National retrospective registry survey on the epidemiology of sarcoidosis in Finland 2002-2022.

BACKGROUND: The prevalence of sarcoidosis is known to be high in the Nordic countries. There are no recent research data on the incidence or prevalence of sarcoidosis in Finland. Our aim was to investigate the epidemiology of sarcoidosis in Finland through a retrospective registry-based study. METHODS: We made an information request to the Hilmo database on patients who had been treated in Finnish specialised care with a main diagnosis related to sarcoidosis. Data were requested for the period 1 January-31 December for the years 2002, 2012 and 2022. In addition, we examined the age and gender distribution and regional differences in these variables between the five university hospital districts covering the whole of Finland. RESULTS: The incidence of sarcoidosis was 17‒19/100 000/year throughout the follow-up period. The prevalence of sarcoidosis in the ≥18-year-old population had risen from 85/100 000 in 2002-106/100 000 in 2022. There were considerable differences between university hospital districts: The highest prevalence rate was 170/100 000 in the Tampere University Hospital district in 2022, which was twice as high as in the Helsinki University Hospital district (84/100 000). The proportion of pulmonary sarcoidosis in all sarcoidosis cases decreased from 62% to 45% while the proportion of multiorgan sarcoidosis (D86.8) increased from 11% to 34%. The incidence of sarcoidosis was 15/100 000 and the prevalence was 82/100 000 in the age groups of ≥60 years in 2002. In 2022, the incidence in this same age group had risen to 20/100 000 and the prevalence to 109/100 000. In the ≥60-year-old population, the proportion of D86.8 increased from 11% to 35%. CONCLUSIONS: Sarcoidosis was a more common disease in Finland than in previous studies. Multiorgan sarcoidosis among the elderly has increased over the past 20 years. This might be explained by changes in environmental factors associated with sarcoidosis. Significant regional differences in prevalence might be partly explained by familial clustering.

Identifying sarcoidosis trends using web search and real-world data in Sweden: a retrospective longitudinal study.

Web search data are associated with disease incidence, population interest, and seasonal variations. This study aimed to investigate seasonal and geographical variations of web search data for sarcoidosis and to explore its association with external factors and sarcoidosis incidence in Sweden. Therefore, sarcoidosis-related data from Google Ads Keyword Planer (2017-2020) were generated for Sweden according to its 21 counties. The relationship between search volume and season, region, population demographics, environmental factors, and the sarcoidosis incidence listed in the National Patient Register was assessed. Analyses revealed seasonal variations for Sweden with an overall peak in the spring and autumn. Geographical differences were observed, with a higher search volume for north-western counties and the lowest search volume for Stockholm County. At the country level, the search volume was positively associated with the sarcoidosis incidence. Higher male proportion and older mean age were associated with a higher search volume, while a higher proportion of foreign-born residents, humidity, and mean temperature were associated with a lower search volume. Our analyses detected correlations between web search data, sarcoidosis incidence, and external factors. Analyses of sarcoidosis web search data therefore appear to be a valuable approach to disease surveillance to address medical needs and public interest.

Progress for all: addressing disparities in sarcoidosis.

PURPOSE OF REVIEW: The impact of healthcare disparities in the treatment, care, and outcomes of patients with sarcoidosis has been described. There is paucity of literature on ways to address these disparities with a goal to improving health outcomes for patients with sarcoidosis. RECENT FINDINGS: Recent findings in other respiratory and systemic diseases suggest that multifaceted interventions directed at improving care at various levels including individual, family, and larger societal levels have been successful in dismantling some of the social and structural barriers to care and consequently have resulted in a reduction in disparate disease outcomes. We explore what some of these interventions would look like in sarcoidosis. SUMMARY: The impact of healthcare disparities in the treatment, care, and outcomes of patients with sarcoidosis has been described. We outline various steps and approaches aimed at addressing these health disparities with a goal to improving outcomes for those most impacted by disease.

Air pollution and incident sarcoidosis in central Pennsylvania.

Sarcoidosis is a chronic granulomatous disease predominantly affecting the lungs and inducing significant morbidity and elevated mortality rate. The etiology of the disease is unknown but may involve exposure to an antigenic agent and subsequent inflammatory response resulting in granuloma formation. Various environmental and occupational risk factors have been suggested by previous observations, such as moldy environments, insecticides, and bird breeding. Our study investigated the association of air pollution with diagnosis of sarcoidosis using a case-control design. Penn State Health electronic medical records from 2005 to 2018 were examined for adult patients with (cases) and without (controls) an International Classification of Disease (ICD)-9 or -10 code for sarcoidosis. Patient addresses were geocoded and 24-hr residential-level air pollution concentrations were estimated using spatio-temporal models of particulate matter <2.5 µm (PM2.5), ozone, and PM2.5 elemental carbon (EC) and moving averages calculated. In total, 877 cases and 34,510 controls were identified. Logistic regression analysis did not identify significant associations between sarcoidosis incidence and air pollution exposure estimates. However, the odds ratio (OR) for EC for exposures occurring 7-10 years prior did approach statistical significance, and ORs exhibited an increasing trend for longer averaging periods. Data suggested a latency period of more than 6 years for PM2.5 and EC for reasons that are unclear. Overall, results for PM2.5 and EC suggest that long-term exposure to traffic-related air pollution may contribute to the development of sarcoidosis and emphasize the need for additional research and, if the present findings are substantiated, for public health interventions addressing air quality as well as increasing disease surveillance in areas with a large burden of PM2.5 and EC.

Stroke associated with sarcoidosis: A systematic review of reported cases.

BACKGROUND: Sarcoidosis can be associated with stroke. Whether granulomatous vasculitis directly causes stroke in patients with sarcoidosis remains unclear. This systematic review aims to consolidate reports of concurrent sarcoidosis and stroke. METHODS: Medline and Embase were searched for terms encompassing sarcoidosis and stroke with a censoring date of March 25, 2023. Cases were reviewed by two authors, with the inclusion criteria: biopsy-confirmed systemic sarcoidosis, stroke confirmed by imaging or pathology, clinical description of individual patient history, and English language publications. RESULTS: Of 1628 articles screened, 51 patients from 49 articles were included (65% male, mean age 41 years). Seventy-one percent of strokes were ischemic and 29% were hemorrhagic. Lesions were supratentorial in 78% of cases, infratentorial in 34%, and multifocal in 45%. Presenting symptoms were variable, with the most common being headache (38%) followed by weakness (35%). 10 patients had recurrent strokes. Stroke was the presenting symptom of sarcoidosis in 65%. 21 patients had brain biopsies. The most common neuropathologic findings were perivascular (33%) or intramural (33%) non-caseating granulomas. On imaging, 32 patients had findings suggestive of neurosarcoidosis, including 35% with evidence of meningeal enhancement. 63% of patients were treated with corticosteroids and/or other immunomodulatory therapy, with varying clinical improvement. CONCLUSIONS: Stroke associated with sarcoidosis generally follows trends in stroke incidence, with infarction being more common than hemorrhage and male sex carrying a higher risk. Most patients were diagnosed with sarcoidosis during or following their stroke episode. Brain biopsy infrequently shows clear granulomatous vasculitis.

Obstructive Sleep Apnea and Sarcoidosis Interactions.

Obstructive sleep apnea (OSA) is very prevalent in sarcoidosis patients. Sarcoidosis of the upper respiratory tract may affect upper airway patency and increase the risk of OSA. Weight gain due to steroid use, upper airway myopathy due to steroids and sarcoidosis itself, and interstitial lung disease with decreased upper airway patency are other reasons for the higher OSA prevalence seen in sarcoidosis. Several clinical manifestations such as fatigue, hypersomnolence, cognitive deficits, and pulmonary hypertension are common to both OSA and sarcoidosis. Therefore, early screening and treatment for OSA can improve symptoms and overall patient quality of life.

Occupational exposures and sarcoidosis: a rapid review of the evidence.

BACKGROUND: Sarcoidosis is a rare, multisystem, inflammatory condition associated with the formation of granulomas. Diagnosis can be challenging because of non-specific symptoms complicating epidemiological investigations of its aetiology. Despite research efforts, a review of the current state of the evidence is needed. AIMS: To assess the evidence for an association between occupational exposures and the development of sarcoidosis. To determine if workers in any occupation are at a greater risk of developing sarcoidosis. METHODS: This rapid review follows the methodology suggested by the World Health Organization. Two electronic databases were systematically searched until April 2022. The methodological quality of the studies was critically appraised, and a best-evidence approach was used to synthesize the results. RESULTS: Titles and abstracts of 2916 articles were screened, with 67 full-text articles reviewed for eligibility. Among the 13 studies eligible for this review, none were of high quality (i.e. low risk of bias). Six studies exploring the association between sarcoidosis and a range of occupations and exposures, and one previous systematic review were of low quality reporting inconsistent findings. Six studies examined the risk of sarcoidosis associated with occupational silica exposure, two of which were of acceptable quality. Overall, the study methodologies and results were inadequate to support causal relationships. CONCLUSIONS: There is limited evidence of acceptable methodological quality to assess the risk of sarcoidosis associated with occupational exposures. There is a growing body of research examining occupational exposure to silica and sarcoidosis. Additional high-quality confirmatory research is needed.

Comparison of prognosis in isolated versus systemic manifestations of cardiac sarcoidosis.

BACKGROUND: Isolated cardiac sarcoidosis (iCS) is a poorly understood and under-recognised entity. Previous research has postulated that those with iCS have worsened outcomes compared to those with other manifestations of the disease, however, there have been studies which both support and refute this hypothesis. PURPOSE OF REVIEW: This review will summarise the literature which focuses on differences in the epidemiology, imaging findings and patient outcome of those with isolated cardiac sarcoidosis (iCS) versus 'systemic' cardiac sarcoidosis (sCS) which is not isolated to the heart. SUMMARY: Variations in study design make accurate comparison between current papers challenging, and that the factors which indicate poor prognosis in patients with iCS is not yet fully understood. Current literature suggests those with iCS are more likely to be male, have higher numbers of abnormal uptake patterns on cardiac imaging, and may have poorer prognosis than sCS patients. Multi-centre, prospective studies analysing isolated cardiac sarcoidosis across geographical regions are needed to improve our understanding of this phenomenon and ultimately improve patient outcome.

The causal relationship between sarcoidosis and autoimmune diseases: a bidirectional Mendelian randomization study in FinnGen.

Background: Sarcoidosis has been considered to be associated with many autoimmune diseases (ADs), but the cause-and-effect relationship between these two diseases has not been fully explored. Therefore, the objective of this study is to explore the possible genetic association between sarcoidosis and ADs. Methods: We conducted a bidirectional Mendelian randomization (MR) study using genetic variants associated with ADs and sarcoidosis (4,041 cases and 371,255 controls) from the FinnGen study. The ADs dataset comprised 96,150 cases and 281,127 controls, encompassing 44 distinct types of autoimmune-related diseases. Subsequently, we identified seven diseases within the ADs dataset with a case size exceeding 3,500 and performed subgroup analyses on these specific diseases. Results: The MR evidence supported the causal association of genetic predictors of ADs with an increased risk of sarcoidosis (OR = 1.79, 95% CI = 1.59 to 2.02, P IVW-FE = 1.01 × 10-21), and no reverse causation (OR = 1.05, 95% CI 0.99 to 1.12, P IVW-MRE = 9.88 × 10-2). Furthermore, subgroup analyses indicated that genetic predictors of type 1 diabetes mellitus (T1DM), celiac disease, and inflammatory bowel disease (IBD) were causally linked to an elevated risk of sarcoidosis (All P < 6.25 × 10-3). Conversely, genetic predictors of sarcoidosis showed causal associations with a higher risk of type 1 diabetes mellitus (P < 6.25 × 10-3). Conclusion: The present study established a positive causal relationship between genetic predictors of ADs (e.g. T1DM, celiac disease, and IBD) and the risk of sarcoidosis, with no evidence of reverse causation.

Organ involvement in newly diagnosed sarcoidosis patients in the Netherlands: The first large European multicentre prospective study.

BACKGROUND: Clinical presentation and prevalence of organ involvement is highly variable in sarcoidosis and depends on ethnic, genetic and geographical factors. These data are not extensively studied in a Dutch population. AIM: To determine the prevalence of organ involvement and the indication for systemic immunosuppressive therapy in newly diagnosed sarcoidosis patients in the Netherlands. METHODS: Two large Dutch teaching hospitals participated in this prospective cohort study. All adult patients with newly diagnosed sarcoidosis were prospectively included and a standardized work-up was performed. Organ involvement was defined using the WASOG instrument. RESULTS: Between 2015 and 2020, a total of 330 patients were included, 55% were male, mean age was 46 (SD 14) years. Most of them were white (76%). Pulmonary involvement including thoracic lymph node enlargement was present in 316 patients (96%). Pulmonary parenchymal disease was present in 156 patients (47%). Ten patients (3%) had radiological signs of pulmonary fibrosis. Cutaneous sarcoidosis was present in 74 patients (23%). Routine ophthalmological screening revealed uveitis in 29 patients (12%, n = 256)). Cardiac and neurosarcoidosis were diagnosed in respectively five (2%) and six patients (2%). Renal involvement was observed in 11 (3%) patients. Hypercalcaemia and hypercalciuria were observed in 29 (10%) and 48 (26%, n = 182) patients, respectively. Hepatic involvement was found in 6 patients (2%). In 30% of the patients, systemic immunosuppressive treatment was started at diagnosis. CONCLUSIONS: High-risk organ involvement in sarcoidosis is uncommon at diagnosis. Indication for systemic immunosuppressive therapy was present in a minority of patients.

Causal influence of celiac disease on the risk of sarcoidosis: A Mendelian randomization study.

Observational research shows a link between celiac disease (CeD) and sarcoidosis, but the causal link between CeD and sarcoidosis is still unknown. A two-sample Mendelian randomization (MR) study was conducted to ascertain the causal connection between the 2 disorders. In our two-sample MR analysis, we identified independent genetic variants associated with CeD using publicly accessible GWAS data from people of European ancestry. Summary data for sarcoidosis were obtained from the FinnGen Consortium, the UK-Biobank, and a large GWAS dataset. To assess the association between CeD and sarcoidosis, our MR analysis used inverse variance weighted (IVW) as the primary method, incorporating the MR-Egger, weighted median (WM), and MR-PRESSO (outliers test) as a complementary method. In order to ensure that the findings were reliable, several sensitivity analyses were performed. Our study indicated that CeD had a significant causal relationship with sarcoidosis (IVW odds ratio (OR) = 1.13, 95% confidence interval (CI): 1.07-1.20, P = 5.58E-05; WM OR = 1.12, 95% CI: 1.03-1.23, P = 1.03E-02; MR-Egger OR = 1.07, 95% CI: 0.96-1.19, P = 2.20E-01). Additionally, we obtain the same results in the duplicated datasets as well, which makes our results even more reliable. The results of this investigation did not reveal any evidence of horizontal pleiotropy or heterogeneity. Our MR analysis showed a causal effect between CeD and an elevated risk of sarcoidosis. Further study is still needed to confirm the findings and look into the processes underlying these relationships.

Characteristics and Outcomes of Hospitalized Patients With Heart Failure and Sarcoidosis: A Propensity-Matched Analysis of the Nationwide Readmissions Database 2010-2019.

BACKGROUND: Sarcoidosis is associated with a poor prognosis. There is a lack of data examining the outcomes and readmission rates of sarcoidosis patients with heart failure (SwHF) and without heart failure (SwoHF). We aimed to compare the impact of non-ischemic heart failure on outcomes and readmissions in these two groups. METHODS: The US Nationwide Readmission Database was queried from 2010 to 2019 for SwHF and SwoHF patients identified using the International Classification of Diseases, 9th and 10th Editions. Those with ischemic heart disease were excluded, and both cohorts were propensity matched for age, gender, and Charlson Comorbidity Index (CCI). Clinical characteristics, length of stay, adjusted healthcare-associated costs, 90-day readmission and mortality were analyzed. RESULTS: We identified 97,961 hospitalized patients (median age 63 years, 37.9% male) with a diagnosis of sarcoidosis (35.9% SwHF vs 64.1% SwoHF). On index admission, heart failure patients had higher prevalences of atrioventricular block (3.3% vs 1.4%, P < .0001), ventricular tachycardia (6.5% vs 1.3%, P < .0001), ventricular fibrillation (0.4% vs 0.1%, P < .0001) and atrial fibrillation (22.1% vs 7.5%, P < .0001). SwHF patients were more likely to be readmitted (hazard ratio 1.28, P < .0001), had higher length of hospital stay (5 vs 4 days, P < .0001), adjusted healthcare-associated costs ($9,667.0 vs $9,087.1, P < .0001) and mortality rates on readmission (5.1% vs 3.8%, P < .0001). Predictors of mortality included heart failure, increasing age, male sex, higher CCI, and liver disease. CONCLUSION: SwHF is associated with higher rates of arrhythmia at index admission, as well as greater hospital cost, readmission and mortality rates compared to those without heart failure.

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.

Trends and Disparities in Cardiovascular Death in Sarcoidosis: A Population-Based Retrospective Study in the United States From 1999 to 2020.

BACKGROUND: Despite significant cardiac involvement in sarcoidosis, real-world data on death due to cardiovascular disease among patients with sarcoidosis is not well established. METHODS AND RESULTS: We queried the Centers for Disease Control and Prevention's Wide-Ranging Online Data for Epidemiologic Research database for data on patients with sarcoidosis aged ≥25 years from 1999 to 2020. Diseases of the circulatory system except ischemic heart disease were listed as the underlying cause of death, and sarcoidosis was stated as a contributing cause of death. We calculated age-adjusted mortality rate (AAMR) per 1 million individuals and determined the trends over time by estimating the annual percentage change using the Joinpoint Regression Program. Subgroup analyses were performed on the basis of demographic and geographic factors. In the 22-year study period, 3301 cardiovascular deaths with comorbid sarcoidosis were identified. The AAMR from cardiovascular deaths with comorbid sarcoidosis increased from 0.53 (95% CI, 0.43-0.65) per 1 million individuals in 1999 to 0.87 (95% CI, 0.75-0.98) per 1 million individuals in 2020. Overall, women recorded a higher AAMR compared with men (0.77 [95% CI, 0.74-0.81] versus 0.58 [95% CI, 0.55-0.62]). People with Black ancestry had higher AAMR than people with White ancestry (3.23 [95% CI, 3.07-3.39] versus 0.39 [95% CI, 0.37-0.41]). A higher percentage of death was seen in the age groups of 55 to 64 years in men (23.11%) and women (21.81%), respectively. In terms of US census regions, the South region has the highest AAMR from cardiovascular deaths with comorbid sarcoidosis compared with other regions (0.78 [95% CI, 0.74-0.82]). CONCLUSIONS: The increase of AAMR from cardiovascular deaths with comorbid sarcoidosis and higher cardiovascular mortality rates among adults aged 55 to 64 years highlight the importance of early screening for cardiovascular diseases among patients with sarcoidosis.

Role of screening for uveitis in subjects with sarcoidosis.

BACKGROUND AND OBJECTIVES: Ocular involvement is common in sarcoidosis. Our study aimed to evaluate the role of screening for uveitis in subjects with sarcoidosis. METHODS: Retrospective case series of 88 subjects with a pre-existing diagnosis of sarcoidosis, with no previous diagnosis of uveitis, reviewed by Ophthalmology at Auckland District Health Board between January 2016 and May 2022. RESULTS: Among those undergoing a screening examination, uveitis was observed in 27.8% (15 out of 54 subjects). In those presenting with acute eye symptoms, uveitis was observed in 94.1% (32 out of 34 subjects). Sarcoid uveitis was diagnosed in a total of 50 out of 88 subjects (56.8%). 45 subjects required ocular treatment. Sarcoid uveitis was observed in 6 out of 27 subjects (22.2%) who were entirely asymptomatic at screening. On multivariate analysis, blurring of vision (OR 26.2 p < 0.001), eye pain (OR 7.3 p = 0.014) and respiratory disease (OR 7.1 p = 0.044) were associated with increased risk of sarcoid uveitis. In the 41 subjects with no uveitis at initial examination, 3 subjects (7.3%) subsequently developed uveitis. CONCLUSION: Our study highlights the importance of ophthalmic screening of all patients with systemic sarcoidosis, even in asymptomatic patients. With a high correlation of ocular symptoms in diagnosis of sarcoid uveitis, ophthalmologists should educate patients to look out for the development of symptoms of ocular inflammation, and clinicians who continue follow up for systemic sarcoidosis should remind patients to watch carefully for these symptoms to facilitate timely diagnosis and intervention.

Racial disparities among patients with cardiac sarcoidosis and arrhythmias in the United States: A propensity matched-analysis from the national inpatient sample database 2016-2020.

BACKGROUND: Cardiac sarcoidosis (CS) is frequently associated with conduction abnormalities and arrhythmias. In this study, we aim to evaluate racial disparities in the frequency of arrhythmias, and associated co-morbidities, among patients with CS. METHODS: White and African American (AA) patients diagnosed with CS were identified and compared from the 2016-2020 National Inpatient Sample (NIS) database whilst adjusting for confounders via logistic regression models. RESULTS: A total of 7,935 patients with CS were included in the study. The propensity-matched sample comprised of 5,570 patients, of whom 2,785 were White and 2,785 were AA. AA patients had a longer mean length of hospital stay (LOS) (7.84 vs. 6.94, p<0.01), a higher mean Charlson Comorbidity Index (CCI) score (3.10 vs. 2.84, p<0.01), and significantly higher incidences of cardiogenic shock [(9.2% vs 6.3%, p<0.01), aOR 1.45 (95% CI 1.17-1.78), p<0.01] and acute kidney injury (AKI) [(34.3% vs. 26.9%, p<0.01), aOR 1.41 (95% CI 1.24-1.61), p<0.01]. From an arrhythmia perspective, AA CS patients were shown to have a lower frequency of: (1) ventricular tachycardia (32.5% vs. 37.9%, p<0.01), (2) ventricular fibrillation (5.4% vs.7.2%, p<0.01), (3) first-degree AV block (1.8% vs. 4.1%, p<0.01), (4) complete AV block (6.3% vs. 14.2%, p<0.01), and (5) atrial fibrillation (31.8% vs. 34.8%, p=0.016) when compared to Whites with CS. Mortality remained higher for AAs (3.8% vs. 2.7%, p=0.024). CONCLUSION: Our study demonstrates a higher incidence of cardiac arrhythmias among White patients but a higher incidence of cardiogenic shock, AKI, mean LOS, and mortality among AA patients with cardiac sarcoidosis.

Diagnostic and management strategies in cardiac sarcoidosis.

Cardiac sarcoidosis (CS) is increasingly recognized in the context of with otherwise unexplained electrical or structural heart disease due to improved diagnostic tools and awareness. Therefore, clinicians require improved understanding of this rare but fatal disease to care for these patients. The cardinal features of CS, include arrhythmias, atrio-ventricular conduction delay and cardiomyopathy. In addition to treatments tailored to these cardiac manifestations, immunosuppression plays a key role in active CS management. However, clinical trial and consensus guidelines are limited to guide the use of immunosuppression in these patients. This review aims to provide a practical overview to the current diagnostic challenges, treatment approach, and future opportunities in the field of CS.

Epidemiology of Sarcoidosis.

Sarcoidosis is a systemic, granulomatous disease with variable presentation earning it the term "the great mimicker." The current epidemiology confirms that the disease occurs worldwide, affecting both sexes, and all races, ethnicities, and ages. To date, no causal exposure or agent has been identified. The organ systems most frequently affected by sarcoidosis are also those with greatest exposure to the natural world suggesting environmental and lifestyle contributions to the disease. These include particulate matter, microorganisms, nicotine, and obesity. In this article, we review the epidemiology of sarcoidosis and discuss these non-genetic risk factors in the hope of providing important insight into sarcoidosis and stimulating future research.

Menopausal hormone therapy and risk of sarcoidosis: a population-based nested case-control study in Sweden.

Sarcoidosis incidence peaks in women between 50 and 60 years old, which coincides with menopause, suggesting that certain sex hormones, mainly estrogen, may play a role in disease development. We investigated whether menopausal hormone therapy (MHT) was associated with sarcoidosis risk in women and whether the risk varied by treatment type. We performed a nested case-control study (2007-2020) including incident sarcoidosis cases from the Swedish National Patient Register (n = 2593) and matched (1:10) to general population controls (n = 20,003) on birth year, county, and living in Sweden at the time of sarcoidosis diagnosis. Dispensations of MHT were obtained from the Swedish Prescribed Drug Register before sarcoidosis diagnosis/matching. Adjusted odds ratios (aOR) of sarcoidosis were estimated using conditional logistic regression. Ever MHT use was associated with a 25% higher risk of sarcoidosis compared with never use (aOR 1.25, 95% CI 1.13-1.38). When MHT type and route of administration were considered together, systemic estrogen was associated with the highest risk of sarcoidosis (aOR 1.51, 95% CI 1.23-1.85), followed by local estrogen (aOR 1.25, 95% CI 1.11-1.42), while systemic estrogen-progestogen combined was associated with the lowest risk compared to never users (aOR 1.12, 95% CI 0.96-1.31). The aOR of sarcoidosis did not differ greatly by duration of MHT use. Our findings suggest that a history of MHT use is associated with increased risk of sarcoidosis, with women receiving estrogen administered systemically having the highest risk.