Spontaneous Vitiligo in a Captive Rhesus Monkey (Macaca Mulatta).

Vitiligo affects a significant portion of human and animal populations. The disease causes irregular and multifocal progressive loss of fur, skin, and mucous membrane pigmentation due to the loss or absence of melanocytes. While etiopathogenesis is not completely understood, autoimmunity, environmental, and genetic factors are implicated We present a case report on a 16-y-old female rhesus macaque (Macaca mulatta ) with depigmented areas that are progressively increasing on the skin and coat and are distributed on the head and back. Histopathology revealed alterations compatible with vitiligo characterized by the absence of melanocytes in the epidermis and dermis. The clinical history and complementary exams support this diagnosis.

Autoimmune diseases affecting skin melanocytes in dogs, cats and horses: vitiligo and the uveodermatological syndrome: a comprehensive review.

Autoimmune dermatoses targeting melanocytes have gained attention in human medicine due to their progressive nature and the social impact suffered by affected individuals. In veterinary medicine, vitiligo and the uveodermatological syndrome are the two autoimmune diseases that are known to affect skin melanocytes.In the first part of this article, we will review the signalment, clinical signs, histopathology and the treatment outcome of vitiligo in dogs, cats and horses; where pertinent, we compare the animal diseases to their human homologue. In a similar fashion, the information on the uveodermatological syndrome in dogs is reviewed and, where relevant, it is compared to the Vogt-Koyanagi-Harada (VKH) syndrome in humans.Canine, feline and equine vitiligo have many features that mirror their human counterparts. The most effective treatment and outcome of vitiligo in animals remain unclear. The canine uveodermatological syndrome resembles the incomplete VKH variant in humans; for affected individuals, an immediate diagnosis and aggressive treatment are crucial to prevent the development of blindness.

Genetic and environmental risk factors for vitiligo and melanoma in Pura Raza Español horses.

BACKGROUND: Vitiligo and melanoma are relatively common disorders in grey Pura Raza Español horses and other horse breeds with grey-coloured coats. OBJECTIVES: To determine the breed prevalence, environmental risks factors and estimate the genetic parameters for vitiligo and melanoma in Pura Raza Español horses. STUDY DESIGN: Retrospective cohort study. METHODS: We analysed data from a large worldwide population of Pura Raza Español horses. The database included the vitiligo and melanoma scores, on either a four- or six-point linear scale, of 11,436 horses. Genetic parameters were estimated using a Bayesian genetic animal model including the four associated environmental risk factors as systematic effects. Inbreeding was used as a covariate, and animal and residual effects were included as random effects. RESULTS: Of the horses included in the study, 2.8 and 20.5% showed some traces of vitiligo around the eyes and mouth, respectively, while 1.6% showed varying degrees of melanoma. Age, coat colour and inbreeding were significantly associated with the three outcomes studied. The estimated heritability for the whole population was 0.09 (s.d. +0.019), 0.44 (s.d. +0.031) and 0.13 (s.d. +0.037), for eye vitiligo score, nostril vitiligo score and melanoma scores respectively. The genetic correlations ranged from 0.42 (s.d. +0.084) between eye and nostril vitiligo score to 0.15 (s.d. +0.096) between nostril vitiligo and melanoma. MAIN LIMITATIONS: Vitiligo scores for the perianal regions were not collected. The veterinarian responsible for each assessment was not recorded. CONCLUSIONS: Vitiligo and melanoma are prevalent in this population and those environmental risk factors and genetics both have an effect on the clinical expression of the diseases. These findings may help to reduce prevalence through breeding programmes.

Water Buffalo (Bubalus bubalis) as a spontaneous animal model of Vitiligo.

Vitiligo is a multifactorial acquired depigmenting disorder. Recent insights into the molecular mechanisms driving the gradual destruction of melanocytes in vitiligo will likely lead to the discovery of novel therapies, which need to be evaluated in animal models that closely recapitulate the pathogenesis of human vitiligo. In humans, vitiligo is characterized by a spontaneous loss of functional melanocytes from the epidermis, but most animal models of vitiligo are either inducible or genetically programmed. Here, we report that acquired depigmentation in water buffalo recapitulates molecular, histological, immunohistochemical, and ultrastructural changes observed in human vitiligo and hence could be used as a model to study vitiligo pathogenesis and facilitate the discovery and evaluation of therapeutic interventions for vitiligo.

Generalized vitiligo in a dog with primary hypoadrenocorticism.

BACKGROUND: Vitiligo is presumed to be an autoimmune disorder in the dog; primary adrenal insufficiency (Addison's disease) is associated with immune-mediated destruction of the adrenal cortex. HYPOTHESIS/OBJECTIVES: In this case report we describe a dog with primary hypoadrenocorticism that developed generalized vitiligo. CASE REPORT: A 4-year-old spayed female cross-bred dog developed signs of Addison's disease and this was confirmed by biochemical testing; the dog was treated with fludrocortisone acetate and then desoxycorticosterone pivalate. Three months after the diagnosis, the dog developed depigmentation of the whole hair coat and of several focal areas of the skin. Histopathological findings were consistent with vitiligo. CONCLUSIONS AND CLINICAL IMPORTANCE: Dogs with immune-mediated disease may develop other manifestations of immune-mediated disease, including a combination of Addison's disease and vitiligo. The cause in this case was not determined.

Genome resequencing and bioinformatic analysis of SNP containing candidate genes in the autoimmune vitiligo Smyth line chicken model.

BACKGROUND: The Smyth line (SL) chicken is the only animal model for autoimmune vitiligo that spontaneously displays all clinical and biological manifestations of the human disorder. To understand the genetic components underlying the susceptibility to develop SL vitiligo (SLV), whole genome resequencing analysis was performed in SLV chickens compared with non-vitiliginous parental Brown line (BL) chickens, which maintain a very low incidence rate of vitiligo. RESULTS: Illumina sequencing technology and reference based assembly on Red Jungle Fowl genome sequences were used. Results of genome resequencing of pooled DNA of each 10 BL and SL chickens reached 5.1x and 7.0x coverage, respectively. The total number of SNPs was 4.8 and 5.5 million in BL and SL genome, respectively. Through a series of filtering processes, a total of ~1 million unique SNPs were found in the SL alone. Eventually of the 156 reliable marker SNPs, which can induce non-synonymous-, frameshift-, nonsense-, and no-start mutations in amino acid sequences in proteins, 139 genes were chosen for further analysis. Of these, 14 randomly chosen SNPs were examined for SNP verification by PCR and Sanger sequencing to detect SNP positions in 20 BL and 70 SL chickens. The results of the analysis of the 14 SNPs clearly showed differential frequencies of nucleotide bases in the SNP positions between BL and SL chickens. Bioinformatic analysis showed that the 156 most reliable marker SNPs included genes involved in dermatological diseases/conditions such as ADAMTS13, ASPM, ATP6V0A2, BRCA2, COL12A1, GRM5, LRP2, OBSCN, PLAU, RNF168, STAB2, and XIRP1. Intermolecular gene network analysis revealed that candidate genes identified in SLV play a role in networks centered on protein kinases (MAPK, ERK1/2, PKC, PRKDC), phosphatase (PPP1CA), ubiquitinylation (UBC) and amyloid production (APP). CONCLUSIONS: Various potential genetic markers showing amino acid changes and potential roles in vitiligo development were identified in the SLV chicken through genome resequencing. The genetic markers and bioinformatic interpretations of amino acid mutations found in SLV chickens may provide insight into the genetic component responsible for the onset and the progression of autoimmune vitiligo and serve as valuable markers to develop diagnostic tools to detect vitiligo susceptibility.

Diagnosis and treatment of vitiligo in a sub-adult eastern black rhinoceros (Diceros bicornis michaeli).

A captive-born female sub-adult Eastern black rhinoceros (Diceros bicornis michaeli) developed areas of non-ulcerated, non-pruritic depigmentation around the nares at 2 yr of age. Over the subsequent 18 mo, the symmetrical multifocal depigmented macules increased in size and distribution to include facial fold crypts, interdigital skin, lips, nares, palmar carpi, ventral abdomen, ventral mandible, axillae, lateral brachium and antebrachium, lateral thighs, ventral tail, and perineal region with an estimated 15% of the skin affected. Facial fold skin biopsies revealed multifocal hypopigmentation with melanin incontinence and mild perivascular lymphohistiocytic dermatitis. The gross appearance and histologic lesions were consistent with vitiligo. Treatment with UV-B narrowband phototherapy was performed on the lateral thighs, lateral elbows, palmar carpi, and rostral maxilla for a period of 12 mo. Significant repigmentation of the treatment areas was achieved.

Apoptosis in feathers of Smyth line chickens with autoimmune vitiligo.

Vitiligo is an acquired dermatological disorder characterized by a loss of epidermal melanocytes resulting in depigmentation of the skin. Mechanisms underlying the destruction of melanocytes in vitiligo remain unclear. An animal model to study spontaneously occurring autoimmune vitiligo is the mutant Smyth line (SL) of chickens. This investigation was designed to determine whether the pathogenesis of depigmentation in Smyth line chicken vitiligo (SLV) involves an apoptotic mechanism. Terminal deoxynucleotide transferase-mediated fluorescein-dUTP nick end labeling (TUNEL) was used to detect in situ cell apoptosis in cryostat sections of 2-week-old regenerating feathers. Two-week-old regenerating feathers were obtained from SL chickens and their normally pigmented controls including the parental Brown line (BL) and Light Brown Leghorn (LBL) chickens at 6, 8, 10 and 12 weeks of age. In feathers from vitiliginous SL chickens, the number of TUNEL+ cells was significantly (P

Molecular characterization of the Smyth chicken sublines and their parental controls by RFLP and DNA fingerprint analysis.

The Smyth line (SL) chicken, a model for autoimmune human vitiligo, is characterized by a spontaneous posthatch epidermal pigment loss (vitiligo). Even though the immunological and morphological changes accompanying the vitiligo process have been well studied, the genetics of this phenomenon remains elusive. The SL lines have been maintained by nonpedigreed matings since their inception, and therefore, the inbreeding status is unknown. The present study was designed to provide an estimate of the inbreeding coefficients and the molecular genetic profiles of the SL sublines, each homozygous for a different MHC haplotype and their MHC-matched parental control (BL) sublines. The DNA fingerprint analysis revealed that there is a moderate level of inbreeding within the SL and BL parental sublines. Of the two SL sublines studied, SL101 had the highest level of inbreeding (0.948). Similarly, its parental control line (BL101) was more inbred than the parental subline of SL102 (BL102). The very high level of similarity between the SL sublines and their respective parental control lines is shown further by the similarity index (SI) estimates (SI between SL101 and BL101 was 0.949 and that between SL102 and BL102 was 0.932). Restriction fragment length polymorphism (RFLP) analysis of the endogenous viral genes (avian leukosis virus subgroup E, ALVE) showed that five ALVE-related BamH1 fragments were present in the SL101 and four in SL102 sublines, whereas the parental BL101 and BL102 sublines had five and six fragments, respectively. SL101 and SL102 shared two fragments, but the frequencies were different. Similarly, BL101 and BL102 shared two fragments. SL101 and BL101 shared three fragments, and SL102 and BL102 also shared three fragments.

Profiles of pulp infiltrating lymphocytes at various times throughout feather regeneration in Smyth line chickens with vitiligo.

Smyth line (SL) chickens develop a spontaneous, autoimmune, posthatch loss of pigment cells (vitiligo) in regenerating feather tissue. Smyth line vitiligo (SLV) is associated with lymphocyte infiltrations prior to and throughout the development of the disorder. It was the purpose of this study to determine the type, relative amounts, and proportions of pulp-infiltrating lymphocytes at various times throughout the growth of regenerating feathers. Feathers were plucked from 8-week-old chickens with and without SLV. Feather pulp cell suspensions were prepared when the regenerating feathers were 2, 3, 4, and 6 weeks of age. Cells were fluorescently labeled using a panel of mouse monoclonal antibodies specific for chicken lymphocytes. Both T and B cells infiltrated the feather pulp of chickens with SLV. T cell levels remained elevated throughout the 6 weeks of feather growth, while B cell levels steadily declined to control levels over the same time. The pulp-infiltrating cells were primarily T cells with an alphabeta T cell receptor expressing the Vbeta1 gene (TCR2+). The ratio between CD4+ and CD8+ cells was 1.42 and 0.75 in 2- and 6-week-old regenerating feathers from chickens with autoimmune SLV, respectively. In non-vitiliginous chickens this ratio was always near 1. These data suggest that TCR2+ T cells play an important role in SLV. CD4+ cells may play a recruiting/activating role, whereas CD8+ cells may have cytotoxic activity specifically directed against melanocytes. Additionally, this is the first report demonstrating the infiltration of B cells into the feather pulp of vitiliginous chickens. These B cells may directly/indirectly contribute to melanocyte destruction in SLV.

Lymphocyte populations in dermal lymphoid aggregates of vitiliginous Smyth line and normally pigmented light brown Leghorn chickens.

Smyth line (SL) chickens develop a spontaneous, autoimmune loss of melanocytes (vitiligo) from the feather. To determine whether lymphocyte infiltration into two-week-old regenerating feathers of vitiliginous chickens was accompanied by lymphocyte infiltration into the skin, skin biopsies were conducted in SL chickens at two-week intervals throughout the development of vitiligo (SLV) when the chicks were 6 to 14 weeks of age. Control skin samples were obtained from age-matched, normally-pigmented Light Brown Leghorn (LBL) chickens. Frozen skin sections were labelled with a panel of mouse mAb to identify various lymphocyte populations. There was no lymphocyte infiltration into the skin of SL or control chickens. However, in both lines of chickens, dermal lymphoid aggregates (DLA), consisting primarily of T cells, were observed. In the DLA of SL chickens, the ratio between CD4+ and CD8+ T cells was lower (P = 0.005) and the percentage of gamma delta T cells higher (P = 0.027) than in the controls. Additionally, in SL chickens the lymphocyte populations in the DLA varied depending on the developmental stage of vitiligo. These data suggest a relationship between the DLA and autoimmune vitiligo in the SL model.

Alterations in blood leukocyte populations in Smyth line chickens with autoimmune vitiligo.

Smyth line (SL) chickens spontaneously develop a posthatch autoimmune loss of pigment cells (vitiligo) in the feather. Concurrent with the development of Smyth line vitiligo (SLV), mononuclear cell infiltration and altered T cell profiles can be observed in the pulp of developing feathers. To determine whether the development of SLV is preceded by or associated with alterations in blood lymphocyte and leukocyte populations, blood leukocyte profiles were established at various times prior to and throughout the spontaneous development of SLV. The proportions among various blood leukocyte populations (percentage of lymphocytes, monocytes, heterophils, eosinophils, and basophils) were determined by immunofluorescence and flow cytometric analyses. Lymphocyte markers included fluorescence-conjugated monoclonal antibodies to identify T cells (CD3), T helper cells (CD4), cytotoxic T cells (CD8), and B cells (IgM). The proportions among blood lymphocyte populations examined did not differ between SL and MCH-matched parental Brown line (BL) control chickens prior to and throughout the development of SLV. Compared to BL controls, SL chickens had, however, increased proportions of inflammatory leukocytes in the blood, particularly at the time when most hatchmates developed SLV. Examination of leukocyte alterations with respect to first observation of SLV revealed that inflammatory leukocyte levels were elevated early in SLV. Although altered leukocyte profiles in the blood were observed during the development of SLV, blood from SL chickens did not reflect alterations in lymphocyte populations known to occur at the site of melanocyte destruction. The role of inflammatory blood leukocytes in the development of SLV needs to be further investigated.

Vitiligo in two water buffaloes: histological, histochemical, and ultrastructural investigations.

Vitiligo, a skin disease, characterized by the spontaneous loss of melanin, has been described in several animals as well as in humans. Most of the reports of large domestic animals have dealt with clinical investigations without morphological data. In this report, the histological and ultrastructural characteristics of two cases of vitiligo in water buffaloes (Bubalus bubalis) are presented. Interestingly, many of the ultrastructural observations for vitiliginous buffaloes resemble those previously described for other species, e.g., humans, mouse, and chicken. These data suggest that one or more forms of human vitiligo may have a similar etiopathogenesis to that of the buffalo. Therefore, it is proposed that vitiliginous buffalo may prove to be a useful animal model for the human disease.

Immune mechanisms in vitiligo.

The cause of vitiligo is not known. It is reasonable to suspect that immune mechanisms are involved because some cell surface antigens are selectively expressed on pigmented cells; the immune system has the ability to respond to these antigens, but seems to do so most in persons or animals who have vitiligo, and the progression of vitiligo in chickens is slowed by suppression of immunity. It is not known whether the specific immune abnormalities seen in vitiligo are a cause or an effect of the disease, nor whether they damage melanocytes, simply aggravate melanocyte injury initiated by other causes, or are interesting but irrelevant epiphenomena.

Ocular pathology in the minimally depigmented subline of the vitiliginous Smyth chicken.

Choroidal melanocytes and the retinal pigmented epithelium (RPE) were studied morphologically and histochemically in the Smyth chicken, an avian model for human vitiligo. The sequence of cytological events occurring in the ocular tissue of minimally depigmented Smyth birds was determined. Abnormalities of melanocytes and the associated inflammation was least severe in peripheral areas of the choroid and most pronounced in the back of the eye at the base of the optic nerve head. In the peripheral choroid, morphologically normal melanocytes and an occasional mononuclear leukocyte were observed. However, some of these morphologically normal melanocytes histochemically demonstrated atypical tyrosinase activity at the trans area of the Golgi apparatus. Toward the back of the eye, the melanocytes first appeared swollen and had retracting dendrites. Ultrastructurally these melanocytes demonstrated an increase in extramelanosomal cytoplasm. Later, melanocytes became spherical and had membrane bound, autophagosome-like compartments of pigment granules. As the melanocyte injury progressed, macrophages invaded the tissue and phagocytized melanocytic dendrites. These were followed by numerous plasma cells. Eventually, the back of the eye contained no pigment and was infiltrated with numerous mononuclear inflammatory cells. The retinal pigment epithelium also demonstrated a gradient in the degree of destruction, related to its topography. These cytological features consisted of the retraction of apical RPE processes, the disappearance of the basal plasma membrane infoldings, and the replacement of Bruch's membrane by collagen-like fibrils. These results demonstrate that the uveitis which develops in vitiligo appears to be a consequence of an inherent choroidal melanocyte defect.