Sarcoidosis diagnosis and treatment in Sweden: A register-based assessment of variations by region and calendar period

Rossides, Marios; Kullberg, Susanna; Eklúnd, Anders; Grünewald, Johan; Arkema, Elizabeth V.

doi:10.1016/j.rmed.2019.105846

Cited by 17 publications

(17 citation statements)

References 17 publications

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“…ICD codes are listed in supplementary table S1. Because most sarcoidosis cases are diagnosed in outpatient clinics [10], we allowed for 2 years of outpatient visit data to accumulate in the NPR so that we could capture newly diagnosed cases.…”

Section: Study Populationmentioning

confidence: 99%

Risk of first and recurrent serious infection in sarcoidosis: a Swedish register-based cohort study

et al. 2020

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Serious infections (SI) impair quality of life and increase costs. Our aim was to determine if sarcoidosis is associated with a higher rate of SI and whether this varies by age, sex, time since diagnosis, or treatment status around diagnosis.We compared individuals with sarcoidosis (≥2 ICD codes in the Swedish National Patient Register 2003–2013; n=8737) and general population comparators matched 10:1 on age, sex, and residential location (n=86 376). Patients diagnosed 2006–2013 who were dispensed ≥1 immunosuppressant ±3 months from diagnosis (Prescribed Drug Register) were identified. Cases and comparators were followed in the National Patient Register for hospitalisations for infection. Using Cox and flexible parametric models, we estimated adjusted hazard ratios and 95% confidence intervals (aHR;CI) for first and recurrent SIs (new SI >30 days after the previous).We identified 895 first SIs in sarcoidosis and 3881 in comparators. The rate of SI was 1.8-fold increased in sarcoidosis compared to the general population (aHR 1.81 [95%CI 1.65, 1.98]). The aHR was higher in females than males and during the first 2 years of follow-up. Sarcoidosis cases treated with immunosuppressants around diagnosis had a threefold increased risk whereas non-treated patients had a 50% increased risk. The rate of SI recurrence was 2.8-fold higher in cases than in comparators.SIs are more common in sarcoidosis than in the general population, particularly during the first few years after diagnosis. Patients who need immunosuppressant treatment around diagnosis are twice as likely to develop a serious infection than those who do not.

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Section: Study Populationmentioning

confidence: 99%

Risk of first and recurrent serious infection in sarcoidosis: a Swedish register-based cohort study

et al. 2020

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“…A likely mechanism for reverse causation could be an underlying immune disturbance due to preclinical (asymptomatic) sarcoidosis that spans years before diagnosis. In support of this notion, studies in sarcoidosis have shown that individuals appear to enter a diseased state characterized by sick leave absence, impaired productivity, visits to the doctor, and increased medication dispensing many years before diagnosis is established [26,29,30,37]. This phenomenon, although not unique to sarcoidosis [38,39], may be more pronounced here because of the phenotypic heterogeneity of the disease.…”

Section: Discussionmentioning

confidence: 86%

“…In brief, we estimated bias-corrected ORs from three simulation analyses for differential exposure misclassification and from one simulation for unmeasured confounding. For reverse causation bias, we opted for three bias scenarios to account for the uncertainty around the bias parameters because data on the proportion of cases that had preclinical sarcoidosis were not available [26].…”

Section: Discussionmentioning

confidence: 99%

“…Individuals with progressive sarcoidosis or debilitating symptoms receive pharmacologic treatment, commonly, systemic corticosteroids, methotrexate, or azathioprine in Sweden [25,26]. Because there is no information on sarcoidosis severity in the register data, we used a previously developed proxy [27] which defines severe sarcoidosis phenotype as cases who were dispensed any of the three treatments in the Prescribed Drug Register within 3 months before or after the index date (Table S1).…”

Section: Sarcoidosis Cases and General Population Controlsmentioning

confidence: 99%

“…Sarcoidosis at a preclinical stage may last for more than 2 years before diagnosis in some cases [26,[29][30][31], hence increasing the risk for reverse causation bias. To mitigate the possibility of capturing infectious diseases occurring while cases were at the preclinical stage, visits or dispensations occurring within 3 years before index date in both cases and controls were not considered in main analyses (Fig.…”

Section: History Of Infectious Disease and Latency Periodmentioning

confidence: 99%

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Are infectious diseases risk factors for sarcoidosis or a result of reverse causation? Findings from a population-based nested case–control study

et al. 2020

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Findings from molecular studies suggesting that several infectious agents cause sarcoidosis are intriguing yet conflicting and likely biased due to their cross-sectional design. As done in other inflammatory diseases to overcome this issue, prospectivelycollected register data could be used, but reverse causation is a threat when the onset of disease is difficult to establish. We investigated the association between infectious diseases and sarcoidosis to understand if they are etiologically related. We conducted a nested case-control study (2009-2013) using incident sarcoidosis cases from the Swedish National Patient Register (n = 4075) and matched general population controls (n = 40,688). Infectious disease was defined using inpatient/ outpatient visits and/or antimicrobial dispensations starting 3 years before diagnosis/matching. Adjusted odds ratios (aOR) of sarcoidosis were estimated using conditional logistic regression and tested for robustness assuming the presence of reverse causation bias. The aOR of sarcoidosis associated with history of infectious disease was 1.19 (95% confidence interval [CI] 1.09, 1.29; 21% vs. 16% exposed cases and controls, respectively). Upper respiratory and ocular infections conferred the highest OR. Findings were similar when we altered the infection definition or varied the infection-sarcoidosis latency period (1-7 years). In bias analyses assuming one in 10 infections occurred because of preclinical sarcoidosis, the observed association was completely attenuated (aOR 1.02; 95% CI 0.90, 1.15). Our findings, likely induced by reverse causation due to preclinical sarcoidosis, do not support the hypothesis that common symptomatic infectious diseases are etiologically linked to sarcoidosis. Caution for reverse causation bias is required when the real disease onset is unknown.

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History and Familial Aggregation of Immune-Mediated Diseases in Sarcoidosis

Rossides,

Kullberg,

Arkema

2024

CHEST

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Sarcoidosis diagnosis and treatment in Sweden: A register-based assessment of variations by region and calendar period

Cited by 17 publications

References 17 publications

Risk of first and recurrent serious infection in sarcoidosis: a Swedish register-based cohort study

Risk of first and recurrent serious infection in sarcoidosis: a Swedish register-based cohort study

Are infectious diseases risk factors for sarcoidosis or a result of reverse causation? Findings from a population-based nested case–control study

History and Familial Aggregation of Immune-Mediated Diseases in Sarcoidosis

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