Frequency of Autoimmune Diseases in Those Suffering from Vitiligo in Comparison with Normal Population
Shahla Babaee Nejad,
Hamideh Herizchi Qadim,
Vitiligo is more common in people with certain autoimmune diseases. Here we studied the association between vitiligo and autoimmune diseases. In this case control study, 86 patients with vitiligo were questioned about the location of vitiligo, family history, treatment and therapeutic response. All patients were examined both clinically and with laboratory tests to detect the presence of autoimmune disorders including autoimmune thyroid disease, pernicious anemia, insulin dependent diabetes, and Systemic Lupus Erythematic (SLE) and Addison disease. We compared the prevalence of autoimmune disorder in vitiligo patients with that in a group of age-and gender-matched normal population. Average age of disease onset was 21.8±11 years; 61% of patients were female and 39% were male. The most common locations of vitiligo were hands (33.7%) and face (32.1%). The most common pattern of onset was vulgaris type (40%). Nearly one-fourth of patients had a positive family history of vitiligo. Prevalence of thyroid disorders in vitiligo patients and control group was 21.1 and 7%, respectively. The difference was statistically significant (p = 0.008). The most common autoimmune disorder in patient with vitiligo was hypothyroidism. Family history had a poor prognostic effect on response to therapy.
Received: December 08, 2012;
Accepted: February 16, 2013;
Published: March 28, 2013
Vitiligo is a pigmentation disorder in which melanocytes (the cells that make
pigment) in the skin are destroyed. It is the most prevalent acquired disease
of pigmentation disorder appearing as skin and rarely mucus pigmented patches
(Prindaville and Rivkees, 2011). It affects all races,
but may be more noticeable in people with darker skin (Silva
de Castro et al., 2012) It usually starts as small areas of pigment
loss that spread with time. Clinically, half of the cases begin before 20 years
old (Gonul et al., 2011). Hypomelanotic macules
are initially considered in areas exposed to sun light. The disease progresses
gradually and the lesions become amelanotic after some times (Oiso
et al., 2011). About 30-40% of patients state vitiligo family records.
Previous studies suggest that vitiligo is an autoimmune disease resulting from
complex reactions between several congenital risk factors and environmental
susceptive factors (Narita et al., 2011). In
a study conducted on 2624 cases of vitiligo, it was made clear that disease
outbreak age is lower in family cases. Prevalence of concurrent thyroid diseases
was 19.4% which is about ten times more than its prevalence in normal population.
Also, pernicious anemia, Addison and lupus had more prevalence than healthy
population (Alkhateeb et al., 2003). In other
studies, prevalence of thyroid diseases has been reported as 34% in those suffering
from vitiligo (Yaghoobi et al., 2011). Considering
objectives of the study, i.e. evaluating frequency of autoimmune diseases especially
thyroid in vitiligo and probability of intensifying or starting of this cutaneous
disease in those suffering from autoimmune diseases, the obtained evidences
indicate higher prevalence of autoimmune diseases in vitiligo patients (Nunes
and Esser, 2011; Poojary 2011). At present, vitiligo
patients are screened just in some centers considering other autoimmune diseases.
Therefore, the hypothesis of autoimmune nature of vitiligo will be reinforced
if this association is approved. Additionally, use of treatments playing a controller
role in immune system will be more appropriate and may be more effective in
treating vitiligo diseases (Boissy and Nordlund, 2011;
Sandoval-Cruz et al., 2011). The aim of this
study was to evaluate the frequency of autoimmune diseases in those suffering
from Vitiligo in comparison with normal population.
MATERIALS AND METHODS
In this case-control study, patients referring with pigmented patches manifestations
to skin clinic of Tabriz Sina Training and Therapeutic Center were evaluated
and examined regarding vitiligo. The disease was diagnosed based on clinical
examinations. If suspected, skin biopsy was conducted. The required information
including patients age, disease outbreak age, gender, existence of records
of similar disease in 1st and 2nd class relatives, location of the initial lesions,
previous treatments and treatment response (at the opinion of the patient) were
asked from the patients and inserted in case group checklist. Cases were excluded
from the study whose job posed probability of depigmentation due to contact
with substances. The patients were examined considering developing of lesions
and determining disease type. Autoimmune disease symptoms were asked from the
patients. Symptoms such as light sensitivity, malar rash, lymphadenopathy, arthritis,
mouth sore, skin telangiectasia, possible paleness, and existence of erythemato
lupus discoid were evaluated. The patients were asked about records of thyroid
diseases, lupus, Addison, pernicious anemia, spasm or psychosis, diarrhea or
constipation. Other autoimmune diseases such as hypoparathyroidism, hypogonadism
and etc., were not evaluated due to less prevalence and lack of evidences in
the previous studies. Positive points were registered in the checklist. Required
tests including ESR, FBS, ANA, T3, T4, TSH, Na, K, and Hb were conducted after
describing them to the patients and acquiring their satisfaction. In this study,
Anti-TPO and Anti-TG were not asked from the patients because of its high expensed.
Patients with laboratory changes based on autoimmune disease were only referred
to oncologist. According to the oncologists, the above-mentioned tests were
not necessary in most patients. Also, reportable obvious changes were not observed
in those patients underwent these tests. The patients returned after conducting
the tests and the obtained results were inserted in the checklist. The control
group was selected from patients referring to the skin clinic with melasma,
wart, molosecum and eczema diagnoses. Similar to the case group, this group
was also examined considering autoimmune diseases and underwent paraclinical
tests willingly. The case and control groups were matched considering background
variables (age and gender). The results were analyzed using SPSS-15 statistical
software and compared applying Chi-Square and t-tests. Tests significant level
(p-value) was considered less than 0.05 (p<0.05).
Following results were obtained through evaluating frequency of autoimmune
diseases in 86 patients suffering from vitiligo and their comparison with normal
population: mean age of those suffered from vitiligo was 28.11±12.5 years.
They were constituted of 52 females (61.2%) and 33 males (38.8%). Mean age of
disease outbreak was 21.86±11.7 years. Half of the patients had disease
outbreak age less than 20 years. Mean of diseases duration was calculated as
6 years. Hands (33.7%) and then face (32.1%) were the most common areas affected
by the disease. At referring, vulgaris was the most prevalent development type
of the lesion (40%). In this study, 21 patients (24.7%) stated records of vitiligo
in their family (1st and 2nd class relatives). Thirty nine patients referred
to treat the problem for the first time. In 47 patients were under treatment,
topical steroid was the most commonly used treatment (51%). Some patients used
topical methoxsalen to treat the problem. Twenty patients (42.5%) did not mention
the treatments, 16 patients (34%) had partial response and 12 (25.5%) complete
or near to complete recovery. Out of 86 patients with vitiligo, 18 ones suffered
from thyroid disease (21.1%), 6 (7%) from under clinical hypothyroidism (normal
T3 and T4 and high TSH), 6 (7%) from hypothyroidism (low T3 and T4, and high
TSH), 6 (7%) from hyperthyroidism (low T3, T4 and TSH). In this group, disease
outbreak age was compared with other patients and it was made clear that the
difference was not statistically meaningful (p = 0.5). There were no cases of
pernicious anemia, SLE, Addison, ulcerative colitis. Of course, none of the
patients had any clinical symptom susceptible to these diseases. There was high
FBS in 4 patients (4.7%). Out of them, 3 were Type II and one patient was Type
I diabetes. ANA was positive in 3 patients (3.5%). According to treatment results,
the patients were divided into two general class of without response and clinical
response (including partial and complete). Treatment results were evaluated
based on vitiligo family records and using Fischer Exact Test. The difference
was statistically meaningful (p = 0.013) (Table 1). Mean age
of the control group was 32.6±13.8 years. It was compared with mean age
of the case group and no significant difference was observed (p = 0.2). The
control group was constituted of 35 males (41.2%) and 50 females (58.8%). Gender
difference between case and control groups was compared using Chi-Square test.
There was no statistically difference (p = 0.1). There was thyroid disease in
6 patients (7%) of the control group (4 cases with hypothyroidism, 1 case with
subclinical hypothyroidism and 1 patient with hyperthyroidism).
|| Response to treatment according to family history
|| Autoimmune disorders in study population
Frequency ratio of thyroid disease in control and case groups was compared
using Chi-Square test. The difference was statistically meaningful (p = 0.008).
Prevalence of other laboratory disorders in case and control group has been
stated in Table 2. Prevalence of diabetes, positive ANA, high
ESR and anemia was compared in the case and control groups and no statistically
significant difference was observed (p>0.05).
In this study, mean age of the disease outbreak and its average were respectively
21.86 and 20 years. In other studies, it has been stated that half of the patients
are affected by the disease before 20 years old Viles et
al. (2010). Outbreak age was 22.4 years in Caucasian race which was
very close to our study. Schallreuter and Salem (2010)
The patients were constituted of 61% female and 39% male. Similar to other studies,
women constitute more part of the patients which may be attributed to their
more reference to treat their problem. Other studies based on voluntary participation
of the patients, report high ratio of women to men (Pajvani
et al., 2006). According to previous studies the lesions are started
at darker parts of the skin (Akay et al., 2010).
In our study, most patients have stated hands (32.7%) and face (32%) involvement
as the first locations of the disease. Considering that these areas are exposed
to sun light, it can be assumed as disease starting factor (Abu
Tahir et al., 2010) Considering mental issues, anatomic distribution
of the disease is very effective because it is exposed to sight. Feeling of
stress and being ashamed of the problem in encountering with strangers, feeling
of sin and decrease of self-confidence especially regarding areas which are
exposed to sight may be considered (Hartmann, 2009).
Family records of vitiligo have been mentioned as 18-40% in other studies. In
this study, family records was positive in 24.7% which is in correspondence
with the previous studies (Laberge et al., 2005).
Treatment response in family and sporadic cases were respectively 20% and 37.5%.
The difference was statistically meaningful (p = 0.013). Therefore, more strong
treatments will be needed if the patient has experienced vitiligo family records.
Also, it is better that the patient is provided with required information regarding
probability of no recovery. Other studies have not referred to this finding
(Bordere et al., 2009). In this study, 42% of
patients (about half of them) had no treatment response. Complete or near to
complete recovery as seen just in 25% of cases. The ratios state disease weak
prognosis even with appropriate treatments. In previous studies, association
of thyroid diseases with vitiligo has been introduced as the most common association
from among autoimmune diseases and its prevalence has been mentioned as 21,
34, 19.4% (Hari Kumar et al., 2012; Kroon
et al., 2012). In the present study, prevalence of thyroid diseases
was 21.1% which corresponds with the previous studies. In comparison with the
control group (7%), association of vitiligo and thyroid diseases was statistically
more prevalent than its prevalence in the normal population. In other studies,
prevalence of thyroid autoimmune diseases in the normal population has been
mentioned as 2% (Nunes and Esser, 2011). Therefore,
high prevalence of the disease in our country is considerable. In the previous
studies, thyroid diseases prevalence in vitiligo was 8 times more than normal
population (Fernandes and Campos, 2009). In our study,
although the difference is statistically meaningful, it is attributed to higher
prevalence of thyroid disorders in normal population of the country. Hypothyroidism
was the most prevalent thyroid disease (60%). The same results have been obtained
in other studies. Sedighe and Gholamhossein (2008)
In this study, there was no difference considering prevalence of autoimmune
diseases except to thyroid in the case and control groups. There were not clinical
symptoms susceptible to other autoimmune diseases in patients of both groups.
Meanwhile, records of doubtful symptoms of the diseases were not observed in
files of patients and the control group. Therefore, expensive and unnecessary
tests were excluded and susceptible cases were referred to the related specialist
and no disease was reported. Also, routine tests helpful in primary diagnosis
of the diseases were asked. Results of both groups were not different considering
other autoimmune diseases. In our study, response to treatment was 20% in family
cases while it was equal to 37.5% in sporadic cases. The difference was statistically
meaningful. Therefore, positive family records are regarded as the negative
prognosis factor in response to treatment. High expenses of some tests required
to exactly diagnose the autoimmune diseases was regarded as limitations of the
research. It is hoped that the problem will be solved in future through exact
studies as research plan.
According to this study and previous ones and considering that the disease is often seen in youths and it is started before twenty years old in half of the cases, apparent lesions may play a significant role in developing mental problems and decreasing patients self-confidence. Lesions seen in areas such as hands and face which are exposed to sun light, introduce it as one of the etiological factors. In spite of providing different treatments, complete or near complete treatment response is seen in 25% of cases. Thyroid diseases are the most prevalent autoimmune disease associated with vitiligo and is seen in 20% of cases. Its prevalence is at least three times more than that of the normal population. Treatment response in the group with positive family records was less that other patients such that family records is effective in treatment response.
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