Crystal Deposition in Joints: Prevalence and Relevance for Arthritis

Editorial Crystal Deposition in Joints: Prevalence and Relevance for Arthritis

Within the present world of arthritis research and practice, surfaces as one manifestation of systemic urate metabolism investigators of crystal-associated arthritis appear to be a disorders13. While MSU crystals deposit on cartilage sur- small, aging, and dwindling endangered species whose faces, these crystals can accumulate and erode into carti- interests are seen to be peripheral to those of most rheuma- lage. In contrast, CPPD crystal deposition is restricted to tologists. This contrasts dramatically with the high preva- hyaline and fibrocartilages and reflects a metabolic disorder lence of these diseases1,2. Both gout [urate crystal within cartilage itself14. While CPPD crystals have been (monosodium urate, MSU) arthropathy] and pseudogout said to form principally in cartilage mid-zone, this study [calcium pyrophosphate dihydrate (CPPD) crystal arthropa- and our own unpublished observations show that CPPD thy] are common and distinct forms of arthritis that were crystals can form in hyaline cartilage superficial zones, distinguished and characterized clinically decades ago3-7. It within the cartilage surface and sometimes without deeper is easy to speculate on the reasons for the current clinical underlying deposits. MSU and CPPD crystal deposits on lack of interest. These include: specific therapy for gout, cartilage surfaces cannot be distinguished from each other absence of specific therapy for pseudogout, and blurring of by the naked eye. However, these crystals can be identified the clinical distinction between these diseases and by experienced observers using compensated polarized osteoarthritis (OA). It is an important but separate issue that light microscopy or by more elaborate methods such as OA itself, as a clinical disease descriptor, encompasses a Fourier transform infra-red spectroscopy or powder x-ray or wide range of diseases, distinguished only sometimes as pri- electron diffraction. mary OA and secondary OA, the latter encompassing many The immunohistochemistry studies in this article are different forms of joint disease. Carol Muehleman and col- intriguing and bear repeating in other study sets of cartilage leagues in this issue of The Journal have produced a land- affected by OA or by crystal deposits8. Of particular note is mark contribution on the prevalence of crystal deposition in the extensive association of type X collagen in joints where joints in a “normal” population selected as organ donors8. crystal deposits are found. This association is present even Further, the joint selected for examination, the tibial talar in cartilage matrix domains, where crystals are absent and joint, is usually spared from OA. This joint, a gliding syn- where chondrocytes are not hypertrophic. The increased ovial joint, is noted for its stability and its mobility restric- cartilage superficial zone protein staining, present even in tion to the physiologic range of motion. the deeper layers of crystal-bearing cartilage, is indicative, Compared to previous studies of other joints, particular- along with the morphologic lesions, that both MSU and ly the knee joint9-12, the tibial talar joint is relatively spared CPPD crystal deposition induce deleterious and reparative of crystal deposition. However, when crystal deposition changes in cartilage. does occur, there is a 92% association with cartilage The observations in this article present the rheumatology lesions8. This compares to the joints without crystal deposi- community with a considerable challenge. Crystal deposition, where only 61% of samples demonstrated cartilage tion in joints is associated with both morphologic and changes. Further, compared to non-crystal-bearing joints, immunohistochemical changes associated with cartilage there is a 2.4-times greater likelihood of grade II (fissures) degeneration and repair. While these changes may be simi- and grade III cartilage lesions (erosions) in joints containing lar in MSU and CPPD crystal deposition diseases, they crystals. appear specific to crystal deposition and appear to be dif- It is well recognized that MSU crystals deposit on joint ferent from osteoarthritic changes. On a population basis,

See Association between crystals and cartilage degeneration in the ankle, page 1108

Downloaded on September 27, 2021 from www.jrheum.org crystal deposition in joints appears to bring propensity for REFERENCES cartilage degeneration. In the current study, these disease 1. Levinson DJ, Becker MA. Clinical gout and the pathogenesis of characteristics were observed in a joint that has a low inci- hyperuricemia. In: McCarty DJ, Koopman WJ, editors. Arthritis and allied conditions: A textbook of rheumatology. 12th ed. dence of OA. How much more extensive, then, is the prob- Philadelphia: Lea and Febiger; 1993:1773-805. lem for patients with joints affected both by OA and crystal 2. Ryan LM, McCarty DJ. Calcium pyrophosphate crystal deposition deposits? disease; pseudogout; articular chondrocalcinosis. In: McCarty DJ, As shown in this study, MSU crystal deposition is asso- Koopman WJ, editors. Arthritis and allied conditions: A textbook of ciated with obesity, presently a chronic epidemic. For MSU, rheumatology. 12th ed. Philadelphia: Lea & Febiger; 1993:1835-55. 3. Hernborg J, Linden B, Nilsson BE. Chondrocalcinosis: a secondary the problem to solve may be better recognition of a disease finding in osteoarthritis of the knee. Geriatrics 1977;32:123-4. for which both specific diagnosis and specific therapy exist. 4. McCarty D. Crystals, joints, and consternation. Ann Rheum Dis Nonetheless, gout is still a common disease and can present 1983;42:243-53. as chronic arthritis. For CPPD, we know that up to 35% of 5. McCarty DJ Jr, Kohn NN, Faires JS. The significance of calcium patients presenting for total knee arthroplasty for OA have phosphate crystals in the synovial fluid of arthritic patients: The 10 “pseudogout syndrome”. I. Clinical aspects. Ann Intern Med CPPD arthropathy in the surgical pathology specimens 1962;56:711-37. and that chondrocalcinosis is more common in osteoarthrit- 6. Rubenstein J, Pritzker KPH. Crystal-associated arthropathies. Am J ic knees3,9,11. Some of these cases represent CPPD crystal Radiol 1989;152:685-95. arthropathy and some mixed OA and CPPD, with the CPPD 7. Zitnan D, Sit’aj S. Chondrocalcinosis articularis: Section I. Clinical confined to meniscal fibrocartilage10. From imaging studies, and radiological study. Ann Rheum Dis 1963;22:142-52. 8. Muehleman C, Li J, Aigner T, et al. Association between crystals chondrocalcinosis of the knee affects up to 70% of the pop- and cartilage degeneration in the ankle. J Rheumatol 2008; 12 ulation by age 70 . It is recognized that CPPD deposition 35:1108-17. becomes progressively more common with advancing age15. 9. Derfus BA, Kurian JB, Butler JJ, et al. The high prevalence of The present study adds to the evidence that CPPD deposi- pathologic calcium crystals in pre-operative knees. J Rheumatol tion is not just an “epiphenomenon,” but is an active con- 2002;29:570-4. 10. Pritzker KPH, So P. Osteoarthritis and calcium pyrophosphate tributing factor to cartilage degeneration. As for self-inter- dihydrate crystal arthropathy [abstract]. Osteoarthritis Cartilage est, it can be expected that even rheumatologists age and a 2004;12 Suppl B:S51. substantial proportion will be affected by CPPD crystal- 11. Sokoloff L, Varma AA. Chondrocalcinosis in surgically resected associated arthropathy. joints. Arthritis Rheum 1988;31:750-6. Clearly, crystal-associated arthritis is more than acutely 12. Wilkins E, Dieppe P, Maddison P, Evison G. Osteoarthritis and articular chondrocalcinosis in the elderly. Ann Rheum Dis inflamed joints, or painless periarticular lumps or radiolog- 1983;42:280-4. ic features of erosion and/or calcification. Chronic persist- 13. Pritzker KPH, Zahn CE, Nyburg SC, Luk SC, Houpt JB. The ence of crystals in joints affects cartilage adversely, con- ultrastructure of urate crystals in gout. J Rheumatol 1978;5:7-18. tributing to loss of function. Is it not past time to bring a new 14. Pritzker KPH. Calcium pyrophosphate crystal arthropathy. A generation of investigators to study our patient populations biomineralization disorder. Hum Pathol 1986;17:543-5. 15. Hogan DB, Pritzker KPH. Synovial fluid analysis — another look with these diseases more closely? To achieve this we need to at the mucin clot test. J Rheumatol 1985;12:242-4. advocate vigorously for incremental broad-based research to control, cure, or prevent arthritis-associated crystal deposition diseases, both MSU and CPPD.

KENNETH P.H. PRITZKER, MD, FRCPC, Professor, Laboratory Medicine and Pathobiology; Surgery, University of Toronto, Pathologist-in-Chief and Director, Pathology and Laboratory Medicine, Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario M5G 1X5, Canada E-mail: [email protected]

Address reprint requests to Dr. Pritzker.

Downloaded on September 27, 2021 from www.jrheum.org