Epidermal kinetic alterations required to generate the psoriatic phenotype: a reappraisal.

OBJECTIVES: Although there have been major advances in understanding immunopathogenesis of psoriasis, the basic processes causing psoriatic morphology remain to be identified. MATERIALS AND METHODS: Our group has designed a systematic review of studies (1962-2009) on keratinocyte kinetics in psoriasis. We obtained data from MEDLINE, PubMed, Current Contents, reference lists and specialist textbooks. A general equation for evolution of the differentiated epidermis has been analysed. Necessary conditions for observed qualitative change in homeostasis between normal skin and established psoriatic lesions were determined. RESULTS AND DISCUSSION: Increase in the number of cell divisions (or imbalance in symmetric division rates of committed progenitor cells) and/or decrease in physiological apoptosis in the germinative compartment, together with feedback loops that limit thickening of the skin, are required to generate psoriatic morphology, that is, to increase the absolute size but decrease relative size of the differentiated cell compartment with respect to the germinative compartment.

Time-kinetic study of repigmentation in vitiligo patients by tacrolimus or pimecrolimus.

New topical immunomodulators have been reported to cause repigmentation of vitiligo lesions. However, time-kinetics of such repigmentation in different anatomic locations is not well known. We performed a randomized double-blind placebo control study with tacrolimus versus the vehicle and a nonrandomized control study with pimecrolimus to evaluate the time to reach significant pigmentation, its duration and extent in treated areas. Antioxidant status of serum was also assessed. Twenty patients, in the tacrolimus study, had one pair of lesions on different localizations, and 20 on face and/or upper limbs for pimecrolimus. The extent of repigmentation was evaluated by slides and mapmakings at baseline and every 4 weeks during 7 months. Adverse events were recorded. The derivatives of oxygen metabolites, the ferric reducing ability of serum and vitamin E were assessed. Three groups of patients were identified with the tacrolimus study. Eight had no significant change in response characterized by a parallel increase of repigmentation or none in treated and control areas. Nine had a better repigmentation to tacrolimus at fifth month of treatment. Three had a marked repigmentation in control areas at the end of treatment. Repigmentation was significant on the face compared to upper-limbs with pimecrolimus from fourth to seventh month. A significant reduction of oxidative stress and an increase in antioxidant capacity in serum of patients treated with topical tacrolimus was observed, while those treated with pimecrolimus did not show any significant changes but an increase in vitamin E. Our work defines three periods in repigmentation, triggering during the first 4 months, increase in pigmentation with tacrolimus and a plateau or a sustained repigmentation. The continuity of the treatment seems necessary to ensure a prolonged repigmenting effect and even an enhanced one, such as the one we observed on the face with pimecrolimus. The extent of repigmentation was more significant on the face compared to other locations probably due to differences in melanocyte density. Furthermore, we did not find any relationship between repigmentation and the duration of vitiligo. Tacrolimus was able to reduce the systemic oxidative stress independently from its repigmenting capacity. Both drugs were well tolerated.

[Interest of immunohistochemic markers (Ki67, HMB45, p53) in risk analysis of congenital naevi of little and middle size]. / Intérêt des marqueurs immunohistochimiques (Ki67, HMB45, p53) dans l'analyse de risque des naevi congénitaux de petite et moyenne taille.

The risk to develop melanoma from small or medium size congenital naevus remain controversial. The main goal of the present study was to determine the interest of three immunohistochemical markers (Ki67, HMB45 and p53) in predicting malignant transformation of these congenital naevi and to see if a specific immunohistochemical profile of such transformed naevi can be identified. The markers (Ki67, HMB45 and p53) have been used retrospectively on sections of small or medium size congenital naevi (group NC, n = 15), of melanoma developed on small or medium size congenital naevi (group MNC, n = 15) and of melanoma developed on acquired naevi (group MNA, n = 15). The labelled cells have been counted in different cutaneous layers: junction, superficial dermal layer and deep dermal layer. No reactivity was observed for the three markers in group NC. The percentage of labelled cells was significantly different for the three markers between the group NC and the groups MNC and MNA. There was no difference between the groups MNC and MNA. In the groups MNC and MNA, a gradient in the percentage of labelled cells was observed between superficial and deep layers. These three markers do not differentiate melanoma developed from congenital naevi of small or medium size and melanoma developed from acquired naevi. Moreover, the results suggest that these three markers are useless in predicting the risk of malignant transformation of small or medium size congenital naevi.

Black Skin Dermatology Online, from the project to the website: a needed collaboration between North and South.

BACKGROUND: Whereas teledermatology is an emerging discipline, to date, no teledermatology service has been developed, which is specifically dedicated to black skins. OBJECTIVES: To create and develop a teledermatology service that provides a complete range of communication, information, telediagnosis and teaching services. METHODS: A multilingual clinical description of the lesion was provided for each photograph using a five-level disease classification from the 10th revised International Classification of Diseases. In parallel, a usability study to assess and improve the functionality of the platform was also conducted. RESULTS: A web prototype has been developed which integrates image acquisition, submission, clinical description, translation as well as validation, security and data protection aspects and almost 2000 images were obtained from which 600 have been integrated in the 'store and forward' telemedicine system (http://www.black-skin.org). Initial usability tests with native French medical students show good perceived usefulness, perceived usability and internal consistency (Cronbach's alpha = 0.80 and 0.84). CONCLUSION: The Black Skin project (North and South collaboration project) offers possibilities for continuous medical education (pedagogical cases), teleteaching (educational quiz) or asking for a second opinion ('Ask a specialist' item).

[Management of cutaneous toxicities induced by epidermal growth factor receptor inhibitors: a review]. / Prise en charge des toxicités cutanées des thérapies dirigées contre les récepteurs du facteur de croissance epidermique: revue de la littérature.

The epidermal growth factor receptor (EGFR) is overexpressed in many solid tumors. Its inactivation has an inhibitory effect on the growth and spread of the tumoral cells. It therefore represents an attractive target to treat different cancers. Several molecules have already been registered while others are still under evaluation. One of the common side effects of these therapies is the development of cutaneous toxicities, more precisely a cutaneous rash, sometimes major and distressing. The physiopathology of these cutaneous side effects is poorly understood. Moreover a correlation between the severity of the rash and the tumoral response has been demonstrated in some studies. If this link is confirmed, the rash could be used as a marker for the anti-tumoral activity. This review will summarize the clinical presentations and the current recommendations for the management of cutaneous toxicities induced by EGFR inhibitors.

[Extracorporeal photochemotherapy: review of its mechanisms of action and clinical applications]. / La photochimiothérapie extracorporelle: revue de son mode d'action et de ses indications.

Extracorporeal photochemotherapy is an immunomodulatory treatment wich is carried out in three steps: first leukapheresis, then ex vivo PUVA treatment and finally autologous transfusion. Its current "evidence-based" indications are erythrodermic cutaneous lymphoma, graft versus host disease and cardiac graft rejection. However this treatment has already been used with success in many other diseases such as systemic sclerosis, multiple sclerosis, type 1 diabetes and various autoimmune dermatologic diseases. Randomised controlled studies are needed to confirm the efficacy of photopheresis in these diseases. We also review the different hypotheses explaining the mechanism of action of photopheresis.

Skin biopsies in DC vaccines for stage III-IV melanoma patients: role of neutrophils?

Dendritic cell (DC) vaccines are used for the induction of anti-tumor T cell reaction in melanoma patients. DC are generated in vitro, pulsed with antigen and matured prior to injection. They are supposed to migrate to lymph nodes and to present the processed antigen to naive T cells allowing activation of tumor-specific lymphocytes. It has been suggested that intradermal injection allows a superior migration to the lymph node. Eight HLA-A2 positive patients with stage III or IV melanomas expressing NA 17 antigen were collected. They were included in a pilot trial of vaccination in which they received IL3/INFb DC presenting the NA17 A2 antigen. In each patient, a skin biopsy was performed at the injection site, 24 h after inoculation. The striking features of the biopsies were the presence of a perivascular CD3+/CD8+ T cell infiltrate with a slight population of CD4+ cells and the presence of a massive neutrophilic infiltrate associated with the injected DC still present, realizing a suppurative granuloma. The persistence of DC 24 h after the injection suggests that migration in the lymph node is not necessary for the induction of the immune response. The skin itself could be the location of a reaction starting with a massive recruitment of neutrophils.

[The treatment of psoriasis: basic principles and new options]. / Le traitement du psoriasis: sa stratégie et les nouvelles options.

Psoriasis is a frequent chronic disease with a typical cutaneous expression described as erythemato-squamous lesions, and sometimes, joint involvement. This disorder rarely causes death in patients, but often alters their quality of life. A better understanding of the pathophysiology of psoriasis has led to the development of new therapeutic options among which are treatments targeted on blocking T-cell activation. Thanks to these therapies we can offer the patients long lasting remission, albeit not a curative approach. The therapeutic approach towards psoriasis will be selected in a multidisciplinary spirit, and after considering the patient himself, his disease and his lifestyle.

Impact of cosmetic care on quality of life in breast cancer patients during chemotherapy and radiotherapy: an initial randomized controlled study.

BACKGROUND: Breast cancer is the most common cancer in women and therefore represents a major problem in public health. Data from patients' self-report questionnaires provide valuable information about the side-effects that patients may view as having a significantly detrimental impact on their quality of life (QOL) and yet are not always recognized as important by healthcare professionals. Cosmetology is a specific care for patients and there is actually no scientific evidence regarding effects on QOL for women with breast cancer. OBJECTIVE: The purpose of this study is to assess the impact of cosmetic care on QOL in breast cancer patients during chemotherapy and radiotherapy. METHODS: We developed a prospective, multicentre, randomized, controlled study including 27 patients. All the patients had to fill in a French-validated dermatologic specific quality-of-life questionnaire to compare the QOL of the two groups, the cosmetic group and the control group, at three different times of the adjuvant treatment. RESULTS: The results show a statistically significant difference between the cosmetic group and the control group in two areas of QOL: mood state and self-perception of the disease. CONCLUSION: This study emphasizes the interest of cosmetic care in breast cancer patients. However, further larger trials are needed to confirm this study.

Fluorescence diagnosis of face-located basal cell carcinomas: a new dermatological procedure which may help the surgeon.

Cutaneous Fluorescence Diagnosis (FD) is a new promising dermatological procedure which is based on the combination of a local application of a photosensitizer such as 5-aminolevulinic acid (ALA) or its methyl ester (MAL) and the use of a light source (red light) adapted to the absorption spectrum of these molecules. The targeted photosensitization of skin cancers, particularily superficial and extensive lesions including superficial basal cell carcinoma and Bowen's disease, by ALA or MAL induced porphyrins leads to a selective red fluorescence which can be demonstrated by Wood's lamp. This technique may be useful either to define better the choice of margins or to detect earlier and or multifocal recurrences.

Imported melioidosis with an isolated cutaneous presentation in a 90-year-old traveller from Bangladesh.

Melioidosis is a tropical disease caused by infection with the bacterium Burkholderia pseudomallei. Most cases present as an acute febrile illness with severe pneumonia and sepsis. Sub-acute and late onset disease can also occur Melioidosis has been diagnosed among travellers who contracted the disease while staying in endemic areas during the rainy season. We report a case of travel-associated B. pseudomallei cutaneous infection in a febrile 90-year-old woman with diabetes mellitus, with early stage manifestations of an isolated inoculation lesion. A 32 weeks' treatment with oral amoxicillin-clavulanate and doxycycline combination regimen led to resolution of the lesion and lack of relapse over fifteen months of follow-up. Melioidosis should be considered in the differential diagnosis of unusual subacute cutaneous lesions in a febrile patients returning from endemic areas, as successful management largely depends on early diagnosis and specific long-term suppressive antimicrobial therapy at an early stage of the course of the disease.

[The strategy of prevention and early detection of cutaneous melanoma]. / La stratégie de prévention et de dépistage du mélanome cutané.

Dermatology, and more specifically cutaneous oncology, has evolved from a descriptive science concept towards multifaceted medico-surgical medicine which is nowadays based not only on observation. In this view, the importance of prevention and early detection of skin cancers including cutaneous melanoma has been recognized and has created a new challenge. Thanks to this proactive approach, the improvement in the prognosis of newly diagnosed melanomas has been demonstrated, but many efforts have to be brought to reduce the incidence and the mortality of this potentially aggressive tumor.

Anti-tumor necrosis factor alpha-induced psoriasiform eruptions: three further cases and current overview.

The increasing use of anti-TNF-alpha agents led to a better knowledge of their side effects. Among the cutaneous reactions, psoriasiform eruptions are increasingly described. We encountered 3 further psoriasiform eruptions during anti-TNF-alpha treatment for rheumatologic conditions and review the literature in order to identify the common characteristics of these cases. We found 30 case reports by using a comprehensive search of the 1966-2005 Medline database with a wild variety concerning the psoriasis type of eruption, the anti-TNF-alpha agent, the treatment duration and the presence or absence of a personal or familial history of psoriasis. We conclude that a psoriasiform eruption during anti-TNF-alpha treatment seems to be a class effect, without any as yet known identified predisposing factors, but it is more often self-limited and does not require treatment discontinuation.

[Dermatitis artefacta: retrospective study in 31 patients]. / Pathomimie: étude rétrospective de 31 malades.

BACKGROUND: The outcome for patients with dermatitis artefacta is not well known. The primary objective of this single-centre retrospective study was to describe the initial clinical aspects and the prognosis of the disease. The secondary objective was to describe the somatic and psychological management and long-term treatment of these patients. PATIENTS AND METHODS: Records of patients with dermatitis artefacta followed in the dermatology department over the 15 last years were reviewed independently by 2 dermatologists. Diagnostic criteria consisted of evocative clinical pictures and the exclusion of other forms of dermatosis. Data collection included: file analysis, photographs, review questionnaires sent to general practitioner or completed during a phone call to patients (follow-up data). RESULTS: Thirty-one patient files were selected: 23 women and 8 men, mean age 31 years (SD = 14.8). Clinical aspects included: erythema (50%), ulceration (37%), crust (23%) and blisters (17%). The main sites were the face (67%) and arms (43%). Topical treatment was prescribed in all cases and systemic treatment was prescribed in 23% of cases. Psychological support was offered to 65% of the patients and was accepted by 50%. A follow-up study was performed for 17 patients and showed serious complications in 4 cases consisting of psychosis (n=2) and/or severe self-mutilation (n=3) occurring over several years following diagnosis (5 years for one patient and 12 years for 2 patients). DISCUSSION: The results confirm the usual and characteristics of dermatitis artefacta such as predominance in young female patients, with lesions affecting visible areas (face, upper legs). In contrastwith published studies, no cases of attempted suicide were observed in our series, although severe dermatitis artefacta was evidenced in only a minority of patients.