RESUMEN
Importance: Inconsistent reporting of outcomes in clinical trials of rosacea is impeding and likely preventing accurate data pooling and meta-analyses. There is a need for standardization of outcomes assessed during intervention trials of rosacea. Objective: To develop a rosacea core outcome set (COS) based on key domains that are globally relevant and applicable to all demographic groups to be used as a minimum list of outcomes for reporting by rosacea clinical trials, and when appropriate, in clinical practice. Evidence Review: A systematic literature review of rosacea clinical trials was conducted. Discrete outcomes were extracted and augmented through discussions and focus groups with key stakeholders. The initial list of 192 outcomes was refined to identify 50 unique outcomes that were rated through the Delphi process Round 1 by 88 panelists (63 physicians from 17 countries and 25 patients with rosacea in the US) on 9-point Likert scale. Based on feedback, an additional 11 outcomes were added in Round 2. Outcomes deemed to be critical for inclusion (rated 7-9 by ≥70% of both groups) were discussed in consensus meetings. The outcomes deemed to be most important for inclusion by at least 85% of the participants were incorporated into the final core domain set. Findings: The Delphi process and consensus-building meetings identified a final core set of 8 domains for rosacea clinical trials: ocular signs and symptoms; skin signs of disease; skin symptoms; overall severity; patient satisfaction; quality of life; degree of improvement; and presence and severity of treatment-related adverse events. Recommendations were also made for application in the clinical setting. Conclusions and Relevance: This core domain set for rosacea research is now available; its adoption by researchers may improve the usefulness of future trials of rosacea therapies by enabling meta-analyses and other comparisons across studies. This core domain set may also be useful in clinical practice.
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Ensayos Clínicos como Asunto , Consenso , Técnica Delphi , Rosácea , Rosácea/terapia , Rosácea/diagnóstico , Humanos , Ensayos Clínicos como Asunto/normas , Evaluación de Resultado en la Atención de Salud/normas , Resultado del TratamientoRESUMEN
BACKGROUND: Little data support the optimal distance of cuticular suture placement from the wound edge to achieve the most cosmetically appealing scar. OBJECTIVE: To compare Patient and Observer Scar Assessment Scale (POSAS) scores for cutaneous sutures spaced 2 mm versus 5 mm from the wound edge in head and neck defects repaired via linear closure. METHODS: Fifty patients were enrolled in this randomized, evaluator blinded, split-scar study. Surgical wounds were repaired with cuticular sutures 2 mm from the wound edge on one side and 5 mm on the other. POSAS scores and scar width were compared 3 months postoperatively. RESULTS: The sum observer POSAS score for this study had a mean (SD) of 16.06 (6.49) on the 2-mm side and 15.82 (6.83) on the 5-mm side (P = .807). Similarly, no difference was seen between scar width with a mean (SD) of 0.100 cm (0.058 cm) on the 2-mm side and with mean (SD) 0.100 cm (0.076 cm) on the 5-mm side (P = .967). LIMITATIONS: Linear repairs were studied on head and neck defects after extirpation of cutaneous malignancies, resulting in a homogeneous elderly white patient population. CONCLUSION: Cuticular sutures placed 2 or 5 mm from the wound edge did not result in different cosmetic outcomes in linear closures on the head and neck.
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Cicatriz , Técnicas de Sutura , Anciano , Cicatriz/etiología , Cicatriz/patología , Cicatriz/prevención & control , Humanos , Cirugía de Mohs/efectos adversos , Cirugía de Mohs/métodos , Suturas , Cicatrización de HeridasRESUMEN
Decreased cortical serotonergic and catecholaminergic innervation of the frontal cortex has been reported at early stages of Parkinson's disease (PD). However, the limited availability of animal models that exhibit these pathological features has hampered our understanding of the functional significance of these changes during the course of the disease. In the present study, we assessed longitudinal changes in cortical serotonin and catecholamine innervation in motor-symptomatic and asymptomatic monkeys chronically treated with low doses of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Densitometry and unbiased stereological techniques were used to quantify changes in serotonin and tyrosine hydroxylase (TH) immunoreactivity in frontal cortices of 3 control monkeys and 3 groups of MPTP-treated monkeys (motor-asymptomatic [N = 2], mild parkinsonian [N = 3], and moderate parkinsonian [N = 3]). Our findings revealed a significant decrease (P < 0.001) in serotonin innervation of motor (Areas 4 and 6), dorsolateral prefrontal (Areas 9 and 46), and limbic (Areas 24 and 25) cortical areas in motor-asymptomatic MPTP-treated monkeys. Both groups of symptomatic MPTP-treated animals displayed further serotonin denervation in these cortical regions (P < 0.0001). A significant loss of serotonin-positive dorsal raphe neurons was found in the moderate parkinsonian group. On the other hand, the intensity of cortical TH immunostaining was not significantly affected in motor asymptomatic MPTP-treated monkeys, but underwent a significant reduction in the moderate symptomatic group (P < 0.05). Our results indicate that chronic intoxication with MPTP induces early pathology in the corticopetal serotonergic system, which may contribute to early non-motor symptoms in PD.
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1-Metil-4-fenil-1,2,3,6-Tetrahidropiridina , Enfermedad de Parkinson , 1-Metil-4-fenil-1,2,3,6-Tetrahidropiridina/farmacología , Animales , Desnervación , Macaca mulatta , Serotonina , Tirosina 3-MonooxigenasaRESUMEN
Patients with primary immunodeficiency are at increased risk for malignancy, especially hematologic neoplasms. This paper reports a unique case of a 47-year-old man with X-linked agammaglobulinemia who presented with progressive asymptomatic violaceous papules and plaques on his face, hands, and trunk for 1 year. Skin biopsies revealed deep, nodular infiltrates of histiocytes and CD8-positive lymphocytes, with a CD4:CD8 ratio of 1:10. Laboratory studies showed cytopenias. Flow cytometry in the skin, blood, and bone marrow (BM) showed a CD3+/CD8+/CD57+ large granular lymphocyte population. BM biopsy showed 30% involvement with these atypical T-cells. T-cell gene rearrangement studies of skin, blood, and BM revealed identical T-cell clones. He was diagnosed with T-large granular lymphocyte leukemia (T-LGLL) with an associated CD8+ cutaneous lymphoproliferation. Skin involvement was suspected to represent infiltration by T-LGLL. However, co-existence of two lymphoproliferative disorders (LPDs), T-LGLL and CD8+ granulomatous LPD, remains a possibility. In general, cutaneous infiltrates associated with LGLL are rare and poorly understood. It has been suggested that they are markers of poor prognosis. Our case report describes skin, blood, and BM findings in an immunosuppressed patient with T-LGLL in detail. These findings have not yet been reported and their significance requires further investigation.
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Agammaglobulinemia/genética , Linfocitos T CD8-positivos/patología , Enfermedades Genéticas Ligadas al Cromosoma X/genética , Leucemia Linfocítica Granular Grande/genética , Leucemia Linfocítica Granular Grande/patología , Adyuvantes Inmunológicos/administración & dosificación , Adyuvantes Inmunológicos/uso terapéutico , Agammaglobulinemia/complicaciones , Agammaglobulinemia/diagnóstico , Agammaglobulinemia/patología , Biopsia , Médula Ósea/patología , Linfocitos T CD8-positivos/inmunología , Fármacos Dermatológicos/administración & dosificación , Fármacos Dermatológicos/uso terapéutico , Diagnóstico Diferencial , Quimioterapia Combinada , Reordenamiento Génico de Linfocito T , Enfermedades Genéticas Ligadas al Cromosoma X/complicaciones , Enfermedades Genéticas Ligadas al Cromosoma X/diagnóstico , Enfermedades Genéticas Ligadas al Cromosoma X/patología , Histiocitos/patología , Humanos , Imiquimod/administración & dosificación , Imiquimod/uso terapéutico , Terapia de Inmunosupresión/efectos adversos , Leucemia Linfocítica Granular Grande/complicaciones , Leucemia Linfocítica Granular Grande/tratamiento farmacológico , Masculino , Metotrexato/administración & dosificación , Metotrexato/uso terapéutico , Persona de Mediana Edad , Piel/patología , Resultado del TratamientoRESUMEN
BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening conditions that may present with similar findings to other severe dermatologic diseases. OBJECTIVE: The primary objective of this exploratory study was to explore factors associated with SJS/TEN and develop a model that provides the predicted probability of SJS/TEN for patients for whom the diagnosis of SJS/TEN is considered. METHODS: Retrospective review of consultations for patients with suspected SJS, TEN, or overlap at 4 academic dermatology consultation services. RESULTS: Overall, 208 patients were included; 59 (28.4%) had a final diagnosis of SJS/TEN, and 149 (71.6%) were given a different diagnosis. The most common mimickers were drug hypersensitivity syndrome (n = 21, 10.1%), morbilliform drug eruption (n = 18, 8.7%), erythema multiforme (n = 15, 7.2%), and acute generalized exanthematous pustulosis (n = 13, 6.2%). Nikolsky sign, atypical targets, fever, and lymphopenia were included in a model for predicting the probability of SJS/TEN. LIMITATIONS: All cases were obtained from academic centers, which may limit the generalization of findings to community-based settings. This was an exploratory study with a small number of cases, and external validation of the model performance is needed. CONCLUSION: Early dermatologic evaluation of patients with suspected SJS/TEN is key to separating patients with this condition from those who ultimately receive diagnoses of other serious skin diseases.
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Modelos Biológicos , Derivación y Consulta , Síndrome de Stevens-Johnson/diagnóstico , Adulto , Anciano , Diagnóstico Diferencial , Femenino , Hospitalización , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Medición de Riesgo/métodosRESUMEN
Secukinumab (also known as AIN-457) is a human monoclonal antibody targeting IL-17A, which has been recently FDA-approved for the treatment of moderate to severe psoriasis and psoriatic arthritis with coexistent moderate to severe plaque psoriasis based on clinical trials demonstrating excellent efficacy. This review will address the rationale for targeting the IL-23/Th17/IL-17 axis, the role of IL-17 and Th17 cells in psoriasis and other chronic inflammatory diseases, and will examine pre-clinical studies, pharmacologic properties, clinical efficacy, and the safety profile of secukinumab.
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Anticuerpos Monoclonales/uso terapéutico , Artritis Psoriásica/tratamiento farmacológico , Psoriasis/tratamiento farmacológico , Animales , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales Humanizados , Artritis Psoriásica/patología , Fármacos Dermatológicos/efectos adversos , Fármacos Dermatológicos/uso terapéutico , Humanos , Interleucina-17/antagonistas & inhibidores , Psoriasis/patología , Índice de Severidad de la EnfermedadRESUMEN
Refining diagnostic criteria has identified key characteristics differentiating rosacea, a chronic skin disorder, from other common cutaneous inflammatory conditions. The current classification system developed by the National Rosacea Society Expert Committee consists of erythematotelangiectatic, papulopustular, phymatous, and ocular subtypes. Each subtype stands as a unique entity among a spectrum, with characteristic symptoms and physical findings, along with an intricate pathophysiology. The main treatment modalities for rosacea include topical, systemic, laser, and light therapies. Topical brimonidine tartrate gel and calcineurin inhibitors are at the forefront of topical therapies, alone or in combination with traditional therapies such as topical metronidazole or azelaic acid and oral tetracyclines or isotretinoin. Vascular laser and intense pulsed light therapies are beneficial for the erythema and telangiectasia, as well as the symptoms (itching, burning, pain, stinging, swelling) of rosacea. Injectable botulinum toxin, topical ivermectin, and microsecond long-pulsed neodymium-yttrium aluminum garnet laser are emerging therapies that may prove to be extremely beneficial in the future. Once a debilitating disorder, rosacea has become a well known and manageable entity in the setting of numerous emerging therapeutic options. Herein, we describe the treatments currently available and give our opinions regarding emerging and combination therapies.
RESUMEN
There is an increasing trend shifting the aesthetic focus downward from the face with a significant number of new treatments aimed at the aging neck and below. Clinical characteristics of neck youth include clear skin texture and tone without laxity or fat, in addition to a well-defined cervicomental angle and distinct mandibular border. Similarly to treating facial aging, the neck requires a comprehensive assessment of all factors involved in the aging process--loss of volume, increased skin laxity, worsening texture and clarity, and crepe skin/wrinkling--as each requires a combination approach for improvement. It is essential to address each above factors for more than minimal improvement. A multitude of options including neuromodulators, energy based devices, surgery, and injectable agents for fat reduction are available in our armamentarium and understanding these options solo, or ideally in combination, is essential for best practice and optimal results. Herein, we describe synergic approaches to the treatment of neck aging.
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Técnicas Cosméticas , Rejuvenecimiento , Envejecimiento de la Piel , Terapia Combinada , Humanos , Cuello , Ritidoplastia/métodosRESUMEN
Refining diagnostic criteria has identified key characteristics differentiating rosacea, a chronic skin disorder, from other common cutaneous inflammatory conditions. The current classification system developed by the National Rosacea Society Expert Committee consists of erythematotelangiectatic, papulopustular, phymatous, and ocular subtypes. Each subtype stands as a unique entity among a spectrum, with characteristic symptoms and physical findings, along with an intricate pathophysiology. The main treatment modalities for rosacea include topical, systemic, laser, and light therapies. Topical brimonidine tartrate gel and calcineurin inhibitors are at the forefront of topical therapies, alone or in combination with traditional therapies such as topical metronidazole or azelaic acid and oral tetracyclines or isotretinoin. Vascular laser and intense pulsed light therapies are beneficial for the erythema and telangiectasia, as well as the symptoms (itching, burning, pain, stinging, swelling) of rosacea. Injectable botulinum toxin, topical ivermectin, and microsecond long-pulsed neodymium-yttrium aluminum garnet laser are emerging therapies that may prove to be extremely beneficial in the future. Once a debilitating disorder, rosacea has become a well known and manageable entity in the setting of numerous emerging therapeutic options. Herein, we describe the treatments currently available and give our opinions regarding emerging and combination therapies.