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Background Actinic lentigos (AL) are benign hyperpigmented skin lesions associated with photoageing. Despite their high prevalence, biological mechanisms driving their formation remain unclear. Objectives To provide new insights about the physiopathology of AL through a comprehensive description of their histological and molecular features. Methods Quantitative analysis of dermoscopic images was used to select AL containing elongated patterns, predicted to display a highly deformed dermal-epidermal junction (DEJ), on the back of hands of 15 Caucasian women. Biopsies from lesional and adjacent non-lesional (NL) areas were processed for histological analysis or gene expression profiling. Results Histological staining confirmed a drastic deformation of the DEJ in AL, with deep epidermal invaginations into the dermis. Although the melanin content was significantly higher in AL compared to NL epidermis, the distribution of melanocytes along the DEJ was unchanged. Transcriptomic analysis revealed a signature of 529 genes differently expressed in AL versus NL skin. Alteration of epidermal homeostasis was confirmed by the dysregulation of keratinocyte proliferation and differentiation markers. Surprisingly, canonical genes involved in melanogenesis were not significantly modulated in AL. A striking finding was the overexpression of a large group of genes involved in dermal extracellular matrix organization and remodelling. Dermal alterations were confirmed by immunolabellings on AL and NL sections. Conclusions Drastic disorganization of the cutaneous structure in AL is accompanied by a specific molecular signature revealing alterations in both epidermal and dermal compartments. Particularly, our results suggest that local modifications of the dermal extracellular matrix might contribute to hyperpigmentation in AL. This article is protected by copyright. All rights reserved.

Summary Background Acral naevi are a peculiar subtype of naevus with specific dermoscopic patterns. Little is known about congenital melanocytic naevi affecting acral volar skin in children. Objectives To determine the dermoscopic features of acquired and congenital acral melanocytic naevi in children and to assess their key differences in this age group. Methods This was a prospective observational controlled study conducted in two outpatient dermatology university hospitals in Nice, France. We recruited 24 children with 24 congenital acral melanocytic naevi (CAMNs) and 26 children with 33 acquired acral melanocytic naevi (AAMNs), and determined the clinical and dermoscopic features of both. Images were evaluated and compared by two dermatologists. Fourteen patients with CAMN were followed up. Results CAMNs were larger, and more asymmetrical and comma shaped than AAMNs. The parallel furrow pattern was predominant in CAMN (75%) and AAMN (79%). Globules were more frequent in CAMN (88%) than in AAMN (61%) (P = 0·026), often with a ‘pearl necklace’ distribution along skin markings. Central blue-grey pigmentation was present in 50% of CAMNs vs. 9% of AAMNs (P = 0·001). A new dermoscopic feature of central enlarged pink ridges was observed in 54% of CAMNs vs. 6% of AAMNs (P

Background A ready-to-use betamethasone valerate 0.1% (BMV) dressing was found to be superior to placebo dressing and a reference 0.1% BMV cream in the treatment of patients with chronic plaque psoriasis (CPP). Methods This multicentre, prospective, randomized, investigator-blinded, controlled, non-inferiority trial compared the efficacy and safety of the BMV dressing to the calcipotriol–betamethasone dipropionate (CBD) ointment during a 4-week treatment of patients with mild to moderate CPP. The primary efficacy endpoint was the 4-item psoriasis total severity score (TSS-4) at week 4, and the associated non-inferiority margin was 1 point. Secondary outcome measures included the psoriasis global assessment (PGA) score and patients’ quality of life (QoL). Safety was assessed through adverse events (AE) reporting in each treatment group. Results Of 325 screened patients, 324 were randomized to BMV (N = 165) or CBD (N = 159), and were considered evaluable for the safety and intention-to-treat (ITT) efficacy analyses. Per protocol (PP) populations included 133 and 131 patients in the BMV and CBD groups respectively. The mean adjusted TSS-4 significantly decreased through the study from baseline in both groups. The PP (primary) analysis of week 4 data revealed a −0.288 (95% CI: −0.610 to 0.034) not significant between-group difference in adjusted means, demonstrating non-inferiority of BMV to CBD. Non-inferiority was also demonstrated in the ITT analysis. The PGA and other secondary outcomes were significantly improved from baseline in both groups at week 4. The QoL score was slightly better in the CBD group at week 4, but no difference was observed at follow-up. No safety or tolerability concerns were observed in either group. Conclusions BMV dressing is non-inferior to CBD ointment in patients with mild to moderate CPP. Both treatments significantly improve patients’ psoriasis and QoL.

Background Blanching creams are used to depigment and to achieve uniform skin tone in widespread vitiligo.Length of the treatment and side-effects strongly limit their use in common practice.Objectives To assess the long-term efficacy and tolerance of Q-Switched (QS) lasers for depigmenting theremaining unaffected skin in vitiligo.Methods Retrospective study of vitiligo patients treated with QS lasers in the Department of Dermatology of theUniversity Hospital of Nice, France, from 2002 to 2011. Localizations and the percentage of body surface area oftreated lesions, the total number of sessions and the possible relapses and side-effects, were analysed. Globalsatisfaction of the patients was evaluated on a visual analogical scale.Results Sixteen areas of normally pigmented skin were treated in six patients. The median number of sessions toachieve a complete depigmentation was 2 (1–6). The mean duration of follow-up was 36 months (19–120). One thirdof the patients had no relapse. A complete repigmentation was observed after 21 months in one patient; a 50%repigmentation was noted in one patient, 7 months after the end of the treatment. Two patients showed a minimalrepigmentation (

Summary Background Certolizumab pegol (CZP) is a PEGylated antitumour necrosis factor agent. Objectives To evaluate the efficacy and safety of CZP in patients with plaque psoriasis. Methods In a randomized, placebo-controlled, double-blind study, 176 patients with moderate to severe psoriasis received placebo or CZP 400 mg at week 0 followed by placebo or CZP (200 or 400 mg) every other week until week 10. Co-primary endpoints were ≥ 75% improvement from baseline in Psoriasis Area and Severity Index (PASI 75) and a Physician’s Global Assessment (PGA) of clear-almost clear at week 12. A re-treatment extension study was conducted in 71 CZP PASI 75 responders who relapsed during a 12- to 24-week observation period without treatment. Results PASI 75 was achieved by 44/59 (75%), 48/58 (83%) and 4/59 (7%) patients in the CZP 200 mg, CZP 400 mg and placebo groups, respectively (P

Summary Background The treatment of vitiligo remains unsatisfactory. Objectives To assess in patients with vitiligo the effect of a laser dermabrasion in addition to the association of topical steroids and ultraviolet (UV) B in difficult-to-treat areas. Methods This was a single-centre prospective randomized trial including patients with nonsegmental vitiligo who had at least two symmetrical lesions located on bony prominences and/or extremities. An erbium laser-assisted dermabrasion was first performed on one side (randomly assigned). After 48 h, hydrocortisone 17-butyrate cream applied daily for three periods of 3 weeks followed by a 1-week steroid-free interval and narrowband UVB treatment was performed on both sides twice weekly for 12 weeks. The evaluation was performed on standardized pictures by two physicians blinded to the type of treatment received. The criterion of success was a repigmentation of at least 50%, 1 month after the end of the treatment. Results Eighteen patients were included (24 paired lesions treated). Two patients dropped out for personal reasons. Almost 50% of lesions achieved at least 50% repigmentation in the dermabrasion side while only 4·2% did so with topical steroids and UVB alone (P

Summary Background Infliximab is indicated for treatment of moderate-to-severe plaque psoriasis in adults whose disease cannot be controlled with other systemic therapies, including methotrexate (MTX). To date, no studies have directly compared the efficacy and safety of infliximab and MTX. Objectives To compare the efficacy and safety of infliximab vs. MTX in adults with moderate-to-severe plaque psoriasis. Methods MTX-naïve patients (n =868) were randomized 3 : 1 to receive infliximab 5 mg kg−1 at weeks 0, 2, 6, 14 and 22 or MTX 15 mg weekly with a dose increase to 20 mg weekly at week 6 if the Psoriasis Area and Severity Index (PASI) response was < 25%. At week 16, patients with < PASI 50 response could switch treatment groups. The primary efficacy endpoint was PASI 75 response at week 16. Major secondary efficacy endpoints were PASI 75 response at week 26, and the proportion of patients achieving a Physician’s Global Assessment (PGA) score of cleared (0) or minimal (1) at weeks 16 and 26. Others included Dermatology Life Quality Index, 36-Item Short Form Health Survey, and PGA, PASI 50, PASI 75 and PASI 90 responses over time. Results The primary endpoint was achieved by a significantly greater proportion of infliximab-treated patients (508/653, 78%) than MTX-treated patients (90/215, 42%; P Conclusions Infliximab was well tolerated and more efficacious than MTX in patients with moderate-to-severe plaque psoriasis. Infliximab also was efficacious in patients who failed MTX and switched to infliximab.

Aberrant expression of Secreted Protein Acidic and Rich in Cysteine (SPARC)/osteonectin has been associated with an invasive tumor cell phenotype and poor outcome in human melanomas. Although it is known that SPARC controls melanoma tumorigenesis, the precise role of SPARC in melanoma cell survival is still unclear. Here, we show that SPARC has a cell-autonomous survival activity, which requires Akt-dependent regulation of p53. Suppression of SPARC by RNA interference in several human melanoma cells and xenografted A375 tumors triggers apoptotic cell death through the mitochondrial intrinsic pathway and activation of caspase-3. Cell death induced by depletion of SPARC is dependent on p53 and induction of Bax, and results in the generation of ROS. Stabilization of p53 in SPARC-depleted cells is associated with a decrease in Akt-mediated activating phosphorylation of MDM2. Inhibition of Akt signaling pathway is important for the observed changes as overexpression of constitutively active Akt protects cells against apoptosis induced by SPARC depletion. Conversely, increased expression of SPARC stimulates Akt and MDM2 phosphorylation, thus facilitating p53 degradation. Finally, we show that overexpression of SPARC renders cells more resistant to the p53-mediated cytotoxic effects of the DNA-damaging drug actinomycin-D. Our study indicates that SPARC functions through activation of Akt and MDM2 to limit p53 levels and that acquired expression of SPARC during melanoma development would confer survival advantages through suppression of p53-dependent apoptotic pathways.

Background Ustekinumab, a human anti-interleukin-12/23 monoclonal antibody, has been shown to effectively treat moderate-to-severe psoriasis which significantly affects health-related quality of life (HRQoL), including patients’ sexual lives. Objectives The aim of this study was to determine if sexual difficulties associated with psoriasis are related to disease severity and whether sexual difficulties improve with skin disease during ustekinumab treatment. Methods In phase III PHOENIX 1 and 2 trials, psoriasis patients were randomized to ustekinumab (n = 1334) at weeks 0 and 4 and q12 weeks thereafter or placebo (n = 662) at weeks 0 and 4 with crossover to ustekinumab at week 12. Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI) were used to assess psoriasis severity and patient-reported HRQoL respectively. Based on DLQI Question #9, impaired sexual function was defined as ‘very much’ or ‘a lot’ of sexual difficulties. Results At baseline, mean DLQI was 12.0, indicating a very large negative effect on patients’ lives. Impaired sexual function was reported by 22.6% (women = 27.1%; men = 20.8%) and was significantly associated with increased psoriasis severity. At week 12, ustekinumab-treated patients had a greater mean improvement in DLQI (−9.13 vs. −0.53 with placebo, P

Background Few large clinical studies have evaluated whether switching tumour necrosis factor antagonists (anti-TNFs) is likely to improve psoriasis in patients with prior anti-TNF treatment. Objective The aim of this subanalysis of the BELIEVE study was to assess the efficacy and safety of adalimumab for psoriasis in patients with and without previous anti-TNF treatment. Methods The BELIEVE study enrolled patients with moderate to severe psoriasis and prior failure, intolerance or contraindication to ≥2 systemic therapies. In this 16-week, double-blind, randomized, controlled trial, patients received adalimumab (80 mg, week 0; 40 mg every other week, weeks 1–15) with either topical vehicle or topical calcipotriol/betamethasone dipropionate (C/B) applied once daily for 4 weeks, then as needed. The primary endpoint was ≥75% improvement from baseline in Psoriasis Area and Severity Index score (PASI 75) at week 16. This post hoc subanalysis evaluated the safety and efficacy of adalimumab, with and without topical therapy, in BELIEVE patients who had prior exposure to anti-TNFs. Results Of 730 patients enrolled, 282 (38.6%) had prior anti-TNFs and 448 (61.4%) were anti-TNF-naive. Combining topical vehicle and topical C/B study populations, 61.7% of patients with prior anti-TNFs achieved PASI 75 at week 16, compared with 71.7% of anti-TNF-naive patients (P = 0.095). Adalimumab resulted in clinically meaningful improvement regardless of which prior anti-TNF agent had been used, the number of prior anti-TNFs tried, or reasons for discontinuation of prior anti-TNF therapy. Adverse event incidences were similar between patients with and without prior anti-TNF therapy. Conclusion Adalimumab was effective and well-tolerated in patients with psoriasis previously treated with anti-TNF therapy.

We have previously demonstrated that the thiazolidinedione ciglitazone inhibited, independently of PPARγ activation, melanoma cell growth. Further investigations now show that ciglitazone effects are mediated through the regulation of secreted factors. Q-PCR screening of several genes involved in melanoma biology reveals that ciglitazone inhibits expression of the CXCL1 chemokine gene. CXCL1 is overexpressed in melanoma and contributes to tumorigenicity. We show that ciglitazone induces a diminution of CXCL1 level in different human melanoma cell lines. This effect is mediated by the downregulation of microphthalmia-associated transcription factor, MITF, the master gene in melanocyte differentiation and involved in melanoma development. Further, recombinant CXCL1 protein is sufficient to abrogate thiazolidinedione effects such as apoptosis induction, whereas extinction of the CXCL1 pathway mimics phenotypic changes observed in response to ciglitazone. Finally, inhibition of human melanoma tumor development in nude mice treated with ciglitazone is associated with a strong decrease in MITF and CXCL1 levels. Our results show that anti-melanoma effects of thiazolidinediones involve an inhibition of the MITF/CXCL1 axis and highlight the key role of this specific pathway in melanoma malignancy.

Epidermolysis bullosa simplex (EBS) is an inherited skin disorder characterized by separation of the epidermis from the underlying dermis, with the cleavage plane lying within the basal-cell layer of the epithelium. The major clinical subtypes of EBS have a dominant inheritance and have been associated with genetic defects in specific domains of keratins K5 and K14 that result in abnormal organization of the keratin network and cell disruption. Autosomal recessive forms of EBS associated with extracutaneous manifestations, such as muscular dystrophy (MIM 226670) or pyloric atresia (MIM 612138), have been linked to genetic mutations in the gene for plectin (PLEC). PLEC mutations have also been found in 2 families with the rare dominant Ogna form of EBS. This article reviews current knowledge on EBS.

Summary Background The 308-nm excimer laser and 308-nm excimer lamp have both been shown to be effective in treating vitiligo but a direct comparison has never been performed. Objectives To test the equivalence of these two devices for treating nonsegmental vitiligo. Patients and methods A randomized monocentric study was undertaken. One lesion was treated with the 308-nm excimer laser and its counterpart with the 308-nm excimer lamp. Lesions were treated twice weekly with the same dose on both sides for a total of 24 sessions. The evaluation was done by two independent physicians blinded to the treatment on direct light and ultraviolet light photos. Results Twenty patients were included: 17 completed the study and 104 lesions were treated. The two treatments showed similar results in terms of efficacy for a repigmentation of at least 50% (P = 0·006). The lamp induced more erythema than the laser. Conclusions The 308-nm excimer lamp and laser showed a similar efficacy in treating vitiligo. For the same fluence, the lamp induced more erythema suggesting photobiological differences between the two devices.

Resume Introduction La mucinose papuleuse generalisee est une affection rare, de pathogenie encore obscure et de traitement difficile. Nous en rapportons un cas resistant au traitement par corticoides et controle par des immunoglobulines intraveineuses (IVIG). Observation Une femme de 60 ans consultait pour l’apparition progressive de lesions papuleuses de 2 a 5 mm de diametre, d’allure cireuse, de couleur chair, infiltrees et prurigineuses. Le reste de l’examen clinique etait normal. Il existait une dysglobulinemie de signification indeterminee IgG lambda. L’examen histologique d’une biopsie cutanee confirmait la suspicion clinique de mucinose papuleuse. La maladie progressait malgre une corticotherapie a 0,5 mg/kg par jour de prednisone et un traitement par thalidomide mal tolere cliniquement. Une serie de six cures mensuelles d’IVIG a la posologie de 2 g/kg repartis sur cinq jours permettait une regression de plus de 50 % des lesions papuleuses. A l’issue de ces cures, une corticotherapie a faible dose etait maintenue, mais une recidive des lesions survenait deux mois apres la derniere cure. Un traitement d’entretien par IVIG a la meme posologie etait alors administre toutes les six semaines, permettant de stabiliser la maladie et d’eviter les recidives. Discussion L’evolution de la mucinose papuleuse generalisee reste imprevisible et son traitement particulierement difficile. Les IVIG ont recemment ete rapportees pour etre efficaces dans cette pathologie, mais il semble que le traitement ne soit que suspensif et que des cures d’entretien soient necessaires. L’efficacite observee chez notre malade, mais egalement la recidive rapide des lesions semblent confirmer ces donnees.

Skin color is controlled by pigmentary genes that regulate constitutive skin pigmentation and by environmental factors, the most obvious of them being solar U.V. At this time, more than 125 distinct pigmentary genes are known. They affect embryogenesis and survival of the melanocyte system, melanosome biogenesis, melanogenesis, melanosome transport and transfer, eumelanins/pheomelanins ratio and epidermal melanosome turn-over and elimination. The pigmentary disorders of the skin are common and represent an important part of dermatologist activity. They concern at the same time the general dermatology and the aesthetic dermatology.

Objective To assess patient-reported outcomes (PRO) in patients with moderate-to-severe plaque psoriasis receiving continuous or paused etanercept treatment. Methods In a multicentre European open-label study, one group (n = 352) received continuous therapy: 25 mg subcutaneously (SC) twice weekly (BIW) throughout 54-weeks. The other group (n = 359) received paused therapy: 50 mg SC BIW ( Results At baseline, mean DLQI for patients in the continuous (12.8) and paused group (13.8), indicated significant quality-of-life impairment; mean EQ-5D utility scores were 0.65 and 0.66 for continuous and paused patients, respectively; 30.0% of continuous and 37.0% of paused patients had at least mild symptoms of depression; 40.2% and 48.6%, respectively, had at least mild symptoms of anxiety. At week 54, both groups showed statistically significant (P Conclusions At baseline, patients exhibited significant quality-of-life impairment. Both continuous and paused etanercept treatment provided improvements in PRO measures. Either regimen could be considered and care should be individualized.

Melanoma is a highly aggressive tumour characterized by a strong resistance to apoptotic stimuli that give rise to a selective advantage for tumour progression and metastasis formation. Therefore, it is of paramount importance to better understand the mechanisms involved in this resistance to apoptosis. In this report, we focused our attention on FKHRL1, a member of the forkhead family of transcription factors, which controls expression of genes involved in cell cycle progression and apoptosis. In melanoma cells, we show that IGF1, which exerts pro-survival properties, induces the phosphorylation and nuclear exclusion of FKHRL1 in a PI3K/AKT-dependent pathway. Moreover, we observe that over-expression of a non-phosphorylable mutant of FKHRL1 (FKHRL1-TM), constitutively localized to the nucleus, promotes apoptotic cell death of melanoma cells. Finally, we find that FKHRL1-TM decreases the expression of survivin, a member of the inhibitor of apoptosis protein and that survivin re-expression partially rescues the deleterious effects of FKHRL1. Taken together, these findings reveal, in melanoma cells, that endogenous FKHRL1 is a downstream target of the PI3K/AKT pathway and suggest that the phosphorylation of this transcription factor may be involved in the pro-survival effects of growth factors such as IGF1. On the other hand, forced nuclear localization of FKHRL1 decreases melanoma cell growth and may serve as a therapeutic strategy against melanoma.

Background Medical skin care products are topical preparations with mainly moisturizing properties. A new line of medical skin products with an excellent tolerability profile and improved hydration for dry skin has been developed, but beneficial effects have not yet been investigated on damaged skin. Aim To investigate if these products maintain barrier function and hydration status, improve subjective symptoms due to irritant contact dermatitis and to prove their tolerability on damaged skin. Design and methods Single-centre, blinded, randomized, controlled study in 20 healthy Caucasian women. 5% sodium lauryl sulphate solution was used to induce skin irritation. Two sites on the inside surface of both forearms of each subject were treated daily for 5 days (irritation period). Lipo Cream, Lipo Milk (water-in-oil emulsions) and Lipo Ointment (water-free formulation) were applied twice daily to three of the four test sites on days 1–5. The fourth site was used as a control. Visual readings, subjective symptom assessments, transepidermal water loss (TEWL) and colorimetric measurements, corneometry and skin microrelief macrophotographies were done on days 1–6. Results On day 6, TEWL was increased vs baseline on all sites; however, TEWL with Lipo Cream or Lipo Ointment was significantly lower than control. At day 6, skin capacitance was 94%, 100% and 85% of baseline value for the cream, milk and ointment, respectively, versus 72% for control. All test products were well tolerated. Conclusions Lipo Line products showed both protective properties against epidermal dysfunction and significant hydrating effect.

Resume Introduction Le mycosis fongoide est un lymphome cutane T epidermotrope. Les stades precoces ont un bon pronostic mais posent des problemes therapeutiques par leur chronicite et les recidives frequentes. Nous avons realise une etude retrospective anatomo-clinique sur 10 malades atteints de mycosis fongoide afin d’evaluer l’efficacite du laser excimer a 308 nm dans cette indication. Methodes Dix malades dont le diagnostic de mycosis fongoide avait ete confirme histologiquement, ont ete inclus dans l’etude. Un traitement par laser excimer a 308 nm a ete realise sur un total de 29 lesions dont 25 lesions peu ou pas infiltrees, trois plaques infiltrees et un nodule. Apres determination de la dose erythemateuse minimale, les seances ont ete debutees au rythme de deux par semaine avec une augmentation progressive des doses en fonction de la tolerance. Un suivi clinique a ete ensuite realise. Des biopsies cutanees ont ete realisees, lorsque cela etait possible, avant, a la fin et a distance du traitement afin de realiser une etude histologique et immuno-histochimique. Resultats Quatre-vingt-six pour cent des lesions peu ou pas infiltrees ou en plaques etaient en remission complete a la fin du traitement et 14 p. 100 en remission partielle avec un taux global de reponse de 100 p. 100. Le nombre moyen de seances a ete de 15 (6 a 46 seances), soit une duree moyenne de traitement de 2 mois, et la dose cumulee de 5 J/cm2 (1,3 a 16,1 J/cm2). Dix-neuf lesions ont pu etre suivies a distance du traitement avec une duree mediane de suivi de 15 mois (8 a 26 mois). Une reponse complete s’est maintenue pour 13 lesions (12 lesions peu ou pas infiltrees et une plaque) sur 19, soit 68 p. 100. Une reponse partielle s’est maintenue pour trois lesions (une lesion peu ou pas infiltree et deux plaques) sur 19, soit 16 p. 100. Une rechute est survenue pour deux lesions (deux lesions peu ou pas infiltrees) sur 19, soit 11 p. 100. Ces deux rechutes ont toutes deux ete observees a 7 mois. Le seul nodule traite n’a pas repondu au traitement. Les resultats histologiques et immuno-histochimiques concordaient avec l’aspect clinique montrant une guerison histologique en cas de guerison clinique hormis un cas qui a montre la persistance de quelques cellules de type mycosis en exocytose alors que la lesion paraissait guerie cliniquement. Discussion Cette etude montre l’efficacite du laser excimer dans les mycosis fongoides au stade Ia. Compte tenu de la faible disponibilite de ce traitement et de son caractere onereux, le laser excimer a 308 nm reste indique en seconde intention apres echec ou recidive d’un traitement par dermocorticoides bien conduit.

Resume Introduction Le laser a colorant pulse (LCP) est une methode seduisante pour traiter les verrues. Cependant, les donnees concernant son efficacite reposent essentiellement sur des cas cliniques ou des series ouvertes avec des resultats tres variables d’une etude a l’autre. L’objectif de cette etude etait de comparer l’efficacite et la tolerance du laser a colorant pulse par rapport a un placebo dans le traitement d’un groupe homogene de malades ayant des verrues palmo-plantaires. Methodes Il s’agissait d’une etude prospective controlee contre placebo, randomisee, en simple insu menee de decembre 2004 a juillet 2005 chez des malades venant consulter dans le service de dermatologie du CHU de Nice pour des verrues palmo-plantaires. Les parametres de traitement par le laser a colorant pulse a 595 nm etaient : diametre du spot de 5 mm, duree d’impulsion de 0,45 ms, fluence de 9 J/cm 2 avec une repetition de cinq coups a une frequence de 1 Hz. Des impulsions de refroidissement (systeme integre a la machine) par spray de cryogene etaient utilisees avec une duree de 40 ms et un debit de 50 avant chaque tir laser. Chez les malades du groupe placebo, seules les impulsions de refroidissement etaient utilisees. Pour les verrues plantaires (dans les deux groupes) un decapage manuel au bistouri de l’hyperkeratose etait effectue avant chaque seance. Au maximum, trois seances, espacees de 3 semaines chacune, etaient realisees. Le type et le nombre de verrues etaient comptabilises et reportes sur un schema avant le debut du traitement, lors de chaque seance et 5 semaines apres la derniere seance. La tolerance globale du traitement etait evaluee sur une echelle visuelle analogique allant de 0 (intolerable) a 10 (tolerance parfaite). Resultats Dix-neuf malades ont ete retenus dans le groupe laser et 16 dans le groupe placebo. Soixante-quatre pour cent (48/75) des verrues du groupe laser ont totalement disparu versus 13 p. 100 (4/30) dans le groupe placebo (p Discussion Le laser a colorant pulse apparait comme un traitement efficace des verrues palmo-plantaires mais son efficacite semble equivalente a celle des traitements conventionnels (cryotherapie ou preparation a base d’acide salicylique). Sa tolerance est excellente et constitue l’un des principaux interets de cette technique. L’absence de superiorite prouvee, en terme d’efficacite, par rapport aux traitements conventionnels et son cout eleve incitent a utiliser le laser a colorant pulse comme un traitement de deuxieme intention chez des malades desireux de ne pas etre genes dans leur activite professionnelle.

There have been very few well-conducted trials in melasma and this makes the process of comparing treatment outcome between trials difficult. The Pigmentary Disorders Academy has examined the issues relating to clinical trials on melasma, and has proposed recommendations on how they should be conducted. This covers all aspects including correct diagnosis of the condition, evaluation of efficacy and safety outcome, and overall clinical trial design. It is anticipated that the establishment of accepted guidelines on the conduct of clinical trials in melasma will greatly assist the dermatological community.

Contains fulltext : 50504.pdf (Publisher’s version ) (Closed access) BACKGROUND: Psoriasis is a chronic, inflammatory skin disorder that has a significant impact on quality of life and, particularly in moderate to severe cases, adversely affects the patient's overall health and well-being. Biological treatments, such as etanercept, are being widely adopted across Europe for treatment of moderate to severe psoriasis due to favourable safety and efficacy profiles. The increase in usage, combined with a growing body of clinical evidence, has identified a need to clarify the best use of etanercept within its current treatment label. OBJECTIVE: To prepare a series of recommendations agreed by an expert group of dermatologists, relating to the most effective use of etanercept for psoriasis in Europe, within the product license. METHODS: An expert panel of dermatologists from across Europe completed a Delphi survey to address the current use of etanercept in psoriasis in Europe. In June 2005 the results were presented to the expert panel at their nominal group meeting, and a consensus was agreed. RESULTS: It was recommended that, where possible, patients are initiated on the 50 mg twice-weekly (BIW) dose. Etanercept should be given until remission is achieved (maximum 24 weeks) and retreatment should be initiated according to the physician's judgement. Before commencing treatment, contraindications, such as infection or previous malignancy (within 5 years), should be ruled out. CONCLUSIONS: The consensus presented herein provides valuable clarification of use of etanercept according to the label, which may have wider implications relating to the use of all biological therapies in psoriasis.

Background and Objectives To determine the true efficacy of the 308-nm excimer laser for the treatment of vitiligo, while taking into account confounding factors such as anatomic site of treatment, age, sex, skin type, MED, and duration of evolution of the vitiligo. Study Design/Materials and Methods Thirty-five patients with vitiligo were included. Each lesion was treated twice a week by the 308-nm excimer laser for a maximum of 24 sessions. Efficacy was blindly evaluated by two independent physicians. Results Repigmentation was noted in 46 plaques/52 (88.5%). Repigmentation rate (75%) was obtained in 14 (26.9%). In “UV sensitive” areas (face, neck, trunk), 8/14 lesions (57.1%) had a repigmentation rate, 75% versus 6/38 (15.8%) in “UV resistant” areas (bony prominences and extremities) (P = 0.031). No relationship could be established between response to the treatment and the following variables: age, sex, skin type, MED, and duration of evolution of the vitiligo (respectively, P = 1, 0.666, 0.566, 0.628, 0.521). Conclusions An aesthetically reasonable result is achieved essentially in “UV sensitive” areas, thus appearing to be the appropriate places of choice for this treatment. Lasers Surg. Med. 35:152–156, 2004. © 2004 Wiley-Liss, Inc.

Background Recognition of psoriasis as a T-cell-mediated immune disease has led to the development of various therapeutic approaches directed against the pathogenic T cells. Alefacept, a novel and selective biological recombinant protein, binds CD2 on T cells to block T-cell activation and proliferation and interacts with FcγRIII receptors on accessory cells to produce selective T-cell apoptosis. Objective To demonstrate the efficacy and safety of once-weekly alefacept IM compared with placebo given for 12 weeks to patients with chronic plaque psoriasis. Methods Multicentre (63 sites in Europe, the USA, and Canada), randomized, double-blind, parallel-group study comparing 10 mg and 15 mg of alefacept and placebo administered IM once weekly for 12 weeks. Patients were followed for an additional 12 weeks after cessation of therapy. Patients were eligible for enrolment if they were ≥ 18 years of age, had chronic plaque psoriasis for ≥ 12 months involving ≥ 10% body surface area, and had CD4+ T-cell counts at or above the lower limit of normal. Results 507 patients were enrolled into three treatment groups, which were well balanced for demographic, baseline disease characteristics, and treatment history. A significantly greater percentage of patients treated with alefacept 15 mg IM achieved ≥ 75% PASI reduction from baseline 2 weeks after the last dose compared with placebo (21% vs. 5%, P

To establish the efficacy and duration of remission post-treatment of calcitriol 3 micro g/g ointment in comparison with betamethasone dipropionate 0.05% ointment.A randomized, multicentre trial was conducted in 258 adult patients with chronic plaque psoriasis. Calcitriol 3 microg/g ointment or betamethasone dipropionate 0.05% ointment was applied twice daily for 6 weeks or until complete clearance of lesions. Patients whose psoriasis cleared or were significantly improved and did not require treatment continuation at treatment endpoint were contacted over the following 8 weeks to determine whether relapse had occurred.Both treatments were efficacious; improvement in psoriasis or clearance of lesions (residual erythema was allowed) was recorded for 79% and 82% of patients receiving calcitriol or betamethasone dipropionate, respectively. Global improvement and global severity scores at treatment endpoint showed statistically significant differences in favour of betamethasone dipropionate (p0.05); however, the absolute reduction in mean PASI (psoriasis area and severity index) was comparable between the groups. A statistically significantly (p0.01) higher proportion of responders remained in remission (no worsening of the disease warranting new treatment) following calcitriol therapy (48%) than betamethasone therapy (25%). This is of potential importance to patients, physicians and healthcare suppliers.Twice-daily applications of either calcitriol 3 microg/g ointment or betamethasone dipropionate 0.05% ointment can be used to good effect in the treatment of chronic plaque psoriasis. However, the beneficial effect is likely to persist for longer following calcitriol treatment.

Introduction Le brodalumab (AMG 827), anticorps monoclonal inhibiteur du recepteur de l’interleukine 17 (IL17), a demontre son efficacite dans le traitement du psoriasis en plaque modere a severe. Cette etude a evalue l’efficacite a long terme et la tolerance du brodalumab chez les sujets issus d’un essai de phase 2 ayant recu du placebo ou du brodalumab (70, 140 ou 210 mg/2 semaines ou 280 mg/4 semaines). Patients et methodes Dans cette etude d’extension en ouvert, les patients ont initialement recu 210 mg de brodalumab toutes les 2 semaines. Suivant un amendement au protocole mis en place environ un an apres l’inclusion, les sujets de ≤ 100 kg ont change de traitement et recu une dose de 140 mg/2 semaines a la visite suivante ; les sujets de > 100 kg ont ete maintenus sous le traitement a la dose de 210 mg/2 semaines. Les criteres d’evaluation ont inclus les scores PASI 75, PASI 90, PASI 100 et les evenements indesirables (EI). Observations Parmi les 181 patients inclus dans l’extension, 165 etaient encore dans l’etude a 48 semaines (groupe 140 mg, n = 48 ; groupe 210 mg, n = 17) et 153 a 96 semaines (groupe 140 mg, n = 105 ; groupe 210 mg, n = 48). A 12 semaines, 95,4 % des patients (IC 95 % : 91,2 ; 98,0) ont atteint le PASI 75, 85,1 % (79,0 ; 90,1) le PASI 90 et 62,9 % (55,2 ; 70,0) le PASI 100. A 48 semaines, 93,3 % (IC 95 % : 88,4 ; 96,6) ont atteint le PASI 75, 83,0 % (76,4 ; 88,4) le PASI 90 et 61,8 % (53,9 ; 69,3) le PASI 100. A 96 semaines, 89,5 % (IC 95 % : 83,6 ; 93,9) ont atteint le PASI 75, 78,4 % (71,1 ; 84,7) le PASI 90 et 52,9 % (44,7 ; 61,1) le PASI 100. Durant les 96 semaines de l’extension, 93,4 % des patients traites ont presentes des EI. Les EI les plus frequents (≥ 10 % des patients) ont inclus rhinopharyngites (25 %), infections des voies respiratoires superieures (18 %), arthralgies (13 %). Des EI de grade ≥ 3 ont ete rapportes chez 22 patients (12,2 %), des EI graves (EIG) chez 12 patients (6,6 %). Les EI relies au traitement ont ete rapportes chez 26,5 % des patients, dont 5 (2,8 %) avec un EI de grade ≥ 3 et 3 (1,7 %) avec un EIG. Les EIG rapportes entre les semaines 48 et 96 ont inclus cholecystite aigue, constipation (consideree comme reliee au traitement), polynephrite et tumeur parathyroide benigne ( n = 1 pour chaque). Un EIG de type adenocarcinome oesophagien a ete rapporte, ainsi qu’une rupture d’anevrisme aortique fatale, tous deux avant la semaine 48. Discussion Lors de toutes les evaluations faites entre la semaine 8 et presque 2 ans apres le debut du traitement par brodalumab, la majorite des patients a atteint le PASI 100. Les EI les plus frequents ont compris des affections communes (par ex. rhinopharyngite, infection des voies respiratoires superieures), principalement de grade ≤ 2. Conclusion Le rapport benefice/risque a long terme du brodalumab justifie de poursuivre les etudes chez les patients atteints de psoriasis en plaque modere a severe.

The anchoring filament protein laminin 5 is composed of three polypeptide chains (alpha 3, beta 3 and gamma 2) each encoded by separate genes (LAMA3, LAMB3 and LAMC2, respectively). Mutations in any of these three genes may give rise to the autosomal recessive blistering skin disease, junctional epidermolysis bullosa. At present, there is no easy way of predicting which of these three genes might harbour the pathogenetic laminin 5 mutations in a case of junctional epidermolysis bullosa. In this study, we assessed whether immunohistochemistry might be helpful in this regard. We performed immunohistochemical labelling of the dermal-epidermal junction using alpha 3, beta 3 and gamma 2 chain-specific antibodies in 11 patients with junctional epidermolysis bullosa, in whom the laminin 5 mutations had been previously delineated. Although, labelling for the laminin 5 chain bearing the mutations was attenuated or undetectable in all cases, a complete absence of labelling or a reduction in the staining intensity for the other two chains was also seen in all cases. The results showed that immunohistochemical labelling of the dermal-epidermal junction using alpha 3, beta 3 and gamma 2 chain-specific antibodies is not a specific indicator for which of the laminin 5 chain genes contains the pathogenetic mutations, and is therefore unreliable in screening for individual laminin 5 gene mutations in cases of junctional epidermolysis bullosa.

Basal cell carcinoma (BCC) is a frequent skin cancer with low metastatic potential. Expression of the anchoring filament proteins, native laminin-5 and its individual alpha 3, beta 3 and gamma 2 chains, uncein. and linear IgA antigen was examined by immunostaining in 17 BCC with different histological subtypes. Immunoreactivity of the hemidesmosomal proteins, integrin alpha 6 beta 4, 230-kDa bullous pemphigoid antigen (BP-230 Ag) and plectin/HD-1, and that of dermal-epidermal junction (DEJ) components, integrin alpha 2 beta 1, laminin-1, collagen IV, and collagen VII was also analysed. Around tumour nests, the labelling of laminin-5 was absent or markedly reduced in 12 BCC (comprising eight solid BCC, three adenoid BCC and one keratotic BCC) and strong in five BCC (comprising three adenoid BCC, one keratotic BCC and one adenoid and keratotic BCC). Intriguingly, in tumour cells of 12 BCC including laminin-5 negative tumours, a cytoplasmic reactivity of the laminin gamma 2 chain was detected, but not that of the alpha 3 and beta 3 chains. In the basement membrane of the epidermis overlying tumour nests, the labelling of laminin-5 was always strong. Uncein, linear IgA disease antigen, and integrin alpha 6 beta 4 were absent in solid BCC and weakly expressed in adenoid or keratotic BCC. For plectin/HD-1 and BP-230 Ag, a cytoplasmic reactivity was detected in the majority of the tumour cells. The labelling of integrin alpha 2 beta 1, laminin-1, collagen IV and collagen VII indicated no alteration in the synthesis of these proteins. In peritumoral lacunae, immunoreactivity of hemidesmosome and anchoring filament proteins was absent, except for plectin/HD-1 on the tumour side and sometimes for laminin-5 on the stromal side, while laminin-1, collagen IV and collagen VII were detected on the stromal side. These findings suggest that the components of the hemidesmosome-anchoring filament complex are not synthetized or assembled properly in BCC, and that the alteration of these adhesion structures may be the cause of peritumoral lacunae.

Background: limited data exist on transitioning patients with psoriasis from conventional systemic agents to biologics. Objectives: the TRANSIT study aimed to assess the efficacy and safety of two methotrexate-to-ustekinumab transition strategies. Methods: patients with moderate-to-severe psoriasis and inadequate methotrexate response were randomized 1 : 1 to receive ustekinumab with immediate (arm 1) or 4-week gradual (arm 2) methotrexate withdrawal. Patients weighing ≤ 100 kg or > 100 kg received ustekinumab 45 mg or 90 mg, respectively. The primary endpoint was the frequency of adverse events (AEs) at week 12. Secondary endpoints included additional safety, efficacy and patient-reported outcomes. We report the 12-week efficacy and safety results. Results: overall, 244 patients in arm 1 and 245 in arm 2 were randomized and received ustekinumab. Four patients per arm discontinued the trial by week 12. At week 12 in arms 1 and 2, respectively, 61% and 65% of patients experienced an AE, 2·9% and 2·4% had a serious AE, and 1·2% and 0·4% had an AE leading to ustekinumab discontinuation. In arms 1 and 2, respectively, median Psoriasis Area and Severity Index (PASI) score decreased from 15·2 and 15·4 at baseline to 2·9 and 2·8 at week 12; 58% and 62% of patients achieved a 75% reduction from baseline in PASI score (PASI 75) at week 12; median baseline Dermatology Life Quality Index fell from 8 and 9 at baseline to 1 (both arms) at week 16. Conclusions: ustekinumab was well tolerated and effective in patients who had an inadequate response to methotrexate. Both transition strategies resulted in similar week 12 safety and efficacy outcomes.

Background: There are limited long-term, ‘real-world’ data on ustekinumab, or the effect of dose adjustment in suboptimal responders. Objectives: We describe 52-week data from TRANSIT, which initiated ustekinumab by licensed regimen and investigated exploratory dose adjustment. Methods: Patients with moderate-to-severe psoriasis and inadequate methotrexate response received ustekinumab, with immediate or gradual methotrexate withdrawal. Outcomes were similar between treatment arms at week 12 (primary endpoint), so week 52 data were pooled. Patients weighing ≤ 100 kg or > 100 kg were administered ustekinumab 45 or 90 mg, respectively. Patients weighing ≤ 100 kg without 75% improvement in Psoriasis Area and Severity Index (PASI 75) response at weeks 28 or 40 received a dose adjustment to 90 mg. The primary analysis used observed data. Results: Overall, 391 and 98 patients received ustekinumab 45 and 90 mg, respectively. Forty-four patients (9%) discontinued before week 52 (0·4% due to adverse events). At week 52 (in the overall population), 369 patients (83%) achieved a PASI score ≤ 5, and 341 patients (77%) achieved PASI 75; the median PASI score decreased from 15 at baseline to 1·8. At weeks 28 and 40, 84 and 31 patients, respectively, did not achieve PASI 75 and received a dose adjustment; by week 52, 35/82 (43%) and 15/31 (48%) of these patients, respectively, achieved PASI 75 (two discontinued between weeks 28 and 40). Conclusions: Ustekinumab showed sustained 1-year efficacy and was well tolerated when initially administered according to label. Adjusting the ustekinumab dose to 90 mg may result in clinically meaningful improvement in response in patients weighing ≤ 100 kg with suboptimal initial response.

Plectin is a widely expressed cytomatrix component involved in the attachment of the cytoskeleton to the plasma membrane. We have recently reported that the skin and muscles of three patients affected by epidermolysis bullosa simplex with muscular dystrophy (MD-EBS), a genetic disorder characterized by skin blistering associated with muscle involvement, are not reactive with antibodies specific to plectin. We demonstrated that in the skin, lack of plectin leads to failure of keratin filaments to connect to the plasma membrane via the hemidesmosomes, whereas in the muscle the deficient expression of the molecule correlates with an aberrant localization of desmin in the muscle fibers. In this study we demonstrate that in a MD-EBS kindred with two affected members, the disease results from a homozygous nonsense mutation in the plectin (PLEC1) gene leading to a premature stop codon (CGA to TGA) and decay of the aberrant plectin messenger RNA. The segregation of the mutated allele implicates the mutation in the pathology of the disorder. These results confirm the critical role of plectin in providing cell resistance to mechanical stresses both in the skin and the muscle.

Resume Introduction Nous rapportons un effet secondaire neuropsychiatrique inattendu de l’hydroxychloroquine (Plaquenil®) a type d’hallucinations cenesthesiques chez une malade traitee pour un lichen plan erosif plantaire. Observation Une femme de 75 ans etait hospitalisee pour un lichen erosif plantaire invalidant. Un traitement par hydroxychloroquine (400 mg par jour) etait debute, associe a des dermocorticoides et a une courte corticotherapie orale (methylprednisolone 0,5 mg/kg/j). Apres 10 jours de traitement, survenait un bref episode de desorientation temporo-spatiale, suivi d’une sensation de depersonnalisation et d’hallucinations cenesthesiques a type de sensations corporelles. Ces manifestations avaient ete precedees par la survenue de cauchemars. L’hydroxychloroquine etait arretee spontanement par la malade une semaine plus tard. Cet arret conduisait a une disparition progressive des hallucinations avec retour a un etat mental normal en un mois. Le recul de 2 ans et demi n’a pas montre de recidive des manifestations psychiatriques. Discussion Chloroquine et hydroxychloroquine peuvent etre a l’origine d’effets secondaires graves sur le plan psychiatrique, a type de psychose. Ces manifestations sont exceptionnelles, peu connues, et ont ete decrites essentiellement au cours du traitement du paludisme. La presentation clinique de la psychose aux antipaludeens de synthese est assez homogene d’une observation a l’autre : survenue chez un malade sans antecedents psychiatriques de manifestations a type de delire, hallucinations, episode maniaque, ou depression, apres un delai de quelques heures a 40 jours, cedant en moyenne une semaine apres l’arret des antipaludeens de synthese. Il n’y a pas de relation entre la dose d’antipaludeens de synthese administree et la survenue de troubles psychiatriques. Les mecanismes de survenue sont inconnus ; il semble s’agir d’une reaction idiosyncrasique. Notre observation permet d’attirer l’attention du dermatologue prescripteur sur la possibilite de survenue d’effets secondaires psychiatriques potentiellement graves.

Resume Introduction Les infections cutanees a Mycobacterium fortuitum ( M. fortuitum ) sont rares, le plus souvent iatrogenes. Nous rapportons un cas avec atteinte cervicale survenue apres une intervention pour lifting. Observation Une femme de 65 ans, sans antecedent, avait eu un lifting facial chirurgical bilateral. Il s’etait complique d’une necrose cutanee traitee par cicatrisation dirigee a domicile. Six semaines plus tard, apparaissaient un nodule abcede sous-maxillaire gauche, draine chirurgicalement, puis d’autres nodules inflammatoires pre-auriculaires et cervicaux gauches, sans adenopathie, ni fievre. Les prelevements bacteriologiques isolaient un M. fortuitum . L’antibiotherapie, initialement probabiliste par clarithromycine, secondairement adaptee par amikacine et ciprofloxacine puis amikacine et imipeneme, pour une duree totale de 3 mois, permettait d’obtenir une guerison clinique. Discussion M. fortuitum est une mycobacterie a croissance rapide, ubiquitaire, responsable d’infections nosocomiales chez les sujets immunocompetents, notamment apres chirurgie plastique. La contamination survient en un site de rupture de la barriere cutanee, par contact avec un vecteur (eau, materiel chirurgical, antiseptique…). Le traitement, mal codifie, consiste en l’association d’un traitement chirurgical et d’une antibiotherapie pendant plusieurs mois.

GB36, a mouse monoclonal antibody (mAb) raised against an epithelial antigen of the human trophoblast, reacts with the epithelial basement membrane of chorionic villi; it does not react with the invasive extravillous cytotrophoblast. Expression and characterization of the antigen of GB36 (designated GBA36) were investigated in normal keratinocytes by immunoprecipitation, immunofluorescence and immunoelectron microscopic studies. Immunoprecipitation experiments demonstrated that the proteins identified on keratinocytes by mAb GB36 and a rat mAb anti-integrin alpha 6 (GoH3) were the same. Using immunofluorescence and immunoelectron microscopic methods, GBA36 was localized on the cell membrane facing the epithelial basal lamina of basal keratinocytes. GBA36 distribution in benign and malignant skin tumours was evaluated by immunostaining methods (immunofluorescence and immunoperoxidase). Analysis of tumours revealed that whereas benign epithelial tumours and intradermal naevi displayed high levels of GBA36, the expression of this antigen decreased progressively in spinocellular and basal cell carcinomas, and in cutaneous melanomas in relation to invasiveness. During cell transformation, GBA36 undergoes quantitative alterations, and expression is down-regulated. Although the functional relevance of these changes remains unknown, the correlation of decreased GBA36 expression with tumour progression may indicate a role for altered integrin expression in tissue invasion by human skin carcinoma and melanoma.

In 1990, Anhalt et al described a newly autoimmune bullous disease: paraneoplastic pemphigus, in five patients. It was characterized by a distinct set of circulating autoantibodies from those in the sera of patients with pemphigus vulgaris and superficial pemphigus. We report a 71 year-old man with chronic lymphocytic leukemia of 4 years duration who developed a severe mucocutaneous eruption with clinical and immunofluorescence findings of pemphigus vulgaris evolving into an oral bullous lichen planus presentation. Evaluation of his serum confirmed the presence of autoantibodies specific for paraneoplastic pemphigus by indirect immunofluorescence on rat-bladder and immunoprecipitation. Subsequently, additional cases have been reported in the literature. All occurred in patients with various neoplastic conditions. These patients present with polymorphous skin lesions and severe erosive oral disease. Histologic examination shows interface dermatitis and keratinocyte necrosis in addition to acantolysis. Direct immunofluorescence may reveal deposition of immunoglobulin and/or complement at the basement membrane as well as deposition on epithelial cell surfaces. Circulating IgG anti-cell-surface antibodies are detectable with both stratified and stratified epithelia as substrates. These antibodies immunoprecipitate a complex of four desmosomal proteins, including desmoplakin I (250 kDa), the bullous pemphigoid antigen (230 kDa), desmoplakin II (210 kDa) and a 190 kDa antigen.

The aim of this study was to characterize cell-cell and cell-matrix interaction by evaluating the expression of different integrins in the nail matrix. Nail biopsies were obtained from two cadaver fingers, and eight patients with ingrowing toenails. Frozen sections were stained by indirect immunofluorescence using anti-alpha 1, anti-alpha 2, anti-alpha 3, anti-alpha 4, anti-alpha 5, anti-alpha 6, anti-alpha v, anti-beta 1, anti-beta 4 and anti-ICAM-1 monoclonal antibodies. Biopsies from normal human foreskin were evaluated as controls. alpha 1, alpha 4 and alpha 5 subunits were absent from both nail matrix and normal human skin. alpha 2, alpha 3 and beta 1 subunits were expressed in the basal and suprabasal layers of nail matrix, but only in the basal layer of skin epidermis. alpha 6 and beta 4 subunits were strongly expressed in the basement membrane zone and in the basal layer of both nail matrix and epidermis. The alpha v subunit was expressed in the basal layer of nail matrix. ICAM-1 was not expressed in nail matrix epidermis. Our findings show that despite the distinctive features of the nail apparatus, compared with the epidermis, the pattern of integrin expression is similar, although some differences in the distribution of alpha 2, alpha 3 and beta 1 subunits are detectable. These are probably related to the peculiar differentiation and keratinization of the nail.

The occurrence of morphea-like changes during the course of eosinophilic fasciitis is considered to be rare. We observed such a case with simultaneous occurrence of both types of lesions. Histologically, fibrosis and inflammatory infiltrate were seen in the entire dermis, the subcutis and the fascia, suggesting that the same process might account for all skin changes. In addition, our patient had an antiphospholipid antibody, neurologic symptoms and livedo-like cutaneous lesions. However, whether the antiphospholipid antibody played a pathogenic role or not remains unclear. Corticosteroid treatment was successful.

P>Background Data are lacking on the use of topical therapies in combination with tumour necrosis factor blockers for the treatment of psoriasis. Objectives To assess the efficacy and safety of adalimumab (ADA) with topical calcipotriol/betamethasone (C/B) in patients with psoriasis resembling those treated in routine clinical practice. Methods A 16-week, randomized, vehicle-controlled trial was conducted in patients with moderate to severe psoriasis and previous failure, intolerance or contraindications to two or more systemic treatments. All patients received ADA (80 mg, week 0; 40 mg every other week, weeks 1-15) in addition to either topical C/B or drug-free vehicle applied once daily for 4 weeks, and as needed thereafter. The primary endpoint was 75% improvement from baseline in Psoriasis Area and Severity Index (PASI 75) at week 16. Results A total of 730 patients received either ADA + C/B (n = 366) or ADA + vehicle (n = 364). PASI 75 response was initially higher with the combination therapy [14 center dot 8% for ADA + C/B vs. 5 center dot 8% for ADA + vehicle at week 2 (P < 0 center dot 001); and 40 center dot 7% vs. 32 center dot 4%, respectively, at week 4 (P = 0 center dot 021)]. After week 4, the trend was towards a higher response with ADA monotherapy, with no statistical difference in the PASI 75 response at week 16 (64 center dot 8% for ADA + C/B vs. 70 center dot 9% for ADA monotherapy, P = 0 center dot 086). Safety findings were consistent with previous ADA trials. Conclusions ADA + C/B resulted in more rapid and higher efficacy within the first 4 weeks; thereafter, the trend was towards a higher response with ADA monotherapy. There was no statistical difference in the PASI 75 response at week 16. Both treatment regimens were well tolerated.

The expression of tenascin, a recently discovered extracellular matrix protein, was studied by immunohistochemical techniques in scleroderma skin and compared with its distribution in normal skin. In progressive systemic sclerosis, a marked increase in tenascin content was observed in the superficial reticular dermis. In localized scleroderma, the deposition of tenascin was increased both in the superficial and deep dermis of involved skin, whereas in clinically uninvolved skin the distribution of tenascin was the same as in normal control skin, i.e. the papillary dermis and peri-appendiceal zone. The distribution of tenascin did not strictly parallel that of fibronectin. These findings and the current knowledge of tenascin biology suggest that the overproduction of tenascin in scleroderma dermis could be secondary to stimulation of fibroblasts by immune cell-derived cytokines, or could be due to abnormal fibroblasts, or a subpopulation of fibroblasts, producing high levels of this extracellular matrix protein.

Topical tretinoin improves mottling and hyperpigmented lesions of photodamaged skin. The basic mechanisms underlying these effects are not known. It is demonstrated that retinoids inhibit the growth and enhance the differentiation of melanoma cells in vitro, and stimulate the constitutive melanogenesis in melanoma cells in vitro. On the other hand, they inhibit hormonally or pharmacologically induced melanogenesis in these cells. Very few data are available concerning the effect of retinoic acid on normal human melanocytes, but there is some inhibition of growth as in melanoma cells. Retinoic acid appears to have little effect on the melanogenesis of normal human melanocytes grown in vitro using serum-free culture medium. Changes in the shape of these melanocytes suggest that retinoic acid acts on cytoskeleton proteins. Further studies, both in vitro and in vivo, are needed to clarify the effects of retinoic acid on melanocytes.

Objective/Aim To examine approaches to therapy for melasma in Latin Americans and to propose treatment algorithms for patients with mild, moderate and severe melasma. Background Melasma is prevalent in up to 10% of the Latin American population. It is found in all racial groups and is more common in subjects with darker skin phototypes. A number of topical treatments and procedures have been used for melasma. Topical treatments containing hydroquinone are the most popular. Care must be taken when treating melasma to avoid inducing post-inflammatory hyperpigmentation and ochronosis. Determination of the severity of melasma (using the Melasma Area Severity Index and/or Physician's Global Assessment) and choice of the most effective and suitable treatment and/or procedure for individual patients is therefore essential. Sun protection is mandatory for all melasma patients. Methods Thirty-one clinical studies of topical treatments, chemical peels and laser and other therapies used for treating melasma were assessed for the level and quality of clinical evidence, by the Latin American Pigmentary Disorders Academy. The results of this analysis were combined with differential diagnosis guidelines and methods for assessing treatment success to establish algorithms for treating mild and moderate-to-severe melasma. Results The most appropriate first-line treatment for mild melasma is hydroquinone 4%, triple combination cream containing hydroquinone 4%, tretinoin 0.05% and fluocinolone acetate 0.01%, double combination (e.g. 4% hydroquinone and 0.1% tretinoin) or non-phenolic therapy where there is an allergy to compounds. In moderate-to-severe melasma, triple combination cream is the recommended first-line treatment. Second-line treatment is double combination or hydroquinone 4% where triple therapy is not available or if allergic to compounds. Sun avoidance measures and broad spectrum sunscreens with high SPF are fundamental for the successful management of the disease.

Summary Background Patients with psoriasis experience remission and gradual reappearance of erythematous and scaly plaques and require individualized treatment over time. A goal of psoriasis treatment is to provide optimal efficacy with a flexible therapeutic regimen that may include treatment pauses. Objectives To determine whether patients receiving initial treatment with etanercept who then pause therapy would subsequently recapture response during re-treatment. Patients and methods A post-hoc analysis of 226 patients with moderate-to-severe psoriasis from a large multicentre trial was performed. Patients had received etanercept 50 mg twice weekly subcutaneously until a target clinical response had been achieved, then had paused treatment and eventually relapsed. They were then re-treated with etanercept 25 mg twice weekly. The number of patients recapturing a Physician Global Assessment (PGA) of psoriasis rating of ≤ 2 (clear, almost clear or mild) on first re-treatment was assessed. Patient satisfaction during the initial treatment and first re-treatment period was also determined. Results A total of 187 (83%) patients recaptured the target clinical response of a PGA of ≤ 2 after re-treatment. The majority of patients [219 of 226 (97%)] reported satisfaction with etanercept re-treatment. No new safety concerns emerged during re-treatment. Conclusions In this post-hoc analysis, patients with psoriasis who were re-treated with etanercept 25 mg twice weekly effectively recaptured clinical responses that patients found satisfactory. A flexible treatment option is available to dermatologists and patients for individualized care.

Contains fulltext : 80789.pdf (Publisher’s version ) (Closed access) Of the 131 studies on monotherapy or combination therapy assessed, 56 studies on the different forms of phototherapy fulfilled the criteria for inclusion in the guidelines. Approximately three-quarters of all patients treated with phototherapy attained at least a PASI 75 response after 4 to 6 weeks, and clearance was frequently achieved (levels of evidence 2 and 3). Phototherapy represents a safe and very effective treatment option for moderate to severe forms of psoriasis vulgaris. The onset of clinical effects occurs within 2 weeks. Of the unwanted side effects, UV erythema from overexposure is by far the most common and is observed frequently. With repeated or long-term use, the consequences of high, cumulative UV doses (such as premature aging of the skin) must be taken into consideration. In addition, carcinogenic risk is associated with oral PUVA and is probable for local PUVA and UVB. The practicability of the therapy is limited by spatial, financial, human, and time constraints on the part of the physician, as well as by the amount of time required by the patient. From the perspective of the cost-bearing institution, phototherapy has a good cost-benefit ratio. However, the potentially significant costs for, and time required of, the patient must be considered.

Background It has been generally believed that the four main causes of melasma are pregnancy, hormonal contraception, family history and sun exposure; however, there are few published comprehensive studies that confirm these assertions. The Pigmentary Disorders Academy - an international group of experts in pigmentary disorders - designed and conducted a global survey of women to investigate the effect of these factors on onset and chronicity of melasma and the course of the disease in order to gain a better understanding of the causative factors associated with this disorder, with a particular focus on hormonal factors and UV exposure in females. Methods A 40-item largely self-administered questionnaire was completed by 324 women being treated for melasma in nine clinics worldwide. Results The mean age at onset of melasma was 34 years, and 48% of subjects questioned had a family history of melasma (97% in a first-degree relative). Subjects with family history of melasma tended to have darker skin (90% types III-VI) compared to those without (77% types III-VI). The most common time of onset was after pregnancy (42%), often years after the last pregnancy, with 29% appearing pre-pregnancy and 26% during pregnancy. Onset was related to darker skin type post-pregnancy (P = 0.002). Risk of onset during pregnancy was associated with having spent more time outdoors (an extra 10 h per week spent working outside increases the odds of onset of melasma during pregnancy by approximately 27%) and an increased maternal age at pregnancy (increased by approximately 8% for each year of age at first pregnancy; P = 0.02). The odds of melasma occurring for the first time during a pregnancy were also increased with multiple pregnancies (twice the odds if 2 vs. 1 pregnancies, three times higher if 3 or more vs. 1 pregnancy). Of the women, 25% who had used hormonal contraception claimed that melasma appeared for the first time after its use, the rate being higher for those without vs. with a family history. Conclusions The results suggest that, whilst accepted causes do affect onset of melasma, a combination of these factors often triggers this disorder. These factors may provide further insights into how physicians can manage individual melasma cases, support recommendation of preventative measures and even anticipate treatment results and recurrence.