You are in: eMedicine Specialties > Orthopedic Surgery > SYSTEMIC DISEASES ChondrocalcinosisArticle Last Updated: Jun 14, 2006AUTHOR AND EDITOR INFORMATIONSection 1 of 12
  Author: Neil J Barkin, MD, FAAOS, Consulting Surgeon, Capitol Orthopaedics & Rehabilitation, LLC Neil J Barkin is a member of the following medical societies: American Academy of Orthopaedic Surgeons Coauthor(s): Anne Wolbert, PA-C, Physician Assistant, Capitol Orthopaedics & Rehabilitation, LLC Editors: Jegan Krishnan, MBBS, FRACS, PhD, Chair, Senior Clinical Director, Department of Orthopedic Surgery, Flinders Medical Centre and Repatriation General Hospital, Flinders University of South Australia; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Paul E Di Cesare, MD, Chair and Professor, Department of Orthopedic Surgery, University of California Davis School of Medicine; Dinesh Patel, MD, FACS, Associate Clinical Professor of Orthopedic Surgery, Harvard Medical School; Chief of Arthroscopic Surgery, Department of Orthopedic Surgery, Massachusetts General Hospital; Harris Gellman, MD, Consulting Surgeon, Broward Hand Center, Voluntary Clinical Professor of Orthopedic Surgery and Plastic Surgery, Departments of Orthopedic Surgery and Surgery, University of Miami School of Medicine Author and Editor Disclosure Synonyms and related keywords: calcium pyrophosphate dihydrate deposition disease, CPPD, CPPDD, calcium pyrophosphate dihydrate crystal deposition disease, pseudogout, tophaceous pseudogout, osteoarthritis, OA INTRODUCTIONSection 2 of 12
  Calcium pyrophosphate dihydrate deposition (CPPD) disease is an arthritis variant. CPPD is actually a chemical aberration that manifests as at least 4 separate, yet related, diseases. Chondrocalcinosis has been described as the streaking of soft tissues with calcium. The term chondrocalcinosis sometimes is misapplied as a synonym for CPPD disease, but, technically, it refers to the visible presence of calcification within tissues on an imaging study. ProblemCPPD consists of the deposition of calcium pyrophosphate crystals into soft tissue. They have been found in high concentrations in hyaline cartilage, synovial tissue, capsule, meniscus, labrum, ligamentum flavum, the soft tissue of the hand, and, rarely, in the fibrocartilage of the temporomandibular joint. FrequencyEstimates on the frequency of CPPD disease in the United States vary widely. Rates range from 4% to more than 25% of the population by age 80 years. Prevalence clearly increases with age. CPPD manifests clinically approximately half as often as gout in the typical practice setting. The male-to-female ratio is approximately 1.4:1. EtiologySee Pathophysiology. PathophysiologyThe exact physiological dysfunction is not clear, but studies appear to implicate the chondrocyte and surrounding matrix as the responsible agents. Some noxious event (perhaps chemical, perhaps physical) appears to incite a cascade that evolves toward the hypertrophy and degeneration of chondrocytes. Intracellular material escapes to the surrounding matrix and potentially alters the calcium-binding effect of the matrix proteoglycans. Calcium pyrophosphate crystals grow adjacent to these hypertrophic chondrocytes within the affected matrix. The breakdown of collagen cells has been proposed to be the source of the inorganic pyrophosphate. ClinicalFollowing are the 4 separate and distinct manifestations of this disease: Pseudogout An acute presentation appears very similar to gout. Technically, this is designated pseudogout, although the term is often used synonymously with all CPPD diseases. Gout can be distinguished from pseudogout in that gout crystals (sodium urate) are needle shaped and have negative birefringence, while pseudogout crystals (calcium pyrophosphate) are rod or rhomboid shaped and have no or weak positive birefringence. Advanced techniques such as electron microscopy can be used for a definitive diagnosis. Pseudogout is estimated to affect a small percentage (<25%) of individuals with demonstrated CPPD disease. Onset is usually monoarticular or pauciarticular and is often preceded by injury or surgery to the area. Not infrequently, pseudogout has been identified soon after parathyroid adenoma excision. The onset is aggressive, reaching a peak in hours, and creating pain, swelling, heat, and redness. Fever is present in approximately half the patients with pseudogout. The knee most often is affected. The shoulder, elbow, ankle, and familiar first metatarsophalangeal (MTP) joint are also frequently involved. The natural course is spontaneous resolution over a few days or, at most, weeks. Treatment accelerates recovery. Tophaceous pseudogout The calcium pyrophosphate material can deposit in large accumulations, producing a pseudotumor. These can be massive, with all of the consequences of any other space-filling lesion. They often are discretely painful. A review of the literature reveals reports of rare lesions in the temporomandibular joint, sternoclavicular joint, transverse ligament of C1, metatarsophalangeal joints, spinal facet joints, cubital tunnel, and other sites. Involvement in the spine is frequently associated with neural impingement symptoms and spinal stenosis, requiring surgical decompression. Familial calcium pyrophosphate dihydrate deposition A familial pattern appears at a much earlier age, often as early as the third decade of life. It tends to be more aggressive, with a more ominous long-term prognosis. The longevity of satisfactory joint function is reduced in these individuals. Genetic studies have implicated a responsible gene with an autosomal dominant mode of inheritance. Families with a rate of sibling involvement as high as 70% have been documented. Familial studies and mouse genetics have been used to identify a mutation in the ANKH gene, which, when present, significantly increases the risk of developing calcium crystal formation. The mouse homologue of the ANKH gene was shown to code for a protein necessary for transporting inorganic pyrophosphate across the cell membrane into the extracellular environment. Mutations in this gene result in increased intracellular inorganic pyrophosphate levels. The low extracellular levels of inorganic pyrophosphate permit hydroxyapatite deposition in and around the articular hyaline cartilage and fibrocartilage and thus, promote calcium hydroxyapatite crystal formation in the mouse. The ANKH gene has clearly been linked to CPPD in humans, but the molecular dynamics are not as well understood. Osteoarthritis The most common presentation is that of osteoarthritis (OA) alone. Symptoms are identical to those of the typical patient with OA, with the exception that at some point, the presence of calcium pyrophosphate crystals is appreciated. Most often, this is identified by the presence of chondrocalcinosis. Chondrocalcinosis increases in frequency with age. Injury and surgery may aggravate symptoms. Some reports of symptom onset following viscosupplementation injection also are recorded in the literature. Most patients in the typical orthopedic practice are in the latter category. Associated with the general category of CPPD diseases and, therefore, presumably including all the presentations listed above, are other metabolic diseases. The incidence of CPPD is increased in persons with hyperparathyroidism, hemochromatosis, hemosiderosis, hypomagnesemia, and hypophosphatemia. INDICATIONSSection 3 of 12
The persistence of symptoms despite aggressive nonsurgical management should be considered an indication to perform surgical evaluation and treatment. RELEVANT ANATOMYSection 4 of 12
An intraoperative photograph (see Image 1) demonstrates extensive precipitate deposition of the calcium pyrophosphate crystals in the articular cartilage, meniscus, and synovium of a knee. CONTRAINDICATIONSSection 5 of 12
Patients who demonstrate symptoms of OA or CPPD disease have no contraindications to performing arthroscopic surgery as needed. For persons with more advanced OA, the available surgical procedures, up to and including total knee arthroplasty, also are not contraindicated by the presence of this disease. WORKUPSection 6 of 12
Lab Studies
Imaging Studies
Diagnostic Procedures
Histologic FindingsSoft tissues demonstrate the presence of crystal deposition with adjacent chondroid metaplasia. Synovial hyperplasia with inflammatory changes often is visualized and may be mild to moderate, consisting of mononuclear cells. In tophaceous pseudogout, giant cells often are visualized. TREATMENTSection 7 of 12
Medical therapyTreatment depends on the degree of involvement. For patients who demonstrate the most common presentation (ie, arthritic symptoms), treatment should follow the algorithm assigned to patients with OA. This includes modified activity, physical therapy, and nonsteroidal anti-inflammatory drugs (NSAIDs). Surgical intervention is indicated when the response to these modalities is unsatisfactory. For individuals with acute episodes, who usually present with an enhanced level of pain and disability, arthrocentesis in combination with administration of an intra-articular steroid provides reliable prompt relief. NSAIDs and colchicine may be used to prevent recurrent episodes. Limited studies have shown favorable results from diminishing the calcium deposits with ethylene diamine tetraacetic acid (EDTA) treatment. EDTA strongly binds to divalent cations (including calcium) and has the potential to eliminate them from the affected area. The role of EDTA in the treatment of chondrocalcinosis will require more extensive investigation because this agent has significant adverse effects. Pulsed ultrasonography has been show to be an effective treatment for some calcification diseases. Patients often show reduced pain. Ebenbichler et al reported that 47% of patients demonstrated a decrease of at least 50% of the calcification after 6 weeks of treatment. At 9-month follow-up, 65% of patients presented with at least a 50% reduction of calcification, with nearly half showing complete resolution. Surgical therapyArthroscopic surgery allows debridement of superficial deposits of the calcium pyrophosphate precipitate. This alone may not materially affect the course of the disease. Surgical treatment of OA with debridement, microfracture chondroplasty, radiofrequency chondroplasty, osteochondral transfers, osteotomy, and, ultimately, partial or total joint replacement completes the armamentarium. When large space-occupying tophaceous lesions are present, surgical excision is indicated. Although the impact of crystal deposition on the viability and future performance of the articular cartilage and meniscus is not clear, many surgeons believe that the presence of this precipitate renders the tissues more fragile. Not infrequently, meniscal tears or chondral lesions are located directly at the site of the densest accumulation of crystals. Cause and effect have not been determined, yet the impression is created that the deposition is responsible for undermining the integrity of the tissue. Intraoperative detailsChanges of OA often are present. These may range from mild to severe. White crystal precipitate is identified in various locations throughout the joint. This ranges from sparse to extensive. Tissue disruption in the form of tears (eg, meniscus) to chondral lesions (eg, articular hyaline cartilage) may or may not be present with the crystal deposition. The white precipitate appears to be both superficially attached and deeply embedded. Often, very little effort is required to sweep the soft tissue with a blunt probe, freeing large quantities of the crystalline material into the joint fluid to be easily suctioned from the joint. Postoperative detailsPostoperative management is unchanged from that for the typical patient with OA. Follow-upNo specific moderations must be made in the postoperative period. COMPLICATIONSSection 8 of 12
Practitioners who have examined numerous joints arthroscopically often report the impression that chondrocalcinosis increases susceptibility to developing osteoarthritis in those tissues that exhibit the precipitate. OUTCOME AND PROGNOSISSection 9 of 12
The most interesting issue regarding CPPD disease is its overall impact on the progression of the OA with which it coexists. The literature tends to be ambiguous on this issue. Some studies imply that the presence of CPPD disease accelerates the deterioration of OA, while other studies refute this. A Framingham OA study of 598 knee patients from 1983-1992 concluded that the presence of chondrocalcinosis had no demonstrable impact on the natural progression of the disease. FUTURE AND CONTROVERSIESSection 10 of 12
As the etiology of calcium pyrophosphate disease is clarified, more focused metabolic treatment regimens will be used. The goal will be to reduce the inflammation associated with the crystal deposition and to provide reduced frequency and intensity of symptoms. Continuing genetic and molecular insight, such as that provided by studies of the ANKH gene mutation, will allow for a detailed understanding of the disease's manifestations and will allow for targeted treatments. MULTIMEDIASection 11 of 12
REFERENCESSection 12 of 12
Article Last Updated: Jun 14, 2006 | |||||||||||||||||||
