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Background: From a dermatologist's perspective, there are four major types of cutaneous porphyrias (CPs): porphyria cutanea tarda (PCT), erythropoietic protoporphyria (EPP), variegate porphyria (VP) and hereditary coproporphyria (HCP). Scarce data are available regarding the epidemiology of CPs. Objectives: To describe the epidemiology of CPs in Israel, including distribution, incidence and prevalence rates of major types. Methods: This retrospective study includes all patients who were diagnosed with CPs between the years 1988–2018. It is based on data from Israel's National Service for the Biochemical Diagnoses of Porphyrias, and Israeli patients' nationwide electronic medical charts. Incidence and prevalence rates were calculated. Results: Of 173 patients with CPs diagnosed during a 30‐year period, 65 (38%) had VP, 62 (36%) had PCT, 31 (18%) had HCP and 15 (9%) had EPP; with incidence rates of 0.29, 0.30, 0.17, 0.07, and prevalence rates of 6.3, 4.8, 2.9, 1.6, respectively, per million population. Characteristics of patients with PCT differed from those with other CPs with regard to lack of family history, older mean age at diagnosis [51 vs. 36 (VP), 35 (HCP) and 25 (EPP) years] and male predominance (81% vs. similar distribution). All patients with PCT were diagnosed at adulthood, while 20%, 19% and 15% of patients with VP, HCP and EPP, respectively, were diagnosed during childhood or adolescence. Conclusions: Variegate porphyria and PCT were found to be the most prevalent in Israel; however, CPs might be underdiagnosed, thus dermatologists' awareness of these rare disorders is highly important. [ABSTRACT FROM AUTHOR]

Objectives: Belimumab has recently been approved for the treatment of systemic lupus erythematosus (SLE) refractory to standard therapy. Following one case of an SLE flare after cessation of belimumab, we hypothesized that this might lead to a rebound phenomenon and possible exacerbation of SLE.Method: Members of the Israeli Society of Rheumatology were contacted by e-mail and asked to report cases of an SLE flare following cessation of belimumab treatment.Results: Three cases of SLE patients who experienced a severe SLE flare following cessation of belimumab therapy were reported. In all cases, belimumab was given as treatment for active mucocutaneous manifestations and/or polyarthritis with improvement in all three patients, one of whom achieved disease remission. In all three cases, patients experienced a severe flare in previously uninvolved major organ systems, including one case of class IV lupus nephritis accompanied by a new-onset severe headache with elevated cerebrospinal fluid (CSF) protein and white matter lesions on brain magnetic resonance imaging (MRI), one case of severe pneumonitis and haemolytic anaemia, and one case of a systemic flare, fatigue, arthritis, and severe abdominal pain.Conclusions: Belimumab therapy has been shown to be beneficial in the management of active SLE, mostly in patients with mucocutaneous and musculoskeletal manifestations. We suggest a possible rebound effect following cessation of belimumab that could be due to an increase in B-cell activating factor (BAFF) levels and lead to a disease flare. Future assessment of BAFF levels in patients stopping belimumab therapy and clinical correlation may support this hypothesis. Further studies are needed to confirm this observation. [ABSTRACT FROM AUTHOR]

The aim of this study was to analyse pregestational and pregnancy risk factors for adverse fetal and maternal outcome in lupus pregnancy. Twenty women with systemic lupus erythematosus (SLE) (29 pregnancies) were prospectively evaluated. Mean patient age was 29.5 ± 4.7 years, and mean disease duration, 6.3 ± 6.5 years. Twenty-two pregnancies (75.9%) ended in live births; preterm delivery occurred in 17.4%, intrauterine growth restriction in 50%, preeclampsia in 3.7%, and gestational hypertension in 8%. Six pregnancies (20.7%) ended in spontaneous abortions. Adverse live-birth outcome was significantly associated with low pregestational serum albumin level, elevated gestational anti-dsDNA antibody, and diabetes mellitus. Spontaneous abortion was directly associated with low levels of pregestational serum albumin, positive anticardiolipin IgA, anti-β2-glycoprotein I IgM, and anti-La antibodies, and inversely associated with number of patients' children. Postgestational lupus flare-up was noted in six pregnancies. Risk factors included high pregestational SLE Disease Activity Index (SLEDAI), lower serum albumin, elevated serum antibody to dsDNA, proteinuria, and use of prednisone and hydroxychloroquine. We conclude that despite high rate of obstetrical complications and postpartum lupus flare-up, pregnancy poses low risk for the majority of women with SLE. [ABSTRACT FROM AUTHOR]

ABSTRACT Chronic periaortitis (CP) is an umbrella term used to describe a group of nosologically allied conditions that include idiopathic retroperitoneal fibrosis (Ormond's disease), inflammatory abdominal aortic aneurysm, and perianeurysmal retroperitoneal fibrosis. Retroperitoneal fibrosis encompasses a range of diseases characterized by the presence of a fibro-inflammatory tissue, which usually surrounds the abdominal aorta and the iliac arteries and extends into the retroperitoneum to envelop neighboring structures-ureters. Retroperitoneal fibrosis is generally idiopathic, but can also be secondary to the use of certain drugs, malignant diseases, infections, and surgery. Here we describe a 5 years follow up (2006-2011) of 5 patients admitted to our hospital with symptoms, laboratory, imaging and pathologic finding compatible with retroperitoneal fibrosis. We review our clinical course of our patient with respect to the literature.

Resumo Introdução: A crioglobulinemia é uma vasculite de pequenos vasos mediada por imunocomplexos que normalmente envolvem a pele, os rins e os nervos periféricos. A síndrome antifosfolipídica (SAF) é um transtorno da hipercoagulabilidade autoimune que provoca trombose dos vasos sanguíneos. Pode se manifestar como um distúrbio microtrombótico que afeta múltiplos órgãos, denominado SAF catastrófica. Objetivo: Esta série de casos objetiva descrever os desafios de diagnóstico e tratamento que surgem quando esses dois graves transtornos estão presentes simultaneamente no mesmo paciente. Métodos: Foram descritos quatro pacientes internados em nosso hospital em decorrência de danos graves a múltiplos órgãos mediados pela vasculite crioglobulinêmica com SAF concomitante. Resultados: As manifestações clínicas incluíram úlceras de perna, livedo reticular, insuficiência renal e neuropatia periférica. As etiologias sugeridas para a combinação de síndromes foram a hepatite C, o lúpus eritematoso sistêmico e a doença mieloproliferativa retal associada a linfoma de zona marginal tipo células B. Todos os pacientes foram tratados com anticoagulantes, altas doses de corticosteroides, rituximabe, gamaglobulinas intravenosas e troca de plasma. Conclusão: A rara associação entre a SAF grave ou catastrófica e a crioglobulinemia deve ser considerada por médicos que atendem pacientes com isquemia ou necrose de múltiplos órgãos.

Behçet's disease (BD) is a multisystem disease, in which recurrent aphthous stomatitis (RAS) is a universal finding. We studied the expression of RAS in patients with BD, and the correlation between major or minor RAS and systemic expression and severity of the disease. Thirty-five patients with BD were studied, of whom 13 (37%) had major, 21 (60%) had minor and one (3%) had herpetiform RAS. The frequency of major RAS was significantly higher compared with a control group of patients with idiopathic RAS (37% vs 9%, P < 0.05). The BD patients with major RAS had significantly more relapses of oral ulceration in a year, higher numbers of oral ulcers per relapse, and longer duration of aphthous episodes, compared with patients with minor RAS. Oral ulcers also appeared at a significantly younger age in patients with major than with minor RAS. However, the systemic expression of the disease, as well as the disease severity score, were similar in patients with major and minor RAS. The results of this study indicate that major RAS is common in patients with BD, and is associated with a more severe, repeated and prolonged oral disease. Nevertheless, the presence of major RAS in BD does not predict a more severe systemic illness. [ABSTRACT FROM AUTHOR]

The purpose of the present study was to investigate a possible seasonal pattern in various clinical and laboratory manifestations in a group of systemic lupus erythamatosus (SLE) patients. One hundred and five SLE patients were followed up during a 4 yr period. Data on each of the clinical and laboratory variables examined, as well as the results of the disease activity index (SLEDAI), were plotted against the month during which they were obtained. Photosensitivity was the only variable to show a seasonal pattern, having higher scores during the summer months (1.04 +/- 0.16 in July vs 0.58 +/- 0.12 in December). We were unable to show seasonal patterns in any of the other variables examined. As a group, SLE patients do not show any significant seasonal pattern in disease manifestations and activity, except for photosensitivity. However, such a pattern may exist for the individual patient. [ABSTRACT FROM PUBLISHER]

Objectives: Autologous hematopoietic stem cell transplantation (AHSCT) has been shown to improve long-term survival for early diffuse progressive SSc compared with CYC. CYC, however, does not provide a long-term benefit in SSc. The combination of MMF and rituximab is a potent alternative regimen. We aimed to retrospectively compare the outcomes of SSc patients who underwent AHSCT to patients who met the eligibility criteria for AHSCT but received upfront combination therapy with MMF and rituximab., Methods: Repeated assessments of modified Rodnan Skin Score (mRSS), forced vital capacity (FVC), and diffusing capacity (DLCO) values were conducted. Clinical improvement was defined as an mRSS decrease >25% or an FVC increase >10%. Event-free survival (EFS) was defined in the absence of persistent major organ failure or death., Results: Twenty-one SSc patients in the combination therapy group were compared with 16 in the AHSCT group. Age, sex and disease duration were similar between the two groups. Clinical improvement at 12 months was seen in 18 (86%) patients in the combination group compared with 13 (81%) in the AHSCT group (P = 0.7). The hazard ratio for EFS at 24 months favoured the combination group (HR = 0.09, P = 0.04). During follow-up, both groups exhibited a significant and comparable reduction in mRSS and an increase in FVC values at each time interval up to 24 months., Conclusion: MMF and rituximab compared with AHSCT in SSc patients eligible for AHSCT resulted in similar skin and lung clinical improvement with a better safety profile at 24 months., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: The CLASS (Classification Criteria of Anti-Synthetase Syndrome) project is a large international multicentre study that aims to create the first data-driven anti-synthetase syndrome (ASSD) classification criteria. Identifying anti-aminoacyl tRNA synthetase antibodies (anti-ARS) is crucial for diagnosis, and several commercial immunoassays are now available for this purpose. However, using these assays risks yielding false-positive or false-negative results, potentially leading to misdiagnosis. The established reference standard for detecting anti-ARS is immunoprecipitation (IP), typically employed in research rather than routine autoantibody testing. We gathered samples from participating centers and results from local anti-ARS testing. As an "ad-interim" study within the CLASS project, we aimed to assess how local immunoassays perform in real-world settings compared to our central definition of anti-ARS positivity., Methods: We collected 787 serum samples from participating centres for the CLASS project and their local anti-ARS test results. These samples underwent initial central testing using RNA-IP. Following this, the specificity of ARS was reconfirmed centrally through ELISA, line-blot assay (LIA), and, in cases of conflicting results, protein-IP. The sensitivity, specificity, positive likelihood ratio and positive and negative predictive values were evaluated. We also calculated the inter-rater agreement between central and local results using a weighted κ co-efficient., Results: Our analysis demonstrates that local, real-world detection of anti-Jo1 is reliable with high sensitivity and specificity with a very good level of agreement with our central definition of anti-Jo1 antibody positivity. However, the agreement between local immunoassay and central determination of anti-non-Jo1 antibodies varied, especially among results obtained using local LIA, ELISA and "other" methods., Conclusions: Our study evaluates the performance of real-world identification of anti-synthetase antibodies in a large cohort of multi-national patients with ASSD and controls. Our analysis reinforces the reliability of real-world anti-Jo1 detection methods. In contrast, challenges persist for anti-non-Jo1 identification, particularly anti-PL7 and rarer antibodies such as anti-OJ/KS. Clinicians should exercise caution when interpreting anti-synthetase antibodies, especially when commercial immunoassays test positive for non-anti-Jo1 antibodies.

Objectives: To determine the value of plasma and urine sTREM-1 levels as a biomarker of lupus nephritis (LN) as well as extra-renal systemic lupus erythematosus (SLE)., Methods: Consecutive adult patients with SLE attending a tertiary lupus clinic in 2016-2018 were prospectively divided into 3 groups according to SLEDAI-2K and renal-SLEDAI scores: active renal lupus (ARL), active non-renal lupus (ANL), and inactive lupus (IL). Blood and spot urine samples from each group and matched healthy subjects were analysed by means of ELISA for plasma and urine sTREM-1 levels., Results: The cohort included 59 patients (mean age 41.5+2.9 years, 85% female) with SLE: 15 ARL, 14 ANL, and 30 IL. The ARL group had higher scores on the SLEDAI-2K and renal-SLEDAI, and higher urine protein/creatinine ratio than the other patient groups (p=0.0001 for all). Plasma sTREM-1 level was highest in the ANL group (p=0.0085). Urine sTREM-1 level was higher in the whole SLE cohort than the healthy controls (p=0.0249), and higher in the ARL group than the others (p=0.0044). Neither plasma nor urine sTREM-1 level was associated with non-renal SLE features. On Spearman correlation analysis, urine sTREM-1 level, but not plasma sTREM-1 level, was correlated positively with renal-SLEDAI score (r=0.34, p=0.018), inversely with serum C3 and C4 levels (r=-0.42, p=0.0027 and r=-0.28, p=0.056, respectively), and positively with proteinuria (UPCR: r=0.32, p=0.0305)., Conclusions: Urine sTREM-1 might serve as a potential biomarker of active renal SLE.

Objective: We aimed to characterize the course of COVID-19 in autoimmune inflammatory rheumatic disease (AIIRD) patients in Israel, taking into consideration several remarkable aspects, including the outcomes of the different outbreaks, the effect of vaccination campaigns, and AIIRD activity post-recovery., Methods: We established a national registry of AIIRD patients diagnosed with COVID-19, including demographic data, AIIRD diagnosis, duration and systemic involvement, comorbidities, date of COVID-19 diagnosis, clinical course, and dates of vaccinations. COVID-19 was diagnosed by a positive SARS-CoV-2 polymerase chain reaction., Results: Israel experienced 4 outbreaks of COVID-19 until 30.11.2021. The first three outbreaks (1.3.2020 - 30.4.2021) comprised 298 AIIRD patients. 64.9% had a mild disease and 24.2% had a severe course; 161 (53.3%) patients were hospitalized, 27 (8.9%) died. The 4 th outbreak (delta variant), starting 6 months after the beginning of the vaccination campaign comprised 110 patients. Despite similar demographic and clinical characteristics, a smaller proportion of AIIRD patients had negative outcomes as compared to the first 3 outbreaks, with regards to severity (16 patients,14.5%), hospitalization (29 patients, 26.4%) and death (7 patients, 6.4%). COVID-19 did not seem to influence the AIIRD activity 1-3 months post-recovery., Conclusions: COVID-19 is more severe and has an increased mortality in active AIIRD patients with systemic involvement, older age and comorbidities. Vaccination with 3 doses of the mRNA vaccine against SARS-CoV-2 protected from severe COVID-19, hospitalization and death during the 4 th outbreak. The pattern of spread of COVID-19 in AIIRD patients was similar to the general population., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kharouf, Eviatar, Braun, Pokroy-Shapira, Brodavka, Zloof, Agmon-Levin, Toledano, Oren, Lidar, Zisman, Tavor, Amit-Vazina, Sabbah, Breuer, Dagan, Beshara-Garzuzi, Markovits, Elias, Feld, Tayer-Shifman, Gazitt, Reitblatt, Rubin, Haddad, Giryes, Paran, Peleg, Molad, Elkayam, Mevorach, Balbir-Gurman and Braun-Moscovici.)

Background: Epidemiological studies have shown a connection between ethnic origin and the incidence and outcome of systemic lupus erythematosus (SLE)., Objectives: To evaluate the SLE outcomes among Ashkenazi Jews, non-Ashkenazi Jews, and Arabs., Methods: We conducted a retrospective study of patients who were diagnosed with SLE and followed in lupus clinics at two large tertiary medical centers. The data were obtained from patient medical records. Patients were stratified into three ethnic origins: Ashkenazi Jews, non-Ashkenazi Jews, and Arabs. The primary outcomes were all-cause mortality, development of end-stage kidney disease (ESKD), and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) 2K ≤ 4 at last visit., Results: We included 570 patients in this study. The Arab group showed the highest number of SLE classification criteria at diagnosis and last encounters compared to non-Ashkenazi and Ashkenazi Jewish groups (6.0 vs. 5.0 and 4.0, respectively at diagnosis, P < 0.001; 8.0 vs. 7.0 and 6.0 at last visit, P = 0.01). In multivariate models, Arab patients had three times higher risk of all-cause mortality than Ashkenazi Jews (hazard ratio 2.99, 95% confidence interval [95%CI] 1.32-6.76, P = 0.009). ESKD was similar among the study groups. Low disease activity (SLEDAI 2K ≤ 4) at last visit was lower in the Arab group than the Ashkenazi Jews (odds ratio 0.50, 95%CI 0.28-0.87, P = 0.016), depicting a medium-to-high disease activity among the former., Conclusions: Physicians should consider the influence of the ethnicity of the SLE patient when deciding on their care plan.

Objective: We sought to determine the association of anti-Ro/SS-A antibody with organ involvement and disease outcome in patients with systemic sclerosis (SSc)., Methods: A retrospective, long-term study of a cohort of incident patients diagnosed with SSc and continuously followed at our rheumatology clinic during 1990-2018., Results: Included were 105 patients with known anti-Ro/SS-A antibody status, 92.4% female, mean age at diagnosis 52.0 ± 15.6 years, and median follow-up of 10 years; 64% were diagnosed with limited cutaneous SSc, 18% with diffuse cutaneous SSc, and 18% had SSc siné scleroderma or undetermined disease type. Anti-Ro/SS-A antibody tested positive in 21% of patients. In univariate analysis, anti-Ro/SS-A antibody positivity was significantly associated with SSc overlap with Sjögren's syndrome (p < .001). Predicted forced vital capacity deterioration at last encounter was significantly associated with anti-Ro/SS-A antibody positivity. In multivariate regression for anti-Ro/SS-A antibody-positive SSc patients and disease outcome [adjusted for age > 50 years, smoking, and baseline predicted forced vital capacity (pFVC) < 80%], positive anti-Ro/SS-A antibody was significantly associated with a higher all-cause mortality rate (HR 5.17, CI 95%, 1.18-22.67, p = .029), and greater deterioration of pFVC defined as a decrement of last available pFVC compared to first available pFVC of ≥10% (HR 3.65, CI 95%, 1.07-12.38, p = .038)., Conclusions: Anti-Ro/SS-A antibody is an independent risk factor for worse pulmonary outcome and higher all-cause mortality in patients with SSc., (© Japan College of Rheumatology 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)