Three-month tapering and discontinuation of long- term, low-dose glucocorticoids in senior patients with rheumatoid arthritis is feasible and safe: placebo-controlled double blind tapering after the GLORIA trial.

OBJECTIVE: The randomised placebo-controlled GLORIA (Glucocorticoid LOw-dose in RheumatoId Arthritis) trial evaluated the benefits and harms of prednisolone 5 mg/day added to standard care for 2 years in patients aged 65+ years with rheumatoid arthritis (RA). Here, we studied disease activity, flares and possible adrenal insufficiency after blinded withdrawal of study medication. METHODS: Per protocol, patients successfully completing the 2-year trial period linearly tapered and stopped blinded study medication in 3 months. We compared changes in disease activity after taper between treatment groups (one-sided testing). Secondary outcomes (two-sided tests) comprised disease flares (DAS28 (Disease Activity Score 28 joints) increase >0.6, open-label glucocorticoids or disease-modifying antirheumatic drug (DMARD) increase/switch after week 4 of tapering) and symptoms/signs of adrenal insufficiency. In a subset of patients from 3 Dutch centres, cortisol and ACTH were measured in spot serum samples after tapering. RESULTS: 191 patients were eligible; 36 met treatment-related flare criteria and were only included in the flare analysis. Mean (SD) DAS28 change at follow-up: 0.2 (1.0) in the prednisolone group (n=76) vs 0.0 (1.2) in placebo (n=79). Adjusted for baseline, the between-group difference in DAS28 increase was 0.16 (95% confidence limit -0.06, p=0.12). Flares occurred in 45% of prednisolone patients compared with 33% in placebo, relative risk (RR) 1.37 (95% CI 0.95 to 1.98; p=0.12). We found no evidence for adrenal insufficiency. CONCLUSIONS: Tapering prednisolone moderately increases disease activity to the levels of the placebo group (mean still at low disease activity levels) and numerically increases the risk of flare without evidence for adrenal insufficiency. This suggests that withdrawal of low-dose prednisolone is feasible and safe after 2 years of administration.

Systemic and Local Medical or Surgical Therapies for Ear, Nose and/or Throat Manifestations in ANCA-Associated Vasculitis: A Systematic Literature Review.

BACKGROUND: Ear, nose and throat (ENT) manifestations are common in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), yet how to treat these manifestations remains controversial. Therefore, we systematically reviewed the literature on the efficacy of therapies on ENT manifestations in AAV. METHODS: A systematic review was conducted in accordance with the PRISMA guidelines, searching Medline, Embase and Cochrane libraries, including clinical studies between January 2005 and January 2022, in adults with AAV and ENT involvement, reporting on the effects of local and systemic therapy. The critical appraisal was performed using tools provided by the Cochrane Library and the level of evidence (LoE) was scored according to the Oxford Centre for Evidence-based Medicine. RESULTS: After screening 5609 identified studies, 136 full-text articles were assessed. Finally, 31 articles were included for critical appraisal and data-extraction. Nearly all studies (n = 29) were retrospective and scored low on LoE. The included studies evaluated local interventions (n = 11), glucocorticoids combined with conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs) (n = 8), rituximab (n = 6), or mepolizumab (n = 6). Due to heterogeneity across studies meta-analysis was not performed. Four studies on mepolizumab for sinonasal symptoms (n = 92) showed response in 33-100% and relapse in 35%. Local therapy for subglottic stenosis was effective in 80-100% of patients in 11 studies (n = 157), but relapses were common (up to 83%). In five studies, hearing improvement was observed in 56-100%, with better outcomes when glucocorticoids were combined with csDMARDs compared to glucocorticoids only. CONCLUSION: Response rates of ENT manifestations varied widely in studies and relapses were observed frequently. Heterogeneity among studies impaired comparison.

The effect of nasal Staphylococcus aureus colonization and antibiotic treatment on disease activity in ANCA-associated vasculitis: a retrospective cohort study in the Netherlands.

The aim of this study was to identify the role of nasal Staphylococcus aureus (S. aureus) colonization and the effect of systemic or local antibiotic treatment on disease activity in patients with antineutrophil cytoplasmic antibodies (ANCA) associated vasculitis and ear nose and throat (ENT) involvement. Clinical, laboratory and histological data from all patients with ANCA-associated vasculitis and ENT involvement, who were diagnosed in two medical centres in The Netherlands between 1981 and 2020, were retrospectively collected. Nasal S. aureus colonization was defined as at least one positive nasal swab during follow-up. Data on systemic (cotrimoxazole and azithromycin) and local (mupirocin) antibiotic use were collected. Disease activity was divided into systemic and local disease activity. Univariate analyses and regression analyses (negative binomial Poisson and binary regression) were used. Two-hundred and thirteen patients were available for analysis. Median follow-up time was 8 (IQR 3-17) years. S. aureus colonization was tested in 100 (46.9%) cases of whom 44 patients (44%) tested positive. In these 100 patients, systemic and local disease activity at baseline and at last visit were comparable between patients with and without S. aureus colonization. Twenty-eight of the 44 S. aureus positive patients received antibiotics aimed at eradication of S. aureus. No statistically significant difference was found between the treated versus non-treated group with regard to systemic and local disease activity. Nasal S. aureus colonization does not influence systemic or local disease activity. Antibiotic treatment aimed at eradication did not modify disease activity.

Immunosuppressive Therapies in Ear, Nose, and Throat Involvement in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: Results From a Multicenter Retrospective Cohort Study.

OBJECTIVE: The aim of this study was to evaluate the response of ear, nose, and throat (ENT) symptoms to different immunosuppressive therapies in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV). METHODS: In this cohort study, patients with AAV treated between January 2010 and April 2020 at 2 Dutch hospitals were included. Clinical, histological, and laboratory data were collected retrospectively. ENT involvement was defined as follows: (1) ≥ 1 ENT symptom according to the Birmingham Vasculitis Activity Score (version 3; BVAS3), and/or (2) presence of saddle nose deformity. Associations between therapy and ENT activity were assessed using logistic regression analysis. RESULTS: A total of 320 patients with AAV were included, of whom 209 (65.3%) had ENT involvement at some point throughout the disease course. In these 209 patients, median age at disease onset was 52.0 years (IQR 40.0-62.0) and 45.5% were male. Median BVAS3 was 12.0 (IQR 6.0-18.0) at diagnosis. Despite immunosuppressive therapy, 50% (n = 77) of the patients had ENT symptoms at relapse and 29.1% (n = 59) had ENT activity at their last visit. No statistically significant difference in ENT activity at last visit was observed between patients treated with oral or intravenous cyclophosphamide (CYC, n = 137) compared to rituximab (RTX, n = 55; adjusted odds ratio 0.59, 95% CI 0.33-1.06; P = 0.08). Lower age at disease onset and female sex were independently associated with ENT activity at last follow-up. CONCLUSION: In this cohort, CYC and RTX therapy had similar therapeutic effects on ENT symptoms in AAV. Persistent ENT activity is a common feature despite immunosuppressive therapy.

Low dose, add-on prednisolone in patients with rheumatoid arthritis aged 65+: the pragmatic randomised, double-blind placebo-controlled GLORIA trial.

BACKGROUND: Low-dose glucocorticoid (GC) therapy is widely used in rheumatoid arthritis (RA) but the balance of benefit and harm is still unclear. METHODS: The GLORIA (Glucocorticoid LOw-dose in RheumatoId Arthritis) pragmatic double-blind randomised trial compared 2 years of prednisolone, 5 mg/day, to placebo in patients aged 65+ with active RA. We allowed all cotreatments except long-term open label GC and minimised exclusion criteria, tailored to seniors. Benefit outcomes included disease activity (disease activity score; DAS28, coprimary) and joint damage (Sharp/van der Heijde, secondary). The other coprimary outcome was harm, expressed as the proportion of patients with ≥1 adverse event (AE) of special interest. Such events comprised serious events, GC-specific events and those causing study discontinuation. Longitudinal models analysed the data, with one-sided testing and 95% confidence limits (95% CL). RESULTS: We randomised 451 patients with established RA and mean 2.1 comorbidities, age 72, disease duration 11 years and DAS28 4.5. 79% were on disease-modifying treatment, including 14% on biologics. 63% prednisolone versus 61% placebo patients completed the trial. Discontinuations were for AE (both, 14%), active disease (3 vs 4%) and for other (including covid pandemic-related disease) reasons (19 vs 21%); mean time in study was 19 months. Disease activity was 0.37 points lower on prednisolone (95% CL 0.23, p<0.0001); joint damage progression was 1.7 points lower (95% CL 0.7, p=0.003). 60% versus 49% of patients experienced the harm outcome, adjusted relative risk 1.24 (95% CL 1.04, p=0.02), with the largest contrast in (mostly non-severe) infections. Other GC-specific events were rare. CONCLUSION: Add-on low-dose prednisolone has beneficial long-term effects in senior patients with established RA, with a trade-off of 24% increase in patients with mostly non-severe AE; this suggests a favourable balance of benefit and harm. TRIAL REGISTRATION NUMBER: NCT02585258.

Meanderella rijsii, a new opportunist in the fungal order Pleosporales.

Subcutaneous phaeohyphomycosis is an implantation disease caused by melanized fungi and affect both immunocompetent as well as immunocompromised individuals. Diagnosis and treatment require proper isolation and accurate identification of the causative pathogen. We isolated a novel fungus from a case of subcutaneous phaeohyphomycosis in an immunocompetent patient. The 56-year-old patient suffered from a slowly progressive swelling on the metatarsophalangeal join of the left food. The isolated fungus lacked sporulation and sequences of the ribosomal operon did not match with any known species. In a multi-locus phylogenetic analysis involving five markers, the fungus formed a unique lineage in the order Pleosporales, family Trematosphaeriaceae. A new genus, Meanderella and a new species, Meanderella rijsii are here proposed to accommodate the clinical isolate. Whole genome analysis of M. rijsii revealed a number of genes that can be linked to pathogenicity and virulence. Further studies are however needed to understand the role of each gene in the pathogenic process and to determine the origin of pathogenicity in the family of Trematosphaeriaceae.

Medication adherence in older people with rheumatoid arthritis is lower according to electronic monitoring than according to pill count.

OBJECTIVES: Suboptimal medication adherence is a serious problem in the treatment of chronic inflammatory diseases. To measure medication adherence, electronic monitoring is regarded as superior to pill count. GLORIA is an ongoing two-year trial on the addition of low-dose (5 mg/d) prednisolone or placebo to standard care in older people (65+ years) with RA. During the entire trial, adherence is measured with electronic caps, and with pill counts. The objective is to describe medication adherence patterns, and to compare the adherence results of the two methods. METHODS: The recorded adherence patterns of patients (blinded for treatment group) were classified according to descriptive categories. The cutoff for good adherence was set at 80% of prescribed pills taken. RESULTS: Trial inclusion closed in 2018 at 451 patients, but trial follow-up is ongoing; the current dataset contains adherence data of 371 patients. Mean number of recorded 90-day periods per patient was 4 (range 1-8). Based on pill count over all periods, 90% of the patients had good adherence; based on cap data, only 20%. Cap data classified 30% of patients as non-user (<20% of days an opening) and 40% as irregular user (different adherence patterns, in or between periods). CONCLUSION: In our trial of older people with RA, the majority appeared to be adherent to medication according to pill count. Results from caps conflicted with those of pill counts, with patterns suggesting patients did not use the bottle for daily dispensing, despite specific advice to do so. TRIAL REGISTRATION: NCT02585258. ClinicalTrials.gov (https://www.clinicaltrials.gov/).

Cardiovascular risk in patients with new gout diagnosis: is monosodium urate volume at ankles and feet on dual-energy computed tomography associated with previous cardiovascular events?

OBJECTIVES: Chronic inflammation associated with hyperuricaemia and urate deposition may contribute to an increased risk of developing cardiovascular (CV) events (CVE) in patients with gout. The aim of this study was to explore whether urate deposition on dual-energy CT (DECT) present at the diagnosis of gout is associated with a history of CVE. METHODS: Patients from a study on clinical value of DECT with mono or oligoarthritis who had gout according the 2015 EULAR/ACR classification criteria were included in this cross-sectional study. Urate volume on DECT was calculated. Patients underwent a structured CV consultation, including assessment of CVE-history and of CV risk factors, scored with the Dutch risk prediction SCORE and the Framingham score. The data were analysed using logistic regression analyses. RESULTS: Sixty-eight patients were included. In the multivariable model, -next to significant associations of age (OR per year 1.1, 95% CI 1.04 to 1.02, p=0.02), HDLc per mmol/l (OR 0.04, 95% CI 0.002 to 0.8, p=0.03), and diabetes yes/no (OR 4, 95% CI 0.8 to 20.9, p=0.09)-, urate volumes at ankles/feet on DECT in the third and fourth quartile with first quartile as reference showed a trend of association (OR 4.8, 95% CI 0.6 to 42, p=0.1 and 6.4, 0.7 to 63, 0.1, respectively) with past CVE events (yes/ no). This association could be bidirectional. Almost two-third of newly classified gout patients had a high or very high CV risk. CONCLUSIONS: CVE history probably is associated with urate volumes already present at the time of diagnosis of gout. Our data corroborate the need of assessing and treating CV risk factors when diagnosing gout.

Palmar Fasciitis and Polyarthritis Syndrome: A Rare Paraneoplastic Syndrome in a Patient With Prostate Carcinoma.

A 73-year-old patient was seen in our hospital for treatment of metastatic adenocarcinoma of the prostate (pT1aN0M1a R0, BRCA-2 gene mutation). Prostatectomy and regional radiotherapy were performed and goserelin, a luteinizing hormone-releasing hormone (LHRH) analog, had been started because of disease progression. Castration-resistant progressive disease developed, and enzalutamide was added. A decrease of the prostate-specific antigen (PSA) level was achieved. Before the start of enzalutamide, the patient developed bilateral pain and stiffness of both hands combined with thickening of the hands. The symptoms progressed rapidly to bilateral flexion and extension contractures. The patient became unable to tie his shoelaces and had to use adjusted cutlery to eat. Consultation of the rheumatologist, X-rays, ultrasound and palmar skin biopsy of the hands were performed. The clinical picture resembles descriptions of "palmar fasciitis and polyarthritis syndrome" (PFPAS), a rare paraneoplastic syndrome. Positive effects of immunosuppressive medication have been reported in some cases. In our patient, treatment with oral prednisone (30 mg daily) showed no effect, therefore treatment was switched to methylprednisone pulses and methotrexate. PFPAS is an uncommon paraneoplastic syndrome characterized by rapid onset of bilateral arthritis of the hands, fasciitis of the palms, progressive stiffness and contractures. The scarcity of knowledge about PFPAS makes it difficult to recognize it at an early stage. As a paraneoplastic syndrome, it has been linked to various malignancies. Thus far, PFPAS has been described in only two other cases of prostate cancer.

The performance of dual-energy CT in the classification criteria of gout: a prospective study in subjects with unclassified arthritis.

OBJECTIVE: To establish the performance of (subsets of) the 2015 ACR/EULAR gout classification criteria in patients with unclassified arthritis, and to determine the value of dual-energy CT (DECT) herein. Reference was the MSU crystal detection result in SF at polarization microscopy. METHODS: We included subjects with acute, unclassified mono or oligoarthritis, who underwent SF analysis and DECT. Performance was assessed by calculating area under the receiver operating characteristic curve of (i) the clinical criteria subset, (ii) the clinical+serum urate subset and (iii) the full set (including DECT). RESULTS: Of the 89 subjects enrolled, 40 met the clinical+serum urate subset criteria, and 49 (55%) subjects did not. Of these 49, 30 had a negative microscopy result, of whom 15 had positive DECT; of these 15, 14 met the full set criteria only after adding the positive DECT result. For the clinical-only subset, the areas under the curves (AUCs) were 0.68 and 0.69 without and with DECT result, respectively, and for the clinical+serum urate subset without and with DECT, AUCs were 0.81 and 0.81, respectively (results not significant). CONCLUSION: Adding the serum urate results to the clinical subset improves the performance, but adding the DECT result does not, neither does adding the DECT results to the clinical+serum urate subset. However, DECT seems to have an additive value in gout classification, especially when microscopy of SF is negative; 14/89 of patients (16%) only met the classification criteria with the use of DECT. TRIAL REGISTRATION: ClinicalTrials.gov, http://clinicaltrials.gov, NCT03038386.

Cardiovascular risk in patients with new gout: should we reclassify the risk?

OBJECTIVES: Chronic inflammation, as seen in gout, may contribute to an increased risk of developing cardiovascular (CV) events (CVE). The aim of the study was to explore the effect of adding gout as a chronic inflammatory disease to the Dutch SCORE, a tool predicting 10-year CV mortality and morbidity. METHODS: This was a cross-sectional substudy including new patients with gout according the 2015 EULAR/ACR classification criteria who had participated in a trial on diagnostic accuracy of DECT with mono or oligoarthritis. Patients underwent a structured CV consultation, including assessment of CVE-history and of CV risk factors with the Dutch risk prediction SCORE. Chi-square test for trends was used to test for significance reclassification of the CV risk before and after adding gout to the Dutch SCORE. RESULTS: Seventy-six gout patients were included. SCORE was applied in 60 patients; 16 patients had experienced a prior CVE. The 10-year risk scores without gout as risk factor were high in 29 patients (48.3%), moderate in 6 (10%) and low in 25 (41.7%); with gout, the risk of 23/60 patients (38.3%) was reclassified from low to moderate in 6 patients (10%), from low to high in 11 (18.3%) and from moderate to high in 6 (10%), p<0.001 for trend. CONCLUSIONS: Adding gout to the risk prediction tools led to significant and clinically relevant reclassification of CV risk in new gout patients. Studies with large follow-up are warranted to validate these findings.

Effectiveness and safety over 3 years after the 2-year U-Act-Early trial of the strategies initiating tocilizumab and/or methotrexate.

OBJECTIVES: U-Act-Early was a 2-year, randomized placebo controlled, double-blind trial, in which DMARD-naïve early RA patients were treated to the target of sustained remission (SR). Two strategies initiating tocilizumab (TCZ), with and without methotrexate (MTX), were more effective than a strategy initiating MTX. The aim of the current study was to determine longer-term effectiveness in daily clinical practice. METHODS: At the end of U-Act-Early, patients were included in a 3-year post-trial follow-up (PTFU), in which treatment was according to standard care and data were collected every 3 months during the first year and every 6 months thereafter. Primary end point was disease activity score assessing 28 joints (DAS28) over time. Mixed effects models were used to compare effectiveness between initial strategy groups, correcting for relevant confounders. Between the groups as randomized, proportions of patients were tested for DMARD use, SR and radiographic progression of joint damage. RESULTS: Of patients starting U-Act-Early, 226/317 (71%) participated in the PTFU. Over the total 5 years, mean DAS28 was similar between groups (P > 0.20). During U-Act-Early, biologic DMARD use decreased in both TCZ initiation groups and increased in the MTX initiation group, but during follow-up this trend did not continue. SR was achieved at least once in 99% of patients. Of the 226 patients, only 30% had any radiographic progression over 5 years, without significant differences between the groups. CONCLUSION: Although in the short-term the strategies initiating TCZ yielded the most clinical benefit, in the longer-term differences in important clinical outcomes between the strategies disappeared, probably due to continuation of the treat-to-target principle.

Predictors of biologic-free disease control in patients with rheumatoid arthritis after stopping tumor necrosis factor inhibitor treatment.

BACKGROUND: The aim of this study was to identify predictors of prolonged disease control after discontinuation of tumor necrosis factor inhibitor (TNFi) treatment in patients with rheumatoid arthritis (RA). METHODS: Post-hoc analysis of 439 RA patients (67.3% rheumatoid factor positive) with longstanding RA in remission or with stable low disease activity, randomized to stopping TNFi treatment in the multicenter POET trial. Prolonged acceptable disease control was defined as not restarting TNFi treatment within 12 months after stopping. Baseline demographic and disease-related variables were included in univariate and multivariate logistic regression analysis for identifying predictors of relapse. RESULTS: One year after baseline, 220 patients (50.1%) had not restarted TNFi treatment. Use of an anti-TNF monoclonal antibody (versus a receptor antagonist, OR = 2.41; 95% CI: 1.58-3.67), ≤10 yrs. disease duration (OR = 2.15; 95% CI: 1.42-3.26) and low or moderate multi-biomarker disease activity (MBDA) scores (OR = 2.00; 95% CI: 1.10-3.64) at baseline were independently predictive of successful TNFi discontinuation (area under the receiver operating characteristic curve = 0.66; 95% CI: 0.61-0.71). Results were similar when using no physician-reported flare as the criterion. TNFi-free survival was significantly different for patient groups based on the number of predictors present, ranging from 21.4% of patients with no predictor present to 66.7% of patients with all three predictors present. CONCLUSION: Patients using an anti-TNF monoclonal antibody, with shorter disease duration and low or moderate baseline MBDA score are most likely to achieve prolonged disease control after TNFi discontinuation. TRIAL REGISTRATION: Netherlands Trial Register NTR3112, 21 October 2011.

Impact of Stopping Tumor Necrosis Factor Inhibitors on Rheumatoid Arthritis Patients' Burden of Disease.

OBJECTIVE: To determine the impact of stopping tumor necrosis factor inhibitor (TNFi) treatment on patient-reported outcomes (PROs) of physical and mental health status, health utility, pain, disability, and fatigue in patients with established rheumatoid arthritis (RA). METHODS: In the pragmatic, 12-month POET trial, 817 RA patients with ≥6 months of remission or stable low disease activity were randomized 2:1 to stopping or continuing TNFi. In case of flare, TNFi was restarted at the discretion of the rheumatologist. PROs were assessed every 3 months. RESULTS: TNFi was restarted within 12 months in 252 of 531 patients (47.5%) in the stop group. At 3 months, mean PRO scores were significantly worse in the stop group, and a larger proportion of patients experienced a minimum clinically important difference (MCID) on all PROs. Effect sizes (ES) were strongest for health utility (ES -0.24) and pain (ES -0.30). Mean scores improved again after this point, but disability scores remained significantly different at 12 months. After 12 months, the relative risk of experiencing an MCID ranged from 1.16 for mental health status to 1.58 for fatigue. Mean PRO scores for patients restarting TNFi within 6 months were no longer significantly different from those that did not restart TNFi at 12 months. CONCLUSION: Stopping TNFi had a significant negative short-term impact on a broad range of PROs. Long-term negative consequences appeared to be limited, and outcomes in patients needing to restart TNFi within the first 6 months tended to be restored at 12 months.

The value of rheumatoid factor and anti-citrullinated protein antibodies as predictors of response to infliximab in rheumatoid arthritis: an exploratory study.

OBJECTIVE: It remains unclear whether autoantibodies are useful biomarkers to tailor the choice of biological treatment in RA. We investigated the relationship between the presence and levels of different RF and ACPA isotypes and the response to TNF blockade in an exploratory study. METHODS: A total of 101 active RA patients were prospectively treated with infliximab (3 mg/kg). Changes in disease activity were monitored by the 28-joint DAS (DAS-28). Serum levels of different isotypes [immunoglobulins M, G and A (IgM, IgG and IgA)] of RF and anti-citrullinated peptide antibodies were measured by ELISA. RESULTS: The mean DAS-28 decreased from 5.9 (1.1) at baseline to 4.0 (1.3) at Week 16 of infliximab treatment (P < 0.001). High baseline levels of different isotypes of RF (all P < 0.008), ACPA IgM (P = 0.008) and ACPA IgG (P = 0.07) were associated with an absolute decrease in DAS-28 after TNF blockade. This relationship persisted after adjusting for DAS-28 at baseline. However, the different isotypes of baseline RF and ACPA levels accounted for only a small proportion of variance in treatment response (RF: R² between 7 and 12% and ACPA: R² between 4 and 7%). The simultaneous presence of all three isotypes of RF or ACPA had no additive value. CONCLUSION: Presence as well as the titres of RF and IgM ACPA at baseline are significantly correlated with better response to infliximab treatment. However, this correlation is not strong enough to allow a reliable prediction in individual patients. Trial Registration. ISRCTN Register, http://www.controlled-trials.com/isrctn/, ISRCTN36847425.

[Vasculitis associated with Churg-Strauss syndrome]. / Vasculitis bij het syndroom van Churg-Strauss.

A 52-year-old man was admitted to hospital with abdominal pain, erythema and mild eosinophilia. Medical history revealed fatigue and dyspnoea on exertion after returning from the Gambia a year previously, and allergic rhinitis with nasal polyps that were surgically excised. Before a cause of the abdominal symptoms was determined he developed mononeuropathy, severe eosinophilia and arthralgia in combination with positive anti-neutrophil cytoplasmic antibodies (ANCA) against myeloperoxidase, which lead to the diagnosis of 'Churg-Strauss syndrome'. Despite treatment with high-dose corticosteroids (prednisone 1 mg/kg) his abdominal complaints intensified. A CT-scan of the abdomen showed a soft tissue mass around the caecum. Subsequent colonoscopy showed severe ulcerative lesions and signs of colonic ischemia. When PCR for cytomegalovirus appeared to be negative, treatment was intensified with cyclophosphamide 2 mg/kg, resulting in resolution of the abdominal complaints and healing of the ulcerative lesions in the colon.

Body mass index and clinical response to infliximab in rheumatoid arthritis.

OBJECTIVE: Adipose tissue has immunomodulating effects in rheumatoid arthritis (RA), although the exact role is, at present, unclear. The purpose of this study was to determine whether body mass index (BMI) affects response to infliximab in RA patients investigated prospectively. METHODS: In 89 patients with active RA, the BMI was calculated before initiation of infliximab treatment (3 mg/kg intravenously). After 16 weeks of treatment, changes in disease activity were assessed with the Disease Activity Score in 28 joints (DAS28). RESULTS: The mean ± SD BMI was 26 ± 5 kg/m(2) (range 17-42). The BMI correlated positively with the DAS28 at baseline (r = 0.34, P = 0.001). Since selection of study patients according to DAS28 values could influence the clinical response to tumor necrosis factor (TNF) blockade due to regression to the mean because the clinical response is itself based on the change in the DAS28 values, analysis of covariance was used to correct for the baseline DAS28. A highly significant, negative association between the BMI and the absolute decrease in the DAS28 after 16 weeks (P = 0.001) was found also when adjusted for anti-citrullinated protein antibodies. CONCLUSION: Although the infliximab dosage is based on body weight, RA patients with a high BMI responded less well to infliximab, a finding that held true when adjusted for the baseline DAS28 or anti-citrullinated protein antibody status. These results support the notion that adipose tissue may be involved in the pathophysiology of RA and could have implications for other immune-mediated inflammatory conditions treated with TNF antagonists.

The relationship between synovial lymphocyte aggregates and the clinical response to infliximab in rheumatoid arthritis: a prospective study.

OBJECTIVE: Some patients with rheumatoid arthritis (RA) exhibit lymphocyte aggregates in the synovium. This study was undertaken to address whether the presence of lymphocyte aggregates before treatment could serve as a biomarker for the clinical response to tumor necrosis factor (TNF) blockade, and to confirm whether the aggregation of synovial lymphocytes is reversible after anti-TNF treatment. METHODS: Synovial tissue biopsy samples were obtained from 97 patients with active RA before the initiation of infliximab treatment. Lymphocyte aggregates in the synovial tissue were counted and also graded for size. Logistic regression analysis was performed to identify whether the presence of lymphocyte aggregates could be a predictor of the clinical response at week 16. Furthermore, the effects of TNF blockade on lymphocyte aggregates were compared between patients with RA and patients with psoriatic arthritis (PsA). RESULTS: Fifty-seven percent of RA synovial tissue samples contained lymphocyte aggregates, and 32% of the patients had large aggregates. Aggregates were found in 67% of clinical responders compared with 38% of nonresponders. The presence of aggregates at baseline was a highly significant predictor of the clinical response to anti-TNF treatment (R(2) = 0.10, P = 0.008). Positivity for lymphocyte aggregates increased the power to predict the clinical response (R(2) = 0.29), when analyzed in a prediction model that included baseline disease activity evaluated by the Disease Activity Score in 28 joints, anti-cyclic citrullinated peptide antibody positivity, and synovial TNFalpha expression. There was a reduction in lymphocyte aggregates after anti-TNF antibody therapy in both RA and PsA. CONCLUSION: RA patients with synovial lymphocyte aggregates have, on average, a better response to infliximab treatment than those with only diffuse leukocyte infiltration. Moreover, the aggregation of synovial lymphocytes is reversible after anti-TNF antibody treatment.