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A rare case of IgG4-related pachymeningitis is presented. The manuscript describes the multidisciplinary treatment of a rare entity in an exceptional location, prompting emergent surgical treatment. However, the correct intraoperative hypothesis led to a minimal surgical approach with fewer risks and good disease control. Finding a balance between maximising treatment outcome and minimising risks is often difficult for clinicians worldwide who encounter the same clinical dilemma. The known cases are summarised, as are radiological characteristics and common treatments. [ABSTRACT FROM AUTHOR]

The patients who received RTX later than one year after the onset of scleritis exhibited recurrences and/or failure of RTX treatment more often (p = 0.03). Scleritis is characterized by intense pain, redness, potentially destructive complications, and frequently insufficient response to local and systemic treatments (Sainz de la Maza et al. 2012; Wieringa et al. 2013). Rituximab (RTX) was introduced as treatment for scleritis after its successful use for systemic autoimmune diseases associated with scleritis. [Extracted from the article]

Objectives To investigate whether the auto-inflammatory nature and the pathergic reaction in Behçet's disease (BD) are driven by a disturbed toll-like receptor (TLR) response. Methods We compared both TLR expression by flow-cytometry and TLR response by stimulation assay in 18 BD patients (both pathergy positive and pathergy negative) with 15 healthy controls. Results Expression of TLR1 and 2 was significantly elevated in B-lymphocytes of BD patients compared with healthy controls. TLR1, 2 and 4 were significantly more highly expressed in both CD4+ and CD8+ T-lymphocytes of BD patients. Granulocytes of BD patients displayed significantly higher expression of TLR1, 2, 4 and 6. TLR2, 4 and 5 expression was significantly increased on classical monocytes of BD patients. Intermediate monocytes of BD patients showed an increase in expression of TLR2. Furthermore, TLR2 and 5 were significantly more highly expressed in non-classical monocytes of BD patients. In pathergy positive patients, TLR5 was even more highly expressed compared with pathergy negative patients on B- and T-lymphocytes and granulocytes. Furthermore, TLR2 and 5 showed an elevated TNF-α response to stimulation with their cognate ligands. Conclusion Immune cells of BD patients overexpress TLR1, 2, 4, 5 and 6. Furthermore, after stimulation of TLR2 and 5, BD patients demonstrate a more potent TNF-α response. Although this is a small cohort, in the pathergy positive patients, TLR5 expression is even further augmented, suggesting that a microbial (flagellin) or damage (HMGB1) associated signal may trigger the exaggerated immune response that is characteristic for the pathergy phenomenon in BD. In conclusion, these results point to an exaggerated TLR response in the auto-inflammatory nature of BD. [ABSTRACT FROM AUTHOR]

Background: In Behçet's disease (BD), an auto-inflammatory vasculitis, an unbalanced gut microbiota can contribute to pro-inflammatory reactions. In separate studies, distinct pro- and anti-inflammatory bacteria associated with BD have been identified. Methods: To establish disease-associated determinants, we performed gut microbiome profiling in BD patients from the Netherlands (n = 19) and Italy (n = 13), matched healthy controls (HC) from the Netherlands (n = 17) and Italy (n = 15) and oral microbiome profiling in Dutch BD patients (n = 18) and HC (n = 15) by 16S rRNA gene sequencing. In addition, we used fecal IgA-SEQ analysis to identify specific IgA coated bacterial taxa in Dutch BD patients (n = 13) and HC (n = 8). Results: In BD stool samples alpha-diversity was conserved, whereas beta-diversity analysis showed no clustering based on disease, but a significant segregation by country of origin. Yet, a significant decrease of unclassified Barnesiellaceae and Lachnospira genera was associated with BD patients compared to HC. Subdivided by country, the Italian cohort displays a significant decrease of unclassified Barnesiellaceae and Lachnospira genera, in the Dutch cohort this decrease is only a trend. Increased IgA-coating of Bifidobacterium spp., Dorea spp. and Ruminococcus bromii species was found in stool from BD patients. Moreover, oral Dutch BD microbiome displayed increased abundance of Spirochaetaceae and Dethiosulfovibrionaceae families. Conclusions: BD patients show decreased fecal abundance of Barnesiellaceae and Lachnospira and increased oral abundance of Spirochaetaceae and Dethiosulfovibrionaceae. In addition, increased fecal IgA coating of Bifidobacterium, Ruminococcus bromii and Dorea may reflect retention of anti-inflammatory species and neutralization of pathosymbionts in BD, respectively. Additional studies are warranted to relate intestinal microbes with the significance of ethnicity, diet, medication and response with distinct pro- and inflammatory pathways in BD patients. [ABSTRACT FROM AUTHOR]

The soluble interleukin 2 receptor (sIL-2R) has been proposed as a marker of disease activity in patients with sarcoidosis. However, no studies have evaluated whether serum sIL-2R measurement is of use in establishing the diagnosis of sarcoidosis in patients who are suspected of sarcoidosis among other diseases. A cohort study was conducted, consisting of new patients who visited the immunology outpatient clinic and whose serum sIL-2R levels were available before a definitive diagnosis was established between February 2011 and February 2016. All patients underwent standard diagnostic testing for sarcoidosis (e.g. laboratory tests, radiographic and/or nuclear imaging and/or affected site biopsy). This resulted either in the diagnosis of sarcoidosis or the exclusion of sarcoidosis with the diagnosis of another disease. Results of sIL-2R and angiotensin-converting enzyme (ACE) levels, radiographic and nuclear imaging and histology results were collected and definitive diagnoses were recorded. Sensitivity, specificity, the concordance statistic from the receiver operating characteristic curve and Youden's Index were calculated to assess the performance of sIL-2R in the diagnosis of sarcoidosis and were compared to ACE, currently one of the most used diagnostic biomarkers in the diagnosis of sarcoidosis. In total 983 patients were screened for inclusion, of which 189 patients met the inclusion criteria. A total of 101 patients were diagnosed with sarcoidosis after diagnostic workup, of whom 79 were biopsy-proven. In 88 patients a diagnosis other than sarcoidosis was made. The sensitivity and specificity of serum soluble interleukin 2 receptor levels to detect sarcoidosis were 88% and 85%. The sensitivity and specificity of ACE were 62% and 76%. Receiver operating characteristic curve analysis revealed that sIL-2R receptor is superior to ACE (p<0.0001). Serum sIL-2R is a sensitive biomarker and superior to ACE in establishing the diagnosis of sarcoidosis and can be used to rule out sarcoidosis in patients suspected of sarcoidosis. [ABSTRACT FROM AUTHOR]

IgG4‐related disease (IgG4‐RD) is an immune‐mediated systemic fibro inflammatory disease. Treatment of IgG4‐related orbital disease (IgG4‐ROD) is often indicated to relieve the symptoms and to prevent complications. For IgG4‐ROD, no international formal treatment guidelines are available and the optimal treatment strategy is uncertain. In this systematic review, we describe the efficacy of conventional and biologic disease‐modifying antirheumatic drugs (DMARDs) in IgG4‐ROD. A systematic search of Embase, Medline, Web‐of‐Science, PubMed publisher, Cochrane and Google Scholar was performed for treatment outcomes in IgG4‐ROD. Relevant articles on treatment of IgG4‐ROD were retrieved to last date of inclusion 3 January 2018. The following inclusion criteria were used: articles in English or English translation, studies evaluating the use of DMARDs (conventional and biologic) in the treatment of IgG4‐ROD. Meta‐analysis and review articles were excluded. A final selection after full‐text evaluation was made by independent reviewers, based on treatment of IgG4‐ROD with DMARDs and the availability of treatment outcomes. With this systematic review, we identified 35 studies and case reports/series on IgG4‐ROD, describing 95 patients, treated with conventional and/or biologic DMARDs. The success of conventional DMARDs varies between 36% and 75% in patients with IgG4‐ROD, while rituximab is successful in the majority (93%) of the patients. Based on this systematic review, rituximab is the most effective DMARD in IgG4‐ROD, while the efficacy of conventional DMARDs is limited. We propose early initiation of rituximab in case of refractory and organ‐ or life‐threatening disease. [ABSTRACT FROM AUTHOR]

Serum CCL17 distinguishes sarcoid uveitis from TB-uveitis and QFT-negative uveitis Sarcoidosis and tuberculosis (TB) display highly overlapping clinical features commonly involving the lungs and lymphatics. Although serum CCL17 in sarcoidosis patients was not significantly higher than in TB patients ( I p i = 0 0.0641), a clear trend towards higher serum CCL17 levels in sarcoidosis was observed (Fig. [Extracted from the article]

Rationale: Although chest radiography is currently recommended for the initial evaluation of patients with new-onset uveitis, the efficacy of this diagnostic screening modality is not known.Objectives: To evaluate the diagnostic value of chest radiographs in patients with active uveitis of recent onset in a tertiary center in Western Europe.Methods: A retrospective cross-sectional study was conducted by reviewing all chest imaging for adults with new-onset (<1 yr) uveitis of unknown origin undergoing initial evaluation in the Department of Ophthalmology at Erasmus University Medical Center (Rotterdam, the Netherlands). Radiographic findings were related to clinical and other imaging characteristics and to final diagnoses.Results: Screening chest radiographs were abnormal for 30 of 200 patients (15%) included in this study. Twenty-two of the 200 patients (11%) had biopsy-confirmed sarcoidosis, and an additional 12 patients were presumed to have sarcoidosis. The finding of chest radiographic abnormalities interpreted as typical of sarcoidosis was specific (91%; 95% confidence interval, 85.9-94.4%) but not sensitive (64%; 95% confidence interval, 43.0-80.3%) for biopsy-confirmed sarcoidosis. The combination of elevated serum angiotensin-converting enzyme level and chest radiographic findings typical of sarcoidosis increased the sensitivity to 79%. Biopsy-confirmed sarcoidosis was more common in patients with panuveitis (17 of 84; 20%) compared to patients with other anatomical locations of uveitis (5 of 116, 4%; P < 0.001). One patient was diagnosed with active pulmonary and ocular tuberculosis.Conclusions: Abnormal chest radiographs were found in 15% of patients with active uveitis of unknown origin and onset within 1 year of referral to a tertiary center in the Netherlands. A majority of the abnormal chest radiographs showed findings compatible with a diagnosis of sarcoidosis. [ABSTRACT FROM AUTHOR]

Background: B-cell depletion can improve a variety of chronic inflammatory diseases, but does not appear beneficial for patients with Crohn’s disease. Objective: To elucidate the involvement of B cells in Crohn’s disease, we here performed an ‘in depth’ analysis of intestinal and blood B-cells in this chronic inflammatory disease. Methods: Patients with Crohn’s disease were recruited to study B-cell infiltrates in intestinal biopsies (n = 5), serum immunoglobulin levels and the phenotype and molecular characteristics of blood B-cell subsets (n = 21). The effects of infliximab treatment were studied in 9 patients. Results: Granulomatous tissue showed infiltrates of B lymphocytes rather than Ig-secreting plasma cells. Circulating transitional B cells and CD21low B cells were elevated. IgM memory B cells were reduced and natural effector cells showed decreased replication histories and somatic hypermutation (SHM) levels. In contrast, IgG and IgA memory B cells were normally present and their Ig gene transcripts carried increased SHM levels. The numbers of transitional and natural effector cells were normal in patients who responded clinically well to infliximab. Conclusions: B cells in patients with Crohn’s disease showed signs of chronic stimulation with localization to granulomatous tissue and increased molecular maturation of IgA and IgG. Therapy with TNFα-blockers restored the defect in IgM memory B-cell generation and normalized transitional B-cell levels, making these subsets candidate markers for treatment monitoring. Together, these results suggest a chronic, aberrant B-cell response in patients with Crohn’s disease, which could be targeted with new therapeutics that specifically regulate B-cell function. [ABSTRACT FROM AUTHOR]

The article discusses research which examined the applicability of myxovirus resistance protein 1 (MxA) enzyme immunoassay (EIA) in detecting type I interferon (IFN) activation in individuals with systemic lupus erythematosus (SLE) and systemic sclerosis (SSc). Topics explored include the measurement of MxA protein levels in patients with SLE, observations on the IFN scores and autoantibodies of SLE patients, and the cost-effectiveness demonstrated by MxA-EIA.

The author comments on the article "Exploring the variability in Behc¸et's Disease Prevalence: A Meta-Analytical Approach" by Carla Maldini et al. He explores the origin of Behc¸et's disease, a multisystem auto-inflammatory disorder named after Turkish dermatologist Hulusi Behc¸et. He explains the rarity of the disease and its potential environmental of genetic causes, as well as its immunological mechanistic pathways.

A letter to the editor is presented in response to the article "Hemophagocytic lymphohistiocytosis associated with Bartonella henselae infection in an HIV-infected patient," by A. Le Joncour and colleagues in a 2016 issue.

An abstract of the conference paper "Case series: rituximab in the treatment of refractory sight-threatening scleritis," by several researchers including, Kiki van Bilsen, P. Martin van Hagen, and Tom Missotten is presented.

A letter to the editor which discusses the occurrence of adrenal insufficiency on a patient with adrenal metastasis of renal cell cancer is presented.

Purpose Methods Results Conclusions We report the long-term effect of rituximab (RTX) in scleritis and determine the value of B-cell monitoring for the prediction of relapses.We retrospectively studied 10 patients with scleritis, who were treated with RTX. Clinical characteristics were collected, and blood B-cell counts were measured before the start of RTX, and at various time points after treatment.Clinical activity of scleritis decreased after RTX treatment in all patients within a median time of 8 weeks (range 3–13), and all reached remission. The median follow-up was 101 months (range 9–138). Relapses occurred in 6 out of 10 patients. All relapses, where B-cell counts were measured (11 out of 19), were heralded by returning B cells. However, B cells also returned in patients with long-term remissions.RTX is a promising therapeutic option for scleritis. Recurrence of B cells after initial depletion does not always predict relapse of scleritis. [ABSTRACT FROM AUTHOR]

An abstract of the article "Basophil Activation Test in the prediction of anaphylactic reactions against Hymenoptera venom in patients suffering from Systemic Mastocytosis," by Mark J. A. Rietveld and colleagues is presented.

An abstract of the article "Distal renal tubular acidosis in primary Sjögren syndrome," by Tim Both and colleagues is presented.

An abstract of the conference paper "Somatostatin receptor scintigraphy in sarcoidosis," by several researchers including, Jan A. M. van Laar, Paul L. A. van Daele, and G. Seerp Baarsma is presented.

A letter to the editor is presented which discusses a case study of a 53-year-old man with long-standing malaise and fatigue and received a diagnosis of Immunoglobulin-4 (IgG4)-related disease and renal amyloid.

Background: Despite enormous clinical improvements, due to better management strategies and the availability of biologicals, immune-mediated inflammatory diseases (IMIDs) still have a significant impact on patients' lives. To further reduce disease burden, provider- as well as patient-reported outcomes (PROs) should be taken into account during treatment and follow-up. Web-based collection of these outcomes generates valuable repeated measurements, which could be used (1) in daily clinical practice for patient-centered care, including shared decision-making; (2) for research purposes; and (3) as an essential step toward the implementation of value-based health care (VBHC). Our ultimate goal is that our health care delivery system is completely aligned with the principles of VBHC. For aforementioned reasons, we implemented the IMID registry., Objective: The IMID registry is a digital system for routine outcome measurement that mainly includes PROs to improve care for patients with IMIDs., Methods: The IMID registry is a longitudinal observational prospective cohort study within the departments of rheumatology, gastroenterology, dermatology, immunology, clinical pharmacy, and outpatient pharmacy of the Erasmus MC, the Netherlands. Patients with the following diseases are eligible for inclusion: inflammatory arthritis, inflammatory bowel disease, atopic dermatitis, psoriasis, uveitis, Behçet disease, sarcoidosis, and systemic vasculitis. Generic and disease-specific (patient-reported) outcomes, including adherence to medication, side effects, quality of life, work productivity, disease damage, and activity, are collected from patients and providers at fixed intervals before and during outpatient clinic visits. Data are collected and visualized through a data capture system, which is linked directly to the patients' electronic health record, which not only facilitates a more holistic care approach, but also helps with shared decision-making., Results: The IMID registry is an ongoing cohort with no end date. Inclusion started in April 2018. From start until September 2022, a total of 1417 patients have been included from the participating departments. The mean age at inclusion was 46 (SD 16) years, and 56% of the patient population is female. The average percentage of filled out questionnaires at baseline is 84%, which drops to 72% after 1 year of follow-up. This decline may be due to the fact that the outcomes are not always discussed during the outpatient clinic visit or because the questionnaires were sometimes forgotten to set out. The registry is also used for research purposes and 92% of the patients with IMIDs gave informed consent to use their data for that., Conclusions: The IMID registry is a web-based digital system that collects provider- and PROs. The collected outcomes are used to improve care for the individual patient with an IMID and facilitate shared decision-making, and they are also used for research purposes. The measurement of these outcomes is an essential step toward the implementation of VBHC., International Registered Report Identifier (irrid): DERR1-10.2196/43230., (©Agnes E M Looijen, Reinier C A van Linschoten, Jan-Dietert Brugma, Dirk Jan Hijnen, Pascal H P de Jong, P Hugo M van der Kuy, Jan A M van Laar, C Janneke van der Woude, Annelieke Pasma. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 30.03.2023.)

Purpose: During the SARS-CoV-2 pandemic, national and international societies have recommended continuing biological agents in patients with immune-mediated inflammatory diseases (IMID) in the absence of SARS-CoV-2 symptoms. However, adherence to biological treatment might decrease, because these recommendations contradict patients' beliefs. Especially an increased concern about side effects could have influenced the adherence to biological treatment during the first lockdown. The primary objective was to investigate the impact of the first SARS-CoV-2 lockdown on adherence to biological treatment in IMID patients., Patients and Methods: In this prospective cohort study, IMID patients who received a biological agent before and during the first SARS-CoV-2 lockdown (March 2020- June 2020) were included. Patients were excluded if they did not complete the medication adherence report scale-5 (MARS-5) questionnaire at ≥1 visit before the lockdown and ≥1 visit during the lockdown. Adherence to biological treatment was measured with the MARS-5 and Medication Possession Ratio (MPR)., Results: We included 157 IMID patients. The percentage of adherent patients, defined as MARS-5 score >21, was significantly lower during the lockdown compared to the period before the lockdown (88.5% vs 84.1%, p<0.001). Additionally, the overall percentage of adherent patients during the lockdown based on the MPR ≥90% was significantly lower compared to adherence based upon the MARS-5 (65.1% vs 84.1%, p<0.001)., Conclusion: This study showed that the first SARS-CoV-2 lockdown negatively impacts adherence to biological treatment in IMID patients. Therefore, treating physicians should be aware of this problem to minimize the potential harmful effects of non-adherence., Competing Interests: The authors report no conflicts of interest in this work., (© 2023 van der Groef et al.)

Background: Behçet's disease (BD) is an auto-inflammatory vasculitis characterized by aphthous oro-genital ulcers, inflammatory skin changes and uveitis. Treatment is mainly immunosuppressive. Interestingly, elevated endotheline-1 (ET-1) levels suggest a possible beneficial effect of treatment with an ET-1 receptor antagonist., Objective: The aim of our study was to investigate the possible beneficial effect of the ET-1 inhibitor bosentan., Methods: We performed a prospective double-blind placebo controlled pilot study into the effect and safety of bosentan in BD patients. Disease activity was measured using the Behçet Disease Current Activity Form. The primary objective of the study was to determine whether bosentan is therapeutically effective in patients with BD. Secondary endpoints were safety, tapering of medication and the effect of bosentan on possible disease activity markers such as ET-1, circulating endothelial cells (CECs), soluble interleukin-2 receptor (sIL2R) and cytokine levels., Results: Ten patients were randomized to either bosentan or placebo. Overall, no effect on disease activity was observed, although one patient responded clinically and continued treatment after the study period. Despite one SAE, bosentan seems safe to use. No effect on tapering of medication, CECs, sIL2R and cytokine levels was found. In the bosentan group, ET-1 levels were elevated during the treatment period, with no correlation with disease activity., Conclusions: Although this is a small pilot study, bosentan appears to be safe in BD patients. One patient had a durable and significant clinical response. Our observations should be confirmed and extended in a larger patient cohort to be of significant impact in the treatment options for BD.

Objectives: The aim of this study is to investigate the cumulative incidence and the severity of COVID-19 infections in patients with Behçet's disease., Methods: A retrospective cohort study of patients with Behçet's disease was conducted. We obtained the data systematically from electronic patient files and through telephone interviews between February 2020 and May 1, 2021. Main outcomes were COVID-19 infection, disease duration, hospitalisation, intensive care admission and mortality. Secondary outcome was adherence to quarantine measures as recommended by the government., Results: 185 Behçet's disease patients were included (mean age 42.2 years, 54% female); 58% of the patients were receiving colchicine, 30% anti-TNFα, 16% azathioprine and 8% systemic steroids. 30 patients (16.2%) were positive for COVID-19. Within our cohort, the cumulative incidence of COVID-19 was therefore 16.2% (95% CI 11.2-22.3%), which is significantly increased when compared to the general Dutch population (8.7% (95% CI 8.72-8.73%)) (p < 0.001). Four out of 30 (13%) patients were admitted to the hospital. There was no COVID-19 related mortality observed. Patients adhered to government measures; except in the period between the 1st of June and the 28th of September, this cohort received more visitors than in period 1 and 3., Conclusions: In this cohort, Behçet's disease patients have a higher risk for COVID-19 infection, without an increase of virus-related mortality. The course of COVID-19 disease in this cohort is relatively mild, with a lower admission rate than expected of patients using immunosuppressive medication.