A new HLA-B*27 allele (B*2719) identified in a Lebanese patient affected with ankylosing spondylitis.

Eighteen different HLA-B*27 alleles (B*2701-B2718) have so far been recognized by the WHO Nomenclature Committee for Factors of the HLA System. Frequency and disease association of these alleles with spondyloarthropathies differ among ethnic groups. We describe here a novel HLA-B*27 subtype identified in a Lebanese patient suffering from ankylosing spondylitis (AS). This new variant differs from the common HLA-B*2705 DNA sequence at five different nucleotide positions. These nucleotide changes lead to three amino acid differences in the alpha2 domain; Thr to Ile at position 94, Leu to Ile at position 95 and Asn to Arg at position 97. Since this novel allele is encountered in an AS patient, the associated sequence changes are not expected to affect significantly neither the presentation of a putative arthritogenic peptide nor the conformation-dependent recognition by effector cells.

Interleukin 1 gene cluster polymorphisms in multiplex families with spondylarthropathies.

Interleukin 1alpha (IL-1alpha) has been implicated in the pathogenesis of infectious, auto-immune and inflammatory diseases. Polymorphisms in the genes encoding IL-1alpha, IL-1beta and the IL-1 receptor antagonist (ILRN) molecules have been associated with several inflammatory diseases. As the marker D2S160 has been characterized as a candidate locus for Ankylosing Spondylitis (AS) after a genome-wide scan, and since this locus is located approximately 0.3 cM telomeric to the IL-1 gene cluster, we hypothesized that these cytokines might be good candidates for Spondylarthropathies (SpA). Therefore we tested this hypothesis using the transmission disequilibrium test (TDT) in 37 families representing 217 subjects from three intragenic IL-1 gene cluster polymorphisms, the IL1B Taq I, the ILRN 2nd intron, and the IL1A Nco I, taking HLA B27 status into account or not. In conclusion, by means of intra-familial TDT analysis we found no linkage or intra-familial association between SpA and the three IL-1 gene-cluster polymorphisms in SpA multiplex family material.

Common intra-articular T cell expansions in patients with reactive arthritis: identical beta-chain junctional sequences and cytotoxicity toward HLA-B27.

Spondyloarthropathies constitute a group of autoimmune diseases of special interest because of their tight association with the MHC class I molecule HLA-B27 and the bacterial triggering of some clinical forms called reactive arthritis (ReA). One current hypothesis is the presentation by HLA-B27 of a so-called arthritogenic peptide to T cells. To better focus on the relevant T cell populations within the joint, we performed an extensive beta-chain T cell repertoire analysis of synovial fluid compared with PBL in seven patients, four of whom were characterized as having ReA triggered by Yersinia enterocolitica, Chlamydia trachomatis, or Shigella sonnei. Analysis of the size diversity of the beta-chain complementarity-determining region 3 (CDR3) allowed us to evaluate the degree of T cell clonality in the samples. Oligoclonal T cell expansions were frequently observed in the joint. In one patient, CDR3 amino acid sequences of major expansions using two different BV genes were identical. One dominant T cell expansion and several CDR3 amino acid sequences were identical in two different patients. Furthermore, one sequence was identical with a sequence reported independently in a Salmonella-induced ReA patient. Together, these data indicate a surprisingly high degree of conservation in the T cell responses in recent-onset ReA triggered by different micro-organisms. A CD8+ synovial line expressing shared clonotypes was established and reacted toward several B*2705 lymphoblastoid cell lines, therefore supporting a molecular mimicry phenomenon at the T cell level in the disease mechanism.

Appearance of systemic lupus erythematosus after thymectomy: four case reports and review of the literature.

The appearance of systemic lupus erythematosus (SLE) after thymectomy (or thymomectomy) is presented in four patients together with a comparative review of additional reports found in a Medline search for the years 1966-94 in the English and French literature. Fourteen women and two men of average age of 39 years (range 11-66 years) at presentation, developed SLE after thymectomy (11 patients) or thymomectomy (five patients). Half developed SLE within 3 years after surgery (range 3 months to 18 years). The most common SLE manifestation was polyarthritis occurring in 15 of 16 patients either at presentation or during the first year. Other frequent manifestations included skin rashes, fever, cytopenias and pleuritis. Two rare manifestations of SLE, optic neuritis and transverse myelitis, were reported in two patients. Thymic hormone activity was measured in one patient and was undetectable compared with normal controls. HLA studies in eight patients showed the combination of A1, B8 in four. In conclusion, the appearance of SLE after thymectomy or thymomectomy appears to be more than a coincidence. It may provide insights into the pathogenesis of SLE.

Treatment of carrageenan induced arthritis by the platelet activating factor antagonist BN 50730.

OBJECTIVE: To evaluate the role of platelet activating factor (PAF) in the early stage of arthritis. METHODS: Arthritis was induced in rabbits by weekly intra-articular injections of carrageenan. A PAF receptor antagonist, BN 50730, was used as a preventive or curative agent. RESULTS: BN 50730 was able partially to prevent the development of arthritis, and was also active on established arthritis. The joint arthritis scores of BN treated animals were significantly lower than those of the non-treated animals. The blood concentrations of PAF, PAF bound to lipoproteins (lipo-PAF), and its precursor, lyso-PAF, were not correlated with clinical variations. CONCLUSIONS: The present data demonstrate a therapeutic action of a PAF antagonist in experimental arthritis and suggest a critical role for PAF during the early stage of arthritis.

[Osteoarthritis of rare etiology]. / Arthroses d'étiologie rare.

Although osteoarthritis is characterized by a uniform pattern of clinical and radiological manifestations, it is a syndrome that can be produced by a variety of causative factors. Rare causes of osteoarthritis can be categorized as follows: 1) systemic metabolic disorders due to known biochemical and/or genetic abnormalities, such as hemochromatosis, ochronosis, Wilson's disease, Ehlers-Danlos syndrome (and probably the "idiopathic" joint hypermobility syndrome), sickle cell anemia, and thalassemia; 2) endocrine disorders, such as acromegaly, whose joint manifestations are now well-known, and hypothyroidism; 3) Paget's disease of bone, osteopetrosis (which induces changes in bone elasticity), and other systemic bone diseases; 4) dysplasias, which form a vast group including familial polyepiphyseal dysplasia, spondyloepiphyseal dysplasia congenita (especially its milder forms), Stickler's syndrome, osteo-onychodysplasia, Kniest's dysplasia, trichorhinopharyngeal syndrome, and a group of diseases that affect the epiphyses; 5) endemic forms of osteoarthritis, e.g., Mselini disease, Kashin-Beck disease, and Malnad disease, which are unknown in western Europe but have been reported to affect thousands of individuals in endemic areas. All these disorders are usually responsible for premature osteoarthritis, whose presentation sometimes bears the imprint of the causative abnormality but can be identical to that of common osteoarthritis. The effects of toxic substances (Kashin-Beck disease) or genetically-determined collagen II abnormalities (epiphyseal dysplasias) may explain the occurrence of these rare forms of premature osteoarthritis.

Substance P levels in the synovium and synovial fluid from patients with rheumatoid arthritis and osteoarthritis.

Experimental results suggest that substance P (SP) may play an important role in pain and inflammation in rheumatic diseases. Measurements of SP-like immunoreactivity (SPLI) were performed in synovial fluid (SF) and synovial tissue from 40 patients with rheumatoid arthritis (RA) or osteoarthritis (OA). High levels of SPLI were found in the SF of patients with RA compared with OA. Conversely, SPLI content in synovial tissue was higher in OA than in RA, suggesting that there is an active secretory process of SPLI into the SF in RA, thus depleting SPLI stores in the synovium. Our data support the involvement of SP in the perpetuation and exacerbation of inflammation in RA, and may also explain some clinical features of this disease.

[Camptocormia in the elderly. A new entity by paravertebral muscle involvement?]. / Camptocormie du sujet âgé. Une nouvelle entité par atteinte des muscles paravertébraux?

"Camptocormism" in the elderly is an acquired kyphosis which increases during walking and is totally reducible in dorsal horizontal position in two thirds of cases. The authors report 16 cases of camptocormism in patients with a mean age of 76 (12 women, 4 men). Camptocormism was accompanied in 5 cases by an extrapyramidal syndrome, in 3 cases by articular chondrocalcinosis, in 1 case by giant cell arteritis and in 1 by rheumatoid arthritis. There was no inflammatory syndrome and muscle enzymes were raised in only 4 cases. Electromyogram of the paravertebral muscles was pathological in 5 cases, with neurogenic changes in 4 cases and a myogenic type tracing in one. CT scan or magnetic resonance imaging showed evidence in all cases of atrophy with fatty involution of the paravertebral muscles. Biopsies of the paravertebral muscles revealed moderate mononuclear cell infiltrates in 4 cases with similar abnormalities in peripheral muscles. Corticosteroids had a beneficial effect in 11 cases out of 13 and the most prolonged results were seen after bolus doses of methylprednisolone. These findings suggest that camptocormism in the elderly could be linked to inadequacy of the paravertebral muscles or, in certain cases, to interstitial myositis.

Presence of paf-acether in rheumatic diseases.

Paf-acether (paf) is a naturally occurring phospholipid involved in inflammatory processes. The presence of paf, its precursor lyso paf, and lipo-paf has been determined in blood and synovial fluid from 13 patients with rheumatoid arthritis (RA), 11 with spondylarthropathies, eight with other inflammatory rheumatisms, 13 with chondrocalcinosis, 15 with osteoarthritis, and also in blood from nine healthy subjects. Paf and lipo-paf were measured by rabbit platelet aggregation after isolation by high performance liquid chromatography, whereas lyso paf was first chemically acetylated to give paf. Lipo-paf in blood was higher in patients than in controls; lipo-paf concentrations in blood and in synovial fluid were significantly higher in rheumatoid arthritis than in osteoarthritis and chondrocalcinosis. By contrast, paf and lyso paf reached their lower values in rheumatoid arthritis. The amounts of lipid mediators were not correlated with biological parameters of inflammation. Lipo-paf, which is considered as a storage form of paf, may be the important form of paf in active inflammatory rheumatism.

[Treatment of rheumatoid polyarthritis with methotrexate]. / Traitement de la polyarthrite rhumatoïde par le méthotrexate.

This retrospective study involved 60 patients (7 men, 53 women) with rheumatoid arthritis (RA) and given methotrexate between 1985 and 1990. The mean time that RA had been present was 12 years and more than half of the patients had received more than 3 types of general treatment in the past. The mean total duration of MTX was 17.3 months, with a total dose of 790 mg. The efficacy of MTX was confirmed by a significant improvement in clinical and laboratory parameters. Treatment was withdrawn permanently in 21 cases (35% of patients). Adverse reactions, responsible for two thirds of treatment withdrawals (14/21) occurred in most instances during the first year of treatment. Hepatic toxicity was commonest. Two cases of aplasia were reported as well as 3 cases of pneumonitis, one fatal. These involved two cases of secondary infection and one of pneumonitis directly imputable to MTX. Withdrawals for inefficacy were rare, occurring in less than 10 p. cent of patients. Treatment continuation rates were 77 p. cent at 1 year, 66 p. cent at 18 months, 55 p. cent at 2 years, 42 p. cent at 3 years and 32 p. cent at 4 years. MTX is effective treatment for RA but is not free of adverse reactions, sometimes potentially fatal. Prolonged monitoring is necessary because of the sometimes delayed onset of adverse reactions.

[Oligo-arthritis associated with type IV hyperlipoproteinemia]. / Oligo-arthrite associée à une hyperlipoprotéinémie de type IV.

A case of chronic, corticosteroid-responsive arthritis affecting particularly one ankle in a patient with type IV hyperlipoproteinaemia is reported. After gout or inflammatory rheumatism of another nature had been excluded, and following synovial fluid examination and synovial membrane biopsy, a diagnosis of type IV hyperlipoproteinaemia rheumatism was made. At electron microscopy, the synovial membrane showed numerous large spumous cells and a peculiar appearance of the capillary vessels.

[Multicentric reticulohistiocytosis. A case with unusual clinical, radiologic and ultrastructural aspects]. / Réticulo-histiocytose multicentrique. Un cas avec aspects cliniques, radiologiques et ultrastructuraux inhabituels.

We are reporting a case of multicentric reticulo-histiocytosis which is exceptional because of its gravity and the diversity of the clinical lesions: huge subcutaneous nodules, bone destruction in the spine responsible for spondylolisthesis, pulmonary fibrosis, acute pericarditis, laryngeal compression requiring a permanent tracheostomy. From ultrastructural observations, various hypotheses to explain the intra-macrophagic accumulation of membrane granules and lipids are discussed.

[Chronic osteitis and arthritis of palmoplantar pustulosis. A familial form of B-27 negative spondylarthropathy]. / Les ostéites et arthrites chroniques de la pustulose palmo-plantaire. Une forme familiale de spondylarthropathie B27 négative.

A 35-year old woman presented with pustulosis palmaris et plantaris evolving in acute episodes parallel to those of a rheumatic disease consisting of bilateral sacro-iliac arthritis, manubriosternal fusion and sterno-clavicular arthritis. Her brother had spondylitis compatible with the diagnosis of pustular osteo-arthritis though without pustulosis. He presented with bilateral sacro-iliac arthritis, manubriosternal fusion, sterno-clavicular arthritis and an ossified fragment detached from the antero-inferior angle of C6. The two patients had the same HLA phenotype: A1, A9, B5, B41, CW4, DR2, DR4, absence of B27. In a specimen from the sacro-iliac joint the authors found active bone remodelling and inflammatory osteitis with fibrosis and infiltrates rich in mononucleate cells. An electron microscopic study--to the authors' knowledge, the first to be performed in such cases--demonstrated intracytoplasmic filamentous inclusions in two macrophages of the synovial fringe. Only one other case of the familial form has been published so far. Like the rheumatism of acne conglobata, the spondylitis of pustulosis palmaris et plantaris is one of the causes of sterno-costo-clavicular hyperostosis.

[The rheumatism in type IIa hypercholesterolemia]. / Le rhumatisme de l'hypercholestérolémie de type IIa.

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.

Erythrocyte sedimentation rate of healthy subjects--chronological aspects.

Thanks to an elaborated mathematical approach, based on statistics and signal processing, the chronological changes of the Erythrocyte Sedimentation Rate (ESR) of young healthy subjects, considered from a collective point of view, have been discriminated into genuine and well-defined rhythms. These rhythms are tied up either to natural (year, season) or 'social' (month, week, holidays) cycles, or to some other causes, still unknown and possibly intrinsic (such is probably the case of a 26.5-day strongly marked period). The solar induced time variation strictly obeys a frequency modulation law, the relative amplitude of which is 10 per cent. Two axes of symmetry are found, centered on 8 August and 8 February. The rhythm is roughly in accordance with seasons. The modulation frequency is maximum at summer time. Oscillations of the ESR are observed during the week and the month. Fridays and the last fortnight of each month appear to be low ESR time.

Frequency and diagnostic value of the virus-like filamentous intranuclear inclusions in giant cell tumor of bone, not associated with Paget's disease. A study of 43 cases.

This paper deals with the paramyxovirus-like intranuclear inclusions observed in giant cells tumours of bone (GCTB). Twenty-one (49%) of 43 cases of GCTB (1977-1985), either fresh and/or cultured, show these ultrastructural inclusions. Fifty samples of various bone lesions in which giant cell lesions occurred, including aneurysmal cysts, hyperparathyroidism, osteoblastoma, human and rat osteopetrosis, GCT of tendon sheaths, and non skeletal granuloma were used as controls. These, together with 20 samples of normal bone (osteoclasts) did not contain intranuclear or intracytoplasmic viral inclusions.