate crystals appear as non-birefringent. Ann real shock wave therapy has been tal identification, and treatment due Rheum Dis. 1999;58(9):582-584. 5. Lawrence RC, Felson DT, Helmick CG, et al; Na- shown to be effective when used to coexisting comorbid conditions tional Arthritis Data Workgroup. Estimates of the with conscious sedation.49,50 Nee- and polypharmacy commonly seen prevalence of arthritis and other rheumatic condi- tions in the United States. Part II. Arthritis Rheum. dling or barbotage in association in veterans. Overall morbidity as- 2008;58(1):26-35. with lavage and steroid injections sociated with calcium-containing 6. Pego-Reigosa JM, Rodriguez-Rodriguez M, Hurtado-

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Hernandez Z, et al. Calcium pyrophosphate deposi- 22. Rothschild B, Yakubov LE. Prospective 6-month, factor administration for neutropenia. Mod Rheuma- tion disease mimicking : a double-blind trial of hydroxychloroquine treatment tol. 2007;17(5):445-446. prospective followup study of predictive factors for of CPDD. Compr Ther. 1997;23(5):327-331. 39. Pasquetti P, Selvi E, Righeschi K, et al. Joint this condition in patients presenting with polymyal- 23. Chollet-Janin A, Finckh A, Dudler J, Guerne PA. lavage and pseudogout. Ann Rheum Dis. gia symptoms. Arthritis Rheum. 2005;53(6):931-938. Methotrexate as an alternative therapy for chronic 2004;63(11):1529-1530. 7. Bouvet JP, le Parc JM, Michalski B, Benlahrache C, calcium pyrophosphate deposition disease: an ex- 40. Doherty M, Watt I, Dieppe P. Localised chondro- Auquier L. Acute neck pain due to calcifications ploratory analysis. Arthritis Rheum. 2007;56(2): calcinosis in post-meniscectomy knees. Lancet. surrounding the odontoid process: the crowned 688-692. 1982;1(8283):1207-1210. dens syndrome. Arthritis Rheum. 1985;28(12): 24. Finckh A, Mc Carthy GM, Madigan A, et al. Meth- 41. Rubin MR, Silverberg SJ. Rheumatic manifesta- 1417-1420. otrexate in chronic-recurrent calcium pyrophos- tions of primary hyperparathyroidism and para- 8. Muthukumar N, Karuppaswamy U. Tumoral cal- phate deposition disease: no significant effect in thyroid hormone therapy. Curr Rheumatol Rep. cium pyrophosphate dihydrate deposition dis- a randomized crossover trial. Arthritis Res Ther. 2002;4(2):179-185. ease of the ligamentum flavum. Neurosurgery. 2014;16(5):458. 42. Ea HK, Lioté F. Diagnosis and clinical manifesta- 2003;53(1):103-109. 25. Moltó A, Ea HK, Richette P, Bardin T, Lioté F. Ef- tions of calcium pyrophosphate and basic calcium 9. Armas JB, Couto AR, Bettencourt BF. Spondylo- ficacy of anakinra for refractory acute calcium phosphate crystal deposition diseases. Rheum Dis arthritis, diffuse idiopathic skeletal hyperostosis pyrophosphate crystal arthritis. Joint Bone Spine. Clin North Am. 2014;40(2):207-229. (DISH) and chondrocalcinosis. Adv in Exp Med Biol. 2012;79(6):621-623. 43. Paul H, Reginato AJ, Ralph Schumacher HR. Aliza- 2009;649:37-56. 26. Harty LC, Lai D, Connor S, et al. Prevalence and rin red s staining as a screening test to detect cal- 10. Abhishek A, Doherty M. Epidemiology of calcium progress of joint symptoms in hereditary hemochro- cium compounds in synovial fluid. Arthritis Rheum. pyrophosphate crystal arthritis and basic calcium matosis and symptomatic response to venesection. J 1983;26(2):191-200. phosphate . Rheum Dis Clin North Clin Rheumatol. 2011;17(4):220-222. 44. Molloy ES, McCarthy GM. Basic calcium phosphate Am. 2014;40(2):177-191. 27. Doherty M, Dieppe PA. Double blind, placebo con- crystals: pathways to joint degeneration. Curr Opin 11. Abhishek A, Doherty S, Maciewicz R, Muir K, trolled trial of magnesium carbonate in chronic Rheumatol. 2006;18(2):187-192. Zhang W, Doherty M. Chondrocalcinosis is com- pyrophosphate arthropathy. Ann Rheum Dis. 45. Carroll GJ, Stuart RA, Armstrong JA, Breidahl mon in the absence of knee involvement. Arthritis 1983;42(suppl 1):106-107. PD, Laing BA. Hydroxyapatite crystals are a fre- Res Ther. 2012;14(5):R205. 28. Rho YH, Zhu Y, Zhang Y, Reginato AM, Choi quent finding in osteoarthritic synovial fluid, but 12. Lumbreras B, Pascual E, Frasquet J, González-Sa- HK. Risk factors for pseudogout in the general are not related to increased concentrations of linas J, Rodríguez E, Hernández-Aguado I. Anal- population. Rheumatology (Oxford). 2012;51(11): keratan sulfate or interleukin 1 beta. J Rheumatol. ysis for crystals in synovial fluid: training of the 2070-2074. 1991;18(6):861-866. analysts results in high consistency. Ann Rheum Dis. 29. Park CH, Kim EH, Roh YH, Kim HY, Lee SK. The 46. Derfus BA, Kurian JB, Butler JJ, et al. The high 2005;64(4):612-615. association between the use of proton pump in- prevalence of pathologic calcium crystals in pre- 13. Szscygiel J, Reginato AM SS. Quality improvements hibitors and the risk of hypomagnesemia: a sys- operative knees. J Rheumatol. 2002;29(3):570-574. in the identification of crystals from synovial fluid: tematic review and meta-analysis. PLoS One. hospital laboratory versus rheumatology depart- 2014;9(11):e112558. 47. Ho AM, Johnson MD, Kingsley DM. Role of the ment evaluation. Poster presented at: 2014 ACR/ 30. Zhang Y, Terkeltaub R, Nevitt M, et al. Lower preva- mouse ank gene in control of tissue calcification ARHP Annual Meeting; November 15, 2014; Bos- lence of chondrocalcinosis in Chinese subjects in and arthritis. Science. 2000;289(5477):265-270. ton, MA. Beijing than in white subjects in the United States: 48. Macmullan P, McCarthy G. Treatment and manage- 14. Grassi W, Meenagh G, Pascual E, Filippucci E. the Beijing Osteoarthritis Study. Arthritis Rheum. ment of pseudogout: insights for the clinician. Ther “Crystal clear”-sonographic assessment of gout and 2006;54(11):3508-3512. Adv Musculoskelet Dis. 2012;4(2):121-131. calcium pyrophosphate deposition disease. Semin 31. Rosenthal AK, Ryan LM. Probenecid inhibits trans- 49. Gerdesmeyer L, Wagenpfeil S, Haake M, et al. Arthritis Rheum. 2006;36(3):197-202. forming growth factor-beta 1 induced pyrophos- Extracorporeal shock wave therapy for the treat- 15. Scutellari PN, Galeotti R, Leprotti S, Ridolfi M, phate elaboration by chondrocytes. J Rheumatol. ment of chronic calcifying tendonitis of the rota- Franciosi R, Antinolfi G. The crowned dens syn- 1994;21(5):896-900. tor cuff: a randomized controlled trial. JAMA. drome. Evaluation with CT imaging. Radiol Med. 32. Cheung HS, Sallis JD, Demadis KD, Wierzbicki A. 2003;290(19):2573-2580. 2007;112(2):195-207. Phosphocitrate blocks calcification-induced articu- 50. Lee SY, Cheng B, Grimmer-Somers K. The midterm 16. Zhang W, Doherty M, Pascual E, et al. EULAR lar joint degeneration in a guinea pig model. Arthri- effectiveness of extracorporeal shockwave therapy recommendations for calcium pyrophosphate de- tis Rheum. 2006;54(8):2452-2461. in the management of chronic calcific shoulder ten- position. Part II: management. Ann Rheum Dis. 33. Sun Y, Mauerhan DR, Honeycutt PR, et al. Calcium dinitis. J Shoulder Surg. 2011;20(5):845-854. 2011;70(4):571-575. deposition in osteoarthritic meniscus and meniscal 51. Pfister J, Gerber H. Chronic calcifying tendi- 17. Martinon F, Pétrilli V, Mayor A, Tardivel A, cell culture. Arthritis Res Ther. 2010;12(2):R56. nitis of the shoulder-therapy by percutaneous Tschopp J. Gout-associated crystals 34. Daumen-Legre V, Pham T, Acquaviva PC, Laf- needle aspiration and lavage: a prospective activate the NALP3 inflammasome. Nature. forgue P. Evaluation of safety and efficacy of vis- open study of 62 . Clin Rheumatol. 2006;440(7081):237-241. cosupplementation in knee osteoarthritis with 1997;16(3):269-274. 18. Nuki G. Colchicine: its mechanism of action and chondrocalcinosis. In: Arthritis and Rheumatism. 52. del Cura JL, Torre I, Zabala R, Legórburu A. So- efficacy in crystal-induced inflammation. Curr Rheu- Vol. 42. Lippincott Williams and Wilkins; 1999: nographically guided percutaneous needle la- matol Rep. 2008;10(3):218-227. S158-S158. vage in calcific tendinitis of the shoulder: 19. Borisy GG, Taylor EW. The mechanism of ac- 35. Disla E, Infante R, Fahmy A, Karten I, Cuppari GG. short- and long-term results. AJR Am J Roentgenol. tion of colchicine. Colchicine binding to sea ur- Recurrent acute calcium pyrophosphate dihydrate 2007;189(3):W128-W134. chin eggs and the mitotic apparatus. J Cell Biol. arthritis following intraarticular hyaluronate injec- 53. Yoo JC, Koh KH, Park WH, Park JC, Kim SM, Yoon 1967;34(2):535-548. tion. Arthritis Rheum. 1999;42(6):1302-1303. YC. The outcome of ultrasound-guided needle de- 20. Borisy GG, Taylor EW. The mechanism of action 36. Doherty M, Dieppe PA. Effect of intra-articularYt- compression and steroid injection in calcific tendi- of colchicine. Binding of colchincine-3H to cellular trium-90 on chronic pyrophosphate arthropathy of nitis. J Shoulder Elbow Surg. 2010;19(4):596-600. protein. J Cell Biol. 1967;34(2):525-533. the knee. Lancet. 1981;2(8258):1243-1246. 54. Wiper JD, Garrido A. Images in clinical medi- 21. Daoussis D, Antonopoulos I, Andonopoulos AP. 37. Wendling D, Tisserand G, Griffond V, Saccomani C, cine. Acute calcific tendinitis. N Engl J Med. ACTH as a treatment for acute crystal-induced Toussirot E. Acute pseudogout after pamidronate 2008;359(23):2477. arthritis: update on clinical evidence and mecha- infusion. Clin Rheumatol. 2008;27(9):1205-1206. 55. Halverson PB, Carrera GF, McCarty DJ. Mil- nisms of action. Semin Arthritis Rheum. 2014;43(5): 38. Ames PRJ, Rainey MG. Consecutive pseudogout at- waukee shoulder syndrome. Arch Intern Med. 648-653. tacks after repetitive granulocyte colony-stimulating 1990;150(3):677-682.

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