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1.
Medicine (Baltimore) ; 98(38): e17208, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31567972

RESUMO

Ulcerative colitis (UC) and Crohn disease (CD) are the most common forms of inflammatory bowel disease (IBD). Because these subtypes of IBD are characterized by periods of activity and remission, an understanding of the modulation of biochemical markers with the clinical features of IBD or its treatment, may be useful for determining the correct treatment protocol.This study aimed to evaluate the serum levels of 27 protein biomarkers to determine their association with IBD, correlation with clinical findings of disease, and modulation according to the pharmacologic therapy.A case-control study was carried out in Zacatecas, Mexico. The 27 protein profiles of serum from 53 participants (23 UC, 11 CD, and 19 controls) were evaluated using the Pro Human Cytokine 27-Plex immunoassay (Bio-Rad).Considering the controls as a reference, the group with IBD endoscopic activity showed higher serum levels of granulocyte colony-stimulating factor (G-CSF), interleukin 1 receptor antagonist (IL-1Ra), and platelet-derived growth factor BB (PDGF-BB) (P < .05). Interferon-induced protein 10 (IP-10) was associated with extraintestinal symptoms of disease (P = .041). Both PDGF-BB and interleukin 6 (IL-6) showed the strongest correlations with clinical features of IBD. Levels of IL-6, IL-7, and monocyte chemoattractant protein 1 were higher with 5-aminosalicylic acid (5-ASA) + Azathioprine therapy than controls (P < .05). Combined therapy with 5-ASA + Adalimumab led to the strongest changes in marker modulation: IL-4, IL-5, IL-15, and PDGF-BB, were upregulated (P < .05).Elevated serum levels of G-CSF, IL-1Ra, and PDGF-BB were associated with IBD endoscopic activity, and of IP-10 with extraintestinal manifestations of IBD. Combined therapy of 5-ASA + Adalimumab produced significant upregulation of IL-4, IL-5, IL-15, and PDGF-BB. This information may be useful for deciding on the course of pharmacologic therapy for patients with IBD and for generating new therapy alternatives to improve the outcome of patients with IBD.


Assuntos
Quimiocinas/sangue , Citocinas/sangue , Doenças Inflamatórias Intestinais/sangue , Peptídeos e Proteínas de Sinalização Intercelular/sangue , Adalimumab/uso terapêutico , Adulto , Idoso , Anti-Inflamatórios/uso terapêutico , Azatioprina/uso terapêutico , Becaplermina/sangue , Biomarcadores/sangue , Estudos de Casos e Controles , Quimiocina CXCL10/sangue , Feminino , Fator Estimulador de Colônias de Granulócitos/sangue , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Interleucina-6/sangue , Masculino , Mesalamina/uso terapêutico , Pessoa de Meia-Idade , Receptores de Interleucina-1/sangue
2.
Lancet ; 394(10201): 882-894, 2019 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-31498102

RESUMO

Pemphigus consists of a group of rare and severe autoimmune blistering diseases mediated by pathogenic autoantibodies mainly directed against two desmosomal adhesion proteins, desmoglein (Dsg)1 and Dsg3 (also known as DG1 and DG3), which are present in the skin and surface-close mucosae. The binding of autoantibodies to Dsg proteins induces a separation of neighbouring keratinocytes, in a process known as acantholysis. The two main pemphigus variants are pemphigus vulgaris, which often originates with painful oral erosions, and pemphigus foliaceus, which is characterised by exclusive skin lesions. Pemphigus is diagnosed on the basis of either IgG or complement component 3 deposits (or both) at the keratinocyte cell membrane, detected by direct immunofluorescence microscopy of a perilesional biopsy, with serum anti-Dsg1 or anti-Dsg3 antibodies (or both) detected by ELISA. Corticosteroids are the therapeutic mainstay, which have recently been complemented by the anti-CD20 antibody rituximab in moderate and severe disease. Rituximab induces complete remission off therapy in 90% of patients, despite rapid tapering of corticosteroids, thus allowing for a major corticosteroid-sparing effect and a halved number of adverse events related to corticosteroids.


Assuntos
Azatioprina , Imunossupressores , Pênfigo , Rituximab , Corticosteroides/efeitos adversos , Azatioprina/uso terapêutico , Desmogleína 1 , Ensaio de Imunoadsorção Enzimática , Humanos , Imunoglobulina G/imunologia , Imunossupressores/uso terapêutico , Pênfigo/classificação , Pênfigo/diagnóstico , Pênfigo/tratamento farmacológico , Pênfigo/patologia , Rituximab/uso terapêutico , Resultado do Tratamento
3.
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
4.
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
5.
Presse Med ; 48(9): 968-979, 2019 Sep.
Artigo em Francês | MEDLINE | ID: mdl-31324351

RESUMO

Glucocorticoids (GC) remain the gold standard of the treatment of giant cell arteritis provided objectives of GC-tapering are accurately followed: 15 to 20mg/day at 3 months, 10mg/day at 6 months, 5mg/day at 9-12 months and withdrawal between 12 and 18 months. In case of corticodependance at ≥7.5 mg/day of prednisone or intolerance to GC, a GCsparing therapy has to be introduced, mainly methotrexate or tocilizumab. Individual characteristics of each patient, data about the efficacy of the treatment, its cost and how easy the follow-up under this treatment is are important factors to consider for choosing the right GC-sparing therapy. For all these reasons, except particular situations, we prefer using methotrexate before tocilizumab. Prevention of cardiovascular events is an important aspect of the treatment of GCA. We recommend using aspirin (75-100mg/day) during the first month of treatment or longer in case of occurrence of an ischemic complication. Each patient treated for GCA should receive a prevention of osteoporosis with respect of usual recommendations.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Arterite de Células Gigantes/tratamento farmacológico , Glucocorticoides/uso terapêutico , Metotrexato/uso terapêutico , Prednisona/uso terapêutico , Abatacepte/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Aspirina/uso terapêutico , Azatioprina/uso terapêutico , Esquema de Medicação , Arterite de Células Gigantes/complicações , Glucocorticoides/administração & dosagem , Humanos , Imunossupressores/uso terapêutico , Leflunomida/uso terapêutico , Ustekinumab/uso terapêutico
6.
Clin Exp Rheumatol ; 37 Suppl 117(2): 137-143, 2019 Mar-Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31162031

RESUMO

OBJECTIVES: Rituximab was proven superior to azathioprine for maintenance treatment of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). The high cost of rituximab might, however, limit its routine use. This study determined the cost-effectiveness of intravenous rituximab (5 x 500 mg until month 18), versus oral azathioprine (2 mg/kg per day, gradually decreased between month 12 and 22), for maintenance treatment of patients with granulomatosis with polyangiitis, microscopic polyangiitis, or renal-limited vasculitis, aged 18-75. METHODS: We performed a single-trial based economic evaluation. MAINRITSAN was a 28-month multicentre, prospective, randomised, controlled open-label trial. We estimated the cost of healthcare resources and quality of life using prospectively collected data. Healthcare costs were estimated from the perspective of the French Social Health Insurance's perspective, using 2016 tariffs for reimbursement. Utilities were derived from Short Form 36 scores. We estimated total average cost, incremental cost per incremental relapse averted and per quality-adjusted life-year (QALY) gained. Sensitivity analyses were performed to assess uncertainty over relapses, severe adverse events, discount rate, utility weights, time horizon and the cost of rituximab. Costs drivers were tested using a generalised linear model. RESULTS: Total average costs were €13,387 (€11,605-€15,646) and €10,217 (€7,567-12,949) in the rituximab and azathioprine groups respectively. The incremental cost-effectiveness ratio (ICER) was €12,824 per relapse averted and the incremental cost-utility ratio (ICUR) €37,782 per QALY gained. Besides the unit cost of rituximab, the major cost drivers were relapses and severe adverse events. CONCLUSIONS: Maintenance treatment by rituximab could be cost-effective for preventing relapses in patients with AAV.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Azatioprina/economia , Rituximab/economia , Adolescente , Adulto , Idoso , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/economia , Anticorpos Anticitoplasma de Neutrófilos , Azatioprina/uso terapêutico , Análise Custo-Benefício , Feminino , Humanos , Quimioterapia de Manutenção , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Qualidade de Vida , Rituximab/uso terapêutico , Adulto Jovem
7.
Pan Afr Med J ; 32: 65, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31223357

RESUMO

Hailey-Hailey disease (HHD) is a rare autosomal dominant hereditary blistering and erosions disorder affecting the intertriginous regions of the body. There is still no treatment protocol for this disease thus clinicians are highly advised to draw up individualized treatment plan. In this case report, we discuss a case of HHD in a 58-year-old Chinese man who was successfully treated with azathioprine in Hubei province.


Assuntos
Azatioprina/uso terapêutico , Fatores Imunológicos/uso terapêutico , Pênfigo Familiar Benigno/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Pênfigo Familiar Benigno/fisiopatologia , Resultado do Tratamento
8.
Clin Exp Rheumatol ; 37(5): 858-861, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31074729

RESUMO

OBJECTIVES: To study the efficacy in terms of muscle strength, and corticosteroid tapering as well as the prevalence of adverse effects in patients with the antisynthetase syndrome (ASyS) treated with azathioprine (AZA) compared to those treated with methotrexate (MTX). METHODS: We compared the clinical outcomes in ASyS patients treated with AZA versus MTX including change in corticosteroid dose, strength, and creatine kinase (CK) as well as the prevalence of adverse effects. RESULTS: Among 169 patients with ASyS, 102 were treated at some point exclusively with either AZA or MTX (± corticosteroids). There were no significant differences in the rate of muscle strength recovery, CK decrease or corticosteroid tapering between those ASyS patients treated with MTX versus AZA. The prevalence of adverse events in patients treated with AZA and MTX was similar (29% vs. 25%, p>0.05); elevated liver enzymes (17% AZA vs. 12% MTX) and gastrointestinal involvement (10% AZA vs. 8% MTX) were the most common adverse events. While no patients treated with AZA developed lung complications, two of the patients treated with MTX experienced reversible pneumonitis with MTX cessation. CONCLUSIONS: AZA and MTX showed similar efficacy and adverse events in patients with ASyS. Pneumonitis is a rare but important event in patients receiving MTX.


Assuntos
Azatioprina , Metotrexato , Miosite/tratamento farmacológico , Corticosteroides , Azatioprina/efeitos adversos , Azatioprina/uso terapêutico , Creatina Quinase/sangue , Humanos , Metotrexato/efeitos adversos , Metotrexato/uso terapêutico , Força Muscular/efeitos dos fármacos , Força Muscular/fisiologia
9.
Mymensingh Med J ; 28(2): 461-464, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31086167

RESUMO

Sympathetic ophthalmitis (SO) is defined as bilateral granulomatous panuveitis occurring after penetrating ocular trauma or intraocular surgery. It is now rare due to micro-surgical repair of ocular injury and use of steroid. An 18 years old boy admitted into Ophthalmology department of Mymensingh Medical College Hospital, Mymensingh, Bangladesh on 2nd March 2018. He got penetrating corneal injury in R/E with sharp pointed object 01 month back. It was conservatively managed but his right eye became phthisical. After 04 weeks his left eye was affected in which VA became 3/60, features of panuveitis developed. It was managed with high dose steroid and immunomodulatory drug (Azathioprine). Ultimately his vision of left eye is fully preserved (6/6). So, after a trauma or surgery to one eye, another eye should be meticulously examined and followed up. Early diagnosis and prompt treatment of Sympathetic Ophthalmitis may prevent from blindness.


Assuntos
Ferimentos Oculares Penetrantes/complicações , Oftalmia Simpática/etiologia , Adolescente , Azatioprina/uso terapêutico , Ferimentos Oculares Penetrantes/cirurgia , Humanos , Imunomodulação , Imunossupressores/uso terapêutico , Masculino , Oftalmia Simpática/tratamento farmacológico , Doenças Raras , Esteroides/administração & dosagem , Resultado do Tratamento , Acuidade Visual
10.
BMC Infect Dis ; 19(1): 404, 2019 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-31077135

RESUMO

BACKGROUND: Symptomatic primary Epstein-Barr virus infection is a usually self-limiting illness in adolescents. We present a case of an adolescent who had been receiving azathioprine for inflammatory bowel disease for four years and developed a life-threatening primary Epstein-Barr virus infection successfully treated with rituximab. CASE PRESENTATION: An 11-year-old girl presented with chronic, bloody diarrhea. Endoscopic biopsies confirmed a diagnosis of chronic ulcerative colitis with features of Crohn's disease. Azathioprine was initiated after one year due to active colitis. She responded well and remission was achieved. At the age of 16 years she developed a life-threatening Epstein-Barr virus infection including severe multiple organ failure and was critically ill for 4 weeks in the intensive care unit. Natural killer cells were virtually absent in the lymphocyte subset analysis. Azathioprine was stopped on admission. She was initially treated with corticosteroids, acyclovir and intravenous immunoglobulin. Approximately 30 days after admission, she developed signs of severe hepatitis and pneumonitis and received weekly rituximab infusions for 8 weeks. Primary immunodeficiency was excluded by whole exome sequencing in two independent laboratories. Persistent viremia stopped when the natural killer cell count started to rise, approximately 90 days after the cessation of azathioprine. CONCLUSIONS: We found 17 comparable cases in the literature. None of the previous cases reported in the literature, who had been treated with azathioprine and developed either a severe or a fatal Epstein-Barr virus infection, underwent full genetic and prospective immunological workup to rule out known primary immunodeficiencies. Recently, azathioprine has been shown to cause rather specific immunosuppression, resulting in natural killer cell depletion. Our case demonstrates that slow recovery from azathioprine-induced natural killer cell depletion, 3 months after the stopping of azathioprine, coincided with the clearance of viremia and clinical recovery. Finally, our choice of treating the patient with rituximab, as previously used for patients with a severe immunosuppression and Epstein-Barr virus viremia, appeared to be successful in this case. We suggest testing for Epstein-Barr virus serology before starting azathioprine and measuring natural killer cell counts during the treatment to identify patients at risk of developing an unusually severe primary Epstein-Barr virus infection.


Assuntos
Azatioprina/efeitos adversos , Infecções por Vírus Epstein-Barr/etiologia , Imunossupressores/efeitos adversos , Doenças Inflamatórias Intestinais/complicações , Células Matadoras Naturais , Azatioprina/uso terapêutico , Biópsia , Criança , Infecções por Vírus Epstein-Barr/imunologia , Infecções por Vírus Epstein-Barr/virologia , Feminino , Herpesvirus Humano 4/imunologia , Humanos , Imunossupressores/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Células Matadoras Naturais/efeitos dos fármacos , Contagem de Linfócitos , Estudos Prospectivos , Rituximab/uso terapêutico , Resultado do Tratamento
11.
Medicine (Baltimore) ; 98(22): e15927, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31145359

RESUMO

INTRODUCTION: A network meta-analysis was conducted to regard the effects of available immunosuppressive medications in pediatric frequently-relapsing nephrotic syndrome (FRNS) and steroid-dependent nephrotic syndrome (SDNS). METHODS: We reviewed systematically 26 randomized controlled trials (1311 patients) that compared any of the following immunosuppressive agents to placebo/nontreatment (P/NT) or another drug for FRNS/SDNS treatment in children. RESULTS: The main outcomes were efficacy and acceptability. At the 6-month, cyclophosphamide, chlorambucil, levamisole, and rituximab had better efficacy than P/NT (odds ratio [OR]: 0.09, 0.03, 0.28, and 0.07, respectively); cyclophosphamide was significantly more effective than azathioprine and chlorambucil. At 12 months, cyclophosphamide, chlorambucil, cyclosporine, levamisole, and rituximab had better efficacy than P/NT (0.10, 0.03, 0.10, 0.23, and 0.07, respectively); Chlorambucil were found to be more efficacious than levamisole and MMF (0.12 and 0.09, respectively). At 24 months, cyclophosphamide, chlorambucil, and levamisole had better efficacy than P/NT (0.09, 0.04, and 0.03, respectively); cyclophosphamide had better efficacy than cyclosporine and vincristine (0.17 and 0.39, respectively). CONCLUSION: No significant differences in acceptability were found. Our results suggest that cyclophosphamide may be preferred initially in children with FRSN/SDNS, chlorambucil, and rituximab may be acceptable medications for patients with FRSN/SDNS. Long-term follow-up trials focused on gonadal toxicity and limitation of maximum dosage of cyclophosphamide should been carried out.


Assuntos
Glucocorticoides/uso terapêutico , Imunossupressores/uso terapêutico , Síndrome Nefrótica/tratamento farmacológico , Adolescente , Azatioprina/uso terapêutico , Criança , Pré-Escolar , Clorambucila/uso terapêutico , Ciclofosfamida/uso terapêutico , Ciclosporina/uso terapêutico , Quimioterapia Combinada , Feminino , Humanos , Lactente , Levamisol/uso terapêutico , Masculino , Meta-Análise em Rede , Ensaios Clínicos Controlados Aleatórios como Assunto , Recidiva , Rituximab/uso terapêutico , Prevenção Secundária/métodos , Resultado do Tratamento
12.
Ter Arkh ; 91(4): 99-106, 2019 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-31094483

RESUMO

Loeffler's endocarditis remains is a very rare disease, develops due to eosinophilic inflammation predominantly of the endocardium with an outcome in fibrosis and massive thrombus formation and. He is generally characterized by an unfavorable prognosis. Clinical case of a 42-year-old patient with Loeffler endocarditis is presented. The development of the disease was preceded by a polyvalent allergy, mild dry eye syndrome and pansinusitis with a single eosinophilia of blood up to 16%. The reason for the hospitalization was the appearance of biventricular heart failure. During the previous year, the level of blood eosinophils remained normal, a threefold increase in the level of eosinophilic cationic protein was observed once. A 20-fold increase in the pANCA level, a 2.5-fold increase in the level of antibodies to DNA, an antibody to the nuclei of cardiomyocytes 1:160 were detected. The diagnosis was made on the basis of electrocardiography data (low QRS voltage, atrial hypertrophy), echocardiography, multispiral computed tomography and magnetic resonance imaging of the heart (thickening and delayed contrasting of the endocardium, massive thrombosis of the left ventricular apex with obliteration of its cavity, encapsulated fluid in the pericardium with compression of the right ventricle). Systolic dysfunction, severe signs of restriction and arrhythmias were absent. Trombectomy, tricuspid valve plasty, pericardial resection, suturing of an open oval window were performed. Signs of active inflammation with single eosinophils, vasculitis, perimuscular sclerosis, endocardial sclerosis were detected in morphological and immunohistochemical studies of endo-, myo-, pericardium. Viral genome was not found. The therapy with methylprednisolone 24 mg/day, azathioprine 75 mg/day was started. Six months after the operation, the symptoms of heart failure are completely absent, the thrombosis did not recur.


Assuntos
Anticorpos Anticitoplasma de Neutrófilos/efeitos dos fármacos , Azatioprina/uso terapêutico , Síndrome Hipereosinofílica/tratamento farmacológico , Síndrome Hipereosinofílica/cirurgia , Metilprednisolona/uso terapêutico , Miocardite , Adulto , Ecocardiografia , Eletrocardiografia , Humanos , Síndrome Hipereosinofílica/diagnóstico , Masculino , Resultado do Tratamento
13.
Paediatr Drugs ; 21(2): 81-93, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31087279

RESUMO

Childhood-onset Takayasu arteritis (c-TA) is the third most common systemic vasculitic disorder in children. Vascular stenosis is the main complication, and aneurysms are reported in 19-65% of cases, often in combination with stenotic lesions. Management of patients with c-TA is largely based on studies involving predominantly patients with adult-onset TA (a-TA). More widely used criteria for patients with c-TA have been devised by the joint European League Against Rheumatism, Pediatric Rheumatology International Trials Organization, and Pediatric Rheumatology European Society. Of the available imaging modalities, those that do not use radiation (color Doppler ultrasound and magnetic resonance angiogram) are preferred over 18F-labeled fluoro-2-deoxyglucose (18F-FDG) positron-emission tomography, computed tomography (CT), and CT angiogram in children. Remission rates have been reported to be lower in c-TA than in a-TA, and published mortality rates in c-TA range from 16 to 40%, which is much higher than reported in patients with a-TA. The usual drug therapy options include steroids plus steroid-sparing second-line immunosuppressants, such as mycophenolate, azathioprine, methotrexate, cyclophosphamide, and cyclosporine, along with antiplatelet agents. Interleukin-6 inhibitors such as tocilizumab, as well as the tumor necrosis factor inhibitors, are other aggressive therapeutic options. As yet, no randomized controlled trials have been conducted in c-TA.


Assuntos
Arterite de Takayasu/tratamento farmacológico , Adolescente , Adulto , Idade de Início , Anticorpos Monoclonais Humanizados/uso terapêutico , Azatioprina/uso terapêutico , Criança , Pré-Escolar , Diagnóstico Diferencial , Feminino , Humanos , Imunossupressores/uso terapêutico , Lactente , Arterite de Takayasu/diagnóstico por imagem , Fator de Necrose Tumoral alfa/antagonistas & inibidores
14.
Actas dermo-sifiliogr. (Ed. impr.) ; 110(3): 227-231, abr. 2019. tab
Artigo em Espanhol | IBECS | ID: ibc-181713

RESUMO

Antecedentes; La dermatitis atópica (DA) es una enfermedad inflamatoria crónica de la piel típicamente infantil cuyas formas graves pueden afectar intensamente la calidad de vida del paciente. Existen formas refractarias al tratamiento convencional en las que es preciso emplear inmunosupresores sistémicos como la azatioprina (AZA) para alcanzar un buen control de la enfermedad. Objetivo: Evaluar la eficacia y la tolerancia de la AZA en niños con DA grave. Pacientes y métodos: Se realizó una revisión retrospectiva de niños con DA grave tratados con AZA entre enero de 2007 y mayo de 2017. Resultados: Se revisaron 11 pacientes (6 varones, 5 mujeres) con una edad promedio de 13 años (rango 8-18 años). La edad media ± DE al inicio del tratamiento fue de 10,9 ± 2,2 años (IC 95% 8,6-13,1). La media de la dosis inicial de AZA fue de 1,8 ± 0,2 mg/kg/d. Evaluamos la respuesta al tratamiento de nuestros pacientes a las 4 semanas, entre la semana 12 y la 16, y a partir de los 6 meses. La media del tratamiento fue de 10,8 ± 5,7 meses. Dos pacientes tuvieron que suspender el tratamiento por efectos adversos. Siete de los 9 pacientes restantes presentaron un aclaramiento completo o casi completo de la DA a los 6 meses de tratamiento. Conclusión: En nuestra experiencia, la AZA es bien tolerada y puede ser considerada como una opción terapéutica en los niños con DA grave refractaria a tratamientos convencionales


Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease that typically affects children. Severe forms may have a profound effect on patients’ quality of life. Some forms are resistant to conventional treatment and require the use of systemic immunosuppressants such as azathioprine (AZA) to adequately manage the disease. Objective: To evaluate the effectiveness and tolerance of AZA in children with severe AD. Patients and methods: We performed a retrospective study of children with severe AD treated with AZA between January 2007 and May 2017. Results: We reviewed the cases of 11 patients (6 boys and 5 girls) with a mean age of 13 years (range, 8-18 years). The mean (SD) age at start of treatment was 10.9 (2.2) years (95% CI 8.6-13.1). The mean initial dosage of AZA was 1.8 (0.2) mg/kg/d. We evaluated treatment response after 4 weeks, 12 to 16 weeks, and 6 months. Mean treatment duration was 10.8 (5.7) months. Treatment had to be suspended in 2 patients because of adverse effects. Seven of the 9 remaining patients presented complete or almost complete clearance of the AD after 6 months of treatment. Conclusion: In our experience, AZA is well tolerated and may be considered as a treatment option in children with severe AD resistant to conventional treatment


Assuntos
Humanos , Masculino , Feminino , Criança , Adolescente , Dermatite Atópica/tratamento farmacológico , Azatioprina/efeitos adversos , Avaliação de Eficácia-Efetividade de Intervenções , Azatioprina/uso terapêutico , Estudos Retrospectivos , Resultado do Tratamento , Esteroides/administração & dosagem
16.
BMJ Case Rep ; 12(4)2019 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-30988103

RESUMO

A 47-year-old HIV-positive man with good immune and virological status presented with chronic multiple enlarged lymph nodes, lung disease and eosinophilia. Radiologic tests showed enlarged cervical, thoracic and axillary lymph nodes, with interstitial lung damage. After several non-specific histologic studies, an elevated serum IgG4 level led us to request immunohistochemistry of a lymph node sample. The test confirmed the diagnosis of IgG4-related disease.


Assuntos
Dispneia/etiologia , Infecções por HIV/fisiopatologia , Doença Relacionada a Imunoglobulina G4/diagnóstico , Doenças Pulmonares Intersticiais/diagnóstico , Linfonodos/patologia , Azatioprina/uso terapêutico , Dispneia/imunologia , Dispneia/fisiopatologia , Glucocorticoides/uso terapêutico , Infecções por HIV/imunologia , Humanos , Imunoglobulina G/sangue , Doença Relacionada a Imunoglobulina G4/fisiopatologia , Imuno-Histoquímica , Imunossupressores/uso terapêutico , Doenças Pulmonares Intersticiais/imunologia , Doenças Pulmonares Intersticiais/fisiopatologia , Masculino , Pessoa de Meia-Idade , Prednisona/uso terapêutico , Tomografia Computadorizada por Raios X , Resultado do Tratamento
17.
Medicina (Kaunas) ; 55(4)2019 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-30986917

RESUMO

Background and objectives: Oxidative stress signalling plays a monumental role in inflammatory bowel disease (IBD). Reduction of oxidative stress might control inflammation, block tissue damage, and reverse natural history of IBD. We assessed the serum concentrations of free thiols (FT) and uric acid (SUA), together constituting a large part of nonenzymatic serum antioxidant capacity, as well as total antioxidant status (TAS) with reference to IBD phenotype, activity, co-occurrence of anemia, and treatment with azathioprine (AZA) and corticosteroids (CS). Additionally, we appraised the potential of uric acid, thiol stress, and TAS as mucosal healing (MH) markers in ulcerative colitis. Materials and methods: SUA, FT, and TAS were measured colorimetrically using, respectively, uricase, Ellman's and 2,2'-azino-bis-3-ethylbenzthiazoline-6-sulphonic acid (ABTS) methods. Results: The study group consisted of 175 individuals: 57 controls, 71 ulcerative colitis (UC), and 47 Crohn's disease (CD) patients. When compared to controls, SUA levels were significantly lower in patients with CD, and FT and TAS levels were significantly lower in patients with CD and UC. In UC patients, SUA, FT, and TAS inversely correlated with the severity of bowel inflammation. As MH markers, SUA displayed better overall accuracy and higher specificity than FT. In active CD, FT, and SUA were significantly lower in patients with anemia. FT was significantly lower in patients treated with corticosteroids. Conclusions: IBD patients, regardless the disease phenotype, have systemic thiol stress, depleted total antioxidant capacity, and reduced concentrations of uric acid, reflecting, to various degrees, clinical and local disease activity as well as presence of anaemia, the most common extraintestinal manifestation of IBD. Evaluation of systemic total antioxidant status may be useful in noninvasive assessment of mucosal healing. Our findings on thiol stress provide an additional aspect on adverse effects of corticosteroids therapy.


Assuntos
Corticosteroides/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Colite Ulcerativa/sangue , Colite Ulcerativa/tratamento farmacológico , Doença de Crohn/sangue , Doença de Crohn/tratamento farmacológico , Estresse Oxidativo , Corticosteroides/efeitos adversos , Adulto , Análise de Variância , Anemia/sangue , Anemia/complicações , Anti-Inflamatórios/efeitos adversos , Azatioprina/uso terapêutico , Biomarcadores/sangue , Estudos de Casos e Controles , Colite Ulcerativa/complicações , Doença de Crohn/complicações , Feminino , Hospitais Universitários , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Polônia , Estatísticas não Paramétricas , Compostos de Sulfidrila/sangue , Ácido Úrico/sangue
18.
BMJ Case Rep ; 12(3)2019 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-30936327

RESUMO

Azathioprine (AZA) is an immunosuppressive drug that is widely used in the treatment of autoimmune diseases. Although AZA is used widely, many studies reported that AZA-related hepatotoxicity is rather rare. We aimed to present a case with severe cholestatic hepatitis due to AZA use for Behcet's disease. Three weeks after starting AZA for the treatment of uveitis, the patient was admitted to our clinic with cholestasis and constitutional symptoms. In liver biopsy, findings were in accordance with drug reaction, and the AZA treatment was stopped. After 2 months, bilirubin levels and liver tests results became normal. As a result, given that AZA may cause severe cholestasis, the drug should be stopped if idiosyncrasy or hypersensitivity develops. If there is a debate in the diagnosis, histopathological evaluation of the liver would be the major issue because of the correct diagnosis of the drug toxicity and excluding other aetiologies.


Assuntos
Azatioprina/efeitos adversos , Síndrome de Behçet/tratamento farmacológico , Colestase/induzido quimicamente , Imunossupressores/efeitos adversos , Fígado/patologia , Prurido/induzido quimicamente , Uveíte/tratamento farmacológico , Adulto , Azatioprina/uso terapêutico , Síndrome de Behçet/complicações , Síndrome de Behçet/fisiopatologia , Doença Hepática Induzida por Substâncias e Drogas , Colestase/tratamento farmacológico , Colestase/patologia , Humanos , Imunossupressores/uso terapêutico , Icterícia/induzido quimicamente , Fígado/efeitos dos fármacos , Masculino , Náusea/induzido quimicamente , Prurido/tratamento farmacológico , Prurido/patologia , Resultado do Tratamento , Uveíte/etiologia , Vômito/induzido quimicamente
19.
BMJ Case Rep ; 12(4)2019 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-30948393

RESUMO

Chronic non-granulomatous supraglottitis (CNGS) is a rare disorder of the supraglottic larynx, characterised by chronic supraglottic inflammation in the absence of granulomata, vasculitis, neoplasia, autoimmune disease or infective changes on histology. We present the case of a male adolescentwho attended with progressively worsening exertional dyspnoea, stridor and symptoms of obstructive sleep apnoea. Flexible nasendoscopy revealed marked supraglottic subepithelial thickening sparing the glottis and subglottis, confirmed on microlaryngoscopy. MRI of the head and neck demonstrated diffuse, homogenous supraglottic oedema. At the peak of his symptomology, the patient was admitted for further investigations and intravenous steroid therapy, and switched to prolonged oral steroids on discharge. Tracheostomy was avoided. After 3 months, he was successfully weaned from steroids to azathioprine with gradual symptomatic improvement. This case represents the first successful use of a steroid-sparing agent in the management of CNGS.


Assuntos
Azatioprina/uso terapêutico , Imunossupressores/uso terapêutico , Supraglotite/tratamento farmacológico , Adolescente , Doença Crônica , Epiglote/patologia , Humanos , Masculino , Supraglotite/patologia , Resultado do Tratamento
20.
Am J Case Rep ; 20: 300-305, 2019 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-30842390

RESUMO

BACKGROUND The aim of this study was to describe the case of a 27-year-old woman who developed Vogt-Koyanagi-Harada (VKH) disease in the 13th week of pregnancy, who was treated with high-dose oral corticosteroids and azathioprine due to its persistent course. CASE REPORT A 27-year-old East Indian woman in her 13th week of pregnancy presented with bilateral decreased visual acuity and metamorphopsia due to bilateral serous retinal detachments and was diagnosed with Vogt-Koyanagi-Harada (VKH) disease. Multimodal imaging, including blue light fundus autofluorescence (FAF), structural spectral domain optical coherence tomography (SD-OCT), en-face OCT, and OCT angiography (OCT-A), was performed at presentation and follow-up, being particularly helpful for identifying recurrences. Her treatment consisted of high-dose corticosteroid therapy, and azathioprine had to be added as an adjuvant due to the aggressive behavior of the disease. She gave birth to a healthy baby at 31 weeks of gestation and remained with 20/20 vision at 8 weeks postpartum. CONCLUSIONS To the best of our knowledge, this is the first report on the use of azathioprine in VKH disease during pregnancy with a successful outcome. Multimodal imaging avoiding the use of fundus fluorescein angiography is key in the diagnosis and follow-up of VKH disease in pregnant women.


Assuntos
Azatioprina/uso terapêutico , Imunossupressores/uso terapêutico , Complicações na Gravidez/diagnóstico por imagem , Complicações na Gravidez/tratamento farmacológico , Síndrome Uveomeningoencefálica/diagnóstico por imagem , Síndrome Uveomeningoencefálica/tratamento farmacológico , Adulto , Angiografia , Feminino , Humanos , Imagem Multimodal , Gravidez , Primeiro Trimestre da Gravidez , Tomografia de Coerência Óptica
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