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Brigitte Dréno

Publications and source records attributed to Brigitte Dréno.

At least 19 recordsLinked to original sources

Assessing quality of life in patients with acne vulgaris: implications for treatment.

Diagnosing acne is easy. However, treatment must be adapted to the type and severity of acne, and must also take into account the impact of acne on patients' quality of life. As there is not always a correlation between the severity of acne and its impact on quality of life, it can be helpful for the dermatologist to use a quality of life scale to determine the psychological impact of acne on patients. Either global scales or specific scales for acne can be used. This article reviews the different scales used for evaluation of quality of life in patients with acne.Consideration of specific scales suggests that the Acne Disability Index/Cardiff Acne Disability Index is the easiest scale to use in routine dermatology practice. The Acne Quality of Life scale is particularly useful for evaluating anxiety and depression. The Acne-Specific Quality of Life questionnaire has been mainly validated in adult acne. The Assessment of the Psychological and Social Effects of Acne scale has yet to be validated. Clinical trials indicate that use of global and specific scales together has complementary benefits. In the management of acne, evaluation of quality of life may help to detect depression in teenagers. It may also help to enhance adherence to treatment, which is a crucial factor for success. Finally, there are now validated quality of life scales that are easy to use during patient consultations (taking <2 minutes to complete) by clinicians wishing to evaluate quality of life in patients with acne.

Acne Vulgaris↗

Phase 1/2 study of subcutaneous and intradermal immunization with a recombinant MAGE-3 protein in patients with detectable metastatic melanoma.

The purpose of this phase 1/2 study was to evaluate toxicity, tumor evolution and immunologic response following administration of a fixed dose of a recombinant MAGE-3 protein by subcutaneous and intradermal routes in the absence of immunologic adjuvant. Thirty-two patients with detectable metastatic melanoma expressing gene MAGE-3 were included and 30 received at least one injection with a fixed dose of a ProtD-MAGE-3 fusion protein. The immunization schedule included 6 intradermal and subcutaneous injections at 3-week intervals. Afterward, patients without major tumor progression who required other treatments received additional vaccinations at increasing time intervals. The vaccine was generally well tolerated. Among the 26 patients who received at least 4 vaccinations, we observed 1 partial response and 4 mixed responses. For these 5 responding patients, time to progression varied from 3.5 to 51+ months. An anti-MAGE-3 CD4 T-lymphocyte response was detected in 1 out of the 5 responding patients. The majority of patients had no anti-MAGE-3 antibody response. The clinical and immunologic responses generated by the vaccine are rather limited. Nevertheless, given the potential antitumor efficacy and the very mild toxicity of vaccinations, further studies combining MAGE proteins and/or peptides with potent immunologic adjuvants are warranted, not only in metastatic melanoma, but also in the adjuvant setting.

Adult↗

Tumoral and immunologic response after vaccination of melanoma patients with an ALVAC virus encoding MAGE antigens recognized by T cells.

PURPOSE: To evaluate the toxicity, antitumoral effectiveness, and immunogenicity of repeated vaccinations with ALVAC miniMAGE-1/3, a recombinant canarypox virus containing a minigene encoding antigenic peptides MAGE-3(168-176) and MAGE-1(161-169), which are presented by HLA-A1 and B35 on tumor cells and can be recognized by cytolytic T lymphocytes (CTLs). MATERIALS AND METHODS: The vaccination schedule comprised four sequential injections of the recombinant virus, followed by three booster vaccinations with the MAGE-3(168-176) and MAGE-1(161-169) peptides. The vaccines were administered, both intradermally and subcutaneously, at 3-week intervals. RESULTS: Forty patients with advanced cancer were treated, including 37 melanoma patients. The vaccines were generally well tolerated with moderate adverse events, consisting mainly of transient inflammatory reactions at the virus injection sites. Among the 30 melanoma patients assessable for tumor response, a partial response was observed in one patient, and disease stabilization in two others. The remaining patients had progressive disease. Among the patients with stable or progressive disease, five showed evidence of tumor regression. A CTL response against the MAGE-3 vaccine antigen was detected in three of four patients with tumor regression, and in only one of 11 patients without regression. CONCLUSION: Repeated vaccination with ALVAC miniMAGE-1/3 is associated with tumor regression and with a detectable CTL response in a minority of melanoma patients. There is a significant correlation between tumor regression and CTL response. The contribution of vaccine-induced CTL in the tumor regression process is discussed in view of the immunologic events that could be analyzed in detail in one patient.

Adult↗

[Pathophysiology of acne].

Acne is a disease that develops in pilosebaceous follicles. Acne was long considered was an infectious disease related to Propionibac-terium acnes, but studies show that the production of inflammatory substances in situ was much more important to the action of this bacterium than was simple infection. It was once thought that only the androgens could stimulate the seba-ceous gland, but today we know that neuromediators can also stimulate sebum production. This finding provides physiological support to the clinical observation that stress can induce acne.

Acne Vulgaris↗

[The treatment of acne].

The treatment of acne is based on local and systemic treatments. It must be adapted to the type of acne and take some prognostic factors into account. Because of the possibility of drug resistance, systemic and local antibiotics should be used for only limited periods and preferably as part of combined treatments. Prescription of isotretinoin to women must follow strict rules. Some new-generation contraceptive pills are an interesting alternative for acne treatment in women. Zinc, which basically targets inflammatory acne, is a possible option for pregnant women and during the summer. Cosmetic care is also a fundamental part of acne treatment.

Acne Vulgaris↗

In vitro induction of matrix metalloproteinase-2 and matrix metalloproteinase-9 expression in keratinocytes by boron and manganese.

Matrix metalloproteinase (MMP)-2 and MMP-9 are involved in keratinocyte migration and granulation tissue remodeling during wound healing. Thermal water cures are sometimes proposed as complementary treatment for accelerating healing of wounds resulting from burns and/or surgery, but their mechanisms of action remain unknown. Some thermal waters are rich in trace elements such as boron and manganese. Interestingly, clinical studies have shown the beneficial effects of trace elements such as boron and manganese for human wound healing. To try to specify the role of trace elements in cutaneous healing, the present study investigated the effects of these trace elements on the production of MMP-2 and MMP-9 by normal human keratinocytes cultured in vitro. Immunohistochemistry and Western blot showed that intracellular MMP-9 expression in keratinocytes was induced when incubated for 6 h with boron at 10 micro g/ml or manganese at 0.2 micro g/ml. Moreover, gelatin zymography on keratinocyte supernatants showed an increase of gelatinase secretion after 24 h of incubation of keratinocytes with boron or manganese, regardless of concentration. Gelatinase secretion was not associated with keratinocyte proliferation induced by trace elements. Thus, our results suggest that boron and manganese could play a role in the clinical efficiency of thermal water on wound healing.

Blotting, Western↗

Monoclonal anti-MAGE-3 CTL responses in melanoma patients displaying tumor regression after vaccination with a recombinant canarypox virus.

We have analyzed the T cell responses of HLA-A1 metastatic melanoma patients with detectable disease, following vaccination with a recombinant ALVAC virus, which bears short MAGE-1 and MAGE-3 sequences coding for antigenic peptides presented by HLA-A1. To evaluate the anti-MAGE CTL responses, we resorted to antigenic stimulation of blood lymphocytes under limiting dilution conditions, followed by tetramer analysis and cloning of the tetramer-positive cells. The clones were tested for their specific lytic ability and their TCR sequences were obtained. Four patients who showed tumor regression were analyzed, and an anti-MAGE-3.A1 CTL response was observed in three of these patients. Postvaccination frequencies of anti-MAGE-3.A1 CTL were 3 x 10(-6), 3 x 10(-3), and 3 x 10(-7) of the blood CD8 T cells, respectively. These three responses were monoclonal. No anti-MAGE-1.A1 CTL response was observed. These results indicate that, like peptide immunization, ALVAC immunization produces monoclonal responses. They also suggest that low-level antivaccine CTL responses can initiate a tumor regression process. Taken together, our analysis of anti-MAGE-3.A1 T cell responses following peptide or ALVAC vaccination shows a degree of correlation between CTL response and tumor regression, but firm conclusions will require larger numbers.

Antigens, Neoplasm↗

[Epidemiology of melanoma].

A WORRYING INCIDENCE: In frequency, the melanoma, is placed just after breast, colic and pulmonary cancer with around 6 000 new cases per year in France. Moreover, it is the tumour that is increasing the most and its frequency has doubled over the past 10 years. It is presently estimated as 7 to 9/100 000 in France. THE IMPACT OF PREVENTIVE MEASURES: Primary and secondary prevention is therefore crucial, as is the identification of patients at risk. However, till now, the impact of educational and preventive campaigns with regard to sun exposure, which plays a major role in the development of a melanoma, are still insufficient

Adult↗

[The clinical diagnosis of melanoma].

EARLY DIAGNOSIS FOR EFFICIENT MANAGEMENT: The melanoma is a cutaneous tumour of poor prognosis and its incidence is increasing. Some risk factors are now well established ( field, phototype, family history) and its early discovery is clinically possible since the lesions are visible to the eye. When diagnosed early, the prognosis is clearly improved. CLINICAL FORMS OF VARYING PROGNOSIS: Depending on the clinical, histopathological and progressive differences, it is possible to distinguish a Superficial Spreading Melanoma (60 to 70%), nodular melanoma (10 to 15%), Dubreuilh's melanoma (5 to 10%) and acrolentigenous melanoma (5%). Apart from these 4 major clinical forms, there is also the sub-ungual melanoma and the mucosal melanoma. Particular situations may also exist: the discovery of metastasis without identification of cutaneous tumour, a melanoma in a pregnant woman or a child, a familial melanoma or multiple melanomas. THE ELEMENTS OF DIAGNOSIS: The semiological analysis of an often-pigmented lesion of the skin, relying on the ABCDE rule and the notion of rapid progression, is the first stage in the diagnostic approach. It is completed, following complete exeresis, by anatomopathological exploration (Breslow's index, existence of ulceration, signs of regression, Clark's classification, histological type and mitotic activity). Two further elements should also be taken into account: the results of a dermatoscopy and the analysis of the sentinel nodes.

Adult↗

[Treatment of melanoma].

At the stage of primary tumour and lymph node extension, the treatment of melanoma is mainly surgical. Interferon alpha has obtained marketing authorisation to be used as adjuvant therapy at different doses in the treatment of these two stages of the disease and must therefore be discussed with the patient. At the metastatic stage, no real progress in chemotherapy has been noted for more than 20 years. Combined therapy with chemotherapy and cytokines (interferon alpha or interleukine 2) increases the percentage of response but without increasing the overall survival. THREE IMMUNOTHERAPY TECHNIQUES: Cellular immunotherapy represents the main hope of these future years in the treatment of melanoma, with the injection of in vitro expanded cytotoxic T cells, vaccination and dendritic cells. Although clinical results are starting to be published, cellular immunotherapy remains in the field of clinical research, within the framework of clinical trials.

Antineoplastic Agents↗

Mutation spectrum of human SLC39A4 in a panel of patients with acrodermatitis enteropathica.

Acrodermatitis enteropathica is rare autosomal recessive disorder characterized by a severe nutritional zinc deficiency. We and others have recently identified the human gene encoding an intestinal zinc transporter of the ZIP family, SLC39A4, as the mutated gene in acrodermatitis enteropathica (AE). A first mutation screening in 8 AE families (15 patients out of 36 individuals) revealed the presence of six different mutations described elsewhere. Based on these results, we have evaluated the involvement of SLC39A4 in 14 patients of 12 additional AE pedigees coming either from France, Tunisia, Austria or Lithuania. A total of 7 SLC39A4 mutations were identified (1 deletion, 2 nonsense, 2 missense, and 2 modifications of splice site), of which 4 are novel: a homozygous nonsense mutation in 3 consanguineous Tunisian families [c.143T>G (p.Leu48X)], a heterozygous nonsense mutation (c.1203G>A (p.Trp401X)) in a compound heterozygote from Austria also exhibiting an already known missense mutation, and distinct homozygous mutations in families from France or Tunisia [c.475-2A>G and c.184T>C (p.Cys62Arg)]. Furthermore, two other potential mutations [c.850G>A (p.Glu284Lys) and c.193-113T>C] were also observed at homozygous state in a French family formerly described. This study brings to 21 the number of reported SLC39A4 mutations in AE families.

Acrodermatitis↗

Randomized trial of adoptive transfer of melanoma tumor-infiltrating lymphocytes as adjuvant therapy for stage III melanoma.

The aim of this study was to demonstrate the interest of using tumor-infiltrating lymphocytes (TIL) as adjuvant therapy for stage III (regional lymph nodes) melanoma. After lymph node excision, patients without any detectable metastases were randomly assigned to receive either TIL plus interleukin-2 (IL-2) for 2 months, or IL-2 only. The primary endpoint was determination of the duration of the relapse-free interval. Eighty-eight patients determined as eligible for treatment were enrolled in the study. After a median follow-up of 46.9 months, for the study population the analysis did not show a significant extension of the relapse-free interval or overall survival. However, a significant interaction ( P<0.001) was found between the treatment and the number of invaded lymph nodes. In the group with only one invaded lymph node, the estimated relapse rate was significantly lower ( P(adjusted)=0.0285) and the overall survival was increased ( P(adjusted)=0.039) in the TIL+IL-2 arm compared with the IL-2 only arm. No differences between the two arms, either as regards the duration of disease-free survival or overall survival, were noted in the group with more than one invaded lymph node whatever the number of invaded lymph nodes. Treatment was compatible with normal daily activity. This study demonstrates for the first time that the efficiency of TIL in stage III melanoma (AJCC) is directly related to the number of invaded lymph nodes, indicating that tumor burden might be a crucial factor in the efficacy and/or in vitro expansion of T cells specific for autologous tumor antigen, a finding which could be of value in future vaccine development for the treatment of melanoma.

Adjuvants, Immunologic↗

Therapeutic efficacy of melanoma-reactive TIL injected in stage III melanoma patients.

Adoptive therapy for cancer using tumor-infiltrating lymphocytes (TIL) has mainly been investigated in cancer patients with advanced stage disease. The limited clinical success has not been encouraging, although this might be explained by poor TIL specificity and/or high tumor burden. To re-evaluate the effectiveness of adoptive therapy, we analyzed the capacity of tumor-reactive TIL injection in preventing the further development of disease in stage III melanoma patients after complete tumor resection. A phase II/III randomized trial was performed on 88 melanoma patients, who received autologous TIL plus interleukin-2 (IL-2) or IL-2 only. The duration of relapse-free survival was analyzed, taking into account the immunological specificity of injected TIL and the number of metastatic lymph nodes removed before treatment. Kaplan-Meyer analysis revealed that the injection of tumor-reactive TIL was statistically correlated with prolonged relapse-free survival in patients with only one metastatic lymph node. Therefore, improved clinical outcome could be obtained after adoptive therapy by selecting appropriate groups of patients and monitoring the specificity of the injected TIL populations.

Adjuvants, Immunologic↗

Identification of SLC39A4, a gene involved in acrodermatitis enteropathica.

We have characterized the human gene SLC39A4, which encodes a protein with features characteristic of a ZIP zinc transporter. The chromosomal location and expression of SLC39A4, together with mutational analysis of eight families affected with acrodermatitis enteropathica, suggest that SLC39A4 is centrally involved in the pathogenesis of this condition.

Acrodermatitis↗

[General antibiotic therapy in acne].

The primary indication for systemic antibiotics is acute therapy for moderate-to-severe inflammatory acne. The preferred agents include tetracyclines and derivatives; macrolides, co-trimoxazole, and trimethoprim may represent acceptable alternatives. Antibiotics act mainly on inflammatory lesions (papules and pustules) and are only slightly comedolytic. Oral antibiotics reduce the number of Propionibacterium acnes. In addition, they have an anti-inflammatory activity. The side effects associated with oral antibiotics for acne depend on the drug; however, severe side effects are not common. Resistant strains of Propionibacterium acnes to antibiotics are increasing. Thus, general guidelines are useful when utilizing oral antibiotic therapy in acne.

Acne Vulgaris↗

[Herpes as viewed by the French: result of a survey conducted on 10,000 persons].

Herpes is a viral infection which increases, specifically genital herpes. The aim of this survey was to assess the perception of herpes in the general population and in patients with herpes in France using a self-administered questionnaire. A total of 10,000 persons answered the questionnaire among which 128 patients presented herpes. This study showed that only 5% of the French population knew that herpes was a viral infection, and 7% a sexually transmitted disease. Among patients with genital herpes only 34% indicated a sexual relationship and a mode of contamination. The interference with sexual and social life is important. Development of information and communication on herpes appears crucial.

Adolescent↗

Physiopathology of acne vulgaris: recent data, new understanding of the treatments.

Acne is the most frequent reason for seeing a dermatologist, but its physiopathology is not completely well-known. Yet understanding of the mechanisms of action of the different acne treatments is very important to optimize their use. A lot of new data on the physiopathology have recently been published in the acne field. This paper summarizes the main points of these new facts.

Acne Vulgaris↗