Clinical and Epidemiological Study of Vitiligo Patients at a Dermatology Service in Northern Brazil

Background: Vitiligo is an acquired hypomelanosis that affects between 0.5% and 4% of the world population, characterized by distinct acromic macules of various shapes and sizes, and may appear in any region of the skin. Worldwide, there are few publications on vitiligo that address epidemiological characteristics. Thus, the objective was to describe the clinical and epidemiological profile of patients with this condition at the State University of Pará’s Dermatology Clinic, in the city of Belém, Northern of Brazil.


Introduction
Vitiligo is the most common acquired hypomelanosis described in literature.This disease affects between 0.5 and 4% of the world population, with no distinction of gender, age or ethnicity for its development.It is characterized by white patches, with sharp margins, of varying shapes and sizes and a trend of centrifugal development, which can arise in any region of the integument.As most patients develop the disease early in adulthood, vitiligo ultimately influences the personal, psychological, and professional development of the individual.A significant number of patients present symptoms of depression and anxiety, and may also negatively influence their social life, leading to isolation [1,2,3,4].
Vitiligo is a dermatosis that can be identified by white patches, initially hypochromic (with little pigmentation), which are usually noticed in areas with greater sun exposure, such as the face, elbow, back of the hands and around body orifices.White spots are most commonly seen on the extremities (hands and feet), areas of extension and flexion (knees and elbows), on the head and genitals.Toes, hands and face are often the first ones affected [2,3,5].
This disease can be classified as localized and generalized.The localized form is composed of two types: focal, which is characterized by the presence of acromic maculae in a given area, without specific distribution; and segmental, characterized by the presence of macules covering a unilateral segment of the body, which may follow the distribution of a dermatome.The generalized form has three types: acrofacial, with the presence of distal lesions on the extremities and on the face; vulgar, characterized by acromic patches that have a variable distribution; and mixed, in which the two or more types combine [6].
The pigmentary alteration that occurs in vitiligo happens due to melanocyte impairment and some theories may clarify the origin of this disease.The most acceptable hypothesis is that it is autoimmune, because the melanocytes are destroyed secondary to the presence of autoantibodies.This theory is corroborated by the similarity with other autoimmune diseases such as pernicious anemia, Addison's disease, scleroderma, thyroiditis, among others [2,6,7].
Among the most frequent environmental trigger factors are: nutritional deficiency, emotional stress, physical trauma (Köebner's phenomenon), drugs, infections, exposure to sun and chemicals, sepsis and toxins, among others [8,6].
Vitiligo does not cause symptoms in other systems, and does not threaten the individual's physical health.However, due to the presence of the maculae, vitiligo patients may develop personality changes, low self-esteem and stress, also there are reports of interference with sexual relations due to embarrassment [7,9].
Empirical data demonstrate that the esthetic problem is often more significant than the disease itself, thereby causing greater emotional and social the generalized clinical form, achieved improvement of the lesions with the proposed treatment, and only a minority presented progression of the disease.It is concluded that vitiligo is a disease with great therapeutic difficulty, and it is emphasized the importance of an early diagnosis, since in the early stages is easier to resolve the disease.
suffering on the patients.Therefore, these patients' life quality becomes compromised, requiring health professionals to intervene with a focus on these factors [10].
Vitiligo's treatment is necessary when the patient suffers socially and/or emotionally.There are many options available, many of them aimed at restoring skin color; among them, we can mention the corticosteroid ointments and the photochemotherapy with psoralen drugs.The treatment choice takes into account the extent of hypochromia, the skin tone, and the psychological state of the patient.Thus, the treatment generally contributes to the significant improvement of the patient's self-esteem and life quality [7,9].
Currently, in the Brazilian literature, there is a shortage of papers that demonstrate the clinical and epidemiological profile of this dermatosis.Thus, this work aimed to describe this profile with the purpose of showing how this disease behaves in an Amazonian population and also to stimulate physicians to fully evaluate patients with vitiligo, in addition to early identification of patients with this disease, accelerating the onset of treatment and thus reduce the negative psychosocial impacts of this disease and, consequently, its morbidity.In this study, the medical records of patients with vitiligo treated at the UEPA's Dermatology Clinic were included between July 2000 and July 2014, with no age limits, race, marital status, social class, education or religion.Medical records of patients seen outside this period and incomplete, illegible and/or damaged were excluded from the study.

Materials and Methods
The sample consisted initially of 217 patients' diagnosed with vitiligo medical records, of which 37 were excluded, statistically and qualitatively justified, leaving the final sample established at 180 medical records.To perform the present study from a target population (total number of records) of N = 217 patients with vitiligo, a random sampling without replacement was performed.By the application of the sampling technique, the sample error was previously set at 5%.The application of the formula n = N / (1+ (N-1) * Error ^ 2) resulted in the sample size n = 180.
For the data collection a protocol was used, and it consisted of patient's gender and age; age of lesions onset and initiation of treatment; presence of family history; skin color; lesions classification, type (localized or generalized); if classified as localized, the subtype (focal or segmental); if it was of the generalized type, the subtype (acrofacial, vulgar or mixed); location (head and neck, trunk, upper limbs, lower limbs or mucous membranes); related triggering factor (stress, physical trauma, none or uninformed); disease activity (with or without progression); regular monitoring; improvement with treatment and maintenance of treatment.
To identify the main factors in a sample of 180 patients with vitiligo, descriptive and inferential statistical methods were applied.Quantitative variables were presented by measures of central tendency and variation.The qualitative variables were presented by absolute and relative frequency distributions.The qualitative variables were compared using the Chi-square test, and when the npq < 5 constraint occurred then the G test [11] was applied.The comparison between the quantitative variables was performed by T Student test.The significance level alpha = 0.05 was previously set for rejection of the null hypothesis.Statistical processing was performed using software GrafTable version 2.0 and BioEstat version 5.3.

Results
One hundred and eighty (180) patients with vitiligo were studied during the research period.There was a predominance of the female gender (72.2%), absence of a family history of vitiligo (46.7%), affecting mostly the adult age group (55%), with 57.2% of disease onset in children and 72.8% of uninformed skin color.The patients' age range was from 3 to 84 years old, with a central tendency to 31.9 years old and a standard deviation of 19.5 years old.They were divided by age groups: children (0 to 19 years old), adults (20 to 59 years old) and elderly (above 60 years old).As for the skin color, among the records in which the information was reported, there was a predominance of the brown color (23.9%) (Table 1).
When comparing the male and female genders, there was no statistically significant difference between them in the vitiligo age of onset, the type of vitiligo more frequent and the triggering factor (Figure 1).Regarding the types of generalized and localized vitiligo, there was no statistically significant difference between them when compared in the age groups (Figure 2).
As for the progression of vitiligo, there was no statistically significant difference in any of the age groups (Figure 3).

Discussion
Regarding the epidemiological characterization of the patients there was predominance of females.Similar results have been found in other studies [6,12,13,14], although some authors claim that vitiligo affects both sexes equally [4,15].It is inferred that the female sex tends to seek health services more, and particularly in cases of vitiligo, there is a greater aesthetic concern and social impact for women [12,14].
In the present study, there was a predominance of the disease in the adults, from 20 to 59 years old, in agreement with studies performed in Brazil [6,12], Cuba [16] and Turkey [17].A study carried out in India found out that vitiligo is more common in the age group from 2 to 20 years old [18].These divergences in the literature indicate that vitiligo can occur at any age, although it tends to affect young individuals.
The onset of vitiligo can occur at any age, but usually happens in childhood or in young adults.The onset peak is between 10 and 30 years old, with 50% of cases appearing before the second decade of life [19,20,21].The results of this study are in agreement with these data when demonstrates that vitiligo began predominantly in the age group that included individuals from 0 to 19 years.Among the various theories that explain the onset of the disease, it is proposed that vitiligo is a multifactorial cause pathology, with genetic and environmental factors involved in its onset.Therefore, the same causal mechanism may not apply to all patients and different pathophysiological pathways may converge together for the same clinical manifestation [22].
Approximately 20% of vitiligo patients have a family history of the disease in at least one firstdegree relative [21].Vitiligo is a polygenic or multifactorial disease.Genetically, it has been associated with more than a dozen genes, which plays a role in different immunity changes in the pigment loss process [23].Similar to the present study, Reghu et al. [18] found that 18.8% of those affected by the disease had a family history of vitiligo.In a hospital in Santa Catarina, south of Brazil, Nunes and Esser [6] observed that 10.6% of patients with vitiligo had a family history of dyschromia.
It was observed that in most of the charts of this survey there was no filling of patients' skin color.However, the brown color was predominant, which corroborates the clinical and epidemiological analysis of vitiligo in childhood, carried out in Minas Gerais, Brazil, by Silva et al. [20].Nunes and Esser [6] and Barros et al. [12] also noted that the majority of patients were of phototype IV, which corresponds to brown color.This fact probably reflects the characteristics of the skin color of the Brazilian population and the patients seen at the University (UEPA) outpatient clinic (northern region of the country).In addition, there is more evidence of lesions in darkskinned people, although vitiligo affects people of all races [20].
The prevalence of generalized type vitiligo was found in this study, agreeing with the results found by other researchers and presenting statistical relevance.For Marinho et al. [2], in a series of 94 children and 25 adolescents conducted in Rio de Janeiro, Brazil; and in the study by Sori et al. [24], which analyzed the most prevalent hypomelanoses in childhood in an Indian dermatology service with a population of 23 patients with vitiligo, the prevalent clinical form of the disease was also the generalized type.In a study carried out in Mexico, in a sample of 218 patients, the generalized clinical form was observed in 88% of the patients [25].Nunes and Esser [6] and Barros et al. [12] also showed similar results in populations of all ages.
When analyzing separately the localized and generalized types of this dermatosis and its various forms of manifestations (subtypes), for the first type the predominance of localized vitiligo followed by the segmental agrees with Nunes and Esser [6], Santander [25] and Sori et al. [24].For the generalized type of the disease, the highest incidence of the vulgar form was also observed by the same authors, followed by the acrofacial and mixed forms.However, the difficulty of comparison with other studies is highlighted due to the use of several classifications, low adherence and failure of the consensus suggested by The Vitiligo Global Issues Consensus Conference [1], being the present investigation performed corresponding to the classification used in the consensus.
Thus, among the patients investigated, there was a greater occurrence of common generalized presentation of the disease.Taking into account the multifactorial and polygenic etiology of this disorder and the various factors that may be associated with the appearance of new lesions, such as physical trauma (Köebner's phenomenon), emotional stress and infections, this event may be related to the characteristic of the vulgar form of vitiligo (random acoustic macules) to admit greater variability of presentations [4,8].
The most common location of vitiligo in this study was the head and neck, followed by the upper limbs, lower limbs, trunk, and mucosae.On one hand, the location mainly in the head and neck coincides with literature data [20,26,27].Other studies have reported upper limbs as the most frequent site [6,17,28].On the other hand, the data found in the present study differ from those found by Schwartz and Janniger [29], who state that there is a predilection for orifices -eyes, nostrils, mouth, nipples, belly button and genitalia.
In this investigation, the presence of triggering factor -emotional stress and physical trauma -did not occur in a significantly different way.This corroborates with studies in which the triggered investigators of emotional stress, physical trauma or none also did not have statistically significant importance [6,12].
The data found disagreed with Reghu et al. [18] and Shah et al. [30], in which the major vitiligo precipitating factor was physical trauma/injury, compared to emotional disturbance.Whereas for Cavalcante et al. [31] the most prevalent triggering factor was emotional stress.
The aggravating factor found in this analysis is that the variables related to the triggering factor and skin color presented a large amount of individuals with no such information in the collected charts, which may have interfered in the results found regarding the statistical significance.This underscores the need for a more complete and descriptive completion of information related to the patient.
This study showed that most of the patients presented lesions without progression, which was corroborated by some studies: one from Tunisia and three from Brazil.In the demonstration of Ben Ahmed et al. [32], 66.6% had vitiligo in regression or stable, statistic similar to that found by Correia and Borloti.[33]; in the study by Nunes and Esser [6], it was observed that only 21.2% of the patients had the disease progressing and for Castro [34], a progression was observed in 27.3% of the cases.Oppositely, a more recent study by Barros et al. [12] at a dermatology institute in São Paulo showed unstable disease activity, that is, with progression in 63.4% of the patients.
Based on the assumption that stopping disease progression is a prerequisite for successful repigmentation in the treatment of vitiligo, knowing the progression prevalence and origin is an important step in the treatment choice and the possible cure of this disease [35].
Studies that aimed to clarify the immunological component in the vitiligo pathophysiology points to specific CD8+ T lymphocytes against melanocytes, a capacity of destroying them in the individuals diagnosed with this disease, and those who have progressing disease also have this cells in greater numbers [36].
Another elucidation of this analysis was that the majority of patients performed regular follow-up at the dermatology service, and obtained improvement with the treatment, consequently, maintained clinical therapeutics.These results are confirmed by other studies.Marinho et al. [2] found a rate of 84% of patients who maintained regular follow-up and treatment; for Correia and Borloti [33], 96.82% of the patients started medical follow-up, but of these, only 36% followed all the prescribed recommendations; drawing attention to the fact that 77% of the patients studied had performed some treatment not recommended by doctors.In this study it was observed that 49% of patients abandoned treatment.In contrast, in a South Korean study, the vast majority of patients (94.5%) did not improve with the proposed treatment [37].
In the present registry, it was observed that there was no statistically significant difference in the vitiligo onset age between males and females.Marino et al [2] have shown that vitiligo appears later in men.However, it was noted that studies that establish these differences and observations are still scarce.
When comparing gender with the most frequent type of vitiligo, the generalized type predominated in the male and female genders, and there were no significant differences between the results found.Similar results were found in a study performed in Turkey by Gönül et al. [38], where the generalized type, especially the involvement of the trunk, was significantly higher in women, which can be explained by the Köebner phenomenon, since women wear tighter clothes and bras.In the same Turkish study, the generalized type also predominated in the male gender, but the genital involvement was significantly higher, which according to the authors may also be due to the Köebner phenomenon, but because of sexual activity.
The difference between genders and the triggering factor was not significant as well, which was in agreement with data from Gönül et al. [38], who investigated the association of vitiligo with triggers among men and women, such as depression, but found no significant statistical difference in the compared data.
When comparing the patients' age with the current disease type, it was observed the generalized type predominance, taking into account the average age as well as when the analysis according to the age groups was made separately.However, in none of the comparisons was there a statistically significant difference.These findings are in agreement with other studies [22,39,40].However, other authors point to the occurrence of 87% of vitiligo in individuals under 20 years old [23].
The present study showed that there was no difference in the propensity for vitiligo progression among the age groups, contrasting with another registry in which children and adolescents were more likely to have stable vitiligo than adults and the elderly [12].
Out of the 217 patients' records with this condition in the dermatology service in question, 37 were not used because they were not in good conditions (illegible, incomplete or damaged).The importance of the proper filling and handling of this document by all professionals is emphasized in order to safeguard the information of the patient's medical history and to guarantee support and safety for medical practice in cases of contestations.When taking into account and interpreting the several variables that characterize clinically and epidemiologically the vitiligo patients, great differences and peculiarities are observed according to each population investigated, referring to the intrinsic aspects of the investigated individuals, such as gender, age group, etc.The understanding of the clinics of the vitiligo patients, both physically and psychically, is indispensable for a better therapeutic behavior, using the greatest arsenal of knowledge about the factors related to etiopathogenesis, evolution and available treatment of this disease, in order to promote satisfactory life quality to the patient.It also warns of the importance of similar studies in order to get a better understanding of the different characteristics of the users of dermatology services with the purpose of increase and benefit the results of the relationship between the binomial: doctor and patient.

Conclusion
The characteristics of the vitiligo patients residing in the Amazon region were known and it was observed that the patients predominantly presented the generalized clinical form, despite the follow-up in a specialized service; the majority of the patients obtained lesions improvement with the proposed treatment and only a minority presented progression of the disease.It is concluded that vitiligo is a disease with great therapeutic difficulty, and it is emphasized the importance of an early diagnosis, since this disease in the early stages is easier to solve.
International Archives of Medicine is an open access journal publishing articles encompassing all aspects of medical science and clinical practice.IAM is considered a megajournal with independent sections on all areas of medicine.IAM is a really international journal with authors and board members from all around the world.The journal is widely indexed and classified Q2 in category Medicine.

Figure 1 :
Figure 1: Vitiligo age of onset, type of vitiligo and presence of triggering factor according to the gender of patients with vitiligo treated at a Dermatology Service in Belém/PA, Brazil, from 2000 to 2014 (p-va-lue> 0.5, Chi-square of independence).

Figure 2 :
Figure 2: Vitiligo type according to age group of patients treated at a Dermatology Service in Belém/PA, Brazil, from 2000 to 2014 (p-value> 0.5, Qui-square of independence).

Figure 3 :
Figure 3: Disease progression according to the age range of patients with vitiligo, treated at a Dermatology Service in Belém/ PA, Brazil, from 2000 to 2014 (p-value> 0.05, Qui-square of independence).

Table 1 .
Characterization of patients with vitiligo, treated at a Dermatology Service in Belém/ PA, Brazil, between 2000 and 2014.

Table 2 .
Characterization of vitiligo type of patients treated at a Dermatology Service in Belém/ PA, Brazil, between 2000 and 2014.