Idiopathic Systemic Lupus Erythematosus Research Articles

Evaluating anchor variables and variation in meaningful score differences for PROMIS® Pediatric measures in children and adolescents living with a rheumatic disease.

Meaningful score differences (MSDs), as defined by recent FDA guidance, can improve the interpretation of outcome measure scores and score changes. Well-accepted methods for estimating MSDs typically rely on external anchor variables, but the applications of these methods are limited in children and adolescents with rheumatic diseases. This project explored multiple candidate anchors for the PROMIS® Pediatric measures of Physical Activity, Fatigue, Pain Interference, and Mobility for children with juvenile idiopathic arthritis (JIA) or systemic lupus erythematosus (SLE). Longitudinal data were extracted from the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry. Candidate anchors included patient-reported domain-specific global impressions of change (GIC) along with other parent- and clinician-reported variables. Prior to MSD estimation, the quality of the anchors was assessed using a priori criteria (correlation ≥0.30, n≥10, <10% missing). Anchors meeting criteria were used to calculate MSDs. Among 289 children with JIA and 47 with SLE, the GIC did not meet criteria inhalf of the scenarios. Other candidate anchors performed slightly better. The calculated MSDs varied by external anchor across measures, diagnoses, and direction of change (better vs worse). Many of the candidate external anchoring variables did not meet pre-specified criteria for calculating MSDs. Even for those that did, the choice of anchoring variable had a strong impact on the estimated MSD value and were different from other published values. As in adults, establishing pediatric MSDs requires selection of high-quality anchors, as changes in the variables used as anchors can impact MSD values and any subsequent score interpretations.

The association of cardiovascular disease risk with coronary artery calcification and thoracic aortic dilation: a study in idiopathic inflammatory myopathies and systemic lupus erythematosus.

We aim to explore the prevalence of coronary artery calcification (CAC) and ascending/descending thoracic aorta (AA/DA) dilation in idiopathic inflammatory myopathies (IIM) and systemic lupus erythematosus (SLE) patients, and to assess associations between cardiovascular disease (CVD) risk factors and these imaging signatures. This study recruited 151 IIM patients, 140 SLE patients, and 195 controls. The CAC and AA/DA diameters were quantified using non-gated chest CT images. The independent samples t-test or Mann-Whitney test was chosen for comparisons of continuous variables between patients and healthy controls. For categorical data, comparisons were made using the chi-square test or Fisher's exact test. Multivariate regression or Spearman's correlation analysis was employed to probe the associations between CVD risk factors and Framingham risk score (FRS) with imaging signatures. The IIM and SLE patients showed significantly higher prevalence of CAC and AA/DA dilatation (P < 0.01). Age was a risk factor for both CAC and AA/DA dilatation in all cohorts (P < 0.01). In IIM patients, the AA/DA dilatation was associated with BMI (P = 0.05). In SLE patients, CAC was associated with the elevated CRP level (P = 0.05). Without CAC, both IIM and SLE patients showed significant correlations between AA/DA diameters and FRS (P < 0.01, P < 0.01). Only in SLE patients, the interleukin-6 (IL-6) level correlated with AA/DA diameters. The IIM and SLE patients more commonly exhibit CAC and AA/DA dilation. These subclinical atherosclerosis signs are associated with traditional CVD risk factors. For AID patients without CAC, AA/DA diameters could serve as a potential biomarker for early CVD risk. Key Points • The study characterized the manifestation of subclinical atherosclerosis imaging biomarkers (CAC, AA/DA dilation) in IIM and SLE patients. • AA/DA diameters could serve as an early imaging biomarker in clinical management for IIM and SLE patients with early-onset and no CAC present.

Single center clinical analysis of macrophage activation syndrome complicating juvenile rheumatic diseases

BackgroundMacrophage activation syndrome (MAS), an example of secondary hemophagocytic lymphohistiocytosis, is a potentially fatal complication of rheumatic diseases. We aimed to study the clinical and laboratory characteristics, treatment schemes, and outcomes of different rheumatic disorders associated with MAS in children. Early warning indicators of MAS have also been investigated to enable clinicians to make a prompt and accurate diagnosis.MethodsFifty-five patients with rheumatic diseases complicated by MAS were enrolled between January 2017 and December 2022. Clinical and laboratory data were collected before disease onset, at diagnosis, and after treatment with MAS, and data were compared between patients with systemic juvenile idiopathic arthritis (sJIA), Kawasaki disease (KD), and systemic lupus erythematosus (SLE). A random forest model was established to show the importance score of each variable with a significant difference.ResultsMost (81.8%) instances of MAS occurred during the initial diagnosis of the underlying disease. Compared to the active stage of sJIA, the platelet count, erythrocyte sedimentation rate, and fibrinogen level in sJIA-MAS were significantly decreased, whereas ferritin, ferritin/erythrocyte sedimentation rate, aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, and D-dimer levels were significantly increased. Ferritin level, ferritin/erythrocyte sedimentation rate, and platelet count had the greatest predictive value for sJIA-MAS. The level of IL-18 in the sJIA-MAS group was significantly higher than in the active sJIA group, whereas IL-6 levels were significantly lower. Most patients with MAS were treated with methylprednisolone pulse combined with cyclosporine, and no deaths occurred.ConclusionsThrombocytopenia, ferritin levels, the ferritin/erythrocyte sedimentation rate, and elevated aspartate aminotransferase levels can predict the occurrence of MAS in patients with sJIA. Additionally, our analysis indicates that IL-18 plays an important role in the pathogenesis of MAS in sJIA-MAS.

#2600 Idiopathic full-house non-lupus nephropathy

Abstract Background and Aims A full-house pattern at immunofluorescence (IF) in kidney biopsies is usually associated with Lupus Nephritis (LN). However, it can be also secondary to other causes, such as infections, or it can idiopathic, without a defined origin. Idiopathic Full House non-lupus Nephropathy (iFH-N) represents a rare entity previously identified in small cohorts of patients, with different clinical features and outcomes. A limited number of the described cases developed overt systemic lupus erythematosus (SLE) during follow up, while renal outcome varied across different studies. A retrospective observational study aimed at evaluating clinical presentation and outcomes of patients with iFH-N in a Tertiary Center has been performed. Long-term renal function and development of overt SLE have been considered as main outcomes of the study. Method All native kidney biopsies performed from January 2012 to December 2022 in our Institution were considered. Full-house pattern was defined as simultaneous positivity for IgG, IgM, IgA, C3 and C1q staining at IF. Inclusion criteria were: age ≥18, full-house pattern at kidney biopsy, patients not meeting criteria for SLE diagnosis according to American College of Rheumatology (ACR) 1997 classification or Systemic Lupus International Collaborating Clinics (SLICC) 2012 criteria. Exclusion criteria: diagnosis of SLE, secondary causes of full-house pattern at kidney biopsy. We considered histological, clinical and laboratory features, performed therapies, renal function and SLE development during follow up. Results In the considered period, 2110 patients underwent a native kidney biopsy at our Institution. Of these, 91 patients had a histological finding of full-house nephropathy and were initially included for further evaluation. Of the 91 patients, 84 had received a diagnosis of SLE and were excluded, while 7 did not meet the criteria for a diagnosis of SLE. Two of these 7 were further excluded, having a full house pattern secondary to other conditions. Five patients were finally labelled as iFH-N. At kidney biopsy, all 5 included subjects had a Membranous Nephropathy, with extracapillary proliferation in 2 cases. They were all females, 4 Caucasians (80%), 1 Black (20%). At presentation, mean age was 28.2 years (range 21–40). All had impairment of kidney function, 2 of 5 had a full-blown nephrotic syndrome, 3 of 5 a nephrotic range proteinuria. Mean serum creatinine was 2.1 mg/dl (SD± 0.47), mean eGFR 35.2 ml/min/1.73 m2 (SD ±11), mean proteinuria 7.1 gr/24 h (SD ±3.3). Antinuclear antibodies (ANA) were negative in 4 of 5 patients; anti-dsDNA, anti-extractable nuclear antigens (ENAs) and antiphospholipid antibodies were negative in all subjects; slightly low C3 was present in 3 of 5 subjects. All patients received immunosuppressive therapy, including high dose intravenous (iv) steroids in association with cyclophosphamide (CYC) or mycophenolate mofetil, or Intensified B Cell Depletion Protocol (i.e. iv steroids + CYC and Rituximab). Mean follow-up from the time of kidney biopsy was 7.4 year (SD ± 2.4) (range 3–10 years). During follow up, 4 patients (80%) developed end stage renal disease (ESRD) needing renal replacement therapy, 3 of them within 24 months after presentation. The two patients with crescents had a severe prognosis, starting dialysis within 10 months after presentation. The fifth patient developed chronic kidney disease stage 4. One patient formally developed an ACR negative, SLICC positive SLE two years after presentation, with new positivity for ANA and anti-dsDNA antibodies at high titer and low C3, in addition to renal involvement. Conclusion All patients with iFH-N had similar presentation, being all young females, with a Membranous Nephropathy, nephrotic proteinuria and impairment of kidney function. They all had an aggressive form of kidney disease, refractory to different regimens of immunosuppression and with poor long-term renal outcome. Only one case developed SLE on the long term, although without systemic signs. The relationship between idiopathic full-house nephropathy and SLE remains controversial.

P061 A comparative analysis of Systemic Lupus Erythematosus, Rheumatoid arthritis and Juvenile Idiopathic Arthritis pregnancy outcomes: Results from a three-year prospective, case-controlled, single centre study of 183 patients

Abstract Background/Aims Patients with inflammatory rheumatic diseases (IRD) have an increased risk of adverse pregnancy outcomes (APO), although the comparative risk of APO in rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA) and systemic lupus erythematosus (SLE) pregnancies has not been directly compared. Therefore, this study examined pregnancy outcomes (PO) of subjects with RA, JIA, and SLE, who had all received pre-pregnancy counselling to ensure disease control, to identify whether there are any differences in APO between each individual IRD group. Pregnancy outcomes were compared with healthy pregnant subjects lacking IRD, to determine the comparative risk of APO in RA, JIA and SLE pregnancies. Methods A prospective case-controlled study was conducted at University College London Hospital from February 2018 to February 2021. A total of 183 patients were enrolled into the study, consisting of 120 pregnant patients including 60 patients with an IRD (n = 29 RA, n = 12 JIA and n = 19 SLE), 60 pregnant patients without any IRD and 63 non-pregnant patients with IRD (n = 30 RA, n = 12 JIA, n = 21 SLE). Pregnancy outcome data was obtained from all pregnant patients and the individual IRD groups’ outcomes were compared to each other and against outcomes from pregnancies without an IRD. Results Patients were predominantly Caucasian, ranging from 17-45 years of age. Of 111 reported PO, 99.09% (n = 110) resulted in a live birth (n = 27 (100.00%) RA, n = 11 (100.00%) JIA, n = 18 (94.74%) SLE versus n = 54 (100.00%) pregnancies without IRD). Overall, 5.56% (n = 1 SLE pregnancy) resulted in a spontaneous early trimester miscarriage, 6.36% (n = 7) were pre-term births (n = 3 (11.11%) RA, n = 1 (9.09%) JIA, n = 2 (11.11) SLE pregnancies versus n = 1 (1.85%) pregnancy without IRD). No stillbirths/foetal deaths were reported. Only two maternal complications were reported (n = 1 Group B strep infection, n = 1 gestational diabetes in RA pregnancies). In total six foetal complications were observed in four RA (n = 1 each for enlarged kidney, tongue tied, neonatal jaundice and Group B strep infection), n = 1 JIA (tongue tied) and n = 1 SLE (prolapsed cord) pregnancies. In relation to disease activity statuses in pregnancy, the majority of IRD pregnant patients were in remission (n = 42 (73.68%), n = 18 RA, n = 6 JIA and n = 18 SLE), 28 (49.12%) IRD patients had low disease activity (n = 8 RA, n = 2 JIA and n = 18 SLE) and nine (15.79%) had moderate/high disease activity (n = 6 RA, n = 2 JIA and n = 1 SLE). Only two (3.51%) RA patients reported disease flares during pregnancy, whereas no JIA/SLE patients experienced any flares. Conclusion This first prospective case-controlled study of RA, JIA, SLE and healthy pregnancies has identified favourable and comparable PO between IRD pregnancies with good disease control. This study highlights the importance and need for IRD pregnant women to undergo pre-pregnancy counselling and maintenance of disease control during pregnancy to enhance the chances of successful pregnancy outcomes. Disclosure H. Nguyen: None. D.A. Isenberg: Consultancies; AstraZeneca, Merck Serono, Eli Lilly, Servier, Genentech. D.J. Williams: Grants/research support; National Institute for Health Research University College London Hospitals Biomedical Research Centre. I. Giles: Grants/research support; UCB Pharma.

E55 Macrophagic activation syndrome in pediatric rheumatology: about 12 cases

Abstract Introduction Macrophage activation syndrome (MAS) is a serious clinical condition due to inappropriate stimulation of macrophages. It can be primary or secondary to underlying neoplastic, infectious or autoimmune diseases. Some pediatric inflammatory diseases are highly complicated by MAS with a higher incidence in systemic juvenile idiopathic arthritis (SJIA) or systemic lupus erythematosus (SLE). Objective We aim to highlight the features of MAS occurring in the context of pediatric inflammatory diseases according to our epidemiology and local conditions. Materials and methods This is a retrospective, descriptive and analytical study seen over a period of 4 years (from January 2019 to December 2022). The diagnosis of MAS was confirmed according to Ravelli criteria published in 2016 in the presence of mandatory persistent fever and at least four of the following abnormalities: hyperferritinemia&amp;gt; 684 ng/ml, platelet count &amp;lt; 181x103/mm3, liver cytolysis aspartate amino transferase (AST) &amp;gt; 48UI/l, triglyceridemia &amp;gt; 1.56 g/l, fibrinogenemia &amp;lt; 3.6 g/l, after having ruling out infections. The presence of hemophagocytes in the bone marrow aspiration was considered sufficient for the diagnosis in presence of long lasting fever. Results Among 70 patients followed for inflammatory disease, 12 presented with MAS. The age of the patients ranged from 8 months to 17 years during the MAS episode, with a mean age of 8 years 9 months and male: female ratio was 1.4 (7 boys/5 girls). All patients had fever and altered general condition, two had associated hemorrhagic syndrome. On clinical examination, 3 patients had splenomegaly, 3 had hepatomegaly, 2 of which combined splenomegaly and hepatomegaly. Adenopathies were reported in 3 patients. No patient had jaundice or neurological signs. Biological parameters revealed a platelet count&amp;lt; 181 000/mm3 in 58.3% (7 cases), an AST level &amp;gt; 48IU/l in 91,6% (11 cases), hypertriglyceridemia &amp;gt; 156mg/l in 69.2% (9 cases), hypofibrinogenemia &amp;lt; 360 mg/dl in 66.6% (8 cases), and hyperferritinemia &amp;gt;684 ng/ml in 91,6% (11 cases). Eight had bone marrow aspiration, which was inflammatory in 37.5%, normal in 37.5% and hemophagocytosis in 25%. In our series, MAS preceeded the diagnosis of paediatric inflammatory disease in 9 patients, and complicating the evolution of an inflammatory disease in 3 patients. The main aetiology was SLE in 58.3% (7 cases). Other causes were reported such as SJIA in 1, NLRC 4 deficiency without genetic confirmation in 1, PIMS in 1, primary immune deficiency with hypogammaglobulinemia and sarcoidosis like picture in 1 and one case of primary MAS. Recurrence was noted in 3 patients, including 1 SLE, 1 primary MAS and the NLRC 4 deficiency. All patients received bolus intravenous corticosteroids, followed by oral corticosteroids which was weaned off over a period of four months if no disease progression. Ciclosporin A was added to corticosteroids in 4 (33,3%). Biotherapy was administered to 2 patients, the first with NLRC4 deficiency, who received Tocilizumab and infliximab before responding favorably to anakinra 10 mg/kg/d. The second for a PIMS complicated by severe MAS, who received Tocilizumab once without any improvement before switching to anakinra 2 mg/kg/day for 4 months with complete remission. Conclusion and Discussion MAS is a severe syndrome, characterized by non-specific clinical and biological signs, making the diagnosis very difficult. Recently, clinical and biological criteria have been proposed according to the disease, however, the most discriminating biological parameter is hyperferritinemia. This condition must be detected and treated without delay to avoid death. Our series is characterized by the predominance of SLE as the major aetiology of MAS, by its inaugural presentation worsening the prognosis of the underlying inflammatory disease probably related to a delay in consultation, by the low percentage of hemophagocytes in bone marrow aspiration, which could be explained by a lack of knowledge on the part of our cytologists and by a low use of biotherapies.

Updated American College of Rheumatology/American Association of Hip and Knee Surgeons guideline for the perioperative management of antirheumatic medication in patients with rheumatic diseases undergoing elective total hip or total knee arthroplasty 2022

The article presents updated guidelines developed by the American College of Rheumatology and the American Association of Hip and Knee Surgeons on the perioperative treatment of patients with rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, juvenile idiopathic arthritis and systemic lupus erythematosus undergoing elective total hip or total knee arthroplasty. The perioperative use of anti-rheumatic drug therapy, including traditional disease-modi fying antirheumatic drugs, biologic agents, targeted synthetic small-molecule drugs and glucocorticoids. All recommendations are conditional and based on the results of retrospective clinical studies, which should be taken into account in decisionmaking when choosing perioperative antirheumatic therapy.

Mind the Gap: A Longitudinal Analysis of the Experiences of Adolescents and Parents in a Rheumatology Transition Clinic.

The transition from pediatric to adult care is a critical time when adolescent patients and their families face many challenges. This period can be associated with an increase in disease-related morbidity and mortality. The aim of our study is to identify gaps in transition-related care to help guide areas for improvement. Patients (14-19 years) with juvenile idiopathic arthritis or systemic lupus erythematosus and one of their parents were recruited from the McMaster Rheumatology Transition Clinic. Both were asked to complete the Mind the Gap questionnaire, a validated tool to assess experience and satisfaction with transition care in a clinic setting. The questionnaire, addressing 3 important domains of care: management of the environment, provider characteristics, and process issues, was completed twice-once based on their current clinical experience and again based on their ideal clinical encounter. Positive scores suggest current care is less than ideal; negative scores suggest current care exceeds the ideal experience. Most patients (n = 65, 68% female) had a diagnosis of juvenile idiopathic arthritis (87%). Patients identified mean gap scores between 0.2 and 0.3 for each domain of Mind the Gap, with female patients having higher gap scores compared with male patients. Parents (n = 51) identified gap scores between 0.0 and 0.3. Patients identified process issues as having the largest gap, whereas parents identified management of the environment as having the largest gap. We identified several gaps in transition clinic care relative to what patients and parents identify as ideal. These can be used to improve the rheumatology transition care that is currently being provided.

Characterization of gene alterations during Macrophage Activation Syndrome associated with central nervous system disorders

Abstract Macrophage activation syndrome (MAS) is the immense proinflammatory condition that occurs most frequently in patients with systemic juvenile idiopathic arthritis (SJIA) and systemic lupus erythematosus (SLE). An important feature of MAS is central nervous system dysfunction as evident in the form of seizures as well as altered mental status. In current study, MAS was induced in C57Bl/6 female mice by repeated injections of CpG. We performed transcriptome analysis of spleen from MAS and vehicle-treated control mice. Differential expression analysis revealed significantly altered expression of 3873 genes in mice harboring MAS. Pathway analysis indicated upregulation of heme biosynthesis while downregulation of pathways involved in 14-3-3 mediated signaling, oxytocin signaling and dopamine receptor signaling. Decreased expression of genes involved in these pathways was associated with incidents of depression, schizophrenia and Parkinsonism. The major downregulated genes were dopamine receptor D5 (DRD5), glutamate decarboxylase 1 (GAD1) and protein kinase C (PRKC) family of genes. Decreased activity of these genes are reported in depression, schizophrenia, epilepsy and Parkinson’s. At the same time, significant increase in the expression of glutamate ionotropic receptor NMDA type subunit associated protein 1 (GRINA), synuclein alpha (SNCA), glucocerebrosidase (GBA) and tubulin (TUB) genes were observed in MAS induced mice. In this study, we unravel the novel pathways as well as differential expression of genes associated with central nervous system dysfunction during episodes of MAS. (Supported by NIH grants P01AT003961, P20GM103641, R01ES030144, R01AI129788, R01AI123947 and R01AI160896 to PN and MN). Supported by NIH grants P01AT003961, P20GM103641, R01ES030144, R01AI129788, R01AI123947 and R01AI160896 to PN and MN

Clinical Significance of Different Profiles of anti-Ro Antibodies in Connective Tissue Diseases.

Anti-Ro60 and anti-Ro52 antibodies are associated with different connective tissue diseases (CTDs). However, the clinical significance of anti-Ro antibodies is not always consistent among different global regions. The aim of this study was to investigate the clinical characteristics of patients with anti-Ro antibodies. A total of 1596 inpatients with anti-Ro antibodies were included in the study. Demographic, clinical, and serological data were compared between individuals with different profiles of anti-Ro antibodies: patients with anti-Ro52 antibodies alone, patients with anti-Ro60 antibodies alone, and patients with combined anti-Ro52 and anti-Ro60 antibodies. Of the 1596 patients, 1362 (85.3%) were female, the mean age was 45.5 years, and systemic lupus erythematosus (SLE) (46.0%) and Sjogren's syndrome (SS) (19.0%) were the most common CTD diagnoses. Among the patients with anti-Ro52 antibodies alone, idiopathic inflammatory myopathy (18.8%) and SLE (17.6%) were the most common CTD diagnoses. The coexistent autoantibodies of this group were significantly lower compared with those of the other two groups, while the presence of anti-Jo1 antibodies were significantly higher compared with those of the other two groups (3.7% vs. 0.6% vs. 1.9%, p = 0.029). In addition, the patients with isolated anti-Ro52 antibodies were more likely to suffer from interstitial lung disease (35.5% vs. 11.3% vs. 13.7%, p < 10-4) and pulmonary arterial hypertension (10.1% vs. 5.3% vs. 3.6%, p = 0.001) compared with the other two groups of patients. Compared with patients with isolated anti-Ro52 or anti-Ro60 antibodies, the patients with combined anti-Ro52 and anti-Ro60 antibodies were more likely to suffer from xerophthalmia and xerostomia. Furthermore, hypocomplementemia, hyperglobulinemia, and proteinuria were particularly prevalent in patients with anti-Ro60 antibodies. Different profiles of anti-Ro antibodies were significantly associated with clinical phenotypic features in CTDs, indicating the potential diagnostic and prognostic value of these antibodies in clinical practice.

Knowledge and practices of vaccination for children with rheumatic diseases: A single-center study in China

ABSTRACT Patients with pediatric rheumatic diseases (PRDs) have higher morbidity and mortality associated with infectious diseases. Vaccination is an effective way to prevent infection. This study aimed to understand the vaccination status, vaccination-related attitudes, and adverse reactions in patients with PRDs in one of the largest Pediatric Rheumatic and Immune centers in China. A cross-sectional study using an online questionnaire was conducted among the caregivers of patients with PRDs admitted to the Children’s Hospital of Chongqing Medical University. 189 valid questionnaires were collected. The most two common PRDs in this study were juvenile idiopathic arthritis (29.6%) and systemic lupus erythematosus (19.6%). Univariate analysis and multivariate logistic regression were used to identify potential factors associated with vaccination completion among these patients. Univariate analysis suggested that the age of onset, course of the disease, treatment duration, disease duration <1 month, disease duration ≥24 months, treatment duration <1 month, use of biological agents, at least one hospitalization, whether with one-time intravenous human immunoglobulin, caregiver concerns about vaccination before or after illness, and vaccine hesitancy may affect the scheduled vaccination completion by age in patients (p < .05). Multivariate logistic regression analysis showed that the age of onset (OR, 1.013; 95% CI, 1.005–1.022; p = .002) and caregiver concerns about vaccination before illness (OR, 0.600; 95% CI, 0.428–0.840; p = .003) independently influenced patients’ completion of scheduled vaccinations. This study suggests that rheumatic disease and treatment may influence age-appropriate vaccination. Appropriate education for patients and carers may improve vaccination cognition and attitudes.

Construct validity of Patient-Reported Outcomes Measurement Information System Paediatric measures in juvenile idiopathic arthritis and systemic lupus erythematosus: cross-sectional evaluation

ObjectivesEvaluate construct validity of Patient-Reported Outcomes Measurement Information System (PROMIS) Paediatric measures of symptoms and functioning against measures of disease activity among youth with juvenile idiopathic arthritis (JIA) or systemic...

77 Case series of juvenile scleroderma from Nigeria

BackgroundThe word scleroderma means ‘hard skin’ that develops due to excessive accumulation of collagen. It is the third most frequent rheumatic disease in paediatric rheumatology after juvenile idiopathic arthritis and systemic lupus erythematosus. When it occurs in individual <16 years, it is called juvenile scleroderma. It is a rare disease that occurs in one per million children, documented to be more common in African adults with poorer survival states compared with Caucasians.Objectives To describe the clinical and laboratory characteristics of children with juvenile scleroderma seen in our clinic, thus, increasing its awareness.MethodsRetrospective review of records of three children diagnosed with juvenile scleroderma at the paediatric Rheumatology Clinic of Lagos State University Teaching Hospital(LASUTH) between May 2018 to April 2022.Results Case 1 A 12-year-old girl presented with skin tightness of the left hand and thigh of one year, contracture of the 3rd, 4th and 5th proximal interphalangeal joints, arthritis of the left wrist, skin induration of the dorsum of the left hand involving the 4th and 5th finger and extending to the wrist and skin and induration of the anterolateral aspect of the left thigh. Her blood tests showed an erythrocyte sedimentation rate (ESR) at 20 mm/h, an ANA titre of 1:2560, a negative anti-Scl 70/anti-centromere antibodies, a normal complete blood count and serum electrolytes/urea/creatinine. A diagnosis of linear scleroderma was made, the patient had prednisolone, methotrexate and folic acid, in addition to topical emollients. She improved clinically as observed during follow up visits six weeks after initiation of treatment but later defaulted from the clinic due to unknown reason. Case 2 A 4-year-old girl presented with constitutional symptoms, swollen hands and feet, sclerodactyly, narrowing of oral aperture, ulcers at tips of the fingers, inflammatory pain of the large joints, hypopigmented macules on the face, trunk, abdomen and back and also abnormal capillaroscopy. Erythrocyte sedimentation rate was 22 mm/h with normal levels of electrolytes/urea/creatinine, thrombocytosis, ANA titre of 1:640 and negative anti-centromere and anti-U1RNP antibodies. A diagnosis of diffuse systemic sclerosis was made. She started prednisolone, methotrexate, nifedipine and omeprazole and was asked to do an ECG, an Echocardiogram, a spirometry and a chest HRCT but she couldn’t afford to do these investigations due to severe financial constraints. She was clinically stable for four months until she presented at the emergency room with sudden loss of consciousness and congestive cardiac failure. She died during resuscitation attempt. Case 3 An 11-year-old girl known patient of haematology unit with sickle cell anaemia, presented with inflammatory arthritis of the small joints of the hands, elbows and knees of nine-month duration, sclerodactyly, contractures of the PIP of the fingers, narrowing of oral aperture, generalized hypopigmented macules and abnormal nailfold capillaroscopy. Investigation showed an ANA titre of 1:640, positive anti-Scl 70 antibodies, negative anti-centromere antibodies, ESR of 130 mm/h and thrombocytosis. The echocardiogram showed a normally structured heart with severe restriction on spirometry and features of interstitial lung disease on HRCT of the chest. She started mycophenolate mofetil, prednisolone and nifedipine. She later received 2 doses of rituximab due to slow clinical improvement. She is being followed up.ConclusionMost data on scleroderma are from adult studies, we reported these three cases due to the rare occurrence of scleroderma in children, thus increasing its awareness.

002 Paediatric rheumatology training: a naive subject to medical trainees in Tanzania

Abstract Background Pediatric rheumatic disorders are common and result in significant impairment in the quality of life, morbidity and mortality. Tanzania with a population of over 60 million out which children and youth (0–17 years) comprise of &amp;gt; 50% has only one paediatric rheumatologist. Given the low number of trained experts in this sub specialty, it is expected training of medical students and residents will provide adequate training in paediatric rheumatology. This survey was aimed at determining paediatric rheumatology training among medical students and residents in Tanzania. Methods This was a survey conducted among senior medical undergraduate students who had completed paediatric rotations and final year residents from medical schools in Tanzania. Survey questionnaire was administered through interview to final year medical students and final year paediatric resident’s medical schools, the questions asked included duration of rotation in paediatric for undergraduate students and duration of paediatric residency programs. Results There are 11 universities in Tanzania that offer undergraduate (UG) medical degree, and 5 of them offer residency programs for pediatrics and child health. The duration for undergraduate rotation in pediatrics varied among universities with the longest being 12 weeks and the shortest being 7 weeks. The duration for paediatric residency programs is 3 years in all the universities with an exception of one university which the program for 4 years. There were only two universities that reported to train pediatric rheumatology to undergraduate students in the country, and the topics taught to both of the universities were juvenile idiopathic arthritis. Five universities that provide undergraduate training were excluded due to absence of final year UG students. Final year residents in three out of five universities which offer paediatric residency programs reported to have trained in pediatric rheumatology. One university did not have any class session on pediatric rheumatology, and the other was excluded since there were no final year residents. Common paediatric rheumatology topics covered for residents in the three universities were juvenile idiopathic arthritis and systemic lupus erythematosus. Only one of the three universities had an extra class on dermatomyositis. Conclusion and Recommendations Pediatric rheumatology is not adequately taught to university trainees at both undergraduates and paediatric residency levels. There is a need to put emphasis on exposing all trainees in pediatric to catall common pediatric rheumatology conditions because of the severe shortage of rheumatology trained practitioners in Tanzania.

Tolerance to exercise in adolescents with rheumatic diseases taking into account systolic heart function

Aim: to determine the systolic heart function and adaptive capabilities to physical activity in adolescents with juvenile idiopathic arthritis and systemic lupus erythematosus. Materials and methods. We examined 72 adolescents with RD at the age of 10–18 (13.11 ± 0.89) years, 58 were girls and 14 were boys. The control group consisted of 46 healthy adolescents of the corresponding age (14.73 ± 0.32 years) and gender (29 girls and 17 boys). An ultrasound examination of the heart using a General Electric LOGIO V2 apparatus (USA) was performed for all patients. The six-minute walk test was performed to determine the tolerance to minimal physical activity. Before the test and after completion during the first minute of the recovery period, heart rate was calculated, blood pressure was measured and the Allgower’s index was calculated. The 6 minute walking distance was measured in meters. Results. It was found that adolescents with RD had a significant decrease in EFrv against the background of a significant increase in SVrv and MVCrv, which was accompanied by higher HR values. In patients with JIA, reliably lower EF of both ventricles of the heart was established against the background of significantly higher heart rate values and a decrease in SVlv and MVClv, while SVrv and MVCrv were significantly higher. When analyzing 6MWT indicators, the distance was significantly shorter in adolescents with RD, and the percentage of increase in heart rate after the test was higher. Allgower’s index was significantly higher before 6MWT and significantly increased after the test. In adolescents with low EFrv, there was a significant decrease in SVrv and MVCrv against the background of significantly low HR values, but the Allgower’s index after 6MWT was significantly higher. Conclusions. In adolescents with RD, while the systolic function of the left ventricle is preserved, there is a decrease in the systolic function of the right ventricle of the heart, an increase in SVrv and MVCrv on the background of an increase in heart rate. Tolerance to physical activity remains within normal limits due to a significant increase in the activity of regulatory systems. With a progressive decrease in the systolic function of the right ventricle, a decrease in its stroke and minute volumes was established, which may indicate the participation of other regulatory systems in adequate support of the circulatory system.

ЮВЕНИЛЬНЫЙ ИДИОПАТИЧЕСКИЙ АРТРИТ И СИСТЕМНАЯ КРАСНАЯ ВОЛЧАНКА В ДЕТСКОМ ВОЗРАСТЕ: ЧАСТОТА, ПРИЧИНЫ, КЛАССИФИКАЦИЯ, КЛИНИЧЕСКИЕ ПРОЯВЛЕНИЯ

Juvenile idiopathic arthritis (JIA) is one of the most common and most disabling rheumatic diseases in children. Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with unknown etiology, which is based on a genetically determined dysregulation of immunity. In recent years, the view of JIA and SLE as potentially incurable and prognostically unfavorable diseases has been revised. This is largely due to the expansion of the possibilities of early diagnosis of JIA, SLE, which allows starting active therapy at the onset of the disease, the development of a new class of basic anti-inflammatory drugs, and scientific research in the genetics of both diseases. A large number of genes associated with immune responses can, induce an autoimmune response - the leading pathogenetic link in both diseases. The article presents modern data on the possible pathogenesis, spectrum of clinical manifestations of juvenile idiopathic arthritis (JIA) and systemic lupus erythematosus (SLE) in children. A brief description of the pathological changes in JIA and SLE is given. Possible factors are considered, incl. genetic, affecting the predisposition to the disease, the process of the formation of organ damage. The issues of assessing the activity of diseases, assessing the quality of life of patients are discussed in detail.

Ограниченная склеродермия у новорожденного ребенка (случай из практики)

Scleroderma is a rare condition in pediatrics although it ranks third (after juvenile idiopathic arthritis and systemic lupus erythematosus) among rheumatic diseases in children. Congenital scleroderma is considered casuistic since only single case reports are available in publications worldwide. The etiology of congenital scleroderma remains elusive. The principal pathogenic mechanisms are vascular network impairment, immune system dysfunction with abnormal regulation of cytokine release and altered collagen synthesis with fibroblast proliferation and fibrosis. This paper describes a newborn girl with congenital localized nodular scleroderma whose clinical presentations were detected at birth. The authors discuss difficulties with the diagnosis based on clinical and routine lab and instrumental tests. The role of modern morphological studies (given the lack of specific lab tests) to diagnose scleroderma in a newborn is emphasized. Finally, this paper provides a brief review of published data on congenital scleroderma. KEYWORDS: congenital scleroderma, children, diagnostics, differential diagnosis, morphological studies. FOR CITATION: Akhmina N.I., Utkin P.S., Shalatonin M.P. et al. Localized scleroderma in a newborn (case report). Russian Journal of Woman and Child Health. 2022;5(2):169–172 (in Russ.). DOI: 10.32364/2618-8430-2022-5-2-169-172.

Особливості порушень функціонування нирок у дітей із системним червоним вовчаком та ювенільним ідіопатичним артритом

Актуальність. При системних захворюваннях сполучної тканини автоімунної природи ураження нирок в одних випадках є синдромом захворювання, а в інших — наслідком основного процесу. Мета роботи — встановити частоту та характер порушень функціонування нирок у дітей та підлітків, хворих на ювенільний ідіопатичний артрит (ЮІА) та системний червоний вовчак (СЧВ), залежно від тривалості та активності цих захворювань. Матеріали та методи. Обстежені 113 дітей у віці від 7 до 18 років, із них хворих на ЮІА — 70, 43 дитини — з СЧВ. Розподіл на групи проведений залежно від тривалості та активності захворювання. Стан функції нирок оцінювали за допомогою геморенальних проб (рівень креатиніну сироватки крові), визначення швидкості клубочкової фільтрації. Установлювали рівень протеїнурії в добовій сечі, а також вивчали концентраційну функцію нирок за допомогою аналізу сечі за Зимницьким. Статистична обробка проводилася за допомогою пакета статистичних програм Statgrafics 16.0. Результати. Так, у дітей з ЮІА при тривалості хвороби більше ніж 3 роки відбувалися зміни функції нирок, що виражалися протеїнурією, порушенням швидкості клубочкової фільтрації та зниженням концентраційної функції нирок. При вивченні частоти порушень залежно від активності патологічного процесу встановлено що у групі з 0 ст. було зниження як швидкості клубочкової фільтрації (25,0 %), так і концентраційної функції нирок (12,5 %). У групі з I ст. активності виявлені мікропротеїнурія (4,4 %), порушення швидкості клубочкової фільтрації (12,3 %) та зниження концентраційної функції нирок (6,6 %). У групі з II ст. також виявлені мікропротеїнурія (14,2 %) та певне зниження швидкості клубочкової фільтрації (14,2 %), а в групі з III ст. майже у всіх хворих зареєстровані мікропротеїнурія (66,6 %) та зниження концентраційної функції нирок (33,3 %). При вивченні функції нирок залежно від активності патологічного процесу привертали увагу приріст рівня мікропротеїнурії (р &lt; 0,01) та зниження клубочкової фільтрації в групі з III ступенем активності (р &lt; 0,01). Також установлено зростання рівня протеїнурії в групі з тривалістю захворювання понад 3 роки. Таким чином, установлено, що ураження нирок супроводжується значним зниженням клубочкової фільтрації та протеїнурією, тобто порушенням функції клубочкового апарату нирок. У хворих на СЧВ дітей із тривалістю захворювання від 1 до 3 років в 68,1 % випадків зареєстровані наявність протеїнурії та в поодиноких випадках — зміни швидкості клубочкової фільтрації. У групі дітей із тривалістю патологічного процесу понад 3 роки виявлено більш глибокі зміни функції нирок. Так, майже в усіх хворих установлена протеїнурія (90,4 %), частота зниження швидкості клубочкової фільтрації збільшилась до 19,0 %, у 14,2 % випадків встановлено зниження концентраційної функції нирок. При аналізі частоти порушень функції нирок залежно від активності СЧВ привертали увагу зростання рівня протеїнурії (р &lt; 0,05) та зниження швидкості клубочкової фільтрації (р &lt; 0,02) саме у хворих із II ступенем активності захворювання. При вивченні показників функції нирок залежно від тривалості захворювання на СЧВ установлено, що в групі з тривалістю хвороби понад 3 роки відбувається зниження швидкості клубочкової фільтрації (р &lt; 0,03), зростання рівня мікроальбумінурії (р &lt; 0,03) та зниження максимальної щільності сечі (р &lt; 0,03). При дослідженні показників функції нирок залежно від активності патологічного процесу виявлено зростання рівня мікроальбумінурії при II ступені активності (р &lt; 0,01). Таким чином, майже у третини дітей із СЧВ із тривалістю захворювання понад 3 роки та збереженням активності патологічного процесу відбувається формування ознак ураження нирок із порушенням функції як клубочкового, так і канальцевого апарату нирок, що надалі буде сприяти розвитку хронічної ниркової недостатності. Висновки. У дітей, хворих на ЮІА та на СЧВ, із тривалістю захворювання понад 3 роки при збереженні активності патологічного процесу формуються порушення функції нирок. Ознаками ураження нирок є наявність протеїнурії, зниження клубочкової фільтрації, зниження концентраційної здатності нирок.

Favorable antibody responses to human coronaviruses in children and adolescents with autoimmune rheumatic diseases

BackgroundDifferences in humoral immunity to coronaviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), between children and adults remain unexplained, and the effect of underlying immune dysfunction or suppression is unknown. Here, we sought to examine the antibody immune competence of children and adolescents with prevalent inflammatory rheumatic diseases, juvenile idiopathic arthritis (JIA), juvenile dermatomyositis (JDM), and juvenile systemic lupus erythematosus (JSLE) against the seasonal human coronavirus (HCoV)-OC43 that frequently infects this age group.MethodsSera were collected from JIA (n = 118), JDM (n = 49), and JSLE (n = 30) patients and from healthy control (n = 54) children and adolescents prior to the coronavirus disease 19 (COVID-19) pandemic. We used sensitive flow-cytometry-based assays to determine titers of antibodies that reacted with the spike and nucleoprotein of HCoV-OC43 and cross-reacted with the spike and nucleoprotein of SARS-CoV-2, and we compared them with respective titers in sera from patients with multisystem inflammatory syndrome in children and adolescents (MIS-C).FindingsDespite immune dysfunction and immunosuppressive treatment, JIA, JDM, and JSLE patients maintained comparable or stronger humoral responses than healthier peers, which was dominated by immunoglobulin G (IgG) antibodies to HCoV-OC43 spike, and harbored IgG antibodies that cross-reacted with SARS-CoV-2 spike. In contrast, responses to HCoV-OC43 and SARS-CoV-2 nucleoproteins exhibited delayed age-dependent class-switching and were not elevated in JIA, JDM, and JSLE patients, which argues against increased exposure.ConclusionsConsequently, autoimmune rheumatic diseases and their treatment were associated with a favorable ratio of spike to nucleoprotein antibodies.FundingThis work was supported by a Centre of Excellence Centre for Adolescent Rheumatology Versus Arthritis grant, 21593, UKRI funding reference MR/R013926/1, the Great Ormond Street Children’s Charity, Cure JM Foundation, Myositis UK, Lupus UK, and the NIHR Biomedical Research Centres at GOSH and UCLH. This work was supported by the Francis Crick Institute, which receives its core funding from Cancer Research UK, the UK Medical Research Council, and the Wellcome Trust.

Antifibrotic drugs in connective tissue disease-related interstitial lung disease (CTD-ILD): from mechanistic insights to therapeutic applications.

Fibrosing interstitial lung disease (ILD) is one of the most important causes of morbidity and mortality in patients with connective tissue diseases (CTDs), which include systemic sclerosis, rheumatoid arthritis, Sjögren’s syndrome, idiopathic inflammatory myositis and systemic lupus erythematosus. The treatment of CTD-ILDs is challenging due to the paucity of proven effective treatments. Recently, two antifibrotic drugs conditionally approved for use in patients with idiopathic pulmonary fibrosis, nintedanib and pirfenidone, have been trialled in CTD-ILDs based on overlapping pathological and clinical features between the two diseases. In this narrative review, we discuss the experimental evidence and clinical trials investigating the efficacy and safety of antifibrotic drugs in patients with CTD-ILDs and the potential mechanisms of action involved. Results from clinical trials suggest that nintedanib use retards lung function decline in progressive fibrotic CTD-ILDs. By contrast, the evidence for the efficacy of pirfenidone in these groups is not equally compelling. Further, well-designed randomized clinical trials are needed to evaluate the efficacy and safety of individual antifibrotic drugs in specific CTD-ILD subgroups.