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Park SJ, Ahn MB, Jeong DC. Endocrine and metabolic comorbidities in juvenile-onset systemic lupus erythematosus. Front Med (Lausanne) 2025; 12:1429337. [PMID: 39981087 PMCID: PMC11839645 DOI: 10.3389/fmed.2025.1429337] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2024] [Accepted: 01/20/2025] [Indexed: 02/22/2025] Open
Abstract
Background and aims Juvenile-onset systemic lupus erythematosus (JSLE) is a chronic autoimmune disease affecting individuals under 18, causing multi-system impairment. Patients with JSLE exhibit more severe disease when compared to patients with adult-onset SLE. This study aimed to evaluate the prevalence of endocrine and metabolic comorbidities in patients with JSLE, and analyze the factors associated with each comorbidity. Methods Anthropometric, clinical, laboratory data, and the details of glucocorticoids and disease-modifying anti-rheumatic drugs use were collected. Results A total of 57 patients with JSLE (48 girls and 9 boys) were included in this study. Endocrine and metabolic comorbidities were observed in 64.9% of the patients. The most prevalent comorbidities were dyslipidemia (40.4%), being overweight or obese (26.3%), subclinical hypothyroidism (24.6%), autoimmune thyroid disease (AITD) (21.1%), and low bone mass (20.9%). The risk of dyslipidemia and AITD increased in patients who were overweight or obese. The risk of being overweight or obese was associated with skin involvement at diagnosis and rheumatoid factor positivity. Younger age at diagnosis and longer duration of glucocorticoid exposure increased the risk of low bone mass. The overall prevalence of endocrine and metabolic comorbidities was associated with short stature at diagnosis, being overweight or obese at follow-up, skin involvement at diagnosis, and rheumatoid factor positivity. Conclusion Patients with JSLE have higher burdens of endocrine and metabolic comorbidities and should be routinely monitored. Prevention of obesity may be helpful in lowering the risk of comorbidities.
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Affiliation(s)
- Su Jin Park
- Division of Endocrinology, Department of Pediatrics, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Moon Bae Ahn
- Division of Endocrinology, Department of Pediatrics, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Dae Chul Jeong
- Division of Rheumatology, Department of Pediatrics, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
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Kalashnikova E, Isupova E, Gaidar E, Lubimova N, Sorokina L, Chikova I, Kaneva M, Raupov R, Kalashnikova O, Aliev D, Gaydukova I, Kostik M. Outcomes of a 12-month course of early and late rituximab BCD020 biosimilar administration in juvenile systemic lupus erythematosus: A retrospective study. World J Nephrol 2024; 13:98393. [PMID: 39723361 PMCID: PMC11572657 DOI: 10.5527/wjn.v13.i4.98393] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2024] [Revised: 08/23/2024] [Accepted: 09/05/2024] [Indexed: 11/07/2024] Open
Abstract
BACKGROUND Juvenile systemic lupus erythematosus (SLE) is a severe, life-threatening disease. However, the role of rituximab in managing juvenile SLE remains undefined, although early biological intervention may improve disease outcomes. AIM To assess the differences in the outcomes of different types of rituximab administration (early and late). METHODS In this retrospective cohort study, the information of 36 children with SLE with early (less than 6 months from onset) rituximab administration (ERA), and late (more than 1 year) rituximab administration (LRA) was analyzed. We compared initial disease characteristics at onset, at baseline (start of rituximab), and at the end of the study (EOS) at 12 months, as well as outcomes and treatment characteristics. RESULTS The main differences at baseline were a higher daily median dose of corticosteroids, increased MAS frequency, and a higher Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) in the ERA group. No differences in the main SLE outcomes between groups at the EOS were observed. The part of lupus nephritis patients who achieved remission changed from 44% to 31% in ERA and 32% to 11% in the LRA group. Patients with ERA had a shorter time to achieve low daily corticosteroid dose (≤ 0.2 mg/kg) at 1.2 (0.9; 1.4) years compared to 2.8 (2.3; 4.0) years (P = 0.000001) and higher probability to achieve this low dose [hazard ratio (HR) = 57.8 (95% confidence interval (CI): 7.2-463.2), P = 0.00001 and remission (SLEDAI = 0); HR = 37.6 (95%CI: 4.45-333.3), P = 0.00001]. No differences in adverse events, including severe adverse events, were observed. CONCLUSION ERA demonstrated a better steroid-sparing effect and a possibility of earlier remission or low disease activity, except for lupus nephritis. Further investigations are required.
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Affiliation(s)
- Elvira Kalashnikova
- Hospital Pediatry, Saint-Petersburg State Pediatric Medical University, Saint Petersburg 194100, Sankt-Peterburg, Russia
| | - Eugenia Isupova
- Hospital Pediatry, Saint-Petersburg State Pediatric Medical University, Saint Petersburg 194100, Sankt-Peterburg, Russia
| | - Ekaterina Gaidar
- Hospital Pediatry, Saint-Petersburg State Pediatric Medical University, Saint Petersburg 194100, Sankt-Peterburg, Russia
| | - Natalia Lubimova
- Research Laboratory of Autoimmune and Autoinflammatory Diseases, World-Class Research Centre for Personalized Medicine, Almazov National Medical Research Centre, Saint Petersburg 197341, Sankt-Peterburg, Russia
| | - Lyubov Sorokina
- Hospital Pediatry, Saint-Petersburg State Pediatric Medical University, Saint Petersburg 194100, Sankt-Peterburg, Russia
| | - Irina Chikova
- Hospital Pediatry, Saint-Petersburg State Pediatric Medical University, Saint Petersburg 194100, Sankt-Peterburg, Russia
| | - Maria Kaneva
- Hospital Pediatry, Saint-Petersburg State Pediatric Medical University, Saint Petersburg 194100, Sankt-Peterburg, Russia
| | - Rinat Raupov
- Pediatric Rheumatology, H. Turner National Medical Research Center for Children’s Orthopedics and Trauma Surgery, Saint Petersburg 196603, Sankt-Peterburg, Russia
| | - Olga Kalashnikova
- Hospital Pediatry, Saint-Petersburg State Pediatric Medical University, Saint Petersburg 194100, Sankt-Peterburg, Russia
| | - Damir Aliev
- Department of Internal Medicine, Rheumatology, Examination of Temporary Disability Examination and Quality of Medical Care named after E.E. Eichwald, I.I. Mechnikov North-Western State Medical University, Saint Petersburg 191015, Sankt-Peterburg, Russia
- Department of Rheumatology, Clinical Rheumatological Hospital #25, Saint Petersburg 190068, Sankt-Peterburg, Russia
| | - Inna Gaydukova
- Department of Internal Medicine, Rheumatology, Examination of Temporary Disability Examination and Quality of Medical Care named after E.E. Eichwald, I.I. Mechnikov North-Western State Medical University, Saint Petersburg 191015, Sankt-Peterburg, Russia
- Department of Rheumatology, Clinical Rheumatological Hospital #25, Saint Petersburg 190068, Sankt-Peterburg, Russia
| | - Mikhail Kostik
- Hospital Pediatry, Saint-Petersburg State Pediatric Medical University, Saint Petersburg 194100, Sankt-Peterburg, Russia
- Research Laboratory of Autoimmune and Autoinflammatory Diseases, World-Class Research Centre for Personalized Medicine, Almazov National Medical Research Centre, Saint Petersburg 197341, Sankt-Peterburg, Russia
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Lupu A, Sasaran MO, Jechel E, Azoicai A, Alexoae MM, Starcea IM, Mocanu A, Nedelcu AH, Knieling A, Salaru DL, Burlea SL, Lupu VV, Ioniuc I. Undercover lung damage in pediatrics - a hot spot in morbidity caused by collagenoses. Front Immunol 2024; 15:1394690. [PMID: 38994372 PMCID: PMC11236559 DOI: 10.3389/fimmu.2024.1394690] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2024] [Accepted: 06/11/2024] [Indexed: 07/13/2024] Open
Abstract
Connective tissue represents the support matrix and the connection between tissues and organs. In its composition, collagen, the major structural protein, is the main component of the skin, bones, tendons and ligaments. Especially at the pediatric age, its damage in the context of pathologies such as systemic lupus erythematosus, scleroderma or dermatomyositis can have a significant negative impact on the development and optimal functioning of the body. The consequences can extend to various structures (e.g., joints, skin, eyes, lungs, heart, kidneys). Of these, we retain and reveal later in our manuscript, mainly the respiratory involvement. Manifested in various forms that can damage the chest wall, pleura, interstitium or vascularization, lung damage in pediatric systemic inflammatory diseases is underdeveloped in the literature compared to that described in adults. Under the threat of severe evolution, sometimes rapidly progressive and leading to death, it is necessary to increase the popularization of information aimed at physiopathological triggering and maintenance mechanisms, diagnostic means, and therapeutic directions among medical specialists. In addition, we emphasize the need for interdisciplinary collaboration, especially between pediatricians, rheumatologists, infectious disease specialists, pulmonologists, and immunologists. Through our narrative review we aimed to bring up to date, in a concise and easy to assimilate, general principles regarding the pulmonary impact of collagenoses using the most recent articles published in international libraries, duplicated by previous articles, of reference for the targeted pathologies.
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Affiliation(s)
- Ancuta Lupu
- Mother and Child Medicine Department, "Grigore T. Popa" University of Medicine and Pharmacy, Iasi, Romania
| | - Maria Oana Sasaran
- Faculty of Medicine, "George Emil Palade" University of Medicine, Pharmacy, Science and Technology, Targu Mures, Romania
| | - Elena Jechel
- Mother and Child Medicine Department, "Grigore T. Popa" University of Medicine and Pharmacy, Iasi, Romania
| | - Alice Azoicai
- Mother and Child Medicine Department, "Grigore T. Popa" University of Medicine and Pharmacy, Iasi, Romania
| | - Monica Mihaela Alexoae
- Mother and Child Medicine Department, "Grigore T. Popa" University of Medicine and Pharmacy, Iasi, Romania
| | - Iuliana Magdalena Starcea
- Mother and Child Medicine Department, "Grigore T. Popa" University of Medicine and Pharmacy, Iasi, Romania
| | - Adriana Mocanu
- Mother and Child Medicine Department, "Grigore T. Popa" University of Medicine and Pharmacy, Iasi, Romania
| | - Alin Horatiu Nedelcu
- Faculty of Medicine, "Grigore T. Popa" University of Medicine and Pharmacy, Iasi, Romania
| | - Anton Knieling
- Faculty of Medicine, "Grigore T. Popa" University of Medicine and Pharmacy, Iasi, Romania
| | - Delia Lidia Salaru
- Faculty of Medicine, "Grigore T. Popa" University of Medicine and Pharmacy, Iasi, Romania
| | - Stefan Lucian Burlea
- Public Health and Management Department, "Grigore T. Popa" University of Medicine and Pharmacy, Iasi, Romania
| | - Vasile Valeriu Lupu
- Mother and Child Medicine Department, "Grigore T. Popa" University of Medicine and Pharmacy, Iasi, Romania
| | - Ileana Ioniuc
- Mother and Child Medicine Department, "Grigore T. Popa" University of Medicine and Pharmacy, Iasi, Romania
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Hassan MR, Hossain A, Mahata J, Srivastava V, Sarkar S. Hematological manifestation of Pediatric Systemic Lupus Erythematosus (SLE) - A single centered cross-sectional study. J Family Med Prim Care 2024; 13:1787-1792. [PMID: 38948621 PMCID: PMC11213417 DOI: 10.4103/jfmpc.jfmpc_1583_23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2023] [Revised: 12/15/2023] [Accepted: 12/23/2023] [Indexed: 07/02/2024] Open
Abstract
Introduction Systemic lupus erythematosus (SLE), the commonest type of lupus, is an autoimmune multisystemic disorder that can affect any organ system of the body, especially blood vessels and connective tissues, causing widespread inflammation. Pediatric onset of SLE is a rare condition with more hematological involvement. Aim This study was undertaken to observe various hematological abnormalities and their association with various autoantibodies present in pediatric SLE in Eastern India. Methodology It was a single-centered, cross-sectional, observational, hospital-based study conducted in the Department of Pediatric Medicine in collaboration with the Department of Rheumatology in IPGME and R and SSKM Hospital, Kolkata. The duration of the study was 1.5 years, and a total of 30 children up to 12 years of age of either gender were enrolled. Study participants were evaluated for various parameters like demographic, hematological (anemia, neutropenia, leucopenia, lymphopenia, and thrombocytopenia), biochemical (CRP, Lactate dehydrogenase (LDH), and bilirubin), autoantibodies (anti-dsDNA, anti-Ro 52, and anti-Ribonucleoprotein [RNP]), and SLE related pathologies (Cutaneous, nephritis, serositis). Results In the present study, most of the participants had arthritis, muscle pain (86.66%), and hematological involvement (80%). Among cytopenias, anemia was the commonest. dsDNA autoantibody was positive in most of the patients (83%), and about one-third suffered from autoimmune hemolytic anemia (AIHA). No association was observed between autoantibodies and various hematological manifestations. Conclusion It can be concluded from the present study that anemia is the most common cytopenia in pediatric SLE, but there is no association between autoantibodies and these cytopenias. However, study on larger population may give better results.
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Affiliation(s)
- Md Rakibul Hassan
- Department of Pediatrics, IPGME&R and SSKM Hospital, Kolkata, West Bengal, India
| | - Ashik Hossain
- Department of Pediatrics, IPGME&R and SSKM Hospital, Kolkata, West Bengal, India
| | - Joyanti Mahata
- Department of Biochemistry, Burdwan Medical College, Burdwan, West Bengal, India
| | - Vartika Srivastava
- Department of Pharmacology, Kalinga Institute of Medical Sciences, KIIT Deemed to be University, Bhubaneswar, Odisha, India
| | - Sougata Sarkar
- Department of Clinical and Experimental Pharmacology, School of Tropical Medicine, Kolkata, West Bengal, India
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Kalashnikova E, Isupova E, Gaidar E, Sorokina L, Kaneva M, Masalova V, Dubko M, Kornishina T, Lubimova N, Kuchinskaya E, Chikova I, Raupov R, Kalashnikova O, Kostik M. BCD020 rituximab bioanalog compared to standard treatment in juvenile systemic lupus erythematosus: The data of 12 months case-control study. World J Clin Pediatr 2024; 13:89049. [PMID: 38596443 PMCID: PMC11000064 DOI: 10.5409/wjcp.v13.i1.89049] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2023] [Revised: 02/02/2024] [Accepted: 01/30/2024] [Indexed: 03/06/2024] Open
Abstract
BACKGROUND Systemic lupus erythematosus (SLE) is the most frequent and serious systemic connective tissue disease. Nowadays there is no clear guidance on its treatment in childhood. There are a lot of negative effects of standard-of-care treatment (SOCT), including steroid toxicity. Rituximab (RTX) is the biological B-lymphocyte-depleting agent suggested as a basic therapy in pediatric SLE. AIM To compare the benefits of RTX above SOCT. METHODS The data from case histories of 79 children from the Saint-Petersburg State Pediatric Medical University from 2012 to 2022 years, were analyzed. The diagnosis of SLE was established with SLICC criteria. We compared the outcomes of treatment of SLE in children treated with and without RTX. Laboratory data, doses of glucocorticosteroids, disease activity measured with SELENA-SLEDAI, and organ damage were assessed at the time of initiation of therapy and one year later. RESULTS Patients, treated with RTX initially had a higher degree of disease activity with prevalence of central nervous system and kidney involvement, compared to patients with SOCT. One year later the disease characteristics became similar between groups with a more marked reduction of disease activity (SELENA-SLEDAI activity index) in the children who received RTX [-19 points (17; 23) since baseline] compared to children with SOCT [-10 (5; 15.5) points since baseline, P = 0.001], the number of patients with active lupus nephritis, and daily proteinuria. During RTX therapy, infectious diseases had three patients; one patient developed a bi-cytopenia. CONCLUSION RTX can be considered as the option in the treatment of severe forms of SLE, due to its ability to arrest disease activity compared to SOCT.
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Affiliation(s)
- Elvira Kalashnikova
- Hospital Pediatry Department, Saint-Petersburg State Pediatric Medical University, Saint-Petersburg 194100, Russia
| | - Eugenia Isupova
- Hospital Pediatry Department, Saint-Petersburg State Pediatric Medical University, Saint-Petersburg 194100, Russia
| | - Ekaterina Gaidar
- Hospital Pediatry Department, Saint-Petersburg State Pediatric Medical University, Saint-Petersburg 194100, Russia
| | - Lyubov Sorokina
- Hospital Pediatry Department, Saint-Petersburg State Pediatric Medical University, Saint-Petersburg 194100, Russia
| | - Maria Kaneva
- Hospital Pediatry Department, Saint-Petersburg State Pediatric Medical University, Saint-Petersburg 194100, Russia
| | - Vera Masalova
- Hospital Pediatry Department, Saint-Petersburg State Pediatric Medical University, Saint-Petersburg 194100, Russia
| | - Margarita Dubko
- Hospital Pediatry Department, Saint-Petersburg State Pediatric Medical University, Saint-Petersburg 194100, Russia
| | - Tatiana Kornishina
- Hospital Pediatry Department, Saint-Petersburg State Pediatric Medical University, Saint-Petersburg 194100, Russia
| | - Natalia Lubimova
- Research Laboratory of Autoimmune and Autoinflammatory Diseases, Almazov National Medical Research Centre, Saint Petersburg 197341, Russia
| | - Ekaterina Kuchinskaya
- Research Laboratory of Autoimmune and Autoinflammatory Diseases, Almazov National Medical Research Centre, Saint Petersburg 197341, Russia
| | - Irina Chikova
- Hospital Pediatry Department, Saint-Petersburg State Pediatric Medical University, Saint-Petersburg 194100, Russia
| | - Rinat Raupov
- Hospital Pediatry Department, Saint-Petersburg State Pediatric Medical University, Saint-Petersburg 194100, Russia
- Department of Rheumatology, Turner National Medical Research Center for Сhildren’s Orthopedics and Trauma Surgery, Saint-Petetrsburg 197136, Russia
| | - Olga Kalashnikova
- Hospital Pediatry Department, Saint-Petersburg State Pediatric Medical University, Saint-Petersburg 194100, Russia
| | - Mikhail Kostik
- Hospital Pediatry Department, Saint-Petersburg State Pediatric Medical University, Saint-Petersburg 194100, Russia
- Research Laboratory of Autoimmune and Autoinflammatory Diseases, Almazov National Medical Research Centre, Saint Petersburg 197341, Russia
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Soliman HM, Fahmy BS, Ali MG, Shafie ES. Circulating prolactin level in Juvenile Systemic Lupus Erythematosus and its correlation with disease activity: a case control study. Pediatr Rheumatol Online J 2023; 21:128. [PMID: 37864188 PMCID: PMC10588056 DOI: 10.1186/s12969-023-00915-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2023] [Accepted: 10/15/2023] [Indexed: 10/22/2023] Open
Abstract
BACKGROUND The linkage between prolactin (PRL) and systemic lupus erythematosus (SLE) is still vague. Determination of serum levels of prolactin to reveal its role in patients with SLE is the aim of the study. METHODS This is a case-control study performed on 40 children with SLE and 40 age- and sex-matched controls. Cases were further subdivided according to disease activity into mild, moderate, and severe groups using the SLEDAI (Systemic Lupus Erythematosus Disease Activity Index) score. Serum prolactin levels were assayed by ELISA (enzyme-linked immunosorbent assay). RESULTS prolactin level was significantly higher in SLE patients (17.3 ± 6.6 µg/L) than in controls (13.5 ± 5.3 µg/L) (P value = 0.005). Although the prolactin level was highest in severe cases (19.3 ± 7.7 µg/L), followed by moderate cases (17.0 ± 5.3 µg/L), and lowest in mild cases (14.0 ± 6.2 µg/L), the variance between the 3 groups was not statistically significant (P value = 0.212). A significant positive correlation between prolactin level and SLEDAI score was detected (r = 0.368) (P value = 0.019). Hyperprolactinemia was found in 8 patients (20%) but not in controls; 4 out of 8 patients with hyperprolactinemia (50%) showed neurological manifestations compared to only 3 out of 32 patients with a normal prolactin level (9.4%) (P value = 0.007). CONCLUSION A relationship between serum prolactin levels and juvenile SLE disease was detected. Neurological manifestations were more prevalent among SLE patients with hyperprolactinemia.
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Affiliation(s)
- Hend Mehawed Soliman
- Pediatrics Department, Faculty of Medicine, Children`s Hospital, Kasr Alainy, Cairo University, Cairo, Egypt
| | - Balsam Sherif Fahmy
- Clinical and Chemical Pathology Department, Faculty of Medicine, Kasr Alainy, Cairo University, Cairo, Egypt.
| | - Moataz Gamal Ali
- Pediatrics Department, Sheikh Zayed Specialized Hospital, Sheikh Zayed City, Egypt
| | - Eman Shafik Shafie
- Pediatrics Department, Faculty of Medicine, Children`s Hospital, Kasr Alainy, Cairo University, Cairo, Egypt
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Kostik M, Kalashnikova E, Rinat R, Isupova E, Gaidar E, Soloviev AA, Masalova V, Snegireva L, Kornishina T, Abramova N, Suspitsin E, Sorokina L, Kaneva M, Dubko MF, Lubimova N, Kuchuinskaya E, Kalashnikova O, Chasnyk V. Rituximab Biosimilar BCD020 Shows Superior Efficacy above Conventional Non-Biologics Treatment in Pediatric Lupus Nephritis: The Data of Retrospective Cohort Study. Biomedicines 2023; 11:biomedicines11051503. [PMID: 37239173 DOI: 10.3390/biomedicines11051503] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2023] [Revised: 05/14/2023] [Accepted: 05/17/2023] [Indexed: 05/28/2023] Open
Abstract
BACKGROUND Pediatric lupus nephritis (LN) is one of the most serious manifestations of systemic lupus erythematosus (SLE) in children, determining the outcomes of the disease. There are no standardized treatment protocols for pediatric LN, and the role of biologics has not yet been conclusively defined. OBJECTIVES analyze the safety and efficacy of rituximab biosimilar BCD020 in pediatric patients with lupus nephritis. METHODS in a retrospective cohort study, the data from the case histories of 25 patients with LN (10 boys and 15 girls) with an onset age of 13 (9-16) years, who failed conventional non-biologic treatment or developed corticosteroid dependence/toxicity, were included. The diagnosis was made using Systemic Lupus International Collaborating Clinics (SLICC) classification criteria. Rituximab biosimilar BCD020 was prescribed in a dosage of 375 mg/m2 every week (2-4 infusions) with repeated courses every 6-12 months (2-4 infusions) according to disease activity, B-cell depletion, and IgG levels. The dynamics of clinical and laboratory data, the activity of the disease by SLEDAI, and corticosteroid doses were assessed at the onset and during the rituximab trial. RESULTS The main patient's characteristics were: Pre-rituximab non-biologic conventional treatment included: cyclophosphamide 15 (60%), MMF 8 (32%), azathioprine 3 (12%), hydroxychloroquine 12 (48%), and pulse therapy of methylprednisolone followed by oral methylprednisolone 25 (100%). The time before rituximab was 7.0 (3.0-24.0) months, and the whole observation period was 7.0 (0; 24) months. The initial pre-rituximab treatment slightly reduced SLEDAI levels and the proportion of patients with LN. A significant reduction of SLEDAI, the anti-dsDNA level, proteinuria, hematuria, C4 complement, ESR, and the median corticosteroid dose by 80% from the initial value, as well as the proportion of patients without corticosteroids, was observed after rituximab administration. Two deaths were observed due to catastrophic SLE with macrophage activation syndrome, accompanied by a severe infection (invasive aspergillosis, n = 2). Three patients developed serious adverse events: pneumonia (n = 2), transient agranulocytosis (n = 1) after the third rituximab infusion, and meningitis, caused by Listeria monocytosis, after the first rituximab infusion. Eight patients received antibacterial treatment for different respiratory infections without hospital admissions. CONCLUSIONS Rituximab biosimilar BCD020 showed effectiveness in LN, whereas previous non-biologic treatment was insufficiently effective. Randomized controlled trials are required to evaluate the efficacy and safety of rituximab and evaluate the benefits when compared with conventional SLE treatment.
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Affiliation(s)
- Mikhail Kostik
- Hospital Pediatry, Saint-Petersburg State Pediatric Medical University, 194100 Saint Petersburg, Russia
- Almazov National Medical Research Centre, 197341 Saint Petersburg, Russia
| | - Elvira Kalashnikova
- Hospital Pediatry, Saint-Petersburg State Pediatric Medical University, 194100 Saint Petersburg, Russia
| | - Raupov Rinat
- Hospital Pediatry, Saint-Petersburg State Pediatric Medical University, 194100 Saint Petersburg, Russia
| | - Eugenia Isupova
- Hospital Pediatry, Saint-Petersburg State Pediatric Medical University, 194100 Saint Petersburg, Russia
| | - Ekaterina Gaidar
- Hospital Pediatry, Saint-Petersburg State Pediatric Medical University, 194100 Saint Petersburg, Russia
| | - Anton A Soloviev
- Hospital Pediatry, Saint-Petersburg State Pediatric Medical University, 194100 Saint Petersburg, Russia
| | - Vera Masalova
- Hospital Pediatry, Saint-Petersburg State Pediatric Medical University, 194100 Saint Petersburg, Russia
| | - Ludmila Snegireva
- Hospital Pediatry, Saint-Petersburg State Pediatric Medical University, 194100 Saint Petersburg, Russia
| | - Tatyana Kornishina
- Hospital Pediatry, Saint-Petersburg State Pediatric Medical University, 194100 Saint Petersburg, Russia
| | - Natalia Abramova
- Hospital Pediatry, Saint-Petersburg State Pediatric Medical University, 194100 Saint Petersburg, Russia
| | - Evgeny Suspitsin
- Hospital Pediatry, Saint-Petersburg State Pediatric Medical University, 194100 Saint Petersburg, Russia
- N.N. Petrov National Research Center of Oncology, 197758 Saint Petersburg, Russia
| | - Lubov Sorokina
- Hospital Pediatry, Saint-Petersburg State Pediatric Medical University, 194100 Saint Petersburg, Russia
| | - Maria Kaneva
- Hospital Pediatry, Saint-Petersburg State Pediatric Medical University, 194100 Saint Petersburg, Russia
| | - Margarita F Dubko
- Hospital Pediatry, Saint-Petersburg State Pediatric Medical University, 194100 Saint Petersburg, Russia
| | - Natalia Lubimova
- Almazov National Medical Research Centre, 197341 Saint Petersburg, Russia
| | | | - Olga Kalashnikova
- Hospital Pediatry, Saint-Petersburg State Pediatric Medical University, 194100 Saint Petersburg, Russia
| | - Vyacheslav Chasnyk
- Hospital Pediatry, Saint-Petersburg State Pediatric Medical University, 194100 Saint Petersburg, Russia
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Kalashnikova EM, Raupov RK, Lyubimova NA, Kuchinskaya EM, Masalova VV, Isupova EA, Gaidar EV, Dubko MF, Snegireva LS, Sorokina LS, Kornishina TL, Kaneva MA, Chikova IA, Likhacheva TS, Kolobova OL, Kalashnikova OV, Chasnyk VG, Kostik MM. The experience of rituximab therapy in patients with juvenile systemic lupus erythematosus: the preliminary results of two-center cohort study. ROSSIYSKIY VESTNIK PERINATOLOGII I PEDIATRII (RUSSIAN BULLETIN OF PERINATOLOGY AND PEDIATRICS) 2023. [DOI: 10.21508/1027-4065-2023-68-1-74-84] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/06/2023]
Abstract
Systemic lupus erythematosus is an immunopathological disease which is characterized by a poor prognosis. Biologics applied in the disease treatment allow reducing the corticosteroid toxicity and controlling the disease.Purpose. To evaluate the efficacy and safety of rituximab therapy in children with systemic lupus erythematosus.Material and methods. The retrospective study included data of 48 patients with systemic lupus erythematosus treated with rituximab. Systemic lupus erythematosus was diagnosed based on the SLICC classification criteria. Patients were assessed at baseline disease status, at the time of rituximab initiation and follow-up. The indications for the rituximab were: lupus nephritis, CNS involvement, and hematological involvement resistant to the standard therapy, and in cases of severe corticosteroid toxicity.Results. During rituximab therapy the significant decrease of the SELENA–SLEDAI activity index was observed. There was a significant decrease of the level of antibodies against dsDNA, normalization of the levels of hemoglobin, ESR, complement C4. The proportion of patients with cytopenia decreased up to their complete absence in patients receiving therapy for three years. The number of patients with active lupus nephritis decreased from 16 at the time of rituximab initiation to 1 after 3 years of therapy. Significant dynamics of proteinuria and hematuria was noted, except for 1 patient. The daily dose of corticosteroids was reduced by 90% from baseline in patients treated for 3 years. Serious adverse events included three deaths in patients with high systemic lupus erythematosus activity with uncontrolled macrophage activation syndrome associated with infections. Various infectious complications, hypogammaglobulinemia, which required replacement therapy with intravenous immunoglobulin, were also recorded.Conclusion. Rituximab can be considered as an option for the treatment of severe forms of systemic lupus erythematosus which are resistant to standard therapy. Further studies are required to evaluate efficacy and safety.
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Affiliation(s)
| | - R. K. Raupov
- Saint Petersburg State Pediatric Medical University; Turner National Medical Research Center for Children’s Orthopedics and Trauma Surgery
| | | | | | | | | | - E. V. Gaidar
- Saint Petersburg State Pediatric Medical University
| | - M. F. Dubko
- Saint Petersburg State Pediatric Medical University
| | | | | | | | - M. A. Kaneva
- Saint Petersburg State Pediatric Medical University
| | | | | | | | | | | | - M. M. Kostik
- Saint Petersburg State Pediatric Medical University; Almazov National Medical Research Center
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9
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Pauli E, Ma Z, Sha Y, Zhang X, Brackett J, Towa L, Upadhyay B, Satcher R. Development of an Immediate-Release Prototype Tablet Formulation of Hydroxychloroquine Sulfate with an Interwoven Taste-Masking System. J Pharm Sci 2023; 112:830-836. [PMID: 36356935 DOI: 10.1016/j.xphs.2022.11.002] [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: 08/04/2022] [Revised: 11/02/2022] [Accepted: 11/02/2022] [Indexed: 11/09/2022]
Abstract
Hydroxychloroquine sulfate (HCQS) was granted US-FDA approval in 1955 for the prevention and treatment of malaria. Since then, its uses have expanded to treat systemic lupus erythematosus and rheumatoid arthritis. For each indication, HCQS is a crucial option for the treatment of pediatric, juvenile, adult, and elderly populations. Existing currently on the market are only 200-mg strength tablets exclusively for adult administration. To facilitate weight-based administration for pediatric and juvenile patients, an HCQS suspension is made by compounding a 200-mg HCQS tablet and suspending the crushed granules into water and Ora-Plus®. The Ora-Plus® suspension does not alter the extreme bitterness of HCQS such that it facilitates oral administration. Additional research has been executed to affirm that a slightly buffered, ion-pairing system, reduces the bitterness of HCQS. The buffered, ion-pairing system can be interwoven into an immediate-release tablet formulation likely without compromising tablet performance. With the taste-masking system embedded, the tablet could be more easily be compounded and suspended in water to generate a palatable oral suspension. Such a novel HCQS 200-mg tablet would be tailored for adult usages wherein the interwoven task-masking system could be utilized to facilitate weight-based administration for pediatric and juvenile patients. The dual quality target product profile of the tablet and the tablet compounded for suspension in water would make the tablet formulation applicable to a wide patient population ranging from pediatric to elder adults to facilitate in improving compliance and overall health outcomes.
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Affiliation(s)
- Elliott Pauli
- RTI International, 3040 Cornwallis Road, Research Triangle Park, NC 27709, United States.
| | - Zhelun Ma
- AustarPhama, LLC 18 Mayfield Ave, Edison, NJ 08837, United States
| | - Ying Sha
- AustarPhama, LLC 18 Mayfield Ave, Edison, NJ 08837, United States
| | - Xiaowen Zhang
- AustarPhama, LLC 18 Mayfield Ave, Edison, NJ 08837, United States
| | - John Brackett
- Celsus Group, 6800 West Doolin, Ponca City, OK 74601, United States
| | - Lili Towa
- Alpha MOS Inc, 802 Cromwell Park, Glen Burnie, MD 21061, United States
| | - Bindu Upadhyay
- RTI International, 3040 Cornwallis Road, Research Triangle Park, NC 27709, United States
| | - Richard Satcher
- RTI International, 3040 Cornwallis Road, Research Triangle Park, NC 27709, United States
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10
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Mike TB, Rajbhandari P. Persistent Tachycardia in a 10-year-old. Pediatr Rev 2022; 43:590-592. [PMID: 36180537 DOI: 10.1542/pir.2021-004930] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/13/2023]
Affiliation(s)
- Thomas B Mike
- Division of Pediatric Hospital Medicine, Department of Pediatrics, Akron Children's Hospital, Akron, OH
| | - Prabi Rajbhandari
- Division of Pediatric Hospital Medicine, Department of Pediatrics, Akron Children's Hospital, Akron, OH
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11
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Bose S, Madke B. A comprehensive review of immunosuppressive drugs in pediatric dermatoses: Part II – methotrexate and mycophenolate mofetil. INDIAN JOURNAL OF PAEDIATRIC DERMATOLOGY 2022. [DOI: 10.4103/ijpd.ijpd_84_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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12
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Andrade Balbi V, Artur Silva C, Nascimento Pedrosa T, Maria Rodrigues Pereira R, Maria de Arruda Campos L, Pires Leon E, Duarte N, Melechco Carvalho V, Gofint Pasoto S, Cordeiro do Rosário D, Kolachinski Brandao L, I Brunner H, Bonfá E, Emi Aikawa N. Hydroxychloroquine blood levels predicts flare in childhood-onset lupus nephritis. Lupus 2021; 31:97-104. [PMID: 34965782 DOI: 10.1177/09612033211062515] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
OBJECTIVE Low hydroxychloroquine (HCQ) blood levels are predictors of flare in adult lupus. Childhood-onset systemic lupus erythematosus (cSLE) has high morbidity with renal involvement in up to 80% of cases. The aim of this study is to determine the HCQ cut-off levels which predicts flare in childhood-onset lupus nephritis (LN). METHODS Sixty LN patients on HCQ use for at least 6-months were prospectively evaluated at baseline (BL) and about 6-months later for cSLE flare and HCQ blood levels (ng/mL) measured by liquid chromatography-tandem mass spectrometry. RESULTS There were 19 patients (32%) with flare, during the study with median SLEDAI increase of 4 (0-8). Median (IQR) BL HCQ levels of the flare group were lower compared to stable patients [557.5 (68.6-980.3) vs. 1061.9 (534.8-1590.0 ng/mL); p=0.012]. ROC curve analysis demonstrated that HCQ levels≤1075 ng/mL were associated with a 5.08 (95%CI 1.28-20.13; p=0.021) times increased risk of flare. Six-month HCQ levels revealed that most patients 24/54 (44%) had persistently low levels (≤1075) during follow-up. Among those, 11/24 (46%) had flare. Multiple logistic regression analysis including prednisone use, baseline SLEDAI-2K, adherence based on pharmacy refill and BL HCQ blood levels as possible predictors of flare revealed that only HCQ blood level was independently associated with flare (OR 0.999, 95%CI 0.998-1.0, p=0.013). CONCLUSIONS We demonstrated that HCQ blood cut-off level under 1075 ng/mL predicts flare in childhood-onset LN patients under prescribed HCQ dose of 4.0-5.5 mg/kg/day. We further observed that most of these patients have compliance issues reinforcing the need for a close surveillance particularly in those with levels below the defined cut-off.
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Affiliation(s)
- Verena Andrade Balbi
- Rheumatology Unit, Instituto da Criança da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
| | - Clovis Artur Silva
- Pediatria, Faculdade de Medicina da Universidade de São Paulo, Sao Paul, Brazil
| | - Tatiana Nascimento Pedrosa
- Rheumatology Unit, Instituto da Criança da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
| | | | | | - Elaine Pires Leon
- Rheumatology Division, Hospital das Clínicas HCFMUSP, Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, Brazil
| | - Nilo Duarte
- Division of Central Laboratory, Hospital das Clínicas HCFMUSP, Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, Brazil
| | | | - Sandra Gofint Pasoto
- Rheumatology Division, Hospital das Clínicas HCFMUSP, Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, Brazil
| | - Debora Cordeiro do Rosário
- Rheumatology Division, Hospital das Clínicas HCFMUSP, Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, Brazil
| | - Leticia Kolachinski Brandao
- Rheumatology Division, Hospital das Clínicas HCFMUSP, Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, Brazil
| | - Hermine I Brunner
- Peds Rheum, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
| | - Eloisa Bonfá
- Division of Central Laboratory, Hospital das Clínicas HCFMUSP, Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, Brazil
| | - Nadia Emi Aikawa
- Rheumatology Unit, Instituto da Criança da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
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Said MA, Silva LSTE, de Oliveira Rocha AM, Alves GGB, Piotto DGP, Len CA, Terreri MT. Adverse drug reactions associated with treatment in patients with chronic rheumatic diseases in childhood: a retrospective real life review of a single center cohort. Adv Rheumatol 2020; 60:53. [PMID: 33153496 DOI: 10.1186/s42358-020-00154-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2020] [Accepted: 10/11/2020] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Adverse drug reactions (ADRs) are the sixth leading causes of death worldwide; monitoring them is fundamental, especially in patients with disorders like chronic rheumatic diseases (CRDs). The study aimed to describe the ADRs investigating their severity and associated factors and resulting interventions in pediatric patients with CRDs. METHODS A retrospective, descriptive and analytical study was conducted on a cohort of children and adolescents with juvenile idiopathic arthritis (JIA), juvenile systemic lupus erythematosus (JSLE) and juvenile dermatomyositis (JDM). The study evaluated medical records of the patients to determine the causality and the management of ADRs. In order to investigate the risk factors that would increase the risk of ADRs, a logistic regression model was carried out on a group of patients treated with the main used drug. RESULTS We observed 949 ADRs in 547 patients studied. Methotrexate (MTX) was the most frequently used medication and also the cause of the most ADRs, which occurred in 63.3% of patients, followed by glucocorticoids (GCs). Comparing synthetic disease-modifying anti-rheumatic drugs (sDMARDs) vs biologic disease-modifying anti-rheumatic drugs (bDMARDs), the ADRs attributed to the former were by far higher than the latter. In general, the severity of ADRs was moderate and manageable. Drug withdrawal occurred in almost a quarter of the cases. In terms of risk factors, most patients who experienced ADRs due to MTX, were 16 years old or younger and received MTX in doses equal or higher than 0.6 mg/kg/week. Patients with JIA and JDM had a lower risk of ADRs than patients with JSLE. In the multiple regression model, the use of GCs for over 6 months led to an increase of 0.5% in the number of ADRs. CONCLUSIONS Although the ADRs highly likely affect a wide range of children and adolescents with CRDs they were considered moderate and manageable cases mostly. However, triggers of ADRs need further investigations.
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Affiliation(s)
- Manar Amanouil Said
- Division of Pediatric Rheumatology, Department of Pediatrics, Federal University Sao Paulo (Unifesp), Rua Borges Lagoa, 802, Sao Paulo, ZIP CODE: 04038-001, Brazil.
| | - Liana Soido Teixeira E Silva
- Division of Pediatric Rheumatology, Department of Pediatrics, Federal University Sao Paulo (Unifesp), Rua Borges Lagoa, 802, Sao Paulo, ZIP CODE: 04038-001, Brazil
| | - Aline Maria de Oliveira Rocha
- Division of Pediatric Rheumatology, Department of Pediatrics, Federal University Sao Paulo (Unifesp), Rua Borges Lagoa, 802, Sao Paulo, ZIP CODE: 04038-001, Brazil
| | - Gustavo Guimarães Barreto Alves
- Division of Pediatric Rheumatology, Department of Pediatrics, Federal University Sao Paulo (Unifesp), Rua Borges Lagoa, 802, Sao Paulo, ZIP CODE: 04038-001, Brazil
| | - Daniela Gerent Petry Piotto
- Division of Pediatric Rheumatology, Department of Pediatrics, Federal University Sao Paulo (Unifesp), Rua Borges Lagoa, 802, Sao Paulo, ZIP CODE: 04038-001, Brazil
| | - Claudio Arnaldo Len
- Division of Pediatric Rheumatology, Department of Pediatrics, Federal University Sao Paulo (Unifesp), Rua Borges Lagoa, 802, Sao Paulo, ZIP CODE: 04038-001, Brazil
| | - Maria Teresa Terreri
- Division of Pediatric Rheumatology, Department of Pediatrics, Federal University Sao Paulo (Unifesp), Rua Borges Lagoa, 802, Sao Paulo, ZIP CODE: 04038-001, Brazil
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14
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Aygun D, Kuskucu MA, Sahin S, Adrovic A, Barut K, Yıldız M, Sharifova S, Midilli K, Cokugras H, Camcıoglu Y, Kasapcopur O. Epstein-Barr virus, cytomegalovirus and BK polyomavirus burden in juvenile systemic lupus erythematosus: correlation with clinical and laboratory indices of disease activity. Lupus 2020; 29:1263-1269. [PMID: 32646294 DOI: 10.1177/0961203320940029] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
OBJECTIVES Clinical and laboratory investigations have revealed that Epstein-Barr virus (EBV) is involved in altered immunological response of systemic lupus erythematosus (SLE). Higher seroprevalence rates of anti-EBV antibodies and increased viral load are demonstrated in adult SLE patients. The prevalence of BK polyomavirus (BKV) reactivation is also suggested to be higher in SLE. Herein, we aimed to evaluate the immune response of children with SLE to EBV antigens in addition to EBV and BKV DNA. We also tried to evaluate whether these serological results differ from another connective tissue disease - juvenile systemic sclerosis (jSS) - and healthy individuals. METHODS Serum levels of EBV early antigen diffuse (EA-D) IgG, EBV nuclear antigen-1 IgG, EBV viral capsid antigen (VCA), cytomegalovirus (CMV) IgG, EBV DNA, CMV DNA and urinary BKV DNA were evaluated in healthy controls and in patients with a diagnosis of juvenile SLE (jSLE) and jSS. RESULTS A total of 70 jSLE patients, 14 jSS patients and 44 sex-matched healthy individuals were involved in the study. EBV VCA was positive in 84.2% of jSLE patients, 85.7% of jSS patients and 36.3% of healthy controls. EBV EA-D IgG positivity was significantly higher in jSLE patients compared to jSS patients and healthy controls (20% vs. 7.1% and 0%, p = 0.005). EBV VCA positivity was associated with malar rash and immunological disorder, but there was no statistical significance in other antibody positivity in terms of clinical and haemogram findings and autoantibody positivity. CMV DNA positivity was present in only 2.8% of jSLE patients. None of the jSS patients or the healthy controls had CMV DNA positivity. EBV DNA and BKV DNA were also negative in all three groups. CONCLUSION The results of our study assume a relationship between SLE and EBV, but we could not demonstrate an association between CMV and BKV. The negative DNA results in contrast to serological positivity can be interpreted as an altered and impaired immune system and increased viral susceptibility. These results suggest that EBV contributes to disease continuity, even if it does not directly cause development.
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MESH Headings
- Adolescent
- Adult
- Antibodies, Viral/blood
- Antigens, Viral/blood
- Antigens, Viral/immunology
- BK Virus/immunology
- BK Virus/isolation & purification
- Capsid Proteins/immunology
- Case-Control Studies
- Child
- Cytomegalovirus/immunology
- Cytomegalovirus/isolation & purification
- Disease Progression
- Epstein-Barr Virus Infections
- Herpesvirus 4, Human/immunology
- Herpesvirus 4, Human/isolation & purification
- Humans
- Lupus Erythematosus, Systemic/blood
- Lupus Erythematosus, Systemic/virology
- Scleroderma, Localized/blood
- Scleroderma, Localized/virology
- Scleroderma, Systemic/blood
- Scleroderma, Systemic/virology
- Viral Load
- Young Adult
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Affiliation(s)
- Deniz Aygun
- Department of Pediatric Infectious Disease, Istanbul University-Cerrahpasa, Cerrahpasa Medical School, Istanbul, Turkey
| | - Mert Ahmet Kuskucu
- Department of Microbiology and Clinical Microbiology, Istanbul University-Cerrahpasa, Cerrahpasa Medical School, Istanbul, Turkey
| | - Sezgin Sahin
- Department of Pediatric Rheumatology, Istanbul University-Cerrahpasa, Cerrahpasa Medical School, Istanbul, Turkey
| | - Amra Adrovic
- Department of Pediatric Rheumatology, Istanbul University-Cerrahpasa, Cerrahpasa Medical School, Istanbul, Turkey
| | - Kenan Barut
- Department of Pediatric Rheumatology, Istanbul University-Cerrahpasa, Cerrahpasa Medical School, Istanbul, Turkey
| | - Mehmet Yıldız
- Department of Pediatric Rheumatology, Istanbul University-Cerrahpasa, Cerrahpasa Medical School, Istanbul, Turkey
| | - Sabina Sharifova
- Department of Pediatric Infectious Disease, Istanbul University-Cerrahpasa, Cerrahpasa Medical School, Istanbul, Turkey
| | - Kenan Midilli
- Department of Microbiology and Clinical Microbiology, Istanbul University-Cerrahpasa, Cerrahpasa Medical School, Istanbul, Turkey
| | - Haluk Cokugras
- Department of Pediatric Infectious Disease, Istanbul University-Cerrahpasa, Cerrahpasa Medical School, Istanbul, Turkey
| | - Yıldız Camcıoglu
- Department of Pediatric Infectious Disease, Istanbul University-Cerrahpasa, Cerrahpasa Medical School, Istanbul, Turkey
| | - Ozgur Kasapcopur
- Department of Pediatric Rheumatology, Istanbul University-Cerrahpasa, Cerrahpasa Medical School, Istanbul, Turkey
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15
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Trachana M, Pratsidou-Gertsi P, Kanakoudi-Tsakalidou F, Tzimouli V, Printza N, Papachristou F. Impact of the longitudinal quantitative assessment of juvenile systemic lupus erythematosus severity on the disease outcome. Clin Rheumatol 2020; 40:675-682. [PMID: 32638251 DOI: 10.1007/s10067-020-05252-8] [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: 03/28/2020] [Revised: 06/16/2020] [Accepted: 06/19/2020] [Indexed: 10/23/2022]
Abstract
OBJECTIVES This study on juvenile SLE patients aimed to evaluate retrospectively the impact of a tertiary center's management policy of the disease severity on its long-term progression and cumulative damage development as well as provision of quality-driven medical care (QmC). METHODS Disease activity was assessed by the Physician Global Assessment and SLEDAI-2K, flares by SELENA/SLEDAI, and damage by the pediatric SLICC/DI at diagnosis, 6 months post-diagnosis, and annually thereafter. At the same time, QmC was evaluated by relevant indices and quality of life was captured by the Greek version of the General Health Questionnaire only at the last visit. RESULTS A total of 35 patients (25/35 females) aged at diagnosis 5.5-15.16 years (median 11.83) with a median lag time to diagnosis 1.8 months had a follow-up of 5 (35/35) and 10 years (13/35), respectively. The predominant baseline manifestations were consistent with those previously reported. Out of 35 patients, 24 (68.5%) were clinically inactive at year 5, and 5/13 (38%) at year 10. All patients received immunosuppressives and 7/35 biologics in addition. At the end of their follow-up, damage was found in 9/35 patients, but none of them had a neuropsychiatric disorder. Over the study, 28/35 patients were compliant with the QmC recommendations. CONCLUSIONS An early diagnosis combined with a longitudinal quantitative assessment of the disease activity and severity contributes to the continuous evaluation of the disease state. They are the key determinants for the selection of an early, targeted, and personalized management; they restrict the cumulative damage development and contribute to an optimal outcome. Key Points • Juvenile SLE has a heavier introductory profile than in adults and an unpredictable trajectory. • The application of contemporary metric tools for assessing the disease state leads to an objective assessment and regimen selection. • An early diagnosis combined with longitudinal quantitative assessment is a key determinant for an optimal management and a minimal damage development.
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Affiliation(s)
- Maria Trachana
- Pediatric Immunology and Rheumatology Referral Center, 1st Dept. of Pediatrics, Hippokration General Hospital Aristotle University, 10, 49, Konstantinoupoleos Street, GR54642, Thessaloniki, Greece.
| | - Polyxeni Pratsidou-Gertsi
- Pediatric Immunology and Rheumatology Referral Center, 1st Dept. of Pediatrics, Hippokration General Hospital Aristotle University, 10, 49, Konstantinoupoleos Street, GR54642, Thessaloniki, Greece
| | - Florence Kanakoudi-Tsakalidou
- Pediatric Immunology and Rheumatology Referral Center, 1st Dept. of Pediatrics, Hippokration General Hospital Aristotle University, 10, 49, Konstantinoupoleos Street, GR54642, Thessaloniki, Greece
| | - Vasiliki Tzimouli
- Pediatric Immunology and Rheumatology Referral Center, 1st Dept. of Pediatrics, Hippokration General Hospital Aristotle University, 10, 49, Konstantinoupoleos Street, GR54642, Thessaloniki, Greece
| | - Nikoleta Printza
- Pediatric Nephrology Unit, 1st Dept. of Pediatrics, Hippokration General Hospital, Aristotle University, Thessaloniki, Greece
| | - Fotis Papachristou
- Pediatric Nephrology Unit, 1st Dept. of Pediatrics, Hippokration General Hospital, Aristotle University, Thessaloniki, Greece
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16
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Pauli E, Joshi H, Vasavada A, Brackett J, Towa L. Evaluation of an Immediate-Release Formulation of Hydroxychloroquine Sulfate With an Interwoven Pediatric Taste-Masking System. J Pharm Sci 2020; 109:1493-1497. [DOI: 10.1016/j.xphs.2019.12.014] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2019] [Revised: 12/11/2019] [Accepted: 12/18/2019] [Indexed: 01/12/2023]
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17
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Ma J, Yu Q, Zhang T, Zhang Y. Chinese family care patterns of childhood rheumatic diseases: A cluster analysis. Int J Nurs Sci 2019; 7:41-48. [PMID: 32099858 PMCID: PMC7031127 DOI: 10.1016/j.ijnss.2019.11.005] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2019] [Revised: 11/14/2019] [Accepted: 11/27/2019] [Indexed: 12/31/2022] Open
Abstract
Objectives The purpose is to distinguish family care (FC) patterns of childhood rheumatic diseases in Chinese families and to determine the predictors of FC patterns. Methods This secondary analysis contained two cross-section surveys with a convenient sample of totally 398 caregivers who have a child with rheumatic diseases from four pediatric hospitals. Caregivers were required to completed Family Management Measure questionnaire. Cluster analysis was used to distinguish patterns and multinomial logistic regression analysis was used to find predictors. Results Four patterns were identified: the normal-perspective and collaborative (28.4%), the effortless and contradictory (24.6%), the chaotic and strenuous (18.3%), and the confident and concerning (28.7%). Disease category (χ2 = 21.23, P = 0.002), geographic location (χ2 = 8.41, P = 0.038), maternal educational level (χ2 = 12.69, P = 0.048) and family monthly income (χ2 = 33.21, P < 0.001) predicted different patterns. Conclusions FC patterns were different among families. Disease-related and family-related factors were vital predictors to distinguish patterns consistent with the Family Management Style Framework. The result assisted that clinicians recognize FC patterns and predictors effectively to provide tailored advice in time.
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Affiliation(s)
- Jiali Ma
- School of Nursing, Shanghai Jiao Tong University, Shanghai, China
| | - Qinglin Yu
- Department of Nephrology and Rheumatology, Children's Hospital of Shanghai Jiao Tong University, Shanghai, China
| | - Taomei Zhang
- School of Nursing, Shanghai Jiao Tong University, Shanghai, China
| | - Ying Zhang
- School of Nursing, Shanghai Jiao Tong University, Shanghai, China
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19
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Kontaxi E, Trachana M, Pratsidou-Gertsi P, Volakli E, Violaki A, Sdougka M. Paediatric Acute Respiratory Distress Syndrome as the introductory manifestation in a patient with Childhood Onset Systemic Lupus Erythematosus. Mediterr J Rheumatol 2019; 30:135-138. [PMID: 32185354 PMCID: PMC7045961 DOI: 10.31138/mjr.30.2.135] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2019] [Revised: 04/02/2019] [Accepted: 04/06/2019] [Indexed: 11/04/2022] Open
Affiliation(s)
- Efstratia Kontaxi
- Pediatric Immunology and Rheumatology Referral Center, First Department of Pediatrics, Aristotle University, Ippokration Hospital, Thessaloniki, Greece
| | - Maria Trachana
- Pediatric Immunology and Rheumatology Referral Center, First Department of Pediatrics, Aristotle University, Ippokration Hospital, Thessaloniki, Greece,,Corresponding author: Maria Trachana, Associate Professor in Pediatric Rheumatology, Pediatric Immunology and Rheumatology Referral Center, First Department of Pediatrics, Aristotle University, Ippokration Hospital Kleious 6, 54633 Thessaloniki, Greece, E-mail:
| | - Polyxeni Pratsidou-Gertsi
- Pediatric Immunology and Rheumatology Referral Center, First Department of Pediatrics, Aristotle University, Ippokration Hospital, Thessaloniki, Greece
| | - Eleni Volakli
- Pediatric Intensive Care Unit, Ippokration Hospital, Thessaloniki, Greece
| | - Asimenia Violaki
- Pediatric Intensive Care Unit, Ippokration Hospital, Thessaloniki, Greece
| | - Maria Sdougka
- Pediatric Intensive Care Unit, Ippokration Hospital, Thessaloniki, Greece
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20
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Affiliation(s)
- Stephanie Jessica Wan
- 1 University of Toronto, Toronto, Ontario, Canada.,2 The Hospital for Sick Children, Toronto, Ontario, Canada
| | - Irene Lara-Corrales
- 1 University of Toronto, Toronto, Ontario, Canada.,2 The Hospital for Sick Children, Toronto, Ontario, Canada
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21
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Schranz M, Lucà MG, D’Antiga L, Fagiuoli S. The Liver in Systemic Illness. PEDIATRIC HEPATOLOGY AND LIVER TRANSPLANTATION 2019:361-396. [DOI: 10.1007/978-3-319-96400-3_22] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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22
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Krishnan Y, Grodzinsky AJ. Cartilage diseases. Matrix Biol 2018; 71-72:51-69. [PMID: 29803938 PMCID: PMC6146013 DOI: 10.1016/j.matbio.2018.05.005] [Citation(s) in RCA: 286] [Impact Index Per Article: 40.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2018] [Revised: 05/14/2018] [Accepted: 05/15/2018] [Indexed: 01/13/2023]
Abstract
Hyaline cartilages, fibrocartilages and elastic cartilages play multiple roles in the human body including bearing loads in articular joints and intervertebral discs, providing joint lubrication, forming the external ears and nose, supporting the trachea, and forming the long bones during development and growth. The structure and organization of cartilage's extracellular matrix (ECM) are the primary determinants of normal function. Most diseases involving cartilage lead to dramatic changes in the ECM which can govern disease progression (e.g., in osteoarthritis), cause the main symptoms of the disease (e.g., dwarfism caused by genetically inherited mutations) or occur as collateral damage in pathological processes occurring in other nearby tissues (e.g., osteochondritis dissecans and inflammatory arthropathies). Challenges associated with cartilage diseases include poor understanding of the etiology and pathogenesis, delayed diagnoses due to the aneural nature of the tissue and drug delivery challenges due to the avascular nature of adult cartilages. This narrative review provides an overview of the clinical and pathological features as well as current treatment options available for various cartilage diseases. Late breaking advances are also described in the quest for development and delivery of effective disease modifying drugs for cartilage diseases including osteoarthritis, the most common form of arthritis that affects hundreds of millions of people worldwide.
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Affiliation(s)
- Yamini Krishnan
- Department of Chemical Engineering, MIT, Cambridge, MA 02139, USA
| | - Alan J Grodzinsky
- Department of Biological Engineering, MIT, Cambridge, MA 02139, USA; Department of Mechanical Engineering, MIT, Cambridge, MA 02139, USA; Department of Electrical Engineering and Computer Science, MIT, Cambridge, MA 02139, USA.
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Ferreira JCOA, Trindade VC, Espada G, Morel Z, Bonfá E, Magalhães CS, Silva CA. Epidemiology and management practices for childhood-onset systemic lupus erythematosus patients: a survey in Latin America. Clin Rheumatol 2018; 37:3299-3307. [PMID: 30094748 DOI: 10.1007/s10067-018-4254-4] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2018] [Revised: 07/18/2018] [Accepted: 08/02/2018] [Indexed: 01/06/2023]
Abstract
To assess epidemiology and management practices of Latin America Pediatric Rheumatologists (LAPR) about childhood-onset systemic lupus erythematosus (cSLE). A cross-sectional study was performed in 288 LAPR PANLAR members based on online survey about cSLE practices. The response rate of web-based survey by LAPR was 170/288(59%) and the majority worked in university hospitals (63%). The ACR and/or SLICC classification criteria (99%) and disease activity tools (97%) were almost universally used by LAPR, whereas damage index (70%) and CHAQ (58%) instruments were less frequently used. Laboratory exams, diagnostic imaging, and biopsies were generally available (> 75%), however low availability for densitometry (66%). Drug access was excellent for the most common prescribed medications (> 75%), except for belimumab (11%). Emerging mosquito-borne diseases were also reported: dengue (20%), chikungunya (11%), and Zika (8%). Groups were further divided in two, according to the median number of cSLE patients followed by LAPR in the last year: groups A and B (≥ 25 and < 25, respectively). Frequencies of condom in combination with other contraceptive methods were significantly higher in group A than B (p = 0.01). The frequencies of reported pregnancy (p < 0.001) and non-adherence to therapy were significantly higher in group A (p = 0.023). Alcohol intake (p = 0.004) and illicit drug use (p = 0.007) were also reported more frequently by LAPR of group A in at least one cSLE patient. This first large web-based survey demonstrated an overall excellent access for diagnosis and therapy by LAPR, probably related to their high rate of practices in tertiary care of university hospitals. Adherence to therapy, pregnancy, and substance abuse was identified as major challenges in this population, particularly in larger centers.
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Affiliation(s)
- Juliana C O A Ferreira
- Pediatric Rheumatology Unit, Children's Institute, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, Av. Dr. Eneas Carvalho de Aguiar, 647 - Cerqueira César, São Paulo, SP, 05403-000, Brazil
| | - Vitor C Trindade
- Pediatric Rheumatology Unit, Children's Institute, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, Av. Dr. Eneas Carvalho de Aguiar, 647 - Cerqueira César, São Paulo, SP, 05403-000, Brazil
| | - Graciela Espada
- Pediatric Rheumatology Unit, Hospital de Niños Dr Ricardo Gutierrez, Buenos Aires, Argentina
| | - Zoilo Morel
- Pediatric Rheumatology Unit, Pediatric Service, Hospital de Clinicas, Universidad Nacional De Asunción, Asunción, Paraguay
| | - Eloisa Bonfá
- Division of Rheumatology, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brazil
| | - Claudia S Magalhães
- Pediatric Rheumatology Unit, São Paulo State University (UNESP) - Faculdade de Medicina de Botucatu, São Paulo, Brazil
| | - Clovis Artur Silva
- Pediatric Rheumatology Unit, Children's Institute, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, Av. Dr. Eneas Carvalho de Aguiar, 647 - Cerqueira César, São Paulo, SP, 05403-000, Brazil.
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24
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Harry O, Yasin S, Brunner H. Childhood-Onset Systemic Lupus Erythematosus: A Review and Update. J Pediatr 2018; 196:22-30.e2. [PMID: 29703361 DOI: 10.1016/j.jpeds.2018.01.045] [Citation(s) in RCA: 74] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2017] [Revised: 10/30/2017] [Accepted: 01/12/2018] [Indexed: 12/13/2022]
Affiliation(s)
- Onengiya Harry
- Division of Rheumatology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH
| | - Shima Yasin
- Division of Rheumatology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH
| | - Hermine Brunner
- Division of Rheumatology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
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25
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Xiao ZX, Zheng X, Hu L, Wang J, Olsen N, Zheng SG. Immunosuppressive Effect of B7-H4 Pathway in a Murine Systemic Lupus Erythematosus Model. Front Immunol 2017; 8:1765. [PMID: 29321778 PMCID: PMC5732181 DOI: 10.3389/fimmu.2017.01765] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2017] [Accepted: 11/27/2017] [Indexed: 12/17/2022] Open
Abstract
B7-H4, one of the co-stimulatory molecules of the B7 family, has been shown to play an important role in negatively regulating the adaptive immune response by inhibiting the proliferation, activation, and cytokine production of T cells. In this study, we investigate the role of B7-H4 in development of systemic lupus erythematosus (SLE). We investigated a murine model of SLE using transfer of bone marrow-derived dendritic cells (BMDCs) that were incubated with activated syngeneic lymphocyte-derived DNA. The recipient mouse produced anti-ds-DNA antibodies as well as displayed splenomegaly and lymphadenopathy as shown by significantly increased weights, and the kidneys showed lupus-like pathological changes include urine protein and glomerulonephritis with hyperplasia in glomeruli and increased mesangial cells and vasculitis with perivascular cell infiltration, glomerular deposition of IgG and complement C3. We showed that B7-H4 deficiency in BMDCs could cause greater production of anti-ds-DNA antibodies in transferred mice, and the lymph tissue swelling and the kidney lesions were also exacerbated with B7-H4 deficiency. Treatment with a B7-H4 antagonist antibody also aggravated the lupus model. Conversely, B7-H4 Ig alleviated the lupus manifestations. Therefore, we conclude that B7-H4 is a negative check point for the development of SLE in this murine model. These results suggest that this approach may have a clinical potential in treating human SLE.
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Affiliation(s)
- Ze Xiu Xiao
- Department of Clinical Immunology, Third Hospital at Sun Yat-sen University, Guangzhou, Guangdong, China.,Laboratory of Immunotherapy, Sun Yat-Sen University, Guangzhou, China
| | - Xu Zheng
- Laboratory of Immunotherapy, Sun Yat-Sen University, Guangzhou, China
| | - Li Hu
- Laboratory of Immunotherapy, Sun Yat-Sen University, Guangzhou, China
| | - Julie Wang
- Division of Rheumatology, Milton S. Hershey Medical Center at Penn State University, Hershey, PA, United States
| | - Nancy Olsen
- Division of Rheumatology, Milton S. Hershey Medical Center at Penn State University, Hershey, PA, United States
| | - Song Guo Zheng
- Department of Clinical Immunology, Third Hospital at Sun Yat-sen University, Guangzhou, Guangdong, China.,Division of Rheumatology, Milton S. Hershey Medical Center at Penn State University, Hershey, PA, United States
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26
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Iweala OI, Copenhaver C, Wu EY, Moran TP. Hydroxychloroquine as a steroid-sparing agent in an infant with chronic urticaria. Ann Allergy Asthma Immunol 2017; 120:102-104. [PMID: 29157861 DOI: 10.1016/j.anai.2017.10.011] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2017] [Revised: 10/05/2017] [Accepted: 10/08/2017] [Indexed: 01/19/2023]
Affiliation(s)
- Onyinye I Iweala
- Department of Pediatrics, Division of Allergy, Immunology, and Rheumatology, University of North Carolina School of Medicine, Chapel Hill, North Carolina.
| | | | - Eveline Y Wu
- Department of Pediatrics, Division of Allergy, Immunology, and Rheumatology, University of North Carolina School of Medicine, Chapel Hill, North Carolina
| | - Timothy P Moran
- Department of Pediatrics, Division of Allergy, Immunology, and Rheumatology, University of North Carolina School of Medicine, Chapel Hill, North Carolina
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27
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Vitor J, Marques A, Rosas A, Nogueira T, Rodrigues M, Fonseca A, Sztajnbok F, Diniz C, Almeida R, Oliveira S. REMISSÃO EM PACIENTES PEDIÁTRICOS COM NEFRITE LÚPICA APÓS TRATAMENTO DE INDUÇÃO. REVISTA BRASILEIRA DE REUMATOLOGIA 2017. [DOI: 10.1016/j.rbr.2017.07.457] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022] Open
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