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Sarcoidosis is a multisystem granulomatous syndrome that arises from a persistent immune response to a triggering antigen(s). There is no "gold standard" test or algorithm for the diagnosis of sarcoidosis, making the diagnosis one of exclusion. The presentation of the disease varies substantially between individuals, in both the number of organs involved, and the manifestations seen in individual organs. These qualities dictate that health care providers diagnosing sarcoidosis must consider a wide range of possible alternative diagnoses, from across a range of presentations and medical specialties (infectious, inflammatory, cardiac, neurologic). Current guideline-based diagnosis of sarcoidosis recommends fulfillment of three criteria: 1) compatible clinical presentation and/or imaging 2) demonstration of granulomatous inflammation by biopsy (when possible) and, 3) exclusion of alternative causes, but do not provide guidance on standardized strategies for exclusion of alternative diagnoses. In this review, we provide a summary of the most common differential diagnoses for sarcoidosis involvement of lung, eye, skin, central nervous system, heart, liver, and kidney. We then propose a framework for testing to exclude alternative diagnoses based on pretest probability of sarcoidosis, defined as high (typical findings with sarcoidosis involvement confirmed in another organ), moderate (typical findings in a single organ), or low (atypical/findings suggesting of an alternative diagnosis). This work highlights the need for informed and careful exclusion of alternative diagnoses in sarcoidosis.
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RATIONALE: The proportion of patients who develop progressive pulmonary fibrosis (PPF), along with risk factors for progression remain poorly understood. OBJECTIVES: To examine factors associated with an increased risk of developing PPF among patients at a referral center. METHODS: We identified patients with a diagnosis of interstitial lung disease (ILD) seen within the Cleveland Clinic Health System. Utilizing a retrospective observational approach we estimated the risk of developing progression by diagnosis group and identified key clinical predictors using the FVC component of both the original progressive fibrotic interstitial lung disease (PFILD) and the proposed PPF (ATS) criteria. RESULTS: We identified 5934 patients with a diagnosis of ILD. The cumulative incidence of progression over the 24 months was similar when assessed with the PFILD and PPF criteria (33.1 % and 37.9 % respectively). Of those who met the ATS criteria, 9.5 % did not meet the PFILD criteria. Conversely, 4.3 % of patients who met PFILD thresholds did not achieve the 5 % absolute FVC decline criteria. Significant differences in the rate of progression were seen based on underlying diagnosis. Steroid therapy (HR 1.46, CI 1.31-1.62) was associated with an increased risk of progressive fibrosis by both PFILD and PPF criteria. CONCLUSION: Regardless of the definition used, the cumulative incidence of progressive disease is high in patients with ILD in the 24 months following diagnosis. Some differences are seen in the risk of progression when assessed by PFILD and PPF criteria. Further work is needed to identify modifiable risk factors for the development of progressive fibrosis.
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Progressão da Doença , Doenças Pulmonares Intersticiais , Humanos , Doenças Pulmonares Intersticiais/fisiopatologia , Doenças Pulmonares Intersticiais/epidemiologia , Doenças Pulmonares Intersticiais/complicações , Masculino , Feminino , Estudos Retrospectivos , Capacidade Vital/fisiologia , Pessoa de Meia-Idade , Idoso , Fatores de Risco , Fibrose Pulmonar/fisiopatologia , Fibrose Pulmonar/complicações , Fibrose Pulmonar/epidemiologia , IncidênciaRESUMO
BACKGROUND: An effective HIV vaccine will most likely need to have potent immunogenicity and broad cross-subtype coverage. The aim of the HIV Vaccine Trials Network (HVTN) 124 was to evaluate safety and immunogenicity of a unique polyvalent DNA-protein HIV vaccine with matching envelope (Env) immunogens. METHODS: HVTN 124 was a randomised, phase 1, placebo-controlled, double-blind study, including participants who were HIV seronegative and aged 18-50 years at low risk for infection. The DNA vaccine comprised five plasmids: four copies expressing Env gp120 (clades A, B, C, and AE) and one gag p55 (clade C). The protein vaccine included four DNA vaccine-matched GLA-SE-adjuvanted recombinant gp120 proteins. Participants were enrolled across six clinical sites in the USA and were randomly assigned to placebo or one of two vaccine groups (ie, prime-boost or coadministration) in a 5:1 ratio in part A and a 7:1 ratio in part B. Vaccines were delivered via intramuscular needle injection. The primary outcomes were safety and tolerability, assessed via frequency, severity, and attributability of local and systemic reactogenicity and adverse events, laboratory safety measures, and early discontinuations. Part A evaluated safety. Part B evaluated safety and immunogenicity of two regimens: DNA prime (administered at months 0, 1, and 3) with protein boost (months 6 and 8), and DNA-protein coadministration (months 0, 1, 3, 6, and 8). All randomly assigned participants who received at least one dose were included in the safety analysis. The study is registered with ClinicalTrials.gov (NCT03409276) and is closed to new participants. FINDINGS: Between April 19, 2018 and Feb 13, 2019, 60 participants (12 in part A [five men and seven women] and 48 in part B [21 men and 27 women]) were enrolled. All 60 participants received at least one dose, and 14 did not complete follow-up (six of 21 in the prime-boost group and eight of 21 in the coadminstration group). 11 clinical adverse events deemed by investigators as study-related occurred in seven of 48 participants in part B (eight of 21 in the prime-boost group and three of 21 in the coadministration group). Local reactogenicity in the vaccine groups was common, but the frequency and severity of reactogenicity signs or symptoms did not differ between the prime-boost and coadministration groups (eg, 20 [95%] of 21 in the prime-boost group vs 21 [100%] of 21 in the coadministration group had either local pain or tenderness of any severity [p=1·00], and seven [33%] vs nine [43%] had either erythema or induration [p=0·97]), nor did laboratory safety measures. There were no delayed-type hypersensitivity reactions or vasculitis or any severe clinical adverse events related to vaccination. The most frequently reported systemic reactogenicity symptoms in the active vaccine groups were malaise or fatigue (five [50%] of ten in part A and 17 [81%] of 21 in the prime-boost group vs 15 [71%] of 21 in the coadministration group in part B), headache (five [50%] and 18 [86%] vs 12 [57%]), and myalgia (four [40%] and 13 [62%] vs ten [48%]), mostly of mild or moderate severity. INTERPRETATION: Both vaccine regimens were safe, warranting evaluation in larger trials. FUNDING: US National Institutes of Health and US National Institute of Allergy and Infectious Diseases.
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Vacinas contra a AIDS , Anticorpos Anti-HIV , Infecções por HIV , HIV-1 , Vacinas de DNA , Humanos , Vacinas contra a AIDS/administração & dosagem , Vacinas contra a AIDS/imunologia , Vacinas contra a AIDS/efeitos adversos , Adulto , Masculino , Feminino , Método Duplo-Cego , Vacinas de DNA/administração & dosagem , Vacinas de DNA/imunologia , Vacinas de DNA/efeitos adversos , Infecções por HIV/prevenção & controle , Infecções por HIV/imunologia , Pessoa de Meia-Idade , Adulto Jovem , Anticorpos Anti-HIV/sangue , Adolescente , HIV-1/imunologia , Estados Unidos , Imunização Secundária , Imunogenicidade da Vacina , Proteína gp120 do Envelope de HIV/imunologia , Proteína gp120 do Envelope de HIV/genética , Anticorpos Neutralizantes/sangueRESUMO
BACKGROUND: Due to the heterogeneity of sarcoidosis, there is a need to define clinical phenotypes to allow for tailoring of clinical care and identification of more homogenous populations to facilitate research. METHODS: We utilized data from a prospectively collected registry of sarcoidosis patients seen at a single quaternary referral center between January 2019 and February 2021. We used multiple correspondence analysis (MCA) and k-means clustering to investigate if the clusters previously identified in the GenPhenReSa study were reproducible in a US population. We also investigated if these clusters were stable when the population was stratified by race. RESULTS: We replicated 3 of the 5 clusters seen in the GenPhenReSa study in our cohort. We likewise identified similar clusters between White and Black patients with sarcoidosis. Differences in organ manifestations associations between White and Black patients were seen primarily in relation to cardiac, neurologic, and ocular involvement. CONCLUSIONS: The organ clusters of liver-spleen, isolated pulmonary, and musculoskeletal-skin were reproducible in a US cohort, and in both Black and White patients.
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Negro ou Afro-Americano , Sistema de Registros , Sarcoidose , População Branca , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Negro ou Afro-Americano/estatística & dados numéricos , Análise por Conglomerados , Fígado/patologia , Fígado/diagnóstico por imagem , Estudos Prospectivos , Sarcoidose/etnologia , Sarcoidose/patologia , Sarcoidose/epidemiologia , Dermatopatias/etnologia , Dermatopatias/patologia , Baço/patologia , Estados Unidos/epidemiologia , População Branca/estatística & dados numéricos , BrancosRESUMO
BACKGROUND: Community advisory boards (CABs) are increasingly recognized as a means of incorporating patient experience into clinical practice and research. The power of CABs is derived from engaging with community members as equals throughout the research process. Despite this, little is known of community member experience and views on best practices for running a CAB in a rare pulmonary disease. RESEARCH QUESTION: What are CAB members' views on the best practices for CAB formation and maintenance in a rare pulmonary disease? STUDY DESIGN AND METHODS: In August 2021, we formed the Cleveland Clinic Sarcoidosis Health Partners (CC-HP) as a CAB to direct research and clinic improvement initiatives at a quaternary sarcoidosis center. We collaboratively evaluated our process for formation and maintenance of the CC-HP with the patient members of the group. Through the series of reflection/debriefing discussions, CAB patient members developed a consensus account of salient obstacles and facilitators of forming and maintaining a CAB in a rare pulmonary disease. RESULTS: Clinician and community members of the CC-HP found published guidelines to be an effective tool for structuring formation of a CAB in a rare pulmonary disease. Facilitators included a dedicated coordinator, collaborative development of projects, and a focus on improving clinical care. Obstacles to CAB functioning were formal structure, focus on projects with academic merit but no immediate impact to patients, and overreliance on digital resources. INTERPRETATION: By centering our evaluation of our CAB on community member experience, we were able to both identify facilitators and impediments to CAB as well as improve our own processes.
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Comitês Consultivos , Humanos , Sarcoidose/terapiaRESUMO
Cardiac involvement is a major cause of morbidity and mortality in patients with sarcoidosis. It is important to distinguish between clinical manifest diseases from clinically silent diseases. Advanced cardiac imaging studies are crucial in the diagnostic pathway. In suspected isolated cardiac sarcoidosis, it's key to rule out alternative diagnoses. Therapeutic options can be divided into immunosuppressive agents, guideline-directed medical therapy, antiarrhythmic medications, device/ablation therapy, and heart transplantation.
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Cardiomiopatias , Transplante de Coração , Sarcoidose , Humanos , Cardiomiopatias/diagnóstico , Cardiomiopatias/etiologia , Cardiomiopatias/terapia , Sarcoidose/diagnóstico , Sarcoidose/terapia , Diagnóstico por Imagem/métodosRESUMO
One view of sarcoidosis is that the term covers many different diseases. However, no classification framework exists for the future exploration of pathogenetic pathways, genetic or trigger predilections, patterns of lung function impairment, or treatment separations, or for the development of diagnostic algorithms or relevant outcome measures. We aimed to establish agreement on high-resolution CT (HRCT) phenotypic separations in sarcoidosis to anchor future CT research through a multinational two-round Delphi consensus process. Delphi participants included members of the Fleischner Society and the World Association of Sarcoidosis and other Granulomatous Disorders, as well as members' nominees. 146 individuals (98 chest physicians, 48 thoracic radiologists) from 28 countries took part, 144 of whom completed both Delphi rounds. After rating of 35 Delphi statements on a five-point Likert scale, consensus was achieved for 22 (63%) statements. There was 97% agreement on the existence of distinct HRCT phenotypes, with seven HRCT phenotypes that were categorised by participants as non-fibrotic or likely to be fibrotic. The international consensus reached in this Delphi exercise justifies the formulation of a CT classification as a basis for the possible definition of separate diseases. Further refinement of phenotypes with rapidly achievable CT studies is now needed to underpin the development of a formal classification of sarcoidosis.
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Consenso , Técnica Delphi , Fenótipo , Sarcoidose Pulmonar , Tomografia Computadorizada por Raios X , Humanos , Sarcoidose Pulmonar/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Pulmão/diagnóstico por imagemRESUMO
PURPOSE: To investigate the response to Acthar Gel® in patients with moderate to severe sarcoidosis uveitis. METHODS: This is a prospective open-label study that enrolled patients with moderate to severe sarcoidosis uveitis to receive 80 units daily of Acthar Gel for ten days followed by maintenance treatment with 80 units twice weekly. The primary outcome was the proportion of patients meeting at least one of the following variables 1) improved visual acuity, 2) resolution of intraocular inflammation, 3) ability to taper ocular or oral steroids by at least 50% or 4) reduction of cystoid macular edema, with no worsening of any single measure and no need for additional sarcoidosis therapies at 24 weeks. RESULTS: A total of nine patients were enrolled in the study. Four patients completed the full 24-week course of Acthar Gel, and three of these met the primary endpoint. Among the five patients who did not complete the 24-week course of treatment, four discontinued the treatment due to worsening ocular inflammation. One patient discontinued treatment due to severe adverse effects. The most common adverse effects were fluid retention (77%), insomnia (44%), hypertension (44%) and hyperglycemia (44%). CONCLUSIONS: We observed a clinical response to Acthar Gel in some patients with moderate to severe sarcoidosis uveitis, but a substantial proportion either failed to respond or did not tolerate the therapy. These observations may serve as preliminary data for controlled trials of Acthar Gel, but they do not support its role prior to failure of other agents.
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Sarcoidose , Uveíte , Humanos , Estudos Prospectivos , Uveíte/tratamento farmacológico , Sarcoidose/complicações , Sarcoidose/tratamento farmacológico , Transtornos da Visão , InflamaçãoRESUMO
Pulmonary hypertension (PH) is a risk factor for mortality in patients with sarcoidosis. Severe PH in chronic lung disease has previously been defined as mean pulmonary arterial pressure (mPAP) ≥ 35 mmHg or mPAP 25 ≥ mmHg with cardiac index (CI) ≤ 2 L/min/m2. However, there is no clear definition denoting severity of sarcoidosis-associated PH (SAPH). We aimed to determine pulmonary hemodynamic cut-off values where transplant-free survival was worse among patients with SAPH. This was a retrospective cohort analysis of the Registry of SAPH database focusing on pulmonary hemodynamic predictors of transplant-free survival among patients with precapillary SAPH. Cox regression was performed to determine which pulmonary hemodynamic values predicted death or lung transplantation. Kaplan-Meier survival analysis was performed on statistically significant predictors to determine pulmonary hemodynamic cut-off values where transplant-free survival was decreased. Decreased transplant-free survival occurred among SAPH patients with mPAP ≥ 40 mmHg and SAPH patients with pulmonary vascular resistance (PVR) ≥ 5 Woods units (WU). Transplant-free survival was not decreased in patients who fulfilled prior criteria of severe PH in chronic lung disease. We identified new cut-offs with decreased transplant-free survival in the SAPH population. Neither cut-off of mPAP ≥ 40 mmHg nor PVR ≥ 5 WU has previously been shown to be associated with decreased transplant-free survival in SAPH. These values could suggest a new definition of severe SAPH. Our PVR findings are in line with the most recent European Society of Cardiology/European Respiratory Society guideline definition of severe PH in chronic lung disease.
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Sarcoidosis is a complex systemic disease. Our study aimed to (1) identify novel alleles associated with sarcoidosis susceptibility; (2) provide an in-depth evaluation of HLA alleles and sarcoidosis susceptibility and (3) integrate genetic and transcription data to identify risk loci that may more directly impact disease pathogenesis. We report a genome-wide association study of 1335 sarcoidosis cases and 1264 controls of European descent (EA) and investigate associated alleles in a study of African Americans (AA: 1487 cases and 1504 controls). The EA and AA cohort was recruited from multiple United States sites. HLA alleles were imputed and tested for association with sarcoidosis susceptibility. Expression quantitative locus and colocalization analysis were performed using a subset of subjects with transcriptome data. Forty-nine SNPs in the HLA region in HLA-DRA, -DRB9, -DRB5, -DQA1 and BRD2 genes were significantly associated with sarcoidosis susceptibility in EA, rs3129888 was also a risk variant for sarcoidosis in AA. Classical HLA alleles DRB1*0101, DQA1*0101 and DQB1*0501, which are highly correlated, were also associated with sarcoidosis. rs3135287 near HLA-DRA was associated with HLA-DRA expression in peripheral blood mononuclear cells and bronchoalveolar lavage from subjects and lung tissue and whole blood from GTEx. We identified six novel SNPs (out of the seven SNPs representing the 49 significant SNPs) and nine HLA alleles associated with sarcoidosis susceptibility in the largest EA population. We also replicated our findings in an AA population. Our study reiterates the potential role of antigen recognition and/or presentation HLA class II genes in sarcoidosis pathogenesis.
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Estudo de Associação Genômica Ampla , Sarcoidose , Humanos , Predisposição Genética para Doença , Cadeias alfa de HLA-DR/genética , Leucócitos Mononucleares , Sarcoidose/genética , Cadeias HLA-DRB1/genética , AlelosRESUMO
There is expansive literature documenting the presence of health disparities, but there are disproportionately few studies describing interventions to reduce disparity. In this narrative review, we categorize interventions to reduce health disparity in pulmonary disease within the US health care system to support future initiatives to reduce disparity. We identified 211 articles describing interventions to reduce disparity in pulmonary disease related to race, income, or sex. We grouped the studies into the following four categories: biologic, educational, behavioral, and structural. We identified the following five main themes: (1) there were few interventional trials compared with the breadth of studies describing health disparities, and trials involving patients with asthma who were Black, low income, and living in an urban setting were overrepresented; (2) race or socioeconomic status was not an effective marker of individual pharmacologic treatment response; (3) telehealth enabled scaling of care, but more work is needed to understand how to leverage telehealth to improve outcomes in marginalized communities; (4) future interventions must explicitly target societal drivers of disparity, rather than focusing on individual behavior alone; and (5) individual interventions will only be maximally effective when specifically tailored to local needs. Much work has been done to catalog health disparities in pulmonary disease. Notable gaps in the identified literature include few interventional trials, the need for research in diseases outside of asthma, the need for high quality effectiveness trials, and an understanding of how to implement proven interventions balancing fidelity to the original protocol and the need to adapt to local barriers to care.
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Asma , Atenção à Saúde , Humanos , Classe Social , Renda , Asma/terapia , Escolaridade , Disparidades em Assistência à SaúdeRESUMO
Efzofitimod is a first-in-class biologic based on a naturally occurring splice variant of histidyl-tRNA synthetase (HARS) that downregulates immune responses via selective modulation of neuropilin-2 (NRP2). Preclinical data found high expression of NRP2 in sarcoidosis granulomas. Treatment with efzofitimod reduced the granulomatous inflammation induced by P. acnes in an animal model of sarcoidosis. A dose escalating trial of efzofitimod in sarcoidosis with chronic symptomatic pulmonary disease found that treatment with efzofitimod was associated with improved quality of life with a trend towards reduced glucocorticoid use and stable to improved pulmonary function. These studies have led to a large Phase 3 trial of efzofitimod in symptomatic pulmonary sarcoidosis.
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PURPOSE: Real-world studies have reported reduced mortality in patients with idiopathic pulmonary fibrosis (IPF) treated with antifibrotic therapy; however, the initiation or discontinuation of therapy during these studies may have introduced bias. This study investigated the effect of antifibrotic therapy on mortality and other outcomes in patients with IPF using causal inference methodology. METHODS: Data from a multicenter US registry of patients with IPF were used to assess the effect of antifibrotic therapy (nintedanib or pirfenidone) on death, death or lung transplant, respiratory-related hospitalization, and acute worsening of IPF (defined as any health care encounter deemed due to acute worsening of IPF). This study used the Gran method, which accounts for differences in patient characteristics and for treatment initiations and discontinuations during follow-up. The analysis cohort was limited to patients who started antifibrotic therapy on or after the day of enrollment or had never taken it. FINDINGS: Among the 499 patients analyzed, 352 (70.5%) received antifibrotic therapy. Estimated event rates of death at 1 year were 6.6% (95% CI, 6.1-7.1) for treated patients and 10.2% (95% CI, 9.5-10.9) for control patients. There was a numerical reduction in the risk of death (hazard ratio [HR], 0.53; 95% CI, 0.28-1.03; P = 0.060) but numerical increases in risks of respiratory-related hospitalization (HR, 1.88; 95% CI, 0.90-3.92; P = 0.091) and acute worsening of IPF (HR, 1.71; 95% CI, 0.36-8.09; P = 0.496) in treated versus control patients. IMPLICATIONS: Analyses based on causal inference methodology suggest that patients with IPF who receive antifibrotic therapy have improved survival.
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Fibrose Pulmonar Idiopática , Humanos , Fibrose Pulmonar Idiopática/tratamento farmacológico , Fibrose Pulmonar Idiopática/induzido quimicamente , PiridonasRESUMO
BACKGROUND: Pulmonary sarcoidosis is characterized by the accumulation of immune cells that form granulomas affecting the lungs. Efzofitimod (ATYR1923), a novel immunomodulator, selectively binds neuropilin 2, which is upregulated on immune cells in response to lung inflammation. RESEARCH QUESTION: What is the tolerability, safety, and effect on outcomes of efzofitimod in pulmonary sarcoidosis? STUDY DESIGN AND METHODS: In this randomized, double-blind, placebo-controlled study evaluating multiple ascending doses of efzofitimod administered intravenously every 4 weeks for 24 weeks, randomized patients (2:1) underwent a steroid taper to 5 mg/d by week 8 or < 5 mg/d after week 16. The primary end point was the incidence of adverse events (AEs); secondary end points included steroid reduction, change in lung function, and patient-reported outcomes on health-related quality-of-life scales. RESULTS: Thirty-seven patients received at least one dose of study medication. Efzofitimod was well tolerated at all doses, with no new or unexpected AEs and no dose-dependent AE incidence. Average daily steroid doses through end of study were 6.8 mg, 6.5 mg, and 5.6 mg for the 1 mg/kg, 3 mg/kg, and 5 mg/kg groups compared with 7.2 mg for placebo, resulting in a baseline-adjusted relative steroid reduction of 5%, 9%, and 22%, respectively. Clinically meaningful improvements were achieved across several patient-reported outcomes, several of which reached statistical significance in the 5 mg/kg dose arm. A dose-dependent but nonsignificant trend toward improved lung function also was observed for 3 and 5 mg/kg. INTERPRETATION: Efzofitimod was safe and well tolerated and was associated with dose-dependent improvements of several clinically relevant end points compared with placebo. The results of this study support further evaluation of efzofitimod in pulmonary sarcoidosis. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT03824392; URL: www. CLINICALTRIALS: gov.
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Sarcoidose Pulmonar , Humanos , Sarcoidose Pulmonar/tratamento farmacológico , PulmãoRESUMO
Background: Tumor necrosis factor (TNF) inhibitors have been used in the treatment of cardiac sarcoidosis, infliximab being the most commonly used. We have previously reported a case of effective treatment of cardiac sarcoidosis using adalimumab. Objective: To describe our experience of using adalimumab in the treatment of cardiac sarcoidosis. Methods: We conducted a retrospective study to evaluate patients with cardiac sarcoidosis who received adalimumab treatment at the University of Illinois Health between 2011 and 2022. The outcome was evaluated by assessing safety, tolerability, and ability to taper systemic corticosteroids therapy following initiation of adalimumab. Results: Seven patients met the inclusion criteria. Clinical responses to adalimumab were universally positive. Corticosteroid therapy was discontinued in five patients and the dose was reduced in two patients. Furthermore, adalimumab was well tolerated, and no adverse events were reported. Conclusion: Adalimumab was safe and well-tolerated in seven patients with cardiac sarcoidosis seen at our medical center and exhibited corticosteroid-sparing effects. Our observation further warrants large prospective studies to evaluate the safety and efficacy of adalimumab in the treatment of cardiac sarcoidosis.
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INTRODUCTION: Clinically overt granulomatous involvement of the nervous system (i.e. neurosarcoidosis) can be seen in up to 10% of patients with sarcoidosis. Establishing a diagnosis of neurosarcoidosis is often challenging due to the heterogeneity of clinical presentations that are sometimes nonspecific, and inaccessibility of tissue confirmation. Recommended treatments are based on expert opinions that are derived from clinical experience and limited data from retrospective studies, as data from randomized controlled studies are limited. AREA COVERED: In this article, we comprehensively review all available literature on epidemiology, clinical presentations, diagnosis, treatment, and outcomes of neurosarcoidosis. We also offer our opinions on diagnostic approach and treatment strategy. EXPERT OPINION: Given the invasive nature and the limited sensitivity of biopsy of the nervous system, diagnosis of neurosarcoidosis is usually made when ancillary tests (such as magnetic resonance imaging and cerebrospinal fluid analysis) are compatible, and alternative diagnoses are reasonably excluded in patients with established extraneural sarcoidosis. Several factors must be taken into consideration to formulate the initial treatment strategy, including the extent of the disease, severity, functional impairment, comorbidities, and patient's preference. In addition, treatment regimen of neurosarcoidosis should be formulated with an emphasis on long-term strategy.
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Doenças do Sistema Nervoso Central , Sarcoidose , Doenças do Sistema Nervoso Central/tratamento farmacológico , Doenças do Sistema Nervoso Central/terapia , Humanos , Imageamento por Ressonância Magnética , Estudos Retrospectivos , Sarcoidose/tratamento farmacológico , Sarcoidose/terapiaRESUMO
PURPOSE OF REVIEW: The treatment of sarcoidosis remains uncertain, despite 70 years of study. The conventional approach is to initiate corticosteroids in individuals who require treatment. The position of more aggressive regimes is unknown. RECENT FINDINGS: Recent recognition that many patients will require prolonged therapy, and the observation that corticosteroids lead to overt and insidious toxicities, have led to suggestions that steroid-sparing medications be used earlier in the management of sarcoidosis. Individuals with poor prognostic features, designated as 'high-risk' sarcoidosis may, especially benefit from a broader palette of therapeutic options in the initial treatment regimen. An even more aggressive approach, known as 'top-down' or 'hit-hard and early' therapy has emerged in the fields of gastroenterology and rheumatology in the past 15 years, on the premise that highly effective early control of inflammation leads to better outcomes. These regimens typically involve early initiation of biologic therapies. SUMMARY: For certain subpopulations of sarcoidosis patients, 'top-down' therapy could be helpful. Severe pulmonary sarcoidosis, neurosarcoidosis, cardiac sarcoidosis and multiorgan sarcoidosis are phenotypes that may be most relevant for revised therapeutic algorithms. Precision medicine approaches and randomized trials will be necessary to confirm a role for top-down therapy in the routine management of sarcoidosis.
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Doenças do Sistema Nervoso Central , Sarcoidose Pulmonar , Sarcoidose , Corticosteroides/uso terapêutico , Doenças do Sistema Nervoso Central/tratamento farmacológico , Humanos , Inflamação/tratamento farmacológico , Sarcoidose/tratamento farmacológico , Sarcoidose Pulmonar/tratamento farmacológicoRESUMO
RATIONALE: Transbronchial cryobiopsy has been increasingly used to diagnose interstitial lung diseases. However, there is uncertainty regarding its accuracy and risks, mainly due to a paucity of prospective or randomized trials comparing cryobiopsy to surgical biopsy. OBJECTIVES: To evaluate the diagnostic yield and complications of cryobiopsy in patients selected by multidisciplinary discussion. METHODS: This was a prospective cohort from 2017 to 2019. We included consecutive patients with suspected interstitial lung diseases being considered for lung biopsy presented at our multidisciplinary meeting. MEASUREMENTS AND MAIN RESULTS: Of 112 patients, we recommended no biopsy in 31, transbronchial forceps biopsy in 16, cryobiopsy in 54 and surgical biopsy in 11. By the end of the study, 34 patients had had cryobiopsy and 24 patients, surgical biopsy. Overall pathologic and multidisciplinary diagnostic yield of cryobiopsy was 47.1% and 61.8%, respectively. The yield increased over time for both pathologic (year 1: 28.6%, year 2: 54.5%, year 3: 66.7%, p = 0.161) and multidisciplinary (year 1: 50%, year 2: 63.6%, year 3: 77.8%, p = 0.412) diagnosis. Overall rate of grade 4 bleeding after cryobiopsy was 11.8%. Cryobiopsy required less chest tube placement (11.8% vs 100%, p < 0.001) and less hospitalizations compared to surgical biopsy (26.5% vs 95.7%, p < 0.001), but hospitalized patients had a longer median hospital stay (2 days vs 1 day, p = 0.004). CONCLUSIONS: Diagnostic yield of cryobiopsy increased over time but the overall grade 4 bleeding rate was 11.8%.