Sarcoidosis Mortality in North Carolina: Role of Region, Race, and Other Sociodemographic Variables.

Background: There is regional variability in sarcoidosis mortality across the United States. North Carolina ranks highly in sarcoidosis-related mortality, especially among African Americans (AA). We sought to determine any regional variability of sarcoidosis-related mortality and the relationship to sociodemographic determinants of health in North Carolina. Methods: Counties in North Carolina were categorized into three distinct geographic regions: Western, Piedmont, and Eastern. Sarcoidosis deaths were stratified by region, race, and gender. We conducted a mapping and cluster analysis utilizing ArcGIS; Global and Local Moran's I was used to determine the prevalence, spatial autocorrelation, and clustering of mortality vis-a-vis various sociodemographic variables, occupational/environmental exposures, and levels of atmospheric particulate matter less than 2.5 microns in size (PM2.5). Multivariate linear regression with exposure limited to the county level was used to determine the relationship between sarcoidosis mortality and the variables of interest. Results: Eastern North Carolina (ENC) had the highest age-adjusted sarcoidosis mortality rate (1.16/100,000 versus 0.49/100,000 in Piedmont and 0.32/100,000 in the Western region) with statistically significant high-high mortality clusters (P < .001 for Global Moran's I). Several sociodemographic and occupational factors (proportion of AA, obese adults, and individuals working in nature) were more prevalent in ENC. Region and proportion of AA were the significant mortality predictors in our multivariate analysis. Limitations: This was a cross-sectional study with exposure limited to the county level. Associations do not imply causality and risks cannot be extrapolated to the individual level. Conclusion: There is regional variability of sarcoidosis mortality in North Carolina. Eastern North Carolina had the highest mortality with high-high mortality clusters.

Comparison of organ involvement clusters in Black and White American sarcoidosis patients from a prospectively collected patient registry.

BACKGROUND: Due to the heterogeneity of sarcoidosis, there is a need to define clinical phenotypes to allow for tailoring of clinical care and identification of more homogenous populations to facilitate research. METHODS: We utilized data from a prospectively collected registry of sarcoidosis patients seen at a single quaternary referral center between January 2019 and February 2021. We used multiple correspondence analysis (MCA) and k-means clustering to investigate if the clusters previously identified in the GenPhenReSa study were reproducible in a US population. We also investigated if these clusters were stable when the population was stratified by race. RESULTS: We replicated 3 of the 5 clusters seen in the GenPhenReSa study in our cohort. We likewise identified similar clusters between White and Black patients with sarcoidosis. Differences in organ manifestations associations between White and Black patients were seen primarily in relation to cardiac, neurologic, and ocular involvement. CONCLUSIONS: The organ clusters of liver-spleen, isolated pulmonary, and musculoskeletal-skin were reproducible in a US cohort, and in both Black and White patients.

Sarcoidosis among US Hispanics in a Nationwide Registry.

BACKGROUND: Sarcoidosis has been well studied in multiple races and ethnic groups. However, there is a paucity of data that describes sarcoidosis in Hispanics. We aimed to determine the prevalence of Hispanic ethnicity, clinical characteristics and impact of sarcoidosis among Hispanics from a US based national registry. METHODS: We conducted a national registry-based study investigating 3835 respondents to the Sarcoidosis Advanced Registry for Cures questionnaire. This registry is a web-based, self-reported questionnaire that provides data related to demographics, diagnostics, organ involvement, treatment modalities, and the physical and psychosocial impact of sarcoidosis. We compared Hispanic patients to non-Hispanics. We performed multivariate logistic regression analysis adjusting for age, gender, education, income and insurance status and looked at the association between Hispanic ethnicity with depression, chronic pain syndrome, chronic fatigue syndrome, impact on family finances, employment-based disability and job termination. RESULTS: Nine percent of the patients reported a Hispanic ethnicity and the majority of these patients self-identified as white women. The most common organs involved were the lungs (74.9%), central lymph nodes (53.8%), and peripheral lymph nodes (37.1%). Hispanics reported more peripheral nerves and peripheral lymph nodes involvement than non-Hispanics. Hispanics experienced more depression, sleep apnea, and chronic pain syndrome than non-Hispanics. The use of mobility assistive devices was more common among Hispanics, as well as employment-based disability, and disease-related job termination compared to non-Hispanics. The majority of Hispanics reported significantly more pain that interfered with the enjoyment of life than non-Hispanics. On multivariate logistic regression analysis, Hispanic ethnicity was associated with depression (adjusted odds ratio (aOR) = 1.5; 95% CI: 1.01-2.2), chronic pain syndrome (aOR = 1.7; 1.1-2.6), job termination due to sarcoidosis (aOR = 1.7; 1.1-2.7) and higher impact on family finances (aOR = 1.7; 1.1-2.5). CONCLUSION: The clinical presentation of sarcoidosis in Hispanic patients differs from that in non-Hispanic patients living in the United States. These differences should be considered when managing Hispanic patients with sarcoidosis. We encourage more studies that investigate phenotyping among Hispanics with sarcoidosis.

Genome-Wide Association Study of Ocular Sarcoidosis Confirms HLA Associations and Implicates Barrier Function and Autoimmunity in African Americans.

Purpose: Identify genes associated with ocular sarcoidosis (OS).Methods: We genotyped 1.1 million genetic variants to identify significant OS associations, defined as those that achieved p < 5 × 10-8 in a genome-wide comparison of OS cases to healthy controls in our European- or African-American cohorts (EA, AA). Potential functional roles of all associated variants were assessed.Results: Eight significant non-HLA variants were found in AA OS cases compared to healthy controls and confirmed as at least suggestive when comparing OS to non-OS cases. Seven of these were within MAGI1 and include transcription factor binding sites and expression quantitative trait loci. Our EA cohort, while showing similar effect sizes at variants within MAGI1, had no significant variants. Association analysis of HLA-DRB1 alleles confirmed association to OS in EA to *04:01.Conclusion: Our results support organ-specific genetic risk in OS in a compelling candidate, MAGI1, known to be associated with barrier function and autoimmunity.

Sarcoidosis Epidemiology: Race Matters.

Rather than a single disease entity, sarcoidosis may be a constellation of "sarcoidoses" with a characteristic pattern of organ involvement and clinic course, depending upon the triggering exposure and underlying epidemiologic factors such as race. This review examines the racial disparities inherent to sarcoidosis disease course and mortality and discusses factors that may be responsible for these findings. In the United States, black patients with sarcoidosis experience more severe pulmonary disease, more multiorgan involvement, and an overall worse prognosis with higher rates of hospitalization and mortality. Beyond inherent genotype, ascertainment and access to medical care, physician implicit bias, and patient perceived discrimination likely play a role. Moving forward, epidemiologic concepts can be used to formulate strategies for control, treatment, and even prevention of disease in black Americans at risk for developing life-altering or life-threatening sarcoidosis phenotypes. Identification and rectification of modifiable risk factors such as socioeconomic status, lack of insurance, and financial barriers to care as well as the incorporation of implicit bias training for physician will likely lead to improvement in discordant outcomes.

Sarcoidosis epidemiology: recent estimates of incidence, prevalence and risk factors.

PURPOSE OF REVIEW: The aim of this review is to describe the latest studies on sarcoidosis incidence, prevalence and risk factors with a special focus on reports in the last 2 years. The potential biases affecting these studies are discussed. RECENT FINDINGS: The prevalence and incidence of sarcoidosis vary greatly depending on region of the world. Variations in data sources and settings can affect estimates of the burden of sarcoidosis, sometimes making them difficult to compare across countries. It is not well understood how the distribution of sarcoidosis phenotypes differs across populations. Age, sex and race are the most important sources of variation in incidence and prevalence. Recent epidemiological studies provide new insights on the role of genetic and nongenetic risk factors for sarcoidosis. SUMMARY: High-quality and systematically collected data, with depth (detailed information per individual) and breadth (many individuals), is needed to further understand the complexity and heterogeneity of sarcoidosis.

Clinical characteristics and organ system involvement in sarcoidosis: comparison of the University of Minnesota Cohort with other cohorts.

BACKGROUND: Sarcoidosis is a systemic granulomatous disease of unknown etiology. Clinical cohort studies of different populations are important to understand the high variability in clinical presentation and disease course of sarcoidosis. The aim of the study is to evaluate clinical characteristics, including organ involvement, pulmonary function tests, and laboratory parameters, in a sarcoidosis cohort at the University of Minnesota. We compare the organ system involvement of this cohort with other available cohorts. METHODS: We conducted a retrospective data collection and analysis of 187 subjects with biopsy-proven sarcoidosis seen at a tertiary center. Organ system involvement was determined using the WASOG sarcoidosis organ assessment instrument. Clinical phenotype groups were classified using the Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis criteria. RESULTS: Mean subject age at diagnosis was 45.8 ± 12.4, with a higher proportion of males (55.1%), and a higher proportion of blacks (17.1%) compared to the racial distribution of Minnesota residents (5.95%). The majority (71.1%) of subjects required anti-inflammatory therapy for at least 1 month. Compared to the A Case Control Etiologic Study of Sarcoidosis cohort, there was a higher frequency of extra-thoracic lymph node (34.2% vs. 15.2%), eye (20.9% vs. 11.8%), liver (17.6% vs. 11.5%), spleen (20.9% vs. 6.7%), musculoskeletal (9.6% vs. 0.5%), and cardiac (10.7% vs. 2.3%) involvement in our cohort. A multisystem disease with at least five different organs involved was identified in 13.4% of subjects. A restrictive physiological pattern was observed in 21.6% of subjects, followed by an obstructive pattern in 17.3% and mixed obstructive and restrictive pattern in 2.2%. Almost half (49.2%) were Scadding stages II/III. Commonly employed disease activity markers, including soluble interleukin-2 receptor and angiotensin-converting enzyme, did not differ between treated and untreated groups. CONCLUSIONS: This cohort features a relatively high frequency of high-risk sarcoidosis phenotypes including cardiac and multiorgan disease. Commonly-utilized serum biomarkers do not identify subpopulations that require or do better with treatment. Findings from this study further highlight the high-variability nature of sarcoidosis and the need for a more reliable biomarker to predict and measure disease severity and outcomes for better clinical management of sarcoidosis patients.

Neurosarcoidosis: Longitudinal experience in a single-center, academic healthcare system.

OBJECTIVE: To characterize patients with neurosarcoidosis within the University of Utah healthcare system, including demographics, clinical characteristics, treatment, and long-term outcomes. METHODS: We describe the clinical features and outcomes of patients with neurosarcoidosis within the University of Utah healthcare system (a large referral center for 10% of the continental United States by land mass). Patients were selected who met the following criteria: (1) at least one International Classification of Diseases Clinical Modification, 9th revision code 135 or International Classification of Diseases Clinical Modification, 10th revision code D86* (sarcoidosis) and (2) at least one outpatient visit with a University of Utah clinician in the Neurology Department within the University of Utah electronic health record. RESULTS: We identified 56 patients meeting the study criteria. Thirty-five patients (63%) were women, and most patients (84%) were white. Twelve patients (22%) met the criteria for definite neurosarcoidosis, 36 patients (64%) were diagnosed with probable neurosarcoidosis, and 8 patients (14%) were diagnosed with possible neurosarcoidosis. A total of 8 medications were used for the treatment of neurosarcoidosis. Prednisone was the first-line treatment in 51 patients (91%). Infliximab was the most effective therapy, with 87% of patients remaining stable or improving on infliximab. Treatment response for methotrexate and azathioprine was mixed, and mycophenolate mofetil and rituximab were the least effective treatments in this cohort. CONCLUSIONS: This is a comprehensive characterization of neurosarcoidosis within a single healthcare system at the University of Utah that reports long-term response to treatment and outcomes of patients with neurosarcoidosis. Our results suggest the use of infliximab as a first-line therapy for neurosarcoidosis.

Geoepidemiological big data approach to sarcoidosis: geographical and ethnic determinants.

In sarcoidosis, a rare multiorgan disease of unknown aetiology characterised by non-caseating epitheloid cell granulomas, three geoepidemiological factors are major aetiopathogenic factors: geolocation, ethnicity, and personal environment. Geographically, sarcoidosis is mainly reported in the Northern Hemisphere, with the highest incidence rates uniformly reported in countries located at the highest latitudes. The main geoepidemiological-driven differences across the world are of greater female involvement in Southern Europe, the Southern US and Japan, a differentiated radiological pattern (predominance of stage I in Southern Europe and Middle East/Asia and of stage II in Northern Europe, China and India, with the US and Japan having the highest frequencies of stages III/IV) and the extrathoracic phenotype: the most frequent extrathoracic organs involved are the skin in Southern Europe and Middle East/Asia, the eyes in Northern Europe, Northeast US and Japan, the liver in India and the lymph nodes in China. In addition, there are large ethnicity-driven variations in the frequency, epidemiology, clinical expression and outcome of sarcoidosis. The highest incidence rates are uniformly reported in Black/African-American people, independently of the geographical location, with rates between 2- and 10-fold higher than those reported in White people living in the same geographical area. Furthermore, ethnicity heavily influences the clinical phenotype by modifying the age at diagnosis and the rates of thoracic and extrathoracic involvements. Geoepidemiological studies enhanced by big data may yield important clues to understanding the role of these factors in the frequency and clinical phenotypes of sarcoidosis.

Ethnicity and association with ocular, systemic manifestations and prognosis in 194 patients with sarcoid uveitis.

OBJECTIVE: To determine the ophthalmological and extra-ophthalmological clinical characteristics and visual prognosis of patients with sarcoid uveitis in different ethnic groups. METHODS: We retrospectively analysed the data from patients with sarcoid uveitis seen at two departments of Ophthalmology between December 2003 and December 2017. Patients presented biopsy-proven sarcoidosis and/or presumed sarcoid uveitis based on the following criteria: compatible thoracic imaging, associated with elevated angiotensin-conversion enzyme (ACE) and/or lymphocytic alveolitis on bronchoalveolar lavage fluid analysis (> 15% lymphocytes and CD4/CD8 > 3.5). Ophthalmological and general characteristics, as well as visual and global prognoses, were compared in three pre-defined ethnic groups: White Europeans, North Africans and Afro-Caribbeans. RESULTS: A total of 194 patients were included: 145 with biopsy-proven and 49 with presumed sarcoid uveitis. Overall, 68% were White Europeans while 20.6% were North Africans and 11.3% were Afro-Caribbeans. Sixty-nine per cent were women and the median age at presentation was 52.1 years. Median ages at first ocular manifestation of the disease in Afro-Caribbeans and North Africans were respectively 34.3 and 43.1 years, while it was 57.8 years in White Europeans (p < 0.001). Ocular involvement was bilateral in 77.8% (n = 151) of the cases and nearly half of the patients had panuveitis (48.5%). Anterior uveitis was more frequent in Afro-Caribbeans (59.1%; p < 0.0001), while White Europeans presented more frequently with intermediate uveitis. There was a significantly higher frequency of systemic involvement of sarcoidosis in North Africans while White Europeans showed a higher frequency of isolated ocular involvement at onset and during follow-up. Afro-Caribbeans, who had a complete visual recovery in 72.7% of the cases, had a better visual prognosis than other ethnic groups (p = 0.025). CONCLUSION: In this large European series of sarcoid uveitis, we observed ethnicity-related differences regarding uveitis clinical presentation and visual outcome. Although good overall, the visual prognosis seems to be better in Afro-Caribbeans than in other ethnic groups.

Extended methods for gene-environment-wide interaction scans in studies of admixed individuals with varying degrees of relationships.

The etiology of many complex diseases involves both environmental exposures and inherited genetic predisposition as well as interactions between them. Gene-environment-wide interaction studies (GEWIS) provide a means to identify the interactions between genetic variation and environmental exposures that underlie disease risk. However, current GEWIS methods lack the capability to adjust for the potentially complex correlations in studies with varying degrees of relationships (both known and unknown) among individuals in admixed populations. We developed novel generalized estimating equation (GEE) based methods-GEE-adaptive and GEE-joint-to account for phenotypic correlations due to kinship while accounting for covariates, including, measures of genome-wide ancestry. In simulation studies of admixed individuals, both methods controlled family-wise error rates, an advantage over the case-only approach. They demonstrated higher power than traditional case-control methods across a wide range of underlying alternative hypotheses, especially where both marginal and interaction effects were present. We applied the proposed method to conduct a GEWIS of a known sarcoidosis risk factor (insecticide exposure) and risk of sarcoidosis in African Americans and identified two novel loci with suggestive evidence of G × E interaction.

Sarcoidosis deaths in the United States: 1999-2016.

BACKGROUND: It has been over a decade since a comprehensive study has been published that has examined sarcoidosis deaths at the national level. The purpose of this study was to analyze sarcoidosis as the underlying cause of death using current national death certificate data. Results from this project can be used to evaluate and compare trends of sarcoidosis reported deaths across the U.S. METHODS: Mortality data from 1999 to 2016 were provided by the National Vital Statistics System (NVSS) with sarcoidosis (ICD-D86.X) as the underlying cause of death from all resident death certificates filed in the 50 states and the District of Columbia (DC). Data were analyzed using CDC WONDER, a web-based public health database and analysis tool. Queries were used to generate number of deaths, along with unadjusted and age-adjusted death rates with 95% confidence intervals and standard errors for groups including year, census region, gender, age group, race/ethnicity and state. Joinpoint regression analysis was used to test the significance of trends in race and gender-specific rates for the 1999-2016 study period. RESULTS: From 1999 to 2016, there were a total of 16,665 sarcoidosis reported deaths in the U.S. The overall age-adjusted mortality rate increased from 2.1 (deaths per 1,000,000) in 1999 to 3.1 in 2002, but then remained relatively stable thereafter until the end of the study period. Female deaths increased 32.0% (from 2.5 to 3.3 per 1,000,000), while male deaths increased 73.3% (from 1.5 to 2.6 deaths per 1,000,000). The highest age-adjusted death rates were among black females (17.0 deaths per 1,000,000), and black males (12.4 deaths per 1,000,000). At the regional level, the southern U.S. had the highest overall mean age-adjusted mortality rate (3.7 deaths per 1,000,000), while black females in the Midwest (18.7 per 1,000,000) had the highest race-specific reported death rate. DISCUSSION: The detected increase in the total number of deaths and age-adjusted rates of sarcoidosis deaths in the U.S. is a serious health concern. Factors that contribute to sarcoidosis deaths remain uncertain and more epidemiological research studies are needed to compliment current bench science to explore and examine factors that contribute to this multifactorial, chronic disease.

Neurosarcoidosis in a public safety net hospital: a study of 82 cases.

OBJECTIVE: To characterize clinical presentation, laboratory and imaging data, and treatment outcomes for neurosarcoidosis in an urban safety net hospital. METHODS: The research database of Cook County Health and Hospitals system was queried for all cases of sarcoidosis from 2006 to 2013. These cases plus those identified through a survey of neurology faculty were reviewed and flagged if suspected to be neurosarcoidosis. Data were extracted in a standardized fashion, upon review by two experienced neurologists; patients were classified as definite, probable or possible neurosarcoidosis. Disagreements on classification were resolved by consensus conference. RESULTS: 1706 cases of sarcoidosis were identified, with 82 (4.8%) classified as neurosarcoidosis. The cohort was predominantly African American (89%). Six were classified as definite, 34 as probable, and 42 as possible neurosarcoidosis. Neurosarcoidosis was the presenting symptom of sarcoidosis in 74% of cases. The most common presenting phenotype was myelopathy (21.7%), followed by optic nerve/chiasm involvement (16.0%) and epilepsy (11.3%). The facial nerve was involved in only 2% of cases. Chest x-ray showed abnormalities of sarcoidosis in 43.3% of cases, while chest CT did so in 78.6%. Corticosteroids were the initial treatment in 91% of cases, and outcomes were good in 53% of cases. CONCLUSION: Neurosarcoidosis remains a challenging diagnosis with the majority of patients without a previous diagnosis of systemic sarcoidosis. Chest imaging was supportive of the diagnosis in a majority of patients. Our cohort differs from others in the literature due to a low prevalence of facial nerve involvement. Prospective registry studies are needed.

A prospective study of patients diagnosed with sarcoidosis: factors - environmental exposure, health assessment, and genetic outlooks.

This original research is a directional study that determined the habits of individuals using four analyses to find statistical significance in the data collected from the surveys of 801 qualified of 1,340 individuals who agreed to participate. Results from the self-reported diagnosis of individuals affected by sarcoidosis produced seven statistically significant indicators of future research needed. The demographics revealed a significantly greater number of women and African-Americans participants than other minorities in the United States and suggested a sense of urgency to find a cure. Most important are the seven statistically significant findings that also gave credence to the researchers' four subdiagnostic classifications. They are acute sarcoidosis (AS) and chronic sarcoidosis with limited dissemination (CSLD), while more severe cases include those with chronic sarcoidosis with full dissemination including cutaneous involvement (CSFDIC) and chronic sarcoidosis with neurosarcoidosis (CSN). The most severe sarcoidosis cases (CSN) were on the "most likely" side of every statistically significant category except drinking alcohol, and the "least likely" to participate in physical activities. Conversely, the least severe case of sarcoidosis (AS) was the opposite. The complete list of statistically significant areas was related to alcohol use, tobacco use, ciprofloxacin use, environmental exposure to metals (copper, iron), infectious diseases (candidiasis), genetics, and physical exercise. Statistically, the most crucial study needed; emerged from the Rh blood grouping of the participants.

Clinical Features of Extrapulmonary Sarcoidosis Without Lung Involvement.

BACKGROUND: Compared with pulmonary sarcoidosis, sarcoidosis without lung involvement may involve other immunopathologic mechanisms and be associated with other demographic and clinical features. METHODS: This was a retrospective analysis of clinical data collected in real time on 1,686 patients with biopsy-proven sarcoidosis from two large university sarcoidosis outpatient clinics in the United States. We compared differences in demographics characteristics and clinical presentation between pulmonary and nonpulmonary sarcoidosis (NPS). Patients were considered to have NPS only if they had normal chest imaging and no features consistent with pulmonary involvement on the basis of currently accepted criteria. RESULTS: A total of 8.3% of this sarcoidosis cohort met criteria for NPS. NPS was significantly more common in white than black patients, and more common in women than men. The skin was the most common organ involved, and was observed in nearly one-half of patients with NPS. Isolated skin sarcoidosis was the overwhelmingly most common pattern of organ involvement seen in the NPS group (25%), and no other pattern of involvement was found in more than 5% of patients with NPS. CONCLUSIONS: Significant demographic and sex differences were observed between patients with pulmonary and nonpulmonary sarcoidosis. These differences reflect previous data concerning differences between patients with skin and lung sarcoidosis because the skin was the major organ involved with NPS. Although the lungs are likely the primary site of exposure in pulmonary sarcoidosis, the high prevalence of skin involvement in NPS suggests the skin is the most conducive site of antigen capture outside of the respiratory tract.

Associations between sarcoidosis clinical course and ANXA11 rs1049550 C/T, BTNL2 rs2076530 G/A, and HLA class I and II alleles.

BACKGROUND: A genetic background may be responsible for the different clinical courses in sarcoidosis. We analyzed associations between sarcoidosis clinical course and HLA class I/II alleles and susceptibility gene SNPs ANXA11 rs1049550 C/T and BTNL2 rs2076530 G/A in a Portuguese population, investigating possible gene-gene interactions. METHODS: We studied 138 unrelated Caucasian sarcoidosis patients (78 women, 56.5%; mean age, 37.2 ± 12.1 years). Disease that persisted after 2 years was considered chronic. Samples were genotyped for ANXA11 rs1049550 C/T and BTNL2 rs2076530 G/A SNPs using TaqMan Real-Time PCR Assays. HLA class I/II alleles were typed using PCR sequence-specific primers. RESULTS: Sixty-six patients experienced disease resolution and 72 (52%) developed chronic disease. Comparison of rs1049550 and rs2076530 allele frequencies showed no significant differences. Only the HLA DRB1*03 allele was significantly associated with disease resolution (21.2% vs 4.9% for chronic disease; RR = 0.35; P < .01 after Bonferroni correction). In the logistic regression models evaluating the association between HLA alleles and chronic sarcoidosis adjusted for rs1049550 and rs2076530, only DRB1*03 was significantly associated with disease resolution. No significant interactions were found in any of the logistic regression analyses. CONCLUSIONS: In this population of Caucasian patients with sarcoidosis, only DRB1*03 was associated with disease resolution after 2 years' follow-up, with no significant interactions found for susceptibility gene SNPs ANXA11 rs1049550 or BTNL2 rs2076530.

Disease Burden and Variability in Sarcoidosis.

Sarcoidosis is a systemic inflammatory disease with substantial morbidity and increasing mortality. As part of the National Heart, Lung, and Blood Institute's workshop to better understand this disease and improve the outcomes of patients with sarcoidosis, we reviewed the available data on health care burden and outcomes of this disease in the United States. Disparities in outcomes exist by race, ethnicity, sex, and socioeconomic groups, with African Americans having disproportionately more severe disease. Mortality rates are highest in African Americans, but may be increasing in white individuals. The health care burden of sarcoidosis is defined not only by its somatic manifestations, but is also greatly impacted by psychosocial, economic, and comorbid conditions associated with this disease. Fatigue, depression, cognitive dysfunction, treatment side effects, and pain syndromes are highly prevalent in this population and contribute to poor outcomes. The direct and indirect economic costs to patients and society are likely also substantial, although not well defined. We recommend leveraging existing and future technology and infrastructure to more accurately define and monitor the overall total sarcoidosis-attributable health care burden and patient outcomes in the United States.

Clinical and Biological Insights from the University of California San Francisco Prospective and Longitudinal Cohort.

INTRODUCTION: Sarcoidosis is a systemic inflammatory disease characterized by non-necrotizing granulomas in involved organs, most commonly the lung. Description of patient characteristics in the Western United States is limited. Furthermore, blood-based measures that relate to clinical sarcoidosis phenotypes are lacking. We present an analysis of a prospective, longitudinal sarcoidosis cohort at a Northern Californian academic medical center. METHODS: We enrolled 126 sarcoidosis subjects and 64 healthy controls and recorded baseline demographic and clinical characteristics. We used regression models to identify factors independently associated with pulmonary physiology. We tested whether blood transcript levels at study entry could relate to longitudinal changes in pulmonary physiology. RESULTS: White, non-Hispanics composed ~70% of subjects. Hispanics and Blacks had a diagnostic biopsy at an age ~7 years younger than whites. Obstructive, but not restrictive, physiology characterized Scadding Stage IV patients. Subjects reporting use of immunosuppression had worse FEV1%p, FVC%p, and DLCO%p compared to subjects never treated, regardless of Scadding stage. We defined sarcoidosis disease activity by a drop in pulmonary function over 36 months and found that subjects meeting this definition had significant repression of blood gene transcripts related to T cell receptor signaling pathways, referred to as the "TCR factor." CONCLUSION: Obstructive pulmonary physiology defined Stage IV patients which were mostly white, non-Hispanics. Genes comprising the composite gene expression score, TCR factor, may represent a blood-derived measure of T-cell activity and an indirect measure of active sarcoidosis inflammation. Validation of this measure could translate into individualized treatment for sarcoidosis patients.

Characteristics of sarcoidosis in Maori and Pacific Islanders.

BACKGROUND AND OBJECTIVE: Ethnicity is strongly associated with variable clinical presentation in sarcoidosis but the association between ethnicity and clinical characteristics has not previously been described in patients of Polynesian ancestry, Maori and Pacific Islander (PI). The objective of this study was to describe the clinical characteristics of sarcoidosis in Maori and PI patients and determine if those were different to European patients. METHODS: A retrospective review of the medical records of 406 patients (69 Maori/PI) attending a specialist interstitial lung disease (ILD) clinic. RESULTS: The population (207 females, mean age at presentation: 36) reflected the current New Zealand census data (2013) with only people of Indian ethnicity over-represented. Parenchymal lung involvement was uncommon in Maori and PI patients (21% Scadding stage 2, 2% stage 3), and no patient had extensive pulmonary fibrosis (stage 4). Computed tomography (CT) patterns of sarcoid parenchymal lung involvement were less commonly reported for Maori/PI. There were no differences in respect of baseline lung function or requirement for treatment. Ocular and skin involvement occurred more frequently in Maori and PI (P = 0.0045, P = 0.03), and erythema nodosum was more common in Caucasians (P = 0.0008). CONCLUSION: People of Polynesian ancestry appear to have less pulmonary and more extra-pulmonary manifestations of sarcoidosis. This adds to our knowledge that sarcoidosis heterogeneity is influenced by ethnicity.