Diagnostic and prognostic values of antikeratin antibodies (AKA) and collagen III propeptides (PIIINP) in juvenile rheumatoid arthritis

Background: The need for specific and sensitive diagnostic as well as prognostic markers for juvenile rheumatoid arthritis (JRA) has urged  scientific research toward this field.Objective: We sought to assess the diagnostic and prognostic values of serum and synovial fluid collagen III propeptides (PIIINP) and antikeratin antibodies(AKA) in JRA.Methods :Thirty-one JRA patients with a mean age of 10.6±4.2 years were enrolled in the study. They were compared to 10 SLE patients with arthritis and 15 age and sex matched healthy children as control groups. All  patients were subjected at enrollment to laboratory evaluation by CBC,  ESR, CRP, serum PIIINP and AKA. Patients with knee effusion were  subjected to AKA and PIIINP analysis in their synovial fluid samples. Clinical evaluation was done by examination of joint swelling, tenderness and limitation of movement scores. Also, radiological evaluation by plain X-ray films for hands, knees and feet using modified Larsen score (MLS) was performed. Laboratory, clinical and radiological evaluation methods were re-performed after 3 months of proper treatment. A third radiological evaluation was done one year after the first evaluation.Results: Serum PIIINP was significantly elevated in JRA patients  (12.8±8.7) ìg/L in comparison to healthy controls (7.0±1.9 ìg/L, p<0.05). However, no significant difference was observed when compared to SLE patients. Reduction of serum PIIINP was observed after 3 months of treatment with no significant difference between JRA patients (10.5±8.8 ìg/L) and the healthy controls. Synovial fluid PIIINP (56.4±6.6 ìg/L) was significantly higher than that of the serum (p<0.05). Neither serum nor synovial fluid PIIINP correlated with any of the laboratory, clinical or radiological parameters. The serum AKA positivity rate was significantly higher in JRA patients (77% at the study onset and 90% after three months) as compared to the control group (7%, p<0.001). Serum AKA values recorded a sensitivity, specificity and diagnostic efficiency in JRA patients of 77%, 93% and 83% at the study onset. These values increased after 3 months to 90%, 93% and 91% respectively. Synovial AKA levels displayed no significant difference in comparison to that of the serum.Conclusion :AKA is a specific and sensitive diagnostic marker for JRA. Meanwhile, PIIINP was significantly elevated during JRA disease activity particularly in the synovial fluid. Neither AKA nor PIIINP proved to have prognostic values in JRA.Key words: juvenile rheumatoid, arthritis, antikeratin antibodies, collagen III propeptides, SLE

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

Egyptian consensus on treat-to-target approach for osteoporosis: a clinical practice guideline from the Egyptian Academy of bone health and metabolic bone diseases

Background: This study was carried out to achieve an Egyptian expert consensus on a treat-to-target managementstrategy for osteoporosis using Delphi technique. A scientific committee identified researchers and clinicians with expertise in osteoporosis in Egypt. Delphi process was implemented (2 rounds) to establish a consensus on 15 clinical standards: (1) concept, (2) diagnosis, (3) case identification, (4) whom to treat, (5) who should treat?, (6) case stratification and intervention thresholds, (7) falls risk, (8) investigations, (9) treatment target, (10) management, (11) optimum treatment duration, (12) monitoring, (13) drug holiday, (14) osteoporosis in men, and (15) post-fracture care and fracture liaison service. Results: The surveys were sent to an expert panel (n = 25), of whom 24 participated in the two rounds. Respondents were drawn from different governorates and health centres across Egypt including the Ministry of Health. Most of the participants were rheumatologists (76%), followed by internists (8%), orthopaedic doctors (4%), rehabilitation doctors (4%), primary care (4%), and ortho-geriatrics (4%) physicians. Seventy-two recommendations, categorised into 15 sections, were obtained. Agreement with the recommendations (rank 7–9) ranged from 83.4 to 100%. Consensus was reached (i.e. ≥ 75% of respondents strongly agreed or agreed) on the wording of all 15 clinical standards identified by the scientific committee. An algorithm for the management of postmenopausal osteoporosis has been suggested. Conclusion: A wide and representative panel of experts established a consensus regarding the management of osteoporosis in Egypt. The developed guidelines provide a comprehensive approach to the assessment and management of osteoporosis for all Egyptian healthcare professionals who are involved in its management

African League Against Rheumatism (AFLAR) preliminary recommendations on the management of rheumatic diseases during the COVID-19 pandemic

Objectives To develop recommendations for the management of rheumatic and musculoskeletal diseases (RMDs) during the COVID-19 pandemic. Method A task force comprising of 25 rheumatologists from the 5 regions of the continent was formed and operated through a hub-and-spoke model with a central working committee (CWC) and 4 subgroups. The subgroups championed separate scopes of the clinical questions and formulated preliminary statements of recommendations which were processed centrally in the CWC. The CWC and each subgroup met by several virtual meetings, and two rounds of voting were conducted on the drafted statements of recommendations. Votes were online-delivered and recommendations were pruned down according to predefined criteria. Each statement was rated between 1 and 9 with 1–3, 4–6 and 7–9 representing disagreement, uncertainty and agreement, respectively. The levels of agreement on the statements were stratified as low, moderate or high according to the spread of votes. A statement was retired if it had a mean vote below 7 or a ‘low’ level of agreement. Results A total of 126 initial statements of recommendations were drafted, and these were reduced to 22 after the two rounds of voting. Conclusions The preliminary statements of recommendations will serve to guide the clinical practice of rheumatology across Africa amidst the changing practices and uncertainties in the current era of COVID-19. It is recognized that further updates to the recommendations will be needed as more evidence emerges

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

Multicenter validation of the value of BASFI and BASDAI in Chinese ankylosing spondylitis and undifferentiated spondyloarthropathy patients

The objectives of this study were to evaluate the reliability of Bath ankylosing spondylitis functional index (BASFI) and Bath ankylosing spondylitis disease activity index (BASDAI) in Chinese ankylosing spondylitis (AS) and undifferentiated spondyloarthropathy (USpA) patients. 664 AS patients by the revised New York criteria for AS and 252 USpA patients by the European Spondyloarthropathy Study Group criteria were enrolled. BASDAI and BASFI questionnaires were translated into Chinese. Participants were required to fill in BASFI and BASDAI questionnaires again after 24 h. Moreover, BASDAI and BASFI were compared in AS patients receiving Enbrel or infliximab before and after treatment. For AS group, BASDAI ICC: 0.9502 (95% CI: 0.9330–0.9502, α = 0.9702), BASFI ICC: 0.9587 (95% CI: 0.9521–0.9645, α = 0.9789). For USpA group, BASDAI ICC: 0.9530 (95% CI: 0.9402–0.9632, α = 0.9760), BASFI ICC: 0.9900 (95% CI: 0.9871–0.9922, α = 0.9950). In the AS group, disease duration, occipital wall distance, modified Schober test, chest expansion, ESR, and CRP showed significant correlation with BASDAI and BASFI (all P < 0.01). In the USpA group, onset age, ESR, and CRP were significantly correlated with BASDAI (all P < 0.05), while modified Schober test, ESR, and CRP were significantly associated with BASFI (all P < 0.05). The change in BASDAI and BASFI via Enbrel or infliximab treatment showed a significant positive correlation (P < 0.01). The two instruments have good reliability and reference value regarding the evaluation of patient’s condition and anti-TNF-α treatment response

A systematic review of interventions to improve knowledge and self-management skills concerning contraception, pregnancy and breastfeeding in people with rheumatoid arthritis

This systematic review aimed to determine the effectiveness of interventions for improving knowledge and/or self-management skills concerning contraception, pregnancy and breastfeeding in people with rheumatoid arthritis (RA). We searched four databases (MEDLINE, CINAHL, Cochrane Trials, PsycINFO) using a comprehensive search strategy. Studies were eligible if they were prospective, published in English from 2004 to 2015, included participants with RA and tested an intervention designed to improve knowledge and/or self-management skills relating to family planning, pregnancy or breastfeeding. As no studies met the latter criterion, the search strategy was expanded to include all prospective studies evaluating RA educational and/or self-management interventions. Data on study characteristics, participant characteristics and programme content were extracted to summarise the evidence base for interventions to support people with RA during their reproductive years. Expanded literature searches identified 2290 papers, of which 68 were eligible. Of these, nine papers (13 %) specifically excluded pregnant women/breastfeeding mothers or recruited only older people.Only one study (1 %) explicitly evaluated pregnancy-focused education via a motherhood decision aid, while eight studies (12 %) incorporated relevant (albeit minor) components within broader RA educational or self-management interventions. Of these, three studies provided methotrexate education in relation to conception/pregnancy/breastfeeding; three incorporated discussions on RA and relationships, impact of RA on the family or sexual advice; one provided information regarding contraception and fertility; and one issued a warning regarding use of biologic therapy in pregnancy/breastfeeding. In conclusion, information regarding family planning, pregnancy or breastfeeding represents a negligible part of published RA educational interventions, with scope to develop targeted resources

Depression and anxiety in patients with rheumatoid arthritis: prevalence rates based on a comparison of the Depression, Anxiety and Stress Scale (DASS) and the hospital, Anxiety and Depression Scale (HADS)

<p>Abstract</p> <p>Background</p> <p>While it is recognised that depression is prevalent in Rheumatoid Arthritis (RA), recent studies have also highlighted significant levels of anxiety in RA patients. This study compared two commonly used scales, the Depression Anxiety and Stress Scale (DASS) and the Hospital Anxiety and Depression Scale (HADS), in relation to their measurement range and cut points to consider the relative prevalence of both constructs, and if prevalence rates may be due to scale-specific case definition.</p> <p>Methods</p> <p>Patients meeting the criteria for RA were recruited in Leeds, UK and Sydney, Australia and asked to complete a survey that included both scales. The data was analysed using the Rasch measurement model.</p> <p>Results</p> <p>A total of 169 RA patients were assessed, with a repeat subsample, resulting in 323 cases for analysis. Both scales met Rasch model expectations. Using the 'possible+probable' cut point from the HADS, 58.3% had neither anxiety nor depression; 13.5% had anxiety only; 6.4% depression only and 21.8% had both 'possible+probable' anxiety and depression. Cut points for depression were comparable across the two scales while a lower cut point for anxiety in the DASS was required to equate prevalence.</p> <p>Conclusions</p> <p>This study provides further support for high prevalence of depression and anxiety in RA. It also shows that while these two scales provide a good indication of possible depression and anxiety, the estimates of prevalence so derived could vary, particularly for anxiety. These findings are discussed in terms of comparisons across studies and selection of scales for clinical use.</p

MUC1 Limits Helicobacter pylori Infection both by Steric Hindrance and by Acting as a Releasable Decoy

The bacterium Helicobacter pylori can cause peptic ulcer disease, gastric adenocarcinoma and MALT lymphoma. The cell-surface mucin MUC1 is a large glycoprotein which is highly expressed on the mucosal surface and limits the density of H. pylori in a murine infection model. We now demonstrate that by using the BabA and SabA adhesins, H. pylori bind MUC1 isolated from human gastric cells and MUC1 shed into gastric juice. Both H. pylori carrying these adhesins, and beads coated with MUC1 antibodies, induced shedding of MUC1 from MKN7 human gastric epithelial cells, and shed MUC1 was found bound to H. pylori. Shedding of MUC1 from non-infected cells was not mediated by the known MUC1 sheddases ADAM17 and MMP-14. However, knockdown of MMP-14 partially affected MUC1 release early in infection, whereas ADAM17 had no effect. Thus, it is likely that shedding is mediated both by proteases and by disassociation of the non-covalent interaction between the α- and β-subunits. H. pylori bound more readily to MUC1 depleted cells even when the bacteria lacked the BabA and SabA adhesins, showing that MUC1 inhibits attachment even when bacteria cannot bind to the mucin. Bacteria lacking both the BabA and SabA adhesins caused less apoptosis in MKN7 cells than wild-type bacteria, having a greater effect than deletion of the CagA pathogenicity gene. Deficiency of MUC1/Muc1 resulted in increased epithelial cell apoptosis, both in MKN7 cells in vitro, and in H. pylori infected mice. Thus, MUC1 protects the epithelium from non-MUC1 binding bacteria by inhibiting adhesion to the cell surface by steric hindrance, and from MUC1-binding bacteria by acting as a releasable decoy