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Elahi T, Ahmed S, Mubarak M. Relationship of lupus nephritis and pregnancy: A narrative review. World J Nephrol 2024; 13:99700. [PMID: 39723351 PMCID: PMC11572653 DOI: 10.5527/wjn.v13.i4.99700] [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: 07/28/2024] [Revised: 10/22/2024] [Accepted: 10/29/2024] [Indexed: 11/07/2024] Open
Abstract
Pregnancy in women with lupus, particularly those with lupus nephritis (LN), carries an increased risk of adverse outcomes. Women with active LN at the time of conception are at a high risk of poor maternal and fetal outcomes. Recent studies indicate that even in the presence of quiescent disease, factors such as hypertension and positive lupus anticoagulant are predictors of worse pregnancy outcomes. Consequently, pre-conception evaluation is essential to ensure that pursuing pregnancy is safe and timely, and to facilitate proper planning for optimizing medical regimens, discontinuing teratogenic agents, and treating active disease. Additionally, pre-existing LN is associated with higher rates of preeclampsia and hemolysis, elevated liver enzymes, and low platelet count syndrome. Women with lupus and prior LN can have successful pregnancies, but a multidisciplinary approach with close monitoring is essential for optimal outcomes. By systematically reviewing the available evidence, this narrative review aims to provide a comprehensive update on the complex interaction between LN and pregnancy, offering insights to guide clinical practice and future research in this field.
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Affiliation(s)
- Tabassum Elahi
- Department of Nephrology, Sindh Institute of Urology and Transplantation, Karachi 74200, Sindh, Pakistan
| | - Saima Ahmed
- Department of Nephrology, Sindh Institute of Urology and Transplantation, Karachi 74200, Sindh, Pakistan
| | - Muhammed Mubarak
- Department of Histopathology, Sindh Institute of Urology and Transplantation, Karachi 74200, Sindh, Pakistan
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Moroni G, Reggiani F, Ponticelli C. Immune-mediating and immunosuppressive pharmacotherapies for proliferative lupus nephritis. Expert Opin Pharmacother 2024; 25:2061-2076. [PMID: 39402707 DOI: 10.1080/14656566.2024.2416038] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2024] [Accepted: 10/09/2024] [Indexed: 11/01/2024]
Abstract
INTRODUCTION Proliferative lupus nephritis is a common and severe complication of systemic lupus erythematosus. Affected patients are at an increased risk of developing chronic kidney disease, end-stage kidney disease, and extra-renal comorbidities. In recent years, the prognosis for patients with proliferative lupus nephritis has improved thanks to advancements in management regimens. Despite these advances, lupus nephritis continues to present therapeutic complexities and unmet needs. AREAS COVERED Research was conducted across major databases to identify the most relevant articles pertaining to immune-mediating and immunosuppressive therapies in lupus nephritis. EXPERT OPINION The prognosis for patients with proliferative lupus nephritis remains severe. Some drugs used in this disease may be unable to control activity, and most of them have a low therapeutic index and may cause severe and life-threatening side effects. Nonetheless, better management of traditional drugs and the introduction of novel therapies have improved renal prognosis and reduced local and systemic adverse events in patients with proliferative lupus nephritis.
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Affiliation(s)
- Gabriella Moroni
- Nephrology and Dialysis Unit, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
| | - Francesco Reggiani
- Nephrology and Dialysis Unit, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
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Xu M, Tian LL, Li XL, Bao C, Zhang HW, Chen HW. Ovarian function in patients with systemic lupus erythematosus: Pathogenesis, drug application and prospective therapies. World J Exp Med 2024; 14:88867. [PMID: 38948422 PMCID: PMC11212741 DOI: 10.5493/wjem.v14.i2.88867] [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: 10/12/2023] [Revised: 02/27/2024] [Accepted: 04/09/2024] [Indexed: 06/19/2024] Open
Abstract
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease in which multiple organs are damaged that prevails in fertile women. Currently, glucocorticoids and immunosuppressants are widely used to treat SLE patients. However, ovarian dysfunction occurs following the use of these drugs in women with SLE. Here, we summarize recent progress in terms of understanding ovarian injury, the effects of drug application and strategies to improve ovarian function in women with SLE. This review could be helpful to precisely cure SLE in women desiring to have offspring.
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Affiliation(s)
- Min Xu
- Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, Clinical College of Nanjing University of Chinese Medicine, Nanjing 210008, Jiangsu Province, China
| | - Li-Li Tian
- Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, Clinical College of Nanjing University of Chinese Medicine, Nanjing 210008, Jiangsu Province, China
| | - Xiao-Liu Li
- Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, Clinical College of Nanjing University of Chinese Medicine, Nanjing 210008, Jiangsu Province, China
| | - Cheng Bao
- School of Life Science, Nanjing Normal University, Nanjing 210023, Jiangsu Province, China
- Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, Nanjing 210008, Jiangsu Province, China
| | - Hai-Wei Zhang
- Department of Rheumatology and Immunology, Nanjing Pukou People’s Hospital, Nanjing 211800, Jiangsu Province, China
| | - Hong-Wei Chen
- Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, Clinical College of Nanjing University of Chinese Medicine, Nanjing 210008, Jiangsu Province, China
- Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, The Affiliated Hospital of School of Medicine, Nanjing University, Nanjing 210008, Jiangsu Province, China
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Souza AWSD, Dantas JG, Montandon ACDOES, Calich AL, Mont' Alverne ARDS, Gasparin AA, Bianchi D, Yuki EFN, Sacilotto N, Dos Reis Neto ET, Monticielo OA, Pereira IA. Position statement of the Brazilian society of Rheumatology on mesna use as a preventive therapy for bladder disease in patients with systemic autoimmune diseases and systemic vasculitis under cyclophosphamide treatment. Adv Rheumatol 2024; 64:41. [PMID: 38773538 DOI: 10.1186/s42358-024-00380-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2023] [Accepted: 05/06/2024] [Indexed: 05/24/2024] Open
Abstract
OBJECTIVE To review current literature to support the use of mesna as a preventive therapy for hemorrhagic cystitis and bladder cancer in patients with systemic autoimmune diseases and systemic vasculitis treated with cyclophosphamide. MATERIALS AND METHODS The search for articles was conducted systematically through MEDLINE, LILACS, Cochrane Library, and Embase databases. Only articles in English were selected. For available records, titles and abstracts were selected independently by two investigators. RESULTS Eighteen studies were selected for analysis. The known adverse effects of cyclophosphamide were hematological toxicity, infections, gonadal toxicity, teratogenicity, increased risk for malignancy and hemorrhagic cystitis. Long-term toxicity was highly dependent on cyclophosphamide cumulative dose. The risk of bladder cancer is especially higher in long-term exposure and with cumulative doses above 36 g. The risk remains high for years after drug discontinuation. Hemorrhagic cystitis is highly correlated with cumulative dose and its incidence ranges between 12 and 41%, but it seems to be lower with new regimens with reduced cyclophosphamide dose. No randomized controlled trials were found to analyze the use of mesna in systemic autoimmune rheumatic diseases and systemic vasculitis. Retrospective studies yielded conflicting results. Uncontrolled prospective studies with positive results were considered at high risk of bias. No evidence was found to support the use of mesna during the treatment with cyclophosphamide for autoimmune diseases or systemic vasculitis to prevent hemorrhagic cystitis and bladder cancer. In the scenarios of high cumulative cyclophosphamide dose (i.e., > 30 g), patients with restricted fluid intake, neurogenic bladder, therapy with oral anticoagulants, and chronic kidney disease, mesna could be considered. CONCLUSION The current evidence was found to be insufficient to support the routine use of mesna for the prophylaxis of hemorrhagic cystitis and bladder cancer in patients being treated for systemic autoimmune diseases and systemic vasculitis with cyclophosphamide. The use may be considered for selected cases.
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Affiliation(s)
- Alexandre Wagner S de Souza
- Rheumatology Division, Department of Medicine, Escola Paulista de Medicina - Universidade Federal de São Paulo, São Paulo, SP, Brazil.
| | - João Gabriel Dantas
- Rheumatology Division, Department of Medicine, Escola Paulista de Medicina - Universidade Federal de São Paulo, São Paulo, SP, Brazil
| | | | - Ana Luísa Calich
- Rheumatology Division, Department of Medicine, Escola Paulista de Medicina - Universidade Federal de São Paulo, São Paulo, SP, Brazil
- Hospital Sírio Libanês, São Paulo, SP, Brazil
| | | | - Andrese Aline Gasparin
- Rheumatology Division, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
| | | | | | | | - Edgard Torres Dos Reis Neto
- Rheumatology Division, Department of Medicine, Escola Paulista de Medicina - Universidade Federal de São Paulo, São Paulo, SP, Brazil
| | - Odirlei André Monticielo
- Rheumatology Division, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
| | - Ivanio Alves Pereira
- Rheumatology Division, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil
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Balbi GGM, Ahmadzadeh Y, Tektonidou MG, Pengo V, Sciascia S, Ugarte A, Belmont HM, Lopez-Pedrera C, Fortin PR, Wahl D, Gerosa M, de Jesús GR, Ji L, Atsumi T, Efthymiou M, Branch DW, Nalli C, Rodriguez Almaraz E, Petri M, Cervera R, Knight JS, Artim-Esen B, Willis R, Bertolaccini ML, Cohen H, Roubey R, Erkan D, de Andrade DCO. Damage measured by Damage Index for Antiphospholipid Syndrome (DIAPS) in antiphospholipid antibody-positive patients included in the APS ACTION registry. Rheumatology (Oxford) 2024; 63:772-779. [PMID: 37307082 PMCID: PMC11494613 DOI: 10.1093/rheumatology/kead292] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2023] [Revised: 04/27/2023] [Accepted: 05/15/2023] [Indexed: 06/13/2023] Open
Abstract
OBJECTIVES Our primary objective was to quantify damage burden measured by Damage Index for Antiphospholipid Syndrome (DIAPS) in aPL-positive patients with or without a history of thrombosis in an international cohort (the APS ACTION cohort). Secondly, we aimed to identify clinical and laboratory characteristics associated with damage in aPL-positive patients. METHODS In this cross-sectional study, we analysed the baseline damage in aPL-positive patients with or without APS classification. We excluded patients with other autoimmune diseases. We analysed the demographic, clinical and laboratory characteristics based on two subgroups: (i) thrombotic APS patients with high vs low damage; and (ii) non-thrombotic aPL-positive patients with vs without damage. RESULTS Of the 826 aPL-positive patients included in the registry as of April 2020, 586 with no other systemic autoimmune diseases were included in the analysis (412 thrombotic and 174 non-thrombotic). In the thrombotic group, hyperlipidaemia (odds ratio [OR] 1.82; 95% CI 1.05, 3.15; adjusted P = 0.032), obesity (OR 2.14; 95% CI 1.23, 3.71; adjusted P = 0.007), aβ2GPI high titres (OR 2.33; 95% CI 1.36, 4.02; adjusted P = 0.002) and corticosteroid use (ever) (OR 3.73; 95% CI 1.80, 7.75; adjusted P < 0.001) were independently associated with high damage at baseline. In the non-thrombotic group, hypertension (OR 4.55; 95% CI 1.82, 11.35; adjusted P = 0.001) and hyperlipidaemia (OR 4.32; 95% CI 1.37, 13.65; adjusted P = 0.013) were independent predictors of damage at baseline; conversely, single aPL positivity was inversely correlated with damage (OR 0.24; 95% CI 0.075, 0.77; adjusted P = 0.016). CONCLUSIONS DIAPS indicates substantial damage in aPL-positive patients in the APS ACTION cohort. Selected traditional cardiovascular risk factors, steroids use and specific aPL profiles may help to identify patients more prone to present with a higher damage burden.
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Affiliation(s)
- Gustavo G M Balbi
- Universidade de São Paulo, São Paulo, São Paulo, Brazil
- Universidade Federal de Juiz de Fora, Juiz de Fora, Minas Gerais, Brazil
| | - Yasaman Ahmadzadeh
- Barbara Volcker Center for Women and Rheumatic Disease, Hospital for Special Surgery, Weill Cornell Medicine, New York, NY, USA
| | | | | | - Savino Sciascia
- Center of Research of Immunopathology and Rare Diseases, University of Turin, Turin, Italy
| | - Amaia Ugarte
- Hospital Universitario Cruces, País Vasco, Barakaldo, Spain
| | | | - Chary Lopez-Pedrera
- Rheumatology Service, IMIBIC/Reina Sofia Hospital, University of Cordoba, Cordoba, Spain
| | - Paul R Fortin
- CHU de Québec-Université Laval, Québec, Québec, Canada
| | - Denis Wahl
- Université de Lorraine, INSERM, DCAC, Nancy, France
- Vascular Medicine Division and Regional Competence Center for Rare Vascular and Systemic Autoimmune Diseases, CHRU-Nancy, Nancy, France
| | - Maria Gerosa
- Clinical Immunology & Rheumatology Unit, IRCCS Istituto Auxologico Italiano, Milan, Italy
| | | | - Lanlan Ji
- Rheumatology and Immunology Department, Peking University First Hospital, Beijing, China
| | | | - Maria Efthymiou
- Haemostasis Research Unit, Department of Haematology, University College London, London, UK
| | - D Ware Branch
- University of Utah and Intermountain Healthcare, Salt Lake City, UT, USA
| | - Cecilia Nalli
- Rheumatology and Immunology Unit, ASST Spedali Civili of Brescia, Brescia, Italy
| | | | - Michelle Petri
- Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Ricard Cervera
- Department of Autoimmune Diseases, Hospital Clínic, Barcelona, Catalonia, Spain
| | - Jason S Knight
- Division of Rheumatology, University of Michigan, Ann Arbor, MI, USA
| | | | - Rohan Willis
- Antiphospholipid Standardization Laboratory, University of Texas Medical Branch, Galveston, TX, USA
| | - Maria Laura Bertolaccini
- Academic Department of Vascular Surgery, King’s College London British Heart Foundation Centre of Excellence, School of Cardiovascular Medicine & Sciences, London, UK
| | - Hannah Cohen
- Haemostasis Research Unit, Department of Haematology, University College London, London, UK
| | | | - Doruk Erkan
- Barbara Volcker Center for Women and Rheumatic Disease, Hospital for Special Surgery, Weill Cornell Medicine, New York, NY, USA
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Bhaduri M, Sarris I, Bramham K. Female Infertility in Chronic Kidney Disease. Diagnostics (Basel) 2023; 13:3216. [PMID: 37892037 PMCID: PMC10606530 DOI: 10.3390/diagnostics13203216] [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: 09/13/2023] [Revised: 10/06/2023] [Accepted: 10/10/2023] [Indexed: 10/29/2023] Open
Abstract
This review summarises the current literature regarding infertility in women with chronic kidney disease (CKD), describing the epidemiology, pathophysiology, investigations, and management options. The pathophysiology is multifactorial, with proposed mechanisms including disruption of the hypothalamus-pituitary-ovarian axis, chronic inflammation, oxidative stress, psychological factors, and gonadotoxic effects of medications such as cyclophosphamide. Diagnostic investigations in CKD patients seeking to conceive should be considered earlier than in the healthy population. Investigations should include hormonal profiling, including markers such as Anti-Mullerian Hormone and imaging such as ultrasound, to evaluate ovarian reserve and identify gynaecology pathology. Treatment options for infertility in CKD patients include GnRH agonists to preserve ovarian function during cyclophosphamide treatment, as well as assisted reproductive technologies including in vitro fertilisation and ovulation induction. However, these treatments must be tailored to the individual's health status, comorbidities, fertility requirements, and CKD stage. In conclusion, fertility is an important consideration for women with CKD, necessitating early investigation and tailored management. Early discussions regarding fertility are important in order to understand patients' family planning and allow for prompt referral to fertility services. While challenges exist, ongoing research aims to clarify the underlying mechanism and optimise treatment strategies, which are crucial for improving quality of life and overall health outcomes.
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Lima Corrêa de Araújo B, Victor DR, Farias Fontes HM, Caminha Mendes Gomes RM, Lima Corrêa de Araújo L. Antisynthetase Syndrome With Predominant Pulmonary Involvement: A Case Report. Cureus 2023; 15:e43966. [PMID: 37746430 PMCID: PMC10515292 DOI: 10.7759/cureus.43966] [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] [Accepted: 08/21/2023] [Indexed: 09/26/2023] Open
Abstract
Antisynthetase syndrome (ASyS) is an autoimmune disease characterized by the presence of aminoacyl-transfer RNA synthetase antibodies. Its clinical presentation is variable and may include interstitial lung disease (ILD), myositis, arthritis, fever, Raynaud's phenomenon, and "mechanic's hands." ILD is more prevalent in this entity when compared to other idiopathic inflammatory myopathies and imparts greater severity to the condition. Here, we report the case of a 42-year-old female patient who sought care for severe ILD and persistent fever. Her diagnosis was made only after the detection of anti-Jo1 autoantibodies. Treatment was refractory to both prednisone monotherapy and cyclophosphamide pulse therapy, requiring the introduction of rituximab. A high degree of clinical suspicion is required to allow early diagnosis of ASyS in patients with pulmonary involvement in the absence of accompanying muscle weakness or other clinical symptoms.
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Khallaf WAI, Sharata EE, Attya ME, Abo-Youssef AM, Hemeida RAM. LCZ696 (sacubitril/valsartan) mitigates cyclophosphamide-induced premature ovarian failure in rats; the role of TLR4/NF-κB/NLRP3/Caspase-1 signaling pathway. Life Sci 2023; 326:121789. [PMID: 37201697 DOI: 10.1016/j.lfs.2023.121789] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2023] [Revised: 05/06/2023] [Accepted: 05/15/2023] [Indexed: 05/20/2023]
Abstract
AIM Cyclophosphamide (CP) is used to treat a variety of cancers and autoimmune illnesses. CP has been found to frequently cause premature ovarian failure (POF). The study's objective was to assess LCZ696's potential for protection against CP-induced POF in a rat model. MAIN METHODS Rats were randomly assigned into seven groups as follows: control, valsartan (VAL), LCZ696, CP, CP + VAL, CP + LCZ696, and CP + triptorelin (TRI). Ovarian malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD), interleukin-18 (IL-18), IL-1β, and tumor necrosis factor-alpha (TNF-α) were assessed using ELISA. Serum anti-mullerian hormone (AMH), estrogen, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) were also measured using ELISA. The expression of NLRP3/Caspase-1/GSDMD C-NT and TLR4/MYD88/NF-B P65 proteins was estimated using western blot assay. The histopathology of the ovaries was also investigated. The estrous cycle, body, and ovarian weights were also monitored. KEY FINDINGS CP treatment significantly elevated levels of MDA, IL-18, IL-1β, TNF-α, FSH, LH, and up-regulated TLR4/NF-κB/NLRP3/Caspase-1 proteins, as compared to the control group, however, ovarian follicles count, and levels of GSH, SOD, AMH, and estrogen were reduced with CP administration. All the aforementioned biochemical and histological abnormalities were considerably alleviated by the LCZ696 therapy compared to valsartan alone. SIGNIFICANCE LCZ696 effectively mitigated CP-induced POF, offering promising protection that could be related to its suppression power on NLRP3-induced pyroptosis and TLR4/NF-B P65 pathway.
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Affiliation(s)
- Waleed A I Khallaf
- Department of Pharmacology & Toxicology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, Egypt.
| | - Ehab E Sharata
- Department of Pharmacology & Toxicology, Faculty of Pharmacy, Deraya University, Minia 61111, Egypt.
| | - Mina Ezzat Attya
- Department of Pathology, Faculty of Medicine, Minia University, Minia 61519, Egypt.
| | - Amira M Abo-Youssef
- Department of Pharmacology & Toxicology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, Egypt.
| | - Ramadan A M Hemeida
- Department of Pharmacology & Toxicology, Faculty of Pharmacy, Deraya University, Minia 61111, Egypt; Department of Pharmacology & Toxicology, Faculty of Pharmacy, Al-Azhar University, Assiut branch, Assiut 71524, Egypt.
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Different monoclonal antibodies and immunosuppressants administration in patients with neuromyelitis optica spectrum disorder: a Bayesian network meta-analysis. J Neurol 2023; 270:2950-2963. [PMID: 36884069 DOI: 10.1007/s00415-023-11641-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2022] [Revised: 02/19/2023] [Accepted: 02/20/2023] [Indexed: 03/09/2023]
Abstract
BACKGROUND A variety of novel monoclonal antibodies and immunosuppressant have been proved effective in treating Neuromyelitis Optica Spectrum Disorder (NMOSD). This network meta-analysis compared and ranked the efficacy and tolerability of currently used monoclonal antibodies and immunosuppressive agents in NMOSD. METHODS Electronic database including PubMed, Embase and Cochrane Library were searched for relevant studies evaluating monoclonal antibodies and immunosuppressants in patients with NMOSD. The primary outcome measures were annualized relapse rate (ARR), relapse rate, the Expanded Disability Status Scale (EDSS) score, and total adverse events (AEs). RESULTS We identified 25 studies with 2919 patients in our meta-analysis. For the primary outcome, rituximab (RTX) (SUCRA: 0.02) ranked first in reduction ARR with a significant difference compared with azathioprine (AZA) (MD - 0.34, 95% CrI - 0.55 to - 0.12) and mycophenolate mofetil (MMF) (MD -0.38, 95% CrI - 0.63 to - 0.14). Tocilizumab (SUCRA: 0.05) ranked first in relapse rate, which was superior to satralizumab (lnOR - 25.4, 95% CrI - 74.4 to - 2.49) and inebilizumab (lnOR - 24.86, 95% CrI - 73.75 to - 1.93). MMF (SUCRA: 0.27) had the fewest AEs followed by RTX (SUCRA: 0.35), both of which showed a significant difference compared with AZA and corticosteroids (MMF vs AZA: lnOR - 1.58, 95% CrI - 2.48 to - 0.68; MMF vs corticosteroids: lnOR - 1.34, 95% CrI - 2.3 to - 0.37) (RTX vs AZA: lnOR - 1.34, 95% CrI - 0.37 to - 2.3; RTX vs corticosteroids: lnOR - 2.52, 95% CrI - 0.32 to - 4.86). In EDSS score, no statistical difference was found between different interventions. CONCLUSION RTX and tocilizumab showed better efficacy than traditional immunosuppressants in reducing relapse. For safety, MMF and RTX had fewer AEs. However, studies with larger sample size on newly developed monoclonal antibodies are warranted in the future.
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Trautmann A, Boyer O, Hodson E, Bagga A, Gipson DS, Samuel S, Wetzels J, Alhasan K, Banerjee S, Bhimma R, Bonilla-Felix M, Cano F, Christian M, Hahn D, Kang HG, Nakanishi K, Safouh H, Trachtman H, Xu H, Cook W, Vivarelli M, Haffner D. IPNA clinical practice recommendations for the diagnosis and management of children with steroid-sensitive nephrotic syndrome. Pediatr Nephrol 2023; 38:877-919. [PMID: 36269406 PMCID: PMC9589698 DOI: 10.1007/s00467-022-05739-3] [Citation(s) in RCA: 79] [Impact Index Per Article: 39.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2022] [Revised: 08/03/2022] [Accepted: 08/22/2022] [Indexed: 01/19/2023]
Abstract
Idiopathic nephrotic syndrome is the most frequent pediatric glomerular disease, affecting from 1.15 to 16.9 per 100,000 children per year globally. It is characterized by massive proteinuria, hypoalbuminemia, and/or concomitant edema. Approximately 85-90% of patients attain complete remission of proteinuria within 4-6 weeks of treatment with glucocorticoids, and therefore, have steroid-sensitive nephrotic syndrome (SSNS). Among those patients who are steroid sensitive, 70-80% will have at least one relapse during follow-up, and up to 50% of these patients will experience frequent relapses or become dependent on glucocorticoids to maintain remission. The dose and duration of steroid treatment to prolong time between relapses remains a subject of much debate, and patients continue to experience a high prevalence of steroid-related morbidity. Various steroid-sparing immunosuppressive drugs have been used in clinical practice; however, there is marked practice variation in the selection of these drugs and timing of their introduction during the course of the disease. Therefore, international evidence-based clinical practice recommendations (CPRs) are needed to guide clinical practice and reduce practice variation. The International Pediatric Nephrology Association (IPNA) convened a team of experts including pediatric nephrologists, an adult nephrologist, and a patient representative to develop comprehensive CPRs on the diagnosis and management of SSNS in children. After performing a systematic literature review on 12 clinically relevant PICO (Patient or Population covered, Intervention, Comparator, Outcome) questions, recommendations were formulated and formally graded at several virtual consensus meetings. New definitions for treatment outcomes to help guide change of therapy and recommendations for important research questions are given.
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Affiliation(s)
- Agnes Trautmann
- Division of Pediatric Nephrology, Center for Pediatrics and Adolescent Medicine, University of Heidelberg, Heidelberg, Germany
| | - Olivia Boyer
- Department of Pediatric Nephrology, Reference Center for Idiopathic Nephrotic Syndrome in Children and Adults, Imagine Institute, Paris University, Necker Children's Hospital, APHP, Paris, France
| | - Elisabeth Hodson
- Cochrane Kidney and Transplant, Centre for Kidney Research, The Children's Hospital at Westmead, Sydney, Australia
| | - Arvind Bagga
- Division of Nephrology, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India
| | - Debbie S Gipson
- Department of Pediatrics, Division of Nephrology, University of Michigan, Ann Arbor, MI, USA
| | - Susan Samuel
- Section of Pediatric Nephrology, Department of Pediatrics, Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Canada
| | - Jack Wetzels
- Department of Nephrology, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Khalid Alhasan
- Pediatric Department, College of Medicine, King Saud University, Riyadh, Saudi Arabia
| | - Sushmita Banerjee
- Department of Pediatric Nephrology, Institute of Child Health, Kolkata, India
| | | | - Melvin Bonilla-Felix
- Department of Pediatrics, University of Puerto Rico-Medical Sciences Campus, San Juan, Puerto Rico
| | - Francisco Cano
- Department of Pediatric Nephrology, Luis Calvo Mackenna Children's Hospital, University of Chile, Santiago, Chile
| | - Martin Christian
- Children's Kidney Unit, Nottingham Children's Hospital, Nottingham, UK
| | - Deirdre Hahn
- Division of Pediatric Nephrology, Department of Paediatrics, The Children's Hospital at Westmead, Sydney, Australia
| | - Hee Gyung Kang
- Division of Pediatric Nephrology, Department of Pediatrics, Seoul National University Children's Hospital & Seoul National University College of Medicine, Seoul, Korea
| | - Koichi Nakanishi
- Department of Child Health and Welfare (Pediatrics), Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan
| | - Hesham Safouh
- Pediatric Nephrology Unit, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Howard Trachtman
- Department of Pediatrics, Division of Nephrology, University of Michigan, Ann Arbor, MI, USA
| | - Hong Xu
- Department of Nephrology, Children's Hospital of Fudan University, Shanghai, China
| | - Wendy Cook
- Nephrotic Syndrome Trust (NeST), Somerset, UK
| | - Marina Vivarelli
- Division of Nephrology and Dialysis, Department of Pediatric Subspecialties, Bambino Gesù Pediatric Hospital IRCCS, Rome, Italy
| | - Dieter Haffner
- Department of Pediatric Kidney, Liver and Metabolic Diseases, Hannover Medical School Children's Hospital, Hannover and Center for Rare Diseases, Hannover Medical School, Hannover, Germany.
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Luan Y, Yu SY, Abazarikia A, Dong R, Kim SY. TAp63 determines the fate of oocytes against DNA damage. SCIENCE ADVANCES 2022; 8:eade1846. [PMID: 36542718 PMCID: PMC9770984 DOI: 10.1126/sciadv.ade1846] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 08/09/2022] [Accepted: 11/16/2022] [Indexed: 06/17/2023]
Abstract
Cyclophosphamide and doxorubicin lead to premature ovarian insufficiency as an off-target effect. However, their oocyte death pathway has been debated. Here, we clarified the precise mechanism of ovarian depletion induced by cyclophosphamide and doxorubicin. Dormant oocytes instead of activated oocytes with high PI3K activity were more sensitive to cyclophosphamide. Checkpoint kinase 2 (CHK2) inhibitor rather than GNF2 protected oocytes from cyclophosphamide and doxorubicin, as cyclophosphamide up-regulated p-CHK2 and depleted primordial follicles in Abl1 knockout mice. Contrary to previous reports, TAp63 is pivotal in cyclophosphamide and doxorubicin-induced oocyte death. Oocyte-specific Trp63 knockout mice prevented primordial follicle loss and maintained reproductive function from cyclophosphamide and doxorubicin, indicated by undetectable levels of BAX and cPARP. Here, we demonstrated that TAp63 is fundamental in determining the signaling of oocyte death against DNA damage. This study establishes the role of TAp63 as a target molecule of adjuvant therapies to protect the ovarian reserve from different classes of chemotherapy.
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Affiliation(s)
- Yi Luan
- Olson Center for Women’s Health, Department of Obstetrics and Gynecology, College of Medicine, University of Nebraska Medical Center, Omaha, NE, USA
| | - Seok-Yeong Yu
- Olson Center for Women’s Health, Department of Obstetrics and Gynecology, College of Medicine, University of Nebraska Medical Center, Omaha, NE, USA
| | - Amirhossein Abazarikia
- Olson Center for Women’s Health, Department of Obstetrics and Gynecology, College of Medicine, University of Nebraska Medical Center, Omaha, NE, USA
| | - Rosemary Dong
- Olson Center for Women’s Health, Department of Obstetrics and Gynecology, College of Medicine, University of Nebraska Medical Center, Omaha, NE, USA
| | - So-Youn Kim
- Olson Center for Women’s Health, Department of Obstetrics and Gynecology, College of Medicine, University of Nebraska Medical Center, Omaha, NE, USA
- Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA
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12
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Castellanos Gutierrez AS, Figueras F, Morales-Prieto DM, Schleußner E, Espinosa G, Baños N. Placental damage in pregnancies with systemic lupus erythematosus: A narrative review. Front Immunol 2022; 13:941586. [PMID: 36059466 PMCID: PMC9428442 DOI: 10.3389/fimmu.2022.941586] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2022] [Accepted: 07/12/2022] [Indexed: 11/17/2022] Open
Abstract
Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease of unknown cause, which mainly affects women of childbearing age, especially between 15 and 55 years of age. During pregnancy, SLE is associated with a high risk of perinatal morbidity and mortality. Among the most frequent complications are spontaneous abortion, fetal death, prematurity, intrauterine Fetal growth restriction (FGR), and preeclampsia (PE). The pathophysiology underlying obstetric mortality and morbidity in SLE is still under investigation, but several studies in recent years have suggested that placental dysfunction may play a crucial role. Understanding this association will contribute to developing therapeutic options and improving patient management thus reducing the occurrence of adverse pregnancy outcomes in this group of women. In this review, we will focus on the relationship between SLE and placental insufficiency leading to adverse pregnancy outcomes.
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Affiliation(s)
- Aleida Susana Castellanos Gutierrez
- BCNatal, Barcelona Center for Maternal-Fetal and Neonatal Medicine (Hospital Clínic and Hospital Sant Joan de Déu), Institut Clínic de Ginecologia, Obstetrícia i Neonatologia Fetal i+D Fetal Medicine Research Center, Barcelona, Spain
- Placenta Lab, Department of Obstetrics, Jena University Hospital, Jena, Germany
| | - Francesc Figueras
- BCNatal, Barcelona Center for Maternal-Fetal and Neonatal Medicine (Hospital Clínic and Hospital Sant Joan de Déu), Institut Clínic de Ginecologia, Obstetrícia i Neonatologia Fetal i+D Fetal Medicine Research Center, Barcelona, Spain
- Institut d’Investigacions Biomèdiques Pi i Sunyer (IDIBAPS), Barcelona, Spain
| | - Diana M. Morales-Prieto
- Placenta Lab, Department of Obstetrics, Jena University Hospital, Jena, Germany
- *Correspondence: Núria Baños, ; Diana M. Morales-Prieto,
| | - Ekkehard Schleußner
- Placenta Lab, Department of Obstetrics, Jena University Hospital, Jena, Germany
| | - Gerard Espinosa
- Institut d’Investigacions Biomèdiques Pi i Sunyer (IDIBAPS), Barcelona, Spain
- Department of Autoimmune Diseases, Hospital Clinic, Barcelona, Spain
| | - Núria Baños
- BCNatal, Barcelona Center for Maternal-Fetal and Neonatal Medicine (Hospital Clínic and Hospital Sant Joan de Déu), Institut Clínic de Ginecologia, Obstetrícia i Neonatologia Fetal i+D Fetal Medicine Research Center, Barcelona, Spain
- *Correspondence: Núria Baños, ; Diana M. Morales-Prieto,
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13
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Statache G, Brown S. Vitamin D in Lupus Patients of Childbearing Age: Are We Doing Enough? FRONTIERS IN REPRODUCTIVE HEALTH 2022; 4:936810. [PMID: 36303678 PMCID: PMC9580657 DOI: 10.3389/frph.2022.936810] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2022] [Accepted: 06/01/2022] [Indexed: 11/14/2022] Open
Abstract
Systemic lupus erythematosus patients have long been observed to suffer from vitamin D deficiency. This can be related to either environmental factors, medication, or other comorbidities like renal disease. Moreover, lupus patients have reported conception issues including ovarian failure or recurrent miscarriages. There are vast data regarding vitamin D's ability to support the development of a healthy pregnancy and prevent complications, such as pre-eclampsia and gestational diabetes, likely through its ability to regulate both innate and adaptive immune systems. Although there is an agreement in the medical world that pregnant lupus patients should be screened and receive vitamin D supplements, there are no official guidelines on screening and often the recommended doses are suboptimal. Further research is needed to look at the potential of vitamin supplementation in pregnant lupus patients.
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14
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Giambalvo S, Garaffoni C, Silvagni E, Furini F, Rizzo R, Govoni M, Bortoluzzi A. Factors associated with fertility abnormalities in women with systemic lupus erythematosus: a systematic review and meta-analysis. Autoimmun Rev 2022; 21:103038. [PMID: 34995765 DOI: 10.1016/j.autrev.2022.103038] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2021] [Accepted: 01/01/2022] [Indexed: 11/28/2022]
Abstract
BACKGROUND Fertility is thought to be not affected in women with systemic lupus erythematosus (SLE), however disease-related factors, psychosocial effects of chronic disease, as well as medications exposure might impair gonadal function. OBJECTIVE This systematic literature review (SLR) aimed to explore clinical, hormonal, serological and treatment factors associated with fertility outcomes in women of childbearing age with SLE. METHODS This SLR was conducted following the Preferred Reporting Items for systematic reviews and Meta-analysis (PRISMA) statement. All articles available in English (1972 - 30th April 2021) in Pubmed, EMBASE, Scopus and Cochrane Library were screened. Study selection and data collection were performed by two independent reviewers. All data were extracted using a standardized template. The risk of bias of the included studies was assessed using the NIH risk-of-bias tool. RESULTS Of 789 abstracts evaluated, we included in this review 46 studies, of which 1 SLR, 16 cross-sectional studies, 18 cohort studies, 10 observational studies and 1 case-series, with data pertaining to 4704 patients (mean age 31.5 ± 3.7 years, disease duration 83.27 ± 38.3 months). Definitions of premature ovarian failure (POF) adopted in the studies varied in terms of the number of months of amenorrhea considered and the age of onset of amenorrhea. Clinical factors associated with the development of POF were older age at the time of initiation of therapy, and older age at the onset of SLE disease. Cyclophosphamide exposure (CYC) and its cumulative dose influenced gonadal function in SLE women, leading to amenorrhoea and POF, as reported in 19 studies. Mycophenolate, azathioprine, calcineurin inhibitors and steroids associated with a lower risk of POF compared to CYC. POF was less frequent in patients co-treated with CYC and gonadotropin-releasing hormone analogues (GnRH-a) compared with patients not receiving GnRH-a (risk ratio 0.798, 95%-CI [0.1417; 0.5525]). 11 studies evaluated the impact of damage accrual and disease activity on ovarian reserve with conflicting evidence. Finally, 18 studies investigated exposure to hormonal and serological factors and, among others, neither Anti-Müllerian Hormone nor anti-corpus luteum antibodies were associated with POF. CONCLUSION The strongest evidence regarding management factors associated with fertility in SLE women of childbearing age remains the treatment with CYC, as well as its cumulative dosage. Hormonal and serological factors appeared not to impact fertility outcomes, but they might be used as a surrogate of fertility, especially during the treatment with disease-specific drugs.
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Affiliation(s)
- S Giambalvo
- Unit of Rheumatology, Department of Medical Sciences, University of Ferrara, Azienda Ospedaliera-Universitaria Sant'Anna of Ferrara, Italy
| | - C Garaffoni
- Unit of Rheumatology, Department of Medical Sciences, University of Ferrara, Azienda Ospedaliera-Universitaria Sant'Anna of Ferrara, Italy
| | - E Silvagni
- Unit of Rheumatology, Department of Medical Sciences, University of Ferrara, Azienda Ospedaliera-Universitaria Sant'Anna of Ferrara, Italy
| | - F Furini
- Unit of Rheumatology, Ospedale Maggiore, Bologna, Italy
| | - R Rizzo
- Department of Chemical, Pharmaceutical and Agricultural Science, University of Ferrara, Italy
| | - M Govoni
- Unit of Rheumatology, Department of Medical Sciences, University of Ferrara, Azienda Ospedaliera-Universitaria Sant'Anna of Ferrara, Italy
| | - A Bortoluzzi
- Unit of Rheumatology, Department of Medical Sciences, University of Ferrara, Azienda Ospedaliera-Universitaria Sant'Anna of Ferrara, Italy.
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15
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Ozcan MCH, Snegovskikh V, Adamson GD. Oocyte and embryo cryopreservation before gonadotoxic treatments: Principles of safe ovarian stimulation, a systematic review. WOMEN'S HEALTH (LONDON, ENGLAND) 2022; 18:17455065221074886. [PMID: 35130799 PMCID: PMC8829712 DOI: 10.1177/17455065221074886] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/17/2021] [Revised: 12/10/2021] [Accepted: 01/04/2022] [Indexed: 05/05/2023]
Abstract
OBJECTIVE Review the safety of fertility preservation through ovarian stimulation with oocyte or embryo cryopreservation, including cycle and medication options. EVIDENCE REVIEW A systematic review of peer-reviewed sources revealed 2 applicable randomized control trials and 60 cohort studies as well as 20 additional expert opinions or reviews. RESULTS The capacity for future family building is important for the majority of reproductive age people, despite life-altering medical or oncologic diagnosis. Modern fertility preservation generates a high rate of oocyte yield while utilizing protocols that can be started at multiple points in the menstrual cycle and suppressing supra-physiologic levels of estrogen. Finally, more than one quarter of fertility preservation patients will return to later utilize fertility services. CONCLUSION For most patients, fertility preservation can safely be pursued and completed within 2 weeks without affecting disease severity or long-term survival.
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Affiliation(s)
- Meghan CH Ozcan
- Department of Obstetrics and Gynecology, Warren Alpert Medical School of Brown University, Women & Infants Hospital, Providence, RI, USA
| | - Victoria Snegovskikh
- Department of Obstetrics and Gynecology, Warren Alpert Medical School of Brown University, Women & Infants Hospital, Providence, RI, USA
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16
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Bhattad S, Mohite R, Singh N. Growth and development in children with rheumatic diseases: Maintaining a balance between drugs and disease activity. INDIAN JOURNAL OF RHEUMATOLOGY 2022. [DOI: 10.4103/injr.injr_54_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
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17
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Edens C. Early Sexual Health and Reproductive Implications in Pediatric Rheumatic Diseases. Rheum Dis Clin North Am 2021; 48:91-112. [PMID: 34798961 DOI: 10.1016/j.rdc.2021.09.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
A comprehensive review of reproductive health subtopics, including puberty, menarche, sexual orientation, gender identity, and gynecologic cancers as they pertain to patients with pediatric rheumatic diseases and those who care for them. Rheumatic disease medications and their effect on reproductive health across childhood and adolescence are also reviewed.
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Affiliation(s)
- Cuoghi Edens
- Department of Pediatrics, Section Pediatric Rheumatology, University of Chicago Medicine, 5841 South Maryland Avenue, C104-A, MC5044, Chicago, IL 60637, USA; Department of Internal Medicine, Section of Rheumatology, University of Chicago Medicine, 5841 South Maryland Avenue, C104-A, MC5044, Chicago, IL 60637, USA.
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18
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Morales-Martínez FA, Salas-Castro C, García-Garza MR, Valdés-Martínez O, García-Luna SM, Garza-Elizondo M, Vidal-Gutiérrez O, Saldívar-Rodríguez D, Sordia-Hernández LH. Evaluation of the Ovarian Reserve in Women With Systemic Lupus Erythematosus. J Family Reprod Health 2021; 15:38-44. [PMID: 34429735 PMCID: PMC8346742 DOI: 10.18502/jfrh.v15i1.6076] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Objective: Systemic lupus erythematosus (SLE) is a chronic multisystem autoimmune disorder where the disease activity itself and the medications used for its treatment, may have adverse effects on ovarian function. This study aimed to assess the ovarian reserve (OR) in SLE patients. Materials and methods: The anti-müllerian hormone (AMH) and the antral follicle count (AFC), two markers to evaluate the OR was assessed in 64 SLE patients and compared to normal individuals. Additionally, we assessed whether the disease per se or the pharmacological treatments affect the OR. Results: Patients with SLE displayed alterations in the OR regardless of the presence of alterations of the menstrual cycle. The AFC and AMH were significantly lower in SLE patients with and without menstrual alterations when compared to control individuals (p<0.0001). However, the AFC and AMH levels were significantly correlated (p=0.006) in the SLE patients with menstrual alterations. Except for hydroxychloroquine that was statistically higher in SLE patients with menstrual alterations (p=0.04), the cumulative dose for cyclophosphamide, corticosteroid, and methotrexate was similar in SLE patients regardless of the occurrence of menstrual alterations. Conclusion: The monitoring of AMH and AFC in SLE patients should be used to detect the rapid and irreversible decline of the OR to provide a possibility of pregnancy to the SLE patients.
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Affiliation(s)
- Felipe Arturo Morales-Martínez
- University Center of Reproductive Medicine, Dr. José Eleuterio González Hospital, Free University of New León, Monterrey, Mexic
| | - Celina Salas-Castro
- University Center of Reproductive Medicine, Dr. José Eleuterio González Hospital, Free University of New León, Monterrey, Mexic
| | - Manuel Rolando García-Garza
- University Center of Reproductive Medicine, Dr. José Eleuterio González Hospital, Free University of New León, Monterrey, Mexic
| | - Otto Valdés-Martínez
- University Center of Reproductive Medicine, Dr. José Eleuterio González Hospital, Free University of New León, Monterrey, Mexic
| | - Selene Marysol García-Luna
- University Center of Reproductive Medicine, Dr. José Eleuterio González Hospital, Free University of New León, Monterrey, Mexic
| | - Mario Garza-Elizondo
- Reumatology ward, Dr. José Eleuterio González Hospital, Free University of New León, Monterrey, Mexic
| | - Oscar Vidal-Gutiérrez
- Departament of Gynecology and Obstetrics, Dr. José Eleuterio González Hospital, Free University of New León, Monterrey, Mexic
| | - Donato Saldívar-Rodríguez
- Departament of Gynecology and Obstetrics, Dr. José Eleuterio González Hospital, Free University of New León, Monterrey, Mexic
| | - Luis Humberto Sordia-Hernández
- University Center of Reproductive Medicine, Dr. José Eleuterio González Hospital, Free University of New León, Monterrey, Mexic
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19
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Blomjous BS, Johanna I P DV, Zijlstra E, Cramer K, Voskuyl AE, Bultink AIEM. Desire to have children and preferences regarding to pre-pregnancy counselling in women with SLE. Rheumatology (Oxford) 2021; 60:2706-2713. [PMID: 33241288 PMCID: PMC8489423 DOI: 10.1093/rheumatology/keaa684] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2020] [Revised: 09/17/2020] [Indexed: 11/13/2022] Open
Abstract
OBJECTIVES Pre-pregnancy counselling in women with systemic lupus erythematosus (SLE) is important in order to improve knowledge on the risks of pregnancy and to optimize pregnancy outcomes. Knowledge on the preferences of women with SLE regarding pre-pregnancy counselling have not yet been studied. In a closely monitored cohort of women with SLE we enquired about the present status of their wish to have children, and wish for and experiences with pre-pregnancy counselling. METHODS A questionnaire developed by physicians in collaboration with two women with SLE was sent to all (n = 177) women participating in the Amsterdam SLE cohort. The questionnaire comprised 32 items, of which 15 focused on the above-mentioned three themes. RESULTS A total of 124 women (70%) returned the questionnaire. The median disease duration was 13 years (interquartile range 9-19). Childlessness occurred in 51 women and 31% declared this was due to SLE [conscious decision (21%), stringent medical advice (6%), infertility due to medication (4%)]. Half of the women preferred the first pre-pregnancy counselling immediately after the SLE diagnosis (53%), together with their partner (69%). Information given by healthcare providers (81%) was preferred over information provided via brochures (35%) or the internet (26%). Pre-pregnancy face-to-face counselling from a rheumatologist and/or gynaecologist separately was preferred in 54%. CONCLUSION One-third of women attributed their childlessness to SLE-related reasons. Pre-pregnancy counselling was preferred shortly after the onset of the disease in a non-multidisciplinary setting. The results of this study underline the importance of timely pre-conceptional counselling by healthcare providers on fertility, risks and pregnancy outcomes in women with SLE.
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Affiliation(s)
- Birgit S Blomjous
- Department of Rheumatology and Clinical Immunology, Amsterdam Rheumatology and immunology Center, Amsterdam Infection & Immunity, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.,Department of Obstetrics and Gynecology, Amsterdam Reproduction & Development, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
| | - de Vries Johanna I P
- Department of Obstetrics and Gynecology, Amsterdam Reproduction & Development, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
| | | | - Kyra Cramer
- Patient Research Partner, Amsterdam, The Netherlands
| | - Alexandre E Voskuyl
- Department of Rheumatology and Clinical Immunology, Amsterdam Rheumatology and immunology Center, Amsterdam Infection & Immunity, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
| | - And Irene E M Bultink
- Department of Rheumatology and Clinical Immunology, Amsterdam Rheumatology and immunology Center, Amsterdam Infection & Immunity, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
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20
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Reynolds ML, Poulton CJ, Blazek LN, Hogan SL, Falk RJ, Derebail VK. Subfertility and early menopause in women with glomerular disease. Nephrol Dial Transplant 2021; 36:948-950. [PMID: 33508104 DOI: 10.1093/ndt/gfab005] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2020] [Accepted: 01/06/2021] [Indexed: 11/12/2022] Open
Affiliation(s)
- Monica L Reynolds
- UNC Kidney Center, Division of Nephrology and Hypertension, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Caroline J Poulton
- UNC Kidney Center, Division of Nephrology and Hypertension, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Lauren N Blazek
- UNC Kidney Center, Division of Nephrology and Hypertension, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Susan L Hogan
- UNC Kidney Center, Division of Nephrology and Hypertension, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Ronald J Falk
- UNC Kidney Center, Division of Nephrology and Hypertension, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Vimal K Derebail
- UNC Kidney Center, Division of Nephrology and Hypertension, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
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21
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Gurcan M, Esatoglu SN, Hamuryudan V, Saygin D, Ugurlu S, Seyahi E, Melikoglu M, Fresko I, Yurdakul S, Yazici H, Hatemi G. Long term follow-up of Behçet's syndrome patients treated with cyclophosphamide. Rheumatology (Oxford) 2021; 59:2264-2271. [PMID: 31840168 DOI: 10.1093/rheumatology/kez598] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2019] [Revised: 10/31/2019] [Indexed: 02/06/2023] Open
Abstract
OBJECTIVES CYC remains an important treatment option for Behçet's syndrome (BS) patients with life-threatening manifestations. However, adverse events may occur with CYC and this has led to increased use of biologic agents in other vasculitides. We investigated short and long term adverse events associated with CYC use in BS patients. METHODS We conducted a retrospective chart review of all BS patients treated with CYC between 1972 and 2006. Patients were called in and a standard form was used for collecting demographic characteristics, indication for CYC, its cumulative dose and short term adverse events, defined as those causing discontinuation of CYC, hospitalization and/or death, long term adverse events, including infertility and malignancy, and outcome. RESULTS Of 5790 BS patients, 198 (3.4%) had used at least one dose of CYC. Main indications were vascular or neurological involvement. After a median follow-up of 17 years, 52 (26%) patients had died, 113 (57%) could be contacted, and 33 (17%) were lost to follow-up. Vascular involvement was the leading cause of death (n = 27). Seventeen (9%) patients experienced short term adverse events with haemorrhagic cystitis being the most common. After a median follow-up of 25 years (interquartile range: 15-26 years), 17 malignancies occurred in 15 (8%) patients. Infertility was experienced by 26 (30%) patients. CONCLUSION Long term adverse events such as malignancy and infertility were major problems in our BS patients treated with CYC. These results underline the need for safer treatment modalities that are at least as effective as CYC.
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Affiliation(s)
- Mert Gurcan
- Department of Internal Medicine, Cerrahpasa Medical School, Istanbul University-Cerrahpasa, Istanbul, Turkey
| | - Sinem Nihal Esatoglu
- Division of Rheumatology, Department of Internal Medicine, Cerrahpasa Medical School, Istanbul University-Cerrahpasa, Istanbul, Turkey
| | - Vedat Hamuryudan
- Division of Rheumatology, Department of Internal Medicine, Cerrahpasa Medical School, Istanbul University-Cerrahpasa, Istanbul, Turkey
| | - Didem Saygin
- Department of Internal Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Serdal Ugurlu
- Division of Rheumatology, Department of Internal Medicine, Cerrahpasa Medical School, Istanbul University-Cerrahpasa, Istanbul, Turkey
| | - Emire Seyahi
- Division of Rheumatology, Department of Internal Medicine, Cerrahpasa Medical School, Istanbul University-Cerrahpasa, Istanbul, Turkey
| | - Melike Melikoglu
- Division of Rheumatology, Department of Internal Medicine, Cerrahpasa Medical School, Istanbul University-Cerrahpasa, Istanbul, Turkey
| | - Izzet Fresko
- Division of Rheumatology, Department of Internal Medicine, Cerrahpasa Medical School, Istanbul University-Cerrahpasa, Istanbul, Turkey
| | - Sebahattin Yurdakul
- Division of Rheumatology, Department of Internal Medicine, Cerrahpasa Medical School, Istanbul University-Cerrahpasa, Istanbul, Turkey
| | - Hasan Yazici
- Division of Rheumatology, Department of Internal Medicine, Cerrahpasa Medical School, Istanbul University-Cerrahpasa, Istanbul, Turkey
| | - Gulen Hatemi
- Division of Rheumatology, Department of Internal Medicine, Cerrahpasa Medical School, Istanbul University-Cerrahpasa, Istanbul, Turkey
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22
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Tsuchida Y, Harada M, Shoda H, Goto A, Suzuki N, Murashima A, Osuga Y, Fujio K. Fertility preservation in patients receiving gonadotoxic therapies for systemic autoimmune diseases in Japan. Mod Rheumatol 2021; 31:1004-1009. [PMID: 33236975 DOI: 10.1080/14397595.2020.1856020] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
Abstract
OBJECTIVES Gonadotoxic therapies, mainly cyclophosphamide, are used for the treatment of various systemic autoimmune diseases. In Japan, the number of patients who undergo gonadotoxic therapy for autoimmune diseases, fertility preservation procedures performed in these patients, and problems associated with performing such procedures have not been reported. This study was performed to address these issues. METHODS A questionnaire was sent to Certified Educational Facilities of the Japanese Society of Rheumatology, and a single rheumatologist at each center completed the questionnaire. RESULTS A total of 63 facilities completed the questionnaire. Between April 2014 and March 2019, a total of 1302 men and premenopausal women had received gonadotoxic therapies for systemic autoimmune disease. Nearly half of the respondents reported that gonadotropin releasing hormone analog therapy was available in their area. However, the availability of other fertility preservation procedures was limited, and the number of patients undergoing fertility preservation procedures was limited. 85.7% of the respondents responded that measures to preserve fertility in patients receiving gonadotoxic therapies for autoimmune diseases were inadequate. CONCLUSIONS A substantial number of patients are receiving gonadotoxic therapies for the treatment of autoimmune diseases in Japan, and those patients may not be receiving adequate care regarding their fertility.
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Affiliation(s)
- Yumi Tsuchida
- Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Miyuki Harada
- Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Hirofumi Shoda
- Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Ayane Goto
- Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Nao Suzuki
- Department of Obstetrics and Gynecology, St. Marianna University School of Medicine, Kawasaki, Japan
| | - Atsuko Murashima
- Center for Maternal-Fetal-Neonatal and Reproductive Medicine, National Center for Child Health and Development, Tokyo, Japan
| | - Yutaka Osuga
- Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Keishi Fujio
- Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
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23
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Wang L, Liu K, Tan X, Zhou L, Zhang Y, Liu X, Fu Y, Qiu W, Yang H. Remedial Effect of Intravenous Cyclophosphamide in Corticosteroid-Refractory Patients in the Acute Phase of Neuromyelitis Optica Spectrum Disorder-Related Optic Neuritis. Front Neurol 2021; 11:612097. [PMID: 33584513 PMCID: PMC7874161 DOI: 10.3389/fneur.2020.612097] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2020] [Accepted: 12/16/2020] [Indexed: 01/29/2023] Open
Abstract
Background: To investigate the remedial efficacy and safety of intravenous cyclophosphamide (CP) in the acute phase in patients with neuromyelitis optica spectrum disorder-related optic neuritis (NMOSD-ON) who are refractory to intravenous methylprednisolone (MP) treatment. Design: This study was a single-center, retrospective, observational case-control cohort study. Methods: Thirty-six patients who had acute NMOSD-ON attacks and were refractory to MP treatment were included. Patents were divided into two groups: the remedial CP group, and the MP group. The best-corrected visual acuity (BCVA), mean deviation (MD) of the visual field (VF), visual evoked potential amplitude (VEP-A), visual evoked potential latency (VEP-T), and average thickness of the retinal nerve fiber layer (RNFL) at onset, 1 month (m), 3 m, and 6 m after the attack were analyzed. Routine blood test results, liver and kidney function, routine urinalysis results and general condition were analyzed for safety issues at each follow-up. Fisher's exact test, the Mann-Whitney U test, the Kruskal-Wallis test and the Wilcoxon rank-sum test were used for statistical analysis. Results: The remedial CP group showed significant improvement over 6 m with regard to BCVA and MD (P < 0.05),whereas MP group only showed significant improvement in MD (P < 0.05). Regarding remedial CP intervention time window, the CP ≤ 30 days group showed significant improvement over 6 m with regard to BCVA (P = 0.002), MD (P = 0.003), and VEP-A (P = 0.036), while those CP > 30 days group did not. Both two subgroups showed significantly RNFL thickness reduction, however, BCVA, MD, VEP-A, VEP-T, and RNFL thickness showed no significant differences between the two subgroups at any follow-up point (P > 0.05). Conclusion: CP within 30 days of attack onset is safe and might have a beneficial degree of therapeutic efficacy for acute-phase treatment of NMOSD-ON that is refractory to MP treatment alone.
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Affiliation(s)
- Ling Wang
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
| | - Kaiqun Liu
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
| | - Xiao Tan
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
| | - Lin Zhou
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
| | - Yuxin Zhang
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
| | - Xiaoning Liu
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
| | - Yue Fu
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
| | - Wei Qiu
- Department of Neurology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Hui Yang
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
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24
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Reynolds ML, Herrera CA. Chronic Kidney Disease and Pregnancy. Adv Chronic Kidney Dis 2020; 27:461-468. [PMID: 33328062 DOI: 10.1053/j.ackd.2020.04.003] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2020] [Revised: 04/27/2020] [Accepted: 04/27/2020] [Indexed: 12/14/2022]
Abstract
Women with chronic kidney disease (CKD) are at high risk for adverse outcomes in pregnancy. In the United States, pregnancy rates in women with risk factors for CKD such as obesity and advanced maternal age are increasing; thus, more pregnancies are likely to be affected by CKD. Strategies that involve coordinated multidisciplinary care to optimize preconception health, perform meticulous antenatal monitoring, and provide continued care in the postpartum "fourth trimester" appear to be most beneficial for both the mother and baby. Discussions surrounding preconception risk stratification should be individualized based on CKD stage/serum creatinine level, degree of hypertension and proteinuria, and comorbid conditions. Preparation for pregnancy should include optimization of comorbidities and medication adjustments to those compatible with pregnancy. Unless contraindicated, all women with CKD should be prescribed low-dose aspirin in pregnancy to reduce risk of preeclampsia. After delivery, women with CKD may benefit from an early postpartum visit (within 7-10 days) for blood pressure check and may require serial monitoring of serum creatinine and proteinuria as appropriate. Breastfeeding is safe and can be recommended for most women with CKD. A contraceptive plan that includes patients' preferences, feasibility, medical eligibility, duration, and effectiveness of the contraceptive method should be implemented.
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25
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Sharma SK, Jain S, Bahl P, Potturi P, Rathi M, Naidu S, Sachdeva N, Dhir V, Jain S. Ovarian dysfunction with moderate-dose intravenous cyclophosphamide (modified NIH regimen) and mycophenolate mofetil in young adults with severe lupus: a prospective cohort study. Arthritis Res Ther 2020; 22:189. [PMID: 32799907 PMCID: PMC7429750 DOI: 10.1186/s13075-020-02292-y] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2020] [Accepted: 08/07/2020] [Indexed: 01/22/2023] Open
Abstract
Background Ovarian toxicity is a dreaded complication of cyclophosphamide (CYC). With the use of lower cumulative doses of intravenous CYC (modified NIH regimens) and availability of better markers of ovarian toxicity, the incidence of ovarian dysfunction needs reassessment. Lupus disease activity, by itself, is also believed to affect ovarian function negatively. Methods This single-centre prospective cohort study recruited 50 female patients of severe lupus aged 18–40 years. Twenty-five patients each received induction with either monthly intravenous CYC (0.5–0.75 g/m2) for 6–9 months or daily oral mycophenolate mofetil (MMF). Details of menstrual irregularities; serum levels of FSH, LH, estradiol, AMH, and inhibin B; and sonographic assessment of ovarian volume and antral follicular count were done at baseline and 6 months after treatment. Amenorrhoeic patients were re-evaluated at 1 year. Results Mean (SD) age of subjects in the CYC and MMF groups was 31.4 (6.3) and 28.4 (4.4) years, respectively. Mean (SD) SLEDAI at the initiation of therapy was 7.2 (2.5) in the CYC group and 5.8 (3.4) in the MMF group. The mean cumulative dose of CYC used was 4.6 (1.8) g. Three patients in the CYC group (versus none in MMF) had amenorrhoea at 6 months—two of these regained menses within 6 months, while only one (4%) developed sustained amenorrhoea (lasting more than 12 months) at 41 years of age, likely menopause. Serum FSH levels increased (p = 0.03), while AMH (p = 0.002) and inhibin B (p < 0.001) levels decreased significantly with 6 months of CYC therapy. Ovarian volume also reduced significantly (p = 0.005) with 6 months of CYC therapy, while antral follicular count reduced numerically (p = 0.32). Levels of AMH, inhibin-B, estradiol, ovarian volume, and antral follicular count after 6 months therapy were significantly lesser in the CYC group compared to the MMF group, despite being similar before the start of therapy. Conclusions Ovarian dysfunction with monthly intravenous CYC (modified NIH regimen) was predominantly subclinical, with a negative effect on ovarian reserve. No premature ovarian failure was noted at 1 year. No ovarian dysfunction occurred in the MMF group, despite having patients with severe background lupus. Use of intravenous CYC for induction may thus not be restricted in young lupus females with incomplete families for fear of gonadotoxicity, especially in life- or organ-threatening situations, where the benefits outweigh this subclinical risk.
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Affiliation(s)
- Shefali Khanna Sharma
- Clinical Immunology and Rheumatology Division, Department of Internal Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
| | - Siddharth Jain
- Clinical Immunology and Rheumatology Division, Department of Internal Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Pooja Bahl
- Department of Obstetrics and Gynaecology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Pragna Potturi
- Clinical Immunology and Rheumatology Division, Department of Internal Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Manish Rathi
- Department of Nephrology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Shankar Naidu
- Clinical Immunology and Rheumatology Division, Department of Internal Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Naresh Sachdeva
- Department of Endocrinology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Varun Dhir
- Clinical Immunology and Rheumatology Division, Department of Internal Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Sanjay Jain
- Clinical Immunology and Rheumatology Division, Department of Internal Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India
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26
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Poirot C, Fortin A, Lacorte JM, Akakpo JP, Genestie C, Vernant JP, Brice P, Morice P, Leblanc T, Gabarre J, Delmer A, Badachi Y, Drouineaud V, Gouy S, Chalas C, Egels S, Dhédin N, Touraine P, Dommergues M, Lebègue G, Wolf JP, Capron F, Lefebvre G, Boissel N. Impact of cancer chemotherapy before ovarian cortex cryopreservation on ovarian tissue transplantation. Hum Reprod 2020; 34:1083-1094. [PMID: 31116405 DOI: 10.1093/humrep/dez047] [Citation(s) in RCA: 47] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2018] [Revised: 02/27/2019] [Accepted: 03/07/2019] [Indexed: 12/18/2022] Open
Abstract
STUDY QUESTION How efficacious is transplantation of ovarian cortex previously exposed to chemotherapy? SUMMARY ANSWER Prior exposure to chemotherapy did not disrupt the function of cryopreserved ovarian tissue after transplantation. WHAT IS KNOWN ALREADY Ovarian tissue cryopreservation (OTC) followed by ovarian tissue transplantation (OTT) is an efficacious technique for restoration of female fertility. At least 130 children have been born following this procedure. To date, little is known about the efficacy of OTT in patients exposed to cancer chemotherapy prior to OTC. STUDY DESIGN, SIZE, DURATION This study evaluates the recovery of ovarian function and fertility in 31 consecutive patients who had received OTT, between 2005 and 2015. PARTICIPANTS/MATERIALS, SETTING, METHODS Thirty one patients, wanting children, were transplanted with autologous ovarian cortex, among which 22 patients (71%) had been exposed to chemotherapy before OTC. Recovery of ovarian function was considered total once menstruation occurred. Ovarian function recovery (OFR), ovarian graft survival, and incidence of pregnancy were related to previous chemotherapy exposure, type of chemotherapy and graft characteristics (number of grafted fragments and follicular density). MAIN RESULTS AND ROLE OF CHANCE The amount of ovarian tissue collected was the only parameter to show any significant change between patients with versus without previous chemotherapy. At 1 year after OTT, the cumulative incidence of OFR was 83% (93% in patients exposed to chemotherapy and 67% in others (P = 0.14)). A low follicular density (<0.3 foll/mm2) in the transplant and a low number of grafted fragments (<16) were significantly associated with a delayed OFR. Graft survival at 2 years after OTT was 77%. It was significantly lower in patients exposed to bifunctional alkylating agents before ovarian cryopreservation and in patients with a low follicular density. The proportion of women who succeeded in having at least one live birth was 23% in the total population, 0% (0/9) in the group 'no previous chemotherapy', and 32% (7/22) in the group 'previous chemotherapy'. The cumulative incidence of pregnancy (Kaplan-Meier) at 3 years after OTT was 36% overall and 49% in case of previous chemotherapy, with no difference related to previous chemotherapy exposure. In total there were 13 pregnancies and 8 births in 7 patients. LIMITATIONS, REASONS FOR CAUTION The pathology in the two groups of patients was not comparable. In the group of patients who had chemotherapy before OTC, there were 95% of hematological malignancies. In the group of patients who did not have chemotherapy before OTC only 1 out of 9 patients had a malignant hematological disease while 44% had some pathology affecting the ovaries. Few women are available for study and only large changes are likely to have statistical significance. WIDER IMPLICATIONS OF THE FINDINGS These results suggest that prior cancer chemotherapy should no longer be considered a limitation to cryopreservation of ovarian tissue and current recommendations in this regard should be revised. STUDY FUNDING/COMPETING INTEREST(S) This study was supported by the Agence de la Biomédecine (France's biomedical office). There are no competing interests to report. TRIAL REGISTRATION NUMBER NCT02184806.
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Affiliation(s)
- C Poirot
- Department of Hematology, Adolescents and Young Adults Unit, Fertility Preservation, Assistance Publique-Hôpitaux de Paris (AP-HP) Saint Louis Hospital, Paris, France.,Médecine Sorbonne Université, Paris, France
| | - A Fortin
- Department of Obstetrics Gynecology, AP-HP Pitié-Salpêtrière-Charles Foix University Hospital, Paris, France
| | - J M Lacorte
- Médecine Sorbonne Université, Paris, France.,Department of Hormonal Biochemistry, AP-HP Pitié-Salpêtrière-Charles Foix University Hospital, Paris, France
| | - J P Akakpo
- Department of Radiology, AP-HP Pitié-Salpêtrière-Charles Foix University Hospital, Paris, France
| | - C Genestie
- Department of Pathology, Gustave Roussy Institute, Villejuif, France
| | - J P Vernant
- Médecine Sorbonne Université, Paris, France.,Department of Hematology, AP-HP Pitié-Salpêtrière-Charles Foix University Hospital, Paris, France
| | - P Brice
- Department of Hematology/Oncology, AP-HP Saint Louis Hospital, Paris, France
| | - P Morice
- Department of Oncological Surgery, Gustave Roussy Institute, Villejuif, France.,Paris-Sud XI University, Le Kremlin-Bicêtre, France
| | - T Leblanc
- Department of Pediatric Hematology, AP-HP Robert Debré University Hospital, Paris, France
| | - J Gabarre
- Department of Hematology, AP-HP Pitié-Salpêtrière-Charles Foix University Hospital, Paris, France
| | - A Delmer
- Department of Clinical Hematology, Robert Debré Hospital, Reims, France.,Reims Champagne-Ardenne University, Reims, France
| | - Y Badachi
- Department of Radiology, AP-HP Pitié-Salpêtrière-Charles Foix University Hospital, Paris, France
| | - V Drouineaud
- Department of Reproductive Biology, AP-HP Cochin Hospital, Paris, France
| | - S Gouy
- Department of Oncological Surgery, Gustave Roussy Institute, Villejuif, France
| | - C Chalas
- Department of Reproductive Biology, AP-HP Cochin Hospital, Paris, France
| | - S Egels
- Department of Radiology, AP-HP Pitié-Salpêtrière-Charles Foix University Hospital, Paris, France
| | - N Dhédin
- Department of Hematology, Adolescents and Young Adults Unit, Fertility Preservation, Assistance Publique-Hôpitaux de Paris (AP-HP) Saint Louis Hospital, Paris, France
| | - P Touraine
- Médecine Sorbonne Université, Paris, France.,Department of Endocrinology, AP-HP Pitié-Salpêtrière-Charles Foix University Hospital, Paris, France
| | - M Dommergues
- Médecine Sorbonne Université, Paris, France.,Department of Obstetrics Gynecology, AP-HP Pitié-Salpêtrière-Charles Foix University Hospital, Paris, France
| | - G Lebègue
- Department of Obstetrics Gynecology, AP-HP Pitié-Salpêtrière-Charles Foix University Hospital, Paris, France
| | - J P Wolf
- Department of Reproductive Biology, AP-HP Cochin Hospital, Paris, France.,Paris Descartes University, Paris, France
| | - F Capron
- Médecine Sorbonne Université, Paris, France.,Department of Pathology, AP-HP Pitié-Salpêtrière-Charles Foix University Hospital, Paris, France
| | - G Lefebvre
- Department of Obstetrics Gynecology, AP-HP Pitié-Salpêtrière-Charles Foix University Hospital, Paris, France
| | - N Boissel
- Department of Hematology, Adolescents and Young Adults Unit, Fertility Preservation, Assistance Publique-Hôpitaux de Paris (AP-HP) Saint Louis Hospital, Paris, France.,Paris Diderot University, Paris, France
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ANCA-associated vasculitides: Recommendations of the French Vasculitis Study Group on the use of immunosuppressants and biotherapies for remission induction and maintenance. Presse Med 2020; 49:104031. [PMID: 32645418 DOI: 10.1016/j.lpm.2020.104031] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2019] [Accepted: 05/21/2020] [Indexed: 12/13/2022] Open
Abstract
Treatment of vasculitides associated with anti-neutrophil cytoplasm antibodies (ANCA) (AAVs) has evolved dramatically in recent years, particularly since the demonstration of rituximab efficacy as remission induction and maintenance therapy for granulomatosis with polyangiitis and microscopic polyangiitis. In 2013, the French Vasculitis Study Group (FVSG) published recommendations for its use by clinicians. Since then, new data have made it possible to better specify and codify prescription of rituximab to treat AAVs. Herein, the FVSG Recommendations Committee, an expert panel comprised of physicians with extensive experience in the treatment and management of vasculitides, presents its consensus guidelines based on literature analysis, the results of prospective therapeutic trials and personal experience.
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Krysko KM, Graves JS, Dobson R, Altintas A, Amato MP, Bernard J, Bonavita S, Bove R, Cavalla P, Clerico M, Corona T, Doshi A, Fragoso Y, Jacobs D, Jokubaitis V, Landi D, Llamosa G, Longbrake EE, Maillart E, Marta M, Midaglia L, Shah S, Tintore M, van der Walt A, Voskuhl R, Wang Y, Zabad RK, Zeydan B, Houtchens M, Hellwig K. Sex effects across the lifespan in women with multiple sclerosis. Ther Adv Neurol Disord 2020; 13:1756286420936166. [PMID: 32655689 PMCID: PMC7331774 DOI: 10.1177/1756286420936166] [Citation(s) in RCA: 58] [Impact Index Per Article: 11.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2020] [Accepted: 05/28/2020] [Indexed: 02/06/2023] Open
Abstract
Multiple sclerosis (MS) is an autoimmune inflammatory demyelinating central nervous system disorder that is more common in women, with onset often during reproductive years. The female:male sex ratio of MS rose in several regions over the last century, suggesting a possible sex by environmental interaction increasing MS risk in women. Since many with MS are in their childbearing years, family planning, including contraceptive and disease-modifying therapy (DMT) counselling, are important aspects of MS care in women. While some DMTs are likely harmful to the developing fetus, others can be used shortly before or until pregnancy is confirmed. Overall, pregnancy decreases risk of MS relapses, whereas relapse risk may increase postpartum, although pregnancy does not appear to be harmful for long-term prognosis of MS. However, ovarian aging may contribute to disability progression in women with MS. Here, we review sex effects across the lifespan in women with MS, including the effect of sex on MS susceptibility, effects of pregnancy on MS disease activity, and management strategies around pregnancy, including risks associated with DMT use before and during pregnancy, and while breastfeeding. We also review reproductive aging and sexual dysfunction in women with MS.
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Affiliation(s)
- Kristen M Krysko
- Department of Neurology, UCSF Weill Institute for Neurosciences, University of California San Francisco, 675 Nelson Rising Lane, Suite 221, San Francisco, CA 94158, USA
| | - Jennifer S Graves
- Department of Neurosciences, University of California San Diego, UCSD ACTRI, La Jolla, CA, USA
| | - Ruth Dobson
- Preventive Neurology Unit, Wolfson Institute of Preventive Neurology, Queen Mary University of London, London, UK
| | - Ayse Altintas
- Department of Neurology, School of Medicine, Koc University, Istanbul, Turkey
| | - Maria Pia Amato
- Department NEUROFARBA, Section of Neurosciences, University of Florence, Florence, Italy
| | - Jacqueline Bernard
- Department of Neurology, Oregon Health Science University, Portland, OR, USA
| | - Simona Bonavita
- Department of Advanced Medical and Surgical Sciences, University of Campania, "Luigi Vanvitelli", Naples, Italy
| | - Riley Bove
- Department of Neurology, UCSF Weill Institute for Neurosciences, University of California San Francisco, San Francisco CA, USA
| | - Paola Cavalla
- Department of Neuroscience and Mental Health, City of Health and Science University Hospital of Torino, Turin, Italy
| | - Marinella Clerico
- Department of Clinical and Biological Sciences, University of Torino, San Luigi Gonzaga Hospital, Orbassano, Turin, Italy
| | - Teresa Corona
- Clinical Laboratory of Neurodegenerative Disease, National Institute of Neurology and Neurosurgery of Mexico, Mexico City, Mexico
| | - Anisha Doshi
- Department of Neuroinflammation, Queen Square Multiple Sclerosis Centre, University College London (UCL) Institute of Neurology, London, UK
| | - Yara Fragoso
- Multiple Sclerosis & Headache Research Institute, Santos, SP, Brazil
| | - Dina Jacobs
- Department of Neurology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA
| | - Vilija Jokubaitis
- Department of Neuroscience, Monash University, Melbourne, VIC, Australia
| | - Doriana Landi
- Department of Systems Medicine, Multiple Sclerosis Center and Research Unit, Tor Vergata University and Hospital, Rome, Italy
| | | | | | | | - Monica Marta
- Neurosciences and Trauma Centre, Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK
| | - Luciana Midaglia
- Department of Neurology-Neuroimmunology, Multiple Sclerosis Centre of Catalonia, Vall d'Hebron University Hospital, Barcelona, Spain
| | - Suma Shah
- Department of Neurology, Duke University, Durham, NC, USA
| | - Mar Tintore
- Department of Neurology-Neuroimmunology, Multiple Sclerosis Centre of Catalonia, Vall d'Hebron University Hospital, Barcelona, Spain
| | | | - Rhonda Voskuhl
- Department of Neurology, University of California Los Angeles, Los Angeles, CA, USA
| | - Yujie Wang
- Department of Neurology, Johns Hopkins University, Baltimore, MD, USA
| | - Rana K Zabad
- Department of Neurological Sciences, University of Nebraska Medical Center, Omaha, NE, USA
| | - Burcu Zeydan
- Department of Radiology, Mayo Clinic, Rochester, MN, USA
| | - Maria Houtchens
- Department of Neurology, Partners MS Center, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Kerstin Hellwig
- Department of Neurology, St. Josef Hospital, Ruhr University Bochum, Bochum, Germany
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Luong SN, Isaacs A, Liu Z, Sin FE, Giles I. A systematic review and meta-analysis of the gonadotoxic effects of cyclophosphamide and benefits of gonadotropin releasing hormone agonists (GnRHa) in women of child-bearing age with autoimmune rheumatic disease. Expert Rev Clin Immunol 2020; 16:321-333. [PMID: 32005081 DOI: 10.1080/1744666x.2020.1724091] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
Objectives: To systematically review risk of sustained amenorrhea with intravenous (IV) cyclophosphamide in autoimmune rheumatic disease (ARD), and evaluate efficacy of gonadotropin-releasing hormone agonists (GnRHa) to reduce this risk.Methods: Systematic search for papers reporting incidence of sustained amenorrhea ≥12 months in ARD following: IV cyclophosphamide; or GnRHa and IV cyclophosphamide compared to IV cyclophosphamide alone.Results: From 31 articles and 1388 patients (mean age 27.7 years) sustained amenorrhea occurred in 273 patients (19.7%). Of 56 patients (mean age range 23.9-25.6 years) receiving GnRHa and IV cyclophosphamide, and 37 controls (mean age range 25-30.1 years) given IV cyclophosphamide only, sustained amenorrhea occurred in 2/56 (3.6%) patients treated with GnRHa, compared to 15/37 (40.5%) controls. Pooled odds ratio of sustained amenorrhea with GnRHa and cyclophosphamide versus cyclophosphamide alone was 0.054 (95% CI 0.0115-0.2576 p < 0.001), corresponding to a number needed to treat of 2.7 (95% CI 1.955-4.388) and absolute risk reduction of 36.95% (95% CI 35.6-38.4%).Conclusion: Sustained amenorrhea with IV cyclophosphamide was observed in patients with ARD, especially with increasing age and cumulative doses >5 g. GnRHa reduced this risk and should be considered with IV cyclophosphamide in women of childbearing age with ARD.
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Affiliation(s)
- Shi-Nan Luong
- Department of Rheumatology, University College London Hospital, London, UK.,Centre for Rheumatology, Division of Medicine, Rayne Institute, University College London, London, UK.,South Western Sydney Clinical School, Faculty of Medicine, University of New South Wales, Sydney, Australia
| | - Anthony Isaacs
- Department of Rheumatology, University College London Hospital, London, UK
| | - Zhixin Liu
- Stats Central, Mark Wainwright Analytical Centre, University of New South Wales, Sydney, Australia
| | - Fang E Sin
- Department of Rheumatology, University College London Hospital, London, UK
| | - Ian Giles
- Department of Rheumatology, University College London Hospital, London, UK.,Centre for Rheumatology, Division of Medicine, Rayne Institute, University College London, London, UK
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30
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Nusbaum JS, Mirza I, Shum J, Freilich RW, Cohen RE, Pillinger MH, Izmirly PM, Buyon JP. Sex Differences in Systemic Lupus Erythematosus: Epidemiology, Clinical Considerations, and Disease Pathogenesis. Mayo Clin Proc 2020; 95:384-394. [PMID: 32029091 DOI: 10.1016/j.mayocp.2019.09.012] [Citation(s) in RCA: 93] [Impact Index Per Article: 18.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2019] [Revised: 08/17/2019] [Accepted: 09/20/2019] [Indexed: 12/12/2022]
Abstract
Systemic lupus erythematosus (SLE) is a chronic, multiorgan, systemic autoimmune disease that is more common in women than men and is typically diagnosed during reproductive age, necessitating sex-specific considerations in care. In women there is no substantive evidence to suggest that SLE reduces fertility, but subfertility may occur as a result of active disease, immunosuppressive drugs, and age-related declines in fertility related to delays in childbearing. Although pregnancy outcomes have improved, SLE still poses risks in pregnancy that contribute to poorer maternal and fetal outcomes. Cyclophosphamide, an important agent for the treatment of severe or life-threatening lupus, may adversely affect fertility, particularly with increases in dose and patient age. Fertility preservation techniques are therefore an important consideration for women and men before cytotoxic treatment. There is mixed evidence as to whether exogenous estrogen in the form of oral contraceptive pills or hormone replacement therapy may increase the risk for the development of SLE, but among women with SLE already diagnosed, combined oral contraceptive pills and hormone replacement therapy do not confer risk for severe flare and remain important in reproductive care. The higher incidence of SLE in women may nonetheless be attributable to effects of endogenous estrogen, as well as failures in X chromosome inactivation, increased Toll-like receptor gene products, and changes in microRNA function. A greater appreciation of the biological underpinnings and consequences of sex differences in SLE may lead to more targeted treatments and improved outcomes for patients with SLE.
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Affiliation(s)
- Julie S Nusbaum
- Division of Rheumatology, Department of Medicine, New York University School of Medicine, New York.
| | - Ibraheem Mirza
- Division of Rheumatology, Department of Medicine, New York University School of Medicine, New York
| | - Justine Shum
- Division of Rheumatology, Department of Medicine, New York University School of Medicine, New York
| | - Robert W Freilich
- Division of Rheumatology, Department of Medicine, New York University School of Medicine, New York
| | - Rebecca E Cohen
- Division of Rheumatology, Department of Medicine, New York University School of Medicine, New York
| | - Michael H Pillinger
- Division of Rheumatology, Department of Medicine, New York University School of Medicine, New York
| | - Peter M Izmirly
- Division of Rheumatology, Department of Medicine, New York University School of Medicine, New York
| | - Jill P Buyon
- Division of Rheumatology, Department of Medicine, New York University School of Medicine, New York
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Wiles K, Anckaert E, Holden F, Grace J, Nelson-Piercy C, Lightstone L, Chappell LC, Bramham K. Anti-Müllerian hormone concentrations in women with chronic kidney disease. Clin Kidney J 2019; 14:537-542. [PMID: 33623676 PMCID: PMC7886554 DOI: 10.1093/ckj/sfz164] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2019] [Accepted: 10/23/2019] [Indexed: 01/01/2023] Open
Abstract
Background Serum anti-Müllerian hormone (AMH) is a biomarker of ovarian reserve. There are limited data to guide the clinical interpretation of AMH in women with chronic kidney disease (CKD). The purpose of this study was to examine AMH concentrations in women with CKD compared with women without CKD. Methods We conducted a prospective cohort study of serum AMH concentrations in 163 non-pregnant women with CKD. Serum AMH concentrations were compared with age-specific AMH centiles from 887 healthy female controls. Results Participants included 30 women with Stage 1 CKD, 37 women with Stage 2 CKD, 26 women with Stage 3a CKD, 31 women with Stage 3b CKD and 39 women with Stages 4 and 5 CKD. The median estimated glomerular filtration rate (eGFR) was 51 (interquartile range 31–80) mL/min/1.73 m2. Serum AMH concentrations were lower in all CKD stages compared with women without CKD. Women ages 20–24 years with CKD had comparable serum AMH concentrations (median 1.959 ng/mL) to women ages 35–39 years without CKD (median 1.995 ng/mL). There was no evidence that eGFR was an independent modifier of serum AMH concentrations. More than half of women with CKD (58%) were predicted to have a low response to gonadotrophin stimulation. Conclusions Women with CKD have a lower ovarian reserve and are predicted to have a lower ovarian response to gonadotrophin stimulation compared with women without CKD of a similar age. Women with CKD who fail to conceive within 6 months of regular unprotected intercourse should be considered for fertility assessment and intervention.
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Affiliation(s)
- Kate Wiles
- Department of Women and Children's Health, King's College London, London, UK.,Guy's and St Thomas NHS Foundation Trust, London, UK
| | - Ellen Anckaert
- Laboratory of Hormonology and Tumour Markers, Universitair Ziekenhuis Brussel, Free University of Brussels, Brussels, Belgium
| | - Francesca Holden
- Department of Renal Medicine, King's College Hospital NHS Foundation Trust, London, UK
| | - Jan Grace
- Guy's and St Thomas NHS Foundation Trust, London, UK
| | - Catherine Nelson-Piercy
- Guy's and St Thomas NHS Foundation Trust, London, UK.,Imperial Healthcare NHS Trust, London, UK
| | - Liz Lightstone
- Imperial Healthcare NHS Trust, London, UK.,Faculty of Medicine, Centre for Inflammatory Disease, Imperial College London, London, UK
| | - Lucy C Chappell
- Department of Women and Children's Health, King's College London, London, UK.,Guy's and St Thomas NHS Foundation Trust, London, UK
| | - Kate Bramham
- Department of Women and Children's Health, King's College London, London, UK.,Department of Renal Medicine, King's College Hospital NHS Foundation Trust, London, UK
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33
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Fluorescent cyclic phosphoramide mustards and their cytotoxicity against cancer and cancer stem cells. Polyhedron 2019. [DOI: 10.1016/j.poly.2019.05.046] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
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Liu H, Zhang Y, Li M, Luo P. Beneficial effect of Sepia esculenta ink polysaccharide on cyclophosphamide-induced immunosuppression and ovarian failure in mice. Int J Biol Macromol 2019; 140:1098-1105. [DOI: 10.1016/j.ijbiomac.2019.08.200] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2019] [Revised: 08/21/2019] [Accepted: 08/23/2019] [Indexed: 12/01/2022]
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Wiles K, Chappell L, Clark K, Elman L, Hall M, Lightstone L, Mohamed G, Mukherjee D, Nelson-Piercy C, Webster P, Whybrow R, Bramham K. Clinical practice guideline on pregnancy and renal disease. BMC Nephrol 2019; 20:401. [PMID: 31672135 PMCID: PMC6822421 DOI: 10.1186/s12882-019-1560-2] [Citation(s) in RCA: 111] [Impact Index Per Article: 18.5] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2019] [Accepted: 09/16/2019] [Indexed: 01/13/2023] Open
Affiliation(s)
- Kate Wiles
- NIHR Doctoral Research Fellow in Obstetric Nephrology, Guy's and St. Thomas' NHS Foundation Trust and King's College London, London, UK.
| | - Lucy Chappell
- Guy's and St. Thomas' NHS Foundation Trust and King's College London, London, UK
| | | | - Louise Elman
- Expert Patient, c/o The Renal Association, Bristol, UK
| | - Matt Hall
- Nottingham University Hospital, Nottingham, UK
| | - Liz Lightstone
- Imperial College London and Imperial College Healthcare NHS Trust, London, UK
| | | | | | - Catherine Nelson-Piercy
- Guy's and St. Thomas' NHS Foundation Trust and Imperial College Healthcare NHS Trust, London, UK
| | | | | | - Kate Bramham
- King's College Hospital NHS Foundation Trust and King's College London, London, UK
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36
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Cui W, Stern C, Hickey M, Goldblatt F, Anazodo A, Stevenson WS, Phillips KA. Preventing ovarian failure associated with chemotherapy. Med J Aust 2019; 209:412-416. [PMID: 30376664 DOI: 10.5694/mja18.00190] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2018] [Accepted: 04/23/2018] [Indexed: 12/17/2022]
Abstract
Alkylating chemotherapy is often used to treat pre-menopausal women for various malignancies and autoimmune diseases. Chemotherapy-associated ovarian failure is a potential consequence of this treatment which can cause infertility, and increases the risk of other long term adverse health sequelae. Randomised trials, predominantly of women undergoing alkylating chemotherapy for breast cancer, have shown evidence for the efficacy of gonadotropin-releasing hormone agonists (GnRHa) in preventing chemotherapy-associated ovarian failure. The European St Gallen and United States National Comprehensive Cancer Network guidelines recommend the use of concurrent GnRHa to reduce the risk of ovarian failure for pre-menopausal women undergoing chemotherapy for breast cancer. The GnRHa goserelin, a monthly 3.6 mg depot subcutaneous injection, has recently been listed on the Australian Pharmaceutical Benefits Scheme to reduce risk of ovarian failure for pre-menopausal women receiving alkylating therapies for malignancy or autoimmune disease. The first dose of goserelin should ideally be administered at least 1 week before commencement of alkylating treatment and continued 4-weekly during chemotherapy. Concurrent goserelin use should now be considered for all pre-menopausal women due to commence alkylating chemotherapy (except those with incurable cancer), regardless of their childbearing status, in an effort to preserve their ovarian function. For women who have not completed childbearing, consideration of other fertility preservation options, such as cryopreservation of embryos or oocytes, is also important.
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Affiliation(s)
- Wanyuan Cui
- Peter MacCallum Cancer Centre, Melbourne, VIC
| | | | | | - Fiona Goldblatt
- Flinders Medical Centre and Flinders University, Adelaide, SA
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Vanni VS, De Lorenzo R, Privitera L, Canti V, Viganò P, Rovere-Querini P. Safety of fertility treatments in women with systemic autoimmune diseases (SADs). Expert Opin Drug Saf 2019; 18:841-852. [PMID: 31238745 DOI: 10.1080/14740338.2019.1636964] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Abstract
Introduction: Systemic Autoimmune Diseases (SADs) include systemic lupus erythematosus, antiphospholipid antibody syndrome, rheumatoid arthritis, systemic sclerosis, Sjogren's syndrome, mixed connective tissue disease, idiopathic inflammatory myopathies and vasculitis. SADs often occur in women of childbearing age and can affect fertility. Both infertility treatments and fertility preservation techniques are thus often indicated. Areas covered: The literature regarding the safety of fertility-related drugs for both fertility preservation and infertility treatment in patients affected by SADs was reviewed. Based on current knowledge, all the options for fertility preservation should be contemplated in patients with SADs who are at risk for fertility loss, including GnRH analogue administration, oocyte/embryo vitrification and ovarian tissue cryopreservation. Similarly, if pregnancy is not contraindicated in a patient with a SAD, neither should be any fertility treatment. Expert opinion: Women with SADs should postpone conception until a stable disease has been achieved for at least 6 months. When infertility treatments are needed, women with antiphospholipid antibodies should receive concomitant anticoagulation. If in vitro fertilization/intra-cytoplasmic sperm injection and embryo transfer is required, ovarian hyperstimulation and the inherent risk of thrombosis should be eliminated by GnRH-agonist trigger and cycle segmentation. Counselling about adherence to anti-rheumatic therapy to prevent disease exacerbations is also critical.
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Affiliation(s)
- V S Vanni
- a Reproductive Sciences Laboratory, Division of Genetics and Cell Biology, IRCCS San Raffaele Scientific Institute , Milan , Italy.,b Vita-Salute San Raffaele University , Milan , Italy
| | - R De Lorenzo
- b Vita-Salute San Raffaele University , Milan , Italy
| | - L Privitera
- c Division of Obstetrics and Gynecology, IRCCS San Raffaele Scientific Institute , Milan , Italy
| | - V Canti
- b Vita-Salute San Raffaele University , Milan , Italy
| | - P Viganò
- a Reproductive Sciences Laboratory, Division of Genetics and Cell Biology, IRCCS San Raffaele Scientific Institute , Milan , Italy
| | - P Rovere-Querini
- b Vita-Salute San Raffaele University , Milan , Italy.,d Division of Immunology, Transplantation & Infectious Diseases, IRCCS San Raffaele Scientific Institute , Milan , Italy
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38
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Chehab G, Krüssel J, Fehm T, Fischer-Betz R, Schneider M, Germeyer A, Suerdieck MB, Kreuzer V, Liebenthron J. Successful conception in a 34-year-old lupus patient following spontaneous pregnancy after autotransplantation of cryopreserved ovarian tissue. Lupus 2019; 28:675-680. [PMID: 30907296 PMCID: PMC6515711 DOI: 10.1177/0961203319839482] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Premature gonadal failure is a common problem in patients with systemic lupus erythematosus (SLE) when gonadotoxic therapies are applied. The preservation of gonadal function and fertility is of great importance to many predominantly young SLE patients. Some fertility preservation methods are well established and well known, whereas others are considered more cautiously. In particular, the cryopreservation of ovarian tissue is a rarely chosen fertility preservation option for SLE patients of (pre)fertile age. We report the first case of successful conception and pregnancy of an SLE patient after autotransplantation of cryopreserved ovarian tissue. A 26-year-old SLE patient decided to undergo cryopreservation of ovarian tissue when receiving cyclophosphamide for lupus nephritis. Tissue removal, preparation, cryopreservation and quality control was performed, as described, according to current state-of-the-art techniques. After 6 years of being in remission using azathioprine and belimumab, her ovarian tissue was autotransplanted because of premature ovarian failure, diagnosed at the age of 32, and a wish to conceive. She conceived spontaneously 8 months later, having a diamniotic-dichoriotic twin pregnancy. The children were born prematurely due to preterm premature rupture of membranes in the 32nd week of gestation; mother and children are doing very well 8 months later. We regard the procedure to be an option worth consideration for our predominantly young SLE patients.
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Affiliation(s)
- G Chehab
- 1 Policlinic of Rheumatology and Hiller Research Unit Rheumatology, Heinrich-Heine-University, Düsseldorf, Germany
| | - J Krüssel
- 2 Department of Obstetrics/Gynecology and Reproductive Endocrinology and Infertility (UniKiD), Heinrich-Heine-University, Düsseldorf, Germany.,3 UniCareD, University Cryobank for Assisted Reproductive Medicine and Fertility Protection at UniKiD Düsseldorf, Heinrich-Heine-University, Düsseldorf, Germany
| | - T Fehm
- 4 Department of Obstetrics and Gynecology, Heinrich-Heine-University, Düsseldorf, Germany
| | - R Fischer-Betz
- 1 Policlinic of Rheumatology and Hiller Research Unit Rheumatology, Heinrich-Heine-University, Düsseldorf, Germany
| | - M Schneider
- 1 Policlinic of Rheumatology and Hiller Research Unit Rheumatology, Heinrich-Heine-University, Düsseldorf, Germany
| | - A Germeyer
- 5 Department of Gynecological Endocrinology and Fertility Disorders, University Women's Hospital, Heidelberg, Germany
| | | | - V Kreuzer
- 2 Department of Obstetrics/Gynecology and Reproductive Endocrinology and Infertility (UniKiD), Heinrich-Heine-University, Düsseldorf, Germany.,3 UniCareD, University Cryobank for Assisted Reproductive Medicine and Fertility Protection at UniKiD Düsseldorf, Heinrich-Heine-University, Düsseldorf, Germany
| | - J Liebenthron
- 3 UniCareD, University Cryobank for Assisted Reproductive Medicine and Fertility Protection at UniKiD Düsseldorf, Heinrich-Heine-University, Düsseldorf, Germany
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39
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Keri KC, Blumenthal S, Kulkarni V, Beck L, Chongkrairatanakul T. Primary membranous nephropathy: comprehensive review and historical perspective. Postgrad Med J 2019; 95:23-31. [DOI: 10.1136/postgradmedj-2018-135729] [Citation(s) in RCA: 38] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2018] [Accepted: 12/01/2018] [Indexed: 11/04/2022]
Abstract
Membranous nephropathy (MN) is the most common cause of nephrotic syndrome in non-diabetic Caucasian adults over 40 years of age. It has an estimated incidence of 8–10 cases per 1 million. Fifty per cent of patients diagnosed with primary MN continue to have nephrotic syndrome and 30% of patients may progress to end-stage renal disease over 10 years. Although it was recognised as a distinct clinic-pathological entity in 1940s by immunofluorescence and electron microscopy, the pathogenesis and treatment have become more apparent only in the last decade. Discovery of M-type phospholipase A2 receptor (PLA2R) antibodies and thrombospondin type 1 domain-containing 7A antibodies has given new perspectives in understanding the pathogenesis of the disease process. Anti-PLA2R antibody is the first serologic marker that has promising evidence to be used as a tool to prognosticate the course of the disease. More importantly, therapeutic agents such as rituximab and adrenocorticotropic hormone analogues are the newer therapeutic options that should be considered in the therapy of primary MN.
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40
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Abstract
Most glomerular diseases are immunologically mediated disorders of the kidney and are common causes of ESKD. In addition to supportive therapy, a wide range of immunosuppressive agents are used in the management of patients with these conditions. Immunosuppression requires a careful balance of risk and benefits, and many of these agents have a narrow therapeutic window and require close monitoring. This review describes the side effects of immunosuppressive agents used in recent randomized, controlled trials of glomerular disease, and highlights some of the key adverse events that determine the choice and prescription of these medications.
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Affiliation(s)
- J Ashley Jefferson
- Division of Nephrology, Department of Medicine, University of Washington, Seattle, Washington
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41
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Traitements immunosuppresseurs et préservation de la fertilité : indications et modalités pratiques. Rev Med Interne 2018; 39:557-565. [DOI: 10.1016/j.revmed.2018.02.010] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2017] [Revised: 01/23/2018] [Accepted: 02/05/2018] [Indexed: 12/17/2022]
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42
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Koga T, Umeda M, Endo Y, Ishida M, Fujita Y, Tsuji S, Takatani A, Shimizu T, Sumiyoshi R, Igawa T, Fukui S, Nishino A, Kawashiri SY, Iwamoto N, Ichinose K, Tamai M, Nakamura H, Origuchi T, Murakami N, Kitajima M, Kawakami A. Effect of a gonadotropin-releasing hormone analog for ovarian function preservation after intravenous cyclophosphamide therapy in systemic lupus erythematosus patients: a retrospective inception cohort study. Int J Rheum Dis 2018; 21:1287-1292. [DOI: 10.1111/1756-185x.13318] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Affiliation(s)
- Tomohiro Koga
- Division of Advanced Preventive Medical Sciences; Department of Immunology and Rheumatology; Nagasaki University Graduate School of Biomedical Sciences; Nagasaki Japan
- Center for Bioinformatics and Molecular Medicine; Nagasaki University Graduate School of Biomedical Sciences; Nagasaki Japan
| | - Masataka Umeda
- Division of Advanced Preventive Medical Sciences; Department of Immunology and Rheumatology; Nagasaki University Graduate School of Biomedical Sciences; Nagasaki Japan
- Medical Education Development Center; Nagasaki University Hospital; Nagasaki Japan
| | - Yushiro Endo
- Division of Advanced Preventive Medical Sciences; Department of Immunology and Rheumatology; Nagasaki University Graduate School of Biomedical Sciences; Nagasaki Japan
| | - Midori Ishida
- Division of Advanced Preventive Medical Sciences; Department of Immunology and Rheumatology; Nagasaki University Graduate School of Biomedical Sciences; Nagasaki Japan
| | - Yuya Fujita
- Division of Advanced Preventive Medical Sciences; Department of Immunology and Rheumatology; Nagasaki University Graduate School of Biomedical Sciences; Nagasaki Japan
| | - Sosuke Tsuji
- Division of Advanced Preventive Medical Sciences; Department of Immunology and Rheumatology; Nagasaki University Graduate School of Biomedical Sciences; Nagasaki Japan
| | - Ayuko Takatani
- Division of Advanced Preventive Medical Sciences; Department of Immunology and Rheumatology; Nagasaki University Graduate School of Biomedical Sciences; Nagasaki Japan
| | - Toshimasa Shimizu
- Division of Advanced Preventive Medical Sciences; Department of Immunology and Rheumatology; Nagasaki University Graduate School of Biomedical Sciences; Nagasaki Japan
| | - Remi Sumiyoshi
- Division of Advanced Preventive Medical Sciences; Department of Immunology and Rheumatology; Nagasaki University Graduate School of Biomedical Sciences; Nagasaki Japan
| | - Takashi Igawa
- Division of Advanced Preventive Medical Sciences; Department of Immunology and Rheumatology; Nagasaki University Graduate School of Biomedical Sciences; Nagasaki Japan
| | - Shoichi Fukui
- Division of Advanced Preventive Medical Sciences; Department of Immunology and Rheumatology; Nagasaki University Graduate School of Biomedical Sciences; Nagasaki Japan
- Unit of Advanced Preventive Medical Sciences; Department of Community Medicine; Nagasaki University Graduate School of Biomedical Sciences; Nagasaki Japan
| | - Ayako Nishino
- Division of Advanced Preventive Medical Sciences; Department of Immunology and Rheumatology; Nagasaki University Graduate School of Biomedical Sciences; Nagasaki Japan
- Center for Comprehensive Community Care Education; Nagasaki University Graduate School of Biomedical Sciences; Nagasaki Japan
| | - Shin-ya Kawashiri
- Division of Advanced Preventive Medical Sciences; Department of Immunology and Rheumatology; Nagasaki University Graduate School of Biomedical Sciences; Nagasaki Japan
- Unit of Advanced Preventive Medical Sciences; Department of Community Medicine; Nagasaki University Graduate School of Biomedical Sciences; Nagasaki Japan
| | - Naoki Iwamoto
- Division of Advanced Preventive Medical Sciences; Department of Immunology and Rheumatology; Nagasaki University Graduate School of Biomedical Sciences; Nagasaki Japan
| | - Kunihiro Ichinose
- Division of Advanced Preventive Medical Sciences; Department of Immunology and Rheumatology; Nagasaki University Graduate School of Biomedical Sciences; Nagasaki Japan
| | - Mami Tamai
- Division of Advanced Preventive Medical Sciences; Department of Immunology and Rheumatology; Nagasaki University Graduate School of Biomedical Sciences; Nagasaki Japan
| | - Hideki Nakamura
- Division of Advanced Preventive Medical Sciences; Department of Immunology and Rheumatology; Nagasaki University Graduate School of Biomedical Sciences; Nagasaki Japan
| | - Tomoki Origuchi
- Division of Advanced Preventive Medical Sciences; Department of Immunology and Rheumatology; Nagasaki University Graduate School of Biomedical Sciences; Nagasaki Japan
| | - Naoko Murakami
- Department of Obstetrics and Gynecology; Nagasaki University Graduate School of Biomedical Sciences; Nagasaki Japan
| | - Michio Kitajima
- Department of Obstetrics and Gynecology; Nagasaki University Graduate School of Biomedical Sciences; Nagasaki Japan
| | - Atsushi Kawakami
- Division of Advanced Preventive Medical Sciences; Department of Immunology and Rheumatology; Nagasaki University Graduate School of Biomedical Sciences; Nagasaki Japan
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Nguyen QN, Zerafa N, Liew SH, Morgan FH, Strasser A, Scott CL, Findlay JK, Hickey M, Hutt KJ. Loss of PUMA protects the ovarian reserve during DNA-damaging chemotherapy and preserves fertility. Cell Death Dis 2018; 9:618. [PMID: 29795269 PMCID: PMC5966424 DOI: 10.1038/s41419-018-0633-7] [Citation(s) in RCA: 91] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2018] [Revised: 04/15/2018] [Accepted: 04/26/2018] [Indexed: 12/14/2022]
Abstract
Female gametes are stored in the ovary in structures called primordial follicles, the supply of which is non-renewable. It is well established that DNA-damaging cancer treatments can deplete the ovarian reserve of primordial follicles, causing premature ovarian failure and infertility. The precise mechanisms underlying this chemotherapy-driven follicle loss are unclear, and this has limited the development of targeted ovarian-protective agents. To address this fundamental knowledge gap, we used gene deletion mouse models to examine the role of the DNA damage-induced pro-apoptotic protein, PUMA, and its transcriptional activator TAp63, in primordial follicle depletion caused by treatment with cyclophosphamide or cisplatin. Cyclophosphamide caused almost complete destruction of the primordial follicle pool in adult wild-type (WT) mice, and a significant destructive effect was also observed for cisplatin. In striking contrast, Puma-/- mice retained 100% of their primordial follicles following either genotoxic treatment. Furthermore, elimination of PUMA alone completely preserved fertility in cyclophosphamide-treated mice, indicating that oocytes rescued from DNA damage-induced death can repair themselves sufficiently to support reproductive function and offspring health. Primordial follicles were also protected in TAp63-/- mice following cisplatin treatment, but not cyclophosphamide, suggesting mechanistic differences in the induction of apoptosis and depletion of the ovarian reserve in response to these different chemotherapies. These studies identify PUMA as a crucial effector of apoptosis responsible for depletion of primordial follicles following exposure to cyclophosphamide or cisplatin, and this indicates that inhibition of PUMA may be an effective ovarian-protective strategy during cancer treatment in women.
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Affiliation(s)
- Quynh-Nhu Nguyen
- Department of Obstetrics and Gynaecology, The University of Melbourne, Parkville, VIC, Australia
- Development and Stem Cells Program, Monash Biomedicine Discovery Institute, and Department of Anatomy and Developmental Biology, Monash University, Clayton, VIC, Australia
| | - Nadeen Zerafa
- Development and Stem Cells Program, Monash Biomedicine Discovery Institute, and Department of Anatomy and Developmental Biology, Monash University, Clayton, VIC, Australia
| | - Seng H Liew
- Development and Stem Cells Program, Monash Biomedicine Discovery Institute, and Department of Anatomy and Developmental Biology, Monash University, Clayton, VIC, Australia
| | - F Hamish Morgan
- Development and Stem Cells Program, Monash Biomedicine Discovery Institute, and Department of Anatomy and Developmental Biology, Monash University, Clayton, VIC, Australia
| | - Andreas Strasser
- The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia
- Department of Medical Biology, University of Melbourne, Parkville, VIC, Australia
| | - Clare L Scott
- The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia
- Department of Medical Biology, University of Melbourne, Parkville, VIC, Australia
| | - Jock K Findlay
- Centre for Reproductive Health, Hudson Institute of Medical Research, Clayton, VIC, Australia
- Monash University, Clayton, VIC, Australia
| | - Martha Hickey
- Department of Obstetrics and Gynaecology, The University of Melbourne, Parkville, VIC, Australia
- The Royal Womens Hospital, Parkville, VIC, 3052, Australia
| | - Karla J Hutt
- Development and Stem Cells Program, Monash Biomedicine Discovery Institute, and Department of Anatomy and Developmental Biology, Monash University, Clayton, VIC, Australia.
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Ahmed SB, Vitek WS, Holley JL. Fertility, Contraception, and Novel Reproductive Technologies in Chronic Kidney Disease. Semin Nephrol 2018; 37:327-336. [PMID: 28711071 DOI: 10.1016/j.semnephrol.2017.05.004] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
Chronic kidney disease (CKD) affects hypothalamic-pituitary-gonadal axis function, leading to menstrual abnormalities, sexual dysfunction, functional menopause, and loss of fertility. Pregnancy in a patient with CKD is associated with a higher risk of complications to both the mother and the fetus, highlighting the importance of contraceptive counseling at all stages of CKD. There has been limited research on the safety and efficacy of different contraceptive methods in the CKD population, and it is important to tailor the choice of contraception to the patient's lifestyle and comorbidity status. Cyclophosphamide is a commonly used immunosuppressive agent that impairs fertility in a dose-dependent fashion, with greater impact in older women of child-bearing age. Strategies to reduce the impact of cyclophosphamide on ovarian reserve as well as fertility preservation technologies are options to consider when treating immune-mediated CKD. A multidisciplinary approach in counseling the woman with CKD who wishes to contemplate or avoid pregnancy is necessary to optimize outcomes. Further research in this important area is required.
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Affiliation(s)
- Sofia B Ahmed
- Department of Medicine, University of Calgary, Calgary, Alberta, Canada; Alberta Kidney Disease Network, Alberta, Canada; Libin Cardiovascular Institute of Alberta, Calgary, Alberta, Canada.
| | - Wendy S Vitek
- Department of Obstetrics and Gynecology, University of Rochester Medical Center, Rochester, NY
| | - Jean L Holley
- Department of Medicine, University of Illinois, Urbana-Champaign, IL
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45
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Wiles K, Lightstone L. Glomerular Disease in Women. Kidney Int Rep 2018; 3:258-270. [PMID: 29725630 PMCID: PMC5932310 DOI: 10.1016/j.ekir.2018.01.010] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2018] [Revised: 01/26/2018] [Accepted: 01/27/2018] [Indexed: 12/28/2022] Open
Abstract
Gender differences exist in the prevalence of glomerular diseases. Data based on histological diagnosis underestimate the prevalence of preeclampsia, which is almost certainly the commonest glomerular disease in the world, and uniquely gender-specific. Glomerular disease affects fertility via disease activity, the therapeutic use of cyclophosphamide, and underlying chronic kidney disease. Techniques to preserve fertility during chemotherapy and risk minimization of artificial reproductive techniques are considered. The risks, benefits, and effectiveness of different contraceptive methods for women with glomerular disease are outlined. Glomerular disease increases the risk of adverse outcomes in pregnancy, including preeclampsia; yet, diagnosis of preeclampsia is complicated by the presence of hypertension and proteinuria that precede pregnancy. The role of renal biopsy in pregnancy is examined, in addition to the use of emerging angiogenic biomarkers. The safety of drugs prescribed for glomerular disease in relation to reproductive health is detailed. The impact of both gender and pregnancy on long-term prognosis is discussed.
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Affiliation(s)
- Kate Wiles
- Obstetric Nephrology, Guy’s and St. Thomas’ NHS Trust and King’s College London, London, UK
| | - Liz Lightstone
- Division of Immunology and Inflammation, Department of Medicine, Imperial College London, Hammersmith Campus, London, UK
- Correspondence: Liz Lightstone, Section of Renal Medicine and Vascular Inflammation, Department of Medicine, Imperial College London, Hammersmith Campus, Du Cane Road, London W12 0NN, UK.
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46
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Deakin CT, Campanilho‐Marques R, Simou S, Moraitis E, Wedderburn LR, Pullenayegum E, Pilkington CA. Efficacy and Safety of Cyclophosphamide Treatment in Severe Juvenile Dermatomyositis Shown by Marginal Structural Modeling. Arthritis Rheumatol 2018; 70:785-793. [PMID: 29342499 PMCID: PMC5947636 DOI: 10.1002/art.40418] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2017] [Accepted: 01/11/2018] [Indexed: 12/15/2022]
Abstract
OBJECTIVE In patients with severe or refractory juvenile dermatomyositis (DM), second-line treatments may be required. Cyclophosphamide (CYC) is used to treat some connective tissue diseases, but evidence of its efficacy in juvenile DM is limited. This study was undertaken to describe clinical improvement in juvenile DM patients treated with CYC and model the efficacy of CYC treatment compared to no CYC treatment. METHODS Clinical data on skin, global, and muscle disease for patients recruited to the Juvenile DM Cohort and Biomarker Study were analyzed. Clinical improvement following CYC treatment was described using unadjusted analysis. Marginal structural models (MSMs) were used to model treatment efficacy and adjust for confounding by indication. RESULTS Compared to the start of CYC treatment, there were reductions at 6, 12, and 24 months in skin disease (P = 1.3 × 10-10 ), global disease (P = 2.4 × 10-8 ), and muscle disease (P = 8.0 × 10-10 ) for 56 patients treated with CYC in unadjusted analysis. Limited evidence suggested a reduction in glucocorticoid dose (P = 0.047) in patients treated with CYC. MSM analysis showed reduced global disease and skin disease in patients who started an ~6-month course of CYC treatment >12 months ago compared to patients never or not yet treated with CYC. In the treated patients, the modified skin Disease Activity Score for juvenile DM was 1.19 units lower (P = 0.0085) and the physician's global assessment was 0.66 units lower (P = 0.027). Minor adverse events were reported in 3 patients within 1 year of stopping CYC. CONCLUSION Our findings indicate that CYC is efficacious with no short-term side effects. Improvements in skin, global, and muscle disease were observed. Further studies are required to evaluate longer-term side effects.
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Affiliation(s)
- Claire T. Deakin
- University College London Great Ormond Street Institute of Child HealthLondonUK
| | - Raquel Campanilho‐Marques
- University College London Great Ormond Street Institute of Child HealthLondonUK
- Hospital de Santa MariaCentro Hospitalar Lisboa NorteLisbon Academic Medical Centre and Instituto Português de ReumatologiaLisbonPortugal
| | - Stefania Simou
- University College London Great Ormond Street Institute of Child HealthLondonUK
| | - Elena Moraitis
- University College London Great Ormond Street Institute of Child HealthLondonUK
| | - Lucy R. Wedderburn
- University College London Great Ormond Street Institute of Child HealthGreat Ormond Street Hospital for ChildrenNIHR Biomedical Research Centre at Great Ormond Street Hospital for ChildrenNHS Foundation Trustand Arthritis Research UK Centre for Adolescent Rheumatology at University College LondonUniversity College London Hospitaland Great Ormond Street HospitalLondonUK
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Blom K, Odutayo A, Bramham K, Hladunewich MA. Pregnancy and Glomerular Disease: A Systematic Review of the Literature with Management Guidelines. Clin J Am Soc Nephrol 2017; 12:1862-1872. [PMID: 28522651 PMCID: PMC5672957 DOI: 10.2215/cjn.00130117] [Citation(s) in RCA: 63] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
During pregnancy, CKD increases both maternal and fetal risk. Adverse maternal outcomes include progression of underlying renal dysfunction, worsening of urine protein, and hypertension, whereas adverse fetal outcomes include fetal loss, intrauterine growth restriction, and preterm delivery. As such, pregnancy in young women with CKD is anxiety provoking for both the patient and the clinician providing care, and because the heterogeneous group of glomerular diseases often affects young women, this is an area of heightened concern. In this invited review, we discuss pregnancy outcomes in young women with glomerular diseases. We have performed a systematic review in attempt to better understand these outcomes among young women with primary GN, we review the studies of pregnancy outcomes in lupus nephritis, and finally, we provide a potential construct for management. Although it is safe to say that the vast majority of young women with glomerular disease will have a live birth, the counseling that we can provide with respect to individualized risk remains imprecise in primary GN because the existing literature is extremely dated, and all management principles are extrapolated primarily from studies in lupus nephritis and diabetes. As such, the study of pregnancy outcomes and management strategies in these rare diseases requires a renewed interest and a dedicated collaborative effort.
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Affiliation(s)
- Kimberly Blom
- Division of Nephrology, Department of Medicine, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada; and
| | - Ayodele Odutayo
- Division of Nephrology, Department of Medicine, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada; and
| | - Kate Bramham
- Department of Renal Medicine, Division of Transplantation Immunology and Mucosal Biology, King’s College, London, United Kingdom
| | - Michelle A. Hladunewich
- Division of Nephrology, Department of Medicine, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada; and
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Morishita KA, Tiller G, Cabral DA. Therapeutic Management of Pediatric Antineutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis. CURRENT TREATMENT OPTIONS IN RHEUMATOLOGY 2017. [DOI: 10.1007/s40674-017-0077-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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Gordon C, Amissah-Arthur MB, Gayed M, Brown S, Bruce IN, D’Cruz D, Empson B, Griffiths B, Jayne D, Khamashta M, Lightstone L, Norton P, Norton Y, Schreiber K, Isenberg D. The British Society for Rheumatology guideline for the management of systemic lupus erythematosus in adults. Rheumatology (Oxford) 2017; 57:e1-e45. [DOI: 10.1093/rheumatology/kex286] [Citation(s) in RCA: 172] [Impact Index Per Article: 21.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2016] [Indexed: 12/15/2022] Open
Affiliation(s)
- Caroline Gordon
- Rheumatology Research Group, Institute of Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham,
- Rheumatology Department, City Hospital, Sandwell and West Birmingham Hospitals NHS Trust,
- Rheumatology Department, University Hospitals Birmingham NHS Foundation Trust, Birmingham,
| | - Maame-Boatemaa Amissah-Arthur
- Rheumatology Research Group, Institute of Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham,
| | - Mary Gayed
- Rheumatology Research Group, Institute of Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham,
- Rheumatology Department, University Hospitals Birmingham NHS Foundation Trust, Birmingham,
| | - Sue Brown
- Royal National Hospital for Rheumatic Diseases, Bath,
| | - Ian N. Bruce
- Arthritis Research UK Centre for Epidemiology, Centre for Musculoskeletal Research, Institute for Inflammation and Repair, University of Manchester, Manchester Academic Health Sciences Centre,
- The Kellgren Centre for Rheumatology, NIHR Manchester Musculoskeletal Biomedical Research Unit, Central Manchester University Hospitals NHS Foundation Trust, Manchester,
| | - David D’Cruz
- Louise Coote Lupus Unit, Guy’s Hospital, London,
| | - Benjamin Empson
- Laurie Pike Health Centre, Modality Partnership, Birmingham,
| | | | - David Jayne
- Department of Medicine, University of Cambridge,
- Lupus and Vasculitis Unit, Addenbrooke’s Hospital, Cambridge,
| | - Munther Khamashta
- Lupus Research Unit, The Rayne Institute, St Thomas’ Hospital,
- Division of Women’s Health, King’s College London,
| | - Liz Lightstone
- Section of Renal Medicine and Vascular Inflammation, Division of Immunology and Inflammation, Department of Medicine, Imperial College London, London,
| | | | | | | | - David Isenberg
- Centre for Rheumatology, University College London, London, UK
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