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Cruz-Ávila HA, Ramírez-Alatriste F, Martínez-García M, Hernández-Lemus E. Comorbidity patterns in cardiovascular diseases: the role of life-stage and socioeconomic status. Front Cardiovasc Med 2024; 11:1215458. [PMID: 38414921 PMCID: PMC10897012 DOI: 10.3389/fcvm.2024.1215458] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2023] [Accepted: 01/29/2024] [Indexed: 02/29/2024] Open
Abstract
Cardiovascular diseases stand as a prominent global cause of mortality, their intricate origins often entwined with comorbidities and multimorbid conditions. Acknowledging the pivotal roles of age, sex, and social determinants of health in shaping the onset and progression of these diseases, our study delves into the nuanced interplay between life-stage, socioeconomic status, and comorbidity patterns within cardiovascular diseases. Leveraging data from a cross-sectional survey encompassing Mexican adults, we unearth a robust association between these variables and the prevalence of comorbidities linked to cardiovascular conditions. To foster a comprehensive understanding of multimorbidity patterns across diverse life-stages, we scrutinize an extensive dataset comprising 47,377 cases diagnosed with cardiovascular ailments at Mexico's national reference hospital. Extracting sociodemographic details, primary diagnoses prompting hospitalization, and additional conditions identified through ICD-10 codes, we unveil subtle yet significant associations and discuss pertinent specific cases. Our results underscore a noteworthy trend: younger patients of lower socioeconomic status exhibit a heightened likelihood of cardiovascular comorbidities compared to their older counterparts with a higher socioeconomic status. By empowering clinicians to discern non-evident comorbidities, our study aims to refine therapeutic designs. These findings offer profound insights into the intricate interplay among life-stage, socioeconomic status, and comorbidity patterns within cardiovascular diseases. Armed with data-supported approaches that account for these factors, clinical practices stand to be enhanced, and public health policies informed, ultimately advancing the prevention and management of cardiovascular disease in Mexico.
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Affiliation(s)
- Héctor A Cruz-Ávila
- Graduate Program in Complexity Sciences, Autonomous University of México City, México City, Mexico
- Immunology Department, National Institute of Cardiology 'Ignacio Chávez', México City, Mexico
| | | | - Mireya Martínez-García
- Immunology Department, National Institute of Cardiology 'Ignacio Chávez', México City, Mexico
| | - Enrique Hernández-Lemus
- Computational Genomics Division, National Institute of Genomic Medicine, México City, Mexico
- Center for Complexity Sciences, Universidad Nacional Autónoma de México, México City, Mexico
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Hu Y, Yuan J, Wang B, Ma L, Zha Y. Efficacy of belimumab for severe childhood-onset systemic lupus erythematosus with diffuse proliferative glomerulonephritis: A case report. Medicine (Baltimore) 2023; 102:e34800. [PMID: 37653777 PMCID: PMC10470770 DOI: 10.1097/md.0000000000034800] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2023] [Accepted: 07/27/2023] [Indexed: 09/02/2023] Open
Abstract
INTRODUCTION Therapy of childhood-onset systemic lupus erythematosus (cSLE) with drugs is unsatisfactory. Some new drugs such as belimumab and rituximab may improve the course of severe cSLE, although there are few reports on treatment efficiency for these new drugs, especially belimumab. CASE PRESENTATION Here we report on a 16-year-old girl who was diagnosed with cSLE at the age of 13. After several immunosuppressive treatments, which included high-dose steroids, hydroxychloroquine sulfate, cyclophosphamide, etc for blood system damage, she showed little clinical improvement and developed severe pericarditis. Induction treatment with a combination of intravenous high-dose steroids, methylprednisolone, and cyclophosphamide was started, but, after 55 days, the patient developed lupus encephalopathy, lung infection, and lupus nephritis. After using high-dose steroids, cyclophosphamide, plasma exchange, gamma globulin, and appropriate anti-pulmonary inflammation drugs, treatment with tacrolimus was attempted but poorly tolerated by the patient and withdrawn. Eventually, in December 2019, belimumab was initiated on an off-label basis as a last resource to treat lupus nephritis. Belimumab was well tolerated by the patient and resulted in a rapid and marked improvement in clinical symptoms and reduction in proteinuria, serum complement levels and anti-double strand DNA antibodies titer; of note, the patient developed no infectious complications. CONCLUSION Treatment with belimumab could result in prompt remission of severe cSLE with multiple organ damage without the pulmonary infection side effects for children deemed intolerant to conventional and second-line induction therapies. Belimumab should be considered as a potentially efficacious treatment in patients in severe childhood-onset systemic lupus erythematosus.
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Affiliation(s)
- Ying Hu
- Department of Nephrology, People’s Hospital of Guizhou Province, Guiyang, China
- Division of Nephrology, West China Hospital of Sichuan University, Chengdu, China
| | - Jing Yuan
- Department of Nephrology, People’s Hospital of Guizhou Province, Guiyang, China
| | - Bo Wang
- Division of Nephrology, West China Hospital of Sichuan University, Chengdu, China
| | - Liang Ma
- Division of Nephrology, West China Hospital of Sichuan University, Chengdu, China
| | - Yan Zha
- Department of Nephrology, People’s Hospital of Guizhou Province, Guiyang, China
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Kumar S, Kirubakaran N, Punnen A, Prabha R, Agarwal I. Therapeutic drug monitoring of mycophenolate mofetil for the treatment of pediatric lupus nephritis: A cross-sectional study. INDIAN JOURNAL OF RHEUMATOLOGY 2022. [DOI: 10.4103/injr.injr_130_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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Follow-up and management of serologically active clinically quiescent cases in pediatric systemic lupus erythematosus. Reumatologia 2021; 59:244-251. [PMID: 34538955 PMCID: PMC8436786 DOI: 10.5114/reum.2021.108353] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2021] [Accepted: 07/27/2021] [Indexed: 12/05/2022] Open
Abstract
Objectives Our aim is to identify the presence of serologically active clinically quiescent (SACQ) episodes in pediatric systemic lupus erythematosus (SLE) patients. We aim to identify serologic biomarkers associated with SACQ episodes and discuss risks and benefits of escalating treatments. Material and methods We evaluated 25 pediatric SLE patients, 13 of whom experienced SACQ episodes. Serologically active clinically quiescent was defined as two consecutive clinic visits without any clinical symptoms or clinical examination findings of a lupus flare with a clinical Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score of zero, but either elevated anti-ds-DNA antibodies or low complement (C3 and/or C4) levels. Results Among the 13 patients who experienced a SACQ episode, there were a total of 24 episodes, with each patient experiencing 1–4 SACQ episodes. Erythrocyte sedimentation rate (ESR) was the most commonly elevated laboratory marker in a SACQ episode, followed by low hemoglobin levels, and then elevated anti-dsDNA antibodies. Of the 17 episodes treated during a SACQ episode, 15 (88%) did not progress to a clinical flare within six months, while two did. Furthermore, of the 7 patients who were not treated during their SACQ episode, 2 (29%) continued to be SACQ without flare, whereas 5 led to a clinical flare within six months. Conclusions Serologically active clinically quiescent episodes were identified in pediatric SLE patients, suggesting that the presence of SACQ is not limited to adults with SLE. Serologic markers such as increased ESR, hemoglobin, and elevated anti-dsDNA antibodies are preliminarily associated with pediatric SACQ episodes. Treating these SACQ episodes in pediatric SLE patients was less likely to lead to a clinical flare within six months when compared to not treating (p < 0.05). More research with a larger sample size is needed to define SACQ episodes, determine the prevalence in pediatric SLE patients, and establish SACQ treatment guidelines.
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Basu K, Karmakar S, Sengupta M, Roychowdhury A, Ghosh A, Bandopadhyay M. Pediatric lupus nephritis - An evil cousin of its adult counterpart: A single-center based experience from a tertiary care hospital of Eastern India. INDIAN J PATHOL MICR 2021; 63:397-404. [PMID: 32769328 DOI: 10.4103/ijpm.ijpm_995_19] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
Context Systemic lupus erythematosus is an autoimmune multisystem disease with a high predilection for renal involvement. Lupus nephritis develops in 20% to 75% within the first two years. Presentation varies from subnephrotic proteinuria to end-stage renal disease. Aims To study clinical features, biochemical, and serological parameters and correlate with histological activity and chronicity score [modified National Institute of Health (NIH) score]. Settings and Design Retrospective, cross-sectional, single-center based study in a tertiary care hospital of Eastern India. Subjects and Methods We incuded 36 children with lupus nephritis diagnosed from February 2018 to March 2019. Laboratory data included were complete blood count (CBC), blood glucose, urine analysis, serum urea, creatinine, blood urea nitrogen (BUN), albumin, cholesterol, HBsAg, antihepatitis C virus (HCV) antibody, antistreptolysin O (ASO) titer, antinuclear antibody (ANA), myeloperoxidase antineutrophil cytoplasmic antibody (MPO ANCA), proteinase 3 antineutrophil cytoplasmic antibody (PR3 ANCA), double-stranded DNA (dsDNA), C3, and C4. Clinical parameters were age, sex, blood pressure (BP), skin lesions, arthralgia, edema, obesity. Renal biopsies examined with light microscopy, hematoxylin and eosin (H and E), periodic acid-Schiff (PAS), silver methanamine, Masson's trichrome (MT) stains. Immunofluorescence microscopy done with IgG, IgM, IgA, C3c, C1q, kappa, lambda antibodies. Statistical Analysis Used Kruskal-Wallis and χ2 tests. Results Mean age was 15.12 ± 3.49 and 12.5 ± 1.73 years for lupus nephritis (LN) with activity and LN without activity, respectively. Mean dsDNA was higher and mean C3 was lower (52.35 ± 22.21 mg/dl) in active LN. Mean 24-hour urinary protein was higher in LN without activity. Serum creatinine was raised in active LN. LN class III and IV showed higher activity than chronicity. Conclusions Pediatric LN is proliferative and more active as compared with adult counterparts. Activity scores are much higher than chronicity scores.
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Affiliation(s)
- Keya Basu
- Department of Pathology, Institute of Post Graduate Medical Education and Research, Kolkata, West Bengal, India
| | - Subhrajyoti Karmakar
- Department of Pathology, Institute of Post Graduate Medical Education and Research, Kolkata, West Bengal, India
| | - Moumita Sengupta
- Department of Pathology, Institute of Post Graduate Medical Education and Research, Kolkata, West Bengal, India
| | - Arpita Roychowdhury
- Department of Nephrology, Institute of Post Graduate Medical Education and Research, Kolkata, West Bengal, India
| | - Alakendu Ghosh
- Department of Rheumatology, Institute of Post Graduate Medical Education and Research, Kolkata, West Bengal, India
| | - Manimoy Bandopadhyay
- Director, Institute of Post Graduate Medical Education and Research, Kolkata, West Bengal, India
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Wedge E, Abrahamson E, Tudor-Williams G, Nadel S, Deal J. When water is thicker than blood: recognising a systemic cause of haemoptysis. Arch Dis Child Educ Pract Ed 2017; 102:210-219. [PMID: 27780827 DOI: 10.1136/archdischild-2015-308957] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2015] [Revised: 05/27/2016] [Accepted: 09/08/2016] [Indexed: 11/04/2022]
Abstract
The case of an 11-year-old child presenting with acute haemoptysis and breathlessness is described. The girl was Malaysian and had recently arrived in the UK. She subsequently deteriorated, developing respiratory failure. The course of the illness is described, with reference to the diagnostic process at each stage. The case demonstrates the importance of having a broad investigatory approach in acute haemoptysis.
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Affiliation(s)
- Eileen Wedge
- Department of Paediatrics, St Mary's Hospital, London, UK
| | - Ed Abrahamson
- Paediatric Emergency Medicine, Chelsea and Westminster Hospital, London, UK
| | - Gareth Tudor-Williams
- Paediatric Infectious Diseases, Department of Paediatrics, St Mary's Hospital, London, UK
| | - Simon Nadel
- Paediatric Intensive Care Unit, Department of Paediatrics, St Mary's Hospital, London, UK
| | - Jane Deal
- Paediatric Renal Medicine, Department of Paediatrics, St Mary's Hospital, London, UK
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Abstract
In systemic lupus erythematosus renal involvement is more frequent in children than in adults. Overall, 60-80% of children with systemic lupus erythematosus have urinary or renal function abnormalities early in the disease course. In 90% of patients, renal disease occurs within two years from disease onset. Clinically significant renal involvement ranges from asymptomatic urinary findings to nephrotic syndrome and renal failure. Long-term prognosis is similar to that observed in adults. Treatment aspects that are peculiar to children include drug side-effects, such as growth inhibition induced by steroids, the need to consider morbidity-related issues with respect to the very long life expectancy of patients and the problems related to the impact of disease in adolescents. The recent availability of a childhood SLE definition of improvement and the presence of large international paediatric rheumatology networks should, in the future, facilitate the implementation of controlled clinical trials devoted to paediatric SLE.
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Affiliation(s)
- F Perfumo
- Nephrology Unit, University of Genoa, Istituto G. Gaslini, Genoa, Italy
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González B, Hernández P, Olguín H, Miranda M, Lira L, Toso M, Quezada A, Norambuena X, Talesnik E, Méndez C, Navarrete C. Changes in the survival of patients with systemic lupus erythematosus in childhood: 30 years experience in Chile. Lupus 2016; 14:918-23. [PMID: 16335587 DOI: 10.1191/0961203303lu2183xx] [Citation(s) in RCA: 38] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
The objective of this study was to analyse the survival rate and cause of death in children with systemic lupus erythematosus (SLE) during the past 30 years in Chile. A retrospective analysis was performed between 1969 and 2000 on patients attending pediatric rheumatology centres in Santiago, Chile. Survival and causes of death in 31 children followed from 1969 to 1980 fulfilling the 1982 American College of Rheumatology criteria for SLE and treated with oral steroids were compared with 50 other patients who were treated with oral steroids and an aggressive treatment of IV bolus of cyclophosphamide (38 patients) and azathioprine (12 patients). Global survival at five and 10 years follow-up for the patients studied from 1969 to 1980 was 68 and 40%, respectively. During the second study period these values were significantly improved and global survival reached 95% at five years and 90% at 10 years follow-up (P, 0.05). Survival at 10 years follow-up for patients with lupus nephropathy increased from 28% (study period 1964-1980) to 86% (study period 1984-2000). Twelve children died (38%) during the 1964-1980 study period. The causes of death were six due to kidney failure, three due to infectious conditions and another three of unknown causes. During the 1980-2000 study period mortality reached 6% (three cases), two cases died of a lupus flare-up and one case due to infection. In the last three decades, we have seen an important increase in the survival of children with SLE, especially in those patients with renal involvement. Management with immunosuppressive drugs, such as IV cyclophosphamide or azathioprine has changed the prognosis in these children. These results demonstrate that our children with SLE increased their life expectancy but are now faced with new types of morbidity because of the sequelae related to the disease itself.
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Affiliation(s)
- B González
- Pediatric Rheumatology and Immunology Unit, Luis Calvo Mackenna Hospital, Santiago, Chile.
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9
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Silva CAA, Hilário MO, Febrônio MV, Oliveira SK, Terreri MT, Sacchetti SB, Sztajnbok FR, Marini R, Quintero MV, Bica BE, Pereira RM, Bonfá E, Ferriani VP, Robazzi TC, Magalhães CS. Risk factors for amenorrhea in juvenile systemic lupus erythematosus (JSLE): a Brazilian multicentre cohort study. Lupus 2016; 16:531-6. [PMID: 17670855 DOI: 10.1177/0961203307079300] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
We evaluated the prevalence and clinical associations of amenorrhea in 298 female juvenile systemic lupus erythematosus (JSLE) patients (ACR criteria) followed in 12 Brazilian Paediatric Rheumatology centres. Amenorrhea was observed in 35 patients (11.7%) with a mean duration of 7.2 ± 3.6 months. The hormones were performed in 32/35 patients and none of them had FSH and LH levels above and estradiol below the normal range according to pubertal changes. JSLE patients with amenorrhea were younger (15.04 ± 2.5 versus 17.8 ± 3.1 years; P = 0.001), and had a shorter period of time between menarche and current age (3.4 ± 2.9 versus 6.7 ± 5.4 years; P = 0.001). Interestingly, the frequency, cumulative dose, number of pulses and duration of intravenous cyclophosphamide treatment were alike in patients with and without amenorrhea ( P > 0.05). In contrast, patients with amenorrhea had significantly higher SLEDAI ( P = 0.01) and SLICC/ACR-DI ( P = 0.024) scores compared to those without this condition. Independent risk factors identified by multivariate analysis were higher SLEDAI (OR = 1.059; CI = 1.004—1.116; P = 0.034) and SLICC/ACR-DI (OR = 2.125; IC = 1.373—3.291; P = 0.001) scores. Our data suggest that in spite of immunosuppressive therapy, JSLE patients have an adequate ovarian follicular reserve and amenorrhea is particularly associated with disease activity and damage. Lupus (2007) 16, 531—536.
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Affiliation(s)
- C A A Silva
- Pediatric Rheumatology Unit, University of São Paulo, Brazil.
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Long-term outcomes with multi-targeted immunosuppressive protocol in children with severe proliferative lupus nephritis. Lupus 2015; 25:399-406. [DOI: 10.1177/0961203315615220] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2015] [Accepted: 09/30/2015] [Indexed: 11/15/2022]
Abstract
We have previously reported the one-year outcomes of 16 children with severe proliferative lupus nephritis (LN) who were treated using a multi-targeted induction protocol based on intravenous (IV) pulse methylprednisolone (MP), mycophenolate mofetil (MMF) and cyclosporine (CSA). This study examined the long-term renal outcomes of these 16 children, followed up for a median duration of 9.2 years (range 5.8–14.2 years). Primary treatment outcome was complete renal remission. Secondary outcomes included patient and renal survival as well as relapse-free and event-free survival. All patients achieved complete renal remission within 24 months (median 8.7 months, range 4.0–24.0 months). Comparing clinical and laboratory parameters at induction and last follow-up, respectively, Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score (25.4 ± 8.7 vs 0.4 ± 0.8), serum complement C3 (47 ± 21 vs 107 ± 27 mg/dL), estimated glomerular filtration rate (eGFR) (72 ± 57 vs 109.7 ± 43 ml/min/1.73m2) and urine protein (6.97 ± 7.09 vs 0.2 ± 0.02 g/day/1.73m2) improved significantly ( p < 0.05). Kaplan–Meier survival analysis showed a cumulative ten-year renal relapse-free survival of 73.3% when considering relapses with severe proteinuria >1 g/day/1.73m2. Cumulative probability that hospitalization would not be required was 93.8% at one year, and 71.4% at ten years. Our multi-targeted protocol for induction and maintenance therapy in Asian children with severe proliferative LN resulted in good long-term patient survival and renal preservation, with a good safety profile.
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Chou HH, Chen MJ, Chiou YY. Enteric-coated mycophenolate sodium in pediatric lupus nephritis: a retrospective cohort study. Clin Exp Nephrol 2015; 20:628-636. [DOI: 10.1007/s10157-015-1171-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2014] [Accepted: 09/22/2015] [Indexed: 02/04/2023]
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Batinić D, Milošević D, Čorić M, Topalović-Grković M, Jelušić M, Turudić D. Lupus nephritis in Croatian children: clinicopathologic findings and outcome. Lupus 2014; 24:307-14. [DOI: 10.1177/0961203314563133] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
We report clinical and histopathological features, treatment and outcome of 37 Croatian children with biopsy-proven lupus nephritis seen over a 30-year period. The mean age at lupus nephritis presentation was 12.11 ± 2.59 years (range 4.66–17.0). The most frequent histopathological finding was class IV (37.8%), followed by class III (35.1%), class V (16.2 %) and class II (10.8 %) lupus nephritis. Compared with other classes there were more boys among patients with class IV lupus nephritis, and hypertension, nephrotic syndrome and decreased estimated glomerular filtration rate at presentation were more common. The median histopathological activity and total scores were highest in class IV lupus nephritis patients. The mean follow-up was 7.14 ± 4.71 years, ranging from 1.1 years to 21.0 years. Kaplan–Meier estimates of patient and kidney (without renal failure) survival rates were 90.5% and 87 % at five years. The renal survival rate of class IV lupus nephritis patients was found significantly lower compared with other histological classes combined. Decreased estimated glomerular filtration rate at the time of diagnosis, class IV lupus nephritis versus other lupus nephritis classes, and high total histological score were the parameters significantly associated with adverse outcome. The therapy with cyclophosphamide showed as superior to the therapy with azathioprine.
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Affiliation(s)
- D Batinić
- Clinical Hospital Centre Zagreb, University Zagreb School of Medicine, Department of Paediatric Nephrology, Zagreb, Croatia
| | - D Milošević
- Clinical Hospital Centre Zagreb, University Zagreb School of Medicine, Department of Paediatric Nephrology, Zagreb, Croatia
| | - M Čorić
- Clinical Hospital Centre Zagreb, University Zagreb School of Medicine, Department of Pathology and Cytology, Zagreb, Croatia
| | - M Topalović-Grković
- Clinical Hospital Centre Zagreb, University Zagreb School of Medicine, Department of Anaesthesiology and Intensive Care, Zagreb, Croatia
| | - M Jelušić
- Clinical Hospital Centre Zagreb, University Zagreb School of Medicine, Department of Paediatric Rheumatology, Zagreb, Croatia
| | - D Turudić
- University Zagreb School of Medicine, Zagreb, Croatia
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Chen S, Chen H, Liu Z, Zhang H, Hu W, Tang Z, Liu Z. Pathological spectrums and renal prognosis of severe lupus patients with rapidly progressive glomerulonephritis. Rheumatol Int 2014; 35:709-17. [PMID: 25281226 DOI: 10.1007/s00296-014-3140-x] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2014] [Accepted: 09/20/2014] [Indexed: 11/30/2022]
Abstract
The objectives of the study were to investigate the pathological features and renal prognosis of severe lupus patients with rapidly progressive glomerulonephritis. One hundred and one cases of biopsy-proven severe LN with rapidly progressive glomerulonephritis (RPGN) were analyzed in this retrospective study. Another 200 severe LN patients without RPGN were randomly enrolled as a control group. Their clinicopathological data and long-term outcome were compared. There were 76 females and 25 males with an average age of 31.9 ± 14.2 years followed for a median period of 4 years. Compared with controls, patients with RPGN had shorter LN duration (p = 0.008), higher level of creatinine (p < 0.001), severe anemia (p = 0.037), heavier hematuria (p < 0.001), severe tubular injury parameters [NAG (p < 0.001), RBP (p < 0.001), C3 (p < 0.001)], higher scores of AI (p = 0.001) and CI (p = 0.004), higher proportions of glomerular sclerosis (0.033) and crescents (p < 0.001), severe tubulointerstitial lesions (p < 0.001) and interstitial inflammation (p < 0.001), lower rate of complete remission (33.9 vs 68.2 %) and higher rate of treatment failure (46.8 vs 7.9 %). The 3-, 5- and 10-year cumulative renal survival rates of RPGN and non-RPGN patients were 65.1 versus 53.9 versus 42.9 and 96.9 versus 94.9 versus 91.7 %, respectively. Multivariate analysis revealed that SCr concentration and the proportion of crescents were the most important risk factors for end-stage renal disease (ESRD) in severe LN with RPGN (p < 0.001). In conclusion, RPGN occurred in 3.6 % of LN and is associated with severe renal manifestations, serious sclerotic and crescentic glomeruli lesions, severe tubulointerstitial inflammation, atrophy and fibrosis, prominent leukocyte infiltration and worse treatment response. Multivariate analysis revealed that SCr concentration and the proportion of crescents were the most important risk factors for ESRD. 57.1 % of severe LN patients with RPGN might progress to ESRD within 10 years.
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Affiliation(s)
- Shasha Chen
- National Clinical Research Centre of Kidney Desease, Jinling Hospital, Nanjing University School of Medicine, Nanjing, 210002, China
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Ulinski T, Davourie-Salandre A, Brocheriou I, Aoun B. Immunoadsorption: a new strategy to induce remission in membranous lupus nephritis. Case Rep Nephrol Dial 2014; 4:37-41. [PMID: 24803916 PMCID: PMC4000301 DOI: 10.1159/000361014] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
Abstract
We report the case of an 11-year-old previously healthy girl who presented for microscopic hematuria and nephrotic proteinuria with normal renal function, which persisted after 6 months of steroids, angiotensin-converting enzyme inhibitors (ACEi)/angiotensin receptor blockers, hydroxychloroquine, mycophenolic acid and a low-salt diet. A serum investigation suggested lupus nephritis and a renal biopsy, performed 2 weeks after the first proteinuria detection, revealed membranous lupus nephritis. We decided to perform ten sessions of daily immunoadsorption. Proteinuria decreased significantly over these ten sessions from 8 to 0.12 g/l. After the tenth immunoadsorption session, the patient received the first rituximab (RTX) infusion leading to complete B-cell depletion. The patient was maintained on ACEi associated with mycophenolic acid and hydroxychloroquine. Three RTX reinjections were performed when CD19-positive cells reappeared in peripheral blood. Despite complete B-cell recovery and positive anti-dsDNA-Ab, the patient remained in complete remission 18 months after the initial diagnosis with negative proteinuria and a normal renal function.
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Affiliation(s)
- Tim Ulinski
- Department of Pediatric Nephrology, APHP, DHU i2B Inflammation-Immunopathology-Biotherapy, Armand-Trousseau Hospital, Paris, France ; University Pierre and Marie Curie, Tenon Hospital, APHP, Paris, France
| | - Aurélie Davourie-Salandre
- Department of Pediatric Nephrology, APHP, DHU i2B Inflammation-Immunopathology-Biotherapy, Armand-Trousseau Hospital, Paris, France ; University Pierre and Marie Curie, Tenon Hospital, APHP, Paris, France
| | - Isabelle Brocheriou
- University Pierre and Marie Curie, Tenon Hospital, APHP, Paris, France ; Department of Pathology, Tenon Hospital, APHP, Paris, France
| | - Bilal Aoun
- Department of Pediatric Nephrology, APHP, DHU i2B Inflammation-Immunopathology-Biotherapy, Armand-Trousseau Hospital, Paris, France
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Tanaka H, Watanabe S, Aizawa-Yashiro T, Oki E, Kumagai N, Tsuruga K, Ito E. Long-term tacrolimus-based immunosuppressive treatment for young patients with lupus nephritis: a prospective study in daily clinical practice. NEPHRON. CLINICAL PRACTICE 2013; 121:c165-c173. [PMID: 23327881 DOI: 10.1159/000346149] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/24/2012] [Accepted: 11/28/2012] [Indexed: 11/19/2022]
Abstract
BACKGROUND The optimal long-term treatment for lupus nephritis (LN) in pubertal patients remains to be determined. Tacrolimus (Tac) inhibits T cell activation, and is therefore expected to be effective in patients with LN. However, little has been published about the long-term efficacy and safety of Tac-based immunosuppressive treatment of young patients with LN in daily clinical practice. METHODS Nineteen consecutive patients with biopsy-proven LN were recruited for an open-label, prospective, long-term Tac-based treatment regimen. Tac was administered once daily at a dose of 3 mg as induction- or reinduction-maintenance treatment. Four patients (21%) with new-onset LN received mizoribine at a dose of 150 mg once daily in addition to Tac. Treatment outcomes were defined by the European Consensus Lupus Activity Measurement (ECLAM) index, urinary protein/creatinine ratio (Up/cr), serum creatinine and serological lupus markers (complement C3, complement hemolytic activity, CH50, and anti-dsDNA antibody titer). Data on these parameters were collected prospectively. The median follow-up was 42 months. RESULTS Baseline characteristics of the patients were as follows: mean age, 18 years; Up/cr, 0.89 ± 1.17; serum C3, 68.1 ± 23.2 mg/dl (normal, 79-152 mg/dl); serum CH50, 26.4 ± 10.5 U/ml (normal, 23-46 U/ml); serum anti-dsDNA antibody titer, 69.3 ± 67.5 IU/ml (normal, <12.0 IU/ml); serum creatinine, 0.55 ± 0.18 mg/dl, and ECLAM index, 4.6 ± 1.9. Despite gradually tapering the dose of concomitantly administered prednisolone, a marked improvement compared with baseline values was observed in all outcome measures as early as 3 months after the initiation of treatment, and the favorable changes persisted throughout the treatment period in most of the patients. Sustained improvements in the outcome measures compared with the baseline values were confirmed after a mean of 42 months of treatment: ECLAM index, 1.1 ± 1.1; serum CH50, 36.0 ± 12.8 U/ml, anti-dsDNA antibody titer, 22.5 ± 26.5 IU/ml (all p < 0.01); Up/cr ratio, 0.35 ± 0.58, and serum C3 level, 79.7 ± 17.6 mg/dl (both p < 0.05). Serum creatinine level remained within the normal range in all the study participants. Complete response was achieved in 12 patients (63%), and a partial response was achieved in 5 patients (26%). The remaining 2 patients showed no response. No serious adverse effects were observed. CONCLUSION The data suggest that long-term, relatively low-dose Tac-based immunosuppressive treatment is beneficial and has low cytotoxicity, and therefore represents an attractive option for the treatment of young patients with LN in daily clinical practice. Further studies involving a larger number of patients are needed to confirm these results.
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Affiliation(s)
- Hiroshi Tanaka
- Department of Pediatrics, Hirosaki University Hospital, Hirosaki, Japan.
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Intravenous cyclophosphamide combined with steroids in pediatric onset severe lupus nephritis. Int Urol Nephrol 2012; 45:1301-8. [PMID: 23225077 PMCID: PMC3824347 DOI: 10.1007/s11255-012-0331-9] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2012] [Accepted: 11/09/2012] [Indexed: 11/30/2022]
Abstract
Background Intravenous cyclophosphamide (IVCY) has been used to treat severe lupus nephritis (LN) for many years. Because of the wide variety of manifestations of the condition and the long-term nature of the disease, outcomes vary widely. Objective To evaluate and compare the immediate and long-term results of IVCY in pediatric onset severe LN and between patients with normal and abnormal initial renal function. Methods Patients aged <18 years who attended the Department of Pediatrics, Prince of Songkla University, diagnosed with severe LN, and who were given a 36-month IVCY course, were included. Comparison of overall survival between the two groups was assessed using Kaplan–Meier survival curves. Results 108 patients with a mean age of 12.6 ± 2.7 years were studied, with a mean follow-up time of 5.7 ± 4.3 years. 48 patients completed the IVCY course. 36 patients had abnormal renal function and 72 patients had normal renal function at the start of therapy. Both groups responded well initially to treatment; proteinuria reduced to normal levels after 1 and 2 treatments in the normal and abnormal groups, respectively, while creatinine clearance returned to normal levels after 8 treatments in the abnormal group. Overall survival was not different between the two groups; however, the abnormal renal function group had a higher crude mortality rate than the normal group (13/36 vs 10/72, p value = 0.02). At the time of analysis, some patients who had completed their IVCY course still required other therapy to control their disease activity. Conclusion Three years of IVCY treatment provided similar outcomes in both normal and abnormal renal function groups. Immediate outcomes were favorable but long-term remission was not promising.
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Tanaka H, Tsuruga K, Aizawa-Yashiro T, Watanabe S, Imaizumi T. Treatment of young patients with lupus nephritis using calcineurin inhibitors. World J Nephrol 2012; 1:177-83. [PMID: 24175257 PMCID: PMC3782217 DOI: 10.5527/wjn.v1.i6.177] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2011] [Revised: 08/13/2012] [Accepted: 09/25/2012] [Indexed: 02/06/2023] Open
Abstract
Recent advances in the management of lupus nephritis, together with earlier renal biopsy and selective use of aggressive immunosuppressive therapy, have contributed to a favorable outcome in children and adolescents with systemic lupus erythematosus (SLE). Nevertheless, we believe that a more effective and less toxic treatment is needed to attain an optimal control of the activity of lupus nephritis. Recent published papers and our experiences regarding treatment of young patients with lupus nephritis using calcineurin inhibitors are reviewed. Although it has been reported that intermittent monthly pulses of intravenous cyclophosphamide (IVCY) are effective for preserving renal function in adult patients, CPA is a potent immunosuppressive agent that induces severe toxicity, including myelo- and gonadal toxicity, and increases the risk of secondary malignancy. Thus, treatment for controlling lupus nephritis activity, especially in children and adolescents, remains challenging. Cyclosporine A (CsA) and tacrolimus (Tac) are T-cell-specific calcineurin inhibitors that prevent the activation of helper T cells, thereby inhibiting the transcription of the early activation genes of interleukin (IL)-2 and suppressing T cell-induced activation of tumor necrosis factor-α, IL-1β and IL-6. Therefore, both drugs, which we believe may be less cytotoxic, are attractive therapeutic options for young patients with lupus nephritis. Recently, a multidrug regimen of prednisolone (PDN), Tac, and mycophenolate mofetile (MMF) has been found effective and relatively safe in adult lupus nephritis. Since the mechanisms of action of MMF and Tac are probably complementary, multidrug therapy for lupus nephritis may be useful. We propose as an alternative to IVCY, a multidrug therapy with mizoribine, which acts very similarly to MMF, and Tac, which has a different mode of action, combined with PDN for pediatric-onset lupus nephritis. We also believe that a multidrug therapy including CsA and Tac may be an attractive option for young patients with SLE and lupus nephritis.
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Affiliation(s)
- Hiroshi Tanaka
- Hiroshi Tanaka, Department of School Health Science, Faculty of Education Hirosaki University, Hirosaki 036-8562, Japan
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Abdel Kader MSEM, Abd Elaziz MM, Ahmed DH. Role of serum anti-C1q antibodies as a biomarker for nephritis activity in pediatric and adolescent Egyptian female patients with SLE. ACTA ACUST UNITED AC 2012; 6:489-98. [PMID: 23480832 PMCID: PMC3581052 DOI: 10.1517/17530059.2012.715632] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
Objective To evaluate serum anti-C1q antibodies as a biomarker of systemic lupus erythematosus (SLE) flare and as a proposed noninvasive alternative to renal biopsy which is still the “gold standard” to determine renal activity in SLE. Methods Serum anti-C1q antibodies were measured in our patients (all were females), they were followed at the nephrology and pediatric nephrology units at the Faculties of Medicine of Cairo University and Misr University for science and technology (MUST). Our study included 120 patients in the pediatric and adolescent age group and they were categorized into three groups with (mean ± SD of 16.7 ± 3, 16.1 ± 2, 15.9 ± 3) respectively: Group 1 including 40 patients with SLE and active lupus nephritis; Group 2 including 40 patients with SLE and without active lupus nephritis, but with some extra renal activity mainly arthritis; and Group 3 including 40 healthy subjects. Results Anti-C1q antibodies were found to be significantly higher in patients with active lupus nephritis than those without active nephritis than control individuals with a median (range) of [27.5 (14 – 83), 9 (2.5 – 30), 7 (2 – 13)] respectively. In those with active lupus nephritis, anti-C1q was found to correlate significantly with other parameters assessing lupus nephritis activity like C3 (r = -0.33, p < 0.04), C4 (r = -0.32, p < 0.044), daily urinary protein excretion (r = 0.32, p < 0.036), renal SLEDAI (r = 0.64, p < 0.001), and activity index (r = 0.71, p < 0.001). Conclusions Anti-C1q antibodies can be used as a considerable marker for LN activity in that age group with 97.5% sensitivity and 65% specificity with the cutoff level 12 U/l. These levels are clearly higher than those for traditional markers of disease activity such as C3/C4 consumption and anti-dsDNA.
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Affiliation(s)
- Mohamed Salah Eldin Mohamed Abdel Kader
- Misr University for Science and Technology (MUST), Faculty of Medicine, Department of Pediatrics , Villa 1, Queen Zebeada Square, Mohandseen Cairo 12411 , Egypt +00201223100406 ; +0020233044431 ;
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Pereira T, Abitbol CL, Seeherunvong W, Katsoufis C, Chandar J, Freundlich M, Zilleruelo G. Three decades of progress in treating childhood-onset lupus nephritis. Clin J Am Soc Nephrol 2011; 6:2192-9. [PMID: 21799148 PMCID: PMC3359002 DOI: 10.2215/cjn.00910111] [Citation(s) in RCA: 41] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2011] [Accepted: 06/05/2011] [Indexed: 12/14/2022]
Abstract
BACKGROUND AND OBJECTIVES Childhood-onset lupus nephritis (LN) carries a worse renal prognosis compared with adults. Controlled treatment trials in children are lacking. We compared renal and patient survival in a cohort of pediatric patients followed over 3 decades. DESIGN, SETTINGS, PARTICIPANTS, & MEASUREMENTS A retrospective analysis was conducted on 138 patients with childhood-onset systemic lupus erythematosus from 1980 to 2010. The core cohort included 95 with severe LN: 28 progressed to end-stage renal disease (ESRD group) whereas 67 did not (no-ESRD group). Patients were stratified into four "eras" according to the introduction of the primary immuno-suppressive drug: era 1: triple oral therapy with corticosteroids (CS), cyclophosphamide (CYC), and azathioprine (AZA); era 2: intravenous CYC; era 3: mycophenolate mofetil (MMF) ± CYC; era 4: rituximab (RTX) ± CYC ± MMF. RESULTS Mean age at diagnosis was 12.3 ± 2.9 years with median follow-up of 5 years. Poor renal function (estimated GFR < 60 ml/min per 1.73 m(2)) and nephrotic proteinuria at diagnosis imparted a poor prognosis. Increasing proteinuria correlated with progression of kidney disease. The addition of MMF in era 3 improved 5-year renal survival from 52% to 91% and overall patient survival from 83% to 97%. African-American ethnicity was associated with significant risk for progression to ESRD whereas Hispanic ethnicity conferred an advantage. Infection and cardiovascular disease were the primary causes of patient demise. CONCLUSIONS Renal and patient survival in childhood-onset LN has improved during the past 3 decades with progressive treatment regimens. Future trials in children are very much warranted.
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Affiliation(s)
- Tanya Pereira
- Department of Pediatrics, Division of Pediatric Nephrology, Holtz Children's Hospital, University of Miami Miller School of Medicine, Miami, Florida
| | - Carolyn L. Abitbol
- Department of Pediatrics, Division of Pediatric Nephrology, Holtz Children's Hospital, University of Miami Miller School of Medicine, Miami, Florida
| | - Wacharee Seeherunvong
- Department of Pediatrics, Division of Pediatric Nephrology, Holtz Children's Hospital, University of Miami Miller School of Medicine, Miami, Florida
| | - Chryso Katsoufis
- Department of Pediatrics, Division of Pediatric Nephrology, Holtz Children's Hospital, University of Miami Miller School of Medicine, Miami, Florida
| | - Jayanthi Chandar
- Department of Pediatrics, Division of Pediatric Nephrology, Holtz Children's Hospital, University of Miami Miller School of Medicine, Miami, Florida
| | - Michael Freundlich
- Department of Pediatrics, Division of Pediatric Nephrology, Holtz Children's Hospital, University of Miami Miller School of Medicine, Miami, Florida
| | - Gastón Zilleruelo
- Department of Pediatrics, Division of Pediatric Nephrology, Holtz Children's Hospital, University of Miami Miller School of Medicine, Miami, Florida
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Gargah T, Goucha-Louzir R, Lakhoua MR. Place du mycophénolate mofétil dans la néphropathie lupique proliférative de l’enfant. Nephrol Ther 2010; 6:564-8. [DOI: 10.1016/j.nephro.2010.07.001] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2010] [Revised: 07/06/2010] [Accepted: 07/06/2010] [Indexed: 11/15/2022]
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Renal involvement in childhood-onset systemic lupus erythematosus in Egypt. Rheumatol Int 2010; 32:47-51. [DOI: 10.1007/s00296-010-1554-7] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2010] [Accepted: 07/11/2010] [Indexed: 10/19/2022]
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Mina R, Brunner HI. Pediatric lupus--are there differences in presentation, genetics, response to therapy, and damage accrual compared with adult lupus? Rheum Dis Clin North Am 2010; 36:53-80, vii-viii. [PMID: 20202591 DOI: 10.1016/j.rdc.2009.12.012] [Citation(s) in RCA: 191] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
Some complement deficiencies predispose to systemic lupus erythematosus (SLE) early in life. Currently, there are no known unique physiologic or genetic pathways that can explain the variability in disease phenotypes. Children present with more acute illness and have more frequent renal, hematologic, and central nervous system involvement compared to adults with SLE. Almost all children require corticosteroids during the course of their disease; many are treated with immunosuppressive drugs. Mortality rates remain higher with pediatric SLE. Children and adolescents accrue more damage, especially in the renal, ocular and musculoskeletal organ systems. Conversely, cardiovascular mortality is more prevalent in adults with SLE.
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Affiliation(s)
- Rina Mina
- Division of Rheumatology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, MC 4010, Cincinnati, OH 45229, USA
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An unusual case of ANA negative systemic lupus erythematosus presented with vasculitis, long-standing serositis and full-house nephropathy. Rheumatol Int 2010; 33:219-22. [PMID: 20532511 DOI: 10.1007/s00296-010-1540-0] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2010] [Accepted: 05/16/2010] [Indexed: 12/24/2022]
Abstract
Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease that may affect any organ of the body. We report here an unusual case of seronegative SLE presented as vasculitis with rash, lower gastrointestinal system bleeding and acute renal failure. The patient was a 13-year-old boy, with abdominal distention, pretibial edema, arthritis and petechia on bilateral ankles. He had deteriorated renal functions (creatinine 1.65 mg/dl), hypoalbuminemia (1.6 g/dl) and hypocomplementemia with nephrotic range proteinuria and hematuria. He developed pleural effusion and peritonitis. Serum ANA, anti dsDNA, p ANCA, c ANCA, anticardiolipin IgM and IgG titers were negative. A renal biopsy was performed which revealed diffuse proliferative glomerulonephritis with full-house staining pattern in immunofluorescent microscopic examination suggesting Class IV Lupus Nephritis. He was administered a total of six courses of monthly intravenous pulse methyl prednisolone, dipyridamole, oral cyclophosphamide followed by azothiopirine and oral prednisolone therapy. The renal functions and serum albumin levels turned normal but peritonitis persisted and disappeared after the third pulse steroid therapy. In conclusion, we presented this patient to remind the possibility of SLE in such seronegative patients with unusual findings in order to avoid the delay in the management of this disease with high mortality and morbidity if not treated. Full-house nephropathy is an important clue especially for the diagnosis of ANA negative SLE.
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Cubero Santos A, Molinos Quintana A, de la Cerda Ojeda F, Bedoya Pérez R. Presentación atípica y agresiva de lupus eritematoso sistémico en adolescente. An Pediatr (Barc) 2010; 72:442-3. [DOI: 10.1016/j.anpedi.2010.02.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2009] [Revised: 02/07/2010] [Accepted: 02/09/2010] [Indexed: 10/19/2022] Open
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Silva CA, Deen MEJ, Febrônio MV, Oliveira SK, Terreri MT, Sacchetti SB, Sztajnbok FR, Marini R, Quintero MV, Bica BE, Pereira RM, Bonfá E, Ferriani VP, Robazzi TC, Magalhães CS, Hilário MO. Hormone profile in juvenile systemic lupus erythematosus with previous or current amenorrhea. Rheumatol Int 2010; 31:1037-43. [PMID: 20306266 DOI: 10.1007/s00296-010-1389-2] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2009] [Accepted: 02/27/2010] [Indexed: 10/19/2022]
Abstract
To identify the underlying mechanism of amenorrhea in juvenile systemic lupus erythematosus (JSLE) patients, thirty-five (11.7%) JSLE patients with current or previous amenorrhea were consecutively selected among the 298 post-menarche patients followed in 12 Brazilian pediatric rheumatology centers. Pituitary gonadotrophins [follicle-stimulating hormone (FSH) and luteinizing hormone (LH)] and estradiol were evaluated in 32/35 patients, and prolactin and total testosterone in 29/35 patients. Patient's medical records were carefully reviewed according to demographic, clinical and therapeutic findings. The mean duration of amenorrhea was 7.2 ± 3.6 months. Low FSH or LH was observed in 7/32 (22%) JSLE patients and normal FSH or LH in 25 (78%). Remarkably, low levels of FSH or LH were associated with higher frequency of current amenorrhea (57% vs. 0%, P = 0.001), higher median disease activity (SLEDAI) and damage (SLICC/ACR-DI) (18 vs. 4, P = 0.011; 2 vs. 0, P = 0.037, respectively) and higher median current dose of prednisone (60 vs. 10 mg/day, P = 0.0001) compared to normal FSH or LH JSLE patients. None of them had decreased ovarian reserve and premature ovarian failure. Six of 29 (21%) patients had high levels of prolactin, and none had current amenorrhea. No correlations were observed between levels of prolactin and SLEDAI, and levels of prolactin and SLICC/ACR-DI scores (Spearman's coefficient). We have identified that amenorrhea in JSLE is associated with high dose of corticosteroids indicated for active disease due to hypothalamic-pituitary-ovary axis suppression.
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Affiliation(s)
- Clovis A Silva
- Faculdade de Medicina da Universidade de São Paulo, Rua Araioses, São Paulo, Brazil.
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Abstract
Although more commonly presenting in adulthood, approximately 15-20% of systemic lupus erythematosus (SLE) cases occur before age 16 years. Unfortunately, SLE is usually more severe when presenting in childhood, and frequently involves vital organs such as the kidney. Over the past several decades, mortality rates have dropped, largely due to earlier diagnosis, improved management of the SLE and improved general medical care to reduce infection. Treatment strategies for nephritis in children is largely adopted from experience in adults, and the recent advances in therapeutic options for adults have brought new treatment to children. However, determining efficacy is difficult due to the absence of clinical trial data. Furthermore, determination of safety in a developing child or adolescent cannot be extrapolated from adult studies. As survival has improved, numerous secondary complications have emerged, including early atherosclerosis. As for adults with SLE, it is generally accepted that atherogenesis in SLE results from both disease- and treatment-related factors. Most surprising is that persons with childhood-onset SLE can develop myocardial ischaemia as early as 20-30 years of age. Better understanding of the pathogenesis and development of preventative strategies is needed to ensure that these young people do not succumb to atherosclerosis instead of to SLE.
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Affiliation(s)
- Emily von Scheven
- Pediatric Rheumatology, University of California, San Francisco, CA 94143, USA.
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Baskin E, Ozen S, Cakar N, Bayrakci US, Demirkaya E, Bakkaloglu A. The use of low-dose cyclophosphamide followed by AZA/MMF treatment in childhood lupus nephritis. Pediatr Nephrol 2010; 25:111-117. [PMID: 19727839 DOI: 10.1007/s00467-009-1291-x] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2009] [Revised: 06/22/2009] [Accepted: 06/23/2009] [Indexed: 10/20/2022]
Abstract
Cyclophosphamide (CYC) has been the landmark in the treatment of lupus nephritis. However, long-term treatment with CYC is associated with significant side effects. We aimed to evaluate the efficacy of short-term intravenous (IV) CYC treatment as a remission induction treatment followed by azathioprine (AZA) or mycophenolate mofetil (MMF) as a maintenance treatment. Twenty patients (18 girls) with biopsy-proven class III (5) and IV (15) lupus nephritis were included in to the study. Detailed clinical and laboratory data and patient outcomes were evaluated. All patients received three methylprednisolone (MP) IV pulses, followed by oral prednisone 0.5-1 mg/kg per day and one IV pulse of CYC per month for 6 months. Azathioprine was started as a remission-maintaining treatment. In ten of 20 patients, treatment was switched to MMF. The mean age at the time of diagnosis was 16.11 +/- 3.49 years, and the mean duration of follow-up was 49.6 +/- 27 months. Fourteen patients (70%) had complete remission, three (15%) had partial remission, one (5%) continued to have active disease, and two (10%) progressed to end-stage renal disease. Nine of the patients (45%) with complete remission had received AZA, and switching to MMF increased complete remission rate (additional five patients; 25%). In conclusion, short-term (6-month) IV bolus CYC treatment followed by AZA is a safe and effective treatment in children with severe lupus nephritis, and using MMF increases remission rate in resistant cases.
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Affiliation(s)
- Esra Baskin
- Department of Pediatric Nephrology, Baskent University, 6.cadde 72/3, Bahcelievler, 06 490 Ankara, Turkey.
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Hobbs DJ, Barletta GM, Rajpal JS, Rajpal MN, Weismantel DP, Birmingham JD, Bunchman TE. Severe paediatric systemic lupus erythematosus nephritis--a single-centre experience. Nephrol Dial Transplant 2009; 25:457-63. [PMID: 19755473 DOI: 10.1093/ndt/gfp481] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Abstract
BACKGROUND Paediatric patients with systemic lupus erythematosus (SLE) often have severe presentations including lupus nephritis (LN). Few paediatric studies have evaluated the anticardiolipin antibody (aCL) and renal histology. The purpose of this study was to evaluate clinicopathologic features, including aCL, short-term clinical and renal histologic outcomes of paediatric patients with new-onset SLE nephritis. METHODS We conducted a single centre, retrospective inception cohort study. Charts were reviewed at presentation (initial renal biopsy), 6-month (follow-up biopsy) and 12-month follow-up. RESULTS The population consisted of 21 patients (median age, 14.5 years): 19/21 were female, 6/21 African American, 3/21 Asian, 9/21 Caucasian and 3/21 Hispanic. At presentation, 19/21 had elevated aCL, 15/21 hypertensive, 12/21 nephrotic and 7/21 required haemodialysis (HD)-2/7 HD patients had thrombotic microangiopathy, 1/7 crescentic glomerulonephritis. Two patients had thromboembolism: both had aCL, were taking oral contraceptives and required HD, one was nephrotic and the other had elevated lupus anticoagulant. Initial biopsies revealed 6/21 ISN/RPS class II nephritis, 3/21 class III, 7/21 class IV and 5/21 class V. Treatment consisted of methylprednisolone, corticosteroids, cyclophosphamide or mycophenolate mofetil. Follow-up biopsies revealed 12/13 to have improved histology. Indication for a follow-up biopsy was severe illness at presentation. At 12-month follow-up, no patients were nephrotic (P < 0.001) or required HD (P < 0.001), and 3/14 had elevated aCL (P < 0.001). CONCLUSION Elevated aCL, hypertension, nephrotic syndrome and need for HD were common presentations among our paediatric SLE nephritis population. Renal histology and aCL were helpful in the therapeutic management.
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Affiliation(s)
- David J Hobbs
- Pediatric Nephrology, Helen DeVos Children's Hospital and Michigan State University College of Human Medicine, Grand Rapids, MI, USA
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Jesus A, Silva C, Carneiro-Sampaio M, Sheinberg M, Mangueira C, Marie S, Liphaus B. Anti-C1q Antibodies in Juvenile-Onset Systemic Lupus Erythematosus. Ann N Y Acad Sci 2009; 1173:235-8. [DOI: 10.1111/j.1749-6632.2009.04675.x] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
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Demircin G, Oner A, Erdoğan O, Delibaş A, Baysun S, Bülbül M, Bek K, Oksal A. Long-term efficacy and safety of quadruple therapy in childhood diffuse proliferative lupus nephritis. Ren Fail 2008; 30:603-9. [PMID: 18661410 DOI: 10.1080/08860220802132171] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022] Open
Abstract
In this study, we evaluated the frequency, clinical presentation, treatment protocols, prognostic factors, and outcome in children with diffuse proliferative lupus nephritis (DPLN). Between June 1990 and December 2004, 46 patients were diagnosed to have systemic lupus erythematosus (SLE), and 26 of them (56.5%) were found to have DPLN. Renal manifestations were present in 25 patients, and the majority of them presented with severe renal findings, such as nephrotic syndrome and renal failure. All patients were given a quadruple therapy protocol including 6-12 monthly courses of methyl prednisolone pulse therapy combined with oral prednisolone, oral cyclophosphamide, azathioprine, and dipyridamole. Nineteen of these patients were regularly followed up with a mean follow-up period of 5.9 years. Complete remission was achieved in 15 of 19 patients, and chronic renal failure developed in four patients. Renal survival rate was calculated to be 78.9% at the end of 5, 10, and 14 years. Although nephrotic range proteinuria, hypoalbuminemia, renal failure, and activity index above 12/24 at presentation seemed to be associated with poor prognosis, no significant difference could be found. Hypertension and chronicity index greater than 6/12 were found to be bad prognostic predictors. We concluded that satisfactory results were achieved with our quadruple therapy protocol; thus, more aggressive and expensive therapies can be avoided and preserved for more serious and persistent diseases.
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Affiliation(s)
- Gülay Demircin
- Department of Pediatric Nephrology, Dr Sami Ulus Children's Hospital, Ankara, Turkey.
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Benseler SM, Bargman JM, Feldman BM, Tyrrell PN, Harvey E, Hebert D, Silverman ED. Acute renal failure in paediatric systemic lupus erythematosus: treatment and outcome. Rheumatology (Oxford) 2008; 48:176-82. [DOI: 10.1093/rheumatology/ken445] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
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Fujinaga S, Ohtomo Y, Hara S, Umino D, Someya T, Shimizu T, Kaneko K. Maintenance therapy with mycophenolate mofetil for children with severe lupus nephritis after low-dose intravenous cyclophosphamide regimen. Pediatr Nephrol 2008; 23:1877-82. [PMID: 18414900 DOI: 10.1007/s00467-008-0800-7] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2007] [Revised: 01/22/2008] [Accepted: 02/18/2008] [Indexed: 11/30/2022]
Abstract
Although recent studies on adults with lupus nephritis indicate that mycophenolate mofetil (MMF) may be effective in maintaining remission for patients who previously received short-term intravenous cyclophosphamide (IVCY) induction therapy, the experience with the new immunosuppressive agent in children with severe lupus nephritis has not been as satisfactory thus far. To assess the efficacy and safety of maintenance therapy with MMF, we prospectively analyzed four patients with biopsy-proven severe lupus nephritis (three girls, one boy; mean age 12 years; two with class IIIA, two with class IVG(A); mean duration of lupus nephritis 7 months) receiving MMF for at least 6 months after induction treatment. These patients had been treated previously with 6 months of low-dose IVCY combined with oral mizoribine and steroids for induction, followed by therapy with MMF adjusted to maintain predose mycophenolic acid (C0-MPA) levels at 2-5 mcg/ml. Mean follow-up after staring MMF was 27.5 months (range 6-41). The mean MMF dose required was 405 +/- 49 mg/m(2) per 12 h, which maintained mean C0-MPA levels of 3.3 +/- 0.41 mcg/ml. No patient experienced renal flares during maintenance therapy with MMF, which permitted a significant reduction in mean prednisolone dose from 11.9 +/- 1.3 to 3.9 +/- 2.6 mg/day (P = 0.003). No significant gastrointestinal or hematologic side effects of MMF were noted. This preliminary study demonstrates that maintenance therapy with MMF after a low-dose IVCY regimen appears to be a promising intervention without adverse effects in children with severe lupus nephritis. These data should be confirmed by a prospective randomized multicenter clinical trial.
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Affiliation(s)
- Shuichiro Fujinaga
- Division of Nephrology, Saitama Children's Medical Center, Saitama-city Saitama, 339 8551, Japan.
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Lau KK, Ault BH, Jones DP, Butani L. Induction therapy for pediatric focal proliferative lupus nephritis: cyclophosphamide versus mycophenolate mofetil. J Pediatr Health Care 2008; 22:282-8. [PMID: 18761229 DOI: 10.1016/j.pedhc.2007.07.006] [Citation(s) in RCA: 33] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2007] [Revised: 07/11/2007] [Accepted: 07/11/2007] [Indexed: 11/29/2022]
Abstract
PURPOSE OF THE STUDY Although cyclophosphamide has been used with success in children, mycophenolate may be a better alternative with less toxicity. The objective of this study is to determine the efficacy of mycophenolate compared with cyclophosphamide as induction therapy in children with class III lupus nephritis. METHODS We retrospectively studied pediatric patients with class III lupus nephritis from two pediatric centers from January 1991 to December 2005 who were treated either with monthly cyclophosphamide or mycophenolate mofetil for the first 6 months. Thirteen patients were studied, with seven patients in the cyclophosphamide group and six patients in the mycophenolate group. RESULTS At 6 months, in the cyclophosphamide group, no patient had achieved complete remission, while 57% were in partial remission. In the mycophenolate group, 66% had achieved complete remission, 17% were in partial remission, and 17% were not in remission. DISCUSSION In a small group of children with class III lupus nephritis, we observed a trend of more patients in the mycophenolate group achieving remission at 6 months. However, the long-term benefit of using mycophenolate as an induction agent is still unclear.
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Affiliation(s)
- Keith K Lau
- Department of Pediatrics, University of California, Davis, Sacramento, 95817, USA.
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Plank C, Kalb V, Hinkes B, Hildebrandt F, Gefeller O, Rascher W. Cyclosporin A is superior to cyclophosphamide in children with steroid-resistant nephrotic syndrome-a randomized controlled multicentre trial by the Arbeitsgemeinschaft für Pädiatrische Nephrologie. Pediatr Nephrol 2008; 23:1483-93. [PMID: 18481113 PMCID: PMC2730636 DOI: 10.1007/s00467-008-0794-1] [Citation(s) in RCA: 81] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2007] [Revised: 02/01/2008] [Accepted: 02/04/2008] [Indexed: 01/08/2023]
Abstract
First line immunosuppressive treatment in steroid-resistant nephrotic syndrome in children is still open to discussion. We conducted a controlled multicentre randomized open label trial to test the efficacy and safety of cyclosporin A (CSA) versus cyclophosphamide pulses (CPH) in the initial therapy of children with newly diagnosed primary steroid-resistant nephrotic syndrome and histologically proven minimal change disease, focal segmental glomerulosclerosis or mesangial hypercellularity. Patients in the CSA group (n = 15) were initially treated with 150 mg/m(2) CSA orally to achieve trough levels of 120-180 ng/ml, while patients in the CPH group (n = 17) received CPH pulses (500 mg/m(2) per month intravenous). All patients were on alternate prednisone therapy. Patients with proteinuria >40 mg/m(2) per hour at 12 weeks of therapy were allocated to a non-responder protocol with high-dose CSA therapy or methylprednisolone pulses. At week 12, nine of the 15 (60%) CSA patients showed at least partial remission, evidences by a reduction of proteinuria <40 mg/h per m(2). In contrast, three of the 17 (17%) CPH patients responded (p < 0.05, intention-to-treat). Given these results, the study was stopped, in accordance with the protocol. After 24 weeks, complete remission was reached by two of the 15 (13%) CSA and one of the 17 (5%) CPH patients (p = n.s.). Partial remission was achieved by seven of the 15 (46%) CSA and two of the 15 (11%) CPH patients (p <0.05). Five patients in the CSA group and 14 patients in the CPH group were withdrawn from the study, most of them during the non-responder protocol. The number of adverse events was comparable between both groups. We conclude that CSA is more effective than CPH in inducing at least partial remission in steroid-resistant nephrotic syndrome in children.
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Affiliation(s)
- Christian Plank
- Department of Pediatrics, University Erlangen-Nuremberg, Loschgestrasse 15, 91054, Erlangen, Germany.
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Outcome of lupus nephritis in Iranian children: prognostic significance of certain features. Pediatr Nephrol 2008; 23:749-55. [PMID: 18270752 DOI: 10.1007/s00467-007-0713-x] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2006] [Revised: 11/06/2007] [Accepted: 11/08/2007] [Indexed: 10/22/2022]
Abstract
The objective of this study was to determine the clinical and histopathological features and outcome of children with lupus nephritis (LN). Of 84 children with systemic lupus erythematosus (SLE), we retrospectively studied 58 children (69%) under 15 years of age with biopsy-proven LN who had been followed between October 1989 and January 2005. The mean age at diagnosis or initial referral was 10.6 +/- 2.25 years, and the mean follow-up was 5.3 +/- 4.1 years. Class IV LN was observed in 34 (58.6%) patients. The 5-year patient and renal survival rates were 82.5 and 78.5%, respectively, in the total group, and 75 and 85.8%, respectively, in patients with Class IV LN. No independent predictor of unfavorable outcome, including renal histology, was detected by multivariate analysis. The mid-term patient and the renal survival rates of Iranian children with biopsy-proven LN are high. Within 5 years of follow-up, renal histology was not a predictor for survival.
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Tanaka H, Tsugawa K, Oki E, Suzuki K, Ito E. Mizoribine intermittent pulse protocol for induction therapy for systemic lupus erythematosus in children: an open-label pilot study with five newly diagnosed patients. Clin Rheumatol 2008; 27:85-89. [PMID: 17483980 DOI: 10.1007/s10067-007-0635-9] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2007] [Revised: 04/13/2007] [Accepted: 04/15/2007] [Indexed: 11/26/2022]
Abstract
The objective of the current work is to report our preliminary experience with the mizoribine (MZR) intermittent pulse protocol for induction therapy for newly diagnosed pediatric-onset systemic lupus erythematosus (SLE). Five consecutive patients who were newly diagnosed as having SLE with biopsy-proven lupus nephritis were recruited for an open-label trial of prednisolone (PDN) and MZR intermittent pulse therapy (10 mg/kg for 2 days of the week for 12 months). Data on the renal response and serologic lupus activity were collected prospectively. The baseline characteristics of the patients were: mean age, 11 years; urinary protein/creatinine ratio (U-prot./cre.), 0.99 +/- 0.91; serum complement hemolytic activity (CH50), 10.6 +/- 1.3 (normal, 23-46 U/ml); serum anti-dsDNA antibody titer, 258.6 +/- 125.5 IU/ml (normal, <12.0 IU/ml); serum creatinine, 0.5 +/- 0.1 mg/dl; European Consensus Lupus Activity Measurement index (ECLAM), 7.4 +/- 1.1. The primary endpoint was the interval until the development of a flare of SLE. Despite gradual tapering of the PDN dose, significant improvement as compared to the baseline values was observed in all the parameters examined at 3, 6, and 12 months of treatment. After 12 months therapy, complete response was achieved in all of the patients, except for 1 patient who showed poor drug compliance. In two patients who had severe lupus nephritis at the first renal biopsy, marked histologic improvement was confirmed at the second renal biopsy. No serious adverse effects were observed. We believe that the MZR pulse protocol combined with PDN for induction therapy may be the treatment of choice in selected young patients with SLE. Further studies to confirm the long-term efficacy and safety of our current protocol in larger numbers of patients are, however, needed.
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Affiliation(s)
- Hiroshi Tanaka
- Department of Pediatrics, Hirosaki University School of Medicine, Hirosaki, 036-8562, Japan.
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Askenazi D, Myones B, Kamdar A, Warren R, Perez M, De Guzman M, Minta A, Hicks MJ, Kale A. Outcomes of children with proliferative lupus nephritis: the role of protocol renal biopsy. Pediatr Nephrol 2007; 22:981-6. [PMID: 17334789 DOI: 10.1007/s00467-007-0447-9] [Citation(s) in RCA: 46] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2006] [Revised: 01/05/2007] [Accepted: 01/16/2007] [Indexed: 11/30/2022]
Abstract
Outcomes in children with proliferate lupus nephritis (PLN) show 9-15% progress to end-stage renal disease (ESRD) at 5 years. Immunosuppression improves outcome, but significant side effects are possible. Clinical and laboratory analyses are poor predictors of class and progression in PLN. We describe 28 patients with systemic lupus erythematosus (SLE), between 1990 and 2005, whose initial biopsy (Bx1) showed PLN and who received nine monthly doses of intravenously administered cyclophosphamide (CYP) (500-750 mg/m(2) up to 1 g to maintain their absolute neutrophil count (ANC) > 3,000). Continued therapy with additional quarterly intravenous (i.v). administration of CYP was dictated by repeat renal biopsy (Bx2). Bx1 was done 1 +/- 1.6 years after diagnosis of SLE. Bx2 showed histological improvement by WHO classification in 20/25 children; 3/25 were unchanged, 1/25 was categorized as new class V, and 1/25 was worse. Four patients (14%) had infectious complications requiring hospitalization (one of these died). Mean follow-up (f/u) after Bx2 was 3.5 +/- 2.3 years. At last follow-up, 26 patients had normal glomerular filtration rate (GFR), with a mean of 126 +/- 42.8 ml/min per 1.73 m(2) body surface area, one non-compliant patient had ESRD, and one had chronic renal failure. At last follow-up, most patients had minimal to no proteinuria. Clinical and biopsy results greatly improved after 9 monthly intravenously administered CYP pulses in most children with class IV PLN. Those who did not improve are at risk for flares and progression of disease. The tailoring of therapies based on findings from a biopsy after induction may improve outcomes.
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Affiliation(s)
- David Askenazi
- Department of Pediatrics, University of Alabama at Birmingham, 1600 7th Avenue South, ACC 516, Birmingham, AL, 35233, USA.
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Faco MMM, Leone C, Campos LMA, Febrônio MV, Marques HHS, Silva CA. Risk factors associated with the death of patients hospitalized for juvenile systemic lupus erythematosus. Braz J Med Biol Res 2007; 40:993-1002. [PMID: 17653454 DOI: 10.1590/s0100-879x2006005000110] [Citation(s) in RCA: 51] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2006] [Accepted: 03/20/2007] [Indexed: 11/22/2022] Open
Abstract
We assessed the risk factors associated with death in patients hospitalized for juvenile systemic lupus erythematosus (JSLE) and evaluated the autopsy reports. A total of 57,159 hospitalizations occurred in our institution from 1994 to 2003, 169 of them involving 71 patients with JSLE. The most recent hospitalization of these patients was evaluated. Patients were divided into two groups based on mortality during hospitalization: those who survived (N = 53) and those who died (N = 18). The main causes of hospitalization were JSLE activity associated with infection in 52% and isolated JSLE activity in 44%. Univariate analysis showed that a greater risk of death was due to severe sepsis (OR = 17.8, CI = 4.5-70.9), systemic lupus erythematosus disease activity index (SLEDAI) >or=8 (OR = 7.6, CI = 1.1-53.8), general infections (OR = 6.1, CI = 1.5-25), fungal infections (OR = 5.4, CI = 3.2-9), acute renal failure (OR = 5.1, CI = 2.5-10.4), acute thrombocytopenia (OR = 3.9, CI = 1.9-8.4), and bacterial infections (OR = 2.3, CI = 1.2-7.5). Stratified analysis showed that severe sepsis and SLEDAI >or=8 were not confounder variables. In the multivariate analysis, logistic regression showed that the only independent variable in death prediction was severe sepsis (OR = 98, CI = 16.3-586.2). Discordance between clinical diagnosis and autopsy was observed in 6/10 cases. Mortality of hospitalized JSLE patients was associated with severe sepsis. Autopsy was important to determine events not detected or doubtful in dead patients and should always be requested.
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Affiliation(s)
- M M M Faco
- Unidades de Reumatologia e Infectologia Pediátricas, Instituto da Criança, Departamento de Pediatria, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brasil
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Baskin E, Agras PI, Menekşe N, Ozdemir H, Cengiz N. Full-house nephropathy in a patient with negative serology for lupus. Rheumatol Int 2007; 27:281-284. [PMID: 16972085 DOI: 10.1007/s00296-006-0198-0] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2005] [Accepted: 08/06/2006] [Indexed: 10/24/2022]
Abstract
A 10-year-old girl presented with a complaint of recurrent abdominal pain. Physical examination findings were unremarkable. Laboratory investigations revealed BUN of 17 mg/dl and creatinine of 1 mg/dl, and complement levels were normal. She had neither hematuria nor proteinuria, and glomerular filtration rate was 60.9 ml/min/1.73 m(2). ANA, anti-DNA, p-ANCA and c-ANCA were all negative. Renal biopsy revealed findings of class III lupus nephritis in light, "full-house" nephropathy in immune fluorescent and tubuloreticular inclusions in electron microscopic examinations. After 17 months of treatment, her last creatinine is 2.5 mg/dl and GFR is 17.9 ml/min/1.73 m(2) and ANA and anti-DNA remain still negative. This case presents an example that decreased GFR can be the first presenting symptom of full-house nephropathy. Those patients who have negative lupus serology and renal biopsy findings of full-house nephropathy and tubuloreticular inclusions may behave and should be treated as lupus nephritis.
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Affiliation(s)
- Esra Baskin
- Department of Pediatric Nephrology, Baskent University, 6, Cadde No: 72/3, O6490, Bahcelievler, Ankara, Turkey.
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Wong SN, Tse KC, Lee TL, Lee KW, Chim S, Lee KP, Wai-Po Chu R, Chan W, Fong KW, Hui J, Po-Siu Li S, Yeung PS, Yuen SF, Chi-Hang Ho A, Chuk-Kwan Leung L, Luk D, Tong PC, Chan SY, Cheung HM, Chow CM, Lau D. Lupus nephritis in Chinese children--a territory-wide cohort study in Hong Kong. Pediatr Nephrol 2006; 21:1104-12. [PMID: 16639624 DOI: 10.1007/s00467-006-0052-3] [Citation(s) in RCA: 40] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/09/2005] [Revised: 11/18/2005] [Accepted: 11/18/2005] [Indexed: 10/24/2022]
Abstract
We report a multicenter study of Chinese children in Hong Kong with systemic lupus erythematosus (SLE) nephritis. Children were included if: they fulfilled the ACR criteria, had significant proteinuria or casturia, were Chinese and younger than 19 years and had been diagnosed with SLE between January 1990 and December 2003. Investigators in each center retrieved data on clinical features, biopsy reports, treatment and outcome of these patients. There were 128 patients (eight boys, 120 girls; mean age: 11.9+/-2.8 years). About 50% presented with multisystem illness and 40% with nephritic/nephrotic symptoms. Negative anti-dsDNA antibodies were found in 6% of the patients. Renal biopsy revealed WHO Class II, III, IV and V nephritis in 13 (10%), 22 (17%), 69 (54%) and 13 (10%) patients, respectively. The clinical severity of the nephritis did not accurately predict renal biopsy findings. The follow-up period ranged from 1 to 16.5 years (mean+/-SD: 5.76+/-3.61 years). During the study five patients died (two from lupus flare, one from cardiomyopathy, two from infections). Four patients had endstage renal failure (ESRF) (one died during a lupus flare). All deaths and end-stage renal failure occurred in the Class IV nephritis group. Chronic organ damage was infrequent in the survivors. The actuarial patient survival rates at 5, 10 and 15 years of age were 95.3, 91.8, and 91.8%, respectively. For Class IV nephritis patients, the survival rates without ESRF at 5, 10, and 15 years were 91.5, 82.3 and 76%, respectively. The survival and chronic morbidity rates of the Chinese SLE children in the present study are comparable to those of other published studies.
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Affiliation(s)
- Sik-Nin Wong
- Department of Paediatrics & Adolescent Medicine, Tuen Mun Hospital, Tsing Chung Koon Road, Tuen Mun, Hong Kong, People's Republic of China.
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Balzar E. Therapie der Lupusnephritis. Monatsschr Kinderheilkd 2006. [DOI: 10.1007/s00112-006-1387-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
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Tanaka H, Tsugawa K, Suzuki K, Nakahata T, Ito E. Long-term mizoribine intermittent pulse therapy for young patients with flare of lupus nephritis. Pediatr Nephrol 2006; 21:962-966. [PMID: 16773408 DOI: 10.1007/s00467-006-0120-8] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2005] [Revised: 02/01/2006] [Accepted: 02/02/2006] [Indexed: 10/24/2022]
Abstract
Mizoribine (MZR) is a novel purine synthesis inhibitor that was developed in Japan. We previously reported the efficacy and safety of oral MZR intermittent pulse therapy, which is associated with elevated peak serum MZR levels, in selected patients with lupus nephritis. However, the efficacy and safety of long-term MZR intermittent pulse therapy (administered for over 24 months) in lupus nephritis patients at high risk for relapse has not yet been reported. Our study included five patients with a long history of systemic lupus erythematosus (SLE), including four patients with proliferative lupus nephritis (WHO class IV) and one patient with WHO class II lupus nephritis, in whom remission had been achieved through treatment with high-dose corticosteroids combined with cytotoxic agents. For the most recent flares, all the patients were treated with MZR intermittent pulse therapy without increase in the dose of corticosteroids. MZR was administered at 5-10 mg/kg per day (up to 500 mg) as a single daily dose on two days of the week (Monday and Thursday) for over 24 months. Concomitantly administered corticosteroid dose was gradually reduced or continued unchanged. At presentation, the urinary protein excretion, serum complement hemolytic activity (CH50) and serum anti-dsDNA antibody titer were 1.7+/-1.0 g/day, 16.6+/-3.8 U/mL (normal, 23-46 U/mL) and 143.7+/-151.1 IU/mL (normal,<12.0 IU/mL), respectively. At the latest observation point, after a mean interval of 31 months (24-34 months) after the initiation of MZR pulse therapy, the urinary protein excretion and serum anti-dsDNA antibody titer were significantly decreased (0.3+/-0.2 g/day and 18.5+/-19.1 IU/mL, respectively; P<0.05), and the serum CH50 value had returned to within normal range (33.6+/-7.8 U/mL, P<0.05). Despite the reduced minimum dose of prednisolone required to maintain clinical remission at the time of the post-treatment evaluation after MZR pulse therapy as compared with that at the time of the pretreatment evaluation (9.0+/-4.5 vs. 17.5+/-7.9 mg/day; P=0.0656), the calculated flare rate was significantly decreased (0.15+/-0.2 vs. 0.6+/-0.11 times per year; P<0.05). The serum creatinine level remained within normal range in all the study participants. Furthermore, the platelet count increased following the MZR pulse therapy in two patients who had suffered from chronic thrombocytopenia. No serious adverse effects were observed. From the view point of the balance between suppression of disease activity and the adverse effects of treatment, we believe that long-term MZR pulse therapy may be the treatment of choice in selected patients with lupus nephritis at high risk for relapse. However, this was only a pilot study conducted on a small number of subjects, without a control group. Further studies to confirm the long-term efficacy and safety of oral MZR intermittent pulse therapy in larger numbers of patients are needed.
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Affiliation(s)
- Hiroshi Tanaka
- Department of Pediatrics, Hirosaki University School of Medicine, 5 Zaifu-cho, Hirosaki,, 036-8562, Japan.
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Lau KK, Jones DP, Hastings MC, Gaber LW, Ault BH. Short-term outcomes of severe lupus nephritis in a cohort of predominantly African-American children. Pediatr Nephrol 2006; 21:655-62. [PMID: 16570203 DOI: 10.1007/s00467-006-0060-3] [Citation(s) in RCA: 35] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2005] [Revised: 12/06/2005] [Accepted: 12/07/2005] [Indexed: 10/24/2022]
Abstract
Renal involvement is one of the major determinants of the outcome in patients with systemic lupus erythematosus. Although African-American ethnicity has been suggested to be a poor prognostic factor in severe lupus nephritis in adult patients, information on outcomes of African-American children with this disease is still very limited. We retrospectively studied the patients diagnosed with severe lupus nephritis by renal biopsy at Le Bonheur Children's Medical Center from January 1990 to December 2003. All patients were below the age of 18 years at the time of biopsy. Clinical features assessed included age, gender, race, estimated glomerular filtration rate (GFR), presence of hypertension, gross hematuria, degree of proteinuria, complement 3 and 4 levels, serum albumin, renal histology and dose of oral prednisone. Forty-four patients were studied: 82% were African-American and 89% were female. Mean age at biopsy was 14.2+/-3 years (median 15.0 years; range 4.7 years to 17.0 years). Renal biopsies were assessed according to the WHO classification. Twenty-seven percent, 43%, and 30% were in class III, IV and V, respectively. At presentation, 55% had hypertension and 23% had a history of macroscopic hematuria. The patients had varying degrees of proteinuria, including 18% with nephrotic syndrome. Eighteen percent had moderate renal insufficiency with estimated GFRs less than 50 ml/1.73 m2 body surface area per minute. All the patients were treated with corticosteroids. Sixty-eight percent also received cyclophosphamide and 20% received either mycophenolate mofetil (MMF) or azathioprine (AZA). Two patients developed end stage renal disease and required chronic dialysis within 12 months of biopsy. At the 12-month follow-up visit, 23% of patients had complete remission and 48% had partial remission. The mean estimated GFR had increased from 96.0 ml/1.73 m2 per minute to 124 ml/1.73 m2 per minute (P=0.03). Mean serum creatinine levels decreased from 1.62 mg/dl to 0.91 mg/dl (P=0.03). Complement 3 levels increased from 54.3 mg/dl to 90.3 mg/dl (P<0.01). Mean serum albumin levels also increased from 2.8 mg/dl to 3.6 mg/dl (P<0.01) and urine protein-to-creatinine ratio decreased from 5.8 to 1.0 (P<0.01). The average prednisone dose decreased from 0.96 mg/kg per day to 0.41 mg/kg per day (P=0.64). In our center, with predominantly African-American children, patients with lupus nephritis presented similarly to those in other studies with predominantly Caucasian patients, and short-term renal outcomes were not different.
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Affiliation(s)
- Keith K Lau
- Department of Pediatrics, Le Bonheur Children's Medical Center, Room 301, West Patient Tower, 50 North Dunlap, University of Tennessee Health Science Center, Memphis, Tennessee, TN 38103, USA.
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Nozu K, Iijima K, Kamioka I, Fujita T, Yoshiya K, Tanaka R, Nakanishi K, Yoshikawa N, Matsuo M. High-dose mizoribine treatment for adolescents with systemic lupus erythematosus. Pediatr Int 2006; 48:152-7. [PMID: 16635174 DOI: 10.1111/j.1442-200x.2006.02178.x] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
BACKGROUND In treating pediatric patients with systemic lupus erythematosus (SLE), it is necessary to quickly attain remission to avoid sequelae in various organs and to maintain it over a long period. However, to maintain remission, the prolonged use of immunosuppressants which have various adverse effects, is often necessary in addition to steroids, and complications due to such immunosuppressants pose very important problems. A regimen of mizoribin (MZR) at 150 mg/day divided into two or three doses has been recommended, but while this regimen has been safe, its efficacy has not been satisfactory. However, MZR produces effects dose-dependently, and the dose recommended to date may have been insufficient for the treatment of children with SLE. METHODS The authors administered oral MZR at 300 mg/day in two divided doses, which is twice the conventional dose for adults, to five adolescents with SLE. Three of these five were markedly steroid-dependent patients and two had previously been treated with steroids only. Thereafter, the authors evaluated the safety and efficacy of the regimen by following the patients for at least 7 months after the beginning of treatment. RESULTS Patients 1 and 2 had been treated with prednisolone (PSL) and cyclosporine (CyA), but as the duration of CyA administration became long, it was replaced with 300 mg MZR. This transition could be accomplished smoothly. Patient 3 showed repeated recurrence during the treatment with PSL and CyA or CPM, but the symptoms could be controlled by the addition of 300 mg MZR. In patients 4 and 5, the control of symptoms with PSL alone was judged to be difficult, and concomitant administration of MZR at 300 mg was started. This resulted in a decrease in the dose of PSL. The Cmax (C2) of MZR was 1.33 microg/mL or higher in all five patients, and the efficacy of the treatment was satisfactory. Concerning side-effects, hyperuricemia was noted in two patients, but it was resolved in one of them by reducing the dose of MZR and in the other spontaneously while the treatment was continued. Temporary exacerbation of hair loss was observed in two patients, but it disappeared in both of them after a few months. CONCLUSION MZR could be administered at a high dose effectively and safely. However, monitoring of the serum uric acid level was necessary. High-dose MZR therapy showed an efficacy and safety that would warrant its application to steroid-dependent pediatric patients with SLE.
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Affiliation(s)
- Kandai Nozu
- Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan.
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Machado V, Pontes T, Brito I, Afonso C. Systemic lupus erythematosus (SLE) presenting with nephrotic syndrome and membranous glomerulopathy in a 10-year-old girl. Acta Paediatr 2005; 94:1507-9. [PMID: 16299888 DOI: 10.1111/j.1651-2227.2005.tb01829.x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
UNLABELLED The authors report the case of a 10-y-old girl with clinical diagnosis of systemic lupus erythematosus (SLE), made at the age of 6 y, based upon arthritis, serositis, haematological disorder and positive antinuclear antibody. The first manifestation of disease--Raynaud's phenomenon--appeared at the age of 4 y. Seven months after the diagnosis, she developed nephrotic proteinuria with haematuria. Percutaneous renal biopsy showed membranous glomerulonephritis, the least common form of lupus nephritis. CONCLUSION Intravenous cyclophosphamide therapy associated with oral prednisolone proved effective in inducing complete remission of nephrotic syndrome.
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Affiliation(s)
- Vânia Machado
- Department of Paediatrics, Hospital de São João, Porto, Portugal.
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Fujinaga S, Kaneko K, Ohtomo Y, Murakami H, Takada M, Akashi S, Hira M, Yamashiro Y. Induction therapy with low-dose intravenous cyclophosphamide, oral mizoribine, and steroids for severe lupus nephritis in children. Pediatr Nephrol 2005; 20:1500-3. [PMID: 16021476 DOI: 10.1007/s00467-005-1983-9] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2005] [Revised: 04/03/2005] [Accepted: 04/07/2005] [Indexed: 10/25/2022]
Abstract
Although immunosuppressive regimens of corticosteroids combined with high-dose intravenous cyclophosphamide (IVCY) have been reported to suppress the activity of lupus nephritis, there is controversy regarding its application for children and adolescents, because of its potential toxicity including gonadal dysfunction. On the basis of the recent finding that a low-dose IVCY regimen for induction therapy in adult lupus nephritis effectively achieves renal remission comparable with that achieved with a conventional high-dose IVCY regimen, we treated two children with severe lupus nephritis by low-dose (fixed dose of 500 mg m(-2), cumulative dose 3 g m(-2), approximately one-fourth of the conventional high-dose IVCY regimen) IVCY and oral mizoribine (5 mg kg(-1) day(-1)) and steroids (3 methylprednisolone pulse followed by oral prednisolone). They responded well to this regimen, showing remarkable improvement in both histological and clinical manifestations in a short period of time. From these findings we suggest that the new low-dose IVCY regimen may be as effective as the conventional high-dose IVCY regimen, without significant adverse effect, for induction therapy in children with severe lupus nephritis (class III or IV).
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Affiliation(s)
- Shuichiro Fujinaga
- Division of Nephrology, Saitama Children's Medical Center, Saitama, Japan.
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Bakr A. Epidemiology treatment and outcome of childhood systemic lupus erythematosus in Egypt. Pediatr Nephrol 2005; 20:1081-6. [PMID: 15940546 DOI: 10.1007/s00467-005-1900-2] [Citation(s) in RCA: 32] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2004] [Revised: 02/08/2005] [Accepted: 02/08/2005] [Indexed: 10/25/2022]
Abstract
To highlight the characteristics of Egyptian children with systemic lupus erythematosus (SLE), the records of 52 SLE patients (48 girls and four boys aged 11.9+/-2.6 years) were retrospectively analyzed. The median duration of follow up was 22 months (range 1-94.5). The most common extrarenal manifestation was fever (76.6%), followed by joint involvement (65.4%). Hemolytic anemia was demonstrated in 51%, thrombocytopenia in 29.2%, and leucopenia in 27.5%. Antinuclear antibodies were positive in 92.7%, while positive anti-double-stranded DNA and hypocomplementemia were demonstrated in 95.6% and 67.4%, respectively. Lupus nephritis (LN) was evident in 80.8%. The renal manifestations of LN patients were proteinuria (83.3%), hematuria (71.5%), hypertension (35.7%), and elevated serum creatinine (16.7%). The histopathological findings of the initial renal biopsies were class I (4.9%), class II (22%), class III (36.3%), and class IV (36.3%). Among patients without LN, 85.7% gained remission and nonimmediately died. At last observation, 55.6% of LN patients had complete remission, 22.2% had active disease, and 22.2% died. Most patients who died had class IV LN. In conclusion, the characteristics of Egyptian SLE children are comparable with those in most Arab and Western series. However, LN may be more prevalent and severe, with unfavorable outcomes.
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Affiliation(s)
- Ashraf Bakr
- Pediatric Nephrology, Mansoura University Children's Hospital, Egypt.
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Moorthy LN, Harrison MJ, Peterson M, Onel KB, Lehman TJA. Relationship of quality of life and physical function measures with disease activity in children with systemic lupus erythematosus. Lupus 2005; 14:280-7. [PMID: 15864914 DOI: 10.1191/0961203305lu2075oa] [Citation(s) in RCA: 32] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
The objective of this study is to assess relationship of systemic lupus erythematosus (SLE) activity with quality of life (QOL) and physical function and determine which is more closely correlated with SLE activity in children; and identify factors critical to children's QOL. In this cross-sectional study, children with SLE and parents completed corresponding versions of physical function (Childhood Health Assessment Questionnaire CHAQ), and QOL (Pediatric Quality of Life Inventory-PedsQL Generic/Rheumatology modules) questionnaires. SLE Disease Activity Index (SLEDAI), Systemic Lupus International Collaborating Clinics/ACR Damage Index (SDI), severity, self-concept and socioeconomic status (SES) were measured. For 24 children, CHAQ scores significantly correlated with SLEDAI (rho = 0.4, p = 0.04), SDI (rho = 0.6, p = 0.004), and associated with severity (p = 0.03). PedsQL scores did not significantly correlate with above parameters. Higher self-concept/SES correlated (p < 0.05) with better physical function and QOL. For 19 parents, the only significant correlation was between SLEDAI and Worry domain-Rheumatology module (rho = 0.5, p = 0.01). Lack of strong correlation of disease activity with QOL and physical function suggests that they are different constructs with partial overlap, and should be considered collectively while evaluating the impact of SLE on children/families. Self-concept and SES should be assessed while measuring QOL in children. Larger sample is required to confirm results.
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Affiliation(s)
- L N Moorthy
- Hospital For Special Surgery, Cornell Graduate School, New York, USA.
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Edelbauer M, Jungraithmayr T, Zimmerhackl LB. Rituximab in childhood systemic lupus erythematosus refractory to conventional immunosuppression: case report. Pediatr Nephrol 2005; 20:811-3. [PMID: 15772840 DOI: 10.1007/s00467-004-1760-1] [Citation(s) in RCA: 38] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2004] [Revised: 10/18/2004] [Accepted: 10/21/2004] [Indexed: 10/25/2022]
Abstract
Rituximab, a chimeric monoclonal antibody specific for human CD20, has recently been used for the treatment of autoimmune diseases. A 14-year-old patient with severe systemic lupus erythematosus (SLE) and class IV glomerulonephritis presented with immunologic and clinical resistance to conventional immunosuppressive therapy for 10 months after diagnosis. To induce remission of active SLE, treatment with 6 monthly rituximab at 375 mg/m(2), oral mycophenolate and prednisone was initiated followed by maintenance rituximab every 3 months. The SLEDAI decreased significantly from 31 at diagnosis to 14 after nine applications of rituximab. Extrarenal symptoms of SLE improved significantly. However, after induction therapy with rituximab the patient presented a reversible intrinsic acute renal insufficiency for a period of 3 weeks. The discontinuation of the daily medication (oral prednisone and mycophenolate) by the patient herself may explain the progression of active SLE associated with the reversible acute renal failure. Under intensive immunosuppressive therapy improvement of active disease manifestations and stabilization of plasma creatinine concentrations to normal values was observed. However, proteinuria remained elevated and improved only after a protracted period (median protein-to-creatinine ratio 5.2 g/g, range 0.8-11.2 g/g). Hematuria and urinary cell casts persisted. In conclusion, the extrarenal symptoms of the patient responded particularly well to rituximab. However, despite complete B-cell elimination, renal remission of SLE was not achieved. Thus, it may be possible that humoral and cellular immune mechanisms have a fundamental involvement in the pathogenesis of SLE nephritis.
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Affiliation(s)
- Monika Edelbauer
- Department of Pediatrics, Medical University of Innsbruck, Austria.
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