RESUMO
BACKGROUND: Though patient needs are key drivers of treatment decisions, they are rarely systematically investigated in routine care. OBJECTIVE: This study aimed at analysing needs and expectations from the patient perspective in the German and Swiss psoriasis registries PsoBest and Swiss Dermatology Network of Targeted Therapies (SDNTT) with respect to treatment choice, age and gender. METHODS: The German and Swiss psoriasis registries observe patients recruited at first-time use of systemic drugs. Within 10 years, clinical [Psoriasis Area Severity Index (PASI), Body Surface Area (BSA)] and patient-reported outcomes are documented, including the Dermatology Quality of Life Index (DLQI) and the Patient Benefit Index (PBI), characterizing patient needs for treatment. The analysis data set includes n = 4894 patients from PsoBest and n = 449 from SDNTT with mean follow-up time of 7.5 months. RESULTS: A total of 5343 patients registered between 2008 and 2016 were included in the analyses (at baseline: 59.6% male, mean age 47.6 years ± 14.5, PASI 14.2 ± 9.7, BSA 22.7 ± 19.7, DLQI 11.3 ± 7.2). The most important patient needs were to 'get better skin quickly' and to 'be healed of all skin defects'. Subgroup analyses by age revealed significant differences in needs, especially higher needs regarding social impairments in patients younger than 65 years. Patients 65 years or older attributed more importance to sleep quality, less dependency on medical visits, fewer side-effects and confidence in the therapy. Out of 25 items reflecting patient needs, 20 items were rated significantly more important by women than men, with the greatest differences regarding feeling of depression, sleep quality and everyday productivity. Divided by treatment, needs were rated differently, recommending individualized and targeted choice of therapy. CONCLUSION: Age and gender stratify patient needs. Women showed higher expectations and rated specific needs in psoriasis treatment higher than men. Analysing the patient needs on an individual level will facilitate shared decisions by patient and physician in finding the optimal personalized treatment.
Assuntos
Fármacos Dermatológicos/uso terapêutico , Necessidades e Demandas de Serviços de Saúde , Planejamento de Assistência ao Paciente , Preferência do Paciente , Psoríase/tratamento farmacológico , Adulto , Fatores Etários , Depressão/etiologia , Fármacos Dermatológicos/efeitos adversos , Feminino , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação das Necessidades , Psoríase/psicologia , Sistema de Registros , Fatores Sexuais , Sono , Participação Social , SuíçaRESUMO
BACKGROUND: Several treatment options are currently available for the treatment of psoriasis. OBJECTIVE: To explore the main associations between patients' characteristics and systemic treatments prescribed for psoriasis in a large group of patients observed in real-life clinical practice. METHODS: This was a retrospective analysis of baseline data collected within the Swiss Dermatology Network for Targeted Therapies registry in Switzerland between March 2011 and December 2017. Semantic map analysis was used in order to capture the best associations between variables taking into account other covariates in the system. RESULTS: A total of 549 patients (mean age 46.7 ± 14.7 years) were included in the analysis. Conventional therapies such as retinoids and methotrexate were associated with no previous systemic therapies for psoriasis, a moderate quality of life (QoL) at therapy onset and older age (≥60 years). Fumaric acid derivatives were associated with mild psoriasis (psoriasis area severity index < 10) and long disease duration (≥20 years). On the other side, cyclosporine and psoralen and ultraviolet A/ultraviolet B treatments were linked to a more severe condition, including impaired QoL, hospitalization and inability to work. Regarding biological therapies, both infliximab and adalimumab were connected to the presence of psoriatic arthritis, severe disease condition and other comorbidities, including chronic liver or kidney diseases and tuberculosis. Etanercept, ustekinumab and secukinumab were all connected to a complex history of previous systemic treatments for psoriasis, moderate disease condition, overweight and university education. CONCLUSIONS: The analysis shows multifaceted associations between patients' characteristics, comorbidities, disease severity and systemic treatments prescribed for psoriasis. In particular, our semantic map indicates that comorbidities play a central role in decision-making of systemic treatments usage for psoriasis. Future studies should further investigate specific connections emerging from our data.
Assuntos
Fármacos Dermatológicos/uso terapêutico , Psoríase/tratamento farmacológico , Adulto , Algoritmos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Psoríase/fisiopatologia , Sistema de Registros , SuíçaRESUMO
BACKGROUND: Epidermodysplasia verruciformis (EV) is a genodermatosis leading to infections with cutaneous HPV, persistent plane warts and a high rate of non-melanoma skin cancer (NMSC). Biallelic loss-of-function mutations in TMC6 and TMC8 are known to be causative. OBJECTIVE: The aim of this study was to report EV-causing mutations in four patients with EV and to give an overview of all described patients with EV. PATIENTS AND METHODS: We investigated four patients with classical features of EV from two families. All patients were affected by plane warts with typical EV histology since early childhood, and ß-HPVs were detected on their skin. One patient had recurring cutaneous squamous cell carcinomas (cSCC) and carcinomas in situ (Bowen type). We sequenced both TMC6/8 for disease-causing mutations and quantified levels of gene expression. We also performed a systematic literature review to discuss these patients in the context of previously reported cases, mutations already identified, as well as HPV types. RESULTS: Three patients of one family carried a homozygous splice site mutation in TMC8 resulting in aberrantly spliced transcripts that were not degraded. By contrast, no TMC6/8 mutation was detected in the patient from the other family. A systematic literature review revealed 501 described patients with EV. Around 40% of patients with EV analysed for genetic alterations carried no mutation in TMC6/8. While ß-HPVs were identified in the majority of cases, α-HPVs were detected in several individuals. CONCLUSION: The relatively high proportion of EV patients without mutation in TMC6/8 indicates the existence of EV-causing mutations in additional, presently unknown gene(s). However, a homozygous TMC8 splice site mutation in our patients resulted in aberrant transcripts which cannot retain the healthy phenotype. The literature review revealed that HPV-5 is the most commonly identified HPV in patients with EV, but HPV-3, HPV-14 and HPV-20 were unexpectedly identified more frequently than HPV-8.
Assuntos
Epidermodisplasia Verruciforme/genética , Proteínas de Membrana/genética , Mutação , Infecções por Papillomavirus/complicações , Splicing de RNA , Adolescente , Criança , Epidermodisplasia Verruciforme/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: The ribosomal protein S6 is part of the translation machinery and is activated by phosphorylation via the mammalian target of rapamycin pathway, which is activated in psoriatic skin. OBJECTIVES: To investigate which S6 sites are phosphorylated in psoriasis and atopic dermatitis (AD), and to study whether S6 phosphorylation is associated with inflammation and/or keratinocyte hyperproliferation. METHODS: Healthy skin and skin lesions of patients with psoriasis and AD were investigated by immunostaining using antibodies that stain proliferating cells, leucocytes and distinct phosphorylated sites of S6. RESULTS: All psoriasis and AD lesions revealed abnormal S6 phosphorylation in the epidermis. The extent of S6 phosphorylation was diverse, generally stronger in psoriasis and correlated, in both diseases, with inflammation. S6 showed differential phosphorylation in distinct epidermal layers, which was most pronounced in hyperproliferative regions. CONCLUSIONS: Differential S6 phosphorylation may have a role in abnormal keratinocyte proliferation/differentiation.
Assuntos
Dermatite Atópica/metabolismo , Psoríase/metabolismo , Proteína S6 Ribossômica/metabolismo , Estudos de Casos e Controles , Epiderme/metabolismo , Imunofluorescência , Humanos , Fosforilação/fisiologiaAssuntos
Alopecia/genética , Displasia Ectodérmica/genética , Hiperpigmentação/genética , Hipo-Hidrose/genética , Queratina-14/genética , Ceratodermia Palmar e Plantar/genética , Doenças da Unha/genética , Fenótipo , Neoplasias Cutâneas/genética , Alelos , Alopecia/diagnóstico , Alopecia/patologia , Displasia Ectodérmica/diagnóstico , Displasia Ectodérmica/patologia , Mutação da Fase de Leitura , Humanos , Hiperpigmentação/diagnóstico , Hiperpigmentação/patologia , Hipo-Hidrose/diagnóstico , Hipo-Hidrose/patologia , Ceratodermia Palmar e Plantar/diagnóstico , Ceratodermia Palmar e Plantar/patologia , Doenças da Unha/diagnóstico , Doenças da Unha/patologia , Pele/patologia , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/patologiaRESUMO
BACKGROUND: Autosomal dominant adermatoglyphia (ADG) is characterized by lack of palmoplantar epidermal ridges. Recently, ADG was found to be caused in one family by a mutation in SMARCAD1, a member of the SNF subfamily of the helicase protein superfamily. OBJECTIVES: To investigate the genetic basis of ADG. METHODS: We used direct sequencing and global gene expression analysis. RESULTS: We identified three novel heterozygous mutations in SMARCAD1 (c.378 + 2T > C, c.378 + 5G > C and c.378 + 1G > A) in a total of six patients. Surprisingly, all four ADG-causing mutations identified to date disrupt a single conserved donor splice site adjacent to the 3' end of a noncoding exon and are predicted to result in haploinsufficiency for a skin-specific isoform of SMARCAD1. These data indicate a pivotal role for the SMARCAD1-skin specific isoform in dermatoglyph formation. In order to better understand the consequences of ADG-associated mutations, we ascertained the global transcription profiles of primary keratinocytes downregulated for SMARCAD1 and of patient-derived keratinocytes. A total of eight genes were found to be differentially expressed in both patient-derived and knocked down keratinocytes. Of interest, these differentially expressed genes have been implicated in epidermal ontogenesis and differentiation, and in psoriasis, which is characterized by abnormal finger ridge patterns. CONCLUSIONS: The present data suggest that ADG is genetically homogeneous and result from perturbed expression of epidermal differentiation-associated genes.
Assuntos
DNA Helicases/genética , Mutação/genética , Dermatopatias Genéticas/genética , Diferenciação Celular/genética , Células Epidérmicas , Regulação da Expressão Gênica/genética , Heterozigoto , Humanos , Transcriptoma/genéticaRESUMO
BACKGROUND: Urgent consultations for skin disorders are commonly done in different settings. Scarce data exist about the characteristics of these patients. OBJECTIVE: The aim of this study was to analyse specific characteristics of patients receiving an urgent consultation at a dermatology department in a university hospital. METHODS: We prospectively recorded the data of all patients having had an urgent consultation during a period of 12 months. RESULTS: We registered 2,222 urgent consultations. The most frequent diagnoses were eczemas (24.8%), dermatomycoses (5.1%) and dermatitis not otherwise specified (4.8%). The most frequent treatments were topical steroids, emollients, topical antibiotics, systemic antihistamines, antibiotics and virostatics. 2.2% of patients were hospitalized, 78.8% asked for a consultation for a disease lasting less than 4 weeks, and 6.9% presented the same day as the skin disease appeared. CONCLUSIONS: This study shows the characteristics of patients receiving an urgent dermatologic consultation. It underlines the need for collaboration between dermatologists, other physicians, general practitioners and nurses.
Assuntos
Dermatologia , Emergências , Pacientes Internados/estatística & dados numéricos , Pacientes Ambulatoriais/estatística & dados numéricos , Encaminhamento e Consulta/estatística & dados numéricos , Dermatopatias/epidemiologia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Fármacos Dermatológicos/uso terapêutico , Feminino , Departamentos Hospitalares , Hospitais Universitários , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Dermatopatias/diagnóstico , Dermatopatias/tratamento farmacológico , Suíça/epidemiologia , Resultado do TratamentoRESUMO
BACKGROUND: There are about 10,000 monogenic diseases and around 30% demonstrate alterations in the skin and its appendages. As there are so many genetic different skin diseases, clear diagnosis is often very difficult. AIM: The goal of this review is to give the clinicians some key features on nails and teeth which might help to identify rare genodermatoses. DISCUSSION: In the daily work genodermatoses manifest more commonly as incomplete or oligosymptomatic syndromes than as complete symptom complexes. To diagnose a rare disorder in such situations, a knowledge of key features which are characteristic for a genodermatoses is essential, so that a diagnosis can be advanced and the underlying gene defect identified. Changes in nails and teeth sometimes may be useful as diagnostic key features. Both structures originate from ectoderm and therefore they often appear in combination in diseases with major ectodermal malformations. Enamel defects resembling the lines of Blaschko are highly suggestive for focal dermal hypoplasia, even if other important signs and symptoms are missing. Enamel defects combined with gingival fibromas are highly suggestive for tuberous sclerosis. On the other side, triangular lunulae with malformation and dystrophy of the nail plate suggests nail-patella syndrome.
Assuntos
Síndrome da Unha-Patela/patologia , Unhas/patologia , Dermatopatias Genéticas/genética , Dermatopatias Genéticas/patologia , Doenças Dentárias/patologia , Dente/patologia , Esclerose Tuberosa/patologia , Diagnóstico Diferencial , Humanos , Síndrome da Unha-Patela/genética , Doenças Dentárias/genética , Esclerose Tuberosa/genéticaAssuntos
Peptídeos e Proteínas de Sinalização Intracelular/genética , Pitiríase Rubra Pilar/genética , Psoríase/genética , Ubiquitina-Proteína Ligases/genética , Proteínas Adaptadoras de Sinalização CARD/genética , Estudos de Casos e Controles , Feminino , Mutação da Fase de Leitura , Guanilato Ciclase/genética , Humanos , Masculino , Proteínas de Membrana/genética , FenótipoRESUMO
Erythrokeratodermia variabilis (EKV, OMIM 133200) is an autosomal dominant genodermatosis with considerable intra- and interfamilial variability. It has a disfiguring phenotype characterized by the independent occurrence of two morphologic features: transient figurate red patches and localized or generalized hyperkeratosis. Both features can be triggered by external factors such as trauma to the skin. After initial linkage to the RH locus on 1p, EKV was mapped to an interval of 2.6 cM on 1p34-p35, and a candidate gene (GJA4) encoding the gap junction protein alpha-4 (connexin 31, Cx31) was excluded by sequence analysis. Evidence in mouse suggesting that the EKV region harbours a cluster of epidermally expressed connexin genes led us to characterize the human homologues of GJB3 (encoding Cx31) and GJB5 (encoding Cx31.1). GJB3, GJB5 and GJA4 were localized to a 1.1-Mb YAC in the candidate interval. We detected heterozygous missense mutations in GJB3 in four EKV families leading to substitution of a conserved glycine by charged residues (G12R and G12D), or change of a cysteine (C86S). These mutations are predicted to interfere with normal Cx31 structure and function, possibly due to a dominant inhibitory effect. Our results implicate Cx31 in the pathogenesis of EKV, and provide evidence that intercellular communication mediated by Cx31 is crucial for epidermal differentiation and response to external factors.
Assuntos
Conexinas/genética , Eritema/genética , Mutação , Sequência de Aminoácidos , Sequência de Bases , Cromossomos Humanos Par 1 , Feminino , Ligação Genética , Humanos , Masculino , Dados de Sequência Molecular , Linhagem , Homologia de Sequência de AminoácidosRESUMO
Health or disease is a result of the genetic constellation and environmental influences. The phenotype of monogenic diseases is highly influenced by one single mutation. According to the WHO more than 10,000 monogenic diseases exist while for 1,000 diseases a molecular genetic test is available. Genodermatoses are well-documented and characterized; the most important data base for the diagnosis is the Online Mendelian Inheritance of Men data base, which can be searched in Google with the keyword "OMIM". Here genetic diseases are categorized and clinically described. We present our own epidemiologic data from the Department of Dermatology, University Hospital Basel, concerning genodermatoses. Our results show that the most common genodermatoses seen in the daily practice are porokeratoses, ichthyoses, Darier disease, neurofibromatosis and epidermolysis bullosa. They account for 91% of all genodermatoses seen in a hospital-based dermatology department of Dermatology.
Assuntos
Bases de Dados Genéticas , Marcadores Genéticos/genética , Dermatopatias Genéticas/epidemiologia , Dermatopatias Genéticas/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Dermatopatias Genéticas/classificação , Adulto JovemRESUMO
Ichthyosis with confetti (IWC) was first described as ichthyose en confettis and subsequently as congenital reticular ichthyosiform erythroderma. Because of the development of hundreds to thousands of pale, normal-appearing confetti-like spots during childhood, the disease was named IWC. Patients with IWC show erythroderma, prominent scaling and palmoplantar keratoderma. Our female index patient was described in 1990 as the fourth patient reported worldwide; at that time she did not show any confetti-like spots. She was periodically examined at our clinic from birth until adulthood; hence we are able to describe the natural course of IWC in detail for the first time. We furthermore identified two novel deletions in KRT10, one of them leading to a frameshift and consequently to an arginine tail of keratin 10. Our report is the first independent confirmation of the KRT10 gene defect and revertant mosaicism mechanism in patients with IWC and it expands the clinical findings.
Assuntos
Cromossomos Humanos Par 17/genética , Mutação da Fase de Leitura/genética , Deleção de Genes , Eritrodermia Ictiosiforme Congênita/genética , Queratina-10/genética , Polimorfismo de Nucleotídeo Único/genética , Adulto , Éxons/genética , Feminino , Heterozigoto , HumanosRESUMO
Invasive malignant melanoma is the most common fatal form of skin cancer. Fluorine-18-fluorodeoxyglucose positron emission tomography-computed tomography demonstrates a very high sensitivity and specificity for the detection of melanoma metastases. Here, we report an unusual case of toxoplasma lymphadenitis in a male adult patient mimicking a malignant cervical lymphadenopathy. Toxoplasmosis is a zoonosis caused by the intracellular parasite Toxoplasma gondii, which is usually asymptomatic in immunocompetent hosts.
Assuntos
Fluordesoxiglucose F18 , Linfadenite/diagnóstico por imagem , Melanoma/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/métodos , Neoplasias Cutâneas/diagnóstico por imagem , Toxoplasmose/diagnóstico por imagem , Anticorpos Antiprotozoários/sangue , Diagnóstico Diferencial , Reações Falso-Positivas , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Linfadenite/sangue , Masculino , Melanoma/sangue , Pessoa de Meia-Idade , Imagem Multimodal , Valor Preditivo dos Testes , Neoplasias Cutâneas/sangue , Tomografia Computadorizada por Raios X , Toxoplasmose/sangueRESUMO
We describe an otherwise healthy 7-year-old boy who developed confetti-like hypopigmented macules on the dorsal aspects of the hands and feet, spreading to the palms and soles a few months after birth. In 1964 Siemens introduced the term acromelanosis albo-punctata to describe the skin features of a patient who has remained the only reported case in the literature so far and who strongly resembles our patient. By genetic testing we excluded mutations in genes known to be involved in diseases with acral hypo- or hyperpigmentation. We review the differential diagnosis of acral localized spotty dyspigmentation and conclude that acromelanosis albo-punctata may represent a distinct entity.
Assuntos
Dermatoses da Mão/genética , Melanose/genética , Criança , Diagnóstico Diferencial , Dermatoses da Mão/patologia , Humanos , Masculino , Melanose/patologiaRESUMO
BACKGROUND: Epidermodysplasia verruciformis (EV) is a rare genodermatosis that is characterized by susceptibility to infection with specific human papillomavirus (HPV) genotypes. Among polyomaviruses, the novel Merkel cell polyomavirus (MCPyV) has been found in different epithelial skin neoplasias. OBJECTIVE: To examine whether EV is associated with cutaneous MCPyV infection. METHODS: We used MCPyV-specific PCR to study skin neoplasms of 6 congenital EV patients and of 1 patient with acquired EV. RESULTS: In all congenital EV patients, MCPyV DNA was found in carcinomas in situ, in invasive squamous cell carcinomas and in common warts. In 4 of these patients, the MCPyV-positive skin lesions were from different anatomic locations. In addition, 1 immunosuppressed patient suffering from acquired EV harbored MCPyV DNA in 2 common warts. In contrast, 7 normal skin samples tested negative for MCPyV DNA. Only 2 out of 24 carcinomas in situ (8.3%) and 2 out of 30 common warts (6.7%) from immunocompetent individuals were positive for MCPyV DNA. CONCLUSIONS: The strong association of EV-associated skin neoplasms with MCPyV suggests a unique susceptibility of EV patients to infections with MCPyV. Both MCPyV and EV-HPV may act as synergistic oncogenic cofactors in the development of EV-associated skin neoplasms.
Assuntos
Betapapillomavirus/isolamento & purificação , Carcinoma de Célula de Merkel/virologia , Epidermodisplasia Verruciforme/virologia , Hospedeiro Imunocomprometido , Infecções por Polyomavirus/imunologia , Polyomavirus/isolamento & purificação , Neoplasias Cutâneas/virologia , Infecções Tumorais por Vírus/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Célula de Merkel/complicações , Epidermodisplasia Verruciforme/complicações , Epidermodisplasia Verruciforme/genética , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Infecções por Polyomavirus/complicações , Neoplasias Cutâneas/complicações , Infecções Tumorais por Vírus/complicaçõesAssuntos
Cistos Aracnóideos/congênito , Cistos Aracnóideos/diagnóstico por imagem , Melanose/diagnóstico por imagem , Síndromes Neurocutâneas/diagnóstico por imagem , Ultrassonografia Pré-Natal , Adulto , Feminino , Humanos , Lactente , Recém-Nascido , Imageamento por Ressonância Magnética , Exame Neurológico , Gravidez , Terceiro Trimestre da Gravidez , Ultrassonografia Doppler TranscranianaAssuntos
Cisto Dermoide/patologia , Granuloma/cirurgia , Doenças Orbitárias/patologia , Neoplasias Orbitárias/patologia , Dermatopatias/patologia , Neoplasias Cutâneas/cirurgia , Criança , Cisto Dermoide/cirurgia , Diagnóstico Diferencial , Feminino , Granuloma/patologia , Humanos , Doenças Orbitárias/cirurgia , Neoplasias Orbitárias/cirurgia , Dermatopatias/cirurgia , Neoplasias Cutâneas/patologia , Resultado do TratamentoRESUMO
Lymphogranuloma venereum is a sexually transmitted disease caused by Chlamydia trachomatis, serotypes L1, L2 and L3. The classical clinical manifestation is a painful inguinal lymphadenopathy, resulting without treatment in severe complications. Over the last years, however, the emergence of massive ulcerative proctitis has been observed, especially in men who have sex with men. Because the clinical symptoms are unspecific, Chlamydia trachomatis should actively be looked for. Reliable and rapid molecular tests have now been established to diagnose lymphogranuloma venereum. The therapeutic recommendation is tetracycline for 3 weeks. We present 5 cases to illustrate this disease.