|
|
 |
|
|
|
|
 |
Editorial
Crystal Deposition in Joints: Prevalence and Relevance for Arthritis
KENNETH P.H. PRITZKER, MD, FRCPC,
Pathology and Laboratory Medicine, Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario M5G 1X5, Canada E-mail: kpritzker@mtsinai.on.ca Address reprint requests to Dr. Pritzker. Within the present world of arthritis research and practice, investigators of crystal-associated arthritis appear to be a small, aging, and dwindling endangered species whose interests are seen to be peripheral to those of most rheumatologists. This contrasts dramatically with the high prevalence of these diseases1,2. Both gout [urate crystal (monosodium urate, MSU) arthropathy] and pseudogout [calcium pyrophosphate dihydrate (CPPD) crystal arthropathy] are common and distinct forms of arthritis that were distinguished and characterized clinically decades ago3-7. It is easy to speculate on the reasons for the current clinical lack of interest. These include: specific therapy for gout, absence of specific therapy for pseudogout, and blurring of the clinical distinction between these diseases and osteoarthritis (OA). It is an important but separate issue that OA itself, as a clinical disease descriptor, encompasses a wide range of diseases, distinguished only sometimes as primary OA and secondary OA, the latter encompassing many different forms of joint disease. Carol Muehleman and colleagues in this issue of The Journal have produced a landmark contribution on the prevalence of crystal deposition in joints in a "normal" population selected as organ donors8. Further, the joint selected for examination, the tibial talar joint, is usually spared from OA. This joint, a gliding synovial joint, is noted for its stability and its mobility restriction to the physiologic range of motion. Compared to previous studies of other joints, particularly the knee joint9-12, the tibial talar joint is relatively spared of crystal deposition. However, when crystal deposition does occur, there is a 92% association with cartilage lesions8. This compares to the joints without crystal deposition, where only 61% of samples demonstrated cartilage changes. Further, compared to non-crystal-bearing joints, there is a 2.4-times greater likelihood of grade II (fissures) and grade III cartilage lesions (erosions) in joints containing crystals. It is well recognized that MSU crystals deposit on joint surfaces as one manifestation of systemic urate metabolism disorders13. While MSU crystals deposit on cartilage surfaces, these crystals can accumulate and erode into cartilage. In contrast, CPPD crystal deposition is restricted to hyaline and fibrocartilages and reflects a metabolic disorder within cartilage itself14. While CPPD crystals have been said to form principally in cartilage mid-zone, this study and our own unpublished observations show that CPPD crystals can form in hyaline cartilage superficial zones, within the cartilage surface and sometimes without deeper underlying deposits. MSU and CPPD crystal deposits on cartilage surfaces cannot be distinguished from each other by the naked eye. However, these crystals can be identified by experienced observers using compensated polarized light microscopy or by more elaborate methods such as Fourier transform infra-red spectroscopy or powder x-ray or electron diffraction. The immunohistochemistry studies in this article are intriguing and bear repeating in other study sets of cartilage affected by OA or by crystal deposits8. Of particular note is the extensive association of type X collagen in joints where crystal deposits are found. This association is present even in cartilage matrix domains, where crystals are absent and where chondrocytes are not hypertrophic. The increased cartilage superficial zone protein staining, present even in the deeper layers of crystal-bearing cartilage, is indicative, along with the morphologic lesions, that both MSU and CPPD crystal deposition induce deleterious and reparative changes in cartilage. The observations in this article present the rheumatology community with a considerable challenge. Crystal deposition in joints is associated with both morphologic and immunohistochemical changes associated with cartilage degeneration and repair. While these changes may be similar in MSU and CPPD crystal deposition diseases, they appear specific to crystal deposition and appear to be different from osteoarthritic changes. On a population basis, crystal deposition in joints appears to bring propensity for cartilage degeneration. In the current study, these disease characteristics were observed in a joint that has a low incidence of OA. How much more extensive, then, is the problem for patients with joints affected both by OA and crystal deposits? As shown in this study, MSU crystal deposition is associated with obesity, presently a chronic epidemic. For MSU, the problem to solve may be better recognition of a disease for which both specific diagnosis and specific therapy exist. Nonetheless, gout is still a common disease and can present as chronic arthritis. For CPPD, we know that up to 35% of patients presenting for total knee arthroplasty for OA have CPPD arthropathy in the surgical pathology specimens10 and that chondrocalcinosis is more common in osteoarthritic knees3,9,11. Some of these cases represent CPPD crystal arthropathy and some mixed OA and CPPD, with the CPPD confined to meniscal fibrocartilage10. From imaging studies, chondrocalcinosis of the knee affects up to 70% of the population by age 7012. It is recognized that CPPD deposition becomes progressively more common with advancing age15. The present study adds to the evidence that CPPD deposition is not just an "epiphenomenon," but is an active contributing factor to cartilage degeneration. As for self-interest, it can be expected that even rheumatologists age and a substantial proportion will be affected by CPPD crystal-associated arthropathy. Clearly, crystal-associated arthritis is more than acutely inflamed joints, or painless periarticular lumps or radiologic features of erosion and/or calcification. Chronic persistence of crystals in joints affects cartilage adversely, contributing to loss of function. Is it not past time to bring a new generation of investigators to study our patient populations with these diseases more closely? To achieve this we need to advocate vigorously for incremental broad-based research to control, cure, or prevent arthritis-associated crystal deposition diseases, both MSU and CPPD. 2. Ryan LM, McCarty DJ. Calcium pyrophosphate crystal deposition disease; pseudogout; articular chondrocalcinosis. In: McCarty DJ, Koopman WJ, editors. Arthritis and allied conditions: A textbook of rheumatology. 12th ed. Philadelphia: Lea & Febiger; 1993:1835-55. 3. Hernborg J, Linden B, Nilsson BE. Chondrocalcinosis: a secondary finding in osteoarthritis of the knee. Geriatrics 1977;32:123-4. 4. McCarty D. Crystals, joints, and consternation. Ann Rheum Dis 1983;42:243-53. [MEDLINE] 5. McCarty DJ Jr, Kohn NN, Faires JS. The significance of calcium phosphate crystals in the synovial fluid of arthritic patients: The "pseudogout syndrome". I. Clinical aspects. Ann Intern Med 1962;56:711-37. 6. Rubenstein J, Pritzker KPH. Crystal-associated arthropathies. Am J Radiol 1989;152:685-95.[MEDLINE] 7. Zitnan D, Sit'aj S. Chondrocalcinosis articularis: Section I. Clinical and radiological study. Ann Rheum Dis 1963;22:142-52. 8. Muehleman C, Li J, Aigner T, et al. Association between crystals and cartilage degeneration in the ankle. J Rheumatol 2008; 35:1108-17. 9. Derfus BA, Kurian JB, Butler JJ, et al. The high prevalence of pathologic calcium crystals in pre-operative knees. J Rheumatol 2002;29:570-4. [MEDLINE] 10. Pritzker KPH, So P. Osteoarthritis and calcium pyrophosphate dihydrate crystal arthropathy [abstract]. Osteoarthritis Cartilage 2004;12 Suppl B:S51. 11. Sokoloff L, Varma AA. Chondrocalcinosis in surgically resected joints. Arthritis Rheum 1988;31:750-6. [MEDLINE] 12. Wilkins E, Dieppe P, Maddison P, Evison G. Osteoarthritis and articular chondrocalcinosis in the elderly. Ann Rheum Dis 1983;42:280-4. [MEDLINE] 13. Pritzker KPH, Zahn CE, Nyburg SC, Luk SC, Houpt JB. The ultrastructure of urate crystals in gout. J Rheumatol 1978;5:7-18. 14. Pritzker KPH. Calcium pyrophosphate crystal arthropathy. A biomineralization disorder. Hum Pathol 1986;17:543-5. [MEDLINE] 15. Hogan DB, Pritzker KPH. Synovial fluid analysis — another look at the mucin clot test. J Rheumatol 1985;12:242-4. [MEDLINE]
|
