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Abstract
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.
- Sarcoidosis
- Clinical Epidemiology
- Rare lung diseases
Data availability statement
All data relevant to the study are included in the article or uploaded as online supplemental information.
This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
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WHAT IS ALREADY KNOWN ON THIS TOPIC
Sarcoidosis is a systemic disease of unknown cause with a high prevalence in the Nordic countries.
WHAT THIS STUDY ADDS
The incidence and prevalence of sarcoidosis in the age group 60 years or more had increased, and D86.8 (sarcoidosis of other and combined sites) was the most common diagnosis code used in this age group in Finland in 2022.
HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY
Multiorgan sarcoidosis in the elderly is a disease that future research should focus on, as this group comprises a significant proportion of patients with sarcoidosis.
Introduction
Sarcoidosis is a disease of unknown origin, in which granuloma formation in different organs, typically in the lungs, is characteristic.1 Traditionally, sarcoidosis has been regarded as a disease of young-aged and middle-aged adults with a slightly higher disease rate of women.2 However, it seems that age at the disease onset might have increased during past decades.3
Sarcoidosis is most common in Nordic countries and African Americans.4–7 The prevalence of sarcoidosis has been 50‒143/100 000 among white North Americans and 60‒80/100 000 in Northern countries, namely Denmark and Sweden.4–7 The prevalence of sarcoidosis in Finland was 28/100 000 about 40 years ago when 3.6%–4.7% of sarcoidosis population was related to familial clustering.8 9 The comparison of studies on prevalences, however, is difficult, because the definition of sarcoidosis and the time frame for which the prevalence has been determined has varied. Furthermore, access to healthcare services also affects the number of cases recorded in different healthcare service registers.
Finnish healthcare services form a single entity, which is a favourable setting for collecting national data on diseases.10 A right to public healthcare is fundamental for Finnish citizens, and the client fees are nominal. The role of primary care in identifying sarcoidosis or suspecting recurrence of the disease is essential.11 In Finland, patients with suspected sarcoidosis are usually referred from primary care to specialised care, either to central or university hospitals, for further diagnostic studies and treatment planning. All sarcoidosis patients in Finnish specialised care are treated by one or multiple medical specialties according to the organ manifestations of the disease. Further description of Finnish public healthcare system is in online supplemental E-figure 1, E-table 1.
Supplemental material
Although it has shown that the prevalence and incidence of sarcoidosis are high in Northern countries, the recent data on sarcoidosis epidemiology in Finland are missing. Furthermore, longitudinal studies observing the changes in the age and gender distribution and the incidence of different sarcoidosis phenotypes are few. In this study, we aimed to investigate nationwide prevalence and incidence rates of sarcoidosis by making an information request regarding sarcoidosis-related visits in Finnish specialised care. We aimed to resolve the changes in the incidence and prevalence rates during the past 20 years as well as sex and age distribution and geographic variability, with a focus on the diagnosis codes used for patients with lung manifestation of sarcoidosis.
Methods
Study subjects and design
The data for this study were requested from the Care Register for Health Care (Hilmo). Hilmo, provided by the Finnish Institution of Health and Welfare, includes information on the number of patients and their treatment periods either in outpatient clinics or in hospital wards of specialised care, where practically all sarcoidosis patients in Finland are treated. The Hilmo register data cover the whole population of Finland, and the quality of the register data has been good.12
We made an information request to Hilmo of the patients whose first recorded ICD-10 (International Classification of Diseases 10th Revision) diagnosis code was either D86.0 (sarcoidosis of lung), D86.1 (sarcoidosis of lymph nodes), D86.2 (sarcoidosis of lung with sarcoidosis of lymph nodes) or D86.8 (sarcoidosis of other and combined sites). These diagnosis codes were selected because the main focus of the study was to find the patients with thoracic manifestation of sarcoidosis, which is observed in 90% of sarcoidosis cases.13 In addition, we requested the total numbers of patients whose first diagnosis code began with D86 (D86.X), thus including also the patients with D86.3 (sarcoidosis of skin) and D86.9 (sarcoidosis, unspecified) into the total number of patients. The data request was limited to only persons aged 18 and older. We requested the annual numbers of patients with at least one contact with Finnish specialised care during the year at review, which were the years 2002, 2012 or 2022. From those patients who had several visits with sarcoidosis-related ICD-10 code/codes during the year at review, only the ICD-10 code related to the first visit of the year was recorded. We also requested other parameters of the study patients, including gender, age group and university hospital district where the patient had been treated. The five Finnish university hospital districts and their population bases are shown in online supplemental file.
We made another information request on the number of the patients who had their sarcoidosis diagnosis (D86.X) recorded for the first time during the year at review. If a person had had sarcoidosis-related visits since 1996, counted before the year under review, he/she was excluded. The year 1996 was chosen as the starting point because it was the year when ICD-10 codes began to be used in the Hilmo database.
The demographic data of continental Finland and each university hospital district were received from an open database of Statistics of Finland (https://pxdata.stat.fi/). Åland, the smallest region and hospital district in Finland, located in an archipelago in the Baltic Sea, was excluded from the data because of the small population (about 30 000 inhabitants).
Statistical analysis
The statistical analysis was made with SPSS (IBM, Released 2020. IBM SPSS Statistics for Windows, V.27.0., IBM) and Microsoft Excel (for Microsoft 365 MSO (V.2401 Build 16.0.17231.20194) 32-bit Corporation, Northampton, Massachusetts, USA), was used for graphs. Prevalences were estimated by using demographic data of the ≥18-year-old population of the demographic area as denominators. For men, women and different age groups (18–29, 30–39, 40–49, 50–59, 60–69 and 70+), prevalences were calculated separately by using the population of each gender and/or age group as denominators. The prevalence was reported as the number of cases per 100 000 persons. Incidence was calculated by using the ≥18-year-old population at risk (population of the demographic area minus patients with earlier D86 diagnosis) as denominators. Incidence was also calculated separately for over 18-year-old men and women and the age groups mentioned above. Incidence-prevalence ratio was counted by dividing the number of newly diagnosed sarcoidosis patients by the total number of sarcoidosis patients. Those D86.X patients with a history of more than one visit in specialised care because of sarcoidosis at the year of review were calculated by the following formula: (1 - incidence/prevalence -ratio)×prevalence.
Results
Prevalence of sarcoidosis had increased in elderly
The total number of prevalent sarcoidosis patients in Finnish specialised care had increased from 3436 patients in 2002 to 4764 in 2022, and the prevalence had risen from 84.6/100 000 to 105.9/100 000 (table 1, online supplemental E-table 2, figure 1A‒C). The prevalence of the D86.X patients with more than one contact in specialised care was 65.1/100 000 in 2002 and 87.9/100 000 in 2022. An increase in the prevalence of sarcoidosis patients was observed in every university hospital district (figure 1A‒C). There were significant differences between the five hospital districts: The highest prevalence was 170/100 000 in the Tampere University Hospital district (TAUH) in 2022, which was twice as high as in the Helsinki University Hospital district (84/100 000) (online supplemental E-figure 2A).
Prevalence of sarcoidosis (patients with ≥1 visit in Finnish specialised care) by gender and university hospital district in 2002, 2012 and 2022
Prevalence (A‒C) and incidence (D‒F) of sarcoidosis in Finland and in university hospital districts. Data are expressed as number of cases per 100 000 per year. FIN, Finland; HUH, Helsinki University Hospital; KUH, Kuopio University Hospital; OUH, Oulu University Hospital; TAUH, Tampere University Hospital; TUH, Turku University Hospital.
There was no clear gender predominance in 2002 (50.3% men) and 2012 (49.9% men), but in 2022 slight female predominance had appeared (54.8%) (online supplemental E-table 2). The prevalence of women had exceeded that of men in all hospital districts in 2022, although in 2012, the prevalence was higher among men than women everywhere in Finland (table 1).
The total number and the prevalence of the patients with D86 diagnosis peaked at the age group of 50‒59 years (online supplemental E-figure 3, figure 2A–C). Both in men and women, the age distribution had changed during the past 20 years, having increased in the age groups 50 years or more and decreased in the age groups less than 40 years (online supplemental E-figure 3, figure 2A‒C). In women, the peak prevalence of sarcoidosis between the ages of 50 and 69 remained unchanged throughout the study period. However, in men, the prevalence peak shifted from 30‒59 years to 40‒69 years. The most dramatic increase in the number and prevalence of patients had occurred at the age group of 70 or more in both genders.
Prevalence (A‒C) and incidence (D‒F) of sarcoidosis in different age groups by gender. Data are presented as patients per 100 000 persons per year at each age group.
The onset age of sarcoidosis had increased regardless of sex
Incidence of sarcoidosis had remained at the same level in Finland for 20 years, namely 17–19 cases per 100 000 per year (table 2, figure 1D‒F). In TAUH, a decrease from 33 per 100 000 to 26 per 100 000 was observed, and in Kuopio University Hospital District increase from 13 per 100 000 to 20 per 100 000 was found. The incidence-prevalence ratio declined from 0.23 to 0.17 during the past 20 years (online supplemental E-table 2). There was no gender predominance in newly diagnosed sarcoidosis patients in 2002 (393 men and 392 women), but slight female predominance in 2012 (352 men and 380 women) and in 2022 (400 men and 421 women).
The sarcoidosis incidence in Finland in total and by gender and university hospital district in 2002, 2012 and 2022
The number of new sarcoidosis cases had increased in the age groups elder than 60 years and decreased in younger age groups, which could be observed in both men and women (online supplemental E-figure 4). The peak incidence had shifted from patients aged 30‒39 years to 50‒59 years. The two-peaked incidences were observed in men (age groups 30‒49 and 60‒69) and women (age groups 30‒39 and 50‒59) in 2002, but this disappeared in both genders during the follow-up time (figure 2D‒F).
The subgroup of newly diagnosed patients elder than 70 years had increased: the total number of patients more than doubled in both genders and the incidence increased especially in women, from 11/100 000 per year to 17/100 000 per year (figure 2D‒F). A steep decrease in the incidence of patients aged less than 40 years was observed in both genders (figure 2D‒F).
The number of patients with lung sarcoidosis had decreased in all age groups
The proportion of patients with lung sarcoidosis (either D86.0 or D86.2) decreased from 62% to 45%, whereas the proportion of patients with sarcoidosis of other sites (D86.8) increased from 11% to 34% (figure 3, online supplemental E-table 2). This development was observed in all university hospital districts (online supplemental E-table 3). Code D86.8 became more common in all age groups during the study period, the increase being highest at the age group ≥70 years, in which it accounted for 9% of patients in 2002 and 32% in 2022 (online supplemental E-table 4). In contrast, D86.0 became less common in all age groups. The proportion of D86.8 patients in incident cases of sarcoidosis also increased, with an absolute increase exceeding 10% in all age groups over 30 years of age. This increase was greatest in the 60–69 age group, which saw an increase from 11% in 2002 to 24% in 2022 (online supplemental E-table 4).
The proportion of lung sarcoidosis (D86.0 and D86.2) of all prevalent sarcoidosis cases had decreased between 2002 and 2012.
Gender distribution in different diagnostic subgroups
The gender distribution varied slightly in all different diagnosis groups during the study period (online supplemental E-table 2). In both genders, the most common diagnosis code was D86.0 in 2002 and 2012, accounting for 48.5% of men with sarcoidosis and 43.9% of women in 2002, and 41.9% of men and 36.5% of women in 2012. In 2022, however, D86.2 patients formed the largest subgroup among men (32.0%) and D86.8 among women (38.3%).
Discussion
We have introduced a nationwide data on prevalence and incidence of sarcoidosis in Finnish specialised care. The prevalence of sarcoidosis was higher than expected and it had increased during the past decades from 84.6/100 000 to 105.9/100 000 when the incidence had remained the same, being 17‒19/100 000. The number of incident and prevalent sarcoidosis patients had increased especially in the age group 70 years or more both in men and women. In addition, the proportion of pulmonary sarcoidosis of all sarcoidosis subtypes had decreased.
The prevalence in this study, according to the broad definition (patients with one or more visits in specialised care with D86.X diagnosis within the year at review) was high, 105.9 per 100 000 in 2022, compared with other Nordic countries or the earlier Finnish study.4 5 8 However, this number might exaggerate the prevalence rate because the initial diagnosis may change after additional diagnostic studies are implemented after the first visit to specialised care. If only the cases with at least two visits in specialised care were taken into account, the prevalence was 87.9/100 000, which is more in line with other Nordic countries. According to the study covering Southwest Finland, the prevalence of lung and lung and lymph node sarcoidosis was 25‒51/100 000 in 2014‒2018, which is in line with our results when considering that in this current study about 50% of sarcoidosis was recorded with other diagnosis codes than D86.0 and D86.2.14 A clear increase in the prevalence of sarcoidosis during the past 20 years was observed in this study, which has not been reported earlier.
The prevalence of sarcoidosis had increased in Finland at the same time as the incidence-prevalence rate had decreased and the incidence rate remained the same. The increase in prevalent cases is, therefore, assumably due to the accumulation of sarcoidosis patients in specialised care, which is likely due to that patients are treated and followed up longer in specialised care than in recent decades. One can speculate if this is due to the increase in the number of sarcoidosis phenotypes belonging to the group D86.8 (sarcoidosis of other sites), the phenotype which comprises more serious, multiorgan presentations of sarcoidosis. The prevalence of sarcoidosis had also increased in Denmark between 2000 and 2015 similarly to Finland.5 However, in Denmark, the incidence had also increased, partially explaining the increase in prevalence, which was attributed to the development of imaging technologies and the rise in mild accidental findings.5
The proportion of lung sarcoidosis (D86.0 or D86.2) of all sarcoidosis cases had decreased during the past 20 years while the proportion of sarcoidosis of other sites (D86.8) increased, especially in elderly age groups. Similar development has not been reported in earlier studies. Ungprasert et al speculated that the increase in the sarcoidosis in elder age groups might be explained by the effect of diminishing environmental triggers and longer cumulative exposure times for them.3 These factors might also explain the shift from milder sarcoidosis manifestations to multiorgan presentations in Finnish population. It is probable that the cases coded with D86.8 also included lung sarcoidosis patients with other organ manifestations. However, an increase in the number of D86.8 patients has been observed in all university hospital districts since 2002, although there are no national recommendations on the use of ICD-10 codes in sarcoidosis. It is also possible that awareness of sarcoidosis has increased, which has improved the recognition of extrapulmonary manifestations. Nevertheless, an increase in the number of D86.8 cases was observed even before the publication of the ERS clinical practice guidelines on treatment of sarcoidosis in 2021.15 Thus, it appears that multiorgan manifestations of sarcoidosis have increased in Finland.
The sex distribution of sarcoidosis has varied in earlier studies. In our study, we observed an even distribution of sarcoidosis cases between the genders in 2012 and earlier, but a shift towards female predominance between 2012 and 2022. A similar shift in gender distribution of sarcoidosis has not been reported in earlier studies. Male predominance has been reported in Poland and in Denmark, whereas female predominance has been reported in the USA, in Canada, in Finland 30 years ago, in Japan and in South Korea.5–8 16–19 The reason for female predominance in Finland might be the higher number of more severe manifestations of sarcoidosis in women than in men, namely the diagnosis code D86.8 (sarcoidosis of other sight) was more common in women than in men, which may cause the increase of these patients in specialised care.
The age distribution of Finnish sarcoidosis patients had changed during the follow-up since the incidence peak shifted from 30‒39 years to 50‒59 years during the past 20 years. Although the prevalence peak remained at the age of 50–59 years, the number of prevalent patients aged more than 60 years increased to 2.4-fold between 2002 and 2022. The shift in the incidence and prevalence peaks to older age groups has been observed also in the USA, where the peak incidence of females shifted from 40‒59 years to 50‒69 years, and of males from 30‒49 years to 40‒59 years between 1950 and 2010.3 In the same study, the incidence of sarcoidosis in 70-year-old and elder patients had increased in both genders, which is consistent with our results.3
In earlier studies, the incidence and prevalence have peaked in two age groups. For instance, incidence peaked in women aged 25‒29 and 65‒69 years in Denmark in 1980‒1994 and in women aged 20‒34 and 50‒60 years in Japan in 2004.17 18 In Korea, the peak prevalence and incidence were observed only among men at 30‒39 years and at 60‒69 years in 2009‒2016, which was also the case in Denmark in 2001‒2015, although the later incidence peak was at 50‒59 years in Denmark.5 19 In our study, the prevalence was not two-peaked in the general population or in either sex at any point, but there were two-peaked incidences in both men and women in 2002, while in 2022 these incidence peaks had disappeared. This has not been reported in earlier studies, and due to the methodological differences, earlier reports are not fully comparable with ours.
The geographical differences in prevalence and incidence rates of sarcoidosis were observed in this study. Geographical variation of prevalence and incidence has also been reported in Sweden and Denmark.4 5 The reasons explaining these findings might be related to familial clustering of cases or different environmental factors causing sarcoidosis in geographically different areas. Future studies should investigate whether genetics plays a role in local differences in incidence and prevalence in Finland.
A multidisciplinary approach to the diagnosis and treatment of sarcoidosis patients has been highlighted in recent publications.11 20 The increased number of multiorgan sarcoidosis patients in this study supports the need for this approach. In Finland, interstitial lung disease multidisciplinary meetings (ILD-MDM) are used in whole country in the diagnosis and treatment of patients with ILD.21 Patients with sarcoidosis are also discussed in these meetings. Our results indicate that the need for multidisciplinary approach in treatment of sarcoidosis is increasing, and implementation of MDMs focusing on sarcoidosis patients only is worth considering.
The weakness of the study includes the possible inaccuracy in the use of ICD-10 diagnosis codes and the lack of detailed patient information to identify the phenotypes of individual patients. We only took account the first sarcoidosis-related diagnosis code recorded for a single patient during the year at review. By doing this, we wanted to ensure that a single patient would not be recorded multiple times with several sarcoidosis diagnosis codes in our data. There might be some patients who had been diagnosed with new sarcoidosis manifestations after their recorded visit to special care. A data request which would have considered the changes in recorded diagnosis codes of individual patients might have slightly increased the proportion of sarcoidosis patients recorded with D86.8, which, on the other hand, would not have altered the main result of this study. The definite information on sarcoidosis phenotypes would require access to detailed patient data, which is not possible by using the methodology of this study.
The treatment responsibility for sarcoidosis patients with stable, inactive disease and no medical treatment, may be transferred to primary care, in which case these patients cannot be found in the Hilmo database search. Variability in sarcoidosis patients’ treatment and follow-up practices might partially explain the differences in the prevalence and incidence rates of different university hospital districts rather than the actual differences in the total numbers of sarcoidosis patients. However, in Finland, access to public healthcare services is good for all citizens regardless of wealth and social status, which improves the representativeness of our study.
To conclude, we observed an increase in the incidence and prevalence of elderly sarcoidosis patients in both genders and cumulation of D86.8 coded patients in Finnish specialised care during the past 20 years. We also found geographical variability in the incidence and prevalence of Finnish sarcoidosis patients. These findings might indicate that potential environmental and genetic factors associated with sarcoidosis are enriched in different parts of Finland.
Data availability statement
All data relevant to the study are included in the article or uploaded as online supplemental information.
Ethics statements
Patient consent for publication
Ethics approval
The information request was accepted by Findata on 13 December 2023. The data were aggregated and anonymous and did not include identifying information. The study was implemented in accordance with Finnish and EU data privacy legislation.
Acknowledgments
We would like to thank Eveliina Halttunen (Kulmakuvaamo) for the help in editing images
References
Supplementary materials
Supplementary Data
This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.
Footnotes
Contributors JS made the data request to Findata, analysed the data, prepared the first draft of the manuscript, prepared the graphs and submitted the study. Both authors, JS and RK, participated in the study design and in the interpretation of the data. RK managed the study. Both authors commented on previous versions of the manuscript and read and approved the final manuscript. JS is the guarantor of the study, who accepted full responsibility for the work, had access to the data and controlled the decision to publish.
Funding This work was supported by a state subsidy from Oulu University Hospital and the Research Foundation of Pulmonary Diseases, Helsinki, Finland.
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Competing interests JS reports congress fees and travel costs from Sanofi and GlaxoSmithKline, outside of the submitted work. RK has received lecture fees from Boehringer-Ingelheim and Roche, advisory board fees from MSD and Boehringer-Ingelheim and virtual congress costs from Novartis outside of the submitted work.
Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
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