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Neoplasias , Humanos , Estudios Retrospectivos , Femenino , Masculino , Estudios de Casos y Controles , Persona de Mediana Edad , Anciano , Neoplasias/complicaciones , Neoplasias/diagnóstico , Enfermedades de la Piel/diagnóstico , Enfermedades de la Piel/etiología , Enfermedades de la Piel/epidemiología , Adulto , Factores de Riesgo , Anciano de 80 o más AñosRESUMEN
Hidradenitis suppurativa (HS) is a chronic and debilitating inflammatory disease derived from the pilosebaceous unit, that affects approximately 1% of the general population. Clinically, it is characterized by inflammatory nodules, abscesses, and tunnels in the intertriginous areas of the body, especially in the axillary, inguinal, and anogenital regions. The etiopathogenesis of HS is not completely understood, although it is considered to be multifactorial, and the result of a complex interaction between genetic, hormonal, environmental, and immunological factors. In this sense, several proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α), interleukin (IL)-L-1ß, and IL-17, among others, appear to play a crucial role in the pathogenesis of the disease. Currently, HS is recognized as a systemic disease associated with numerous comorbidities, including cardiovascular, immune-mediated, and endocrine-metabolic diseases. The treatment of HS must be carried out with an individualized and patient-oriented approach, considering medical and surgical treatment modalities.
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Hidradenitis Supurativa , Humanos , Hidradenitis Supurativa/diagnóstico , Hidradenitis Supurativa/etiología , Hidradenitis Supurativa/terapia , Piel , Factor de Necrosis Tumoral alfa , Interleucina-17RESUMEN
Histiocytoses encompass a group of exceptionally rare disorders characterized by the abnormal infiltration of tissues by histocytes. Among these, Erdheim-Chester disease (ECD) stands out as a multisystem histiocytosis that typically affects bones and various other tissues. Historically, the treatment of ECD has been challenging. However, recent breakthroughs in our understanding, particularly the discovery of somatic mutations in the RAS-MAPK pathway, have opened new opportunities for targeted therapy in a significant subset of patients with ECD and other histiocytoses. In this report, we present the case of a patient with ECD harboring a previously unidentified microduplication in the NRAS gene in a small fraction of skin cells. This discovery played a pivotal role in tailoring an effective therapeutic approach involving kinase inhibitors downstream of NRAS. This case underscores the crucial role of deep sequencing of tissue samples in ECD, enabling the delivery of personalized targeted therapy to patients.
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Enfermedad de Erdheim-Chester , Humanos , Enfermedad de Erdheim-Chester/tratamiento farmacológico , Enfermedad de Erdheim-Chester/genética , Proteínas Proto-Oncogénicas B-raf/genética , Mutación , Proteínas de la Membrana/genética , GTP Fosfohidrolasas/genéticaAsunto(s)
Dermatitis , Enfermedades del Oído , Humanos , Adulto , Estudios Retrospectivos , Oído Externo , Estudios de Casos y Controles , Fumar TabacoRESUMEN
Mineralized tissues, such as bones or teeth, are essential structures of all vertebrates. They enable rapid movement, protection, and food processing, in addition to providing physiological functions. Although the development, regeneration, and pathogenesis of teeth and bones have been intensely studied, there is currently no tool to accurately follow the dynamics of growth and healing of these vital tissues in space and time. Here, we present the BEE-ST (Bones and tEEth Spatio-Temporal growth monitoring) approach, which allows precise quantification of development, regeneration, remodeling, and healing in any type of calcified tissue across different species. Using mouse teeth as model the turnover rate of continuously growing incisors was quantified, and role of hard/soft diet on molar root growth was shown. Furthermore, the dynamics of bones and teeth growth in lizards, frogs, birds, and zebrafish was uncovered. This approach represents an effective, highly reproducible, and versatile tool that opens up diverse possibilities in developmental biology, bone and tooth healing, tissue engineering, and disease modeling.
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Diente , Pez Cebra , Ratones , Animales , Diente/fisiología , Raíz del Diente , Huesos , Desarrollo ÓseoRESUMEN
Mechanosensory ion channels are proteins that are sensitive to mechanical forces. They are found in tissues throughout the body and play an important role in bone remodeling by sensing changes in mechanical stress and transmitting signals to bone-forming cells. Orthodontic tooth movement (OTM) is a prime example of mechanically induced bone remodeling. However, the cell-specific role of the ion channels Piezo1 and Piezo2 in OTM has not been investigated yet. Here we first identify the expression of PIEZO1/2 in the dentoalveolar hard tissues. Results showed that PIEZO1 was expressed in odontoblasts, osteoblasts, and osteocytes, while PIEZO2 was localized in odontoblasts and cementoblasts. We therefore used a Piezo1floxed/floxed mouse model in combination with Dmp1cre to inactivate Piezo1 in mature osteoblasts/cementoblasts, osteocytes/cementocytes, and odontoblasts. Inactivation of Piezo1 in these cells did not affect the overall morphology of the skull but caused significant bone loss in the craniofacial skeleton. Histological analysis revealed a significantly increased number of osteoclasts in Piezo1floxed/floxed;Dmp1cre mice, while osteoblasts were not affected. Despite this increased number of osteoclasts, orthodontic tooth movement was not altered in these mice. Our results suggest that despite Piezo1 being crucial for osteoclast function, it may be dispensable for mechanical sensing of bone remodeling.
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Células del Tejido Conectivo , Osteoblastos , Animales , Ratones , Osteoclastos , Osteocitos , Remodelación Ósea , Canales IónicosRESUMEN
Hidradenitis suppurativa (HS) is a chronic inflammatory disease whose pathogenesis is not fully understood at present. The role of proinflammatory cytokines, several adipokines, retinol-binding protein 4, angiopoietin-2 and other molecules has been previously reported. Angiopoietin-like 2 protein (ANGPTL2) is a glycoprotein belonging to the angiopoietin-like family that may play a pivotal role in the pathogenesis of several chronic inflammatory diseases. To our knowledge, the role of serum ANGPTL2 levels in HS has not been assessed to date. In the current case-control study, we aimed to investigate serum ANGPTL2 levels in HS patients and controls and to assess whether ANGPTL2 levels could be associated with the severity of HS. Ninety-four patients with HS and sixty controls of similar age and sex were included in the study. Demographic, anthropometric, and clinical data, as well as routine laboratory parameters and serum concentrations of ANGPTL2, were assessed in all participants. HS patients had significantly higher serum ANGPTL2 levels than controls after adjusting for confounders. Moreover, ANGPTL2 concentrations positively correlated with disease duration and severity. Our results indicate for the first time that serum ANGPTL2 concentrations are elevated in HS patients compared to controls and correlate with the duration of the disease. Besides, ANGPTL2 might serve as a biomarker of HS severity.
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Hidradenitis suppurativa (HS) is a chronic inflammatory disease of the hair follicles. The aim of this case-control study was to assess whether HS is associated with disturbances in trabecular bone score, bone mineral density, bone remodelling markers, and calciotropic hormones. A total of 81 patients and 79 controls of similar age and sex were included. Demographic, anthropometric, laboratory data, trabecular bone score, bone mineral density, serum 25-hydroxyvitamin D (25OHD), serum amino-terminal pro-peptide of type 1 collagen (PINP), and C-terminal telopeptide of type 1 collagen (CTX) concentrations were assessed in both groups. Patients with HS had lower serum 25OHD levels than controls, and approximately 62% of them had vitamin D deficiency. Serum PINP was increased and CTX was decreased in patients with HS. Fully adjusted trabecular bone score values were lower in patients with HS compared with controls. Adjusted lumbar bone mineral density was similar in HS and controls, whilst total hip bone mineral density was lower in patients with HS. There were no statistical differences regarding disease severity in terms of 25OHD, serum turnover markers, bone mineral density, or trabecular bone score values. This study shows that patients with HS have lower trabecular bone score and total hip bone mineral density values than population-based controls. In addition, the prevalence of vitamin D deficiency is high in subjects with HS.
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Hidradenitis Supurativa , Deficiencia de Vitamina D , Humanos , Estudios de Casos y Controles , Colágeno Tipo I , Deficiencia de Vitamina D/diagnóstico , Deficiencia de Vitamina D/epidemiología , Folículo PilosoRESUMEN
Hidradenitis suppurativa (HS) is a chronic inflammatory disease associated with an increased prevalence of subclinical atherosclerosis and cardiovascular risk. Angiopoietin-2 (Ang-2), asymmetric dimethylarginine (ADMA), and osteoprotegerin (OPG) are molecules related to endothelial dysfunction (ED) and atherosclerosis, but also to disease severity in patients with chronic inflammatory disorders. In this case-control study, we aimed to investigate serum Ang-2, ADMA, and OPG levels in patients with HS, and to assess the potential relationship between these levels and disease severity. Seventy-five patients with HS and 60 controls were assessed. Serum Ang-2, ADMA, and OPG concentrations were determined in all participants. HS patients had significantly higher Ang-2 and ADMA levels than controls after adjusting for confounders. Besides, Ang-2 concentrations positively correlated with disease severity in the adjusted multivariable analysis. Nevertheless, serum OPG levels did not significantly differ between HS patients and controls. Our results indicate that serum Ang-2 and ADMA levels are significantly increased in patients with HS. Furthermore, Ang-2 might be a suitable marker of HS severity.
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Aterosclerosis , Hidradenitis Supurativa , Angiopoyetina 2 , Arginina , Aterosclerosis/diagnóstico , Biomarcadores , Estudios de Casos y Controles , Enfermedad Crónica , Hidradenitis Supurativa/complicaciones , Humanos , OsteoprotegerinaRESUMEN
Alopecia after mesotherapy with dutasteride is an extremely rare complication. Dutasteride is a second-generation 5a-reductase enzyme inhibitor that decreases serum dihydrotestosterone levels by 90%. It inhibits both type 1 and 2 enzymes, whereas finasteride inhibits only type 2. Mesotherapy with dutasteride is a novel treatment for hair fall which involves microinjection of the drug into the dermis with negligible systemic absorption. Frequent mild transitory side effects in the site of injection are described in medical literature, but few cases of secondary alopecia have been reported. This stands out given that mesotherapy is becoming such an increasingly common procedure with a great number of patients treated with this technique. We present 2 cases of patchy alopecia after mesotherapy with dutasteride in a male and a female with androgenetic alopecia. One of them developed skin atrophy on the affected areas without improvement at short term follow-up. These cases highlight the possible paradoxical side effects of mesotherapy as a therapeutic technique for hair loss.
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Considerable amount of research has been focused on dentin mineralization, odontoblast differentiation, and their application in dental tissue engineering. However, very little is known about the differential role of functionally and spatially distinct types of dental epithelium during odontoblast development. Here we show morphological and functional differences in dentin located in the crown and roots of mouse molar and analogous parts of continuously growing incisors. Using a reporter (DSPP-cerulean/DMP1-cherry) mouse strain and mice with ectopic enamel (Spry2+/- ;Spry4-/- ), we show that the different microstructure of dentin is initiated in the very beginning of dentin matrix production and is maintained throughout the whole duration of dentin growth. This phenomenon is regulated by the different inductive role of the adjacent epithelium. Thus, based on the type of interacting epithelium, we introduce more generalized terms for two distinct types of dentins: cementum versus enamel-facing dentin. In the odontoblasts, which produce enamel-facing dentin, we identified uniquely expressed genes (Dkk1, Wisp1, and Sall1) that were either absent or downregulated in odontoblasts, which form cementum-facing dentin. This suggests the potential role of Wnt signalling on the dentin structure patterning. Finally, we show the distribution of calcium and magnesium composition in the two developmentally different types of dentins by utilizing spatial element composition analysis (LIBS). Therefore, variations in dentin inner structure and element composition are the outcome of different developmental history initiated from the very beginning of tooth development. Taken together, our results elucidate the different effects of dental epithelium, during crown and root formation on adjacent odontoblasts and the possible role of Wnt signalling which together results in formation of dentin of different quality. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
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Dentina , Odontoblastos , Animales , Diferenciación Celular , Epitelio , Proteínas de la Matriz Extracelular/genética , Incisivo , Ratones , OdontogénesisRESUMEN
Abstract Carcinoma of the mammary crease is a very rare variant of breast carcinoma, in which the skin lesions are usually the presenting sign. The authors present the case of an 88-year-old woman with an exophytic plaque in the mammary crease of approximately ten years duration. The histopathological and immunohistochemical studies confirmed the diagnosis of infiltrative breast carcinoma (carcinoma of the mammary crease variant). This case highlights the important role of the dermatologist in the early diagnosis of this rare variant of breast cancer.
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Humanos , Femenino , Anciano de 80 o más Años , Neoplasias de la Mama/diagnóstico , Carcinoma , Tórax , MamaRESUMEN
Perianal hyperhidrosis (HH) is a rare form of primary focal HH and may become a major problem for the patient with a significant psychosocial burden and negative impact on the quality of life. Botulinum toxin injections are widely used as a second-line treatment option for axillary, palmar, and plantar HH with a good safety profile. Herein, we pre-sent a case of primary perianal HH successfully treated with Botulinum toxin A at a dose higher than that previously reported in literature, with a longer response, a higher degree of satisfaction, and no adverse effects. Moreover, we review the main aspects of the perianal anatomy that are essential to carry out the technique correctly and make dermatologists achieve expertise with the procedure.
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Carcinoma of the mammary crease is a very rare variant of breast carcinoma, in which the skin lesions are usually the presenting sign. The authors present the case of an 88-year-old woman with an exophytic plaque in the mammary crease of approximately ten years duration. The histopathological and immunohistochemical studies confirmed the diagnosis of infiltrative breast carcinoma (carcinoma of the mammary crease variant). This case highlights the important role of the dermatologist in the early diagnosis of this rare variant of breast cancer.
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Neoplasias de la Mama , Carcinoma , Anciano de 80 o más Años , Mama , Neoplasias de la Mama/diagnóstico , Femenino , Humanos , TóraxRESUMEN
Dear Editor, Nivolumab is a fully human monoclonal antibody that targets the programmed cell death 1 (PD-1) immune checkpoint. It has been approved for its use in several types of advanced solid tumors, including melanoma, lung cancer, and renal cell carcinoma (RCC). The inhibition of PD-1 leads to an enhanced adaptive immune response against tumor cells through the activation of T-cells. Vitiligo-like depigmentation (VLD) is a well-known side-effect in patients with melanoma that are being treated with anti PD-1 therapies (1). However, its development in patients undergoing treatment with nivolumab for cancers other than melanomas has been described very rarely. To our knowledge, herein we report the second case of nivolumab-induced VLD in a patient with metastatic RCC (2). The patient was a 63-year-old man who had a medical history of advanced RCC. He had initially undergone nephrectomy, and three months later he presented with local relapse and lung metastases. He had then received different treatment regimes, presenting with progression each time, until he finally started treatment with nivolumab. Five months after its introduction, the patient developed a disseminated hypochromic eruption. No other drugs were started over that period. He had no personal or family history of vitiligo or other autoimmune disorders. Dermatological examination revealed multiple, symmetrical, well-demarcated, depigmented macules involving his face, neck, torso, hands, and forearms. (Figure 1, a). Preservation of pigment in hair follicles could be seen on the dorsal aspect of his hands (Figure 1, b). Two 4-mm punch biopsies were taken, one from one from a depigmented patch and another from normally pigmented skin. In the first one, immunohistochemical analysis with Melan-A immunostaining demonstrated the absence of melanocytes, whereas melanocytes were present in the second one. A CD-8+ positive infiltrate was present in both biopsies, especially in the first one (Figure 2). The patient was diagnosed with VLD associated with nivolumab therapy. Since the patient was asymptomatic, no treatment was prescribed. He was advised to protect the achromic areas from sun exposure. In our patient, a causal association between the onset of VLD and the treatment with nivolumab cannot be completely ruled out. However, the clinical presentation with flecked macules in sun-exposed areas was consistent with what has been described in other patients presenting with VLD after starting treatment with this chemotherapeutic agent. The time to onset in our case was also within the limits which have been previously reported for this side-effect (16-52 weeks) (3). Therefore, we believe that a causal association is very probable. In patients with advanced melanoma who are treated with PD-1 inhibitors, the development of vitiligo-like lesions has been proved to be associated with improved progression-free and overall survival rates (4,5). This mechanism is not fully understood, but it has been suggested that inhibition of PD-1 could cause a loss of tolerance to melanocytic antigens, thus leading to a CD-8 T-cell dependent destruction of melanocytes present in the melanoma as well as in healthy skin (3,5). The presence of CD8 T-lymphocytes in our patient's biopsies supports this theory. However, the development of this condition in patients suffering from non-melanoma cancers suggests that different mechanisms, independent from melanoma, could also be involved. Larger studies are needed in order to determine if VLD also correlates with better survival rates in patients treated with nivolumab for non-melanoma malignancies. In conclusion, new checkpoint inhibitors can cause VLD not only in patients suffering from melanoma but also in those affected by other tumors. We believe dermatologists should play a key role in the management of this side-effect. Therefore, we ought to be familiar with it in order to be able to identify and treat it appropriately without discontinuation of anticancer treatment.
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Carcinoma de Células Renales , Neoplasias Renales , Vitíligo , Carcinoma de Células Renales/tratamiento farmacológico , Humanos , Neoplasias Renales/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Nivolumab/efectos adversos , Vitíligo/inducido químicamenteRESUMEN
INTRODUCTION: Recent studies suggest a role of adipokines in the pathogenesis of hidradenitis suppurativa (HS). Omentin-1 and apelin are two recently identified adipokines that have been involved in the regulation of metabolic and inflammatory responses. AIM: To investigate serum omentin-1 and apelin levels in patients with HS and to assess their associations with metabolic parameters, disease severity and HS risk. MATERIAL AND METHODS: This case-control study included 139 non-diabetic individuals (78 HS patients and 61 ageand sex-matched controls). Serum concentrations of omentin-1 and apelin and the homeostasis model assessment of insulin resistance (HOMA-IR) were measured in all participants. RESULTS: Serum omentin-1 concentrations were significantly higher in HS patients compared to controls, whereas apelin serum levels did not significantly differ between both groups. These differences in omentin-1 concentrations remained significant even after adjusting for age, sex, and body mass index (BMI). The results of logistic regression analysis showed that increased omentin-1 plasma levels were an independent risk factor for HS. However, we found no association between serum levels of both omentin-1 and apelin with HS severity. CONCLUSIONS: Our results show that patients with HS have raised omentin-1 serum levels, which are associated with HS risk.
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Harlequin syndrome (HS) is a rare entity derived from the dysfunction of the sympathetic nervous system. It is characterised by unilateral facial flushing and sweating induced by exercise, heat and emotion. Most cases are primary with an unknown pathogenic mechanism. In these cases, the prognosis is favourable. Medical or surgical treatments are not usually required for idiopathic HS. However, symptomatic treatment may be indicated when symptoms affect the quality of life of patients. We present the case of a patient with idiopathic HS successfully treated with oxybutynin and propranolol. In this patient, a marked improvement in both hyperhidrosis and facial erythema was noted with this combined therapy. We consider it of interest to highlight the response of our patient to the treatment employed, which may be advantageous in future cases of this rare disorder.