BACKGROUND:One approach to categorizing patients using chest CT imaging manifestations of pulmonary sarcoidosis is to use 3 classifications: fibrotic, nonfibrotic, or no parenchymal abnormality. This study aimed to evaluate the relationships between these imaging subtypes and demographic and physiological variables in a large group of patients with sarcoidosis with chest CT imaging. RESEARCH QUESTION:Do individuals with fibrotic sarcoidosis have more severe physiological impairment than those with nonfibrotic sarcoidosis and those with no parenchymal abnormality, and are there CT subtypes of fibrosis that are associated with different physiological subtypes? STUDY DESIGN AND METHODS:The study included individuals with sarcoidosis from 2 large medical centers who were seen between 2008 and 2018 and from the Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis (GRADS) consortium and who received high-resolution CT imaging and spirometry and lung diffusing capacity within 180 days (N = 932). Pulmonary function phenotypes were characterized based on spirometry findings and lung diffusing capacity. CT patterns were systematically classified as fibrotic, nonfibrotic, or no parenchymal abnormality based on standardized visual assessment. Multinomial logistic regression analyzed the relationship between pulmonary function and CT categories. RESULTS:Among the 942 patients, 353 (38%) had fibrosis, 380 (41%) had nonfibrotic abnormalities, and 199 (21%) had no parenchymal abnormality. Individuals with fibrotic abnormalities were older and had a longer time since diagnosis, more impaired spirometry and diffusing capacity, and larger pulmonary artery diameter than those without (all, P < .001). Among participants with fibrosis, those with a conglomerate mass were 9 times more likely to have a mixed pattern of spirometric impairment (P < .01). INTERPRETATION:Our results show that individuals with fibrotic pulmonary sarcoidosis display distinct demographic and spirometric differences. Subtypes of fibrosis exhibit different lung function abnormalities.

OBJECTIVE:Cognitive complaints are common among individuals with sarcoidosis, though little is known about objective cognitive performance in this group. This study examined performance on neuropsychological testing in patients with sarcoidosis who had subjective cognitive complaints, comparing performance between individuals with and without neurologic involvement (i.e., neurosarcoidosis [NS]). METHOD:This is a retrospective, observational study of individuals with sarcoidosis who were referred for neuropsychological evaluation due to cognitive complaints. Mean test performances and rates of impairment on cognitive tests were examined and compared between individuals with NS and systemic sarcoidosis (SS). RESULTS:Thirty-seven individuals with sarcoidosis (n = 14 with NS) were included (Mage = 53.2 ± 10.0 years, Meducation = 14.5 ± 2.4 years, 83.8% White, 67.6% female), of whom 40.5% demonstrated cognitive impairment (CI; 2+ tests impaired). Impairments were most common on tests of verbal memory (24.2% immediate, 33.3% delayed), problem solving (25.8%), and verbal fluency (22.6%). All but one of the individuals with CI in the NS group had intracranial involvement. The main difference observed between NS and SS was worse performance on a measure of auditory attention/working memory, t(35) = -2.24, p = .03. CONCLUSIONS:CI was observed in nearly half of patients with sarcoidosis who had subjective cognitive complaints. Additional research is needed to better understand the potential physiological underpinnings.

Background: Non-occupational exposures are increasingly recognized as a driver of poor outcomes in patients with interstitial lung disease (ILD), including urban and rural populations. However, both populations also experience barriers to care and higher social vulnerability that may be associated with higher risk for progression. The impact of agricultural antigen exposure and concomitant social vulnerability has not been well characterized. Objectives: To evaluate the risk of progression in both urban and agricultural antigen-exposed communities in patients with ILD. Design: Retrospective cohort study. Methods: We identified individuals with a diagnosis of ILD in a large health system. Proximity to agricultural antigens was mapped utilizing satellite-derived crop data. Residence in a community impacted by structural disadvantage was estimated using the social vulnerability index (SVI). We used geographically weighted regression analysis to estimate the risk of progression, defined as a greater than 10% relative decrease in forced vital capacity within the 24 months from first documented diagnosis. Results: Residence in a high SVI community was associated with an increased risk of disease progression by FVC criteria in both agriculturally exposed and urban communities. The greatest risk of progression was seen in those residing in high SVI, rural communities (HR 1.19, CI: 1.09–1.31). Conclusion: Within a large cohort of geographically diverse patients with ILD, residential social vulnerability increased the risk of ILD progression with effects similar in individuals with agricultural antigen exposure and urban exposures.

Sarcoidosis is a complex systemic granulomatous disease that can affect multiple organs, with pulmonary involvement being the most common. Its pathogenesis involves genetic predisposition and chronic immune dysregulation, which increase susceptibility to environmental or endogenous triggers, leading to an aberrant immune response. Imaging plays a central role in diagnosis and has evolved from traditional chest radiography Scadding staging to a computed tomography-based classification and radiomics that improves disease phenotyping. Due to its variable presentation, diagnosing sarcoidosis and attributing symptoms to the disease can be challenging; therefore, awareness and consideration of alternative diagnoses remain essential. The clinical course of sarcoidosis is unpredictable; many patients do not require therapy. Treatment decisions must be individualised, balancing disease severity, risk of organ damage, quality of life and potential toxicity of medication. However, the lack of both reliable prognostic tools and clear criteria for high-risk cases contributes to substantial heterogeneity in disease management. While the guidelines still recommend corticosteroids as first-line treatment, recent data show that methotrexate and prednisone have comparable effects on pulmonary function, although differ in side-effect profiles and time to efficacy. For refractory cases, second-line therapy involves combining or switching drugs, with anti-tumour necrosis factor agents representing third-line options, ideally in expert hands. Novel therapies targeting pathways involved in disease pathogenesis are under investigation. There is growing consensus on the need to revise current treatment algorithms to minimise corticosteroid use and adopt more evidence-based approaches. Future priorities include identifying prognostic biomarkers, refining trial design and establishing meaningful end-points to improve individualised care for the heterogeneous population of patients with sarcoidosis.

Dysregulated calcium and vitamin D metabolism pose unique challenges for clinicians caring for patients with sarcoidosis. These patients often require supplementation to support their metabolic bone health; however, such interventions may theoretically increase the risk of hypercalcemia and hypercalciuria, along with their associated complications. This article presents 4 clinical vignettes that illustrate common dilemmas encountered in managing these patients.

Background: Oral corticosteroids (OCS) have been first-line therapy for sarcoidosis but are associated with substantial toxicity. Steroid-sparing agents (SSAs) are recommended to mitigate corticosteroid-associated morbidity, however, real-world treatment patterns and how SSA modulate comorbidity risk remain incompletely characterized. Methods: We conducted a retrospective cohort study using linked electronic health record data from two tertiary health systems between 1999 and 2025. Adults with sarcoidosis were categorized by treatment strategy: no treatment, steroid monotherapy (SM), or SSA use with or without concomitant corticosteroids. Outcomes were incident corticosteroid-associated comorbidities (cataracts, diabetes, hypertension, osteoporosis, and glaucoma) after the diagnosis of sarcoidosis. Results: Among 11,211 patients (median follow-up 88 months), 56% received treatment, including 34% with SM and 22% with SSA therapy. Patients on therapy with either SM or SSA had higher rates of incident comorbidities compared to patients who did not require therapy. In multivariate analysis SM use when compared to SSA was associated with greater hazard ratio of new cataracts (HR 1.4, 95% CI 1.1-2.0), diabetes (HR 1.4, 95% CI 1.2-1.8), hypertension (HR 1.4, 95% CI 1.2-1.7), and osteoporosis (HR 1.8, 95% CI 1.4-2.4). The benefit of SSA was consistent across race, gender and socioeconomic groups. Conclusions: Steroid monotherapy remains a common treatment strategy in sarcoidosis management. Use of steroid-sparing agents reduced steroid-associated morbidity compared to steroid monotherapy.

Cardiac imaging is a cornerstone in the initial diagnosis, management, and follow-up of cardiac sarcoidosis. However, ordering thresholds, access, and follow-up imaging vary across the globe. A Delphi study was conducted to define areas of consensus and areas requiring further study in the use of cardiac imaging in suspected or established cardiac sarcoidosis. An international, multidisciplinary panel of experts in cardiac sarcoidosis completed a modified 2-round Delphi study. The study evaluated clinical decision making regarding the use of cardiac imaging, including indication thresholds, interpretation, and interval follow-up imaging. Consensus was defined a priori as ≥70% agreement or disagreement. A total of 89 experts in cardiac sarcoidosis (89 in round 1 and 75 in round 2) participated, representing 61 centers in 13 countries. Consensus was reached on 22 of 46 items (48%) in round 1 and 21 of 29 items (72%) in round 2. There was a low threshold to order advanced cardiac imaging for new rhythm abnormalities or ventricular dysfunction detected on echocardiography in patients with established extracardiac sarcoidosis. 18F-fluorodeoxyglucose (FDG) positron emission tomography was an important co-primary modality with cardiac magnetic resonance (CMR) for initial diagnosis. If CMR was the first test, there was consensus to proceed to FDG-positron emission tomography after any abnormal CMR result or even after normal CMR result in the setting of moderate or high pretest probability for cardiac sarcoidosis. There was consensus that late gadolinium enhancement quantification was important, but there was no consensus on the threshold of risk or on how best to quantify late gadolinium enhancement. Similarly, reduction in FDG uptake was an important factor in guiding treatment response, but there was no consensus on how to best quantify FDG uptake or what constituted an adequate radiographic response. Several consensus areas for cardiac imaging in suspected and established cardiac sarcoidosis were identified. This consensus study identified areas of priority for future prospective, controlled, multicenter research studies.

For over seven decades, oral corticosteroids have been the cornerstone of sarcoidosis management. Oral corticosteroids suppress sarcoidosis inflammation rapidly, but long-term oral corticosteroids result in toxicity and some patients are unable to taper oral corticosteroids without experiencing disease flare ups. The routine use of oral corticosteroids as first-line therapy, as recommended in sarcoidosis guidelines, could have unintentionally promoted the long-term use of oral corticosteroids. We believe that oral corticosteroids should no longer be considered as first-line therapy in all patients with sarcoidosis requiring treatment. Furthermore, we view long-term use of oral corticosteroids in sarcoidosis as an undesirable outcome. When initial oral corticosteroids are required, we propose that oral corticosteroids be used as bridging therapy, ideally for no longer than 3-4 months. There is an urgent need to address the widespread use of long-term maintenance therapy with oral corticosteroids in patients with sarcoidosis, and we advocate the systematic withdrawal of steroid therapy with replacement, if necessary, by other immunosuppressive agents.

BACKGROUND:Corticosteroids, the most commonly prescribed treatment for sarcoidosis, are associated with significant toxicity, especially with long-term usage. New intervention trials designed to reduce or eliminate corticosteroids require pertinent and precise clinical trial end-points. However, consensus is lacking. The aim of the current study is to develop consensus for trial end-points in pulmonary sarcoidosis. METHODS:A Delphi survey was developed by an Expert Panel of 30 sarcoidosis investigators. For Round 1, the panel created 97 statements regarding potential end-points for a clinical trial of symptomatic pulmonary corticosteroid-treated sarcoidosis patients. After anonymous voting in Round 2, the 97 statements were refined by all Stakeholders, including the Expert Panel and an additional 70 individuals interested in sarcoidosis therapies. RESULTS:After Round 2, the Expert Panel achieved consensus for combination end-points on 38 statements across six domains that supported the following end-points: prednisone reduction by 50% or discontinuation, 10% predicted or greater improvement in forced vital capacity % predicted, forced expiratory volume in 1 s % predicted and diffusing capacity of the lung for carbon monoxide % predicted, and improvement in the King's Sarcoidosis Questionnaire Lung and General Health domains. Additionally, the majority of Stakeholders agreed to all statements which reached consensus by the Expert Panel. CONCLUSIONS:Utilising the Delphi technique, international sarcoidosis experts successfully achieved consensus for 38 specific clinical trial end-points which can be utilised in the development of novel steroid-sparing and eliminating therapies for pulmonary sarcoidosis.

We evaluated relationships between changes in lung function and changes in patient-reported outcomes (PROs) in 736 patients with idiopathic pulmonary fibrosis (IPF) enrolled in the IPF-PRO Registry. Weak correlations were observed between changes in percent predicted values for forced vital capacity or diffusing capacity of the lungs (DLco) and changes in St George’s Respiratory Questionnaire (SGRQ) total and activity scores and the 12-item Short Form Survey (SF-12) physical component summary score over 12-month periods. Patients who had a deterioration in SGRQ activity score or SF-12 PCS score of ≥ 5 units had numerically larger declines in lung function than other patients, but the differences were small. The weak relationships observed between changes in lung function and changes in PROs underscore the importance of evaluating both changes in lung function and changes in HRQL in clinical practice and clinical trials.

Over the past few years, an increased number of clinical trials have been performed evaluating specific therapies for pulmonary and cardiac sarcoidosis. However, a lack of consensus remains for appropriate clinical trial endpoints. In 2024, the World Association of Sarcoidosis and Other Granulomatous disease (WASOG) established a clinical trial endpoint Task Force to update the 2011 WASOG Task Force. This initiative was spearheaded by five sarcoidosis specialists (RPB, EEL, DAC, MAJ, AUW) and enlisted a total of 55 stakeholders, including 37 health care providers, 14 industry representatives, and 4 patients. In March 2025, 46 stakeholders participated in a one-day meeting which included twenty focused talks regarding clinical trial endpoints for pulmonary and cardiac sarcoidosis trials. A compilation of individual talk summaries was prepared and distributed to all stakeholders, including those unable to attend the meeting. Based on feedback from all stakeholders, the team leaders developed a series of statements reflecting the presentations and discussions with subsequent anonymous voting by all stakeholders. The majority of the voters endorsed thirteen specific clinical trial endpoint statements: two evaluating overall trial design, seven regarding pulmonary sarcoidosis, and four discussing cardiac sarcoidosis.

PURPOSE:Surgical lung biopsy (SLB) offers the highest histopathologic yield for interstitial lung disease (ILD). We sought to identify risk factors for complications, and developed a predictive model to help stratify risk for patients being considered for SLB. METHODS:Large single center retrospective study of outpatient SLBs with individually confirmed biopsy indication. Demographics, pulmonary function, and echocardiogram reports were analyzed for association with complications, measured by length of stay (LOS). A LOS ≥7 days (including readmissions) in the first 90 post procedure days was taken to represent serious complications. Logistic regression was used to determine who could safely undergo SLB, defined as a LOS ≤2 days. RESULTS:172 of 231 (75 %) patients had a LOS ≤2 days. Serious complications occurred in 13 (5.6 %), including 6 (2.6 %) exacerbations and 5 (2.2 %) deaths. Forced vital capacity (FVC)% was independently associated with LOS (OR of 0.98, 95 % CI 0.97-0.99). Right ventricular systolic pressure (RVSP) was also independently associated with LOS >2 days (OR 1.51, 95 % CI 1.09, 2.14). INTERPRETATION:In our experience SLB remains an important tool in the management of patients with ILD. Risk stratification suggests that patients with lower FVC% and pulmonary hypertension are at higher risk for increased LOS and a more complicated post-procedure recovery. The odds of complications increase by 51 % with each 1 mm Hg increase in RVSP as assessed by echocardiography. Risk might be mitigated by referring patients for SLB earlier, rather than reserving it for when more severe disease has developed.

BACKGROUND:Cardiac imaging is a cornerstone in the initial diagnosis, management, and follow-up of cardiac sarcoidosis. However, ordering thresholds, access, and follow-up imaging vary across the globe. OBJECTIVES:A Delphi study was conducted to define areas of consensus and areas requiring further study in the use of cardiac imaging in suspected or established cardiac sarcoidosis. METHODS:An international, multidisciplinary panel of experts in cardiac sarcoidosis completed a modified 2-round Delphi study. The study evaluated clinical decision making regarding the use of cardiac imaging, including indication thresholds, interpretation, and interval follow-up imaging. Consensus was defined a priori as ≥70% agreement or disagreement. RESULTS:A total of 89 experts in cardiac sarcoidosis (89 in round 1 and 75 in round 2) participated, representing 61 centers in 13 countries. Consensus was reached on 22 of 46 items (48%) in round 1 and 21 of 29 items (72%) in round 2. There was a low threshold to order advanced cardiac imaging for new rhythm abnormalities or ventricular dysfunction detected on echocardiography in patients with established extracardiac sarcoidosis. 18F-fluorodeoxyglucose (FDG) positron emission tomography was an important co-primary modality with cardiac magnetic resonance (CMR) for initial diagnosis. If CMR was the first test, there was consensus to proceed to FDG-positron emission tomography after any abnormal CMR result or even after normal CMR result in the setting of moderate or high pretest probability for cardiac sarcoidosis. There was consensus that late gadolinium enhancement quantification was important, but there was no consensus on the threshold of risk or on how best to quantify late gadolinium enhancement. Similarly, reduction in FDG uptake was an important factor in guiding treatment response, but there was no consensus on how to best quantify FDG uptake or what constituted an adequate radiographic response. CONCLUSIONS:Several consensus areas for cardiac imaging in suspected and established cardiac sarcoidosis were identified. This consensus study identified areas of priority for future prospective, controlled, multicenter research studies.