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2.
Toxicol Lett ; 213(1): 39-44, 2012 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-21810456

RESUMO

Coal tar ointments (CTO) are frequently used in the treatment of psoriasis and eczema, but CTO contain carcinogenic polycyclic aromatic hydrocarbons (PAH). PAH are absorbed and metabolized in the skin. In psoriasis, the skin barrier is altered and therefore, absorption and metabolism of PAH may differ from healthy skin. In this study, levels of urinary 1-hydroxypyrene and PAH-DNA adducts in the skin were studied in psoriatic patients and healthy volunteers. Three punch biopsies were taken from the lower back of 10 male volunteers and from a psoriatic plaque in 10 male patients. A surface of 6.25 cm(2) was treated with CTO. After 96 h CTO was removed and another three skin biopsies were collected from the treated area. DNA was isolated from skin biopsies and urine was collected during and after the exposure period. After 24h, a twofold lower 1-hydroxypyrene urinary excretion was observed in patients compared to healthy volunteers and after 48 h, this difference reached statistical significance (p<0.05). Over 96 h the median level of the sum of PAH-DNA adducts, analyzed by (32)P-post-labeling, increased from 3.5 before CTO administration to 21.1 adducts per 10(8) nucleotides in volunteers, and from 1.0 to 3.6 adducts per 10(8) nucleotides in patients. At 96 h, PAH-DNA levels were higher in healthy volunteers than in patients (p<0.05). Biomarkers for uptake, bioavailability and bioactivation of PAH were lower in patients compared to volunteers. These data suggest a lower risk of carcinogenic effects of CTO in psoriatic skin compared to healthy skin.


Assuntos
Alcatrão/farmacocinética , Adutos de DNA/análise , Psoríase/tratamento farmacológico , Pirenos/análise , Pele/química , Adolescente , Adulto , Idoso , Biópsia , Estudos de Casos e Controles , Alcatrão/efeitos adversos , Alcatrão/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Psoríase/metabolismo , Adulto Jovem
4.
Br J Dermatol ; 158(2): 375-81, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18067483

RESUMO

BACKGROUND: Calcipotriol ointment and short-contact dithranol cream therapy are well-established topical treatments for psoriasis. Quality of life, i.e. the physical, psychological, and social functioning and well-being of the patient, has become an essential outcome measure in chronic skin disease. OBJECTIVES: To compare the quality-of-life outcomes of calcipotriol ointment with that of short-contact dithranol cream in a supervised treatment regimen, and to determine the degree of improvement in quality of life these topical treatments can accomplish. METHODS: In a multicentre randomized controlled trial in six centres in the Netherlands, 106 patients with chronic plaque psoriasis were included, 54 receiving calcipotriol ointment twice daily and 52 dithranol cream once daily in a 12-week intensive treatment programme. Patients were treated at the day-care centre, using the care instruction principle of daily visits during the first week and twice-weekly visits subsequently for up to 12 weeks. Quality of life was assessed with the Skindex-29 and the Medical Outcomes Study 36-item Short-Form General Health Survey (SF-36). RESULTS: At the end of treatment, no statistically significant differences were found between the calcipotriol and the dithranol group in any of the quality-of-life domains or scales of the Skindex-29 and the SF-36. Over time, a significant improvement of quality of life was found on all three scales of the dermatology-specific Skindex-29, predominantly of a moderate magnitude. In the calcipotriol group, a significant change of a small magnitude was found in the Physical Component Summary of the SF-36. No significant changes were found in the Mental Component Summary (or on any of the eight scales composing the questionnaire) of the SF-36. CONCLUSIONS: The hypothesis was confirmed, that no statistically significant differences in improvement of quality of life could be found between calcipotriol ointment and dithranol short-contact cream in a day-care setting. Given this result, both calcipotriol and dithranol can be welcome alternatives for the patient. Calcipotriol, being more practical and patient friendly, can be considered as a first-line approach in clinical practice. However, in patients recalcitrant to calcipotriol and/or other topical treatments, preference should be given to the dithranol regimen. Topical treatment in combination with interventions explicitly focusing on improvement of coping behaviour and psychosocial functioning may further increase the degree of improvement in the psychosocial domains of quality of life. The results of this study are likely to give further evidence to the notion that the generic SF-36 is little or not responsive to small to moderate changes in quality of life in mild to moderate psoriasis.


Assuntos
Antralina/uso terapêutico , Calcitriol/análogos & derivados , Fármacos Dermatológicos/uso terapêutico , Psoríase/tratamento farmacológico , Administração Tópica , Antralina/administração & dosagem , Calcitriol/administração & dosagem , Calcitriol/uso terapêutico , Hospital Dia , Fármacos Dermatológicos/administração & dosagem , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos , Pomadas , Estudos Prospectivos , Qualidade de Vida , Resultado do Tratamento
5.
Br J Dermatol ; 158(1): 101-8, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17999699

RESUMO

BACKGROUND: In dermatological research and clinical practice, there is a need for comprehensive self-report instruments that assess a broad spectrum of health implications of chronic skin diseases, including generic and skin-specific aspects of disease-related quality of life. The advantages of dermatology-specific, multidimensional instruments over generic instruments or single-dimensional quality-of-life measures are in the detailed and specific information they provide about health areas that are affected by the skin condition and that may change through therapeutic intervention. OBJECTIVES: The development of a multidimensional health status inventory for chronic skin diseases (Impact of Chronic Skin Disease on Daily Life, ISDL) is described. The dermatology-specific part of the inventory assesses dimensions of physical functioning, more specifically skin status, physical symptoms of itch, pain and fatigue and scratching responses as well as disease-related stressors like stigmatization. The generic part gauges dimensions of psychological functioning, disease-related impact, illness cognitions and social support by means of existing scales validated for other chronic diseases. METHODS: Reliability and validity of the questionnaire were studied in various samples of patients with psoriasis and atopic dermatitis. RESULTS: The ISDL showed high reliability and test-retest reliability in both patient groups. Convergent validity was indicated by moderate to strong correlations with other validated questionnaires. The scales proved sensitive to change both for dermatological ultraviolet B radiation therapy and cognitive behavioural treatment for itching. CONCLUSION: With its convincing results for reliability and validity the present evaluation supports the usefulness and applicability of the instrument for different chronic skin diseases.


Assuntos
Indicadores Básicos de Saúde , Qualidade de Vida , Dermatopatias/reabilitação , Atividades Cotidianas , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença Crônica , Fadiga/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dor/etiologia , Prurido/etiologia , Reprodutibilidade dos Testes , Dermatopatias/complicações , Dermatopatias/psicologia
6.
Br J Dermatol ; 156(6): 1346-9, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17535233

RESUMO

BACKGROUND: Physical symptoms of skin diseases have been shown to negatively affect patients' wellbeing. Although insight into physical symptoms accompanying skin diseases is relevant for the management and treatment of skin diseases, the prevalence of physical symptoms among patients with skin diseases is a rather unexplored territory. OBJECTIVES: The goal of the present study was to examine the prevalence of physical symptoms of itch, pain and fatigue in patients with skin diseases. METHODS: On the basis of a systematic morbidity registration system in primary care, questionnaires were sent to 826 patients with skin diseases. Eventually, questionnaires from 492 patients were suitable for our analyses. RESULTS: Results indicated that patients with skin diseases particularly experience symptoms of itch and fatigue. Approximately 50% of all patients report experiencing these symptoms and about 25% experience these symptoms as relatively severe. Pain was relatively less frequently reported by 23% of all patients, and was on average somewhat less intense. The physical symptoms showed relatively strong correlations with disease-related quality of life and self-reported disease severity. In contrast, only moderate correlations were found with comorbidity and demographic variables, which suggests that the physical symptoms of itch, pain and fatigue are consequences of the skin diseases. CONCLUSIONS: Itch and fatigue and, to a somewhat lesser extent, pain have a high prevalence among patients with skin diseases. Clinicians should be encouraged to carefully assess itch, pain and fatigue in patients with skin diseases, and where appropriate focus treatment to these symptoms.


Assuntos
Fadiga/epidemiologia , Dor/epidemiologia , Prurido/epidemiologia , Dermatopatias/epidemiologia , Adulto , Medicina de Família e Comunidade/estatística & dados numéricos , Fadiga/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Dor/psicologia , Prurido/psicologia , Qualidade de Vida/psicologia , Dermatopatias/psicologia , Inquéritos e Questionários
7.
J Eur Acad Dermatol Venereol ; 21(5): 662-8, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-17447981

RESUMO

BACKGROUND: Skin diseases are a substantial part of the problems dealt with by general practitioners. Although the psychosocial consequences of skin diseases in secondary care has been extensively studied, little is known about the psychosocial well-being of patients with skin diseases in primary care. OBJECTIVE: To investigate the psychosocial well-being of patients with skin diseases in primary care. PATIENTS/METHODS: Questionnaires about the psychosocial consequences of skin diseases were sent to patients with a skin disease who were registered within a research network (continuous morbidity registration) of general practices that continuously have recorded morbidity data since 1971. Questionnaires completed by 532 patients were eventually suitable for analyses. RESULTS: Compared with the general population, patients with skin diseases reported significantly lower scores for psychosocial well-being. Furthermore, a lower psychosocial wellbeing was significantly related with higher levels of disease-severity, lower disease-related quality of life, longer disease duration, more comorbidity and more physical symptoms of itch, pain and fatigue. After demographic variables and comorbidity were controlled for, sequential regression analyses showed that disease duration, disease severity and physical symptoms (itch, pain and fatigue) were significant predictors of psychosocial well-being. CONCLUSION: The psychosocial well-being of patients with skin diseases in primary care is lower than that of the general population. Special attention has to be directed to those patients with lowered psychosocial well-being who might be at risk of developing severe psychosocial impairments such as clinical depression.


Assuntos
Medicina de Família e Comunidade , Dermatopatias/psicologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Qualidade de Vida , Sistema de Registros , Análise de Regressão , Dermatopatias/epidemiologia , Inquéritos e Questionários
8.
Br J Dermatol ; 155(4): 800-7, 2006 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16965431

RESUMO

BACKGROUND: Calcipotriol has become a first-line treatment for psoriasis. Its efficacy and safety have been shown in many comparative clinical trials carried out in outpatients. In a comparative study in patients visiting the outpatient department once every 14 days, it was shown that calcipotriol was more effective and better tolerated compared with dithranol. OBJECTIVES: To compare the clinical efficacy of calcipotriol ointment with that of dithranol cream in a supervised treatment regimen. METHODS: In a multicentre randomized controlled trial in six centres in the Netherlands, 106 patients with chronic plaque psoriasis were included, 54 receiving calcipotriol ointment twice daily and 52 dithranol cream once daily. Patients were treated at the day-care centre, using the care instruction principle of daily visits during the first week and twice-weekly visits subsequently for up to 12 weeks. RESULTS: This study failed to prove that calcipotriol is as efficacious as dithranol when used in a day-care setting (noninferiority test). The mean percentage reduction in Psoriasis Area and Severity Index from baseline to end of treatment was 57.0% in the calcipotriol group vs. 63.6% in the dithranol group. However, the two-sided test for superiority indicated no statistically significant difference between the treatment groups (P = 0.39). At the end of treatment, 15% of the patients treated with calcipotriol ointment and 25% of those treated with dithranol cream did not require any further treatment. Although calcipotriol ointment appeared to be more effective during the first 8 weeks, a difference was no longer apparent at 12 weeks. In comparison with the high number of drop-outs due to cutaneous side-effects in the calcipotriol group, the frequency of a tolerable degree of irritation appeared to be higher in patients treated with dithranol. However, concomitant corticosteroid treatment of dithranol irritation in seven patients may have contributed to this difference between both treatments. Moreover, patients receiving therapy with calcipotriol ointment experienced fewer application-related skin and subcutaneous tissue disorders than patients treated with dithranol cream: 21 of 53 (40%) and 37 of 52 (71%), respectively. This difference is statistically significant (P = 0.001). CONCLUSIONS: The hypothesis that calcipotriol ointment might be at least as effective as dithranol cream in the day-care setting could not be proven in the present study. Whereas calcipotriol has become a mainstay in the routine outpatient treatment of psoriasis not requiring a day-care setting, dithranol treatment, being difficult as a routine outpatient therapy, has increased efficacy and improved tolerability if the treatment is carried out in a day-care setting.


Assuntos
Antralina/uso terapêutico , Calcitriol/análogos & derivados , Fármacos Dermatológicos/uso terapêutico , Psoríase/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antralina/administração & dosagem , Antralina/efeitos adversos , Calcitriol/administração & dosagem , Calcitriol/efeitos adversos , Calcitriol/uso terapêutico , Hospital Dia , Fármacos Dermatológicos/administração & dosagem , Fármacos Dermatológicos/efeitos adversos , Esquema de Medicação , Humanos , Pessoa de Meia-Idade , Pomadas , Estudos Prospectivos , Índice de Gravidade de Doença , Resultado do Tratamento
9.
Br J Dermatol ; 152(6): 1275-81, 2005 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15948993

RESUMO

BACKGROUND: Chronic skin diseases, such as atopic dermatitis and psoriasis, are known to affect quality of life by heightening psychological distress. Knowledge about factors contributing to psychological distress is essential for supporting physicians in diagnostic and multidisciplinary treatment options for patients psychologically at risk. OBJECTIVES: To examine whether generic physical, psychological and social factors relevant to patients with chronic diseases might contribute to psychological distress in adults with psoriasis and atopic dermatitis. METHODS: Self-report data on clinical skin status, physical symptoms of itching and fatigue, impact of the disease on daily life, illness cognitions and social support were collected from 128 patients with psoriasis and 120 patients with atopic dermatitis (aged over 16 years). RESULTS: For patients with either skin disease, clinical status and physical symptoms of itching scarcely affected psychological distress. Instead, higher levels of fatigue, perceived helplessness and less social support best predicted psychological distress in patients with both skin diseases in multiple regression analyses. CONCLUSIONS: Results demonstrate that generic physical, psychological and social aspects play a role in chronic skin diseases and suggest that multidisciplinary care for patients with psoriasis and atopic dermatitis can be greatly improved by integrating common screening and treatment components for chronic diseases.


Assuntos
Dermatopatias/psicologia , Estresse Psicológico/etiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Dermatite Atópica/psicologia , Fadiga/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Psoríase/psicologia , Análise de Regressão , Apoio Social , Inquéritos e Questionários , Urticária/psicologia
10.
J Eur Acad Dermatol Venereol ; 19(2): 176-9, 2005 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15752286

RESUMO

The irritant response of perilesional skin is a serious limitation of dithranol therapy in psoriasis. No data are available on the actual prevalence and severity of irritation during 24-h dithranol treatment in an inpatient setting. Using a retrospective analysis of 68 patients with psoriasis visiting our inpatient department for dithranol treatment, the occurrence of dithranol irritation was studied. We found a relatively high frequency of dithranol irritation. Furthermore, most irritation occurs at the start of the therapy with relatively low concentrations.


Assuntos
Antralina/efeitos adversos , Antralina/uso terapêutico , Anti-Inflamatórios/efeitos adversos , Anti-Inflamatórios/uso terapêutico , Psoríase/tratamento farmacológico , Administração Tópica , Adulto , Idoso , Feminino , Humanos , Pacientes Internados , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo
11.
J Eur Acad Dermatol Venereol ; 19(2): 249-51, 2005 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15752305

RESUMO

Recently, tacrolimus ointment has proved to be effective and well tolerated in patients with facial psoriasis. A few months ago we had the opportunity to treat a patient with tacrolimus ointment who had severe and recalcitrant plaque psoriasis of the face. This present case illustrates the impressive improvement of facial plaque psoriasis following 5 months of treatment with tacrolimus 0.1% ointment twice a day. Significant improvement of facial plaque psoriasis was seen after 1 month and complete clearance after 5 months of therapy. Based on the available literature and illustrated by the present case we may conclude that tacrolimus ointment 0.1% can be recommended as a first-line treatment for facial psoriasis.


Assuntos
Dermatoses Faciais/tratamento farmacológico , Imunossupressores/uso terapêutico , Psoríase/tratamento farmacológico , Tacrolimo/uso terapêutico , Administração Tópica , Humanos , Imunossupressores/administração & dosagem , Masculino , Pessoa de Meia-Idade , Pomadas , Tacrolimo/administração & dosagem
12.
Leuk Lymphoma ; 45(11): 2327-32, 2004 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-15512825

RESUMO

In this paper a patient with a non-Hodgkin's lymphoma (NHL) and paraneoplastic pemphigus (PNP) is described. PNP is a very rare, painful mucocutaneous intraepithelial blistering disease associated with occult or confirmed malignancy. Patients with PNP show severe, progressive mucocutaneous disease with a high mortality rate, because of drug-induced infectious complications. The patients sometimes benefit from high doses of oral corticosteroids. However, pulse therapy with high doses of prednisolone (or dexamethasone) in combination with other immunosuppressants induces variable and inconstant results. Intravenous immunoglobulin (IVIg) has been applied in different cases of PNP with encouraging results. Plasmapheresis or plasma exchange (PE) in combination with corticosteroids and/or cyclophosphamide or azathioprine showed similar rapid and beneficial results in association with decreasing auto-antibody levels in this group of refractory pemphigus. Another interesting therapeutic option is rituximab, a chimeric monoclonal antibody directed against the CD20 antigen, which is found on the surface of normal and malignant B-lymphocytes. Administration of rituximab for patients with PNP in combination with follicular NHL is not always successful regarding oral lesions as we report in this case. PE leading to prompt depletion of autoreactive antibodies combined with immunosuppressants or synchronisation of PE with IVIg seems the best treatment modality for this refractory group, but the therapeutic value and appropriate timing of rituximab obviously deserve further evaluation in patients with low grade NHL and PNP.


Assuntos
Linfoma Folicular/tratamento farmacológico , Linfoma não Hodgkin/tratamento farmacológico , Corticosteroides/farmacologia , Idoso , Anticorpos Monoclonais/metabolismo , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais Murinos , Antígenos CD20/biossíntese , Antineoplásicos/farmacologia , Antineoplásicos Hormonais/farmacologia , Azatioprina/farmacologia , Linfócitos B/metabolismo , Ciclofosfamida/farmacologia , Dexametasona/farmacologia , Glucocorticoides/farmacologia , Humanos , Imunoglobulinas Intravenosas/farmacologia , Imunossupressores/farmacologia , Masculino , Síndromes Paraneoplásicas/tratamento farmacológico , Pênfigo/tratamento farmacológico , Troca Plasmática , Prednisolona/farmacologia , Prognóstico , Rituximab , Fatores de Tempo
13.
Eur J Dermatol ; 14(3): 159-65, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15246941

RESUMO

The efficacy of UVB-phototherapy (UVB) and dithranol treatment for psoriasis is well established. However, well-conducted clinical trials on the efficacy of dithranol are not available, making comparison between these time-honoured treatments with currently available therapies impossible. We studied the effectiveness of dithranol in a care instruction programme using short time exposures (short contact treatment), UVB-phototherapy and dithranol treatment in an inpatient setting. In an open randomised study we included 250 patients with moderate to severe psoriasis. The intention to treat group existed of 238 patients. 100 patients were treated with short contact dithranol, 78 Patients were treated with UVB and 60 patients underwent inpatient dithranol treatment. We found UVB and dithranol treatment to be effective and safe in moderate to severe psoriasis. The efficacy of short contact dithranol treatment equals the efficacy of UVB-phototherapy. Dithranol treatment at the inpatient department showed superior efficacy in clinical response rate and treatment duration as compared to UVB and short contact treatment. The median number of days in remission was significantly longer after short contact treatment as compared to inpatient treatment. Although the use of dithranol is hampered by skin irritation and staining, the present study shows that dithranol treatment has an outstanding efficacy and safety profile. Comparison between different antipsoriatic treatments should, besides clearing capacity, reconcile duration of remission, safety, patient acceptability and costs.


Assuntos
Antralina/administração & dosagem , Anti-Inflamatórios/administração & dosagem , Psoríase/tratamento farmacológico , Psoríase/radioterapia , Terapia Ultravioleta , Administração Cutânea , Antralina/efeitos adversos , Anti-Inflamatórios/efeitos adversos , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Psoríase/patologia , Recidiva , Índice de Gravidade de Doença , Resultado do Tratamento
14.
Contact Dermatitis ; 48(6): 293-9, 2003 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-14531866

RESUMO

Hand dermatitis is a multifactorial skin disorder in which skin barrier impairment is involved in the pathogenesis. The development of topical agents that improve skin barrier function is therefore a promising approach for the management of hand dermatitis. Topically applied lipids may interfere with skin barrier function, and emollients containing skin-related lipids have been suggested to facilitate repair of the skin barrier. However, evidence for the superiority of emollients containing skin-related lipids over the more traditional emollients is still lacking. The aim of this study was to compare an emollient containing skin-related lipids (Locobase Repair) with a traditional petrolatum-based emollient for the management of hand dermatitis. Adult males and females (n = 30) with mild to moderate chronic hand dermatitis were treated twice daily for 2 months either with an emollient containing skin-related lipids or with a pet.-based emollient. In the case of exacerbation, the patients of both treatment groups were allowed to use a mild corticosteroid according to instructions. Both treatment regimes significantly improved clinical signs of hand dermatitis as assessed by the investigator global assessment, hand eczema area and severity score. We did not observe significant differences in the improvement of clinical signs, itching, patients' assessment of efficacy, cosmetic acceptability or usage of topical corticosteroids between both treatment groups. In conclusion, this study confirms that the frequent use of emollients may be useful in the therapy of hand dermatitis. However, we could not demonstrate the superiority of this particular emollient containing skin-related lipids in patients with chronic hand dermatitis.


Assuntos
Emolientes/uso terapêutico , Dermatoses da Mão/terapia , Vaselina/uso terapêutico , Administração Tópica , Adulto , Idoso , Esquema de Medicação , Estética , Feminino , Glucocorticoides/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Compostos Orgânicos , Satisfação do Paciente , Projetos Piloto , Índice de Gravidade de Doença , Inquéritos e Questionários , Resultado do Tratamento , Triancinolona/uso terapêutico
15.
Arch Dermatol Res ; 295(1): 29-32, 2003 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-12709818

RESUMO

BACKGROUND: New therapeutic approaches have to be considered in the treatment of irritant contact dermatitis (ICD). Recently, phosphodiesterase 4 (PDE-4) inhibitors have been introduced as nonsteroidal, antiinflammatory agents. These agents inhibit the secretion of the cytokines thought to be involved in the pathogenesis of ICD. We investigated the effect of a new selective PDE-4 inhibitor (cipamfylline) in human models using single and repeated exposures to an irritant in a blind, randomized pilot study with healthy volunteers. We compared the effect of cipamfylline ointment with a strong corticosteroid (betamethasone-17-valerate) and with a placebo ointment. METHODS: Ten volunteers were patch tested at four investigation sites with sodium dodecyl sulphate (1%) for 24 h. In a model that simulates chronic damage, 11 volunteers were patch tested with sodium dodecyl sulphate (0.2%) for 4 h daily for four consecutive days. The investigation sites were treated once a day with the above-mentioned agents. One site was left untreated. We used erythema scoring, measurements of transepidermal water loss (TEWL) and several immunohistochemical markers for epidermal proliferation and differentiation. RESULTS: Repeated application revealed that betamethasone-17-valerate caused a statistically significant reduction in erythema and TEWL compared to cipamfylline and placebo. We also observed a significant suppression of proliferating cells and cytokeratin 16 expression at sites treated with betamethasone compared to the other sites. In the model for acute ICD, no significant differences were seen between the investigated sites. CONCLUSIONS: Our results show that betamethasone-17-valerate may modulate the response in ICD. In this human model of ICD we could not confirm the efficacy of cipamfylline. Clinical studies are needed before the effect of PDE-4 inhibitors in ICD can be refuted with certainty.


Assuntos
3',5'-AMP Cíclico Fosfodiesterases/antagonistas & inibidores , Dermatite Irritante/tratamento farmacológico , Inibidores Enzimáticos/uso terapêutico , Xantinas/uso terapêutico , Adulto , Idoso , Valerato de Betametasona/uso terapêutico , Divisão Celular/efeitos dos fármacos , Nucleotídeo Cíclico Fosfodiesterase do Tipo 4 , Dermatite Irritante/complicações , Dermatite Irritante/metabolismo , Dermatite Irritante/patologia , Relação Dose-Resposta a Droga , Método Duplo-Cego , Eritema/etiologia , Eritema/patologia , Feminino , Glucocorticoides/uso terapêutico , Humanos , Queratinas/antagonistas & inibidores , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Dodecilsulfato de Sódio/administração & dosagem , Tensoativos/administração & dosagem , Perda Insensível de Água/efeitos dos fármacos
16.
Artigo em Inglês | MEDLINE | ID: mdl-12566824

RESUMO

Dithranol has been a mainstay in the treatment of psoriasis for more than 80 years. Although a safe approach, the irritation of the clinically uninvolved perilesional skin remains a major limitation of this treatment. Corticosteroids and coal tar solution have an anti-inflammatory potential. The aim of the present study was to investigate the clinical and cell-biological effects of two topical corticosteroids and a coal tar preparation on dithranol-irritated skin. During 4 consecutive days, 2% dithranol cream was applied to six uninvolved skin sites (3 cm in diameter) on the lower back of 9 patients with psoriasis. Dithranol was left on the skin for 1 h, subsequently removed with water and soap and the skin was dried with a towel. Subsequently, SITE 1 was treated with 0.05% clobetasol-17-propionate ointment (CP), SITE 2 with unguentum cetomacrogolis (vehicle 1), SITE 3 with 0.005% fluticasonpropionate ointment (FP), SITE 4 with 10% coal tar solution in lanettewax cream (CTS), SITE 5 was left untreated (control) and SITE 6 was treated with lanettewax cream (vehicle 2). Erythema, oedema and vesicle formation was scored every day. On day 5, punch biopsies were taken from the six sites. The expression of epidermal proliferation, differentiation and inflammation markers and the clinical irritation scores indicate that the application of a high potency corticosteroid (CP) is the best approach to minimise dithranol irritation, whereas CTS had virtually no effect on dithranol irritation during this 4-day experimental model.


Assuntos
Antralina/efeitos adversos , Anti-Inflamatórios/efeitos adversos , Anti-Inflamatórios/uso terapêutico , Clobetasol/análogos & derivados , Alcatrão/uso terapêutico , Eritema/tratamento farmacológico , Psoríase/tratamento farmacológico , Administração Tópica , Adulto , Idoso , Idoso de 80 Anos ou mais , Androstadienos/administração & dosagem , Androstadienos/uso terapêutico , Antralina/administração & dosagem , Antralina/uso terapêutico , Anti-Inflamatórios/administração & dosagem , Divisão Celular/efeitos dos fármacos , Clobetasol/administração & dosagem , Clobetasol/uso terapêutico , Alcatrão/administração & dosagem , Eritema/induzido quimicamente , Feminino , Fluticasona , Glucocorticoides , Humanos , Macrófagos/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Monócitos/efeitos dos fármacos , Veículos Farmacêuticos , Pele/efeitos dos fármacos , Pele/patologia , Linfócitos T/efeitos dos fármacos
17.
Skin Pharmacol Appl Skin Physiol ; 15(6): 393-400, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-12476013

RESUMO

Dithranol, although a time-honoured treatment and from the beginning of the previous century still going strong, remains an empirical treatment. There is growing evidence that the biochemical basis for the mechanism of action of dithranol at the molecular level is related to the redox activity leading to the production of active oxygen species, which include singlet oxygen, superoxide anion radical and hydroxyl radical. Some authors suggest that epidermal proliferation and/or keratinisation may be the target for dithranol, while others refer to aspects of cutaneous inflammation as crucial in the antipsoriatic effect of dithranol. The present study aims to analyse the effect of single and repeated applications of dithranol on aspects of epidermal proliferation, keratinisation and inflammation in the psoriatic plaque. The most marked effect of dithranol proved to be that on epidermal proliferation (the number of Ki-67-positive nuclei) with an early reduction already 1 day following the single application. This reduction lasted for 16 days. However, such an application induced only a modest clinical improvement. Repeated challenges, resulting in a decrease in the number of Ki-67-positive nuclei of 66%, led to a substantial clinical improvement after 12 days. Repeated challenges resulted in a significant reduction of the number of polymorphonuclear leucocytes. However, this reduction was less pronounced as compared to the effect on epidermal proliferation. It is concluded that epidermal proliferation is a sensitive marker to demonstrate an early effect of dithranol. The dynamics of the cell-biological responses suggest that intermittent applications might be a promising new approach. As dithranol does not reduce the number of T lymphocytes, it is attractive to speculate that the combination of dithranol with immunosuppressive treatments might be a very effective combination.


Assuntos
Antralina/administração & dosagem , Psoríase/tratamento farmacológico , Pele/efeitos dos fármacos , Administração Tópica , Adulto , Idoso , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/fisiologia , Feminino , Humanos , Imuno-Histoquímica , Células de Langerhans/citologia , Células de Langerhans/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Pacientes/estatística & dados numéricos , Psoríase/patologia , Pele/citologia , Pele/patologia , Linfócitos T/citologia , Linfócitos T/efeitos dos fármacos
18.
Skin Pharmacol Appl Skin Physiol ; 15(6): 385-92, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-12476012

RESUMO

Dithranol is one of the most effective topical treatments for patients with psoriasis. The well-known irritation is a serious limitation. In an earlier study we investigated the inflammatory response to single and repeated applications with dithranol 2% cream in skin from healthy volunteers. In the present study, we assessed the clinical and cell-biological response of single and repeated challenges with dithranol 2% cream in uninvolved skin of patients with psoriasis. A striking difference between the two studies is the late phase in the single-challenge group after 8 days, showing a longer-lasting response in the uninvolved skin compared to normal skin with respect to proliferation and inflammation markers. A controlled and synchronised irritation by dithranol might induce anti-inflammatory processes and as such constitute an antipsoriatic principle. It is attractive to speculate that in psoriasis the induction of anti-inflammatory responses is defective. Following repeated applications of dithranol, a more uniform course of proliferation, differentiation and inflammation markers was observed in the uninvolved psoriatic skin as compared to the skin of healthy volunteers. Again a defect in the induction of anti-inflammatory responses might account for this event. In view of these differences between normal skin and psoriatic uninvolved skin, it may be advisable to use the uninvolved skin of patients with psoriasis in further studies on the interference between dithranol irritancy and various anti-inflammatory agents.


Assuntos
Antralina/administração & dosagem , Psoríase/tratamento farmacológico , Pele/efeitos dos fármacos , Administração Tópica , Adulto , Idoso , Idoso de 80 Anos ou mais , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/fisiologia , Feminino , Humanos , Imuno-Histoquímica , Células de Langerhans/citologia , Células de Langerhans/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Monócitos/citologia , Monócitos/efeitos dos fármacos , Pacientes/estatística & dados numéricos , Psoríase/patologia , Pele/citologia , Pele/patologia , Linfócitos T/citologia , Linfócitos T/efeitos dos fármacos
19.
Artigo em Inglês | MEDLINE | ID: mdl-12218288

RESUMO

The irritative response of uninvolved skin is a serious limitation of dithranol therapy in psoriasis. A characterisation in cell biological terms may be helpful in finding an effective counteraction to this well-known irritation. Therefore, we studied the effect of single and repeated applications of dithranol on normal human skin. Besides a clinical evaluation, we studied aspects of epidermal proliferation, differentiation and inflammation. On day 2, after single dithranol challenge, we observed an induction of both the cornified envelope precursor protein involucrin and the cross-linking enzyme transglutaminase I. Subsequently, epidermal hyperproliferation was observed with a maximum on day 8. The epidermal response to dithranol appears to be a reinforcement of the barrier function. Remarkably, however, filaggrin was found to be decreased. Profilaggrin breakdown might be an attempt to compensate for xerosis of uninvolved skin that accompanies dithranol therapy. T lymphocytes and to a lesser extent polymorphonucleocytes were found to be significantly increased. The reduction of Langerhans cells suggests a dose-dependent toxic effect of dithranol or one of its metabolites on Langerhans cells. The dynamics in the induction of changes after repeated challenge are comparable with those after single challenge. However, the induction of hyperproliferation following repeated application appeared to continue between day 8 and 12. Based on the dynamics of dithranol-induced irritation, it may be of interest to study the efficacy of intermittent dithranol treatment. Our results indicate that an optimal timing for biopsies in future dithranol irritation studies lies between 4 and 8 days after the first dithranol challenge.


Assuntos
Antralina/efeitos adversos , Antralina/farmacologia , Pele/efeitos dos fármacos , Administração Cutânea , Adulto , Antralina/administração & dosagem , Diferenciação Celular/efeitos dos fármacos , Divisão Celular/efeitos dos fármacos , Feminino , Proteínas Filagrinas , Humanos , Técnicas Imunoenzimáticas , Inflamação/induzido quimicamente , Inflamação/patologia , Masculino , Pessoa de Meia-Idade , Pele/patologia
20.
Br J Dermatol ; 147(3): 538-44, 2002 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-12207597

RESUMO

BACKGROUND: This study was part of a large national cost-effectiveness analysis, and was funded by the National Fund for Investigational Medicine of the Health Care Insurance Board. OBJECTIVE: To compare the costs of treatment of moderate to severe psoriasis by dithranol short contact therapy in a care instruction programme (short contact therapy) with ultraviolet B phototherapy (UVB) and inpatient dithranol treatment (inpatient treatment), and relate these costs to treatment effectiveness. METHODS: An open randomized controlled multicentre study was performed. The costs (both medical and non-medical) were calculated for the following periods: during treatment, per month during remission, after a relapse, and following an unsuccessful treatment. The effectiveness measures were the clinical response rate and the number of clearance days during follow-up. RESULTS: The data from 216 patients were analysed. The mean overall costs per patient during treatment were euro;1641, euro;1258 and euro;7706 for short contact treatment, UVB and inpatient treatment, respectively. During the clearance period the mean costs per month per patient were euro;19, euro;5 and euro;25, respectively. The clinical response rates were 57%, 57% and 85%, respectively. The mean number of clearance-days after short contact treatment was 160 [median 119; interquartile range (0-357)], which was not significantly different from the other two strategies: 211 clearance-days after inpatient treatment [241 (99-350)] and 136 clearance-days after UVB [81 (0-266)]. CONCLUSIONS: Short contact treatment is an attractive alternative for patients with moderate to severe psoriasis currently treated by inpatient treatment, as the costs of short contact treatment were significantly lower and the number of clearance days was comparable. Considering the higher costs, short contact treatment is not a first choice treatment when compared with UVB.


Assuntos
Antralina/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Análise Custo-Benefício , Psoríase/tratamento farmacológico , Terapia Ultravioleta/economia , Administração Tópica , Adulto , Assistência Ambulatorial/economia , Antralina/economia , Anti-Inflamatórios/economia , Terapia Combinada , Esquema de Medicação , Feminino , Custos de Cuidados de Saúde , Custos Hospitalares , Hospitalização/economia , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos , Psoríase/economia , Psoríase/radioterapia , Resultado do Tratamento
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