Sacroiliitis presenting as sciatica.
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Adult↗
Biomedical subjects
B Kirkham
Publications and source records attributed to B Kirkham.
Adalimumab in clinical practice. Outcome in 70 rheumatoid arthritis patients, including comparison of patients with and without previous anti-TNF exposure.
OBJECTIVE: To assess the efficacy and safety of the fully human recombinant monoclonal anti-TNF antibody adalimumab in routine clinical practice, including comparison of patients with and without previous anti-TNF exposure. METHODS: We prospectively studied the outcome of 70 rheumatoid arthritis patients treated with adalimumab in normal clinical practice. The primary outcome measures were Disease Activity Score 28 (DAS28), EULAR (European League Against Rheumatism) response and Health Assessment Questionaire (HAQ). RESULTS: Seventy-seven per cent achieved a EULAR response (26% good, 51% moderate) and 19% were in remission. The mean decrease in DAS28 was 2.1 (6.3-4.2; P<0.001). The mean decrease in HAQ score was 0.34 (2.07-1.73; P<0.001), 66% achieving a clinically significant decrease of greater than 0.22. Twenty-three per cent stopped treatment because of side-effects (7%) or failure to respond (16%). Of the 26 patients who had previously tried 29 biologicals, 65% responded to adalimumab. There was no significant difference in the change in mean DAS (P = 0.69) or HAQ (P = 0.88) between groups with and without previous anti-TNF exposure. Of the 13 patients with previous secondary failure to infliximab, 77% responded to adalimumab. Patients with previous secondary failure had significantly better improvement in DAS (P = 0.023) than patients with previous primary failure. CONCLUSION: Our clinical experience confirms that adalimumab is effective and safe in the treatment of RA. It also shows adalimumab is effective in patients with previous biological failures, particularly patients with secondary failure to infliximab.
Adalimumab↗
Leflunomide in rheumatoid arthritis: recommendations through a process of consensus.
OBJECTIVES: To determine, by consensus, the optimal use of leflunomide in rheumatoid arthritis (RA), using a multidisciplinary panel of experts and performing meta-analyses of available data. METHODS: A multidisciplinary panel of experts in RA was convened. Important questions, pertinent to the use of leflunomide in the treatment of RA, were defined by consensus at an initial meeting. Each question was allocated to subgroups of two or three members, who worked separately to prepare a balanced opinion, based on published literature, data from individual patients taking part in phase II and phase III clinical trials provided by Aventis, and data from a USA-based medical claims database (AETNA). The full group then reconvened to agree on an overall consensus statement. Recommendations concerning efficacy and tolerability versus comparator drugs and placebo were derived from two new meta-analyses. RESULTS: Leflunomide was at least as effective as sulphasalazine and methotrexate, and equally well tolerated on meta-analysis of trial data. Overall withdrawal rates for all adverse events were similar for all three drugs. Avoidance of the loading dose reduces 'nuisance' side-effects (e.g. nausea), but probably delays the onset of action. Adverse events could usually be managed by dose reduction and/or symptomatic therapy. CONCLUSIONS: On the basis of efficacy, safety and cost, leflunomide should be considered in patients with RA who have failed first-line DMARD drug therapy. In refractory cases, leflunomide may be used in combination with, for example, methotrexate before biological agents. Therapy should be initiated by a specialist, but repeat prescribing in general practice on a shared care basis is acceptable using agreed protocols. Clear mechanisms are required to monitor toxicity, with good communication between the patient and rheumatologist to manage nuisance side-effects and avoid unnecessary discontinuation of leflunomide.
Anti-Inflammatory Agents, Non-Steroidal↗
Endocarditis and ulnar artery aneurysm as presenting features of antiphospholipid syndrome and polyarteritis nodosa.
Antiphospholipid syndrome in association with vasculitis is highlighted in this report. The combination of thrombotic and inflammatory processes resulted in endocarditis, aneurysm formation and thrombosis. To our knowledge this is the first presentation of a large vessel aneurysm in these conditions. Anticoagulation and immunosuppression are the treatment modalities of choice.
Aneurysm↗
Successful treatment of severe psoriasis and psoriatic arthritis with adalimumab.
Adalimumab, a fully human-derived recombinant monoclonal antibody against tumour necrosis factor-alpha, has been shown to be effective for the treatment of patients with moderately to severely active rheumatoid arthritis. We report two patients with long-standing recalcitrant psoriasis and psoriatic arthritis who, after multiple treatment failures with conventional and experimental antipsoriatic medications, both responded to treatment with adalimumab. Significant clinical improvement was noted in both skin and joint disease in the two patients after several weeks of treatment with adalimumab. We are unaware of previous published reports of adalimumab therapy in patients with psoriasis and psoriatic arthritis.
Adalimumab↗
Antigen-induced IL-17 response in the peripheral blood mononuclear cells (PBMC) of healthy controls.
IL-17 is a T cell cytokine with a complex and important role in the immune system. It has been detected in rheumatoid arthritis (RA) synovial membrane and found to stimulate the production of the proinflammatory cytokines IL-6, IL-8, tumour necrosis factor-alpha (TNF-alpha) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in vitro. To date, there are few data available on the agents that stimulate IL-17 production. We therefore investigated the in vitro IL-17 response to a variety of mitogens and antigens, and compared the IL-17 response to interferon-gamma (IFN-gamma), IL-4, IL-10 and TNF-alpha. In this study we used a type-0 antigen, tetanus toxoid (TT), a type-1 antigen, PPD from Mycobacterium tuberculosis, a potential type-2 rye grass (RG) antigen (Lol I) and an autoantigen SS.B (La), to stimulate PBMC from healthy controls. Cytokine mRNA was measured using semiquantitative reverse transcriptase-polymerase chain reaction and cytokine protein measured using specific ELISA techniques, while the frequency of IL-17-producing T cells was determined by flow cytometry. The mitogens concanavalin A, phytohaemagglutinin and phorbol myristate acetate/ionomycin induced a significant increase in IL-17, with the highest levels being produced by anti-CD3/anti-CD28 stimulation. The antigens TT and PPD significantly increased IL-17 mRNA expression over time, but failed to have such an effect at the protein level. IL-17 protein was also detectable in both antigen-specific (TT, SS. B) and non-specific T cell clones, but at levels lower than IFN-gamma. IL-17 production did not correlate with either the type-1 cytokine IFN-gamma or TNF-alpha or the type-2 cytokine IL-4 or IL-10 at either the mRNA or protein level.
Adult↗
Synovial membrane p53 protein immunoreactivity in rheumatoid arthritis patients.
OBJECTIVES: To examine the expression of the p53 protein in synovial membrane of rheumatoid arthritis (RA) patients and to compare this with the expression in normal synovial tissues in subjects without RA. METHODS: Immunohistological expression of the p53 protein was studied using a streptavidin-biotin-peroxidase method and the monoclonal antibody DO-7, an antibody directed against both wild and mutant forms of p53 protein, in synovial tissues of RA patients (n=10) and from subjects with no known joint disease (n=4). RESULTS: p53 protein expression was present in a small percentage of synovial cells in the majority of the RA patients (n=8; 80%) and in half of the normal control cases with no inflammatory joint disease (n=2; 50%). No sample had more than 5% cells staining with intranuclear pattern. The difference in synovial p53 immunoreactivity between the RA patients and normal controls is not statistically significant (p= 0.64; chi(2) contingency test). CONCLUSIONS: This study has shown that p53 protein is only weakly expressed in the rheumatoid synovial membrane, with a low percentage of p53 protein immunostaining cells present, with intranuclear staining. These results suggest this is wild type p53 protein rather than mutant protein. These findings suggest that synovial p53 protein expression may not be important in the pathogenesis of RA and may only represent a reactive repair process to DNA damage secondary to the immune and inflammatory reactions associated with the disease.
Adolescent↗
Intraarticular variability of synovial membrane histology, immunohistology, and cytokine mRNA expression in patients with rheumatoid arthritis.
OBJECTIVE: To assess the variability of synovial histology, immunohistology, and cytokine mRNA expression at different sites within the knee joints of subjects with rheumatoid arthritis receiving slow acting antirheumatic drugs. The effects of intraarticular bupivacaine and adrenaline, and a comparison of synovial fluid cell and synovial membrane cytokine expression, were also investigated. METHODS: Arthroscopically directed synovial biopsies were taken at 3 or 4 predetermined sites from the knee joints of 11 patients. Histology for synovial lining layer, sublining cellularity and vascularity, and immunohistology for T cells, T cell subsets, and macrophages were assessed. Messenger RNA expression of interleukins 1beta, 2, 4, 6, 8, 10, granulocyte-monocyte colony stimulating factor, tumor necrosis factor-alpha, and interferon-gamma was detected using the reverse transcription/polymerase chain reaction technique. RESULTS: Synovial histology, immunohistology, and cytokine mRNA expression did not vary significantly. CD8 cell immunohistology was variable. Intraarticular bupivacaine and adrenaline did not change synovial characteristics. Synovial fluid cell and membrane cytokine expression did not match in 35% of comparisons. CONCLUSION: Biopsies from the suprapatellar pouch, medial gutter, and cartilage-pannus junction will provide a representative sample of synovial membrane pathology in patients with rheumatoid arthritis.
Adolescent↗
Dilated cardiomyopathy associated with anti-neutrophil cytoplasmic antibodies.
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Adult↗
Use of sequential DTPA clearance and high resolution computerized tomography in monitoring interstitial lung disease in dermatomyositis.
Interstitial lung disease complicating polymyositis-dermatomyositis has a grave prognosis. We report the case of a 50-yr-old woman with dermatomyositis and interstitial lung disease monitored by sequential high-resolution computerized tomography (HRCT) of lung and aerosol clearance times of the radionuclide 99Technetium-diethylene triamine pentacetate (DTPA). She was treated with oral cyclophosphamide and prednisolone with good outcome. Pulmonary response to therapy was followed with sequential HRCT and DTPA scanning. DTPA clearance a measure of lung inflammation, and HRCT paralleled clinical course during the treatment of interstitial lung disease. Sequential HRCT and DTPA were useful adjuncts in the initial assessment and monitoring of interstitial lung disease in association with dermatomyositis.
Anti-Inflammatory Agents↗
Clinical associations of anti-lamin autoantibodies.
BACKGROUND: The clinical associations of anti-lamin autoantibodies were first described in 1973. Since then a number of individual case reports and two small series have been published. These have suggested an association with connective tissue disorders and autoimmune liver disease. AIMS: To identify the clinical and laboratory associations of anti-lamin autoantibodies in an Australian population. METHODS: Retrospective review of routine antinuclear antibody testing between 1990-1994 for characteristics linear staining of nuclear envelope on indirect immunofluorescence on HEp-2 cells with clinical status defined by retrospective review of case records. RESULTS: Twenty-eight patients were identified and the clinical status of 27 patients defined. Eleven patients had associated IgG anti-cardiolipin antibodies; anti-phospholipid syndrome was present in nine. Seven further patients had liver disease; five had autoimmune liver disease, with associated autoantibodies. The remaining nine patients had a diverse group of diseases. There was no correlation between the titre of the autoantibody and clinical status. An association with anti-cardiolipin antibodies was found although the cause remains obscure. CONCLUSION: Anti-lamin autoantibodies, as identified by indirect immunofluorescence, are associated with a diverse group of diseases but particularly with anti-phospholipid syndrome and liver disease. Testing for anti-phospholipid antibodies and more specific markers of systemic lupus erythematosus and autoimmune disease, for example anti-dsDNA antibodies, anti-smooth muscle antibodies and anti-mitochondrial antibodies should be pursued when anti-lamin autoantibodies are detected.
Adult↗
Neurological side effects in two patients receiving gold injections for rheumatoid arthritis.
We describe two patients who developed neurological side effects as part of the spectrum of nitritoid reactions. Both reactions occurred late in the course of treatment. The first patient developed mild nitritoid symptoms and pain in a band-like distribution, corresponding to T10-T12 dermatomes, shortly after gold sodium thiomalate (GSTM) injection. Further injections were followed by similar symptoms in addition to paraesthesiae and altered pin-prick sensation of anterior thigh and legs with no residual deficit. She has had no further episodes since substitution of aurothioglucose. The second patient experienced mild nitritoid symptoms following several GSTM injections prior experiencing a cerebrovascular accident within several hours of her next injection. She subsequently haemorrhaged into the infarcted area with residual neurological deficits. These cases highlight that nitritoid reactions can be severe and may be heralded by milder symptoms. Patients who develop these reactions whilst receiving GSTM can be successfully changed to aurothioglucose.
Adult↗
Dermatomyositis with lung involvement in a patient treated with simvastatin.
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Aged↗
Histiocytic necrotising lymphadenitis in systemic lupus erythematosus.
Histiocytic necrotising lymphadenitis is the pathognomonic histological appearance of lymph nodes in Kikuchi's disease, a condition characterised by a brief systemic illness and lymphadenopathy. The case is described of a young man, originally diagnosed as having Kikuchi's disease by lymph node histology, who subsequently developed systemic lupus erythematosus with symmetrical polyarthritis, Coombs' positive haemolytic anaemia and haemorrhagic pneumonitis. The case emphasises that a range of diseases is associated with histiocytic necrotising lymphadenitis, belying the unitary impression given by the term Kikuchi's disease.
Adult↗
Serial estimation of interleukin 6 as a measure of systemic disease in rheumatoid arthritis.
Disease activity in rheumatoid arthritis (RA) is frequently associated with a marked acute phase response, thrombocytosis, hypergammaglobulinemia and the presence of rheumatoid factors (RF). Interleukin 6 (IL-6) is a cytokine that stimulates hepatocytes to produce acute phase reactants and B lymphocytes to produce immunoglobulin. We measured serum IL-6 in patients with active RA during induction of intramuscular gold therapy. Levels of IL-6 correlated strongly with the erythrocyte sedimentation rate and RF titers and to a lesser degree with platelet counts. It may, therefore, be responsible for many of the systemic manifestations of RA and its measurement in the serum may be a convenient and reproducible variable for the assessment of disease activity in this very common disease.
Arthritis, Rheumatoid↗
Normal sedimentation rates and giant cell arteritis.
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Blood Sedimentation↗
Anterolateral rupture of popliteal cysts in rheumatoid arthritis.
Popliteal cysts occur commonly in both normal and arthritic knees. Most cysts are formed by distension of the medially situated semimembranosus bursa. Popliteus bursa distension occurs uncommonly as a lateral popliteal cyst. Two cases of rupture of lateral cysts which produced symptoms related to the anterolateral lower leg are reported. The difficulty of diagnosing the condition because of this unusual site of inflammation and subsequent management problems are discussed.
Aged↗