[The role of new molecular tests in the diagnosis of melanoma in a setting of congenital nævus in an infant]. / Apport des nouveaux tests moléculaires dans le diagnostic d'un mélanome sur nævus congénital chez un nourrisson.

INTRODUCTION: Congenital and infantile melanomas are extremely rare. We report a case of a child presenting at birth with a giant congenital nevus complicated by melanoma and on long-term follow-up with exploration using new immunohistochemistry and molecular biology tools. OBSERVATION: A new-born girl presented at birth with a large congenital cervico-mandibular tumour with para-pharyngeal extension and underlying osteolysis. At 7 months, histology and immunohistochemistry of the operative specimen revealed nodules with atypical features (mitotic figures, necrosis and positive expression of KI67 and P53 in approximatively 50 % of the melanocytic nuclei). A diagnosis was made of infantile melanoma associated with congenital nevi. Repeated surgery and monitoring (clinical and imaging) were performed. At the age of 7 years, as there was no evidence of metastatic lesions, further analyses were performed on the initial operative specimen. Investigation of transcription factor expression using immunohistochemistry, comparative genomic hybridization and histology-guided mass spectrometry, although suspect, did not in itself support a diagnosis of melanoma. Finally, at the age of 7 years, hepatic and pulmonary metastases were reported. Despite combined immunotherapy with ipilimumab and nivolumab, the child died 5 months later. CONCLUSION: This case illustrates the complexity of diagnosis of infantile melanoma and the risk of metastatic involvement long after the initial diagnosis. Diagnosis may be difficult and necessitates expert advice and the application of several recent methods to reach a conclusion and initiate appropriate treatment.

Efficacy of anti-programmed cell death-1 immunotherapy for skin carcinomas and melanoma metastases in a patient with xeroderma pigmentosum.

Xeroderma pigmentosum (XP) is an orphan disease of poor prognosis. We report one case of parallel efficacy with anti-programmed cell death-1 (PD-1) antibody on both melanoma and skin carcinoma in a patient with XP. A 17-year-old patient presented with metastatic melanoma and multiple nonmelanoma skin cancers. He was treated with pembrolizumab, a monoclonal anti-PD-1 antibody, at a dose of 2 mg kg-1 , every 3 weeks. Parallel therapeutic efficacy of anti-PD-1 was observed in metastatic melanoma and skin carcinomas, and maintained at week 24. This observation suggests anti-PD-1 may be considered in patients with XP and metastatic melanoma in addition to advanced nonmelanoma skin cancer.

[Multiple hypochromic or achromic macules in children and risk of tuberous sclerosis]. / Macules hypochromiques ou achromiques multiples de l'enfant et risque de sclérose tubéreuse de Bourneville.

AIM: To describe in a large paediatric cohort the characteristics of hypopigmented and depigmented (hypochromatic and achromic) macules with no clear diagnosis but potentially evocative of tuberous sclerosis (TS). PATIENTS AND METHODS: This was a retrospective multicentre study performed between 2010 and 2017 at a reference centre for rare skin diseases; it included all children consulting for hypochromic and achromic macules. A descriptive analysis was made of the characteristics of macules with no clear diagnosis, enabling them to be classified in three secondary groups: TS certain, TS ruled out, TS uncertain. RESULTS: Of the 3300 children seen during this 7-year period 7,265 were consulting for hypochromic or achromic macules, with no clear diagnosis in 18 cases: 7 girls and 11 boys of median age at 7.21 years (range: 4 months to 16 years and 7 months). The lesions were congenital in 7 cases. The number of macules varied, with over 20 in some cases. The majority were in the form of ash-leaf spots, followed by the oval form. Two children were diagnosed at clinical examination, and 16 underwent it is not examinations, resulting in a diagnosis of certain ST in 6 of these cases. No particular characteristics of the macules appeared to guide the clinical examination towards ST or isolated lesions. Café-au-lait spots were more frequent in the group in which ST was ruled out than in the other two groups: 67% vs. 33% and 33%. Neurologic involvement was more common in children with certain or uncertain ST than in children in whom ST was ruled out (83% and 67% vs. 11%). CONCLUSION: No identified characteristics of stains enabled the clinical examination to confirm or rule out tuberous sclerosis. Screening for acute any signs of ST is essential. Diagnostic efficacy is enhanced by additional exams.

Stay in NICU and infantile haemangioma development.

BACKGROUND: Infantile haemangiomas (IHs) are more frequent in low birth weight babies, especially premature. OBJECTIVE: To compare the characteristics of infants with IHs who stayed in neonatal intensive care unit (NICU) vs. those with IHs who did not. METHODS: Prospective observational multicentric study. Consecutive infants consulting for IHs in two departments of paediatric dermatology were included and a questionnaire specifically designed was filled for each patient. To identify factors associated with hospitalization in NICU vs. no hospitalization in NICU, we conducted univariate logistic regression analyses. RESULTS: A total of 210 infants with 323 IHs were included (56 boys, 154 girls, F/M sex ratio 2.75/1); 27 stayed in NICU, whereas 183 did not. Limbs involvement and multiple IHs were more frequent in NICU infants. Similarly, infants who had stayed in NICU had an earlier onset of their IH. Multiple IH was more frequent in infants with a history of congenital onset of IH. CONCLUSION: Infants staying in NICU and those with congenital lesion are at risk for specific type and involvement of their IH and should be early addressed to a dermatologist in case of suspicion of IH to provide them an early diagnosis and to start a treatment if necessary as soon as possible.

Treatment of port wine stains with pulsed dye laser and topical timolol: a multicenter randomized controlled trial.

BACKGROUND: Neoangiogenesis occurs within days following laser treatment of port wine stains (PWS), and plays a central role in treatment failures. Topical use of timolol can significantly reduce the production of vascular endothelial growth factor in vitro, and in animal models. OBJECTIVES: The aim of this study was to assess the efficacy of topical timolol in combination with pulsed dye laser (PDL) treatment, compared with PDL alone, for treating PWS. METHODS: This was a prospective multicenter controlled trial performed in children with PWS of the face who had not previously received laser treatment. After randomization, one group was treated with PDL alone, and the other with PDL followed by twice daily applications of timolol gel. Three laser sessions were performed at 1-month intervals with fixed parameters. The evaluation was performed on standardized pictures by two independent physicians blinded to the treatment received. The primary endpoint was marked or complete improvement of the PWS [Investigator Global Assessment (IGA) 3 or 4] 1 month after the third session. RESULTS: Twenty-two children were included. Two patients were lost to follow-up. There was no difference in the success rate between the two groups (IGA 3 or 4 observed in one of 10 patients and two of 12 patients, for PDL alone, and for PDL associated with topical timolol, respectively; P = 1·0). No side-effect related to the application of topical timolol was observed. CONCLUSIONS: The addition of timolol gel for preventing neoangiogenesis failed to significantly improve the efficacy of PDL treatment of PWS.

Factors influencing quality of life in patients with inherited ichthyosis: a qualitative study in adults using focus groups.

BACKGROUND: There is limited information regarding quality of life in patients with inherited ichthyosis. OBJECTIVES: To identify factors influencing quality of life in patients with inherited ichthyosis. METHODS: The study used focus groups and involved adult patients suffering from inherited ichthyosis from three French hospital centres. Group discussions were conducted by two facilitators and were continued until data saturation was reached. The verbatim transcripts were analysed independently by two investigators. Categories considered as key factors in the modulation of quality of life were negotiated until agreement was obtained. RESULTS: Data saturation was reached after the fifth group. A total of 25 patients affected by various forms of ichthyosis attended these focus groups. The identified factors influencing quality of life were related to physical health, daily life, relations with others or oneself. However, together with difficulties related to ichthyosis, patients also underlined some positive aspects of the disease and described specific measures used to improve their quality of life. CONCLUSIONS: This is the first study investigating the different factors that could impact quality of life in patients with ichthyosis. This provides an essential framework from which physicians can develop strategies to improve patient care and quality of life and to develop a specific quality of life questionnaire.

Significant delay in the introduction of systemic treatment of moderate to severe psoriasis: a prospective multicentre observational study in outpatients from hospital dermatology departments in France.

BACKGROUND: There is a low rate of systemic treatment usage in moderate to severe psoriasis. OBJECTIVES: The primary objective of the present study was to assess the time period between lack of control of moderate to severe psoriasis with topical treatment or phototherapy as perceived by patients and the medical decision to introduce a systemic treatment. METHODS: This was a prospective multicentre study, which included patients with moderate to severe psoriasis. A standardized questionnaire was completed by physicians and patients at the time the decision was taken to introduce a systemic treatment. The primary outcome was the duration of uncontrolled psoriasis, as estimated by the patient, prior to the introduction of systemic treatment. Factors associated with a delay in systemic treatment defined as > 2 years of uncontrolled psoriasis were assessed. The agreement between patients and physicians on the duration of uncontrolled psoriasis was estimated. RESULTS: The study included 142 patients. The mean age was 48 years, the mean Psoriasis Area and Severity index (PASI) was 18·5 and the mean Dermatology Life Quality Index (DLQI) was 12. The median duration of uncontrolled psoriasis estimated by patients and physicians was 3 years and 2 years, respectively. Factors associated with a delay in the introduction of systemic treatment as assessed by patients were fewer than three physician visits since psoriasis was uncontrolled [odds ratio (OR) 3·05; 95% confidence interval (CI) 1·29-7·21], Hospital Anxiety and Depression (HAD) scale < 10 (OR 2·83; 95% CI 1·19-6·71), continuous psoriasis evolution (OR 2·67; 95% CI 1·12-6·42), low consumption of topical treatment (OR 2·35; 95% CI 1·03-5·34). CONCLUSIONS: There is a significant delay in the introduction of systemic treatment in moderate to severe psoriasis. Patients with low level anxiety and limited use of healthcare resources appear to be at higher risk of experiencing long delays.

Contact photoallergy to isothipendyl chlorhydrate.

Isothipendyl chlorhydrate is an azaphenothiazine, an active ingredient of an antipruriginous gel, Apaisyl gel® (Merck Médication Familiale, Dijon, France). Although Apaisyl gel is registered and used worldwide, we present the first case of contact photoallergy to isothipendyl chlorhydrate to our knowledge. The diagnosis suspected on the basis of a positive UVA photopatch test to chlorpromazine was confirmed by a strongly positive UVA Apaisyl gel photopatch test and our photophysical studies. This case confirms the need to keep the phenothiazines in the photopatch test standard series as a diagnostic marker of phenothiazine photoallergy.

Cytophagic histiocytic panniculitis after H1N1 vaccination: a case report and review of the cutaneous side effects of influenza vaccines.

Cytophagic histiocytic panniculitis (CHP) is a rare disease mostly caused by viral infections and/or lymphoproliferative diseases. We describe a case of CHP associated with H1N1 vaccine during the winter 2009-2010 vaccination campaign and discuss the cutaneous side effects of influenza vaccines. A 6-year-old child presented with inflammatory subcutaneous nodules, which had appeared 1 month after the first injection of H1N1 vaccine and 1 week after the second injection. There was no history of recent infection. The skin lesions spontaneously disappeared without scarring. In CHP the abnormal cytokine secretion from neoplastic or reactive T cells promotes monocyte-macrophage activation and haemophagocytosis. Vaccination is not a common cause of CHP, but it seems possible that, as in infectious diseases, reactive T cells to the vaccine antigen could trigger CHP.

Methotrexate in psoriasis: a systematic review of treatment modalities, incidence, risk factors and monitoring of liver toxicity.

BACKGROUND/AIM: To define practical use and to specify the ideal method for monitoring the liver toxicity of MTX in the management of psoriasis. OBJECTIVE: To systematically review the literature regarding treatment modalities with methotrexate (MTX) in psoriasis, risk of MTX-mediated liver fibrosis and monitoring of hepatic toxicity. METHODS: A systematic literature search was carried out in Medline, Embase and Cochrane Library databases from 1980 to 2010 searching for randomized controlled trials and observational studies on methods of administering MTX in psoriasis and risk factors and assessment of liver toxicity. We limited the literature search to articles on human subjects over 19 years of age, articles in English or French on psoriasis and articles including psoriatic arthritis and original data. RESULTS: Among 949 references identified, 23 published studies were included. There were no studies focusing directly on the question of MTX treatment modalities. Treatment outcome appears to be dose dependent. A single study in rheumatoid arthritis showed the slightly superior efficacy of subcutaneous administration vs. oral dosing with a similar safety profile. Combination with folic acid may decrease the efficacy of MTX while improving tolerability. The extreme variability of the incidence of hepatic fibrosis in the literature does not allow the risk of hepatic fibrosis to be quantified. Type 2 diabetes and obesity, were associated with a significant increased risk of liver fibrosis. Hepatitis B and C and alcohol consumption were associated with a modest and non-significant increased risk of liver fibrosis. Procollagen III for detection of hepatic fibrosis dosing was the most extensively validated method to monitor liver fibrosis showing a sensitivity of 77.3% and a specificity of 91.5%. The Positive Predictive Value and Negative Predictive Value fluctuated depending on the prevalence of hepatic fibrosis. The sensitivities of the FibroTest and the fibroscan were of 83 and 50%, respectively, with specific features amounting to 61 and 88% respectively. CONCLUSIONS: Based on expert experience, the starting dose of MTX is between 5 and 10 mg/week for the first week. Fast dose escalation is recommended in order to obtain a therapeutic target dose of 15-25 mg/week. The maximum recommended dose is 25 mg/week. A folic acid supplement is necessary. The initiation of treatment by oral administration is preferred. In cases where inadequate response is obtained or in the event of poor gastrointestinal tolerance, subcutaneous dosing can be proposed at the same dose. Published data do not confirm the incidence of hepatic fibrosis. Type 2 diabetes and obesity appear to be significant risk factors in fibrosis. A combination of FibroTests and fibroscans together with measurement of the type III serum procollagen aminopeptide seem to be ideal method for monitoring liver toxicity.

Evidence-based recommendations on conventional systemic treatments in psoriasis: systematic review and expert opinion of a panel of dermatologists.

BACKGROUND: There is a high level of heterogeneity regarding the practical use of conventional systemic treatment in psoriasis. OBJECTIVES: The aim of this study was to develop evidence-based recommendations for the use of traditional systemic treatments in psoriasis in daily clinical practice: methotrexate (MTX), cyclosporin and retinoids. METHODS: A scientific committee selected clinically relevant questions concerning the use of MTX, cyclosporin and retinoids in psoriasis. This selection was made using the Delphi method. A systematic literature search was performed in Medline, Embase and the Cochrane Library. The articles selected for analysis were reviewed and the level of evidence was appraised according to the Oxford Levels of Evidence. An Expert consensus meeting took place in June 2010, including 66 dermatologists. Recommendations for daily use of psoriasis systemic treatments were made during interactive workshops where the evidence was reviewed. Agreement among participants and the impact of the recommendations on clinical practice were systematically assessed using voting procedure in a plenary session. RESULTS: A total of 2800 references were identified, among which 122 articles were included in the systematic reviews. Three key recommendations on the use of MTX in psoriasis were formulated, including optimal dosage and route, use of folic acid, risk factors for liver fibrosis and monitoring of hepatotoxicity. The recommendations for cyclosporin in psoriasis focused on the modalities of cyclosporin prescription: dosage, scheme of treatment, optimal duration of treatment, renal toxicity monitoring and evidence for use of cyclosporin in non-plaque psoriasis (erythrodermic, pustular and ungueal). Recommendations were also made concerning the efficacy and safety of retinoids (mainly acitretin) in plaque and non-plaque psoriasis. CONCLUSIONS: These recommendations for the use of traditional systemic therapies in psoriasis are evidence based and supported by a panel of dermatologists. The next step will be to disseminate these recommendations and assess the agreement of physicians who were not involved in generating the recommendations.

Oral cyclosporin in psoriasis: a systematic review on treatment modalities, risk of kidney toxicity and evidence for use in non-plaque psoriasis.

BACKGROUND: Although cyclosporin (CyA) has been in use in psoriasis for more than 20 years, there is still controversy regarding treatment strategy, monitoring of kidney function and utility in non-plaque psoriasis. OBJECTIVES: To prepare for evidence-based recommendations concerning the practical use of CyA in psoriasis, we performed a systematic review to better define treatment strategy, risk of kidney toxicity and evidence for use in non-plaque psoriasis. METHODS: A systematic search was performed on PubMed, Cochrane and Embase databases, using the key-words 'psoriasis', 'CyA', 'nephrotoxicity' during the period from 1980 to June 2010. RESULTS: The initial literature search identified 428 articles. The final selection included 16 randomized controlled trials (RCT) for treatment strategy, 25 articles (histological studies and RCT) for risk of kidney toxicity and 10 articles (RCT, prospective studies and case series) for use in non-plaque psoriasis. Higher doses of CyA of 5 mg/kg produced Psoriasis Area Severity Index (PASI) 75 response in between 50 and 97% of patients, whereas lower doses of 2.5 mg/kg yielded PASI 75 in between 28 and 85%. CyA could maintain remission at doses of at least 3 mg/kg/day. Low calory diet in obese patients was shown to improve CyA efficacy. More than 50% of the patients treated with CyA may have an increase in serum creatinin value over 30% of baseline if treatment is prolonged for 2 years. CyA at a dose of 2.5 mg/kg/day was effective for 89% of patients with palmoplantar pustulosis. More than 50% of the patients with erythrodermic psoriasis obtained a significant improvement at doses between 3 and 5 mg/kg/day at 2-4 months. CyA was more effective than etretinate on nail psoriasis. CONCLUSION: Oral CyA is indicated for patients with plaque psoriasis, pustular psoriasis or erythrodermic psoriasis. The starting dose of 5 mg/kg is associated with a higher degree of clearance. The benefit-risk appears to be better for patients without risk factors for nephrotoxicity: non-obese patients without hypertension and aged below 60. Although CyA is ideally suited for crisis intervention, continuous maintenance treatment with CyA may be envisaged in some patients provided serum creatinin is regularly monitored and the cumulative treatment duration is preferably limited to 2 years or less.

Efficacy and safety of oral retinoids in different psoriasis subtypes: a systematic literature review.

BACKGROUND: There is limited evidence regarding the efficacy and safety of retinoids in different psoriasis subtypes. OBJECTIVE: To systematically review the available literature on: (i) modalities of administration and prescription of oral retinoids as single agent or combined therapy for the treatment of plaque-type psoriasis (PV), nail psoriasis and localized and generalized pustular psoriasis : initial and optimal dosage; (ii) skeletal toxicity of retinoid for the treatment of psoriasis. METHODS: A systematic literature search was carried out in MEDLINE, EMBASE, and Cochrane Library databases from 1975 to 2010 searching for randomized controlled trials and observational studies evaluating 1) various dosages of retinoid in psoriasis and 2) skeletal toxicity of retinoid in psoriasis. Articles were limited to human subjects and English/French languages. RESULTS: Efficacy of retinoids in psoriasis. Among 1348 identified references, 44 published studies were included. Starting daily dosages between 10 and 25 mg and stepwise escalation were associated with higher clinical efficacy and lower incidence of adverse events in comparison with higher doses and regimens rapidly reaching optimal dose. Retinoids as single agent therapy appeared to show limited efficacy in PV, while the good clinical efficacy reported in pustular forms should be cautiously considered, given the spontaneously remitting course of the disease. Combining retinoids with phototherapy appeared to be highly effective in patients with PV. Potential skeletal toxicity of retinoids. 15 published studies out of 105 identified references were included. There is no strong evidence of an increased risk of skeletal abnormalities in psoriasis patients treated with retinoids. CONCLUSION: Acitretin appears to provide better efficacy in pustular psoriasis than in PV as a single agent treatment. There is no evidence for skeletal toxicity of retinoids in the setting of psoriasis, and accordingly monitoring this risk through X-ray is not warranted.

Joint clinical and pathological review meetings improve patient care: a prospective evaluation in dermatology.

BACKGROUND: Joint clinical and pathological review meeting exists in most academic dermatology departments. OBJECTIVE: The primary objective of the study was to assess the impact of the joint clinical and pathological review meeting in dermatology on patient care. METHODS: Prospective descriptive study over 6 months (May to October 2008) on all clinical cases of dermatology reviewed at the joint clinical and pathological review meeting in our University Hospital. RESULTS: A total of 139 cases were reviewed during the 6-month period. In 97 cases (69.8%), the joint clinical and pathological review meeting had a positive impact on final diagnosis and/or on patient management. For 27 cases, a consensus diagnosis different from the initial proposal was established. In 21 cases, the joint clinical and pathological review meeting led to additional investigations or therapeutic proposals. The impact of the joint clinical and pathological review meeting was highest for inflammatory skin diseases. CONCLUSIONS: The joint clinical and pathological review meeting is a useful procedure to improve diagnostic accuracy in difficult cases.

Coordination of pollution-related MSFD measures in the Mediterranean - Where we stand now and insights for the future.

Various pollutants keep threatening the environmental status of the Mediterranean Sea, while the Marine Strategy Framework Directive requires that Good Environmental Status needs to be achieved in European Seas by 2020. Previous reviews already established that the ambition levels of national Programmes of Measures (PoMs) are low. This study focuses on the analyses of the levels of coherence and coordination of the proposed PoMs in the Mediterranean, concentrating on nutrient, contaminant, and marine litter pollution, as well as the introduction of non-indigenous species. Coherence and pollinator analyses of the proposed measures of Mediterranean EU Member States (MS) were performed. The results demonstrate that while the current coordination between MS is almost non-existent, several measures are already addressing the same pressures in similar ways and could be easily coordinated on transnational level. Increased coordination and coherence of PoMs in the Mediterranean are vital for achieving good environmental status in future years.

Use of high-pressure freeze fixation and freeze fracture electron microscopy to study the influence of the phospholipid molar ratio in the morphology and alignment of bicelles.

The high-pressure freeze fixation and freeze fracture electron microscopy techniques were combined with the (31)P nuclear magnetic resonance to study the morphological transitions of two different dimyristoyl-phosphatidilcholine/dihexanoyl-phosphocholine aggregates by the effect of temperature. Through these techniques, the relationship between magnetic alignment and the morphology of alignable and non-alignable aggregates was evaluated. The micrographs related to the non-alignable dimyristoyl-phosphatidilcholine/dihexanoyl-phosphocholine sample presented rounded objects at a temperature below the dimyristoyl-phosphatidilcholine phase transition (T(m)) and, above this temperature an increase of viscosity was followed by the appearance of large elongated aggregates. The micrographs related to the alignable dimyristoyl-phosphatidilcholine/dihexanoyl-phosphocholine sample presented discoidal objects below T(m). Above T(m), when the best alignment was achieved, the images showed large areas of lamellar stacked bilayers and the presence of some multilamellar vesicles. Our results reveal that the composition of the aggregates is a key factor determining the morphological transitions of the bicellar systems. Understanding of the rules governing these transitions is crucial to modulate characteristics of these systems and to adequate them for different applications.

Liposome formation with wool lipid extracts rich in ceramides.

Internal wool lipids (IWLs) are rich in cholesterol, free fatty acids, cholesteryl sulfate, and, mainly, ceramides. The repairing effect of these lipids structured as liposomes was demonstrated by reinforcing the skin-barrier integrity and increasing the water-holding capacity when applied onto the skin. This work was focused on the formation of liposomes with IWLs rich in ceramides, obtained at pilot plant level with organic solvent extraction by using methanol and acetone. The lipid composition of the two extracts was quantitatively analyzed. IWL extracts containing different amounts of sterol sulfate were used to form liposomes at physiologic p(H). Vesicle size distribution, polydispersity index, and zeta potential of all liposomes were determined to characterize them and to study their stability. The results obtained showed that IWL extract composition, which was different depending on the extraction methodologies used, greatly influences the characteristics of the liposomes formed. Vesicular size and polydispersity index liposomes were smaller when the extract composition contained a higher proportion of either free fatty acids or sterol sulfate. Moreover, liposome stability was improved when some amount of sterol sulfate was added to the composition of methanol and acetone extracts. This natural mixture with keratinaceous origin could have a special interest for cosmetic or dermopharmaceutical companies.

[Evaluation of dermatology consultations in a prospective multicenter study involving a French teaching hospital]. / Evaluation de l'activité hospitalière de consultation liaison en dermatologie à partir d'une enquête prospective multicentrique au sein d'un CHU français.

BACKGROUND: Dermatologic practice occurs mainly in the inpatient setting. This activity is also referred to as consultation-liaison dermatology (DL). STUDY AIMS: To describe and quantify this dermatologic consultation activity in a hospital setting in Marseille; to establish the relationship between presumptive dermatologic diagnosis and the final diagnosis retained by the dermatologist. PATIENTS AND METHODS: This was a prospective study carried out three university teaching hospitals and an army teaching hospital for a period of three months. Of particular note is that services requesting consultation were asked in each case to supply their presumptive dermatologic diagnosis at the time consultation was requested. The statistical analysis was carried out using the SPSS 15.0 software package. A total of 352 notes for dermatology consultations were requested and 336 of these were evaluated, representing 5% of all consultations activities within these dermatology departments over this period. Ninety-three percent of the consultations were established by dermatology interns and 86% of consultations took place within 24 hours following their demand. Thirty-one percent of consultations were for patients aged over 75 years and 61% of the requests emanated from medical departments. The main requests concerned elementary lesions, symptoms or non-specific eruptions (56%), recommendations for treating infectious skin diseases (17%), inflammatory diseases (7%) and skin cancer (5%), recommendations for nursing care (14%) and the remainder for various reasons. No diagnosis was established in the face of of non-specific signs in 26.4% of cases. The diagnosis made by dermatologists differed from that initially evoked by the non-specialists in 56.3% of cases. Initial dermatological diagnosis was least successful regarding drug-induced eruption and skin cancer. The majority of consultations (57%) were considered unrelated to the patients' previous histories or reasons for admission. Twenty-six percent of patients were prescribed systemic therapy and 80% were prescribed topical treatment, of whom a quarter received dressings. Therapeutic acts were prescribed for 40% of the patients. Five percent of the patients were hospitalized after their consultation at the respective dermatology department and 14% were referred for outpatient dermatology consultations. DISCUSSION: This study confirms a number of expected features: common dermatological diseases are often not recognized or is misdiagnosed by non-dermatologists, excessive bedside consultations and very particular profiles of the common diagnoses in this activity (nursing care, drug-induced eruption, fungal infections). Less predictable were the absence of links between the requests and the moderate impact of the activity on hospitalization. CONCLUSION: The study of these dermatologic diagnoses in an in-patient setting suggests a number of approaches to more successful management of these consultations.

New arrangement of proteins and lipids in the stratum corneum cornified envelope.

A new arrangement of proteins and lipids of stratum corneum (SC) cornified envelope (CE) is proposed. The chemical analysis of CE revealed the presence of free fatty acids (FFA), ceramides (Cer), and important percentages of glutamic acid/glutamine (Glx) and serine (Ser) residues. The molecular structure of these components suggests the existence of covalent links not only between Cer and Glx but also between FFA and Ser. The protein distribution of extracellular surface of CE, i.e., the proteins that could be involved in the bonds with lipids, was studied using post- and pre-embedding immunolabeling electron microscopy. Some loricrin (protein rich in Ser) was detected in the outermost part of the CE protein layer. The external arrangement of some domains of this protein may give rise to form linkages with FFA, yielding further insight into the CE arrangement in which Cer-Glx bonds and FFA-Ser bonds would be involved. Although the importance of fatty acids in the cohesion and barrier function of SC has been widely demonstrated, their role could be associated not only to the presence of these lipids in the intercellular lamellae but also in the CE, in the same way that Cer.

Morphological effects of ceramide on DMPC/DHPC bicelles.

Freeze fracture electron microscopy and dynamic light scattering were applied to characterize the morphological changes of DMPC/DHPC bicellar systems induced by the addition of ceramides. The results demonstrate a tendency of the DMPC/DHPC aggregates to evolve forming elongated or tubular structures with the increase of the temperature. At 20 degrees C, low concentrations of ceramide promote the appearance of elongated structures with twisted zones. Higher concentrations of this lipid lead to the formation of liposomes along the elongated structures. The increase of the temperature to 40 degrees C induces the growth of the structures containing low concentrations of ceramide forming branched aggregates. In samples with high amounts of ceramide, the increase of temperature causes phase separation and the formation of a mixed system composed by liposomes and multilamellar tubules. The morphological effects induced by ceramides in this new membrane model give new insights for the role played by this lipid in biological membranes.