RESUMEN
Irradiation-induced alopecia and dermatitis (IRIAD) are two of the most visually recognized complications of radiotherapy, of which the molecular and cellular basis remains largely unclear. By combining scRNA-seq analysis of whole skin-derived irradiated cells with genetic ablation and molecular inhibition studies, we show that senescence-associated IL-6 and IL-1 signaling, together with IL-17 upregulation and CCR6+ -mediated immune cell migration, are crucial drivers of IRIAD. Bioinformatics analysis colocalized irradiation-induced IL-6 signaling with senescence pathway upregulation largely within epidermal hair follicles, basal keratinocytes, and dermal fibroblasts. Loss of cytokine signaling by genetic ablation in IL-6-/- or IL-1R-/- mice, or by molecular blockade, strongly ameliorated IRIAD, as did deficiency of CCL20/CCR6-mediated immune cell migration in CCR6-/- mice. Moreover, IL-6 deficiency strongly reduced IL-17, IL-22, CCL20, and CCR6 upregulation, whereas CCR6 deficiency reciprocally diminished IL-6, IL-17, CCL3, and MHC upregulation, suggesting that proximity-dependent cellular cross talk promotes IRIAD. Therapeutically, topical application of Janus kinase blockers or inhibition of T-cell activation by cyclosporine effectively reduced IRIAD, suggesting the potential of targeted approaches for the treatment of dermal side effects in radiotherapy patients.
Asunto(s)
Radiodermatitis , Receptores CCR6 , Animales , Interleucina-17/genética , Interleucina-17/metabolismo , Interleucina-6/genética , Ratones , Receptores CCR6/genética , Receptores CCR6/metabolismo , TranscriptomaRESUMEN
Solar urticaria is a well-recognized photodermatosis, sometimes accompanied by angioedema. However, isolated solar angioedema (ISA) is a rare and unrecognized entity. The purpose of our work was to systematically review the available data on ISA. Therefore, a systematic review of studies evaluating ISA was performed. Additionally, a case of a 21-years-old patient from our photodermatosis service is presented. The search yielded 421 publications, with 3 eligible for review. Together with our case, 5 cases were included overall. All patients were female. Four out of 5 patients first experienced ISA at childhood or early adulthood (age range 6-22 years). UVA photoprovocation was positive in the 3 out of the 4 patients who were tested. Improvement was noted following NB-UVB hardening (2 out of 5 patients) or a short course of oral prednisone (3 out of 5 patients) combined with regular sunscreen application. To conclude, ISA is an extremely rare entity, although it may be underdiagnosed due to lack of awareness. The clinician must consider ISA in the differential diagnosis of angioedema since it can have a detrimental effect on quality of life. Besides sun avoidance, there is no consensus regarding treatment.
Asunto(s)
Angioedema , Trastornos por Fotosensibilidad , Urticaria , Adolescente , Adulto , Angioedema/diagnóstico , Angioedema/etiología , Niño , Femenino , Humanos , Trastornos por Fotosensibilidad/diagnóstico , Trastornos por Fotosensibilidad/etiología , Calidad de Vida , Luz Solar/efectos adversos , Adulto JovenRESUMEN
Photodynamic therapy (PDT), traditionally used in patients with nonmelanoma skin cancer, has been found to be effective for various inflammatory skin conditions. Daylight-activated PDT (DL-PDT), in which the sun serves as the light source, is substantially less painful than conventional PDT. This study aimed to determine the safety and efficacy of DL-PDT in a series of patients with chronic hand eczema (CHE). A proof-of-concept prospective design was used. Eight patients diagnosed with CHE at a tertiary dermatology clinic underwent DL-PDT. The first treatment was administered at the clinic and subsequent treatments (up to four total) were self-administered at home at 2-week intervals. Outcome was evaluated with the Investigator Global Assessment (IGA; score 0-4), Dermatology Life Quality Index (DLQI; score 0-24), and blinded review of clinical photographs (graded on a quartile scale by percent improvement). There were six male and two female patients of mean age 35 years. All underwent at least three treatments. The IGA score improved by 2.5 points at 1 month, 2.7 at 3 months, and 2.2 at 6 months post-treatment, and the DLQI score improved by 7.9, 6.6, and 6.1 points, respectively. Clinical photograph grades improved by 2.9 points at 3 months. Side effects were mild and transient. All patients had some degree of recurrence after 6 months of treatment. The self-administered DL-PDT is easy to perform, moderately effective, and safe to use in patients with CHE. Repeated treatments might be required to maintain remission.
Asunto(s)
Eccema , Queratosis Actínica , Fotoquimioterapia , Adulto , Ácido Aminolevulínico/uso terapéutico , Eccema/diagnóstico , Eccema/tratamiento farmacológico , Femenino , Humanos , Queratosis Actínica/tratamiento farmacológico , Masculino , Recurrencia Local de Neoplasia/tratamiento farmacológico , Fármacos Fotosensibilizantes/efectos adversos , Estudios ProspectivosAsunto(s)
Gluconato de Sodio Antimonio/uso terapéutico , Antiprotozoarios/uso terapéutico , Leishmaniasis Cutánea/tratamiento farmacológico , Anestesia por Inhalación , Gluconato de Sodio Antimonio/administración & dosificación , Antiprotozoarios/administración & dosificación , Niño , Preescolar , Femenino , Humanos , Inyecciones Intralesiones , Masculino , Estudios RetrospectivosRESUMEN
BACKGROUND: Actinic cheilitis (AC) is a common, chronic premalignant condition resulting from protracted sun exposure affecting the vermilion border of the lower lip. Treatment of AC aims at terminating the progression to squamous cell carcinoma by obliterating the primary lesion, and includes ablative methods; nonablative modalities such as cryotherapy, electrodessication, chemical peeling, topical imiquimod and 5-fluorouracil; and photodynamic therapy (PDT). Daylight-activated PDT, in which natural daylight serves as the light source, showed promising results in the treatment of actinic keratoses with substantially less pain than conventional PDT. PURPOSE: To determine the safety and efficacy of daylight PDT in a series of patients with AC. METHODS: Eleven patients with AC were treated with daylight PDT. All patients underwent repeated treatment sessions until clinical and histological remission were achieved. RESULTS: Cure rate was 91% (10 of 11 patients, three females/eight males; mean age 59.2 ± 14.4 years). Mean number of treatments to attain cure was 2.7. Patients experienced mild erythema and minimal to no pain during treatment. CONCLUSIONS: Daylight PDT is a promising modality for the treatment of AC, with impressive cosmetic results and few side effects.
Asunto(s)
Queilitis/tratamiento farmacológico , Luz , Fotoquimioterapia , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
Natural killer (NK) cells are innate lymphoid cells, and their presence within human tumors correlates with better prognosis. However, the mechanisms by which NK cells control tumors in vivo are unclear. Here, we used reflectance confocal microscopy (RCM) imaging in humans and in mice to visualize tumor architecture in vivo. We demonstrated that signaling via the NK cell receptor NKp46 (human) and Ncr1 (mouse) induced interferon-γ (IFN-γ) secretion from intratumoral NK cells. NKp46- and Ncr1-mediated IFN-γ production led to the increased expression of the extracellular matrix protein fibronectin 1 (FN1) in the tumors, which altered primary tumor architecture and resulted in decreased metastases formation. Injection of IFN-γ into tumor-bearing mice or transgenic overexpression of Ncr1 in NK cells in mice resulted in decreased metastasis formation. Thus, we have defined a mechanism of NK cell-mediated control of metastases in vivo that may help develop NK cell-dependent cancer therapies.
Asunto(s)
Antígenos Ly/metabolismo , Fibronectinas/metabolismo , Interferón gamma/metabolismo , Células Asesinas Naturales/metabolismo , Receptor 1 Gatillante de la Citotoxidad Natural/metabolismo , Neoplasias/metabolismo , Animales , Western Blotting , Femenino , Citometría de Flujo , Técnica del Anticuerpo Fluorescente , Regulación Neoplásica de la Expresión Génica/genética , Humanos , Masculino , Ratones , Microscopía Confocal , Metástasis de la Neoplasia/genética , Neoplasias/patología , Reacción en Cadena en Tiempo Real de la Polimerasa , Transducción de Señal/genéticaRESUMEN
BACKGROUND: Telangiectasias are permanent dilations of blood capillaries which appear in a variety of medical conditions. Cutaneous palmar telangiectasias have been postulated to be associated with smoking. OBJECTIVE: To determine whether a significant correlation exists between palmar telangiectasias and smoking habits. PATIENTS AND METHODS: A total of 124 volunteers participated in this observational study by allowing physical evaluation of their palms and by completing a questionnaire. RESULTS: Palmar telangiectasias were found to be associated with current or past smoking. Neither age nor gender was found to be a co-contributor. DISCUSSION: Palmar telangiectasias were found to constitute highly specific and sensitive markers for prolonged smoking.
Asunto(s)
Piel/irrigación sanguínea , Fumar/efectos adversos , Telangiectasia/etiología , Adulto , Anciano , Femenino , Mano , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Piel/patología , Telangiectasia/diagnósticoRESUMEN
The percutaneous passage of poorly skin absorbed molecules can be improved using nanocarriers, particularly biodegradable polymeric nanospheres (NSs) or nanocapsules (NCs). However, penetration of the encapsulated molecules may be affected by other factors than the nanocarrier properties. To gain insight information on the skin absorption of two fluorescent cargos, DiIC18(5) and coumarin-6 were incorporated in NSs or NCs and topically applied on various human and porcine skin samples. 3D imaging techniques suggest that NSs and NCs enhanced deep dermal penetration of both probes similarly, when applied on excised human skin irrespective of the nature of the cargo. However, when ex vivo pig skin was utilized, the cutaneous absorption of DiIC18(5) was more pronounced by means of PLGA NCs than NSs. In contrast, PLGA NSs noticeably improved the porcine skin penetration of coumarin-6, as compared to the NCs. Furthermore, the porcine skin results were reproducible when triplicated whereas from various human skin samples, as expected, the results were not sufficiently reproducible and large deviations were observed. The overall findings from this comprehensive comparison emphasize the potential of PLGA NCs or NSs to promote cutaneous bioavailability of encapsulated drugs, exhibiting different physicochemical properties but depending on the nature of the skin.
Asunto(s)
Portadores de Fármacos/química , Colorantes Fluorescentes/metabolismo , Nanocápsulas/química , Nanosferas/química , Absorción Cutánea , Administración Cutánea , Animales , Carbocianinas/metabolismo , Cumarinas/metabolismo , Humanos , Piel , PorcinosRESUMEN
Angiolymphoid hyperplasia with eosinophilia (ALHE) is an uncommon dermatosis of unknown etiology that manifests as characteristic red nodules and papules with a predilection for the scalp and periauricular region. Treatment is required for both esthetic and functional reasons, as lesions may ulcerate and bleed. Many treatment approaches have been reported, including excision, systemic medical approaches, topical or intralesional therapies, and non-invasive modalities including cryotherapy, electrosurgery, and laser. Treatments have exhibited variable efficacy, and the recurrence rate is 100 %. We report the combination of pulsed dye laser and CO2 laser in the treatment of ALHE in 14 patients. All patients exhibited clinical response after a mean of 2.4 ± 0.4 treatment sessions. The clinical efficacy of the combined treatment, together with its well-tolerated nature, render the use of pulsed dye laser in combination with CO2 laser, a viable treatment for debulking ALHE lesions. Ongoing maintenance treatments are needed to due to the high degree of relapse.
Asunto(s)
Hiperplasia Angiolinfoide con Eosinofilia/rehabilitación , Láseres de Colorantes/uso terapéutico , Láseres de Gas/uso terapéutico , Adulto , Hiperplasia Angiolinfoide con Eosinofilia/patología , Terapia Combinada , Crioterapia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de NeoplasiaRESUMEN
Cutaneous leishmaniasis (CL) is diverse in its clinical presentation but usually demonstrates an erythematous, infiltrated, ulcerated, and crusted papule or nodule in exposed areas of the body. Rare clinical features have been reported including lymphatic dissemination, usually with subcutaneous nodules along lymphatic channels. Herein, we present six patients suffering from Old World CL with lymphatic dissemination characterized by sporotrichoid subcutaneous nodules along the lymphatic channels draining the primary lesion. Patients' history, clinical and laboratory findings were collected and summarized. Lymphatic dissemination of CL in our patients manifested as subcutaneous nodules without epidermal involvement within the axis of lymphatic drainage toward the regional lymph node, at times accompanied by regional lymphadenopathy. In all patients, the lymphatic dissemination was not present at initial diagnosis of CL, appearing only after local (topical or intralesional) treatment was initiated. In three patients, the subcutaneous nodules resolved without systemic treatment. Lymphatic dissemination of Old World CL is not uncommon and may possibly be triggered by local treatment. It should be recognized by dermatologists, especially those working in endemic areas. Systemic treatment may be not necessary since spontaneous resolution may occur.
Asunto(s)
Leishmaniasis Cutánea/patología , Enfermedades Linfáticas/parasitología , Administración Tópica , Adolescente , Antiprotozoarios/administración & dosificación , Antiprotozoarios/uso terapéutico , Niño , Femenino , Humanos , Lactante , Leishmaniasis Cutánea/complicaciones , Leishmaniasis Cutánea/tratamiento farmacológico , Ganglios Linfáticos/parasitología , Ganglios Linfáticos/patología , Enfermedades Linfáticas/etiología , MasculinoRESUMEN
BACKGROUND: Solar urticarial (SU) is characterized by erythema, whealing, and/or pruritus occurring minutes after sun exposure. Treatment is difficult and often unsatisfactory. OBJECTIVES: To determine the action spectra and minimal urticaria dose (MUD) and to tailor a treatment regimen graded according to disease severity in a series of patients with SU. PATIENTS AND METHODS: Eleven patients (seven females, four males, age range: 5-60 years) with a clinical history suggestive of SU, verified by photo-provocation tests to ultraviolet A (UVA), visible light, and/or UVB, were treated with various combinations of antihistamines and leukotriene receptor antagonist. RESULTS: All patients were sensitive to visible light (median MUD 50 J/cm(2)). Three patients were sensitive to UVA (median MUD 3.75 J/cm(2)), and one patient was sensitive to UVB (MUD of 0.03 J/cm(2)). Two patients experienced a spontaneous remission without treatment. One patient declined treatment. The remaining eight patients were managed by a combination of antihistamines (desloratidine, fexofenadine, cetirizine HCl) and a leukotriene receptor antagonist (montelukast). Seven of the 8 patients experienced a sustained remission of symptoms and signs following treatment. CONCLUSIONS: Photoprovocation for SU with determination of action spectra and MUD enables specifically tailored treatment regimens consisting of combinations of antihistamines and leukotriene receptor antagonist.
Asunto(s)
Acetatos/uso terapéutico , Antagonistas de los Receptores Histamínicos H1 no Sedantes/uso terapéutico , Antagonistas de Leucotrieno/uso terapéutico , Trastornos por Fotosensibilidad/tratamiento farmacológico , Quinolinas/uso terapéutico , Luz Solar/efectos adversos , Urticaria/tratamiento farmacológico , Adolescente , Adulto , Cetirizina/uso terapéutico , Niño , Preescolar , Ciclopropanos , Quimioterapia Combinada , Femenino , Humanos , Loratadina/análogos & derivados , Loratadina/uso terapéutico , Masculino , Persona de Mediana Edad , Trastornos por Fotosensibilidad/etiología , Inducción de Remisión , Remisión Espontánea , Índice de Severidad de la Enfermedad , Sulfuros , Terfenadina/análogos & derivados , Terfenadina/uso terapéutico , Rayos Ultravioleta/efectos adversos , Urticaria/etiología , Adulto JovenRESUMEN
The worldwide prevalence of leishmaniasis is increasing because of ecologic changes and increased medical profession awareness. Furthermore, solitary cases have been recently reported in Western countries. The authors describe the epidemiology, mode of transmission, and diagnosis of leishmaniasis and present 4 oral cases treated with systemic, localized, or combined therapy. The authors suggest that clinicians should maintain a high index of suspicion for atypical, resistant, oral and perioral lesions in individuals with a history of traveling in certain geographic regions. After diagnosis, treatment should be determined jointly by experts from the fields of oral and maxillofacial surgery, oral medicine, and dermatology based on leishmaniasis species and clinical presentation.
Asunto(s)
Antiprotozoarios/uso terapéutico , Leishmaniasis/diagnóstico , Enfermedades de la Boca/parasitología , Adolescente , Adulto , Anciano , Anfotericina B/uso terapéutico , Animales , Gluconato de Sodio Antimonio/uso terapéutico , Diagnóstico Diferencial , Enfermedades Endémicas , Femenino , Humanos , Leishmania braziliensis/aislamiento & purificación , Leishmania infantum/aislamiento & purificación , Leishmania major/aislamiento & purificación , Leishmaniasis/tratamiento farmacológico , Leishmaniasis Cutánea/diagnóstico , Leishmaniasis Cutánea/tratamiento farmacológico , Enfermedades de los Labios/tratamiento farmacológico , Enfermedades de los Labios/parasitología , Masculino , Enfermedades de la Boca/tratamiento farmacológico , Adulto JovenRESUMEN
Two focused libraries based on two types of compounds, that is, thiazolidinediones and dioxazaborocanes were designed. Structural resemblances can be found between thiazolidinediones and well-known furanone type quorum sensing (QS) inhibitors such as N-acylaminofuranones, and/or acyl-homoserine lactone signaling molecules, while dioxazaborocanes structurally resemble previously reported oxazaborolidine derivatives which antagonized autoinducer 2 (AI-2) binding to its receptor. Because of this, we hypothesized that these compounds could affect AI-2 QS in Vibrio harveyi. Although all compounds blocked QS, the thiazolidinediones were the most active AI-2 QS inhibitors, with EC(50) values in the low micromolar range. Their mechanism of inhibition was elucidated by measuring the effect on bioluminescence in a series of V. harveyi QS mutants and by DNA-binding assays with purified LuxR protein. The active compounds neither affected bioluminescence as such nor the production of AI-2. Instead, our results indicate that the thiazolidinediones blocked AI-2 QS in V. harveyi by decreasing the DNA-binding ability of LuxR. In addition, several dioxazaborocanes were found to block AI-2 QS by targeting LuxPQ.
Asunto(s)
Antibacterianos/farmacología , Compuestos de Boro/farmacología , Percepción de Quorum/efectos de los fármacos , Tiazolidinedionas/farmacología , Vibrio/efectos de los fármacos , Antibacterianos/síntesis química , Antibacterianos/química , Compuestos de Boro/síntesis química , Compuestos de Boro/química , Relación Dosis-Respuesta a Droga , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Percepción de Quorum/genética , Relación Estructura-Actividad , Tiazolidinedionas/síntesis química , Tiazolidinedionas/química , Vibrio/crecimiento & desarrolloRESUMEN
LED light sources for photodynamic therapy have become increasingly popular due to their narrow emission spectra that accurately match the absorption spectrum of porphyrins. Photodynamic therapy at low fluence rates has been shown to be as effective as high output irradiation for treatment of non-melanoma skin cancers. Fifteen patients with multiple non-hypertrophic actinic keratoses covering the scalp and the face were treated with aminolaevulinic acid photodynamic therapy using ordinary red LED traffic lamps as light source. All 15 patients improved clinically after one photodynamic therapy session. Only two patients required a second session to obtain satisfactory remission. Pain was minimal during these sessions. Red LED traffic lights constitute a simple alternative to far more complicated and expensive PDT light sources.
Asunto(s)
Ácido Aminolevulínico/administración & dosificación , Queratosis Actínica/terapia , Fotoquimioterapia/instrumentación , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/administración & dosificación , Anciano , Femenino , Humanos , Queratosis Actínica/patología , Masculino , Persona de Mediana EdadRESUMEN
Scabies is an intensely pruritic disorder induced by a delayed type hypersensitivity reaction to infestation of the skin by the mite Sarcoptes scabiei. The diagnosis of scabies is established clinically and confirmed by identifying mites or eggs by microscopic examination of scrapings from the skin or by surface microscopy using a dermatoscope. Reflectance-mode confocal microscopy is a novel technique used for noninvasive imaging of skin structures and lesions at a resolution compatible to that of conventional histology. Recently, the technique was employed for the confirmation of the clinical diagnosis of scabies.We demonstrate the first ever documentation of a larva moving freely inside the skin of a patient infected with scabies.