Asunto(s)
Proteína del Grupo de Complementación A de la Anemia de Fanconi , Anemia de Fanconi , Mutación , Fenotipo , Hermanos , Humanos , Anemia de Fanconi/genética , Anemia de Fanconi/diagnóstico , Proteína del Grupo de Complementación A de la Anemia de Fanconi/genética , Masculino , Femenino , Predisposición Genética a la Enfermedad , Análisis Mutacional de ADN , Piel/patología , NiñoRESUMEN
Body Dysmorphic Disorder (BDD) is an underexplored psychiatric condition in Middle Eastern countries, particularly in patients with dermatologic concerns, where alterations in appearance may elevate the risk of BDD. We studied patients at Jordan University Hospital's general dermatology and cosmetic clinics from July to September 2022, comparing them to healthy controls. Patients with dermatologic conditions were evaluated per the International Classification of Diseases (ICD-10) criteria by trained dermatologists. All participants completed the Dysmorphic Concerns Questionnaire (DCQ), Perceived Stress Scale, Patient Health Questionnaire-2, General Anxiety Disorder Assessment tool-2. We assessed BDD prevalence using four DCQ cutoffs: 9, 11, 14, and 17, reporting effect sizes as odds ratios (OR). Our study involved 1500 participants, with an average age of 29.3 (± 14.8) years and a female-to-male ratio of 3.15-to-1. At the 9, 11, 14, and 17 DCQ cutoffs, BDD prevalence was 78.2%, 54.2%, 26.5%, and 11.7%, respectively. Patients with dermatologic concerns were more likely to exhibit clinical BDD symptoms than controls at the 11-cutoff (OR: 1.26; 95% CI 1.01-1.58; p < 0.05). Conversely, those with cosmetic concerns were more prone to clinical BDD than controls at cutoffs 9 (OR: 2.26; 95% CI 1.28-3.97; p < 0.05) and 11 (OR: 1.50; 95% CI 1.03-2.20; p < 0.05). Our logistic regression revealed consistent associations between higher DCQ scores and elevated anxiety, depression, perceived skin disease-related stigma, and reduced quality of life (p < 0.05). In conclusion, patients with dermatologic issues and those seeking cosmetic procedures are at significant risk of developing BDD, necessitating proactive screening and referrals for specialized care by dermatologists due to the associated psychological distress and unproductive consultations. Providing specialized training for healthcare professionals to establish an integrated care approach to address the needs of patients with BDD should be the focus of future research projects.
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Trastornos de Ansiedad , Trastorno Dismórfico Corporal , Pruebas Psicológicas , Autoinforme , Adulto , Humanos , Masculino , Femenino , Trastorno Dismórfico Corporal/diagnóstico , Trastorno Dismórfico Corporal/epidemiología , Trastorno Dismórfico Corporal/psicología , Jordania , Estudios de Casos y Controles , Prevalencia , Calidad de Vida , Encuestas y CuestionariosRESUMEN
PURPOSE: Skin cancers are among the commonest cancers worldwide, and the incidence of melanoma and non-melanoma skin cancer (NMSC) continues to rise worldwide. However, there are no comprehensive reports on skin cancer incidence in Jordan during the past two decades. This report investigates the incidence of skin cancers in Jordan, in particular their time trends for the period 2000-2016. MATERIALS AND METHODS: Data on malignant melanomas (MMs), squamous cells carcinomas (SCCs), and basal cell carcinomas (BCCs) were extracted from the Jordan Cancer Registry for the period between 2000 and 2016. Age-specific and overall age-standardized incidence rates (ASIRs) were computed. RESULTS: Two thousand seventy patients were diagnosed with at least one BCC, 1,364 with SCC, and 258 with MM. ASIRs were 28, 19, and 4 per 100,000 person-years for BCC, SCC, and MM, respectively. The BCC:SCC incidence ratio was 1.47:1. The risk of men developing SCCs was significantly higher than women (relative risks [RRs], 1.311; 95% CI, 1.197 to 1.436), but significantly lower for BCCs (RR, 0.929; 95% CI, 0.877 to 0.984) or melanomas (RR, 0.465; 95% CI, 0.366 to 0.591). Persons older than 60 years were at a significantly higher risk of developing SCCs (RR, 1.225; 95% CI, 1.119 to 1.340) or melanomas (RR, 2.445; 95% CI, 1.925 to 3.104), but at a significantly lower risk of developing BCCs (RR, 0.885; 95% CI, 0.832 to 0.941). The overall incidence rates of SCCs, BCCs, and melanomas increased over the 16-year study period, but this was not statistically significant. CONCLUSION: To our knowledge, this is the largest epidemiologic study regarding skin cancers in Jordan and in the Arab world. Despite low incidence rates in this study, rates are higher than reported regional figures. This is likely due to standardized, centralized, and mandatory reporting of skin cancers, including NMSC.
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Carcinoma Basocelular , Carcinoma de Células Escamosas , Melanoma , Neoplasias Cutáneas , Masculino , Humanos , Femenino , Incidencia , Jordania , Neoplasias Cutáneas/epidemiología , Melanoma/epidemiología , Carcinoma Basocelular/epidemiología , Carcinoma Basocelular/etiología , Carcinoma de Células Escamosas/complicaciones , Carcinoma de Células Escamosas/epidemiologíaRESUMEN
The morphologic changes in early-stage mycosis fungoides (MF) might overlap with benign inflammatory dermatitis (BID). Previous studies have described altered expression patterns of several proteins in MF, but their diagnostic significance is uncertain. This study aims at examining the frequency of expression of CD45RO, NFkB-p105/p50, JAK3, TOX, and IL-17 proteins by immunohistochemistry. The cohorts included 21 patients of early-stage MF and 19 with benign BID as a control group. CD45RO was positive in all patients of MF and BID. NFkB-p105/p50 showed normal cytoplasmic staining, indicating an inactive status in all patients of both groups. JAK3 was positive in 3 (14%) MF and in 17 (89%) BID patients (p = 0.003). TOX was expressed in 19 (90%) and 13 (68%) patients of MF and BID, respectively (p = 0.120). IL-17 was detected in 13 (62%) MF and in 7 (37%) BID patients (p = 0.056). Co-expression of TOX and IL-17 was seen in 11 (52%) MF patients but in only 3 (16%) BID patients, which was statistically significant (p = 0.021). We conclude that a double expression of TOX and IL-17 may support the diagnosis of MF in the right clinicopathologic setting, while none of the immunohistochemical stains alone provided a significant discrimination between MF and BID.
RESUMEN
This case report describes two severe antiretroviral drug adverse reactions that occurred in the same patient. A 55-year-old HIV-positive African woman received a single epidural triamcinolone injection for pain relief of postherpetic neuralgia. Forty-one days later, she developed severe iatrogenic Cushing's syndrome due to the drug-drug interaction between triamcinolone and her boosted protease inhibitor therapy. The patient's antiretroviral regimen was thus changed to replace her protease inhibitor with the integrase inhibitor raltegravir. Shortly after commencing the drug, the patient developed a severe adverse drug reaction manifesting as Drug Reaction (or Rash) with Eosinophilia and Systemic Symptoms (DRESS) syndrome. First described in 1996, this hypersensitivity syndrome presents with severe skin reaction as well as fever, rash, lymphadenopathy and internal organ involvement with marked eosinophilia. Clinicians should be aware of raltegravir-induced DRESS syndrome as well as the potential for drug-drug interactions due to protease inhibitor-based therapy.
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Antiinflamatorios/uso terapéutico , Síndrome de Hipersensibilidad a Medicamentos , Inhibidores de Integrasa VIH/efectos adversos , Neuralgia Posherpética/tratamiento farmacológico , Seguridad del Paciente , Pirrolidinonas/efectos adversos , Triamcinolona/uso terapéutico , Fármacos Anti-VIH/uso terapéutico , Terapia Antirretroviral Altamente Activa , Interacciones Farmacológicas , Eosinofilia/inducido químicamente , Exantema/inducido químicamente , Femenino , Fiebre/inducido químicamente , Infecciones por VIH/tratamiento farmacológico , Inhibidores de Integrasa VIH/administración & dosificación , Humanos , Pirrolidinonas/administración & dosificación , Raltegravir Potásico , Resultado del TratamientoAsunto(s)
Vesícula/genética , Epidermólisis Ampollosa/genética , Mosaicismo , Enfermedades Periodontales/genética , Trastornos por Fotosensibilidad/genética , Membrana Basal/química , Moléculas de Adhesión Celular/análisis , Niño , Colágeno Tipo VII/análisis , Epidermis/química , Exones , Humanos , Integrina alfa6beta4/análisis , Integrina beta1/análisis , Masculino , Proteínas de la Membrana/análisis , Proteínas de la Membrana/genética , Mutagénesis Insercional , Proteínas de Neoplasias/análisis , Proteínas de Neoplasias/genética , KalininaRESUMEN
BACKGROUND: Epidermolysis bullosa pruriginosa is a rare clinical subtype of dystrophic epidermolysis bullosa characterized by intense pruritus, secondary scratching-induced lesions, and pronounced scarring. OBSERVATIONS: We describe a patient with epidermolysis bullosa pruriginosa who was misdiagnosed as having psychogenic pruritus for several years. Except for nail (toenail) dystrophy, no features of the disease were evident among his immediate family members. An underlying new heterozygous donor splice-site mutation in the type VII collagen gene (IVS55 + 1G>C) was found in both the patient and his family members with nail dystrophy. Inheritance was autosomal dominant. The patient was treated with cyclosporine and experienced significant reduction in pruritus, with subsequent improvement of the skin condition. CONCLUSIONS: Pruritus is an important factor in the development of epidermolysis bullosa pruriginosa and is the focus of management. Patients with this inherited skin disorder can be easily misdiagnosed as having psychogenic pruritus, and this article aims to make physicians aware of this diagnostic pitfall.
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Epidermólisis Ampollosa Distrófica/diagnóstico , Prurito/diagnóstico , Prurito/psicología , Adolescente , Diagnóstico Diferencial , Humanos , MasculinoAsunto(s)
Trasplante de Células/métodos , Colágeno Tipo VII/genética , Epidermólisis Ampollosa Distrófica/terapia , Expresión Génica/efectos de los fármacos , Péptidos y Proteínas de Señalización Intercelular/farmacología , Células Cultivadas , Epidermólisis Ampollosa Distrófica/fisiopatología , Fibroblastos/fisiología , Fibroblastos/trasplante , Expresión Génica/fisiología , Factor de Crecimiento Similar a EGF de Unión a Heparina , Humanos , Péptidos y Proteínas de Señalización Intercelular/genética , Queratinocitos/fisiología , Proteínas Recombinantes/genética , Proteínas Recombinantes/farmacología , Trasplante HomólogoRESUMEN
Autosomal dominant and recessive forms of dystrophic epidermolysis bullosa (DEB) result from mutations in the type VII collagen gene (COL7A1). Although paradigms have emerged for genotype/phenotype correlation in DEB, some pathogenic mutations in COL7A1, notably glycine substitutions within the type VII collagen triple helix, may lead to diagnostic difficulties, since certain glycine substitutions can result in either dominant or recessive mutant alleles. Delineation of glycine substitution mutations into two discrete groups, however, is made difficult by observations that, for some particular glycine substitutions in type VII collagen, the same mutation can result in both dominant and recessive disease. In this report we describe four further glycine missense mutations: p.Gly1483Asp, p.Gly1770Ser, p.Gly2213Arg and p.Gly2369Ser, which can lead to either dominant or recessive DEB, and which result in a spectrum of clinical abnormalities. We also identify a further 30 new glycine substitution mutations that cause either dominant or recessive DEB, but not both. In screening the COL7A1 gene for mutations in individuals with DEB our data highlight that delineation of glycine substitutions in type VII collagen has important implications for genetic counselling.
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Sustitución de Aminoácidos , Colágeno Tipo VII/genética , Epidermólisis Ampollosa Distrófica/genética , Genes Dominantes , Genes Recesivos , Mutación Missense , Piel/patología , Adolescente , Adulto , Biopsia , Niño , Preescolar , Colágeno Tipo VII/química , Análisis Mutacional de ADN , Bases de Datos Genéticas , Epidermólisis Ampollosa Distrófica/etnología , Epidermólisis Ampollosa Distrófica/patología , Femenino , Asesoramiento Genético , Predisposición Genética a la Enfermedad , Pruebas Genéticas , Glicina , Herencia , Humanos , Lactante , Londres , Masculino , Persona de Mediana Edad , Linaje , Fenotipo , Conformación Proteica , Índice de Severidad de la Enfermedad , Relación Estructura-Actividad , Adulto JovenRESUMEN
Familial primary localized cutaneous amyloidosis (FPLCA) is an autosomal dominant disorder associated with chronic itching and skin lichenification. In lesional skin, there are apoptotic basal keratinocytes and deposits of amyloid material on degenerate keratin filaments in the upper dermis. The genetic basis of FPLCA involves mutations in the OSMR and IL31RA genes but the disease pathophysiology is not fully understood. In this study, we identified new pathogenic heterozygous missense mutations in the OSMR gene (p.Val631Leu and p.Asp647Tyr) in two Dutch FPLCA families. We then compared gene expression profiles between FPLCA lesional skin (n = 4) and site-matched control skin (n = 6). There was twofold or greater upregulation of 34 genes and downregulation of 43 genes. Most changes in gene expression (verified by quantitative RT-PCR) reflected alterations in epidermal differentiation and proliferation consistent with lichenification, but we also noted a reduction in several interfollicular keratinocyte stem cell markers in FPLCA skin. Differences in gene expression were also noted for proteins involved in apoptosis and nerve conduction. Collectively, this study expands the molecular basis of FPLCA and provides new insight into the skin pathology of this condition.
Asunto(s)
Amiloidosis Familiar/genética , Amiloidosis Familiar/metabolismo , Mutación Missense/genética , Subunidad beta del Receptor de Oncostatina M/genética , Enfermedades Cutáneas Metabólicas/genética , Enfermedades Cutáneas Metabólicas/metabolismo , Proteínas Reguladoras de la Apoptosis/genética , Diferenciación Celular/genética , Proliferación Celular , Regulación hacia Abajo/genética , Femenino , Perfilación de la Expresión Génica , Heterocigoto , Humanos , Queratinocitos/metabolismo , Masculino , Proteínas del Tejido Nervioso/genética , Países Bajos , Piel/metabolismo , Células Madre/metabolismo , Regulación hacia Arriba/genéticaRESUMEN
Involvement of the genitourinary tract has been described in many different types of epidermolysis bullosa (EB). Pathology may be broadly divided into problems resulting in obstruction, that may in turn lead to hydroureter or hydronephrosis, or disease primarily affecting the renal parenchyma. Left unrecognized and untreated, renal tract disease may lead to chronic renal failure, and consequent problems associated with providing renal replacement therapy. Management of the urogenital tract in EB should therefore focus on detecting symptoms suggestive of obstruction and regular monitoring to detect problems as early as possible.
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Epidermólisis Ampollosa/complicaciones , Hidronefrosis/etiología , Insuficiencia Renal/etiología , Estrechez Uretral/etiología , Humanos , Hidronefrosis/diagnóstico , Hidronefrosis/terapia , Insuficiencia Renal/diagnóstico , Insuficiencia Renal/prevención & control , Estrechez Uretral/diagnóstico , Estrechez Uretral/terapiaRESUMEN
Kindler syndrome is an autosomal recessive disorder characterized by skin atrophy and blistering. It results from loss-of-function mutations in the FERMT1 gene encoding the focal adhesion protein, fermitin family homolog-1. How and why deficiency of fermitin family homolog-1 results in skin atrophy and blistering are unclear. In this study, we investigated the epidermal basement membrane and keratinocyte biology abnormalities in Kindler syndrome. We identified altered distribution of several basement membrane proteins, including types IV, VII, and XVII collagens and laminin-332 in Kindler syndrome skin. In addition, reduced immunolabeling intensity of epidermal cell markers such as beta1 and alpha6 integrins and cytokeratin 15 was noted. At the cellular level, there was loss of beta4 integrin immunolocalization and random distribution of laminin-332 in Kindler syndrome keratinocytes. Of note, active beta1 integrin was reduced but overexpression of fermitin family homolog-1 restored integrin activation and partially rescued the Kindler syndrome cellular phenotype. This study provides evidence that fermitin family homolog-1 is implicated in integrin activation and demonstrates that lack of this protein leads to pathological changes beyond focal adhesions, with disruption of several hemidesmosomal components and reduced expression of keratinocyte stem cell markers. These findings collectively provide novel data on the role of fermitin family homolog-1 in skin and further insight into the pathophysiology of Kindler syndrome.
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Anomalías Múltiples/genética , Integrinas/metabolismo , Proteínas de la Membrana/genética , Mutación/genética , Proteínas de Neoplasias/genética , Anomalías Múltiples/patología , Adolescente , Adulto , Membrana Basal/metabolismo , Membrana Basal/patología , Adhesión Celular , Membrana Celular/metabolismo , Niño , Preescolar , Epidermis/metabolismo , Epidermis/patología , Matriz Extracelular/metabolismo , Regulación de la Expresión Génica , Humanos , Queratina-15/genética , Queratina-15/metabolismo , Queratinocitos/patología , Masculino , Proteínas de la Membrana/metabolismo , Microscopía Fluorescente , Persona de Mediana Edad , Proteínas de Neoplasias/metabolismo , Fenotipo , SíndromeRESUMEN
Epidermolysis bullosa (EB) pruriginosa is an unusual variant of dystrophic EB in which intense itching can lead to striking skin changes resembling acquired skin disorders such as nodular prurigo or hypertrophic lichen planus. The molecular pathology involves mutations in the COL7A1 gene, but the nature of the mutations is similar to those seen in other non-pruritic forms of dystrophic EB. The mechanism of the dramatic phenotypic differences is currently unknown. In this study we assessed the incidence of a common functional polymor-phism in the matrix metalloproteinase-1 gene promoter (1G or 2G at nucleotide -1607) in individuals with EB pruriginosa (n = 27) compared with non-itchy dominant dystrophic EB (n = 23), recessive dystrophic EB (n = 25) and normal controls (n = 50). The hypothesis is that the 2G allele, which was previously shown to increase matrix metalloproteinase-1 activity and lead to increased degradation of type VII collagen, could explain the phenotypic heterogeneity encountered in dominant forms of EB, particularly the itchy EB pruriginosa phenotype. The rationale is that increased type VII collagen degradation could trigger an inflammatory response leading to itchy skin characteristic of EB pruriginosa. All 27 individuals with EB pruriginosa were heterozygous for dominant-negative glycine substitution mutations in the COL7A1 gene, six of which have not been reported previously. The frequency of the 2G allele in these subjects (46.3%) was greater than in the controls (42.0%), but less than in non-itchy dominant dystrophic EB (52.2%) or recessive dystrophic EB (62.0%), indicating that variants of a common functional polymorphism in the matrix metalloproteinase-1 gene promoter do not account for the itchy skin phenotype. The pathophysiology of EB pruriginosa remains unexplained.