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Liquid lipid crystals-induced arthritis crystals are a frequent cause of arthritis. They are disclosed by the microscopic examination of the synovial fluid. They are usually made of monosodium urate, calcium pyrophosphate or apatite. Liquid lipid crystals have a spherical shape with an aspect of Maltese crosses and a positive birefringence. They are sometimes observed outside the leukocytes in rheumatoid or post-traumatic effusions. In some cases, they constitute the solely cause explaining the arthropathy. Then, they are numerous and located in and outside the cells. This observation reports on the case of a 50 year-old woman having developed this type of arthritis related to a right knee hemarthrosis. Awareness of this pathology may be useful because its evolution is usually good with a non-steroidal anti-inflammatory drug or a local steroid infiltration after exclusion of an infectious origin of the effusion.

Five to 40% of patients with agammaglobulineamia develop joint manifestation consisting of septic arthritis or aseptic arthritis of unclear pathogenesis. Intravenous gamma-globulin therapy seems effective on the better condition but is burden-some and expensive. We report the case of a 31-year old woman, having a common variable immunodeficiency that has a chronic oligoarthritis seronegative and not warping. Substitutive treatment with gamma-globulins resulted in a poor improvement. Blood Lymphocyte immunotyping ans analysis of synovial fluid showed high levels of CD8 with a low CD4/CD8 ratio. Synovial biopsy revealed a non specific synovitis with an lymphoid aggregates with a significant predominance of CD8 cells and suspicion of mycoplasm, only after centrifugation, justifying PCR techniques. Doxycycline therapy was effective in relieving the joint symptoms with six month recession.

Cytologic examination of synovial fluid has been shown to be useful in the diagnosis of various joint diseases. Few pathologists are proficient in the interpretation of the occasional synovial fluids that most cytology laboratories receive. The majority of the aspirated synovial fluids are sent only for bacterial culture and valuable information from the cytologic examination is missed. We describe how pathologists should perform analysis of these fluids and what kind of information they can provide to the physician.

Reactive arthritis is differentiated from infectious arthritis by the lack of intraarticular infectious agents. Recently 2 groups, using different techniques have demonstrated intra-articular antigens in cases of reactive arthritis associated with Chlamydia and Yersinia infections. In this article we report the preliminary results of screening cells from synovial fluid for DNA of certain microorganisms by in situ hybridization. Our findings provide complementary evidence of the intra-articular presence of at least parts of microbes.

The authors report two cases of eosinophilic arthritis in allergic patients, which constitute the 9th and 10th reported cases. This condition consists of episodes of mildly painful, mildly incapacitating monoarthritis, essentially involving the knee, which last 2 to 15 days. These monoarthritis occur in young allergic patients; there are no allergic manifestations during the episode of arthritis and there is apparently no provoking allergen, but examination reveals intense dermographism. Apart from the presence of eosinophil polymorphonuclear cells in the synovial fluid, one can also find Charcot-Leyden crystals (one of the two cases in this study). The histological examination of the synovial membrane in one of these patients revealed an infiltration of eosinophil polymorphs. A raised serum IgE is always found. Including these two cases, the authors have found 11 out of 4277 specimens of joint fluid which show articular eosinophilia. The nine other cases consisted of one haemarthrosis, two post-arthrographic effusions, one filarial arthritis, one psoriatic rheumatism, one Gougerot-Sjögren syndrome and three cases of unclassifiable arthritis. Data from the literature show that articular eosinophilia is a rare phenomenon, that it does not constitute a simple local reflection of a blood hypereosinophilia and that it can consist of the cases found in this study.

Synovial fluid lymphocytes were studied by cytofluorometry in 11 patients with classical or definite rheumatoid arthritis. This method allowed the study of the cellular cycle after acridine orange staining and of membrane antigens, expressed by normal and/or activated lymphocytes, which were demonstrated by using various monoclonal antibodies (OKT3, OKT4, OKT8, OKIa1, OKT10). The OKT4/OKT8 ratio was decreased in 4 out of 5 cases and the percentage of HLA DR + cells was clearly increased. In 6 out of the 11 patients, the percentage of dividing cells varied from 2.2 to 7.2 and was less than 1 in the others as in normal blood lymphocytes. Increase in cellular RNA content characterized the non dividing cells. The most elevated values of the cellular RNA content were observed in patients who had the smallest percentage of dividing cells, suggesting that the cellular cycle was stopped between the G1 and S phases. Study of the cellular cycle may reveal a lymphocyte activation parameter which could be unrelated to the expression of differentiation membrane antigens.

The authors investigated 55 determinations of synovial lactic acid in 7 groups of patients: septic arthritis, seropositive rheumatoid arthritis, seronegative rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitic arthritis, reactive arthritis, mechanical fluids of osteoarthritis. Statistical analysis confirmed the diagnostic contribution of this determination in septic arthritis and demonstrated a correlation between the lactic-acid and cell levels within a cell-level range of 5,000-20,000. A significant difference was detected between seronegative and seropositive forms of arthritis. The physiopathologic interpretation of the findings in cases of rheumatoid polyarthritis and in non-rheumatoid inflammatory rheumatism is discussed.

We have studied the synovial and blood lymphocyte populations of 18 patients with rheumatoid arthritis. Two methods have been used: the membrane markers (E rosette, active E, EA, EAC) and lymphocyte electrophoresis. The authors find no significant difference beteween the blood populations of the patients with the PR and that of the controls. On the other hand, the study of the synovial fluid shows a large number of lymphocytes T forming active rosettes having an electrophoretic mobility of about 1,10. In order to explain the presence of lymphocytes with high affinity for sheep red cells, and having a reduced electric charge in the synovial fluid, we propose two explanations: the first one is a selective filtration through the synovialmembrane of a physiological T subpopulation; the second one is a general modification of the lymphocyte membrane in relation with a stimulation or an intraarticular cellular alteration. In the discussion we report the arguments in favour of the two hypothesis.

Optical and electron microscopic studies of the articular fluid in multiple calcification disease reveals the existence of rounded intra- and extracellular crystalline formations. These crystalline formations of calcium and phosphorus are made up of accumulations of tiny crystals shaped like fine needles 200 nm X 15-20 nm and are highly suggestive of hydroxyapatite. Crystals injected into the plantar pads of rats or the knees of rabbits induce an acute inflammatory reaction maximal at 5 hours and recovering in 24 72 hours. Hydroxyapatite crystals are swiftly dissolved in serum and more rapidly still when cells are present. Their dissolution releases calcium into the surrounding area. HLA typing of patients with multiple tendinous calcification (28 cases) or single tendinous calcification (10 cases) shows an increased frequency of HLA A2 and BW 35 in comparison with controls.

An original and easily reproducible technique for isolating and culturating mononucleated phagocytes from rheumatoid synovial fluid was used by the authors to study the synthesis of PGE2, PGF alpha 2 and TxB2 by macrophages taken from 16 patients with rheumatoid arthritis. The functional importance of these macrophages was evaluated by comparing their ratios of prostaglandin synthesis. PGE2 and TxB2 are released in large quantities and are increased after stimulation with zymosan. Two distinct cell populations having different biochemical characteristics were identified from these macrophages based on their capacity to synthesize prostaglandins. Prostaglandin synthesis was correlated with the clinical progression of rheumatoid arthritic disease as evaluated by Lee's index and the time required to loosen up morning joint stiffness in these patients. No correlation was found between prostaglandin synthesis and the quantity of synovial fluid in the affected joint. The first results of a pharmacological study evaluating the activity of non steroid anti-inflammatory drugs using this experimental model are presented here. The addition of indomethacin to culture medium produces dose-dependent inhibition of prostaglandin synthesis.

With reference to an exceptional observation of arthritis due to Loa loa filariasis with eosinophils predominating in the joint fluid, the causes of such joint effusions are reviewed. These effusions are neither specific of nor consistent in articular manifestations of parasitic infections. Demonstration of a high eosinophil count in joint fluid should always suggest a parasitic disease. However, synovial eosinophilia may be found in many other conditions and may even appear to be primary.

The tremendous increase in the number of articles from the world scientific literature dealing with the synovial fluid in recent years, reflects the growing interest of research on that subject. The current review summarizes the scientific works published during the period of 1972 to 1975. This review deals with fundamental as well as applied research or clinical reports adding some diagnostic hints in the knowledge of diseases involving joints. The content of the review is divided in two major chapters. 1) The Physico-Chemical Properties of the Synovial Fluid (viscosity, pH,...); 2) The Composition of the Synovial Fluid (proteins, carbohydrates, lipids, prostaglandins, cells, crystals, micro-organisms).

The authors give a general review of rheumatic manifestations associated with immunodeficiency in children with reference to 7 personal observations. The review demonstrates the high frequency of this association, the variable clinical picture in one, a few, or many joints, the prolonged, relatively mild evolution that is never deforming or ankylosing, the existence of frequent auto-immune and rheumatic manifestations in families, and the usual but variable effectiveness of gammaglobulins. The possibility of immunodeficiency should be considered in cases of mono-, oligo-, and polyarthritis. The results of humoral and cellular immunological studies demonstrated a low level of immunoglobulins, the presence of nonfunctional B cells, and the presence of T cells that were probably qualitatively modified. A physiopathological interpretation is suggested.

329 synovial fluids from various joint diseases were examined. 95% of the fluids from arthrosis contained less than 1 000 cells/ml, figure which seemed to us to be the limit which separates arthrosis from arthritis. Above 100.000 cells/ml, the diagnosis is always pyogenic arthritis. Between 50.000 and 100.000 cells/ml, one may find pyogenic arthritis but also a few cases of rheumatoid arthritis, psoriatic rheumatism, gout and pseudo-gout. In chondrocalcinosis, the fluid variable, often poor in cells. The percentage of polymorphs is of little diagnostic interest; it exceeds 50% in all cases of pyogenic arthritis. R.A. cells are almost constant in fluids with more than 1 000 cells/ml and their diagnostic interest is not great.

The authors studied the cell composition and the cytochemistry and ultrastructure of the frothy cells in two periarticular chyliform effusions in rheumatoid arthritis. Compared with the polymorphonuclear cells, the mononuclear cells were very numerous with many frothy cells. Cholesterol crystals, identified by X-ray diffraction, were detected in fluids by polarised light, but only cytochemically and with the transmission electron microscope in the spumous cells. The latter contained not only neutral fat, but also hydrophobic lipids and phospholipids, but no cholesterol esters. A theory has been advanced that once phagocytosis has been accomplished, cholesterol crystal metabolism is not rapid and is too insufficient for cholesterol or its esters to accumulate in the cytoplasm. The polymorphonuclear leukocytes play only a small role in the phagocytosis of crystals and this probably plays a role in the absence of acute inflammation in structures which contain chyliform effusions.

The authors report three cases of type IIa hypercholesterolemia in which ultrastructural observation of the synovial fluid revealed the presence of frothy cells and microcrystals. A questionnaire-based retrospective investigation amongst a population of 201 patients followed-up for type IIa essential hypercholesterolemia revealed the presence of joint disorders in 92 cases (45.8%). The condition sometimes affected a single joint (17.4%), but was generally polyarticular (82.6%), affecting the large joints. Joint pain was reported in 38 cases (41.3% of the patients presenting joint disease and 18.9% of the group as a whole) and predominantly affected the arms. Acute arthritis (54 cases) occurred preferentially in the legs. In 35 cases (38% of the joint-disease cases and 17.4% of the population as a whole) this resulted in acute rheumatic fever. Nineteen of these cases were unspecified forms of arthritis (20.7% amongst the joint-disease sufferers and 9.5% of the population). This analysis, combined with ultrastructural studies of the synovial fluid from 3 patients, establishes the existence of hypercholesterolemic rheumatism amongst heterozygotes as well as amongst homozygotes.

Analysis of twenty five personal observations of septic osteoarthritis compared with information from the literature led the authors to the following conclusions: 1) Diagnosis of septic osteo-arthritis must be considered when confronted with a picture of acute or subacute arthritis generally inflamed with variable fever, raised sedimentation rates and frequently polymorph neutrophilia, above all especially if there are particular antecedents (local trauma or intra-articular injection, conditions which favor infections: diabetes, alcoholism, impaired immunity, corticosteroid therapy or various therapeutic immuno-suppresives). 2) It may be established on absolute criteria (isolation of the organism at the site of the lesions) or, in the absence of direct bacteriological evidence, by a body of evidence amongst which 4 arguments are of particular value: identification of a pathogenic organism in one or more blood cultures and/or at the site of a closed infection, postive serology and particularly elevation of the antistaphylolysine titres, rapid-onset radiological changes of destruction and/or reconstruction. plus hypercellularity of the fluid greater than 100,000 cells/mm3. 3) Medical treatment sometimes includes local treatment (joint aspiration, local injection of antibiotics) and in all cases immobilisation during the acute phase and systemic antibiotics. The latter will vary according to the organism responsible and its sensitivity. It seems useful to continue this for twelve weeks at the minimum in the normal form, initially making use of the combination of 2 antibiotics and preferably using continuous perfusion and/or intramuscular routes during the first half of treatment. 4) The consistently good results of such medical treatment seem to limit considerably the place of surgery for which the indications have become rare during the acute phase and even more so at later stages.

The joint fluid in cases of algodystrophy was studied in 17 samples. It is poor in cells (275/mm3 with a mean of 15% polymorphs). The protein level was studied 4 times and was equal to or greater than 40 g/l, i.e. double the normal value. A detailed histological examination of 33 biopsies of synovial tissue reveals a typical appearance of the synovium in algodystrophy, defined by 6 features, 2 negative and 4 positive: absence of hyperplasia of the synovial lining, absence of any real inflammatory cell infiltrate, presence of a marked hypervascularity, an oedema of the chorion, especially marked in the first weeks of the disease, hyperplasia of the walls of some arterioles, and fibrosis of the chorion which becomes more marked as the disease progresses and which is predominantly in the deeper layers. The authors recall that articular cartilage can show superficial alterations of structure with areas of fibrosis.

The articular cartilage is frequently destroyed in rheumatic diseases. Among the various responsible factors, enzymes and especially collagenases play a leading role. Their action explains the collagen degradation linked with cartilage destruction. The author recalls the origin, mechanism of action of the articular collagenases and discusses their role in the articular cartilage degradation in rheumatic diseases.

An important role is supposed to be played by the collagenases in the physiological or pathological degradation of collagen. However, their exact effects in rheumatic diseases, especially in rheumatoid arthritis is still controversial. The aim of the authors is to give facts and datas up to date, about this important question of the pathogenic role of collagenases in rheumatoid arthritis, osteoarthritis and in several other rheumatic diseases.

Scanning electron microscopy allows a tridimensional morphological study of the cellular elements of the pathological human synovial fluid. The cells are grouped into two populations: macrophage cells and round cells, whose differentiation is more difficult: polynuclears, lymphocytes and synovial cells. The combination of scanning electron microscopy and X-ray diffraction makes it possible to describe and indentify crystals of sodium urate and of triclinical, dehydrated calcium pyrophosphate.

The immunofluorescent study of 93 synovial membranes of persons suffering from various types of arthropathy has shown that the only element sufficiently specific to have real diagnostic value is the presence of cells with a fluorescent cytoplasm. This appearance was in fact found in 63% of the cases of rheumatoid arthritis, irrespective of their being either seropositive or seronegative, in 69% of the cases of probable rheumatoid arthritis, in only 15% of the unclassified cases of arthritis, in 28% of the cases of various types of arthritis (20% with exclusion of a case of mixed connectivitis and of a case of Waldenström's macroglobulinemia with rheumatoid arthritis) and in 0% of the cases of mechanical arthropathy. The results of immunofluorescent examination compare favorably with those of standard histology: the classical histologic appearance of rheumatoid synovitis with a node-forming tendency of the infiltrate was observed in only 36% of the verified cases of rheumatoid arthritis, while immunofluorescence was positive in 63% of the cases in this group. In the category of unclassified arthritis, these percentages were comparable, viz. 19% and 20%, repectively. The presence of cells with fluorescent cytoplasm during immunofluorescent examination of the synovial membrane may be regarded as an additional criterion supporting the diagnosis of rheumatoid arthritis.

Macrophages from synovial fluid were obtained by joint puncture of patients with rheumatoid arthritis or non-rheumatoid exudative arthropathies. This fluid was subsequently centrifuged and the resulting cell pellet was recovered and distributed for in vitro culture (Falcon Petri dishes: 60 x 15 or 35 x 10). Cells were washed after 4 hours in culture to eliminate non-macrophagic cells. A second cell wash was effected 24 hours later to eliminate non-adherent cells. The culture medium employed was fetal calf serum MMP 119 (Gibco). The macrophagic nature of the cultured cells was ascertained by non specific esterase determinations (Burstone method) and estimation of the phagocytic index (using zymosan). This technique permits the conservation of viable monocytes in culture thus facilitating investigation of their metabolic activity (for example: prostaglandins, prostanoids or fatty acids) and the effects of anti-inflammatory agents.

The authors report the case of a 37-year-old man affected by a seronegative polyarthritis associated at first with erythroderma and then with cutaneous and subcutaneous papulo-nodular structures and a xanthomatous eryption. Histological examination of the cutaneous nodules and of the synovial membrane confirmed the diagnosis of multicentred reticulohistiocytosis by showing the presence of lipid infiltrates in the histiocyte cells and of multinucleate giant cells. A study of the ultrastructure of the histiocytes revealed the presence of numerous intracytoplasmic vacuoles. In spite of antimalaria treatment, with cortisone and then with immuno-depressants, the outcome was fatal with a picture of acute reticulosis and neurological disorders. In discussing this case, the authors also make a general review of the subject.

The clinical significance of synovial monocytosis (greater than 50 p. cent) of inflammatory fluids (greater than 1,000 elements per mm3) was studied retrospectively in 43 patients. An accurate diagnosis was made 35 times: rheumatoid polyarthritis (13 cases), lupus disease (1 case), Gougerot-Sjögren syndrome (1 case), isolated infantile monoarthritis (1 case), sarcoidosis (1 case), seronegative spondylo-arthropathy (3 cases), microcrystalline arthritis (5 cases) arthritis revealing a blood disease (2 cases), idiopathic "lymphocytic" arthritis (3 cases), eosinophilic pseudo-allergenic arthritis (2 cases), aseptic osteonecrosis of the medial condyle (1 case), femoro-patellar arthrosis (1 case). Among the 8 other patient for whom no diagnosis was made, 6 had a spontaneously resolving acute affection, evoking the possibility of a viral etiology.

This paper describes a morphologic, quantitative, cytochemical study of mononuclear non lymphoid cells in knee synovial fluid in osteoarthritis and various arthritides. Morphologic criteria allow to identify among these cells various synoviocytic and monocytic subtypes with in both types, phagocytic subtypes. Quantitative study shows in arthritides an important afflux of monocytes and a hyperexfoliation of synoviocytes. In fluids with intermediate cellularity, Monocytes/Synoviocytes ratio allows the differential cytodiagnosis between osteoarthrosis and arthritis. All monocytic subtypes and especially the phagocytic one are highly significantly increased in arthritides. Synoviocytic subtypes show a lower increase, except the phagocytic one, which is not changed. Giant multinuclear synoviocytes are found in every type of disease and cannot constitute a cytodiagnosis marker. Alcian Blue and hyaluronidase treatment show hyaluronate in a few percentage of Synoviocytes. Cytoenzymologic study shows that synoviocytes and monocytes are positive in all tested hydrolases: beta Glucuronidase, Acid Phosphatase, alpha Naphthyl Acetate Esterase, these activities being always higher in synoviocytes. With peroxidase, synoviocytes are always negative, so this reaction although it marks only a minority of monocytic population can be used as an extra cytologic criterion for discrimination of mononuclear cells in synovial fluid. In these four enzymes there is no significant quantitative difference at cellular level between osteoarthrosis and arthritides. Lysosomal enzymatic activity in both monocytic and synoviocytic cells confirms their heterophagic properties. However synoviocytic heterophagy seems to be a physiological process not or few affected by inflammatory events. On the opposite, monocytic heterophagy and then macrophagic transformation of monocytes appears as a major aspect of intrasynovial inflammatory reaction. If a large majority of exfoliated synoviocytes comes from A type synovial lining cells and if they belong to Mononuclear Phagocyte System, why do they so weakly, or not, participate as phagocytes to inflammatory reaction.

In making a comparative study of different parameters in the examination of synovial fluid (rheumatoid factors, ragocytes, leucocytes, synovial complement, immunoglobulins) the authors show that rheumatoid fluid has characteristics that make differentiation from other inflammatory arthropathies possible on a statistical basis, thanks to the test for the homogeneity of the means. The presence of these characteristics seems to constitute a diagnostic argument which can be measured by mathematical methods.