Defining criteria for disease activity states in systemic juvenile idiopathic arthritis based on the systemic Juvenile Arthritis Disease Activity Score.

OBJECTIVE: To develop and validate cutoff values in the systemic Juvenile Arthritis Disease Activity Score 10 (sJADAS10) that distinguish the states of inactive disease (ID), minimal disease activity (MiDA), moderate disease activity (MoDA), and high disease activity (HDA) in children with systemic juvenile idiopathic arthritis (sJIA), based on subjective disease state assessment by the treating pediatric rheumatologist. METHODS: The cutoffs definition cohort was composed of 400 patients enrolled at 30 pediatric rheumatology centers in 11 countries. Using the subjective physician rating as an external criterion, 6 methods were applied to identify the cutoffs: mapping, calculation of percentiles of cumulative score distribution, Youden index, 90% specificity, maximum agreement, and ROC curve analysis. Sixty percent of the patients were assigned to the definition cohort and 40% to the validation cohort. Cutoff validation was conducted by assessing discriminative ability. RESULTS: The sJADAS10 cutoffs that separated ID from MiDA, MiDA from MoDA, and MoDA from HDA were ≤ 2.9, ≤ 10, and > 20.6. The cutoffs discriminated strongly among different levels of pain, between patients with or without morning stiffness, and between patients whose parents judged their disease status as remission or persistent activity/flare or were satisfied or not satisfied with current illness outcome. CONCLUSION: The sJADAS cutoffs revealed good metrologic properties in both definition and validation cohorts, and are therefore suitable for use in clinical trials and routine practice.

Exists a role for serum irisin in Egyptian Behcet's patients with subclinical atherosclerosis?

OBJECTIVES: To examine the serum irisin level in a group of Behcet's disease patients, its association with illness parameters, and its utility in diagnosing subclinical atherosclerosis. METHODS: This randomized case-control study included 50 patients and 50 age- and sex-matched controls. Carotid Doppler ultrasound for the measurement of the carotid artery intima-media thickness (CIMT) and ankle-brachial pressure index (ABPI) were performed. A clinical evaluation, lipogram, and serum irisin were also performed. RESULTS: Between the patients and the control group, there was a significant difference in CIMT, S. irisin level, and ankle-brachial pressure index; however, gender and BMI did not significantly affect CIMT, ABPI, or S. irisin level. CIMT demonstrated a substantial negative correlation with both S. irisin and ABPI (r = - 0.62, P 0.0001). With a sensitivity of up to 94.30% and a specificity of 93.30%, the ROC analysis revealed that a decrease in S. irisin level in Behcet's patients was indicative of subclinical atherosclerosis. The drop in the ABPI level demonstrated a sensitivity of up to 94.30% and a specificity of 100%. CONCLUSION: Subclinical atherosclerosis is prevalent among Egyptian Behcet's patients, and S. irisin can be employed as a biomarker for diagnosing subclinical atherosclerosis in Behcet's illness. Key Points • Serum irisin has been studied in numerous autoimmune disorders as a marker for subclinical atherosclerosis, although its importance in Behcet's disease remains unclear (BD). • We examined the change in serum irisin levels in Behcet's disease patients and healthy controls. In addition, its association with carotid artery intima-media thickness (CIMT) and ankle-brachial pressure index was investigated (ABPI). • Changes in serum irisin levels are significant in BD, and a decrease in irisin level indicates subclinical atherosclerosis.

Congenital deficiency reveals critical role of ISG15 in skin homeostasis.

Ulcerating skin lesions are manifestations of human ISG15 deficiency, a type I interferonopathy. However, chronic inflammation may not be their exclusive cause. We describe two siblings with recurrent skin ulcers that healed with scar formation upon corticosteroid treatment. Both had a homozygous nonsense mutation in the ISG15 gene, leading to unstable ISG15 protein lacking the functional domain. We characterized ISG15-/- dermal fibroblasts, HaCaT keratinocytes, and human induced pluripotent stem cell-derived vascular endothelial cells. ISG15-deficient cells exhibited the expected hyperinflammatory phenotype, but also dysregulated expression of molecules critical for connective tissue and epidermis integrity, including reduced collagens and adhesion molecules, but increased matrix metalloproteinases. ISG15-/- fibroblasts exhibited elevated ROS levels and reduced ROS scavenger expression. As opposed to hyperinflammation, defective collagen and integrin synthesis was not rescued by conjugation-deficient ISG15. Cell migration was retarded in ISG15-/- fibroblasts and HaCaT keratinocytes, but normalized under ruxolitinib treatment. Desmosome density was reduced in an ISG15-/- 3D epidermis model. Additionally, there were loose architecture and reduced collagen and desmoglein expression, which could be reversed by treatment with ruxolitinib/doxycycline/TGF-ß1. These results reveal critical roles of ISG15 in maintaining cell migration and epidermis and connective tissue homeostasis, whereby the latter likely requires its conjugation to yet unidentified targets.

Systemic lupus erythematosus children in Egypt: Homeland spectrum amid the global situation.

OBJECTIVES: This study aims to present the manifestations of juvenile systemic lupus erythematosus (JSLE) across Egypt, to focus on age at onset and gender-driven influence on disease characteristics, and to compare findings to other countries. METHODS: The study included 404 Egyptian children with systemic lupus erythematosus (SLE) presenting to one of the specialized rheumatology centers corresponding to 13 major governorates. Juvenile cases age was ≤ 16°years at the time of recruitment. The SLE Disease Activity Index (SLEDAI) and damage index (DI) were assessed. RESULTS: The mean age was 13.2 ± 2.4°years; 355 females and 49 males (7.2:1), and the disease duration was 2.3 ± 1.6 years, while age at disease onset was 11.1 ± 2.5°years. Their SLEDAI was 13.5 ± 12.3, and DI, 0.36 ± 0.78. The overall estimated prevalence of childhood-SLE patients in the recruited cohort in Egypt was 1/100,000 population (0.24/100000 males and 1.8/100000 females). 7.4% developed pre-pubertal SLE (≤ 7 years); 73.3%, peri-pubertal; and 19.3% during early adolescence. The differences according to age group were equal for gender and clinical manifestations except skin lesions present in 59.3% of pre-pubertal onset, 74.6% of peri-pubertal, and 84.2% of adolescents (p = 0.029), and renal involvement in 73.8% of peripubertal, 62.1% of pre-pubertal and 58.9% of adolescents (p = 0.03). Laboratory investigations, SLEDAI, and DI were similar among age categories. Lupus nephritis was more common in Egypt compared to JSLE from other countries. CONCLUSION: Our large multicenter study identified that female gender influenced disease characteristics with more frequent skin involvement. Skin lesions were significantly higher in adolescents, while renal involvement in peri-pubertal children.

Rheumatology university faculty opinion on coronavirus disease-19 (COVID-19) vaccines: the vaXurvey study from Egypt.

OBJECTIVES: The aim of the present work was to explore the perspectives of Egyptian Rheumatology staff members as regards the coronavirus disease-19 (COVID-19) vaccine. METHODS: The survey is composed of 25 questions. Some questions were adapted from the global rheumatology alliance COVID-19 survey for patients. RESULTS: 187 rheumatology staff members across Egypt from 18 universities and authorizations actively participated with a valid response. The mean time needed to complete the survey was 17.7 ± 13 min. Participants were 159 (85%) females (F:M 5.7:1). One-third agreed that they will be vaccinated once available, 24.6% have already received at least one dose, 29.4% are unsure while 16% will not take it. Furthermore, 70.1% agreed that they will recommend it to the rheumatic diseases (RD) patients once available, 24.1% are not sure while 5.9% will not recommend it. RD priority to be vaccinated against COVID-19 in descending order include SLE (82.9%), RA (55.1%), vasculitis (51.3%), systemic sclerosis (39.6%), MCTD (31.6%), Behcet's disease (28.3%). The most common drugs to be avoided before vaccination included biologics (71.7%), DMARDs (44.4%), biosimilars (26.7%), IVIg (17.1%) and NSAIDs (9.1%). CONCLUSIONS: The results of the study and specifically the low rate of acceptability are alarming to Egyptian health authorities and should stir further interventions to reduce the levels of vaccine hesitancy. As rheumatic disease patients in Egypt were not systematically provided with the vaccine till present, making the vaccine available could as well enhance vaccine acceptance. Further studies to investigate any possible side effects, on a large scale of RD patients are warranted.

Therapeutic Potential of Digital Nerve Block in Rheumatoid Arthritis Patients: A Clinical and Sonographic Prospective Study.

BACKGROUND: This study attempted to test the effectiveness of digital nerve block (DNB) in active rheumatoid arthritis (RA) joints with respect to local disease control. METHODS: The study included 83 RA patients aged 18 years or above and diagnosed, after American College of Rheumatology/European League Against Rheumatism criteria 2010, with bilateral proximal interphalangeal (PIP) arthritis. PIPs were examined by European League Against Rheumatism-outcome measures in rheumatoid arthritis clinical trials scoring system at 0, 2, and 8 weeks. Visual analog scales for each hand were also done at the same intervals. DNBs of the second and third PIPs were performed to the dominant hand in 50% of participants. The other hand was used as a control, and saline was injected in the same level at the control side. RESULTS: At 2 weeks and 8 weeks intervals, the active side showed significantly less clinical and ultrasound scores when compared to the control side and the baseline values. The mean OMERACT score for the active hand dropped from 3.37±1.43 at 0 time to 2.31±1.66 after 2 weeks and 2.55±1.43 at 8 weeks (P<0.001). Also, visual analog scale decreased from 59 at 0 time to 41 at 2 weeks and 43 at 8 weeks (P<0.001). The amelioration was greater when the active side was the dominant one. The injected PIPs showed maximum improvement at 2 weeks. Improvement was more significant in the second PIP. Early patients achieved better outcomes. CONCLUSION: DNB is a new promising therapy for RA. It can control pain and inflammation of the PIPs. It has relatively short-term effect, yet it could limit escalation of systemic treatment plans.

Impact of COVID-19 pandemic on rheumatoid arthritis from a Multi-Centre patient-reported questionnaire survey: influence of gender, rural-urban gap and north-south gradient.

During the coronavirus disease-2019 (COVID-19) pandemic there were several barriers to treatment access and medication adherence in rheumatoid arthritis (RA) patients. There is no information regarding the RA patient health status in Egypt during the COVID-19. Thus,the aim of this work was to study the impact of the pandemic on RA patients through a patient-reported questionnaire and to determine the influence of gender, geographic regions. This multi-centre study initiated by the Egyptian College of Rheumatology (ECR) was conducted on 1037 RA patients attending rheumatology clinics from 10 governorates. The questionnaire provided covered socio-demographic data, health/disease status, information/knowledge about COVID-19 and medical/family history of the infection. Patients mean age was 44.2 ± 12.3 years;855 females and 182 males; 539(52%) from rural and 497(48%) from urban areas. 41.8% reported a striking difficulty to obtain hydroxychloroquine during the pandemic. The majority (70%) considered maintaining a regular visit to the rheumatologist in addition to remote contact mainly by phone (44.4%) or via WhatsApp (33.1%), in particular among male and urban patients. Urban patients were more likely to be infected by COVID-19 (12.9% vs 6.2%; p < 0.0001) than rural. Northern cities had more patients with suspected COVID-19 (13.9% vs 6.1%; p < 0.0001); was significantly associated with more disease flares (30.8% vs 5.8%) with subsequent change in the RA treatment (20.9% vs 6.4%; p < 0.0001). Patients with RA faced remarkable difficulty to obtain their medications with subsequent change in their disease status. The challenges of the pandemic have hastened changes in the way we deliver health care.

Ankle Evaluation in Active Rheumatoid Arthritis by Ultrasound: A Cross-Sectional Study.

Ankle joint evaluation is underestimated in many clinical and sonographic scores used for evaluation and follow-up of rheumatoid arthritis (RA) patients. Agreement on examination parameters is poor among sonographic scores that include the ankle joint. More effort is needed to detect the value of ankle joint examination in RA and assessment of ultrasonographic signs according to frequency, disease duration and activity. The objective of this study was to use ultrasound (US) to detect ankle involvement in active RA and to compare findings with disease duration, disease activity and assessment of ankle bone erosion. A total of 63 RA patients with active disease and 20 controls were included in the study. The tibiotalar and talonavicular joints were examined by US for synovitis and/or effusion in gray-scale and power Doppler modes. The anterior, lateral and posterior ankle tendons were examined for tenosynovitis and tendinosis. Mean age was 35.1 ± 8.3 y, mean disease duration was 22.7 ± 9.6 mo and the mean 28-joint Disease Activity Score-erythrocyte sedimentation rate was 3.05 ± 0.66. Ankle involvement was seen in 28 patients (44.4%). The most frequent pathologies detected were tenosynovitis (30.2%), followed by synovitis (18.3%), erosion (8.7%) and tendinosis (4%). The earliest sonographic signs were tenosynovitis, followed by synovitis, erosion and tendinosis. The right ankle exhibited greater involvement than the left ankle, which was significant with respect to erosions (p = 0.009). The most common tendon affected by tenosynovitis was the tibialis anterior (22.2%), followed by the tibialis posterior (20.6%). Tenosynovitis, especially of the tibialis anterior and posterior, tibiotalar synovitis and erosions should be considered in future US ankle scores for the assessment of RA.

Low-dose Spironolactone: Treatment for Osteoarthritis-related Knee Effusion. A Prospective Clinical and Sonographic-based Study.

OBJECTIVE: To evaluate the effectiveness of spironolactone as a treatment for osteoarthritis (OA)-related knee effusion in comparison to ibuprofen, cold compresses, and placebo. METHODS: This study was carried out on 200 patients, aged 40 years or older, attending the outpatient clinic of the Rheumatology Department of Sohag University Hospital with unilateral knee effusion related to OA based on clinical examination, musculoskeletal ultrasonography (US), and synovial fluid analysis. In group 1, 50 patients received spironolactone 25 mg daily for 2 weeks; in group 2, 50 patients took ibuprofen 1200 mg daily for 2 weeks; in group 3, 50 patients used cold compresses 2 times daily for 2 weeks; and in group 4, 50 patients received placebo for the same duration. Fluid > 4 mm was considered as effusion. Decrease in fluid to reach below 4-mm thickness was considered complete improvement, and any decrease that did not reach below 4 mm thickness was considered partial improvement. RESULTS: The mean age of the participants was 51.2 ± 8.1 years. The mean duration of effusion was 16.5 ± 3.6 days. In group 1, 66% had complete improvement, 20% partial improvement, and 14% no response. In group 2, 24% had complete improvement, 12% partial improvement, and 64% no response. In group 3, 28% had complete improvement, 14% partial improvement, and 58% no response. In group 4, only 6% had complete improvement, 10% partial improvement, and 84% no response. CONCLUSION: Low-dose spironolactone is a safe and effective medical treatment for OA-related knee effusion.

Amyloid arthropathy associated with multiple myeloma: a systematic analysis of 101 reported cases.

OBJECTIVE: Amyloid deposition in multiple myeloma (MM) may lead to an arthropathy resembling rheumatoid arthritis (RA). Since a systematic description of its natural history is lacking, we have performed a systematic analysis of all published cases. METHODS: Literature review featuring backward and forward database searches and direct inspection of reference lists. Inclusion criteria were as follows: publication between 1931 and 2012, diagnosis of multiple myeloma, and demonstration of light chain amyloid (AL) in any organ or in synovial fluid, arthritis, or synovitis. RESULTS: Overall, 101 cases were identified. Median age was 59 years and the male-to-female ratio was 1:1. A systemic manifestation of MM was reported in 88 cases. In 53 of these, characteristic physical findings (carpal tunnel syndrome, macroglossia, shoulder pad, and soft tissue swelling/masses) were present. Arthritis manifested before the diagnosis of MM in 63 cases, with 33 cases initially misdiagnosed as RA. There were 72 cases of poly-, 17 of oligo-, and three of monoarthritis. The shoulder joint was most commonly affected, followed by knees and small hand joints. Median synovial fluid leukocyte count was 2460 cells/mm(3), and was normal in seven cases. Synovial histopathology often featured mild synovitis without plasma cell infiltration. Imaging revealed articular or periarticular inflammation in many cases and bone lesions near 22% of affected joints. Treatments varied but led to some improvement in the majority of cases. CONCLUSIONS: These results solidify previous experience that MM arthropathy tends to feature a symmetric RF-negative nonerosive polyarthritis. However, the results also highlight the diversity of its presentations and stress the importance of arthropathy as a potentially under-recognized presenting manifestation of MM.