The role of exposome in acne: results from an international patient survey.

BACKGROUND: Acne severity and its response to treatment may be influenced by internal and external factors: the exposome. OBJECTIVES: The aim of this international real-life survey was to assess the most involved exposome factors in acne. METHODS: Eleven thousand individuals, aged between 15 and 39 years, with clinically confirmed acne or without acne, defined by age, gender and prevalence, were invited to participate in an Internet survey of 63 questions in order to assess the frequency of identified acne exposome factors. RESULTS: Data from 6679 questionnaires were used for statistical analysis purposes: 2826 from the acne group and 3853 from the control group. Nibbling, consumption of dairy products, sweets, alcohol or whey proteins, as well as exposure to pollution, stress, certain mechanical factors and humid or hot weather or sun exposure, were significantly (all P ≤ 0.05) more frequently reported for the acne group than for the control group. This was not the case for tobacco consumption. Data regarding the impact of cannabis consumption were insufficient for drawing any conclusions. CONCLUSIONS: Data from this international, anonymized Internet questionnaire conducted with more than almost 6700 participants add new arguments to assumptions made that certain exposome factors have an impact on acne. Nutrition, pollution, stress and harsh skincare, as well as climate and sun exposure may be considered the most frequent factors related to acne.

The influence of exposome on acne.

BACKGROUND: Acne vulgaris is one of the main reasons for dermatological consultations. Severity and response to treatment may be impacted by various external factors or exposome. AIM: To assess the impact of environmental factors on acne and to provide a comprehensive overview of the acne exposome. METHODS: Two consensus meetings of five European dermatologists and a comprehensive literature search on exposome factors triggering acne served as a basis for this review. RESULTS: Acne exposome was defined as the sum of all environmental factors influencing the occurrence, duration and severity of acne. Exposome factors impact on the response and the frequency of relapse to treatments by interacting with the skin barrier, sebaceous gland, innate immunity and cutaneous microbiota. They may be classified into the following six main categories: nutrition, psychological and lifestyle factors, occupational factors including cosmetics, as well as pollutants, medication and climatic factors. Moreover, practical considerations for the dermatologist's clinical practice are proposed. CONCLUSION: Exposome factors including nutrition, medication, occupational factors, pollutants, climatic factors, and psychosocial and lifestyle factors may impact on the course and severity of acne and on treatment efficacy. Identifying and reducing the impact of exposome is important for an adequate acne disease management.

A skincare combined with combination of adapalene and benzoyl peroxide provides a significant adjunctive efficacy and local tolerance benefit in adult women with mild acne.

INTRODUCTION: Acne in adult women is an increasing reason for dermatological consultations. OBJECTIVE: The aim of this study was to assess in adult women with mild acne the efficacy and tolerance of a daily adjunctive application of a skincare (Normaderm® , Laboratoires Vichy, France) to a fixed combination of adapalene/benzoyl peroxide daily or every other evening and a standard emollient. METHODS: Subjects were randomized to receive the fixed combination applied either every evening or every other evening and a daily application of the standard emollient and the test care or a once daily application of the fixed combination and the standard emollient alone. Clinical evaluations at Day 0, Day 45 and Day 90 included the count of acne lesions, assessment of clinical improvement and local tolerance. The quantitative lipid profile of the stratum corneum of the forehead was also determined. RESULTS: After 90 days of application, acne had improved in all 299 subjects with a statistically significant difference in favour of the test care regimens (P < 0.05). Moreover, skin quality, subject satisfaction, skin discomfort and sebum composition were in favour of these regimens. CONCLUSION: In conclusion, the tested skincare combined with a fixed adapalene and benzoyl peroxide combination provides a significant adjunctive efficacy and local tolerance benefit in adult women with mild acne.

[Pain management and the use of analgesics in dermatology]. / Prise en charge de la douleur et consommation d'antalgiques en dermatologie.

OBJECTIVE: To determine pain assessment and management, and the use of analgesics in dermatology. PATIENTS AND METHODS: Two hundred and sixty six patients hospitalised in a dermatology university department (Henri-Mondor, Créteil) between November 1999 and April 2000 were enrolled in a prospective study. Clinical evaluation of pain intensity and evolution were studied using a visual analogic scale (VAS) pain score at presentation, during hospitalisation, and at discharge. Prescription and consumption of analgesics were also studied. RESULTS: Fifty-nine percent of the patients experienced pain. Eighty-four percent of them had mild or moderate to severe pain (VAS<7/10) and were relieved with non or mild opioid analgesics (discharge VAS<4/10). Sixteen percent of them had intense pain requiring morphine (VAS score >=7/10). CONCLUSIONS: Pain management is very important in dermatology. Every physician should know its principles since dermatologists play a crucial role in the patient's care.

[Intravascular large cell lymphoma revealed by diffuse telangiectasia and cauda equina syndrome]. / Lymphome intravasculaire révélé par des télangiectasies diffuses et un syndrome de la queue de cheval.

BACKGROUND: Intravascular lymphoma is a rare disease with usually fatal outcome, characterized by the proliferation within the lumen of small blood vessels of neoplastic large lymphoid cells of B-cell origin. We report a case of intravascular lymphoma revealed by diffuse telangiectasia and cauda equina syndrome. CASE REPORT: A 64-year-old Vietnamese woman presented with unexpected fever and weight loss. Three months after the onset of the first symptoms, an oedema appeared on the lower limbs and the trunk, followed by the eruption of diffuse superficial telangiectasia. Neurologic examination revealed a cauda equina syndrome. The diagnosis of intravascular B cell lymphoma was established on cutaneous and muscular biopsy specimen. A moderate hemophagocytic syndrome was observed, confirmed by bone marrow biopsy. Corticosteroid therapy was started, followed by combination chemotherapy yielding complete response. Six months later death occurred, without evidence of relapse of intravascular lymphoma. DISCUSSION: Clinical presentation of intravascular lymphoma is often confusing, mimicking systemic disease, with a predilection for skin and nervous system involvement. Diagnosis is difficult and often an autopsy finding. Prognosis is generally poor, but favourable responses to chemotherapy have been observed after early diagnosis and treatment. The pathogenesis of intravascular lymphoma remains unknown. Dysfunction of cell-endothelial interaction affecting adhesion molecules has been suspected. The implication of Epstein-Barr virus in intravascular lymphoma remains controversial.

Erythrodermic cutaneous T-cell lymphoma with disseminated pustulosis. Production of high levels of interleukin-8 by tumour cells.

Interleukin (IL) -8 is a neutrophil chemoattractant cytokine with proinflammatory and growth-promoting activities, which is involved in the pathogenesis of several inflammatory diseases. It is found in high amounts in lesional biopsies of pustular diseases such as psoriasis and palmoplantar pustulosis. We report a 50-year-old woman with a 10-year history of erythroderma with disseminated pustulosis. Skin biopsies showed an epidermotropic infiltrate composed of atypical CD4+ CD8+ lymphocytes with numerous admixed neutrophils. Peripheral blood flow cytometric analysis revealed a major clonal subset of CD3+ CD4+ CD8+ T-cell receptor Vbeta22+ atypical lymphocytes. Bone marrow biopsy, lymph node biopsy and computed thoracoabdominal tomography were normal. Serologies for human T-cell lymphotropic virus type I and human immunodeficiency virus were negative. Our patient's status deteriorated despite topical (nitrogen mustard, psoralen plus ultraviolet A) and systemic (interferon, methotrexate, multiagent chemotherapy) treatments, and she finally died. We showed that our patient's peripheral blood lymphocytes (PBL) spontaneously produced high amounts of IL-8. In contrast, PBL of patients with classical Sézary syndrome produced lower amounts of IL-8. The production of IL-8 by tumour T cells could explain this unusual clinical and histopathological presentation of cutaneous T-cell lymphoma as disseminated pustulosis.

Leucoderma associated with flares of erythrodermic cutaneous T-cell lymphomas: four cases. The French Study Group of Cutaneous Lymphomas.

We describe four patients with erythrodermic cutaneous T-cell lymphomas (two with erythrodermic mycosis fungoides, and two with Sézary syndrome) who presented with extensive hypopigmented lesions that occurred during flares of their cutaneous disease. These cases must be distinguished from previously described hypopigmented mycosis fungoides where hypopigmented lesions were the sole manifestation of the lymphoma. In two cases a biopsy was performed on hypopigmented skin, showing an infiltrate of atypical lymphocytes with epidermotropism and absence of melanocytes, as in vitiligo. It is suggested that the hypopigmentation could be due to the cytotoxicity of tumour or reactional lymphocytes directed against melanocytes.

Triggering CD101 molecule on human cutaneous dendritic cells inhibits T cell proliferation via IL-10 production.

Since the CD101 molecule is expressed on a major subpopulation of HLA-DR(+), CD1a(+), CD1c(+) cutaneous dendritic cells (DC), we studied the functional role of CD101 on cutaneous DC. Anti-CD101 monoclonal antibody (mAb) inhibited the proliferation of T cells induced by cutaneous DC. There was a synergistic inhibition between anti-CD101 mAb and anti-CD86/anti-CD80 mAb. Anti-CD101 mAb exerted its inhibitory effect when binding to the CD101 expressed on cutaneous DC. No positive role of CD101 putative ligand expressed by T cells in T cell proliferation was demonstrated, as T cells proliferated in response to soluble anti-CD3 mAb in the presence of CD86-transfected cells but not in the presence of CD101-transfected cells. Of major significance is the fact that IL-10 was produced by cutaneous DC after CD101 triggering with anti-CD101 mAb, while IL-10 secretion was up-regulated in mixed cutaneous DC-T cell cultures after CD101 triggering. Furthermore, IL-10-neutralizing mAb could reverse the inhibition induced by anti-CD101 mAb. Our results demonstrate that the CD101 triggering on cutaneous DC inhibits T cell proliferation via IL-10 production, suggesting an important regulatory role played by the CD101 molecule on DC during T cell activation.

Paraneoplastic pemphigus with circulating antibodies directed exclusively against the pemphigus vulgaris antigen desmoglein 3.

A patient with follicular B-cell lymphoma presented with erythroderma associated with cutaneous and mucosal blisters. Histologic and direct immunofluorescence analysis of lesional skin showed a typical pattern of paraneoplastic pemphigus (PNP). Interestingly, indirect immunofluorescence on rat bladder was negative and immunoblot analysis of the patient's serum on epidermal extracts demonstrated antiepidermal antibodies that only recognized the pemphigus vulgaris antigen desmoglein 3, with no antibodies directed against the different proteins of the plakin family. To our knowledge this has never been reported in the literature. It exemplifies the overlap between pemphigus vulgaris and PNP and the pathogenic role of anti-desmoglein 3 antibodies in PNP. Moreover, it underscores the need to consider clinical, histologic, and immunologic features for the diagnosis of PNP.

CD101 expression by Langerhans cell histiocytosis cells.

AIMS: Our objective was to study the expression of a recently identified cell surface molecule, CD101 and in Langerhans cell histiocytosis (LCH) patients as CD101 has been shown to be present on dendritic cells. We wanted to determine if CD101 expression could be helpful for the diagnosis of LCH in conjunction with other markers (CD1a, S100 protein), and could be predictive of the evolution and dissemination of the disease. METHODS AND RESULTS: The expression of CD101 was studied by immunohistochemical technique in 11 cases of Langerhans cell histiocytosis on frozen sections. The expression of CD101 was positive in nine cases, high in six cases and low in three cases. There was no expression in the other two cases. No correlation with the evolution, the localization or the dissemination of the disease could be evidenced. CONCLUSIONS: CD101 is a new phenotypic marker that might be useful in combination with other markers for the diagnosis of LCH. However, as the anti-CD101 antibody works only in frozen sections, its value is limited compared to anti-CD1a antibody.

Stromal-cell derived factor is expressed by dendritic cells and endothelium in human skin.

Stromal-cell derived factor or SDF-1 is a CXC chemokine constitutively expressed by stromal bone marrow cell cultures that binds to the G-protein-coupled receptor CXCR4. SDF-1/CXCR4 represents a unique, nonpromiscuous ligand/receptor pair that plays an essential role in prenatal myelo- and lymphopoiesis as well as in cardiovascular and neural development. SDF-1 prevents entry of CXCR4-dependent (X4) HIV viruses in T lymphocytes, by binding and internalizing CXCR4. The expression pattern of SDF-1 protein in normal tissues is not known. Here we describe an analysis of SDF-1 mRNA and protein in normal and inflamed skin by in situ hybridization and immunohistochemistry, using a novel anti-SDF-1 monoclonal antibody. We also describe the expression pattern of CXCR4 receptor by immunohistochemistry. Our results show that SDF-1 protein and mRNA are normally expressed by endothelial cells, pericytes, and either resident or explanted CD1a+ dendritic cells. Epithelial cells of sweat glands but not keratinocytes also express SDF-1. In various inflammatory skin diseases, a large number of mononuclear cells and fibroblasts in close contact with CXCR4-positive lymphocytic infiltrates also express SDF-1. CXCR4 was also detected in many different normal cell types, including endothelial and epithelial cells, which points to a role for SDF-1/CXCR4 cell signaling in vascular and epithelial homeostasis. The demonstration of SDF-1 expression in dendritic and endothelial cells provides new insights into the mechanisms of normal and pathological lymphocyte circulation and makes it possible to envisage a role for locally secreted SDF-1 in the selective incapacity of mucosal dendritic cells to support and propagate infection by X4 HIV isolates.

Increased fibroblast elastase activity in acquired cutis laxa.

BACKGROUND: Acquired cutis laxa is a rare disease characterized by sagging skin, premature wrinkling and reduced skin elasticity. OBSERVATION: We report a 21-year-old woman, who presented with acquired cutis laxa on the face and the ear lobes. Urticarial papules had preceded for 6 years. There was no systemic involvement. Skin specimens were obtained from lax skin and urticarial papules, and from healthy controls. Histology showed only few perivascular lymphocytes in lax ear skin and a dense inflammatory infiltrate in urticarial skin. In both biopsies elastic fibres were decreased as demonstrated by computerized morphometric analyses. Elastase activities of fibroblasts in culture were evaluated. There was a 2- to 3-fold increase in elastase activity in urticarial skin fibroblasts, contrasting with a normal elastase activity in lax ear skin. CONCLUSION: Our findings suggest that the inflammatory cells could play a significant role in the destruction of elastic fibres.

[Pilotropic T-cell lymphoma without mucinosis: 5 new cases]. / Lymphomes T pilotropes sans mucinose: 5 nouveaux cas.

BACKGROUND: Pilotropic cutaneous T-cell lymphomas without mucinosis are rare, with 27 cases previously reported. Diagnosis and classification may be difficult. The clinical course and histopathological and immunohistochemical findings in 5 patients are described. PATIENTS AND METHODS: Patients were selected from the register of the French Study Group for cutaneous lymphomas. The criteria for inclusion were clinical pilofollicular manifestations and histological features of pilotropic T-cell lymphoma without mucinosis. RESULTS: Five patients were selected. The most frequent clinical manifestations were follicular keratosis, alopecia and follicular papules. Typical lesions of mycosis fongoides were present for several years in 3 patients, and lymphomatoid papulosis preexisted in one patient. Histopathological analysis showed an infiltrate composed of CD3+ and CD4+ atypical lymphocytes involving the follicular epithelium with alteration of the hair follicle walls. Epidermotropism was associated with pilotropism and situated near the follicular lesions or farther apart. Alcian blue stains results were negative in all specimens. PCR studies showed the presence of a T-cell clone in the skin lesions in all cases. COMMENTS: Diagnosis of pilotropic cutaneous T cell lymphomas without mucinosis may be difficult in case of discrete epidermotropism, minimal infiltrate or involvement of the follicular epithelium. Pilotropism could define a particular variant of T-cell lymphomas.

Immunization through dermal delivery of protein-encoding DNA: a role for migratory dendritic cells.

The early mechanisms by which DNA-dependent immunization occurs remain poorly understood. We determined whether intradermal injection of a cytomegalovirus (CMV) promoter-driven plasmid encoding hen egg lysozyme (pCMV:HEL) induced sensitization against the encoded protein, and whether cutaneous dendritic cells (DC) were involved in this sensitization. Both humoral and cellular responses to HEL were observed. DC that migrated from skin explant culture 3 days after injection of pCMV:HEL DNA contained mRNA encoding HEL. They induced a 3.5-7-fold increase in [3H]thymidine incorporation by HEL protein-primed CD4+ T cells compared to that induced by DC from mice injected with control plasmid. DC emigrating from skin explants recovered from pCMV:HEL injected mice also sensitized naive mice after adoptive transfer and induced the generation of CTL. Thus following DNA delivery within the dermis, DC can induce primary and secondary immune responses.

Polymerase chain reaction analysis of immunoglobulin gene rearrangement in cutaneous lymphoid hyperplasias. French Study Group for Cutaneous Lymphomas.

UNLABELLED: The differential diagnosis of cutaneous lymphoid hyperplasia and B-cell lymphoma may be difficult. Whether the detection of clonal immunoglobulin gene rearrangement in the cutaneous lesion is predictive of a malignant outcome remains controversial. We therefore studied cases of cutaneous lymphoid hyperplasia by polymerase chain reaction analysis. DESIGN: Retrospective study of patients seen between 1988 and 1996. SETTING: Two dermatology university departments. PATIENTS: Twenty-four patients with cutaneous lymphoid hyperplasias were included according to clinical, histopathological, and immunophenotypic criteria. MAIN OUTCOME MEASURES: Clinical, histopathological, and laboratory findings. RESULTS: There were 13 men and 11 women (mean age, 49 years) who presented with erythematous or violaceous papules or nodules. The lesions were unique in 13 cases and multiple in 11 cases. All patients had immunochemical evidence of a mixed T- and B-cell infiltrate with polytypic B cells. Polyclonality was demonstrated in 23 patients, whereas a dominant B-cell clone was detected in 1 patient. No lymphoma developed during the follow-up (median, 4 years). In the same period, we studied 53 cases of B-cell lymphomas. Thirty-five (66%) of the 53 cases had a detectable clonal immunoglobulin gene rearrangement. CONCLUSIONS: In the majority of our cases, polyclonality demonstrated by polymerase chain reaction analysis was in accordance with the diagnosis of cutaneous lymphoid hyperplasia. In 1 of the 24 patients, the presence of a B-cell clone could be evidenced. This fact did not modify the treatment as there were no histological or immunophenotypic signs suggestive of a lymphoma.

Genetic immunization with glycoprotein 63 cDNA results in a helper T cell type 1 immune response and protection in a murine model of leishmaniasis.

Genetic immunization is a promising gene therapy approach for the prevention and treatment of infectious disease. Plasmid DNA expressing genes of pathogens is directly introduced into host cells and specific cell-mediated and/or humoral immune responses are elicited against the encoded protein. Leishmaniasis is a significant world-wide health problem for which no vaccine exists. In susceptible animals, such as BALB/c mice, protection from leishmaniasis requires induction of a Thl immune response. In this study, cell-mediated immunity to Leishmania major (L. major) was induced by injecting BALB/c mice intradermally with plasmid DNA expressing the conserved L. major cell surface glycoprotein gp63 (gp63-pcDNA-3). CD4 T lymphocytes from gp63-pcDNA-3-immunized mice proliferated and produced IFN-gamma (but not IL-4) when stimulated in vitro with freeze-thawed parasites, consistent with a Th1 immune response. In contrast, lymphocyte proliferation in animals immunized with freeze-thawed parasites was associated with IL-4 (but not IFN-gamma) production, suggesting a nonprotective Th2 response. Challenge studies revealed that gp63-pcDNA-3 vaccination protected 30% of susceptible mice (21 of 70) from Leishmania infection while neither gp63 protein (0 of 20) nor freeze-thawed parasite vaccines (0 of 50) were efficacious. Dendritic cells derived from skin of gp63-pcDNA-3-injected mice also immunized naive recipients and protected them from leishmaniasis. We conclude that gp63-pcDNA-3 genetic vaccination results in a CD4-dependent Th1 immune response that correlates with protection from disease, and suggest that skin-derived dendritic cells are involved in priming this response.