RESUMEN
BACKGROUND: Facial (FP) and genital psoriasis (GP) significantly affect patients' quality of life. Despite the advances in treatments, limited data on efficacy and safety are available on these difficult-to-treat areas. Guselkumab is an interleukin (IL)-23 inhibitor which has been proven effective in treating patients with moderate-to-severe plaque psoriasis. OBJECTIVES: The aim of this interim analysis was to report the efficacy and safety of guselkumab in the treatment of patients with FP and/or GP. MATERIALS AND METHODS: GULLIVER is a 52-week Italian observational study to evaluate the effectiveness and safety of guselkumab in a real-life setting in patients with FP and/or GP. Adult patients with facial and/or genital moderate-to-severe psoriasis (sPGA score ≥ 3) were included. The primary endpoint of this analysis was the percentage of patients achieving a facial or genital sPGA score of 0 (clear) or 1 (almost clear), at Week 12. The change in the score of the facial or genital sPGA components in patients with a score ≥3 for each sPGA component was assessed. PASI score in patients with a baseline PASI above or below 10 was evaluated. RESULTS: Overall, 351 patients were included in the study; 83.3% of FP and 76.5% of GP patients achieved the primary endpoint. Similar response rates were observed for the facial or genital sPGA components in patients with a baseline facial or genital sPGA score ≥3 in each component. Among patients with a baseline PASI score >10, mean PASI score improved from 19.0 (SD 8.3) to 2.2 (SD 4.8). Forty-four AEs were observed in 32 patients; two mild and transient AEs (fatigue and nausea) were considered treatment related. No SAEs were observed. CONCLUSIONS: Guselkumab, showing to be effective and safe in treating FP and GP, may be a valid therapeutic option for patients with psoriasis localized in these difficult-to-treat areas.
Asunto(s)
Anticuerpos Monoclonales Humanizados/efectos adversos , Dermatitis Atópica/tratamiento farmacológico , Fármacos Dermatológicos/efectos adversos , Osteoartritis de la Columna Vertebral/inducido químicamente , Adulto , Azetidinas/uso terapéutico , Fármacos Dermatológicos/uso terapéutico , Humanos , Janus Quinasa 1/antagonistas & inhibidores , Janus Quinasa 2/antagonistas & inhibidores , Masculino , Osteoartritis de la Columna Vertebral/diagnóstico , Osteoartritis de la Columna Vertebral/tratamiento farmacológico , Purinas/uso terapéutico , Pirazoles/uso terapéutico , Sulfonamidas/uso terapéuticoRESUMEN
BACKGROUND: Dupilumab, a fully human monoclonal antibody targeting the alpha subunit of IL-4 was recently approved for the treatment of moderate-to-severe atopic dermatitis (AD) in adult patients. OBJECTIVE: To assess dupilumab effectiveness and safety in adults with moderate-to-severe AD in a real-life Italian multicentre retrospective cohort. METHODS: Adult moderate-to-severe AD patients, referring to 39 Italian centers, received dupilumab in the context of a national patient access program. Disease assessment was performed at baseline, after 4 and 16 weeks of treatment using Eczema-Area-and-Severity-Index (EASI) score, itch and sleep numerical-rating-score (itch-NRS, sleep-NRS) and Dermatology-Life-Quality-Index (DLQI). RESULTS: A total of 109 (71 M/38F) patients was studied. There was a significant reduction in EASI score, itch-NRS, sleep-NRS and DLQI from baseline to week 4 and a further significant decline to week 16. EASI 50, EASI75 and EASI90 were achieved by 59.6%, 28.4% and 9.3% of patients at 4 weeks and by 87.2%, 60.6% and 32.4% of them at 16 weeks, respectively. Adverse events were experienced by 19.2% (21/109) of the patients and they were all mild in intensity, being conjunctivitis the most common side effect. CONCLUSIONS: Dupilumab significantly improved disease severity, pruritus, sleep loss and quality of life with an acceptable safety profile.
Asunto(s)
Anticuerpos Monoclonales Humanizados/administración & dosificación , Dermatitis Atópica/tratamiento farmacológico , Prurito , Calidad de Vida , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prurito/tratamiento farmacológico , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Sueño , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Dermographism is a condition characterized by a weal response to a combination of pressure and traction on skin surface, and its diagnosis is based on medical history, clinical criteria and provocation test. The Dermographic Tester® , a pen-sized tool containing a spring-loaded blunt tip, is the most widely used instrument for the provocation test, and it exerts increasing pressures on the skin surface according to an arbitrary units (AU) scale. Analysing the mechanism of function and trying to convert the AUs to SI units (g/mm2 ), we found that this instrument had some defects and limits that would compromise a true and repeatable quantification of the weal response threshold. Consequently, we decided to develop a new instrument, the Digital Dermographic Tester (DDT), which is engineered with an inside force sensor to implement features lacking in the current tools, in the hope of enhancing the precision of the provocation test. AIM: To validate the effectiveness and accuracy of the DDT. METHODS: We tested the DDT on 213 participants purposely sampled to obtain three groups, each with a different pattern of reaction to mechanical stimuli. Based on anamnestic, diagnostic and symptomatic criteria, patients were divided into dermographic urticaria (DU), spontaneous urticaria (SU) and healthy control (HC) groups. The DDT was used to apply 12 levels of pressure to the skin surface, and a frequency distribution of positive reactions was displayed for each group. RESULTS: A force of 36-40 g/mm2 appropriately differentiated physiological from pathological conditions with high sensitivity and specificity. CONCLUSIONS: The DDT was found to be capable of differentiating patients with DU patients from those with SU and from HCs, and was able to precisely identify the weal elicitation threshold.
Asunto(s)
Pruebas Cutáneas/instrumentación , Urticaria/diagnóstico , Adolescente , Adulto , Anciano , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Presión/efectos adversos , Sensibilidad y Especificidad , Piel/patología , Encuestas y Cuestionarios , Urticaria/etiología , Adulto JovenRESUMEN
Polymorphic light eruption (PLE) is described as a delayed-type hypersensitivity reaction (DTHR) toward a de novo light-induced antigen, yet to be identified. In effect, the inflammatory pathways of PLE and allergic contact dermatitis (ACD) share common patterns in terms of the mediators involved from the innate and adaptive immune system participating in the DTHR. As we have previously highlighted the role of interleukin (IL)-1 family members in ACD, we hypothesised that the same mediators could have similar functions in PLE. Our research aimed to assess the expression of certain IL-1family members in PLE patients vs. controls, and to compare it with ACD. The study population comprised 17 patients with PLE, 5 affected by ACD and 10 healthy controls in the same age range. Lesional and healthy skin samples were collected respectively from patients and donors. IL-36α, IL-36ß, IL-36γ, IL-36 receptor antagonist (Ra), IL-1ß, IL-33 gene and protein expressions were evaluated through RT-PCR and immunohistochemistry. Circulating proteins in the PLE patients were analysed by using western blot. The IL-36γ gene expression was significantly increased in PLE lesions compared to that in healthy controls and ACD lesions (***p < 0.001; ##p < 0.01 respectively), whereas the other analyzed ILs were more expressed in ACD. Immunohistochemical analysis revealed that IL-36α and IL-36γ protein levels were increased in PLE lesions compared to those of the healthy samples (***p < 0.001). Furthermore the IL-36γ plasma level was increased in PLE patients vs. controls (*p < 0.05). Our findings indicate that the IL-1 family pro-inflammatory members are increased in PLE with distinct differences from those in ACD, in particular with regard to IL-36γ mRNA regulation. Their role as activators of the local, and perhaps systemic, immune response, or as inhibitors of the immune tolerance machinery, needs further investigation.
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Dermatitis Alérgica por Contacto/metabolismo , Interleucina-1/metabolismo , Trastornos por Fotosensibilidad/metabolismo , Enfermedades Cutáneas Genéticas/metabolismo , Adulto , Anciano , Femenino , Humanos , Interleucina-1/genética , Masculino , Persona de Mediana EdadAsunto(s)
Ciclooxigenasa 2 , Queratinocitos , Línea Celular , Niacina , Niacinamida , Rayos UltravioletaAsunto(s)
Antiinflamatorios no Esteroideos/uso terapéutico , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Etanercept/farmacología , Etanercept/uso terapéutico , Psoriasis/tratamiento farmacológico , Humanos , Psoriasis/patología , Índice de Severidad de la EnfermedadAsunto(s)
Apoptosis/genética , Queratinocitos/fisiología , Trastornos por Fotosensibilidad/genética , Adulto , Análisis de Varianza , Estudios de Casos y Controles , Femenino , Expresión Génica/genética , Regulación de la Expresión Génica/genética , Genes/genética , Predisposición Genética a la Enfermedad/genética , Estudio de Asociación del Genoma Completo , Humanos , Persona de Mediana Edad , Adulto JovenRESUMEN
BACKGROUND: Haptoglobin (Hp) is one of the acute phase proteins, whose main function is to bind free haemoglobin (Hb) and transport it to the liver for degradation and iron recycling. In addition to its role as an Hb scavenger, Hp has been shown to behave as an anti-inflammatory, antioxidant and angiogenic factor. We previously investigated the role of Hp in the pathogenesis of psoriasis, and found that it displays some structural modifications that might be associated with protein function in the disease. Phototherapy is an efficacious treatment for psoriasis, although the biological mechanisms by which phototherapy improves psoriasis are still unclear. AIM: To investigate the effects of ultraviolet (UV)B on Hp to clarify the role of Hp in psoriasis. METHODS: Expression of the genes encoding Hp, interleukin (IL)-6 and IL-10 was assessed in UVB-irradiated and unirradiated HaCaT cells. The biological significance of Hp modulation of UVB treatment was confirmed by ELISA and Western blotting. The Hp gene and protein expression in the skin of patients with psoriasis was also investigated. RESULTS: In vitro results showed that UVB modulated IL-6 and IL-10 gene expression and Hp gene and protein expression in HaCaT cells. The in vivo data also showed that Hp levels were increased in the skin of patients with psoriasis compared with healthy controls. CONCLUSIONS: UVB irradiation was able to modulate Hp production in immortalized keratinocytes. The higher levels of Hp in vivo in both lesional and nonlesional skin suggest that it might have a role in the pathogenesis of the disease.
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Haptoglobinas/efectos de la radiación , Psoriasis/radioterapia , Terapia Ultravioleta , Western Blotting , Estudios de Casos y Controles , Células Cultivadas , Ensayo de Inmunoadsorción Enzimática , Haptoglobinas/fisiología , Humanos , Inmunohistoquímica , Interleucina-10/metabolismo , Interleucina-6/metabolismo , Psoriasis/metabolismoAsunto(s)
Exposición a Riesgos Ambientales , Pediatras , Luz Solar , Niño , Humanos , Italia , Riesgo , Encuestas y CuestionariosAsunto(s)
Miasis/diagnóstico , Adulto , Animales , Brasil , Femenino , Humanos , Miasis/parasitología , ViajeRESUMEN
BACKGROUND: Until relatively recently, psoriasis has been considered to be a mainly T helper (Th)1-driven inflammatory disease; however, several findings have now assessed a major role for Th17 cells in its pathogenesis. Adalimumab is a biological agent that inhibits TNF-α, a pro-inflammatory cytokine with a pivotal role in the mechanisms of the disease. OBJECTIVE: To elucidate the in vivo effects of adalimumab therapy on Th17 pathway. METHODS: Quantitative real-time reverse transcriptase polymerase chain reaction was used to analyse levels of expression of Th17 polarizing cytokines (IL-23A, TGF-ß, IL-1ß, IL-6), Th17 cytokines (IL-17, IL-22) as well as TNF-α, Th1 polarizing cytokine (IFN-α) and Th17 downstream effector mediators, such as chemokines (IL-8, CCL-20) in skin and peripheral blood mononuclear cells before and after 16 weeks of adalimumab therapy. Similarly, gene expression of Th17 induced mediators by keratinocytes (antimicrobial peptides: HBD-2, S100A7) was investigated at skin level. In addition, cutaneous and plasma IL-17 was examined by immunohistochemistry and enzyme-linked immunosorbent assay respectively. Efficacy of the treatment was assessed by several clinical index scores as well as epidermal thickness reduction. RESULTS: Adalimumab therapy led to improvement in skin disease scores in all patients. Moreover, adalimumab treatment down-modulated Th17 pathway at skin level. Plasma IL-17 levels and IL-17-positive cells in psoriatic lesional skin were decreased by adalimumab treatment. CONCLUSIONS: Our data highlight that the immunomodulatory activity of adalimumab is associated with considerable clinical improvements as well as a potent shut down of Th17 response in patients with moderate-to-severe psoriasis.
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Antiinflamatorios/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Citocinas/metabolismo , Psoriasis/tratamiento farmacológico , Adalimumab , Adulto , Ensayo de Inmunoadsorción Enzimática , Humanos , Interleucina-17/sangre , Psoriasis/inmunología , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Células Th17/inmunologíaRESUMEN
Ultraviolet (UV) radiation has profound effects on human skin, causing sunburn, inflammation, cellular-tissue injury, cell death, and skin cancer. Most of these effects are mediated by a number of cytokines produced by keratinocytes. In this study we investigated whether nicotinamide (NCT), the amide form of vitamin B3, might have a protective function in reducing the expression of interleukin (IL)-1ß, IL-6, IL-8, IL-10, monocyte chemoattractant protein (MCP)-1 and tumour necrosis factor (TNF)-α in UV-irradiated keratinocytes. HaCaT cells were treated with UVB in the presence or absence of NCT, and cytokine mRNA levels were examined by quantitative real-time PCR. NCT significantly downregulated IL-6, IL-10, MCP-1 and TNF-α mRNA expression, whereas it did not exert any significant effect on IL-1ß or IL-8 expression. Because of its ability to decrease these cytokine mediators after UV exposure, NCT is a possible therapy to improve or prevent conditions induced or aggravated by UV light.
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Citocinas/metabolismo , Queratinocitos/efectos de los fármacos , Niacinamida/farmacología , Complejo Vitamínico B/farmacología , Quimiocina CCL2/genética , Regulación hacia Abajo , Perfilación de la Expresión Génica , Humanos , Interleucina-10/genética , Interleucina-6/genética , Queratinocitos/metabolismo , Queratinocitos/efectos de la radiación , ARN Mensajero/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Piel/efectos de los fármacos , Piel/metabolismo , Piel/efectos de la radiación , Factor de Necrosis Tumoral alfa/genética , Rayos UltravioletaRESUMEN
A female infant had been delivered prematurely at 33 weeks to a gravida 1, para 0, 32-year-old mother following normal spontaneous vaginal delivery. Because of persistent patent ductus arteriosus the new born underwent surgery after 30 days. Four months later, when the infant arrived at our observation, approximately 13 red, nodular hemangiomas ranging from 0.5 to 30 mm in diameter were scattered over the scalp, trunk, abdomen, and extremities. Laboratory and instrumental tests investigating visceral involvement were all negative. Our diagnosis was of benign neonatal hemangiomatosis. Benign neonatal hemangiomatosis is a condition with multiple congenital hemangiomas limited to the skin. The incidence in the newborn population is between 1.0% and 4% with females 4 times more affected than males. Solitary hemangiomas occur more frequently in premature neonates with a reported incidence, inversely proportional to birth weight. Although the exact mechanism for hemangioma development remains unknown, vascular growth factors seem to play a role in the pathogenesis. Proliferation most likely results from an imbalance between positive and negative angiogenic factors expressed by the hemangioma and adjacent normal tissue. Patency of the ductus arteriosus is a common complication of preterm birth. During the immediate postpartum period, a loss of vasodilatory stimuli and activation of intrinsic contractile mechanisms facilitates ductus lumen occlusion. The imbalance of these forces, linked to premature birth, interrupts the normal maturation process, leaving the immature ductus patent. Our case is the first one of benign neonatal hemangiomatosis and patency ductus arteriosus described.
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Conducto Arterioso Permeable/complicaciones , Hemangioma/complicaciones , Enfermedades del Prematuro , Neoplasias Cutáneas/complicaciones , Femenino , Hemangioma/patología , Humanos , Recién Nacido , Recien Nacido Prematuro , Enfermedades del Prematuro/patología , Neoplasias Cutáneas/patologíaRESUMEN
Vitamin K1 (phytomenadione or phytonadione) is a fat soluble vitamin used to treat certain coagulation disorders. Intra muscular injection of vitamin K1 can occasionally be complicated by different types of skin reactions: erythematous plaques, urticarial rashes or scleroderma-like lesions at the injection site. We report the case of a 52-year-old man presenting with 2 symmetrical erythematous-infiltrated scleroderma-like plaques localized on the right and left lower trunk. To correct the coagulation deficiency with hypoprothrombinemia developed as a consequence of HCV+ hepatitis, the patient was on vitamin K1 therapy, administered by i.m. injection (10 mg Vitamin K1/1 ml) once a day for 2 weeks. Three months after treatment interruption, ivory indurated morphoeiform plaques developed at the injection sites, assuming the typical appearance of a "cowboy's belt with revolver". The scleroderma-like lesions persisted 2 years after vitamin K1 withdrawal. We report this case to highlight the possibility that vitamin K1 injections can occasionally be complicated by different types of skin reactions such as sclerodermatous plaques. Due to the delay in the onset, to the variable clinical picture, to the persistence after therapy interruption, this kind of lesions can represent a tricky diagnostic challenge and in spite of different treatments can endure for years.
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Esclerodermia Localizada/inducido químicamente , Vitamina K 1/efectos adversos , Diabetes Mellitus Tipo 2/complicaciones , Eritema/inducido químicamente , Hepatitis C Crónica/complicaciones , Humanos , Hipoprotrombinemias/tratamiento farmacológico , Hipoprotrombinemias/etiología , Inyecciones Intramusculares , Masculino , Persona de Mediana Edad , Esclerodermia Localizada/complicaciones , Esclerodermia Localizada/patología , Vitamina K 1/administración & dosificación , Vitamina K 1/uso terapéuticoRESUMEN
AIM: Theoretically, skin barrier creams reduce or even prevent the penetration into the skin by building up a physical barrier, like a thin film between the skin and the irritant. Practically, controversial experiences concerning the effectiveness of barrier creams exist. For this, we propose an in vivo method to evaluate the efficacy of barrier creams trough clinical scoring and instrumental analysis. METHODS: Nineteen housewives with hand dermatitis in remission phase were enrolled in the study. Every patient was evaluated clinically and an arbitrary score was assigned by the investigator considering erythema, exudation, lichenification and xerosis. A score was also assigned by every patient to itching and burning. As measurement of the functional state of the skin and of the effectiveness of the barrier cream, transepidermal water loss (TEWL), corneometry, colorimetry and visco-elasticity determination were performed. To investigate the protection properties against irritant products, the 24-h irritancy patch test with sodium lauryl sulphate 1% in water was used. RESULTS: Through the patch test technique the efficacy of the barrier cream was tested compared to other topical products containing corticosteroids, lipids, humectants or urea, with already known anti-inflammatory, lenitive or protective properties. The results showed this methods easy and fast in handling, non-invasive, standardized, and in vivo applicable for evaluation and ranking of barrier creams. CONCLUSION: The study preparation demonstrated high tolerability and indubitable efficacy in improving the skin barrier function even towards a very well known irritant.