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1.
Medicine (Baltimore) ; 103(14): e37821, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38579022

RESUMO

Systemic lupus erythematosus mainly affects young women, and approximately half of systemic lupus erythematosus patients develop lupus nephritis (LN). However, data on the types and remission rates of LN in Saudi Arabia are limited. Therefore, we aimed to highlight the LN remission rates in our population. A retrospective record review was conducted between January 2007 and December 2020 in a tertiary center in the western region of Saudi Arabia to determine the remission rates among patients with biopsy-proven LN who met the EULAR\ACR 2019 classification criteria. We identified 59 patients with biopsy-proven LN, mostly in young women. The common histopathological pattern was Class IV LN in 26 patients (44%). Three induction protocols were identified, along with systemic steroids: the high-dose cyclophosphamide protocol in 21 patients (35.6%), low-dose protocol in 4 patients (6.8%), and mycophenolate mofetil (MMF) in 41 patients (69.5%). Partial response, defined as the reduction of the 24-hour proteinuria by 25% at 3 months and 50% at 6 months, was achieved in 18 patients (33.3%) at 3 months and decreased to 13 patients (24.1%) at 6 months. Complete clinical response, defined as 24-hour urinary protein between 500 and 700 mg at 12 months, was achieved in 44 patients (81.5%). Complete remission was higher among patients with Class IV LN (64.4%). The achievement of partial clinical response at 3 months was significantly lower among patients with hypertension (P = .041). This study presented the LN remission rates in a single center in Saudi Arabia. Similar to previous studies, Class IV LN were the most common histopathological finding in this study. Complete remission at 12 months was achieved in 44 (81%) patients. Delayed remission is associated with hypertension at the time of LN diagnosis.


Assuntos
Hipertensão , Lúpus Eritematoso Sistêmico , Nefrite Lúpica , Humanos , Feminino , Nefrite Lúpica/complicações , Nefrite Lúpica/tratamento farmacológico , Nefrite Lúpica/diagnóstico , Imunossupressores/uso terapêutico , Estudos Retrospectivos , Arábia Saudita/epidemiologia , Resultado do Tratamento , Ciclofosfamida/uso terapêutico , Lúpus Eritematoso Sistêmico/complicações , Ácido Micofenólico/uso terapêutico , Hipertensão/complicações , 60410 , Indução de Remissão
2.
Swiss Med Wkly ; 154: 3630, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38579324

RESUMO

OBJECTIVES: Systemic sclerosis is a chronic autoimmune connective tissue disease leading to microvascular and fibrotic manifestations in multiple organs. Several treatment options and recommendations from different European countries are available. In this study, for which the ambit is Switzerland specifically, we aim to describe the treatment patterns of systemic sclerosis patients with fibrotic manifestations. METHODS: Systemic sclerosis patients were selected from six Swiss tertiary centres recorded in the multicentre, prospective European Scleroderma Trials and Research (EUSTAR) registry. Patients fulfilling the 2013 ACR/EULAR systemic sclerosis classification criteria at baseline were included. To determine the differences in treatment of varying degrees of fibrosis, four groups were identified: (1) patients with a modified Rodnan skin score (mRSS) >0; (2) those with mRSS ≥7; (3) those with interstitial lung disease (SSc-ILD), diagnosed by either chest X-Ray or high-resolution computed tomography; and (4) patients fulfilling one of the additional criteria for extensive interstitial lung disease, defined as interstitial lung disease involvement of >20% in high-resolution computed tomography, dyspnea NYHA-stage 3/4, or a predicted forced vital capacity (FVC) of <70%. RESULTS: A total of 590 patients with systemic sclerosis fulfilled the inclusion criteria. In this cohort, 421 (71.4%) had mRSS >0, of whom 195 (33.1%) had mRSS ≥7; interstitial lung disease was diagnosed in 198 of 456 (43.4%), of whom 106 (18.0 %) showed extensive interstitial lung disease. Regarding non-biologic disease-modifying medications (DMARDs), the most frequently prescribed was methotrexate, followed by hydroxychloroquine and mycophenolate mofetil. Rituximab and tocilizumab were most frequently used among the biologic DMARDs. Specifically, 148/372 (39.8%) of treated patients with skin fibrosis received methotrexate, mycophenolate mofetil or rituximab, and 80/177 (45.2%) with interstitial lung disease received cyclophosphamide, mycophenolate mofetil, tocilizumab or rituximab. Most patients received a proton-pump inhibitor, and few patients underwent hematopoietic stem cell transplantation. CONCLUSION: Overall, in Switzerland, a wide range of medications is prescribed for systemic sclerosis patients. This includes modern, targeted treatments for which randomised controlled clinical trial have been recently reported.


Assuntos
Antirreumáticos , Doenças Pulmonares Intersticiais , Escleroderma Sistêmico , Humanos , Imunossupressores/uso terapêutico , Rituximab/uso terapêutico , Metotrexato/uso terapêutico , Ácido Micofenólico/uso terapêutico , Estudos Prospectivos , Suíça , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/induzido quimicamente , Doenças Pulmonares Intersticiais/tratamento farmacológico , Doenças Pulmonares Intersticiais/etiologia , Doenças Pulmonares Intersticiais/diagnóstico , Fibrose , Antirreumáticos/uso terapêutico
3.
J Infect ; 88(3): 106133, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38432583

RESUMO

OBJECTIVES: To study the effect of mycophenolate mofetil (MMF) on various vaccination responses in kidney transplant recipients. METHODS: In a randomized controlled trial (EudraCT nr.: 2014-001372-66), low immunologically risk kidney transplant recipients were randomized to TAC/MMF or TAC-monotherapy (TACmono), six months post-transplantation. One year after transplantation, in a pre-specified sub-study, recipients were vaccinated against pneumococcus, tetanus and influenza. Blood was sampled before and 21 days after vaccination. Adequate vaccination responses were defined by international criteria. A post-hoc analysis was conducted on SARS-CoV-2 vaccination responses within the same cohort. RESULTS: Seventy-one recipients received pneumococcal and tetanus vaccines (TAC/MMF: n = 37, TACmono: n = 34), with 29 also vaccinated against influenza. When vaccinated, recipients were 60 (54-66) years old, with median eGFR of 54 (44-67) ml/min, tacrolimus trough levels 6.1 (5.4-7.0) ug/L in both groups and TAC/MMF daily MMF dose of 1000 (500-2000) mg. Adequate vaccination responses were: pneumococcal (TAC/MMF 43%, TACmono 74%, p = 0.016), tetanus (TAC/MMF 35%, TACmono 82%, p < 0.0001) and influenza (TAC/MMF 20%, TACmono 71%, p = 0.0092). Only 7% of TAC/MMF responded adequately to all three compared to 36% of TACmono (p = 0.080). Additionally, 40% of TAC/MMF responded inadequately to all three, whereas all TACmono patients responded adequately to at least one vaccination (p = 0.041). Lower SARS-CoV-2 vaccination antibody responses correlated with lower pneumococcal antibody vaccination responses (correlation coefficient: 0.41, p = 0.040). CONCLUSIONS: MMF on top of tacrolimus severely hampers antibody responses to a broad range of vaccinations.


Assuntos
Influenza Humana , Transplante de Rim , Tétano , Humanos , Pessoa de Meia-Idade , Idoso , Ácido Micofenólico/uso terapêutico , Tacrolimo/uso terapêutico , Imunossupressores/uso terapêutico , Influenza Humana/tratamento farmacológico , Formação de Anticorpos , Vacinas contra COVID-19 , Tétano/prevenção & controle , Tétano/tratamento farmacológico
4.
Epidemiol Health ; 46: e2024012, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38476014

RESUMO

OBJECTIVES: This study developed an algorithm for identifying pregnancy episodes and estimating the last menstrual period (LMP) in an administrative claims database and applied it to investigate the use of pregnancy-incompatible immunosuppressants among pregnant women with systemic lupus erythematosus (SLE). METHODS: An algorithm was developed and applied to a nationwide claims database in Korea. Pregnancy episodes were identified using a hierarchy of pregnancy outcomes and clinically plausible periods for subsequent episodes. The LMP was estimated using preterm delivery, sonography, and abortion procedure codes. Otherwise, outcome-specific estimates were applied, assigning a fixed gestational age to the corresponding pregnancy outcome. The algorithm was used to examine the prevalence of pregnancies and utilization of pregnancy-incompatible immunosuppressants (cyclophosphamide [CYC]/mycophenolate mofetil [MMF]/methotrexate [MTX]) and non-steroidal anti-inflammatory drugs (NSAIDs) during pregnancy in SLE patients. RESULTS: The pregnancy outcomes identified in SLE patients included live births (67%), stillbirths (2%), and abortions (31%). The LMP was mostly estimated with outcome-specific estimates for full-term births (92.3%) and using sonography procedure codes (54.7%) and preterm delivery diagnosis codes (37.9%) for preterm births. The use of CYC/MMF/MTX decreased from 7.6% during preconception to 0.2% at the end of pregnancy. CYC/MMF/MTX use was observed in 3.6% of women within 3 months preconception and 2.5% during 0-7 weeks of pregnancy. CONCLUSIONS: This study presents the first pregnancy algorithm using a Korean administrative claims database. Although further validation is necessary, this study provides a foundation for evaluating the safety of medications during pregnancy using secondary databases in Korea, especially for rare diseases.


Assuntos
Lúpus Eritematoso Sistêmico , Nascimento Prematuro , Recém-Nascido , Gravidez , Humanos , Feminino , Nascimento Prematuro/induzido quimicamente , Nascimento Prematuro/tratamento farmacológico , Resultado da Gravidez , Imunossupressores/uso terapêutico , Ciclofosfamida/efeitos adversos , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/epidemiologia , Ácido Micofenólico/uso terapêutico , República da Coreia
5.
Artigo em Russo | MEDLINE | ID: mdl-38465811

RESUMO

OBJECTIVE: Analysis of demographic, clinical, laboratory, electrophysiological and neuroimaging data and pathogenetic therapy of pediatric patients with chronic inflammatory demyelinating polyneuropathy (CIDP). MATERIAL AND METHODS: Patients (n=30) were observed in a separate structural unit of the Russian Children's Clinical Hospital of the Russian National Research Medical University named after. N.I. Pirogova Ministry of Health of the Russian Federation in the period from 2006 to 2023. The examination was carried out in accordance with the recommendations of the Joint Task Force of the European Federation of Neurological Societies and the Peripheral Nerve Society on the Management of CIDP (2021). All patients received immunotherapy, including intravenous immunoglobulin (IVIG) (n=1), IVIG and glucocorticosteroids (GCS) (n=17, 56.7%), IVIG+GCS+plasmapheresis (n=12, 40.0%). Alternative therapy included cyclophosphamide (n=1), cyclophosphamide followed by mycophenolate mofetil (n=1), rituximab (n=2, 6.6%), azathioprine (n=3), mycophenolate mofetil (n=2, 6.6%). RESULTS: In all patients, there was a significant difference between scores on the MRCss and INCAT functional scales before and after treatment. At the moment, 11/30 (36.6%) patients are in clinical remission and are not receiving pathogenetic therapy. The median duration of remission is 48 months (30-84). The longest remission (84 months) was observed in a patient with the onset of CIDP at the age of 1 year 7 months. CONCLUSION: Early diagnosis of CIDP is important, since the disease is potentially curable; early administration of pathogenetic therapy provides a long-term favorable prognosis.


Assuntos
Polirradiculoneuropatia Desmielinizante Inflamatória Crônica , Humanos , Criança , Lactente , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/diagnóstico , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/tratamento farmacológico , Imunoglobulinas Intravenosas/uso terapêutico , Imunoglobulinas Intravenosas/efeitos adversos , Ácido Micofenólico/uso terapêutico , Nervos Periféricos , Ciclofosfamida/uso terapêutico
6.
Skin Res Technol ; 30(3): e13642, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38454597

RESUMO

AIMS AND OBJECTIVES: The purpose of this study is to investigate the effectiveness and safety of oral and injectable systemic treatments, such as methotrexate, azathioprine, cyclosporine, tofacitinib, baricitinib, corticosteroids, statins, zinc, apremilast, etc., for treating vitiligo lesions. METHOD: Databases including PubMed, Scopus, and Web of Science were meticulously searched for studies spanning from 2010 to August 2023, focusing on systemic oral and injectable therapies for vitiligo, using comprehensive keywords and search syntaxes tailored to each database. Key data extracted included study design, treatment efficacy, patient outcomes, patient satisfaction, and safety profiles. RESULTS: In a total of 42 included studies, oral mini-pulse corticosteroid therapy (OMP) was the subject of six studies (14.2%). Minocycline was the focus of five studies (11.9%), while methotrexate, apremilast, and tofacitinib each were examined in four studies (9.5%). Antioxidants and Afamelanotide were the subjects of three studies each (7.1%). Cyclosporine, simvastatin, oral zinc, oral corticosteroids (excluding OMP) and injections, and baricitinib were each explored in two studies (4.8%). Azathioprine, mycophenolate mofetil, and Alefacept were the subjects of one study each (2.4%). CONCLUSION: Systemic treatments for vitiligo have been successful in controlling lesions without notable side effects. OMP, Methotrexate, Azathioprine, Cyclosporine, Mycophenolate mofetil, Simvastatin, Apremilast, Minocycline, Afamelanotide, Tofacitinib, Baricitinib, Antioxidants, and oral/injectable corticosteroids are effective treatment methods. However, oral zinc and alefacept did not show effectiveness.


Assuntos
Azetidinas , Hipopigmentação , Purinas , Pirazóis , Sulfonamidas , Talidomida/análogos & derivados , Vitiligo , Humanos , Metotrexato/uso terapêutico , Azatioprina/uso terapêutico , Vitiligo/tratamento farmacológico , Vitiligo/patologia , Ácido Micofenólico/uso terapêutico , Minociclina/uso terapêutico , Alefacept/uso terapêutico , Ciclosporina/uso terapêutico , Corticosteroides , Sinvastatina/uso terapêutico , Zinco/uso terapêutico
7.
J Dtsch Dermatol Ges ; 22(4): 605-620, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38426689

RESUMO

The updated S2k guideline deals with the diagnosis and therapy of localized scleroderma (LoS). LoS represents a spectrum of sclerotic skin diseases in which, depending on the subtype and localisation, structures such as adipose tissue, muscles, joints, and bones may also be affected. Involvement of internal organs or progression to systemic sclerosis does not occur. LoS can be classified into four main forms: limited, generalized, linear, and mixed forms, with some additional subtypes. For cases of limited skin involvement, the guideline primarily recommends therapy with topical corticosteroids. UV therapy can also be recommended. In subtypes with severe skin or musculoskeletal involvement, systemic therapy with methotrexate is recommended. During the active phase of the disease, systemic glucocorticosteroids can be used additionally. In cases of methotrexate and steroid refractory courses, contraindications, or intolerance, mycophenolate mofetil, mycophenolic acid, or abatacept can be considered as second-line systemic therapies. In the case of linear LoS, autologous adipose-derived stem cell transplantation can also be performed for correcting soft tissue defects.


Assuntos
Fármacos Dermatológicos , Esclerodermia Localizada , Humanos , Metotrexato/uso terapêutico , Esclerodermia Localizada/diagnóstico , Esclerodermia Localizada/terapia , Pele , Fármacos Dermatológicos/uso terapêutico , Ácido Micofenólico/uso terapêutico
8.
J Pediatr Gastroenterol Nutr ; 78(2): 328-338, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38374561

RESUMO

OBJECTIVES: The Starzl Network for Excellence in Pediatric Transplantation identified optimizing immunosuppression (IS) as a priority practice improvement area for patients, families, and providers. We aimed to evaluate associations between clinical characteristics, early IS, and outcomes. METHODS: We analyzed pediatric liver transplant (LT) data from 2013 to 2018 in the United Network for Organ Sharing (UNOS) and the Society of Pediatric Liver Transplantation (SPLIT) registries. RESULTS: We included 2542 LT recipients in UNOS and 1590 in SPLIT. IS choice varied between centers with steroid induction and mycophenolate mofetil (MMF) use each ranging from 0% to 100% across centers. Clinical characteristics associated with early IS choice were inconsistent between the two data sets. T-cell depleting antibody use was associated with improved 1-year graft (hazard ratio [HR] 0.50, 95% confidence interval [CI] 0.34-0.76) and patient (HR 0.40, 95% CI 0.20-0.79) survival in UNOS but decreased 1-year patient survival (HR 4.12, 95% CI 1.31-12.93) and increased acute rejection (HR 1.58, 95% CI 1.07-2.34) in SPLIT. Non-T-cell depleting antibody use was not associated with differential risk of survival nor rejection. MMF use was associated with improved 1-year graft survival (HR 0.73, 95% CI 0.54-0.99) in UNOS only. CONCLUSIONS: Variation exists in center choice of early IS regimen. UNOS and SPLIT data provide conflicting associations between IS and outcomes in multivariable analysis. These results highlight the need for future multicenter collaborative work to identify evidence-based IS best practices.


Assuntos
Transplante de Rim , Transplante de Fígado , Criança , Humanos , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto , Terapia de Imunossupressão/métodos , Imunossupressores/uso terapêutico , Ácido Micofenólico/uso terapêutico
9.
BMJ Open Respir Res ; 11(1)2024 02 27.
Artigo em Inglês | MEDLINE | ID: mdl-38413120

RESUMO

OBJECTIVES: Mycophenolate mofetil (MMF) and azathioprine (AZA) are immunomodulatory treatments in interstitial lung disease (ILD). This systematic review aimed to evaluate the efficacy of MMF or AZA on pulmonary function in ILD. DESIGN: Population included any ILD diagnosis, intervention included MMF or AZA treatment, outcome was delta change from baseline in per cent predicted forced vital capacity (%FVC) and gas transfer (diffusion lung capacity of carbon monoxide, %DLco). The primary endpoint compared outcomes relative to placebo comparator, the secondary endpoint assessed outcomes in treated groups only. ELIGIBILITY CRITERIA: Randomised controlled trials (RCTs) and prospective observational studies were included. No language restrictions were applied. Retrospective studies and studies with high-dose concomitant steroids were excluded. DATA SYNTHESIS: The systematic search was performed on 9 May. Meta-analyses according to drug and outcome were specified with random effects, I2 evaluated heterogeneity and Grading of Recommendations, Assessment, Development and Evaluation evaluated certainty of evidence. Primary endpoint analysis was restricted to RCT design, secondary endpoint included subgroup analysis according to prospective observational or RCT design. RESULTS: A total of 2831 publications were screened, 12 were suitable for quantitative synthesis. Three MMF RCTs were included with no significant effect on the primary endpoints (%FVC 2.94, 95% CI -4.00 to 9.88, I2=79.3%; %DLco -2.03, 95% CI -4.38 to 0.32, I2=0.0%). An overall 2.03% change from baseline in %FVC (95% CI 0.65 to 3.42, I2=0.0%) was observed in MMF, and RCT subgroup summary estimated a 4.42% change from baseline in %DLCO (95% CI 2.05 to 6.79, I2=0.0%). AZA studies were limited. All estimates were considered very low certainty evidence. CONCLUSIONS: There were limited RCTs of MMF or AZA and their benefit in ILD was of very low certainty. MMF may support preservation of pulmonary function, yet confidence in the effect was weak. To support high certainty evidence, RCTs should be designed to directly assess MMF efficacy in ILD. PROSPERO REGISTRATION NUMBER: CRD42023423223.


Assuntos
Azatioprina , Doenças Pulmonares Intersticiais , Humanos , Azatioprina/uso terapêutico , Azatioprina/farmacologia , Imunossupressores/uso terapêutico , Doenças Pulmonares Intersticiais/diagnóstico , Pulmão , Ácido Micofenólico/uso terapêutico , Ácido Micofenólico/farmacologia , Inibidores Enzimáticos/uso terapêutico , Estudos Observacionais como Assunto
10.
J Neuroimmunol ; 388: 578294, 2024 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-38306927

RESUMO

Human T-cell leukemia virus type 1 (HTLV-1) can cause HTLV-1 Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP). Current treatment options for HAM/TSP are limited. We present a woman with rapidly-progressive HAM/TSP with significant, sustained clinical improvement following initiation of mycophenolate mofetil (MMA). Peripheral blood mononuclear cells from the patient, her asymptomatic carrier husband and eight healthy controls were isolated. Frequencies of T-cell populations upon exposure to low and high MMA concentrations and differences in proliferation were analyzed using flow cytometry and a CSFE-proliferation assay. Characterization of T-cell function and proliferation showed higher levels of GranzymeB in HTLV-1+ donors. The improvement and stability of symptoms in this patient with HAM/TSP following MMA initiation requires further study as a potential treatment for HAM/TSP.


Assuntos
Vírus Linfotrópico T Tipo 1 Humano , Paraparesia Espástica Tropical , Humanos , Feminino , Vírus Linfotrópico T Tipo 1 Humano/fisiologia , Ácido Micofenólico/uso terapêutico , Leucócitos Mononucleares , Paraparesia Espástica Tropical/tratamento farmacológico , Paraparesia Espástica Tropical/diagnóstico
11.
Curr Opin Nephrol Hypertens ; 33(3): 311-317, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38411173

RESUMO

PURPOSE OF REVIEW: As the most common primary glomerulonephritis, immunoglobulin A (IgA) nephropathy (IgAN) is an important cause of kidney failure and mortality. Until recently, therapeutic options were limited. Fortunately, there have been numerous recent clinical trials demonstrating efficacy of new therapies in slowing chronic kidney disease (CKD) progression at varying stages of disease. RECENT FINDINGS: The TESTING trial has provided high-quality evidence for slowing estimated glomerular filtration rate (eGFR) decline with a reduced-dose glucocorticoid regimen, while demonstrating an improved safety profile. Targeted-release budesonide represents a well tolerated therapy for reducing eGFR decline. Mycophenolate mofetil may reduce CKD progression in some populations, while hydroxychloroquine is efficacious in reducing proteinuria. Sodium-glucose cotransporter (SGLT2) inhibitors and sparsentan are effective therapies for CKD due to IgAN, but should not be used in lieu of disease-modifying immunosuppressive therapy. Many new therapies are approaching readiness for clinical use. SUMMARY: Numerous therapeutic options now exist and include disease-modifying and nephroprotective drugs. Identifying the right treatment for the right patient is now the clinical challenge and, with new drugs on the horizon, represents the primary unmet research need in this rapidly-developing field.


Assuntos
Glomerulonefrite por IGA , Insuficiência Renal Crônica , Humanos , Glomerulonefrite por IGA/tratamento farmacológico , Padrão de Cuidado , Insuficiência Renal Crônica/tratamento farmacológico , Ácido Micofenólico/uso terapêutico , Glucocorticoides/uso terapêutico , Proteinúria/tratamento farmacológico
12.
J Med Case Rep ; 18(1): 93, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38350929

RESUMO

BACKGROUND: Scleredema adultorum of Buschke is a rare disease characterized by firm and non-pitting edema of the skin. The condition is rare with unknown etiology. Diagnosis is made on the basis of clinical findings and skin biopsy. CASE PRESENTATION: Here, we describe a 14-year-old Iranian girl presenting with non-pitting edema and woody thickening of the skin that progressed within a month. She was evaluated for possible underlying malignancy or connective tissue disorders, which were excluded by multiple laboratory workups. She underwent a skin biopsy which confirmed the diagnosis of scleredema, and she was successfully treated with intravenous immunoglobulin and mycophenolate mofetil. CONCLUSION: While scleredema adultorum of Buschke is a rare disease with no definite treatment, our effort through this report was to highlight the possible benefits of treatment by intravenous immunoglobulin and mycophenolate mofetil.


Assuntos
Escleredema do Adulto , Feminino , Humanos , Adolescente , Escleredema do Adulto/tratamento farmacológico , Imunoglobulinas Intravenosas/uso terapêutico , Ácido Micofenólico/uso terapêutico , Irã (Geográfico) , Doenças Raras , Edema
13.
Medicine (Baltimore) ; 103(6): e36999, 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38335395

RESUMO

RATIONALE: While some systemic lupus erythematosus (SLE) patients may experience varying degrees of liver function abnormalities, only a small portion of these cases have clinical significance, and the majority of patients typically exhibit low levels of serum bilirubin. However, in this article, we present a case of a middle-aged female patient with SLE who exhibited persistent skin jaundice as her initial symptom, offering a fresh perspective on diagnosing and treating patients who exhibit unexplained liver dysfunction and SLE combined with liver injury. PATIENT CONCERNS: A 45-year-old woman was initially admitted to the hospital due to yellowing of the skin and sclera, and her symptoms did not improve significantly during treatment. The results were abnormal after relevant immunological tests. DIAGNOSES: Persistent non-conjugated bilirubin elevation due to lupus hepatitis. INTERVENTIONS: The use of methylprednisolone sodium succinate (40 mg/Qd) and mycophenolate mofetil (0.75 g/d) suppressed immunity, polyolefin choline (20 mL/d) and glutathione (0.6 g/Qd) improved liver function, and nutritional support therapy. OUTCOMES: After 2 weeks of treatment, a significant decrease in the yellow skin and sclera of the patient was observed. LESSONS: Most clinicians overlook that liver function abnormalities are the main manifestation of SLE, resulting in many patients not receiving timely treatment. This study highlights the importance that SLE is also a cause of abnormal liver function.


Assuntos
Hepatopatias , Lúpus Eritematoso Sistêmico , Humanos , Pessoa de Meia-Idade , Feminino , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Ácido Micofenólico/uso terapêutico , Hemissuccinato de Metilprednisolona/uso terapêutico , Bilirrubina
14.
Int J Mol Sci ; 25(4)2024 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-38397035

RESUMO

Immunosuppression management in transplant recipients is a critical component of pharmacotherapy. This becomes particularly crucial when patients are exposed to multiple medications that may lead to pharmacological interactions, potentially compromising the effectiveness of immunosuppression. We present the case of a 46-year-old patient diagnosed with cystic fibrosis in childhood at our hospital, who underwent bilateral lung transplantation and is undergoing immunosuppressive therapy. The patient was hospitalized due to an acute pulmonary exacerbation. During the hospitalization, the patient was administered various classes of antibiotics while continuing the standard antirejection regimen of everolimus and mycophenolate. Plasma concentrations of immunosuppressants, measured after antibiotic therapy, revealed significantly lower levels than the therapeutic thresholds, providing the basis for formulating the hypothesis of a drug-drug interaction phenomenon. This hypothesis is supported by the rationale of antibiotic-induced disruption of the intestinal flora, which directly affects the kinetics of mycophenolate. These levels increased after discontinuation of the antimicrobials. Patients with CF undergoing lung transplantation, especially prone to pulmonary infections due to their medical condition, considering the enterohepatic circulation of mycophenolate mediated by intestinal bacteria, necessitate routine monitoring of mycophenolate concentrations during and immediately following the cessation of antibiotic therapies, that could potentially result in insufficient immunosuppression.


Assuntos
Fibrose Cística , Transplante de Pulmão , Humanos , Pessoa de Meia-Idade , Ácido Micofenólico/uso terapêutico , Ácido Micofenólico/farmacologia , Fibrose Cística/complicações , Fibrose Cística/tratamento farmacológico , Antibacterianos/uso terapêutico , Imunossupressores/efeitos adversos , Inibidores Enzimáticos
15.
Curr Opin Gastroenterol ; 40(3): 126-133, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38363233

RESUMO

PURPOSE OF REVIEW: The primary therapy of autoimmune hepatitis (AIH) has been established for over three decades. This review focuses on updates in the evaluation and management of patients with AIH. RECENT FINDINGS: The evaluation of patients has recently been updated to include more definitive screening for other autoimmune diseases, including thyroid disease and celiac disease. Antibody detection by ELISA, an easier and more commonly available method, has been incorporated into the latest iteration of the AIH scoring system. Corticosteroids and AZA remain the backbone of AIH treatment, but there is growing evidence for mycophenolate mofetil as both first-line and second-line therapy, and growing inquiry into calcineurin inhibitors. Noninvasive markers of liver disease have now been validated in AIH, with the strongest evidence for VCTE in patients with minimal hepatic inflammation. SUMMARY: Recent research of alternative immunosuppressant therapies, noninvasive markers of fibrosis, and updated society guidelines, have improved our ability to evaluate, treat, and follow patients with AIH.


Assuntos
Hepatite Autoimune , Hepatopatias , Humanos , Hepatite Autoimune/diagnóstico , Hepatite Autoimune/tratamento farmacológico , Imunossupressores/uso terapêutico , Ácido Micofenólico/uso terapêutico
16.
Int J Biol Macromol ; 264(Pt 1): 130145, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38382789

RESUMO

Mycophenolate mofetil (MMF) is a viable therapeutic option against various immune disorders as a chemotherapeutic agent. Nevertheless, its application has been undermined by the gastrotoxic metabolites (mycophenolic acid glucuronide, MPAG) produced by microbiome-associated ß-glucuronidase (ßGUS). Therefore, controlling microbiota-produced ßGUS underlines the potential strategy to improve MMF efficacy by overcoming the dosage limitation. In this study, the octyl gallate (OG) was identified with promising inhibitory activity on hydrolysis of PNPG in our high throughput screening based on a chemical collection of approximately 2000 natural products. Furthermore, OG was also found to inhibit a broad spectrum of BGUSs, including mini-Loop1, Loop 2, mini-Loop 2, and mini-Loop1,2. The further in vivo experiments demonstrated that administration of 20 mg/kg OG resulted in predominant reduction in the activity of BGUSs while displayed no impact on the overall fecal microbiome in mice. Furthermore, in the MMF-induced colitis model, the administration of OG at a dosage of 20 mg/kg effectively mitigated the gastrointestinal toxicity, and systematically reverted the colitis phenotypes. These findings indicate that the OG holds promising clinical potential for the prevention of MMF-induced gastrointestinal toxicity by inhibition of BGUSs and could be developed as a combinatorial therapy with MFF for better clinical outcomes.


Assuntos
Colite , Ácido Gálico/análogos & derivados , Microbioma Gastrointestinal , Camundongos , Animais , Ácido Micofenólico/farmacologia , Ácido Micofenólico/uso terapêutico , Imunossupressores/uso terapêutico , Glucuronidase/metabolismo , Bactérias/metabolismo , Colite/tratamento farmacológico
18.
Transplant Proc ; 56(1): 252-256, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38212169

RESUMO

Kidney transplantation remains the optimal therapy for many patients with end-stage kidney disease (ESKD). Chronic pain is one of the most common and distressing symptoms among patients with ESKD, and its treatment is a complex and challenging task to accomplish. The benefits of cannabidiol (CBD) in chronic pain treatment have been reported recently. Cannabidiol is metabolized by cytochrome P450, mainly CYP3A4 and CYP2C19, and can also undergo direct conjugation via UDP-glucuronosyltransferase enzymes, with a growing body of evidence suggesting it is also a potent inhibitor or inducer of these pathways. Cannabidiol was also found to be a potent inhibitor of carboxylesterases in vitro. Because cytochrome P450 enzymes and carboxylesterases are also responsible for the clearance and activation of immunosuppressants, respectively, drug-drug interactions are likely to occur. Here, we report a pharmacokinetic drug interaction between CBD and cyclosporine and mycophenolate mofetil in a patient with ESKD with a kidney transplantation. It is thus crucial to take into account these interactions and monitor drug levels to avoid drug toxicity or a lack of efficacy. This study is in accordance with the guidelines of the Declaration of Helsinki and the Declaration of Istanbul.


Assuntos
Canabidiol , Dor Crônica , Humanos , Ciclosporina/uso terapêutico , Canabidiol/uso terapêutico , Ácido Micofenólico/uso terapêutico , Dor Crônica/tratamento farmacológico , Sistema Enzimático do Citocromo P-450 , Interações Medicamentosas , Hidrolases de Éster Carboxílico
19.
Lupus ; 33(2): 176-182, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38164925

RESUMO

Vaccines offer an effective strategy to prevent infectious diseases with minimal adverse effects. On rare occasions, vaccination can disrupt the immune response leading to induction of autoimmune diseases. We describe a case of new-onset lupus nephritis following COVID-19 vaccination with the first dose of the Pfizer vaccine. Her symptoms and lab values improved with steroids, hydroxychloroquine, and mycophenolate mofetil.


Assuntos
COVID-19 , Lúpus Eritematoso Sistêmico , Nefrite Lúpica , Vacinas , Humanos , Feminino , Imunossupressores/uso terapêutico , Nefrite Lúpica/tratamento farmacológico , Vacinas contra COVID-19 , Quimioterapia Combinada , Lúpus Eritematoso Sistêmico/induzido quimicamente , Ácido Micofenólico/uso terapêutico
20.
Mult Scler Relat Disord ; 83: 105452, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38277981

RESUMO

BACKGROUND: Relapse rates of 47 % have been reported in patients with neuromyelitis optica (NMOSD) using Azathioprine (AZA) and mycophenolate mofetil (MMF). Prediction of non-responders could help determine which patients are most likely to benefit from newer monoclonal antibody treatments from the outset. OBJECTIVES: To identify predictors of AZA and MMF treatment response in NMOSD. METHODS: Multicenter cohort study of NMOSD patients from Brazil and the United Kingdom, treated with AZA and MMF. An unsatisfactory response was defined as one severe or two non-severe attacks in a year. Cox regression was used to identify predictive factors of unsatisfactory response to AZA and MMF. RESULTS: 103 NMOSD patients, mean age 38 years, 83% female, and 65% of Black ethnic group were included. An unsatisfactory IS response was observed in 42% of patients over 2.5 years (IQR 1.0-8.8) years. A severe preceding attack was more common in non-responders (31.1% x 76.7%, p = <0.001). In multivariable analysis, severe attack (RR 3.13; 95 % CI 1.37-7.18, p = 0.007) or higher annualized relapse rate (RR 4.84; 95 % CI 2.01-11.65, p = < 0.001) predicted an unsatisfactory response. Interestingly, Black NMOSD patients had a lower risk of poor response (RR 0.39, 95 % CI 0.17-0.85, p = 0.019). CONCLUSION: Severe attack and a higher annualized relapse rate before AZA or MMF initiation were associated with an unsatisfactory IS response. In patients with these characteristics, treatment with higher-efficacy drugs should be considered from the outset.


Assuntos
Azatioprina , Neuromielite Óptica , Humanos , Feminino , Adulto , Masculino , Azatioprina/uso terapêutico , Ácido Micofenólico/uso terapêutico , Imunossupressores/uso terapêutico , Estudos de Coortes , Resultado do Tratamento , Recidiva
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