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1.
Turk J Ophthalmol ; 51(4): 231-242, 2021 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-34461710

RESUMO

Immunomodulatory agents are often used in the systemic treatment of non-infectious uveitis. These drugs consist of corticosteroids, conventional immunosuppressives, and biological agents. As it is known that they suppress the immune system, the most important concern associated with immunomodulatory therapy (IMT) is the increased risk of infection. The World Health Organization declared COVID-19 a pandemic on 11 March 2020. Although severe acute respiratory distress syndrome secondary to SARS-CoV-2 infection may develop in all people, patients who receive IMT may be at higher risk in terms of both the transmission of the infection and more severe disease course. Therefore, guidelines on the management of patients receiving IMT due to uveitis during the pandemic are needed. In this review, we examined the immunomodulatory drugs used in the treatment of uveitis in terms of infectious complications and the data of patients who received IMT during the COVID-19 pandemic and discussed recommendations for the use of these drugs. According to the latest information, patients who receive IMT may continue their treatment as long as there are no disruptions in regular complete blood count (especially white blood cell count >4,000/µL) and liver and kidney function tests. Patients diagnosed with COVID-19 should be managed with a multidisciplinary approach.


Assuntos
COVID-19/epidemiologia , Glucocorticoides/uso terapêutico , Imunomodulação , Imunossupressores/uso terapêutico , SARS-CoV-2 , Uveíte/tratamento farmacológico , COVID-19/transmissão , Tomada de Decisão Clínica , Transmissão de Doença Infecciosa/prevenção & controle , Humanos , Testes de Função Renal , Contagem de Leucócitos , Testes de Função Hepática , Oftalmologia , Medição de Risco
2.
Biomolecules ; 11(7)2021 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-34356617

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent of the coronavirus disease 2019 (COVID-19) pandemic, which has been a topic of major concern for global human health. The challenge to restrain the COVID-19 pandemic is further compounded by the emergence of several SARS-CoV-2 variants viz. B.1.1.7 (Alpha), B.1.351 (Beta), P1 (Gamma) and B.1.617.2 (Delta), which show increased transmissibility and resistance towards vaccines and therapies. Importantly, there is convincing evidence of increased susceptibility to SARS-CoV-2 infection among individuals with dysregulated immune response and comorbidities. Herein, we provide a comprehensive perspective regarding vulnerability of SARS-CoV-2 infection in patients with underlying medical comorbidities. We discuss ongoing vaccine (mRNA, protein-based, viral vector-based, etc.) and therapeutic (monoclonal antibodies, small molecules, plasma therapy, etc.) modalities designed to curb the COVID-19 pandemic. We also discuss in detail, the challenges posed by different SARS-CoV-2 variants of concern (VOC) identified across the globe and their effects on therapeutic and prophylactic interventions.


Assuntos
Vacinas contra COVID-19/uso terapêutico , COVID-19/terapia , SARS-CoV-2 , Animais , Anticorpos Monoclonais Humanizados/uso terapêutico , Antimaláricos/uso terapêutico , Antivirais/uso terapêutico , COVID-19/tratamento farmacológico , COVID-19/imunologia , COVID-19/prevenção & controle , Cloroquina/uso terapêutico , Dexametasona/uso terapêutico , Gerenciamento Clínico , Glucocorticoides/uso terapêutico , Humanos , Imunização Passiva , Transplante de Células-Tronco Mesenquimais , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/imunologia
3.
Artigo em Inglês | MEDLINE | ID: mdl-34452974

RESUMO

BACKGROUND AND OBJECTIVES: Since the onset of the COVID-19 pandemic, a growing number of reports have described cases of acute disseminated encephalomyelitis (ADEM) and acute hemorrhagic leukoencephalitis (AHLE) following infection with COVID-19. Given their relatively rare occurrence, the primary objective of this systematic review was to synthesize their clinical features, response to treatments, and clinical outcomes to better understand the nature of this neurologic consequence of COVID-19 infection. METHODS: Patients with a history of COVID-19 infection were included if their reports provided adequate detail to confirm a diagnosis of ADEM or AHLE by virtue of clinical features, radiographic abnormalities, and histopathologic findings. Cases purported to be secondary to vaccination against COVID-19 or occurring in the context of a preexisting relapsing CNS demyelinating disease were excluded. Case reports and series were identified via PubMed on May 17, 2021, and 4 additional cases from the authors' hospital files supplemented the systematic review of the literature. Summary statistics were used to describe variables using a complete case analysis approach. RESULTS: Forty-six patients (28 men, median age 49.5 years, 1/3 >50 years old) were analyzed, derived from 26 case reports or series originating from 8 countries alongside 4 patient cases from the authors' hospital files. COVID-19 infection was laboratory confirmed in 91% of cases, and infection severity necessitated intensive care in 67%. ADEM occurred in 31 cases, whereas AHLE occurred in 15, with a median presenting nadir modified Rankin Scale score of 5 (bedridden). Anti-MOG seropositivity was rare (1/15 patients tested). Noninflammatory CSF was present in 30%. Hemorrhage on brain MRI was identified in 42%. Seventy percent received immunomodulatory treatments, most commonly steroids, IV immunoglobulins, or plasmapheresis. The final mRS score was ≥4 in 64% of patients with adequate follow-up information, including 32% who died. DISCUSSION: In contrast to ADEM cases from the prepandemic era, reported post-COVID-19 ADEM and AHLE cases were often advanced in age at onset, experienced severe antecedent infection, displayed an unusually high rate of hemorrhage on neuroimaging, and routinely had poor neurologic outcomes, including a high mortality rate. Findings are limited by nonstandardized reporting of cases, truncated follow-up information, and presumed publication bias.


Assuntos
COVID-19/complicações , Encefalomielite Aguda Disseminada/etiologia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Encefalomielite Aguda Disseminada/mortalidade , Encefalomielite Aguda Disseminada/fisiopatologia , Encefalomielite Aguda Disseminada/terapia , Glucocorticoides/uso terapêutico , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Unidades de Terapia Intensiva , Leucoencefalite Hemorrágica Aguda/etiologia , Leucoencefalite Hemorrágica Aguda/mortalidade , Leucoencefalite Hemorrágica Aguda/fisiopatologia , Leucoencefalite Hemorrágica Aguda/terapia , Imageamento por Ressonância Magnética , Plasmaferese , SARS-CoV-2 , Índice de Gravidade de Doença
4.
Rheumatology (Oxford) ; 60(8): 3868-3871, 2021 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-34340243

RESUMO

OBJECTIVES: Henoch-Schönlein purpura (HScP) may present in children with severe, occasionally refractory, gastrointestinal (GI) involvement. The use of corticosteroids (CSs) is commonplace in the management of the disease, but to date no standardized protocol is available and, although rare, resistance to CS therapy may be challenging to clinicians. IVIG has been proposed as an effective alternative to CSs, but to date no controlled trial has been conducted to ascertain their real efficacy. We share our personal experience of successful IVIG treatment in two cases of GI HScP, comparing it with similar experiences reported in literature. METHODS: Retrospective clinical data collection, comparison with available literature. RESULTS: We describe two children with severe HScP GI vasculitis refractory to high-dose intravenous CSs that responded rapidly to IVIG administration, with complete recovery within a few days. Patient characteristics and response to IVIG administration were comparable to those of other previously reported cases. CONCLUSION: Our observation confirms that IVIG may be useful in the treatment of CS-resistant HScP-related GI vasculitis in children, and highlights the need for more structured research, including a randomized trial against CSs, in order to ascertain their real effectiveness.


Assuntos
Glucocorticoides/uso terapêutico , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Enteropatias/tratamento farmacológico , Púrpura de Schoenlein-Henoch/tratamento farmacológico , Adolescente , Pré-Escolar , Ensaios Clínicos Controlados como Assunto , Resistência a Medicamentos , Humanos , Masculino
6.
Medicine (Baltimore) ; 100(34): e27064, 2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34449500

RESUMO

BACKGROUND: Dexmedetomidine (Dexm), a selective alpha-2 adrenoceptor agonist, and dexamethasone (Dexa), a very potent and highly selective glucocorticoid, have both been proven effectively to prolong the duration of local anesthetics (LA) in regional anesthesia. However, data comparing the efficacy of Dexm and Dexa as perineural adjuvants are inconsistent. Therefore, this systematic review and meta-analysis of randomized and quasi-randomized controlled trials (RCTs) was conducted to compare the effects of Dexm and Dexa when used as LA adjuvants on peripheral nerve block (PNB). METHODS: We systematically searched PubMed, Cochrane Library, EMBASE, Web of Science, and ScienceDirect databases up to October, 2020. The primary outcome was the duration of analgesia. Secondary outcomes included incidence of rescue analgesia, cumulative opioid consumption, time required for onset of sensory and motor blockades, duration of sensory and motor blockades, incidence of postoperative nausea and vomiting (PONV), and side effect-associated outcomes (e.g., bradycardia, sedation, hypotension, rates of infection, and neurological complications). The study was registered on PROSPERO, number CRD42020188796. RESULTS: After screening of full-text relevant articles, 13 RCTs that met the inclusion criteria were retrieved for this systematic review. It was revealed that perineural Dexm provided equivalent analgesic duration to perineural Dexa. Besides, the intake of Dexm increased the incidence of rescue analgesia in limbs surgery, as well as the cumulative opioid consumption, and decreased the time required for onset of sensory and motor blockades for long-acting LA (all P < .05). Other analysis revealed insignificant difference between the 2 groups in terms of the incidence of PONV (P > .05). Additionally, 2 studies demonstrated that Dexm possesses more sedative properties than Dexa (P < .05). CONCLUSIONS: This meta-analysis indicated that the analgesic duration of Dexm and Dexa as LA adjuvants in PNB is the same. Meanwhile, the effects of perineural Dexm and Dexa on some secondary outcomes, including the incidence of rescue analgesia, cumulative opioid consumption, and time required for onset of sensory and motor blockades, are associated with the surgical site and type of LA.


Assuntos
Agonistas de Receptores Adrenérgicos alfa 2/uso terapêutico , Anestesia Local/métodos , Dexametasona/uso terapêutico , Dexmedetomidina/uso terapêutico , Glucocorticoides/uso terapêutico , Bloqueio Nervoso/métodos , Adjuvantes Anestésicos , Agonistas de Receptores Adrenérgicos alfa 2/administração & dosagem , Dexametasona/administração & dosagem , Dexmedetomidina/administração & dosagem , Glucocorticoides/administração & dosagem , Humanos , Nervos Periféricos , Ensaios Clínicos Controlados Aleatórios como Assunto
7.
Can Respir J ; 2021: 9621572, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34457096

RESUMO

Asthmatics are at an increased risk of developing exacerbations after being infected by respiratory viruses such as influenza virus, parainfluenza virus, and human and severe acute respiratory syndrome coronaviruses (SARS-CoV). Asthma, especially when poorly controlled, is an independent risk factor for developing pneumonia. A subset of asthmatics can have significant defects in their innate, humoral, and cell-mediated immunity arms, which may explain the increased susceptibility to infections. Adequate asthma control is associated with a significant decrease in episodes of exacerbation. Because of their wide availability and potency to promote adequate asthma control, glucocorticoids, especially inhaled ones, are the cornerstone of asthma management. The current COVID-19 pandemic affects millions of people worldwide and possesses mortality several times that of seasonal influenza; therefore, it is necessary to revisit this subject. The pathogenesis of SARS-CoV-2, the virus that causes COVID-19, can potentiate the development of acute asthmatic exacerbation with the potential to worsen the state of chronic airway inflammation. The relationship is evident from several studies that show asthmatics experiencing a more adverse clinical course of SARS-CoV-2 infection than nonasthmatics. Recent studies show that dexamethasone, a potent glucocorticoid, and other inhaled corticosteroids significantly reduce morbidity and mortality among hospitalized COVID-19 patients. Hence, while we are waiting for more studies with higher level of evidence that further narrate the association between COVID-19 and asthma, we advise clinicians to try to achieve adequate disease control in asthmatics as it may reduce incidences and severity of exacerbations especially from SARS-CoV-2 infection.


Assuntos
Asma/complicações , Asma/prevenção & controle , COVID-19/complicações , Dexametasona/uso terapêutico , Glucocorticoides/uso terapêutico , COVID-19/mortalidade , COVID-19/terapia , Humanos
8.
BMC Gastroenterol ; 21(1): 331, 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34433425

RESUMO

BACKGROUND: There are few reports about the effect of glucocorticoids in the treatment of acute pancreatitis in humans. This study aims to evaluate the effect of glucocorticoids in the treatment of acute pancreatitis by propensity score matching analysis. RESULTS: Acute pancreatitis patients admitted between 2014 and 2019 were collected from the database and analyzed. Included patients were divided into the glucocorticoids-used group (GC group) and the non-glucocorticoids-used group (NGC group) according to whether glucocorticoids were used. A total of 818 eligible patients were included in the final analysis. Seventy-six patients were treated with glucocorticoids, and 742 patients were treated without glucocorticoids. Before propensity score matching, the triglyceride levels (38.2 ± 18.5 vs. 20.2 ± 16.8, P < 0.05) and Acute Physiology and Chronic Health Evaluation II (APACHE II) scores (7.1 ± 2.5 vs. 4.5 ± 2.1, P < 0.05) at admission were significantly higher in the GC group than in the NGC group. The incidence of multi-organ failure (33.3% vs. 11.9%, P < 0.05) was significantly higher in the GC group than in the NGC group. Patients in the GC group showed a positive balance of fluid intake and output over 72 h. After 1:1 propensity score matching, 59 patients from each group (GC and NGC) were included in the analysis. There were no significant differences in age, sex, body mass index, triglycerides, or APACHE II scores between the two groups (P > 0.05), and the patients' clinical outcomes were reversed. The proportion of patients with organ failure (40.7% vs. 52.5%, p < 0.05) and multi-organ failure (35.0% vs. 67.7%, P < 0.05) was significantly lower in the GC group than in the NGC group. Furthermore, patients in the GC group had significantly shorter lengths of hospital stay (12.9 ± 5.5 vs. 16.3 ± 7.7, P < 0.05) and costs (25,348.4 ± 2512.6vs. 32,421.7 ± 2813.3, P < 0.05) than those in the NGC group. CONCLUSIONS: This study presents preliminary confirmation of the beneficial effect of glucocorticoids in the treatment of acute pancreatitis. More high-quality prospective studies are needed in the future.


Assuntos
Glucocorticoides , Pancreatite , APACHE , Doença Aguda , Glucocorticoides/uso terapêutico , Humanos , Pancreatite/tratamento farmacológico , Pontuação de Propensão
9.
Eur J Pharmacol ; 908: 174374, 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34303662

RESUMO

The efficacy of corticosteroids and its use for the treatment of SARS-CoV-2 infections is controversial. In this study, using data sets of SARS-CoV-2 infected lung tissues and nasopharyngeal swabs, as well as in vitro experiments, we show that SARS-CoV-2 infection significantly downregulates DUSP1 expression. This downregulation of DUSP1 could be the mechanism regulating the enhanced activation of MAPK pathway as well as the reported steroid resistance in SARS-CoV-2 infection. Moreover, chloroquine, an off labeled COVID-19 drug is able to induce DUSP1 and attenuate MAPK pathway; and is expected to improve sensitivity to steroid treatment. However, further mechanistic studies are required to confirm this effect.


Assuntos
COVID-19/tratamento farmacológico , Cloroquina/farmacologia , Fosfatase 1 de Especificidade Dupla/genética , Glucocorticoides/farmacologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Adulto , Idoso , COVID-19/patologia , COVID-19/virologia , Estudos de Casos e Controles , Células Cultivadas , Cloroquina/uso terapêutico , Conjuntos de Dados como Assunto , Regulação para Baixo/efeitos dos fármacos , Resistência a Medicamentos/efeitos dos fármacos , Resistência a Medicamentos/genética , Sinergismo Farmacológico , Fosfatase 1 de Especificidade Dupla/metabolismo , Fibroblastos , Glucocorticoides/uso terapêutico , Voluntários Saudáveis , Humanos , Pulmão/citologia , Pulmão/patologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/genética , Pessoa de Meia-Idade , Nasofaringe/virologia , Uso Off-Label , Cultura Primária de Células , SARS-CoV-2/isolamento & purificação , SARS-CoV-2/patogenicidade
10.
Arthritis Care Res (Hoboken) ; 73(8): 1071-1087, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34235871

RESUMO

OBJECTIVE: To provide evidence-based recommendations and expert guidance for the management of giant cell arteritis (GCA) and Takayasu arteritis (TAK) as exemplars of large vessel vasculitis. METHODS: Clinical questions regarding diagnostic testing, treatment, and management were developed in the population, intervention, comparator, and outcome (PICO) format for GCA and TAK (27 for GCA, 27 for TAK). Systematic literature reviews were conducted for each PICO question. The Grading of Recommendations Assessment, Development and Evaluation methodology was used to rate the quality of the evidence. Recommendations were developed by the Voting Panel, comprising adult and pediatric rheumatologists and patients. Each recommendation required ≥70% consensus among the Voting Panel. RESULTS: We present 22 recommendations and 2 ungraded position statements for GCA, and 20 recommendations and 1 ungraded position statement for TAK. These recommendations and statements address clinical questions relating to the use of diagnostic testing, including imaging, treatments, and surgical interventions in GCA and TAK. Recommendations for GCA include support for the use of glucocorticoid-sparing immunosuppressive agents and the use of imaging to identify large vessel involvement. Recommendations for TAK include the use of nonglucocorticoid immunosuppressive agents with glucocorticoids as initial therapy. There were only 2 strong recommendations; the remaining recommendations were conditional due to the low quality of evidence available for most PICO questions. CONCLUSION: These recommendations provide guidance regarding the evaluation and management of patients with GCA and TAK, including diagnostic strategies, use of pharmacologic agents, and surgical interventions.


Assuntos
Arterite de Células Gigantes/tratamento farmacológico , Glucocorticoides/uso terapêutico , Imunossupressores/uso terapêutico , Reumatologia/normas , Arterite de Takayasu/tratamento farmacológico , Tomada de Decisão Clínica , Consenso , Técnicas de Apoio para a Decisão , Quimioterapia Combinada , Medicina Baseada em Evidências/normas , Arterite de Células Gigantes/diagnóstico , Arterite de Células Gigantes/imunologia , Glucocorticoides/efeitos adversos , Humanos , Imunossupressores/efeitos adversos , Arterite de Takayasu/diagnóstico , Arterite de Takayasu/imunologia , Resultado do Tratamento
11.
Arthritis Care Res (Hoboken) ; 73(8): 1061-1070, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34235889

RESUMO

OBJECTIVE: To provide evidence-based recommendations and expert guidance for the management of systemic polyarteritis nodosa (PAN). METHODS: Twenty-one clinical questions regarding diagnostic testing, treatment, and management were developed in the population, intervention, comparator, and outcome (PICO) format for systemic, non-hepatitis B-related PAN. Systematic literature reviews were conducted for each PICO question. The Grading of Recommendations Assessment, Development and Evaluation methodology was used to assess the quality of evidence and formulate recommendations. Each recommendation required ≥70% consensus among the Voting Panel. RESULTS: We present 16 recommendations and 1 ungraded position statement for PAN. Most recommendations were graded as conditional due to the paucity of evidence. These recommendations support early treatment of severe PAN with cyclophosphamide and glucocorticoids, limiting toxicity through minimizing long-term exposure to both treatments, and the use of imaging and tissue biopsy for disease diagnosis. These recommendations endorse minimizing risk to the patient by using established therapy at disease onset and identify new areas where adjunctive therapy may be warranted. CONCLUSION: These recommendations provide guidance regarding diagnostic strategies, use of pharmacologic agents, and imaging for patients with PAN.


Assuntos
Ciclofosfamida/uso terapêutico , Glucocorticoides/uso terapêutico , Imunossupressores/uso terapêutico , Poliarterite Nodosa/tratamento farmacológico , Reumatologia/normas , Tomada de Decisão Clínica , Consenso , Ciclofosfamida/efeitos adversos , Técnicas de Apoio para a Decisão , Quimioterapia Combinada , Medicina Baseada em Evidências/normas , Glucocorticoides/efeitos adversos , Humanos , Imunossupressores/efeitos adversos , Poliarterite Nodosa/diagnóstico , Poliarterite Nodosa/imunologia , Índice de Gravidade de Doença , Resultado do Tratamento
13.
Arthritis Rheumatol ; 73(8): 1384-1393, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34235883

RESUMO

OBJECTIVE: To provide evidence-based recommendations and expert guidance for the management of systemic polyarteritis nodosa (PAN). METHODS: Twenty-one clinical questions regarding diagnostic testing, treatment, and management were developed in the population, intervention, comparator, and outcome (PICO) format for systemic, non-hepatitis B-related PAN. Systematic literature reviews were conducted for each PICO question. The Grading of Recommendations Assessment, Development and Evaluation methodology was used to assess the quality of evidence and formulate recommendations. Each recommendation required ≥70% consensus among the Voting Panel. RESULTS: We present 16 recommendations and 1 ungraded position statement for PAN. Most recommendations were graded as conditional due to the paucity of evidence. These recommendations support early treatment of severe PAN with cyclophosphamide and glucocorticoids, limiting toxicity through minimizing long-term exposure to both treatments, and the use of imaging and tissue biopsy for disease diagnosis. These recommendations endorse minimizing risk to the patient by using established therapy at disease onset and identify new areas where adjunctive therapy may be warranted. CONCLUSION: These recommendations provide guidance regarding diagnostic strategies, use of pharmacologic agents, and imaging for patients with PAN.


Assuntos
Antirreumáticos/uso terapêutico , Medicina Baseada em Evidências/normas , Poliarterite Nodosa , Reumatologia/normas , Ciclofosfamida/uso terapêutico , Gerenciamento Clínico , Glucocorticoides/uso terapêutico , Humanos , Poliarterite Nodosa/diagnóstico , Poliarterite Nodosa/diagnóstico por imagem , Poliarterite Nodosa/tratamento farmacológico , Estados Unidos
15.
BMJ Case Rep ; 14(7)2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34244184

RESUMO

Ozurdex is a dexamethasone intravitreal implant used for the treatment of macular oedema. A rare but serious complication is the migration of the implant into the anterior chamber (AC) in eyes with absent or incomplete posterior capsules that may lead to corneal decompensation. We report the case of a 75-year-old woman who presented with a 1-day history of decreased vision in her left eye. She had a history of complicated cataract surgery and had received multiple Ozurdex implants for postoperative cystoid macular oedema in the same eye. She had significant left corneal decompensation and a mobile Ozurdex implant in the AC. We report a simple but novel surgical technique for removing an Ozurdex implant from the AC using an intravenous cannula (Venflon). This technique can also be applied to removing a fluocinolone acetonide (Iluvien) implant in similar situations.


Assuntos
Retinopatia Diabética , Edema Macular , Idoso , Câmara Anterior , Cânula , Dexametasona/efeitos adversos , Implantes de Medicamento , Feminino , Fluocinolona Acetonida/uso terapêutico , Glucocorticoides/uso terapêutico , Humanos , Injeções Intravítreas , Edema Macular/tratamento farmacológico
16.
Paediatr Drugs ; 23(4): 331-347, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34244988

RESUMO

Childhood-onset systemic lupus erythematosus (cSLE) is a prototype of a multisystemic, inflammatory, heterogeneous autoimmune condition. This disease is characterized by simultaneous or sequential organ and system involvement, with unpredictable flare and high levels of morbidity and mortality. Racial/ethnic background, socioeconomic status, cost of medications, difficulty accessing health care, and poor adherence seem to impact lupus outcomes and treatment response. In this article, the management of cSLE patients is updated. Regarding pathogenesis, a number of potential targets for drugs have been studied. However, most treatments in pediatric patients are off-label drugs with recommendations based on inadequately powered studies, therapeutic consensus guidelines, or case series. Management practices for cSLE patients include evaluations of disease activity and cumulative damage scores, routine non-live vaccinations, physical activity, and addressing mental health issues. Antimalarials and glucocorticoids are still the most common drugs used to treat cSLE, and hydroxychloroquine is recommended for nearly all cSLE patients. Disease-modifying antirheumatic drugs (DMARDs) should be standardized for each patient, based on disease flare and cSLE severity. Mycophenolate mofetil or intravenous cyclophosphamide is suggested as induction therapy for lupus nephritis classes III and IV. Calcineurin inhibitors (cyclosporine, tacrolimus, voclosporin) appear to be another good option for cSLE patients with lupus nephritis. Regarding B-cell-targeting biologic agents, rituximab may be used for refractory lupus nephritis patients in combination with another DMARD, and belimumab was recently approved by the US Food and Drug Administration for cSLE treatment in children aged > 5 years. New therapies targeting CD20, such as atacicept and telitacicept, seem to be promising drugs for SLE patients. Anti-interferon therapies (sifalimumab and anifrolumab) have shown beneficial results in phase II randomized control trials in adult SLE patients, as have some Janus kinase inhibitors, and these could be alternative treatments for pediatric patients with severe interferon-mediated inflammatory disease in the future. In addition, strict control of proteinuria and blood pressure is required in cSLE, especially with angiotensin-converting enzyme inhibitor and angiotensin receptor blocker use.


Assuntos
Gerenciamento Clínico , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Idade de Início , Anticorpos Monoclonais Humanizados/uso terapêutico , Antirreumáticos/uso terapêutico , Criança , Glucocorticoides/uso terapêutico , Humanos , Imunossupressores/uso terapêutico , Imunoterapia/métodos , Lúpus Eritematoso Sistêmico/imunologia , Ácido Micofenólico/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto
17.
Vnitr Lek ; 67(4): 224-229, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34275308

RESUMO

Giant cell arteritis is the most common vasculitis in adults. The author presents the latest findings in diagnostics and treatment emphasising the growing importance of non-invasive examination methods where a biopsy of the temporal artery is no longer considered the only possible examination that confirms the diagnosis. He emphasises the importance of early diagnosis and initiation of treatment and also points out difficulties in treatment, especially frequent relapses. In addition to glucocorticoids, modern drugs influencing the decisive factors in the pathogenesis of inflammation are beginning to gain ground in treatment. Despite of new findings, there is a number of controversial issues remaining that the author addresses in more details: from terminology and epidemiology to diagnosis and treatment.


Assuntos
Arterite de Células Gigantes , Biópsia , Arterite de Células Gigantes/diagnóstico , Arterite de Células Gigantes/tratamento farmacológico , Glucocorticoides/uso terapêutico , Humanos , Inflamação , Masculino , Artérias Temporais
18.
Front Endocrinol (Lausanne) ; 12: 649405, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34220705

RESUMO

The finding that high-dose dexamethasone improves survival in those requiring critical care due to COVID-19 will mean much greater usage of glucocorticoids in the subsequent waves of coronavirus infection. Furthermore, the consistent finding of adverse outcomes from COVID-19 in individuals with obesity, hypertension and diabetes has focussed attention on the metabolic dysfunction that may arise with critical illness. The SARS coronavirus itself may promote relative insulin deficiency, ketogenesis and hyperglycaemia in susceptible individuals. In conjunction with prolonged critical care, these components will promote a catabolic state. Insulin infusion is the mainstay of therapy for treatment of hyperglycaemia in acute illness but what is the effect of insulin on the admixture of glucocorticoids and COVID-19? This article reviews the evidence for the effect of insulin on clinical outcomes and intermediary metabolism in critical illness.


Assuntos
COVID-19/tratamento farmacológico , Glucocorticoides/efeitos adversos , Insulina/uso terapêutico , Doenças Metabólicas/induzido quimicamente , Doenças Metabólicas/prevenção & controle , COVID-19/complicações , Cuidados Críticos/métodos , Estado Terminal/terapia , Dexametasona/efeitos adversos , Dexametasona/uso terapêutico , Complicações do Diabetes/diagnóstico , Complicações do Diabetes/tratamento farmacológico , Complicações do Diabetes/mortalidade , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/mortalidade , Diabetes Mellitus/virologia , Glucocorticoides/uso terapêutico , Humanos , Hiperglicemia/complicações , Hiperglicemia/tratamento farmacológico , Hiperglicemia/mortalidade , Doenças Metabólicas/etiologia , Obesidade/complicações , Obesidade/tratamento farmacológico , Obesidade/mortalidade , SARS-CoV-2/fisiologia , Resultado do Tratamento
19.
Pediatr Rheumatol Online J ; 19(1): 104, 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34193201

RESUMO

BACKGROUND: H syndrome (HS) is a rare autoinflammatory disease caused by a mutation in the solute carrier family 29, member 3 (SCL29A3) gene. It has a variable clinical presentation and little phenotype-genotype correlation. The pathognomonic sign of HS is cutaneous hyperpigmentation located mainly in the inner thighs and often accompanied by other systemic manifestations. Improvement after tocilizumab treatment has been reported in a few patients with HS. We report the first patient with HS who presented cardiogenic shock, multiorgan infiltration, and digital ischemia. CASE PRESENTATION: 8-year-old boy born to consanguineous parents of Moroccan origin who was admitted to the intensive care unit during the Coronavirus Disease-2019 (COVID-19) pandemic with tachypnoea, tachycardia, and oliguria. Echocardiography showed dilated cardiomyopathy and severe systolic dysfunction compatible with cardiogenic shock. Additionally, he presented with multiple organ dysfunction syndrome. SARS-CoV-2 polymerase chain reaction (PCR) and antibody detection by chromatographic immunoassay were negative. A previously ordered gene panel for pre-existing sensorineural hearing loss showed a pathological mutation in the SCL29A3 gene compatible with H syndrome. Computed tomography scan revealed extensive alveolar infiltrates in the lungs and multiple poor defined hypodense lesions in liver, spleen, and kidneys; adenopathy; and cardiomegaly with left ventricle subendocardial nodules. Invasive mechanical ventilation, broad antibiotic and antifungal coverage showed no significant response. Therefore, Tocilizumab as compassionate use together with pulsed intravenous methylprednisolone was initiated. Improvement was impressive leading to normalization of inflammation markers, liver and kidney function, and stabilising heart function. Two weeks later, he was discharged and has been clinically well since then on two weekly administration of Tocilizumab. CONCLUSIONS: We report the most severe disease course produced by HS described so far in the literature. Our patient's manifestations included uncommon, new complications such as acute heart failure with severe systolic dysfunction, multi-organ cell infiltrate, and digital ischemia. Most of the clinical symptoms of our patient could have been explained by SARS-CoV-2, demonstrating the importance of a detailed differential diagnosis to ensure optimal treatment. Although the mechanism of autoinflammation of HS remains uncertain, the good response of our patient to Tocilizumab makes a case for the important role of IL-6 in this syndrome and for considering Tocilizumab as a first-line treatment, at least in severely affected patients.


Assuntos
Cardiomiopatia Dilatada/fisiopatologia , Doenças Hereditárias Autoinflamatórias/fisiopatologia , Isquemia/fisiopatologia , Insuficiência de Múltiplos Órgãos/fisiopatologia , Choque Cardiogênico/fisiopatologia , Anticorpos Monoclonais Humanizados/uso terapêutico , COVID-19 , Cardiomiopatia Dilatada/diagnóstico por imagem , Cardiomiopatia Dilatada/terapia , Criança , Glucocorticoides/uso terapêutico , Doenças Hereditárias Autoinflamatórias/diagnóstico , Doenças Hereditárias Autoinflamatórias/genética , Doenças Hereditárias Autoinflamatórias/terapia , Humanos , Isquemia/terapia , Nefropatias/diagnóstico por imagem , Nefropatias/fisiopatologia , Nefropatias/terapia , Hepatopatias/diagnóstico por imagem , Hepatopatias/fisiopatologia , Hepatopatias/terapia , Pneumopatias/diagnóstico por imagem , Pneumopatias/fisiopatologia , Pneumopatias/terapia , Linfadenopatia/diagnóstico por imagem , Linfadenopatia/fisiopatologia , Linfadenopatia/terapia , Masculino , Metilprednisolona/uso terapêutico , Insuficiência de Múltiplos Órgãos/terapia , Proteínas de Transporte de Nucleosídeos/genética , Pulsoterapia , Respiração Artificial , SARS-CoV-2 , Choque Cardiogênico/terapia , Esplenopatias/diagnóstico por imagem , Esplenopatias/fisiopatologia , Esplenopatias/terapia , Dedos do Pé/irrigação sanguínea , Tomografia Computadorizada por Raios X , Resultado do Tratamento
20.
BMJ Case Rep ; 14(7)2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34290006

RESUMO

This case report concerns a 63-year-old man affected by metastatic undifferentiated liposarcoma. After receiving pembrolizumab as a second-line treatment in a clinical trial, the patient experienced an immune-mediated myocarditis, myositis and myasteniform syndrome. The last two adverse events showed significant clinical relevance in terms of severity, duration and the required specific treatment.Initial treatment approach consisted in pulses of 1 g of methylprednisolone, followed by 2 mg/kg/day, with clinical improvement. After 12 days, the immune-mediated myasteniform syndrome worsened, with dysphagia, dysphonia, bilateral palpebral ptosis and respiratory difficulty. Due to the refractoriness to glucocorticoid treatment, it was decided to initiate intravenous immunoglobulin at 2 g/kg, followed by 2 mg/kg every 4 weeks once discharged and mycophenolate 500 mg/12 hours, in order to reduce the dose of glucocorticoids.After 2 months, the patient presented an optimal clinical evolution, without muscular weakness and referred to an improvement in dysphagia and speech.


Assuntos
Anticorpos Monoclonais Humanizados , Miosite , Anticorpos Monoclonais Humanizados/efeitos adversos , Glucocorticoides/uso terapêutico , Humanos , Masculino , Metilprednisolona , Pessoa de Meia-Idade , Miosite/induzido quimicamente
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