RESUMEN
Dermatophytic pseudomycetoma is a rare invasive infection, involving both immunocompetent and immunocompromised individuals. Since the discovery of inherited immune disorders such as the impairment of CARD9 gene, extended dermatophyte infections are mostly ascribed to any of these host factors. This study is to present and explore the potential causes in a fatal dermatophytic pseudomycetoma patient. We present a chronic and deep pseudomycetoma caused by the common dermatophyte Microsporum canis which ultimately led to the death of the patient. Mycological examination, genetic studies and host immune responses against fungi were performed to explore the potential factors. The patient had decreased lymphocyte counts with significantly reduced CD4+ T cells, although all currently known genetic parameters proved to be normal. Through functional studies, we demonstrated that peripheral blood mononuclear cells from the patient showed severe impairment of adaptive cytokine production upon fungus-specific stimulation, whereas innate immune responses were partially defective. This is, to our knowledge, the first report of fatal dermatophytic pseudomycetoma in a patient with non-HIV CD4 lymphocytopenia, which highlights the importance of screening for immune deficiencies in patients with deep dermatophytosis.
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Dermatomicosis , Microsporum , Enfermedades Raras , Humanos , Dermatomicosis/genética , Dermatomicosis/inmunología , Dermatomicosis/microbiología , Micetoma/genética , Micetoma/inmunología , Micetoma/microbiología , Femenino , Persona de Mediana Edad , Microsporum/aislamiento & purificación , Resultado Fatal , Caspasa 9/genética , Receptores de Interleucina-7/genética , Mutación , Enfermedades Raras/genética , Enfermedades Raras/inmunología , Enfermedades Raras/microbiología , Recuento de Linfocito CD4 , Inmunidad InnataAsunto(s)
Antineoplásicos Inmunológicos/uso terapéutico , Comercio , Desarrollo de Medicamentos , Inmunoterapia , Neuroblastoma/tratamiento farmacológico , Defensa del Paciente , Enfermedades Raras/tratamiento farmacológico , Terapias en Investigación , Factores de Edad , Antineoplásicos Inmunológicos/economía , Comercio/economía , Análisis Costo-Beneficio , Difusión de Innovaciones , Aprobación de Drogas , Costos de los Medicamentos , Desarrollo de Medicamentos/economía , Gangliósidos/antagonistas & inhibidores , Gangliósidos/inmunología , Humanos , Inmunoterapia/economía , Neuroblastoma/economía , Neuroblastoma/inmunología , Neuroblastoma/patología , Defensa del Paciente/economía , Enfermedades Raras/economía , Enfermedades Raras/inmunología , Enfermedades Raras/patología , Terapias en Investigación/economía , Resultado del TratamientoRESUMEN
INTRODUCTION: The impact of SARS-CoV-2 in rare disease populations has been underreported. Gaucher disease (GD) is a prototype rare disease that shares with SARS-CoV-2 a disruption of the lysosomal pathway. MATERIALS-METHODS: Retrospective analysis of 11 patients with Type 1 GD who developed COVID-19 between March 2020 and March 2021. RESULTS: Seven male and 4 female patients with Type 1 GD developed COVID-19. One was a pediatric patient (8 years old) while the remainder were adults, median age of 44 years old (range 21 to 64 years old). Two patients required hospitalization though none required intensive care or intubation. All 11 patients recovered from COVID-19 and there were no reported deaths. CONCLUSIONS: Our case series suggests that GD patients acquired COVID-19 at a similar frequency as the general population, though experienced a milder overall course despite harboring underlying immune system dysfunction and other known co-morbidities that confer high risk of adverse outcomes from SARS-CoV-2 infection.
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COVID-19/inmunología , Enfermedad de Gaucher/inmunología , Enfermedad de Gaucher/virología , Sistema Inmunológico/inmunología , Enfermedades Raras/inmunología , SARS-CoV-2/inmunología , Adulto , COVID-19/virología , Niño , Comorbilidad , Femenino , Hospitalización , Humanos , Masculino , Persona de Mediana Edad , Pandemias/prevención & control , Estudios Retrospectivos , Adulto JovenRESUMEN
The differential diagnosis for immune-mediated myelopathies is broad. Although clinical manifestations overlap, certain presentations are suggestive of a particular myelopathy etiology. Spine MRI lesion characteristics including the length and location, and the pattern of gadolinium enhancement, help narrow the differential diagnosis and exclude an extrinsic compressive cause. The discovery of specific antibodies that serve as biomarkers of myelitis such as aquaporin-4-IgG and myelin-oligodendrocyte -glycoprotein-IgG (MOG-IgG), has improved our understanding of myelitis pathophysiology and facilitated diagnosis. In this review we will focus on the pathophysiology, clinical presentation, imaging findings and treatment and outcomes of uncommon immune-mediated myelopathies.
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Mielitis , Acuaporina 4 , Autoanticuerpos/sangre , Autoanticuerpos/inmunología , Biomarcadores , Medios de Contraste , Diagnóstico Diferencial , Gadolinio , Humanos , Imagen por Resonancia Magnética , Mielitis/diagnóstico , Mielitis/tratamiento farmacológico , Mielitis/inmunología , Mielitis/fisiopatología , Enfermedades Raras/diagnóstico , Enfermedades Raras/tratamiento farmacológico , Enfermedades Raras/inmunologíaRESUMEN
The pathophysiology of complex neuroimmunological diseases, such as multiple sclerosis and autoimmune encephalitis, remains puzzling - various mechanisms that are difficult to dissect seem to contribute, hampering the understanding of the processes involved. Some rare neuroimmunological diseases are easier to study because their presentation and pathogenesis are more homogeneous. The investigation of these diseases can provide fundamental insights into neuroimmunological pathomechanisms that can in turn be applied to more complex diseases. In this Review, we summarize key mechanistic insights into three such rare but paradigmatic neuroimmunological diseases - Susac syndrome, Rasmussen encephalitis and narcolepsy type 1 - and consider the implications of these insights for the study of other neuroimmunological diseases. In these diseases, the combination of findings in humans, different modalities of investigation and animal models has enabled the triangulation of evidence to validate and consolidate the pathomechanistic features and to develop diagnostic and therapeutic strategies; this approach has provided insights that are directly relevant to other neuroimmunological diseases and applicable in other contexts. We also outline how next-generation technologies and refined animal models can further improve our understanding of pathomechanisms, including cell-specific and antigen-specific CNS immune responses, thereby paving the way for the development of targeted therapeutic approaches.
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Enfermedades del Sistema Inmune/inmunología , Enfermedades del Sistema Nervioso/inmunología , Neuroinmunomodulación/fisiología , Enfermedades Raras/inmunología , Animales , Humanos , Enfermedades del Sistema Inmune/diagnóstico por imagen , Enfermedades del Sistema Inmune/metabolismo , Enfermedades del Sistema Nervioso/diagnóstico por imagen , Enfermedades del Sistema Nervioso/metabolismo , Enfermedades Raras/diagnóstico por imagen , Enfermedades Raras/metabolismo , Síndrome de Susac/diagnóstico por imagen , Síndrome de Susac/inmunología , Síndrome de Susac/metabolismoRESUMEN
BACKGROUND: Immunosuppressed solid organ transplant recipients (SOTRs) have elevated rates of certain rare cancers caused by viruses. Evaluating risk of rare cancers among SOTRs may provide etiological clues for additional cancers linked to poor immunity and viral infections. METHODS: We performed a cohort study of 262 455 SOTRs (1987-2014) from the US SOTR registry linked to 17 population-based cancer registries. First cancers in SOTRs were categorized using an established classification scheme based on site and histology. Standardized incidence ratios (SIRs) compared risk in SOTRs with the general population. We used Poisson regression to calculate incidence rate ratios according to immune-related SOTR characteristics, including time since transplant (ie, duration of immunosuppression). All statistical tests were 2-sided. RESULTS: We examined 694 distinct cancer subtypes, with 33 manifesting statistically significantly elevated SIRs (Bonferroni P < 7.2 × 10-5). All 33 are rare (incidence <6 per 100 000 person-years) and several have known viral etiology (eg, Merkel cell carcinoma: SIR = 24.7, 95% confidence interval [CI] = 20.8 to 29.1). Additional cancers that were increased include squamous cell carcinomas of the lip (SIR range = 18.3-19.8), eye and adnexa (SIR = 13.8, 95% CI = 7.9 to 22.3), salivary gland (SIR = 9.3, 95% CI = 6.1 to 13.5), and nasal cavity and sinuses (SIR = 4.5, 95% CI = 2.8 to 6.8); sebaceous adenocarcinoma (SIR = 34.3, 95% CI = 26.3 to 44.0); malignant fibrous histiocytoma (15.4); and subtypes of bladder, kidney, lung, and colon cancer (SIR range = 3.2-13.3). Incidence of several cancers increased over time since transplant (Ptrend < .05), including squamous cell carcinomas of the lip, salivary gland, and anogenital sites. CONCLUSIONS: SOTRs experience elevated rates of several rare cancers. Because some of these cancers exhibit aggressive behavior with poor outcomes, it is important to further characterize the role of immunity and the potential involvement of oncogenic viruses to improve prevention and treatment.
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Huésped Inmunocomprometido/inmunología , Neoplasias/epidemiología , Trasplante de Órganos/efectos adversos , Enfermedades Raras/epidemiología , Adolescente , Adulto , Anciano , Carcinoma de Células de Merkel/epidemiología , Carcinoma de Células de Merkel/etiología , Carcinoma de Células de Merkel/patología , Carcinoma de Células Escamosas/epidemiología , Carcinoma de Células Escamosas/etiología , Carcinoma de Células Escamosas/inmunología , Carcinoma de Células Escamosas/patología , Femenino , Humanos , Tolerancia Inmunológica/inmunología , Terapia de Inmunosupresión/efectos adversos , Masculino , Persona de Mediana Edad , Neoplasias/etiología , Neoplasias/inmunología , Neoplasias/patología , Enfermedades Raras/etiología , Enfermedades Raras/inmunología , Enfermedades Raras/patología , Sistema de Registros , Factores de Riesgo , Sarcoma de Kaposi/epidemiología , Sarcoma de Kaposi/etiología , Sarcoma de Kaposi/inmunología , Sarcoma de Kaposi/patología , Neoplasias Cutáneas , Receptores de TrasplantesRESUMEN
Imlifidase (IdefirixTM), a cysteine protease derived from the immunoglobulin G (IgG)degrading enzyme of Streptococcus (S.) pyogenes is being developed by Hansa Biopharma AB for treatment of transplant rejection and rare IgG-mediated autoimmune conditions. In August 2020, intravenous imlifidase received its first global approval in the EU for desensitization treatment of highly sensitized adult kidney transplant patients with positive crossmatch against an available deceased donor. Imlifidase is currently undergoing clinical evaluation for the prevention of kidney transplant rejection in the USA, Australia, France and Austria, and clinical development is underway for anti-glomerular basement membrane disease, and for Guillain-Barre syndrome in France, the UK and the Netherlands. This article summarizes the milestones in the development of imlifidase leading to this first approval for desensitization treatment of highly sensitized adult kidney transplant patients with positive crossmatch against an available deceased donor.
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Enfermedad por Anticuerpos Antimembrana Basal Glomerular/tratamiento farmacológico , Proteínas Bacterianas/uso terapéutico , Aprobación de Drogas , Rechazo de Injerto/tratamiento farmacológico , Síndrome de Guillain-Barré/tratamiento farmacológico , Administración Intravenosa , Animales , Enfermedad por Anticuerpos Antimembrana Basal Glomerular/inmunología , Proteínas Bacterianas/farmacología , Ensayos Clínicos Fase I como Asunto , Ensayos Clínicos Fase II como Asunto , Desensibilización Inmunológica/métodos , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos , Unión Europea , Síndrome de Guillain-Barré/inmunología , Antígenos HLA/inmunología , Humanos , Inmunoglobulina G/inmunología , Inmunoglobulina G/metabolismo , Fallo Renal Crónico/cirugía , Trasplante de Riñón/efectos adversos , Ensayos Clínicos Controlados Aleatorios como Asunto , Enfermedades Raras/tratamiento farmacológico , Enfermedades Raras/inmunologíaRESUMEN
BACKGROUND: Decreased tumor content (TC) in resection specimens after neoadjuvant therapy is used to predict prognosis. We investigated whether TC assessed in biopsy specimens or the shift in TC from baseline to on-treatment can be used accordingly to predict response in patients with rare tumors who were treated with pembrolizumab. METHODS: A total of 57 tumors (represented by 173 baseline and 179 on-treatment biopsies) from 57 patients with rare tumors participating in an ongoing phase II clinical trial of pembrolizumab were evaluated. TC was estimated on H&E-stained slides and tumors were dichotomized into low and high TC according to a cut-off of 10%. Necrosis, proliferative fibrosis (PF) and normal tissue were assessed in on-treatment biopsies. TC at baseline and on-treatment, as well as the shift in TC from baseline to on-treatment, was correlated with clinical response defined according to Response Evaluation Criteria in Solid Tumors. RESULTS: A decrease in TC was seen in 14% (n=8); no change in TC was seen in 75% (n=43); and an increase in TC from baseline to on-treatment was seen in 11% (n=6). Objective response was significantly associated with decrease in TC from baseline to on-treatment (38%, 3/8) compared with no change/increase in TC (6%, 3/49) (p=0.031). Patients with a decrease in TC had a significantly increased time to progression (TTP) (75% probability) compared with patients with an increase (20% probability) or no change in TC (19% probability) (p=0.0042). Low TC was seen in 23% (13/57) of the tumors at baseline and in 26% (15/57) on-treatment. High TC was seen in 77% (44/57) of tumors at baseline and in 74% (42/57) on-treatment. No significant associations with response were seen for necrosis, PF or normal tissue in on-treatment biopsies. CONCLUSION: Patients with a decrease in TC from baseline to on-treatment had a significant improvement in objective response and a longer TTP. Our data suggest that the shift in TC might be used to predict response to pembrolizumab in rare tumors. However, further investigations in larger cohorts are needed to determine the clinical value of TC, the shift in TC and the cut-off of 10% assessed in biopsies. TRIAL REGISTRATION NUMBER: NCT02721732.
Asunto(s)
Anticuerpos Monoclonales Humanizados/administración & dosificación , Antineoplásicos Inmunológicos/administración & dosificación , Biomarcadores de Tumor/análisis , Neoplasias/diagnóstico , Enfermedades Raras/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales Humanizados/efectos adversos , Antineoplásicos Inmunológicos/efectos adversos , Biopsia , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/tratamiento farmacológico , Neoplasias/inmunología , Neoplasias/patología , Pronóstico , Enfermedades Raras/tratamiento farmacológico , Enfermedades Raras/inmunología , Enfermedades Raras/patología , Resultado del Tratamiento , Adulto JovenRESUMEN
INTRODUCTION: Rare acquired bleeding disorders include a wide spectrum of coagulopathies characterized by spontaneous or post-trauma and post-surgery hemorrhages in patients without a previous personal or family history of bleeding. AREAS COVERED: This review, based on a Medline/PubMed search during the last 20 years, will focus mainly on rare acquired bleeding disorders caused by autoantibodies against coagulation factors, including autoantibodies against factor VIII (acquired hemophilia A), von Willebrand factor (acquired von Willebrand syndrome) and other coagulation factors (factors V, X, XI, and XIII). The pathogenic, laboratory, and clinical features of these rare hemorrhagic conditions will be discussed, with particular attention to their management. EXPERT OPINION: The treatment of rare acquired bleeding disorders includes the control of bleeding and the elimination of the autoantibody and of the underlying disease, when present. As the bleeding clinical phenotype is often severe, the management of affected patients is particularly challenging. Thus, while an early diagnosis of the acquired coagulopathy is essential to start the most appropriate treatment and to improve patients' outcomes, the support of specialized centers is equally important to provide a correct management of such complicated cases.
Asunto(s)
Autoanticuerpos , Inhibidores de Factor de Coagulación Sanguínea , Factores de Coagulación Sanguínea , Hemofilia A , Enfermedades Raras , Enfermedades de von Willebrand , Autoanticuerpos/sangre , Autoanticuerpos/inmunología , Inhibidores de Factor de Coagulación Sanguínea/sangre , Inhibidores de Factor de Coagulación Sanguínea/inmunología , Factores de Coagulación Sanguínea/inmunología , Factores de Coagulación Sanguínea/metabolismo , Hemofilia A/sangre , Hemofilia A/inmunología , Humanos , Enfermedades Raras/sangre , Enfermedades Raras/inmunología , Enfermedades de von Willebrand/sangre , Enfermedades de von Willebrand/inmunologíaRESUMEN
Plasma cell features are encountered in a variety of non-plasma cell neoplasias, especially carcinomas of a discohesive type, such as those occurring in the digestive tract and breast. Lobular carcinomas of the breast present themselves in a variety of architectural patterns and many cell morphologies, including plasmacytoid types. A matching plasma cell phenotype is sometimes an associated feature. We report a case of a moderate grade invasive lobular carcinoma with focal plasmacytoid morphology and aberrant expression of plasma cell markers in a patient previously diagnosed with multiple myeloma. Paradoxical plasma cell immunoprofiles can be encountered in many malignancies, causing serious diagnostic problems, even more so with those occurring in discohesive carcinomas in multiple myeloma patients.
Asunto(s)
Neoplasias de la Mama/patología , Carcinoma Lobular/patología , Mieloma Múltiple/patología , Células Plasmáticas/patología , Enfermedades Raras/patología , Tejido Adiposo/patología , Anciano , Anticuerpos Antineoplásicos , Neoplasias de la Mama/inmunología , Carcinoma Lobular/inmunología , Femenino , Humanos , Cadenas kappa de Inmunoglobulina/análisis , Inmunohistoquímica , Mieloma Múltiple/inmunología , Adhesión en Parafina/métodos , Fenotipo , Células Plasmáticas/inmunología , Enfermedades Raras/inmunología , Sindecano-1/análisisRESUMEN
Network biology has the capability to integrate, represent, interpret, and model complex biological systems by collectively accommodating biological omics data, biological interactions and associations, graph theory, statistical measures, and visualizations. Biological networks have recently been shown to be very useful for studies that decipher biological mechanisms and disease etiologies and for studies that predict therapeutic responses, at both the molecular and system levels. In this review, we briefly summarize the general framework of biological network studies, including data resources, network construction methods, statistical measures, network topological properties, and visualization tools. We also introduce several recent biological network applications and methods for the studies of rare diseases.
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Biología Computacional/métodos , Enfermedades Raras/genética , Programas Informáticos , Algoritmos , Bases de Datos Genéticas , Redes Reguladoras de Genes , Humanos , Modelos Biológicos , Mapas de Interacción de Proteínas/genética , Enfermedades Raras/etiología , Enfermedades Raras/inmunología , Enfermedades Raras/metabolismoAsunto(s)
Leucemia Linfoide , Enfermedades Raras , Humanos , Leucemia Linfoide/clasificación , Leucemia Linfoide/inmunología , Leucemia Linfoide/patología , Leucemia Linfoide/terapia , Enfermedades Raras/clasificación , Enfermedades Raras/inmunología , Enfermedades Raras/patología , Enfermedades Raras/terapiaRESUMEN
BACKGROUND: Sarcomatoid carcinoma of unknown primary (SCUP) is a rare entity of either poorly differentiated carcinoma with sarcoma-like differentiation or a true mixed lineage neoplasm. Limited data regarding clinicopathological profile and management exists. METHODS: We retrospectively reviewed the MD Anderson Cancer of Unknown Primary database and tumor registry to identify 48 SCUP patients between 2001 and 2017. Patient characteristics, pathology, molecular diagnostics, treatments, and outcomes were obtained. Kaplan-Meier method was used to estimate overall survival (OS) and compared using log rank test. RESULTS: Median age at diagnosis was 59 years (range 27-86). Majority of patients were female (58%) and presented with ≥3 metastatic sites (52%), commonly lymph node (50%), bone (42%), lung (27%), and liver (21%). First line treatment included chemotherapy (35%), surgery (27%), and radiation (24%). Gemcitabine and docetaxel (18%) was the most common chemotherapy regimen. Median OS for entire cohort was 11 months (95% CI: 5.6 to 16.4). Poor performance status (PS), > 1 metastatic site, elevated lactate dehydrogenase (LDH), and high neutrophil-to-lymphocyte ratio (NLR) were significantly associated with worse OS on univariate analyses. On multivariate analyses, poor PS (HR 8.7; 95%CI: 3.0-25.0; p < 0.001) and high NLR (HR 3.4; 95%CI: 1.3-8.8; p = 0.011) emerged as independent prognostic factors for OS. CONCLUSIONS: SCUP is a rare presentation with an aggressive clinical course and limited survival. Diagnosis is difficult to make and requires careful review and synthesis of histology, immunohistochemistry, and molecular diagnostics. Chemotherapy resistance remains a challenge. Early mutational profiling is warranted, and clinical trial participation should be encouraged for this subset.
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Carcinosarcoma/mortalidad , Carcinosarcoma/patología , Neoplasias Primarias Desconocidas/mortalidad , Neoplasias Primarias Desconocidas/patología , Enfermedades Raras/mortalidad , Enfermedades Raras/patología , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/inmunología , Carcinosarcoma/inmunología , Carcinosarcoma/terapia , Terapia Combinada , Resistencia a Antineoplásicos , Femenino , Estudios de Seguimiento , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Terapia Molecular Dirigida , Neoplasias Primarias Desconocidas/inmunología , Neoplasias Primarias Desconocidas/terapia , Pronóstico , Estudios Prospectivos , Enfermedades Raras/inmunología , Enfermedades Raras/terapia , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
The pervasive use of therapeutic antibodies targeting programmed cell death protein 1 (PD-1) to boost anti-tumor immunity has positioned this approach to become the standard-of-care for some solid tumor malignancies. However, little is known as to how blockade of PD-1 may alter the function or phenotype of tumor-infiltrating lymphocytes (TIL). We used our ongoing Phase II clinical trial of pembrolizumab for patients with rare solid tumors from various types (NCT02721732) with matched core biopsies taken at baseline and after initial dose of anti-PD-1 (15-21 days post-dose) to elucidate this question. One fresh core needle biopsy was used to propagate TIL ex vivo to analyze phenotype and function using flow cytometry in both CD8+ and CD4+ TIL populations. An enriched CTLA-4 expression in the CD4+ TIL population was observed in TIL expanded from the on-treatment samples compared to TIL expanded from the matched baseline (n = 22, p = 0.0007) but was not observed in patients who experienced tumor regression. Impact on functionality was evaluated by measuring secretion of 65 soluble factors by expanded TIL from 26 patients at baseline and on-treatment. The CD8+ TIL population demonstrated a diminished cytokine secretion profile post-pembrolizumab. Overall, our study assesses the ramifications of one dose of anti-PD-1 on TIL in rare solid tumor types.
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Anticuerpos Monoclonales Humanizados/administración & dosificación , Antígeno B7-H1 , Linfocitos T CD4-Positivos , Linfocitos T CD8-positivos , Linfocitos Infiltrantes de Tumor , Proteínas de Neoplasias , Neoplasias , Enfermedades Raras , Antígeno B7-H1/antagonistas & inhibidores , Antígeno B7-H1/inmunología , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/patología , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/patología , Antígeno CTLA-4/inmunología , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/inmunología , Humanos , Linfocitos Infiltrantes de Tumor/inmunología , Linfocitos Infiltrantes de Tumor/patología , Masculino , Persona de Mediana Edad , Proteínas de Neoplasias/antagonistas & inhibidores , Proteínas de Neoplasias/inmunología , Neoplasias/tratamiento farmacológico , Neoplasias/inmunología , Neoplasias/patología , Enfermedades Raras/tratamiento farmacológico , Enfermedades Raras/inmunología , Enfermedades Raras/patologíaRESUMEN
The term congenital hypopigmentary disorders refers to a wide group of heterogeneous hereditary diseases, clinically characterized by inborn pigmentary defects of the iris, hair, and/or skin. They include Gray Hair Syndromes (GHSs), a rare group of autosomal recessive genodermatosis hallmarked by inborn silvery gray hair. GHSs encompass Griscelli, Chediakâ»Higashi, Elejalde, and Cross syndromes, which are all characterized by a broad spectrum of severe multisystem disorders, including neurological, ocular, skeletal, and immune system impairment. In this manuscript, we describe in detail the clinical, trichoscopic, and genetic features of a rare case of Griscelli syndrome; moreover, we provide an overview of all the GHSs known to date. Our report highlights how an accurate clinical examination with noninvasive methods, like trichoscopy, may play a crucial rule in diagnosis of rare and potentially lethal genetic syndromes such as Griscelli syndrome, in which timely diagnosis and therapy may modify the clinical course, quality of life, and likelihood of survival.
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Trastornos de la Pigmentación/diagnóstico , Trastornos de la Pigmentación/genética , Enfermedades Raras/diagnóstico , Enfermedades Raras/genética , Anomalías Múltiples/diagnóstico , Anomalías Múltiples/genética , Anomalías Múltiples/inmunología , Anomalías Múltiples/patología , Adulto , Síndrome de Chediak-Higashi/diagnóstico , Síndrome de Chediak-Higashi/genética , Síndrome de Chediak-Higashi/inmunología , Síndrome de Chediak-Higashi/patología , Preescolar , Anomalías Craneofaciales/diagnóstico , Anomalías Craneofaciales/genética , Anomalías Craneofaciales/inmunología , Anomalías Craneofaciales/patología , Diagnóstico Diferencial , Femenino , Cabello/anomalías , Pérdida Auditiva Sensorineural/diagnóstico , Pérdida Auditiva Sensorineural/genética , Pérdida Auditiva Sensorineural/inmunología , Pérdida Auditiva Sensorineural/patología , Humanos , Hipertricosis/inducido químicamente , Iris/anomalías , Masculino , Mutación , Síndromes Neurocutáneos/diagnóstico , Síndromes Neurocutáneos/genética , Síndromes Neurocutáneos/inmunología , Síndromes Neurocutáneos/patología , Piebaldismo/diagnóstico , Piebaldismo/genética , Piebaldismo/inmunología , Piebaldismo/patología , Trastornos de la Pigmentación/inmunología , Trastornos de la Pigmentación/patología , Calidad de Vida , Enfermedades Raras/inmunología , Enfermedades Raras/patología , Anomalías Cutáneas , Proteínas rab27 de Unión a GTP/genéticaRESUMEN
Both profound neutropenia and functional phagocyte disorders render patients susceptible to recurrent, unusual, and/or life-threatening infections. Many disorders also have nonhematologic manifestations and a substantial risk of leukemogenesis. Diagnosis relies on clinical suspicion and interrogation of the complete blood count with differential/bone marrow examination coupled with immunologic and genetic analyses. Treatment of the quantitative neutrophil disorders depends on granulocyte colony-stimulating factor, whereas management of functional phagocyte disease is reliant on antimicrobials and/or targeted therapies. Hematopoietic stem cell transplant remains the only curative option for most disorders but is not used on a routine basis.
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Síndromes Congénitos de Insuficiencia de la Médula Ósea/terapia , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/métodos , Neutropenia/congénito , Fagocitos/metabolismo , Enfermedades Raras/terapia , Niño , Síndromes Congénitos de Insuficiencia de la Médula Ósea/genética , Síndromes Congénitos de Insuficiencia de la Médula Ósea/inmunología , Humanos , Leucemia/genética , Leucemia/inmunología , Leucemia/terapia , Síndromes Mielodisplásicos/genética , Síndromes Mielodisplásicos/inmunología , Síndromes Mielodisplásicos/terapia , Neutropenia/genética , Neutropenia/inmunología , Neutropenia/terapia , Neutrófilos/inmunología , Neutrófilos/metabolismo , Fagocitos/inmunología , Enfermedades Raras/genética , Enfermedades Raras/inmunologíaAsunto(s)
Arteritis/diagnóstico , Lupus Eritematoso Sistémico/complicaciones , Enfermedades Raras/diagnóstico , Enfermedades Cutáneas Vasculares/diagnóstico , Adulto , Arteritis/inmunología , Arteritis/patología , Biopsia , Femenino , Humanos , Lupus Eritematoso Sistémico/inmunología , Persona de Mediana Edad , Enfermedades Raras/inmunología , Enfermedades Raras/patología , Piel/irrigación sanguínea , Piel/inmunología , Piel/patología , Enfermedades Cutáneas Vasculares/inmunología , Enfermedades Cutáneas Vasculares/patologíaRESUMEN
INTRODUCTION: Immune Mediated Inner Ear Disease (IMIED) is a rare form of sensorineural bilateral hearing loss, usually progressing in weeks to months and responsive to immunosuppressive treatment. Despite recent advances, there is no consensus on diagnosis and optimal treatment. METHODS: A review of articles on IMIED from the last 10 years was conducted using PubMed® database. RESULTS: IMIED is a rare disease, mostly affecting middle aged women. It may be a primary ear disease or secondary to autoimmune systemic disease. A dual immune response (both cellular and humoral) seems to be involved. Cochlin may be the inner ear protein targeted in this disease. Distinction from other (core common) forms of neurosensory hearing loss is a challenge. Physical examination is mandatory for exclusion of other causes of hearing loss; audiometry identifies characteristic hearing curves. Laboratory and imaging studies are controversial since no diagnostic marker is available. CONCLUSION: Despite recent research, IMIED diagnosis remains exclusive. Steroids are the mainstay treatment; other therapies need further investigation. For refractory cases, cochlear implantation is an option and with good relative outcome.