SANTA BARBARA, CALIF. — Deposition of calcium pyrophosphate dihydrate into joints can mimic several other conditions, including osteoarthritis, rheumatoid arthritis, and gout, and making a definitive diagnosis can be quite a challenge, Ann K. Rosenthal, M.D., said at a symposium sponsored by the American College of Rheumatology.
A definitive diagnosis of calcium pyrophosphate dihydrate (CPPD) deposition disease can be made only by identifying the crystals directly, using complex techniques such as x-ray diffraction or Fourier transform infrared spectroscopy, techniques that are unavailable in most clinical labs.
“Most of us diagnose CPPD deposition by synovial analysis,” said Dr. Rosenthal of the Medical College of Wisconsin, Milwaukee. “We look under polarizing light microscopy and see the positively birefringent crystals. This really remains the gold standard clinically.”
Unfortunately, CPPD crystals are often only weakly birefringent, with one study indicating that just 17%–40% of the crystals glow under polarizing light (Ann. Rheum. Dis. 1999;58:582–4). In contrast, practically all gout crystals are birefringent. For this reason, nonpolarizing light microscopy may be useful in diagnosing CPPD deposition disease.
The disease is such an excellent imitator of other rheumatic conditions that many physicians never suspect calcium crystals as a cause. In all likelihood, many cases are missed because of poor diagnostic techniques.
An analysis of a patient's risk factors for CPPD deposition disease provides little ammunition to increase the index of suspicion.
The condition is rare in people under the age of 60 but rapidly increases in incidence in older patients. About 50% of patients over the age of 90 have radiographic evidence of CPPD deposition. Women are slightly more likely than men to have CPPD deposition. And prior injury to the joint increases the risk of CPPD deposition.
A variety of metabolic disorders are associated with the formation of CPPD crystals. The most significant are hyperparathyroidism, hemochromatosis, hypomagnesemia, and gout, but case reports have implicated a number of other conditions.
The clinical presentation of CPPD-induced pseudogout, pseudo-rheumatoid arthritis, or pseudoosteoarthritis can differ in subtle ways from the true conditions. For example, pseudoosteoarthritis (the most common CPPD deposition disease) can appear identical to true osteoarthritis, although it may affect unusual joints.
“Perhaps a lot of what we're calling osteoarthritis is actually CPPD deposition disease,” Dr. Rosenthal said. One study demonstrated a 60% prevalence of either CPPD or basic calcium phosphate crystals (called BCP crystals or hydroxyapatite) in knee joints of patients with a preoperative diagnosis of osteoarthritis (J. Rheumatol. 2002;29:570–4).
Chondrocalcinosis is the radiographic hallmark of CPPD deposition disease, but it can be risky to diagnose the condition based on radiographic findings alone, Dr. Rosenthal said. Chondrocalcinosis appears as a linear deposition of calcium, often in the fibrocartilage or lining of the articular cartilage. It is most likely to be found in the symphysis pubis and the triangular cartilage of the wrist.
Ultrasound is the most promising new technique for CPPD diagnosis, with a recent study identifying three patterns that appear highly specific for CPPD deposition disease. The first is a punctate pattern with several thin hyperechoic spots in fibrocartilage and tendons. The second is characterized by homogeneous hyperechoic or oval deposits localized in bursae and articular recesses. The third pattern shows thin hyperechoic bands parallel to the articular surfaces (Ann. Rheum. Dis. 2005;64:638–40).
MRI adds little to a diagnosis, since calcification in cartilage can appear as high or low signal intensity.
On the other hand, CT scans can be quite sensitive and may be particularly useful for cases with spinal involvement. One advantage of CT scanning is that the technique can detect—and in some cases differentiate between—both BCP and CPPD crystals.
CPPD crystals are weakly birefringent under polarizing light microscopy (as shown). Only 17%–40% of CPPD crystals glow using such means.