Macrophage migration inhibitory factor as an incriminating agent in vitiligo

Abstract: Background: Vitiligo is an autoimmune skin disorder in which the loss of melanocytes is mainly attributed to defective autoimmune mechanisms and, lately, there has been more emphasis on autoinflammatory mediators. Among these is the macrophage migration inhibitory factor, which is involved in many autoimmune skin diseases. However, little is known about the contribution of this factor to vitiligo vulgaris. Objective: To determine the hypothesized role of migration inhibitory factor in vitiligo via estimation of serum migration inhibitory factor levels and migration inhibitory factor mRNA concentrations in patients with vitiligo compared with healthy controls. We also aimed to assess whether there is a relationship between the values of serum migration inhibitory factor and/or migration inhibitory factor mRNA with disease duration, clinical type and severity in vitiligo patients. Methods: Evaluation of migration inhibitory factor serum level and migration inhibitory factor mRNA expression by ELISA and real-time PCR, respectively, were performed for 50 patients with different degrees of vitiligo severity and compared to 15 age- and gender-matched healthy volunteers as controls. Results: There was a highly significant increase in serum migration inhibitory factor and migration inhibitory factor mRNA levels in vitiligo cases when compared to controls (p<0.001). There was a significant positive correlation between both serum migration inhibitory factor and migration inhibitory factor mRNA concentrations in vitiligo patients, and each of them with duration and severity of vitiligo. In addition, patients with generalized vitiligo have significantly elevated serum migration inhibitory factor and mRNA levels than control subjects. Study limitations: Small number of investigated subjects. Conclusions: Migration inhibitory factor may have an active role in the development of vitiligo, and it may also be a useful index of disease severity. Consequently, migration inhibitory factor may be a new treatment target for vitiligo patients.

Enfermedad injerto contra huésped cutánea crónica tipo vitiligo. Caso clínico / Vitiligo type cutaneous manifestation of chronic graft-versus-host disease. Case report

Resumen: Introducción: La enfermedad injerto contra huésped (EICH) se produce por una respuesta patoló gica y destructiva del organismo, como resultado de la interacción entre linfocitos T inmunocompetentes del donante y los antígenos del tejido receptor. Se considera la complicación más grave del trasplante de células madres hematopoyéticas, descrito con mayor frecuencia posterior al trasplante de médula ósea (TMO). La piel suele ser el primer órgano y el más comúnmente afectado, tanto en su forma aguda como crónica, con un espectro clínico de presentación variable. Objetivo: Reportar un caso de vitiligo como manifestación de EICH cutánea crónica, signo de baja prevalencia, cuyo reconocimiento podría ayudar a la sospecha de esta grave complicación. Caso clínico: Escolar de sexo masculino de 8 años de edad, con antecedente de leucemia linfoblástica aguda (LLA) diagnosticada a los 3 años de edad, con recaída combinada medular y del sistema nervioso central (SNC) con enfer medad mínima positiva en los 3 años siguientes. Cuatro años posterior al diagnóstico de LLA, recibió TMO alogénico y siete meses después presentó múltiples nevos melanocíticos con hipopigmentación perilesional y máculas acrómicas en cara, tronco y extremidades, asintomáticas. La biopsia de piel fue compatible con EICH crónica tipo vitiligo y esclerodermiforme. Recibió tratamiento tópico con Tacrolimus, logrando estabilización del cuadro. Conclusiones: La EICH conlleva a la aparición de autoanticuerpos que podrían actuar como un factor desencadenante en la aparición de enfermedades autoinmunes, como lo es el vitiligo. En consecuencia podría explicar esta manifestación, poco descri ta en la literatura, de la EICH cutánea crónica.

Abstract: Introduction: Graft-versus-host disease (GVHD) is caused by a pathologic and destructive response of the organism as a result of the interaction between donor immunocompetent T lymphocytes and the recipient tisular antigens. It's considered the most serious complication of hematopoietic stem cell transplantation, most frequently described after bone marrow transplantation (BMT). The skin is usually the first and most commonly affected organ, in both acute and chronic, with a variable clinical spectrum of presentation. Objective: To report a case of vitiligo as a manifestation of cutaneous chronic GVHD, a low prevalence sign, which recognition could help to suspect this severe compli cation. Case report: 8 years old male, diagnosed with acute lymphoblastic leukemia (ALL) at 3 years old, had a combined medullary and central nervous system (NCS) relapse with minimal positive disease 3 years afterwards. After 4 years ALL was diagnosed, he received an allogeneic bone marrow transplant. Seven months after the BMT he presented multiple melanocytic nevi with peripheral hypopigmentation, and some isolated asymptomatic, confluent achromic macules on the face, trunk and limbs. The skin biopsy was compatible with chronic vitiligo and sclerodermiform type GVHD. He received topical treatment with Tacrolimus, achieving clinical stabilization. Conclusions: GVHD leads to the appearance of autoantibodies that could act as a trigger in the onset of autoimmune diseases, such as vitiligo. Consequently it could explain this poorly described manifestation in the literature of chronic cutaneous GVHD.

Diabetes mellitus and the skin

Abstract: Several dermatoses are routinely associated with diabetes mellitus, especially in patients with chronic disease. This relationship can be easily proven in some skin disorders, but it is not so clear in others. Dermatoses such necrobiosis lipoidica, granuloma annulare, acanthosis nigricans and others are discussed in this text, with an emphasis on proven link with the diabetes or not, disease identification and treatment strategy used to control those dermatoses and diabetes.

Relationship of macrophage migration inhibitory factor levels in PBMCs, lesional skin and serum with disease severity and activity in vitiligo vulgaris

Melanocyte loss in vitiligo vulgaris is believed to be an autoimmune process. Macrophage migration inhibitory factor (MIF) is involved in many autoimmune skin diseases. We determined the possible role of MIF in the pathogenesis of vitiligo vulgaris, and describe the relationship between MIF expressions and disease severity and activity. Serum MIF concentrations and mRNA levels in PBMCs were measured in 44 vitiligo vulgaris patients and 32 normal controls, using ELISA and real-time RT-PCR. Skin biopsies from 15 patients and 6 controls were analyzed by real-time RT-PCR. Values are reported as median (25th-75th percentile). Serum MIF concentrations were significantly increased in patients [35.81 (10.98-43.66) ng/mL] compared to controls [7.69 (6.01-9.03) ng/mL]. MIF mRNA levels were significantly higher in PBMCs from patients [7.17 (3.59-8.87)] than controls [1.67 (1.23-2.42)]. There was also a significant difference in MIF mRNA levels in PBMCs between progressive and stable patients [7.86 (5.85-9.13) vs 4.33 (2.23-8.39)] and in serum MIF concentrations [40.47 (27.71-46.79) vs 26.80 (10.55-36.07) ng/mL]. In addition, the vitiligo area severity index scores of patients correlated positively with changes of both serum MIF concentrations (r = 0.488) and MIF mRNA levels in PBMCs (r = 0.426). MIF mRNA levels were significantly higher in lesional than in normal skin [2.43 (2.13-7.59) vs 1.18 (0.94-1.83)] and in patients in the progressive stage than in the stable stage [7.52 (2.43-8.84) vs 2.13 (1.98-2.64)]. These correlations suggest that MIF participates in the pathogenesis of vitiligo vulgaris and may be useful as an index of disease severity and activity.

Herpes simplex labialis virus is a risk factor for vitiligo [post- herpes simplex labialis vitiligo]

Herpes simplex labialis is a common disease and is the major cause of erythema multiforme. Recently post-herpes labialis leukoderma had been noticed on the lips of Iraqi patients. The aim of the present work is to assess this new pigmentary problem. A total of 24 patients with post-herpes labialis leukoderma were included in this study. Full history and a thorough physical examination were done for all patients. Fourteen females [58.37%] and 10 males [41.67%] were studied. Their ages ranged between 7-53 years. Koebner phenomenon was positive in 17 [70.83%] patients. Family history of vitiligo in close relatives was positive in 13 [54.17%] of patients. The findings of the present work are in favor that this type of leukoderma is a variant of vitiligo that may be induced by herpes-simplex labialis.

Síndrome de Nijmegen: una enfermedad genética a considerar en un paciente con microcefalia, retardo mental y lesiones de la piel / Nijmegen breakage syndrome

Se presenta el caso de un paciente masculino que a los 6 años de edad es derivado a Neurología Infantil para su estudio por presentar microcefalia y retardo mental. Tras ser evaluado por Inmunología y Genética se realiza en el Laboratorio de citogenética humana, programa de genética ICBM, Facultad de Medicina Universidad de Chile, PCR para deleción 657 del5 que confirma el diagnóstico de Nijmegen dando como resultado deleción nucleótido 5, mutación 657 del5, característico del Síndrome de Nijmegen. Actualmente el niño tiene 13 años y es tratado en el Servicio de Oncología infantil por el desarrollo de linfoma difuso de células grandes B, patología frecuente en este sindrome.

A case of a male patient at 6 years old was referred to child neurology for study due to microcephaly and mental retardation. After being evaluated for Immunology and Genetics Laboratory is performed in human cytogenetics, genetic program ICBM, Faculty of Medicine University of Chile, PCR for deletion 657 of the 5 that confirms the diagnosis of Nijmegen nucleotide deletion resulting in 5, 657 mutation del 5 Characteristic of the syndrome of Nijmegen. Currently the child is 13 and is treated at the Children’s Oncology Service in the development of lymphoma diffuse large B cell, common pathology in this syndrome.

Vitiligo y terapia con inmunoglobulina intravenosa: a propósito de un paciente con síndrome de Sjögren / Remission of vitiligo during treatment with intravenous immunoglobulin: Report of one case

Vitiligo is associated with other autoimmune diseases. We report a 52-year-old male with a Sjögren syndrome that was treated with monthly pulses of intravenous immunoglobulin for a chronicinflammatory demyelinating polyradiculoneuropathy. The neurological disorder responded adequately to the treatment and the patient also noted a marked remission of his vitiligo with almost compete re-pigmentation of the scalp and face and partial repigmentation of other areas.

Función del peróxido de hidrógeno en el vitíligo / Function of hydrogen peroxide in cases of vitiligo

El vitíligo es un desorden de la pigmentación que tiene una incidencia entre el 0,5 y 3 por ciento en la población mundial. Se caracteriza por una despigmentación de la piel provocada por la presencia de melanocitos afuncionales en la epidermis. Cuando ocurren eventos desencadenantes del estrés oxidativo, las concentraciones de peróxido de hidrógeno se incrementan ostensiblemente en melanocitos y queratinocitos. Los queratinocitos actúan como fuente de especies reactivas de oxígeno y transfieren a los melanocitos grandes cantidades de peróxido de hidrógeno. Evidencias experimentales han demostrado que como consecuencias de las altas concentraciones de peróxido de hidrógeno en la epidermis de pacientes con vitíligo, se afectan las concentraciones de butirilcolinesterasa y acetilcolineterasa, la actividad enzimática en el ciclo de las 6HB4, los péptidos derivados de proopiomelanocortinas y las proteínas del estrés entre otros muchos eventos. Todos estos eventos, tras una situación precipitante sobre un individuo genéticamente predispuesto, podrían promover cambios en la pigmentación de la piel que lo conducen, en última instancia, al vitíligo

Vitiligo is a pigmentation disorder with an incidence between the 0,5 and the 3 percent at worldwide. It is characterized by a skin depigmentation provoked by presence of dysfunctional melanocytes in epidermis. When oxidative stress triggering events are present, hydrogen peroxide concentrations clearly increase in the melanocytes and keratinocytes. The keratinocytes act as a source of oxygen and transfer to melanocytes high amounts of hydrogen peroxide. Experimental evidences have demonstrated that due to the high hydrogen peroxide concentrations in epidermis of vitiligo patients affecting the concentrations of butyryl-cholinesterase and the acetylcholinesterase, the enzymatic activity in 6HB4 cycle, propiomelanocortins and stress protein among many events. All these events after a hasty situation on a genetically predisposing subject could to promote changes in skin pigmentation that as a last resort leading to vitiligo

Abordagem multiprofissional na visão integral do paciente com vitiligo / Multidisciplinary approach in the patient's integral vision with vitiligo

A psicodermatologia é uma área que estuda e integra o trabalho de médicos e psicólogos, objetivando um melhor entendimento das doenças cutâneas. O vitiligo, caracterizado por máculas acrômicas, é causado por destruição adquirida de melanócitos, sendo associado com fatores emocionais. Há três teorias para explicar a destruição dos melanócitos no vitiligo: a imunológica, a citotóxica e a neural. Independentemente da origem, existe a percepção nítida da sua relação com aspectos emocionais. O aparecimento e o alastramento da doença cursam com o aumento das frustrações e preocupações. Vários doentes relatam o aparecimento após traumas emocionais significativos. Quanto maior a área corporal afetada, maior o nível de estresse, depressão e tensão emocional. Provavalmente, alterações emocionais desequilibram o organismo, favorecendo alterações hormanais e imunológicas, podendo desencadear e piorar o vitiligo. A pessoa deve ser vista com um todo, constituída de outras dimensões, como a psíquica, social, econômica e cultural. Este trabalho objetiva demonstrar a visão de homem integral, considerando as influências biopsicossociais e aimportância do trabalho multiprofissional.

Tha Psychodermatology is an area that studies and integrate the doctor's work, psychologists, looking for a better understanding of skin diseases. The vitiligo, marked by achromatic maculates, is caused because there is an adquire destruction of melanocytes, so related with emotional components. There are three theories that explain the destruction of the melanocytes in vitiligo: an immunological response, one that is citolitic and the last one, neural. Causes apart, that is a clear perception about the relation with emotional aspects. The beginning and spreading of the disease courses with frustrations and concerns, both always increasing. A lot of sick people relates the beginning of the disease after some important emotional stress. The higher is the body area affected, higher is the leval of stress, depression and emotional tension. Probably, emotional changing unbalance the organism, favoring hormonal and immunological changes, and it may trigger de vitiligo. The person must be seen as a whole person, consists of other dimensions, such as psychological, social, economic and cultural. This work shows the integral vision of man, considering the influences biopsychosocial and the importance of multidisciplinary working.

socio-demography and clinical profile of vitiligo in Sudan

Vitiligo is a chronic skin disease that causes loss of pigment, resulting in irregular pale patches of skin. The precise cause of vitiligo is complex and not fully understood. There is some evidence suggesting it is caused by a combination of auto-immune, genetic, and environmental factors. The population incidence worldwide is considered to be between 0.1% and 2%. The disease has different clinical types but generally, it consists of areas of macular depigmentation, commonly on extensor aspects of extremities, on the face or neck, and in skin folds. Age of onset is often in young adulthood and the condition tends to progress gradually with lesions enlarging and extending until a quiescent state is reached. To define the socio-demography and clinical profile of vitiligo in Sudan. This study is a cross-sectional, clinico-epidemiological and hospital-based study, done in Khartoum Dermatologic Hospital [KDH]. The data were collected between June 2007 and November 2007. The total number of patients with vitiligo in the study was 113. Male patients were 47 [42%]. Children were 13 [11%], adults were 90 [80%] and elderlies were 10 [9%]. The mean age of onset of the disease was found to be 11.5 yrs in 22.5% of the patients. Patients with acute [< 1 yr] disease were 6 [5.4%], while those with chronic [>/= 1 yr] disease were 107 [94.6%]. The most commonly affected tribe was Algaa/'liyeen tribe [27%]. The commonest precipitating factor for vitiligo has been found to be emotional disturbances [in 27% of patients]. Commonest symptom of the disease was depigmented patch/es [64.8%]. Severe [>/= 10%] involvement of skin surface area was found in 59% of patients, while mild [<10%] involvment was found in 41% Koebner sign was found to be present in 42% of patients. The disease was active in 47.3% of patients. The bilaterally symmetrical pattern of distribution was the commonest pattern [in 85%]. The commonest clinical type of vitiligo was the generalized type [82.3%]. 35% of patients with vitiligo had positive family history. The clinical profile of vitiligo in Sudan was not so different from that found worldwide

[Serum level of folic acid and vitamin B12 in patients with vitiligo]

Vitiligo is an idiopathic and acquired disease; characterized by de-pigmented areas of skin. The precise mechanism involved is not clear. Low levels of folic acid and vitamin B12 have been suggested to play a possible role in the pathogenesis of vitiligo. In this study we checked the serum level of folic acid and vitamin B12 in patients with vitiligo. In this case-control study 50 patients with the mean age of 25.3 +/- 12 years and 50 normal controls with mean age of 31 +/- 12.4 years were evaluated. Radioimmunoassay was used to determine serum level of folic acid and vitamin B12. Patients with pernicious anemia and history of folic acid and vitamin B12 supplement therapy were excluded from this study. Mean serum level of folic acid and vitamin B12 was 7.9 +/- 3.5 ng/ml and 320.5 +/- 183.6 pg/ml, respectively, in patients. The figures for controls were 301.4 +/- 13pg/ml and 6.8 +/- 3.9 ng/ml. According to t test this difference was not significant [p>0.05]. In this study no association was found between the serum level of folic acid and vitamin B12 in patients with vitiligo

Manejo del vitiligo / Handling of the vitiligo

El vitiligo, caracterizado por máculas acrómicas de distribución localizada o generalizada, tiene una prevalencia de 0,1-2%. Su etiología es desconocida y el diagnóstico es generalmente clínico. Se asocia a enfermedades autoinmunes (como tiroiditis de Hashimoto y enfermedad de Graves) y a la afección de órganos que contienen melanocitos (uveitis e hipoacusia neurosensorial). La enfermedad afecta la calidad de vida. El objetivo del tratamiento es estabilizar el proceso de despigmentación y recuperar el pigmento de las lesiones (repigmentacion promedio del 70-75%). El tratamiento puede ser médico o quirúrgico y despigmentación en casos refractarios.Aunque no hay una opción terapéutica efectiva para todos los pacientes existe una variedad de terapias establecida, y recientemente desarrolladas, que podrían beneficiar a muchos de los que lo padecen. Un corto tiempo de evolución de la enfermedad parecería ser un factor que aumenta la posibilidad de éxito con cualquier modalidad terapéutica.

Vitiligo: a sign of systemic disease.

Vitiligo reflects a systemic process that has important implications beyond the skin. These include other autoimmune diseases and ocular and neurological abnormalities. Alezzandrini syndrome and Vogt-Koyanagi-Harada syndrome particularly exemplify this relationship. In addition, vitiligo may be confused with other systemic disorders, including tuberous sclerosis, progressive systemic sclerosis (scleroderma), melanoma, and, in endemic regions, leprosy. We describe these associations and emphasize the importance of depigmenting disorders.

Antithyroglobulin antibody level in vitiligo patients

Vitiligo is an acquired depigmenting disorder characterized by the loss of melanocytes from the epidermis affecting 1-2% among whites, higher among blacks. Its etiology and pathogenesis are as get not completely clarified, many hypotheses have been put forward, auto immune hypotheses is one of the most accepted theories. The association with autoimmune diseases, and organ -specific autoantibodies is well known. The aim of this work is to detect the association of vitiligo with autoimmunelhyroid diseases by estimation of antithyroglobulin antibodies [anti TG], in addition to assess the thyroid function in vitiligo patients. Thirty vitiligo patients and twenty healthy volunteers were selected and after obtaining their consent, blood sample were collected for measurement of T3, T4 and anti TG levels. Results showed that antithyroglobulin antibodies were significantly increased in vitiligo patients. Also we found significant difference between vitiligo patients with progressive course and those with stationary course in T3, T4 and anti TG levels. We conclude that Autoimmunity is one of the important theories that have been put for detecting the pathagenesis of vitiligo as evidenced in this study by finding of elevated antithyrolglobulin antibody titre. There is a significant correlation between anti-TG level and progression of the disease. This means that antibodies increase in the patient serum during activity of the disease with more evidence that autoimmunity plays a major role in the pathogenesis of vitiligo. So, we recommended that Thyroid function should be assessed annually in all vitiligo patients as screeJwig testes of thyroid function for early detection

Hepatitis C virus antibodies and vitiligo disease

Vitiligo is a common skin disorder, characterized by depigmented patches due to selective destruction of melanocytes. The etiology of this disease is unknown. A number of hypotheses including viral theory have been proposed to explain the etiology. To determine the prevalence of antibody to hepatitis C virus infection in vitiligo patients, the present study was performed. Third generation ELISA test was used for detection of antibodies to HCV in human sera. All normal controls were anti-HCV negative whereas only one patient was positive for anti-HCV and there was no significant difference in the prevalence of anti-HCV between patients and controls. These results indicate that hepatitis C virus has not a direct causal role in the pathogenesis of vitiligo, however, this does not rul out a "hit and run" virus induced disease

Vitiligo: new etiology-based treatments

Vitiligo is an acquired depigmentary disorder characterized by a chronic and progressive loss of melanocytes from the epidermis. The etiopathogenesis of vitiligo is still not fully understood, and the major theories include melanocyte destruction [autoimmune, neural and impaired redox status] and melanocyte inhibition or defective adhesion. Recently a new theory, melanocytorrhagy, was forwarded. In this review are also discussed the new etiologybased treatments, mainly topical calcipotriol, topical immunomodulators and topical catalase

Vitiligo and its management update: a review

Vitiligo is a common, acquired, often familial melanocytopenic disorder with focal depigmentation of skin; there are several new treatments which appear to have a higher success rate than previous therapies. There are nuances in the treatment of patients with vitiligo which are not easy to list. Common therapeutic options include phototherapy with psoralens and topically applied steroids with or without PUVA. Those who have tried PUVA without success should quit and look for other treatment options like narrow band ultraviolet B [NBUVB] which has recently been reported to be effective therapy for vitiligo, the only clinical parameter that could differentiate non-responders from responders is previous exposure to PUVA. More recently lasers, vitamin D analogues, tacrolimus and skin grafting have been shown to play some role in the treatments of patients with larger lesions. Targeted phototherapy with single wavelength laser light has proved to be effective and time-efficient therapeutic option for the management of vitiligo. Surgical techniques intend to re-pigment the skin and are an interesting therapeutic option. At this time the exact cause of vitiligo is still unknown, various treatment modalities are available but there is no single cure. The purpose of this review is to describe the different treatment modalities available currently

Surgical treatment of vitiligo

Vitiligo, a common depigmenting disorder, of possible autoimmune etiology, is generally managed by use of PUVA therapy and steroids. Surgery has been increasingly used in recent years for patients with stable lesions which are resistant to medical therapy, and is now recognized as a useful form of treatment. We report our experience in thirteen patients treated with surgery. Various surgical techniques were tried in these patients, as follows; Suction blister grafting in five patients, thin thiersch grafting in six patients and punch grafting in two patients. A total of 35 patches, amounting to about 140sq.cm have been treated. These patients have been followed up to a maximum of 3 years. The results show excellent take of the graft in nearly 94% of lesions. Very few complications were seen. Recurrence of lesions was noted in one patient. Donor area showed only mild pigmentation in all cases. Our xperience shows that suction blister grafting is best suited for small areas and for face. Thin thiersch grafting is recommended for larger areas. Punch grafting, the easiest of these Methods, is best used as an adjuvant to PUVA therapy. The article discusses details of the study with a review of the literature