Underestimation of Human Cutaneous Leishmaniasis Caused by Leishmania infantum in an Endemic Area of the Mediterranean Basin (Balearic Islands)

Leishmaniasis is an infectious zoonotic disease caused by protozoan parasites of the genus Leishmania. In the Mediterranean basin, leishmaniasis is caused by Leishmania infantum and transmitted by bites of sandflies of the genus Phlebotomus, with the dog as the main reservoir host. The most common form is cutaneous leishmaniasis (CL), although visceral cases also occur. The aim of this study was to assess the underestimation of CL in an endemic Mediterranean region. Thus, a retrospective study was performed on all CL cases diagnosed and treated in the Dermatology Service of Manacor Hospital (Majorca, Balearic Islands), and the data obtained were compared with those of local government epidemiological bulletins for the same period. The different clinical presentations were compiled, and data related to sex, age, and lesion type and number were analyzed. The results reveal a clear sub-notification, which indicates that the real incidence of human CL in this area is unknown. Keywords: Leishmania; cutaneous leishmaniasis; Majorca; subnotification of case

Case report: Diffuse cutaneous leishmaniasis by Leishmania infantum in a patient undergoing immunosuppressive therapy: risk status in an endemic Mediterranean area.

This case report highlights the risk of severe cutaneous leishmaniasis (CL) by Leishmania infantum in patients undergoing immunosuppressant therapy who either live in an endemic area or are visiting in the transmission season. The case patient, resident in Majorca (Balearic Islands), presented 12 disseminated erythematous skin lesions, 1 to 6 cm in diameter, located on the scalp, cheek, umbilical region and lower extremities eight years after undergoing anti-TNF therapy. Parasite presence in peripheral blood and high levels of specific antibodies were also observed, indicating a possible risk of CL shifting toward a visceral infection (VL). However, once CL was diagnosed, anti-TNF therapy was discontinued and liposomal amphotericin B was administered, resulting in a complete healing of lesions, no Leishmania DNA detection in blood and an important serological decrease in antibodies. The lack of data on the supposed epidemiological association between leishmaniasis and immunosuppressive therapy highlights the importance of implementing surveillance systems in endemic areas. No obvious relationship was found based on the data provided by the Balearic Islands Epidemiological System, in contrast with data reported in nearby endemic areas. This indicates that, if the suspected association is to be clarified, greater efforts are needed to report information about concomitant diseases and therapies in leishmaniasis patients

Revisión clínico-epidemiológica de casos de leishmaniasis cutánea por Leishmania infantum en Manacor. Diagnóstico en muestras cutáneas mediante RT-PCR y valoración de su utilidad en dermatología

[cat] La leishmaniosi és un grup de malalties infeccioses causades per diferents espècies del protozou Leishmania. A la nostra àrea, és una zoonosis que es transmet per picadures de flebòtoms, té el gos com a principal reservori i està causada per Leishmania infantum. Pot cursar de forma visceral o cutània, tot i que la leishmaniosi cutània (LC) és la més comú. Els objectius de l’estudi van ser conèixer l’epidemiologia de la LC a les Balears i la seva possible subnotificació; descriure els patrons de presentació clínica; determinar el valor de la tècnica molecular de la reacció en cadena de la polimerasa en temps real (RT-PCR) per al diagnòstic de la LC i comparar els resultats amb els dels mètodes diagnòstics directes convencionals, tant parasitològics com d’anatomia patològica; establir que l’obtenció i la recollida de l’exsudat de la lesió en paper de filtre Whatman és un procediment vàlid per detectar infeccions per Leishmania i avaluar la seva utilitat per determinar la presència de DNA de Leishmania amb una RT-PCR; valorar l’eficàcia del tractament tenint en compte el tipus de lesió, l’edat i l’estat immunològic del pacient; proposar un protocol d’actuació estandarditzat que faciliti el diagnòstic de la LC i la seva declaració obligatòria. Es va realitzar un estudi retrospectiu de tots els casos de LC diagnosticats i tractats al Servei de Dermatologia de l’Hospital Comarcal de Manacor (Mallorca, Illes Balears) entre 2013 i 2017. Les dades es varen recopilar i gestionar, però degut a la falta d’un protocol diagnòstic, no va ser possible disposar de les mateixes dades per a tots els pacients. La població de l’estudi comprenia 126 pacients, dels quals 124 presentaven una LC i uns altres dos, leishmaniosi mucosa. Es van incloure 65 dones (51,6 %) i 61 homes (48,4 %), amb una mitja d’edat de 44,6 ± 25,5 anys i un rang de 0 a 86 anys. Es va classificar els pacients per grups d’edat: menors de 18 anys (n = 29; 23 %), de 18 a 65 anys (n = 64; 50,8 %) i majors de 65 anys (n = 33; 26,2 %). Nou pacients (7,1 %) presentaven immunodepressió. La convivència o contacte estret amb gossos només es va recollir en 25 pacients (19,9 %), tots amb resposta afirmativa. Al comparar les nostres xifres amb les dades oficials de Balears sobre leishmaniosi durant el període de l’estudi, va ser evident la subnotificació de la LC. Entre 2013 i 2017, es van declarar només 109 casos en tota la comunitat autònoma. A la sèrie de l’estudi, de 126 casos només se’n van declarar 36 (28,6 %). Per millorar la notificació de la LC a Balears, s’ha desenvolupat un algoritme que es proposa en aquesta tesi. La sospita clínica inicial va ser de certesa de LC en 87 pacients (67,5 %). Aquest alt percentatge s’atribueix a l’experiència dels dermatòlegs del centre. Al estar en un àrea amb LC endèmica, sempre tenen present aquesta malaltia, i a més estan familiaritzats amb les nombroses formes de presentació de la LC, que s’ha arribat a anomenar «la gran imitadora». Les lesions elementals van ser les pàpules i les plaques, amb una mida mitja d’1 cm i localitzades principalment a cap, cara i coll. La majoria de les lesions van ser úniques i van respondre al tractament sense deixar cicatriu. L’antimoniat de meglumina intralesional va ser el tractament més emprat. S‘inclouen nombroses imatges d’arxiu propi per mostrar no tan sols la presentació clàssica del botó d’Orient, sinó també lesions de LC que obliguen a plantejar un diagnòstic diferencial amb altres malalties. A la sèrie de l’estudi, els diagnòstics diferencials de la LC van ser quistos, granuloma asèptic, limfoma cutani, carcinomes cutanis, erisipela, pioderma gangrenós, furóncol, dactilitis, tofus gotós, cel·lulitis, nevus, X èczema i psoriasi. Pel que fa a les poblacions especials, destaquen els pacients amb immunodepressió, que van presentar lesions més grans i més difícils de tractar. El diagnòstic es va confirmar amb vàries combinacions de proves parasitològiques (coloració de Giemsa i test de Tzank), tècniques de diagnòstic histopatològic (tinció d’hematoxilina-eosina) i tècniques de diagnòstic molecular (RT-PCR en fresc i en paper). En els pacients sense un diagnòstic parasitològic, les proves RT-PCR van ser molt valuoses, especialment en aquells amb un diagnòstic histopatològic inespecífic d’infiltrat granulomatós o linfoplasmocitari. La RT-PCR va resultar ser molt sensible, facilitant la presa i conservació de la mostra i identificant a pacients amb totes les altres proves negatives o no realitzades, inclús casos que no s’havien detectat amb la RT-PCR en fresc d’exsudat o biòpsia. Tanmateix, es proposa un algoritme per al diagnòstic de la LC. Davant d’una lesió sospitosa de LC, es recomana utilitzar preferentment proves incruentes com l’examen directe del frotis amb coloració de Giemsa i la RT-PCR en paper o exsudat. Si aquestes proves son negatives, es proposa realitzar tècniques més agressives com la biòpsia de la lesió per detectar el paràsit per tinció amb hematoxilina-eosina o mitjançant RT-PCR.[spa] La leishmaniasis es un grupo de enfermedades infecciosas causadas por distintas especies del protozoo Leishmania. En nuestra área, es una zoonosis que se transmite por picaduras de flebótomos, tiene como principal reservorio el perro y está causada por Leishmania infantum. Puede cursar de forma visceral o cutánea, aunque la leishmaniasis cutánea (LC) es la más común. Los objetivos del estudio fueron conocer la epidemiología de la LC en Baleares y su posible subnotificación; describir los patrones de presentación clínica; determinar el valor de la técnica molecular de la reacción en cadena de la polimerasa en tiempo real (RT-PCR) para el diagnóstico de la LC y comparar los resultados con los de métodos diagnósticos directos convencionales, tanto parasitológicos como de anatomía patológica; establecer que la obtención y la recogida del exudado de la lesión en papel de filtro Whatman es un procedimiento válido para detectar infecciones por Leishmania y evaluar su utilidad para determinar la presencia de DNA de Leishmania mediante una RT-PCR; valorar la eficacia del tratamiento teniendo en cuenta el tipo de lesión, la edad y el estado inmunitario del paciente; proponer un protocolo de actuación estandarizado que facilite el diagnóstico de la LC y su declaración obligatoria. Se realizó un estudio retrospectivo de todos los casos de LC diagnosticados y tratados en el Servicio de Dermatología del Hospital Comarcal de Manacor (Mallorca, Illes Balears) entre 2013 y 2017. Los datos se recopilaron y gestionaron, aunque debido a la falta de un protocolo diagnóstico, no fue posible disponer de los mismos datos para todos los pacientes. La población del estudio estuvo formada por 126 pacientes, de los que 124 presentaban LC y otros 2 pacientes, leishmaniasis mucosa. Se incluyó a 65 mujeres (51,6 %) y 61 hombres (48,4 %), con una media de edad de 44,6 ± 25,5 años y un rango de 0 a 86 años. Se clasificó a los pacientes por grupos de edad: menores de 18 años (n = 29; 23 %), de 18 a 65 años (n = 64; 50,8 %) y mayores de 65 años (n = 33; 26,2 %). Nueve pacientes (7,1 %) presentaban inmunodepresión. La convivencia o contacto estrecho con perros solo se había recogido en 25 pacientes (19,9 %), todos con respuesta afirmativa. Al comparar nuestras cifras con los datos oficiales de Baleares sobre leishmaniasis durante el periodo del estudio, fue evidente la subnotificación de la LC. Entre 2013 y 2017, se declararon solo 109 casos en toda la comunidad autónoma. De la serie del estudio, solo fueron declarados 36 casos (28,6%) de 126. Para mejorar la notificación de la LC en Baleares, se ha desarrollado un algoritmo que se propone en esta tesis. La sospecha clínica inicial fue de certeza de LC en 87 pacientes (67,5 %). Este alto porcentaje se atribuye a la experiencia de los dermatólogos del centro. Al estar en un área con LC endémica, siempre tienen presente esta enfermedad y además están familiarizados con las numerosas formas de presentación de la LC, que se ha llegado a denominar «la gran imitadora». Las lesiones elementales fueron las pápulas y las placas, con un diámetro medio de 1 cm y localizadas sobre todo en cabeza, cara y cuello. La mayoría de lesiones fueron únicas y respondieron al tratamiento, generalmente antimoniato de meglumina intralesional, sin dejar cicatriz. Se incluyen numerosas imágenes de archivo propio para mostrar no solo la presentación clásica del botón de Oriente, sino también lesiones de LC que obligan a plantear un diagnóstico diferencial con otras enfermedades. En la serie del estudio, los diagnósticos diferenciales de la LC incluyeron quistes, granuloma aséptico, linfoma cutáneo, XII carcinomas cutáneos, erisipela, pioderma gangrenoso, forúnculo, dactilitis, tofo gotoso, celulitis, nevus, eccema y psoriasis. En cuanto a las poblaciones especiales, destacan los pacientes con inmunodepresión, que presentaron lesiones de mayor tamaño y más difíciles de tratar. El diagnóstico se confirmó con diversas combinaciones de pruebas parasitológicas (coloración de Giemsa y test de Tzank), técnicas de diagnóstico histopatológico (tinción de hematoxilina-eosina) y técnicas de diagnóstico molecular (RT-PCR en fresco y en papel). En los pacientes sin un diagnóstico parasitológico, las pruebas RT-PCR fueron de gran valor, sobre todo en aquellos con un diagnóstico histopatológico inespecífico de infiltrado granulomatoso o linfoplasmocitario. La RT-PCR en papel del exudado resultó ser muy sensible, facilitando la toma y conservación de la muestra e identificando a pacientes con todas las otras pruebas negativas o no realizadas, incluso casos que no habían sido detectados con la RT-PCR en fresco de exudado o biopsia. Asimismo, se propone un algoritmo para el diagnóstico de la LC. Ante una lesión sospechosa de LC, se recomienda usar preferentemente pruebas incruentas como el examen directo del frotis con coloración de Giemsa y la RT-PCR en muestra fresca o recogida en papel. Si estas pruebas son negativas, se propone realizar técnicas más agresivas como la biopsia de la lesión para detectar el parásito por tinción con hematoxilina-eosina o mediante RT-PCR.[eng] Leishmaniasis is a group of infectious diseases caused by protozoan parasites from different species of Leishmania. In our area, it is a zoonosis transmitted by bites of sandflies of the genus Phlebotomus, with the dog as main reservoir host, and caused by Leishmania infantum. It can present as visceral or cutaneous forms, but cutaneous leishmaniasis (CL) is the most common in the Balearic Islands. The study had multiple objectives: to know the epidemiology of CL in the Balearic Islands and its possible subnotification; to describe patterns of clinical presentation; to determine the worth of the molecular technique real-time polymerase chain reaction (RT-PCR) to CL diagnosis and to compare its results with those of conventional direct methods of diagnosis, both parasitological and anatomopathological; to establish that obtaining and collection of lesion exudate in Whatman filter paper is a valid procedure to detect infections by Leishmania and to assess whether it is useful to determine presence of Leishmania DNA by means of RT-PCR; to evaluate the efficacy of the treatment taking into account lesion type, age and immune status; to suggest a standardized protocol to facilitate CL diagnosis and mandatory notification. A retrospective study was performed to assess all LC cases that had been diagnosed and treated at the Dermatology Department of the Hospital de Manacor (Mallorca, Balearic Islands) from 2013 to 2017. Data were collected and managed, but not the same data were available for all patients because there was not a protocol for CL diagnosis. Study population was composed of 126 patients, 124 presenting with CL and 2 patients with mucosal leishmaniasis. They were 65 women (51.6 %) and 61 men (48.4 %), with a mean age of 44.6 ± 25.5 years and a range from 0 to 86 years. Moreover, patients were classified according to their age in three groups: younger than 18 years (n = 29; 23 %), between 18 and 65 years (n = 64; 50.8 %), and older than 65 years (n = 33; 26.2 %). Nine patients (7.1 %) had immunosuppression. Data on living or having close contact with a dog were available for 25 patients (19.9 %), all them with affirmative answer. When comparing our numbers with official leishmaniasis data in the Balearic Islands during the study period, CL subnotification was evident. Only 109 cases were notified in the whole autonomous community between 2013 and 2017. In the study series, only 36 cases (28.6%) from 126 were notified. To improve CL notification in Baleares, we developed an algorithm that is suggested in this dissertation. Early clinical suspicion was of certainty in 87 patients (67.5%). This high degree of certainty can be attributed to the experience of our dermatologists. As our hospital is located in an area with endemic disease, they have CL always in mind. Furthermore, they are familiar with the many presentation forms of the disease, which has come to be known as “the great imitator”. The elementary lesions were papules and plaques, with a mean diameter of 1 cm and mainly located on the head, face and neck. Most lesions were unique and improved with treatment, which used to be intralesional meglumine antimoniate, and no residual scar was seen. This document includes a large number of pictures from the author’s own file; these photographs show not only the classical presentation of Oriental sore (botón de Oriente), but also Cl lesions that force dermatologists to make a differential diagnosis with other diseases. In the study series, possible diagnosis were cyst, aseptic granuloma, skin lymphoma, skin carcinoma, erysipelas, pyoderma gangrenosum, boil, dactylitis, tophus, cellulitis, nevus, eczema and psoriasis. With regard to special populations, lesions in XIV immunosuppressed patients were larger and more difficult to treat than in immunocompetent patients. Diagnosis was confirmed with several combinations of parasitological tests (Giemsa stain and Tzanck test), histopathological techniques (hematoxylin and eosin staining) and molecular techniques (RT-PCR using fresh and filter paper-collected samples). In patients with no parasitological diagnosis, RT-PCR tests were of high value, especially in those with an unspecific histopathological diagnosis of granulomatous or lymphoplasmocytary infiltrate. RT-PCR on paper with exudate sample was very sensitive, making easier the taking and preservation of samples and allowing the identification of patients with all other tests negative or not performed, even cases not detected by RT-PCR on fresh sample of exudate or biopsy. Furthermore, an algorithm for CL diagnosis is proposed. In front of a suspicious CL lesion, it is recommended to use preferentially non-invasive tests such as direct smear observation using Giemsa stain and RT-PCR in fresh or paper-collected sample. If these tests are negative, more invasive tests such as lesion biopsy to detect the parasite by hematoxylin and eosin staining or by RT-PCR

Complete response of secukinumab in palmoplantar psoriasis

Palmoplantar psoriasis is plaque psoriasis involving the palms and soles. Palmoplantar psoriasis is a treatment challenge for dermatologists and it is difficult to treat with topical and systemic therapies. Owing to its location and manifestations, palmoplantar psoriasis is associated with greater pain, functional limitations, and significant impairment of health-related quality of life. Recently a new biologic agent, secukinumab, has been approved for treatment of moderate to severe plaque psoriasis. GESTURE trial is a study of the secukinumab clinical development that evaluates efficacy and safety in this subpopulation of patients. We present a patient with palmar psoriasis refractory to systemic treatments who showed a gradual and complete response to secukinumab sustained at week 30 and without adverse events. Our patient had a significant improvement in his quality of life and work activity

Underestimation of Human Cutaneous Leishmaniasis Caused by <i>Leishmania infantum</i> in an Endemic Area of the Mediterranean Basin (Balearic Islands)

Leishmaniasis is an infectious zoonotic disease caused by protozoan parasites of the genus Leishmania. In the Mediterranean basin, leishmaniasis is caused by Leishmania infantum and transmitted by bites of sandflies of the genus Phlebotomus, with the dog as the main reservoir host. The most common form is cutaneous leishmaniasis (CL), although visceral cases also occur. The aim of this study was to assess the underestimation of CL in an endemic Mediterranean region. Thus, a retrospective study was performed on all CL cases diagnosed and treated in the Dermatology Service of Manacor Hospital (Majorca, Balearic Islands), and the data obtained were compared with those of local government epidemiological bulletins for the same period. The different clinical presentations were compiled, and data related to sex, age, and lesion type and number were analyzed. The results reveal a clear sub-notification, which indicates that the real incidence of human CL in this area is unknown

Case report: Diffuse cutaneous leishmaniasis by Leishmania infantum in a patient undergoing immunosuppressive therapy: risk status in an endemic Mediterranean area.

This case report highlights the risk of severe cutaneous leishmaniasis (CL) by Leishmania infantum in patients undergoing immunosuppressant therapy who either live in an endemic area or are visiting in the transmission season. The case patient, resident in Majorca (Balearic Islands), presented 12 disseminated erythematous skin lesions, 1 to 6 cm in diameter, located on the scalp, cheek, umbilical region and lower extremities eight years after undergoing anti-TNF therapy. Parasite presence in peripheral blood and high levels of specific antibodies were also observed, indicating a possible risk of CL shifting toward a visceral infection (VL). However, once CL was diagnosed, anti-TNF therapy was discontinued and liposomal amphotericin B was administered, resulting in a complete healing of lesions, no Leishmania DNA detection in blood and an important serological decrease in antibodies. The lack of data on the supposed epidemiological association between leishmaniasis and immunosuppressive therapy highlights the importance of implementing surveillance systems in endemic areas. No obvious relationship was found based on the data provided by the Balearic Islands Epidemiological System, in contrast with data reported in nearby endemic areas. This indicates that, if the suspected association is to be clarified, greater efforts are needed to report information about concomitant diseases and therapies in leishmaniasis patients

Dret administratiu I, setembre 2016

Recurs d'aprenentatge de la Universitat Oberta de Catalunya. Material publicat amb llicència Creative Commons passats 6 semestres des de la data de publicació.Recurso de aprendizaje de la Universitat Oberta de Catalunya. Material publicado con licencia Creative Commons pasados 6 semestres desde la fecha de publicación.Learning resource of the Universitat Oberta de Catalunya. Material published under a Creative Commons license after 6 semesters from the date of publication

Dret administratiu I, setembre 2016

Recurs d'aprenentatge de la Universitat Oberta de Catalunya. Material publicat amb llicència Creative Commons passats 6 semestres des de la data de publicació.Recurso de aprendizaje de la Universitat Oberta de Catalunya. Material publicado con licencia Creative Commons pasados 6 semestres desde la fecha de publicación.Learning resource of the Universitat Oberta de Catalunya. Material published under a Creative Commons license after 6 semesters from the date of publication

Effectiveness and safety of guselkumab for the treatment of psoriasis in real-world settings at 24 weeks: A retrospective, observational, multicentre study by the Spanish Psoriasis Group.

Data on the effectiveness and safety of a drug in real-world clinical practice complement the evidence from clinical trials, which are carried out in a different setting. Little has been published on the effectiveness and safety of guselkumab in the treatment of psoriasis in clinical practice. The ojective of this study was to assess the effectiveness and safety of guselkumab at 24 weeks in patients with moderate to severe plaque psoriasis in routine clinical practice. A retrospective, multicentre study of adult patients with moderate to severe plaque psoriasis treated with guselkumab for at least 24 weeks was carried out in Spain. We studied 343 patients, 249 of whom were followed for 24 weeks. By week 24, the mean (SD) psoriasis area severity index (PASI) had decreased from 11.1 (7.3) to 1.7 (2.8) (-9.3; [-10.2;-8.4]), 85.9% of the patients had achieved PASI score of 4 or less and 77.9% a PASI score of 2 or less. In terms of relative PASI response, 59.4% of the patients achieved a PASI-90 response and 49.0% a PASI-100 response. On multivariate analysis, two factors reduced the probability of a PASI of 2 or less at 24 weeks: a BMI ≥30 (OR, 0.44; 95% CI, 0.22-0.88) and a greater previous exposure to biologic therapy (OR, 0.69; 95% CI, [0.56-0.84]). Adverse events were rare (9.9%) and led to withdrawal from treatment in only nine patients (2.6%) by the end of the follow-up period. The results of this study confirm the high efficacy and safety of guselkumab indicated by the clinical trial data. In clinical practice, the absolute PASI score appears to be a better marker of response to treatment than the relative value