RESUMEN
Primary immunodeficiency diseases (PIDs) are a group of more than 400 disorders representing aberrant functioning or development of immune system. Hypopigmentation syndromes also characterize a distinguished cluster of diseases. However, hypopigmentation may also signify a feature of genetic diseases associated with immunodeficiency, such as Chediak-Higashi syndrome, Griscelli syndrome type 2, Hermansky-Pudlak syndrome type 2 and type 10, Vici syndrome, and P14/LAMTOR2 deficiency, all of which are linked with dysfunction in vesicular/endosomal trafficking. Regarding the highly overlapping features, these disorders need a comprehensive examination for prompt diagnosis and effective management. As an aid to clinician, distinguishing the pathophysiology, clinical phenotype, and diagnosis as well as treatment options of the six mentioned PID disorders associated with hypopigmentation are described and discussed in this review.
Asunto(s)
Pruebas Genéticas , Hipopigmentación/diagnóstico , Enfermedades de Inmunodeficiencia Primaria/diagnóstico , Diagnóstico Diferencial , Humanos , Hipopigmentación/genética , Hipopigmentación/inmunología , Hipopigmentación/terapia , Enfermedades de Inmunodeficiencia Primaria/genética , Enfermedades de Inmunodeficiencia Primaria/inmunología , Enfermedades de Inmunodeficiencia Primaria/terapia , Pigmentación de la Piel/genética , Pigmentación de la Piel/inmunologíaRESUMEN
BACKGROUND: Hypopigmented mycosis fungoides (HMF) is an uncommon variant of mycosis fungoides. AIMS: To study the clinical and histopathology presentation in children with HMF. METHOD: We reviewed 9 children diagnosed with HMF. The clinical data were collected and analyzed. RESULT: Eight boys and 1 girl were included, with a median onset age of 7.4 year old and median age of diagnosis of 10.5 year old. Multiple hypopigmented patches were observed in all patients, and 5 patients exhibited multiple scaly erythema at the center of hypopigmented patches. Histopathology showed atypical lymphocytes with hyperchromatic, irregular, and cerebriform nuclei, infiltrated in the epidermis and dermis. Pautrier's microabscesses was noted in 6 of 9 patients, and papillary dermal fibroplasia was noted in 6 of 9 patients. CD8 predominance was detected in 4 of 6 patients. Four patients were simultaneously subjected to skin biopsy on hypopigmented patches and scaly erythema simultaneously. Compared with hypopigmented specimens, erythema biopsy detected deeper and denser infiltration of atypical lymphoid cells in 3 of 4 patients, higher CD4+/CD8+ ratio in 4 of 4 patients, more CD5 loss in 2 of 4 patients, and more CD7 loss in 2 of 4 patients. TCR gene monoclonal rearrangement was detected in 2 of 5 patients. Narrowband ultraviolet B phototherapy was applied in 7 patients. One of 7 patients achieved complete response, and 6 of 7 patients achieved partial response. No recurrence was noted with the median follow-up period of 6 months. CONCLUSION: HMF could occur in young patients, with indolent and benign course. HMF could gradually seem as scaly erythema based on hypopigmented patches. The histopathology indicated a more advanced stage of the scaly erythema lesions than hypopigmented patches.
Asunto(s)
Hipopigmentación/patología , Micosis Fungoide/patología , Neoplasias Cutáneas/patología , Pigmentación de la Piel , Biomarcadores de Tumor/genética , Niño , Preescolar , Femenino , Reordenamiento Génico de Linfocito T , Genes Codificadores de los Receptores de Linfocitos T , Humanos , Hipopigmentación/genética , Hipopigmentación/inmunología , Hipopigmentación/radioterapia , Linfocitos Infiltrantes de Tumor/inmunología , Masculino , Micosis Fungoide/genética , Micosis Fungoide/inmunología , Micosis Fungoide/radioterapia , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/inmunología , Neoplasias Cutáneas/radioterapia , Pigmentación de la Piel/efectos de la radiación , Resultado del Tratamiento , Terapia UltravioletaRESUMEN
Skin of color patients with psoriasis face unique challenges related to disease characteristics and treatment. Dyspigmentation, including postinflammatory hypo- and hyperpigmentation, more frequently and severely affects patients with skin of color and remains a challenge in psoriasis management. We present the case of a 58-year-old Black male with moderate psoriasis who was treated for 8 weeks with a fixed combination halobetasol propionate 0.01%/tazarotene 0.045% (HP/TAZ) lotion during a phase 3 study (NCT02462070). HP/TAZ was efficacious in this patient, whose Investigator’s Global Assessment score decreased from 3 (moderate) at baseline to 1 (almost clear) within 4 weeks, with maintenance of & "almost clear"; through week 12 (4 weeks posttreatment). Affected body surface area decreased by 50% and quality of life greatly improved from baseline to week 8. The patient experienced dyspigmentation of the affected skin during the trial; hypopigmentation was primarily experienced from weeks 2-8, with the greatest degree at week 4. By week 12, the affected skin area had returned to normal, with only small regions of hyperpigmentation, primarily around the periphery of the lesion. These results indicate that HP/TAZ may be a treatment option for patients with skin of color, who are disproportionally affected by postinflammatory dyspigmentation. J Drugs Dermatol. 2020;19(10):1000-1004. doi:10.36849/JDD.2020.5347.
Asunto(s)
Clobetasol/análogos & derivados , Hipopigmentación/tratamiento farmacológico , Ácidos Nicotínicos/administración & dosificación , Psoriasis/tratamiento farmacológico , Crema para la Piel/administración & dosificación , Administración Cutánea , Negro o Afroamericano , Clobetasol/administración & dosificación , Combinación de Medicamentos , Estética , Humanos , Hipopigmentación/diagnóstico , Hipopigmentación/inmunología , Masculino , Persona de Mediana Edad , Psoriasis/complicaciones , Psoriasis/diagnóstico , Psoriasis/inmunología , Índice de Severidad de la Enfermedad , Pigmentación de la Piel/efectos de los fármacos , Pigmentación de la Piel/inmunología , Resultado del TratamientoRESUMEN
BACKGROUND: The treatment response to new immunotherapy in advanced melanoma patients remains varied between individuals. Immune-related cutaneous side effects might have prognostic value. OBJECTIVE: To determine whether development of ≥1 of the 3 immune-mediated cutaneous events (eczema, lichenoid reaction, or vitiligo-like depigmentation) is associated with improved progression-free survival. METHODS: A cohort study of adults with stage IIIC-IV melanoma treated with pembrolizumab or nivolumab during May 1, 2012-February 1, 2018, at Westmead Hospital, Sydney, Australia. Treatment response was based on iRECIST version 1.1. RESULTS: In total, 82 patients of an average age of 59.9 years were included. Median follow-up was 40.7 months; 33 patients had ≥1 target skin reaction. Skin reactions developed in one-third of individuals by 6 months. At any given time, the instantaneous risk of disease progression and death was lower for individuals who had ≥1 cutaneous adverse event (CAE) develop. Compared with individuals with no CAE, the hazard ratio for disease progression and death for individuals who had ≥1 CAE develop was 0.46 (95% confidence interval 0.23-0.91; P = .025) by the time-dependent Cox proportional hazards model. LIMITATIONS: Single-center study. CONCLUSION: This study demonstrates an association between the development of ≥1 of 3 CAEs and improved progression-free survival in this cohort of patients.
Asunto(s)
Antineoplásicos Inmunológicos/uso terapéutico , Melanoma/tratamiento farmacológico , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Neoplasias Cutáneas/tratamiento farmacológico , Piel/efectos de los fármacos , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos Inmunológicos/farmacología , Australia/epidemiología , Eccema/inducido químicamente , Eccema/epidemiología , Eccema/inmunología , Femenino , Estudios de Seguimiento , Humanos , Hipopigmentación/inducido químicamente , Hipopigmentación/epidemiología , Hipopigmentación/inmunología , Incidencia , Erupciones Liquenoides/inducido químicamente , Erupciones Liquenoides/epidemiología , Erupciones Liquenoides/inmunología , Masculino , Melanoma/inmunología , Melanoma/mortalidad , Persona de Mediana Edad , Pronóstico , Receptor de Muerte Celular Programada 1/inmunología , Supervivencia sin Progresión , Estudios Prospectivos , Piel/inmunología , Neoplasias Cutáneas/inmunología , Neoplasias Cutáneas/mortalidad , Adulto JovenRESUMEN
Skin depigmentation diseases, such as vitiligo, are pigmentation disorders that often destroy melanocytes. However, their pathological mechanisms remain unclear, and therefore, promising treatments or prevention has been lacking. Here, we demonstrate that a zebrafish insertional mutant showing a significant reduction of nicastrin transcript possesses melanosome maturation defect, Tyrosinase-dependent mitochondrial swelling, and melanophore cell death. The depigmentation phenotypes are proven to be a result of γ-secretase inactivation. Furthermore, live imaging demonstrates that macrophages are recruited to and can phagocytose melanophore debris. Thus, we characterize a potential zebrafish depigmentation disease model, a nicastrinhi1384 mutant, which can be used for further treatment or drug development of diseases related to skin depigmentation and/or inflammation.
Asunto(s)
Secretasas de la Proteína Precursora del Amiloide/genética , Hipopigmentación/genética , Glicoproteínas de Membrana/genética , Monofenol Monooxigenasa/metabolismo , Piel/inmunología , Proteínas de Pez Cebra/genética , Secretasas de la Proteína Precursora del Amiloide/metabolismo , Animales , Animales Modificados Genéticamente , Modelos Animales de Enfermedad , Embrión no Mamífero , Humanos , Hipopigmentación/inmunología , Hipopigmentación/patología , Melanosomas/inmunología , Melanosomas/metabolismo , Melanosomas/ultraestructura , Glicoproteínas de Membrana/metabolismo , Microscopía Electrónica de Transmisión , Monofenol Monooxigenasa/antagonistas & inhibidores , Monofenol Monooxigenasa/genética , Mutación , Piel/patología , Pigmentación de la Piel/efectos de los fármacos , Pigmentación de la Piel/genética , Pez Cebra , Proteínas de Pez Cebra/metabolismoAsunto(s)
Autoanticuerpos/sangre , Butanoles/efectos adversos , Hipopigmentación/inmunología , Preparaciones para Aclaramiento de la Piel/efectos adversos , Vitíligo/inmunología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Autoanticuerpos/inmunología , Preescolar , Femenino , Humanos , Hipopigmentación/sangre , Hipopigmentación/inducido químicamente , Masculino , Persona de Mediana Edad , Vitíligo/sangre , Adulto JovenAsunto(s)
Hipopigmentación/patología , Inmunosupresores/uso terapéutico , Tacrolimus/uso terapéutico , Vitíligo/patología , Autoinmunidad , Población Negra , Diagnóstico Diferencial , Femenino , Humanos , Hipopigmentación/tratamiento farmacológico , Hipopigmentación/inmunología , Melanoma/metabolismo , Persona de Mediana Edad , Resultado del Tratamiento , Vitíligo/tratamiento farmacológico , Vitíligo/inmunologíaAsunto(s)
Butanoles/efectos adversos , Linfocitos T CD8-positivos/inmunología , Cosméticos/efectos adversos , Hipopigmentación/inmunología , Vitíligo/inmunología , Linfocitos T CD8-positivos/química , Quimiocina CCL17/sangre , Quimiocina CCL22/sangre , Humanos , Hipopigmentación/inducido químicamente , Hipopigmentación/patología , Recuento de Linfocitos , Receptores CCR4/análisis , Piel/citología , Piel/inmunología , Vitíligo/patologíaAsunto(s)
Butanoles/efectos adversos , Cosméticos/efectos adversos , Hipopigmentación/inmunología , Melanocitos/inmunología , Linfocitos T Citotóxicos/inmunología , Genotipo , Antígeno HLA-A24/genética , Humanos , Hipopigmentación/inducido químicamente , Hipopigmentación/genética , Antígeno MART-1/inmunología , Monofenol Monooxigenasa/inmunologíaRESUMEN
Recently, an unexpected outbreak of patients with leukoderma occurred in Japan with the use of brightening/lightening cosmetics containing rhododendrol (RD). Patients developed leukoderma mostly on the skin sites repeatedly applied with RD, but some patients also had vitiligo-like lesions on the non-applied sites. RD is a tyrosinase-competitive inhibiting substance, thereby serving as an inhibitor of melanin synthesis. Upon inhibition of tyrosinase, RD is converted to new products such as tyrosinase-catalyzed hydroxyl-metabolite, which damage melanocytes. The melanocyte cell lysates seem to induce T-cell response. The frequencies of CD8+ T cells in both lesional skin and peripheral blood are significantly higher in the RD leukoderma as well as non-segmental vitiligo patients than in normal controls. In HLA-A*02:01 positive cases, circulating Melan-A-specific cytotoxic T cells can be detected at a high frequency. It is thus suggested that RD-induced leukoderma is induced by not only cytolysis of melanocytes but also subsequent immune reactions toward melanocytes.
Asunto(s)
Butanoles/efectos adversos , Linfocitos T CD8-positivos , Hipopigmentación/inducido químicamente , Monofenol Monooxigenasa/antagonistas & inhibidores , Butanoles/metabolismo , Cosméticos/efectos adversos , Humanos , Hipopigmentación/enzimología , Hipopigmentación/inmunología , Melanocitos/efectos de los fármacos , Melanocitos/inmunologíaRESUMEN
As reported in the mass media on July 2013, numerous consumers who had used the cosmetic ingredient containing rhododendrol (4-(4-hydroxyphenyl)-2-butanol, Trade name; rhododenol), which is a melanin inhibitor isolated from Acer nikoense Maxim, released from Kanebo Cosmetics Inc. (Tokyo, Japan) noticed leukoderma patches on their face, neck and hands. We have experienced 32 cases that developed leukoderma after using such cosmetics so far and skin biopsy samples in some cases were obtained from both leukoderma and pigmented lesions. A histopathological analysis for skin lesions obtained from such patients notably showed basal hypo-pigmentation, melanin incontinence, and remaining melanocytes in most patients which is not relevant in vitiligo vulgaris. Subsequently, we comprehensively carried out immunohistochemical analyses of immune-competent cells infiltration to assess the effect of the cellular immune response to inducible hypopigmentation. Furthermore, detailed morphological observations performed by electron-microscopy notably showed the presence of melanocytes with only a small number of melanosomes, dermal fibroblasts containing melanosome globules and melanophages whereas no damage associated with melanosome transfer and the basal layer apparatus. These findings provide a cue to diagnose as rhododenol-induced leukoderma differentiate from vitiligo vulgaris and for rhododendrol to induce local immunity in addition to melanocyte damage.
Asunto(s)
Butanoles/efectos adversos , Cosméticos/efectos adversos , Hipopigmentación/inmunología , Hipopigmentación/patología , Relación CD4-CD8 , Fibroblastos , Humanos , Hipopigmentación/inducido químicamente , Antígeno MART-1/análisis , Melanocitos/química , Factor de Transcripción Asociado a Microftalmía/análisis , Piel/inmunología , Piel/ultraestructura , Linfocitos T ReguladoresRESUMEN
PURPOSE: Vitiligo-like depigmentation in patients with melanoma may be associated with more favorable clinical outcome. We conducted a systematic review of patients with stage III to IV melanoma treated with immunotherapy to determine the cumulative incidence of vitiligo-like depigmentation and the prognostic value of vitiligo development on survival. METHODS: We systemically searched and selected all studies on melanoma immunotherapy that reported on autoimmune toxicity and/or vitiligo between 1995 and 2013. Methodologic quality of each study was appraised using adapted criteria for systematic reviews in prognostic studies. Random-effect models were used to calculate summary estimates of the cumulative incidence of vitiligo-like depigmentation across studies. The prognostic value of vitiligo-like depigmentation on survival outcome was assessed using random-effects Cox regression survival analyses. RESULTS: One hundred thirty-seven studies were identified comprising 139 treatment arms (11 general immune stimulation, 84 vaccine, 28 antibody-based, and 16 adoptive transfer) including a total of 5,737 patients. The overall cumulative incidence of vitiligo was 3.4% (95% CI, 2.5% to 4.5%). In 27 studies reporting individual patient data, vitiligo development was significantly associated with both progression-free-survival (hazard ratio [HR], 0.51; 95% CI, 0.32 to 0.82; P < .005) and overall survival (HR, 0.25; 95% CI, 0.10 to 0.61; P < .003), indicating that these patients have two to four times less risk of disease progression and death, respectively, compared with patients without vitiligo development. CONCLUSION: Although vitiligo occurs only in a low percentage of patients with melanoma treated with immunotherapy, our findings suggest clear survival benefit in these patients. Awareness of vitiligo induction in patients with melanoma is important as an indicator of robust antimelanoma immunity and associated improved survival.
Asunto(s)
Inmunoterapia , Melanoma/mortalidad , Melanoma/terapia , Neoplasias Cutáneas/mortalidad , Neoplasias Cutáneas/terapia , Vitíligo , Supervivencia sin Enfermedad , Humanos , Hipopigmentación/epidemiología , Hipopigmentación/inmunología , Incidencia , Estimación de Kaplan-Meier , Melanoma/inmunología , Melanoma/patología , Estadificación de Neoplasias , Oportunidad Relativa , Pronóstico , Neoplasias Cutáneas/inmunología , Neoplasias Cutáneas/patología , Vitíligo/epidemiología , Vitíligo/inmunología , Melanoma Cutáneo MalignoRESUMEN
A case of halo naevi and café au lait macule regression in a renal transplant patient receiving long-term immunosuppressive therapy is described. We propose the direct transfer of an auto-reactive antibody, CD8 T-cells or tumour necrosis factor α from the transplant donor to the recipient as a possible cause. We have also considered insufficient immunosuppressive therapy as a possible mechanism.
Asunto(s)
Manchas Café con Leche/complicaciones , Hipopigmentación/complicaciones , Trasplante de Riñón , Nevo con Halo/complicaciones , Adulto , Humanos , Hipopigmentación/inmunología , Terapia de Inmunosupresión , Masculino , Nevo con Halo/inmunologíaRESUMEN
BACKGROUND: Mycosis fungoides (MF), the most common form of cutaneous T-cell lymphoma, typically presents in middle-aged to elderly individuals. OBJECTIVE: We sought to study the demographics, clinicopathologic features, treatment response, and prognosis of patients with biopsy-proven MF diagnosed before 20 years of age. METHODS: Patients were identified from a prospectively collected database for retrospective analysis. RESULTS: Of 1902 patients with MF, 34 had juvenile-onset MF: 41% were stage IA, 56% were stage IB, and 3% were stage IIB at diagnosis. The male to female ratio was 1.1:1. The median age of symptom onset was 9 years (range 3-19 years), with a delay in diagnosis between 1 month and 14 years. Patients primarily presented with hypopigmented (53%), hyperpigmented (29%), and pink-violaceous (41%) patches/plaques. Immunohistochemistry revealed 39% with CD8(+) immunophenotype, 67% of which had hypopigmented lesions. The phototherapy response rate in 21 patients was 81%. All patients who completely responded to narrowband ultraviolet B phototherapy had hypopigmented MF. LIMITATIONS: This is a single cancer center study. CONCLUSION: Juvenile-onset MF presents with early-stage disease with an overrepresentation of hypopigmented MF and CD8(+) immunophenotype. Narrowband ultraviolet B is an effective treatment option for juveniles, especially for those with the hypopigmented variant.
Asunto(s)
Micosis Fungoide , Terapia PUVA/métodos , Neoplasias Cutáneas , Adolescente , Edad de Inicio , Biopsia , Niño , Preescolar , Estudios Transversales , Bases de Datos Factuales , Femenino , Humanos , Hiperpigmentación/inmunología , Hiperpigmentación/patología , Hipopigmentación/inmunología , Hipopigmentación/patología , Inmunofenotipificación , Masculino , Micosis Fungoide/tratamiento farmacológico , Micosis Fungoide/inmunología , Micosis Fungoide/patología , Pronóstico , Estudios Retrospectivos , Piel/patología , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/inmunología , Neoplasias Cutáneas/patología , Resultado del Tratamiento , Terapia Ultravioleta/métodos , Deficiencia de Vitamina D/inmunología , Deficiencia de Vitamina D/patología , Adulto JovenRESUMEN
Patients with melanoma may develop skin depigmentation spontaneously or following therapy, referred to as melanoma-associated leucoderma (MAL). As clinical presentation of MAL may precede primary/metastatic melanoma detection, recognition of MAL is important to prevent its misdiagnosis as vitiligo and the subsequent application of immunosuppressive treatment. To reveal the immunity involved in MAL development, we investigated the presence of antibody and T-cell immune responses directed against the melanocyte-differentiation-antigens MART-1 (Melan-A), tyrosinase and gp100 in patients with MAL, as compared to patients with vitiligo. Autoantibodies to gp100 and tyrosinase were commonly found in both diseases. Interestingly, MART-1 antibodies were only present in patients with MAL. Melanocyte antigen-specific T cells were found in all patients, with relatively more specific T cells in patients with active vitiligo. Although MAL and vitiligo may appear clinically similar, our results indicate that the humoral immune responses against MART-1 differ between these diseases, which can help to differentiate MAL from vitiligo.
Asunto(s)
Formación de Anticuerpos/inmunología , Hipopigmentación/complicaciones , Hipopigmentación/inmunología , Antígeno MART-1/inmunología , Melanoma/complicaciones , Melanoma/inmunología , Vitíligo/inmunología , Adolescente , Adulto , Anciano , Especificidad de Anticuerpos/inmunología , Linfocitos T CD8-positivos/inmunología , Demografía , Femenino , Humanos , Masculino , Melanocitos/inmunología , Melanocitos/patología , Melanoma/patología , Persona de Mediana Edad , Vitíligo/patología , Adulto JovenRESUMEN
To generate a mouse model of spontaneous epidermal depigmentation, parental h3TA2 mice, expressing both a human-derived, tyrosinase-reactive T-cell receptor on T cells and the matching HLA-A2 transgene, were crossed to keratin 14-promoter driven, stem cell factor transgenic (K14-SCF) mice with intra-epidermal melanocytes. In resulting Vitesse mice, spontaneous skin depigmentation precedes symmetrical and sharply demarcated patches of graying hair. Whereas the SCF transgene alone dictates a greater retinoic acid receptor-related orphan receptor gamma (RORγt)(+) T-cell compartment, these cells displayed markedly increased IL-17 expression within Vitesse mice. Similar to patient skin, regulatory T cells were less abundant compared with K14-SCF mice, with the exception of gradually appearing patches of repigmenting skin. The subtle repigmentation observed likely reflects resilient melanocytes that coexist with skin-infiltrating, melanocyte-reactive T cells. Similar repigmenting lesions were found in a different TCR transgenic model of vitiligo developed on an SCF transgenic background, supporting a role for SCF in repigmentation.
Asunto(s)
Epidermis/patología , Hipopigmentación/complicaciones , Hipopigmentación/inmunología , Inmunidad , Pigmentación , Vitíligo/complicaciones , Vitíligo/inmunología , Animales , Línea Celular , Modelos Animales de Enfermedad , Epítopos , Humanos , Hipopigmentación/patología , Interleucina-17/metabolismo , Ratones Endogámicos C57BL , Ratones Transgénicos , Monofenol Monooxigenasa/metabolismo , Receptores de Antígenos de Linfocitos T/metabolismo , Factor de Células Madre/genética , Linfocitos T Reguladores/inmunología , Transgenes , Vitíligo/patologíaRESUMEN
Vitiligo is a skin condition characterized by white, hypopigmented macules. Melanocyte loss is a feature of the disease, and it has been hypothesized that an autoimmune mechanism could be responsible for the depigmentation. Melanoma is a malignancy that develops in melanocytes; if not detected and treated early, it is often deadly. Leukoderma, a condition characterized by depigmentation of the skin, is sometimes associated with malignant melanoma. An immune response against melanocyte antigens leading to destruction of either melanoma cells or melanocytes has been observed in both vitiligo and melanoma. Studies in animal models and humans have shown that humoral and cell-mediated immune responses are involved in modulating cytotoxic activity against tumor cells and normal melanocytes. The study of factors associated with anti-tumor immunopathogenic mechanisms -autoimmunity for example- may provide us with tools for the diagnosis and treatment of diseases such as vitiligo and malignant melanoma.
Asunto(s)
Hipopigmentación/inmunología , Melanoma/complicaciones , Neoplasias Cutáneas/complicaciones , Animales , Humanos , Melanoma/inmunología , Neoplasias Cutáneas/inmunología , Vitíligo/inmunologíaRESUMEN
Several distinct clinical forms of mycosis fungoides have been described. Hypopigmented mycosis fungoides should be regarded as a subtype of mycosis fungoides, insofar as it presents some peculiar characteristics that contrast with the clinical features of the classical form. Most patients with hypopigmented mycosis fungoides are younger than patients typically diagnosed with classical mycosis fungoides. In addition to typical dark-skinned individuals impairment, hypopigmented mycosis fungoides has also been described in Asian patients. The prognosis for hypopigmented mycosis fungoides is much better than for classical mycosis fungoides: hypopigmented mycosis fungoides is diagnosed when there are only patches of affected skin, and lesions usually will not progress beyond terminal stages, although they can persist for many years. Diagnosis should involve clinicopathologic correlation: skin biopsy analysis often reveals intense epidermotropism, characterized by haloed, large, and atypical CD8+ lymphocytes with convoluted nuclei, in contrast to mild to moderate dermal lymphocytic infiltrate. These CD8+ cells, which participate in T helper 1-mediated immune responses, prevent evolution to mycosis fungoides plaques and tumors and could be considered the main cause of the inhibition of melanogenesis. Therefore, hypopigmentation could be considered a marker of good prognosis for mycosis fungoides.
Ultimamente diferentes formas clínicas da micose fungoide têm sido descritas. A micose fungoide hipocromiante pode ser considerada um subtipo da micose fungoide, apresentando algumas características peculiares que contrastam com os achados da forma clássica da micose fungoide. A maioria dos pacientes com micose fungoide hipocromiante são mais jovens que aqueles acometidos pela micose fungoide clássica. Esta variante é descrita principalmente em indivíduos melanodérmicos (afroamericanos e asiáticos). O prognóstico é melhor que o observado para a forma clássica: ao diagnóstico, os pacientes apresentam somente "patches", que tendem a perdurar por longos períodos, sem evolução para estágios mais avançados. O diagnóstico é feito através da correlação clinicopatológica: biópsia da lesão cutânea frequentemente revela intenso epidermotropismo, caracterizado por linfócitos CD8+ atípicos, grandes, com halo e núcleo convoluto, contrastando com o infiltrado dérmico leve a moderado. Estas células CD8+, que participam do perfil de resposta T helper-1, impediriam a evolução da doença para o desenvolvimento de placas infiltradas e tumores, além de determinar a inibição da melanogênese nas lesões hipocrômicas. Portanto, a hipocromia poderia ser considerada um marcador de bom prognóstico na micose fungoide.
Asunto(s)
Femenino , Humanos , Masculino , Hipopigmentación , Micosis Fungoide , Neoplasias Cutáneas , Biopsia , /inmunología , /patología , Hipopigmentación/inmunología , Hipopigmentación/patología , Hipopigmentación/fisiopatología , Micosis Fungoide/inmunología , Micosis Fungoide/patología , Micosis Fungoide/fisiopatología , Pronóstico , Neoplasias Cutáneas/inmunología , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/fisiopatologíaRESUMEN
Vitiligo is an autoimmune disease characterized by destruction of melanocytes, leaving 0.5% of the population with progressive depigmentation. Current treatments offer limited efficacy. We report that modified inducible heat shock protein 70 (HSP70i) prevents T cell-mediated depigmentation. HSP70i is the molecular link between stress and the resultant immune response. We previously showed that HSP70i induces an inflammatory dendritic cell (DC) phenotype and is necessary for depigmentation in vitiligo mouse models. Here, we observed a similar DC inflammatory phenotype in vitiligo patients. In a mouse model of depigmentation, DNA vaccination with a melanocyte antigen and the carboxyl terminus of HSP70i was sufficient to drive autoimmunity. Mutational analysis of the HSP70i substrate-binding domain established the peptide QPGVLIQVYEG as invaluable for DC activation, and mutant HSP70i could not induce depigmentation. Moreover, mutant HSP70iQ435A bound human DCs and reduced their activation, as well as induced a shift from inflammatory to tolerogenic DCs in mice. HSP70iQ435A-encoding DNA applied months before spontaneous depigmentation prevented vitiligo in mice expressing a transgenic, melanocyte-reactive T cell receptor. Furthermore, use of HSP70iQ435A therapeutically in a different, rapidly depigmenting model after loss of differentiated melanocytes resulted in 76% recovery of pigmentation. Treatment also prevented relevant T cells from populating mouse skin. In addition, ex vivo treatment of human skin averted the disease-related shift from quiescent to effector T cell phenotype. Thus, HSP70iQ435A DNA delivery may offer potent treatment opportunities for vitiligo.
Asunto(s)
Autoinmunidad/inmunología , Terapia Genética , Proteínas HSP70 de Choque Térmico/uso terapéutico , Hipopigmentación/inmunología , Proteínas Mutantes/uso terapéutico , Vitíligo/inmunología , Vitíligo/terapia , Animales , Células Presentadoras de Antígenos/inmunología , Antígenos/inmunología , Células Dendríticas/inmunología , Progresión de la Enfermedad , Proteínas HSP70 de Choque Térmico/genética , Proteínas HSP70 de Choque Térmico/metabolismo , Humanos , Inflamación/patología , Activación de Linfocitos/inmunología , Ratones , Ratones Endogámicos C57BL , Proteínas Mutantes/metabolismo , Péptidos/química , Péptidos/metabolismo , Fenotipo , Piel/inmunología , Piel/patología , Linfocitos T/inmunología , Transcripción Genética , Transfección , Vacunación , Vitíligo/patologíaRESUMEN
Several distinct clinical forms of mycosis fungoides have been described. Hypopigmented mycosis fungoides should be regarded as a subtype of mycosis fungoides, insofar as it presents some peculiar characteristics that contrast with the clinical features of the classical form. Most patients with hypopigmented mycosis fungoides are younger than patients typically diagnosed with classical mycosis fungoides. In addition to typical dark-skinned individuals impairment, hypopigmented mycosis fungoides has also been described in Asian patients. The prognosis for hypopigmented mycosis fungoides is much better than for classical mycosis fungoides: hypopigmented mycosis fungoides is diagnosed when there are only patches of affected skin, and lesions usually will not progress beyond terminal stages, although they can persist for many years. Diagnosis should involve clinicopathologic correlation: skin biopsy analysis often reveals intense epidermotropism, characterized by haloed, large, and atypical CD8+ lymphocytes with convoluted nuclei, in contrast to mild to moderate dermal lymphocytic infiltrate. These CD8+ cells, which participate in T helper 1-mediated immune responses, prevent evolution to mycosis fungoides plaques and tumors and could be considered the main cause of the inhibition of melanogenesis. Therefore, hypopigmentation could be considered a marker of good prognosis for mycosis fungoides.