RESUMO
INTRODUCTION: Overweight is a well-established risk factor for hidradenitis suppurativa (HS). In this cross-sectional study, we compare HS patients with a high body mass index (BMI) with HS patients with a low BMI to investigate differences in disease characteristics. MATERIALS AND METHOD: Patients were recruited from 17 dermatological centres from four continents. A total of 246 patients with a BMI below 25 were compared to 205 patients with a BMI of above 35. RESULTS: Patients with a high BMI suffered more severe disease (Hurley, physician global assessment, number of areas affected and patient-reported severity (PRS), P < 0.001 for all). There was no difference in smoking (P = 0.783) nor in family history (P = 0.088). In both low and high BMI patients, early onset of HS was a predictor of positive family history (P < 0.001, for each). For low BMI patients, an increase in BMI significantly increased PRS (P < 0.001). For patients with a high BMI, number of pack-years significantly increased PRS (P = 0.001). Cluster analysis of eruption patterns was location specific for low BMI patients but severity specific for high BMI patients. DISCUSSION: Patients with a low and high BMI could represent two clinically different subtypes. We suggest a non-linear relationship between BMI and impact of HS. As patients go from a low BMI patient to a high BMI patient (or from high to low), eruption patterns and risk factors may change.
Assuntos
Índice de Massa Corporal , Hidradenite Supurativa/classificação , Hidradenite Supurativa/genética , Índice de Gravidade de Doença , Adulto , Idade de Início , Estudos Transversais , Feminino , Hidradenite Supurativa/complicações , Humanos , Masculino , Obesidade/complicações , Fatores de Proteção , Fatores de Risco , Fumar , Adulto JovemRESUMO
BACKGROUND: Rare highly penetrant gain-of-function mutations in caspase recruitment domain family, member 14 (CARD14) can lead to psoriasis, a chronic inflammatory disease of the skin and other organs. OBJECTIVES: To investigate the contribution of rare CARD14 variants to psoriasis in the Tunisian population and to expand knowledge of CARD14 variants in the European population. METHODS: CARD14 coding exons were resequenced in patients with psoriasis and controls from Tunisia and Europe, including 16 European cases with generalized pustular psoriasis (GPP). Novel variants were evaluated for their effect on nuclear factor (NF)-κB signalling. RESULTS: Rare variants in CARD14 were significantly enriched in Tunisian cases compared with controls. Three were collectively found in 5% of Tunisian cases, and all affected the N-terminal region of the protein harbouring its caspase recruitment domain or coiled-coil domain. These variants were c.349G>A (p.Gly117Ser), c.205C>T (p.Arg69Trp) and c.589G>A (p.Glu197Lys). c.589G>A (p.Glu197Lys) led to upregulation of NF-κB activity in a similar manner to that of previously described psoriasis-associated mutations. p.Arg69Trp led to sevenfold downregulation of NF-κB activity. One Tunisian case harboured a c.1356+5G>A splice alteration that is predicted to lead to loss of exon 9, which encodes part of the coiled-coil domain. No cases of GPP harboured an interleukin-36RN mutation, but one of 16 cases of GPP with a family history of psoriasis vulgaris harboured a c.1805C>T (p.Ser602Leu) mutation in CARD14. CONCLUSIONS: These observations provide further insights into the genetic basis of psoriasis in the Tunisian population and provide functional information on novel CARD14 variants seen in cases from Tunisia and other populations.
Assuntos
Proteínas Adaptadoras de Sinalização CARD/genética , Guanilato Ciclase/genética , Proteínas de Membrana/genética , Mutação/genética , Psoríase/genética , População Branca/genética , Adulto , Regulação para Baixo/genética , Feminino , Humanos , Masculino , NF-kappa B/metabolismo , Psoríase/etnologia , Transdução de Sinais , Tunísia , Regulação para Cima/genética , População Branca/etnologia , Adulto JovemAssuntos
Tinha do Couro Cabeludo/epidemiologia , Adulto , Idoso , Criança , Pré-Escolar , Epidermophyton/isolamento & purificação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tinha do Couro Cabeludo/microbiologia , Trichophyton/isolamento & purificação , Tunísia/epidemiologia , Adulto JovemRESUMO
Psoriasis is a multifactorial disease that involves genetic, immunological and environmental factors. During the last decade, several studies by genome scan on families or cases/controls helped to highlight more than ten loci "PSORS" located on different chromosomes and containing several candidate genes. Psoriasis appears as a genetic disease that follows the mixed model with the involvement of a major gene (PSORS1) and a set of minor genes with a variable penetrance depending on the locus. Genetic data have focused on the involvement of the immune system in the pathogenesis of psoriasis. It is now accepted that psoriasis is an immunological disease involving the response profiles TH1 and TH17. Much remains to be done to better elucidate the mechanisms involved in the genesis of psoriatic lesions to find new therapeutic targets.
Assuntos
Psoríase/etiologia , Psoríase/fisiopatologia , Animais , Diferenciação Celular , Mapeamento Cromossômico , Citocinas/metabolismo , Células Dendríticas/imunologia , Modelos Animais de Doenças , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Inflamação , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Queratinócitos/metabolismo , Queratinócitos/patologia , Camundongos , Camundongos Knockout , Camundongos Transgênicos , Penetrância , Psoríase/genética , Psoríase/imunologia , Psoríase/patologia , Células Th1/imunologia , Células Th17/imunologiaRESUMO
BACKGROUND: Recently, it has been shown that a deletion in the late cornified envelope (LCE) gene cluster (LCE3C_LCE3B-del) is associated with susceptibility to psoriasis in European and Asian populations. However, no study of this deletion has been performed in the North African population. The aim of the present study was to investigate whether this deletion is associated with familial psoriasis in Tunisian population. METHODS: A total of 34 patients and 55 healthy individuals were recruited from 7 multiplex families and a PCR assay was used to determine the association of this deletion. Its effect on susceptibility to psoriasis was assessed using the PDT program. RESULTS: We failed to detect any evidence of association between LCE3C_LCE3B-del and psoriasis in Tunisian families. No epistasic effect was found between the deletion and PSORS1 locus. CONCLUSIONS: These findings indicate that the LCE3C_LCE3B-del does not contribute in a major way to psoriasis susceptibility in Tunisian families.
Assuntos
Cromossomos Humanos Par 1/genética , Proteínas Ricas em Prolina do Estrato Córneo/deficiência , Psoríase/genética , Deleção de Sequência , Adolescente , Adulto , Idoso , Criança , Cromossomos Humanos Par 6/genética , Proteínas Ricas em Prolina do Estrato Córneo/genética , Epistasia Genética , Saúde da Família , Feminino , Predisposição Genética para Doença/genética , Genótipo , Antígenos HLA-C/genética , Humanos , Mutação INDEL , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Psoríase/epidemiologia , Psoríase/etnologia , Tunísia/epidemiologia , Tunísia/etnologia , Adulto JovemAssuntos
Leishmania infantum/isolamento & purificação , Leishmaniose Cutânea/diagnóstico , Doenças Labiais/diagnóstico , Antiprotozoários/uso terapêutico , Carcinoma de Células Escamosas/diagnóstico , Diagnóstico Diferencial , Humanos , Leishmaniose Cutânea/tratamento farmacológico , Leishmaniose Cutânea/epidemiologia , Leishmaniose Cutânea/parasitologia , Doenças Labiais/tratamento farmacológico , Doenças Labiais/parasitologia , Masculino , Meglumina/uso terapêutico , Antimoniato de Meglumina , Pessoa de Meia-Idade , Compostos Organometálicos/uso terapêutico , Neoplasias Cutâneas/diagnóstico , Tunísia/epidemiologiaRESUMO
BACKGROUND: The efficacy of topical antifungals is controversial. OBJECTIVE: To compare the efficacy and safety of a sequential(SEQ) treatment with chemical nail avulsion and topical antifungals to amorolfine nail lacquer in dermatophytic onychomycosis. METHODS: This was a randomized,parallel-group, controlled study comparing a 36-week SEQ treatment with chemical nail avulsion with RV4104A ointment(class I medical device containing 40% urea) followed by ciclopirox cream for 8 weeks and ciclopirox nail lacquer for 25 weeks (SEQ group) to amorolfine nail lacquer for 36 weeks (AMO group). Patients had to have a big toenail onychomycosis,sparing the matrix. The primary efficacy criterion was complete cure at week 48. A cost-effectiveness analysis was performed. RESULTS: A total of 142 patients were randomized. The complete cure rate at week 48 was significantly higher in the SEQ group than in the AMO group (36.6 vs. 12.7%, p = 0.001). Clinical cure at week 48 was observed in 53.5% of patients in the SEQ group versus 17% in the AMO group (p < 0.01). The cost of cure per patient was 50% lower with SEQ treatment (EUR 33) compared with amorolfine(EUR 76). CONCLUSION: A treatment of onychomycosis comprising chemical avulsion of the pathological nail, ciclopirox cream and nail lacquer is significantly more effective than amorolfine nail lacquer.
Assuntos
Dermatoses do Pé/tratamento farmacológico , Dermatoses do Pé/economia , Morfolinas/administração & dosagem , Onicomicose/tratamento farmacológico , Onicomicose/economia , Piridonas/administração & dosagem , Adolescente , Adulto , Idoso , Antifúngicos , Ciclopirox , Análise Custo-Benefício , Combinação de Medicamentos , Quimioterapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Pomadas/administração & dosagem , Piridonas/uso terapêutico , Estudos Retrospectivos , Creme para a Pele/administração & dosagem , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Psoriasis is a relapsing chronic inflammatory skin disease affecting all population groups, with a peak prevalence of 3% in northern European and Scandinavian caucasians. Epidemiological studies have implicated a genetic component to psoriasis. In the past 12 years multiple genome-wide linkage analyses have identified putative susceptibility loci on several chromosomes, with a major locus in the major histocompatibility complex region. OBJECTIVES: To investigate the genetic basis of familial psoriasis in the Tunisian population using a genome-wide linkage scan in seven ultiplex psoriatic families from Tunisia. METHODS: Following single nucleotide polymorphism (SNP) genotyping on the Affymetrix 10K SNP array, we performed nonparametric linkage (NPL) multipoint analyses to identify genotypes and obtain evidence for linkage with psoriasis across the genome. RESULTS: No chromosomal region gave consistent evidence for linkage, providing evidence for genetic heterogeneity in Tunisian psoriasis families. Significant evidence for linkage of psoriasis to chromosome 2p12 was seen in one family. We also identified several regions of tentative psoriasis linkage on chromosomes 2q, 4q, 6p, 11q, 12q, 9q and 13q. One family exhibiting suggestive evidence for linkage to 17q25 (PSORS2) was identified and all affected members harboured a p.Gly117Ser mutation in CARD14 (caspase recruitment domain family, member 14), recently reported to lead to psoriasis in a large family from the U.S.A. CONCLUSIONS: Our results support the genetic heterogeneity of psoriasis in the Tunisian population, provide confirmatory evidence for a novel psoriasis locus at chromosome 2p12 and reveal a psoriasis family with a mutation at PSORS2.
Assuntos
Cromossomos Humanos Par 2/genética , Predisposição Genética para Doença/genética , Polimorfismo de Nucleotídeo Único/genética , Proteínas/genética , Psoríase/genética , Adolescente , Adulto , Idoso , Proteínas Adaptadoras de Sinalização CARD , Criança , Feminino , Ligação Genética/genética , Genoma Humano/genética , Estudo de Associação Genômica Ampla , Genótipo , Guanilato Ciclase , Humanos , Masculino , Proteínas de Membrana , Pessoa de Meia-Idade , Linhagem , Tunísia , Adulto JovemRESUMO
Psoriasis is a common, chronic, systemic, inflammatory disease of the skin that is often associated with inflammatory musculoskeletal disease. Psoriasis impacts on affected individuals and on society at many levels, being associated with considerable economic burden and impaired quality of life. This article aims to provide dermatologists and their allied healthcare professionals, particularly those practicing in Africa and the Middle East, with a review of the current understanding of psoriasis, its treatment and impact, as a backdrop for further discussion of the management of psoriasis in these regions. Insight into the real-life, day-to-day challenges and unmet needs currently facing dermatologists in Africa and the Middle East is provided by the authors, most of whom are experienced dermatologists practicing in this region.
Assuntos
Psoríase/tratamento farmacológico , África , Artrite Psoriásica/diagnóstico , Artrite Psoriásica/prevenção & controle , Doenças Cardiovasculares/etiologia , Dermatologia , Gerenciamento Clínico , Humanos , Oriente Médio , Guias de Prática Clínica como Assunto , Psoríase/complicações , Psoríase/diagnóstico , Fatores de RiscoRESUMO
BACKGROUND: Melasma is a frequent cause of consultations at dermatology departments by dark-skinned patients in Tunisia. OBJECTIVE: To investigate factors that influence melasma severity in a large Tunisian population. METHODS: A total of 197 patients (188 women and 9 men), who attended Tunis Military Hospital for a consultation were included prospectively from August 2005 to August 2006. Disease severity was estimated using the Melasma Area and Severity Index (MASI). Aggravating factors were investigated using multiple logistic regressions. RESULTS: Of the women included, 14% presented phototype III, 45% phototype IV and 41% phototype V; 76% presented a centrofacial melasma phenotype, 23% a malar and 1% a mandibular phenotype. About 60% developed melasma before thirty. Sun exposure was reported as a triggering factor by 51% of women and as an aggravating factor by 84%. Pregnancy was reported as an aggravating factor by 51% of women who had been pregnant, and oral contraceptive use reported by 38% of women exposed to oral contraceptives. The risk of severe melasma was about three times higher for women with age at onset under 30, phototype V and major lifetime sun exposure and about 8 times higher for women exposed to oral contraceptives. CONCLUSION: This study identifies a number of factors associated with the severity of melasma. Further epidemiological studies in this type of population, in particular, to investigate triggering factors, are justified by the aesthetic damage caused by melasma in dark-skinned patients, lack of efficacy of existing treatments, non-compliance with photoprotection recommendations and the challenge of treatment.
Assuntos
Melanose/epidemiologia , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Índice de Gravidade de Doença , Inquéritos e Questionários , TunísiaRESUMO
Tacrolimus 0.03% ointment is licensed for second-line treatment of children with atopic dermatitis (AD). Although data are available from clinical trials, no study has enrolled only second-line patients. This double-blind, non-inferiority study compared tacrolimus 0.03% and fluticasone 0.005% ointments in children with moderate-to-severe AD, who had responded insufficiently to conventional therapies. Children (aged 2-15 yr) were randomized to tacrolimus ointment (n = 240) or fluticasone ointment (n = 239), twice daily until clearance or for a maximum of 3 wk and, if lesions remained, once daily for up to 3 wk further. Primary end-point was week 3 response rate (improvement of >or=60% in modified Eczema Area and Severity Index and not withdrawn for lack of efficacy). Secondary end-points included pruritus and sleep quality, global assessment of clinical response, incidence of new flares and safety. Response rates were 86.3% with tacrolimus ointment and 91.5% with fluticasone. Lower limit of the 95% confidence interval was -11.8%, exceeding the non-inferiority limit of -15% and meeting the primary end-point. Moderate or better improvement on the physicians' global assessment occurred in 93.6% and 92.4% of patients in the tacrolimus ointment and fluticasone arms, respectively, while median pruritus scores improved by 84.0% and 91.5%. Sleep quality improved by approximately 92% in both treatment arms. After day 21, new flare-up occurred in 5.5% and 11.3% of patients receiving tacrolimus ointment and fluticasone, respectively; mean times to new flares were 6.5 +/- 5.0 and 8.6 +/- 5.2 days. Adverse events were similar between the two arms, with the exception of application-site skin burning sensation in the tacrolimus ointment group. In conclusion, efficacy of tacrolimus 0.03% ointment as second-line treatment was not inferior to that of fluticasone 0.005% ointment, with similar benefits on global disease improvement and quality of sleep.
Assuntos
Androstadienos/administração & dosagem , Inibidores de Calcineurina , Dermatite Atópica/tratamento farmacológico , Fármacos Dermatológicos/administração & dosagem , Tacrolimo/administração & dosagem , Adolescente , Androstadienos/efeitos adversos , Criança , Pré-Escolar , Fármacos Dermatológicos/efeitos adversos , Feminino , Fluticasona , Humanos , Masculino , Pomadas , Prurido/tratamento farmacológico , Recidiva , Transtornos do Sono-Vigília/tratamento farmacológico , Tacrolimo/efeitos adversos , Resultado do TratamentoRESUMO
Psoriasis has been hypothesized to be associated with lymphoma. Several studies demonstrated an epidemiological relationship between these two entities. Patients with psoriasis are at increased risk for developing lymphoproliferative malignancies. This risk can be also the consequence of immunosuppressive therapies (methotrexate or cyclosporine). We report a 65-year-old man who presented with diffuse erythematous plaques with pustular or squamous borders. Histopathologic evaluation concluded to a pustular psoriasis. We discover simultaneously a stage 4 bone marrow B lymphoma of low grade of malignancy. This case report highlights the relationships between psoriasis and lymphoma.
Assuntos
Linfoma de Células B/diagnóstico , Síndromes Paraneoplásicas/diagnóstico , Psoríase/diagnóstico , Idoso , Humanos , MasculinoRESUMO
BACKGROUND: No specific data are available on tacrolimus ointment as a second-line treatment in adults with facial eczema. OBJECTIVES: To compare tacrolimus 0.1% and fluticasone 0.005% ointments in adults with moderate to severe atopic dermatitis (AD) of the face in whom conventional treatment was ineffective or poorly tolerated. METHODS: Patients were randomized to double-blind treatment of facial AD with twice-daily tacrolimus ointment (n = 288) or fluticasone ointment (n = 280) for 3 weeks or until clearance. After day 21, patients could continue without the study treatment, apply the same ointment once daily, or switch to the other medication twice daily, depending on lesion clearance and patient/physician satisfaction. The primary endpoint was the day-21 response [> or = 60% reduction in the modified Local Eczema and Severity Index (mLEASI) score]. Secondary endpoints included facial erythema and pruritus, global clinical response, treatment switching at day 21 and safety. RESULTS Response with tacrolimus ointment (93%) was superior to that with fluticasone (88%; P = 0.026). Improvements in mLEASI components were also greater with tacrolimus ointment. Facial erythema and pruritus improved in both groups. Global clinical response was rated 'marked improvement' or better in 88% and 79% of patients in the tacrolimus ointment and fluticasone groups, respectively. At day 21, 9% of patients switched from fluticasone to tacrolimus ointment, while 4.5% switched from tacrolimus ointment to fluticasone. Adverse events were more frequent with tacrolimus ointment as a result of the higher incidence of application-site skin burning sensation. Safety of both drugs was in line with their respective summary of product characteristics. CONCLUSIONS: Tacrolimus 0.1% ointment has superior efficacy to fluticasone 0.005% ointment for twice-daily treatment of adults with moderate to severe facial AD in whom conventional therapy was inadequately effective or not tolerated. Tacrolimus 0.1% ointment is a safe and effective second-line treatment for the control of moderate to severe AD of the face.
Assuntos
Androstadienos/administração & dosagem , Dermatite Atópica/tratamento farmacológico , Fármacos Dermatológicos/administração & dosagem , Dermatoses Faciais/tratamento farmacológico , Imunossupressores/administração & dosagem , Tacrolimo/administração & dosagem , Administração Cutânea , Adolescente , Adulto , Idoso , Método Duplo-Cego , Esquema de Medicação , Feminino , Fluticasona , Humanos , Masculino , Pessoa de Meia-Idade , Pomadas/administração & dosagem , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: The authors wanted to report an uncommon etiology of erythema nodosum. CASE REPORT: A 45-year-old woman presented with numerous encrusted nodular lesions on the left leg and arm. Leishmania was identified after a parasitological examination. Subcutaneous erythematous nodules developed later on the same leg. Erythema nodosum was diagnosed with a biopsy of the nodules. The patient was treated with systemic meglumine 60 mg/kg per day for 13 days. All lesions improved under treatment. DISCUSSION: This was the first reported case of unilateral erythema nodosum with cutaneous leishmaniasis. Clinical and laboratory exams were in the range of normal and led the authors to exclude common causes of erythema nodosum. Subcutaneous nodules occurred before the beginning of treatment with meglumine. Thus, drug allergy (previously reported) was excluded as an etiology of EN.
Assuntos
Eritema Nodoso/tratamento farmacológico , Leishmaniose Cutânea/tratamento farmacológico , Meglumina/uso terapêutico , Biópsia , Hipersensibilidade a Drogas , Eritema Nodoso/complicações , Eritema Nodoso/patologia , Feminino , Humanos , Leishmaniose Cutânea/complicações , Leishmaniose Cutânea/patologia , Pessoa de Meia-IdadeAssuntos
Predisposição Genética para Doença , Psoríase/genética , Adolescente , Adulto , Idoso , Proteínas Adaptadoras de Sinalização CARD , Criança , Feminino , Ligação Genética , Guanilato Ciclase , Humanos , Masculino , Proteínas de Membrana , Repetições de Microssatélites/genética , Pessoa de Meia-Idade , Linhagem , Proteínas/genética , Tunísia , Adulto JovemRESUMO
BACKGROUND: Psoriasis is a chronic inflammatory skin disease. The familial nature of psoriasis has long been recognized. Aim of our study was to describe the epidemiological, clinical and genetic features of familial psoriasis. METHODS: Through a prospective study we investigated during a study period of lyear (2006-2007) 9 Tunisian unrelated multiplex families. Patients with psoriasis and their available family members were examined by the same dermatologist. RESULTS: Thirty nine individual presented psoriasis (25 men and 4 women), with a mean age at onset about 19.8 years. With the systematic exam of member's family we discover 11 cases of unknown psoriasis. The common form of psoriasis was the preponderant one (37 cases). The nails, the scalp, the mucous membranes were involved respectively in 21, 12 and 13 cases. The psoriasis was severe in 11 cases. CONCLUSION: Through this study we find similar epidemiological and clinical features of those reported previously. The intra and inter-familial variability was evident in our patients.
Assuntos
Psoríase/genética , Adolescente , Adulto , Idoso , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem , Estudos Prospectivos , Tunísia , Adulto JovemAssuntos
Líquen Plano/diagnóstico , Corticosteroides/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Betametasona/análogos & derivados , Betametasona/uso terapêutico , Biópsia , Diagnóstico Diferencial , Emolientes/administração & dosagem , Extremidades , Antagonistas não Sedativos dos Receptores H1 da Histamina/uso terapêutico , Humanos , Líquen Plano/tratamento farmacológico , Líquen Plano/patologia , Loratadina/análogos & derivados , Loratadina/uso terapêutico , Masculino , Vaselina/administração & dosagem , Pele/patologia , Adulto JovemRESUMO
A new spectroscopically determined potential energy surface (PES) for HD(16)O is presented. This surface is constructed by adjusting the high accuracy ab initio PES of Polyansky et al. [Science 299, 539 (2003)] by fitting to both published experimental data and our still unpublished data. This refinement used experimentally derived term values up to 25,000 cm(-1) and with J< or =8: a data set of 3478 energy levels once some levels with ambiguous assignment is excluded. To improve the extrapolation properties of the empirical PES, the restraint that the resulting PESs remain close to the ab initio surface was imposed. The new HDO_07 PES reproduces the experimental data, including high J levels not included in the fit, with a root mean square error of 0.035 cm(-1). Predictions for rotation-vibration term values up to J=12 are made.