Approach to Septic Arthritis Horowitz, Diane Lewis, MD; Katzap, Elena, DO; Horowitz, Scott, MD ...
American family physician,
09/2011, Volume:
84, Issue:
6
Journal Article
Peer reviewed
Prompt diagnosis and treatment of infectious arthritis can help prevent significant morbidity and mortality. The acute onset of monoarticular joint pain, erythema, heat, and immobility should raise ...suspicion of sepsis. Constitutional symptoms such as fever, chills, and rigors are poorly sensitive for septic arthritis. In the absence of peripheral leukopenia or prosthetic joint replacement, synovial fluid white blood cell count in patients with septic arthritis is usually greater than 50,000 per mm3 . Isolation of the causative agent through synovial fluid culture is not only definitive but also essential before selecting antibiotic therapy. Synovial fluid analysis is also useful to help distinguish crystal arthropathy from infectious arthritis, although the two occasionally coexist. Almost any microorganism can be pathogenic in septic arthritis; however, septic arthritis is caused by nongonococcal pathogens (most commonly Staphylococcus species) in more than 80 percent of patients. Gram stain results should guide initial antibiotic choice. Vancomycin can be used for gram-positive cocci, ceftriaxone for gram-negative cocci, and ceftazidime for gram-negative rods. If the Gram stain is negative, but there is strong clinical suspicion for bacterial arthritis, treatment with vancomycin plus ceftazidime or an aminoglycoside is appropriate. Evacuation of purulent material with arthrocente-sis or surgical methods is necessary. Special consideration should be given to patients with prosthetic joint infection. In this population, the intraarticular cutoff values for infection may be as low as 1,100 white blood cells per mm3 with a neutrophil differential of greater than 64 percent.
The target organ in many forms of inflammatory arthritis is the synovium. However, synovial tissue has historically been perceived as either difficult to obtain or of little practical value. ...Ultrasound-guided synovial biopsy UGSB is a safe and well-tolerated bedside procedure that is established in Europe and rapidly growing in popularity in the United States. The technique can be mastered by rheumatologists who are already experienced in ultrasound-guided procedures such as joint aspirations. The USGB procedure allows the proceduralist to access small, medium, and large joints and is inexpensive and less invasive compared to surgical alternatives. The relative ease of obtaining this tissue, along with recent research suggesting that synovium may have more clinical and investigational utility than previously thought, has led clinicians and researchers to a new appreciation of the role of synovial biopsy in both the clinical and research setting. In this manuscript, the authors present recommendations on best practices for ultrasound-guided synovial biopsy in the United States, based on our initial training with well-established experts overseas and our own subsequent collective experience in performing numerous synovial biopsies in the United States over the past 7 years for both clinical and research indications. We envision a future where UGSB is more frequently incorporated in the standard diagnostic workup of arthritis and drives novel research initiatives.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Thrombotic microangiopathy (TMA) is a life-threatening, albeit infrequent, complication of systemic lupus erythematosus (SLE) and anti-phospholipid syndrome (APS). Recommendations for the treatment ...of SLE- and APS-related secondary TMA are currently based solely on case reports and expert opinion. Unfortunately, interventions may not yield timely results or effectively halt the progression of TMA. Since complement activation plays a key role in the pathogenesis of secondary TMA due to SLE, APS, a therapy that targets the complement pathway is an attractive intervention. Eculizumab, a recombinant, fully humanized IgG2/IgG4 monoclonal antibody inhibits C5 activation and is FDA-approved for PNH and atypical HUS (aHUS). However, limited case reports are available on its use in treatment of secondary TMA.
We present the largest case series to date that includes 9 patients with SLE and/or APS who were successfully treated with eculizumab for refractory secondary TMA. In this case series, we report significant responses in hematology values, renal function and other organs following treatment with eculizumab. At 4 weeks, 75% improvement in platelet counts was observed in 78% of patients. Two-thirds of patients demonstrated >75% improvement of haptoglobin and LDH at four weeks. At 4 weeks, eGFR improved by 25% in half of the patients, and 43% had reductions in proteinuria. Two of 3 patients that required hemodialysis were able to be taken off hemodialysis.
Based on these observations, we suggest that eculizumab may be a potential treatment option for acutely ill patients with secondary TMA due to SLE and/or APS who have failed standard of care. A collective approach is needed to better elucidate the role and optimal timing of eculizumab use in the management of TMA complicating SLE and/or APS.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Giant Cell Arteritis (GCA) is a large vessel vasculitis that most commonly presents with headache, scalp tenderness, jaw claudication, and vision changes. Various other, less common, manifestations ...have been reported in the literature such as scalp and tongue necrosis. Though most patients respond to corticosteroids, some cases of GCA are refractory to the high doses of corticosteroids.
We present a 73-year-old female with GCA refractory to corticosteroids presenting with tongue necrosis. This patient significantly improved with a dose of tocilizumab, an IL-6 inhibitor.
To the best of our knowledge, this is the first case report of a patient with refractory GCA presenting with tongue necrosis that had rapid improvement with tocilizumab. Prompt diagnosis and treatment can prevent severe outcomes such as tongue amputation in GCA patients with tongue necrosis, and tocilizumab may be effective for corticosteroid-refractory cases.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
ObjectivesIn lupus nephritis the pathological diagnosis from tissue retrieved during kidney biopsy drives treatment and management. Despite recent approval of new drugs, complete remission rates ...remain well under aspirational levels, necessitating identification of new therapeutic targets by greater dissection of the pathways to tissue inflammation and injury. This study assessed the safety of kidney biopsies in patients with SLE enrolled in the Accelerating Medicines Partnership, a consortium formed to molecularly deconstruct nephritis.Methods475 patients with SLE across 15 clinical sites in the USA consented to obtain tissue for research purposes during a clinically indicated kidney biopsy. Adverse events (AEs) were documented for 30 days following the procedure and were determined to be related or unrelated by all site investigators. Serious AEs were defined according to the National Institutes of Health reporting guidelines.Results34 patients (7.2%) experienced a procedure-related AE: 30 with haematoma, 2 with jets, 1 with pain and 1 with an arteriovenous fistula. Eighteen (3.8%) experienced a serious AE requiring hospitalisation; four patients (0.8%) required a blood transfusion related to the kidney biopsy. At one site where the number of cores retrieved during the biopsy was recorded, the mean was 3.4 for those who experienced a related AE (n=9) and 3.07 for those who did not experience any AE (n=140). All related AEs resolved.ConclusionsProcurement of research tissue should be considered feasible, accompanied by a complication risk likely no greater than that incurred for standard clinical purposes. In the quest for targeted treatments personalised based on molecular findings, enhanced diagnostics beyond histology will likely be required.
Background: Lupus nephritis, one of the most severe and therapeutically challenging manifestations of systemic lupus erythematosus (SLE), has been the target of drug development by La Jolla ...Pharmaceutical Company. Abetimus sodium, an example of the La Jolla Pharmaceutical Company's Tolerance Technology
®
is an intravenously administered tetrameric oligonucleotide conjugate that safely reduces antidouble-stranded DNA (anti-dsDNA) antibodies. Given the importance of anti-dsDNA antibodies in the pathogenesis of lupus nephritis, the Phase II and III trials were designed to evaluate whether treatment with abetimus sodium could prolong the time to renal flare in cohorts of patients at high risk of nephritic flares. Objective and methods: The available data regarding abetimus were reviewed and the current status of the drug's development program is reported. Conclusions: Animal studies have demonstrated the ability of abetimus to reduce the titers of anti-dsDNA antibodies as well as of antidsDNA antibody-secreting cells. Administration of abetimus to patients with SLE has uniformly been associated with reductions in circulating anti-dsDNA antibodies. However, two pivotal trials with large numbers of lupus nephritis patients failed to demonstrate statistically signi ficant prolongations in time to renal flare. An event-driven randomized placebo-controlled trial was abruptly terminated in February 2009 after an interim data safety monitoring board determined that achievement of a successful study outcome was futile.
Purpose of Review
In the clinical evaluation of inflammatory arthritis and the research into its pathogenesis, there is a growing role for the direct analysis of synovial tissue. Over the years, ...various biopsy techniques have been used to obtain human synovial tissue samples, and there have been progressive improvements in the safety, tolerability, and utility of the procedure.
Recent Findings
The latest advancement in synovial tissue biopsy techniques is the use of ultrasound imaging to guide the biopsy device, along with evolution in the characteristics of the device itself. While ultrasound guided synovial biopsy (UGSB) has taken a strong foothold in Europe, the procedure is still relatively new to the United States of America (USA).
Summary
In this paper, we describe the expansion of UGSB in the USA, elucidate the challenges faced by rheumatologists developing UGSB programs in the USA, and describe several strategies for overcoming these challenges.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Rheumatoid arthritis is a prototypical autoimmune disease that causes joint inflammation and destruction
. There is currently no cure for rheumatoid arthritis, and the effectiveness of treatments ...varies across patients, suggesting an undefined pathogenic diversity
. Here, to deconstruct the cell states and pathways that characterize this pathogenic heterogeneity, we profiled the full spectrum of cells in inflamed synovium from patients with rheumatoid arthritis. We used multi-modal single-cell RNA-sequencing and surface protein data coupled with histology of synovial tissue from 79 donors to build single-cell atlas of rheumatoid arthritis synovial tissue that includes more than 314,000 cells. We stratified tissues into six groups, referred to as cell-type abundance phenotypes (CTAPs), each characterized by selectively enriched cell states. These CTAPs demonstrate the diversity of synovial inflammation in rheumatoid arthritis, ranging from samples enriched for T and B cells to those largely lacking lymphocytes. Disease-relevant cell states, cytokines, risk genes, histology and serology metrics are associated with particular CTAPs. CTAPs are dynamic and can predict treatment response, highlighting the clinical utility of classifying rheumatoid arthritis synovial phenotypes. This comprehensive atlas and molecular, tissue-based stratification of rheumatoid arthritis synovial tissue reveal new insights into rheumatoid arthritis pathology and heterogeneity that could inform novel targeted treatments.
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GEOZS, IJS, IMTLJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK, ZAGLJ
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