The Systemic Score May Identify Life-Threatening Evolution in Still Disease: Data from the GIRRCS AOSD-Study Group and the AIDA Network Still Disease Registry.

OBJECTIVE: We aimed to evaluate the clinical usefulness of the systemic score in the prediction of life-threatening evolution in Still disease. We also aimed to assess the clinical relevance of each component of the systemic score in predicting life-threatening evolution and to derive patient subsets accordingly. METHODS: A multicenter, observational, prospective study was designed including patients included in the Gruppo Italiano Di Ricerca in Reumatologia Clinica e Sperimentale Adult-Onset Still Disease Study Group and the Autoinflammatory Disease Alliance Network Still Disease Registry. Patients were assessed to see if the variables to derive the systemic score were available. The life-threatening evolution was defined as mortality, whatever the clinical course, and/or macrophage activation syndrome, a secondary hemophagocytic lymphohistiocytosis associated with a poor prognosis. RESULTS: A total of 597 patients with Still disease were assessed (mean ± SD age 36.6 ± 17.3 years; male 44.4%). The systemic score, assessed as a continuous variable, significantly predicted the life-threatening evolution (odds ratio [OR] 1.24; 95% confidence interval [CI] 1.07-1.42; P = 0.004). A systemic score ≥7 also significantly predicted the likelihood of a patient experiencing life-threatening evolution (OR 3.36; 95% CI 1.81-6.25; P < 0.001). Assessing the clinical relevance of each component of the systemic score, liver involvement (OR 1.68; 95% CI 1.48-2.67; P = 0.031) and lung disease (OR 2.12; 95% CI 1.14-4.49; P = 0.042) both significantly predicted life-threatening evolution. The clinical characteristics of patients with liver involvement and lung disease were derived, highlighting their relevance in multiorgan disease manifestations. CONCLUSION: The clinical utility of the systemic score was shown in identifying Still disease at a higher risk of life-threatening evolution in a large cohort. Furthermore, the clinical relevance of liver involvement and lung disease was highlighted.

Effectiveness and Safety of Biosimilars in Pediatric Non-infectious Uveitis: Real-Life Data from the International AIDA Network Uveitis Registry.

INTRODUCTION: Since many biological drug patents have expired, biosimilar agents (BIOs) have been developed; however, there are still some reservations in their use, especially in childhood. The aim of the current study is to evaluate the efficacy and safety of tumor necrosis factor (TNF) inhibitors BIOs as treatment for pediatric non-infectious uveitis (NIU). METHODS: Data from pediatric patients with NIU treated with TNF inhibitors BIOs were drawn from the international AutoInflammatory Disease Alliance (AIDA) registries dedicated to uveitis and Behçet's disease. The effectiveness and safety of BIOs were assessed in terms of frequency of relapses, risk for developing ocular flares, best-corrected visual acuity (BCVA), glucocorticoids (GCs)-sparing effect, drug survival, frequency of ocular complications, and adverse drug event (AE). RESULTS: Forty-seven patients (77 affected eyes) were enrolled. The BIOs employed were adalimumab (ADA) (89.4%), etanercept (ETA) (5.3%), and infliximab (IFX) (5.3%). The number of relapses 12 months prior to BIOs and at last follow-up was 282.14 and 52.43 per 100 patients/year. The relative risk of developing ocular flares before BIOs introduction compared to the period following the start of BIOs was 4.49 (95% confidence interval [CI] 3.38-5.98, p = 0.004). The number needed to treat (NNT) for ocular flares was 3.53. Median BCVA was maintained during the whole BIOs treatment (p = 0.92). A significant GCs-sparing effect was observed throughout the treatment period (p = 0.002). The estimated drug retention rate (DRR) at 12-, 24-, and 36-month follow-up were 92.7, 83.3, and 70.8%, respectively. The risk rate for developing structural ocular complications was 89.9/100 patients/year before starting BIOs and 12.7/100 patients/year during BIOs treatment, with a risk ratio of new ocular complications without BIOs of 7.1 (CI 3.4-14.9, p = 0.0003). Three minor AEs were reported. CONCLUSIONS: TNF inhibitors BIOs are effective in reducing the number of ocular uveitis relapses, preserving visual acuity, allowing a significant GCs-sparing effect, and preventing structural ocular complications. TRIAL REGISTRATION: ClinicalTrials.gov ID NCT05200715.

Efficacy and Safety of Adalimumab in Pediatric Non-infectious Non-anterior Uveitis: Real-life Experience From the International AIDA Network Uveitis Registry.

INTRODUCTION: Scientific evidence of the effectiveness of the tumor necrosis factor inhibitor adalimumab (ADA) in pediatric patients with non-infectious non-anterior uveitis is still limited. The aim of this study is to investigate the therapeutic role of ADA in a cohort of pediatric patients with non-anterior uveitis. METHODS: This is an international multicenter study analyzing real-life data referred to pediatric patients treated with ADA for intermediate uveitis/pars planitis, posterior uveitis and panuveitis. Data were drawn from the AutoInflammatory Disease Alliance (AIDA) registry for patients with uveitis. RESULTS: Twenty-one patients (36 affected eyes) were enrolled, and all patients benefited from ADA administration. In detail, 11 patients (19 affected eyes) did not experience further ocular inflammation after ADA introduction; 10 cases (17 affected eyes) showed a significant clinical improvement consisting of a decrease in severity and/or frequency of ocular relapses. The number of ocular flares dropped from 3.91 to 1.1 events/patient/year after ADA introduction (p = 0.0009); macular edema and retinal vasculitis were respectively observed in 18 eyes and 20 eyes at the start of ADA and in 4 eyes and 2 eyes at the last assessment. The mean daily glucocorticoid dosage significantly decreased from 26.8 ± 16.8 mg/day at the start of ADA to 6.25 ± 6.35 mg/day at the last assessment (p = 0.002). Intermediate uveitis/pars planitis (p = 0.01) and posterior uveitis (p = 0.03) were more frequently observed in patients with full response to ADA; panuveitis (p = 0.001) was significantly more frequent among patients continuing to experience uveitic flares. This could be related to a higher use of systemic glucocorticoids (p = 0.002) and conventional immunosuppressants (p = 0.007) at the start of ADA when treating intermediate uveitis/pars planitis. Regarding the safety profile, only one adverse event was reported during ADA treatment, consisting of the development of generalized adenopathy. CONCLUSIONS: ADA proved to have an effective therapeutic role in all pediatric patients with non-anterior uveitis enrolled in the study. An overall glucocorticoid-sparing effect was observed despite the severity of cases enrolled. A more aggressive treatment of panuveitis and posterior uveitis at start of ADA could increase the likelihood of full response to therapy.

Musculoskeletal manifestations in children with Behçet's syndrome: data from the AIDA Network Behçet's Syndrome Registry.

This study aims to describe musculoskeletal manifestations (MSM) in children with Behçet's syndrome (BS), their association with other disease manifestations, response to therapy, and long-term prognosis. Data were retrieved from the AIDA Network Behçet's Syndrome Registry. Out of a total of 141 patients with juvenile BS, 37 had MSM at disease onset (26.2%). The median age at onset was 10.0 years (IQR 7.7). The median follow-up duration was 21.8 years (IQR 23.3). Recurrent oral (100%) and genital ulcers (67.6%) and pseudofolliculitis (56.8%) were the most common symptoms associated with MSM. At disease onset, 31 subjects had arthritis (83.8%), 33 arthralgia (89.2%), and 14 myalgia (37.8%). Arthritis was monoarticular in 9/31 cases (29%), oligoarticular in 10 (32.3%), polyarticular in 5 (16.1%), axial in 7 (22.6%). Over time, arthritis became chronic-recurrent in 67.7% of cases and 7/31 patients had joint erosions (22.6%). The median Behçet's Syndrome Overall Damage Index was 0 (range 0-4). Colchicine was inefficacious for MSM in 4/14 cases (28.6%), independently from the type of MSM (p = 0.46) or the concomitant therapy (p = 0.30 for cDMARDs, p = 1.00 for glucocorticoids); cDMARDs and bDMARDs were inefficacious for MSM in 6/19 (31.4%) and 5/12 (41.7%) cases. The presence of myalgia was associated with bDMARDs inefficacy (p = 0.014). To conclude, MSM in children with BS are frequently associated with recurrent ulcers and pseudofolliculitis. Arthritis is mostly mono- or oligoarticular, but sacroiliitis is not unusual. Prognosis of this subset of BS is overall favorable, though the presence of myalgia negatively affects response to biologic therapies. ClinicalTrials.gov Identifier: NCT05200715 (registered on December 18, 2021).

Autoinflammatory diseases and the kidney.

The kidney represents an important target of systemic inflammation. Its involvement in monogenic and multifactorial autoinflammatory diseases (AIDs) vary from peculiar and relatively frequent manifestations to some rare but severe features that may end up requiring transplantation. The pathogenetic background is also very heterogeneous ranging from amyloidosis to non-amyloid related damage rooted in inflammasome activation. Kidney involvement in monogenic and polygenic AIDs may present as renal amyloidosis, IgA nephropathy, and more rarely as various forms of glomerulonephritis (GN), namely segmental glomerulosclerosis, collapsing glomerulopathy, fibrillar, or membranoproliferative GN. Vascular disorders such as thrombosis or renal aneurysms and pseudoaneurysms may be encountered in patients with Behcet's disease. Patients with AIDs should be routinely assessed for renal involvement. Screening with urinalysis, serum creatinine, 24-h urinary protein, microhematuria, and imaging studies should be carried out for early diagnosis. Awareness of drug-induced nephrotoxicity, drug-drug interactions as well as addressing the issue of proper renal adjustment of drug doses deserve a special mention and should always be considered when dealing with patients affected by AIDs. Finally, we will explore the role of IL-1 inhibitors in AIDs patients with renal involvement. Targeting IL-1 may indeed have the potential to successfully manage kidney disease and improve long-term prognosis of AIDs patients.

Genome-wide association study for systemic lupus erythematosus in an egyptian population.

Systemic lupus erythematosus (SLE) susceptibility has a strong genetic component. Genome-wide association studies (GWAS) across trans-ancestral populations show both common and distinct genetic variants of susceptibility across European and Asian ancestries, while many other ethnic populations remain underexplored. We conducted the first SLE GWAS on Egyptians-an admixed North African/Middle Eastern population-using 537 patients and 883 controls. To identify novel susceptibility loci and replicate previously known loci, we performed imputation-based association analysis with 6,382,276 SNPs while accounting for individual admixture. We validated the association analysis using adaptive permutation tests (n = 109). We identified a novel genome-wide significant locus near IRS1/miR-5702 (Pcorrected = 1.98 × 10-8) and eight novel suggestive loci (Pcorrected < 1.0 × 10-5). We also replicated (Pperm < 0.01) 97 previously known loci with at least one associated nearby SNP, with ITGAM, DEF6-PPARD and IRF5 the top three replicated loci. SNPs correlated (r 2 > 0.8) with lead SNPs from four suggestive loci (ARMC9, DIAPH3, IFLDT1, and ENTPD3) were associated with differential gene expression (3.5 × 10-95 < p < 1.0 × 10-2) across diverse tissues. These loci are involved in cellular proliferation and invasion-pathways prominent in lupus and nephritis. Our study highlights the utility of GWAS in an admixed Egyptian population for delineating new genetic associations and for understanding SLE pathogenesis.

Efficacy and safety of tocilizumab in adult-onset Still's disease: Real-life experience from the international AIDA registry.

BACKGROUND/OBJECTIVES: Long-term efficacy and safety of tocilizumab (TCZ) in adult-onset Still's disease (AOSD) mostly derive from small case series. Herein we report a registry-based study investigating TCZ efficacy and safety in a cohort of patients with AOSD evaluated by clinical and serum inflammatory markers as well as drug retention rate analysis. METHODS: This is an international multicentre study analyzing data from patients with AOSD regularly enrolled in the AIDA registry. TCZ efficacy was evaluated between baseline and last follow-up assessment in terms of changes in the Pouchot score and laboratory findings. Drug-retention rate was estimated by the Kaplan-Meier method, while Cox-regression analysis was employed to detect potential predictive factors of treatment withdrawal. RESULTS: Data from 31 patients (15 men, 16 women) refractory to the conventional therapies and treated with TCZ were extracted from the AIDA registry. Mean ± SD time of treatment duration with TCZ was 24.32 ± 20.57 months. Median (IRQ) Pouchot score significantly decreased throughout the study period (p=0.001) with a significant difference between baseline [2.00 (4.00)] and 6 month-follow-up [0.00 (0.00)] (p=0.003) and between baseline and last follow-up assessment [0.00 (0.00)] (p=0.032), while no differences were observed between 6 month-evaluation and last follow-up assessment (p=0.823). Similarly, laboratory parameters significantly decreased from baseline to the last follow-up visit. With regard to drug survival, cumulative TCZ retention rate at 12-, 24-, and 36-month follow-up visit were 83.1%, 71.7% and 63.7%, respectively, without significant differences between biologic naïve patients and those previously treated with other biologics (p=0.329). Likewise, no significant differences were observed between chronic articular course of AOSD and other types of disease course (p=0.938) or between patients co-administered with conventional immunosuppressants and patients receiving TCZ as monotherapy (p=0.778). Cox-regression analysis identified no variable associated with a higher hazard of treatment withdrawal. Treatment was discontinued in 9 patients due to long-term remission (n=4), adverse events (n=2), loss of efficacy (n=1), non-medical reason (n=1) and unspecified cause (n=1). Mean glucocorticosteroids daily dose significantly decreased from baseline (18.36 ± 24.72 mg) to the last follow-up assessment (4.02 ± 4.99 mg, p=0.003). CONCLUSIONS: TCZ allows control of disease activity as well as normalization of serum inflammatory markers in both systemic and chronic articular form of AOSD. Additionally, TCZ displays an excellent drug retention rate while minimizing the risk of long-term exposure to corticosteroids.

Development and implementation of the AIDA International Registry for patients with Periodic Fever, Aphthous stomatitis, Pharyngitis, and cervical Adenitis syndrome.

Objective: Aim of this paper is to illustrate the methodology, design, and development of the AutoInflammatory Disease Alliance (AIDA) International Registry dedicated to patients with the Periodic Fever, Aphthous stomatitis, Pharyngitis, and cervical Adenitis (PFAPA) syndrome. Methods: This is a physician-driven, non-population- and electronic-based registry proposed to gather real-world demographics, clinical, laboratory, instrumental and socioeconomic data from PFAPA patients. Data recruitment is realized through the on-line Research Electronic Data Capture (REDCap) tool. This registry is thought to collect standardized information for clinical research leading to solid real-life evidence. The international scope and the flexibility of the registry will facilitate the realization of cutting-edge study projects through the constant updating of variables and the possible merging and transfer of data between current and future PFAPA registries. Results: A total of 112 centers have already been involved from 23 countries and 4 continents starting from August 24th, 2021, to April 6th, 2022. In total 56/112 have already obtained the formal approval from their local Ethics Committees. The platform counts 321 users (113 principal investigators, 203 site investigators, two lead investigators, and three data managers). The registry collects retrospective and prospective data using 3,856 fields organized into 25 instruments, including PFAPA patient's demographics, medical histories, symptoms, triggers/risk factors, therapies, and impact on the healthcare systems. Conclusions: The development of the AIDA International Registry for PFAPA patients will enable the on-line collection of standardized data prompting real-life studies through the connection of worldwide groups of physicians and researchers. This project can be found on https://clinicaltrials.gov NCT05200715.

Development and implementation of the AIDA International Registry for patients with Behçet's disease.

Purpose of the present paper is to point out the design, development and deployment of the AutoInflammatory Disease Alliance (AIDA) International Registry dedicated to pediatric and adult patients with Behçet's disease (BD). The Registry is a clinical physician-driven non-population- and electronic-based instrument implemented for the retrospective and prospective collection of real-life data about demographics, clinical, therapeutic, laboratory, instrumental and socioeconomic information from BD patients; the Registry is based on the Research Electronic Data Capture (REDCap) tool, which is thought to collect standardised information for clinical real-life research, and has been realised to change over time according to future scientific acquisitions and potentially communicate with other existing and future Registries dedicated to BD. Starting from January 31st, 2021, to February 7th, 2022, 110 centres from 23 countries in 4 continents have been involved. Fifty-four of these have already obtained the approval from their local Ethics Committees. Currently, the platform counts 290 users (111 Principal Investigators, 175 Site Investigators, 2 Lead Investigators, and 2 data managers). The Registry collects baseline and follow-up data using 5993 fields organised into 16 instruments, including patient's demographics, history, clinical manifestations and symptoms, trigger/risk factors, therapies and healthcare access. The development of the AIDA International Registry for BD patients will facilitate the collection of standardised data leading to real-world evidence, enabling international multicentre collaborative research through data sharing, international consultation, dissemination of knowledge, inclusion of patients and families, and ultimately optimisation of scientific efforts and implementation of standardised care.Trial registration NCT05200715 in 21/01/2022.

Online medical education in Egypt during the COVID-19 pandemic: a nationwide assessment of medical students' usage and perceptions.

BACKGROUND: The coronavirus (COVID-19) pandemic required a transformation of medical education in Egypt. Public health measures necessitated a rapid shift from traditional face to face lectures to largely online platforms following campus closures. The aim of this study is to characterize medical student use and perception of online medical education in Egypt as well as exploring the efficacy of different e-learning modalities. Additionally, many barriers and opportunities as perceived by students are reviewed to inform future educational improvements. METHODS: A 29-item online survey was created on google forms and distributed by social media to medical students across 26 Egyptian medical schools. The survey was administered from August 20th, 2021, to September 5th, 2021. The survey consisted of a mixture of questions style. The medical students were asked about their experiences with online medical education during the COVID-19 pandemic as well as medical students' anxiety, perceived academic performance, and obstacles related to online education. RESULTS: Of the 4935 responses collected, 43.4% (n = 2140) of respondents were women; 56.6% (n = 2795) were men. Medical students from private medical schools were 13.0% (n = 644), whereas 87.0% (n = 4291) were from public medical schools. 54.6% of students reported that online education is not as effective as face-to-face education. There was a significant rise in hours spent by medical students on online medical education compared to before COVID-19 pandemic. More than half of students (63%) agreed that online recorded video tutorials (e.g., YouTube) were the most effective form of online medical education. CONCLUSION: The shift to online education has significantly impacted medical students in Egypt. Medical students reported various limitations and challenges of online medical education, which must be addressed considering the potential benefits of online platforms over traditional face to face learning. The results of this nationwide study provide a framework for potential areas to implement change to improve the accessibility and structure of online medical education in Egypt.

Relapse of Hepatitis C Virus Cryoglobulinemic Vasculitis After Sustained Viral Response After Interferon-Free Direct-Acting Antivirals.

INTRODUCTION: Direct-acting antiviral agents (DAAs) have modified the management of chronic hepatitis C virus (HCV) infection, including HCV-related cryoglobulinemic vasculitis (CryoVas). However, patients might experience vasculitis relapse, and no reliable predictors of CryoVas relapse after sustained virologic response (SVR) have been established. We aimed to describe HCV-CryoVas relapse rates and factors associated with it. METHODS: An international multicenter cohort where patients with HCV-CryoVas from Egypt, France, and Italy treated with DAA were analyzed retrospectively. Factors associated with relapse-free survival were evaluated in a multivariate-adjusted model. RESULTS: Of 913 patients, 911 (99.8%) obtained SVR. After 35 months of the median follow-up, 798 patients (87.4%) had sustained remission of vasculitis, while 115 (12.6%) experienced CryoVas relapse. By the time of relapse, skin involvement was present in 100%, renal involvement in 85.2%, and peripheral neuropathy in 81.7%. Relapses were treated with glucocorticoids in 90.9%, associated with plasma exchange, cyclophosphamide, or rituximab in 50%, 37.3%, and 6.4%, respectively. The cumulative incidence of CryoVas relapse was 0.7% (95% CI 0.3-1.4), 12.3% (95% CI 10.2-14.6), and 13.1% (95% CI 11.0-15.5) at 12, 24, and 36 months after DAA treatment, respectively. Independent baseline risk factors associated with CryoVas relapse were male sex, skin ulcers, kidney involvement at baseline, and peripheral neuropathy at the end of DAA treatment. Death occurred in 11 relapsers, mainly due to infections. DISCUSSION: A substantial proportion of patients with CryoVas experience relapse after DAA-induced SVR. Relapses are moderate-to-severe and affect survival after 24 months, mainly due to infections. Independent risk factors for relapse or death were found.

Development and Implementation of the AIDA International Registry for Patients with Non-Infectious Uveitis.

INTRODUCTION: The aim of this paper is to point out the design, development and deployment of the AutoInflammatory Disease Alliance (AIDA) International Registry for paediatric and adult patients with non-infectious uveitis (NIU). METHODS: This is a physician-driven, population- and electronic-based registry implemented for both retrospective and prospective collection of real-world demographics, clinical, laboratory, instrumental and socioeconomic data of patients with uveitis and other non-infectious inflammatory ocular diseases recruited through the AIDA Network. Data recruitment, based on the Research Electronic Data Capture (REDCap) tool, is thought to collect standardised information for real-life research and has been developed to change over time according to future scientific acquisitions and potentially communicate with other similar instruments. Security, data quality and data governance are cornerstones of this platform. RESULTS: Ninety-five centres have been involved from 19 countries and four continents from 24 March to 16 November 2021. Forty-eight out of 95 have already obtained the approval from their local ethics committees. At present, the platform counts 259 users (95 principal investigators, 160 site investigators, 2 lead investigators, and 2 data managers). The AIDA Registry collects baseline and follow-up data using 3943 fields organised into 13 instruments, including patient's demographics, history, symptoms, trigger/risk factors, therapies and healthcare utilization for patients with NIU. CONCLUSIONS: The development of the AIDA Registry for patients with NIU will facilitate the collection of standardised data leading to real-world evidence and enabling international multicentre collaborative research through inclusion of patients and their families worldwide.

Genotype-phenotype associations in familial Mediterranean fever: a study of 500 Egyptian pediatric patients.

INTRODUCTION: Familial Mediterranean fever (FMF) is the most prevalent monogenic autoinflammatory disease, caused by recessively inherited MEFV gene mutations. The most frequent MEFV mutations differ in penetrance and disease severity. We investigated the genotype-phenotype associations of the three most frequent MEFV gene mutations (M680I, M694V, and V726A) in Egyptian FMF children, regarding clinical features, severity, and colchicine response. METHODS: We conducted a retrospective analysis of the medical registries of 500 FMF pediatric patients from Metropolitan Cairo between 2010 and 2015. The diagnosis was based on the Tel-Hashomer clinical diagnostic criteria. Clinical data and baseline investigations were collected. Mutation analysis was performed by the amplification-refractory mutation system (ARMS)-PCR method. RESULTS: Males represented 54% and ages ranged from 2 to 18 years. The most frequent symptoms were abdominal pain, fever, and arthralgia. Clinical features mostly associated with M694V mutation either homozygous or heterozygous whether simple, double, or triple. Of the patients, 94.6% completely responded to colchicine. Among patients benefiting from colchicine, 42.5% had M694V/V726A, 21.6% had M694V/V726A/M680I, and 21.1% had M694V genotype. Simple heterozygous M694V or V726A mutations conveyed a moderate phenotype in 57.1% and 50% of cases, respectively. Homozygous M694V mutation showed moderate and severe phenotypes in 21.7% and 65.2% of cases, respectively. Compound M694V/V726A mutation associated with moderate or severe disease in 48.3% and 33.8% of cases, respectively. CONCLUSION: This study encompasses the largest group of Egyptian pediatric FMF up to date to explore their genotype-phenotype associations. Our results support the notion that the genotype influences the phenotype as regards clinical manifestations, disease severity, and colchicine response. KEY POINTS: • This study encompasses the largest group of Egyptian pediatric patients affected by FMF up to date to explore their genotype-phenotype associations. • Our results support the notion that the genotype influences the phenotype as regards the clinical manifestations, the disease severity, and the response to colchicine treatment.

Anakinra and canakinumab for patients with R92Q-associated autoinflammatory syndrome: a multicenter observational study from the AIDA Network.

BACKGROUND: This study aims at describing the therapeutic outcome of patients carrying the R92Q variant in the TNFRSF1A gene treated with anakinra (ANA) or canakinumab (CAN) and identifying any factors predictive of complete response to IL-1 inhibition. METHODS: Clinical data of patients treated with ANA or CAN for recurrent inflammatory attacks due to the presence of the R92Q variant were retrospectively collected and analysed. RESULTS: Data about 20 treatment courses with IL-1 inhibitors (16 with ANA and 4 with CAN) from 19 patients were collected. Mean age at disease onset was 20.2 ± 14.8 years. In 5 cases (26%) the R92Q variant was found in a family member affected by recurrent fever. The therapeutic response was complete in 13(68%) and partial in 2 patients (11%); treatment failure was observed in 4 cases (21%). Median AIDAI decreased from 10 (interquartile range [IQR] = 28) to 0 (IQR = 1) at the 12-month follow-up visit (p < 0.001). Mean ESR and median CRP dropped respectively from 40.8 ± 24.8 to 9.1 ± 4.5 mm/h (p < 0.001) and from 3.0 (IQR = 1.9) to 0.3 (IQR = 0.3) mg/dl (p < 0.001) after 12 months of treatment. A steroid-sparing effect was observed from the third month of treatment (p < 0.01). Thirteen patients (65%) were still on treatment at the last follow-up visit (median duration of treatment 17 (IQR = 38) months). The presence of R92Q mutation in a symptomatic relative (p = 0.022), the relapsing remitting disease course (p < 0.001) and the presence of migratory erythematous skin rashes during fever attacks (p = 0.005) were associated with complete efficacy of IL-1 inhibitors. CONCLUSIONS: R92Q patients showed a favourable response to ANA and CAN, particularly when the mutation segregated in a family member and when a relapsing-remitting disease course or TNF-α receptor-associated periodic syndrome (TRAPS) typical skin rash were observed. In the subgroup of patients not taking advantage of IL-1 blockage different molecular mechanisms underlying the autoinflammatory picture are likely to exist.

COVID-19 Disease Outcomes: Does Gastrointestinal Burden Play a Role?

BACKGROUND: The novel coronavirus disease 2019 presents an urgent threat to global health. As the epidemic grows, prognosis prediction is essential for monitoring risky patient. It is thus important to consider gastrointestinal manifestations and the duration of symptoms as predictors of prognosis. Our aim was to determine the correlation of gastrointestinal symptoms and laboratory markers with disease outcomes and whether symptom duration varies substantially between patients. We also undertook this study to determine the optimal time to predict COVID-19 outcome. PATIENTS AND METHODS: A total of 190 patients with polymerase chain reaction-confirmed COVID-19 were followed up until recovery. We proposed a correlation between gastrointestinal symptoms and disease severity (based on clinical data, and diagnostic investigations) to estimate the duration of symptoms as a predictor of COVID-19 prognosis. RESULTS: The prevalence of gastrointestinal symptoms was 49.5%, consisting mainly of diarrhea in 27.9% of patients. In addition, a longer disease duration and higher temperature were observed in patients with diarrhea. Symptom duration was variable, with a median of 12 days and a range of 1-55 days. Statistical analysis indicated that patients with a duration of symptoms ≥12 day had more severe symptoms and a worse prognosis. Patients who complained of diarrhea had 2.7 times the odds of a longer duration of symptoms, and those with a history of chronic lung disease have 7.2 times the odds of a longer duration of symptoms. CONCLUSION: GIT manifestations (mainly diarrhea) and the duration of symptoms of COVID-19 provide prognostic evidence of COVID-19 outcomes, irrespective of earlier categorization by the World Health Organization. Thus, patients with mild symptoms who present with diarrhea and a duration of symptoms longer than 12 days are expected to have a worse prognosis.

Noninvasive Assessment of Endothelial Dysfunction in Egyptian Patients with Lupus Nephritis.

Systemic lupus erythematosus (SLE) is a multisystem chronic autoimmune disease characterized by tissue inflammation. There is increased cardiovascular mortality in cases with SLE. Endothelial dysfunction is an early stage of atherosclerosis, which can be reversed early. We aimed to study noninvasive assessment of endothelial dysfunction in Egyptian patients with SLE. Three hundred individuals were recruited; 100 SLE patients with lupus nephritis (LN), 100 SLE patients free of LN as well as 100 healthy volunteers. The vascular endothelial function was evaluated through ultrasonographic assessment of brachial artery diameter to determine the flow-mediated dilation (FMD) as well as a blood endothelial marker called platelet endothelial cell adhesion molecule-1, also known as cluster of differentiation 31 (CD31), was measured. CD31 is abnormal in 93% of cases with LN and 79% in cases without nephritis. There was a significant higher level in CD31 in cases of LN compared with lupus without nephritis with P = 0.016. FMD is impaired in all cases with LN, 95% in cases without nephritis, and in 20% of the controls. There was a significant lower FMD in cases of LN compared with lupus without nephritis with P <0.001. Multiple regression analysis showed that FMD of the brachial artery (P <0.001) is an independent factor to predict LN. Endothelial dysfunction is increased in cases with SLE especially those with nephritis. CD31 and FMD can be used as noninvasive methods for early detection of endothelial dysfunction.

Three Patterns of Cutaneous Involvement in Granulomatosis with Polyangiitis.

BACKGROUND: Skin involvement in granulomatosis with polyangiitis (GPA) is common and can appear as an initial presentation of the disease or more commonly through its course. CASE PRESENTATION: We report a case of a 24-year-old male patient, previously diagnosed as having GPA, admitted with fever, hemoptysis, generalized hemorrhagic blisters associated with arthralgia, fatigue, myalgia, nasal crusting, and vertigo. Three weeks prior to admission, he developed erythematous papules on both elbows, and purpuric papules on both lower limbs. Histopathological examination revealed: interstitial granulomatous dermatitis (elbows) and foci of dermal hemorrhage, foci of interstitial histiocytes and zones of altered necrobiotic collagen (lower limbs) consistent with cutaneous lesions of GPA. Two weeks later, his rash progressed to widespread purpura associated with hemorrhagic blisters. Another biopsy revealed leukocytoclastic vasculitis with fibrinoid necrosis of the vessel walls associated with perivascular infiltrate of neutrophils, nuclear dust and extravasated erythrocytes without an associated granulomatous inflammation or necrobiosis. The constellation of the results of the three biopsies together with clinical correlation pointed to a flare of GPA. CONCLUSION: Skin involvement in GPA is quite common, and it can manifest in different forms in the same patient. Our patient developed three different skin pathologies within a short period of time.

Subcutaneous formulation of belimumab in treatment of systemic lupus erythematosus: a critical review with focus on safety and satisfaction.

Belimumab is a novel add-on therapy that has been approved for patients with active and antibody-mediated systemic lupus erythematosus. It is a monoclonal antibody that decreases the activation of B-cells and consequently decreases antibodies' production. Recently, the US Food and Drug Administration approved subcutaneous belimumab for patients who have received training on using it. Subcutaneous belimumab can be administered using either a prefilled syringe or an auto-injector device. Weekly subcutaneous belimumab seems to be as effective as monthly intravenous belimumab with a similar safety margin. In this article, we reviewed the literature on subcutaneous belimumab focusing on safety and patients' experiences and satisfaction. Overall, subcutaneous belimumab appears to be preferred over intravenous belimumab for a number of reasons. However, more studies are still required to prove these findings.

Increased genomic instability following treatment with direct acting anti-hepatitis C virus drugs.

Mixed Cryoglobulinemic Vasculitis (MCV) is a prominent extra-hepatic manifestation of Hepatitis C virus (HCV) infection. HCV has been reported to cause B-cell disorders and genomic instability. Here, we investigated B-cell activation and genome stability in HCV-MCV patients receiving the direct antiviral agent, Sofosbuvir, at multiple centers in Egypt. Clinical manifestations in HCV-MCV patients were improved at the end of treatment (EOT), such as purpura (100%), articular manifestations (75%) and neuropathy (68%). Eighteen patients (56%) showed vasculitis relapse after EOT. BAFF and APRIL were higher at EOT and continued to increase one year following treatment onset. Chromosomal breaks were elevated at EOT compared to baseline levels and were sustained at 3 and 6 months post treatment. We report increased expression of DNA genome stability transcripts such as topoisomerase 1 and TDP1 in HCV-MCV patients after treatment, which continued to increase at 12 months from treatment onset. This data suggest that B-cell activation and DNA damage are important determinants of HCV-MCV treatment outcomes.