Publications by authors named "Mercè Alsina"

33 Publications

Autochthonous and imported tegumentary leishmaniasis in Catalonia (Spain): Aetiological evolution in the last four decades and usefulness of different typing approaches based on biochemical, molecular and proteomic markers.

Transbound Emerg Dis 2021 Apr 17. Epub 2021 Apr 17.

Secció de Parasitologia, Departament de Biologia, Sanitat i Medi Ambient, Facultat de Farmàcia i Ciències de l'Alimentació, Universitat de Barcelona, Barcelona, Spain.

Leishmaniasis is a transmissible disease caused by Leishmania protozoa. Spain is endemic for both visceral and cutaneous leishmaniasis, the autochthonous aetiological agent being Leishmania infantum. Around the world, the L. donovani complex is associated with visceral symptoms, while any species of the Leishmania or Viannia subgenera affecting human can produce tegumentary forms. In a context of growing numbers of imported cases, associated with globalisation, the aim of this study was to analyse the aetiological evolution of human tegumentary leishmaniasis in a region of Spain (Catalonia). Fifty-six Leishmania strains, isolated from 1981 to 2018, were analysed using MLEE, gene sequencing (hsp70, rpoIILS, fh and ITS2) and MALDI-TOF. The utility of these different analytical methods was compared. The results showed an increase in leishmaniasis over the two last decades, particularly imported cases, which represented 39% of all cases studied. Leishmania infantum, L. major, L. tropica, L. braziliensis, L. guyanensis and L. panamensis were identified. The combination of molecular and enzymatic methods allowed the identification of 29 different strain types (A to AC). Strain diversity was higher in L. (Viannia), whilst the different L. major types were relatable with geo-temporal data. Among the autochthonous cases, type C prevailed throughout the studied period (39%). Minor types generally appeared within a short time interval. While all the techniques provided identical identification at the species complex level, MALDI-TOF and rpoIILS or fh sequencing would be the most suitable identification tools for clinical practice, and the tandem hsp70-ITS2 could substitute MLEE in the epidemiological field.
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http://dx.doi.org/10.1111/tbed.14107DOI Listing
April 2021

Effect of Sex in Systemic Psoriasis Therapy: Differences in Prescription, Effectiveness and Safety in the BIOBADADERM Prospective Cohort.

Acta Derm Venereol 2021 01 4;101(1):adv00354. Epub 2021 Jan 4.

Department of Dermatology, Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas de Gran Canaria, Spain. E-mail:

The effect of sex on systemic therapy for psoriasis has not been well studied. The aim of this study was to analyse a large multicentre Spanish cohort of 2,881 patients with psoriasis (58.3% males), followed from January 2008 to November 2018, to determine whether sex influences prescription, effectiveness of therapy, and the risk of adverse events. The results show that women are more likely than men to be prescribed biologics. There were no differences between men and women in effectiveness of therapy, measured in terms of drug survival. Women were more likely to develop adverse events, but the difference in risk was small and does not justify different management. Study limitations include residual confounding and the use of drug survival as a proxy for effectiveness.
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http://dx.doi.org/10.2340/00015555-3711DOI Listing
January 2021

Cutaneous leishmaniasis of the face treated with imiquimod 3.75.

Enferm Infecc Microbiol Clin 2021 Feb 18;39(2):108-109. Epub 2020 May 18.

Servicio de Dermatología, Hospital Clínic de Barcelona, Universitat de Barcelona, España. Electronic address:

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http://dx.doi.org/10.1016/j.eimc.2020.04.005DOI Listing
February 2021

Long-term safety of nine systemic medications for psoriasis: A cohort study using the Spanish Registry of Adverse Events for Biological Therapy in Dermatological Diseases (BIOBADADERM) Registry.

J Am Acad Dermatol 2020 Jul 22;83(1):139-150. Epub 2020 Mar 22.

Research Unit, Fundación Piel Sana Academia Española de Dermatología, Madrid, Spain; Department of Dermatology, Complexo Hospitalario Universitario de Vigo, Vigo, Spain.

Background: Registry studies broadly describing the safety of systemic drugs in psoriasis are needed.

Objective: To describe the safety findings of the systemic drugs acitretin, adalimumab, apremilast, cyclosporine, etanercept, infliximab, methotrexate, secukinumab, and ustekinumab used for the treatment of moderate to severe psoriasis in patients included in the Spanish Registry of Adverse Events for Biological Therapy in Dermatological Diseases (BIOBADADERM) Registry.

Methods: The incidence rate ratio (IRR) and adjusted IRR (including propensity scores) of identified adverse events for each drug, using methotrexate as reference, were determined by means of a prospective cohort.

Results: Our study included 2845 patients (8954 treatment cycles; 9642 patient-years). Ustekinumab and secukinumab had the lowest rate of adverse events for several of the system organ classes, with a statistically significant decreased rate ratio (IRR of <1), whereas cyclosporine and infliximab had the highest, with an increased rate ratio (IRR of ≥5).

Limitations: Observational study, drug allocation not randomized, depletion of susceptibles, and prescribed doses not registered.

Conclusion: Our data provide comparative safety information in the real-life setting that could help clinicians selecting between available products.
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http://dx.doi.org/10.1016/j.jaad.2020.03.033DOI Listing
July 2020

Multiparametric analysis of the effectiveness of cisplatin on cutaneous squamous carcinoma cells using two different types of adjuvants.

PLoS One 2020 6;15(3):e0230022. Epub 2020 Mar 6.

ALBA Synchrotron Light Source, Barcelona, Spain.

The objective of this study was to regulate the cytotoxicity of cisplatin (cisPt) minimizing its adverse effects. For this purpose, the lowest cisPt concentration needed to obtain a significant positive response in cutaneous squamous cell carcinoma (cSCC) was explored. Two adjuvant agents as gold nanoparticles (AuNP) and chelating tricine were tested as enhancers in cisPt treatment. Effectiveness of all treatments was assessed by means of biochemical techniques, which offer quantitative data, as well as two microscopy-based techniques that provided qualitative cell imaging. The present work confirms the effectiveness of free cisplatin at very low concentrations. In order to enhance its effectiveness while the side effects were probably diminished, cisPt 3.5 μM was administered with AuNP 2.5 mM, showing an effectiveness practically equal to that observed with free cisPt. However, the second treatment investigated, based on cisPt 3.5 μM combined with tricine 50 mM, enhanced drug effectiveness, increasing the percentage of cells dying by apoptosis. This treatment was even better in terms of cell damage than free cisPt at 15 μM. Images obtained by TEM and cryo-SXT confirmed these results, since a notable number of apoptotic bodies were detected when cisPt was combined with tricine. Thus, tricine was clearly a better adjuvant for cisPt treatments.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0230022PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7060073PMC
June 2020

Sexually transmitted infections in young people and factors associated with HIV coinfection: an observational study in a large city.

BMJ Open 2019 05 5;9(5):e027245. Epub 2019 May 5.

Epidemiology Service, Public Health Agency of Barcelona (ASPB), Barcelona, Spain.

Objectives: Young people are a critical target group for sexually transmitted infections (STI) surveillance due to their particular behavioural and social related vulnerability. The aim of this study was to describe the epidemiological characteristics and trends in the incidence of gonorrhoea, syphilis, HIV and venereal lymphogranuloma (LGV) among 15-24-year-olds in Barcelona, and to determine factors associated with HIV coinfection.

Design: We performed a population-based incidence study covering the 2007-2015 period.

Participants: All new cases of STI-HIV, gonorrhoea, infectious syphilis and LGV-notified to the epidemiological surveillance system in Barcelona between 2007 and 2015. 1218 cases were studied: 84.6% were men, 19.3% were 15-19 years old and 50.6% were born in Spain. Among men, 73.7% were men who have sex with men (MSM); among women, 85.6% were women that have sex with men.

Primary And Secondary Outcomes: Incidence of HIV, gonorrhoea, infectious syphilis and LGV. HIV coinfection.

Results: There was an increase in the incidence of gonorrhoea, from 1.9 cases per 10 000 people in 2007 to 7.6/10 000 in 2015 (p<0.01), in MSM from 27.1 to 228.8/10 000 (p<0.01). The incidence of syphilis increased from 0.4/10 000 in 2007 to 3.1/10 000 in 2015 (significant in men only, p<0.01), in MSM from 18.1 to 116.9/10 000 (p<0.01). The incidence of HIV showed a non-significant increase in men (p=0.27), and that of LGV remained stable (p=0.59). Factors associated with increased risk of HIV coinfection included being MSM (adjusted OR[ORa]=14.14, 95% CI 3.34 to 59.91) and having >10 sexual partners (ORa=4.11, 95% CI 1.53 to 11.01) or STI diagnosis during the previous 12 months (ORa=2.06; 95% CI 1.13 to 3.77).

Conclusions: The incidence of gonorrhoea and syphilis among 15-24-year-olds increased, while HIV infection remained stable but with a high incidence among MSM. Being MSM, having sex with multiple partners and having a diagnosis of an STI in the previous 12 months were factors associated with HIV coinfection.
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http://dx.doi.org/10.1136/bmjopen-2018-027245DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6502227PMC
May 2019

Effectiveness and safety of ustekinumab 90 mg in patients weighing 100 kg or less: a retrospective, observational, multicenter study.

J Dermatolog Treat 2020 May 2;31(3):222-226. Epub 2019 Apr 2.

Department of Dermatology, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona (UAB), Badalona, Spain.

Scant information from clinical practice is available on the effectiveness and safety of ustekinumab (UST) 90 mg in patients with psoriasis weighing 100 kg or less. To assess the effectiveness and safety at weeks 16 and 24 of UST 90 mg in patients with psoriasis weighing ≤100 kg, and to study the impact on clinical outcomes of body mass index (BMI) and prior exposure to UST 45 mg. A retrospective, observational, and multicenter study of 74 adult patients who were treated with UST 90 mg at least 24 weeks. Mean (standard deviation [SD]) score on psoriasis area and severity index (PASI) was 7.9 (4.8) at baseline, 3.3 (3.5) at week 16, and 2.2 (2.4) at week 24, when 69.7% of the patients had a PASI under 3. Overweight and obese patients achieved a mean PASI of 2.2 by week 24 (= .995). In patients who had previously been treated with UST 45 mg (52/74) with insufficient response, mean (SD) absolute PASI score was 2.7 (2.6) at week 24. No serious adverse events were reported. In patients who weigh 100 kg or less but are overweight or obese and do not present an adequate response with UST 45 mg, increasing the dose to UST 90 mg could be an alternative option.
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http://dx.doi.org/10.1080/09546634.2019.1597245DOI Listing
May 2020

Histologic evidence that mast cells contribute to local tissue inflammation in peripheral spondyloarthritis by regulating interleukin-17A content.

Rheumatology (Oxford) 2019 04;58(4):617-627

Department of Clinical Immunology and Rheumatology, Amsterdam Rheumatology and Immunology Center, Amsterdam, The Netherlands.

Objectives: Synovial mast cells contain IL-17A, a key driver of tissue inflammation in SpA. A recent in vitro study showed that tissue-derived mast cells can capture and release exogenous IL-17A. The present study aimed to investigate if this mechanism could contribute to tissue inflammation in SpA.

Methods: Potential activation of mast cells by IL-17A was assessed by gene expression analysis of the Laboratory of Allergic Diseases 2 (LAD2) mast cell line. The presence of IL-17A-positive mast cells was assessed by immunohistochemistry in synovial tissue obtained before and after secukinumab treatment, as well as in skin and gut tissues from SpA-related conditions.

Results: IL-17A did not induce a pro-inflammatory response in human LAD2 mast cells according to the canonical IL-17A signalling pathway. In SpA synovial tissue, the percentage of IL-17A-positive mast cells increased upon treatment with secukinumab. IL-17A-positive mast cells were also readily detectable in non-inflamed barrier tissues such as skin and gut. In non-inflamed dermis and gut submucosa, IL-17A-positive mast cells are the most prevalent IL-17A-positive cells in situ. Compared with non-inflamed tissues, both total mast cells and IL-17A-positive mast cells were increased in psoriatic skin dermis and in submucosa from inflammatory bowel disease gut. In contrast, the proportion of IL-17A-positive mast cells was strikingly lower in the inflamed compared with non-inflamed gut lamina propria.

Conclusion: IL-17A-positive mast cells are present across SpA target tissues and correlate inversely with inflammation, indicating that their IL-17A content can be regulated. Tissue-resident mast cells may act as IL-17A-loaded sentinel cells, which release IL-17A to amplify tissue inflammation.
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http://dx.doi.org/10.1093/rheumatology/key331DOI Listing
April 2019

Treatment of patients with plaque psoriasis with secukinumab in a real-life setting: a 52-week, multicenter, retrospective study in Spain.

J Dermatolog Treat 2019 Aug 3;30(5):424-429. Epub 2018 Dec 3.

b Department of Dermatology , Hospital del Mar- Institut Mar d'Investigacions Mèdiques , Barcelona , Spain.

The efficacy and safety of secukinumab in patients with plaque psoriasis (PsO) have been demonstrated in randomized clinical trials (RCTs). However, data regarding its efficacy and safety in real-life settings are scarce. To evaluate the efficacy and safety of secukinumab in clinical practice in patients with PsO attending 10 dermatology centers in Spain. Data from 136 patients consecutively treated with secukinumab for at least 52 weeks were collected in a retrospective observational study. After 52 weeks of treatment, 69% and 46% of patients achieved a PASI-75, PASI-90, respectively. PASI-score ≤5 was achieved in 83% of patients, PASI-score ≤3 in 73% and PASI-score ≤1 in 47%. Response rates were found significantly lower in patients with obesity and non-naïve to biologics ( < .05). The most common adverse event (AE) was candidiasis (5/136). Thirty-six patients (26.5%) discontinued treatment by week 52 due to lack or loss of response ( = 29), AEs ( = 2) or other causes ( = 5). These findings complement the efficacy and safety profiles of secukinumab in PsO outlined in RCTs. The effectiveness in clinical practice may be lower in patients with a BMI ≥30 and those previously treated with other biologic agents.
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http://dx.doi.org/10.1080/09546634.2018.1528000DOI Listing
August 2019

Importance of the treatment of rectal Mycoplasma genitalium in men who have sex with men.

Enferm Infecc Microbiol Clin 2019 Oct 30;37(8):544-545. Epub 2018 Aug 30.

Servicio de Enfermedades Infecciosas, Hospital Clínic de Barcelona, Universitat de Barcelona, Barcelona, España.

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http://dx.doi.org/10.1016/j.eimc.2018.07.003DOI Listing
October 2019

Gay Circuit Parties in Barcelona and Their Impact on Gonorrhea Incidence.

Arch Sex Behav 2018 10 16;47(7):2027-2034. Epub 2018 Jul 16.

Epidemiology Service, Public Health Agency of Barcelona, Barcelona, Spain.

This study explored the role of circuit parties on the incidence of gonorrhea among men who have sex with men (MSM) in Barcelona (Spain). Specifically, it aimed to detect cyclic peaks in the number of reported diagnoses of gonorrhea after gay circuit parties. We analyzed monthly cases of gonorrhea reported from January 2007 through December 2016 after the main annual gay circuit parties in Barcelona. We used the integer autoregressive model for time series with discrete values. The performance of the model was tested in heterosexual men and women, in whom the circuit parties could be expected to have no impact. A sensitivity analysis was conducted, changing post-event diagnosis windows to 1 week later/1 week before. In the study period, a total of 4182 of gonorrhea cases were detected, of which 74.8% (n = 2181) occurred in men who identified themselves as MSM. The average annual increase in gonorrhea cases reported among MSM was 32.57%. In an independent analysis of each gay circuit party, cases increased significantly in two of them. The results were also similar for same-sex practices among men only. On controlling for the increasing trend over the study period and the seasonal effect, an average of 1.16 gonorrhea cases in MSM (95% CI: 0.68, 1.64) were attributable to the celebration of one of the gay circuit parties considered. During the expected outbreak, an average of 13 gonorrhea cases were detected and between 5 and 13% were attributable to one of the circuit parties. In view of these findings, participants should consider seeking advice from their healthcare provider and practice safer sex using condoms to prevent sexually transmitted infections. Local public health services should be reinforced to ensure care for participants during and after gay circuit parties. More research is needed to design and implement preventive programs.
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http://dx.doi.org/10.1007/s10508-018-1220-9DOI Listing
October 2018

Pancreatic panniculitis: A case series from a tertiary university hospital in Spain.

Australas J Dermatol 2018 Nov 9;59(4):e269-e272. Epub 2018 May 9.

Department of Dermatology, Hospital Clínic, Universitat de Barcelona, Barcelona, Spain.

Pancreatic panniculitis is a rare type that only occurs in 2-3% of all patients with pancreatic diseases. It is usually described in association with benign pancreatic disease and less commonly in association with pancreatic carcinoma. We describe a case of pancreatic panniculitis as the first manifestation of underlying ampullary adenocarcinoma and a new case of pancreatitis, panniculitis and polyarthritis (PPP-Syndrome). Pancreatic panniculitis may be the cutaneous manifestation of pancreatic allograft rejection after simultaneous pancreas-kidney transplantation.
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http://dx.doi.org/10.1111/ajd.12842DOI Listing
November 2018

Genetic and experimental evidence for the involvement of the CD6 lymphocyte receptor in psoriasis.

Cell Mol Immunol 2018 10 11;15(10):898-906. Epub 2017 Dec 11.

Immunoreceptores del Sistema Innat i Adaptatiu, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, 08036, Spain.

Psoriasis is a chronic inflammatory skin disease with a strong genetic background and is triggered by environmental factors. Available evidence supports CD6, a lymphocyte surface receptor mostly expressed by T cells, as a putative target in autoimmunity. Accordingly, a humanized anti-CD6 antibody has been assayed for the treatment of certain autoimmune disorders, including psoriasis. Here, we present novel evidence in mice and humans for a direct involvement of CD6 in psoriasis pathophysiology. First, an attenuated form of imiquimod-induced psoriasis-like skin inflammation was demonstrated in CD6-deficient mice, as deduced from lower epidermal thickness and local reduced production of pro-inflammatory cytokines, namely, interleukin-17A. Thus, isolated CD4CD62L T cells from CD6-deficient mice displayed decreased in vitro T-helper type 17 polarization. Second, a statistically significant association between CD6 single-nucleotide polymorphisms (rs17824933, rs11230563 and rs12360861) and more severe forms of psoriasis was demonstrated in a cohort of 304 patients at three public hospitals from the metropolitan area of Barcelona. Taken together, these results provide new supportive evidence of the contribution of the CD6 lymphocyte receptor in psoriasis at both experimental and clinical levels.
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http://dx.doi.org/10.1038/cmi.2017.119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6207571PMC
October 2018

Infections in Moderate to Severe Psoriasis Patients Treated with Biological Drugs Compared to Classic Systemic Drugs: Findings from the BIOBADADERM Registry.

J Invest Dermatol 2017 02 25;137(2):313-321. Epub 2016 Sep 25.

Research Unit, Fundación Academia Española de Dermatología y Venereología, Madrid, Spain; Dermatology Derpartment, Complexo Hospitalario Universitario de Vigo, Vigo, Spain.

Information regarding the safety of biological drugs prescribed to psoriasis patients on daily and long-term bases is insufficient. We used data from the BIOBADADERM registry (Spanish Registry of Adverse Events for Biological Therapy in Dermatological Diseases) to generate crude rates of infection during therapy with systemic drugs, including biological drugs (infliximab, etanercept, adalimumab, and ustekinumab) and nonbiological drugs (acitretin, cyclosporine, and methotrexate). We also calculated unadjusted and adjusted risk ratios (RRs) (with propensity score adjustment) of infection, serious infections, and recurrent infections of systemic therapies compared with methotrexate, using Poisson regression. Our study included records of 2,153 patients (7,867.5 person-years). The adjusted RR of overall infection was significantly increased in the groups treated with adalimumab with methotrexate (adjusted RR = 2.13, 95% confidence interval [CI] = 1.2-3.7), infliximab (adjusted RR = 1.71, 95% CI = 1.1-2.65), cyclosporine (adjusted RR = 1.58, 95% CI = 1.17-2.15), ustekinumab with methotrexate (adjusted RR = 1.56, 95% CI = 1.08-2.25), and etanercept (adjusted RR = 1.34, 95% CI: 1.02-1.76) compared with methotrexate alone. Cyclosporine had a significant risk of serious infection (adjusted RR = 3.12, 95% CI = 1.1-8.8), followed by adalimumab combined with methotrexate (adjusted RR = 3.28, 95% CI = 0.8-13.5). Adalimumab in combination with methotrexate had the highest risk of infection recurrence (adjusted RR = 4.33, 95% CI = 2.27-8.24).
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http://dx.doi.org/10.1016/j.jid.2016.08.034DOI Listing
February 2017

Pneumocystis jirovecii pneumonia in a patient with pustular psoriasis with an IL-36RN deficiency treated with infliximab: Case report and review of the literature.

Australas J Dermatol 2017 May 12;58(2):e44-e47. Epub 2016 May 12.

Department of Dermatology, Hospital Clinic, University of Barcelona, Barcelona, Spain.

Pneumocystis jirovecii pneumonia (PCP) is a relatively rare complication in non-HIV patients receiving immunosuppressive treatment. Since the introduction of tumour necrosis factor-α inhibitors cases of this complication have increased. We report the case of a 54-year-old, HIV-negative patient, who presented to our department with a long history of pustular psoriasis with poor response to traditional treatments. During the last admission he developed a severe flare that was unresponsive to cyclosporine, therefore infliximab was initiated. After the third dose he developed PCP that required admission to the intensive care unit, with a positive response to i.v. administration of trimethoprim/sulfamethoxazole. During follow up a mutation in the IL36RN gene compatible with an IL-36RN deficiency was found and anakinra was started, with rapid improvement of his psoriasis. PCP is a severe complication in patients receiving immunosuppressive therapy and is probably underreported by dermatologists. There are no clinical guidelines for PCP prophylaxis in dermatological patients who will receive immunosuppressive or biological treatments. We believe that it is necessary to report the cases of PCP to assess the real impact of this complication and develop appropriate prophylaxis guidelines.
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http://dx.doi.org/10.1111/ajd.12489DOI Listing
May 2017

Epidemiology of infections by HIV, Syphilis, Gonorrhea and Lymphogranuloma Venereum in Barcelona City: a population-based incidence study.

BMC Public Health 2015 Oct 5;15:1015. Epub 2015 Oct 5.

Epidemiology Service, Agencia de Salut Pública de Barcelona, Pl. Lesseps, 1, 08023, Barcelona, Spain.

Background: The aim of this study was to determine the evolution of HIV infection, gonorrhea, syphilis and lymphogranuloma venereum (LGV), and their epidemiological characteristics in Barcelona city.

Methods: Population-based incidence study of all newly occurring diagnoses of HIV infection, syphilis, gonorrhea and LGV detected in Barcelona between January 2007 and December 2011. A descriptive analysis was performed. The annual incidence rates per 100,000 inhabitants were calculated by sex, sexual conduct and educational level. To estimate global sex-specific rates we used the Barcelona city census; for the calculation of rates by sexual conduct and educational level we used estimates of the Barcelona Health Interview Survey. Trends were analysed using the chi-squared test for linear trend.

Results: HIV. 66.8 % of the HIV cases were men who had sex with men (MSM). The incidence rates in MSM over the study period were from 692.67/100,000 to 909.88/100,000 inh. Syphilis. 74.2 % of the syphilis cases were MSM. The incidence rates in MSM were from 224.9/100,000 to 891.97/100,000 inh. and the MSM with a university education ranged from 196.3/100,000 to 1020.8/100,000. Gonorrhea. 45.5 % of the gonorrhea cases were MSM. The incidence rates in MSM were from 164.24/100,000 to 404.79/100,000 inh. and the MSM with university education ranged from 176.7/100,000 to 530.1/100,000 inh.. Lymphogranuloma venereum (LGV). 95.3 % of the LGV cases are MSM. The incidence rates in MSM were from 24.99/100,000 to 282.99/100,000 inh. and the MSM with university education ranged from 9.3/100,000 to 265/100,000 inh.

Conclusion: An increase in cases of STI was observed. These STI mainly affected MSM with a university education. Continuing to monitor changes in the epidemiology of STI, and identifying the most affected groups should permit redesigning preventive programs, with the goal of finding the most efficient way to reach these population groups.
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http://dx.doi.org/10.1186/s12889-015-2344-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4594901PMC
October 2015

Development of clinical prediction models for good or bad response to classic systemic drugs, anti-TNFs, and ustekinumab in psoriasis, based on the BIOBADADERM cohort.

J Dermatolog Treat 2016 25;27(3):203-9. Epub 2015 Sep 25.

o Department of Dermatology , Hospital Universitario 12 de Octubre , Madrid , Spain.

Background: Identifying patients likely to have very good or bad results from systemic psoriasis therapy could improve efficiency of therapy.

Objective: To develop prognostic models for good or bad response to classic systemic drugs, anti-TNFs, and ustekinumab in psoriasis.

Methods: Multivariable logistic regression of a prospective multicenter cohort of psoriatic patients in clinical practice (6449 person-years of follow-up). We used as possible predictors demographic characteristics, comorbidities, characteristics of the psoriasis (type, PASI, arthritis), history of past therapy at entry in the cohort, and history of response to previous cycles while in the cohort. We defined good response to a treatment cycle as either cycle end due to disease remission or a cycle longer than 2 years that does not end later due to inefficacy in the follow-up period. Bad response to a treatment cycle was defined as a cycle that is finished due to inefficacy, based on the physician judgment, after more than 3 months of treatment.

Results: Patients with fewer previous therapies, lower body mass index, older at start of therapy, and with previous history of good responses to therapy are more likely to have positive results of therapy. However, the predictive characteristics of models are poor.

Conclusion: Predictive models of clinical response to systemic drugs in psoriasis with the studied variables do not seem to outperform drug selection by a dermatologist.
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http://dx.doi.org/10.3109/09546634.2015.1088130DOI Listing
October 2016

An erythematous nodule on the nipple: An unusual presentation of primary syphilis.

J Cutan Pathol 2015 Apr;42(4):239-43

Departments of Dermatology, Hospital Clínic, Universitat de Barcelona, Barcelona, Spain.

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http://dx.doi.org/10.1111/cup.12491DOI Listing
April 2015

Use of off-label doses is frequent in biologic therapy for moderate to severe psoriasis: A cross-sectional study in clinical practice.

J Dermatolog Treat 2015 17;26(6):502-6. Epub 2015 Apr 17.

a Department of Dermatology , Hospital Universitari Germans Trías i Pujol, Universitat Autònoma de Barcelona , Badalona , Barcelona , Spain .

Introduction: Biologic medications increase dramatically the burden of a chronic and high prevalent disease like psoriasis. The objective of the study was to quantify the use of dose reduction or dose escalation strategies, not reflected in the drug summary of product characteristics, in clinical practice.

Methods: An observational, cross-sectional study of a subset of patients from the Spanish Registry for Systemic Treatments in Psoriasis (BIOBADADERM) treated for over six consecutive months with the same biologic agent.

Results: The study included 637 patients. At the cut-off date, the initial dose had been reduced in 223 patients (35%; 95% CI: 31.3-38.9%) and escalated in 46 (7.2%; 95% CI: 5.3-9.5%). When compared with the patients treated with standard doses, the patients on reduced doses had a lower PASI score at the cut-off date (a mean 2.6 versus 1; -1.6 points) and exhibited greater improvement in PASI since the start of biologic therapy (mean reduction over baseline 75% versus 87%). By contrast, the patients receiving an escalated dose had higher PASI scores (2.6 versus 8.0) and showed less improvement in PASI (75% versus 46.8%).

Conclusion: Off-label doses of biologic agents for psoriasis are frequent in clinical practice. This information is especially relevant for pharmacoeconomic models.
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http://dx.doi.org/10.3109/09546634.2015.1034070DOI Listing
May 2016

Cutaneous adverse events during treatment of chronic inflammatory rheumatic conditions with tumor necrosis factor antagonists: study using the Spanish registry of adverse events of biological therapies in rheumatic diseases.

Arthritis Care Res (Hoboken) 2013 Dec;65(12):2024-31

Hospital Clínic, Barcelona, Spain.

Objective: To analyze the incidence rate (IR) and risk factors of cutaneous adverse events (CAE) in patients with chronic inflammatory rheumatic diseases treated with tumor necrosis factor (TNF) antagonists.

Methods: We analyzed all patients from the BIOBADASER (Base de Datos de Productos Biológicos de la Sociedad Española de Reumatología) registry treated with a TNF antagonist (infliximab, etanercept, or adalimumab). Data collected included age, sex, diagnosis and duration of rheumatic disease, type of TNF antagonist, and concomitant treatment. Type of CAE was classified as local or systemic cutaneous manifestation related to treatment administration (infusion reaction), infection, malignancy, or autoimmune skin disease. Time of onset of CAE and outcome were also recorded. The IRs of CAE per 1,000 patient-years of exposure with 95% confidence intervals (95% CIs) were estimated. Multivariable analysis was performed to identify potential risk factors for CAE.

Results: A total of 5,437 patients were included, representing 17,330 patient-years of exposure. A total of 920 CAE were reported; the IRs per 1,000 patient-years were 53 (95% CI 50-57) for CAE, 28 (95% CI 25-30) for infection, 15 (95% CI 13-17) for infusion reactions, 5 (95% CI 4-6) for autoimmune skin diseases, and 3 (95% CI 2-4) for skin malignancy. The mean time between starting TNF antagonist treatment and CAE was 1.78 years. In 32% of patients, CAE required TNF antagonist withdrawal. The main risk factors for CAE were female sex and treatment with infliximab, leflunomide, and glucocorticoids.

Conclusion: The IR of CAE in patients treated with TNF antagonists is significant and should be addressed carefully, and withdrawal of therapy is required in some cases.
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http://dx.doi.org/10.1002/acr.22096DOI Listing
December 2013

Jaccoud's arthropathy of the feet presenting as bilateral non-healing interdigital ulcers.

Rheumatology (Oxford) 2012 Aug 16;51(8):1377. Epub 2012 May 16.

Department of Dermatology, Hospital Clínic - Universitat de Barcelona, Villarroel 170, 08036 Barcelona, Spain.

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http://dx.doi.org/10.1093/rheumatology/kes096DOI Listing
August 2012

Risk of serious adverse events associated with biologic and nonbiologic psoriasis systemic therapy: patients ineligible vs eligible for randomized controlled trials.

Arch Dermatol 2012 Apr;148(4):463-70

Department of Dermatology, Complexo Hospitalario de Pontevedra, SERGAS (Servizo Galego de Saude), Pontevedra, Spain.

Objective: To describe the use of systemic therapy for psoriasis (biologic and nonbiologic [classic] drugs) in patients not adequately represented in randomized controlled trials (RCTs) and the risk of serious adverse events (SAEs) in these patients.

Design: A registry inception cohort was used.

Setting: Thirteen dermatology departments in Spain participated.

Patients: A consecutive sample of patients treated with biologics and a systematic sample of patients treated with classic systemic therapy were evaluated. A total of 1042 patients (2179 person-years) were included.

Exposure: Inadequate representation in trials was defined as the presence of any of the following factors: elderly age (>70 years); type of psoriasis other than chronic plaque psoriasis; history of infection caused by hepatitis B, hepatitis C, or human immunodeficiency virus; history of cancer (excluding nonmelanoma skin cancer); and chronic renal or hepatic disease.

Main Outcome Measures: Serious adverse events as defined by the International Conference on Harmonization were evaluated.

Results: In all, 29.8% of patients receiving systemic therapy for psoriasis would not have been eligible for RCTs. These individuals had an increased risk of SAEs (incidence rate ratio, 2.7; 95% CI, 1.5-4.7). Patients exposed to biologics had an adjusted increased risk of SAEs (incidence rate ratio, 2.3; 95% CI, 1.1-4.8) that was similar in patients eligible and ineligible for RCTs.

Conclusions: Patients ineligible for RCTs are an important proportion (30%) of those receiving systemic therapy for psoriasis. These patients have a higher risk of SAEs and should be closely monitored. Patients exposed to biologics (whether these patients are eligible for RCTs or ineligible) are susceptible to the same increase in risk of SAEs, but biologics add to a higher baseline risk in patients who are ineligible for RCTs. The risk-benefit ratio in ineligible patients receiving biologics might be different from the ratio in eligible patients.
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http://dx.doi.org/10.1001/archdermatol.2011.2768DOI Listing
April 2012

FCGR2A/CD32A and FCGR3A/CD16A variants and EULAR response to tumor necrosis factor-α blockers in psoriatic arthritis: a longitudinal study with 6 months of followup.

J Rheumatol 2012 May 1;39(5):1035-41. Epub 2012 Apr 1.

Department of Rheumatology, Arthritis Unit, Hospital Clínic, Barcelona, Spain.

Objective: The efficacy of antibody-based biological therapies currently used in psoriatic arthritis (PsA) depends not only on their blocking effect on the targeted molecule but also on their binding affinity to genetically defined variants of cell-surface Fc-γ receptors. Our objective was to assess the potential influence of functionally relevant FCGR2A/CD32A (H131R) and FCGR3A/CD16A (V158F) genetic polymorphisms on the EULAR response to tumor necrosis factor-α (TNF-α) blocker therapy in PsA.

Methods: In total 103 patients with PsA starting anti-TNF-α therapy were included. The efficacy of therapy was evaluated according to EULAR response criteria at 3 and 6 months. FCGR2A-R131H and FCGR3A-F158V polymorphisms were genotyped. Potential correlations between clinical response and the FCGR2A-R131H and FCGR3A-F158V polymorphisms were evaluated.

Results: EULAR response (moderate plus good) was 85.4% at 3 months and 87.4% at 6 months, while good EULAR response was 61.2% and 62.1%, respectively. More patients with high-affinity FCGR2A genotypes (homozygous or heterozygous combinations) achieved a EULAR response at 6 months compared to patients with the low-affinity genotype (RR; p = 0.034, adjusted comparison error rate < 0.025). This association was due mainly to the group of patients treated with etanercept. No correlation was found for the FCGR3A polymorphism. Similarly, no effect of C-reactive protein levels was observed.

Conclusion: Our data indicate that FCGR2A polymorphism may influence the response to TNF-α blockers (namely etanercept) in PsA in a direction opposite to that previously found in patients with rheumatoid arthritis.
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http://dx.doi.org/10.3899/jrheum.110980DOI Listing
May 2012

High-dose intravenous immunoglobulins for the treatment of autoimmune mucocutaneous blistering diseases: evaluation of its use in 19 cases.

J Am Acad Dermatol 2007 Jun 21;56(6):960-7. Epub 2007 Mar 21.

Department of Dermatology, Hospital Clinic, Barcelona, Spain.

Background: The mainstay of therapy of autoimmune mucocutaneous blistering diseases has been prolonged high-dose systemic corticosteroids and immunosuppressive agents. Recently, high-dose intravenous immunoglobulin (IVIg) has been employed in selected cases, with excellent results in most of them.

Objective: We sought to evaluate the outcome of the use of IVIg in patients with autoimmune mucocutaneous blistering diseases refractory to conventional therapy or with contraindications for it.

Methods: We performed a retrospective analysis of clinical response to monthly cycles of IVIg in 19 patients affected with autoimmune mucocutaneous blistering diseases: 10 patients with pemphigus vulgaris (PV), 2 with pemphigus foliaceus (PF), 4 with mucous membrane pemphigoid (MMP), 2 with epidermolysis bullosa acquisita, and one with linear IgA bullous dermatosis.

Results: Four (21%) of 19 cases presented a complete response (2 PV, 1 MMP and 1 epidermolysis bullosa acquisita). Five (26%) patients did not respond to the treatment (3 PV, 1 PF, 1 MMP). Ten patients (53%) had a partial response.

Limitations: This was a retrospective noncontrolled study with a heterogeneous group of patients.

Conclusion: The effectiveness of IVIg was inferior to that previously reported. This difference could be attributed to the preparations employed, the different severity of the disease, or individual responses in each patient dependent on Fc receptor gamma polymorphisms.
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http://dx.doi.org/10.1016/j.jaad.2006.06.029DOI Listing
June 2007

Dermoscopy improves accuracy of primary care physicians to triage lesions suggestive of skin cancer.

J Clin Oncol 2006 Apr;24(12):1877-82

Department of Dermatology, Second University of Naples, Naples, Italy.

Purpose: Primary care physicians (PCPs) constitute an appropriate target for new interventions and educational campaigns designed to increase skin cancer screening and prevention. The aim of this randomized study was to determine whether the adjunct of dermoscopy to the standard clinical examination improves the accuracy of PCPs to triage lesions suggestive of skin cancer.

Patients And Methods: PCPs in Barcelona, Spain, and Naples, Italy, were given a 1-day training course in skin cancer detection and dermoscopic evaluation, and were randomly assigned to the dermoscopy evaluation arm or naked-eye evaluation arm. During a 16-month period, 73 physicians evaluated 2,522 patients with skin lesions who attended their clinics and scored individual lesions as benign or suggestive of skin cancer. All patients were re-evaluated by expert dermatologists at clinics for pigmented lesions. Referral accuracy of both PCP groups was calculated by their scores, which were compared to those tabulated for dermatologists.

Results: Referral sensitivity, specificity, and positive and negative predictive values were 54.1%, 71.3%, 11.3%, and 95.8%, respectively, in the naked-eye arm, and 79.2%, 71.8%, 16.1%, and 98.1%, respectively, in the dermoscopy arm. Significant differences were found in terms of sensitivity and negative predictive value (P = .002 and P = .004, respectively). Histopathologic examination of equivocal lesions revealed 23 malignant skin tumors missed by PCPs performing naked-eye observation and only six by PCPs using dermoscopy (P = .002).

Conclusion: The use of dermoscopy improves the ability of PCPs to triage lesions suggestive of skin cancer without increasing the number of unnecessary expert consultations.
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http://dx.doi.org/10.1200/JCO.2005.05.0864DOI Listing
April 2006