Study of the environmental and individual factors of autoimmune diseases in the microregion of Águas Formosas – Minas Gerais State, Brazil

Autoimmune diseases lead to numerous limiting conditions. Their incidence and prevalence are known to be affected by several factors; and there is an absence of data in areas of economic vulnerability. The aim of this study was to access the epidemiological profile of autoimmune diseases in the public health system of the microregion of health of Águas Formosas, and to evaluate possible factors involved in the development of these diseases. This was an epidemiological study with a cross-sectional, survey-type, descriptive and exploratory. All patients were selected according to the inclusion criteria, and individual interview was conducted during home visits to apply a sociodemographic questionnaire with 20 variables associated with autoimmune diseases. In this study, it was observed that the municipalities of Machacalis, Umburatiba and Crisólita exhibited prevalence of autoimmune diseases above 90 cases per 10,000 of the population, and the other municipalities showed prevalence between 50 and 60 cases. In the microregion, a total of 407 cases of autoimmune diseases were observed, distributed in 24 different diseases, with a general prevalence of 673.69/100,000 of the population. Hashimoto's Thyroiditis, Graves' Disease, Vitiligo, Rheumatoid Arthritis, Psoriasis, Type 1 Diabetes Mellitus and Systemic Lupus Erythematosus, represent 47% of the cases. This was the first study that addresses the prevalence of autoimmune diseases in the microregion. The lack of registration or diagnosis is a factor that needs to be overcome in new studies to improve the knowledge of autoimmune diseases in this region.


Introduction
The autoimmune diseases are characterized by loss of immunological tolerance to self-antigens, displaying several limitations conditions (Yang et al., 2018;Rose, 2017). Although autoimmune diseases were initially considered uncommon, the effects of these diseases on mortality and morbidity contributed to highlight the importance of these diseases (Bogdanos et al., 2012). Studies show that 3 to 5% of the worldwide population is affected by autoimmune diseases (Bogdanos et al., 2012;Cooper & Stroehla, 2003;Jacobson et al., 1997;Rose, 2017;Yang et al., 2018;Roberts & Erdei, 2020).
The incidence and prevalence of autoimmune diseases are known to be affected by age, gender, ethnicity, geographic location, genetic background and behavioral factors. However, the way that these factors directly influence the development of these diseases remains unknown (Khan & Wang, 2020;Mak & Tay, 2014;Milo & Kahana, 2010;Shukla et al., 2018;Ulmanen et al., 2005;Wahren-Herlenius & Dorner, 2013).
Studies show that different factors may influence the prevalence of autoimmune diseases in specific areas or countries. Multiple sclerosis, for example, is a demyelinating autoimmune disease of the Central Nervous System that is more prevalent in Europe due to environmental characteristics. However, some of the diseases are also prevalent in countries of Latin America, including Brazil, and some of these differences in the prevalence seem to be influenced by the solar display or parasite infections (Correa et al., 2016;Jackson et al., 2018;Krawczak et al., 2017;Milo & Kahana, 2010;Moroni et al., 2012).
National studies were carried out by addressing the prevalence of one or more autoimmune diseases in different Brazilian regions. A high prevalence of autoimmune diseases as Hashimoto thyroiditis, Sjögren's Syndrome and inflammatory myopathies is observed in a study of familial autoimmunity and poliautoimmunity in patients in the central-west Brazil (Horimoto et al., 2016). In some cases the diseases were also associated with the presence of systemic sclerosis. Another study shows a prevalence of 20% of Hashimoto thyroiditis in 56 patients with systemic sclerosis (Costa et al., 2014).
National studies show the prevalence of alone or associated autoimmune diseases; however, there is a lack of data to show the proportion of autoimmune diseases in low income areas such as the Mucuri Valley mesoregion, specifically the microregion of health of Águas Formosas -Minas Gerais State. In this context, the present study aimed to know the epidemiological profile of autoimmune diseases in the public health system of the microregion of health of Águas Formosas, and to evaluate the possible environmental factors involved, in the expectancy to subsidize the adoption of health promotion, prevention and recovery.

Methodology
The project was approved by the Research Ethics Committee of the Federal University of the Jequitinhonha and Mucuri Valleys under registration CAAE:57185316.4.0000.5108 and authorized by the Regional Health Superintendent of Teófilo Otoni and by the Municipal Health bureau of the councils that make up the study. This is an epidemiological study of a quantitative approach with a cross-sectional, survey-type, descriptive and exploratory (Koche, 2011;Ludke & Andre, 2013;Yin, 2015, Zangirolami-Raimundo et al., 2018. The research was carried out in the public health system of the Microregion of Águas Formosas, located in the northeast of Minas Gerais state. The microregion has an estimated total population of 60,413 inhabitants (IBGE, 2016), with an approximate 4,150,700 km² of area; and is composed of eight cities: Águas Formosas, Bertópolis, Crisólita, Fronteira dos Vales, Machacalis, Pavão, Santa Helena de Minas and Umburatiba. Before data collection, a study was carried out in the medical records in the 26 units of primary health care in the Microregion, from January to December 2016, searching for patients that were diagnosed with autoimmune diseases.
The inclusion criteria in this study were man and woman raised in the Microregion of health of Águas Formosas, have been confirmed diagnostic of autoimmune disease, not less than 7 years old. These interviews were carried with the authorization of the subjects and the signing of the Informed Consent Form or Informed Assent Form. The control group was constituted of the individuals healthy, raised in the Microregion of health of Águas Formosas. All the patients were selected according to the inclusion and exclusion criteria.
After the medical records survey of the cases with a positive diagnosis for autoimmune diseases, an individual interview was conducted during home visits by trained nurse, that applied the sociodemographic questionnaire with behavioral variables associated at autoimmune diseases such as: vaccinated against hepatitis B, odontological surgical procedure, physical or psychological trauma, surgical procedures, used hair tints or other chemicals agents by inhalation, treated water consumption, practiced physical exercises and cow milk consumption before 6 months of age.
The collected data were analyzed in BioEstat software version 5.0. The description of the categorical elements was performed by simple logistic regression. Then, multiple logistic regression was used to estimate the odds ratios between the variables. Variables with p < 0.05 were significantly associated.

Figure 1. Prevalence of autoimmune diseases in the health microregion of Águas Formosas -Minas Gerais State -Brazil. (A)
Prevalence of autoimmune diseases in the municipalities that constitute the microregion. (B) Prevalence of different autoimmune diseases in the microregion.

Source: Authors.
In the present study 407 cases of autoimmune disease were observed, distributed in 24 different diseases, with a Research, Society and Development, v. 10, n. 4, e29910414138, 2021 (CC BY 4.0) | ISSN 2525-3409 | DOI: http://dx.doi.org/10.33448/rsd-v10i4.14138 general prevalence of 673.69 cases per 100,000 of the population, distributed among the municipalities of the region ( Figure   1). In the analysis of the sociodemographic profile of autoimmune disease patients, a higher percentage of prevalence was found in women, people in productive age, of whom 87% were older than 30 years, and of brown-skinned group (Table 1).  (Fig. 1B). In these pathologies, the behavioral variables: vaccinated against Hepatitis B; having practiced physical activity; have performed any surgical or dental procedure; have consumed mine or treated water; have consumed cow's milk in the first months of life; among others, presented influences to favor or protect the development of autoimmune diseases (Table 2). It is emphasized that some data were lost because the individuals did not know or refused to answer all the information on the questionnaire.  Development, v. 10, n. 4, e29910414138, 2021 (CC BY 4.0) | ISSN 2525-3409 | DOI: http://dx.doi.org/10.33448/rsd-v10i4.14138

Discussion
The research was carried out in the public health system of the Microregion of Águas Formosas, belonging to the Northeast Macroregion of Minas Gerais state, one of the regions of greater social vulnerability in Brazil, known due to its low social indicators and also to exhibit characteristics of the Northeastern region of Brazil, as long drought period, high levels of poverty, malnutrition, mortality, illiteracy, unemployment, and precarious socioeconomic and political infrastructure (Ribeiro & Galizoni, 2002). In this microregion, there are few official epidemiological data on the incidence and prevalence of autoimmune diseases, being the present study, the only one so far to carry out the survey and the respective prevalence of these pathologies.
Analyzing the obtained data, the overall female / male ratio were 2.3:1, approaching to previous studies which stated that women have a 2.7 times higher risk than men to develop an autoimmune disease and 78% of these pathologies are more common in women according to other studies (Cutolo et al., 2006;Gleicher & Barad, 2007;Quintero et al., 2012). The male immune system may have benefited from the hormonal characteristic in which its phenotype has low levels of estrogen and prolactin, high levels of androgens and cyclic levels of growth hormone.
In addition, the high prevalence in individuals of productive age is also corroborated by previous studies that portray that autoimmune diseases can occur at any age, from childhood to advanced age . When assessing the onset of the various autoimmune diseases in the patient's age, it is observed that there is a variation according to each autoimmune disease. Juvenile idiopathic arthritis and Type 1 diabetes mellitus are diseases that manifest in childhood; the Systemic Lupus Erythematosus is more frequent in young people, and multiple sclerosis is more common in adulthood .
When analyzed the behavioral factors, studies already shown that cow's milk protein intake is associated with progression of the type 1 diabetes in childhood (Lamb et al., 2015). In addition, viral infections are triggers for autoimmune diseases by various mechanisms, including direct cytolysis of virus-infected cells, cellular mimicry, and imbalance between regulatory T cells and autoreactive T cells (Pordeus et al., 2008). Also, studies have shown that the vaccination would lead to autoimmune diseases, especially Rheumatoid Arthritis (Doria et al., 2008;Guimarães et al., 2015;Toussirot & Bereau, 2015).
In this study, it was observed that in Rheumatoid Arthritis, Grave's Disease, Psoriasis, Lupus, Hashimoto's disease, and Vitiligo, the fact of having been vaccinated against Hepatitis B would tend to favor the onset of the disease.
The practice of physical activity has been shown efficiently in control of the different immunological dysfunctions.
Exercise stimulates the release of anti-inflammatory compounds as cortisol and adrenaline and suppresses the release of proinflammatory cytokines (Codella et al., 2015). In the present study, physical exercise was a protective factor for the development of Hashimoto's disease, Vitiligo, Rheumatoid Arthritis, Psoriasis and Systemic Lupus Erythematosus.

Conclusion
This is one of the first studies that address more broadly the prevalence of autoimmune diseases in the microregion.
Many obstacles such as lack of registration or diagnosis are factors that need to be overcome so that new studies can be carried out improving the knowledge of autoimmune diseases in this region of Águas Formosas.
As future perspectives, is suggested to elucidate the behave of the immune response in this particular population, its correlation with the regional environmental factors and its role in the prognosis of the diseases.