RESUMO
OBJECTIVES: Sarcoidosis is a multi-system granulomatous disease of unknown origin. It is mainly thought of as a lung disease but it can affect any organ system. Sinus and endocrine dysfunctions are described but are rare and seldomly linked with sarcoidosis. METHODS: Here we describe a case of a young Caucasian man who already visited multiple care givers for sinusitis, erectile dysfunction and anorexia. He presented at the emergency department with fever and emaciation, polyuria and polydipsia. The results of the blood sampling revealed a hypercalcaemia as well as abnormal thyroid function. RESULTS: After biochemical, radiological and histopathological workup, he was diagnosed with pulmonary sarcoidosis. Treatment with corticosteroids resulted in resolution of the sinusitis and normalisation of the calcemia, as well as the thyroid function while the impotence, polydipsia and polyuria remained. Elaboration revealed extra-pulmonary involvement of the sarcoidosis with dysfunction of the hypothalamic-pituitary axis with hypogonadotropic hypogonadism and diabetes insipidus due to a sellar mass. CONCLUSION: This is a rare case of systemic sarcoidosis with both thoracic and extra thoracic manifestations, with pituitary and sinus involvement. It shows that sarcoidosis can affect any organ system and diagnosis can be difficult in case of extrapulmonary manifestations.
Assuntos
Hipercalcemia , Sinusite , Humanos , Masculino , Hipercalcemia/diagnóstico , Hipercalcemia/etiologia , Adulto , Sinusite/complicações , Sinusite/diagnóstico , Sarcoidose/complicações , Sarcoidose/diagnóstico , Sarcoidose/tratamento farmacológico , Sarcoidose/fisiopatologia , Sarcoidose Pulmonar/complicações , Sarcoidose Pulmonar/diagnóstico , Sarcoidose Pulmonar/fisiopatologia , Sarcoidose Pulmonar/tratamento farmacológico , Doenças Hipotalâmicas/diagnóstico , Doenças Hipotalâmicas/complicaçõesRESUMO
BACKGROUND: Sarcoidosis is a systemic granulomatous disease of unknown etiology primarily affecting the lungs. Treatment is needed when disease symptoms worsen and organ function deteriorates. In pulmonary sarcoidosis, prednisone and methotrexate (MTX) are the most common anti-inflammatory therapies. However, there is large inter-patient variability in response to treatment, and predictive response markers are currently lacking. OBJECTIVE: In this study, we investigated the predictive potential of biomarkers in extracellular vesicles (EVs) isolated from biobanked serum of patients with pulmonary sarcoidosis stored prior to start of therapy. METHODS: Protein concentrations of a four-protein test panel of inflammatory proteins were measured in a discovery (n = 16) and replication (n = 129) cohort of patients with sarcoidosis and 47 healthy controls. Response to therapy was defined as an improvement of the absolute score of > 5% forced vital capacity (FVC) and/or > 10% diffusion lung of carbon monoxide (DLCO) after 24 weeks compared to baseline (before treatment). RESULTS: Serum protein levels differed between EV fractions and serum, and between sarcoidosis cases and controls. Serpin C1 concentrations in the low density lipid particle EV fraction were lower at baseline in the group of patients with a good response to MTX treatment in both the discovery cohort (p = 0.059) and in the replication cohort (p = 0.032). EV Serpin C1 showed to be a significant predictor for response to treatment with MTX (OR 0.4; p = 0.032). CONCLUSION: This study shows that proteins isolated from EVs harbor a distinct signal and have potential as new predictive therapy response biomarkers in sarcoidosis.
Assuntos
Vesículas Extracelulares , Sarcoidose Pulmonar , Sarcoidose , Humanos , Sarcoidose Pulmonar/diagnóstico , Sarcoidose Pulmonar/tratamento farmacológico , Metotrexato/uso terapêutico , Antitrombina III , BiomarcadoresRESUMO
Sarcoidosis is a multisystem granulomatous inflammatory disease of unknown etiology that can involve any organ. Ongoing dyspnea and dry cough in a young to middle-aged adult should increase the suspicion for sarcoidosis. Symptoms can present at any age and affect any organ system; however, pulmonary sarcoidosis is the most common. Extrapulmonary manifestations often involve cardiac, neurologic, ocular, and cutaneous systems. Patients with sarcoidosis can exhibit constitutional symptoms such as fever, unintentional weight loss, and fatigue. The early recognition and diagnosis of sarcoidosis are challenging because there is no diagnostic standard for testing, initial symptoms vary, and patients may be asymptomatic. Consensus guidelines recommend a holistic approach when diagnosing sarcoidosis that focuses on clinical presentation and radiographic findings, biopsy with evidence of noncaseating granulomas, involvement of more than one organ system, and elimination of other etiologies of granulomatous disease. Corticosteroids are the initial treatment for active disease, with refractory cases often requiring immunosuppressive or biologic therapies. Transplantation can be considered for advanced and end-stage disease depending on organ involvement.
Assuntos
Sarcoidose Pulmonar , Sarcoidose , Adulto , Pessoa de Meia-Idade , Humanos , Sarcoidose/terapia , Sarcoidose/tratamento farmacológico , Sarcoidose Pulmonar/diagnóstico , Sarcoidose Pulmonar/tratamento farmacológico , Corticosteroides/uso terapêutico , Dispneia/diagnóstico , Diagnóstico DiferencialRESUMO
Pulmonary sarcoidosis is an immune-mediated disorder closely related to Th17/Treg cell imbalance. Dexamethasone has been shown to regulate inflammation and immune responses in sarcoidosis patients. However, the underlying mechanisms of dexamethasone regulating Th17/Treg balance in sarcoidosis remain elusive. Herein, we elucidated the function role of TGF-ß/Smad3 signaling in pulmonary sarcoidosis development and explored the underlying mechanism of dexamethasone in treating pulmonary sarcoidosis. We found that the TGF-ß/Smad3 pathway was inactivated in pulmonary sarcoidosis patients. Propionibacterium acnes (PA) induced mouse model was generated to investigate the function of TGF-ß/Smad3 signaling in vivo. Data indicated that IL17A inhibition with neutralizing antibody and activation of TGF-ß/Smad3 signaling with SRI-011381 alleviated granuloma formation in the sarcoidosis mouse model. Moreover, we revealed that the Th17/Treg cell ratio was increased with PA treatment in mouse bronchoalveolar lavage fluid (BALF) and peripheral blood. The concentration of cytokines produced by Th17 cells (IL-17A, IL-23) was up-regulated in the BALF of PA-treated mice, while those produced by Tregs (IL-10, TGF-ß1) presented significant reduction. The treatment of IL-17A neutralizing antibody or SRI-011381 was demonstrated to rescue the PA-induced changes in the concentration of IL-17A, IL-23, IL-10, and TGF-ß1. Additionally, we demonstrated that dexamethasone treatment activated the TGF-ß/Smad3 signaling in the lung tissues of pulmonary sarcoidosis mice. Dexamethasone was also revealed to promote the rebalancing of the Th17/Treg ratio and attenuated the granuloma formation in pulmonary sarcoidosis. In conclusion, dexamethasone activates the TGF-ß/Smad3 signaling and induces Th17/Treg rebalance, alleviating pulmonary sarcoidosis, which suggests the potential of dexamethasone in treating pulmonary sarcoidosis.
Assuntos
Dexametasona , Sarcoidose Pulmonar , Animais , Humanos , Camundongos , Anticorpos Neutralizantes/farmacologia , Dexametasona/farmacologia , Dexametasona/uso terapêutico , Granuloma/prevenção & controle , Interleucina-10/metabolismo , Interleucina-17 , Interleucina-23/metabolismo , Sarcoidose Pulmonar/tratamento farmacológico , Linfócitos T Reguladores , Células Th17 , Fator de Crescimento Transformador beta/metabolismo , Fator de Crescimento Transformador beta1RESUMO
Sarcoidosis is the most common granulomatous disease in northern Europe. A distinction is made between acute forms of sarcoidosis and chronic sarcoidosis. Chronic sarcoidosis can affect practically all organs but the lungs are affected in 90-95% of patients. The clinical appearance varies between asymptomatic and oligosymptomatic courses, which are diagnosed more by chance, to courses with acute organ failure. An extensive organ work-up is necessary at the time of the initial diagnosis in order to record the extent of organ involvement and to make appropriate treatment decisions. Asymptomatic courses with purely pulmonary sarcoidosis do not require treatment and can be observed over the course of the disease, whereas courses with extensive organ involvement or organ dysfunction require treatment. The treatment consists primarily of the administration of glucocorticoids. If the effect of the glucocorticoids is insufficient or if there are side effects, various immunosuppressive agents, including biologics can be added.
Assuntos
Sarcoidose Pulmonar , Sarcoidose , Humanos , Glucocorticoides/uso terapêutico , Sarcoidose/diagnóstico , Sarcoidose/tratamento farmacológico , Sarcoidose Pulmonar/diagnóstico , Sarcoidose Pulmonar/tratamento farmacológico , Granuloma , PulmãoRESUMO
A man in his 60s with biopsy-proven pulmonary sarcoidosis, not on treatment, presented with 6 weeks of dyspnea to the emergency department. ECG showed first-degree atrioventricular block and CT thorax demonstrated progressive pulmonary sarcoidosis with new multifocal consolidation. Antibiotics were initiated.A brain natriuretic peptide was elevated at 2024 ng/L and echocardiogram showed global left ventricular systolic dysfunction. Coronary angiogram revealed normal coronary arteries, and cardiac positron emission tomography and MRI demonstrated patterns compatible with cardiac sarcoidosis. The patient significantly improved with diuresis; he was started on prednisone, methotrexate and standard heart failure therapies.We outline the difficulties of attributing cardiac causes of dyspnoea in a patient with known pulmonary sarcoidosis given the rarity of cardiac involvement. We review proposed diagnostic criteria for cardiac sarcoidosis using enhanced imaging techniques without requiring invasive myocardial biopsy. This case discussion also highlights nuances in managing cardiac sarcoidosis based on the best available evidence and expert consensus.
Assuntos
Cardiomiopatias , Miocardite , Sarcoidose Pulmonar , Sarcoidose , Masculino , Humanos , Cardiomiopatias/diagnóstico , Cardiomiopatias/diagnóstico por imagem , Sarcoidose Pulmonar/complicações , Sarcoidose Pulmonar/diagnóstico , Sarcoidose Pulmonar/tratamento farmacológico , Sarcoidose/complicações , Sarcoidose/diagnóstico , Sarcoidose/tratamento farmacológico , Dispneia/etiologia , BiópsiaRESUMO
IMPORTANCE: Anti-tumor necrosis factor-alpha agent (anti-TNF-α) is considered an effective third-line therapy for refractory sarcoidosis,studies observing the efficacy of anti-TNF-α agents show conflicting results. OBJECTIVE: We performed an up-to-date systemic meta-analysis to determine effectiveness and further elucidate the role of anti-TNF-α in the treatment of sarcoidosis. DATA SOURCES: A systematic search was carried out in PubMed/Medline, EMBASE, and Cochrane Library for studies reporting the therapeutic effects of anti-TNF drugs on patients with pulmonary and extra-pulmonary sarcoidosis, published up to April 10, 2022. The study was registered in the international prospective register of systematic reviews (PROSPERO) under ID: CRD42022364614. STUDY SELECTION: Clinical trials written reporting the therapeutic effects of anti-TNF drugs on patients with pulmonary and extra-pulmonary sarcoidosis were included. DATA EXTRACTION AND SYNTHESIS: Statistical analyses were performed with Comprehensive Meta-Analysis software, and the random-effects model was used. The combined overall treatment success was determined for patients with pulmonary and extrapulmonary sarcoidosis. MAIN OUTCOMES AND MEASURES: Overall treatment success rate wasdefined as no disease progression or improvement in symptoms. RESULTS: Eight clinical trial articles were included in the meta-analysis; four used Infliximab, two Etanercept, one Adalimumab, and one Ustekinumab and Golimumab. The mean age of participants was 48.5 years. The duration of drug therapy ranged from 14 to 45 weeks. We found a combined overall treatment success rate, defined as no disease progression or improvement in symptoms, of 69.9% (95% CI 35.0-90.9, I2: 70%) in the pulmonary sarcoidosis group and 74.5% (95% CI 36.3-93.7, I2: 90%) in the extrapulmonary sarcoidosis group. There was no evidence of publication bias in either group. CONCLUSION AND RELEVANCE: Treatment of refractory sarcoidosis with anti-TNF-α agents was effective in both pulmonary and extrapulmonary sarcoidosis, with a slightly higher efficacy seen in extrapulmonary sarcoidosis. Further randomized controlled trials should be conducted to determine the effects of anti-TNF-α agents as a part of the management strategy of sarcoidosis. Patients with pulmonary sarcoidosis should be studied separately from patients with extrapulmonary sarcoidosis to adjust for confounding results.
Assuntos
Antirreumáticos , Sarcoidose Pulmonar , Sarcoidose , Humanos , Pessoa de Meia-Idade , Sarcoidose Pulmonar/tratamento farmacológico , Inibidores do Fator de Necrose Tumoral , Anticorpos Monoclonais Humanizados/uso terapêutico , Revisões Sistemáticas como Assunto , Fator de Necrose Tumoral alfa , Adalimumab , Infliximab , Sarcoidose/tratamento farmacológico , Necrose , Antirreumáticos/uso terapêuticoRESUMO
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.
Assuntos
Sarcoidose Pulmonar , Humanos , Sarcoidose Pulmonar/tratamento farmacológico , PulmãoRESUMO
BACKGROUND: Sarcoidosis is a multi-system disorder with an increasing propensity to present in older patients. Diagnostic uncertainty is common and understandable given the higher prevalence of co-morbidities in older patients and broad differential for multi-system clinical presentations. Excluding malignancy and infection with a high degree of certainty is challenging and may require repeated confirmatory investigation where the diagnosis remains in doubt. SUMMARY OF MAIN FINDINGS: There are a paucity of studies examining late-onset sarcoidosis. Female predominance, pulmonary, ocular, skin and systemic symptoms are common, while more classical presentations such as Lofgren's syndrome are uncommon. Positivity rates of biopsies vary between studies; however, targeted biopsies of accessible sites with organ involvement are the most successful. Therapeutic management is directed at reducing inflammation, and thereby reducing symptom burden, improving quality of life and avoiding progression of organ damage. While most older patients will require corticosteroid therapy, they are also more prone to developing adverse effects. Most older patients will experience a clinical remission; however, the risk of developing chronic sarcoidosis and organ damage is higher compared with younger counterparts. Patients with evidence of pulmonary fibrosis and pulmonary hypertension are at particular risk. IMPACT ON CLINICAL PRACTICE: Health care providers who care for older adults should be aware of the increasing prevalence of late-onset sarcoidosis and consider the diagnosis in those who present with otherwise unexplained systemic symptoms, thoracic abnormalities on imaging and/or evidence of other organ involvement. Earlier diagnosis and therapeutic intervention to halt the development of pulmonary fibrosis and pulmonary hypertension and monitoring for treatment-related adverse effects will confer a mortality benefit.
Assuntos
Hipertensão Pulmonar , Fibrose Pulmonar , Sarcoidose Pulmonar , Sarcoidose , Idoso , Feminino , Humanos , Masculino , Qualidade de Vida , Sarcoidose/diagnóstico , Sarcoidose/epidemiologia , Sarcoidose/terapia , Sarcoidose Pulmonar/diagnóstico , Sarcoidose Pulmonar/tratamento farmacológico , Sarcoidose Pulmonar/patologiaRESUMO
An African American man in his 30s presented with haemoptysis associated with chronic productive cough, exertional dyspnoea, weight loss and skin lesions. Physical examination was notable for multiple cutaneous plaques over upper extremities and face. CT chest showed bilateral upper lobes cavitations and left upper lobe mass like consolidation. Further workup revealed positive serum aspergillus IgG, respiratory culture grew Aspergillus fumigatus, skin biopsy showed non-caseating granuloma. A final diagnosis of concomitant chronic pulmonary aspergillosis and advanced fibrocavitary pulmonary sarcoidosis with cutaneous involvement was made. The patient was initiated on antifungal therapy without steroids due to the concern of worsening the fungal infection. However, he presented later with worsening haemoptysis requiring bronchial artery embolisation. Surgical intervention was recommended but the patient eventually declined. The patient continued to be followed up closely in the clinic and repeated chest imaging showed stable findings 3 months after initial presentation.
Assuntos
Aspergilose Pulmonar , Sarcoidose Pulmonar , Antifúngicos/uso terapêutico , Aspergillus fumigatus , Artérias Brônquicas , Hemoptise/terapia , Humanos , Masculino , Aspergilose Pulmonar/complicações , Aspergilose Pulmonar/diagnóstico , Aspergilose Pulmonar/tratamento farmacológico , Sarcoidose Pulmonar/complicações , Sarcoidose Pulmonar/tratamento farmacológicoRESUMO
BACKGROUND: Miliary sarcoidosis is a rare form of sarcoidosis characterized by numerous miliary-like micronodules dispersed throughout the lungs. It has been documented in less than 1% of all sarcoidosis cases. We first described a rare case of miliary sarcoidosis and then conducted a literature review on the subject. CASE PRESENTATION: A 51-year-old male complained about a progressive loss of appetite, significant weight loss, occasional night sweats, and fatigue. After a thorough clinical exploration, a differential diagnosis of miliary lung disease was suspected - miliary tuberculosis, fungal infection, metastatic pulmonary carcinoma, or sarcoidosis. High-resolution chest computed tomography revealed bilateral diffuse micronodules with mediastinal lymphadenopathy. Histopathological analysis of transbronchial bioptic tissue identified non-caseating epithelioid granulomas, while no malignant cells were found. Lung tuberculosis and fungal infections were excluded. The levels of angiotensin-converting enzyme in the blood, as well as serum's and 24-hour urine calcium levels, were elevated. After a multidisciplinary discussion, the diagnosis of miliary pulmonary sarcoidosis was established. The patient was treated with prednisone for a total of 9 months, with full clinical and radiological recovery. Using PubMed, we also conducted a review of the literature on this topic and discovered only a few case reports of patients with miliary sarcoidosis, with just one systematic review accessible. The key findings of studies investigating patients diagnosed with miliary sarcoidosis are tabularly displayed. CONCLUSIONS: Miliary sarcoidosis is an uncommon type of pulmonary sarcoidosis that can mimic several entities that manifest as miliary nodules. Most patients require treatment since it can have a significant impact on lung function.
Assuntos
Sarcoidose Pulmonar , Sarcoidose , Tuberculose Miliar , Tuberculose Pulmonar , Humanos , Pulmão/diagnóstico por imagem , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Sarcoidose/diagnóstico , Sarcoidose/tratamento farmacológico , Sarcoidose Pulmonar/diagnóstico , Sarcoidose Pulmonar/tratamento farmacológico , Sarcoidose Pulmonar/patologia , Tuberculose Miliar/diagnóstico , Tuberculose Miliar/tratamento farmacológico , Tuberculose Miliar/patologiaRESUMO
PURPOSE: Alpha-melanocyte stimulating hormone (α-MSH) is known to have anti-inflammatory effects. However, the anti-inflammatory properties of α-MSH on normal bronchial epithelial cells are largely unknown, especially in the context of in vitro sarcoidosis models. METHODS: We evaluated the anti-inflammatory effects of α-MSH on two different in vitro sarcoidosis models (lung-on-membrane model; LOMM and three-dimensional biochip pulmonary sarcoidosis model; 3D-BSGM) generated from NBECs and an in vivo sarcoidosis mouse model. RESULTS: Treatment with α-MSH decreased inflammatory cytokine levels and downregulated type I interferon pathway genes and related proteins in LOMM and 3D-BSGM models. Treatment with α-MSH also significantly decreased macrophages and cytotoxic T-cells counts in a sarcoidosis mice model. CONCLUSION: Our results confirm the direct role of type I IFNs in the pathogenesis of sarcoid lung granulomas and highlight α-MSH as a potential novel therapeutic agent for treating pulmonary sarcoidosis.
Assuntos
Sarcoidose Pulmonar , Sarcoidose , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Granuloma/tratamento farmacológico , Inflamação/metabolismo , Camundongos , Sarcoidose/tratamento farmacológico , Sarcoidose Pulmonar/tratamento farmacológico , alfa-MSH/metabolismo , alfa-MSH/farmacologia , alfa-MSH/uso terapêuticoRESUMO
Importance: Sarcoidosis is an inflammatory granulomatous disease of unknown cause that affects an estimated 2 to 160 people per 100â¯000 worldwide and can involve virtually any organ. Approximately 10% to 30% of patients with sarcoidosis develop progressive pulmonary disease. Observation: Among patients with pulmonary sarcoidosis, the rate of spontaneous remission without serious sequelae ranges from 10% to 82%. However, lung disease progression occurs in more than 10% of patients and can result in fibrocystic architectural distortion of the lung, which is associated with a mortality rate of 12% to 18% within 5 years. Overall, the mortality rate for sarcoidosis is approximately 7% within a 5-year follow-up period. Worldwide, more than 60% of deaths from sarcoidosis are due to pulmonary involvement; however, more than 70% of deaths from sarcoidosis are due to cardiac involvement in Japan. Up to 70% of patients with advanced pulmonary sarcoidosis develop precapillary pulmonary hypertension, which is associated with a 5-year mortality rate of approximately 40%. Patients with sarcoidosis and precapillary pulmonary hypertension should be treated with therapies such as phosphodiesterase inhibitors and prostacyclin analogues. Although optimal doses of oral glucocorticoids for pulmonary sarcoidosis are unknown, oral prednisone typically starting at a dose of 20 mg/d to 40 mg/d for 2 to 6 weeks is recommended for patients who are symptomatic (cough, dyspnea, and chest pain) and have parenchymal infiltrates and abnormal pulmonary function test results. Oral glucocorticoids can be tapered over 6 to 18 months if symptoms, pulmonary function test results, and radiographs improve. Prolonged use of oral glucocorticoids may be required to control symptoms and stabilize disease. Patients without adequate improvement while receiving a dose of prednisone of 10 mg/d or greater or those with adverse effects due to glucocorticoids may be prescribed immunosuppressive agents, such as methotrexate, azathioprine, or an anti-tumor necrosis factor medication, either alone or with glucocorticoids combined with appropriate microbial prophylaxis for Pneumocystis jiroveci and herpes zoster. Effective treatments are not available for advanced fibrocystic pulmonary disease. Conclusions and Relevance: Sarcoidosis has a mortality rate of approximately 7% within a 5-year follow-up period. More than 10% of patients with pulmonary sarcoidosis develop progressive disease and more than 60% of deaths are due to advanced pulmonary sarcoidosis. Oral glucocorticoids with or without another immunosuppressive agent are the first-line therapy for symptomatic patients with abnormal pulmonary function test results and lung infiltrates. Patients with sarcoidosis and precapillary pulmonary hypertension should be treated with therapies such as phosphodiesterase inhibitors and prostacyclin analogues.
Assuntos
Sarcoidose Pulmonar/diagnóstico , Sarcoidose Pulmonar/tratamento farmacológico , HumanosRESUMO
Sarcoidosis is a systemic inflammatory disease, characterised by granuloma formation upon an unknown trigger in genetically predisposed individuals. The inflammation is characterised by an activation of both the innate immune system, with macrophages differentiating into epitheloid cells and dendritic cells, and the adaptive immune system, particularly T helper (Th) 1 and Th17 cells. Since all organs can be affected to varying extents, clinical presentation is often diverse. Most commonly, the lungs, lymph nodes, skin and eyes are involved, whereas cardiac, renal and neurological manifestations are less common but associated with higher morbidity. Depending on the clinical symptoms, a detailed evaluation including thorough clinical examination, imaging and laboratory tests should explore all possible organ involvements. In some patients, fatigue manifests as a para-sarcoidosis symptom impacting quality of life, even if sarcoidosis is in remission. Some acute syndromic presentations, such as Löfgren's syndrome, have a good prognosis and are commonly self-limiting. If possible, a topical treatment, for example for cutaneous sarcoidosis or bronchial involvement, should be applied. Treatment of severe cases with persisting disease activity necessitates long-term immunosuppressive drugs, with glucocorticoids as the first-line option. Steroid-sparing and second-line drugs include methotrexate, azathioprine, mycophenolate mofetil and immunomodulators such hydroxychloroquine, with the latter being first-line therapy in cutaneous sarcoidosis. Tumour necrosis factor-alpha inhibitors (particularly adalimumab and infliximab) are used as third-line agents but are administered earlier in cases of persistent disease activity, severe organ-involvement or intolerance to conventional drugs. Treatment decisions should be based on a multidisciplinary approach, depending on organ involvement and treatment tolerability. Para-sarcoidosis manifestations, particularly fatigue, should also be carefully addressed, where the patient could also be enrolled in multidimensional rehabilitation programmes. With various organ involvement and different phenotypes, larger studies including real-world data from registries are necessary to evaluate different sarcoidosis endotypes and preferential treatment pathways.
Assuntos
Sarcoidose Pulmonar , Sarcoidose , Azatioprina/uso terapêutico , Humanos , Imunossupressores/uso terapêutico , Qualidade de Vida , Sarcoidose/diagnóstico , Sarcoidose/tratamento farmacológico , Sarcoidose Pulmonar/tratamento farmacológicoRESUMO
The term "advanced sarcoidosis" is used for forms of sarcoidosis with a significant risk of loss of organ function or death. Advanced sarcoidosis often involves the lung and is described as "advanced pulmonary sarcoidosis" (APS), which includes advanced pulmonary fibrosis, associated complications such as bronchiectasis and infections, and pulmonary hypertension. Although APS affects a small proportion of patients with sarcoidosis, it is the leading cause of poor outcomes, including death. Here we review the major patterns of APS with a focus on the current management as well as potential approaches for improved outcomes for this most serious sarcoidosis phenotype.
Assuntos
Bronquiectasia , Fibrose Pulmonar , Sarcoidose Pulmonar , Sarcoidose , Humanos , Pulmão , Sarcoidose Pulmonar/complicações , Sarcoidose Pulmonar/tratamento farmacológicoAssuntos
Pulmão/diagnóstico por imagem , Pneumocystis carinii , Pneumonia por Pneumocystis/diagnóstico , Dor Abdominal/etiologia , Quimioprevenção , Diagnóstico Diferencial , Feminino , Glucocorticoides/uso terapêutico , Hepatomegalia/complicações , Hepatomegalia/diagnóstico por imagem , Humanos , Hipóxia/etiologia , Pulmão/patologia , Metotrexato/efeitos adversos , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Pneumocystis carinii/isolamento & purificação , Pneumonia por Pneumocystis/complicações , Pneumonia por Pneumocystis/tratamento farmacológico , Pneumonia por Pneumocystis/prevenção & controle , Radiografia , Sarcoidose Pulmonar/diagnóstico , Sarcoidose Pulmonar/tratamento farmacológico , Esplenomegalia/complicações , Esplenomegalia/diagnóstico por imagem , Tomografia Computadorizada por Raios XAssuntos
Nicotina , Sarcoidose Pulmonar , Humanos , Sarcoidose Pulmonar/tratamento farmacológico , Fumaça , Fumar , NicotianaRESUMO
PURPOSE OF REVIEW: The current review summarizes recent guidance in the diagnosis and management of sarcoidosis. Until recently, the main guidelines were the 1999 International Statement on Sarcoidosis. However, in 2020 two new guidelines were published by the American and British Thoracic Societies. They have a number of key updates and this review aims to summarize these. RECENT FINDINGS: The key findings from 2020 revolve around several themes. First, the need for a histological diagnosis should be supported by a multidisciplinary team approach. When a histological biopsy is needed of the lungs, thought is given to the approach taken for this and to whether an endobronchial ultrasound, endoscopic ultrasound or transbronchial biopsy is needed. Second, information regarding supporting tests including blood biomarkers, lung function and imaging. Third, a section specific to cardiac sarcoidosis. Finally, a summary of guidance for treating sarcoidosis including the need to treat fatigue. SUMMARY: The recent guidance suggests that a histological biopsy is only needed in cases of diagnostic uncertainty or in patients with typical long standing features on imaging. The guidelines also provide a clear pathway on the type of lung biopsy needed depending on the extent of mediastinal or parenchymal involvement. Support is given to steroid regimens and indication for second-line immunosuppression.
Assuntos
Sarcoidose Pulmonar , Sarcoidose , Biópsia , Broncoscopia , Endossonografia , Humanos , Sarcoidose/diagnóstico , Sarcoidose/tratamento farmacológico , Sarcoidose Pulmonar/diagnóstico , Sarcoidose Pulmonar/tratamento farmacológicoRESUMO
BACKGROUND: Tobacco smoking is associated with a reduced risk of developing sarcoidosis, and we previously reported that nicotine normalizes immune responses to environmental antigens in patients with active pulmonary sarcoidosis. The effects of nicotine on the progression of pulmonary sarcoidosis are unknown. RESEARCH QUESTION: Is nicotine treatment well tolerated, and will it improve lung function in patients with active pulmonary sarcoidosis? STUDY DESIGN AND METHODS: With local institutional review board approval, a randomized, double-blind, controlled pilot trial was conducted of daily nicotine transdermal patch treatment (21 mg daily) or placebo patch use for 24 weeks. The Ohio State University Wexner Medical Center and Cleveland Clinic enrolled 50 consecutive subjects aged ≥ 18 years with active pulmonary sarcoidosis, based on symptoms (ie, dyspnea, cough) and objective radiographic evidence of infiltrates consistent with nonfibrotic lung disease. Each study group was compared at 26 weeks based on repeated measures of FVC, FEV1, quantitative lung texture score based on CT texture analysis, Fatigue Assessment Score (FAS), St. George's Respiratory Questionnaire (SGRQ), and the Sarcoidosis Assessment Tool. RESULTS: Nicotine treatment was associated with a clinically significant, approximately 2.1% (70 mL) improvement in FVC from baseline to 26 weeks. FVC decreased by a similar amount (2.2%) in the placebo group, with a net increase of 140 mL (95% CI, 10-260) when comparing nicotine vs placebo groups at 26 weeks. FEV1 and FAS improved marginally in the nicotine-treated group, compared with those on placebo. No improvement was observed in lung texture score, FAS, St. George's Respiratory Questionnaire score, or the Sarcoidosis Assessment Tool. There were no reported serious adverse events or evidence of nicotine addiction. INTERPRETATION: Nicotine treatment was well tolerated in patients with active pulmonary sarcoidosis, and the preliminary findings of this pilot study suggest that it may reduce disease progression, based on FVC. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT02265874; URL: www.clinicaltrials.gov.
Assuntos
Nicotina/uso terapêutico , Agonistas Nicotínicos/uso terapêutico , Sarcoidose Pulmonar/tratamento farmacológico , Administração Cutânea , Adulto , Progressão da Doença , Método Duplo-Cego , Feminino , Volume Expiratório Forçado , Humanos , Pulmão/diagnóstico por imagem , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Sarcoidose Pulmonar/diagnóstico por imagem , Sarcoidose Pulmonar/fisiopatologia , Dispositivos para o Abandono do Uso de Tabaco , Tomografia Computadorizada por Raios X , Capacidade VitalRESUMO
BACKGROUND: Patients with pulmonary sarcoidosis commonly present with a dry cough; a productive cough suggests a complicating airway infection or an alternative diagnosis such as tuberculosis or bronchiectasis. CASE PRESENTATION: A 36-year-old European (Frisian) woman recently diagnosed with pulmonary sarcoidosis presented with debilitating exertional dyspnea and cough productive of glazy mucoid sputum. Several different attempts including video-assisted thoracoscopic biopsies failed to reach a second or alternative diagnosis including an infectious, autoimmune or collagen-vascular condition. She responded to steroids but with poor tolerance to this treatment, which could not be tapered. After she was started on anti-tumor necrosis factor alpha (TNF-α) therapy with infliximab, 200 mg at three-monthly intervals, she has been fine for well over a decade. CONCLUSIONS: In this patient with sarcoidosis who had a productive cough accompanied by fever, an extensive workup and prolonged follow-up, an alternative or second diagnosis could be ruled out; we therefore conclude that this highly unusual presentation is part of the clinical spectrum of sarcoidosis.