Belimumab-induced periungual pyogenic granulomas: A case report.

Pyogenic granuloma (PG) is a benign vascular neoformation, presenting as a painful red nodule on the skin, mucosa or nail apparatus. It is usually related to local complications such as bleedings and superinfections. The etiology of PG remains still unclear, and several triggers can lead to its formation. In case of multiple lesions, systemic conditions and drugs remain the main causes. Antineoplastic treatments, retinoids, antiretrovirals, hormones and anticonvulsants are frequently implicated in PG formation. In literature, PG has been rarely described in the course of biological treatment due to rheumatological disease. The present case report describes the development of polydactolous PGs in a 21-year-old woman with juvenile systemic lupus erythematosus (jSLE) during treatment with belimumab, a monoclonal antibody directed against BlyS. The clinical presentation, in particular the timing and the multiplicity of the lesions, and the improvement after belimumab discontinuation allowed us to consider PG as drug-induced. This case highlights the importance of considering PG as a potential complication of rheumatologic treatments.

Juvenile neuropsychiatric systemic lupus erythematosus: A specific clinical phenotype and proposal of a probability score.

OBJECTIVE: Juvenile systemic lupus erythematosus (j-SLE) is a rare chronic auto-immune disease involving several organs. Neuropsychiatric (NP) SLE (NPSLE) is frequent in j-SLE and associated with increased morbidity/mortality. Although NPSLE classification criteria exist, attributing NP features to j-SLE remains a major challenge. The study objective is to thoroughly describe j-NPSLE patients and assist in their diagnosis. METHODS: This is a 4-year retrospective monocentric study of j-SLE patients. NP events were attributed to j-SLE using standardised diagnostic criteria and multidisciplinary paediatric clinical expertise. Clinical features, brain magnetic resonance imaging (MRI)s and samples analysis including cerebrospinal fluid were assessed. A risk of j-NPSLE score was developed based on multivariable logistic regression analysis. RESULTS: Of 39 patients included, 44% were identified as having j-NPSLE. J-NPSLE diagnosis was established at the onset of j-SLE in 59% of patients. In addition to frequent kidney involvement (76%) and chilblains (65%), all j-NPSLE patients displayed psychiatric features: cognitive symptoms (82%), hallucinations (76%), depressed mood (35%), acute confused state (18%) and catatonia (12%). Neurological involvement was often mild and nonspecific, with headache (53%) in about half of the patients. The main features reported on brain MRI were nonspecific T2/FLAIR white matter hyperintensities (65%), and cerebral atrophy (88%). Upon immunosuppressive treatment, clinical improvement of NP features was observed in all j-NPSLE patients. The score developed to attribute j-NPSLE probability, guide further investigations and appropriate treatments is based on hallucinations, memory, sleep and renal involvement (Sensitivity: 0.95 Specificity: 0.85). Cerebrospinal fluid (CSF) neopterin assessment increases the score sensitivity and specificity. CONCLUSION: Physicians should carefully and systematically assess the presence of NP features at diagnosis and early stages of j-SLE. For j-NPSLE patients with predominant psychiatric features, a multidisciplinary collaboration, including psychiatrists, is essential for the diagnosis, management and follow-up.

Juvenile Neuropsychiatric Systemic Lupus Erythematosus: Identification of Novel Central Neuroinflammation Biomarkers.

INTRODUCTION: Juvenile systemic lupus erythematosus (j-SLE) is a rare chronic autoimmune disease affecting multiple organs. Ranging from minor features, such as headache or mild cognitive impairment, to serious and life-threatening presentations, j-neuropsychiatric SLE (j-NPSLE) is a therapeutic challenge. Thus, the diagnosis of NPSLE remains difficult, especially in pediatrics, with no specific biomarker of the disease yet validated. OBJECTIVES: To identify central nervous system (CNS) disease biomarkers of j-NPSLE. METHODS: A 5-year retrospective tertiary reference monocentric j-SLE study. A combination of standardized diagnostic criteria and multidisciplinary pediatric clinical expertise was combined to attribute NP involvement in the context of j-SLE. Neopterin and interferon-alpha (IFN-α) protein levels in cerebrospinal fluid (CSF) were assessed, together with routine biological and radiological investigations. RESULTS: Among 51 patients with j-SLE included, 39% presented with j-NPSLE. J-NPSLE was diagnosed at onset of j-SLE in 65% of patients. No specific routine biological or radiological marker of j-NPSLE was identified. However, CSF neopterin levels were significantly higher in active j-NPSLE with CNS involvement than in j-SLE alone (p = 0.0008). Neopterin and IFN-α protein levels in CSF were significantly higher at diagnosis of j-NPSLE with CNS involvement than after resolution of NP features (respectively p = 0.0015 and p = 0.0010) upon immunosuppressive treatment in all patients tested (n = 10). Both biomarkers correlated strongly with each other (Rs = 0.832, p < 0.0001, n = 23 paired samples). CONCLUSION: CSF IFN-α and neopterin constitute promising biomarkers useful in the diagnosis and monitoring of activity in j-NPSLE.

Prevalence of juvenile systemic lupus erythematosus in Colombia: An approach from the national health registry data.

BACKGROUND: Systemic lupus erythematosus (SLE) is a chronic, systemic, autoimmune disease of multifactorial origin. There are no previous studies in Colombia describing juvenile SLE (jSLE) prevalence, prompting this demographic description. OBJECTIVE: This study aimed for prevalence calculation and epidemiologic analysis of jSLE) in Colombian patients, ages 0-19, from 2015 to 2019. METHODS: This descriptive, cross-sectional study searched the Colombian Ministry of Health database for codes of the International Classification of Diseases, 10th revision (ICD-10) associated with jSLE to estimate the disease prevalence for the total population and for specific age groups at national and regional levels. Calculations used intercensal estimates of population based on the projections of the national statistics administrative department (DANE) from the most recent census. This paper presents a sociodemographic analysis of patients with jSLE. RESULTS: The study identified in Colombia, from 2015 to 2019, 3680 cases with jSLE as the principal diagnosis. Calculated prevalence of jSLE was 25 cases per 100,000 population, with highest frequency in ages 15-19 and females (84%), with a female:male ratio of 5.1:1. CONCLUSION: Estimated prevalence of jSLE in Colombia is at the highest limit of worldwide findings. Consistent with reports in the literature, the disease involves females more frequently than males.

Subclinical macular vessel density alterations in patients with juvenile systemic lupus erythematosus.

OBJECTIVE: The aim is to evaluate subclinical alterations of macular microvasculature in patients with juvenile systemic lupus erythematosus (JSLE). METHODS: This is a cross-sectional study of 29 eyes of 29 patients diagnosed with JSLE and 29 eyes of 29 healthy controls. The vessel density (VD) of the superficial capillary plexus (SCP), intermediate capillary plexus (ICP), deep capillary plexus (DCP), choriocapillaris (CC), and area of foveal avascular zone (FAZ) was measured using optical coherence tomography angiography (OCTA). A multiple linear regression analysis was performed to evaluate the effects of disease duration and activity on OCTA parameters. RESULTS: The VD of total (p = .007) and the superior (p = .014) and inferior (p = .004) quadrants in SCP was significantly lower in children with JSLE. The VD of total and all quadrants in ICP decreased (p = .015, p = .0045, p = .015, p = .033), except that of the temporal quadrant (p = .366). The total (p = .011) and superior quadrant (p<.01) DCP-VD showed a significant decrease in children with JSLE. The decrease in VD in the total (p = .003) and nasal quadrant (p = .017) of CC was also remarkable. No significant difference in the FAZ area was found between the two groups (p = .774). Multiple linear regression analyses adjusted for age, spherical equivalent, and intraocular pressure were conducted. No contributing factor to OCTA parameters was found. CONCLUSIONS: We demonstrated decreased VD in all layers of the retina and CC in patients with JSLE without ocular involvement. Early screening and close follow-up were recommended.

Can vitamin D be an adjuvant therapy for juvenile rheumatic diseases?

Vitamin D, known for its essential role in calcium and bone homeostasis, has multiple effects beyond the skeleton, including regulation of immunity and modulation of autoimmune processes. Several reports have shown suboptimal serum 25 hydroxyvitamin D [25(OH)D] levels in people with different inflammatory and autoimmune rheumatic conditions, and an association between 25(OH)D levels, disease activity and outcomes. Although most available data pertain to adults, insights often are extended to children. Juvenile rheumatic diseases (JRDs) are a significant health problem during growth because of their complex pathogenesis, chronic nature, multisystemic involvement, and long-term consequences. So far, there is no definitive or clear evidence to confirm the preventive or therapeutic effect of vitamin D supplementation in JRDs, because results from randomized controlled trials (RCTs) have produced inconsistent outcomes. This review aims to explore and discuss the potential role of vitamin D in treating selected JRDs. Medline/PubMed, EMBASE, and Scopus were comprehensively searched in June 2023 for any study on vitamin D supplementary role in treating the most common JRDs. We used the following keywords: "vitamin D" combined with the terms "juvenile idiopathic arthritis", "juvenile systemic scleroderma", "juvenile systemic lupus erythematosus", "juvenile inflammatory myopathies", "Behcet disease", "periodic fever syndromes" and "juvenile rheumatic diseases". Observational studies have found that serum 25(OH)D concentrations are lower in juvenile idiopathic arthritis, juvenile systemic lupus erythematosus, juvenile systemic scleroderma, Behcet disease and proinflammatory cytokine concentrations are higher. This suggests that vitamin D supplementation might be beneficial, however, current data are insufficient to confirm definitively the complementary role of vitamin D in the treatment of JRDs. Considering the high prevalence of vitamin D deficiency worldwide, children and adolescents should be encouraged to supplement vitamin D according to current recommendations. More interventional studies, especially well-designed RCTs, assessing the dose-response effect and adjuvant effect in specific diseases, are needed to determine the potential significance of vitamin D in JRDs treatment.

Care provided by nurses to patients with juvenile systemic lupus erythematosus.

OBJECTIVES: To describe the care provided by Brazilian nurses to patients with Juvenile Systemic Lupus Erythematosus (JSLE) using a self-administered questionnaire and to evaluate the possible association of demographic data and knowledge of the disease with availability of tools for diagnosis and treatment in Brazilian pediatric services. METHOD: This is a cross-sectional observational descriptive study that analyzed the care provided by Brazilian nurses to patients with JSLE based on the answers to a self-administered questionnaire. Questions included demographics of professionals, nursing consultation, usage of tools to assess disease activity, diagnostic criteria, general care, available practices, transition program, and practices needed for better care. RESULTS: A total of 111/373 (29.4%) questionnaires were completed, most professionals were female (90.1%). Hospitalization (45.9%) and poor medication adherence (27.9%) were the most reported problems, and lack of knowledge about the institutional transition process to adult care was mentioned by half of the professionals (50.5%). Comparisons of professionals on expected care of patients regarding the type of service, hospitalized patient care, and care provided to patients with JSLE did not reveal statistically significant differences (p > 0.05). Nurses who care for patients with JSLE are more likely to work in a public setting (14.5% vs. 36.8%, p = 0.048) and less likely to verify vaccination records (0.12.9% vs. 36.8%, p = 0.038). Nurses who worked in the inpatient setting with patients with JSLE were less likely to address pain concerns (11.7% vs. 61.6%, p < 0.0001) compared to nurses who didn't work with JSLE patients. However, they were more likely to discuss sunscreen use (54.9% vs. 25%, p < 0.05) and be part of a multi-disciplinary team (84.3 vs. 50%, p < 0.0001). CONCLUSIONS: This study demonstrates that the care provided by nurses to patients with JSLE does not consider all the resources available to assess the disease and occurs differently in the inpatient versus outpatient settings. Future research should address this gap in care. Lack of JSLE awareness was commonly reported among professionals, confirming the need for greater knowledge about JSLE, its treatment, and ways to improve adherence.

Cell activation, PD-1 expression and in vitro cytokine production in patients with juvenile systemic lupus erythematosus.

BACKGROUND: Juvenile systemic lupus erythematosus (jSLE) is known to be more severe and with a higher frequency of renal and central nervous system impairment when compared to systemic lupus erythematosus in adults. The study of immunological characteristics of jSLE patients might help to envisage better treatment strategies to reduce the burden of the disease. OBJECTIVE: To characterize peripheral lymphocytes, assessing activation markers, and PD-1 expression on T cells; to evaluate in vitro cytokine expression upon stimulation in jSLE patients and age-matched controls. METHODOLOGY: Eighteen jSLE patients on low disease activity and 25 matched healthy adolescents were evaluated for immune activation and PD-1 expression on peripheral blood lymphocytes by flow cytometry. Twenty-one cytokines were assessed by X-MAP technology after in vitro stimulation of peripheral blood with phytohemagglutinin. RESULTS: jSLE patients had lower numbers of CD4 T, CD8 T, B, and NK cells; higher central memory CD8 T cell percentages were noted in jSLE adolescents in comparison with controls (p = 0.014). B cells subsets showed a higher percentage of exhausted memory subset than controls (p = 0.014). The expression of PD-1 on CD4 T and CD8 T cells did not show relevant changes in jSLE adolescents. After stimulation of peripheral blood, cell supernatant of jSLE patients showed a trend to lower concentrations of IL-10 (p=0.080) and higher concentrations of IL-23 (p = 0.063) than controls. CONCLUSIONS: jSLE patients on low disease activity maintain lymphopenia of all subsets, with a B cell profile of exhaustion. Upon in vitro stimulation, peripheral blood cell supernatant showed a shift to IL-23, suggesting a role of inhibitors of this cytokine as another potential therapeutic target for those patients.

Hematologic manifestations of juvenile systemic lupus erythematosus: An emphasis on anemia.

OBJECTIVE: Anemia is common in patients with juvenile systemic lupus erythematosus (jSLE). While autoimmune hemolytic anemia (AIHA) is the only etiology included in the classification criteria, the etiology of anemia in jSLE may be diverse. We aimed to investigate the etiology of anemia in jSLE and the relationship between anemia and disease characteristics at onset and during the follow-up period. METHODS: Patients diagnosed with jSLE who met the Systemic Lupus Erythematosus International Collaborating Clinics classification criteria between January 2012 and December 2020 were retrospectively analyzed. RESULTS: Hematologic involvement was observed in 70% of the patients. Anemia was the most common cytopenia among patients (60%). Anemia of chronic disease (ACD) and AIHA were the most common etiological factors, both observed in 23% of patients. Patients with anemia had a significantly higher rate of positive ds-DNA antibody and higher erythrocyte sedimentation rate (ESH) and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores. ESH, serum ferritin, and SLEDAI scores negatively correlated with hemoglobin levels in patients with anemia. Iron deficiency was the sole etiology of new-onset anemia. Patients with new-onset anemia during the follow-up period had significantly lower hemoglobin values at onset and a higher rate of renal involvement. CONCLUSION: Anemia in jSLE is mostly AIHA and ACD, but iron deficiency is not rare. The severity of inflammation is associated with the severity of anemia. During the follow-up period, iron deficiency was the predominant cause of anemia, especially in patients with lower hemoglobin concentrations at onset and renal involvement.

Performance of 2019 EULAR/ACR classification criteria for systemic lupus erythematosus in a paediatric population-a multicentre study.

OBJECTIVES: The European League Against Rheumatism and American College of Rheumatology 2019 (EULAR/ACR-19) criteria for the diagnosis of SLE were recently published, with the stated goal of maintaining the level of sensitivity and raising the level of specificity for classification of SLE in adults. The aim of this study is to examine their application to juvenile SLE (jSLE) patients. METHODS: In this multicentre study the charts of jSLE patients from three tertiary medical centres were reviewed and compared with patients with non-jSLE diagnosis. Paediatric rheumatologists, blinded to the original diagnosis, reviewed and diagnosed all cases. Paediatric patients' clinical and laboratory data were retrospectively extracted and then examined with regard to how they met the new and old criteria. RESULTS: Included were 225 patients (112 jSLE, 113 non-SLE). When applied to juvenile SLE classification, the sensitivity of the new EULAR/ACR-19 criteria was 0.96 (95% CI: 0.9, 0.99) and the specificity was 0.89 (95% CI: 0.82, 0.94). These were comparable to the SLICC criteria. The sensitivity of the EULAR/ACR-19 criteria improves over time and was 0.83 12 months following disease onset, reaching 0.96 after longer than 24 months. CONCLUSION: Among a cohort of jSLE patients, sensitivity of the new EULAR/ACR-19 criteria was found to be high and specificity may have improved slightly compared with the SLICC-12 criteria. We support the use of the new classification criteria for paediatric patients in future jSLE studies, but it should be noted that its specificity is lower than for adults.

Sinus node disfunction in an adolescent with systemic lupus erythematosus.

Cardiac involvement in systemic lupus erythematosus (SLE) is well documented. The pericardium, myocardium and endocardium, as well as the coronary arteries, the valves and the conduction system can all be affected. While pericarditis is common, arrythmias are less frequently described.We present a 13-year-old male, who had fatigue, anorexia, weight loss, myalgias and arthralgias for four months. On physical examination, we identified bradycardia (heart rate 31-50 bpm), oral and nasal ulcers and polyarthritis. The laboratory results showed hemolytic anemia, hypocomplementemia, antinuclear and anti-dsDNA antibodies, hematuria and non-nephrotic proteinuria. Renal function was normal. Lupus nephritis class II was diagnosed by kidney biopsy. On the transthoracic echocardiogram we identified a minimal pericardial effusion, suggesting pericarditis, and, on the electrocardiogram, we detected sinus arrest with junctional rhythm, denoting sinus node dysfunction. The patient was diagnosed with juvenile SLE with cardiac, renal, musculoskeletal and hematologic involvement. Disease remission and cardiac rhythm control were obtained with steroids and mycophenolate mofetil. Currently, the patient is asymptomatic, with normal sinus rhythm.We described an adolescent with SLE who had sinus node dysfunction upon diagnosis. Other cases have been reported in adults but none in juvenile SLE. All SLE patients should have a thorough cardiac examination to promptly diagnose and treat the innumerous cardiac manifestations of this disease.

Adequate tetanus but poor diphtheria and pertussis response to a Tdap booster in adolescents with juvenile systemic lupus erythematosus.

BACKGROUND: Reports on vaccine responses in immunocompromised patients, such as juvenile systemic lupus erythematosus (jSLE), have shown highly variable results. OBJECTIVE: To compare the immune response and safety after a Tdap booster in 26 jSLE patients and 26 matched healthy adolescents.Methodology: Adverse events and disease activity were evaluated. Lymphocyte immunophenotyping was performed by flow cytometry. Tetanus, diphtheria and pertussis toxin antibodies were assessed by ELISA; whole blood was stimulated with whole cell pertussis and supernatants were assessed for cytokines by xMAP. RESULTS: Both groups showed a similar frequency of adverse events. There was no evidence of disease reactivation after Tdap booster in the jSLE cohort. Both groups showed a significant increase in antibody titers for all three antigens on D14 and D28 (p < 0.001). jSLE patients had a significantly lower increase in diphtheria titers than the control group (p = 0.007). jSLE patients had a distinct titer increase of tetanus and pertussis antibodies when compared to controls (p = 0.004 and p < 0.001, respectively). There was a lower frequency of pertussis seroconversion in the jSLE group on D14 (p = 0.009), D28 (p = 0.023), D12m (p = 0.015) and D24m (p = 0.004). Cellular immune response to Bordetella pertussis showed significantly lower levels of IFNγ (p < 0.001) and higher levels of IL10, IL12, IL21 and TNFα in jSLE patients than controls. CONCLUSIONS: jSLE patients had good response to Tdap booster dose for the tetanus antigen, but not for diphtheria and pertussis. This vaccine was safe in relation to adverse events and absence of disease reactivation.

Impact of chronic gingivitis management on the cytokine and anti-PPAD expressions in juvenile systemic lupus erythematosus: A six-month follow-up.

OBJECTIVE: To evaluate how chronic gingivitis treatment impacts the oral and circulating cytokine expressions after six-month follow-up in patients with juvenile systemic lupus erythematosus (jSLE) and also to evaluate the circulating expression of anti-Porphyromonas gingivalis peptidylarginine deiminase antibodies (anti-PPAD) before and after treatment. BACKGROUND: Juvenile systemic lupus erythematosus patients present a worse periodontal condition associated with higher gingival crevicular fluid (GCF) levels of interleukin (IL)-1ß, IL-8, granulocyte colony-stimulating factor (G-CSF), interferon-γ and monocyte chemoattractant protein (MCP)-1. MATERIALS AND METHODS: Twenty-one adolescents with jSLE (mean age: 16.2 ± 1.5 years) were recruited. Participants were rheumatologically and periodontally examined. All individuals were clinically diagnosed with gingival inflammation. Chronic gingivitis treatment consisted of supragingival scaling, prophylaxis and oral hygiene instructions. The cytokine levels were determined by bead-based multiplex assays and the anti-PPAD levels by ELISA. Gingival crevicular fluid (GCF) and serum samples were collected at baseline and 6 months after treatment. RESULTS: We observed a reduction in attachment loss, SLE Disease Activity Index (SLEDAI), IL-1ß, IL-10 and MCP-1 GCF levels, and the IL-4 and IL-5 serum levels 6 months after periodontal treatment. On the contrary, a significant increase in GCF expression of IL-4, IL-12, IL-17, IFN-γ and serum levels of anti-PPAD antibody was observed. CONCLUSION: Juvenile systemic lupus erythematosus patients seem to positively benefit from periodontal treatment by a significantly reduced CAL, a GCF reduction of pro-inflammatory cytokines and an increasing of anti-inflammatory ones. However, an increase in the GCF expression of IL-17 and the serum expression of anti-PPAD antibody 6 months after periodontal treatment might negatively affect the treatment outcome of such patients in the long term.

Biomarkers Associated with Organ-Specific Involvement in Juvenile Systemic Lupus Erythematosus.

Juvenile systemic lupus erythematosus (JSLE) is characterised by onset before 18 years of age and more severe disease phenotype, increased morbidity and mortality compared to adult-onset SLE. Management strategies in JSLE rely heavily on evidence derived from adult-onset SLE studies; therefore, identifying biomarkers associated with the disease pathogenesis and reflecting particularities of JSLE clinical phenotype holds promise for better patient management and improved outcomes. This narrative review summarises the evidence related to various traditional and novel biomarkers that have shown a promising role in identifying and predicting specific organ involvement in JSLE and appraises the evidence regarding their clinical utility, focusing in particular on renal biomarkers, while also emphasising the research into cardiovascular, haematological, neurological, skin and joint disease-related JSLE biomarkers, as well as genetic biomarkers with potential clinical applications.

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.

A rare case of gangrenous foot in juvenile systemic lupus erythematosus.

This report describes a rare case of Juvenile Systemic Lupus Erythematosus (JSLE). A young 13-year-old girl presented to the Civil Hospital Karachi on February 15, 2019 with gangrene as the only manifestation of this autoimmune disease. JSLE has several clinical manifestations such as butterfly rash, fever, joint pain, cardiac problems like pericardial infusion and neuropsychiatric disorders. However, in this case gangrene was the only presenting symptom; only laboratory investigations - anti-SSA and anti-ribosomal P protein - were suggestive of JSLE, while anti dsDNA, considered to be the most sensitive and reliable diagnostic tool for Systemic Lupus Erythematosus (SLE), was negative. Raynaud's phenomenon and gangrene have been described as rare symptoms, with gangrene occurring in only a small percentage of SLE patients. Moreover, the patient had received a blood transfusion a few months ago in Hyderabad which was suspected to be the cause of the transmission of infection which lead to polyclonal activation of lymphocytes.

Persistent Palatal Ulcerations. A Potential Manifestation of Juvenile Systemic Lupus Erythematosus.

Oral ulcerations in children and adolescents is a common occurrence and affects about 20-30% of this population. This case report describes a unique and serious autoimmune condition that presented with distinct oral findings that significantly supported the differential diagnosis of Juvenile Systemic Lupus Erythematosus in a 15 year-old female. Pediatric and general dentists should familiarize themselves with the condition to facilitate diagnosis with collaborative efforts with the medical team.

A Markov Multi-State model of lupus nephritis urine biomarker panel dynamics in children: Predicting changes in disease activity.

BACKGROUND: A urine 'biomarker panel' comprising alpha-1-acid-glycoprotein, ceruloplasmin, transferrin and lipocalin-like-prostaglandin-D synthase performs to an 'excellent' level for lupus nephritis identification in children cross-sectionally. The aim of this study was to assess if this biomarker panel predicts lupus nephritis flare/remission longitudinally. METHODS: The novel urinary biomarker panel was quantified by enzyme linked immunoabsorbant assay in participants of the United Kingdom Juvenile Systemic Lupus Erythematosus (UK JSLE) Cohort Study, the Einstein Lupus Cohort, and the South African Paediatric Lupus Cohort. Monocyte chemoattractant protein-1 and vascular cell adhesion molecule-1 were also quantified in view of evidence from other longitudinal studies. Serial urine samples were collected during routine care with detailed clinical and demographic data. A Markov Multi-State model of state transitions was fitted, with predictive clinical/biomarker factors assessed by a corrected Akaike Information Criterion (AICc) score (the better the model, the lower the AICc score). RESULTS: The study included 184 longitudinal observations from 80 patients. The homogeneous multi-state Markov model of lupus nephritis activity AICc score was 147.85. Alpha-1-acid-glycoprotein and ceruloplasmin were identified to be the best predictive factors, reducing the AICc score to 139.81 and 141.40 respectively. Ceruloplasmin was associated with the active-to-inactive transition (hazard ratio 0.60 (95% confidence interval [0.39, 0.93])), and alpha-1-acid-glycoprotein with the inactive-to-active transition (hazard ratio 1.49 (95% confidence interval [1.10, 2.02])). Inputting individual alpha-1-acid-glycoprotein/ceruloplasmin values provides 3, 6 and 12 months probabilities of state transition. CONCLUSIONS: Alpha-1-acid-glycoprotein was predictive of active lupus nephritis flare, whereas ceruloplasmin was predictive of remission. The Markov state-space model warrants testing in a prospective clinical trial of lupus nephritis biomarker led monitoring.

Serum RANKL, osteoprotegerin (OPG) and RANKL/OPG ratio in children with systemic lupus erythematosus.

BACKGROUND: Systemic lupus erythematosus (SLE) patients have lower bone mineral density (BMD) compared with healthy individuals because of general, genetic, disease and medication-related factors. The disturbance of the receptor activator of nuclear factor-κB ligand (RANKL)/osteoprotegerin (OPG) ratio has been reported to be associated with low BMD in many disorders in adults and children alike. OBJECTIVES: The objectives of this study were (i) to assess serum OPG, RANKL and RANKL/OPG ratio levels in SLE children and controls, (ii) to determine whether the cumulative glucocorticoid (CGCS) dose had any effect on the concentration of serum RANKL, OPG and RANKL/OPG ratio, and (iii) to determine the relation of these parameters to BMD. METHODS: We evaluated 50 SLE children and 50 age- and sex-matched healthy controls. RANKL and OPG were assessed in serum and compared between patients and controls. For SLE patients, a univariate followed by multivariable analysis were carried out to detect the possible predictors of the changes in RANKL, OPG and RANKL/OPG ratio levels. Lumbar BMD for all patients was assessed by dual-energy X-ray absorptiometry (DXA) scan and then correlated to different probable correlated factors. RESULTS: RANKL, OPG and RANKL/OPG ratio were significantly higher in SLE patients (p ≤ 0.001). Univariate analysis showed significant correlations of RANKL with CGCS (p ≤ 0.001) and with DXA scan z-score (p = 0.007): OPG was significantly correlated to Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score (p = 0.001) and anti-double-stranded DNA (p = 0.001), whereas RANKL/OPG was significantly correlated to duration of illness and DXA z-score (p = 0.002). The multivariable analysis showed that DXA z-score was an independent predictor of RANKL and RANKL/OPG ratio (p = 0.019 and 0.008, respectively), whereas SLEDAI score was an independent predictor of OPG levels. BMD was negatively correlated to disease duration (p = 0.008) and CGCS dose (p = 0.015), but no significant correlation has been found between BMD and cumulative SLEDAI score (p = 0.29). CONCLUSIONS: Serum RANKL/OPG ratio is elevated in Egyptian children with SLE and is considered a risk factor for reduced bone mass in these children. Other risk factors for low BMD include high CGCS dose and disease duration, supporting that osteoporosis in SLE is multifactorial.

Clinical, immunological and microbial gingival profile of juvenile systemic lupus erythematosus patients.

Periodontal disease has been associated with rheumatic diseases; however, few studies have evaluated the association with systemic lupus erythematosus (SLE), and its impact on the local inflammatory and microbial profiles. Therefore, this study evaluated the levels of several cytokines in gingival crevicular fluid (GCF) and serum from juvenile SLE (jSLE) patients with gingival inflammation, compared with controls. In addition, we assessed their subgingival microbial profile. Thirty jSLE patients and 29 systemically healthy individuals were recruited. Participants were rheumatologically and periodontally examined, and GCF, serum and intrasulcular biofilm were collected. Cytokines were analysed by bead-based multiplex assays and the bacterial profile by checkerboard DNA-DNA hybridization. jSLE patients presented higher percentages of dental plaque and bleeding than controls, as well as increased mean probing depth and attachment loss. After adjustment for multiple comparisons, GCF levels of interleukin (IL)-1ß, IL-8, granulocyte colony-stimulating factor (G-CSF), interferon-γ and monocyte chemoattractant protein-1 were significantly higher, whereas the levels of granulocyte-macrophage colony-stimulating factor were significantly lower in jSLE patients. In serum, G-CSF levels tended to be higher in jSLE patients (adjusted p-value = 0.06). Intrasulcular counts of Aggregatibacter actinomycetemcomitans were significantly higher in jSLE patients as compared with controls. We conclude that patients with jSLE present a worse periodontal condition associated with altered levels of pro-inflammatory cytokines in GCF and increased counts of A. actinomycetemcomitans in the intrasulcular biofilm.