Recommendations for evaluation and diagnosis of extra-glandular manifestations of primary Sjögren syndrome: results of an epidemiologic systematic review/meta-analysis and a consensus guideline from the Brazilian society of rheumatology (hepatic, gastrointestinal and pancreatic).

Sjogren's syndrome (SS) is an autoimmune disease characterized by lymphocytic infiltration of the exocrine glands and other organs, associated with sicca syndrome but also with systemic involvement with varying degrees of severity. Despite their importance, some systemic manifestations, mainly liver, gastrointestinal, and pancreatic are not routinely evaluated. To address these manifestations, the Sjögren's Syndrome Committee of the Brazilian Society of Rheumatology conducted a broad systematic review of the literature on studies investigating prevalence and diagnosis of these symptoms in Sjogren´s patients and made recommendations based on the findings. Agreement between the experts was achieved using the Delphi method. This is the second part of this guideline, providing 6 recommendations for liver, gastrointestinal, and pancreatic care of SS patients.

Recommendations for evaluation and diagnosis of extra-glandular manifestations of primary sjogren syndrome: results of an epidemiologic systematic review/meta-analysis and a consensus guideline from the Brazilian Society of Rheumatology (articular, pulmonary and renal).

Sjogren's Syndrome (SS) is an autoimmune disease characterized by lymphocytic infiltration of the exocrine glands and other organs, associated with sicca syndrome but also with systemic involvement with varying degrees of severity. Despite their importance, these systemic manifestations are not routinely evaluated and there is no homogenous approach to their diagnosis or evaluation. To close this gap, a panel of experts from the Brazilian Society of Rheumatology conducted a systematic review and meta-analysis on the identification of epidemiologic and clinical features of these manifestations and made recommendations based on the findings. Agreement between the experts was achieved using the Delphi method. The first part of this guideline summarizes the most important topics, and 11 recommendations are provided for the articular, pulmonary, and renal care of SS patients.

Recommendations for evaluation and diagnosis of extra-glandular manifestations of primary Sjögren syndrome: results of an epidemiologic systematic review/ meta-analysis and a consensus guideline from the Brazilian society of rheumatology (hepatic, gastrointestinal and pancreatic)

Abstract Sjogren's syndrome (SS) is an autoimmune disease characterized by lymphocytic infiltration of the exocrine glands and other organs, associated with sicca syndrome but also with systemic involvement with varying degrees of severity. Despite their importance, some systemic manifestations, mainly liver, gastrointestinal, and pancreatic are not routinely evaluated. To address these manifestations, the Sjögren's Syndrome Committee of the Brazilian Society of Rheumatology conducted a broad systematic review of the literature on studies investigating prevalence and diagnosis of these symptoms in Sjogren´s patients and made recommendations based on the findings. Agreement between the experts was achieved using the Delphi method. This is the second part of this guideline, providing 6 recommendations for liver, gastrointestinal, and pancreatic care of SS patients.

Recommendations for evaluation and diagnosis of extra-glandular manifestations of primary sjogren syndrome: results of an epidemiologic systematic review/ meta-analysis and a consensus guideline from the Brazilian Society of Rheumatology (articular, pulmonary and renal)

Abstract Sjogren's Syndrome (SS) is an autoimmune disease characterized by lymphocytic infiltration of the exocrine glands and other organs, associated with sicca syndrome but also with systemic involvement with varying degrees of severity. Despite their importance, these systemic manifestations are not routinely evaluated and there is no homogenous approach to their diagnosis or evaluation. To close this gap, a panel of experts from the Brazilian Society of Rheumatology conducted a systematic review and meta-analysis on the identification of epidemiologic and clinical features of these manifestations and made recommendations based on the findings. Agreement between the experts was achieved using the Delphi method. The first part of this guideline summarizes the most important topics, and 11 recommendations are provided for the articular, pulmonary, and renal care of SS patients.

2021 recommendations of the Brazilian Society of Rheumatology for the gynecological and obstetric care of patients with Sjogren's syndrome.

Sjogren's syndrome (SS) is an autoimmune disease characterized by lymphocytic infiltration of the exocrine glands and other organs. Women with SS often experience gynecological symptoms due to the disease and need extra care regarding their sexual activity, reproductive health and during pregnancy, conditions that are not properly conducted in the clinical practice. To cover this gap, a panel of experts from the Brazilian Society of Rheumatology conducted a systematic review and meta-analysis on the identification of symptoms, diagnosis, monitoring, prognosis, and treatment of these manifestations. A Focus Group meeting was held and included experts in the field and methodologists, based on a previously developed script, with themes related to the objective of the study. The most important topics were summarized and 11 recommendations were provided.

2021 recommendations of the Brazilian Society of Rheumatology for the gynecological and obstetric care of patients with Sjogren's syndrome

Abstract Sjogren's syndrome (SS) is an autoimmune disease characterized by lymphocytic infiltration of the exocrine glands and other organs. Women with SS often experience gynecological symptoms due to the disease and need extra care regarding their sexual activity, reproductive health and during pregnancy, conditions that are not properly conducted in the clinical practice. To cover this gap, a panel of experts from the Brazilian Society of Rheumatology conducted a systematic review and meta-analysis on the identification of symptoms, diagnosis, monitoring, prognosis, and treatment of these manifestations. A Focus Group meeting was held and included experts in the field and methodologists, based on a previously developed script, with themes related to the objective of the study. The most important topics were summarized and 11 recommendations were provided.

Effectiveness and safety of abatacept for the treatment of patients with primary Sjögren's syndrome.

Sjögren's syndrome is an autoimmune disease characterized by inflammation of the exocrine glands. The disease can be primary or secondary (if it is associated with another autoimmune disease). In Barring symptom management, there is no established treatment. To evaluate the effectiveness and safety of abatacept as a treatment of primary Sjögren's syndrome over the course of 24 months. Eleven patients with primary Sjögren's syndrome from the Rheumatology Department of Universidade Santo Amaro, Sao Paulo, Brazil were enrolled for a prospective observational study. Eligible participants were diagnosed according to the 2002 American-European consensus criteria and had a score greater than 3 on the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI). Participants received intravenous abatacept for 24 months at a weight-adjusted dose of 500 mg for patients weighing < 60 kg and 750 mg for those weighing > 60 kg. The outcomes were ESSDAI activity index, non-stimulated salivary flow rate, ocular dryness (Schirmer test, tear film break-up time, and ocular staining score), SF-36 questionnaire, and Fatigue domain of the FACIT (Functional Assessment of Chronic Illness Therapy) index. There was a statistically significant reduction in ESSDAI index and improvement of salivary flow. One subscale of the SF-36 index-emotional role functioning-showed improvement. There was no change in ocular parameters or in the FACIT index. In this sample of 11 patients with primary Sjögren's syndrome, abatacept therapy improved xerostomia and systemic disease activity.Key Points• Abatacept is safe and effective for the treatment of primary Sjögren's syndrome.• Abatacept can improve salivary flow and ESSDAI index in this patient population.

Recommendations from the Brazilian society of rheumatology for the diagnosis of Sjögren's syndrome (Part I): glandular manifestations (systematic review).

BACKGROUND: Primary Sjögren's syndrome (pSS) is a systemic immune-mediated disease whose main characteristic is exocrine gland inflammation and, subsequent reduction in tear and saliva production. A delayed diagnosis is common due to the nonspecific clinical manifestations of disease. The aim of the present study was to develop recommendations for the diagnosis of glandular manifestations of pSS based on evidence and expert opinion. We conducted a systematic literature review to retrieve the best evidence available on the accuracy of diagnostic tests for pSS. We also held two in-person meetings with experts (rheumatologists, pathologists, ophthalmologists and dentists) to establish their level of agreement using the Delphi method. Ultimately, we generated 18 recommendations that aim to facilitate the diagnosis of the glandular manifestations of pSS. CONCLUSION: The diagnosis of glandular manifestations of pSS is complex and multidisciplinary. It requires specific knowledge in the field of ophthalmology, immunology, pathology and imaging, making it compulsory for the rheumatologist to work with professionals from these different areas in order to improve accuracy and early diagnosis. Glandular dysfunction tests, ANA, RF, Anti-Ro, protein electrophoresis, urinalysis, blood count, C-Reactive protein, complement, testing for syphilis and viruses (HCV, HIV) and SGUS should be investigated when dryness or systemic manifestation are present. Minor salivary gland biopsy is recommended for all anti-Ro negative or incomplete criteria cases.

Low-level laser therapy for xerostomia in primary Sjögren's syndrome: a randomized trial.

To evaluate the effectiveness of low-level laser therapy (LLLT) in the treatment of xerostomia in primary Sjögren's syndrome (SS), a randomized clinical trial of patients with dry mouth symptoms associated with primary SS receiving care at a university hospital was conducted. Sixty-six patients were randomly assigned with a 1:1 allocation ratio to receive LLLT (laser group, n = 33) or placebo treatment (placebo group, n = 33). Patients in the laser group received LLLT twice a week for 6 weeks, for a total of 12 treatment sessions. Laser irradiation was performed with an aluminum-gallium-arsenide laser diode at a wavelength of 808 nm, 100-mW output power, and energy density of 4.0 J/cm2 per irradiation point per session. Placebo treatment was performed following the same protocol used for irradiated patients and using the same laser device to mimic a real irradiation, but with no active laser emission and the tip of the laser probe covered with aluminum foil. The outcomes of interest were xerostomia inventory scores, salivary flow rate, salivary beta-2 microglobulin levels, and salivary sodium and chlorine concentrations. Patients in both groups showed no improvement in xerostomia. Likewise, there was no significant improvement in xerostomia inventory scores (p = 0.301) or salivary flow rate (p = 0.643) in either group. There was no difference in salivary beta-2 microglobulin levels, sodium concentration, and chlorine concentration before and after intervention or between the two groups. The LLLT protocol used in this study effected no improvement in xerostomia or salivary flow rate in patients with primary SS. ClinicalTrials.gov Identifier: NCT02066896.

Salivary gland ultrasonography as a predictor of clinical activity in Sjögren's syndrome.

PURPOSE: Primary Sjögren's syndrome is a multisystem autoimmune disease characterized by hypofunction of salivary and lacrimal glands and possible multi-organ system manifestations. Over the past 15 years, three sets of diagnostic criteria have been proposed, but none has included salivary gland ultrasonography. However, recent studies support its role in the diagnosis and prognostic evaluation of patients with Sjögren's syndrome. This study aimed to determine the value of salivary gland ultrasonography in the diagnosis and prognosis of Sjögren's syndrome by relating ultrasonography severity scores to clinical and laboratory data. METHODS: Seventy patients who fulfilled the 2002 American-European Consensus Group diagnostic criteria for primary Sjögren's syndrome were selected from 84 patients receiving care in specialized outpatient clinics at our institution from November 2013 to May 2016. Their serology, European League Against Rheumatism Sjögren's syndrome disease activity index (ESSDAI), salivary flow rate, immunoglobulin G, and salivary and serum beta-2 microglobulin levels were measured. Salivary gland ultrasonography was performed by an experienced radiologist, using scores of 1-4 to classify salivary gland impairment. RESULTS: Salivary gland ultrasonography scores of 1 or 2 were associated with an ESSDAI < 5. Ultrasonography scores of 3 or 4 were associated with an ESSDAI ≥5 (p = 0.064), a positive antinuclear antibody test (p = 0.006), positive anti-Ro/SSA antibodies (p = 0.003), positive anti-La/SSB antibodies (p = 0.077), positive rheumatoid factor (p = 0.034), and immunoglobulin G levels > 1600 mg/dL (p = 0.077). Salivary flow rate was lower in patients with scores 3 or 4 (p = 0.001). CONCLUSION: This study provides further evidence that salivary gland ultrasonography can be used not only for diagnosis but also for prognostic evaluation of primary Sjögren's syndrome. These findings confirm what has been reported in the literature. However, further analyses involving larger matched samples are required to support this finding and include salivary gland ultrasonography as part of the diagnostic criteria for Sjögren's syndrome.

Management of necrotizing scleritis after pterygium surgery with rituximab.

The authors present a case of necrotizing scleritis after pterygium excision successfully treated with rituximab after attempts with high doses of corticosteroids and immunosuppressive drugs. A literature review revealed case reports and a phase I/II dose-ranging randomized clinical trial using rituximab for necrotizing scleritis with or without association with autoimmune disease. This is the only case report on rituximab treatment for necrotizing scleritis after pterygium surgery. In cases with refractoriness to immunosuppressive drugs, a CD20 antibody can be used.

Management of necrotizing scleritis after pterygium surgery with rituximab / Tratamento com rituximabe de esclerite necrosante após cirurgia de pterigeo

ABSTRACT The authors present a case of necrotizing scleritis after pterygium excision successfully treated with rituximab after attempts with high doses of corticosteroids and immunosuppressive drugs. A literature review revealed case reports and a phase I/II dose-ranging randomized clinical trial using rituximab for necrotizing scleritis with or without association with autoimmune disease. This is the only case report on rituximab treatment for necrotizing scleritis after pterygium surgery. In cases with refractoriness to immunosuppressive drugs, a CD20 antibody can be used.

RESUMO Os autores apresentam um caso de sucesso no tratamento com rituximabe de esclerite necrosante após cirurgia de pterígio refratário a altas doses de corticosteroides e drogas imunossupressoras. Uma revisão da literatura direcionada ao uso de rituximabe para tratamento de esclerites necrosantes revelou relatos de casos e um estudo clínico randomizando fase I/II. Este é o único caso descrito de rituximabe para o tratamento de esclerite necrosante pós cirúrgica. O uso de anticorpo anti-CD20 pode ser uma opção em casos refratários aos imunossupressores no tratamento da esclerite necrosante pós-cirúrgica.

Recomendações para o tratamento da síndrome de Sjögren / Recommendations for the treatment of Sjögren's syndrome

RESUMOAs recomendações propostas pela Comissão de Síndrome de Sjögren da Sociedade Brasileira de Reumatologia para tratamento da síndrome de Sjögren foram baseadas em uma revisão sistemática da literatura nas bases de dados Medline (PubMed) e Cochrane até outubro de 2014 e opinião de especialistas na ausência de artigos sobre o assunto. Foram incluídos 131 artigos classificados de acordo com Oxford & Grade. Essas recomendações foram elaboradas com o objetivo de orientar o manejo adequado e facilitar o acesso aos tratamentos para aqueles pacientes com adequada indicação de recebê-los, considerando o contexto socioeconômico brasileiro e os medicamentos disponíveis no país.

ABSTRACTThe recommendations proposed by the Sjögren's Syndrome Committee of the Brazilian Society of Rheumatology for the treatment of Sjögren's syndrome were based on a systematic review of literature in Medline (PubMed) and the Cochrane databases until October 2014 and on expert opinion in the absence of studies on the subject. 131 articles classified according to Oxford & Grade were included. These recommendations were developed in order to guide the management and facilitate the access to treatment for those patients with an appropriate indication, considering the Brazilian socioeconomic context and pharmacological agents available in this country.

Recommendations for the treatment of Sjögren's syndrome.

The recommendations proposed by the Sjögren's Syndrome Committee of the Brazilian Society of Rheumatology for the treatment of Sjögren's syndrome were based on a systematic review of literature in Medline (PubMed) and the Cochrane databases until October 2014 and on expert opinion in the absence of studies on the subject. 131 items classified according to Oxford & Grade were included. These recommendations were developed in order to guide the appropriate management and facilitate the access to treatment for those patients with an appropriate indication, considering the Brazilian socioeconomic context and pharmacological agents available in this country.

Biologic therapy for refractory scleritis: a new treatment perspective.

Scleritis is an umbrella term for a heterogeneous group of ocular diseases that can be associated with autoimmune or systemic disorders. The purpose of this article was to review the literature regarding the use of biologic drugs to treat refractory scleritis. A search of the MEDLINE, Embase, and LILACS electronic databases was conducted, and the reference lists of published articles were hand-searched. No language filters were used. This search strategy yielded no randomized trials of the use of biologic therapies to treat scleritis; only case reports and retrospective studies were retrieved. These studies suggest that monoclonal antibodies (infliximab and adalimumab) are superior to the soluble TNF receptor fusion protein etanercept for the treatment of scleritis in patients that do not respond to corticosteroids and/or to immunosuppressive treatment. Rituximab seems to be the best option for scleritis associated with vasculitis.

Nodular scleritis and granulomatous polyangiitis (Wegener) mimicking tuberculosis / Esclerite nodular e poliangiite granulomatosa (Wegener) mimetizando tuberculose

Granulomatous polyangiitis is a systemic disease that may affect any organ, with a predilection for the upper respiratory tract, lungs and kidneys. This article aims to report a case of a patient with atypical nodular scleritis as the initial manifestation of granulomatous polyangiitis (Wegener), mimicking a case of tuberculosis. The patient presented ocular hyperemia and lower progressive visual acuity for 1.5 years, followed by eye pain for two months. The patient had subpleural nodules with soft tissue density, increased pulmonary lymph nodes and discrete bilateral pleural thickening, with negative alcohol-resistant acid bacilli (BAAR). The histological diagnosis revealed a granulomatous vasculitis suggestive of non-infectious vasculitis (granulomatous polyangiitis). Cyclophosphamide pulse therapy was initiated.

Poliangiite granulomatosa é uma doença sistêmica que afeta qualquer órgão, com predileção pelo trato respiratório superior, pulmões e rins. Este artigo tem como objetivo relatar um caso atípico de uma paciente com esclerite nodular como manifestação inicial da poliangiite granulomatosa (Wegener), mimetizando um quadro de tuberculose. A paciente apresentou hiperemia ocular e baixa acuidade visual progressiva por 1,5 anos, seguido por dor ocular por dois meses. A paciente possuía nódulos subpleurais com densidade de partes moles, linfonodomegalia em janela aorto-pulmonar e espessamento pleural bilateral discreto, negativo para bacilos álcool-ácido resistentes (BAAR). O diagnóstico histológico revelou uma vasculite granulomatosa sugestiva de vasculite não infecciosa (poliangiite granulomatosa). Foi iniciada pulsoterapia com ciclofosfamida.

Diacerein for osteoarthritis.

BACKGROUND: Osteoarthritis (OA) is one of the most prevalent musculoskeletal diseases. There is currently no consensus on what is the best treatment to improve OA symptoms and slow disease progression. Diacerein is an anthraquinone synthesised in 1980 that interferes with interleukin-1, an inflammatory mediator. It has been proposed that diacerein acts as a slow-acting, symptom-modifying and perhaps disease-structure-modifying drug for OA. This is an update of a Cochrane review first published in 2006. OBJECTIVES: To assess the benefits and harms of diacerein for the treatment of adults with OA when compared with placebo and other pharmacologically active interventions (nonsteroidal anti-inflammatory drugs (NSAIDs) and other symptom-modifying, slow-acting drugs) for OA. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) - The Cochrane Library, Issue 10, 2013, MEDLINE (1966 to 2013), EMBASE (1980 to 2013), LILACS (1982 to 2013), and ACP Journal Club, and we handsearched reference lists of published articles. We also searched the World Health Organization International Clinical Trials Platform ( http://www.who.int/trialsearch/Default.aspx) to identify ongoing trials and screened reference lists of retrieved review articles and trials to identify potentially relevant studies. All searches were up to date as of March 2013. Pharmaceutical companies and authors of published articles were contacted. We searched the websites of the regulatory agencies using the keyword 'diacerein' in November 2013. No language restrictions were applied. SELECTION CRITERIA: Studies were included if they were randomised or quasi-randomised controlled trials that compared diacerein with placebo or another active pharmacological intervention in participants with OA. DATA COLLECTION AND ANALYSIS: Data abstraction and quality assessment were performed by two independent investigators, and their results were compared. The Cochrane risk of bias tool was used. The quality of evidence obtained was assessed using the GRADE approach. MAIN RESULTS: We identified three new trials (141 participants), and this updated review now includes 10 trials, totalling 2,210 participants. The most frequent risk of bias was incomplete outcome data, identified in approximately 80% of the studies. Allocation concealment and random sequence generation were unclear in 90% and 40% of the studies, respectively, because of poor reporting.Low-quality evidence from six trials (1,283 participants) indicates that diacerein has a small beneficial effect on overall pain (measured on a 100 mm visual analogue scale) at three to 36 months (mean difference (MD) -8.65, 95% confidence interval (CI) -15.62 to -1.68), which is equivalent to a 9% pain reduction in the diacerein group (95% CI -16% to -2%) compared with the placebo group. This benefit may not be clinically significant.No statistically significant differences in physical function (4 studies, 1006 participants) were noted between the diacerein and placebo groups (Lequesne impairment index, 0 to 24 points) (MD -0.29, 95% CI -0.87 to 0.28).Low-quality evidence from two trials (616 participants) on slowing of joint space narrowing (a decrease greater than 0.50 mm) in the knee or hip favoured diacerein over placebo (risk ratio (RR) 0.85, 95% CI 0.72 to 0.99), with an absolute risk difference of -6% (95% CI -15% to 2%) and a number needed to treat for an additional beneficial outcome (NNTB) of 14 (95% CI 8 to 203). Analysis of the knee joint alone (1 study, 170 participants) did not reach statistical significance (RR 0.94, 95% CI 0.51 to 1.74).None of the trials of diacerein versus placebo measured quality of life. According to one trial (161 participants), which compared diacerein versus non-steroidal anti-inflammatory drugs (NSAIDs), the quality of life of participants in the two groups (as assessed by the Short Form (SF)-36 health survey questionnaire (0 to 800 sum score)) did not differ significantly (MD -40.70, 95% CI -85.20 to 3.80).Low-quality evidence from seven trials showed significantly more adverse events in the diacerein group compared with the placebo group after two to 36 months, mainly diarrhoea (RR 3.52, 95% CI 2.42 to 5.11), with an absolute risk increase of 24% (95% CI 12% to 35%), and a number needed to treat for an additional harmful outcome (NNTH) of 4 (95% CI 3 to 7).No statistically significant differences in participant withdrawal due to adverse events were seen at two to 36 months for diacerein compared with placebo (RR 1.29, 95% CI 0.83 to 2.01).A search of regulatory websites found a recommendation from the European Medicines Agency (EMA) Pharmacovigilance Risk Assessment Committee (PRAC) that the marketing authorization of diacerein should be suspended across Europe because of harms (particularly the risk of severe diarrhoea and potentially harmful effects on the liver) outweighing benefits. However, this guidance is not final as the PRAC recommendation will be re-examined. AUTHORS' CONCLUSIONS: In this update, the strength of evidence for effectiveness outcomes was low to moderate. We confirmed that symptomatic benefit provided by diacerein in terms of pain reduction is minimal. The small benefit derived in terms of joint space narrowing is of questionable clinical relevance and was observed only for OA of the hip. With respect to adverse effects of diacerein, diarrhoea was most frequent. Given the recent guidance issued by the EMA recommending suspension of diacerein in Europe, the EMA website should be consulted for further recommendations regarding the use of diacerein.

Uso dos anti-inflamatórios não hormonais na artrite reumatoide, osteoartrite e na lombalgia / The use of nonsteroidal anti-inflammatory drugs in the treatment of rheumatoid arthritis, osteoarthritis and back pain

Os anti-inflamatórios não hormonais (AINEs) são drogas frequentemente utilizadas para o controle da dor, febre e inflamação. Embora os benefícios obtidos com o uso de AINEs sejam importantes, principalmente nas doenças inflamatórias crônicas, cerca de 25% dos pacientes apresentam efeitos colaterais que restringem seu uso na prática clínica. Os AINEs não são considerados drogas modificadoras de doenças na artrite reumatoide e devem ser utilizados somente como sintomáticos. Pelo fato de terem ambas as funções (propriedades analgésicas e anti-inflamatórias), os pacientes claramente os preferem para tratamento da osteoartrite. Os AINEs são efetivos no tratamento das lombalgias, qualquer classe de AINH pode ser utilizada, não existindo evidências de que uma classe seja mais efetiva que a outra no alívio das dores lombares. Deve-se levar em conta o risco de efeitos colaterais pela idade do paciente ou história prévia de úlcera gástrica e por insuficiência renal.

Osteoartrite / Osteoarthritis

A osteoartrite (OA) é uma desordem articular que leva ao envolvimento global da articulação (osso subcondral, ligamentos, cápsula articular, membrana sinovial e músculos periarticulares). Os desfechos clínicos e patológicos de uma variedade de eventos biológicos e mecânicos levam à falência estrutural e funcional das articulações sinoviais. É a doença articular mais prevalente e é a principal causa de dor e desabilidade em indivíduos idosos. As alterações radiográficas são praticamente universais após os 60 anos de idade, mas as queixas clínicas ocorrem em torno de 20% dos pacientes. O diagnóstico é dado pelas queixas clínicas, os achados no exame físico e as alterações radiográficas. O tratamento atual é dividido em medidas não farmacológicas e farmacológicas.