Virtual rheumatology: using simulators and a formal workshop to teach medical students, internal medicine residents, and rheumatology subspecialty residents arthrocentesis.

BACKGROUND: Arthrocentesis is an important skill for medical practitioners at all levels of training. Previous studies have indicated a low comfort level and performance of arthrocentesis among primary care physicians that could be improved with hands-on training. OBJECTIVES: The objective of this study was to improve comfort with knee and shoulder arthrocentesis at all levels of medical training, including medical students, internal medicine residents, and rheumatology subspecialty residents, and in arthrocentesis of the elbow, wrist, and ankle for advanced subspecialty residents in rheumatology through the use of a formal workshop using simulators. METHODS: Fourth-year medical students and internal medicine residents were recruited from the University of South Florida. The rheumatology advanced subspecialty residents were participants from University of South Florida and from the American College of Rheumatology national meetings in 2008 and 2009. A 1-hour PowerPoint lecture followed by a hands-on practice session using Sawbones models (shoulder and knee for all groups, and elbow, wrist, and ankle additionally for the advanced subspecialty residents). A preworkshop self-assessment survey allowed the participant to rate his/her comfort level with arthrocentesis on a scale of 1 to 5. A survey with identical questions was completed immediately after the workshop. A follow-up survey was distributed by e-mail 3 to 6 months after the workshop. RESULTS: One hundred forty-one medical students, 75 internal medicine residents, and 39 rheumatology subspecialty residents participated from January 2008 until January 2010. Mean comfort level in knee and shoulder arthrocentesis improved from preworkshop comfort level for all joints and among all participants. In addition, rheumatology subspecialty resident mean comfort level improved for ankle from 2.37 to 3.65, elbow from 2.56 to 3.80, and wrist from 2.31 to 3.77 (P < 0.0001). CONCLUSIONS: Our study involved a very large number of participants encompassing different levels of training and is the largest number of advanced subspecialty rheumatology residents studied with regard to joint injection training. We have confirmed that a formal joint injection workshop using simulators is an effective method of improving comfort level in arthrocentesis among participants from all levels of medical training. Future studies should evaluate the effect of such training on actual clinical use and competence.

The evolving story of Chlamydia-induced reactive arthritis.

PURPOSE OF REVIEW: There have been tremendous recent insights into our understanding of the epidemiology, pathophysiology, and treatment of Chlamydia-induced reactive arthritis (CiReA). Some of these advances embellish our previous understanding of CiReA, whereas others suggest that a change in the paradigm is required. RECENT FINDINGS: Epidemiological data suggest that we are underdiagnosing CiReA and emerging data suggest that asymptomatic chlamydial infections might be a common cause. Although the clinical manifestations of CiReA are indistinct from the postenteric variety, there appear to be important differences in the pathophysiology of these clinically congruent entities. The hallmark difference pertains to synovial-based viable chlamydial organisms, although in an aberrant state, known as chlamydial persistence. Specific chlamydial serovars appear to be causative of CiReA. Emerging potential therapies include antitumor necrosis factor treatment and combination antibiotics. However, the data with the former are particularly scant and there are theoretical concerns with their use in this setting. Recent data regarding prolonged combination antibiotics are particularly encouraging. SUMMARY: A history of a chlamydial infection may prove to be a poor guide for the diagnosis of CiReA and prolonged combined antimicrobial therapy could be an effective treatment strategy.

The pathogenic role of Chlamydia in spondyloarthritis.

PURPOSE OF REVIEW: Topics relating to the spondyloarthropathies have been reviewed recently, but the detailed roles of Chlamydia trachomatis and C. pneumoniae in induction of spondyloarthritis have not been discussed. This review focuses on new information regarding how these pathogens elicit joint disease, with emphasis on C. trachomatis in its role in Chlamydia-induced reactive arthritis. RECENT FINDINGS: Molecular methods continue to provide insights into the molecular genetic and cell biologic basis for chlamydial pathogenesis. For chlamydiae, residence in the synovium in patients with acute or chronic Chlamydia-induced arthritis involves organisms in an unusual infection state designated persistence. The profiles of overall metabolism and gene expression characteristic of chlamydial persistence have been assessed and unusual aspects noted, including transcriptional attenuation of one hsp60 paralog and upregulation of expression for another. Strain determinations have demonstrated that genital serotypes of C. trachomatis are not present in the joint; rather, inflammation at that site is elicited by ocular serotypes of the organism. This indicates that much remains to be learned concerning the biology of chlamydial dissemination from the urogenital tract. Analyses of undifferentiated spondyloarthritis continue to suggest that chlamydiae, and perhaps other pathogens function in the etiology of the disease. Progress has been made in developing effective treatment for patients with Chlamydia-induced arthritis. SUMMARY: Molecular genetic analyses regarding the role of chlamydiae in induction of inflammatory arthritis have increased our detailed understanding of the pathogenic mechanisms utilized by these organisms in the joint. Importantly, progress has been made in developing effective therapies for treatment of Chlamydia-induced arthritis.

Patients with Chlamydia-associated arthritis have ocular (trachoma), not genital, serovars of C. trachomatis in synovial tissue.

Some individuals with a genital Chlamydia trachomatis infection develop inflammatory arthritis, but it is unknown whether particular chlamydial serovar(s) engender the disease more often than others. We defined serovar in synovial tissues from arthritis patients infected with this organism. DNA from synovial biopsies of 36 patients with PCR-confirmed synovial C. trachomatis was analyzed. Diagnoses included reactive arthritis, undifferentiated oligoarthritis, rheumatoid arthritis, and osteoarthritis. The chlamydial omp1 and trpA genes were amplified, cloned, and 10 or more clones from each sample were sequenced. The cytotoxin locus also was analyzed. omp1 sequences showed 2 patients having only C. trachomatis A serovar, 1 with only B, and 33 having only C, all ocular serovars. Analyses of trpA and the cytotoxin locus uniformly displayed standard ocular serovar characteristics for each patient. Identification of ocular chlamydial serovars in the synovia of arthritis patients is unexpected. These observations suggest that urogenital chlamydial infections, while consisting primarily of organisms of genital serovars, include some of ocular serovar(s). They further suggest that during such infections unknown selection pressures favor establishment of the latter in the synovium to the exclusion of genital serovar chlamydiae.

Atypical insufficiency fracture of the tibia associated with long-term bisphosphonate therapy.

Osteoporosis is a major public health threat affecting millions of individuals in the United States. Bisphosphonate therapy is currently recognized as a first-line treatment of osteoporosis through the inhibition of osteoclast activity. Concerns have been raised about potential oversuppression of bone turnover and the development of atypical skeletal fragility associated with long-term use of bisphosphonates. A number of case reports in the literature have documented atypical insufficiency fractures in patients on long-term bisphosphonate therapy. This case outlines what we believe is the second documented atypical tibial insufficiency fracture in a patient on long-term bisphosphonate therapy, and highlights the need for increased awareness of atypical insufficiency fractures as well as the need for more data concerning the long-term effects of bisphosphonate therapy.

An analysis of MRI and ultrasound imaging in patients with gout who have normal plain radiographs.

OBJECTIVE: The aim of this study was to analyse the prevalence of occult destructive arthropathy in subjects with gout and normal plain radiographs by utilizing MRI and ultrasound (US). METHODS: The study consisted of two visits. At Visit 1, a plain radiograph of the 'index joint' was obtained. The 'index joint' was defined as a joint that has had the most acute attacks of gout historically. The index joint plain radiograph had to be free of erosive damage in order for the subject to qualify for Visit 2. At Visit 2, the subject had an MRI with contrast and an US of the index joint. Each subject also had an MRI and US of an 'asymptomatic joint'. The 'asymptomatic joint' was defined as a joint that had never experienced an acute attack of gout (determined by standard protocol). The primary endpoint was erosive changes on the MRI and/or US of the index joint. Secondary endpoints included erosive changes on the asymptomatic joint as well as bone marrow oedema (BME) (on MRI), synovial pannus (SP), soft tissue tophi (STT) or oedema (STE) on either the index or asymptomatic joint. RESULTS: Twenty-seven subjects (26 males; 1 female) completed both visits. Their average age and disease duration were 55.1 years (range 21-75 years) and 6.8 years (range 0.25-25 years), respectively. The subjects' average serum uric acid level over the past 5 years was 8.09 mg/dl (range 4.1-12.8 mg/dl); their average on the day of Visit 1 was 7.96 mg/dl (range 4.6-13.9 mg/dl). The first MTP was the most common index joint (17) followed by the ankle (5), mid-tarsal (2), knee (2) and wrist (1). The knee was the most common asymptomatic joint (21) followed by the wrist (3), MTP (2) and ankle (1). All subjects had both MRIs; one subject refused the US. Out of 27 subjects, 15 (56%) had erosions on MRI of their index joint (P < 0.0001); only 1 subject (4%) had erosions identified in the index joint by US (P = NS). Regarding the secondary endpoints on the index joint, the MRI detected SP (13), BME (4), STE (3) and STT (0); the US detected SP (1), STT (1) and STE (0). Regarding the MRI of the asymptomatic joint, positive findings included SP (3), BME (3), STE (2) and erosions (1). There were no positive findings by US in the asymptomatic joint. CONCLUSIONS: A large percentage of patients with gout and normal plain radiographs have occult destructive arthropathy that is only detected by advanced imaging such as MRI and/or US. However, MRI appears to be much more sensitive than US at detecting these findings.

Successful treatment of pemphigus vulgaris with etanercept in four patients.

Pemphigus vulgaris is an autoimmune disease characterized by intraepidermal blister formation. The treatment of pemphigus vulgaris is generally regarded as difficult. Corticosteroids, the drug class of first choice, often must be combined with steroid-sparing agents to prevent hazardous, long-term side effects. The authors describe four patients with severe pemphigus vulgaris who were treated with the tumor necrosis factor (TNF)-alpha antagonist, etanercept, twice weekly. In all four cases, the addition of etanercept produced dramatic clinical improvement and facilitated the reduction of corticosteroids necessary to maintain symptom control. Thus, etanercept may be an effective therapeutic agent for pemphigus vulgaris and should be considered as an alternative treatment option for patients presenting with recalcitrant disease.

Oxidative reactivity difference among the metal oxo and metal hydroxo moieties: pH dependent hydrogen abstraction by a manganese(IV) complex having two hydroxide ligands.

Clarifying the difference in redox reactivity between the metal oxo and metal hydroxo moieties for the same redox active metal ion in identical structures and oxidation states, that is, M(n+)O and M(n+)-OH, contributes to the understanding of nature's choice between them (M(n+)O or M(n+)-OH) as key active intermediates in redox enzymes and electron transfer enzymes, and provides a basis for the design of synthetic oxidation catalysts. The newly synthesized manganese(IV) complex having two hydroxide ligands, [Mn(Me(2)EBC)(2)(OH)(2)](PF(6))(2), serves as the prototypic example to address this issue, by investigating the difference in the hydrogen abstracting abilities of the Mn(IV)O and Mn(IV)-OH functional groups. Independent thermodynamic evaluations of the O-H bond dissociation energies (BDE(OH)) for the corresponding reduction products, Mn(III)-OH and Mn(III)-OH(2), reveal very similar oxidizing power for Mn(IV)O and Mn(IV)-OH (83 vs 84.3 kcal/mol). Experimental tests showed that hydrogen abstraction proceeds at reasonable rates for substrates having BDE(CH) values less than 82 kcal/mol. That is, no detectable reaction occurred with diphenyl methane (BDE(CH) = 82 kcal/mol) for both manganese(IV) species. However, kinetic measurements for hydrogen abstraction showed that at pH 13.4, the dominant species Mn(Me(2)EBC)(2)(O)(2), having only Mn(IV)O groups, reacts more than 40 times faster than the Mn(IV)-OH unit in Mn(Me(2)EBC)(2)(OH)(2)(2+), the dominant reactant at pH 4.0. The activation parameters for hydrogen abstraction from 9,10-dihydroanthracene were determined for both manganese(IV) moieties: over the temperature range 288-318 K for Mn(IV)(OH)(2)(2+), DeltaH(double dagger) = 13.1 +/- 0.7 kcal/mol, and DeltaS(double dagger) = -35.0 +/- 2.2 cal K(-1) mol(-1); and the temperature range 288-308 K for for Mn(IV)(O)(2), DeltaH(double dagger) = 12.1 +/- 1.8 kcal/mol, and DeltaS(double dagger) = -30.3 +/- 5.9 cal K(-1) mol(-1).

The recognition and treatment of vertebral fractures in males with chronic obstructive pulmonary disease.

OBJECTIVE: Males with chronic obstructive pulmonary disease (COPD) are at increased risk for developing osteoporosis (OP) with subsequent vertebral compression fractures. Such fractures with resultant increased thoracic kyphotic angle (TKA) may interfere with these patients' already compromised pulmonary function. A retrospective cross-sectional study was performed to evaluate the recognition and treatment of vertebral fractures in male patients with COPD. METHODS: The study population included male patients with COPD aged 55 years and older who had a lateral chest X-ray (index film) performed between January 1, 2001 and July 5, 2005. Vertebral fractures and the TKA were determined independently by two different radiologists. One radiologist (reviewer #1) used direct measurement including quantitative morphometric analysis to determine fractures and the TKA, whereas the second radiologist (reviewer #2) used visual inspection only. Inter-reader agreement for vertebral fractures and TKA was assessed. The computerized charts were reviewed to determine the initial recognition of vertebral fractures and the subsequent therapy. Logistic regression was employed to determine significant risk factors for vertebral fractures in this male population. RESULTS: Three hundred and fifty male study subjects and their index lateral chest X-rays were reviewed. Ages ranged from 52 to 90 and 9/350 (2.6%) of the study subjects had vertebral fractures identified on the initial radiology report. None of these nine patients were subsequently treated with anti-osteoporotic agents other than calcium and vitamin D, and two of them had a follow-up central bone density. Reviewer #1 measured 361 fractures in 181 subjects and determined the mean TKA to be 31.43 (+/-8.62) degrees. Reviewer #2 identified 27 fractures in 19 subjects and with an estimated mean TKA of 24.84 (+/-8.53) degrees. There was little inter-observer agreement with vertebral fractures (kappa=0.07), but there was a strong positive correlation with the TKA (r=0.79). There was a weak to moderate correlation with the TKA and the presence of vertebral fractures (r=0.26). Significant risk factors for vertebral fractures included smoking status (odds ratio 1.84 [1.08-3.15]) and age (odds ratio 1.06 [1.03-1.09] for each year increase in age). CONCLUSION: A large number of vertebral fractures in males with COPD goes undiagnosed. In those patients with diagnosed vertebral fractures, follow-up therapy is under-utilized. When analyzing lateral chest X-rays for vertebral fractures, visual inspection alone without direct measurement may not be an adequate technique for identifying fractures.

Recent advances and future directions in understanding and treating Chlamydia-induced reactive arthritis.

INTRODUCTION: Reactive arthritis (ReA) is an inflammatory disease that can follow gastrointestinal or genitourinary infections. The primary etiologic agent for post-venereal ReA is the bacterium Chlamydia trachomatis; its relative, C pneumoniae, has also been implicated in disease induction although to a lesser degree. Studies have indicated that the arthritis is elicited by chlamydiae infecting synovial tissue in an unusual biologic state designated persistence. We review clinical aspects, host-pathogen interactions, and treatments for the disease. Areas covered: We briefly discuss both the historic and,more extensively, the current medical literature describing ReA, and we provide a discussion of the biology of the chlamydiae as it relates to elicitation of the disease. A summary of clinical aspects of Chlamydia-induced ReA is included to give context for approaches to treatment of the arthritis. Expert commentary: Basic research into the biology and host-pathogen interactions characteristic of C trachomatis has provided a wealth of information that underlies our current understanding of the pathogenic processes occurring in the ReA synovium. Importantly, a promising approach to cure of the disease is at hand. However, both basic and clinical research into Chlamydia-induced ReA has lagged over the last 5 years, including required studies relating to cure of the disease.

Two cases demonstrating thalidomide's efficacy in refractory lupus nephritis.

Renal involvement in systemic lupus erythematosus (SLE) is common and has been associated with an increased risk of mortality [1]. Early diagnosis is imperative to control proteinuria and prevent the progression to end-stage renal disease. Standard induction therapies include cyclophosphamide (CYC) and mycophenolate mofetil (MMF); however, it has been estimated that approximately 30% of patients are refractory to these standard treatments after 1 year [2]. We present two cases of patients diagnosed with lupus nephritis (LN) who demonstrated persistent proteinuria while on standard treatments that markedly improved after addition of thalidomide (THD). A literature review was performed indicating that THD use with prednisolone (PL) was more efficacious than MMF with PL in resolving lupus nephritis in a mouse model. Thalidomide, which was well tolerated, was associated with a reduction in the protein-to-creatinine ratio with sustained results in both of our patient cases. These cases suggest more clinical data is needed to explore the potential utility of thalidomide in the treatment of LN.

Reactive arthritis: defined etiologies, emerging pathophysiology, and unresolved treatment.

ReA is unique in that it is one of the few disease states of which there is a known trigger. This insight into disease initiation has led to great advances in the pathophysiology. Despite this detailed knowledge, the proper treatment remains elusive. In the years to come it is possible that the specific treatment will be dictated by the triggering microbe.

An MRI assessment of chronic synovial-based inflammation in gout and its correlation with serum urate levels.

It is unclear when the synovial-based inflammatory process of gout begins. The aim of this study was to determine the percentage of patients with inter-critical gout who have chronic synovial-based inflammation as evidenced by synovial pannus on a contrast-enhanced magnetic resonance imaging (MRI) of their most involved joint and determine if the presence and/or severity correlates with their serum urate levels. All patients received a 3 T MRI of their index joint, serum urate level, CRP, and creatinine. The primary endpoint was to determine the prevalence of synovial pannus and the correlation of serum urate levels with the presence and/or severity of the synovial pannus on that same joint. MRI erosions, tophi, swelling, effusion, and osteitis were also documented. Seventy-two of 74 subjects (90% men) completed the protocol. Fifty-three of 72 (74%) index joints were the first metatarsophalangeal joint. Thirty-nine (54.2%) of the patients were on urate-lowering therapy; 15 (20.8%) and 7 (9.7%) were taking colchicine or a NSAID daily, respectively. Of the 72 subjects, 63 (87.5%) had synovial pannus on their MRI with good inter-reader agreement between the two radiologists. The mean serum urate level was 7.93 mg/dL. There was no correlation with the presence (p = 0.33) or severity (p = 0.34) of synovial pannus and serum urate levels. There was also no correlation with the presence or severity of synovial pannus and the secondary endpoints. The majority of patients with inter-critical gout have evidence of chronic synovial-based inflammation. However, the presence and severity of this inflammation do not appear to correlate with serum urate levels.

Inactivation of DAP12 in PMN inhibits TREM1-mediated activation in rheumatoid arthritis.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by dysregulated and chronic systemic inflammatory responses that affect the synovium, bone, and cartilage causing damage to extra-articular tissue. Innate immunity is the first line of defense against invading pathogens and assists in the initiation of adaptive immune responses. Polymorphonuclear cells (PMNs), which include neutrophils, are the largest population of white blood cells in peripheral blood and functionally produce their inflammatory effect through phagocytosis, cytokine production and natural killer-like cytotoxic activity. TREM1 (triggering receptor expressed by myeloid cells) is an inflammatory receptor in PMNs that signals through the use of the intracellular activating adaptor DAP12 to induce downstream signaling. After TREM crosslinking, DAP12's tyrosines in its ITAM motif get phosphorylated inducing the recruitment of Syk tyrosine kinases and eventual activation of PI3 kinases and ERK signaling pathways. While both TREM1 and DAP12 have been shown to be important activators of RA pathogenesis, their activity in PMNs or the importance of DAP12 as a possible therapeutic target have not been shown. Here we corroborate, using primary RA specimens, that isolated PMNs have an increased proportion of both TREM1 and DAP12 compared to normal healthy control isolated PMNs both at the protein and gene expression levels. This increased expression is highly functional with increased activation of ERK and MAPKs, secretion of IL-8 and RANTES and cytotoxicity of target cells. Importantly, based on our hypothesis of an imbalance of activating and inhibitory signaling in the pathogenesis of RA we demonstrate that inhibition of the DAP12 signaling pathway inactivates these important inflammatory cells.

Instabilities in the two-dimensional cubic nonlinear Schrödinger equation.

The two-dimensional cubic nonlinear Schrödinger equation (NLS) can be used as a model of phenomena in physical systems ranging from waves on deep water to pulses in optical fibers. In this paper, we establish that every one-dimensional traveling wave solution of NLS with linear phase is unstable with respect to some infinitesimal perturbation with two-dimensional structure. If the coefficients of the linear dispersion terms have the same sign (elliptic case), then the only unstable perturbations have transverse wavelength longer than a well-defined cutoff. If the coefficients of the linear dispersion terms have opposite signs (hyperbolic case), then there is no such cutoff and as the wavelength decreases, the maximum growth rate approaches a well-defined limit.

Chlamydia trachomatis is present and metabolically active during the remitting phase in synovial tissues from patients with chronic Chlamydia-induced reactive arthritis.

BACKGROUND: Patients with chronic Chlamydia-induced reactive arthritis (ReA) often show a remitting-relapsing disease phenotype. Some information regarding bacterial and host responses to one another during active disease is available but no information for quiescence. This article presents the first molecular genetic insight into the behavior of bacterium and host during remitting ReA. METHODS: Synovial biopsies were procured from the knees of 4 patients with quiescent ReA by the Parker-Pearson technique. Nucleic acids prepared from them were analyzed by real-time polymerase chain reaction (PCR) and reverse transcription-PCR, and results were compared with data averaged from the knee synovial tissue samples of 10 patients with active ReA. RESULTS: Real-time PCR indicated that bacterial load in remitting samples was approximately 20% of that in active disease samples. Transcripts from the p60-encoding gene were equal to or higher than those seen in active disease. Messenger RNAs (mRNAs) from the paralog p60-encoding genes were equal to or lower than those of active disease. Host mRNAs encoding interleukin-10, tumor necrosis factor-α and interferon-γ were 4-fold lower than those in active disease samples, whereas monocyte chemotactic protein 1 and regulated upon activation, normal t-cell expressed, and secreted mRNA levels were equal to or higher. CONCLUSIONS: Bacterial load in synovial tissue of patients with remitting disease is lower than that of active disease, but mRNAs encoding proinflammatory proteins are equal to or higher than those of active disease. Transcription in the host is attenuated for cytokines and chemokines. These initial results demonstrate that organism is present and metabolically active in synovium during the remitting phase of chronic Chlamydia-induced ReA and that the genetic events characterizing quiescence are complex.

Attack rate of Chlamydia-induced reactive arthritis and effect of the CCR5-Delta-32 mutation: a prospective analysis.

OBJECTIVE: Factors that predispose patients to Chlamydia-induced reactive arthritis (CiReA) are poorly defined. Data indirectly suggest chemokine receptor-5 (CCR5)-delta-32 mutation might play a role in CiReA. We investigated the attack rate of CiReA and we hypothesized that the CCR5-delta-32 allele may modulate disease susceptibility. METHODS: Patients who tested positive for Chlamydia trachomatis after either (1) symptoms of an acute venereal disease or (2) sexual contact with an individual known to be positive for the same organism were followed in a prospective fashion. All patients were contacted at Week 6 after their acute infection and queried for symptoms of CiReA. Patients who had new-onset symptoms suggestive of CiReA were followed at Weeks 12, 26, and 52. All subjects were tested for CCR5-delta-32 mutation. RESULTS: A total of 365 study participants were enrolled, with average age 24.4 years, 201 men (55%) and 164 women (45%). We followed up with 149 patients (41%) at Week 6. Twelve of 149 participants (8.1%) had symptoms suggestive of CiReA at Week 6. None of these 12 patients was positive for the CCR5-delta-32 mutation. Of the 12 patients that had symptoms at Week 6, we were able to follow up with 7 through Week 52. All 7 had complete resolution of their symptoms by Week 26. Overall, 25/365 (6.8%) subjects were positive for the CCR5-delta-32 mutation. CONCLUSION: The attack rate of CiReA in our study was higher than previously reported, but the CCR5-delta-32 mutation does not seem to play a role in CiReA disease susceptibility.

Rilonacept in the treatment of acute gouty arthritis: a randomized, controlled clinical trial using indomethacin as the active comparator.

INTRODUCTION: In phase-3 clinical trials, the interleukin (IL-1) blocker, rilonacept (IL-1 Trap), demonstrated efficacy for gout flare prevention during initiation of urate-lowering therapy. This trial evaluated rilonacept added to a standard-of-care, indomethacin, for treatment of acute gout flares. METHODS: Adults, aged 18-70 years, with gout presenting within 48 hours of flare onset and having at least moderate pain as well as swelling and tenderness in the index joint were randomized to subcutaneous (SC) rilonacept 320 mg at baseline plus oral indomethacin 50 mg TID for 3 days followed by 25 mg TID for up to 9 days (n = 74); SC placebo at baseline plus oral indomethacin as above (n=76); or SC rilonacept 320 mg at baseline plus oral placebo (n=75). The primary efficacy endpoint was change in pain in the index joint (patient-reported using a Likert scale (0=none; 4=extreme)) from baseline to the average of values at 24, 48 and 72 hours (composite time point) for rilonacept plus indomethacin versus indomethacin alone. Comparison of rilonacept monotherapy with indomethacin monotherapy was dependent on demonstration of significance for the primary endpoint. Safety evaluation included clinical laboratory and adverse event (AE) assessments. RESULTS: Patient characteristics were comparable among the groups; the population was predominantly male (94.1%), white (75.7%), with mean±SD age of 50.3±10.6 years. All treatment groups reported within-group pain reductions from baseline (P<0.0001). Although primary endpoint pain reduction was greater with rilonacept plus indomethacin (-1.55±0.92) relative to indomethacin alone (-1.40±0.96), the difference was not statistically significant (P=0.33), so formal comparison between monotherapy groups was not performed. Pain reduction over the 72-hour period with rilonacept alone (-0.69±0.97) was less than that in the other groups, but pain reduction was similar among groups at 72 hours. Treatment with rilonacept was well-tolerated with no reported serious AEs related to rilonacept. Across all groups, the most frequent AEs were headache and dizziness. CONCLUSIONS: Although generally well-tolerated, rilonacept in combination with indomethacin and rilonacept alone did not provide additional pain relief over 72 hours relative to indomethacin alone in patients with acute gout flare. TRIAL REGISTRATION: ClinicalTrials.gov registration number NCT00855920.

The molecular basis for disease phenotype in chronic Chlamydia-induced arthritis.

Genital Chlamydia trachomatis infections can elicit an inflammatory arthritis in some individuals, and recent surprising studies have demonstrated that only ocular (trachoma) strains, not genital strains, of the organism are present in the synovial tissues of patients with the disease. This observation suggests an explanation for the small proportion of genitally-infected patients who develop Chlamydia-induced arthritis. Other recent studies have begun to identify the specific chlamydial gene products that elicit the synovial inflammatory response during both active and quiescent disease, although much more study will be required to complete the understanding of that complex process of host-pathogen interaction. Several newly developed experimental methods and approaches for study of the process will enable identification of new therapeutic targets, and possibly strategies for prevention of the disease altogether.