RESUMEN
Little is known about how eosinophils accumulate in bullous pemphigoid (BP) and why these cells rapidly disappear during immunosuppressive therapy. Eosinophils can produce cytokines such as IL-4, IL-5, IL-6, IL-10 and IL13, which can induce endothelial cells to express cellular adhesion molecules (CAMs) such as E-selectin, vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) necessary for the recruitment of eosinophils from the bloodstream to the skin. The present aim was to investigate the cellular expression of these three CAMs in serial biopsies before and during oral low-dose methotrexate therapy. Seventy-four biopsy specimens, 37 from active lesions and 37 from normal skin, were taken at different intervals from eight patients with bullous pemphigoid and stained immunohistochemically with specific monoclonal antibodies for these three CAMs. The expression and distribution of CAMs in the biopsies was evaluated and scored with light-microscopic examination. The basal keratinocytes in active lesions expressed ICAM-1. A strong VCAM-1 expression of endothelial cells and pericytes was correlated to a perivascular inflammatory cell infiltrate that also showed intense immunoreactivity to ICAM-1. Endothelial cell/pericytes also expressed E-selectin strongly in the BP patients before therapy. The expression of CAMs faded during therapy and, to the best of our knowledge, this has not been previously reported. Thus we suggest that the rapid reduction of tissue eosinophils may reflect the altered pattern of cell adhesion molecules during immunosuppressive therapy, which could explain the prompt clinical improvement seen in BP patients treated with methotrexate.
Asunto(s)
Selectina E/metabolismo , Regulación de la Expresión Génica/fisiología , Inmunosupresores/uso terapéutico , Molécula 1 de Adhesión Intercelular/metabolismo , Metotrexato/uso terapéutico , Penfigoide Ampolloso/tratamiento farmacológico , Penfigoide Ampolloso/genética , Piel/patología , Molécula 1 de Adhesión Celular Vascular/metabolismo , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Biopsia , Humanos , Inmunohistoquímica , Penfigoide Ampolloso/patología , Piel/inmunologíaRESUMEN
Using a highly sensitive polymerase chain reaction (PCR) technique, based on general GP5+/GP6+ PCR primers covering 34 different human papillomavirus (HPV) types, the presence of HPV DNA was studied in paraffin-embedded penile biopsies from 20 men treated topically with corticosteroids. Clobetasol propionate was applied for 2-16 (mean 7) weeks by 19 men (age 18-73; mean 40) with lichen sclerosus. High-risk HPV was detected prior to therapy in three patients (16%) who lacked clinical or histopathological signs of HPV infection. Following therapy high-risk HPV was detected in biopsies from four men (21%), of whom three also exhibited clinical and/or light microscopic signs of HPV infection. Low-risk HPV DNA was not detected in any of these samples. Four biopsies were collected during a 5-year period from a 51-year-old man who was treated repeatedly with topical mild-moderate potent corticosteroids at intervals of up to 10 weeks for penile erosive lichen planus, followed by nine clinical outbreaks of typical condylomas that consistently showed the presence of low-risk HPV DNA only. These observations indicate that long-lasting topical corticosteroid therapy occasionally may be associated with opportunistic reactivation of a latent high- and low-risk mucosotrophic HPV type infection. The importance of clinical follow-up is underlined.
Asunto(s)
Clobetasol/análogos & derivados , Clobetasol/efectos adversos , Condiloma Acuminado/diagnóstico , ADN Viral/análisis , Liquen Plano/tratamiento farmacológico , Liquen Escleroso y Atrófico/tratamiento farmacológico , Papillomaviridae/aislamiento & purificación , Infecciones por Papillomavirus/diagnóstico , Administración Tópica , Adolescente , Adulto , Anciano , Biopsia con Aguja , Distribución de Chi-Cuadrado , Clobetasol/administración & dosificación , Condiloma Acuminado/etiología , Técnicas de Cultivo , Humanos , Liquen Plano/patología , Liquen Plano/virología , Liquen Escleroso y Atrófico/patología , Liquen Escleroso y Atrófico/virología , Masculino , Persona de Mediana Edad , Infecciones por Papillomavirus/etiología , Enfermedades del Pene/patología , Enfermedades del Pene/virología , Reacción en Cadena de la Polimerasa , Estudios Prospectivos , Recurrencia , Medición de RiesgoRESUMEN
Soluble iso-forms of cellular adhesion molecules (sCAMs) have been described and reported to be elevated in various inflammatory diseases. Elevated levels of sE-selectin have recently been detected and found to correlate with the number of blisters in bullous pemphigoid (BP) during oral corticosteroid therapy. In this prospective study we analysed levels of sCAMs in 10 elderly BP patients during low-dose oral pulse methotrexate monotherapy. We used standardised ELISA kits for soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1) and sE-selectin on 65 sera from 10 patients and 19 controls. Results were correlated with clinical parameters. Before therapy, we found significant elevation of sE-selectin (P=0.004) and sVCAM-1 (P=0.002) but not of sICAM-1. sE-selectin levels decreased during the efficient therapy and correlated with the number of blisters. Our results further support the proposition that sE-selectin might be a future clinical and predictive tool; but whether the elevation of sVCAM-1 also might reflect the disease activity in BP needs more investigation. The findings also indicate that BP might be more a cellularly mediated disease where interactions of different adhesion molecules play a crucial role.
Asunto(s)
Fármacos Dermatológicos/administración & dosificación , Selectina E/sangre , Molécula 1 de Adhesión Intercelular/sangre , Metotrexato/administración & dosificación , Penfigoide Ampolloso/tratamiento farmacológico , Penfigoide Ampolloso/metabolismo , Molécula 1 de Adhesión Celular Vascular/sangre , Anciano , Anciano de 80 o más Años , Vesícula/metabolismo , Fármacos Dermatológicos/uso terapéutico , Femenino , Humanos , Masculino , Metotrexato/uso terapéutico , Estudios Prospectivos , SolubilidadRESUMEN
BACKGROUND: Treatment with clobetasol propionate 0.05% cream is effective against lichen sclerosus et atrophicus (LSA) of the vulva. OBJECTIVE: The purpose of this study was to retrospectively evaluate whether clinical and histologic responses to topical clobetasol can be accomplished in penile LSA. METHODS: A self-assessment questionnaire was obtained from 22 men with LSA, and a clinical examination was performed in 21 of them. Biopsy specimens from 15 cases were compared before and after treatment. RESULTS: Itching, burning, pain, dyspareunia, phimosis, and dysuria decreased significantly (P < .001 to .05) after 1 to 2 daily applications, for a mean of 7.1 weeks (2-16 weeks). Additional operation for phimosis was required in 6 of the 22 men. All histologic LSA criteria were significantly (P < .01 to .05) reduced after treatment. CONCLUSION: Topical treatment of penile LSA with clobetasol propionate represents a safe and effective therapy with no risk of epidermal atrophy but with some potential for triggering latent infections, most importantly human papillomavirus.