Approximately 25% of patients with CPPD deposition disease exhibit the pseudogout pattern of disease. Signs and symptoms are characterized by acute, typically monoarticular inflammatory arthritis lasting for several days to 2 weeks. These self-limited attacks may vary in intensity but can occur just as abruptly as an acute gout attack. Between episodes, patients are usually asymptomatic. Nearly half of all attacks involve the knees, although pseudogout can affect other joints, including the first metatarsophalangeal joint, which is the most common site of gouty inflammation. However, attacks of pseudogout may occur spontaneously or be provoked by trauma, surgery, or severe medical illness. Differentiation of pseudogout from joint infection may be difficult and requires arthrocentesis with examination of synovial fluid for crystals and culture. Without appropriate analysis of synovial fluid, it may be impossible to differentiate pseudogout from septic arthritis.
Symptoms that mimic rheumatoid arthritis develop in nearly 5% of patients with CPPD deposition disease. These patients have low-grade inflammation in multiple, symmetric joints. Moreover, morning stiffness, fatigue, synovial thickening, joint contractures, and elevated erythrocyte sedimentation rate frequently accompany this form of arthritis. Fever and other constitutional symptoms may also be possible. Given these misleading findings, this particular variant of pseudogout is often misdiagnosed as rheumatoid arthritis. Making matters more confusing, a small percentage of patients with CPPD deposition have low titers of circulating rheumatoid factor.
Nearly half of patients with CPPD deposition have a progressive, degenerative disease termed “pseudo-osteoarthritis.” Although there is some overlap with the pattern of joint involvement in primary osteoarthritis, the distribution of joint degeneration with CPPD deposition may differ. The knees are most commonly affected, followed by the wrists, metacarpophalangeal joints, hips, shoulders, elbows, and ankles. While symmetric involvement is typical, deformities and flexion contractures of affected joints are not uncommon. Several cases have been reported of severe derangement and destruction, mimicking the findings seen in Charcot joint. Valgus deformity of the knees is especially suggestive of underlying CPPD crystal deposition, as is disease localized to the patellofemoral joint. Patients with this pseudo-osteoarthritic pattern may have intermittent episodes of acute joint inflammation of varying severity, superimposed on their baseline disease state.
Rarely, CPPD crystal deposition occurs in the axial skeleton, which may potentially lead to acute neck pain. The ligamentum flavum has been the most regularly reported site of CPPD crystal deposition in the spine. At times, neck pain may be accompanied by stiffness and fever, mimicking meningitis. Crystal deposits, ligament hypertrophy, and cartilage metaplasia contribute to encroachment of the spinal cord. Infrequently, lumbar spine involvement may produce an acute radiculopathy or neurogenic claudication resulting from spinal stenosis. Thus, signs and symptoms of neurologic long tract disease, directly resulting from CPPD deposition and its related changes, may develop in some patients.
That being said, many patients with CPPD crystal deposits lack joint symptoms. Even patients with classic osteoarthritic symptoms in some joints may have other joints with crystal deposition that are completely asymptomatic and clinically normal.
The critical laboratory feature of any form of CPPD crystal deposition disease is the demonstration of CPPD crystals. These are most commonly recognized in synovial fluid (Figure 45–1). Their identification requires the use of compensated polarized light microscopy. CPPD crystals are generally rhomboid-shaped and positively birefringent. They appear blue when parallel to the long axis of the compensator and yellow when perpendicular.
Positive birefringent calcium pyrophosphate dihydrate crystals.
Arthrocentesis of patients with pseudogout (and pseudo-rheumatoid presentations) generally yields cloudy fluid with low viscosity; the white blood cell count typically ranges between 5000 and 25,000 cells/mcL. However, white blood cell counts greater than 100,000 cells/mcL have been observed, a finding that is more typically associated with septic arthritis. The white blood cells in the synovial fluid in pseudogout (or the pseudoseptic presentation) are most commonly polymorphonuclear leukocytes. Meanwhile, the fluid seen in the pseudo-osteoarthritic form is clear, viscous, and has a very low white blood cell count (generally less than 300 cells/mcL). Inflammatory presentation of CPPD crystal deposition disease may be accompanied by a peripheral blood leukocytosis with a shift to the left shift on the differential, along with an elevated erythrocyte sedimentation rate and C-reactive protein.
The radiographic findings of punctate and linear densities in hyaline articular cartilage or fibrocartilaginous tissues are diagnostic of CPPD crystal deposition (Figure 45–2). Other radiographic features include degenerative changes in an uncommon site along with subchondral cyst formation. Radiographs most often demonstrate sites of CPPD crystal deposition in the knees, wrist (triangular cartilage of the radiocarpal joint) (Figure 45–3), and the synthesis pubis. The finding of isolated patellofemoral joint-space narrowing or degenerative change in the wrist may provide helpful clinical clues to the presence of CPPD deposition-related arthropathy.
Chondrocalcinosis of the knees.
Chondrocalcinosis of the radiocarpal triangular cartilage.
When the deposits are typical or unequivocal, the radiographic appearance of pseudogout can be viewed as specific. However, the presence of atypical or calcific deposits can be difficult to interpret, since these changes may be confused with coexisting degenerative findings. Pseudogout can produce severe radiographic changes, marked by subchondral collapse, bone fragmentation, and intra-articular radiodense bodies.
Changes in the metacarpophalangeal joints, such as squaring of the bone ends, subchondral cysts, and hook-like osteophytes, are characteristic features of the arthritis associated with hemochromatosis. However, these changes can also be observed in patients with CPPD crystal deposition alone or related to another metabolic disorder, such as Wilson disease.
A patient can be screened for CPPD crystal deposition with four radiographs. These include an anterior-posterior view of the knees, anterior-posterior view of the pelvis, and a posterior-anterior view of both hands to include the wrists. If these views show no evidence of crystal deposition, it is unlikely that further study will be fruitful. Tomographic views may be required to identify CPPD deposits surrounding the odontoid process.
Because of the recognized association between CPPD deposition and various metabolic diseases, the evaluation of a patient with newly diagnosed CPPD deposition should include tests of serum calcium, phosphorus, magnesium, alkaline phosphatase, thyroid-stimulating hormone levels, and possibly ferritin levels. The serum ceruloplasmin levels should also be assessed if Wilson disease is suspected. Hypophosphatasia and Wilson disease need not be considered in patients who become symptomatic after the age of 60 years.