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1.
Isr Med Assoc J ; 21(7): 438-443, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31507117

RESUMO

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by the progressive death of motor neurons leading to fatal paralysis. The causes of ALS remain unknown; however, evidence supports the presence of autoimmune mechanisms contributing to pathogenesis. Although several environmental factors have been proposed, the only established risk factors are older age, male gender, and a family history of ALS. To date, there are no diagnostic test for ALS, and clinicians rely on the combination of upper motor neuron and lower motor neuron signs in the same body region. The aim of this paper was to provide a comprehensive review of current clinical literature with special focus on the role of autoimmunity in ALS, differential diagnosis, and available therapeutic approaches. Current evidence suggests a contribution of the innate immune system in ALS, with a role of microglial cell activation at the sites of neurodegeneration. The median time from symptom onset to diagnosis of ALS is 14 months, and this time estimate is mainly based on specific clinical signs and exclusion of ALS-like conditions. Several therapeutic approaches have been proposed, including immunosuppressive drugs, to reduce disease progression. Riluzole has been established as the only, although modestly effective, disease modifying therapy, extending mean patient survival by 3to 6 months. Recent advances in understanding the pathophysiology mechanisms of ALS encourage realistic hope for new treatment approaches. To date, the cornerstones of the management of patients with ALS are focused on symptom control, maintaining quality of life and improving survival.


Assuntos
Esclerose Amiotrófica Lateral/fisiopatologia , Neurônios Motores/patologia , Qualidade de Vida , Fatores Etários , Idoso , Esclerose Amiotrófica Lateral/tratamento farmacológico , Esclerose Amiotrófica Lateral/epidemiologia , Diagnóstico Diferencial , Progressão da Doença , Feminino , Humanos , Imunossupressores/uso terapêutico , Masculino , Riluzol/uso terapêutico , Fatores de Risco , Fatores Sexuais
2.
Medicine (Baltimore) ; 98(37): e17094, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31517833

RESUMO

BACKGROUND: Liver disease in patients with HIV is common and typically has complex and multifactorial presentations that represent a major cause of morbidity and mortality. Autoimmune hepatitis (AIH) is rarely reported in patient with HIV and the disease course and clinical outcomes for treatment have not been well characterized. We are aiming to determine the patient characteristics, disease prevalence, and treatment outcomes from published articles of patients with HIV and AIH. METHOD: A systematic search of PubMed, Web of Science, and Google Scholar through February 20, 2019 identified 15 studies that reported the outcomes of AIH in patients with HIV. Because of the small sample sizes and skewed distributions, resampling tests of mean differences using permutation distributions (MAXn = 10,000 permutations) were utilized; analyses were performed using R (v. 3.5.1). Categorical differences were calculated using Fisher exact test for odds ratio = 1 (equal odds), and Cramer V was calculated for effect size; analyses were completed in SPSS (v. 25). RESULTS: By reviewing 15 studies reporting a total of 35 patients with AIH and HIV, male patients were found to have significantly higher aspartate transaminase and alanine transaminase levels at time of diagnosis. No other significant findings identified. The CD4 count and viral load did not show significant correlation with AIH diagnosis or its prognosis. All patients but one who presented with severe immune deficiency and responded to highly active anti-retroviral therapy received immunosuppressive treatment without side effects and achieved remission except 2 lost to follow-up and 3 expired. CONCLUSION: Although rare, but AIH can develop in patients with HIV and physicians should consider it in the differential diagnosis for HIV patients presented with abnormal liver function tests, especially after excluding hepatitis C virus and drug-induced liver injury.Patients with immune deficiency disorders who present with AIH can be treated safely with steroid either as monotherapy or in combination with another immune suppressant therapy.


Assuntos
Infecções por HIV/complicações , Hepatite Autoimune/complicações , Adulto , Alanina Transaminase/análise , Alanina Transaminase/sangue , Aspartato Aminotransferases/análise , Aspartato Aminotransferases/sangue , Feminino , Infecções por HIV/sangue , Infecções por HIV/epidemiologia , Hepatite Autoimune/sangue , Hepatite Autoimune/epidemiologia , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
3.
JAMA ; 322(10): 936-945, 2019 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-31503307

RESUMO

Importance: Methotrexate and mycophenolate mofetil are commonly used immunomodulatory therapies for achieving corticosteroid-sparing control of noninfectious uveitis, but there is uncertainty about which drug is more effective. Objective: To compare the effect of methotrexate and mycophenolate for achieving corticosteroid-sparing control of noninfectious intermediate uveitis, posterior uveitis, and panuveitis. Design, Setting, and Participants: The First-line Antimetabolites as Steroid-sparing Treatment (FAST) uveitis trial screened 265 adults with noninfectious uveitis requiring corticosteroid-sparing immunosuppressive therapy from 9 referral eye centers in India, the United States, Australia, Saudi Arabia, and Mexico between August 22, 2013, and August 16, 2017. Follow-up ended on August 20, 2018. Interventions: Patients were randomized to receive oral methotrexate, 25 mg weekly (n = 107), or oral mycophenolate mofetil, 3 g daily (n = 109). Main Outcomes and Measures: The primary outcome was treatment success at 6 months, which was defined as having control of inflammation in both eyes, no more than 7.5 mg prednisone daily and less than or equal to 2 drops of prednisolone acetate 1%, and no treatment failure due to safety or intolerability. Patients underwent follow-up to 12 months while receiving the same treatment or switched to the other antimetabolite, depending on their 6-month outcome. Results: Among 216 patients who were randomized (median age, 38 years; 135 (62.5%) women), 194 (89.8%) completed follow-up through 6 months. Treatment success occurred in 64 (66.7%) patients in the methotrexate group vs 56 (57.1%) in the mycophenolate group (difference, 9.5% [95% CI, -5.3% to 21.8%]; odds ratio [OR], 1.50 [95% CI, 0.81 to 2.81]; P = .20). Among patients with posterior uveitis or panuveitis, treatment success was achieved in 58 (74.4%) in the methotrexate group vs 42 (55.3%) in the mycophenolate group (difference, 19.1% [95% CI, 3.6% to 30.6%]; OR, 2.35 [95% CI, 1.16 to 4.90]; P = .02); whereas among patients with intermediate uveitis treatment success occurred in 6 (33.3%) in the methotrexate group vs 14 (63.6%) in the mycophenolate group (difference, -30.3% [95% CI, -51.6% to 1.1%]; OR, 0.29 [95% CI, 0.08 to 1.05]; P = .07; P for interaction = .004). Elevated liver enzymes were the most common nonserious laboratory adverse event, occurring in 14 patients (13.0%) in the methotrexate group and 8 patients (7.4%) in the mycophenolate group. Conclusions and Relevance: Among adults with noninfectious uveitis, the use of mycophenolate mofetil compared with methotrexate as first-line corticosteroid-sparing treatment did not result in superior control of inflammation. Further research is needed to determine if either drug is more effective based on the anatomical subtype of uveitis. Trial Registration: ClinicalTrials.gov Identifier: NCT01829295.


Assuntos
Imunossupressores/uso terapêutico , Metotrexato/uso terapêutico , Ácido Micofenólico/uso terapêutico , Uveíte/tratamento farmacológico , Adulto , Anti-Inflamatórios/administração & dosagem , Quimioterapia Combinada , Inibidores Enzimáticos/uso terapêutico , Feminino , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Testes de Função Hepática , Masculino , Metotrexato/administração & dosagem , Metotrexato/efeitos adversos , Pessoa de Meia-Idade , Ácido Micofenólico/administração & dosagem , Ácido Micofenólico/efeitos adversos , Prednisolona/administração & dosagem
4.
Zhonghua Jie He He Hu Xi Za Zhi ; 42(9): 700-704, 2019 Sep 12.
Artigo em Chinês | MEDLINE | ID: mdl-31484245

RESUMO

Objective: To explore the effect of pirfenidone in fibrotic interstitial pneumonia with autoimmune features (IPAF) after treatment with corticosteroids and immunosuppressants. Methods: We conducted a retrospective analysis of 2 adult patients with IPAF in the Peking Union Medical College Hospital. As their fibrotic interstitial lung disease failed to improve with further treatment with corticosteroids and immunosuppressants, they were treated with pirfenidone based on corticosteroids and immunosuppressants. Their clinical, chest radiological data and prognosis were collected and relevant literatures were reviewed. Results: One patient was a 43 year old female, the other was a 53 year old male. IPAF was diagnosed with their classic clinical, serological and radiological features. They were partially responded to corticosteroids and immunosuppressants at the initial period. Pirfenidone was suggested for them as their lung fibrosis was not improved further with immunosuppressive therapy. After 4-5 months treatment with pirfenidone, based on corticosteroids and immunosuppressant administration, their clinical and radiological manifestations improved significantly. Conclusions: Pirfenidone might be a good add-on choice for fibrotic IPAF when the disease did not respond well to corticosteroids and immunosuppressants.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Doenças Autoimunes/diagnóstico , Fibrose Pulmonar Idiopática/tratamento farmacológico , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/tratamento farmacológico , Piridonas/uso terapêutico , Corticosteroides/uso terapêutico , Adulto , Feminino , Humanos , Fibrose Pulmonar Idiopática/diagnóstico , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
5.
Cochrane Database Syst Rev ; 8: CD010233, 2019 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-31425621

RESUMO

BACKGROUND: Crohn's disease (CD) is a chronic relapsing inflammatory condition and maintenance of remission is a major issue as many patients fail to achieve remission with medical management and require surgical interventions. Purine analogues such as azathioprine (AZA) and 6-mercaptopurine (6-MP) have been used to maintain surgically-induced remission in CD, but the effectiveness, tolerability and safety of these agents remains controversial. OBJECTIVES: To assess the efficacy and safety of purine analogues (AZA and 6-MP) for maintenance of surgically-induced remission in CD. SEARCH METHODS: We searched PubMed, MEDLINE, Embase, CENTRAL, and the Cochrane IBD Group Specialized Register from inception to 26 July 2018 (and from inception to 31 July 2019). In addition, we searched reference lists of all included studies and relevant reviews, conference proceedings and trials registers. SELECTION CRITERIA: Randomised controlled trials (RCTs) with a duration of at least three months that enrolled adults and children with surgically-induced remission of CD and compared AZA or 6-MP to no treatment, placebo or any other active intervention were considered for inclusion. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial eligibility, extracted data, assessed the risk of bias and assessed the certainty of the evidence using GRADE. The primary outcome was clinical relapse. Secondary outcomes included endoscopic relapse, radiologic and surgical relapse, adverse events (AEs), serious adverse events (SAEs), withdrawal due to AEs and health-related quality of life. MAIN RESULTS: Ten RCTs with a total of 928 participants were included. Study participants were adults recruited from university clinics and gastroenterology hospitals who received interventions post-surgery for a duration between 12 to 36 months. Most study participants were recruited less than three months after surgery in all except one study where participants were recruited between 6 to 24 months post-surgery. One study was rated as low risk of bias, six studies were rated high risk of bias and three were rated unclear risk of bias.There was moderate certainty evidence that purine analogues are more efficient for preventing clinical relapse than placebo. At 12 to 36 months, 51% (109/215) of AZA/6-MP participants relapsed compared to 64% (124/193) of placebo participants (RR 0.79; 95% CI 0.67 to 0.92; 408 participants; 3 studies; I² = 0%; moderate certainty evidence). The certainty of the evidence regarding the efficacy of AZA or 6-MP for maintaining postoperative clinical remission compared to 5-ASA compounds was low. At 12 to 24 months , 64% (113/177) of purine analogue participants relapsed compared to 59% (101/170) of 5-ASA participants (RR 1.05; 95% CI 0.89 to 1.24; 347 participants; 4 studies; I² = 8%; low certainty evidence). The certainty of evidence that purine analogues are inferior for preventing postsurgical clinical relapse compared to tumour necrosis factor alpha agents (anti-TNF-α) was very low. At 12 to 24 months, 43% (29/67) of AZA participants relapsed compared to 14% (10/72) of anti-TNF-α participants (RR 2.89; 95% CI 1.50 to 5.57; 139 participants; 3 studies; I² = 0%; very low certainty evidence).The effect of purine analogues compounds on AEs compared to placebo or any active treatment was uncertain, as the quality of evidence ranged from very low to low. After 12 to 24 months, 14% (12/87) of purine analogue participants experienced an AE compared to 10% (8/81) of placebo participants (RR 1.36; 95% CI 0.57 to 3.27; 168 participants; 2 studies; I² = 0%; low certainty evidence). The effect of purine analogues on AEs compared to 5-ASA agents was uncertain. After 12 to 24 months, 41% (73/176) of purine analogue participants had an AE compared to 47% (81/171) of 5-ASA participants (RR 0.89; 95% CI 0.74 to 1.07; 346 participants; 4 studies; I² = 15%; low certainty evidence). The effect of purine analogues on AEs in comparison to anti TNF-α agents was uncertain. At 12 to 24 months, 57% (32/56) of AZA participants had an AE compared to 51% (31/61) of anti-TNF-α participants (RR 1.13; 95% CI 0.83 to 1.53; 117 participants; 2 studies; I² = 0%; low certainty evidence). Purine analogue participants were more like than 5-ASA participants to have a SAE (RR 3.39, 95% CI 1.26 to 9.13, 311 participants; 3 studies; I² = 9%; very low certainty evidence), or to withdraw due to an AE (RR 2.21, 95% CI 1.28 to 3.81; 425 participants; 5 studies; I² = 0%; low certainty evidence). Commonly reported AEs across all studies included leucopenia, arthralgia, abdominal pain or severe epigastric intolerance, elevated liver enzymes, nausea and vomiting, pancreatitis, anaemia, nasopharyngitis and flatulence. AUTHORS' CONCLUSIONS: Moderate certainty evidence suggests that AZA and 6-MP may be superior to placebo for maintenance of surgically-induced remission in participants with CD. There was no clear difference in the number of clinical relapses when purine analogues were compared with 5-ASA agents, however this is based on low certainty evidence. There was very low certainty evidence that AZA and 6-MP are more likely to result in more serious adverse events (SAEs) and withdrawals due to an AE (low certainty) when compared to 5-ASA agents. Very low certainty evidence suggests that purine analogues may be inferior to anti-TNF-α agents, however, no firm conclusions can be drawn. Further research investigating the efficacy and safety of AZA and 6-MP in comparison to other active medications in surgically-induced remission of CD is warranted.


Assuntos
Azatioprina/uso terapêutico , Doença de Crohn/tratamento farmacológico , Imunossupressores/uso terapêutico , Quimioterapia de Manutenção/métodos , Mercaptopurina/uso terapêutico , Doença de Crohn/prevenção & controle , Doença de Crohn/cirurgia , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Indução de Remissão/métodos , Prevenção Secundária
6.
Medicine (Baltimore) ; 98(31): e16571, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31374024

RESUMO

RATIONALE: IgG4-related disease (IgG4-RD) is a systemic autoimmune disease and mixed cryoglobulinemia may be caused by autoimmune diseases. However, so far only 1 case of IgG4-RD complicated with mixed cryoglobulinemia is reported. Our case further confirms the close relationship between these 2 diseases. PATIENT CONCERNS: A 55-year-old female was admitted because of dry mouth and teeth falling off. DIAGNOSES: The patient was diagnosed as IgG4-related sialadenitis (IgG4-RS) complicated with type III mixed cryoglobulinemia. IgG4-RS was confirmed by elevated serum IgG4 levels and diffuse IgG4 plasmocyte infiltration and storiform fibrosis in the interstitium of labial gland. Type III mixed cryoglobulinemia was confirmed by positive serum cryoglobulins and no monoclonal immunoglobulin in serum and urine. INTERVENTIONS AND OUTCOMES: After treatment with prednisone and cyclophosphamide, serum cryoglobulins rapidly turned negative with the remission of IgG4-RS. LESSONS: Type III mixed cryoglobulinemia can be caused by IgG4-RS, and the underlying mechanisms need to be further explored.


Assuntos
Crioglobulinemia/complicações , Doença Relacionada a Imunoglobulina G4/complicações , Sialadenite/complicações , Crioglobulinemia/tratamento farmacológico , Feminino , Humanos , Doença Relacionada a Imunoglobulina G4/tratamento farmacológico , Imunossupressores/uso terapêutico , Pessoa de Meia-Idade , Sialadenite/tratamento farmacológico
7.
Medicine (Baltimore) ; 98(31): e16649, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31374037

RESUMO

RATIONALE: Anti-glomerular basement membrane disease (anti-GBM disease) is a rare small vessel vasculitis caused by autoantibodies directed against the glomerular and alveolar basement membranes. Anti-GBM disease is usually a monophasic illness and relapse is rare after effective treatment. This article reports a case of coexistence of recurrent anti-GBM disease and T-cell large granular lymphocytic (T-LGL) leukemia. PATIENT CONCERNS: A 37-year-old man presented with hematuria, edema, and acute kidney injury for 2 months. DIAGNOSIS: Anti-GBM disease was diagnosed by renal biopsy, in which crescentic glomerulonephritis was observed with light microscopy, strong linear immunofluorescent staining for immunoglobulin G on the GBM and positive serum anti-GBM antibody. Given this diagnosis, the patient was treated with plasmapheresis, steroids, and cyclophosphamide for 4 months. The anti-GBM antibody titer was maintained to negative level but the patient remained dialysis-dependent. One year later, the patient suffered with a relapse of anti-GBM disease, after an extensive examination, he was further diagnosed T-LGL leukemia by accident. INTERVENTIONS: The patient received cyclosporine A therapy for T-LGL leukemia. OUTCOMES: After treatment with cyclosporine A, serum anti-GBM antibody became undetectable. During the 16 months follow-up, anti-GBM titer remained normal and abnormal T-lymphocytes in the bone marrow and peripheral blood were also decreased. LESSONS: T-LGL leukemia is an indolent lymphoproliferative disorder that represents a monoclonal expansion of cytotoxic T cells, which has been reported to be accompanied by some autoimmune diseases. This is the first report of coincidence of T-LGL leukemia and anti-GBM disease, and suggests there are some relationships between these 2 diseases. Clinical physicians should exclude hematological tumors when faced with recurrent anti-GBM disease.


Assuntos
Doença Antimembrana Basal Glomerular/complicações , Leucemia Linfocítica Granular Grande/complicações , Adulto , Doença Antimembrana Basal Glomerular/terapia , Humanos , Imunossupressores/uso terapêutico , Masculino , Plasmaferese , Diálise Renal
8.
Medicine (Baltimore) ; 98(31): e16669, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31374043

RESUMO

RATIONALE: With the development of endoscopic technique and the improvement of available accessories, endoscopic therapy became to play an important role in the management of gastrointestinal submucosal tumors (SMTs). PATIENTS CONCERNS: A gastric SMT which was suspected to be gastrointestinal stroma tumor (GIST) was diagnosed in a liver transplant recipient who received transplanted operation 11 months ago. DIAGNOSIS: gastric SMT, post-liver transplantation INTERVENTIONS:: Endoscopic full-thickness resection (EFR) was preformed to remove the tumor. The operation time was 50 minutes and oral immunosuppressant drug was not interrupted in the postoperative period. OUTCOMES: The clinical course was uneventful and slightly elevated liver enzyme was observed on the fourth day after operation. The pathological diagnosis was GIST with complete capsule. LESSONS: Our successful experience showed that EFR is a feasible, safe and efficacious treatment for small (<2 cm) gastric GIST in liver transplant recipients, providing the advantages of little damage, short operative time, stable graft function, without compromising postoperative outcomes.


Assuntos
Gastrectomia/métodos , Tumores do Estroma Gastrointestinal/cirurgia , Neoplasias Gástricas/cirurgia , Transplantados , Adulto , Idoso , Endoscopia/métodos , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Tumores do Estroma Gastrointestinal/patologia , Humanos , Imunossupressores/uso terapêutico , Transplante de Fígado , Masculino , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Resultado do Tratamento
9.
Medicine (Baltimore) ; 98(35): e16830, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31464908

RESUMO

RATIONALE: Amyloidosis accounts for 2% of head and neck tumors. Amyloidosis that develops in the head and neck region is localized amyloidosis. Multifocal amyloidosis in the head and neck region is extremely rare. PATIENT CONCERNS: The patient presented to the clinic of otolaryngology with nasal obstruction, anosmia and left neck mass for several months. DIAGNOSIS: A left nasopharynx tumor was revealed under nasopharyngeal scope. Eosinophilic, proteinaceous material was revealed under a pathology scope in the nasopharynx tissue and neck tumor. Congo red staining demonstrated pale congophilic amorphous material with apple-green birefringence under cross-polarized light, and multifocal amyloidosis was diagnosed. Amyloidosis secondary to systemic lupus erythematosus (SLE) was confirmed after a series of investigations. INTERVENTIONS: The patient underwent local excision for multifocal amyloidosis without following management. To control underlying SLE, the patient accepted steroid pulse therapy and immunosuppressants. The patient eventually achieved disease remission. OUTCOMES: During the 6 months of follow-up in the outpatient department of otolaryngology and rheumatology, complications, recurrence of nasopharyngeal amyloidosis, and SLE flare-up were not observed. LESSONS: Head and neck amyloidosis involving the nasopharynx is a rare presentation of this disease. Head and neck multifocal amyloidosis should be taken as a hint of systemic disease. In head and neck amyloidosis, a comprehensive survey should be performed to clarify the underlying disease predisposing to amyloidosis and organ involvement.


Assuntos
Amiloidose/etiologia , Neoplasias de Cabeça e Pescoço/diagnóstico , Lúpus Eritematoso Sistêmico/diagnóstico , Neoplasias Nasofaríngeas/diagnóstico , Adulto , Amiloidose/cirurgia , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/cirurgia , Humanos , Imunossupressores/uso terapêutico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/cirurgia , Indução de Remissão , Esteroides/uso terapêutico , Resultado do Tratamento
10.
Medicine (Baltimore) ; 98(34): e15415, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31441835

RESUMO

BACKGROUND: Multiple sclerosis is the most common demyelinating disease of the central nervous system with serious social and economic burden. Siponimod is a sphingosine-1-phosphate receptor agonist, and clinical trials in the past decade have shown good prospects for the treatment of multiple sclerosis. But there is a lack of comprehensive understanding of the dose-effect relationship and safety in different subtypes of multiple sclerosis at present. METHODS: We will perform a systematic review and meta-analysis of clinical randomized controlled trials to evaluate the efficacy and safety of siponimod in multiple sclerosis. We will search PubMed, EMBASE, Cochrane Library, Clinical Trials, Cochrane Central Register of Controlled Trials (CENTRAL) using a comprehensive strategy. The reference lists of the articles we select for inclusion will be checked to identify additional studies for potential inclusion. Two reviewers will review all literature independently. Upon inclusion of articles, another 2 reviewers will extract available data using a standardized form and assess the potential bias. Review Manager will be used to conduct data synthesis. There is no requirement of ethical approval and informed consent. RESULT: This is the first systematic assessment of siponimod for the treatment of multiple sclerosis. We predict it will provide high-quality synthesis of existing evidence for the efficacy and safety of siponimod for multiple sclerosis and a relatively comprehensive reference for clinical practice and clinical trials about siponimod to be conducted. CONCLUSION: The results of the systematic review and meta-analysis will provide updated evidence for the use of siponimod for multiple sclerosis. REGISTRATION: The systematic review and meta-analysis is registered in the PROSPERO international prospective register of systematic review (PROSPERO#CRD42018112721).


Assuntos
Azetidinas/uso terapêutico , Compostos de Benzil/uso terapêutico , Imunossupressores/uso terapêutico , Esclerose Múltipla/tratamento farmacológico , Azetidinas/administração & dosagem , Azetidinas/efeitos adversos , Compostos de Benzil/administração & dosagem , Compostos de Benzil/efeitos adversos , Relação Dose-Resposta a Droga , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Esclerose Múltipla/classificação , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa
11.
An Bras Dermatol ; 94(3): 264-278, 2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31365654

RESUMO

Pemphigus vulgaris is a chronic autoimmune bullous dermatosis that results from the production of autoantibodies against desmogleins 1 and 3. It is the most frequent and most severe form of pemphigus, occurring universally, usually between 40 and 60 years of age. It usually begins with blisters and erosions on the oral mucosa, followed by lesions on other mucous membranes and flaccid blisters on the skin, which can be disseminated. There is a clinical variant, pemphigus vegetans, which is characterized by the presence of vegetating lesions in the large folds of the skin. Clinical suspicion can be confirmed by cytological examination, histopathological examination, and direct and indirect immunofluorescence tests. The treatment is performed with systemic corticosteroids, and immunosuppressive drugs may be associated, among them azathioprine and mycophenolate mofetil. More severe cases may benefit from corticosteroids in the form of intravenous pulse therapy, and recent studies have shown a beneficial effect of rituximab, an anti-CD20 immunobiological drug. It is a chronic disease with mortality around 10%, and septicemia is the main cause of death. Patients need long-term and multidisciplinary follow-up.


Assuntos
Pênfigo/diagnóstico , Adulto , Autoanticorpos/imunologia , Desmossomos/imunologia , Diagnóstico Diferencial , Feminino , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Imunossupressores/classificação , Imunossupressores/uso terapêutico , Imunoterapia/métodos , Masculino , Pessoa de Meia-Idade , Pênfigo/classificação , Pênfigo/epidemiologia , Pênfigo/terapia , Pele/patologia , Inquéritos e Questionários
12.
An Bras Dermatol ; 94(3): 337-340, 2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31365665

RESUMO

Necrobiotic xanthogranuloma is a rare chronic condition, belonging to the group C non-Langerhans cell histiocytoses, which is relevant due to the possibility of extracutaneous involvement and association with systemic diseases, particularly hematologic malignancies. The case reported here was only diagnosed after nine years of evolution and was associated with plasma cell dyscrasia. After treatment with cyclophosphamide, dexamethasone, and thalidomide, there was a reduction of cutaneous lesions and serum levels of monoclonal protein.


Assuntos
Xantogranuloma Necrobiótico/tratamento farmacológico , Mieloma Múltiplo Latente/tratamento farmacológico , Ciclofosfamida/uso terapêutico , Dexametasona/uso terapêutico , Feminino , Humanos , Imunossupressores/uso terapêutico , Pessoa de Meia-Idade , Xantogranuloma Necrobiótico/complicações , Xantogranuloma Necrobiótico/patologia , Mieloma Múltiplo Latente/complicações , Mieloma Múltiplo Latente/patologia , Talidomida/uso terapêutico , Resultado do Tratamento
13.
S D Med ; 72(5): 214-216, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31454474

RESUMO

Cirrhosis resulting from autoimmune hepatitis is associated with an increased risk of hepatocellular carcinoma. A common treatment for autoimmune hepatitis, azathioprine, is also associated with the development of many other cancers, predominantly lymphomas. The strongest association is seen for post-transplant lymphoma and hepatosplenic T-cell lymphoma in Crohn's disease and ulcerative colitis patients; there is also an association with a variety of cutaneous malignancies. A relationship between azathioprine and sarcoma has not been demonstrated, though there have been sporadic case reports. We report here the development of leiomyosarcoma in a patient who was treated with azathioprine for autoimmune hepatitis without cirrhosis.


Assuntos
Azatioprina/efeitos adversos , Colite Ulcerativa , Doença de Crohn , Imunossupressores/efeitos adversos , Leiomiossarcoma , Azatioprina/uso terapêutico , Humanos , Imunossupressores/uso terapêutico , Leiomiossarcoma/induzido quimicamente
14.
Rinsho Ketsueki ; 60(7): 779-784, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31391366

RESUMO

Aplastic anemia (AA), a hematopoietic disorder characterized by hypocellular bone marrow, is caused by immunologically-mediated hematopoietic stem cell injury. Viral infection is hypothesized as the underlying cause of hepatitis-associated AA, although its mechanism is still unclear. This report describes a case of AA following suspected drug-induced liver injury (DILI). An 18-year-old man developed severe liver dysfunction after taking oral over-the-counter drugs. The patient was diagnosed with suspected DILI based on drug-induced lymphocyte stimulation test and liver biopsy results. Although liver dysfunction improved after a course of steroid pulse therapy and liver supporting therapy, the man gradually developed pancytopenia within 3 months of DILI diagnosis, prompting the diagnosis of AA following DILI. Paroxysmal nocturnal hemoglobinuria-type cells were detected by high-sensitivity flow cytometry. Immunosuppressive therapy with antithymocyte globulin and cyclosporin was administered, with pancytopenia improvement. To the best of our knowledge, this is the first report in the literature with a case of AA following DILI, and we believe it is important for evaluating the pathogenesis of drug-induced and hepatitis-associated AA.


Assuntos
Anemia Aplástica/etiologia , Doença Hepática Induzida por Substâncias e Drogas/complicações , Adolescente , Anemia Aplástica/tratamento farmacológico , Soro Antilinfocitário/uso terapêutico , Ciclosporina/uso terapêutico , Hemoglobinúria Paroxística , Humanos , Imunossupressores/uso terapêutico , Masculino
15.
Vasc Health Risk Manag ; 15: 209-220, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31371977

RESUMO

Cholesterol-embolization syndrome (CES) is a multisystemic disease with various clinical manifestations. CES is caused by embolization of cholesterol crystals (CCs) from atherosclerotic plaques located in the major arteries, and is induced mostly iatrogenically by interventional and surgical procedures; however, it may also occur spontaneously. Embolized CCs lead to both ischemic and inflammatory damage to the target organ. Therefore, anti-inflammatory agents, such as corticosteroids and cyclophosphamide, have been investigated as treatment for CES in several studies, with conflicting results. Recent research has revealed that CES is actually a kind of autoinflammatory disease in which inflammasome pathways, such as NLRP3 and IL1, are induced by CCs. These recent findings may have clinical implications such that colchicine and IL1 inhibitors, namely canakinumab, may be beneficial in the early stages of CES.


Assuntos
Aterosclerose , Colesterol/sangue , Embolia de Colesterol , Corticosteroides/uso terapêutico , Animais , Anti-Inflamatórios/uso terapêutico , Aterosclerose/sangue , Aterosclerose/diagnóstico , Aterosclerose/tratamento farmacológico , Aterosclerose/epidemiologia , Biomarcadores/sangue , Cristalização , Embolia de Colesterol/sangue , Embolia de Colesterol/diagnóstico , Embolia de Colesterol/epidemiologia , Embolia de Colesterol/prevenção & controle , Humanos , Imunossupressores/uso terapêutico , Inflamassomos/sangue , Mediadores da Inflamação/sangue , Interleucina-1/sangue , Proteína 3 que Contém Domínio de Pirina da Família NLR/sangue , Placa Aterosclerótica , Prognóstico , Fatores de Risco , Síndrome
16.
Medicine (Baltimore) ; 98(33): e16399, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31415347

RESUMO

RATIONALE: Hepatitis E is an infectious disease due to inflammation of the liver caused by hepatitis E virus (HEV) and represents one of the most common causes of acute hepatitis and jaundice in the world. Although data of hepatitis E infection in patients with rheumatoid arthritis (RA) are accumulating, little is known on the course of HEV infection. We reported, for the 1st time, a case of patient with RA with hepatitis E that developed during leflunomide therapy in combination with low-dose steroids. PATIENT CONCERNS: We present a 39-year-old woman, affected by RA and treated with leflunomide, reported diffuse itching and persistent fatigue laboratory data revealed elevated liver enzyme levels. DIAGNOSIS: Positivity for anti-HEV IgM and IgG was observed. HEV-RNA of the genotype 3 was detected, indicating acute E hepatitis. INTERVENTIONS AND OUTCOMES: Leflunomide was stopped and restarted 5 months after the initial diagnosis at the same dosage, with a close clinical and laboratory follow-up. The virus was eradicated from the serum without chronic transformation. The patient is alive and well 7 months after the initial diagnosis. LESSONS: To our knowledge, this report is the 1st case of acute E hepatitis in a patient with RA developed during leflunomide therapy in combination with low-dose steroids. Moreover, geoepidemiology of infection is important, due to the fact that Abruzzo, a central region of Italy, has the highest HEV seroprevalence in general population, related to the zoonotic transmission of the infection from domestic and wild animals. Our case highlighted that immunosuppressive therapy, and in particular leflunomide, could be safely reintroduced after the resolution of the infection and the clearance of the virus. Further studies are needed to evaluate potential advantages in serologic testing for HEV infection as a part of the routine workup done to patients with rheumatic diseases and selected for immunosuppressive therapy.


Assuntos
Artrite Reumatoide/virologia , Vírus da Hepatite E/genética , Hepatite E/tratamento farmacológico , Imunossupressores/uso terapêutico , Leflunomida/uso terapêutico , Adulto , Feminino , Hepatite E/epidemiologia , Hepatite E/virologia , Humanos , Itália/epidemiologia , Estudos Soroepidemiológicos
17.
Acta Gastroenterol Belg ; 82(2): 279-284, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31314189

RESUMO

BACKGROUND AND AIM: Hepatitis B Virus (HBV) screening before starting immunosuppressive treatment is of vital importance in order to prevent HBV reactivation and its associated clinical consequences. Despite all recommendations by international organizations, screening rates are far below desired. The aim of this study was to assess the efficacy of a computer alert programme 'HBVision' for increasing HBV screening rates. MATERIAL AND METHODS: 'HBVision' identifies patients at risk of HBV reactivation by specific ICD-10 codes and immunosuppressive medication reports and sends sequential alert messages to screen for HBsAg, anti-HBc IgG and consult a specialist if one of them is positive. The demographic variables, treatment protocols, HBV screening and consultation rates of oncology and hematology patients who started immunosuppressive treatments within one year before (control group) and after "HBVision" (study group) were retrospectively compared. RESULTS: HBsAg and anti-HBc IgG screening rates (68.6% and 13.1%, respectively) were significantly higher in the study group (n=602) compared to control group (n=815) (55% and 4.3%, respectively) (p<0.001, for both). Subgroup analysis revealed significant improvements in the screening rates of HBsAg (65.8%) and anti-HBc IgG (5.1%) in oncology patients (p<0.001), anti-HBc IgG (89.1%) in hematology patients (p<0.001). CONCLUSION: The computer alert programme significantly increased HBV screening rates before starting immunosuppressive treatments, however the results were still below ideal. Additional efforts, such as modifying the computer programme according to feedbacks, are probably needed.


Assuntos
Antígenos de Superfície da Hepatite B/sangue , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B/sangue , Hepatite B/virologia , Imunossupressores/efeitos adversos , Ativação Viral/efeitos dos fármacos , Hepatite B/induzido quimicamente , Hepatite B/tratamento farmacológico , Antígenos do Núcleo do Vírus da Hepatite B/imunologia , Vírus da Hepatite B/isolamento & purificação , Vírus da Hepatite B/patogenicidade , Humanos , Imunossupressores/uso terapêutico , Programas de Rastreamento/métodos , Estudos Retrospectivos , Software
18.
Acta Gastroenterol Belg ; 82(2): 326-328, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31314197

RESUMO

In this case report we describe the evolution of Cheilitis granulomatosa (GC) in a young patient with Crohn's disease during treatment with anti-TNF-alfa therapy.


Assuntos
Doença de Crohn/diagnóstico , Imunossupressores/uso terapêutico , Imunoterapia , Síndrome de Melkersson-Rosenthal/etiologia , Fator de Necrose Tumoral alfa/uso terapêutico , Doença de Crohn/complicações , Doença de Crohn/tratamento farmacológico , Humanos , Resultado do Tratamento
19.
Medicine (Baltimore) ; 98(27): e16160, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31277118

RESUMO

RATIONALE: Acquired pure red cell aplasia (PRCA) can be a secondary response to some autoimmune disorders. However, there is no data about the possibility of acquired PRCA being a secondary complication to ankylosing spondylitis (AS). PATIENT CONCERNS: A 42-year-old male who had a history of AS for 14 years. He got serious anemia 17 months ago. Bone marrow smear indicated PRCA. DIAGNOSE: He was diagnosed with acquired PRCA secondary to AS. INTERVENTION: The combination treatment of immunosuppressants with hematopoiesis stimuli was successful. OUTCOMES: The patient recovered from PRCA, and showed improvement in his AS. LESSONS: Acquired PRCA can be secondary to AS. Cyclosporine is effective in controlling AS arthritis syndrome and in addition to immunosuppressants, promotion of erythroid hematopoiesis is equally important.


Assuntos
Aplasia Pura de Série Vermelha/etiologia , Espondilite Anquilosante/complicações , Adulto , Ciclosporina/uso terapêutico , Humanos , Imunossupressores/uso terapêutico , Masculino , Aplasia Pura de Série Vermelha/diagnóstico , Espondilite Anquilosante/diagnóstico por imagem , Espondilite Anquilosante/tratamento farmacológico
20.
N Engl J Med ; 381(1): 36-46, 2019 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-31269364

RESUMO

BACKGROUND: B-cell anomalies play a role in the pathogenesis of membranous nephropathy. B-cell depletion with rituximab may therefore be noninferior to treatment with cyclosporine for inducing and maintaining a complete or partial remission of proteinuria in patients with this condition. METHODS: We randomly assigned patients who had membranous nephropathy, proteinuria of at least 5 g per 24 hours, and a quantified creatinine clearance of at least 40 ml per minute per 1.73 m2 of body-surface area and had been receiving angiotensin-system blockade for at least 3 months to receive intravenous rituximab (two infusions, 1000 mg each, administered 14 days apart; repeated at 6 months in case of partial response) or oral cyclosporine (starting at a dose of 3.5 mg per kilogram of body weight per day for 12 months). Patients were followed for 24 months. The primary outcome was a composite of complete or partial remission of proteinuria at 24 months. Laboratory variables and safety were also assessed. RESULTS: A total of 130 patients underwent randomization. At 12 months, 39 of 65 patients (60%) in the rituximab group and 34 of 65 (52%) in the cyclosporine group had a complete or partial remission (risk difference, 8 percentage points; 95% confidence interval [CI], -9 to 25; P = 0.004 for noninferiority). At 24 months, 39 patients (60%) in the rituximab group and 13 (20%) in the cyclosporine group had a complete or partial remission (risk difference, 40 percentage points; 95% CI, 25 to 55; P<0.001 for both noninferiority and superiority). Among patients in remission who tested positive for anti-phospholipase A2 receptor (PLA2R) antibodies, the decline in autoantibodies to anti-PLA2R was faster and of greater magnitude and duration in the rituximab group than in the cyclosporine group. Serious adverse events occurred in 11 patients (17%) in the rituximab group and in 20 (31%) in the cyclosporine group (P = 0.06). CONCLUSIONS: Rituximab was noninferior to cyclosporine in inducing complete or partial remission of proteinuria at 12 months and was superior in maintaining proteinuria remission up to 24 months. (Funded by Genentech and the Fulk Family Foundation; MENTOR ClinicalTrials.gov number, NCT01180036.).


Assuntos
Ciclosporina/uso terapêutico , Glomerulonefrite Membranosa/tratamento farmacológico , Imunossupressores/uso terapêutico , Rituximab/uso terapêutico , Administração Oral , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Ciclosporina/efeitos adversos , Esquema de Medicação , Feminino , Humanos , Fatores Imunológicos/uso terapêutico , Imunossupressores/efeitos adversos , Infusões Intravenosas , Análise de Intenção de Tratamento , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Proteinúria/tratamento farmacológico , Indução de Remissão , Rituximab/efeitos adversos , Falha de Tratamento , Adulto Jovem
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