Ustekinumab in Real-Life Practice: Experience in 116 Patients with Moderate-To-Severe Psoriasis.

INTRODUCTION: Ustekinumab is a monoclonal antibody directed against the p40 subunit common to both IL-12 and IL-23 cytokines. Although the evidence of ustekinumab efficacy and safety in clinical trials is extensively recognized, data on its use in clinical practice is limited. Our objective is to report on the real-life experience of two Portuguese dermatology departments with ustekinumab in patients with moderate to severe psoriasis, and to identify the clinical characteristics associated with a weaker clinical response. MATERIAL AND METHODS: Clinical, demographic, and therapeutic response data was retrospectively collected in 116 patients with moderate to severe psoriasis treated with ustekinumab between November 2009 and December 2015. RESULTS: A PASI75 therapeutic response was observed in 67.2%, 85.3%, 89.6% and 88.7% of patients at weeks 4, 12, 24 and 52, respectively. Ustekinumab was discontinued in seven patients (three due to primary failure, three due to secondary treatment failure, and one due to adverse events). Neither cardiovascular events nor cases of reactivation of previous infections (tuberculosis, hepatitis B) were observed during follow-up. In nine patients methotrexate was used as adjuvant therapy, and fourteen patients required ustekinumab dosage optimization. No side effects were observed in the two latter groups. The therapeutic response was higher in patients naïve to biologic therapies as compared to non-naïve patients. DISCUSSION AND CONCLUSION: A trend towards lower clinical response was observed in patients weighing between 90-100 kg, and dosage optimization in this group of patients may be of value prior to considering biologic switch.

Introdução: O ustekinumab é um anticorpo monoclonal dirigido contra a subunidade p40 presente nas IL-12 e 23. A evidência da sua eficácia e segurança em ensaios clínicos é amplamente conhecida. No entanto a evidência da sua utilização na prática clínica é relativamente limitada na população Portuguesa. O objetivo deste trabalho é relatar a experiência de dois serviços de dermatologia Portugueses no tratamento da psoríase moderada a grave com ustekinumab. Material e Métodos: Foram avaliados os dados clínicos, demográficos, e de resposta terapêutica ao ustekinumab em 116 doentes com psoríase tratados entre novembro de 2009 e dezembro de 2015. Resultados: Observou-se uma resposta terapêutica ≥ PASI75 em 67,2%, 85,3%, 89,6% e 88,7% dos doentes às semanas 4, 12, 24 e 52, respetivamente. O ustekinumab foi descontinuado em sete doentes (três por falências primárias, três por falências secundárias e um por evento adverso). Não foram observados eventos cardiovasculares nem reativações de infecções prévias (tuberculose, hepatite B). Em nove doentes foi utilizado em simultâneo metotrexato, e em catorze foi necessário otimizar a dose de ustekinumab. Não foram observados efeitos colaterais nestes grupos. A resposta terapêutica foi superior nos doentes naïve a terapêuticas biológicas comparativamente com os doentes não-naïve. Observou-se uma tendência para resposta clínica inferior nos doentes com peso entre 90 ­ 100 kg. Discussão e Conclusão: Este estudo confirma a segurança e eficácia de ustekinumab no tratamento da psoríase moderada a grave em doentes da prática clínica real, sustenta a eficácia mesmo nos doentes previamente expostos a terapêutica biológica e aponta para a possível necessidade de ajustar a dose a partir dos 90 kg.

Chronic Urticaria in the Real-Life Clinical Practice Setting in Portugal: Baseline Results from the Non-Interventional Multicentre AWARE Study.

INTRODUCTION: There is a paucity of information regarding chronic urticaria patients' care in a real-world setting. The objective of this study was to report and evaluate the baseline characteristics of Portuguese chronic urticaria patients refractory to H1-antihistamines included in the AWARE study. MATERIAL AND METHODS: This is a non-interventional cohort study. Adult patients with a diagnosis of chronic urticaria with symptoms for at least two months, refractory to H1-antihistamines, consulting one of the 10 participating urticaria centers throughout Portugal have been included in the study. Baseline sociodemographic data, medical history, clinical parameters, medication, weekly urticaria activity score, and dermatology quality of life index have been collected. RESULTS: Seventy six patients were included, of which 76.3% were women. The majority of patients had a diagnosis of chronic spontaneous urticaria (88.2%) and 39.5% had angioedema. Around 91.0% of patients were medicated with non-sedative H1-antihistamines and 35.4% with a third line therapy. Median dermatology quality of life index was 5.0 and median weekly urticaria activity score was 13.0. DISCUSSION: The baseline results suggest that patients with chronic urticaria refractory to H1-antihistamines are being under-treated in the real-world setting. CONCLUSION: The AWARE study demonstrates the real impact of chronic urticaria on Portuguese patients refractory to H1-antihistamines treatment, and 30% report a very large or extremely large deleterious effect on their quality of life. The follow-up of these patients will allow evaluating strategies aimed at optimizing disease control.

Introdução: A informação sobre os doentes com urticária crónica em ambiente de vida real é escassa e este estudo teve por objectivo reportar e avaliar as características basais dos doentes portugueses com urticária crónica refractários aos anti-histamínicos H1 incluídos no estudo AWARE. Material e Métodos: Estudo de coorte não intervencional. Foram incluídos doentes adultos com diagnóstico de urticária crónica sintomáticos durante pelo menos dois meses, refratários aos anti-histamínicos H1, seguidos em 10 centros de urticária em Portugal. Foram recolhidos dados basais sociodemográficos, história clínica, parâmetros clínicos, medicação, índice semanal de atividade de urticária e índice de qualidade de vida dermatológico. Resultados: Foram incluídos 76 doentes, dos quais 76,3% mulheres. A maioria dos doentes estava diagnosticado com urticária crónica espontânea (88,2%) e 39,5% apresentavam angioedema. Cerca de 91,0% dos doentes estavam medicados com anti-histamínicos H1 não sedativos e 35,4% com terapêuticas de terceira linha. A mediana do índice de qualidade de vida dermatológico foi 5,0 e a mediana do índice semanal de atividade de urticária foi 13,0. Discussão: Os resultados basais sugerem que os doentes com urticária crónica refratários ao tratamento com anti-histamínicos H1 estão sub-tratados em ambiente de vida real. Conclusão: O estudo AWARE vem demonstrar o real impacto da urticária crónica nos doentes portugueses refratários ao tratamento com anti-histamínicos H1 onde mais de 30% reporta um impacto elevado ou extremamente elevado da doença na sua qualidade de vida. O seguimento destes doentes permitirá avaliar estratégias para otimização do controlo da doença.

Adult blaschkolinear acquired inflammatory skin eruption (BLAISE) with simultaneous features of lichen striatus and blaschkitis.

Blaschkitis and lichen striatus are generally distinguished in the literature by the age of onset, lesion distribution, and histopathology. However, there is currently no clear consensus among authors about whether to consider blaschkitis and lichen striatus different clinical entities or a spectrum ofthe same disease. We present a case of adult BLAISE with features of both lichen striatus and blaschkitis, which seems to support the theory that these clinical entities may in fact represent a spectrum of the same pathological process.

Allergic contact dermatitis caused by (meth)acrylates in nail cosmetic products in users and nail technicians - a 5-year study.

BACKGROUND: The increasing use of long-lasting nail aesthetic products has led to a growing number of cases of allergic contact dermatitis (ACD) caused by (meth)acrylates in recent years. OBJECTIVES: To provide information on ACD caused by (meth)acrylates related to nail cosmetic products. METHODS: We retrospectively reviewed files of patients with ACD caused by (meth)acrylates related to nail cosmetic products, who were patch tested between January 2011 and December 2015 in 13 departments of dermatology in Portugal. RESULTS: Two-hundred and thirty cases of ACD caused by (meth)acrylates (55 technicians, 56 consumers, and 119 with mixed exposure) had been documented, mostly as chronic hand eczema (93%). The most common sensitizers were: 2-hydroxyethyl methacrylate (HEMA), which was positive in 90% of the tested patients, 2-hydroxypropyl methacrylate (HPMA), which was positive in 64.1%, and ethyleneglycol dimethacrylate, which was positive in 54.5%. CONCLUSION: HEMA and HPMA were the most frequent positive allergens. HEMA, which identified 90% of cases, can be considered to be a good screening allergen. The high number of cases of ACD caused by (meth)acrylates in nail cosmetic products certainly warrants better preventive measures at the occupational level, and specific regulation in the field of consumer safety.

Infantile bullous pemphigoid with "string of pearls sign".

Bullous pemphigoid (BP) is an immune mediated bullous disease that is manifested by urticarial plaques with superimposed subepidermal blisters and significant pruritus. It is generally found in the elderly, but is rare in the pediatric population. A 5-month-old girl previously diagnosed with hand-foot-mouth disease was examined in our dermatology department owing to vesicles and bullae, initially located to the hands and feet, which progressed with new lesions. Tense vesicles and bullae distributed in an annular string of pearls pattern on the abdomen and facial and cervical regions were noted. Histologic and immunologic findings were consistent with the diagnosis of infantile BP. Disease control was obtained with oral prednisolone and dapsone; the patient was still in clinical remission 6 months after treatment cessation. The differential diagnosis of the clinical presentation of the lesions in our patient is of note, given that this blistering pattern is frequently reported in association with linear IgA bullous dermatosis.

Annular elastolytic giant cell granuloma: a "visible" diagnosis.

Annular elastolytic giant cell granuloma (AEGCG) is a rare granulomatous skin disease of undetermined cause, characterized by annular plaques with raised erythematous borders in sun-exposed skin. The typical histologic features are dermal infiltration by multinucleated giant cells, elastin degeneration, and elastophagocytosis. The authors describe a clinical case of AEGCG, which exhibited an excellent response to hydroxycloroquine.

Palmoplantar Psoriasis and Palmoplantar Pustulosis: Current Treatment and Future Prospects.

Palmoplantar psoriasis and palmoplantar pustulosis are chronic skin diseases with a large impact on patient quality of life. They are frequently refractory to treatment, being generally described as a therapeutic challenge. This article aims to review the definitions of palmoplantar psoriasis and palmoplantar pustulosis, highlighting the similarities and differences in terms of epidemiology, clinical presentation, genetics, histopathology, and pathogenesis, as well as treatment options for both entities. Classical management of mild to moderate palmoplantar pustulosis and palmoplantar psoriasis relies on use of potent topical corticosteroids, phototherapy, and/or acitretin. Nevertheless, these drugs have proven to be insufficient in long-term control of extensive disease. Biologic therapy-namely, anti-interleukin-17 agents and phosphodiesterase type 4 inhibitors-has recently shown promising results in the treatment of palmoplantar psoriasis. Knowledge of the pathophysiologic pathways of both entities is of utmost importance and may, in the future, allow development of molecularly targeted therapeutics.

IL-17 Blockade in Psoriasis: Friend or Foe in Cardiovascular Risk?

Psoriasis is a chronic, immune-mediated inflammatory disorder associated with systemic inflammation and a significantly increased risk of cardiovascular disease. Common pathologic mechanisms are likely involved in the pathogenesis of psoriasis and atherosclerosis, including similar inflammatory cytokine profiles and proinflammatory cell types. The hypothesis that aggressive treatment of skin inflammation may decrease the risk of developing atherosclerosis and consequently cardiovascular disease is currently a focus of major attention. Interleukin (IL)-17 may be an important cytokine linking skin disease to vascular disease/inflammation. However, the role of IL-17 in atherosclerosis is still controversial, as IL-17 may exhibit pro-atherogenic or anti-atherogenic effects depending on the specific tissue, cellular, and immune context. Given the development of several IL-17 inhibitors, the investigation of IL-17 inhibition impact on cardiovascular outcome is extremely important.

Psoriasis strikes back! Epicardial adipose tissue: another contributor to the higher cardiovascular risk in psoriasis.

For many years psoriasis was considered an inflammatory condition restricted to the skin. However, nowadays it is considered an immune-mediated, systemic inflammatory condition associated with numerous medical comorbidities, particularly cardiometabolic diseases, and overall cardiovascular mortality. Several studies have suggested that psoriasis may be an independent risk factor for atherosclerosis, indicating that psoriasis itself poses an intrinsic risk for cardiovascular disease, probably due to the disease's inflammatory burden. However, other causes beyond systemic inflammation and traditional cardiovascular risk factors may be implicated in cardiovascular disease in psoriasis. Recently, epicardial adipose tissue, an emerging cardiovascular risk factor, has been shown to be increased in psoriasis patients and to be associated with subclinical atherosclerosis, providing another possible link between psoriasis and atherosclerosis. The reason for the increase in epicardial adipose tissue in patients with psoriasis is unknown, but it is probably multifactorial, with genetic, immune-mediated and behavioral factors having a role. Thus, along with the increased prevalence of cardiometabolic risk factors and systemic inflammation in psoriasis, epicardial adipose tissue is probably another important contributor to the higher cardiovascular risk observed in psoriasis.

Postoperative imaging in cyanotic congenital heart diseases: part 1, Normal findings.

OBJECTIVE: The objective of this article is to illustrate the most common surgical procedures performed in patients with cyanotic congenital heart diseases along with the respective postoperative MRI findings normally seen in clinical practice. CONCLUSION: Radiologists need a solid knowledge of the surgical procedures used to treat patients with cyanotic congenital heart diseases to identify what constitutes normal postoperative findings on MR images and to play an ongoing role in the integral lifelong care of these patients.

Postoperative imaging in cyanotic congenital heart diseases: part 2, Complications.

OBJECTIVE: The purpose of this article is to illustrate the MRI appearance of postoperative complications in the surgical procedures most commonly performed to correct cyanotic congenital heart disease. CONCLUSION: The radiologist must be familiar with the morphologic and functional MRI appearances of surgical complications in patients with palliated or repaired cyanotic congenital heart disease to deliver an accurate diagnosis on which to base management decisions.

[Reconstruction of the right ventricular outflow tract using a Medtronic Freestyle aortic root bioprosthesis]. / Reconstrucción del tracto de salida del ventrículo derecho con raíz aórtica protésica Medtronic Freestyle.

Uncorrected, long-term pulmonary regurgitation leads to right ventricular dilatation and dysfunction in a significant percentage of patients. We used magnetic resonance imaging (MRI) before and after surgery to assess the effect of pulmonary valve replacement with the Medtronic Freestyle bioprosthesis on right ventricular function and volume in nine patients with pulmonary regurgitation or stenosis. Mean follow-up time was 26 (10) months. We observed a decrease in mean end-diastolic volume from 143.6 (85.1) mL/m2 to 74.1 (12.6) mL/m2 (P=.018) and, in end-systolic volume from 88.0 (50.3) mL/m2 to 35.8 (19.3) mL/m2 (P=.016). In pulmonary valve disease, extensive follow-up by MRI is essential for timely evaluation of the degree of right ventricular dilation or dysfunction and for selecting a suitable time for valve replacement. The Medtronic Freestyle bioprosthesis is a good surgical choice for pulmonary valve replacement as its use is associated with low morbidity and mortality and the successful normalization of ventricular volumes.

Reconstrucción del tracto de salida del ventrículo derecho con raíz aórtica protésica Medtronic Freestyle / Reconstruction of the right ventricular outflow tract using a medtronic freestyle aortic root bioprosthesis

La insuficiencia pulmonar no corregida conduce a la dilatación y disfunción del ventrículo derecho a largo plazo en un porcentaje importante de pacientes. Hemos analizado mediante resonancia magnética cardiaca (RMC) preoperatoria y postoperatoria el efecto del recambio valvular pulmonar con prótesis Medtronic Freestyle en la función y los volúmenes del ventrículo derecho en 9 pacientes con insuficiencia y/o estenosis pulmonar con seguimiento de 26 ± 10 meses. Observamos una disminución del volumen telediastólico medio desde 143,6 ± 85,1 hasta 74,1 ± 12,6 ml/m2 (p = 0,018), y del volumen telesistólico medio desde 88 ± 50,3 hasta 35,8 ± 19,3 ml/m2 (p = 0,016). La valvulopatía pulmonar requiere un seguimiento exhaustivo mediante RMC para determinar precozmente el grado de dilatación y disfunción del ventrículo derecho, y así decidir el momento idóneo para la sustitución valvular. La bioprótesis Freestyle en posición pulmonar es una opción quirúrgica adecuada, con una baja morbimortalidad y excelentes resultados en cuanto a restauración volumétrica ventricular (AU)

Uncorrected, long-term pulmonary regurgitation leads to right ventricular dilatation and dysfunction in a significant percentage of patients. We used magnetic resonance imaging (MRI) before and after surgery to assess the effect of pulmonary valve replacement with the Medtronic Freestyle bioprosthesis on right ventricular function and volume in nine patients with pulmonary regurgitation or stenosis. Mean follow-up time was 26 (10) months. We observed a decrease in mean end-diastolic volume from 143.6 (85.1) mL/m2 to 74.1 (12.6) mL/m2 (P=.018) and, in end-systolic volume from 88.0 (50.3) mL/m2 to 35.8 (19.3) mL/m2 (P=.016). In pulmonary valve disease, extensive follow-up by MRI is essential for timely evaluation of the degree of right ventricular dilation or dysfunction and for selecting a suitable time for valve replacement. The Medtronic Freestyle bioprosthesis is a good surgical choice for pulmonary valve replacement as its use is associated with low morbidity and mortality and the successful normalization of ventricular volumes (AU)