Predictors of Mortality in Sarcoidosis.

Sarcoidosis is a systemic granulomatous disorder that affects individuals of all racial/ethnic origins and occurs at any time of life. Spontaneous remission is frequent and may occur in 2 of 3 patients, while the remaining cases have chronic, progressive disease, with some patients presenting with organ- and life-threatening involvements. Many reports have investigated which features may be related to poor outcomes in patients with sarcoidosis. Pulmonary hypertension and respiratory failure from pulmonary fibrosis are the most common complications associated with the cause of death in sarcoidosis. Other major causes of death include cardiac, neurologic, hepatic involvement, and hemoptysis from aspergilloma.

Sarcoidosis-Associated Pulmonary Hypertension.

Pulmonary hypertension is a life-threatening complication of advanced sarcoidosis. Many mechanisms can cause an elevation of pulmonary pressure in sarcoidosis, leading to precapillary or postcapillary pulmonary hypertension. Sarcoidosis-associated pulmonary hypertension contributes to severe exertional dyspnea, reduced exercise capacity, and notably compromised the survival. Despite the critical functional and prognostic implications of pulmonary hypertension in sarcoidosis, there is a scarcity of specific guidelines on the management of these patients due to a lack of evidence. Hence, further research is required to identify subgroups of patients who may benefit from pulmonary arterial hypertension-targeted therapies and/or immunosuppressive therapies.

Fibrotic Pulmonary Sarcoidosis.

Fibrotic pulmonary sarcoidosis (fPS) affects about 20% of patients. fPS carries a significant morbidity and mortality. However, its prognosis is highly variable, depending mainly on fibrosis extent, functional impairment severity, and the development of pulmonary hypertension. Moreover, fPS outcomes are also influenced by several other complications, including acute exacerbations, and infections. fPS natural history is unknown, in particular regarding the risk of progressive self-sustaining fibrosis. The management of fPS is challenging, including anti-inflammatory treatment if granulomatous activity persists, rehabilitation, and in highly selected patients antifibrotic treatment and lung transplantation.

Sarcoidosis cardíaca como causa muy infrecuente de muerte súbita en pacientes jóvenes asintomáticos / Cardiac sarcoidosis as an infrequent cause of sudden death in asymptomatic young patients

La afectación cardíaca en la sarcoidosis ha sido descrita tanto en presencia de síntomas como en su ausencia. Este trabajo ayuda a comprender la sarcoidosis y su presentación clínico-morfológica. Presentamos dos pacientes jóvenes (37 y 27años), con muerte súbita, a quienes se les realizó la autopsia completa con estudio toxicológico. El hombre de 37años presentaba una sarcoidosis pulmonar generalizada, en ganglios mediastínicos y granulomas sarcoideos intramiocárdicos en el ventrículo izquierdo, que producían un espesor de pared de 14mm. Esto derivó en una miocardiopatía dilatada secundaria que debutó como muerte súbita. El segundo caso, un varón de 27años, presentaba sarcoidosis con importante afectación pulmonar y mediastínica. La presencia de granulomas en el tabique cardíaco sobre un fondo fibrótico podría ser el origen de un mecanismo arritmogénico de muerte súbita. La autopsia clásica y el examen del sistema de conducción cardíaco son cruciales en la muerte súbita.(AU)

Cardiac involvement in sarcoidosis has been described in both symptomatic and asymptomatic patients. The aim of this report is to further the understanding of sarcoidosis and its clinical presentation. We report the autopsy and toxicology results of two cases of sudden death in young men. A 37-year-old male had generalized sarcoidosis, in mediastinal glands and intramyocardial sarcoid granulomas in the left ventricle, which had caused a 14mm thickening of the ventricular wall and a secondary dilated myocardiopathy causing sudden death. A 27-year-old male had extensive sarcoidosis of the lungs and mediastinum. Granulomas with a fibrotic background were found in the cardiac wall which could have originated an arrhythmogenic mechanism causing sudden death. Post-mortem study including careful examination of cardiac conduction pathways are vital to ascertain the cause of sudden death.(AU)

Clinical manifestations and associated factors of uveitis in patients with pulmonary sarcoidosis: a case control study.

Sarcoidosis, an idiopathic and inflammatory disease, affects various organs and can manifest as uveitis. Due to limited evidence, researchers investigated the risk factors associated with uveitis in patients with pulmonary sarcoidosis. A retrospective study was conducted on 71 pulmonary sarcoidosis patients, including 19 with uveitis and 52 without. Data on involved organs, imaging findings, spirometry, and analyses from blood and bronchoalveolar lavage fluid were collected. Logistic regression models were used for multivariate analysis. Among the 71 newly diagnosed pulmonary sarcoidosis patients, uveitis was observed in 19 patients (26.8%). No significant differences were found in clinical characteristics between patients with and without uveitis. Fewer patients with uveitis presented lung parenchymal lesions (P = 0.043). In multivariate analysis, skin lesions (aOR 7.619, 95% CI 1.277-45.472, P = 0.026) and ophthalmic symptoms (aOR 4.065, 95% CI 1.192-13.863, P = 0.025) were associated with uveitis. Absence of uveitis was related to lung parenchymal lesions (aOR 0.233, 95% CI 0.062-0.883, P = 0.032). Approximately one-quarter of patients with an initial diagnosis of pulmonary sarcoidosis were diagnosed with uveitis. Presence of skin lesions, ophthalmic symptoms, and absence of lung parenchymal lesions were related to uveitis. These results need to be clarified by further studies to confirm the clinical role of early ophthalmologic screening for pulmonary sarcoidosis patients with these factors.

Molecular Mechanism in the Development of Pulmonary Fibrosis in Patients with Sarcoidosis.

Sarcoidosis is a multisystemic disease of unknown etiology characterized by the formation of granulomas in various organs, especially lung and mediastinal hilar lymph nodes. The clinical course and manifestations are unpredictable: spontaneous remission can occur in approximately two thirds of patients; up to 20% of patients have chronic course of the lung disease (called advanced pulmonary sarcoidosis, APS) resulting in progressive loss of lung function, sometimes life-threatening that can lead to respiratory failure and death. The immunopathology mechanism leading from granuloma formation to the fibrosis in APS still remains elusive. Recent studies have provided new insights into the genetic factors and immune components involved in the clinical manifestation of the disease. In this review we aim to summarize the clinical-prognostic characteristics and molecular pathways which are believed to be associated with the development of APS.

Dyspnoea in a patient with biopsy-proven pulmonary sarcoidosis: the challenges in diagnosing cardiac sarcoidosis.

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.

An expert overview of pulmonary fibrosis in sarcoidosis.

INTRODUCTION: Advanced pulmonary sarcoidosis refers to phenotypes of pulmonary sarcoidosis that often lead to significant loss of lung function, respiratory failure, or death. Around 20% of patients with sarcoidosis may progress to this state which is mainly driven by advanced pulmonary fibrosis. Advanced fibrosis often presents with associated complications of sarcoidosis including infections, bronchiectasis, and pulmonary hypertension. AREAS COVERED: This article will focus on the pathogenesis, natural history of disease, diagnosis, and potential treatment options of pulmonary fibrosis in sarcoidosis. In the expert opinion section, we will discuss the prognosis and management of patients with significant disease. EXPERT OPINION: While some patients with pulmonary sarcoidosis remain stable or improve with anti-inflammatory therapies, others develop pulmonary fibrosis and further complications. Although advanced pulmonary fibrosis is the leading cause of death in sarcoidosis, there are no evidence-based guidelines for the management of fibrotic sarcoidosis. Current recommendations are based on expert consensus and often include multidisciplinary discussions with experts in sarcoidosis, pulmonary hypertension, and lung transplantation to facilitate care for such complex patients. Current works evaluating treatments include the use of antifibrotic therapies for treatment in advanced pulmonary sarcoidosis.

Metastasis of lung cancer?

BACKGROUND: Sarcoidosis is a multi-system, idiopathic, inflammatory disorder that affects the lungs in over 90% of patients. The incidence of bone lesions in sarcoidosis is only 1-13%. CASE REPORT: This study describes a 60-year-old woman with a previous history of thyroid cancer, and a more recent diagnosis of lung cancer with suspicious metastatic lesions, which were confirmed to be sarcoidosis. CONCLUSION: This case suggests that pulmonary neoplasms and pulmonary sarcoidosis can coexist and be easily confused. When lung cancer is accompanied by symmetric hilar lymph node enlargement and multiple lung nodules, sarcoidosis should be considered in addition to metastasis, and a biopsy should be performed for confirmation.

Pulmonary sarcoidosis and immune-mediated necrotizing myopathy: an uncommon coincidence.

INTRODUCTION: Immune-mediated necrotizing myopathy (IMNM) is characterized by acute or subacute, severe proximal muscle weakness and myofiber necrosis with minimal inflammatory cell infiltrate observed on muscle biopsy. On the other hand, sarcoidosis is characterised by the presence of non-caseating granulomas that can develop in several organs. CASE REPORT: We present the unique case of a 49-year-old woman, with no previous medical history, who had a rare concomitant occurrence of IMNM and pulmonary sarcoidosis. This condition was successfully treated with a combination of corticosteroids and rituximab along with rehabilitation program. DISCUSSION: This association has been reported in only two previous case reports. This highlights the importance of further research on the connection between sarcoidosis and other forms of inflammatory myopathies.

Obstructive sinonasal granuloma: a rare complication of systemic sarcoidosis.

Sarcoidosis is a granulomatous disorder which presents with pulmonary involvement in >90% of cases. Sinonasal involvement is rare, occurring in 1% of all patients with sarcoidosis. It typically presents in the setting of active pulmonary disease. Here, we present a rare case of sinonasal sarcoidosis (SNS) in a patient with latent pulmonary sarcoidosis. The patient presented to our clinic with several years of nasal obstruction, rhinorrhea and cough unresponsive to medical management. Eventually, radiographic imaging was performed, revealing a large obstructive mass in the left nasal cavity. The mass was resected, and pathology demonstrated epithelioid granulomas, consistent with sarcoidosis. The patient was subsequently placed on systemic therapy with improvement in her symptoms. In summary, SNS is a rare clinical entity that infrequently presents in patients without active pulmonary involvement. Clinicians should have a low threshold to obtain imaging in patients with sarcoidosis who present with sinonasal complaints.

Rare organ manifestations of sarcoidosis.

PURPOSE: We retrospectively analyzed the frequency and clinical characteristics of organs rarely involved with sarcoidosis in a cohort of 1158 sarcoidosis patients cared for over nearly 11 years in a university outpatient sarcoidosis clinic. METHODS: Data were analyzed from an institution-approved sarcoidosis clinical database containing demographic and clinical characteristics of sarcoidosis outpatients cared for between May 2011 and March 2021 at a university medical center sarcoidosis clinic. The diagnosis of sarcoidosis was established by standard international criteria. Rare organ involvement was defined as an organ not individually listed in the Word Association of Sarcoidosis and Other Granulomatous Disorders Sarcoidosis Organ Assessment Instrument. RESULTS: Twenty-six of the 1158 patients (2.2%) had 27 instances of rare organ involvement. The most common rare organ involved was the GI tract, followed by the testicle and then the female reproductive tract. Only 1 of the 26 patients with rare sarcoidosis organ involvement required therapy for that organ involvement. In comparison with sarcoidosis patients without rare organ involvement, patients with rare organ involvement were more likely to be black, have more total organs involved with sarcoidosis, and more likely require anti-sarcoidosis therapy at some point during the course of their disease. There were no differences between these groups in terms of sex, age at diagnosis, and most recent percent predicted forced vital capacity. CONCLUSIONS: Rare sarcoidosis organ involvement occurred in 2.2 percent of this cohort. Although rare organ involvement rarely required treatment, it was associated with more extensive disease that was more likely to require therapy.

Concomitant occurrence of advanced fibrocavitary pulmonary sarcoidosis and chronic pulmonary aspergillosis.

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.

Novel insights in fibrotic pulmonary sarcoidosis.

PURPOSE OF REVIEW: In chronic pulmonary sarcoidosis, the transition from the inflammatory to the fibrotic stage of the lungs occurs in about 10-20% of cases, eventually causing end-stage fibrotic disease. To date, pathogenetic mechanisms and clinical management remain challenging; thus, we highlight the recent evidence in pulmonary fibrotic processes, clinical signs for an early detection and the potential role of the current investigated antifibrotic agents and promising targeted therapies. RECENT FINDINGS: Recent findings of relevant key cellular pathways can be considered as a glimmer of light in the complexity of sarcoidosis. In some patients, granulomas persist and serve as a nidus for fibrosis growth, sustained by several fibrosis-stimulating cytokines. Preclinical studies have detected profibrotic, antifibrotic and pleiotropic T cells as promoters of fibrosis. Epigenetics, genetics and transcriptomics research can lead to new target therapies. Antifibrotic drug nintedanib has shown a positive effect on non-idiopathic pulmonary fibrosis fibrotic lung diseases including fibrotic sarcoidosis; other antifibrotic drugs are under investigation. SUMMARY: Pulmonary fibrosis strongly impacts the outcome of sarcoidosis, and a better understanding of the underlying pathogenic mechanisms can facilitate the development of novel treatments, improving clinical care and life expectancy of these patients. The greatest challenge is to investigate effective antifibrotic therapies once fibrosis develops. The role of these findings in fibrotic sarcoidosis can be translated into other interstitial lung diseases characterized by the coexistence of inflammatory and fibrotic processes.

Janus kinase inhibitor treatment improved both subcutaneous and pulmonary sarcoidosis in a patient with glaucoma.

This is the first case to provide significant evidence that JAK inhibitor is an effective treatment for both subcutaneous and pulmonary sarcoidosis, and it is also the first case in which tofacitinib was used in a patient who has a contraindication for corticosteroid therapy.

[Sarcoidosis coming from the galaxy]. / Sarcoïdose venant de la galaxie.

Manifestations of sarcoidosis are variable and non-specific. We are reporting on the case of a 23-year-old man who presented multiple bilateral pulmonary nodules spiculated with peripherical micronodules (galaxy sign). He had no clinical symptom. Investigations led to the diagnosis of sarcoidosis. The galaxy sign is a rare manifestation of sarcoidosis which can be useful for diagnosis.