Paleopathologic evidence for the evolution of rheumatoid arthritis

A human skeleton recovered from a Sicilian archaeological site and dating from the Hellenistic period (330–210 B.C. ) presents a pathological pattern suggesting a transition between ankylosing spondylitis and rheumatoid arthritis, providing evidence in support of the hypothesis that rheumatoid arthritis may have recently evolved out of ankylosing spondylitis.     

Pain Threshold and Arthritis

Pain threshold was measured in 106 patients with rheumatoid arthritis, 50 with ankylosing spondylitis, and 50 normal controls using Keele''s algometer. In rheumatoid arthritis patients with a low pain threshold had more severe pain for a greater part of the day and required more tablets for pain relief. In ankylosing spondylitis the pain threshold was higher and was not related to pain or analgesic requirements. There was no evidence that pain threshold affected the course or outcome of rheumatoid arthritis in any way.     

Vitamin E content and lipid peroxidation of blood in some chronic inflammatory diseases

Patients suffering from rheumatoid arthritis, spondylosis, coxarthrosis, ankylosing spondylitis, chronic active and chronic alcoholic hepatitis were studied. The plasma vitamin E content remained unchanged. The TBA-reactive plasma substances (malondialdehyde) content of plasma increased in all patients except those with ankylosing spondylitis. Catalase activity of plasma increased in patients of both sexes suffering from rheumatoid arthritis and spondylosis and coxarthrosis, but decreased in the two hepatitis groups. The glutathione-peroxidase activity of RBC (1:9 haemolysate) increased in female rheumatoid arthritis patients and decreased in those suffering from chronic alcoholic hepatitis. The results showed that chronic inflammatory processes affect the rate of lipid peroxidation and the activity of the biological antioxidant mechanism.     

Raised titres of anti-klebsiella IgA in ankylosing spondylitis,rheumatoid arthritis,and inflammatory bowel disease

Serum titres of IgA are raised in ankylosing spondylitis and increased titres of antibodies to klebsiella have also been reported. The humoral response was investigated in ankylosing spondylitis and other inflammatory disorders. IgA antibodies to klebsiella pneumoniae K43 were measured in patients with ankylosing spondylitis, Crohn''s disease, ulcerative colitis, and rheumatoid arthritis and in controls. Significantly raised median titres of anti-klebsiella IgA, measured as optical density at 405 nm with an enzyme linked immunosorbent assay (ELISA), were seen among the patients with ankylosing spondylitis (0·7), Crohn''s disease (0·8), rheumatoid arthritis (0·6), and ulcerative colitis (0·8) compared with controls (0·4). Activity of disease in ankylosing spondylitis and titres of anti-klebsiella IgA were not correlated. In contrast, titres of anti-klebsiella IgM were significantly lower in patients with ankylosing spondylitis and ulcerative colitis.The increase in the titres of anti-klebsiella IgA may be due to increased permeability of the gut to bacterial antigens, leading to an increased IgA response in the gut mucosa and permitting the release of IgA into the circulation. As the increased antibody titres were seen in Crohn''s disease and rheumatoid arthritis as well as in ankylosing spondylitis the response may be non-specific, occurring because of possible underlying inflammatory bowel disease in these conditions.     

Therapy of ankylosing spondylitis and other spondyloarthritides: established medical treatment,anti-TNF-alpha therapy and other novel approaches

Therapeutic options for patients with more severe forms of spondyloarthritis (SpA) have been rather limited in recent decades. There is accumulating evidence that anti-tumor-necrosis-factor (anti-TNF) therapy is highly effective in SpA, especially in ankylosing spondylitis and psoriatic arthritis. The major anti-TNF-alpha agents currently available, infliximab (Remicade(R)) and etanercept (Enbrel(R)), are approved for the treatment of rheumatoid arthritis (RA) in many countries. In ankylosing spondylitis there is an unmet medical need, since there are almost no disease-modifying antirheumatic drugs (DMARDs) available for severely affected patients, especially those with spinal manifestations. Judging from recent data from more than 300 patients with SpA, anti-TNF therapy seems to be even more effective in SpA than in rheumatoid arthritis. However, it remains to be shown whether patients benefit from long-term treatment, whether radiological progression and ankylosis can be stopped and whether long-term biologic therapy is safe.     

Therapy of ankylosing spondylitis and other spondyloarthritides: established medical treatment, anti-TNF-α therapy and other novel approaches

Therapeutic options for patients with more severe forms of spondyloarthritis (SpA) have been rather limited in recent decades. There is accumulating evidence that anti-tumor-necrosis-factor (anti-TNF) therapy is highly effective in SpA, especially in ankylosing spondylitis and psoriatic arthritis. The major anti-TNF-α agents currently available, infliximab (Remicade^®) and etanercept (Enbrel^®), are approved for the treatment of rheumatoid arthritis (RA) in many countries. In ankylosing spondylitis there is an unmet medical need, since there are almost no disease-modifying antirheumatic drugs (DMARDs) available for severely affected patients, especially those with spinal manifestations. Judging from recent data from more than 300 patients with SpA, anti-TNF therapy seems to be even more effective in SpA than in rheumatoid arthritis. However, it remains to be shown whether patients benefit from long-term treatment, whether radiological progression and ankylosis can be stopped and whether long-term biologic therapy is safe.     

Magnetic resonance imaging in psoriatic arthritis: a review of the literature

Psoriatic arthritis is a diverse condition that may be characterized by peripheral inflammatory arthritis, axial involvement, dactylitis and enthesitis. Magnetic resonance imaging (MRI) allows visualization of soft tissue, articular and entheseal lesions, and provides a unique picture of the disease process that cannot be gained using other imaging modalities. This review focuses on the literature on MRI in psoriatic arthritis published from 1996 to July 2005. The MRI features discussed include synovitis, tendonitis, dactylitis, bone oedema, bone erosions, soft tissue oedema, spondylitis/sacroiliitis and subclinical arthropathy. Comparisons have been drawn with the more extensive literature describing the MRI features of rheumatoid arthritis and ankylosing spondylitis.     

Coexpression and interaction of CXCL10 and CD26 in mesenchymal cells by synergising inflammatory cytokines: CXCL8 and CXCL10 are discriminative markers for autoimmune arthropathies

Leukocyte infiltration during acute and chronic inflammation is regulated by exogenous and endogenous factors, including cytokines, chemokines and proteases. Stimulation of fibroblasts and human microvascular endothelial cells with the inflammatory cytokines interleukin-1beta (IL-1beta) or tumour necrosis factor alpha (TNF-alpha) combined with either interferon-alpha (IFN-alpha), IFN-beta or IFN-gamma resulted in a synergistic induction of the CXC chemokine CXCL10, but not of the neutrophil chemoattractant CXCL8. In contrast, simultaneous stimulation with different IFN types did not result in a synergistic CXCL10 protein induction. Purification of natural CXCL10 from the conditioned medium of fibroblasts led to the isolation of CD26/dipeptidyl peptidase IV-processed CXCL10 missing two NH2-terminal residues. In contrast to intact CXCL10, NH2-terminally truncated CXCL10(3-77) did not induce extracellular signal-regulated kinase 1/2 or Akt/protein kinase B phosphorylation in CXC chemokine receptor 3-transfected cells. Together with the expression of CXCL10, the expression of membrane-bound CD26/dipeptidyl peptidase IV was also upregulated in fibroblasts by IFN-gamma, by IFN-gamma plus IL-1beta or by IFN-gamma plus TNF-alpha. This provides a negative feedback for CXCL10-dependent chemotaxis of activated T cells and natural killer cells. Since TNF-alpha and IL-1beta are implicated in arthritis, synovial concentrations of CXCL8 and CXCL10 were compared in patients suffering from crystal arthritis, ankylosing spondylitis, psoriatic arthritis and rheumatoid arthritis. All three groups of autoimmune arthritis patients (ankylosing spondylitis, psoriatic arthritis and rheumatoid arthritis) had significantly increased synovial CXCL10 levels compared with crystal arthritis patients. In contrast, compared with crystal arthritis, only rheumatoid arthritis patients, and not ankylosing spondylitis or psoriatic arthritis patients, had significantly higher synovial CXCL8 concentrations. Synovial concentrations of the neutrophil chemoattractant CXCL8 may therefore be useful to discriminate between autoimmune arthritis types.     

Diagnosis of “Rheumatoid Variants”: Ankylosing Spondylitis,the Arthritides of Gastrointestinal Diseases and Psoriasis,and Reiter's Syndrome

Four rheumatic diseases—ankylosing spondylitis, the arthritis accompanying ulcerative colitis or regional enteritis, psoriatic arthropathy, and Reiter''s syndrome—formerly considered to be forms of rheumatoid arthritis, are now distinguished from that disorder and should be recognized by the physician as entities. These arthritides may be distinguished from each other by a number of clinical and radiographic characteristics, principally (1) the roentgenographic appearance of the spine when spondylitis is present, (2) the location of periosteal new bone formation, (3) the location of arthritis in the joints of the limbs, and (4) the presence of characteristic skin lesions.     

Serum keratan sulphate levels rise in rheumatoid arthritis patients, but fall in ankylosing spondylitis patients compared with normal controls

Serum levels of keratan sulphate (KS) were found to be significantly elevated in patients with destructive and predominantly seronegative rheumatoid arthritis (RA) compared with a control population. Levels in RA did not correlate with clinical or laboratory indices of joint activity or damage. Conversely levels were depressed in ankylosing spondylitis (AS) compared with controls.     

Lymphocyte transformation to connective tissue antigens in adult and juvenile rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, systemic lupus erythematosus, and a nonarthritic control population

Transformation of peripheral blood lymphocytes after exposure to connective tissue antigens was measured in patients with adult (n = 35) and juvenile rheumatoid arthritis (n = 34), osteoarthritis (n = 21), ankylosing spondylitis (n = 15), and systemic lupus erythematosus (n = 26) and in control subjects (n = 36). The connective tissue antigens included homologous cartilage-type proteoglycan, cyanogen bromide-derived peptides of type I, II, and III collagens, and type I and II helical collagens. Lymphocyte transformation was not detected in the osteoarthritic and control groups, with one exception. Sensitization to at least one connective tissue antigen was detected in approximately one-third of the rheumatoid arthritic and lupus patients and in one-quarter of the juvenile rheumatoid patients. In ankylosing spondylitis, positive responses occurred to proteoglycan in 20% of patients tested but never to collagens or peptides. Sensitivity to proteoglycan was detected only in ankylosing spondylitis except for one patient with juvenile rheumatoid arthritis. In patients with systemic lupus erythematosus and both forms of rheumatoid arthritis, lymphocyte transformation was usually more frequently detected to peptides than to the helical collagens. In adult rheumatoid arthritis, type II peptides elicited an elevated number of responses (14%) as did type I (9%) and III (8%) peptides to lesser degrees. Responses to type I (4%) and II (4%) helical collagens were infrequent. Rheumatoid arthritic patients usually exhibited sensitivity to only one antigen and lymphocyte transformation was often detected when the arthritis was improving. In juvenile rheumatoid arthritis, lymphocyte transformation was detected to peptides of type I (16%), II (9%), and III (29%) collagens and to helical type I (12%) and II (8%) collagens. In systemic lupus erythematosus, sensitization was detected to peptides of type I (13%), II (20%), and III (14%) collagens and to helical type I collagen (18%) but not type II collagen. Simultaneous sensitivity to several antigens often occurred in both systemic lupus erythematosus and juvenile rheumatoid arthritis. Examination of individual patients in all three rheumatic disease groups revealed that immune sensitivity developed to collagen peptides rather than to the helical molecules, particularly in the case of type II collagen. Thus, some patients with inflammatory arthritis exhibit immune responses to connective tissue components which are, as a group, characteristic for each type of arthritis. These responses, which were not obviously associated with disease activity, may develop as a result of inflammation or trauma which destroys connective tissue and exposes molecules, in either a native or degraded state, to cells of the immune system. Expression of sensitivity to these tissue antigens may contribute to the chronicity of the inflammatory arthritides.     

The window of opportunity: a relevant concept for axial spondyloarthritis

The window of opportunity is a concept critical to rheumatoid arthritis treatment. Early treatment changes the outcome of rheumatoid arthritis treatment, in that response rates are higher with earlier disease-modifying anti-rheumatic drug treatment and damage is substantially reduced. Axial spondyloarthritis is an inflammatory axial disease encompassing both nonradiographic axial spondyloarthritis and established ankylosing spondylitis. In axial spondyloarthritis, studies of magnetic resonance imaging as well as tumor necrosis factor inhibitor treatment and withdrawal studies all suggest that early effective suppression of inflammation has the potential to reduce radiographic damage. This potential would suggest that the concept of a window of opportunity is relevant not only to rheumatoid arthritis but also to axial spondyloarthritis. The challenge now remains to identify high-risk patients early and to commence treatment without delay. Developments in risk stratification include new classification criteria, identification of clinical risk factors, biomarkers, genetic associations, potential antibody associations and an ankylosing spondylitis-specific microbiome signature. Further research needs to focus on the evidence for early intervention and the early identification of high-risk individuals.     

Haematology and Biochemistry of Ankylosing Spondylitis

Forty men with ankylosing spondylitis have been reviewed clinically, radiologically, haematologically, and biochemically, and the results of the last two compared with a male group of rheumatoid patients and a control group. In the patients with ankylosing spondylitis the haemoglobin levels were much higher and the E.S.R. significantly lower than in the rheumatoid group, and the E.S.R. in the patients with ankylosing spondylitis was unrelated to disease activity as evidenced by pain. The alkaline phosphatase level was raised in 19 cases and in most was derived from bone. Though 10 patients had abnormal globulin levels, the albumin levels were normal, as was renal function in all cases.     

B lymphocyte involvement in ankylosing spondylitis: the heavy chain variable segment gene repertoire of B lymphocytes from germinal center-like foci in the synovial membrane indicates antigen selection

The synovial membrane (SM) of affected joints in ankylosing spondylitis (AS) is infiltrated by germinal center-like aggregates (foci) of lymphocytes similar to rheumatoid arthritis (RA). We characterized the rearranged heavy chain variable segment (VH) genes in the SM for gene usage and the mutational pattern to elucidate the B lymphocyte involvement in AS.     

Non-secretion of ABO blood group antigens as a host susceptibility factor in the spondyloarthropathies.

Gram negative bacteria precipitate reactive arthritis and may be concerned in the pathogenesis of ankylosing spondylitis and other spondyloarthropathies. Susceptibility to many infectious agents is associated with ABO blood group or secretor state, or both. The distribution of the ABO blood group or secretor state, or both, was therefore determined in 87 patients with ankylosing spondylitis and 32 with other forms of spondyloarthropathy. The prevalence of non-secretors was significantly increased in the total patient group (54/114; 47%) and in the subgroup with ankylosing spondylitis (41/84; 49%) compared with local controls (89/334; 27%) (p less than 0.001). Other subgroups of patients showed a similarly increased prevalence of non-secretion (33-47%). The distribution of ABO blood groups did not differ between patients and controls. The association between non-secretor state and ankylosing spondylitis strengthens the hypothesis that ankylosing spondylitis is a form of reactive arthritis. It also suggests several pathogenic mechanisms which may be relevant to the initial hostparasite interaction in ankylosing spondylitis.     

NONSPECIFIC ANTI-INFLAMMATORY AGENTS—Some Notes on Their Practical Application,Especially in Rheumatic Disorders

A number of acute and chronic inflammatory disorders are amenable to varying degrees of therapeutic control with the administration of nonspecific anti-inflammatory drugs. An evaluation of these suppressive agents in the field of rheumatic diseases and practical suggestions regarding their administration are presented.Eight synthetically modified corticosteroid compounds are available commercially. Each of them exhibits qualitative differences in one or several physiologic actions, each has certain advantages and disadvantages in therapy, and each shares the major deterrent features of corticosteroids. Prednisone, prednisolone, methylprednisolone, fluprednisolone and paramethasone have similar therapeutic indices, and there is little choice between them for the usual rheumatoid patient requiring steroid therapy. Conversely, the therapeutic indices of dexamethasone, betamethasone and triamcinolone are lower than that of prednisolone; they are less desirable for routine use and should be reserved for specially selected cases.Salicylates are preferred to adrenocortical steroids in the treatment of the ordinary patient with acute rheumatic fever. Steroid therapy should be reserved for resistant cases and for those with significant carditis. Salicylates are mainstays for pain relief in rheumatoid arthritis, but with the analgesic doses usually employed their anti-inflammatory action is slight.Phenylbutazone is a highly useful anti-inflammatory agent, especially in management of acute gouty arthritis and ankylosing (rheumatoid) spondylitis; its metabolite, oxyphenylbutazone, does not exhibit clear-cut advantages.Colchicine specifically suppresses acute gouty arthritis. Its analogues, desacetylcolchicine and desacetylthiocolchicine, produce fewer unpleasant gastrointestinal symptoms, but may promote agranulocytosis and alopecia.A number of indole preparations with anti-inflammatory activity have been tested clinically. One of them, indomethacin, has received extensive therapeutic trial; with dosages that can be tolerated the drug is fairly effective in the symptomatic control of ankylosing (rheumatoid) spondylitis but it is of questionable value in peripheral rheumatoid arthritis.     

What epidemiology has told us about risk factors and aetiopathogenesis in rheumatic diseases

This article will review how epidemiological studies have advanced our knowledge of both genetic and environmental risk factors for rheumatic diseases over the past decade. The major rheumatic diseases, including rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, systemic lupus erythematosus, scleroderma, osteoarthritis, gout, and fibromyalgia, and chronic widespread pain, will be covered. Advances discussed will include how a number of large prospective studies have improved our knowledge of risk factors, including diet, obesity, hormones, and smoking. The change from small-scale association studies to genome-wide association studies using gene chips to reveal new genetic risk factors will also be reviewed.     

Infliximab in ankylosing spondylitis: alone or in combination with methotrexate? A pharmacokinetic comparative study

Introduction  

Methotrexate (MTX) has been shown to modify infliximab pharmacokinetics in rheumatoid arthritis. However, its combination with infliximab in the treatment of ankylosing spondylitis (AS) is not recommended. The objective of this study was to examine the influence of MTX on infliximab exposure in patients with AS.     

Colony variability under the spotlight in animal models of arthritis

A recent article by Farkas and colleagues, published in Arthritis Research & Therapy, is from the laboratory of Dr Tibor Glant and his research team in Chicago, who have investigated in considerable depth the immunopathology of experimental arthritis induced by the major cartilage component proteoglycan aggrecan in an animal model that mimics many features of human rheumatoid arthritis and ankylosing spondylitis. This present report takes our understanding a significant step forward by questioning whether genetic drift in distinct colonies of the same inbred strains of mice has an impact on the parity between data published by different laboratories.     

Yersinia enterocolitica arthritis in southern Sweden: a four-year follow-up study.

Thirty-eight cases of suspected yersinia arthritis occurring in southern Sweden in 1975-6 were reviewed four to five years later. In 31 cases the diagnosis was confirmed. At follow-up three of the patients had definite ankylosing spondylitis, three radiologically confirmed sacroiliitis, three extensor tenosynovitis, five isolated articular joint disease, and 10 localised arthralgias; one patient had developed seropositive rheumatoid arthritis. Only six of the 31 patients were free of joint symptoms. These results suggest that although the acute symptoms of yersinia arthritis disappear within 12 months, the long-term prognosis may be less favourable than previously thought.