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International audience; Existing studies in black-box optimization for machine learning suffer from low generalizability, caused by a typically selective choice of problem instances used for training and testing different optimization algorithms. Among other issues, this practice promotes overfitting and poor-performing user guidelines. To address this shortcoming, we propose in this work a benchmark suite, OptimSuite, which covers a broad range of black-box optimization problems, ranging from academic benchmarks to real-world applications, from discrete over numerical to mixed-integer problems, from small to very large-scale problems, from noisy over dynamic to static problems, etc. We demonstrate the advantages of such a broad collection by deriving from it Automated Black Box Optimizer (ABBO), a general-purpose algorithm selection wizard. Using three different types of algorithm selection techniques, ABBO achieves competitive performance on all benchmark suites. It significantly outperforms previous state of the art on some of them, including YABBOB and LSGO. ABBO relies on many high-quality base components. Its excellent performance is obtained without any task-specific parametrization. The OptimSuite benchmark collection, the ABBO wizard and its base solvers have all been merged into the open-source Nevergrad platform, where they are available for reproducible research.

Metastatic melanoma is one of the most aggressive and drug-resistant cancers with very poor overall survival. Circulating melanoma cells (CMCs) were first described in 1991. However, there is no general consensus on the clinical utility of CMC detection, largely due to conflicting results linked to the use of heterogeneous patient populations and different detection methods. Here, we developed a new EPithelial ImmunoSPOT (EPISPOT) assay to detect viable CMCs based on their secretion of the S100 protein (S100-EPISPOT). Then, we compared the results obtained with the S100-EPISPOT assay and the CellSearch&reg, CMC kit using blood samples from a homogeneous population of patients with metastatic melanoma. We found that S100-EPISPOT sensitivity was significantly higher than that of CellSearch&reg, Specifically, the percentage of patients with &ge, 2 CMCs was significantly higher using S100-EPISPOT than CellSearch&reg, (48% and 21%, respectively, p = 0.0114). Concerning CMC prognostic value, only the CellSearch&reg, results showed a significant association with overall survival (p = 0.006). However, due to the higher sensitivity of the new S100-EPISPOT assay, it would be interesting to determine whether this functional test could be used in patients with non-metastatic melanoma for the early detection of tumor relapse and for monitoring the treatment response.

International audience; Melanoma and Merkel cell carcinoma are two aggressive skin malignancies with high disease-related mortality and increasing incidence rates. Currently, invasive tumor tissue biopsy is the gold standard for their diagnosis, and no reliable easily accessible biomarker is available to monitor patients with melanoma or Merkel cell carcinoma during the disease course. In these last years, liquid biopsy has emerged as a candidate approach to overcome this limit and to identify biomarkers for early cancer diagnosis, prognosis, therapeutic response prediction, and patient follow-up. Liquid biopsy is a blood-based non-invasive procedure that allows the sequential analysis of circulating tumor cells, circulating cell-free and tumor DNA, and extracellular vesicles. These innovative biosources show similar features as the primary tumor from where they originated and represent an alternative to invasive solid tumor biopsy. In this review, the biology and technical challenges linked to the detection and analysis of the different circulating candidate biomarkers for melanoma and Merkel cell carcinoma are discussed as well as their clinical relevance.

Type I interferonopathies are a group of Mendelian disorders characterized by a common physiopathology: the up-regulation of type I interferons. To date, interferonopathies include Aicardi-Goutieres syndrome, familial chilblain lupus, spondyenchondromatosis, PRoteasome-associated auto-inflammatory syndrome (PRAAS) and Singleton-Merten syndrome. These diseases present phenotypic overlap including cutaneous features like chilblain lupus, that can be inaugural or present within the first months of life. This novel set of inborn errors of immunity is evolving rapidly, with recognition of new diseases and genes. Recent and improved understanding of the physiopathology of overexpression of type I interferons has allowed the development of targeted therapies, currently being evaluated, like Janus-kinases or reverse transcriptase inhibitors.

Background: Macular arteritis, macular lymphocytic arteritis (MLA) or lymphocytic thrombophilic arteritis all correspond to an identical new clinicopathological entity. Its individualization as a primary cutaneous lymphocytic arteritis is still controversial for certain authors as it could represent a latent form of cutaneous polyarteritis nodosa. Materials and Methods: We report here 3 additional cases of MLA, present a review of the literature and discuss the disease's nosology. Results: MLA is characterized clinically by a benign skin eruption consisting in bilateral asymptomatic erythematous/hyperpigmented macules mainly located on the lower legs and histologically by a medium-sized cutaneous lymphocytic prominent arteritis present in early cutaneous lesions. Conclusion: These findings support that MLA may be considered as a chronic and indolent primary lymphocytic cutaneous arteritis. Nevertheless, in some cases the objective obliteration of cutaneous vessels underlines the need for continuous monitoring in MLA patients.

Background Children with multiple cafe-au-lait macules (CALMs) may be followed for years before a second National Institutes of Health clinical criterion of neurofibromatosis type 1 (NF1) develops to confirm the diagnosis. Objective We sought to assess the prevalence of nevus anemicus (NA) in NF1 and its association with neuro-ophthalmologic complications. Methods This was a prospective multicenter case-control study of 210 consecutive patients with multiple CALMs. Patients with NF1 were matched for age, sex, and center with control subjects. We documented the number, location, and morphologic appearance of NA; dermatologic features of NF1; magnetic resonance imaging results; and family history. Results In all, 77 (51%) patients with NF1 had NA compared with 6 (2%) control subjects. NA was not detected in 26 patients with other genodermatoses associated with CALMs. Patients with NF1 and NA were younger than those without NA (median age: 17 years) ( P = .002). NA was mostly localized to the upper anterior aspect of the chest. NA was not significantly linked with other clinical manifestations of NF1, including optic glioma and unidentified bright objects. Limitations A potential referral bias associated with tertiary care centers is a limitation. Conclusions NA appears to have a high prevalence and specificity in NF1 and might serve as a marker for NF1 in children with multiple CALMs.

Plasmatic proteasome (p-proteasome) has recently been described as a new marker for metastatic melanoma. The objective of this study was to compare the diagnostic and prognostic values of p-proteasome with three other melanoma serological markers: S100B protein, melanoma inhibitory activity protein (MIA) and lactate dehydrogenase (LDH) in the plasma of 121 stage I-IV melanoma patients. Laboratory analyses were performed by standardized ELISA (p-proteasome, MIA), immunoluminometric assay (S100B) and colorimetry (LDH). We found that all markers were relevant for discriminating metastatic from nonmetastatic patients but p-proteasome displayed the highest diagnostic accuracy. P-proteasome and S100B were the most sensitive (58.1%) and p-proteasome and MIA the most specific (98.7 and 100%) in detecting metastatic disease. P-proteasome and S100B had the highest area under receiver operating characteristics curve, 0.811 (95% CI: 0.725-0.897) and 0.822 (95% CI: 0.738-0.906), respectively. These two markers were the best in detecting patients with lymph node metastases. S100B, MIA and LDH diagnostic accuracy was increased when these markers were combined with p-proteasome. As shown with univariate analysis, shorter progression-free and overall survival rates were significantly associated with elevated plasma levels of each markers. The multivariate Cox regression analysis identified p-proteasome as the only independent predictor of a poorer progression-free survival (p = 0.030). In conclusion, this comparative study established that p-proteasome quantification in combination with other melanoma biomarkers is an attractive approach for the biological follow-up of melanoma patients.

BACKGROUND We describe the case of a 71-year-old woman presenting cervical metastatic fasciitis with invasive lobular carcinoma (ILC) of the breast. PATIENTS AND METHODS The patient consulted for a deep and painless skin infiltration of the neck associated with dysphagia and restricted cervical mobility. Skin and muscle biopsies were normal. Muscle fascia biopsy showed a linear infiltration of metastatic cells in "single file", revealing ILC of the right breast. DISCUSSION ILCs have a particular metastatic pattern. They can permeate through tissue planes, infiltrate solid organs and spread on serous membranes in an insidious fashion. CONCLUSION Our case shows that ILC can metastasise into muscular fascia, causing "fasciitis-like" symptoms. Dermatologists should be aware of this particular pattern of dissemination.

Resume Introduction Les leucemies congenitales peuvent s’accompagner de localisations cutanees specifiques. Parmi ces leucemies cutanees congenitales (LCC), il existe une variete extremement rare, dite « aleucemique », c’est-a-dire sans blastose medullaire ni sanguine, qui n’a ete decrite qu’a sept reprises dans la litterature. Son evolution est variable, posant la question de la necessite ou non d’un traitement agressif par polychimiotherapie. Nous rapportons un cas de LCC aleucemique dont l’evolution a ete spontanement favorable, et le comparons aux autres cas de la litterature. Observation Un nourrisson de sexe masculin etait ne avec des lesions cutanees nodulaires diffuses de couleur rouge violace, realisant le syndrome du « blueberry muffin baby ». L’hemogramme et l’examen medullaire ne trouvaient pas de blastes. Le caryotype etait normal. La biopsie cutanee concluait a une leucemie aigue myeloide de type 5. L’abstention therapeutique n’empechait pas une evolution favorable. L’enfant etait en bonne sante a l’âge d’un an. Discussion Il s’agit a notre connaissance de la huitieme observation publiee de LC aleucemique. Trois enfants sont morts, dont deux par acutisation de la leucemie. Le pronostic semble tres fortement dependant de la presence ou non d’un rearrangement de genes – 11q23. Si celui-ci est present, le risque d’acutisation est important et une polychimiotherapie semble necessaire. En l’absence de rearrangement de gene pejoratif, comme notre cas l’illustre une nouvelle fois, l’abstention therapeutique parait possible, voire recommandee.

Plasmatic proteasome (p-proteasome) also called circulating proteasome has recently been described as a tumor marker. We investigated the diagnostic and prognostic accuracies of p-proteasome levels in a melanoma population classified according to the American Joint Committee on Cancer staging system. Using an ELISA test, we measured p-proteasome levels in 90 patients and 40 controls between March 2003 and March 2008. The subunit composition of p-proteasomes was determined in metastatic melanoma by proteomic analysis. The mean p-proteasome levels were correlated with stages (P 4300 ng/ml) were significantly correlated with an increased risk of progression [hazard ratio (HR) = 7.34; 95% CI 3.54-15.21, P < 0.0001] and a risk of death (HR = 5.92; 95% CI 2.84-12.33, P < 0.0001). In multivariate analysis, high p-proteasome levels were correlated with a poorer clinical outcome in the subgroup analysis limited to patients with disease stages I, II and III. Proteomic analysis confirmed the presence of all proteasome and immunoproteasome subunits. Taken together, these results indicate that p-proteasomes are a new marker for metastatic dissemination in patients with melanoma.

Resume Introduction Les angiosarcomes epithelioides de l’aorte (ASE) sont des tumeurs rares dont le diagnostic repose sur l’analyse anatomopathologique de l’aorte. Nous en rapportons un cas revele par des metastases cutanees. Observation Un homme etait hospitalise pour des tumeurs cutanees associees a une alteration de l’etat general et des douleurs intenses du membre inferieur droit. L’examen montrait trois nodules de la region lombaire associes a un livedo etendu au membre inferieur droit. L’evolution etait marquee par la survenue d’une ischemie distale. L’echographie-doppler arterielle, l’arteriographie et la tomodensitometrie mettaient en evidence une ectasie de l’aorte abdominale avec thrombose et une occlusion arterielle sous-poplitee droite. L’examen histologique d’un nodule montrait une proliferation maligne de cellules exprimant les cytokeratines AE1/AE3 et 7, la vimentine et le CD31, mais pas le CD34. L’examen histologique du livedo trouvait un embole vasculaire constitue de cellules d’allure epitheliale exprimant la cytokeratine 7 et le CD31. La tomographie par emission de positons (TEP) montrait un hypermetabolisme de l’aorte etendu a l’artere iliaque droite et des hyperfixations osseuses et cutanees. Le diagnostic d’ASE avec metastases cutanees, metastases osseuses et emboles neoplasiques etait retenu. Discussion Vingt-sept observations d’ASE de l’aorte, authentifiees en immunohistochimie, ont ete decrites. Les lesions siegent essentiellement sur l’aorte abdominale et sont associees a des metastases dans plus de 80 % des cas. Les metastases cutanees realisent des papules, des nodules, des tumeurs ou des lesions vasculaires distales. Les embolies sont responsables d’ischemie et exceptionnellement d’un tableau evoquant une vascularite necrosante. Notre observation permet de souligner : le caractere evocateur de l’association de tumeurs cutanees malignes localisees, d’un livedo etendu, d’une ischemie distale ipsilaterale et d’une alteration de l’etat general avec douleurs intenses ; l’interet diagnostique des marqueurs endotheliaux, en particulier le CD31 et la possible co-expression trompeuse de marqueurs de cytokeratines ; l’interet de la TEP .

Resume Introduction Le syndrome de Volkmann (SV) est une ischemie neuromusculaire secondaire a une augmentation de la pression interstitielle dans un espace anatomique ferme (loge osteo-aponevrotique). Sa survenue en periode neonatale est exceptionnelle. Observation Une enfant etait vue au deuxieme jour de vie pour un œdeme froid et une hypomobilite du membre superieur gauche presents depuis la naissance et compliques de troubles trophiques. La mere avait ete traitee par olanzapine, prazepam et valpromide pendant toute la grossesse. L’accouchement avait ete complique d’une dystocie des epaules ayant necessite des manœuvres d’expulsion successives : hyperflexion des cuisses, compression sus-pubienne, manœuvre de Couder, episiotomie. L’examen clinique montrait un œdeme du membre superieur et du thorax, predominant a la main et a l’avant-bras, un decollement bulleux, une necrose avec ulceration fibrineuse profonde du pli du coude, une flexion et une cyanose digitales. L’angio-IRM montrait un œdeme etendu de la graisse sous-cutanee et des muscles avec un epanchement des fascias, une compression arterielle des arteres du bras et une diminution du flux sanguin arteriel de l’avant-bras. L’evolution etait favorable apres incision de decharge cutaneo-aponevrotique, ouverture du canal carpien et excision de la necrose realisees au troisieme jour de vie. L’angio-IRM postoperatoire etait normale. Au dixieme jour survenaient des episodes de tremulations avec acces d’opisthotonos et presence a l’electroencephalogramme de nombreuses anomalies intercritiques evoquant un syndrome de sevrage aux benzodiazepines. Discussion Les causes exactes du SV ne sont pas connues. Les facteurs de compression mecanique sont surtout retenus : bande amniotique constrictive, compression par un jumeau decede, malposition du bras, cordon ombilical enroule, facteurs locaux ou generaux qui concourent a une extraction difficile : brachypelvie, extraction au forceps, oligo/polyhydramnios, anomalie uterine, gain de poids excessif, diabete, rupture prolongee de la poche des eaux, prematurite, pre-eclampsie, cesarienne. Trois points sont a souligner dans notre observation. L’interet diagnostique de l’angio-IRM precoce, qui montre une association d’œdeme tissulaire etendu, de compression arterielle multiple et d’hypoperfusion. Le role traumatique potentiel, jamais signale auparavant, de la dystocie des epaules. Surtout le role potentiel des medicaments neuroleptiques et anxiolytiques pris par la mere. Le prazepam est une benzodiazepine responsable, chez le nouveau-ne, d’intoxication et de syndrome de sevrage. L’intoxication, precoce, est caracterisee notamment par une somnolence et une diminution de la reactivite spontanee et provoquee. Elle pourrait etre un facteur d’hypomobilite et d’hypotonie fœtale favorisant appuis prolonges et malpositions sources de compression. Les traitements medicaux maternels n’ont jamais ete, jusqu’alors, mentionnes comme facteur etiologique possible de SV neo-natal.

AIMS The goal of this work was to assess the validity of Mohs Micrographic Surgery (MMS) for basal cell carcinoma (BCC) in a routine clinical setting. MATERIAL AND METHODS Our adaptation of the technique described by Mohs and coll allows intraoperative histological examination of all surgical edges of the resection. Sixteen men and 4 women were selected. RESULTS Average operative time was 2 hours 30 minutes. No false results were noted. The cosmetetic and functional outcomes were good. CONCLUSION MMS is a safe and reproducible surgical technique made possible by solid team work. It is adapted for the treatment of BCC with a high risk of recurrence. The cosmetetic and functional results are quite satisfactory. The recurrence rate at 5 years is 10 times less than with other methods of treatment. The additional time required for this surgery be put in balance with the number of tumors for which a second intervention would have been necessary if conventional surgery had been used. All procedures were performed under local anesthesia, and none or the patients required a second intervention.

Uncontrolled proliferation of melanocytes results in melanoma, one of the most aggressive forms of skin cancer, which further metastasizes into a deadly form of cancer. The p16-cyclin D-CDK4/6-reti...

Resume Introduction Le mycosis fongoide pilotrope est une forme particuliere de mycosis fongoide, en raison de ses aspects cliniques, histologiques, de son moins bon pronostic et de sa resistance therapeutique. Nous rapportons l’observation d’un mycosis fongoide pilotrope, sans mucinose, d’emblee tumoral, dont l’evolution terminale a ete marquee par la survenue d’une erythrodermie pustuleuse. Observation Un homme de 69 ans avait en 1998 des plaques erythemato-squameuses infiltrees et des nodules sur les membres associes a des lesions folliculaires predominant sur la region cervico-cephalique. Les examens histologiques montraient un infiltrat pilotrope de cellules T atypiques CD4 + CD8 - CD30 - sans epidermotropisme ni mucinose. L’etude des rearrangements des genes trouvait dans la peau un clone lymphocytaire T. Le diagnostic de mycosis fongoide pilotrope d’emblee au stade tumoral etait porte et, malgre differents traitements, la maladie evoluait vers une erythrodermie pustuleuse fatale. Discussion Le mycosis fongoide pilotrope au debut de son evolution est parfois difficile a distinguer du mycosis fongoide classique ou l’atteinte folliculaire peut frequemment s’observer. Il serait pourtant souhaitable de differencier ces entites en raison du moins bon pronostic des mycosis fongoides pilotropes. Le developpement des techniques de microdissection tissulaire et l’obtention de clones lymphocytaires T a partir de la peau humaine devraient permettre de mieux separer ces sous-groupes de lymphomes T cutanes. Notre observation est particuliere par l’absence de mucinose dermique, l’association a une forme d’emblee tumorale et l’evolution vers une pustulose generalisee. Elle souligne egalement le mauvais pronostic et la resistance therapeutique des mycosis fongoides pilotropes.

Summary Background Proteasomes, nonlysosomal proteolytic structures, are implicated in cell growth and differentiation. An abnormal expression has been described in haematopoietic malignancies and in some solid tumours. Objectives To study the plasma proteasome levels in patients with malignant melanoma (MM) using an enzyme-linked immunosorbent assay (ELISA) technique, and to compare them with the values obtained in a normal population and in patients with severe psoriasis or chronic idiopathic urticaria (CIU). Methods Plasma proteasome level was measured using a sandwich ELISA test in normal donors (n = 14), and in patients with stage I/II (n = 13), stage III (n = 6) and stage IV (n = 10) MM, severe psoriasis (n = 13) and CIU (n = 6). Tissue proteasome expression was also detected by immunohistology using a monoclonal antibody in paraffin-embedded samples of normal tissue, psoriasis skin and MM. Results In normal donors, mean ± SEM plasma proteasome concentration was 2138 ± 221 ng mL−1. Patients with stages III and IV MM exhibited a significantly higher value (3373 ± 470 ng mL−1 and 8931 ± 1232 ng mL−1, respectively). Values in patients with stage I/II MM and CIU were not significantly different from those in normal volunteers. Patients with severe psoriasis also exhibited increased values (3398 ± 374 ng mL−1) but to a lesser extent than in patients with stage IV MM. There was a significant correlation of proteasome levels with serum lactate dehydrogenase in the MM group. Tissue expression as demonstrated by immunohistochemistry paralleled these findings. The strongest expression was seen on MM slides and to a lesser extent in psoriasis samples, the weakest expression being observed in normal skin. Conclusions Proteasomes are strongly expressed in cutaneous MM; high levels of circulating proteasomes are detected in patients with metastatic MM with a high melanoma burden, and at a lesser extent in psoriatic patients, which suggests proteasomes represent a marker more of nonspecific inflammation than of early cancer.

Resume Introduction La PUVAtherapie, l’acitretine et la corticotherapie generale sont actuellement les traitements de premiere ligne du lichen plan cutane dissemine. Nous avons etudie, l’efficacite des UVB a spectre etroit dans cette indication. Malades et methode Il s’agissait d’une etude retrospective sur dossiers etudiant les malades atteints d’un lichen plan cutane dissemine et traites par phototherapie a spectre etroit dans l’unite de phototherapie du CHU de Montpellier pendant la periode de mai 1994 a novembre 2001. Le lichen plan cutane dissemine etait defini comme un lichen affectant au moins 20 p. 100 de la surface cutanee. Vingt malades ont ete inclus. Les UVB etaient delivres 3 fois par semaine par une cabine Philips TL01 (311-313 nm). Le protocole etait celui utilise pour le traitement du psoriasis. Nous avons defini 4 types de reponse : reponse complete (disparition de plus de 90 p. 100 des lesions), reponse partielle (disparition d’au moins 50 p. 100 des lesions), reponse mediocre (amelioration comprise entre 20 et 50 p. 100 des lesions), echec (diminution de moins de 20 p. 100 des lesions). L’evaluation de la recidive a long terme a ete realisee par une enquete telephonique aupres des malades ou de leur medecin traitant. Resultats Une reponse complete a ete obtenue chez 11 malades sur 20 (55 p. 100), une reponse partielle a ete observee chez 4 malades (20 p. 100), ce qui correspond a 75 p. 100 de repondeurs. La reponse a ete obtenue avec un delai median de 3 mois avec des extremes allant de 2 a 6 mois, apres une mediane de 30 seances (12 a 50) et une dose cumulee d’UVB de 36 ± 4,8 joules/cm2. Le phototype, le sexe, l’âge et la duree d’evolution avant traitement n’ont pas eu d’influence sur la reponse. La recidive a ete estimee a 18 p. 100 (2/11) apres 42 mois d’interruption du traitement. Discussion Ces resultats nous paraissent en faveur de l’efficacite des UVB a spectre etroit dans le traitement du lichen plan cutane dissemine. Ils confirment ceux des etudes precedentes et sont superposables a ceux de la PUVAtherapie orale.

Pseudoepitheliomatous hyperplasia is a benign condition defined by an exuberant proliferation of the epithelium with downward progression into the dermis. It may occur in reaction to several conditions including chronic cutaneous wound. We describe an unusual case of a florid pseudoepitheliomatous hyperplasia mimicking a well-differentiated squamous cell carcinoma, restricted to the red part of a rose tattoo.

Notalgia paresthetica (NP) is a common but often unrecognized neurocutaneous condition, with very few cases reported to date. It is characterized by pruritus localized in an area between D2 and D6 dermatomes, sometimes accompanied by sensory neuropathies and/or electrical conductivity disorders. Cutaneous pigmented patches and friction amyloidosis can arise with irritation. Some hereditary cases have been noted mainly in young patients, associated with multiple endocrine neoplasia type 2A. However, NP mainly occurs in older patients and most are sporadic pathologies linked with musculoskeletal compression of spinal nerves. Only capsaicin has shown some (but unfortunately only transient) efficacy in relieving NP symptoms. We present observations on 12 sporadic cases of NP. Spinal X-rays revealed dorsal arthrosis or spinal static disequilibrium in nine of these patients. Six patients underwent spinal and paraspinal ultrasound or radiation (better) physiotherapy, and the symptoms subsided in four of these cases. These results highlighted that spinal disorders could be a determining factor in NP, indicating that patients could benefit from physiotherapy.

Background: Cutaneous exposure to UVB radiation impairs the induction of contact hypersensitivity (CHS). Variable results have been found among studies examining the use of sunscreens to prevent UV-induced immunosuppression. Objective: Our purpose was to determine whether solar-simulated exposure of human skin resulted in an impairment of CHS responses and whether the preapplication of an intermediate sun protection factor (SPF) sunscreen could prevent this locally UV-induced immunosuppression. Methods: Irritant and CHS responses to dinitrochlorobenzene (DNCB) were randomly assessed in 160 human volunteers with or without UV exposure and with or without prior application of an SPF 15 sunscreen with high UVA protection. DNCB sensitization was performed 3 days after acute UV irradiation corresponding to 3 minimal erythema doses. Results: After solar-simulated UV exposure, the percentage of positive responses to DNCB sensitization dropped from 95% to 50% ( p = 0.003). Prior application of the sunscreen formulation did not modify the percentage of positive responses (90%) and maintained the immunization rate at 85% among volunteers exposed to UV. Conclusion: A localized sunburn can impair the afferent arm of CHS reactions in humans. The use of intermediate SPF sunscreens with high UVA protection adequately protects from the suppression of CHS responses that occurs after acute solar-simulated UV exposure. (J Am Acad Dermatol 1997;37:187-94.)

Introduction Le rituximab (RTX), anticorps anti-CD20, a fait recemment la preuve de son interet majeur dans le pemphigus. Il semble egalement actif dans les pemphigoides des muqueuses mais sa place dans la pemphigoide bulleuse (PB) ou gravidique (PG), notamment dans les formes severes resistantes aux traitements conventionnels ou en cas d’effets indesirables limitant de ces derniers est plus incertaine. Nous presentons l’experience francaise avec cette molecule chez 48 patients atteints de PB ou de PG. Materiel et methodes Les patients traites entre 2010 et 2016 par RTX pour une PB ou une PG dans 14 centres francais ont ete inclus dans cette etude retrospective. Les donnees suivantes ont ete recueillies : âge, traitements anterieurs, raison(s) d’emploi du RTX, schema therapeutique utilise, traitements associes eventuels, pourcentage de patients mis en remission clinique complete (RCC) ou partielle (RCP) et donnees de suivi (duree, rechutes eventuelles apres RCC ou RCP, poursuite ou non d’un traitement apres RTX). Resultats Trois PG et 45 PB ont ete inclus. L’emploi du RTX etait motive par : severite de la PB (69 %), echec (81 %) et/ou iatrogenie (33 %) des traitements anterieurs, corticodependance (15 %) ou contre-indication aux traitements conventionnels (25 %). Tous les patients etaient consideres en impasse therapeutique. 63 % ont recu 1 g a j1 et j15 et 37 % 375 mg/m2/sem pendant 4 semaines. Treize patients ont recu plus d’une cure (entretien ou rechute). 70,8 % avait un traitement associe au RTX (corticotherapie locale et/ou orale, immunosuppresseurs). Les taux de RCC, RCP et de non-reponse ont ete respectivement de 31,1 % (25–50 % selon les tranches d’âge), 48,8 et 13,3 % pour les PB versus 66, 0 et 33 % pour les PG soit un taux global de reponse de 79 %. Le delai moyen d’obtention d’une RCC etait 5,1 mois. Le delai moyen de suivi etait de 1,5 an et une rechute a ete observee chez 4/16 et 9/20 patients en RCC et RCP respectivement dans l’annee suivant son obtention (apres delai moyen de 11,8 et 8 mois respectivement). Sept patients (14,6 %) ont presente un effet indesirable grave : 2 decompensations cardiaques et 5 infections dont un cas de nocardiose et un cas de sepsis severe. Discussion Le RTX semble un traitement efficace et bien tolere des PB et PG en particulier severes et/ou refractaires ou en cas de difficultes liees aux traitements habituels. Le taux global de reponse est comparable aux donnees de la litterature sur quelques series retrospectives de plus petits effectifs. Le schema therapeutique optimal se precise puisque la majorite des cas de RCC ont recu 1 g a j1 et j15. Conclusion Ces resultats sont encourageants notamment dans les formes « difficiles ». Un essai controle prospectif est necessaire afin de preciser le schema therapeutique optimal et la strategie specifique d’utilisation du RTX dans les PB/PG, notamment pour un emploi plus precoce.

Summary In a left-right comparative study, the Philips TL-01 sunlamp, a new UVB fluorescent lamp, was evaluated in 15 patients with symmetrical psoriasis. One half of the body was treated in a cabin containing TL-01 lamps, and the other half in a cabin containing TL-12 lamps. The patients were treated three times/week, and the study was conducted in a randomized, double-blind fashion. The percentage response of psoriatic lesions was determined on the tenth and twentieth exposures. The therapeutic effect of the TL-01 lamps was superior to that of the TL-12 lamps, and treatment was better tolerated, particularly with regard to episodes of burning. This new lamp appears to provide more effective and safer phototherapy for psoriasis.

Background: Muir-Torre syndrome (MTS) is an autosomal dominant disorder characterized by the concurrent or sequential development of at least 1 sebaceous gland tumor or keratoacanthoma and 1 or more internal malignancies. It is actually considered as a variant of hereditary nonpolyposis colorectal cancer (HNPCC) as both MTS and HNPCC are more often associated with germline mutations in the DNA mismatch repair (MMR) gene. Objective andMethods: We report the case of MTS diagnosed after the occurrence of a solitary subungual keratoacanthoma (SKA) in a man with a well-known family history of HNPCC and who is carrying a constitutional 1–7 deletion in the MSH2 MMR gene. Results: The link between the germline mutation and the skin tumor was reinforced by immunohistochemical staining. MSH2 immunoreactivity was decreased in SKA tumoral cells when compared to normal adjacent epidermis and to 5 cases of sporadic KA used as controls. Conclusion: This observation indicates that a solitary SKA may be the first clinical manifestation of MTS and brings up the relevance for regular dermatological screening for MTS-associated skin lesions among gene carriers (and symptomatic individuals) for HNPCC syndrome.

Background Constituted only by carbon atoms, CNT are hydrophobic and hardly detectable in biological tissues. These properties make biokinetics and toxicology studies more complex. Methods We propose here a method to investigate the biopersistence of CNT in organism, based on detection of nickel, a metal present in the MWCNT we investigated. Results and conclusion Our results in rats that received MWCNT by intratracheal instillation, reveal that MWCNT can be eliminated and do not significantly cross the pulmonary barrier but are still present in lungs 6 months after a unique instillation. MWCNT structure was also showed to be chemically modified and cleaved in the lung. These results provide the first data of CNT biopersistence and clearance at 6 months after respiratory administration.

International audience; Solar ultraviolet (UV) radiation has hazardous effects on human health that are, in part, associated with its immunosuppressive effects via the induction of interleukin (IL)-10 production. Although IL-10 is produced by both T helper type 2 (Th2) cells and T-regulatory type 1 (Tr1) cells, the relative contribution of either subset in UV radiation-induced immunosuppression has not been established. Here, we show that T cells isolated from non-treated allergic contact dermatitis (ACD) reactions, 48 h following nickel challenge and propagated for 7-10 days in the presence of IL-2, were mainly CD4(+) and produced IL-10, but little interferon-gamma. A single sub-erythematous solar-simulated radiation (SSR) prior to antigen challenge exposure resulted in a clinical attenuation of the intensity of ACD reactions which was associated with a significant increase in both the magnitude of IL-10 production by skin-infiltrating T cells and the frequency of IL-10-producing Tr1 cells. Skin-infiltrating T cells in SSR-exposed, as well as non-exposed, ACD reactions showed a perturbed T-cell receptor (TCR)-Vbeta repertoire, without overexpression of a particular TCR-Vbeta gene product, indicating the presence of high frequencies of nickel non-specific T cells in ACD reactions. These results show that a single sub-erythematous SSR induces immunosuppression via the cutaneous infiltration of IL-10-producing Tr1, and to a lesser extent, Th2 cells.

BACKGROUND Kaposi sarcoma (KS) is an angioproliferative disease that may represent a difficult therapeutic challenge in disseminated stages. The efficacy of taxanes (paclitaxel and docetaxel), as agents with antiangiogenic properties, has been described previously in the treatment of patients with acquired immunodeficiency syndrome (AIDS)-associated KS but remains unknown in the treatment of patients with refractory or life-threatening KS without human immunodeficiency (HIV) infection. METHODS During the past 6 years, 12 non-HIV-infected patients with refractory KS were treated with paclitaxel (175 mg/m2 every 3 wks) or docetaxel (60 mg/m2 every 3 wks). RESULTS All patients improved dramatically after chemotherapy. Partial desinfiltration (n = 6) or complete desinfiltration (n = 6) of all papulonodular skin lesions was observed with marked improvement of lymphedema in 6 patients. According to the AIDS Clinical Trials Group criteria, response was partial in 100% of patients. A major response was obtained among patients who had visceral lesions (n = 3 patients), with rapid and complete remission of digestive or respiratory symptoms. The mean delay to response was 2 courses. Treatment was sustained for 3 patients. For the remaining 9 patients who received a median of 7 courses (range, 2-14 courses), the mean time to recurrence or follow-up without recurrence was 13 months. Tolerance was good except for 3 episodes of Grade 3 or 4 asymptomatic neutropenia and 1 episode of moderate myositis. CONCLUSIONS The results of this study showed that taxanes are beneficial in the treatment of patients with refractory or life-threatening Kaposi sarcoma. Cancer 2006. © 2006 American Cancer Society.

A 66-year-old woman with an 11-year history of melanoma initially treated by surgery, reaching stage IV at age 60 (with cervical and later also pancreatic lymph node metastases), received 9 cycles of 800 mg/m dacarbazine (given every 3 weeks, started at age 63) and 4 cycles of 3 mg/kg ipilimumab (a monoclonal antibody treatment, given every 3 weeks, started at age 64). Three months after the end of ipilimumab treatment, brain CT was normal (Fig. 1). Five months after the end of ipilimumab treatment, fotemustine (an alkylating antineoplastic agent) induction phase treatment was started, followed by 100 mg/m fotemustine every 3 weeks). Ten months after the start of fotemustine treatment, the patient developed mental slowing, cognitive deficit, and tetrapyramidal syndrome. CT and MRI showed dramatic, strictly supratentorial, symmetrical, leukoencephalopathy on FLAIR sequences in absence of gadolinium-enhancement on T1-weighted imaging, together with severe generalised subcortical brain atrophy (Fig. 1). At that time, fotemustine treatment was stopped. Lumbar puncture was performed, and repeated twice during the following 3 months. CSF analysis was strictly normal including PCR for JC virus. The patient refused brain biopsy. The patient worsened progressively, became bedridden, and died 6 months after onset of neurological deficit. The patient’s family refused autopsy. Differential diagnoses in our patient included brain lymphoma, progressive multifocal leukoencephalopathy, and toxic leukoencephalopathy. Symmetrical MRI abnormalities, the respect of deep grey nuclei, the absence of gadolinium-enhancement, and normal CSF analysis made lymphoma diagnosis in our patient unlikely. Absence of repeated PCR for JC virus and the very symmetrical MRI changes were against a diagnosis of progressive multifocal leukoencephalopathy. Toxic leukoencephalopathy has been reported in a large group of drugs including alkylating antineoplastic agents such as cyclophosphamide, carmustine, and busulfan, but not in fotemustine [1, 2]. Strictly toxic leukoencencephalopathy (i.e. non-JC-virus-related) has never been reported in dacarbazine, ipilimumab or other monoclonal antibody drugs. Although delayed toxic leukoencephalopathy due to dacarbazine or ipilimumab, lymphoma, and progressive multifocal leukoencephalopathy could not be ruled out completely (especially in the absence of histological examination), fotemustine-related toxic leukoencephalopathy seemed to be most probably the cause of leukoencephalopathy in our case, since fotemustine was the most recently administered drug preceding onset of neurological deficit and MRI abnormalities. D. Renard (&) C. Campello Department of Neurology, CHU Nimes, Hopital Caremeau, Place du Pr Debre, Nimes Cedex 4 30029, France e-mail: dimitrirenard@hotmail.com

Ross syndrome is a rare partial dysautonomic syndrome of unknown aetiology, characterized by a one-sided or bi-lateral anhidrosis associated with Holmes-Adie syndrome (defined by tonic pupil and hyporeflexia of deep tendons) (1). Since it was first described in 1958 (2), approxima-tely 50 cases have been described in the literature (3). Dermatologists may be confronted with this disorder of thermoregulation, which is often revealed by a segmental “compensatory” hyperhidrosis. We describe here a case of Ross syndrome associated with Sjogren syndrome (SS) and discuss the potential relationship between these two entities. Thermography imaging exploration with an in-frared camera performed in different ambient temperature settings allowed better definition of the thermoregulatory sweating abnormalities in our patient. Moreover, to our knowledge, this examination showed, for the first time, an unexpected body “thermal pattern”, which may be characteristic of Ross syndrome. CASe RepoRTWe present here a case of a 35-year-old woman with a 10-year medical history of localized hyperhidrosis. Her medical history revealed autoimmune thyroid disease and SS. The hyperhidrosis appeared at an ambient tem-perature of approximately 25–27°C and was localized on the left side of her lower back, extending belt-like towards the side and in the controlateral lower back on the right side, as well as on the nape of her neck and shoulders. The rest of the skin was anhidrotic. She was also heat intolerant, with lack of sweating, abnormal increase in body temperature and generalized fati-gability when exposed to high ambient temperatures (32–34°C). Both pupils showed a slow reaction to light and a normal constriction to a near target, and deep tendon jerks were absent without motor deficits (Holmes-Adie syndrome). There were no other signs of autonomic dysfunction. punch biopsies obtained from hyperhidrotic and hypohidrotic skin areas were normal. The skin direct immunofluorescence test was negative. Blood explorations showed an isolated presence of anti-SSA, anti-SSB antibodies and anti-thyroid antibodies. Serum ganglionic (AChR) antibody was negative. Oral and conjunctival Sicca were objectively confirmed by Schirmer’s test. Salivary gland biopsy revealed lympho-cytic infiltration in both periglandular and perivascular regions. All of these Sicca findings fulfilled the diag-nostic criteria for primary SS (4). Brain and spinal cord magnetic resonance imaging (MRI), as well as thoracic and abdominal computed tomography scan findings, were normal. Electrophysiological explorations of both hands and forearms showed an absence or collapse of the sympathetic skin responses. Nerve conduction study findings, EEG and cardiac tilt-test (reflecting the adren-ergic sympathetic and parasympathetic functions) were normal. Thermographic explorations with an infrared camera (A320, FLIRsystems, Inc., Issy Les Moulineaux, France) allowed for evaluating the body’s surface tem-perature at 22°C and after a 20 min exposure to 32°C ambient temperature (Fig. 1). This examination was significantly more efficient than the Minor Starch Test and clearly delimited the skin thermoregulation abnor-malities associated with Ross syndrome. Hyperhidrotic and anhidrotic areas were also clearly visualized as the lowest and highest estimated skin surface temperature. This examination showed large dermatomal-like pat-terns in hyperhidrotic areas (lower back and shoulder regions), but also detected unexpected smaller patch

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Acquired progressive lymphangioma (APL) is a rare, benign proliferation of lymphatic capillary origin, which is characterized histologically by dermal vascular channels and a 'dissection of collagen' appearance. We describe a 30-year-old patient with an extensive, refractory APL on the right breast, which slowly developed over a period of 23 years. Pathologists and dermatologists should be aware of this entity, as early surgical treatment may be totally curative when the lesion is limited in size.