Efficacy and Safety of Dupilumab for the Treatment of Severe Atopic Dermatitis in Clinical Practice: A Single Center Experience.

BACKGROUND: Dupilumab is a new targeted therapy for severe atopic dermatitis (AD) with limited real-world evidence. OBJECTIVE: Explore our experience with dupilumab for AD in clinical practice at a tertiary care center. MATERIAL AND METHOD: Unicentric observational retrospective study including adult and pediatric patients with severe AD receiving dupilumab between December 2017 and December 2021. The Eczema Area and Severity Index (EASI) score, Pruritus Numerical Rating Scale (P-NRS) and Sleep disturbance Numerical Rating Scale (S-NRS) were recovered to assess severity and response. RESULTS: Fifty-nine patients received dupilumab: 52, 48, 26 and 13 patients reached 6, 12, 24 and 36 months of treatment, respectively. The EASI-75 response rates were 94.2%, 95.8%, 92.3% and 100% at months 6, 12, 24 and 36. The EASI-90 response rates were 63.5%, 72.9%, 84.6% and 92.3% at months 6, 12, 24 and 36. The EASI <7 response rates were 92.3%, 91.7%, 88.5% and 100% at months 6, 12, 24 and 36. The P-NRS ≥4 reduction rates were 86%, 87.5%, 92.3% and 100% at months 6, 12, 24 and 36. The S-NRS ≥4 reduction rates were 82.7%, 85.4%, 100% and 100% at months 6, 12, 24 and 36. Adverse events were mild and occurred in 20.3% of patients, all of them adults. CONCLUSION: Our findings support dupilumab's favorable efficacy and tolerability profile in clinical practice. Dupilumab offers a rapid and sustained response, regardless of combined therapy. Longer follow-ups are still required to adequately assess its performance.

Efficacy and Safety of Dupilumab for the Treatment of Severe Atopic Dermatitis in Clinical Practice: A Single Center Experience. / [Artículo traducido]Eficacia y seguridad de dupilumab para el tratamiento de la dermatitis atópica grave en la práctica clínica: experiencia en un centro terciario.

BACKGROUND: Dupilumab is a new targeted therapy for severe atopic dermatitis (AD) with limited real-world evidence. OBJECTIVE: Explore our experience with dupilumab for AD in clinical practice at a tertiary care center. MATERIAL AND METHOD: Unicentric observational retrospective study including adult and pediatric patients with severe AD receiving dupilumab between December 2017 and December 2021. The Eczema Area and Severity Index (EASI) score, Pruritus Numerical Rating Scale (P-NRS) and Sleep disturbance Numerical Rating Scale (S-NRS) were recovered to assess severity and response. RESULTS: Fifty-nine patients received dupilumab: 52, 48, 26 and 13 patients reached 6, 12, 24 and 36 months of treatment, respectively. The EASI-75 response rates were 94.2%, 95.8%, 92.3% and 100% at months 6, 12, 24 and 36. The EASI-90 response rates were 63.5%, 72.9%, 84.6% and 92.3% at months 6, 12, 24 and 36. The EASI <7 response rates were 92.3%, 91.7%, 88.5% and 100% at months 6, 12, 24 and 36. The P-NRS ≥4 reduction rates were 86%, 87.5%, 92.3% and 100% at months 6, 12, 24 and 36. The S-NRS ≥4 reduction rates were 82.7%, 85.4%, 100% and 100% at months 6, 12, 24 and 36. Adverse events were mild and occurred in 20.3% of patients, all of them adults. CONCLUSION: Our findings support dupilumab's favorable efficacy and tolerability profile in clinical practice. Dupilumab offers a rapid and sustained response, regardless of combined therapy. Longer follow-ups are still required to adequately assess its performance.

Performance of Coronary Artery Calcium Testing in Patients With Severe Psoriasis: Risk Assessment and Reclassification Potential in a Low Cardiovascular Risk Population.

BACKGROUND: Patients with severe psoriasis have an increased cardiovascular (CV) risk and prevalence of subclinical coronary artery disease (CAD). Coronary artery calcium (CAC) testing can detect subclinical CAD and improve cardiovascular risk assessment beyond clinical scores. OBJECTIVES: Evaluate the presence and magnitude of subclinical CAD determined by CAC score among the different ESC/EAS CV risk categories, as well as the potential for risk reclassification, in patients with severe psoriasis from a low CV risk population. METHODS: Unicentric cross-sectional study in 111 patients with severe chronic plaque psoriasis from a low CV risk population in the Mediterranean region. Patients were classified into four CV risk categories according to the ESC/EAS guideline recommendations and HeartScore/SCORE calibrated charts. Patients underwent coronary computed tomography to determine their CAC scores. Patients in the moderate-risk category with a CAC score of ≥100 were considered to be reclassified as recommended by the 2019 ESC/EAS guidelines. Reclassification was also considered for patients in the low-risk category with a CAC score>0. RESULTS: Presence of subclinical CAD was detected in 46 (41.4%) patients. These accounted for 86.2% of patients in high/very-high-risk categories and 25.6% of patients in non-high-risk categories. Fourteen (17.1%) of the patients in non-high-risk categories were reclassifiable due to their CAC score. This percentage was higher (25%) when considering the moderate-risk category alone and lower (13.8%) in the low-risk category. Age was the only variable associated with presence of subclinical CAD and reclassification. CONCLUSIONS: Over 40% of patients with severe psoriasis from a low-risk region and up to 25% of those in non-high-risk categories have subclinical CAD. CAC appears to be useful for reclassification purposes in CV risk assessment of patients with severe psoriasis. Further research is required to elucidate how CAC could be implemented in everyday practice at outpatient dermatology clinics dedicated to severe psoriasis.

Contact Allergy in Patients with Rosacea. / Sensibilización alérgica de contacto en pacientes con rosácea.

BACKGROUND AND OBJECTIVE: Rosacea is a chronic acneiform skin disorder in which impaired skin barrier function can lead to sensitization to allergens. We aimed to analyze contact allergies in our patients with rosacea. MATERIAL AND METHODS: Retrospective cohort study of all patients who underwent patch testing in our skin allergy clinic between May 1991 and May 2019. RESULTS: A total of 200 patients with rosacea were referred to our clinic for patch testing during the study period; they represented 2.1% of all patch tested patients in the period. Eighty-one percent were women (mean age, 44.7years). At least 1positive patch test was recorded for 46.5%; 15% were of current relevance. The most frequent positive reaction was to nickel (26%), followed by cobalt chloride (6.5%), isothiazolinones (6%), p-phenylenediamine (5.5%), fragrance mixII (5%), and thimerosal (3.5%). The most common currently relevant patch test reactions were to isothiazolinones in 10 of the 200 patients (5%); to phenylenediamine, fragrance mixII, and toluensulfonamide formaldehyde resin in 4 patients (2%) each; and to tixocortol and fragrance mixI in 2 patients (1%) each. The allergen groups most often implicated were metals (of current relevance in 12.6%) and drugs (of current relevance in 25.8%). Preservatives and fragrances were the next most common allergen groups, and 70.8% and 43.7% of the positive reactions in these groups, respectively, were of current relevance. Cosmetics were the most frequent source of sensitization, followed by topical medications - notably corticosteroids and antifungal agents. CONCLUSIONS: We emphasize the high prevalence of allergic contact dermatitis in patients with rosacea, a finding which supports patch testing, especially if eruptions worsen when these patients use cosmetics and topical medications.

Response of pruritic scrotal epidermolytic acanthomas to pimecrolimus 1% cream.

Epidermolytic acanthomas (EA) are rare benign tumors of unclear etiology that present as flat, sometimes slightly keratotic, pale or whitish papules that are usually asymptomatic. Not uncommonly, their clinical appearance in the anogenital area might lead to misdiagnosis as other lesions that commonly develop at this site, such as condylomata acuminata. Though mainly asymptomatic, there are also reports of EA presenting with persistent genital pruritus. We describe the first reported case of pruritic scrotal EA successfully treated with topical pimecrolimus.

[Urological pathology of lymphatic origin]. / Patología urológica de origen linfático.

OBJECTIVES: Lymphatic disease is a rarely cause of some very unspecific genitourinary manifestations, assuming a diagnostic challenge in most cases. The aim of this paper is to warn about the possible etiology of these urological lymphatic presentations and discuss its management. METHODS: Retrospective review of clinical data in pediatric patients with urological pathology of lymphatic origin between 2008-2014. Three patients, two boys and a girl, were included. The complaints were: redundant prepuce, inguinal scrotal tumor and urinary incontinence. Clinical, diagnosis and treatment protocol is described. RESULTS: The first case is a male with genital lymphedema presented at birth as a redundant prepuce and the subsequent emergence of lower limb lymphedema, treated with compression bandages. The second case, a groin lymphangioma which debuted as a sudden painless inguinal tumor simulating a cord cyst, it was sclerosed and treated with OK- 432. Finally, a preteen who consulted for involuntary leakage of urine, genital lymphedema likely primary cause (lymphodisplasia) or malformation was diagnosed, which improved with two Lipiodol® embolization. CONCLUSIONS: Genitourinary manifestations can be the debut of more complex lymphatic pathology, so it is necessary to consider this cause, uncommon and nonspecific. Its management must be conservative initially by compression bandages, OK-432 or embolization with Lipiodol®.

OBJETIVOS: La patología linfática es infrecuente como causa de manifestaciones genitourinarias inespecíficas, suponiendo un reto diagnóstico en la mayoría de los casos. El objetivo de este trabajo es advertir sobre la posible etiología linfática de estas presentaciones urológicas y discutir su manejo. MATERIAL Y METODOS: Revisión retrospectiva de los datos clínicos de los pacientes pediátricos con patología urológica de origen linfático entre el año 2008-2014. Se incluyeron 3 pacientes, dos niños y una niña. Todos ellos se evaluaron para obtener un diagnóstico fiable. Los motivos de consulta fueron: prepucio redundante, tumoración inguino-escrotal e incontinencia urinaria. Se describe la clínica, el protocolo diagnóstico y el tratamiento de los mismos. CASOS CLINICOS: El primer caso se trata de un lactante varón con un linfedema genital que presentaba un prepucio redundante congénito y la aparición posterior de linfedema en el miembro inferior que es tratado con vendajes compresivos. El siguiente, un linfangioma inguinal que debutó con una tumoración inguinal indolora de aparición súbita simulando un quiste de cordón y tratado mediante esclerosis con OK-432. Por último, una preadolescente que consultó por escapes involuntarios de orina diagnosticada de linfedema genital de probable causa primaria (linfodisplasia) o malformativa que mejoró con dos embolizaciones de Lipiodol®. CONCLUSIONES: Las manifestaciones genitourinarias pueden ser el debut de una patología linfática más compleja, por ello es necesario tener presente esta etiología infrecuente e inespecífica. Su manejo inicialmente debe ser conservador, mediante vendajes compresivos, OK-432 o embolización con Lipiodol®.

Evolution and genetic diversity of the Spain23F-ST81 clone causing adult invasive pneumococcal disease in Barcelona (1990-2012).

OBJECTIVES: We aimed to analyse the clinical epidemiology and genetic diversity of invasive pneumococcal disease (IPD) episodes attributed to the Spain(23F)-ST81 (PMEN1) clone. METHODS: Fifty-eight (2.7%) of 2117 invasive pneumococci isolated from adult patients during the 1990-2012 period shared a PFGE pattern related to the PMEN1 clone. The genotype was confirmed by multilocus sequence typing. The pbp2x, pbp1a, pbp2b and pspA genes were PCR-amplified and sequenced. Polymorphisms in the pspC gene were identified by PCR restriction fragment length polymorphism. The presence of transposons with erythromycin and tetracycline resistance determinants was detected by PCR. RESULTS: The prevalence of the PMEN1 clone increased from 0.8% in 1991 to 6.2% in 2001, and decreased to 0% in 2010-12, concomitant with the introduction of the seven-valent pneumococcal conjugate vaccine for children. A total of 93.1% of patients had pneumonia, meningitis or peritonitis; 87.9% of patients had associated underlying diseases, mainly cancer, chronic obstructive pulmonary disease and diabetes. Two closely related sequence types (STs) (ST81, n = 52; ST85, n = 6) were detected, with different serotypes: 23F (n = 42), 19A (n = 9) and 19F (n = 6). All the isolates were resistant to penicillin, co-trimoxazole and chloramphenicol. All the isolates also shared the same pbp1a allele, whereas multiple alleles of pbp2b, pbp2x, pspA and pspC were detected. Of the isolates, 89.7% were tetracycline resistant and 60.3% (n = 35) were macrolide resistant, and resistance was associated with different Tn916-like transposons. CONCLUSIONS: Adult IPD caused by this clone was mainly detected in patients with underlying conditions, and genetic variability was observed among PMEN1 isolates collected in our area over the past 20 years.

Bone mass behavior after 1 year of different treatment strategies in prostate cancer patients subjected to androgen deprivation therapy.

The aim of this study was to evaluate bone mass changes after 1 year of four different types of pharmacological intervention. Ninety-seven prostate cancer patients treated with androgen deprivation therapy, and severe osteopenia or osteoporosis were retrospectively studied. Patients were divided in four groups. Group 1: 28 patients treated with denosumab, Group 2: 24 patients treated with alendronate, Group 3: 24 patients with no antiresorptive treatment and Group 4: 21 patients previously treated with alendronate and switched to denosumab. Dual X-ray absorptiometry was performed at baseline and after 1 year. Bone mass changes at the L2-L4 lumbar spine, femoral neck and total hip were evaluated. No differences were found at baseline. After 1 year, men receiving denosumab or alendronate (Group 1 and 2) showed a significant bone mass increase at the lumbar spine (+2.4 and +5.0 %, respectively), while no significant changes were observed in Group 3 and 4. At the femoral neck, Group 1 and 2 patients showed a significant bone mass increase (+3.7 and +3.6 %, respectively), while no significant changes were observed in Group 3 and 4. At the total hip, we observed a significant bone mass increase in Group 1 (+2.9 %) and a significant bone mass loss in Group 3 patients (-1.9 %). No significant changes were observed in Group 2 and 4. Denosumab increased significantly bone mass in all three dual X-ray absorptiometry standard sites, while alendronate did not at total hip. No benefit was observed in men previously treated with alendronate who switched to denosumab treatment.

Mammary serum amyloid A3 activates involution of the mammary gland in dairy cows.

The dry period is a nonlactating phase in which senescent mammary cells are regenerated, which is thought to optimize milk production in the subsequent lactation. In bovines, the dry period normally coexists with pregnancy and the lactogenic hormones delay mammary gland involution and impair the activation of immune system to fight the risk of intramammary infections. Conventionally, long dry periods of up to 60 d are required to allow sufficient mammary regeneration for full milk yield in the next lactation. The aim of this study was to evaluate the potential of mammary serum amyloid A3 (M-SAA3) as an activator of the involution of the mammary gland. One milligram of recombinant M-SAA3 and the corresponding negative controls (saline solution and lipopolysaccharide) were infused into the mammary gland via the teat canal, and mammary secretion samples were taken during the first 3 d after drying off to analyze metalloproteinase activity, somatic cell count, protein, and fat contents. Primary mammary gland epithelial cell cultures and bovine dendritic cells, obtained from necropsy tissue and blood, respectively, were incubated with and without M-SAA3 and cytokine expression was quantified. Last, the protective role of the M-SAA3 against infections was evaluated after a Staphylococcus aureus challenge. Matrix metalloproteinase 9 activity, a key protein that directly participates in the onset of the involution process, was greater in quarters treated with the M-SAA3. Protein content was increased in mammary secretions compared with control quarters. M-SAA3 increased cytokines directly related to innate immunity in both epithelial and dendritic cells and reduced the infection by Staphylococcus aureus.

[Vascular rings, our experience with 18 cases]. / Anillos vasculares, nuestra experiencia en 18 casos.

AIM: Vascular rings are a rare cause of compression of the trachea and/or the esophagus, causing stridor and/or severe dysphagia. We present our experience in the diagnosis and management of vascular rings. METHODS: Retrospective study in which we analyzed clinical history, diagnosis and management of 18 patients diagnosed with vascular ring between January 1985 and December 2013. We evaluate endoscopy as a diagnostic method. RESULTS: A total of 18 patients were included, with a median age of 2 years. 83.3% (15/18) had some type of symptom: 46.7% (7/15) had respiratory symptoms such as respiratory distress, stridor, recurrent respiratory infections, bronchospasm with wheezing or asthma in older children; 20% (3/15) had digestive symptoms such as dysphagia, vomiting and regurgitation; and 33.3% (5/15) combined respiratory and digestive symptoms. The remaining patients, 16.7% (3/18) were asymptomatic and the diagnosis was casual. The most common types of vascular rings were double aortic arch (27.8%) and aberrant subclavian right artery (27.8%). In 3 cases (16.7%) a Kommerell diverticulum was associated. 44.4% (n = 8) was operated on, the remaining did not present symp- toms which justify the intervention (n = 10). 37.5% of patients had postoperative complications (iatrogenic recurrent paralysis and persistent tracheomalacia). There was no mortality in our series. The median follow-up was 6.4 years. At the moment, 88.9% of patients are asymptomatic, and 33.3% have been definitely discharged. CONCLUSIONS: Vascular rings are rare, and usually presented with common symptoms in childhood. Therefore, in front of a longstanding and recurrent respiratory symptoms, or dysphagia, we should think of a vascular ring. Not all subjects are candidates for surgical correction; therefore a multidisciplinary evaluation is essential.

Evaluation of pneumatosis intestinalis as a complication of lung transplantation.

INTRODUCTION: Pneumatosis intestinalis is a radiological finding characterized by the presence of gas in the bowel wall that is associated with multiple entities. Our aim is to know its incidence in lung transplant patients, its physiopathology and its clinical relevance. METHODS: A search of patients with pneumatosis intestinalis was performed in the database of the Lung Transplant Unit of our hospital. The presence of pneumatosis after transplantation was confirmed in all of them and relevant demographic, clinical and imaging variables were collected to evaluate its association and clinical expression, as well as the therapeutic approach after the findings. RESULTS: The incidence of pneumatosis intestinalis after lung transplantation in our center was 3.1% (17/546), developing between 9 and 1270 days after transplantation (mean, 198 days; median 68 days). Most of the patients were asymptomatic or with mild symptoms, without any major analytical alterations, and with a cystic and expansive radiological appearance. Pneumoperitoneum was associated in 70% of the patients (12/17). Conservative treatment was chosen in all cases. The mean time to resolution was 389 days. CONCLUSION: Pneumatosis intestinalis in lung transplant patients is a rare complication of uncertain origin, which can appear for a very long period of time after transplantation. It has little clinical relevance and can be managed without other diagnostic or therapeutic interventions.

[Long gap esophageal atresia: Schärli versus Foker]. / Atresia esofágica long-gap. Schärli versus Foker.

PURPOSE. To submit the short and long term results of long-gap esophageal atresia (EA) with two surgical techniques. METHODS. We carried out a retrospective study of long-gap type EA without fistula (n=8) and with fistula (n=2) over the last 18 years, comparing the outcome of the Schärli technique (1992) with that of the Foker technique (1997). RESULTS. We included 10 patients with long gap EA. Mean birth weight was 2,418 grams. 30% had associated diseases (VACTERL, Down Syndrome, DiGeorge Syndrome). Gastrostomy or jejunostomy was initially placed in 7 patients. Schärli technique was performed in 4 patients (mean age: 3.3 months), and Foker technique in 6 patients (median age: 23.5 days of life). Complications were: a) Schärli: dehiscence (25%), stenosis (75%), one patient died from his heart disease (25%), colonic herniation through diaphragmatic hiatus (25%). The mean number of stricture dilatations was 7 sessions (S.D. 9.2). a) Foker: dehiscence (83.3%), stenosis (83.3%), gastroesophageal reflux (GER) (83.3%), fistula (16.7%). Mean number of dilatations was 13.7 sessions (S.D. 12.8). All patients operated on with Schärli technique (6-18 years, median follow-up 12 years) were asymptomatic at the time of the study, although one of them had grade III esophagitis in the last biopsy. As for the Foker's, 5 had undergone antireflux surgery and only one was asymptomatic. The rest had complications that were still being treated (stenosis and development of fistulae). CONCLUSION. Treatment of long gap EA remains a surgical challenge. In our experience patients developed fewer complications with the Schärli technique. Nevertheless, it is difficult to make a comparison with such a limited number of patients.