Defining Criteria for Disease Activity States in Systemic Juvenile Idiopathic Arthritis Based on the Systemic Juvenile Arthritis Disease Activity Score.

OBJECTIVE: Our objective was 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 (MDA), moderate disease activity (MoDA), and high disease activity (HDA) in children with systemic juvenile idiopathic arthritis, based on subjective disease state assessment by the treating pediatric rheumatologist. METHODS: The cutoff 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, six methods were applied to identify the cutoffs: mapping, calculation of percentiles of cumulative score distribution, the Youden index, 90% specificity, maximum agreement, and receiver operating characteristic curve analysis. Sixty percent of the patients were assigned to the definition cohort, and 40% were assigned to the validation cohort. Cutoff validation was conducted by assessing discriminative ability. RESULTS: The sJADAS10 cutoffs that separated ID from MDA, MDA from MoDA, and MoDA from HDA were ≤2.9, ≤10, and >20.6, respectively. The cutoffs discriminated strongly among different levels of pain, between patients with and without morning stiffness, and among patients whose parents judged their disease status as remission or persistent activity or 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.

DKK-1 in psoriatic arthritis: Correlation with disease activity and enthesopathy.

BACKGROUND: Psoriatic arthritis (PsA) is a complex inflammatory disease with varied clinical characteristics. A pathognomonic characteristic of PsA is enthesitis. Entheseal inflammation ultimately leads to the production of new bone (enthesophytes). Dickkopf-related protein-1 (DKK-1) is a wingless (Wnt) inhibitor that inhibits osteoblast function. OBJECTIVES: Assessment of the serum level of DKK-1 and its association with disease activity and enthesopathy in PsA patients. METHODS: This observational case-control study included 50 PsA patients and 50 healthy volunteers matched for age and gender. All participants were subjected to full medical history, clinical assessment, PSA activity using Disease Activity Index for Psoriatic Arthritis (DAPSA) score, the severity and extent of psoriasis were determined by the Psoriasis Area and Severity Index (PASI). Ultrasonographic assessment of the entheses was done in accordance with the Madrid Sonographic Enthesitis Index (MASEI). Serum level of DKK-1 and correlation with disease activity and enthesopathy in PsA patients were assessed. RESULTS: There was no significant difference between patients and controls regarding age and sex. The mean value of SPARCC index, DAPSA score and PASI score were 6.74±4.58, 33.24±15.26, and 8.35±10.93, respectively. There was significant difference between patients and controls regarding the serum levels of DKK-1 and MASEI score (p<0.0001). There was a significant positive correlation between serum DKK-1 and MASEI (r: 0.43527, p: 0.00158), MASEI inflammatory (r: 0.37958, p: 0.00655), and MASEI damage (r: 0.38384, p: 0.00593). CONCLUSIONS: Serum DKK-1 levels were elevated in PsA patients and were found to be correlated with MASEI score for enthesopathy.

DKK-1 in psoriatic arthritis: Correlation with disease activity and enthesopathy / DKK-1 en artritis psoriásica: correlación con la actividad de la enfermedad y la entesopatía

Background: Psoriatic arthritis (PsA) is a complex inflammatory disease with varied clinical characteristics. A pathognomonic characteristic of PsA is enthesitis. Entheseal inflammation ultimately leads to the production of new bone (enthesophytes). Dickkopf-related protein-1 (DKK-1) is a wingless (Wnt) inhibitor that inhibits osteoblast function. Objectives: Assessment of the serum level of DKK-1 and its association with disease activity and enthesopathy in PsA patients. Methods: This observational case–control study included 50 PsA patients and 50 healthy volunteers matched for age and gender. All participants were subjected to full medical history, clinical assessment, PSA activity using Disease Activity Index for Psoriatic Arthritis (DAPSA) score, the severity and extent of psoriasis were determined by the Psoriasis Area and Severity Index (PASI). Ultrasonographic assessment of the entheses was done in accordance with the Madrid Sonographic Enthesitis Index (MASEI). Serum level of DKK-1 and correlation with disease activity and enthesopathy in PsA patients were assessed. Results: There was no significant difference between patients and controls regarding age and sex. The mean value of SPARCC index, DAPSA score and PASI score were 6.74±4.58, 33.24±15.26, and 8.35±10.93, respectively. There was significant difference between patients and controls regarding the serum levels of DKK-1 and MASEI score (p<0.0001). There was a significant positive correlation between serum DKK-1 and MASEI (r: 0.43527, p: 0.00158), MASEI inflammatory (r: 0.37958, p: 0.00655), and MASEI damage (r: 0.38384, p: 0.00593). Conclusions: Serum DKK-1 levels were elevated in PsA patients and were found to be correlated with MASEI score for enthesopathy.(AU)

Antecedentes: La artritis psoriásica (APs) es una enfermedad inflamatoria compleja con características clínicas variadas. Una característica patognomónica de la artritis psoriásica es la entesitis. La inflamación entesófila finalmente conduce a la producción de hueso nuevo (entesófitos). La proteína 1 relacionada con dickkopf (DKK-1) es un inhibidor sin alas (Wnt) que inhibe la función de los osteoblastos. Objetivos: Evaluación del nivel sérico de DKK-1 y su asociación con la actividad de la enfermedad y la entesopatía en pacientes con APs. Métodos: Este estudio observacional de casos y controles; incluyó a 50 pacientes con artritis psoriásica y 50 voluntarios sanos emparejados por edad y sexo. Todos los participantes fueron sometidos a historia clínica completa, evaluación clínica, actividad de APs utilizando la puntuación del Índice de Actividad de la Enfermedad para la Artritis Psoriásica (DAPSA), la gravedad y la extensión de la psoriasis fueron determinadas por el área de psoriasis y el índice de gravedad (PASI). La evaluación ultrasonográfica de las entesis se realizó de acuerdo con el índice de entesitis sonográfica de Madrid (MASEI). Se evaluó el nivel sérico de DKK-1 y la correlación con la actividad de la enfermedad y la entesopatía en pacientes con artritis psoriásica. Resultados: No hubo diferencias significativas entre los pacientes y los controles con respecto a la edad y el sexo. El valor medio del índice SPARCC, la puntuación DAPSA y la puntuación PASI fueron 6,74±4,58, 33,24±15,26 y 8,35±10,93 respectivamente. Hubo diferencia significativa entre pacientes y controles con respecto a los niveles séricos de DKK-1 y la puntuación MASEI (p <0,0001). Hubo correlación positiva significativa entre DKK-1 sérico y MASEI (r: 0,43527, p = 0,00158), y daño MASEI (r: 0.38384, p = 0,00593). Conclusiones: Los niveles séricos de DKK-1 se elevaron en pacientes con APs y se encontró que estaban correlacionados con la puntuación MASEI para la entesopatía.(AU)

Targeted optimum care approach for osteoporotic fragility fractures: tailored strategy based on risk stratification to reduce incidents of falls-an initiative by the Egyptian Academy of bone health based on the FLS national register.

Since falling is the third cause of chronic disability, a better understanding of the frequency, severity, and risk factors of falls across diagnostic groups is needed to design and implement customized, effective fall prevention, and management programs for these individuals, particularly those at risk of sustaining a fragility fracture. OBJECTIVE: (1) To assess the incidence of falls among osteoporotic patients with fragility fractures. (2) To evaluate the potential for stratifying the people at risk of falling in bone health setting aiming to provide targeted optimum care for them. METHODS: This was a multi-center, cross-sectional, observational study. Both men and postmenopausal women, admitted with an osteoporotic fracture (whether major osteoporosis or hip fracture), were consecutively recruited for this work and managed under Fracture Liaison Service. All the patients were assessed for their Fracture risk (FRAX), falls risk (FRAS), and sarcopenia risk (SARC-F) as well as functional disability (HAQ). Blood tests for bone profile as well as DXA scan were offered to all the patients. RESULTS: Four hundred five patients (121 males, 284 females) were included in this work. Mean age was 70.1 (SD = 9.2) years. The incidence of falls was 64.9%. The prevalence of falls was high (64.8%) in the patients presenting with major osteoporosis fractures and in those with hip fractures (61.8%). The prevalence of fragility fractures was positively correlated with HAQ score and the SARC-F score (p = 0.01 and 0.021 respectively). Falls risk score was positively correlated with FRAX score of major osteoporotic fractures, HAQ score, and SARC-F score (p = 0.01, 0.013, and 0.003 respectively). Seventy percent of the osteopenia patients who sustained fragility fracture had high falls risk and/or SARC-F score. CONCLUSION: This study highlighted the importance of falls risk stratification in osteoporotic patients presenting with fragility fractures. Identification of the patients at increased risk of falls should be a component of the standard practice.

Incidence and geographic characteristics of the population with osteoporotic hip fracture in Egypt- by the Egyptian Academy of Bone Health.

This work studies the epidemiology of hip fracture in Egypt. While the incidence of hip fracture in Egypt matches that of the Mediterranean region, there was geographic variation in osteoporotic hip fracture incidence between the north and south of Egypt. PURPOSE: To assess the incidence of hip fracture in Egypt, with special emphasis on the geographic and demographic variation among the Egyptian population. METHODS: The incidence of hip fractures treated in two Egyptian FLS centers was calculated for the period of February 2022-February 2023. Demographic information was recorded for every patient on the national register. All patients completed a baseline questionnaire, had clinical evaluation, fracture risk, falls, and sarcopenia risk assessment. A DXA scan was carried out for every patient. RESULTS: The annual incidence of low-energy hip fracture in individuals aged 40 years or more in Egypt in 2022-2023 was 123.34 per 100,000 in women and 55.19 per 100,000 in men. The incidence of hip fractures was higher in south Egypt (113.62) versus north Egypt (64.8). This was consistent for both genders. Bone mineral density was significantly (p < 0.01) lower in south Egypt at both the spine, distal forearm, as well as hip trochanters, whereas there was no significant difference between both locations in terms of the total hip and neck of the femur. Yet, falls risk, sarcopenia, as well as functional disability rates were significantly (p < 0.001) higher in the north. CONCLUSION: In Egypt, the hip fracture incidence was higher in the south compared to the north. Several modifiable factors contribute to fragility fracture risk independent of BMD, creating complex interrelationships between BMD, risk factors, and fracture risk.

Development of outcome measures for giant cell arteritis for use in clinical trials and standard practice.

BACKGROUND: Developments in outcome measures in the rheumatic diseases are promoted by the development of successful treatments. Giant cell arteritis (GCA) is a multifaceted disorder and, therefore, measurement of multiple outcomes is relevant to this illness. It is a privilege to analyze and monitor/transfer long-term patients' management outcomes particularly if the same outcomes are used in practice and in trials. OBJECTIVE: To classify the outcome measures for GCA with a discriminative ability to identify the disease activity status and response to therapy. METHODS: This study was composed of two steps, instrument design (item generation) and judgmental evidence. A panel of 13 experts was used to validate the instrument through quantitative (content validity) and qualitative (cognitive interviewing) methods. Content validity index was used to assess content validity quantitatively. RESULTS: Five items achieved high content validity where item-content validity index score was >0.79, and in the meantime achieved high content validity response score reflecting greater agreement among panel members. Through qualitative methods, items were improved until saturation was achieved. This agreed with the expert panel ranking of the items included in GCA disease outcome measures set. CONCLUSION: For daily clinical practice, outcome measures should reflect the patients' disease activity status and have to be easily assessed and recorded. The study identified composite outcome measures for GCA able to assess the disease state and monitor response to therapy. Key Points • Despite the cohort studies published in giant cell arteritis (GCA), there are no fully validated outcome measures for use in standard practice or clinical trials. • There is a gap in international standards for assessing GCA disease activity. • Identifying disease specific outcome measures is vital for monitoring response to therapy, treatment case series and therapeutic clinical trials in GCA. • This study was carried out aiming to classify the outcome measures for GCA with a discriminative ability to identify the disease activity status and response to therapy.

Osteoporosis treatment gap in patients at risk of fracture in Egypt: a multi-center, cross-sectional observational study.

Despite the wide availability of a wide variety of approved osteoporosis medications and DXA scan centers in Egypt, only a minority of patients at high risk of sustaining a fragility fracture receive treatment, even after their first fracture. Such big "treatment gap" leaves the most high-risk individuals unprotected against fragility fractures. This study provides a benchmark to monitor national trends in osteoporosis management and service uptake. PURPOSE: To assess the treatment gap among men and postmenopausal women presenting with a fragility fracture, and to analyze the characteristics and fracture risks of the patients presenting with an index fragility fracture. METHODS: This was a multi-center, cross-sectional, observational study. Both men and postmenopausal women, admitted with an osteoporotic fracture (whether major osteoporosis or hip fracture), were consecutively recruited for this work. The fracture risk was assessed based on their FRAX calculation prior to the index fracture. All the patients were assessed for their falls and sarcopenia risks. Blood tests for bone profile as well as DXA scan were offered to all the patients. RESULTS: Two hundred and thirty-six patients presenting with fragility fractures were included in this work. 70.8% were women and 29.2% were men. Mean age was 70.1 (SD = 9.2) years. Ten-year probability of fracture (without BMD) was high in 65.9% of the postmenopausal women and 40.3% of the men. 82.1% of the postmenopausal women and 100% in men identified to be eligible for osteoporosis therapy did not receive any form of osteoporosis therapy. FRAX score correlated significantly with bone mineral density assessment at both hip and spine. Falls, sarcopenia, and functional disability showed significant relation to the fracture risk. CONCLUSIONS: There is a large treatment gap in Egyptian older adults. The recent guidelines for osteoporosis management in Egypt endorsed fracture centric approach to identify people at risk. The gap appears to be related to a low rate of osteoporosis diagnosis and lack of patient education.

Prevalence of glucocorticoid-induced osteoporosis among rheumatology patients in Africa: a systematic review and meta-analysis.

The prevalence of glucocorticosteroid-induced osteoporosis (GIOP) is well established in higher income countries. There are limited studies showing a wide prevalence of GIOP in Africa. Prospective studies are needed on GIOP in African rheumatology patients to implement appropriate management algorithms. PURPOSE: The prevalence of glucocorticosteroid-induced osteoporosis (GIOP) is well established in developed countries, but little is known about GIOP in African adult patients with inflammatory rheumatic musculoskeletal diseases (RMDs). This study aimed to determine the prevalence of GIOP and osteoporotic fracture risk in African patients with inflammatory RMDs according to radiographic and bone mineral density (BMD) findings. METHODS: PubMed, Google Scholar, Scopus, and African Index Medicus were searched up to 31 December 2020. Heterogeneity was assessed using I2 statistic across the included studies. A random-effects model was applied to estimate the pooled effect size across studies. All statistical analyses were performed using STATA™ version 14 software. The study was registered with PROSPERO, number CRD42021256252. RESULTS: In this meta-analysis, a total of 7 studies with 780 participants, stratified by geographical region were included. The pooled prevalence of GIOP based on BMD data was 47.7% (95% CI 32.9-62.8) with 52.2% (95% CI 36.5-67.6) in North African countries and 15.4% (95% 1.9-45.4%) in South Africa with a high heterogeneity (I2 = 93.3%, p = 0.018). There was no data from the rest of African countries. We were unable to complete the meta-analysis of osteoporotic fractures due to the lack of available data. CONCLUSION: This study revealed that the prevalence of GIOP varies significantly in Africa. There is no information, however, for most of Africa, and further prospective studies are needed to develop context-specific GIOP preventive strategies in patients with RMDs.

Consensus Evidence-Based Clinical Practice Recommendations for the Diagnosis and Treat-To-Target Management of Osteoporosis in Chronic Kidney Disease Stages G4-G5D and Post-transplantation: An Initiative of Egyptian Academy of Bone Health.

Objective: The aim of this study was to reach a consensus on an updated version of the recommendations for the diagnosis and Treat-to-Target management of osteoporosis that is effective and safe for individuals with chronic kidney disease (CKD) G4-G5D/kidney transplant. Methods: Delphi process was implemented (3 rounds) to establish a consensus on 10 clinical domains: (1) study targets, (2) risk factors, (3) diagnosis, (4) case stratification, (5) treatment targets, (6) investigations, (7) medical management, (8) monitoring, (9) management of special groups, (10) fracture liaison service. After each round, statements were retired, modified, or added in view of the experts' suggestions, and the percent agreement was calculated. Statements receiving rates of 7-9 by more than 75% of experts' votes were considered as achieving consensus. Results: The surveys were sent to an expert panel (n = 26), of whom 23 participated in the three rounds (2 were international experts and 21 were national). Most of the participants were rheumatologists (87%), followed by nephrologists (8.7%), and geriatric physicians (4.3%). Eighteen recommendations, categorized into 10 domains, were obtained. Agreement with the recommendations (rank 7-9) ranged from 80 to 100%. Consensus was reached on the wording of all 10 clinical domains identified by the scientific committee. An algorithm for the management of osteoporosis in CKD has been suggested. Conclusion: A panel of international and national experts established a consensus regarding the management of osteoporosis in CKD patients. The developed recommendations provide a comprehensive approach to assessing and managing osteoporosis for all healthcare professionals involved in its management.

Serum interleukin-23 levels: relation to depression, anxiety, and disease activity in psoriatic arthritis patients.

OBJECTIVES: Assessment of serum levels of IL-23 in PsA patients and its correlation with depression, anxiety, and disease activity. METHODS: Eighty psoriatic arthritis (PsA) patients and eighty healthy volunteers matched for age and gender were included in this observational case-control study. All participants suspected to detailed history, clinical assessment, PsA activity using Disease Activity Index for Psoriatic Arthritis (DAPSA) score, the severity and extent of psoriasis was assessed by the Psoriasis Area and Severity Index (PASI), and ultrasonographic assessments of the entheses were examined according to the Madrid Sonographic Enthesitis Index (MASEI). Depression and anxiety were assessed by Hospital Anxiety and Depression Scale (HADS). Serum IL-23 was measured and correlated with disease activity, depression, and anxiety. RESULTS: There was no significant difference between patients and controls regarding demographic data. Thirty-six PsA patients (45%) had anxiety and 28 patients (35%) had depression, while in the control group, 16 persons (20%) had anxiety and 12 (15%) had depression, with significant differences between the 2 groups (p < 0.0001). There were significant differences in HADS anxiety and depression scores between patients and controls with significant positive correlations between HADS depression, anxiety scores and IL-23, DAPSA, PASI, and MASEI scores (p < 0.05). IL-23 was positively correlated with DAPSA, PASI, and HADS scores; we observed that interleukin 23, higher DAPSA, and PASI were independently associated with depression and anxiety. CONCLUSION: Serum interleukin-23 levels were elevated in PsA patients and were found to be correlated with depression, anxiety, and disease activity. Key Points • Psoriatic arthritis is a multidimensional disorder with psychiatric drawbacks. • Interleukin-23 is a proinflammatory cytokines that was correlated with depression and anxiety in PsA patients. • Interleukin-23 was correlated with disease activity in PsA. • Depression and anxiety were positively correlated with disease activity in PsA.

Consensus evidence-based recommendations for treat-to-target management of immunoglobulin A vasculitis.

IgA vasculitis (IgAV), formerly known as Henoch-Schönlein purpura, is the most common cause of systemic vasculitis in childhood. Given its potential life-threatening systemic complications, early and accurate diagnosis as well as management of IgAV represent a major challenge for health care professionals. This study was carried out to attain an evidence-based expert consensus on a treat-to-target management approach for IgAV using Delphi technique. The preliminary scientific committee identified a total of 16 key clinical questions according to the patient, intervention, comparison, and outcomes (PICO) approach. An evidence-based, systematic, literature review was conducted to compile evidence for the IgAV management. The core leadership team identified researchers and clinicians with expertise in IgAV management in Egypt upon which experts were gathered from different governorates and health centers across Egypt. Delphi process was implemented (two rounds) to reach a consensus. An online questionnaire was sent to expert panel (n = 26) who participated in the two rounds. After completing round 2, a total of 20 recommendation items, categorized into two sections were obtained. Agreement with the recommendations (rank 7-9) ranged from 91.7-100%. Consensus was reached (i.e. ⩾75% of respondents strongly agreed or agreed) on the wording of all the 20 clinical standards identified by the scientific committee. Algorithms for the diagnosis and management have been suggested. This was an expert, consensus recommendations for the diagnosis and treatment of IgAV and IgA vasculitic nephritis, based on best available evidence and expert opinion. The guideline presented a strategy of care with a pathway to achieve a state of remission as early as possible. PLAIN LANGUAGE SUMMARY: Given its potential life-threatening systemic complications, early and accurate diagnosis of immunoglobulin A vasculitis represents a major challenge for health care professionals. This work provided cornerstone principles for the management of the condition. Adopting PICO approach and implementing Delphi process a consensus was reached on evidence-based treat-to-target treatment recommendations. This will endorse enhancement and consistency of care of this cohort of patients in standard practice.

Juvenile lupus and serum vitamin D levels: A cross-sectional study.

BACKGROUND: Juvenile systemic lupus erythematosus (JSLE) is usually associated with vitamin D deficiency and low bone mineral density. OBJECTIVES: To evaluate serum levels of 25-OH vitamin D in JSLE patients and to correlate these findings with disease activity and bone density. METHODS: This study was conducted on 100 patients with JSLE and 100 healthy children as controls. Disease duration and SLEDAI for disease activity were evaluated. CBC, anti-dsDNA, C3,C4,24hr urinary proteins, creatinine, estimated glomerular filtration rate(e-GFR),Ca,P,PTH, 25 (OH) D levels, and bone mineral density(BMD)Z score were measured. RESULTS: There were significant differences in mean 25(OH)D concentration between patients group (19.37 ± 9.72 ng/ml) and controls 35.90 ± 9.66 ng/ml(p < 0.05), with significant difference between active and inactive patients (p < 0.05).There were significant negative correlations between serum 25(OH)D and SLEDAI (r-0.545, p 0.001), steroid dose (r-0.561, p 0.001), anti-dsDNA (r-0.685, p 0.006), 24 hr-proteinuria (r-0.738, p 0.001) and PTH (r-0.335, p 0.001), significant positive correlations between 25(OH)D and C3 (r0.617, p 0.001),C4 (r0.544, p 0.001) serum Ca (r0.424, p 0.001) and Z score (r0.561, p 0.001),with non-significant correlations between 25(OH)D and serum P and both disease & steroid duration, (p > 0.05). CONCLUSION: Vitamin D deficiency is common in JSLE, it's correlated significantly with disease activity and bone mineral density.