Showing papers in "Clinical and Experimental Rheumatology in 1994"

The role of hyaluronic acid (hyaluronan) in health and disease: interactions with cells, cartilage and components of synovial fluid.

Abstract: Intra-articular administration of hyaluronic acid (Hyaluronan) (HA) is now gaining widespread acceptance for the treatment of osteoarthritis (OA), even though little is known of its mechanism of action. In vitro and in vivo studies have shown that HA is able to modulate a variety of cellular functions, suppress the activities of pro-inflammatory mediators and can attenuate the nociceptive response in arthritic joints. However, recent studies with animal models of non-inflammatory OA have questioned the ability of HA to protect articular cartilage degeneration directly. The objective of this review is to examine some aspects of HA chemistry and pharmacology in relation to its interactions with cells, cartilage and the components of synovial fluid.

Sonographic analysis of enthesopathy in the lower extremities of patients with spondylarthropathy.

Abstract: OBJECTIVE Enthesopathy is one of the features characterizing patients with spondylarthropathies. Its diagnosis is usually based on clinical symptoms such as the presence of calcanear pain or tenderness at the insertion(s) of ligaments. More objective ways to estimate the presence and nature of enthesopathy are needed. Therefore, we analysed both by clinical and sonographic methods the presence of enthesopathy in the lower extremities of patients with spondylarthropathy. METHODS 31 consecutive patients with spondylarthropathies (15 with reactive arthritis, 12 with ankylosing spondylitis, and 4 with psoriatic arthritis) were studied for the presence of enthesopathy in the lower extremities, independently by clinical examination and by high resolution sonography. RESULTS Sonography detected inflammatory lesions in 44 entheses of 20 patients. Oedema at the insertion of the tendon was the most common finding. Signs of enthesitis were more common in the lower portion of the leg. In addition to enthesitis, bursitis was a common finding by sonography. By clinical examination, enthesitis was diagnosed in 56 sites in 20 patients, most frequently at the insertions of the Achilles tendon and the plantar fascia. Bursitis around the calcaneus and synovitis/pain in the hip and knee joints were most frequently misinterpreted to indicate enthesopathy at the clinical examination. In addition, half of the insertions with only oedema at sonography were clinically asymptomatic. CONCLUSIONS Sonographic examination of ligamentous insertions offers morphologic information which is unobtainable by the clinical judgement of tenderness in the estimation of enthesopathy in patients with spondylarthropathies.

Systemic lupus erythematosus : clinical and laboratory aspects related to age at disease onset

Abstract: OBJECTIVE To analyse the clinical and laboratory parameters in patients with SLE according to their age at disease onset a retrospective study was undertaken of 272 Brazilian patients fulfilling the 1982 ARA criteria for SLE who were referred to the University Hospital of Campinas between 1973-1992. METHODS The patients were divided into three groups according to their age at disease onset: Group A: under the age of 16 (39 patients); Group B age 17 to 49 (223 patients); Group C over the age of 50 (10 patients). Various clinical and laboratorial parameters were analysed and compared among these groups. RESULTS There were no significant differences in terms of race, time of disease onset or time of follow-up. Group A had more male patients than Groups B (p < 0.05) or C. Alopecia as an early manifestation, seizures and gastrointestinal involvement were more frequent in Group A (p < 0.05). Raynaud's phenomenon was lower in Group A than in Groups B and C (p < 0.05). Pericarditis was higher in Group C than in Groups A or B (p < 0.05). Nephrotic syndrome was lower in Group C than in Group A (p < 0.05). Positive LE cells were higher in Groups A and C than in Group B (p < 0.05). Anti-DNA antibodies were more prevalent in Group A than in B (p < 0.05). Anti-cardiolipin antibodies were more frequent in adult patients (p < 0.05) (Group B). The mortality rate was higher in Group A than in B or C (p < 0.05). CONCLUSION The clinical presentation and course of SLE may be influenced by the age at disease onset. Younger patients showed a poorer prognosis with more seizures, gastrointestinal involvement, nephrotic syndrome, and a higher rate of mortality than the other groups. Group A included more male patients and also exhibited more positive LE cells and anti-DNA antibodies. Raynaud's phenomenon was lower in these young patients. Elderly patients (C) presented more pericarditis and showed mild disease.

Long-term i.v. Ig treatment in systemic lupus erythematosus.

Abstract: OBJECTIVE Treatment of SLE exacerbations with intravenous gammaglobulins has been shown to be safe and effective, leading to both clinical and serological improvement. In this study we test the hypothesis that intravenous immunoglobulins (IVIg), administered over a long period, would also be effective in patients with chronically active SLE. DESIGN AND PATIENTS An open trial was carried out on 12 patients with SLE refractory to conventional treatments, administering monthly infusions of intravenous immunoglobulins at a dose of 400 mg/kg/day for 5 consecutive days. The therapy (400 mg/kg for 5 days) lasted from 6 up to 24 months. RESULTS Progressive clinical improvement was observed in 11 patients during the entire treatment course. This improvement was associated with an increase in hemoglobin, total serum hemolytic complement activity and C3 and C4 components, and in 2 thrombocytopenic patients in the platelet count, as well as a progressive reduction of ESR, serum immunocomplexes and antinuclear antibodies. A marked improvement in serum urea, creatinine clearance and proteinuria was also observed in those patients with renal involvement. We did not observe any adverse effects. CONCLUSION The results obtained suggest that IVIg therapy may be a promising option in the treatment of chronically active SLE; however, further evaluation of this therapy is essential.

Study of IL-2, IL-6, TNF alpha, IFN gamma and beta in the serum and synovial fluid of patients with juvenile chronic arthritis.

Abstract: In the last few years the important role played by various cytokines in the pathogenesis of chronic inflammatory diseases has emerged. In the present study, serum and synovial fluid levels of IL-2, IL-6, TNF alpha, IFN beta and IFN gamma were evaluated in a group of 66 patients with juvenile chronic arthritis (JCA). At the same time the ESR, CRP, hemoglobin, immunoglobulins, platelet count and Ritchie index were measured. In the serum of pauciarticular patients, IL-6 and TNF alpha levels were only slightly elevated compared with controls, but there was no correlation between these cytokines and clinical and other laboratory parameters. Serum IL-2 and IFN gamma were undetectable. In contrast, in the synovial fluid IL-6 levels were very high in all of the patients examined and there was a significant correlation between synovial fluid IL-6 levels and Ritchie's articular index. TNF alpha tended to be elevated but to a lesser extent, while synovial fluid IL-2 and IFN gamma were undetectable or very low, as in the serum. In polyarticular and systemic patients, on the other hand, serum IL-6 was elevated and statistically correlated with the majority of the laboratory parameters and with the Ritchie articular index. TNF alpha levels were only slightly elevated; on the other hand, IL-2 and IFN gamma were undetectable. There was an inverse correlation between IFN beta levels and the Ritchie articular index and a significant correlation with hemoglobin levels. In conclusion, our study demonstrates that not only IL-1 (as shown in other studies), but also IL-6 and to a lesser extent TNF alpha play a central role in the pathogenesis of JCA. IFN beta on the other hand, would seem to play an anti-inflammatory role.

Ultraviolet-A1 irradiation decreases clinical disease activity and autoantibodies in patients with systemic lupus erythematosus

Abstract: In this study we assess the effect of ultraviolet radiation, exclusively within the UV-A1 (340-400 nm) range, on disease activity in SLE. Ten SLE patients were irradiated for 15 days, four of them then continuing treatment for 8 months, with low doses (60 kJ/m2/d) of UV-A1 irradiation. They were assessed clinically and serologically before, after 3 weeks, and after 8 months of therapy. Clinical indices of disease decreased in the 10 patients after 3 weeks by 39%; they decreased in the four patients irradiated for 8 months by 70%. Antibodies to Sjogren's syndrome A (anti-SSA) or antinuclear antibodies (ANA) decreased or disappeared in most patients. There were no side effects. In this uncontrolled study, UV-A1 irradiation appears to have been an effective and seemingly innocuous therapeutic modality for patients with SLE, decreasing signs and symptoms of disease, diminishing levels of autoantibodies and increasing in effectiveness with time.

Evaluation of the 1982 ARA lupus criteria data set in pediatric patients. Committees of Pediatric Rheumatology of the Brazilian Society of Pediatrics and the Brazilian Society of Rheumatology.

Abstract: Objective: Although commonly used, the 1982 revised criteria for the classification of Systemic Lupus Erythematosus (SLE) have not been completely evaluated in pediatric patients. This study was aimed at evaluating the sensitivity and specificity of the 1982 revised criteria when applied to pediatric patients. Methods: One hundred and three children with SLE and 101 children with other rheumatic diseases were selected from 5 rheumatology centers in Brazil. Diagnosis of SLE by the 1982 criteria were compared with our clinical diagnosis. The diagnosis of other diseases was made according to internationally accepted classification criteria or, when these were not available, according to the physician's own experienced judgement

Low tear production in patients with diabetes mellitus is not due to Sjögren's syndrome.

Abstract: Objectives The purpose of this study was to determine whether low tear production in patients with diabetes mellitus (DM) was related to autonomic nervous system abnormalities, to Sjogren's syndrome, as suggested by a previous study, or to other factors. Design Cross-sectional study assessment of patients with DM. Patients and methods One hundred patients with diabetes mellitus (DM) attending the University of Alberta Outpatient Education Program for DM were consecutively included. All patients were assessed for keratoconjunctivitis sicca with a questionnaire. Tear production was assessed with Schirmer tests and patients with abnormal findings were further examined by an ophthalmologist. The effect of possible confounding factors was also evaluated: all patients underwent standard tests for the diagnosis of autonomic neuropathy and laboratory tests including lipid profiles, fasting blood glucose and levels of HbA1C. Antinuclear antibodies (ANA) were determined using HEp2 cells and various substrates for specific autoantibodies. Results Twenty-one of the patients had symptoms compatible with keratoconjunctivitis, and 25 had an abnormal Schirmer test. None of these 25 had abnormal corneal staining. Sixty one patients had evidence of autonomic neuropathy. Antinuclear antibodies were detected in 6 patients and anti-Ro in one other. Multiple regression analyses using the Schirmer test as a dependent variable, and controlling for all the independent variables, showed an association with autonomic neuropathy. No significant associations were observed with the other variables, including the presence of autoantibodies. Conclusion Our results suggest that the low tear production seen in some DM patients is related to disfunction of the autonomic nervous system and not commonly to Sjogren's syndrome.

Endocarditis associated with ANCA.

Abstract: We report the case of a patient exhibiting subacute bacterial endocarditis (SEB) associated with vasculitis and signs of nephritis. C-ANCA were present at high titer. This observation suggests that ANCA may be associated with vascular injury in SEB.

Modulation of the immune response by the neuro-endocrine axis in rheumatoid arthritis.

Abstract: The neuropeptides are involved in the immune response and in hormonal homeostasis. In this review, we analyse the interactions between the cytokine, the neuropeptide and the hormonal networks in rheumatoid arthritis (RA). We first consider pituitary-adrenal axis dysfunction in RA. An inappropriate response to cortisol in chronic inflammation has been reported, i.e., a decrease of the corticotropin-releasing-hormone (CRH) secretion by the hypothalamus. In contrast, the immunostimulant hormone prolactin (PRL) is upregulated. PRL is released by the pituitary after stimulation by neuropeptides [serotonin, thyroid-releasing-hormone (TRH), or vasoactive-intestinal-peptide (VIP)], and is down-regulated by pro-inflammatory cytokines (IL-1, IL-6). The decreased testosterone concentration observed in male RA patients is associated with HLA B 15. Thus, an altered sex hormone status and a genetic predisposition are related to HLA antigens, and increase the subject's susceptibility to the development of RA. The terminal C fibres release neurotransmitters such as substance P, neurokinin A and calcitonin-gene-related-peptide (CGRP) within the joints, and contribute to local inflammation, synoviocyte proliferation and collagenase production. The parasympathetic system may attenuate the immune response through the neuropeptide VIP. In contrast, the beta 2 adrenergic fibres of the sympathetic nervous system increase joints degradation in RA. This review presents the currently extensive knowledge regarding the immune-neuro-hormonal network, and its implication in the pathogenesis of RA.

Takayasu's arteritis in Mexico: a clinical review of 44 consecutive cases.

Abstract: OBJECTIVES To review our experience in clinical diagnosis of the non-specific arteritis called Takayasu's arteritis (TA), and to assess its possible relationship with previous mycobacterial infections as judged by delayed hypersensitivity skin test. METHODS We examined 44 consecutive patients in Mexico City. All of them fulfilled the ACR criteria for the classification of TA and had a characteristic panaortogram in the absence of any other arterial or systemic disease. RESULTS Forty-three of our patients were Mexican mestizos; only one had a Caucasian appearance. 38 were women, and the age at diagnosis ranged from 15 to 64 years with a mean of 32 and a median of 35. Age at onset of the symptoms was under 30 years in most cases. Five patients had type I disease, and 4 had type II. Most had a diffuse arteritis (type III), and in seven cases involvement of the pulmonary artery (type IV) was recognized. All patients showed abnormal peripheral pulses and blood pressure differences, 35 had systemic arterial hypertension and 7 pulmonary hypertension. A noisy vascular auscultation was very common and cardiac ailments were also found in many cases. Systemic complaints such as fever, weight loss and malaise were present in the active stages of the disease. Arthritis did occur in a single case, arthralgia was frequent and inflammatory nodules involving the shin, perimalleolar area, and the antero-external surface of the distal leg were also common. Polyclonal hypergammaglobulinemia was a frequent finding in active and inactive cases; leukocytosis with neutrophilia, accelerated ESR and high fibrinogen, however, did occur when the disease was active. Eight of our patients had a previous diagnosis of tuberculosis, and 81% developed a delayed skin reactivity to PPD (2U old tuberculin). None had a bacteriologic diagnosis of tuberculosis or mycobacterial disease. CONCLUSION Non-specific arteritis, or Takayasu's disease, frequently affects young women of colored race in Mexico. Late diagnosis is common and cardiovascular features dominate the clinical picture. Arterial compromise is widespread and may involve the pulmonary artery and its branches. Most cases are inactive and morbidity results from systemic arterial hypertension and heart disease; active cases have systemic complaints and laboratory abnormalities suggestive of ongoing inflammation. The close relationship between Takayasu's arteritis and previous contact with Mycobacterium tuberculosis was again confirmed in our series, although further studies are necessary to clarify this probable relationship.

Esophageal motility disorders in the rheumatic diseases : a review of 150 patients

Abstract: Objective Rheumatic diseases are a group of systemic disorders that may be concurrent with Raynaud's phenomenon and involvement of the internal organs, in particular the esophagus. Esophageal motor abnormalities have been widely described in systemic sclerosis, but have not frequently been reported in other diseases. In the present study we have examined the prevalence and pattern of esophageal motility disorders in different rheumatic diseases. Methods Esophageal manometry was performed on 150 patients, 21 males and 129 females, suffering from different rheumatic diseases (SSc, RA, SLE, MCTD, undifferentiated CTD, or DM/PM) and on 30 healthy controls. Results Functional involvement of the esophagus was demonstrated in all the rheumatic diseases considered, although at varying percentages. The frequencies of the functional abnormalities differed when each disease was considered separately. In SSc patients abnormalities were found more frequently in the lower esophageal sphincter (81.8%) and in the esophageal body (84.8%); data for the DM/PM and MCTD patients broadly overlapped. On the contrary, in SLE the lower sphincter appeared to be less (or even not at all) impaired, while the most specific disorder was an isolated abnormal peristalsis. RP did not always correlate with manometric changes in all of the groups studied. Conclusions Three conclusions derive from our study: i) motor disorders affecting the esophagus were not only found in SSc, but also in all forms of non-lupus CTD; ii) the simultaneous involvement of the esophageal body and the lower esophageal sphincter is discriminant between non-lupus CTD and SLE; and iii) RP may be regarded as a condition pathogenetically unrelated to manometrically detected esophageal motor abnormalities.

The prevalence of antinuclear antibodies in healthy young persons and adults, comparing rat liver tissue sections with HEp-2 cells as antigen substrate.

Abstract: The prevalence of antinuclear antibodies (ANA) was studied in 290 healthy adults, aged 20-88 years, and in 219 children, aged 1 month to 15 years. Two antigen substrates, rat liver tissue sections and HEp-2 cells, were compared at different serum dilutions. At titre 1/40, the number of positive adult samples was 6.9% with HEp-2 cells and 6.2% with rat liver. Using a lower serum dilution, HEp-2 cells were shown to be significantly more sensitive than rat liver. However, 25% of the positive samples at serum titre > or = 1/40 could only be found on HEp-2 cells, as compared to 17% for rat liver, even after extended investigation. In children, 7.3% of the samples were positive using HEp-2, as compared to 2.3% with rat liver tissue, at titre 1/10. None of the samples were positive for nDNA or other specific antigens as measured by immunodiffusion. One sample had antibodies against core histones and two samples showed antibodies against subcellular antigens by immunoblot. We conclude that the occurrence of ANA in healthy Swedish children and adults is similar to previous studies from other countries. Both rat liver tissue and HEp-2 cells were found to be suitable for screening purposes, if the increased sensitivity of HEp-2 cells is taken into consideration, particularly with regard to children. Furthermore, it may be necessary to use more than one substrate to exclude ANA positivity in clinical practice.

Cytokine concentrations in the synovial fluid and plasma of rheumatoid arthritis patients: correlation with bony erosions.

Abstract: Cytokines are important protein mediators in inflammatory joint diseases. The synovial fluid and plasma concentrations of interleukin-1 alpha (IL-1 alpha), interleukin-2 (IL-2), tumour necrosis factor-alpha (TNF-alpha), interferon-alpha (IF-alpha) and interferon-gamma (IF-gamma) were measured by RIA and ELISA in 28 rheumatoid arthritis (RA) patients (5 males and 23 females). Ten patients with knee effusions due to other causes (osteoarthritis, psoriasis, gout, rheumatic fever, systemic lupus erythematosus) were also studied. Eight of the RA patients had erosive disease. The synovial fluid IL-1 alpha and IL-2 concentrations were higher in Group 1 (erosive) [IL-1 alpha: 524 pg/ml (SEM: 127), IL-2: 3.28 ng/ml (SEM: 1.0)] than in either Group 2 (non-erosive) [IL-1 alpha: 241 pg/ml (SEM: 24), IL-2: 1.93 ng/ml (SEM: 0.6)] or Group 3 (non-RA) [IL-1 alpha: 267 pg/ml (SEM: 58), IL-2: 0.35 ng/ml (SEM: 0.6)] (p < 0.003 and p < 0.06 respectively). Plasma IL-1 and IL-2 levels were higher in Group 1 [IL-1 alpha: 408 pg/ml (SEM: 107), IL-2: 4.20 ng/ml (SEM: 1.5)] than in Group 2 [IL-1 alpha 150 pg/ml (SEM: 15), IL-2: 2.58 ng/ml (SEM: 0.7)] or Group 3 [IL-1 alpha: 140 pg/ml (SEM: 11), IL-2: 1.93 ng/ml (SEM: 0.3)] (p < 0.01, p < 0.009 respectively). There were no differences in the IFN-alpha, IFN-gamma or TNF-alpha levels between groups. These findings suggest that plasma cytokines levels may reflect synovial levels and that IL-1 alpha may play a significant role in erosive joint disease.

Apoptosis in SLE--too little or too much?

Abstract: Cells of the immune system are, most likely, programmed to die unless recruited into an immune response. An active cell death program may also be induced by a variety of soluble and surface signals, many of which have only recently been recognized. The importance of these pathways in maintaining tolerance is highlighted by the development of lupus-like diseases in three different mouse strains that have spontaneous mutations in the Fas/APO-1 receptor or its ligand. The known function of Fas/APO-1 in signalling apoptosis explains the persistence of self reactive cells in lpr mice although it is unclear, at present, whether Fas defects effect both central and peripheral tolerance. Whereas Fas/APO-1 receptor expression appears to be normal in humans with SLE, other defects in the Fas/APO-1 pathway or other key molecules in the cell death survival require further study.

The neuropathic joint.

Abstract: Neuropathic arthritis is a destructive arthropathy frequently associated with loss of proprioception. A third of patients, however, may have no demonstrable neurological deficit. Patients with diabetes, syphilis, syringomyelia and other neuropathies are particularly prone to developing this joint disease. The diagnosis of Charcot's joints should be considered in anyone who develops what appears to be a severe osteoarthritis or a transverse fracture of the tibia or fibula after minor trauma. Scoliosis with particularly destructive changes on radiography should prompt a search for syringomyelia or syphilis. The most common radiographic abnormalities are those of distension in 3D (Dislocation, Destruction and Degeneration). An atrophic form with resorption of the proximal humerus, most frequently described in syringomyelia, has been observed in diabetes. Loss of the distal end of the clavicle has not been described before in the neuropathies. These changes coupled with speckled calcification or shards of bone in the periarticular soft tissue confirm the diagnosis. Infection and CPPD crystal disease can be difficult to exclude. The joint fluid may be inflammatory and infection may be a complication. Treatment includes anti-inflammatories and splinting. Indications for surgery are limited.

Autoimmune epitheliitis: Sjögren's syndrome.

Abstract: Sjogren's syndrome (SS), an autoimmune exocrinopathy, is a common, chronic disease of females. Clinical studies of kidney involvement in SS patients have shown that the predominant lesion is interstitial nephritis which produces tubular dysfunction. Studies on lung involvement have previously indicated that one fourth of SS patients suffer from subclinical interstitial lung disease. Re-evaluation, however, of the pulmonary disease using functional, radiologic and histopathologic studies showed that the lesion starts peribronchially. Finally, evaluation of liver disease in SS patients revealed that this consists of a pericholangeal round-cell infiltrate resembling the early lesion of primary biliary cirrhosis. These clinical studies suggest that the systemic manifestations of SS are probably due to the attraction of lymphocytes by different epithelial tissues. Studies of the epithelial cells of minor salivary glands from SS patients have shown that these inappropriately and selectively express HLA class II molecules and the proto-oncogene c-myc. Evaluation of cytokines in the minor salivary glands from these patients by in situ hybridization revealed that the proinflammatory cytokines IL-1 and IL-6 are also produced by the epithelial cells. Finally, proviral DNA has been shown to be incorporated in the DNA of epithelial cells. On the basis of these clinical and laboratory observations, we would like to suggest that the target tissue involved in the autoimmune histopathologic lesions of SS is the epithelium, and therefore we propose the term "Autoimmune Epitheliitis" instead of "Sjogren's syndrome" for this disease.

Infection and molecular mimicry in autoimmune diseases of childhood.

Abstract: The etiopathogenesis of childhood chronic autoimmune disease is, in most cases, unknown. Most likely, several factors overlap in determining the loss of tolerance toward certain autoantigens that become the target of the disease and the main cause of its perpetuation. Infectious agents have often been implicated in the pathogenesis of these diseases, but, to date, compelling evidence for a horizontal transmission or for localized epidemics is lacking. Human pathogens may nevertheless play a role in determining the loss of tolerance toward certain self-antigens by means of mechanisms other than classic infection. It is common knowledge that human pathogens often express proteins with high antigenic potential with important homologies with human proteins. Evolutionary pressures based upon the necessity of escaping the host's specific immune responses may have determined this phenomenon, called "molecular mimicry". It is reasonable to assert that certain individuals can develop abnormal immune responses upon contact with an antigen that mimics a self-protein. These responses may ultimately lead to self-reactivity and autoimmune disease. In this model of molecular mimicry, self-reactivity is triggered by cross-recognition of a self and an exogenous protein that bear the same sequence. A disease triggered by such a mechanism should present with: i) some form of an acute or chronic autoimmune clinical manifestation; ii) a documented clinical correlation between contact with a human pathogen and the autoimmune disease; iii) immune cross-reaction between a protein from a pathogen and a homologous human protein. Acute rheumatic fever, Reiter's syndrome and the other reactive arthritides fulfill the above conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Subtypes of HLA-DRB1*03, *08, *11, *12, *13 and *14 in early onset pauciarticular juvenile chronic arthritis (EOPA) with and without iridocyclitis.

Abstract: A set of 200 patients with early onset pauciarticular juvenile chronic arthritis (EOPA-JCA) from Munich (165) and Prague (35) was investigated for the subtypes of HLA-DRB1 * 03, * 08, * 11, * 12, * 13 and * 14. In additionthe relationship of DRB1, DQA1, DQB1 and DPB1 alleles with iridocyclitis in patients with EOPA-JCA was investigated. Subtyping for DRB1 * 03 was not informative, as all DR3 positive patients and all except one of the controls possessed DRB1 * 0301. Thus, the role of DRB1 * 0302 could not be assessed. The subtypes for DRB1 * 12, * 13, and * 14 did not reveal any statistically significant difference between patients and controls

Cervical spine involvement in rheumatoid arthritis: a clinical, neurological and radiological evaluation.

Abstract: Objective This study was designed to reveal any correlation between radiological signs and clinical findings of cervical spine involvement in rheumatoid arthritis (RA). Methods Fifty patients with definite rheumatoid arthritis were evaluated for cervical spine involvement by a clinical neurological examination, a somatosensory evoked potential (SEP) study and different radiological techniques including tomograms, computerized tomography (CT) and magnetic resonance imaging (MRI). Results Anterior atlantoaxial subluxation was a common finding, frequently associated with superior migration of the dens and subaxial subluxation. Two patients presented a posterior atlantoaxial subluxation due to complete erosion of the dens. Both had cervical cord compression and one of them had hypoglossal nerve paresis. The delineation of peridental pannus formation was clearly demonstrated by MRI. In the majority of cases cervical cord compression was caused by pannus formation or by vertical atlantoaxial subluxation. Conclusion The correlation between the severity of the radiological findings and the clinical-neurological signs was poor. A 4-limb SEP study appeared to be a useful screening method for the detection of cervical medullary compression.

Increased levels of intercellular adhesion molecule-1 in the serum of patients with systemic lupus erythematosus.

Abstract: Intercellular adhesion molecule-1 (ICAM-1) is a membrane-bound molecule that is primarily involved in cell-cell adhesive interactions of the immune system. The levels of soluble ICAM-1 (s-ICAM-1) shed into the circulation were studied in the sera of patients with systemic lupus erythematosus (SLE) by an enzyme linked immunosorbent assay. Serum concentrations of s-ICAM-1 were significantly increased in 61 patients with SLE compared to 51 controls (mean± SEM:564±30 versus 348±17 ng/ml, p<0.0001) and 41% of patients had higher serum levels than the normal cut of of 584 ng/ml. Among the various clinical manifestations, skin involvement was significantly associated with high serum levels of s-ICAM-1

Central nervous system involvement in relapsing polychondritis.

Abstract: Central nervous system (CNS) involvement is a rare condition in relapsing polychondritis. We report a case of meningoencephalitis that revealed relapsing polychondritis in a 70-year-old woman. A vasculitic process is presumed. Patient was treated with steroids and dapsone, and no relapse was observed after a follow-up of 2 years.

Autoantibody-defined epitopes on nuclear antigens are conserved, conformation-dependent and active site regions.

Abstract: Antinuclear antibodies in the systemic rheumatic diseases have been powerful reagents for identifying and characterizing nuclear antigens and for elucidating immune mechanisms which drive the autoimmune response. Concepts which have emerged from these studies include the following: the autoimmune response is antigen driven, autoantigens are components of subcellular particles, autoantigens are involved in important biosynthetic functions and epitopes recognized by autoantibodies are active sites or functional domain regions. PCNA (proliferating cell nuclear antigen) is a nuclear protein of 36 kDa and autoantibodies are present in patients with systemic lupus erythematosus. PCNA is a component of the DNA replication complex and is associated with DNA polymerase δ in continuous strand DNA synthesis at the replication fork. Studies have shown that epitopes on PCNA recognized by lupus antibodies are conformation-dependent. Composite peptides synthesized by joining discontinuous linear sequences were used to immunize rabbits rabbits and one such composite peptide induced antibodies with properties strikingly similar to human autoantibodis. Immunogens in the systemic autoimmune diseases are likely to be intranuclear or other intracellular particles composed of protein-protein or protein-nucleic acid complexes which are involved in cellular biosynthetic functions

Familial giant cell arteritis: report of an HLA-typed sibling pair and a review of the literature.

Abstract: We report a brother and sister who developed biopsy-proven giant cell arteritis four years apart and summarize the eight previously well-documented families of first-degree relatives with unequivocal disease. HLA haplotypes for both siblings included DRB1*03 (DR3) and the *0401 allele of DRB1*04 (DR4). The reported association of giant cell arteritis with HLA-DR4 and its occurrence in first-degree relatives support a genetic component in its pathogenesis.

Familial Mediterranean fever presenting with massive cardiac tamponade.

Abstract: A 16-year-old girl, presenting initially with pericarditis and life threatening pericardial tamponade, developed clinical episodes characteristic of FMF few months later. This case report and several others reported previously, suggest that FMF should be considered in patients from certain ethnic groups presenting with pericardial effusion.

HLA associations in juvenile arthritis.

Abstract: This review of the current status of HLA associations in juvenile arthritis begins with a discussion of the terms used to identify these patients and an approach for their clinical classification. The authors suggest that seven different types should be identified on the basis of clinical features and associated immunogenetic factors and that each of them should be recognized and called by a separate name. Different combinations of patients have been included in the studies performed in different cities and this fact may explain some of the observed differences in HLA associations in various reports. Results from an on-going study in Dallas are compared with published reports from Prague, Cincinnati, and Houston. HLA alleles associated with susceptibility in pauciarticular patients include certain DR and DQ alleles, one DP allele (DPB1*0201) and one HLA class I allele (HLA-A*0201). Susceptibility for polyarticular onset disease was found by the authors to be uniquely associated with DPB1*0301. Important interactions were observed between alleles at the different loci, with markedly increased odds ratios when combinations of susceptibility alleles were analyzed. The possibility that interaction between class I and class II susceptibility factors might be due to the effect of an allele at one of the TAP loci was examined by probing for polymorphic variants of the TAP1 and TAP2 genes. In addition, class I alleles associated with resistance for the development of juvenile arthritis were discussed. The main allele associated with rheumatoid arthritis (DRB1*0401) appears to be protective for the development of several forms of arthritis prevalent in children.

Lung function and diffusing capacity for carbon monoxide in patients with juvenile chronic arthritis: effect of disease activity and low dose methotrexate therapy.

Abstract: OBJECTIVE We measured lung function, in terms of lung volumes, forced expiratory flow-volume curves and diffusing capacity of carbon monoxide (DLCO), in a group of 61 patients with juvenile chronic arthritis (42 female; age range 5 to 33 years) to ascertain whether disease activity and treatment with low dose methotrexate (MTX) influenced these parameters. The whole population was divided into subgroups based on onset type (systemic, n = 27; pauciarticular, n = 12; polyarticular, n = 22), disease activity (active, n = 42; inactive, n = 19), and MTX treatment (treated, n = 27; not treated, n = 34). RESULTS We found that maximal-mid expiratory flow (MMEF) was significantly reduced in patients with active disease (p < 0.025). The mean DLCO value, expressed as a percentage of the predicted value, and DLCO corrected for the hemoglobin value were lower than expected (67% and 80%, respectively). Multiple regression analysis showed that the forced vital capacity (FVC), forced expiratory flow in one second (FEV1) and DLCO were all correlated to the clinical subtype of the disease (p < 0.05, p < 0.02, p < 0.02, respectively), and MMEF was related to disease activity (p < 0.025). There was no evidence of any effect of MTX treatment on the pulmonary parameters. CONCLUSION This study confirms that JCA is characterized by an impairment of lung function, mainly involving the small airways, and by interstitial damage. These changes are related to the clinical subtypes of the disease and to disease activity.

Benign edematous polysynovitis in the elderly (RS3PE syndrome).

Abstract: The Authors provide an update on benign edematous polysynovitis in the elderly and propose clinical and laboratory criteria for a correct diagnosis. They also propose the use of the term "polysynovitis" rather than polyarthritis, as they think it describes the histopathological findings of the disease better. Finally, they attempt to correctly distinguish RS3PE syndrome from polymyalgia rheumatica, rheumatoid arthritis and chondrocalcinosis.

Polymorphisms in the TAP2 gene and their association with rheumatoid arthritis

Abstract: The human major histocompatibility complex (MHC) contains two closely related genes (TAP) that encode a family of transporter proteins. It is known that the TAP genes, like other MHC (class I and class II) genes, are polymorphic. In this study we investigated the polymorphisms in the ATP-binding domain of the TAP2 gene and examined the relationship of these polymorphisms to susceptibility to rheumatoid arthritis (RA). On the basis of the distribution of polymorphisms in these genes, three TAP2 alleles could be identified in homozygous typing cell lines, RA patients andnormalsubjects: TAP2 * 0101-1693.G, TAP2 * 0101-1693.A and TAP2 * 0201-1693.G

Growth retardation and osteoporosis in juvenile chronic arthritis.

Abstract: Disturbance of growth and bone metabolism is a serious problem in juvenile chornic arthritis. The major factors appear to the chronic disease activity and steroid therapy. Retardation of linear growth is due to disturbance of the neuroendocrine axis, where there is no obvious growth hormone deficiency, but marked reduction of the serum concentration of its mediator, insulin growth factor 1 (IGF-1). Its reduced serum concentration may be multifactorial. In addition, there is also evidence of target insensitivity to IGF-1. The role of the inflammatory cytokines in these endocrine disturbances is likely to be very important, and is the subject of current research