Hematologic and Oncologic Aspects of Sarcoidosis: Some of the Least Studied but Most Common Dilemmas.

The hematologic system is frequently involved in sarcoidosis. Lymphopenia is the most common hematologic manifestation noted, although anemia and thrombocytopenia also occur. The etiology of these common manifestations can be direct granulomatous infiltration of bone marrow, lymph nodes, or spleen or related to immunologic dysfunction. Although not life threatening, these problems can lead to cytopenias requiring close monitoring in patients receiving a variety of disease treatments. The relationship between sarcoidosis and malignancy remains complex. However, some sarcoidosis patients are at increased risk for the development of malignancies, particularly lymphomas and gastrointestinal cancers. Conversely, cancer patients can experience an increase in the likelihood for the development of breast cancer and lymphomas.

Hematological involvement in sarcoidosis: from cytopenias to lymphoma.

INTRODUCTION: We present an updated overview of the hematological involvementassociated with sarcoidosis, including a management approach forcytopenias and revisiting the association with hematologicalmalignancies. AREAS COVERED: Theetiology of cytopenias in sarcoidosis can be attributed to two majoretiopathogenic mechanisms: infiltration of hematopoietic organs suchas the spleen and bone marrow, and autoimmune-mediated cytopenias.With respect to the association with hematological malignancies, itrequires careful evaluation of patients from a chronologicalperspective. Patients must be classified into one of three pathogenicscenarios, including preexisting hematological malignancies,synchronous development of malignancy and sarcoidosis due to commonpredisposing factors, or sarcoidosis as a predisposing factor formalignancies. EXPERT OPINION: The association between sarcoidosis and hematologic involvement isbest understood as a pathogenic continuum, with cytopenias andhematologic neoplasms intertwined due to various etiopathogenicmechanisms. These mechanisms include sarcoid infiltration ofhematopoietic organs, common predisposing immunogenetics for thedevelopment of autoimmune cytopenias and malignancies, and anincreased risk of neoplasm development in patients with autoimmunecytopenias. Collaboration among the main specialties involved in theclinical management of these patients is crucial for an earlymonitoring and management.

High-Resolution CT Scan Fibrotic Patterns in Stage IV Pulmonary Sarcoidosis: Impact on Pulmonary Function and Survival.

BACKGROUND: Different patterns of fibrosis on high-resolution CT scans (HRCT) have been associated with reduced survival in some interstitial lung diseases. Nothing is known about HRCT scan patterns and survival in sarcoidosis. RESEARCH QUESTION: Will a detailed description of the extent and pattern of HRCT scan fibrosis in patients with stage IV pulmonary sarcoidosis impact pulmonary function and survival? STUDY DESIGN AND METHODS: Two hundred forty patients with stage IV sarcoidosis at two large tertiary institutions were studied. The earliest HRCT scan with fibrosis was reviewed for extent of fibrosis (< 10%, 10%-20%, and > 20%) and presence of bronchiectasis, upper lobe fibrocystic changes, basal subpleural honeycombing, ground-glass opacities (GGOs), large bullae, and mycetomas. Presence of sarcoidosis-associated pulmonary hypertension (SAPH) and pulmonary function testing performed within 1 year of HRCT were recorded. Patients were followed up until last clinic visit, death, or lung transplantation. RESULTS: The mean age was 58.4 years. Seventy-four percent were Black, 63% were female, and mean follow-up was 7.4 years. Death or LT occurred in 53 patients (22%). Thirty-one percent had > 20% fibrosis, 25% had 10%-20% fibrosis, and 44% had < 10% fibrosis. The most common HRCT abnormalities were bronchiectasis (76%), upper lobe fibrocystic changes (36%), and GGOs (28%). Twelve percent had basal subpleural honeycombing, and 32% had SAPH. Patients with > 20% fibrosis had more severe pulmonary impairment, were more likely to have SAPH (53%), and had worse survival (44% mortality; P < .001). Upper lobe fibrocystic changes, basal subpleural honeycombing, and large bullae were associated with worse pulmonary function and worse survival. Patients with basal subpleural honeycombing had the worst pulmonary function and survival (55% mortality; P < .001). GGOs were associated with worse pulmonary function but not worse survival, and mycetomas were associated with worse survival but not worse pulmonary function. A Cox proportional hazards model indicated that basal subpleural honeycombing (hazard ratio, 7.95), diffusion capacity for carbon monoxide < 40% (HR, 5.67) and White race (hazard ratio, 2.61) were independent predictors of reduced survival. INTERPRETATION: HRCT scan features of fibrotic pulmonary sarcoidosis had an impact on pulmonary function and survival. Presence of >20% fibrosis and basal subpleural honeycombing are predictive of worse pulmonary function and worse survival in patients with stage IV pulmonary sarcoidosis.

SACE and IL-2R as serum biomarkers for evaluation of multi-organ involvement and prognosis of sarcoidosis.

BACKGROUND: Serum biomarkers in the evaluation of organ involvement and prognostic monitoring of sarcoidosis have not been determined. The purpose of this study was to identify common biomarkers that could be used to assess organ involvement and monitor outcomes in sarcoidosis patients. METHODS: From Mar 2013 to Sep 2021, patients with newly diagnosed pulmonary sarcoidosis were enrolled in this study in Shanghai Pulmonary Hospital. The information from medical records was retrospectively collected including diagnosis, organ involvement, laboratory tests and follow up data. Differences of continuous variables between groups were analyzed by unpaired Student's t-test. Multivariate logistic regression model was performed to identify potential independent factors associated with multiple organ involvement. RESULTS: A total of 832 patients were included in the study. There were 339 (40.7%) patients with single organ pulmonary involvement, while 493 (59.3%) patients had two to seven organs involved. Among the routine serum tests, only the serum angiotensin converting enzyme (SACE) level was an independent factor of multiple organ involvement. Compared to those patients without involvement, SACE levels were higher in patients with extra-thoracic lymph node, skin, or spleen involvement as well as abnormal calcium metabolism. Interleukin-2 receptor (IL-2R) levels were higher in patients with extra-thoracic lymph node, spleen involvement and abnormal calcium metabolism than in those without it. The mean levels of SACE and IL-2R showed upward trends paralleling the increase on number of organs involved. In follow up, SACE and IL-2R levels were both decreased in an improved patient group, while there was no obvious difference was noticed before and after treatment in patients with persistent disease. CONCLUSION: SACE and IL-2R were useful as serum biomarkers in the initial evaluation of organ involvement as well as monitoring prognosis in sarcoidosis.

Initial behaviors and attitudes towards the COVID-19 vaccine in sarcoidosis patients: results of a self-reporting questionnaire.

BACKGROUND: Individuals with self-declared sarcoidosis are at increased risk of COVID-19 related morbidity and mortality for which vaccination can be lifesaving. Despite this, vaccine hesitancy remains a large barrier to global acceptance of vaccination against COVID-19. We aimed to identify individuals with sarcoidosis who had and had not been vaccinated against COVID-19 vaccine to 1) establish a safety profile of COVID-19 vaccination in those with sarcoidosis and 2) to elucidate factors that contribute to COVID-19 vaccine hesitancy. METHODS: A questionnaire inquiring about COVID-19 vaccination status, vaccination side effects, and willingness for future vaccination was distributed from December 2020 to May 2021 to individuals with sarcoidosis living in the US and European countries. Details regarding sarcoidosis manifestations and treatment were solicited. Vaccine attitudes were classified as pro or anti-COVID-19 vaccination for subgroup analysis. RESULTS: At the time of questionnaire administration, 42% of respondents had already received a COVID-19 vaccination, most of whom either denied side effects or reported a local reaction only. Those off sarcoidosis therapy were more likely to report systemic side effects. Among subjects who had not yet received a COVID-19 vaccine, 27% of individuals reported they would not receive one once available. Reasons against vaccination were overwhelmingly related to the lack of confidence in vaccine safety and/or efficacy and less related to concerns associated with convenience or complacency. Black individuals, women, and younger adults were more likely to decline vaccination. CONCLUSIONS: Among individuals with sarcoidosis, COVID-19 vaccination is well-accepted and well-tolerated. Subjects on sarcoidosis therapy reported significantly less vaccination side effects, and thus the correlation between side effects, vaccine type, and vaccine efficacy requires further investigation. Strategies to improve vaccination should focus on improving knowledge and education regarding vaccine safety and efficacy, as well as targeting sources of misinformation, particularly in young, black, and female subpopulations.

Validation of the Sarcoidosis Diagnostic Score in a Multicontinental Study.

Rationale: The Sarcoidosis Diagnostic Score (SDS) has been established to quantitate the clinical features consistent with sarcoidosis in a monocentric study. Objectives: We aimed to confirm the diagnostic value of SDS in a large, multicontinental study and to assess the utility of SDS in differentiating sarcoidosis from alternative diagnoses, including infectious and noninfectious granulomatous diseases. Methods: We included patients with biopsy-confirmed sarcoidosis at nine centers across the world. Patients without sarcoidosis seen at the same sites served as control patients. Using a modified World Association of Sarcoidosis and Other Granulomatous Disorders organ assessment instrument, we scored all patients for the presence of granuloma on biopsy, highly probable symptoms, and least probable symptoms for each area. Two sarcoidosis scores were generated: SDS Biopsy (with biopsy) and SDS Clinical (without biopsy). SDS Clinical and Biopsy were calculated for all patients. We calculated and compared the area under the curve (AUC) for SDS Clinical and Biopsy according to different diagnosis scenarios. Results: A total of 1,041 patients with sarcoidosis and 1,035 without sarcoidosis were included. The results for SDS Clinical (AUC, 0.888; 95% confidence interval [CI], 0.874-0.902) and SDS Biopsy (AUC, 0.979; 95% CI, 0.973-0.985) according to AUC were good to excellent for differentiating sarcoidosis from alternative diagnosis. SDS Clinical was less discriminatory in males (P = 0.01) and in high tuberculosis prevalence centers (P < 0.001). However, SDS Clinical (AUC, 0.684; 95% CI, 0.602-0.766) and SDS Biopsy (AUC, 0.754; 95% CI, 0.673-0.835) were not sufficiently discriminative for noninfectious granulomatous diseases, but both SDSs could differentiate sarcoidosis from infectious granulomatous diseases. Algorithms were proposed for the SDS Clinical and SDS Biopsy to assist the clinician in the diagnostic process, and cutoff values were proposed for the SDS Clinical and SDS Biopsy, allowing the diagnosis of sarcoidosis to be safely confirmed or rejected in most cases except for noninfectious granulomatous disease. Conclusions: This multicontinental study confirms that both SDS Clinical and SDS Biopsy have good to excellent performance in discriminating sarcoidosis from alternative diagnoses. Differences in the AUC were seen for high tuberculosis prevalence versus low tuberculosis prevalence centers and for males versus females. Both SDSs had good discriminatory function for infectious granulomatous disease but failed in cases of noninfectious granulomatous disease such as berylliosis.

Controversies in the Treatment of Cardiac Sarcoidosis.

There are many challenging aspects of the management of cardiac sarcoidosis (CS) with corticosteroids and other immunosuppressive therapy (IST). First, it is not always clear who will benefit from therapy or when to initiate treatment. Secondly, there are no randomized controlled trials or large prospective studies to guide what medications to use, at what doses, and for how long. The European Respiratory Society (ERS) clinical practice guidelines on the treatment of sarcoidosis makes a strong recommendation for the use of immuno-suppressive therapy in CS patients with functional cardiac abnormalities, including heart blocks, dysrhythmias, or cardiomyopathy where patients are considered at-risk of adverse outcomes. Corticosteroids are the first line immunosuppressive therapy in CS however, early initiation of second-line steroid sparing medications has been advocated and there is data to suggest that concomitant initiation of therapy may be more beneficial. The use of anti-tumor necrosis factor (anti-TNF) agents (including infliximab and adalimumab) considered beneficial third-line anti-sarcoidosis treatment agents in other severe refractory manifestations of disease remains controversial.

Transcriptional coactivator MED1 in the interface of anti-estrogen and anti-HER2 therapeutic resistance.

Breast cancer is one of the most common cancer and leading causes of death in women in the United States and Worldwide. About 90% of breast cancers belong to ER+ or HER2+ subtypes and are driven by key breast cancer genes Estrogen Receptor and HER2, respectively. Despite the advances in anti-estrogen (endocrine) and anti-HER2 therapies for the treatment of these breast cancer subtypes, unwanted side effects, frequent recurrence and resistance to these treatments remain major clinical challenges. Recent studies have identified ER coactivator MED1 as a key mediator of ER functions and anti-estrogen treatment resistance. Interestingly, MED1 is also coamplified with HER2 and activated by the HER2 signaling cascade, and plays critical roles in HER2-mediated tumorigenesis and response to anti-HER2 treatment as well. Thus, MED1 represents a novel crosstalk point of the HER2 and ER pathways and a highly promising new therapeutic target for ER+ and HER2+ breast cancer treatment. In this review, we will discuss the recent progress on the role of this key ER/HER2 downstream effector MED1 in breast cancer therapy resistance and our development of an innovative RNA nanotechnology-based approach to target MED1 for potential future breast cancer therapy to overcome treatment resistance.

Chest high-resolution computed tomography can make higher accurate stages for thoracic sarcoidosis than X-ray.

BACKGROUND: To explore if chest high-resolution computed tomography (HRCT) can make higher accurate stages for thoracic sarcoidosis stage than X-ray (CRX) only. METHODS: Clinical data from medical records of consecutive patients with a confirmed diagnosis of pulmonary sarcoidosis at Shanghai Pulmonary Hospital from January 1 2012 to December 31 2016 and consecutive patients treated at the Sarcoidosis Center of University of Cincinnati Medical Center, Ohio, USA from January 1 2010 to December 31 2015 were reviewed. The clinical records of 227 patients diagnosed with sarcoidosis (140 Chinese and 87 American) were reviewed. Their sarcoidosis stage was determined by three thoracic radiologists based on CXR and HRCT presentations, respectively. The stage determined from CXR was compared with that determined from HRCT. RESULTS: Overall, 50.2% patients showed discordant sarcoidosis stage between CXR and HRCT (52.9% in Chinese and 44.8% in American, respectively). The primary reason for inconsistent stage between CXR and HRCT was failure to detect mediastinal lymph node enlargement in the shadow of the heart in CXR (22.1%) and small nodules because of the limited resolution of CXR (56.6%). Stage determined from HRCT negatively correlated with carbon monoxide diffusing capacity (DLCO) significantly (P < .01) but stage determined from CXR did not. Pleural involvement was detected by HRCT in 58 (25.6%) patients but only in 17 patients (7.5%) by CXR. Patients with pleural involvement had significantly lower forced vital capacity and DLCO than patients without it (both P < .05). CONCLUSION: Revised staging criteria based on HRCT presentations included 5 stages with subtypes in the presence of pleural involvement were proposed. Thoracic sarcoidosis can be staged more accurately based on chest HRCT presentations than based on CXR presentations. Pleural involvement can be detected more accurately by HRCT.

The association of baseline sarcoidosis measurements with 6-month outcomes that are of interest to patients: Results from the On-line Sarcoidosis Assessment Platform Study (OSAP).

INTRODUCTION: The impact of common measures to assess sarcoidosis have not been compared longitudinally to outcomes that are meaningful to patients. We prospectively examined the relationship of baseline measurements of sarcoidosis status to outcomes of interest to patients longitudinally over 6 months. METHODS: Sarcoidosis patients cared for at 6 US medical centers were "phenotyped" at baseline with measurements of pulmonary function, organ involvement, health related quality of life (HRQoL) instruments, and their anti-sarcoidosis treatment history. These patients were followed for 6 months by monitoring outcomes of interest to patients (OIPs) including steps walked, calories expended, sleep, HRQoL measures, workdays missed and health care utilization. For each baseline phenotypic measurement, patients were dichotomized into two groups above and below a specified cutoff value. The area under the OIP versus time curve was compared between these two groups. RESULTS: The cutoff values for many baseline phenotypic measures distinguished the patients into groups with significantly different 6-month OIPs. The chosen cutoff for the patient global estimate of health status distinguished the most OIPs (13/15). The 6-min walk distance cutoff was associated with more OIPs than spirometric measures. All of the HRQOL measure cutoffs were associated with many OIPs, although most of them were other HRQOL measures. INTERPRETATION: Cutoffs for most of the phenotypic measures used to assess sarcoidosis distinguished groups of sarcoidosis patients with differing OIPs over the subsequent 6 months. The patients' global assessment of their disease was the most accurate of these measures. CLINICAL TRIAL REGISTRATION NUMBER: NCT04342403.

Echocardiographic estimate of pulmonary artery pressure in sarcoidosis patients - real world data from a multi-national study.

INTRODUCTION: Echocardiographic measurement of the right ventricular systolic pressure (RVSP) is commonly used for estimating systolic pulmonary artery pressure (PASP) measured during right heart catheterization (RHC) in patients suspected for pulmonary hypertension (PH). Generally, there seems to be a strong correlation. However, this has been reported as less robust in sarcoidosis. We aim to investigate the correlation between RVSP and RHC measurements using real world data and analyzed factors influencing the relationship between RVSP and PASP in sarcoidosis. METHODS & RESULTS: Data of patients with and without sarcoidosis associated PH who had both a measurable echocardiographic RVSP and invasive PASP were collected from the RESAPH registry, PULSAR study and Cincinnati Sarcoidosis Clinic database (n=173, 60.1% female, mean age 56.0±9.5 years). Among them, 124 had PH confirmed by RHC. There was a strong correlation between RVSP and PASP (r=0.640). This correlation was significant in both male and female, white or non-white, forced vital capacity (FVC) >60%, and presence of fibrosis (p<0.001). However, it was less robust in patients with FVC of 50% or less. RVSP was considered inaccurate if the difference with PASP was > 10mmHg. Inaccurate echocardiographic estimation of the invasive PASP occurred in 50.8%, with overestimation mostly in patients without PH, and underestimation in patients with severe PH. An RVSP>50mmHg was associated with worse survival. CONCLUSIONS: In this real world multicenter cohort of sarcoidosis patients, we found a significant correlation between RVSP as determined by echocardiography and invasive PASP. Over- or underestimation of PASP occurred frequently. Therefore, echocardiographic RVSP measurement alone to screen for PH in sarcoidosis should be used with caution.

WASOG statement on the diagnosis and management of sarcoidosis-associated pulmonary hypertension.

Sarcoidosis-associated pulmonary hypertension (SAPH) is an important complication of advanced sarcoidosis. Over the past few years, there have been several studies dealing with screening, diagnosis and treatment of SAPH. This includes the results of two large SAPH-specific registries. A task force was established by the World Association of Sarcoidosis and Other Granulomatous disease (WASOG) to summarise the current level of knowledge in the area and provide guidance for the management of patients. A group of sarcoidosis and pulmonary hypertension experts participated in this task force. The committee developed a consensus regarding initial screening including who should undergo more specific testing with echocardiogram. Based on the results, the committee agreed upon who should undergo right-heart catheterisation and how to interpret the results. The committee felt there was no specific phenotype of a SAPH patient in whom pulmonary hypertension-specific therapy could be definitively recommended. They recommended that treatment decisions be made jointly with a sarcoidosis and pulmonary hypertension expert. The committee recognised that there were significant defects in the current knowledge regarding SAPH, but felt the statement would be useful in directing future studies.

Riociguat for Sarcoidosis-Associated Pulmonary Hypertension: Results of a 1-Year Double-Blind, Placebo-Controlled Trial.

BACKGROUND: Riociguat is effective in delaying the time to clinical worsening (TCW) in patients with groups 1 and 4 pulmonary hypertension. RESEARCH QUESTION: Is riociguat more effective than placebo in prolonging TCW in sarcoidosis-associated pulmonary hypertension (SAPH)? STUDY DESIGN AND METHODS: This was a double-blind placebo-controlled trial. Patients with SAPH confirmed by right heart catheterization were randomized 1:1 to riociguat or placebo. Patients underwent 6-min walk distance (6MWD) and spirometry testing every 8 weeks. The primary end point was TCW, which was defined by the time to the first of the following: (1) all-cause mortality, (2) need for hospitalization because of worsening cardiopulmonary status attributable to progression of disease, (3) > 50 m decrease in the 6MWD test, or (4) worsening of World Health Organization functional class. RESULTS: A total of 16 patients were randomized to riociguat (n = 8) or placebo (n = 8). No difference was found in pulmonary artery mean, pulmonary vascular resistance, initial 6MWD, or FVC between the two groups. Five of eight patients who received placebo met TCW criteria, whereas none of the patients who received riociguat experienced a qualifying event. By log-rank analysis, patients who received riociguat were in the study for a significantly longer period (χ 2 = 6.259; P = .0124). The 6MWD decreased in the placebo group (median, -55.9 m; range, -176.8 to 60 m), but rose in the riociguat group (median, +42.7 m; range, -7.5 to +91.4 m; P = .0149), with a placebo-corrected difference of 94 m (P < .01). Four of eight patients who received riociguat, but only 1 of 8 patients who received placebo, showed a > 30-m improvement in 6MWD (P > .05). No significant adverse events associated with riociguat occurred. INTERPRETATION: Over the 1 year of the study, riociguat was effective in preventing clinical worsening and improving exercise capacity in patients with SAPH. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT02625558; URL: www.clinicaltrials.gov.

Assessment of dyspnea in sarcoidosis using the Baseline Dyspnea Index (BDI) and the Transition Dyspnea Index (TDI).

INTRODUCTION: The Borg and Modified Medical Research Council (mMRC) dyspnea scales have been used to evaluate dyspnea in sarcoidosis. The Baseline Dyspnea Index (BDI) and Transitional Dyspnea Index (TDI) are useful for the assessment of dyspnea in COPD. It is not known if the BDI-TDI accurately assesses dyspnea in sarcoidosis patients. METHODS: Data was analyzed from the Registry for Advanced Sarcoidosis (ReAS), a multi-national database enrolling patients with advanced sarcoidosis and a comparison group of sarcoidosis patients with non-advanced disease. At baseline, patients completed a BDI questionnaire along with spirometry, 6-min walk distance (6MWD), mMRC, Borg score, fatigue assessment score (FAS) and HRQoL assessments using Kings Sarcoidosis Questionnaire (KSQ) and St Georges Respiratory Questionnaire (SGRQ). At 12-months, patients with advanced disease completed a TDI questionnaire along with the other measures. Correlations between BDI and baseline variables, and between TDI and changes in baseline variables were evaluated. RESULTS: There was significant correlation (p < 0.001 for all) between BDI and baseline 6MWD (rho = 0.336), FVC% (rho = 0.387), FEV1% (rho = 0.285), DLCO% (rho = 0.355), mMRC (rho = -0.721), Borg score (rho = -0.389), FAS (rho = -0.669), SGRQ (rho = -0.785), and KSQ (rho = 0.318 to 0.724). At follow-up, TDI correlated with BDI, but not with changes in pulmonary function or other dyspnea measures. CONCLUSION: BDI scores correlated with pulmonary function, 6MWD, and other dyspnea measures. TDI scores did not correlate with changes in pulmonary function or other dyspnea measures. BDI may be a useful independent measure of dyspnea in sarcoidosis patients. The role of TDI needs further evaluation in longitudinal studies associated with changes in clinical parameters.

Roflumilast (Daliresp®) to reduce acute pulmonary events in fibrotic sarcoidosis: a multi-center, double blind, placebo controlled, randomized clinical trial.

BACKGROUND: Fibrotic sarcoidosis patients often have acute events of increased cough and sputum production. We evaluated the impact of roflumilast in fibrotic sarcoidosis patients with repeated episodes of increased cough and sputum. METHODS: Sarcoidosis patients with pulmonary fibrosis and at least two acute episodes in the previous year were randomized to receive either roflumilast (ROF) or placebo (PLA) in a double blind, placebo controlled multi-center trial. Subjects were assessed initially and every three months for 12 months. At each visit, spirometry and health related quality of life questionnaires were completed. For each subject, the best forced expiratory volume at 1 second (FEV-1) was noted. RESULTS: Of the 38 subjects who enrolled in the study, 28 subjects (14 in each group) received at least three months of treatment and 10 in each arm completing all 12 months of study. During the treatment, patients treated with ROF were less likely to have visits in which the FEV-1 was less than 90% of the best FEV-1 (Odds ratio=0.34 (0.16 to 0.76 95% confidence interval, p=0.0073). At the end of treatment with ROF, patients had a significant improvement in their KSQ LUNG (Initial visit: 45.3 ± 6.89 (Mean ± S.D.); Last visit: 52.6± 7.91, p<0.05) with no change for PLA treated patients. CONCLUSION: Patients treated with at least three months of roflumilast had fewer follow-up visits with an FEV-1 of less than 90% of best value. At the end of treatment, ROF treated patients had a better quality of life as assessed by KSQ LUNG. CLINICAL TRIAL REGISTRATION: NCT01830959.

The impact of demographic disparities in the presentation of sarcoidosis: A multicenter prospective study.

OBJECTIVE: To study how demographic differences impact disease manifestation of sarcoidosis using the WASOG tool in a large multicentric study. METHODS: Clinical data regarding 1445 patients with sarcoidosis from 14 clinical sites in 10 countries were prospectively reviewed from Feb 1, 2020 to Sep 30, 2020. Organ involvement was evaluated for the whole group and for subgroups differentiated by sex, race, and age. RESULTS: The median age of the patients at diagnosis was 46 years old; 60.8% of the patients were female. The most commonly involved organ was lung (96%), followed by skin (24%) and eye (22%). Black patients had more multiple organ involvement than White patients (OR = 3.227, 95% CI: 2.243-4.643) and females had more multiple organ involvement than males (OR = 1.238, 95% CI: 1.083-1.415). Black patients had more frequent involvement of neurologic, skin, eye, extra thoracic lymph node, liver and spleen than White and Asian patients. Women were more likely to have eye (OR = 1.522, 95%CI: 1.259-1.838) or skin involvement (OR = 1.369, 95%CI: 1.152-1.628). Men were more likely to have cardiac involvement (OR = 1.326, 95%CI: 1.096-1.605). A total of 262 (18.1%) patients did not receive systemic treatment for sarcoidosis. Therapy was more common in Black patients than in other races. CONCLUSION: The initial presentation and treatment of sarcoidosis was related to sex, race, and age. Black and female individuals are found to have multiple organ involvement more frequently. Age at diagnosis<45, Black patients and multiple organ involvement were independent predictors of treatment.