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Coincidence of monosodium urate monohydrate, calcium pyrophosphate dihydrate, and basic calcium phosphate crystals in the synovial fluid from a single joint

The finding of two different crystal species in the same synovial fluid, although unusual, has been recognized for monosodium urate monohydrate (MSU) and calcium pyrophosphate dihydrate (CPP) crystals (1) and, more rarely, for CPP and basic calcium phosphate (BCP) crystals (2). We describe a rarely reported example of the coexistence of three different crystal types in a single joint effusion. A 70-year-old man presented to the hospital with acute pain and swelling of the left knee. He had a 10day history of migrating polyarthralgias with malaise, weight loss, fatigue, and fever with no skin rash. The patient had suffered a partial meniscectomy because of a degenerative meniscus tear of his left knee 15 years ago. Apart from that, his medical history did not suggest a predisposition to a specific musculoskeletal disorder. Laboratory tests, including serum C-reactive protein and uric acid levels, were unremarkable and no rheumatoid arthritis, vasculitic syndrome, connective tissue disorder, spondyloarthropathy, infection, or malignancy was demonstrated. Physical examination of the patient showed a swollen and tender knee with a painful restriction of active and passive movement. An X-ray of the knee revealed severe osteoarthritis and signs of chondrocalcinosis. On magnetic resonance imaging, the remaining meniscus was seen to be multifragmented and displayed advanced cartilage degeneration. Ultrasound evidenced a significant joint effusion and arthrocentesis was performed. We received 7 mL of yellow translucent to cloudy fluid with white floating clots (Figure 1A). The cell count in cytospin preparations was 4260/mm with 56% neutrophilic polymorphonuclear leucocytes. Cultures and stains failed to demonstrate any micro-organisms. Under polarized light microscopy, two types of birefringent crystals were evidenced: MSU and CPP crystals (Figure 1B). In addition, Alizarin red S (Figure 1C) and Von Kossa (Figure 1D) stains revealed calcium deposits suggestive of BCP (hydroxyapatite) crystals. The patient was started on high-dose prednisone with notable relief of his symptoms. While simultaneous occurrence of two different crystal species in synovial fluid has long been recognized for MSU and CPP crystals (1, 2), there are only two previous descriptions of three crystals in a single joint (3, 4). When more than one crystal is present, the interrelationships are not easily determined and it is difficult to assign responsibility for the clinical picture observed to a single crystal (1, 2, 5, 6). It is possible that factors favouring deposition of one crystal may also favour deposition of others (3), in the same way that the deposition of MSU crystals can predispose to the development of CPP crystals (1, 5). In addition, it has been suggested that BCP and CPP crystals are more likely to occur together than alone and that CPP crystals tend to correlate with joint degeneration (3, 6). There is no evidence that mixed crystal composition has any adverse significance (1). It is usual to consider that an acute attack in patients with mixed crystal-induced arthritis is chiefly related to the presence of MSU crystals, and that the presence of CPP crystals is of secondary importance. However, it is well known that MSU and CPP crystals posses similar inflammatory potential (2). Furthermore, BCP crystals, which are related to the severity of joint degeneration associated with osteoarthritis, can also cause acute synovitis (7). BCP crystals are not birefringent and their detection in synovial fluid can be elusive. Alizarin red S and Von Kossa stains are suitable for calcium but they are non-specific for hydroxyapatite crystals (2, 7). Nevertheless, when characteristic morphological and staining features are present, a presumptive diagnosis of BCP crystals can be applied (7). Phagocytosis of any of these crystals in the joint is able to stimulate a brisk, neutrophilmediated inflammatory response (4). In our case, we assumed MSU and CPP crystals to be the cause of the arthritis. In addition, the presence of CPP and BCP crystals was related to the presence of osteoarthritis. Furthermore, the patient had suffered a partial meniscectomy, which is a known factor for early articular chondrocalcinosis and pseudogout (1). Joint aspiration is recommended in cases of acute or recent-onset swelling of the knee for immediate reduction of painful intra-articular hypertension as well as for diagnosis (8). Cultures, if septic arthritis is suspected, and assessment of crystals should be completed. The coexistence of different crystal types should be Letters 167