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BACKGROUND: The OVAMA (Outcome Measures for VAscular MAlformations) project determined quality of life (QoL) as a core outcome domain for evaluating treatment effect in vascular malformations. To correctly evaluate treatment effect on QoL, patient-reported outcome measures (PROMs) are needed that are responsive to changes. In children with vascular malformations, we explored if two widely used PROMs were responsive to changes: the Pediatric Quality of Life Inventory (PedsQL) and the Children's Dermatology Life Quality Index (CDLQI). METHODS: In an international multicenter prospective study, conservatively and invasively treated children completed the PedsQL and CDLQI at baseline and after follow-up of 6-8 weeks. At follow-up, change in health was assessed by a global rating of change (GRC) scale. Responsiveness was assessed by testing hypotheses on expected correlation strength between change scores of the PROMs and the GRC scale, and by calculating the area under the receiver operating characteristics curve (AUC). The PROMs were considered responsive if ≥75% of the hypotheses were confirmed or if the AUC was ≥0.7. RESULTS: Twenty-nine children were recruited in three centers in the Netherlands and United States, of which 25 completed all baseline and follow-up measurements. For both the PedsQL and CDLQI, less than 75% of the hypotheses were confirmed and the AUC was <0.7. DISCUSSION: The results suggest that these PROMs are not sufficiently responsive for evaluating treatment effect in peripheral vascular malformations. Our study emphasizes the need for assessing responsiveness before using a PROM in evaluating treatment effect.
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BACKGROUND: The OVAMA (Outcome Measures for Vascular Malformations) project determined quality of life (QoL) as a core outcome domain for patients with vascular malformations. In order to measure how current therapeutic strategies alter QoL in these patients, a patient-reported outcome measurement (PROM) responsive to changes in QoL is required. OBJECTIVES: To assess the responsiveness of two widely used generic QoL PROMs, the Medical Outcomes Study Short Form 36 (SF-36) and Skindex-29, in adult patients with vascular malformations. METHODS: In an international multicentre prospective study, treated and untreated patients completed the SF-36 and Skindex-29 at baseline and after a follow-up period of 6-8 weeks. Global rating of change (GRC) scales assessing various QoL-related outcome domains were additionally completed. Per subscale, responsiveness was assessed using two methods: by testing hypotheses on expected correlation strength between change scores of the questionnaires and the GRC scales, and by calculating the area under the receiver operating characteristics curve (AUC). The questionnaires were considered responsive if ≥ 75% of the hypotheses were confirmed or if the AUC was ≥ 0·7. RESULTS: Eighty-nine participants were recruited in three centres in the Netherlands and the U.S.A., of whom 67 completed all baseline and follow-up questionnaires. For all subscales of the SF-36 and Skindex-29, < 75% of the hypotheses were confirmed and the AUC was < 0·7. CONCLUSIONS: Our findings suggest that the SF-36 and Skindex-29 seemed unresponsive to change in QoL. This suggests that alternative PROMs are needed to measure - and ultimately improve - QoL in patients with vascular malformations. What's already known about this topic? Quality of life is often impaired in patients with vascular malformations. Quality of life is considered a core outcome domain for evaluating treatment of vascular malformations. To measure the effect of treatment on quality of life, a patient-reported outcome measure is required that is responsive to changes in quality of life. What does this study add? This is the first study assessing the responsiveness of quality-of-life measures in patients with vascular malformations. The results seem to indicate that the Medical Outcomes Study Short Form 36 (SF-36) and Skindex-29 are not responsive to changes in quality of life in patients with vascular malformations. What are the clinical implications of this work? Medical Outcomes Study Short Form 36 (SF-36) and Skindex-29 are not ideal to assess the effect on quality of life over time, of treatment strategies for peripheral vascular malformations.
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Calidad de Vida , Malformaciones Vasculares , Adulto , Humanos , Países Bajos , Estudios Prospectivos , Encuestas y Cuestionarios , Malformaciones Vasculares/terapiaRESUMEN
BACKGROUND: Vascular proliferation is considered an important feature in psoriasis. Early psoriatic changes are characterized by vascular network expansion; healing of the lesions ultimately results in a decreasing size of the vascular network. Currently, the response of the vasculature in psoriatic lesions during treatment of adalimumab is still obscure. OBJECTIVE: To investigate the response of the vasculature in psoriatic lesions during adalimumab treatment, using parameters such as endothelial cell proliferation, vascular network size and alternations in vessel diameter. METHODS: The endothelial cell response (endothelial cell proliferation rate, vascular network size and vessel diameter) was studied, using an immunohistochemical double-staining of Ki67/CD31, in subsequent biopsies of psoriatic lesions from 10 patients treated with adalimumab at baseline, 10 days and 16 weeks after initiation of treatment. RESULTS: In active psoriatic skin the endothelial cell proliferation ratio is high and an increased vascular network size and vessel diameter is found. An evident decrease in all these parameters is found during 16 weeks treatment with adalimumab. Keratinocyte proliferation already decreased significantly and substantially after 10 days treatment. DISCUSSION: Adalimumab treatment of psoriasis causes an evident reduction in endothelial cell proliferation, vascular network size and vessel diameter, parallel to the clinical improvement. Vascular parameters do not capture early improvement to adalimumab treatment, however (non-)invasive measurement of vascular function parallels, the clinical improvement and may be a valuable marker for disease activity.
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Adalimumab/uso terapéutico , Antirreumáticos/uso terapéutico , Vasos Sanguíneos/efectos de los fármacos , Células Endoteliales/efectos de los fármacos , Psoriasis/tratamiento farmacológico , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Piel/efectos de los fármacosRESUMEN
BACKGROUND: An important limitation in vascular malformation research is the heterogeneity in outcome measures used for the evaluation of treatment outcome. OBJECTIVES: To reach international consensus on a core outcome set (COS) for clinical research on peripheral vascular malformations: lymphatic (LM), venous (VM) and arteriovenous malformations (AVM). In this consensus study, we determined what domains should constitute the COS. METHODS: Thirty-six possibly relevant outcome domains were proposed to an international group of physicians, patients and the parents of patients. In a three-round e-Delphi process using online surveys, participants repeatedly rated the importance of these domains on a five-point Likert scale. Participants could also propose other relevant domains. This process was performed for LM, VM and AVM separately. Consensus was predefined as 80% agreement on the importance of a domain among both the physician group and the patient/parent group. Outcomes were then re-evaluated in an online consensus meeting. RESULTS: 167 physicians and 134 patients and parents of patients with LM (n = 50), VM (n = 71) and AVM (n = 29) participated in the study. After three rounds and a consensus meeting, consensus was reached for all three types of vascular malformations on the core domains of radiological assessment, physician-reported location-specific signs, patient-reported severity of symptoms, pain, quality of life, satisfaction and adverse events. Vascular malformation type-specific signs and symptoms were included for LM, VM and AVM, separately. CONCLUSIONS: Our recommendation is that therapeutic-efficacy studies on peripheral vascular malformations should measure at least these core outcome domains.
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Malformaciones Vasculares/terapia , Malformaciones Arteriovenosas/terapia , Consenso , Técnica Delphi , Humanos , Sistema Linfático/anomalías , Resultado del TratamientoRESUMEN
BACKGROUND: Infantile haemangioma (IH) is a benign, common and self-limiting tumour of infancy; only a minority of cases need active treatment. Currently, propranolol appears superior to classic treatments. OBJECTIVES: To document in a prospective study indications and side-effects of propranolol for complicated IH in a large patient group. METHODS: Analysis of prospectively collected data was performed on 174 patients with IH treated with propranolol in a tertiary referral centre from September 2008 to January 2012. RESULTS: The group consisted of children with a potentially threatening and/or complicated IH; the girl/boy ratio was 123/51, and the mean age at the start of treatment was 4·8 months. In 173 cases (99·4%), treatment was successful, as assessed nonquantitatively by clinical observation. This striking effect was characterized by immediate cessation of growth, softening, fading of the erythema and rapid induction of regression. The mean duration of treatment was 10·7 months. The most important adverse effects were hypotension (3·4%), wheezing (9·2%), nocturnal restlessness (22·4%) and cold extremities (36·2%). In one patient, propranolol was stopped. In 15 patients it was necessary to reduce the dose, although the lower dose was still effective. CONCLUSIONS: In this study, propranolol was effective and safe in almost all patients with complex IH. Administration of systemic medication to an infant with a benign condition requires careful consideration, as only a minority of patients with IH require an active medical intervention. A shift of the indication of propranolol for IH is evident, expanding its application for life-threatening situations or severe functional impairment to early prevention of disfigurement or cosmetically permanent sequelae. However, the indication for such an active approach should be determined by experienced physicians.
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Antagonistas Adrenérgicos beta/administración & dosificación , Hemangioma/tratamiento farmacológico , Propranolol/administración & dosificación , Neoplasias Cutáneas/tratamiento farmacológico , Administración Oral , Antagonistas Adrenérgicos beta/efectos adversos , Esquema de Medicación , Femenino , Hemangioma/complicaciones , Humanos , Lactante , Masculino , Propranolol/efectos adversos , Estudios Prospectivos , Neoplasias Cutáneas/complicaciones , Resultado del TratamientoRESUMEN
AIM: This paper is a report of a study to identify the determinants of physical activity (PA) in patients with venous leg ulcers to develop recommendations for behavioural interventions aimed at enhancing physical activity. BACKGROUND: Physical activity promotes wound healing and prevents the recurrence of wounds in venous patients with leg ulcers. Many patients with leg ulcers, however, have a sedentary lifestyle. METHOD: A random sample of 25 patients from two clinics were interviewed in 2003 using a combination of prestructured and open-ended questions. All these patients were being treated at an outpatient dermatology clinic and had a leg ulcer with venous or mixed aetiology at the time of the interview or in the month prior to the interview. FINDINGS: Only nine of the 25 patients (36%) reported sufficient levels of moderate strenuous physical activity, defined as 30 minutes a day on at least 5 days a week. The results show limited knowledge about the relationship between physical activity and leg ulceration, and low self-efficacy for increasing physical activity. In addition, multi-morbidity, pain and social support were identified as main determinants of physical activity. CONCLUSION: Suggestions for improving physical activity levels include influencing knowledge, beliefs and self-efficacy. Patient's individual physical limitations, pain, adequate footwear and social support should be taken into account. Programmes offered by specialized dermatology nurses to stimulate physical activity might fulfil patient needs and help enhance physical activity levels.
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Ejercicio Físico , Conductas Relacionadas con la Salud , Úlcera de la Pierna/terapia , Úlcera Varicosa/terapia , Anciano , Anciano de 80 o más Años , Estudios Transversales , Ejercicio Físico/psicología , Femenino , Humanos , Estilo de Vida , Masculino , Persona de Mediana Edad , Encuestas y CuestionariosRESUMEN
Lichen sclerosus is a chronic disorder of skin and mucosa which affects patients of all age groups, particularly women, but also men. It is most commonly seen on the female genital skin, but it also occurs on extragenital areas. Most patients complain of itching and, less frequently, a burning sensation, dyspareunia, dysuria and painful defecation are reported. The cause of lichen sclerosus is largely unknown. However, it has been suggested that a genetic predisposition to inflammatory disorders, an immunological constitution, hormonal influences and local factors might play a role. Anogenital lichen sclerosus is associated with an increased incidence of malignancies, especially vulvular squamous-cell carcinomas. The life-time risk of developing this carcinoma is about 5%. Extragenital lichen sclerosus and lichen sclerosus in children do not seem to be correlated with malignancy. Potent local corticosteroids form the mainstay of treatment for lichen sclerosus. The condition is characterised by remissions and exacerbations. Long-term follow-up is required for the early diagnosis of malignant changes.
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Corticoesteroides/uso terapéutico , Liquen Escleroso y Atrófico/patología , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/epidemiología , Carcinoma de Células Escamosas/etiología , Niño , Diagnóstico Diferencial , Femenino , Predisposición Genética a la Enfermedad , Humanos , Liquen Escleroso y Atrófico/epidemiología , Liquen Escleroso y Atrófico/etiología , Liquen Escleroso y Atrófico/terapia , Masculino , Pronóstico , Neoplasias de la Vulva/diagnóstico , Neoplasias de la Vulva/epidemiología , Neoplasias de la Vulva/etiologíaRESUMEN
OBJECTIVE: To gain insight in gait and calf muscle endurance in patients with severe chronic venous insufficiency. METHODS: Fifteen patients with severe chronic venous insufficiency (healed or active ulcers) and 19 healthy controls were selected for this study. Subjects had to perform eight trials at preferred walking speed and eight trials at instructed walking speed (1.25 m/s) during which the gait parameters were recorded. The calf muscle endurance was tested by use of the heel-rise test. RESULTS: Patients had a significantly lower preferred walking speed (1.25 m/s +/- 0.31) compared with healthy controls (1.44 m/s +/- 0.0.15) (p = 0.039). During preferred walking speed patients had a wider base of support (p = 0.003), a bigger step time (p = 0.005), and a bigger stride time (p = 0.004) compared with healthy controls. At instructed walking speed only base of support was different between the two groups (p = 0.016). Patients had a significantly (p = 0.003) smaller number of heel rises (14.6 +/- 7.34), indicating decreased calf muscle endurance compared with controls (23.5 +/- 6.54). CONCLUSION: This study indicates a disturbed gait and decreased calf muscle endurance in patients with severe chronic venous insufficiency. The results of this study point to a possible role for gait and strength training in the rehabilitation process of patients with severe chronic venous insufficiency.
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Marcha , Pierna/irrigación sanguínea , Músculo Esquelético , Resistencia Física , Insuficiencia Venosa/fisiopatología , Adulto , Anciano , Estudios de Casos y Controles , Enfermedad Crónica , Femenino , Humanos , Masculino , Persona de Mediana Edad , Países Bajos , Insuficiencia Venosa/rehabilitaciónRESUMEN
BACKGROUND: The aim of the current study was to investigate whether the StethoDop can serve as a valid and reproducible instrument for measuring the ankle-brachial index (ABI) and assessing venous reflux, even when used by inexperienced investigators, in comparison with the classic Doppler. METHODS: I) During four weeks, four ankle-brachial index (ABI) measurements were performed on 44 patients: one measurement with the classic Doppler by an experienced investigator, one with the classic Doppler by an inexperienced investigator and two measurements with the StethoDop by the inexperienced investigator. II) 36 patients were screened for venous insufficiency by detecting venous reflux with the StethoDop and classic Doppler at the saphenofemoral and saphenopoplitial junctions by an inexperienced investigator. The results were compared with the results of the duplex as gold standard and with the results of the examination by an experienced dermatologist with the classic Doppler. RESULTS: I) The confidence interval of ABI measurement for both the classic Doppler and the StethoDop by the inexperienced investigator was within an acceptable +/- 0.21 interval of significant change. II) For venous reflux determination, the overall sensitivity and specificity of the StethoDop were comparable with the sensitivity and specificity of the classic Doppler: sensitivity 76.0 and 75.0%, specificity 94.8 and 94.2%, respectively. The positive predictive value of the StethoDop, compared with the duplex, was 87.5%; the negative predictive value was 90.0%. CONCLUSION: I) For ABI measurement, the StethoDop is a valid instrument with reproducible results, even when used by inexperienced investigators. II) For venous reflux determination, the StethoDop is a valid screening instrument for venous insufficiency. However, as with determination with the classic Doppler, the reflux assessment by StethoDop gives no information about the deep veins and may miss up to 24% of apparent reflux.
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Extremidad Inferior/irrigación sanguínea , Estetoscopios , Ultrasonografía Doppler , Insuficiencia Venosa/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Tobillo/irrigación sanguínea , Tobillo/fisiopatología , Presión Sanguínea/fisiología , Arteria Braquial/diagnóstico por imagen , Arteria Braquial/fisiopatología , Femenino , Vena Femoral/diagnóstico por imagen , Vena Femoral/fisiopatología , Humanos , Extremidad Inferior/fisiopatología , Masculino , Persona de Mediana Edad , Países Bajos/epidemiología , Arteria Poplítea/diagnóstico por imagen , Arteria Poplítea/fisiopatología , Valor Predictivo de las Pruebas , Prevalencia , Factores de Riesgo , Vena Safena/diagnóstico por imagen , Vena Safena/fisiopatología , Sensibilidad y Especificidad , Insuficiencia Venosa/epidemiología , Insuficiencia Venosa/fisiopatologíaRESUMEN
Clearance and relapse characteristics of clobetasol lotion under hydrocolloid occlusion once weekly versus clobetasol ointment twice daily were assessed in a comparative flow cytometric study. Quantitative analysis of markers for epidermal proliferation, differentiation and inflammation was performed on epidermal single cell suspensions prepared from 3-mm punch biopsies taken from 15 patients with psoriasis vulgaris before therapy, at clearance and 6 weeks after clearance. After treatment both therapy regimens resulted in substantial changes of all flow cytometric parameters, but clearance was induced earlier in the corticosteroid under hydrocolloid occlusion-treated group. With respect to the relapse phase no difference was observed between both treatments. Although it is remotely possible that the outcome in the treatment of more extensive psoriatic lesions might be different, the present study suggests that the robust clinical efficacy of the treatment with a topical corticosteroid under hydrocolloid occlusion is not associated with a rebound phenomenon.
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Antiinflamatorios/administración & dosificación , Clobetasol/administración & dosificación , Coloides/administración & dosificación , Citometría de Flujo , Psoriasis/tratamiento farmacológico , Administración Tópica , Antiinflamatorios/farmacocinética , Vendas Hidrocoloidales , Clobetasol/farmacocinética , Coloides/farmacocinética , Esquema de Medicación , Citometría de Flujo/métodos , Glucocorticoides , Humanos , Pomadas , Psoriasis/metabolismo , Psoriasis/patología , RecurrenciaRESUMEN
Scalp psoriasis is a frequent expression of the common skin disease psoriasis, and scaling and itching are the two major complaints. Topical treatments are the mainstay of the treatment of psoriasis of the scalp, with the vehicle as well as the active ingredient relevant to efficacy, tolerability and compliance. Vehicles can be shampoos, lotions, gels, foams, creams and more greasy ointments. Active ingredients are keratolytics, coal tar (liquor carbonis detergens), dithranol, corticosteroids and vitamin D3 analogues. Some effect has also been described from topical or systemic imidazole derivatives. Topical corticosteroids remain the mainstay in the treatment of scalp psoriasis. The effects are rapid, the formulations are patient friendly and the adverse effects seem limited, although no data are available to support safety during prolonged use (more than 4 weeks). Topical vitamin D3 analogues have been available for the treatment of psoriasis since 1992. In the lotion formulation in particular, vitamin D3 analogues are a patient friendly, tolerable and effective alternative to corticosteroids, although the effects are optimal after 8 weeks, in contrast to 2-3 weeks for topical corticosteroids. Facial irritation (often temporary) can also be a disadvantage of vitamin D3 analogues, although only a small proportion of patients stop treatment for this reason. All other treatment options for psoriasis, such as tazarotene, phototherapy and systemic treatment with methotrexate, acitretin and cyclosporin are often not indicated or not suitable for treatment of the scalp. In daily practice, to make a choice from the available therapeutic arsenal for psoriasis, each patient should be examined individually. Deteriorating factors have to be excluded. For scaling, keratolysis is the first step. Subsequently, active treatment can be chosen depending on the clinical picture. When the psoriatic lesions are mainly characterised by inflammation, anti-inflammatory drugs such as topical corticosteroids are indicated. When scaling is the more important clinical feature, vitamin D3 analogues are indicated. Generally, intermittently used topical corticosteroids alternating with vitamin D3 derivatives either combined or not with liquor carbonis detergens containing shampoo is the most suitable treatment for most patients. Because psoriasis capitis is a chronic disease, long term treatment should, in addition to medical advice, also provide patient support and motivation.
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Corticoesteroides/uso terapéutico , Psoriasis/tratamiento farmacológico , Cuero Cabelludo , Administración Tópica , Colecalciferol/análogos & derivados , Colecalciferol/uso terapéutico , Guías como Asunto , Humanos , Fototerapia , Psoriasis/fisiopatología , Psoriasis/terapiaRESUMEN
It is well established that the efficacy of corticosteroids under occlusion with hydrocolloids (HCD) is superior compared to monotherapy with topical corticosteroids. However, following treatment with more potent corticosteroids, increased side effects and a more pronounced rebound might be expected. In the present clinical study, the efficacy of relapse after and the safety characteristics of two treatment modalities were compared: clobetasol-17-propionate lotion under an HCD dressing once weekly versus clobetasol-17-propionate ointment without an HCD twice daily. Clinical assessments were recorded and skin biopsies were taken before therapy, at clearance and 6 weeks after clearance. A panel of monoclonal antibodies to characterize epidermal proliferation, differentiation and inflammation were selected. In addition, clinical and histological assessments for skin atrophy were made. Both therapies had a major therapeutic effect, which was reflected in the clinical and immunohistochemical parameters. The only difference between the two therapies was a faster remission induction time in patients treated with corticosteroids combined with HCD. Six weeks after discontinuation of treatment, similar clinical and histological signs of relapse were observed for both therapies. Clinically, there were no signs of skin atrophy but histologically, epidermal thinning occurred to the same extent with both therapies but proved to be reversible within 6 weeks of discontinuation of treatment. From this study it can be concluded that the combination of HCD and corticosteroids is able to induce relatively fast remission compared to corticosteroid monotherapy but relapse and safety characteristics are comparable to the unoccluded corticosteroid therapy.
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Antiinflamatorios/administración & dosificación , Clobetasol/análogos & derivados , Coloides , Apósitos Oclusivos , Psoriasis/tratamiento farmacológico , Administración Tópica , Adulto , Anciano , Antiinflamatorios/efectos adversos , Antiinflamatorios/uso terapéutico , Clobetasol/administración & dosificación , Clobetasol/efectos adversos , Clobetasol/uso terapéutico , Esquema de Medicación , Femenino , Glucocorticoides , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Pomadas , Psoriasis/metabolismo , Recurrencia , Inducción de Remisión , Piel/metabolismoAsunto(s)
Amlodipino/efectos adversos , Antihipertensivos/efectos adversos , Hiperplasia Gingival/inducido químicamente , Telangiectasia/inducido químicamente , Amlodipino/uso terapéutico , Antihipertensivos/uso terapéutico , Preescolar , Femenino , Hiperplasia Gingival/patología , Humanos , Hipertensión/tratamiento farmacológico , Telangiectasia/patologíaRESUMEN
Tenascin-C is an extracellular matrix glycoprotein that is markedly upregulated in the dermis of psoriatic skin. In this study, we have addressed the question whether the presence of tenascin-C in the lesion or in serum is a marker for disease activity. Immunohistochemical staining of tenascin-C before and after treatment with different topical and systemic medication showed that tenascin-C remained abundant after clinical remission of lesions, indicating that downregulation of tenascin-C to normal values is a slow process. By using a sensitive enzyme-linked immunosorbent assay to measure levels of serum tenascin-C in psoriatic patients and unaffected individuals, we found that tenascin-C levels in most patients were within the normal range. Moreover, tenascin-C values did not correlate with disease activity. We conclude that tenascin-C is not useful as a marker for disease activity in psoriasis.
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Psoriasis/metabolismo , Tenascina/metabolismo , Biomarcadores/sangre , Femenino , Humanos , Inmunohistoquímica , Masculino , Psoriasis/tratamiento farmacológico , Inducción de Remisión , Piel/química , Piel/efectos de los fármacos , Piel/patología , Tenascina/efectos de los fármacosRESUMEN
A parallel-group, double-blind, randomised study was performed to establish the effect of the vitamin D3 analogue KH 1060, in an ointment versus vehicle only, on the epidermal cell characteristics of chronic idiopathic lichen planus; KH 1060 also has marked immunosuppressive activity. A group of 10 patients were treated for 8 weeks with either KH 1060 ointment or vehicle only. In addition to the assessment of clinical scores, keratotome biopsies were taken before and after 8 weeks' treatment. Epidermal cell suspensions were prepared with trypsin and the suspensions incubated with TO-PRO-3 (DNA marker), RKSE 60 (marker for keratin 10-positive cells) and antivimentin (marker for all non-keratinocytes). In nine of the 10 patients, keratotome biopsies were obtained both before and after 8 weeks treatment. The vehicle alone had no significant effect on the clinical severity scores or epidermal cell characteristics. In contrast, the KH 1060 ointment resulted in a statistically significant reduction in the percentage of cells in S- and G2M phase and the percentage of vimentin-positive cells, but it did not affect the percentage of keratin 10-positive cells.
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Calcitriol/análogos & derivados , Inmunosupresores/uso terapéutico , Liquen Plano/tratamiento farmacológico , Calcitriol/uso terapéutico , Método Doble Ciego , Femenino , Humanos , Queratinocitos/patología , Liquen Plano/patología , Masculino , Persona de Mediana Edad , Mitosis , Fase S , Piel/efectos de los fármacosRESUMEN
Lichen planus (LP) and discoid lupus erythematosus (DLE) are separate disease entities. Nevertheless, patients with a so-called "overlap syndrome" have been described occasionally. The aim of the present study was to establish whether the LE/LP overlap syndrome, based on clinical and routine histological features, could be delineated from DLE or LP using immunohistochemical techniques. Formalin-fixated, paraffin-embedded skin biopsies of patients with DLE, LP and the overlap syndrome were compared regarding immunohistochemical markers for epidermal growth and differentiation and extracellular matrix components. With the markers for extracellular matrix proteins, it was possible to delineate the overlap syndrome from LP. This was not possible for the overlap syndrome and DLE. These findings might indicate that the LE/LP overlap syndrome could be considered as LP-like DLE rather than as a distinct disease entity.
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Factor de Crecimiento Epidérmico/análisis , Proteínas de la Matriz Extracelular/análisis , Liquen Plano/patología , Lupus Eritematoso Discoide/patología , Adulto , Anciano , Biomarcadores/análisis , Biopsia con Aguja , Técnicas de Cultivo , Diagnóstico Diferencial , Femenino , Humanos , Inmunohistoquímica , Queratinas/análisis , Masculino , Persona de Mediana Edad , SíndromeRESUMEN
Dithranol has been used successfully in the treatment of psoriasis for more than 75 years, and much in vitro and in vivo research has been done on the elucidation of the mode of action of this potent and safe antipsoriatic therapy. In vivo research has revealed major effects of dithranol on epidermal proliferation and inflammation. Information on the in vivo effects on epidermal differentiation is limited. Therefore, the dynamics of a set of differentiation markers (keratin 16, filaggrin, keratinocyte transglutaminase, involucrin) and markers for proliferation and inflammation (Ki-67, T lymphocytes, polymorphonuclear leucocytes) were studied in skin biopsies of six patients with psoriasis during 4 weeks of dithranol therapy. The treatment regimen involved a short contact protocol at our out-patient day treatment centre with an easily washed off cream. Treatment resulted in a decrease of the PASI score of 48% in 4 weeks. Immunohistochemically, a major decrease of keratin 16 content and virtually complete restoration of the filaggrin positive cell layer were seen. These changes proved to be significant by comparison of the markers over the group of six patients. Although many other topical treatments for psoriasis (occlusive therapy and vitamin D3 analogues) result in a prominent reduction in the amount of transglutaminase and involucrin positive cell layers, the effect of dithranol on these markers is minimal.
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Antralina/uso terapéutico , Epidermis/efectos de los fármacos , Psoriasis/tratamiento farmacológico , Administración Cutánea , Adulto , Diferenciación Celular/efectos de los fármacos , Enfermedad Crónica , Epidermis/patología , Femenino , Proteínas Filagrina , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Psoriasis/patología , Coloración y EtiquetadoRESUMEN
Micanol, in which dithranol is micro-encapsulated in crystalline monoglycerides, is easy to wash off and staining and irritation are inconspicuous. These features make it appropriate to use in an out-patient setting. In this study the immunohistochemical effects of this new dithranol formulation were studied and compared with UVB and the combination of these therapies in skin biopsies of 8 patients with psoriasis. Markers for epidermal differentiation, proliferation and cutaneous inflammation were assessed. The present study suggests that Micanol predominantly had diminishing effects on inflammation markers, hardly affecting the epidermis. UVB had a broad spectrum of reductions. It is feasible that the combination resulted in various synergistic effects. Previous studies, however, revealed a relative persistence of the inflammatory infiltrate with more effects on epidermal processes following dithranol treatment. Based on the present study and on previous studies, it is hypothesised that Micanol delivers the active substance more directly in the dermal infiltrate, leaving the epidermis relatively unaffected. This might explain the low irritancy of Micanol treatment.