Vitiligo is an acquired skin disorder caused by the disappearance of pigment cells from the epidermis that gives rise to well defined white patches which are often symmetrically distributed. In vitiligo, melanocytes in the skin, the mucous membranes, and the retina are destroyed. As a result, white patches of skin appear on different parts of the body. The hair that grows in areas affected by vitiligo usually turns white. The lack of melanin pigment makes the lesional skin more sensitive to sunburn. Vitiligo can be cosmetically disfiguring and it is a stigmatizing condition, leading to serious psychologic problems in daily life. It occurs worldwide in about 0.5% of the population and it occurs as frequently in males as it does in females.
Since a causative (gene) treatment is not (yet) available, current modalities are directed towards stopping progression and to achieving repigmentation in order to repair the morphology and functional deficiencies of the depigmented skin areas. Many treatments have been used for some time; however; there are some new developments: narrowband ultraviolet (UV) B (311 nm) therapy, the combination of corticosteroid cream + UVA therapy, and the transplantation of autologous pigment cells in various modalities. In widespread vitiligo, residual pigment can be removed by depigmentation agents.
The cause of vitiligo is not known, but might involve genetic factors, autoimmunity, neurologic factors, toxic metabolites, and lack of melanocyte growth factors.
Mahmoud and Kamal (1998) studied 84 patients (57 males and 27 females, aged from 4 weeks to 58 years) with alopecia areata (AA). They found two patients with vitiligo; also having a family history of the disease.
[Mahmoud SF, Kamal AM. Nail changes in minimal alopecia areata. Gulf J Dermatol. 1998; 5(1): 36-39.]
Young and Lieber (1987) published the first report on the occurrence of vitiligo in members of an Arab family from Jordan.
Al-Fouzan et al. (1995) studied HLA polymorphisms of class I and class II MHC through employing microcytotoxicity assay on 40 controls and 40 Kuwaitis suffering from vitiligo at Sabah Hospital in Kuwait. The assay showed a significant increase for HLA-B21, Cw6, and DR53 in affected cases compared with normal controls (P = 0.00001, 0.00001 and 0.0053, respectively), whereas a significant decrease was noticed in HLA-A19 and DR52 (P = 0.00236 and 0.05, respectively). Flow cytometry, to measure T-cells, T4 and T8 as CD2, CD4 and CD8, demonstrated a significant increase in CD4 levels in the patient group compared to controls with a P-value of 0.03. Al-Fouzan et al. (1995) proposed that HLA-B21, Cw6, and DR53 are considered susceptible genes of vitiligo, whereas A19 and DR52 were considered as protective genes in the Kuwaiti population.
Mahmoud et al. (1998) studied lymphocyte subpopulations by employing flow cytometry and monoclonal antibodies against CD4, CD8, CD20, CD25, CD45RA, and HLA-DR in 34 subjects suffering from non-segmental vitiligo. Out of the 34, 12 subjects obtained no treatment while 22 subjects obtained at least one course of PUVA therapy which was discontinued 4 months preceding the study. A significant increase in CD25 and HLA-DR were found in vitiligo cases upon comparison with matched controls. An opposite association was detected among HLA-DR and case status with regard to treatment (p = 0.001). Based on the results, Mahmoud et al. (1998) suggested that T-cells had a role in the pathogenesis of vitiligo and that prior PUVA therapy might be reflected through a modification in circulating DR positive cells.
Nanda et al. (1999) conducted a prospective survey of pediatric dermatology clinic patients in Kuwait. Of 10,000 consecutive patients analyzed, mostly (96%) children of Arab descent, 149 had vitiligo. The incidence of vitiligo showed a steady increase from 0.4% in infants to 1% in preschool children, and 3.5% in preadolescents. Vitiligo was significantly more prevalent in female children than in males (ratio 1.7:1).
Mahmoud et al. (2002) conducted a study to describe the immunophenotype of peripheral blood T cells of vitiligo patients by employing the analysis of peripheral blood in order to utilize an analytical and diagnostic tool for the disorder. The study consisted of 32 subjects suffering from non-segmental vitiligo and 28 normal, healthy, age and gender matched controls. 2-color flow cytometry was used on whole venous blood samples for each subject to look for immunologically-relevant lymphocyte subsets. The test demonstrated that vitiligo patients experienced a lower total number of lymphocytes (p < 0.039) when compared to controls, and vitiligo patients suffered from elevated percentages of memory (CD4+CD45RO+) T cells. It was found that NK-T cells (CD3+CD16+CD56+) and naïve T cells (CD4+CD45RA+) occurred at lower total numbers and percentages among healthy controls. Blood obtained from severely afflicted subjects showed an increased CD3+HLADR+ and CD4+CD45RO+ with lower percentages of NK-T cells in comparison to blood from subjects with mild cases. Mahmoud et al. (2002) concluded that the hypothesis of T cell activation as a main feature of the disease was found to be consistent with the disease associated peripheral lymphocyte immunophenotypic profiles of vitiligo patients. These profiles consisted of elevated memory and reduced naïve T cell percentages and increased expression of the activation-associated surface antigen CD25.
Al-Mutairi et al. (2005) performed a prospective hospital-based study on 612 subjects (88 children) suffering from vitiligo at the Farwaniya region. Female patients represented 56.8% while 27.3% of patients represented positive family history with 24 subjects describing first- and second-degree relatives affected by vitiligo. The age of onset of vitiligo was divided into three groups including children from birth to 4 years (18.2%), 4-8 years (30.7%), and 8-12 years (51%), showing a mean age of onset of 6.2 years. Vitiligo vulgaris was found to be the most common clinical form of vitiligo (47.7%) followed by the focal (26%), segmental (8%), acrofacial (13.6%), mucosal (3.4%), and universal (1.1%) types. The associated diseases with vitiligo included diabetes mellitus (1 case), alopecia areata (1 case), antithyroid antibodies (3 cases), atopic dermatitis (6 cases), and microcytic-hypochromic anemia (8 cases). A year later, Al-Mutairi and Sharma (2006) carried out a clinico-epidemiological study of vitiligo in the Farwaniya region to reveal the clinical prototype of the disorder, the associated socio-demographic factors, and the related diseases amongst patients. The study included 612 patients (448 were adults and 164 were children and adolescents) with females constituting 58% and males 42%, while the age of onset was partitioned to three groups including children (12 years and less), adolescents (13-18 years), and adults (18 years and above). Family positive history occurred in 116 subjects including 24 children, 16 adolescents, and 76 adults. Thirteen subjects demonstrated anti-thyroid antibodies without any clinical evidence of thyroid disease, while nine suffered from insulin dependent diabetes, 21 subjects experienced alopecia areata, and 49 subjects demonstrated atopic dermatitis. Al-Mutairi and Sharma (2006) suggested that several patients should monitor anti-thyroid antibodies for a potential development of clinical thyroid dysfunction. [Al-Mutairi N, Sharma AK. Profile of vitiligo in farwaniya region in Kuwait. Kuwait Med J. 2006; 38(2): 128-31.]
In 2008, Nanda described a patient with neurofibromatosis type 1 having an association with vitiligo.
Venkataraman et al. (1995) studied the frequency of specific HLA antigens in 50 Omani patients with vitiligo and compared the results to a control sample. About 66% of the patients came from consanguineous families. However, only 32% of this sub-group of patients showed a positive family history. About 82% and 40% of the patients were found to contain the HLA Bw6 and DR7 antigen, respectively, as compared to only 49% and 9% of the control group. Interestingly, the HLA DR7 antigen was found more commonly in patients with the acrofacial form of the disease (57%), as compared to the focal form (24%). All patients with a positive family history were found to contain the HLA Bw4 antigen, while only 4% of patients with consanguineous parents carried this antigen.
Soliman et al. (1996) studied the prevalence of vitiligo in 500 patients with IDDM, 60 children with NIDDM, and measured the thyroid and adrenal functions as well as the glucose tolerance and C-peptide response to I/V glucagon in 15 children with vitiligo and 20 age-matched normal children. The association between IDDM and vitiligo was confirmed by finding that its prevalence was higher in those with IDDM (3%) than those with NIDDM (1%). As regarding the children, they had normal blood tests (renal, hepatic, hematological, and hormonal parameters - thyroid function and basal and ACTH - evoked cortisol levels) and no antibodies (kidney/liver microsomal antibody, glomerular antibody, kidney basement membrane antibody, and gastric parietal cell antibody) were detected, except for insulin antibody in one child with vitiligo who had normal glucose tolerance and C-peptide response to glucagon. On the other hand, another child with vitiligo had impaired glucose tolerance test with impaired C-peptide response to glucagons, but no insulin antibody was detected. One child with vitiligo had thyroid microsomal antibody but normal thyroid function test.
[See also: United Arab Emirates > Galadari et al. (1997)].
El-Tonsy et al. (1998) studied 87 patients (33 Qatari and 54 non-Qatari; 73 males and 14 females; 76 adults and 11 children; aged 2 to 56 years) with alopecia areata (AA). They found three patients (3.4%) to have vitiligo, and seven patients (8.1%) were found to have a family history for the disease.
[El-Tonsy MH, Azadeh B, Kamal AM, El-Domyati MBM, Ibrahim FA. Auto antibodies and immunohistochemical studies in alopecia areata. Gulf J Dermatol. 1998; 5(1): 40-45.]
Abanmi et al. (2006) investigated the HLA loci antigens and alleles in a group of 40 unrelated Saudi patients with vitiligo (18 males, 22 females) and compared the results to that in a group of 40 matched controls. Among the patients, 34 were diagnosed with generalized vitiligo, while the remaining had a universal type of vitiligo. A positive family history of skin disorder was seen in 16 of the patients. The results of the HLA typing study indicated that HLA-B7, Bw6, Cw6, Cw7, and DRB4*010101 could provide susceptibility to vitiligo, and that HLA-A9, B5, DQ1, and DRB3*010101 might confer resistance against the condition. In a later study, Abanmi et al. (2008) investigated the association between IL-10 polymorphisms and vitiligo in Saudi patients. The study included 83 Saudi vitiligo patients (40 males, 43 females) and 101 healthy controls. PCR was used to detect the presence of three SNPs in the IL-10 gene in this population; G(-1082)A, C(-592)A, and C(-819)T. The results showed that the -1802GG, -819CC, and -592CC genotypes were susceptible to vitiligo, while -1082GA, -819CT, and -592CA offered protection against the condition. Abanmi et al. (2008) surmised that these findings did not support the inflammatory theory of vitiligo.
Galadari et al. (1997) studied the clinical and immunological changes encountered in patients with vitiligo in Al-Ain population, United Arab Emirates (UAE). They conducted a prospective descriptive hospital-based study on 65 patients who were seen at Al-Ain hospital for skin diseases during 1996. Most of the patients were nationals from the United Arab Emirates and Oman. Non-Arab patients were also observed (e.g., Pakistanis). Positive family history of vitiligo was found in 19% of the patients. Association with other immune diseases was found in 6% of the patients while one or more organ specific antibodies, all of whom were females, most of them had positive history of autoimmune diseases (Galadari et al., 1997). In 2005, Galadari et al. studied serum level of soluble interleukin-2 receptor in 32 patients (21 males and 11 females) with vitiligo seen at Al Ain hospital in 2003. Fifteen healthy individuals were selected as control group. Serum level of slL-2R were significantly higher in vitiligo patients (112 +/- 129.2) than in healthy control (61.1 +/- 44.3 Pmol/L) P < 0.0001 and patients with short duration of the disease showed higher slL-2R serum levels.
Dessoukey et al. (1997) undertook a linkage study on 24 multi-case families from the Arabian Gulf region to clarify whether a genetic factor linked to ABO blood groups is involved in the pathogenesis of vitiligo with aggregation or not. Selection of the families was based on the criteria that at least two siblings are affected with vitiligo and the availability of the parent for blood grouping. All members of the family were examined for any signs of vitiligo and typed for the ABO blood group. Linkage analysis was performed using LIPED algorithm. The highest Lod score achieved from the linkage analysis between the ABO blood group and a hypothetical dominant disease susceptibility gene with two alleles was found to be (-0.08) at a recombination fraction 0.4 and penetrance rate of 20% for the disease susceptibility gene. The levels of Lod score for the two alleles with recessive inheritance model were found much lower than that achieved with the dominant inheritance model. Dessoukey et al. (1997) concluded that a disease susceptibility gene weakly linked at a recombination fraction 0.4 to the ABO blood group with a dominant inheritance model and penetrance rate 20% is a remote possibility in the pathogenesis of vitiligo.
[Dessouky, M.W.; Abdel Dayem, Hussein; Omar, Mohamed F. Vitiligo: genetic linkage analysis. Gulf J. Dermatol. Venerol. 1997; 4(1): 19-21.]