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In the framework of the INDAAF (International Network to study Deposition and Atmospheric chemistry in AFrica) programme, part of the ACTRIS European Research Infrastructure for the long-term observation of Aerosols, Cloud, and Trace gases, this paper aims to study trends and seasonal variability of surface atmospheric NO2 and HNO3 concentrations, and OMI (Ozone Monitoring Instrument) NO2 over 6 sites in tropical Africa. Sites are located in west and central Africa to represent the major African biomes: dry savanna (Banizoumbou, Niger and Katibougou, Mali), wet savanna (Djougou, Benin and Lamto, Cote d’Ivoire) and forest (Bomassa, Republic of Congo and Zoetele, Cameroon). Ground-based NO2 and HNO3 concentrations were obtained over the period 1998–2015 using INDAAF passive samplers at a monthly basis, and NO2 Vertical Column Densities (VCDs) from OMI for a 1° grid cell around each sites were obtained from 2005 to 2015. Mean annual NO2 concentrations ranged from 2.3 ± 1.2 to 0.9 ± 0.4 ppb from dry savannas to forests, representing a north south gradient. In dry savannas, we observe two concentration peaks of NO2 appearing at the beginning and the end of the wet season both for ground-based and satellite measurements, whereas at wet savannas and forest sites, NO2 concentrations are highest in the dry season. The seasonality of surface NO2 observations provide further evidence for a large role of microbial soil NOx emissions in dry savannas and of biomass burning NOx emissions in wet savanna and forest sites. Mean annual HNO3 concentrations ranged from 0.4 to 0.5 ppb in dry and wet savannas to 0.2–0.3 ppb in forest. In dry ecosystems, higher HNO3 concentrations are measured in the early wet season, consistent with NO2 results. The analysis of a long-term dataset of surface O3 concentrations indicates that HNO3 production can mainly be explained by the photooxidation of NOx. Mann-Kendall and Seasonal Kendall statistical tests showed that NO2 surface concentrations have a significant decreasing seasonal and annual trends at multiple sites (p-value

The multidisciplinary project Prediction of Air Pollution in Latin America and the Caribbean (PAPILA) is dedicated to the development and implementation of an air quality analysis and forecasting system to assess pollution impacts on human health and economy. In this context, a comprehensive emission inventory for South America was developed on the basis of the existing data on the global dataset CAMS-GLOB-ANT v4.1 (developed by joining CEDS trends and EDGAR v4.3.2 historical data), enriching it with data derived from locally available emission inventories for Argentina, Chile, and Colombia. This work presents the results of the first joint effort of South American researchers and European colleagues to generate regional maps of emissions, together with a methodological approach to continue incorporating information into future versions of the dataset. This version of the PAPILA dataset includes CO, NOx, NMVOCs, NH3, and SO2 annual emissions from anthropogenic sources for the period 2014–2016, with a spatial resolution of 0.1∘ × 0.1∘ over a domain that covers 32–120∘ W and 34∘ N–58∘ S. The PAPILA dataset is presented as netCDF4 files and is available in an open-access data repository under a CC-BY 4 license: https://doi.org/10.17632/btf2mz4fhf.3 (Castesana et al., 2021). A comparative assessment of PAPILA–CAMS datasets was carried out for (i) the South American region, (ii) the countries with local data (Argentina, Colombia, and Chile), and (iii) downscaled emission maps for urban domains with different environmental and anthropogenic factors. Relevant differences were found at both country and urban levels for all the compounds analyzed. Among them, we found that when comparing PAPILA total emissions versus CAMS datasets at the national level, higher levels of NOx and considerably lower levels of the other species were obtained for Argentina, higher levels of SO2 and lower levels of CO and NOx for Colombia, and considerably higher levels of CO, NMVOCs, and SO2 for Chile. These discrepancies are mainly related to the representativeness of local practices in the local emission estimates, to the improvements made in the spatial distribution of the locally estimated emissions, or to both. Both datasets were evaluated against surface concentrations of CO and NOx by using them as input data to the WRF-Chem model for one of the analyzed domains, the metropolitan area of Buenos Aires, for summer and winter of 2015. PAPILA-based modeling results had a smaller bias for CO and NOx concentrations in winter while CAMS-based results for the same period tended to deliver an underestimation of these concentrations. Both inventories exhibited similar performances for CO in summer, while the PAPILA simulation outperformed CAMS for NOx concentrations. These results highlight the importance of refining global inventories with local data to obtain accurate results with high-resolution air quality models.

Introduction Dans l’essai de phase 2 evaluant le cemiplimab (CEM) chez des patients (pts) ayant un carcinome epidermoide cutane (CEC) localement evolue ou metastatique, le taux de meilleure reponse (TMR) etait de 47 % et la survie globale (SG) a un an de 81 %. Une autorisation temporaire d’utilisation (ATU) nominative a permis a ces pts d’acceder au CEM hors protocole. Notre objectif etait d’analyser les donnees d’efficacite et de tolerance de cette ATU. Materiel et methodes Les 58 centres ayant inclus des pts entre le 08/18 et le 10/19 dans cette etude retrospective ont ete sollicites pour completer une fiche standardisee par pt. L’objectif principal etait le TMR, les objectifs secondaires etaient la survie sans progression (SSP), la SG, la duree de la reponse (DDR) et la tolerance. La reponse etait evaluee dans les centres. Les effets indesirables (EI) etaient evalues selon la classification CTCAEv5. La SSP, la SG et la DDR ont ete calculees par la methode de Kaplan–Meier. La date de point etait le 19/06/20. Resultats Les cas de 245 pts (178H/67F, âge moyen 77,1 ± 13) ont ete analyses. Il y avait 189 pts inclus dans l’ATU nominative et 56 dans celle de cohorte ; 59 % des pts avaient deja recu une radiotherapie et 52 % des pts ont recu le CEM en 1re ligne de traitement systemique ; 68 % des CEC etaient localises a la tete et au cou. Ils etaient localement evolues (35 %), regionaux (39 %) ou metastatiques a distance (26 %) ; 24 % des pts etaient immunodeprimes : hemopathies, 15 % ; VIH, 3 % ; transplantes, 3 % ; immunosuppresseurs, 2 %, autre, 1 % ; 3 % avaient une genodermatose et 12 % une dermatose chronique. Un neurotropisme etait present dans 23 % des CEC. Le PS etait ≥ 2 chez 28 % des pts. Le nombre moyen de perfusions de CEM etait de 10 (4–22). Parmi les 240 pts ayant recu ≥ 1 perfusion, le TMR (IC 95 %) etait de 50,4 % (43,9–56,9) avec 51 RC (21 %) et 70 RP (29 %). Le suivi median etait de 12,6 mois. La SSP mediane (IC95 %) etait de 8,2 mois (6,7–11,7). Les medianes de SG/DDR n’etaient pas atteintes ; la SG (IC95 %) a 1 an etait de 63,1 % (56,8–70,1). La duree mediane de traitement etait de 5,5 mois et 29 % des pts etaient encore traites a un an. Des EI survenaient chez 75 pts (31 %) ; les plus frequents (> 2,5 %) etaient asthenie, diarrhees, cholestase et prurit ; 22 pts (9 %) ont presente ≥ 1 EI de grade 3–4. Un pt est decede d’un syndrome de Lyell lie au CEM et 16 pts (7 %) ont arrete le CEM du fait d’un EI. Discussion Ces premieres donnees d’etude en vie reelle permettent de caracteriser les pts susceptibles d’etre traites par CEM. Ils incluent une frequence elevee (15 %) de pts atteints d’hemopathies. Elles confirment le taux de reponse eleve du CEM ainsi que sa bonne tolerance. L’inclusion dans cette etude d’une proportion importante de pts immunodeprimes et de pts au PS altere, habituellement non inclus dans les essais, a pu contribuer a une SG a un an plus faible que dans l’essai de phase 2.

Introduction La tularemie est une zoonose endemique, potentiellement mortelle, causee par la bacterie intracellulaire Francisella tularensis. L’atteinte cutanee est peu frequente. Nous rapportons le cas d’une tularemie ganglionnaire avec atteinte cutanee. Observation Un patient de 63 ans, au principal antecedent de polyarthrite rhumatoide sous methotrexate (MTX), etait hospitalise pour alteration de l’etat general avec hyperthermie a 40°. Six semaines auparavant, ce garde-chasse avait remarque la presence de cadavres de lievres et de lapins lors d’une de ses balades en foret. Un traitement par amoxicilline pendant cinq jours etait sans efficacite. L’evolution etait marquee a J15 par l’apparition de vesicules et papules erythemateuses non prurigineuses localisees au dos et a la partie proximale des bras, ainsi qu’un erytheme violace legerement infiltre des mains. Les serologies VIH, leptospirose et syphilis etaient negatives. Le bilan auto-immun et l’enzyme de conversion de l’angiotensine etaient normaux. La biopsie cutanee etait non specifique. Une tomodensitometrie thoraco-abdomino-pelvienne a la recherche d’un foyer infectieux profond mettait en evidence des adenopathies mediastino-hilaires droites d’aspect necrotique, evoquant principalement une tuberculose ou une sarcoidose. Les cytoponctions ganglionnaires par echoendoscopie bronchique (EBUS) recueillaient un liquide purulent sur lequel la recherche de bacilles acido-alcoolo resistantc et les cultures (germes standards et mycobacteries) etaient negatives, mais la PCR Francisella tularensis revenait positive. La serologie Francisella tularensis positive confirmait le diagnostic de tularemie. Un traitement par levofloxacine, 500 mg deux fois par jour, etait debute pour une duree de 15 jours. Deux jours plus tard, la cicatrisation des lesions etait obtenue avec persistance de macules pigmentees et regression des signes generaux. Discussion La tularemie, maladie a declaration obligatoire, est consideree comme un agent de bioterrorisme. Les modes de transmission sont multiples : contact direct avec animaux infectes (peaux ou secretions), ingestion d’eau ou nourriture contaminee, inhalation d’aerosols contamines ou encore piqure d’arthropodes. Il n’y a pas de transmission interhumaine. Le dermatologue doit y penser devant toute eruption erythemateuse maculo-papuleuse dans un contexte de mode de vie rural ou de balades en foret. La serologie reste l’examen diagnostic de reference. Notre cas est original par la methode diagnostique (EBUS) et la severite liee a l’immunodepression induite par le MTX motivant sa suspension. Les lesions papuleuses palmaires sont parfois appelees « tularemides ». La biopsie cutanee est habituellement aspecifique. Conclusion Nous rapportons le cas d’une tularemie du sujet immunodeprime avec atteinte ganglionnaire et cutanee. Il est important d’evoquer ce diagnostic du fait de sa gravite et de la simplicite du traitement.

The mandate of the Task Force Hemispheric Transport of Air Pollution (TF HTAP) under the Convention on Long-Range Transboundary Air Pollution (CLRTAP) is to improve the scientific understanding of the intercontinental air pollution transport, to quantify impacts on human health, vegetation and climate, to identify emission mitigation options across the regions of the Northern Hemisphere, and to guide future policies on these aspects. The harmonization and improvement of regional emission inventories is imperative to obtain consolidated estimates on the formation of global-scale air pollution. An emissions data set has been constructed using regional emission grid maps (annual and monthly) for SO2, NOx, CO, NMVOC, NH3, PM10, PM2.5, BC and OC for the years 2008 and 2010, with the purpose of providing consistent information to global and regional scale modelling efforts. This compilation of different regional gridded inventories – including that of the Environmental Protection Agency (EPA) for USA, the EPA and Environment Canada (for Canada), the European Monitoring and Evaluation Programme (EMEP) and Netherlands Organisation for Applied Scientific Research (TNO) for Europe, and the Model Inter-comparison Study for Asia (MICS-Asia III) for China, India and other Asian countries – was gap-filled with the emission grid maps of the Emissions Database for Global Atmospheric Research (EDGARv4.3) for the rest of the world (mainly South America, Africa, Russia and Oceania). Emissions from seven main categories of human activities (power, industry, residential, agriculture, ground transport, aviation and shipping) were estimated and spatially distributed on a common grid of 0.1° × 0.1° longitude-latitude, to yield monthly, global, sector-specific grid maps for each substance and year. The HTAP_v2.2 air pollutant grid maps are considered to combine latest available regional information within a complete global data set. The disaggregation by sectors, high spatial and temporal resolution and detailed information on the data sources and references used will provide the user the required transparency. Because HTAP_v2.2 contains primarily official and/or widely used regional emission grid maps, it can be recommended as a global baseline emission inventory, which is regionally accepted as a reference and from which different scenarios assessing emission reduction policies at a global scale could start. An analysis of country-specific implied emission factors shows a large difference between industrialised countries and developing countries for acidifying gaseous air pollutant emissions (SO2 and NOx) from the energy and industry sectors. This is not observed for the particulate matter emissions (PM10, PM2.5), which show large differences between countries in the residential sector instead. The per capita emissions of all world countries, classified from low to high income, reveal an increase in level and in variation for gaseous acidifying pollutants, but not for aerosols. For aerosols, an opposite trend is apparent with higher per capita emissions of particulate matter for low income countries.

Alemtuzumab is a monoclonal antibody targeting CD52 receptors on B and T lymphocytes and is an effective induction agent in pediatric renal transplantation. We report a seven-yr experience using alemtuzumab induction and steroid-free protocol in the pediatric population as safe and effective. Twenty-one pediatric deceased donor renal transplants were performed at a single academic institution. All received induction with single-dose alemtuzumab and were maintained on a steroid-free protocol using TAC and MMF immunosuppression. There were 15 males and six females in the study whose ages ranged from one to 19 yr. The average follow-up was 32 months (range from 12 to 78.2 months and median 33.7 ± 23.7 months). All patients had immediate graft function. Graft survival was 95%, and patient survival was 100%. Mean 12 and 36 months eGFR were 63.33 ± 21.01 and 59.90 ± 15.27 mL/min/1.73m(2), respectively. Three patients developed acute T-cell-mediated rejection due to non-adherence while no recipients developed cytomegalovirus infection, PTLD, or polyoma BK viral nephropathy. Steroid avoidance with single-dose alemtuzumab induction provides adequate and safe immunosuppression in pediatric deceased donor renal transplant recipients receiving TAC and low-dose MMF maintenance therapy.

Introduction Les inhibiteurs du recepteur du facteur de croissance epidermique (anti-EGFR) sont des therapies ciblees developpees dans le traitement de cancers metastatiques, notamment pulmonaires et colorectaux. Les principaux effets indesirables sont cutanes ; en revanche, l’atteinte du cuir chevelu est rarement decrite. Nous rapportons le premier cas de pustulose du cuir chevelu avec alopecie sous afatinib. Observations Une patiente de 69 ans, aux antecedents de cancer du sein en 2012, en remission, d’adenocarcinome broncho-pulmonaire metastatique, etait traitee par afatinib depuis janvier 2016. Elle presentait 3 mois apres l’introduction de cet anti-EGFR, un rash cutane pustuleux acneiforme, associe a des paronychies avec bourgeons charnus des orteils et des lesions pustulo-crouteuses du cuir chevelu, avec modification de la texture des cheveux devenus crepus et une alopecie. Le prelevement bacteriologique d’une pustule etait sterile. Un traitement pour doxycycline 200 mg/j etait instaure associe a l’application de dermocorticoides sur le cuir chevelu, d’emollients sur le corps et de nitrate d’argent sur les bourgeons charnus. La posologie de l’afatinib n’etait pas modifiee. A un mois, l’evolution etait favorable avec disparition quasi complete des lesions pustulo-crouteuses mais persistance d’une alopecie. A 3 mois, on observait une repousse partielle des cheveux ; la patiente nous signalait neanmoins avoir arrete l’afatinib 3 semaines auparavant en raison d’une progression du carcinome bronchique. Discussion Les effets indesirables les plus frequents des anti-EGFR sont les effets indesirables cutanes ; le plus souvent ; il s’agit d’un rash acneiforme et de paronychies comme presentait notre patiente. Les atteintes du cuir chevelu sont moins decrites ; il s’agit le plus souvent de modifications de la texture des cheveux ou d’alopecie. Quelques cas d’atteintes pustuleuses du cuir chevelu sont decrits chez des patients traites par erlotinib et gefitinib. Le delai d’apparition apres l’introduction du traitement est variable. La prise en charge repose sur l’administration de cyclines et l’application de dermocorticoides comme dans notre cas. Une reduction de posologie du traitement anti-EGFR est parfois necessaire, voire l’arret du traitement. Aucun cas n’est rapporte sous afatinib. Dans notre cas, la repousse observee a 3 mois suggere une reversibilite a l’arret du traitement ( Fig. 1 et 2 ). Conclusion Nous rapportons le premier cas de pustulose du cuir chevelu avec alopecie sous afatinib. La pustulose du cuir chevelu est un effet indesirable peu decrit des anti-EGFR mais pouvant considerablement alterer la qualite de vie. Sa prise en charge repose sur l’administration de cyclines, parfois a forte dose, et l’application de dermocorticoides. La prise en charge des toxicites cutanees, en coordination avec l’oncologue, est necessaire pour une prise en charge optimale des patients.

Introduction Le pyoderma gangrenosum est une maladie neutrophilique revelant souvent une pathologie systemique, notamment hematologique, et classiquement majore par les traumatismes (phenomene de pathergie). Parfois, ces facteurs co-existent, complexifiant alors la prise en charge therapeutique. Observations Il s’agit d’un homme de 54 ans suivi pour un syndrome myelodysplasique (SMD). En raison d’une resistance a l’erythropoietine, un traitement par azacitidine etait instaure par voie sous-cutanee (SC). Quelques jours apres le premier cycle (7 injections SC), il developpait en regard des differents sites d’injection des papulo-pustules inflammatoires evoluant rapidement vers une ulceration douloureuse, fibrineuse, violacee, centrifuge, a bordure nette. Les prelevements microbiologiques etaient negatifs. Une antibiotherapie probabiliste ne permettait pas d’amelioration. Une biopsie cutanee etait realisee, montrant une infiltration dermique lympho-plasmocytaire associee a des capillaires congestifs, sans necrose. Le diagnostic de pyoderma gangrenosum (PG) etait retenu. Le patient etait traite par corticotherapie orale, et l’azacitidine etait suspendu pendant plus d’un mois, entrainant une regression des lesions mais la progression du SMD. Un nouveau cycle d’azacitidine etait donc debute mais rapidement arrete en raison de la recidive des lesions cutanees malgre le maintien de la corticotherapie ( Fig. 1 et 2 ). Discussion Le PG revele parfois une maladie systemique comme le SMD. Notre cas montre la difficulte de faire la difference entre un PG induit par un medicament et un PG compliquant un SMD sur phenomene de pathergie (par injection SC). Seuls 3 autres cas de PG secondaires a l’azacitidine (nouvel analogue de la pyrimidine) sont decrits. Ce medicament ayant nettement ameliore le pronostic du SMD, se pose alors la question delicate de son imputabilite et de sa poursuite. Dans un cas, l’arret du traitement sans meme l’utilisation d’immunosuppresseur a permis la resolution de la symptomatologie. Dans une autre observation, l’utilisation d’un autre traitement utilise par voie SC n’est pas suivie de l’apparition de lesions de PG. Dernier argument, le syndrome de Sweet, autre dermatose neutrophilique, est egalement decrit apres injection d’azacitidine, ce qui renforce encore son imputabilite. Dans notre cas, la survenue des lesions sur les sites d’injection et la recidive rapide a la reintroduction nous font poser le diagnostic de PG a l’azacitidine. L’arret du traitement se discute car les recidives sont possibles apres reintroduction, les lesions pouvant meme s’etendre aux organes profonds avec engagement du risque vital. Conclusion Il s’agit du 4e cas a notre connaissance de PG induit par l’azacitidine. Il illustre le defi auquel est confronte le dermatologue de distinguer les causes medicamenteuses des autres causes, afin d’adapter la prise en charge therapeutique en consequence.

Resume Introduction Les modalites pratiques de surveillance du melanome, apres prise en charge chirurgicale de la tumeur primitive, ne font l’objet d’aucun consensus international. L’objectif majeur de cette surveillance est de depister les recidives dont le diagnostic precoce presente un interet en termes de survie, c’est-a-dire les metastases en transit et ganglionnaires, accessibles a une exerese chirurgicale, ainsi que l’apparition eventuelle d’un second melanome primitif. Objectif Le but de notre etude etait d’identifier les acteurs et les modalites du diagnostic de recidive cutanee ou ganglionnaire de melanome, ou de second melanome. Patients et methodes Il s’agit d’une etude retrospective monocentrique portant sur tous les malades suivis pour un melanome ayant presente une recidive cutanee ou ganglionnaire, ou un second melanome, entre janvier 2005 et decembre 2007. Etaient etudies le type de la recidive, ainsi que les acteurs et les modalites de son diagnostic. Resultats Quatre-vingt-quatorze malades ont presente une recidive ; 66 % de ces recidives etaient ganglionnaires et 34 % cutanees. Trente-trois pour cent des diagnostics avaient ete poses par le patient, 21 % par le service de dermatologie, 22 % par un dermatologue liberal, 18 % par un radiologue et 6 % par un generaliste. Cinquante-quatre pour cent des malades de moins de 50 ans avaient depiste eux-memes leur recidive contre 18 % des plus de 70 ans. Un second melanome etait diagnostique chez six malades. Discussion Cette etude permet de souligner l’interet majeur de l’autopalpation dans la surveillance du melanome, puisqu’un tiers des recidives ont ete depistees par le patient lui-meme. L’autosurveillance apparait plus performante chez les sujets jeunes ; il existe donc un interet a sensibiliser ceux de plus de 50 ans. Par ailleurs, cette etude souligne le role majeur du dermatologue dans le suivi du melanome.

The mandate of the Task Force Hemispheric Transport of Air Pollution (HTAP) under the Convention on Long-Range Transboundary Air Pollution (CLRTAP) is to improve the scientific understanding of the intercontinental air pollution transport, to quantify impacts on human health, vegetation and climate, to identify emission mitigation options across the regions of the Northern Hemisphere, and to guide future policies on these aspects. The harmonization and improvement of regional emission inventories is imperative to obtain consolidated estimates on the formation of global-scale air pollution. An emissions dataset has been constructed using regional emission gridmaps (annual and monthly) for SO2, NOx, CO, NMVOC, NH3, PM10, PM2.5, BC and OC for the years 2008 and 2010, with the purpose of providing consistent information to global and regional scale modelling efforts. This compilation of different regional gridded inventories, including the Environmental Protection Agency (EPA)'s for USA, EPA and Environment Canada's for Canada, the European Monitoring and Evaluation Programme (EMEP) and Netherlands Organisation for Applied Scientific Research (TNO)'s for Europe, and the Model Inter-comparison Study in Asia (MICS-Asia)'s for China, India and other Asian countries, was gap-filled with the emission gridmaps of the Emissions Database for Global Atmospheric Research (EDGARv4.3) for the rest of the world (mainly South-America, Africa, Russia and Oceania). Emissions from seven main categories of human activities (power, industry, residential, agriculture, ground transport, aviation and shipping) were estimated and spatially distributed on a common grid of 0.1° × 0.1° longitude–latitude, to yield monthly, global, sector-specific gridmaps for each substance and year. The HTAP_v2.2 air pollutant gridmaps are considered to combine latest available regional information within a complete global dataset. The disaggregation by sectors, high spatial and temporal resolution and detailed information on the data sources and references used will provide the user the required transparency. Because HTAP_v2.2 contains primarily official and/or widely used regional emission gridmaps, it can be recommended as a global baseline emission inventory, which is regionally accepted as a reference and from which different scenarios assessing emission reduction policies at a global scale could start. An analysis of country-specific implied emission factors shows a large difference between industrialised countries and developing countries for all air pollutant emissions from the energy and industry sectors, but not from the residential one. A comparison of the population weighted emissions for all world countries, grouped into four classes of similar income, reveals that the per capita emissions are, with increasing income group of countries, increasing in level but also in variation for all air pollutants but not for aerosols.

Background: Erythrasma is a superficial cutaneous infection caused by Corynebacterium minutissimum and is characterized by fluorescence under Wood's light (UV) because of the presence of porphyrins. These molecules are photosensitizing and we propose to assess efficacy of red light that activates porphyrins (photodynamic reaction) in treatment of this pathology. Objectives: Assessment of effects of photodynamic action of red light for treatment of erythrasma without exogenous photosensitizing molecules. Methods: Thirteen patients with erythrasma were treated by one illumination (80 J/cm2) by red light (broad band, peak at 635 nm) without exogenous photosensitizing molecules. Disappearance or reduction of extent of lesions were observed 2 weeks later. If lesions were still present, a second irradiation was conducted with the same method. Results: Preliminary results are presented. As a result of red light irradiation, we noticed a complete recovery for three patients and, in most other cases, reduction of extent of lesions (mean: −29% after one session). The treatment was well tolerated. Conclusion: We report first cases of photodynamic treatment of erythrasma. There are other reports of clinical applications of antimicrobial action of photodynamic therapy in dermatology (acne vulgaris, leishmaniasis, warts, etc.). But there are few applications without addition of exogenous photosensitizing agent. The originality and interest of our study is to use spontaneous presence of porphyrins in the lesions. This technique seems to be an interesting alternative, inexpensive and easy, for the treatment of this localized infection. But an optimal method is still to be determined to improve efficacy.

Resume Introduction L’angiodermite necrotique est une variete d’ulcere de jambe, caracterisee par son caractere tres algique et rapidement extensif. La cicatrisation est longue, en moyenne 4 a 11 mois. Le traitement est actuellement peu satisfaisant et difficile. Seule la realisation de greffes cutanees precoces permettrait une sedation rapide des douleurs et d’interrompre l’extension de la lesion. Cependant cette technique, realisee en phase evolutive, expose a un certain nombre de greffes perdues. Nous avons voulu confirmer l’efficacite de l’autohemotherapie locale proposee dans 2 etudes non controlees. Malades et methode Onze malades, ayant une angiodermite necrotique, ont ete inclus dans une etude prospective, non controlee. L’autohemotherapie locale etait realisee trois fois par semaine pendant un mois avec une hospitalisation initiale de quinze jours. Les criteres d’evaluation etaient : l’evolution de la douleur, de la surface de l’ulcere, de l’echelle colorimetrique et le delai de disparition du halo violace. Resultats Dix malades ont ete soulages par le traitement, avec un sevrage progressif en antalgiques. Un arret de l’evolution avec disparition du halo violace peripherique a ete note en moyenne a J6 (2-21j). Le pourcentage de tissu de granulation par rapport a la surface de l’ulcere representait 45,4 p. 100 a J0, 80 p. 100 a J14 et 85 p. 100 a J28. Conclusion L’autohemotherapie utilisee a la phase initiale du traitement permet de diminuer les douleurs et de preparer la lesion a une greffe secondaire de recouvrement.

Resume Les profils de liberation de la troponine Ic et de la CK-MB ont ete etudies apres pontage coronarien effectue avec ou sans CEC. Chez les sujets n'ayant pas presente de complications cardiaques postoperatoires, les concentrations de troponine Ic sont maximales a la 24 e heure pour les deux types de pontage. En ce qui concerne la CK-MB, le pic de liberation est observe a la 24 e heure en cas de pontage sans CEC ; en revanche, il est atteint des la troisieme heure lorsque le pontage est effectue avec CEC. De plus, dans ce type d'intervention, les concentrations de troponine Ic et de CK-MB sont deux a trois fois plus elevees qu'en l'absence de CEC. Chez les patients ayant presente un infarctus peri-operatoire, les concentrations de troponine Ic et de CK-MB sont maximales 24 heures apres le pontage qu'il soit effectue avec ou sans CEC. Le diagnostic d'une telle pathologie peut etre suspecte a la 24 e heure avec des valeurs seuils de troponine Ic sept et trois fois superieures au seuil de positivite en cardiologie medicale (courbe ROC), respectivement en presence ou en l'absence de CEC.

Resume Introduction L’urticaire solaire est une forme rare d’urticaire, survenant quelques minutes apres exposition solaire, tres invalidante car limitant les activites exterieures. Les antihistaminiques et/ou la phototherapie sont parfois decevants. Observation Une femme de 32 ans avait une urticaire solaire severe depuis novembre 2000, confirmee par les explorations photobiologiques. Les antihistaminiques a fortes doses (fexofenadine 180 mg 2/j) etaient inefficaces. Malgre une desensibilisation UVA prealable, la PUVAtherapie n’apportait qu’une amelioration partielle avec une duree de protection courte et la persistance d’un handicap important dans la vie quotidienne. En mars 2002, en raison de l’echec therapeutique, un traitement de deuxieme intention, par les immunoglobulines polyvalentes intraveineuses (IgIV) : 0,5 g/kg le 1 er jour puis 1 g/kg/j les 2 jours suivants, etait commence. Une nette augmentation des doses urticariennes minimales etait constatee : en UVA de 1 J/cm 2 avant perfusion a 15,6 J/cm 2 a 48 h et en polychromatique de 100 mJ/cm 2 a 2 200 mJ/cm 2 . Cliniquement, l’amelioration etait significative pour les activites courantes mais incomplete avec persistance de reactions urticariennes lors des expositions prolongees. Une PUVAtherapie pouvait etre reintroduite, sans desensibilisation UVA prealable, permettant d’obtenir, pour la premiere fois, une remission complete prolongee de plus de 2 mois grâce a la triple association d’une cure d’IgIV, de la PUVAtherapie et d’un traitement antihistaminique au long cours. Le traitement a ete ensuite renouvele avec succes en juillet 2002. Discussion Les traitements de premiere intention de l’urticaire solaire (antihistaminiques, PUVAtherapie) sont parfois insuffisants. Des alternatives therapeutiques ont ete proposees (plasmaphereses, ciclosporine, doxepine, cimetidine), inconstamment efficaces, non denuees d’effets indesirables et parfois contraignantes. Nous rapportons le second cas d’urticaire solaire ameliore par IgIV. Les IgIV, malgre leur cout, nous paraissent une option therapeutique de deuxieme intention pouvant notamment permettre d’eviter la desensibilisation UVA prePUVAtherapie dans les formes severes d’urticaire solaire.

Urologic considerations during the kidney transplantation process, starting with initial recipient evaluation and continuing through the post-transplant, long-term follow-up, are critical for minimizing urologic complications and improving graft survival. Appropriate, targeted, preoperative urologic evaluation of the recipient allows for an optimized urinary tract to accept the graft, whereas post-transplant urologic follow-up and monitoring decrease the risk of graft lost secondary to a urologic cause, particularly in patients with a urologic reason for their kidney failure and in those patients with concomitant urologic diagnoses. Urologic complications comprise the second most common adverse post-transplant event, occurring in 2.5% to 14% of patients and are associated with high morbidity, graft loss, and mortality. Early and late urologic complications, including hematuria, hematoma, lymphocele, urine leak, ureteral stricture, nephrolithiasis, and vesicoureteral reflux, and their causes and treatment options are explored. A multidisciplinary team approach to kidney transplantation, including transplant surgery, urology, and nephrology, optimizes outcomes and graft survival. Although the current role of the urologist in kidney transplantation varies greatly by institution, appropriate consultation, participation, and monitoring in select patients is essential.

Introduction Le fibroxanthome atypique (FXA) est une tumeur fibrohistiocytaire rare de malignite intermediaire. Il survient chez les sujets âges et siege sur les zones photo-exposees. Nous rapportons un cas de regression complete spontanee de FXA apres recidive explosive precoce. Seul un cas de regression spontanee a jusqu’alors ete rapporte a notre connaissance. Observation Un homme de 81 ans aux antecedents de carcinomes epidermoides cutanes multiples traites chirurgicalement presentait lors de son suivi une lesion nodulaire et ulceree sous-auriculaire gauche. Une biopsie etait realisee et l’examen histologique revelait un FXA. Une exerese chirurgicale avec marge de 1 centimetre etait effectuee, emportant une partie du muscle sternocleidomastoidien devant un aspect macroscopiquement suspect en peroperatoire. L’histologie avec double lecture confirmait le diagnostic de FXA d’exerese complete avec recoupes profondes saines. Trois semaines apres l’intervention, on notait une recidive precoce et explosive, confirmee par une biopsie, avec apparition brutale d’une tumeur bourgeonnante de 3 cm sur le site de la cicatrice. Devant un terrain fragile et la complexite d’une reprise chirurgicale, une radiotherapie etait proposee mais finalement non realisee. En effet, de maniere surprenante, 6 semaines plus tard, une regression complete et spontanee etait constatee, avant meme que la radiotherapie n’ait ete debutee. Il ne persistait qu’une zone discretement atrophique d’allure cicatricielle. Aucune recidive n’a ete constatee apres un an de suivi ( Fig. 1 et 2 ). Discussion La regression, probablement d’origine immunologique, est un phenomene connu dans les tumeurs cutanees de type melanique, epidermique ou lymphoide mais tres rare dans les tumeurs mesenchymateuses. Une etude histopathologique (serie de 8 FXA) a deja decrit des regressions focales, caracterisees par une sclerose extensive avec remplacement du tissu tumoral par de la fibrose. Mais seul un cas de regression totale clinique de FXA a ete decrit (regression spontanee 2 semaines apres un traumatisme local). Ces observations font suspecter une possible reaction immunitaire anti-tumorale, exceptionnellement cliniquement complete, le plus souvent partielle (histologique) qu’il pourrait etre interessant de stimuler, dans le cadre d’essais cliniques, par les nouvelles immunotherapies actuellement disponibles, notamment les anti-PD1, pour les formes metastatiques ou recidivantes de FXA. Conclusion Nous rapportons un cas de regression spontanee complete d’un FXA. Il s’agit d’un phenomene exceptionnel avec seulement un cas rapporte dans la litterature, d’autant plus spectaculaire que survenant apres une recidive explosive, massive et precoce. La physiopathologie de ce phenomene reste inexpliquee. L’hypothese d’une regression par reaction immunitaire identique a celle deja constatee au cours de l’evolution de certains melanomes et de carcinomes de Merkel pourrait etre avancee.

Introduction Le syndrome de Warner et Wilson Jones (ou granulome pyogenique recidivant avec multiples satellites) est un phenomene rare mais benin dont nous rapportons 2 cas. Observations Un homme de 50 ans, sans antecedent particulier, consultait en dermatologie pour avis concernant une lesion bourgeonnante de la narine gauche, saignant facilement au contact, apparue suite a une coupure. La lesion etait evocatrice cliniquement d’un granulome pyogenique epidermise. Une exerese chirurgicale par electrocoagulation confirmait le diagnostic. Quelques semaines plus tard, de multiples papules angiomateuses millimetriques apparaissaient sur le pourtour de la cicatrice d’exerese initiale. Les biopsies cutanees realisees etaient en faveur d’un bourgeon charnu, sans atypies cytonucleaires. Le diagnostic de syndrome de Warner et Wilson Jones etait retenu. Un traitement par laser CO2 sera prochainement realise. Le second patient est un enfant de 7 ans de sexe masculin, sans antecedent notable. Il consultait en dermatologie pour avis concernant une lesion du dos evoluant depuis plusieurs mois. L’aspect clinique et histologique apres exerese etait en faveur d’un botriomycome epidermise. A un mois de l’exerese apparaissaient de multiples lesions satellites identiques a la premiere. Le diagnostic de syndrome de Warner et Wilson Jones etait retenu. Un traitement par cryotherapie etait propose, sans efficacite. Le patient sera prochainement reevalue ( Fig. 1 et 2 ). Discussion Le syndrome de Warner et Wilson Jones est un phenomene rare qui atteint preferentiellement les enfants et adolescents de sexe masculin. Les facteurs de risque sont la localisation sur le tronc du botriomycome initial, son exerese incomplete ou un traumatisme de celui-ci. Cliniquement, il se presente sous forme de lesions bourgeonnantes d’allure angiomateuses infra-centimetriques, localisees preferentiellement sur le tronc (notamment les regions interscapulaire ou lombaire). Le delai de survenue apres l’exerese initiale est de 1 a 4 mois, mais peut aller jusqu’a 2 ans, avec un developpement progressif sur 1 a 3 semaines. L’histologie permet d’eliminer les diagnostics differentiels (melanome achromique, metastases cutanees, maladie de Kaposi, angiomes rubis). L’histologie des lesions recidivantes etant moins typique, il n’est pas necessaire de reiterer les biopsies. L’abstention therapeutique est privilegiee, la regression etant souvent spontanee en 6 a 12 mois. Les traitements envisageables sont l’exerese chirurgicale, l’electrocoagulation, le laser CO2 ou Nd-YAG, la cryotherapie ou la cryochirurgie. Conclusion Le syndrome de Warner et Wilson Jones est un phenomene rare devant etre connu du dermatologue au vu de son caractere benin et spontanement regressif.

Endotoxin and nanobacteria in polycystic kidney disease.BackgroundMicrobes have been suspected as provocateurs of polycystic kidney disease (PKD), but attempts to isolate viable organisms have failed. Bacterial endotoxin is the most often reported microbial product found in PKD fluids. We assessed potential microbial origins of endotoxin in cyst fluids from 13 PKD patients and urines of PKD and control individuals.MethodsFluids were probed for endotoxin and nanobacteria, a new bacterium, by the differential Limulus Amebocyte Lysate assay (dLAL), genus-specific antilipopolysaccharide (LPS) antibodies, monoclonal antibodies to nanobacteria, and hyperimmune serum to Bartonella henselae (HS-Bh). Selected specimens were also assessed by transmission electron microscopy (TEM) and nanobacterial culture methods.ResultsLPS or its antigenic metabolites were found in more than 75% of cyst fluids tested. Nanobacteria were cultured from 11 of 13 PKD kidneys, visualized in 8 of 8 kidneys by TEM, and immunodetected in all 13 PKD kidneys. By immunodetection, nanobacterial antigens were found in urine from 7 of 7 PKD males, 1 of 7 PKD females, 3 of 10 normal males, and 1 of 10 normal females. “Nanobacterium sanguineum” was dLAL positive and cross-reactive with antichlamydial LPS and HS-Bh. Some cyst fluids were also positive for LPS antigens from Escherichia coli, Bacteroides fragilis and/or Chlamydia, and HS-Bh, as were liver cyst fluids from one patient. Tetracycline and citrate inhibited nanobacterial growth in vitro.ConclusionNanobacteria or its antigens were present in PKD kidney, liver, and urine. The identification of candidate microbial pathogens is the first step in ascertaining their contribution, if any, to human disease.

Introduction Le dabrafenib est un inhibiteur de BRAF indique en monotherapie dans le traitement des patients adultes atteints d’un melanome non resecable ou metastatique porteur d’une mutation BRAF V600. Son effet inducteur enzymatique implique certaines precautions d’emploi. Nous rapportons une nouvelle interaction medicamenteuse entre dabrafenib et immunosuppresseurs observee chez un transplante cardiaque. Observation Un homme de 47 ans, transplante cardiaque en septembre 2012, presentait en janvier 2013 un melanome du dos mute BRAF V600E. Son traitement immunosuppresseur comprenait tacrolimus 4 mg/jour, prednisone 5 mg/jour et everolimus 2 mg/jour. En mai 2014, cinq metastases cutanees apparaissaient. Le traitement initial par vemurafenib etait rapidement interrompu suite a l’apparition d’une insuffisance renale aigue iatrogene. Secondairement, un traitement par dabrafenib 300 mg/jour etait introduit, permettant une regression totale des lesions. Un mois plus tard, les concentrations plasmatiques de l’everolimus et du tacrolimus, dosees de maniere systematique, s’effondraient, passant respectivement de 3,7 μg/L a 1,37 μg/L, et de 6,80 ng/mL a moins de 2 ng/mL. Le traitement par dabrafenib etait interrompu. Les biopsies endomyocardiques eliminaient tout rejet. Une semaine plus tard, les metastases cutanees reapparaissaient. En accord avec l’equipe de greffe cardiaque, le dabrafenib etait reintroduit a pleine dose sous couvert d’une surveillance biologique etroite des doses d’immunosuppresseurs. Leur posologie etait progressivement majoree (tacrolimus a 12 mg/jour et everolimus a 10 mg/jour). Trois mois plus tard, en raison d’un echappement therapeutique, le dabrafenib etait interrompu. Progressivement, les doses de tacrolimus et d’everolimus etaient diminuees. Discussion L’effet inducteur enzymatique du dabrafenib est responsable d’une synthese accrue des cytochromes CYP3A4, CYP2Cs et CYP2B6. En consequence, les concentrations plasmatiques des medicaments metabolises par ces enzymes diminuent, pouvant entrainer une baisse, voire une perte de leur effet clinique, faisant redouter un rejet de greffe. L’induction apparait apres 3 jours de prise de dabrafenib. A l’arret du traitement, elle disparait graduellement. Les patients doivent donc faire l’objet d’une recherche de toxicite, et les posologies des medicaments doivent etre ajustees. Certains immunosuppresseurs (tacrolimus, everolimus), anticoagulants (warfarine), antalgiques (methadone), antibiotiques (doxycycline) ou antiepileptiques (acide valproique) sont metabolises par le CYP3A4, et donc soumis a l’effet inducteur enzymatique du dabrafenib. Conclusion En raison de l’effet inducteur enzymatique du dabrafenib, une surveillance biologique etroite des medicaments metabolises par le cytochrome CYP3A4, notamment des immunosuppresseurs, est indispensable afin d’eviter tout effet indesirable grave, tel que le rejet de greffe.

Background: To the best of our knowledge, only 52 cases of squamous cell carcinoma (SCC) complicating hidradenitis suppurativa (HS) have been reported since 1958. We describe 13 new cases. Methods: We propose a clinical and histological analysis of our cases. We include these results in a review of previously reported cases to analyze a total of 65 patients. In our series of 13 cases, we also investigate the presence of human papillomavirus (HPV) in tumor samples, by polymerase chain reaction (PCR) on paraffin-embedded material. Results: Malignant transformation affects mainly men with a long-term history of genitoanal HS. Although our cases were 7 well-differentiated carcinomas and 6 verrucous carcinomas, lymphatic and visceral metastasis occurred in 2 and 3 cases, respectively. With PCR, we demonstrated presence of HPV in genitoanal tumoral lesions, principally HPV-16. Conclusion: SCC complicating HS evolves poorly, despite a good histological prognosis. Our results sustain the implication of HPV in the malignant transformation of HS.

A widely held view is that the role of testis in prostatic growth is through its ability to secrete androgen. Our earlier observation suggested a non-androgenic role for the testis, and perhaps the epididymis, in promoting growth of the ventral prostate in rats. The present study was conducted to evaluate the separate role of the testis and the epididymis in this phenomenon. In the first study, increasing quantities of silastic tubing filled with crystalline testosterone were implanted into adult Sprague-Dawley rats at the time of bilateral epididymo-orchiectomy or sham-operation. Twenty-eight days later, growth of the ventral prostate, as determined by fresh weight, DNA, and protein content, was significantly greater in sham-operated rats than in those receiving combined epididymo-orchiectomy, confirming our previous observation using dihydrotestosterone. In the second and third studies, rats were subjected to selective surgical procedures to evaluate the independent role of the testis and the epididymis. At the same time, 12 cm silastic tubing filled with testosterone or dihydrotestosterone were implanted subcutaneously into each of these animals for 28 days. Results indicated that the ventral prostate was significantly smaller in rats receiving the combined epididymo-orchiectomy than that of sham-operated controls. Simple orchiectomy or simple epididymectomy resulted in an increased weight of the ventral prostate between the two values obtained from the above two groups. Ligation of either the efferent duct or the vas deferens yielded ventral prostatic weights comparable to the androgen-treated, sham-operated controls. These results indicated that in order to achieve a maximal effect on androgen-supported growth of the ventral prostate, the presence of both the testis and the epididymis is required. Accepted for publication February 10, 1992.

We treated 15 men who had chronic bacterial prostatitis refractory to trimethoprim-sulfamethoxazole and/or carbenicillin with 400 mg. norfloxacin twice daily for 28 days. All pathogens were susceptible to norfloxacin and absent in prostatic fluid cultures obtained during therapy. One patient had negative post-therapy prostatic fluid cultures but was lost to followup at 1 month. Of the 14 patients followed for at least 6 months 9 (64%) were cured of the original infection, including 6 who have remained uninfected and have had negative prostatic secretion and urine cultures for at least 2 years (1), 1 year (2) or 6 months (3). In 3 patients urinary tract infections recurred with new pathogens at 6, 560 and 820 days after post-therapy negative prostatic fluid cultures. Bacterial prostatitis with the original pathogen recurred in 5 patients within 2 months of completing therapy. The bacteria remained susceptible to norfloxacin but could not be eradicated with 30 to 90 days of additional norfloxacin therapy. Cures were achieved in 9 of 12 patients with Escherichia coli, none of 2 with Pseudomonas prostatitis and 3 of 5 with prostatic calculi. No patient experienced significant adverse effects. The data suggest that norfloxacin is effective and safe for the treatment of refractory chronic bacterial prostatitis.

Necrotic angiodermatitis is a variety of leg ulcer, characterized by very painful and rapidly spreading lesions. Healing takes time, a mean of 4 to 11 months. Current treatment is difficult and rarely satisfactory. Only early skin grafts lead to rapid sedation of pain and stop the lesion from extending. However, this technique, performed during a progressive phase, enhances the risk of losing a certain number of grafts. We wanted to confirm the efficacy of local auto-haemo-therapy proposed in 2 non-controlled studies.Eleven patients with necrotic angiodermatitis were included in our non-controlled prospective study. The topical hemotherapy was applied three times a week for one month, with initial hospitalization for 15 days. The criteria of assessment were: evolution of pain, surface of the ulcer, colorimetric scale and the date of disappearance of the purple halo.Ten patients were relieved by the treatment, with progressive withdrawal of the analgesics. The progression of the lesion had stopped and the purple halo had disappeared in general by D6 (range: 2 to 21 days). The percentage of granulation tissue with regard to the surface of the ulcer was of 45.4 p. 100 on D0, 80 p. 100 on D14 and 85 p. 100 on D28.Topical hemotherapy applied during the initial phase of treatment would reduce the pain and prepare the lesion for a secondary skin graft.

The Boolean Constraint Propagation (BCP) is a well-known helpful technique implemented in most state-of-the-art efficient satisfiability solvers. We propose in this paper a new use of the BCP to deduce sub-clauses from the associated implication graph. Our aim is to reduce the length of clauses thanks to the subsumption rule. We show how such extension can be grafted to modern SAT solvers and we provide some experimental results of the sub-clauses deduction as a pretreatment process. This work is supported by the Region Picardie under HTSC project.

Solar urticaria is a rare form of urticaria occurring a few minutes after solar exposure. It is particularly incapaciting because it limits outdoor activities. Antihistamine and phototherapy are sometimes disappointing.A 32 Year-old woman had been suffering from severe solar urticaria since November 2000, which was confirmed by photobiological data. High-dose antihistamine treatment (fexofenadine 180 mg twice a day) was inefficient. Despite a first UVA desensitization, PUVAtherapy produced only a partial improvement and short lasting for protection, with an important handicap in daily life. In March 2002, among the others treatments, we chose intravenous immunoglobulins: 0.5 g/kg the first day then 1 g/kg the second and the third days. The minimal urticaria dose was raised from 1 J/cm2 in UVA before perfusion up to 15.6 J/cm2 48 hours later and in UVB from 100 mJ/cm2 up to 2,200 mJ/cm2. Clinically the improvement was significant but partial in daily activities. It was possible to reintroduce PUVAtherapy without UVA-desensitization and, for the first time, to obtain complete remission for more than 2 Months with an association of intravenous immunoglobulins, PUVAtherapy and antihistamine treatment. In July 2002, treatment was successfully repeated.First intention treatments (antihistamine and PUVAtherapy) are sometimes inefficient. Others treatments (plasmapheresis, ciclosporin, doxepin, cimetidine) are restrictive, not always efficient and can induce severe side-effects. We report the second case of solar urticaria improved by intravenous immunoglobulins. In spite of the cost, intravenous immunoglobulins seem to be an interesting treatment, at least by avoiding UVA-desensitization in severe cases of solar urticaria.

Introduction La maladie de Paget extra-mammaire (MPEM) est un adenocarcinome (ADK) intra-epidermique qui se developpe dans les zones riches en glandes apocrines (regions axillaires et genito-perineales). La MPEM primitive est un ADK primitivement cutane non associe a un autre cancer. La MPEM secondaire serait liee a l’invasion epidermique par une tumeur sous-jacente. Les localisations multiples de MPEM sont tres rarement observees dans les populations caucasiennes. Observations Un homme de 68 ans consultait pour un intertrigo evoluant depuis plusieurs annees resistant a differents traitements topiques. Il presentait depuis 1993 une plage erythemateuse, infiltree, bien limitee s’etendant du pli inguinal droit et une 2e lesion similaire adjacente du scrotum droit. Il existait egalement un placard erythemateux non infiltre du pli axillaire droit evoluant depuis 2011. Les biopsies cutanees des 3 localisations confirmaient le diagnostic de MPEM. Il n’y avait pas d’infiltration du derme. A l’immunomarquage, la cytokeratine 7 (CK7) etait positive et la cytokeratine 20 (CK20) negatif. Le bilan d’extension a la recherche d’un cancer avait mis en evidence un adenocarcinome prostatique infiltrant. Discussion Les MPEM de localisations multiples sont essentiellement decrites au Japon avec une soixantaine de cas rapportes avec 3 ou 4 localisations simultanees par patients. A notre connaissance, il existe 6 cas rapportes dans la population caucasienne. De maniere similaire au cas japonais il existe une predominance masculine avec 5 hommes pour une femme pour ces cas caucasiens. On observait une triple localisation pour les 5 cas masculins rapportes et une quintuple localisation pour le cas feminin decrit. Sur les 6 cas, il y avait un cas de cancer prostatique ayant precede la MPEM et un cas de cancer de pulmonaire concomitant a la MPEM. D’apres les observations de Ohnishi et al., l’immunophenotypage CK7+/CK20− serait en faveur d’une MPEM primitive, ce qui n’est pas le cas chez notre malade. Van Hamme et al. ont aussi rapporte un cas de triple localisation de MPEM secondaire avec un immunophenotype CK7+/CK20−. Conclusion Les localisations multiples de MPEM sont exceptionnelles. Le traitement de choix est l’exerese chirurgicale large des lesions. Neanmoins, meme en cas de lesion intra-epidermique, le caractere etendu des lesions rend parfois difficile la prise en charge chirurgicale. En cas de lesions tres etendues, les alternatives sont la radiotherapie, la phototherapie dynamique et l’imiquimod.

Parvovirus B19, a recently discovered single-stranded DNA virus, is a known cause of chronic anemia in immunocompromised patients. This virus has been identified as the etiologic agent of the common childhood mild febrile exanthem erythema infectiosum, or “fifth disease”, as well as a chronic arthralgia in children and adults that is symptomatically similar to rheumatoid arthritis. At least one fatality from acute myocarditis in a one-year-old child has been reported (1). Transient aplastic anemia has been reported in infected patients with congenital hemolytic anemia such as sickle cell disease (2), whereas chronic anemia affects immunocompromised hosts with acquired immunodeficiency syndrome (3) and acute lymphocytic leukemia (4, 5), and it has been reported in a 14 year-old girl following bone marrow transplantation (6). Only one previous report of parvovirus B19–producing anemia in a solid-organ transplant, that of a cadaveric renal transplant recipient receiving cyclosporine, appears in the literature (7). We report the case of a pediatric en bloc renal transplant recipient on FK506 with pure red cell aplasia and peripheral pancytopenia caused by parvovirus B19 that were responsive to commercial immunoglobulin administration. The patient was a 62 year-old man with diabetic and hypertensive nephropathies and a history of gout, who underwent cadaveric renal transplantation using pediatric-donor kidneys in an en bloc fashion in February, 1990. At the time of transplant, the recipient's serologic titers were negative for hepatitis B surface antigen, anti–hepatitis B antibody, anticytomegalovirus IgM, and anti–human immunodeficiency virus antibody, while titers were positive for anticytomegalovirus IgG at 1:69, and for antihepatitis A IgG by ELISA. The donor was a 16-month-old girl who died of suspected cardiac arrest secondary to anoxia. She exhibited flu-like symptoms approximately 48 hr prior to the arrest. Donor serologic titers were negative for anti–cytomegalovirus, hepatitis, and human immunodeficiency virus antibodies. Parvovirus titers were not performed on donor or recipient sera, as they are not included in routine pretrans-plant serologic testing. The recipient was discharged 17 days posttransplant with a creatinine of 1.5 mg/dl and a hematocrit of 33.1% on an immunosuppressive regimen of FK506 (0.1 mg/kg b.i.d.) and prednisone (10 mg q.d.). He remained well until readmission one year posttransplant for an exacerbation of gouty arthritis affecting multiple joints, confirmed by fluid aspiration and treated by steroid injections and colchicine. At the time of admission, the patient was noted to be pancytopenia Total WBC count was 1700/mm3, hematocrit 22.7%, platelet count 52,000, and reticulocyte count 0.1%, with normal red cell indices. Bone marrow aspiration and biopsy at that time revealed markedly decreased erythroid maturation with normal myeloid series and megakaryocytes, and increased iron stores (Fig. 1A). No viral inclusions were present. The serum anticytomegalovirus IgG titer was positive at 1:106 and the IgM titer was equivocal at 1:15. However, urine, throat swab, and buffy coat CMV cultures and the early antigen assay remained negative. Colchicine and prophylactic trimethoprim/sulfamethoxazole were discontinued as they were thought to be likely causes of the patient's erythroid hypoplasia. His leukopenia and thrombocytopenia improved, and, following transfusion, the patient's hematocrit stabilized at 27.7%. During the subsequent month, the patient received ten outpatient transfusions of packed red blood cells. He was readmitted one month after discharge with chest pain, and subsequently a myocardial infarction was excluded by enzyme and EKG criteria. At this second admission, his hematocrit was 21.6%, his total WBC count was 1700/mm3, his platelet count was 111,000, and his reticulocyte count was 0.1%. A peripheral blood smear revealed moderate microcytosis with rare anisocytosis and hypochromia. The serum erythropoietin level was elevated at 2820 mU/ml (normal 4–26). His chest pain resolved completely after transfusion of two units of packed red blood cells. Repeat cytomegalovirus cultures and early antigen detection were negative. Antiparvovirus IgG was detected by western blot analysis of the patient's serum (Specialty Laboratories, Los Angeles. CA)—however, antiparvovirus IgM was undetectable. Repeat bone marrow aspiration and biopsy revealed essentially complete erythroid aplasia (Fig. 1C) except for rare giant pronormoblasts (Fig. 1B). Numerous eosinophilic intranuclear inclusions were noted in marrow cells (Fig. 1C, arrows) suggestive of viral infection. The presence of parvovirus B19 DNA was detected in the patient's serum by polymerase chain reaction (PCR), screening by dot-blot DNA hybridization, and finally by Southern blot analysis (University of Iowa, S.J.N.). The patient was treated with a ten-day course of an intravenous commercial pooled human immunoglobulin preparation with subsequent elevation of his reticulocyte count and resolution of the anemia (Fig. 2). He was discharged home seven days after completion of immunoglobulin therapy in good condition. Hematocrit rose to 30.3 and 37.9% at the time of discharge and twelve days later, respectively. Four months later, the patient's hematocrit slowly drifted down to 29.9%. Repeat bone marrow biopsy showed no evidence of viral infection. While on oral iron therapy, his hematocrit stabilized at 36.1% two weeks later, and remains at 42.1% one year after immunoglobulin therapy. Figure 1 Bone Marrow Morphology. (A) Bone marrow core biopsy on previous admission demonstrating erythroid hypoplasia. Myeloid cells and megakaryocytes are present. Intranuclear inclusions are not seen (HE ×400). (B) Giant pronormoblast present ... Figure 2 Resolution of anemia following a course of i.v. pooled immunoglobulin. Hematocrit levels are indicated by closed squares, and absolute reticulocyte counts by closed triangles. Arrows indicate transfusion of packed erythrocytes. Bone marrow biopsy specimens obtained from the patient two months prior to treatment, one week prior to treatment, and four months after treatment were removed from paraffin blocks under sterile conditions for PCR, dot-blot, and Southern Blot analysis. Parvovirus B19 DNA was detected by Southern analysis of PCR product from both bone marrow specimens obtained before immunoglobulin therapy, but it was not detected in the posttreatment specimen. Parvovirus B19 disease is now a recognized cause of aplastic crisis and anemia in patients who are immunocompromised by leukemia, hemolytic anemia, and acquired immunodeficiency syndrome. However, few cases of such infections have been reported in solid-organ transplant recipients. The shortage of available kidneys for transplantation has prompted many transplant centers to search for means of expanding the donor pool. At our institution we have utilized en bloc transplantation of pediatric cadaver kidney grafts for adult recipients. This technique uses both donor kidneys with donor aorta and vena cava intact for anastomosis to recipient iliac vessels. Periaortic and pericaval lymphatic tissue is carefully removed during preparation of the grafts for transplant. We report the case of a pediatric-donor renal transplant recipient who had pure red cell aplasia secondary to parvovirus B19 infection one year after transplantation, confirmed by PCR and Southern analysis. Serology demonstrated the lack of an IgM response, a finding that is not uncommon in immunosuppressed patients infected with this virus (8, 9). In the case reported here, the infant donor exhibited a viral prodrome prior to sudden death, and, since at least one case of death from myocarditis caused by parvovirus in an infant has been reported (1), this case raises the question of whether parvovirus B19 was transmitted from donor to recipient via the allograft. We retrieved autopsy specimens of myocardium and bone marrow from the infant donor in this case, both of which were tested by PCR and Southern-blot hybridization and found to be negative for parvovirus DNA. These tests do not, however, completely rule out the possibility of the presence of the virus in donor tissues. Further investigation into the prevalence of parvovirus B19 disease in transplant patients is warranted, as this infection may prove to be a common cause of anemia and aplastic crisis in the solid-organ transplant recipient.

Polycystic kidney disease (PKD) is one of the most common genetic diseases in humans. We contend that it may be an emerging infectious disease and/or microbial toxicosis in a vulnerable human subpopulation. Use of a differential activation protocol for the Limulus amebocyte lysate (LAL) assay showed bacterial endotoxin and fungal (1-->3)-beta-D-glucans in cyst fluids from human kidneys with PKD. Fatty acid analysis of cyst fluid confirmed the presence of 3-hydroxy fatty acids characteristic of endotoxin. Tissue and cyst fluid from three PKD patients were examined for fungal components. Serologic tests showed Fusarium, Aspergillus, and Candida antigens. IgE, but not IgG, reactive with Fusarium and Candida were also detected in cyst fluid. Fungal DNA was detected in kidney tissue and cyst fluid from these three PKD patients, but not in healthy human kidney tissue. We examine the intertwined nature of the actions of endotoxin and fungal components, sphingolipid biology in PKD, the structure of PKD gene products, infections, and integrity of gut function to establish a mechanistic hypothesis for microbial provocation of human cystic disease. Proof of this hypothesis will require identification of the microbes and microbial components involved and multifaceted studies of PKD cell biology.