LAUSR

We reported a case of an 84-year-old woman with an old inability to actively elevate her left upper limb, with recent shoulder pain. X-ray showed an important arthropathy of the left gleno-humeral joint with epiphyseal osteonecrosis (Fig. 1a). Ultrasound examination showed a sub-acromial bursal thickening with a heterogeneous echogenicity (Fig. 1b). Bursal aspiration revealed a thick and yellowish synovial fluid (Fig. 1c). Microscopic examination revealed typical aspect of monohydrate cholesterol crystal (CC) (Fig. 1d–g). After centrifugation, some calcium pyrophosphate (CPP) crystals were also observed in synovial fluid. Apart from an inflammatory syndrome (CRP 56.6 mg/L), no other biological abnormalities were observed (negative rheumatoid factor and anti-citrullinated protein antibodies, normal carbohydrate-lipid). Neurogenic arthropathy was disproved with negative syphilitic serology and absence of diabetes mellitus. Long term synovial fluid bacterial culture was negative. Spinal, knee and pelvis X-rays revealed widespread CPP-crystal deposition. Final diagnosis was an advanced osteoarthritis probably induced by a CPP-deposition disease. Shoulder arthroplasty was suggested but the general state of this old woman did not allow this surgery. Crystal-induced arthritis is frequent, mostly through monosodium urate monohydrate (UMS), CPP and calcium hydroxyapatite. CC could represent about 0.1–0.7% of all synovial fluid, not always recognized by clinicians or described by laboratory [1]. Two morphologic forms are described: a rod-shaped helical birefringent crystal (2–20 μm) (anhydrate cholesterol) and large flat rectangular plates that are doubly refracting with notched corners (8–100 μm) (monohydrate cholesterol) [1]. CC are described not only in chronic bursitis or synovitis, mainly in rheumatoid arthritis (RA), but also in gout, osteoarthritis, ankylosing spondylitis and systemic lupus erythematous. Main joint locations are shoulder and knee. Other authors have described the combination of other crystals with CC, such as CPP crystals. Cases of CC-induced arthritis or bursitis reported in literature are available on Supplementary data. The origin of the presence of CC in joint is not clear. A dyslipidemia (i.e. familial hypercholesterolemia) does not lead to the appearance of joint cholesterol crystals [2]. Synovial cholesterol concentration is higher than serum concentration in several cases of identification CC in joint [1]. Recurrent hemarthrosis, poor drainage of synovial fluid or high synovial capillary permeability have been suggested to explain this high synovial cholesterol concentration [3]. The phlogistic potential of CC appeared to be lower than CPP or UMS, which would result in a lower crystallization power. CC injection into the knees of animal models (rabbit) induced a chronic synovitis, without acute flare-up [4]. The pathophysiology of this chronic synovitis remains unclear, but CC insolubility and resistance to cellular degradation could explain CC persistence in synovial tissue and the development of a granulomatous inflammatory reaction [1, 4]. But why particularly in rheumatoid synovitis? Synovial cholesterol concentration is higher (40–60% of serum concentration) in RA [5] than in a normal or osteoarthritis joint, but lower than in gout. The lipoprotein fractions appear to be similar in rheumatoid synovium and serum while their density is lower, suggesting an ultrafiltrate on contradictory data [5, 6]. Finally, synovial lipid concentrations appear to increase in chronic synovial inflammation [6] and CC can affect other serosa such as pleuropericarditis [7] in RA. Another hypothesis would be the implication of autoantibodies directed against low and very low Inflammation Research