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M.M. Ostrovskyi, K.V. Shvets Regional Age-Related, Gender, and Geo-Industrial Aspects of the Prevalence and Clinical Course of Sarcoidosis in Patients from Ivano-Frankivsk Region Department of Phthisiology and Pulmonology with a course of Industrial Diseases Ivano-Frankivsk National Medical University, Ivano-Frankivsk, Ukraine Abstract. The research work is related to the problem of sarcoidosis in Ivano-Frankivsk region. The objective of the research work was to study the prevalence and incidence, age-related structure of sarcoidosis. Materials and methods. Statistical data were obtained processing the medical records of 287 patients from Ivano-Frankivsk regional phthysio -pulmonary centre at the age of 18 years and older whose diagnosis of sarcoidosis was confirmed either histologically or by means of helical computed tomography of thoracic organs. Results. The average incidence index was 3.37 cases per 100 thousand people, while the prevalence index was 14.35 cases per 100 thousand people. The highest indices were recorded in Kalush and Kolomyia districts, which are considered as the territories with increased anthropogenic load. The morbidity rate in the regions with well-developed woodworking industry was subaverage, though the incidence was considerably higher in males, who are actually engaged in this field of industry. The number of males and females diagnosed with sarcoidosis was identical in the regional centre and in Kalush district, while in Kolomyia district the incidence rate was higher among female population. The study found that the peak incidence in male population was at the age of 20 to 29 years, and females more often developed the disease at the age of 40 to 49 years. The most common comorbidities included the disorders of cardiovascular and respiratory systems. Conclusions. Geographic and ecological factors have a considerable influence on the incidence, prevalence and development of sarcoidosis. In 25.0% of cases sarcoidosis leads to pulmonary failure and, as a result, reduces the quality of life and causes disablement in the population. Keywords: sarcoidosis, etiology, prevalence Problem statement and analysis of the recent research Pulmonary sarcoidosis (also known as Boeck’s sarcoidosis, Besnier-Boeck-Schaumann disease) is a multisystemic disease of unknown etiology. The history of the disease dates back to1899 when the Norwegian scientist Caesar Boeck described skin nodules as dense compact lesions consisting of epithelioid cells with large nuclei and giant cells, which he later called “benign sarcoid of the skin”. Over the period of more than 100 years the science has greatly evolved, although the causes of sarcoidosis still remain unknown. Pulmonary sarcoidosis is the most common (80-90%) and in most world’s countries it constitutes a considerable clinical entity among interstitial lung pathologies (in Belgium its rate makes up – 27%, in Greece – 37.4%) [2, 21]. The worldwide morbidity rate ranges from 0.125 to 24.0 cases per 100 thousand people, and its prevalence makes up from 1 to 64 cases per 100 thousand people [1, 2]. The climatic factor is considered to be the leading one in the development, prevalence and incidence of sarcoidosis [3, 4]. This pathology is known to prevail in geographical zones with temperate and frigid climate. Correspondingly, the sarcoidosis morbidity rate is the lowest in African and Asian countries, as well as countries of Central and South America, while in Nordic countries this rate is the highest (Denmark – 10.1; Finland – 11.4; Norway – 15.4 and Sweden – 24.0 cases per 100 thousand people) [22]. According to the research data of V.K. Havrysiuk and co-authors, it is considered that the lowest incidence (1.1 case per 100 thousand people) and prevalence (4.6 cases per 100 thousand people) rates in Ukraine were noticed in the Crimea, while the highest rates were marked in Zhytomyr region (incidence – 2.62 cases per 100 thousand people, prevalence – 7.9 cases per 100 thousand people) [3, 4, 6, 7]. The prevalence and incidence rates of sarcoidosis among US dark-skinned population are 3 times higher as compared to fair-skinned one [14, 25 ]. In Ukraine the level of morbidity ranges from 1.1 to 2.62 and the level of prevalence ranges from 4.6 to 7.9 cases per 100 thousand people [4]. Since sarcoidosis most commonly affects the lungs, skin and eyes, the majority of researches were focused on the search and study of air-borne agents causing the disease. The results of the first investigations established the relationship of disease development in rural areas with the factors such as wood dust and smoke from wood heaters [24]. Afterwards the impact of inorganic particles, insecticides, mould, heavy metals, formaldehyde, and phenol resins was described. The analysis of occupational factors showed high morbidity level among the workers of metal-based manufacturing industry, as well as significant incidence of the disease was revealed among fire-fighters who participated in the recovery works after terrorist attack in New-York in 2001 [24]. Some scientists do not rule out the influence of Mycobacterium tuberculosis, the antibodies of which are often found in the blood of patients with sarcoidosis.
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The influence of genetic factors on the disease development is also taken into account. The first case of family sarcoidosis was recorded in two sisters in 1923. Several etiologic investigations found out that individuals whose family members suffered from sarcoidosis (among parents, siblings) fall ill 5 times more often [24, 25]. The objective of the research work was to study the age-related, gender characteristics of concomitant pathology, prevalence and incidence of sarcoidosis in Ivano-Frankivsk region. Materials and methods of the investigation Statistical data were obtained processing hospital records of 287 patients from Ivano-Frankivsk regional phthysio-pulmonary centre, where they had undergone treatment during the period from 2012 to 2014. The investigation involved male and female patients at the age of 18 years and older whose diagnosis of sarcoidosis was confirmed either histologically or by means of helical computed tomography of thoracic organs. The patients were divided into groups according to different parameters: district of the region, sex, age, radiologic stage of disease, bad habits, concomitant pathologies and others. The results of the investigation were processed by means of mathematical calculations and Microsoft Excel program. Results and discussion While studying the epidemiology and structure of sarcoidosis the morbidity rate in Ivano-Frankivsk region was found to be significantly higher as compared to other regions of Ukraine. If we consider the index of 2.62 to be the maximum for Ukraine [2], this rate in Precarpathian region was 1.28 times higher and made up 3.37 cases per 100 thousand people in 2014, and the prevalence rate was 1.81 times higher and comprised 14.35 cases per 100 thousand people. In most cases the disease was diagnosed with the help of helical computed tomography of thoracic organs (84.1 %), and only in 15.9 % of cases the diagnosis was confirmed histologically. The detailed analysis of the indices recorded in different districts of the region made it possible to establish that the highest morbidity rate was stated in Kalush (7.3 cases per 100 thousand people) and Kolomyia (7.0 cases per 100 thousand people) districts, while the lowest indices were noticed in Sniatyn (0.5 cases per 100 thousand people) and Halych (0.4 cases per 100 thousand people) ones.
8 7 6
7.3 7.0
5 4 3 2 1 0
4.4
4.0 3.7 4.2
3.3
3.9
3.37 2.62
2.5 1.6 1.1 0.4 1.1
0.5 1.1 1.1
Figure 1. The morbidity rate in different districts of Ivano-Frankivsk region (cases per 100 thousand people) Kalush district is known for its chemical industry, while oil-and-gas industry is well-developed in Kolomyia district. According to the data provided by the Department of Environmental Protection of the region they are considered to be the area of increased anthropogenic load, because high contents of harmful substances, like nitrogen dioxide, carbon monoxide, formaldehyde are annually found in the air, and significantly exceed the level of allowable concentrations [10]. The average morbidity level in these districts made up 7.15 cases per 100 thousand people, that was 2.12 time higher than the average incidence rate in the region (р<0.05).
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As evidenced by the data of research literature, wood dust is one of the most common etiological non-infectional factors of sarcoidosis. Woodworking industry is widely developed in Precarpathian region. There are about 40 large and average, and 300 small enterprises in the region, most of which are concentrated in Nadvirna, Rozhniativ, Kosiv and Verkhovyna districts. The average morbidity rate here was made up 3.19 cases per 100 thousand people being somewhat below the average rate recorded in the region with considerable prevalence of male cases, who are actually involved in the woodworking industry. While evaluating the climatic factors which are considered to be the leading cause of the disease development, the average morbidity rate was recorded in the northern part of the region (Rohatyn, Halych and Kalush districts) and made up 4.63 cases per 100 thousand people, and in the southern part (Sniatyn, Kosiv and Verkhovyna districts) this rate was 2.80 cases per 100 thousand people. In the northern part of the region this rate was 1.65 times higher (р<0.05) meeting the tendency in Ukraine and abroad. It is well-known fact, that the sarcoidosis morbidity rate is the lowest in African and Asian countries, while in Nordic countries this rate is the highest [3, 22]. According to the research data of V.K. Havrysiuk, the lowest incidence (1.1 per 100 thousand people) rates in Ukraine were noticed in the Crimea, and the highest rates were marked in Zhytomyr region (2.62 cases per 100 thousand people) [3, 4, 6, 7]. Significant prevalence of the disease among female population was recorded in Kolomyia district (67.6 % of female cases and 32.4 % of male ones). The distribution of the disease among male and female population was almost identical in Kalush district and Ivano-Frankivsk: 51.5 % of female and 48.5 % of male cases in Kalush, 50.0 % of female and 50.0 % of male cases in the regional centre. The number of male patients with sarcoidosis was twice higher as compared to the number of female cases in Kosiv district (р<0.05). The morbidity rate of female population increased at the age of 18 - 40 years and rapidly decreased after 49 years of age. The peak incidence in male population was at the age of 20 - 29 years and decreased up to 60 (incidence of the disease was rare in this age group) years of age. The pathology rarely developed in both male and female population at the age of 19-20 years (Figure 2).
females males
Figure 2. Age-related structure of patients with sarcoidosis in Ivano-Frankivsk region Chronic forms of sarcoidosis prevailed considerably and made up 173 (86.0 %) cases, while the acute form (Löfgren’s syndrome) made up 28 (14.0 %) cases. The largest number of patients with acute form of the disease – 57.0 % of cases, was recorded in Kalush district (11 cases) and in Kolomyia (5 cases). More than 70 % of cases were followed by the damage to the pulmonary parenchyma, and 25.8 % of patients were diagnosed with broncho-obstructive syndrome (Table 1). Table 1 Distribution of patients with sarcoidosis according to the stage of disease in Ivano-Frankivsk region Stage of disease I II III IV
Females absolute 17 46 4 27
Males percent 8.4 22.88 1.99 13.4
absolute 13 44 6 16
percent 6.46 21.89 2.98 7.96
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Cardiovascular pathologies (coronary heart disease, hypertension) and respiratory diseases (chronic bronchitis, COPD) were recorded as the most common (Figure 3).
0.99
Pathology of the cardiovascular system Pathology of the airways
0.99
Ophthalmic pathology
5.4 4.9
24.3
5.4 5.4 7.4
15.4 9.9 12.9
Pathology of the gastrointestinal tract Chronic pulmonary heart Otorhinolaryngologic pathology Pathology of the thyroid gland Pathology of the urinary system Anemia Diabetes mellitus Pathology of the skin integument
Figure 3. The structure of concomitant pathology in patients with sarcoidosis in Ivano-Frankivsk region Conclusions 1. The incidence of sarcoidosis in Ivano-Frankivsk region was 1.28 times higher than the maximal rate in Ukraine and made up 3.37 cases per 100 thousand people, and the prevalence rate was 1.81 times higher and comprised 14.35 cases per 100 thousand people. 2. The highest incidence indices in the region were recorded in Kalush, Kolomyia districts and Ivano-Frankivsk that may be associated with the anthropogenic load. Districts with highly developed woodworking industry are characterized by increased morbidity rate among males, who are actually engaged in this branch of national economy. 3. The assessment of climatic factors made it possible to determine that the incidence rate was 1.65 times higher in the northern part of the region as compared to the southern districts corresponding with the tendency in both Ukraine and other world’s countries. 4. Sarcoidosis led to the development of secondary broncho-obstructive syndrome resulting in the decrease of life quality in 25.8 % of cases. The most common comorbidities included the cardiovascular pathologies (coronary heart disease, hypertension) and respiratory diseases (chronic bronchitis, COPD). Prospects for further research The study of the structure of sarcoidosis allows us to deepen understanding of the etiologic and pathogenetic factors influencing the disease development and thus increase the effectiveness of treatment. References 1. Vizel A.A. Sarcoidosis. Pulmonologiya: Natsionalnoye rukovodstvo pod red. A.G. Chuchalina. GEOTAR-Media. Moscow. 2009; 681-695. 2. Gavrysyuk V.K. Pulmonary sarcoidosis. Zdorovia Ukraiiny. 2010; 2: 29-31.
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3. Gavrysyuk V.K., Merenkova E.A., Shadrina O.V., Berenda E.A., Kuts V.V. Incidence of pulmonary sarcoidosis: the rate of new cases depending on geographical latitude. Ukraiinskyi pulmonolohichnyi zhurnal. 2013; 2: 36-40. 4. Gavrysyuk V.K., Merenkova E.A., Shadrina O.V. et al. Incidence of sarcoidosis in southern and northern regions of Ukraine in 2011. Ukraiinskyi pulmonolohichnyi zhurnal. 2013; 3: 41–45. 5. Gavrysyuk V.K., Gumeniuk G.L., Merenkova E.A., Strafun O.V. A case of familial pulmonary sarcoidosis. Ukraiinskyi pulmonolohichnyi zhurnal. 2014; 3: 45-48. 6. Gavrysyuk V.K., Merenkova E.A., Gumeniuk G.L., Shadrina O.V. et al. Pulmonary sarcoidosis: epidemiology, structure of patients, results of treatment. Ukraiinskyi terapevtychnyi zhurnal. 2014; 2: 95-100. 7. Gavrysyuk V.K., Merenkova E.A., Gumeniuk G.L., Shadrina O.V. Pulmonary sarcoidosis: epidemiology, clinical forms and stages, results of treatment. Zdorovia Ukraiiny. 2014; 1(25): 32-33. 8. Gumeniuk G.L. Structure of patients with pulmonary sarcoidosis and results of treatment based on data of retrospective study. Tavricheskiy mediko-biologicheskiy vestnik. 2014; 1(65): 38-42. 9. Ilkovich M.M., Kokosova A.N. Interstitial lung disease: guidelines. Nordmedizdat. Sankt Petersburg. 2005; 560. 10. Regional report on the state of environment in Ivano-Frankivsk region for the period from 2010 to 2013. 11. Feshchenko Yu.I., Protsyk L.M., Cherednyk Yu.O. Pulmonary sarcoidosis: current state of the problem. Ukraiinskyi pulmonolohichnyi zhurnal. 2006; 3: 5-10. 12. Bratkovskis M., Barzdina I., Melgaile M. Epidemiology of Sarcoidosis and Tuberculosis in Latvia, common parallels. Abstract book of 7th WASOG Congress in Stockholm June 16–19 2002, Abstr. N 19. 13. Byg K.E., Milman N., Hansen S. et al. Sarcoidosis in Denmark 1980–1994. A registry-based incidence study comprising 5536 patients. Sarcoidosis Vasc. Diffuse Lung Dis. 2003; 20(1): 46-52. 14. Cozier Y.C., Berman J.S., Palmer J.R. et al. Sarcoidosis in black women in the United States: data from the Black Women’s Health Study et. al. Chest. 2011; 139: 144-150. 15. Djuric B. Sarcoidosis in Eastern Europe. Sarcoidosis. 1985; 2(1): 35-37. 16. Duncan M.E., Goldacre M.J. Mortality trends for tuberculosis and sarcoidosis in England. Int. J. Tuberc. Lung Dis. 2012; 16(1): 38-42. 17. Edmondstone W.M., Wilson A.G. Sarcoidosis in Caucasians, Blacks and Asians in London. Brit. J. Dis. Chest. 1985; 79(1): 27-36. 18. Gribbin J., Hubbard R.B., Le Jeune I. et al. Incidence and mortality of idiopathic pulmonary fibrosis and sarcoidosis in the UK. Thorax. 2006; 61: 980-985. 19. Gupta D., Singh A.D., Agarwal R. et al. Is tobacco smoking protective for sarcoidosis? A case-control study from North India. Sarcoidosis Vasc. Diffuse Lung Dis. 2010; 27(1): 19-26. 20. Hunninghake G.W. et al. ATS/ERS/WASOG Statement on Sarcoidosis. Sarcoidosis Vasc. Diffuse Lung Dis. 1999; 16: 149-173. 21. Karakatsanis A., Papakosta D., Rapti A. et al. Epidemiology of interstitial lung desease in Greece. Respir. Med. 2009; 103(8): 1122-1129. 22. Kurata A. Hygiene hypothesis: why sough/north geographical differences in prevalence of asthma and sarcoidosis. Med. Hypotheses. 2012; 79(3): 363-364. 23. Mana J., Badrinas F., Morera J. et al. Sarcoidosis in Spain. Sarcoidosis. 1992; 9(2): 118-122. 24. Michael C.I., Benjamin A.R., Alvin S.T. Sarcoidosis. N. Engl. J. Med. 2007; 357: 2153-2165. 25. Reich J. M. Sarcoidosis and acute leukemia. J. Roy. Soc. Med. 1992; 85: 306.
