RESUMEN
Of the 131 studies on monotherapy or combination therapy assessed, 56 studies on the different forms of phototherapy fulfilled the criteria for inclusion in the guidelines. Approximately three-quarters of all patients treated with phototherapy attained at least a PASI 75 response after 4 to 6 weeks, and clearance was frequently achieved (levels of evidence 2 and 3). Phototherapy represents a safe and very effective treatment option for moderate to severe forms of psoriasis vulgaris. The onset of clinical effects occurs within 2 weeks. Of the unwanted side effects, UV erythema from overexposure is by far the most common and is observed frequently. With repeated or long-term use, the consequences of high, cumulative UV doses (such as premature aging of the skin) must be taken into consideration. In addition, carcinogenic risk is associated with oral PUVA and is probable for local PUVA and UVB. The practicability of the therapy is limited by spatial, financial, human, and time constraints on the part of the physician, as well as by the amount of time required by the patient. From the perspective of the cost-bearing institution, phototherapy has a good cost-benefit ratio. However, the potentially significant costs for, and time required of, the patient must be considered.
Asunto(s)
Psoriasis/tratamiento farmacológico , Adalimumab , Alefacept , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales Humanizados , Ciclosporina/efectos adversos , Ciclosporina/uso terapéutico , Fármacos Dermatológicos/efectos adversos , Fármacos Dermatológicos/uso terapéutico , Etanercept , Humanos , Inmunoglobulina G/efectos adversos , Inmunoglobulina G/uso terapéutico , Infliximab , Metotrexato/efectos adversos , Metotrexato/uso terapéutico , Terapia PUVA/efectos adversos , Receptores del Factor de Necrosis Tumoral/uso terapéutico , Proteínas Recombinantes de Fusión/efectos adversos , Proteínas Recombinantes de Fusión/uso terapéutico , Retinoides/efectos adversos , Retinoides/uso terapéuticoRESUMEN
This study demonstrates the presence of tight junction antigens in adult and developing human epidermis. Indirect immunofluorescence labeling and immunoelectron microscopy with antibodies to ZO-1 and occludin localized tight junction components ZO-1 and occludin to a narrow zone of the granular cells of adult epidermis. Double immunolabeling for tight junction components with adherens junction or desmosome proteins suggested that occludin is more specific for tight junctions than ZO-1, which may also be associated with adherens junctions. In developing skin, tight junctions interconnected the peridermal cells, and after the fetal stratification localized to the granular cell layer. Immunolabeling of psoriasis, lichen planus, and ichthyosis vulgaris, representing aberrant differentiation of the epidermis, showed that these conditions were associated with relocation of ZO-1 and occludin to the spinous cells. Cultures of epidermal keratinocytes, which offer a useful model for the formation of cellular contacts, revealed that tight junction components, ZO-1 and occludin, displayed a marked degree of colocalization relatively late during the process when the fusion zone had assumed a linear appearance. This suggests that the formation of adherens junctions and desmosomes precedes that of tight junctions. We speculate that the epidermal barrier, isolating the human body from the external environment, is in part formed by tight junctions of stratum granulosum.
Asunto(s)
Epidermis/metabolismo , Queratinocitos/citología , Queratinocitos/metabolismo , Proteínas de la Membrana/metabolismo , Fosfoproteínas/metabolismo , Enfermedades de la Piel/metabolismo , Piel/embriología , Piel/metabolismo , Uniones Estrechas/metabolismo , Adulto , Anciano , Diferenciación Celular , Células Cultivadas , Proteínas del Citoesqueleto/metabolismo , Desmoplaquinas , Embrión de Mamíferos/fisiología , Desarrollo Embrionario y Fetal , Humanos , Ictiosis Vulgar/metabolismo , Liquen Plano/metabolismo , Persona de Mediana Edad , Ocludina , Psoriasis/metabolismo , Valores de Referencia , Piel/ultraestructura , Proteína de la Zonula Occludens-1RESUMEN
Neurofibromin enhances the inactivation of protooncogene p21ras and has been suggested to function as a regulator of cell growth and differentiation. In normal skin, neurofibromin is particularly abundant in the basal keratinocytes of epidermis. The present study utilized antibodies raised against two synthetic peptides corresponding to different regions of neurofibromin. One of the antibodies recognized all forms of neurofibromin and the other was specific for type II neurofibromin. The following specimens were analyzed for neurofibromin immunoreactivity: 1) skin of apparently healthy volunteers, 2) active lesions of 15 psoriatic patients, 3) apparently healthy skin of the same patients at the time of the active phase of the disease, and 4) the previously lesional areas after anti-psoriatic treatment of the same patients. The presence of neurofibromin mRNA in normal epidermis and in keratinocytes cultured from normal skin was demonstrated by reverse transcriptase-polymerase chain reaction or by Northern hybridization. In marked contrast to normal epidermis, active psoriatic lesions were characterized by a weak immunosignal for types I and II neurofibromin in the basal cell layer of the epidermis. Previously lesional, clinically healed areas displayed variable, yet clearly detectable, expression of neurofibromin. Our results demonstrate that the epidermis of psoriatic lesions displays reduced immunostaining for type I and II neurofibromins compared to normal epidermis, and that neurofibromin immunoreactivity is partially restored concomitant with clinical healing of the lesions. The question whether the changes in neurofibromin expression in psoriasis are causal or consequential with respect to the pathogenesis of psoriasis remains to be elucidated.
Asunto(s)
Proteínas/inmunología , Psoriasis/metabolismo , Piel/química , Adolescente , Adulto , Secuencia de Aminoácidos , Secuencia de Bases , Femenino , Humanos , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Neurofibromina 1 , Proteínas/genética , Proteínas/fisiología , Psoriasis/etiología , Psoriasis/patología , ARN Mensajero/análisis , Piel/patologíaRESUMEN
Intracellular calcium plays an important part in the regulation of proliferation and differentiation of keratinocytes. Detached from their in vivo environment, cultured psoriatic keratinocytes were investigated by monitoring free intracellular calcium concentration, which was measured using fura-2/AM as a calcium-sensitive probe. The mean increase in intracellular calcium of psoriatic keratinocytes was significantly reduced compared with control keratinocytes when intracellular calcium stores were mobilized from endoplasmic reticulum with thapsigargin. This finding suggests defective capacitative calcium influx of psoriatic cells. Intracellular calcium stores were similar in psoriatic and control keratinocytes, when extracellular calcium was chelated with ethyleneglycol-bis(beta-aminoethyl ether)-N,N,N',N',-tetraacetic acid and intracellular calcium was depleted with thapsigargin. Mechanical wounding of keratinocyte monolayer resulted in a significantly reduced rise in intracellular calcium of psoriatic cells in low (< 0.1 mM) and high (1.8 mM) extracellular calcium suggesting defective intercellular coupling of psoriatic keratinocytes. Blocking of gap-junctions with heptanol in wounded keratinocytes did not affect the intracellular calcium response in psoriatic keratinocytes in contrast to healthy keratinocytes. Adding adenosine triphosphate to culture medium resulted in a more pronounced intracellular calcium increase than thapsigargin in psoriatic keratinocytes, suggesting that inositol triphosphate-mediated, P2-purinergic signaling was enhanced in these cells. Moreover, psoriatic keratinocytes maintained their defective responses up to at least fifth passage suggesting that psoriatic keratinocytes have an inborn error in calcium metabolism, rather than a localized defect in response to altered extracellular calcium gradient observed in vivo.
Asunto(s)
Calcio/metabolismo , Psoriasis/metabolismo , Adenosina Trifosfato/farmacología , Calcio/farmacología , Calcio/fisiología , Carcinógenos/farmacología , Técnicas de Cultivo de Célula , Quelantes/farmacología , Regulación hacia Abajo/fisiología , Ácido Edético/farmacología , Femenino , Humanos , Recién Nacido , Queratinocitos/patología , Masculino , Persona de Mediana Edad , Psoriasis/patología , Antagonistas del Receptor Purinérgico P2 , Receptores Purinérgicos P2/metabolismo , Transducción de Señal/fisiología , Tapsigargina/farmacología , Heridas y Lesiones/metabolismoRESUMEN
The expression and subcellular localization of neurofibromatosis type 1 tumor suppressor was studied in keratinocytes induced to differentiate by increased Ca2+ concentration of the culture medium. Differentiating keratinocytes became intensely immunoreactive for neurofibromatosis type 1 protein, which was apparently associated with cellular fibrils. Double immunolabeling with antibodies to cytokeratin 14 and neurofibromatosis type 1 protein suggested an association of intermediate type cytoskeleton and neurofibromatosis type 1 protein. The presence of neurofibromatosis type 1 protein in cell preparations treated with cytoskeletal buffer indicated a high affinity interaction between intermediate filaments and neurofibromatosis type 1 protein. Further studies utilizing double immunolabelings revealed that the intense neurofibromatosis type 1 tumor suppressor signal on intermediate filaments was temporally limited to the period in keratinocyte differentiation in which the formation of desmosomes takes place. Keratinocytes were also cultured from nine patients with type 1 neurofibromatosis and were studied with respect to cell morphology, and association of neurofibromatosis type 1 protein with intermediate cytoskeleton. The results showed that keratinocytes cultured from patients with neurofibromatosis type 1 displayed a highly variable cell size and morphology compared to controls. The latter findings represent predicted alterations in a situation where cytoskeletal organization is disturbed. Furthermore, differentiating neurofibromatosis type 1 keratinocytes were characterized by a reduced number of cytokeratin bundles that were decorated neurofibromatosis type 1 protein. The results of this study suggest that neurofibromatosis type 1 tumor suppressor exerts its effects in part by controlling organization of cytoskeleton during the formation of cellular contacts.
Asunto(s)
Genes Supresores de Tumor/fisiología , Adulto , Anciano , Calcio/farmacología , Adhesión Celular , Células Cultivadas , Medios de Cultivo Condicionados , Citoesqueleto/efectos de los fármacos , Desmosomas/química , Humanos , Queratinocitos/citología , Melanocitos/citología , Persona de Mediana EdadRESUMEN
BACKGROUND: Neurofibromas represent proliferation of the connective tissue cells of peripheral nerves and deposition of collagenous extracellular matrix. There is evidence that the appearance and growth of neurofibromas may be associated with prior or ongoing mechanical trauma in patients with neurofibromatosis type 1 (NF1). OBJECTIVE: To study the histologic characteristics of apparently healthy skin of patients with NF1. DESIGN: The histologic features of healthy-looking skin of patients with NF1 were analyzed. SETTING: University hospital. PATIENTS: Ten patients who fulfilled the criteria for NF1. INTERVENTIONS: Punch biopsy specimens of healthy-looking skin of the forearm from 9 volunteer patients and of the upper eyelid during cosmetic operation from 1 volunteer patient were obtained. MAIN OUTCOME MEASURES: The main outcomes were not predicted, and the hypothesis was formulated during data collection. RESULTS: Apparently unaffected skin of 5 patients with NF1 was studied by routine histologic testing with respect to expression of S100 protein. Unexpectedly, analysis of the samples revealed the presence of a small neurofibroma tumor in one of the samples. The tumor was located in deep dermis around a hair follicle. In addition, neurofibromatous tissue not large enough to be called a tumor was found on the same anatomical location in another patient. In further studies, 10 punch biopsy specimens of apparently healthy skin from patients with NF1 were similarly sectioned and analyzed. No tumors were found in these additional samples. In 4 patients, however, abundant S100 protein-positive cells were located within collagenous extracellular matrix surrounding hair follicles. CONCLUSIONS: The skin of patients with NF1 might be more widely affected than previously thought and occult neurofibromas are not rare.
Asunto(s)
Neoplasias Primarias Desconocidas/patología , Neurofibroma/patología , Neurofibromatosis 1/metabolismo , Neurofibromatosis 1/patología , Proteínas S100/metabolismo , Neoplasias Cutáneas/patología , Neoplasias de los Párpados/patología , Antebrazo , Humanos , Neoplasias Primarias Desconocidas/etiología , Neurofibroma/etiología , Neoplasias Cutáneas/etiologíaAsunto(s)
Neurofibromatosis 1/genética , Neurofibromina 1/genética , Columna Vertebral/patología , Secuencia de Bases , Western Blotting , Análisis Mutacional de ADN , ADN Complementario/química , ADN Complementario/genética , ADN de Neoplasias/química , ADN de Neoplasias/genética , Salud de la Familia , Femenino , Humanos , Masculino , Neurofibromatosis 1/metabolismo , Neurofibromatosis 1/patología , LinajeAsunto(s)
Quemaduras/etiología , Terapia PUVA/efectos adversos , Automedicación/efectos adversos , Vitíligo/tratamiento farmacológico , Adulto , Quemaduras/diagnóstico , Femenino , Finlandia , Estudios de Seguimiento , Humanos , Puntaje de Gravedad del Traumatismo , Terapia PUVA/métodos , Medición de RiesgoRESUMEN
BACKGROUND: Acne fulminans is an ulcerative form of acne with an acute onset and systemic symptoms. It most commonly affects adolescent boys. OBJECTIVE: Clinical and laboratory findings and treatment results of patients with acne fulminans were reviewed to obtain a better understanding of the clinical course and outcome of the disease. METHODS: Data of patients with severe acne were collected from the Dermatology Departments of Finnish hospitals during the years 1970 to 1991. RESULTS: Twenty-four patients with acne fulminans are described. All patients had ulcerative acne with acute onset. In 22 patients acne was associated with high fever for at least 1 week. All patients had musculoskeletal pain. Increased uptake in bone scan or radiographic findings compatible with an infectious origin were detected in 17 patients. Eight patients were treated with antibiotics alone, but the response was poor; three patients had a relapse of musculoskeletal symptoms. Ten patients were given systemic steroids in addition to antibiotics. In this group the response was rapid, but acne and musculoskeletal symptoms tended to relapse when the steroid dosage was reduced. Four patients were treated with a combination of antibiotics, systemic steroids, and isotretinoin; all responded well, but one of these patients also had a relapse. CONCLUSION: Musculoskeletal symptoms are common in patients with acne fulminans. Systemic steroid treatment rapidly controls the skin lesions and systemic symptoms. The duration of steroid treatment should be 2 to 4 months to avoid relapses. Therapy with isotretinoin, antibiotics, or both was often combined with steroids, but the role of these agents is still uncertain.
Asunto(s)
Acné Vulgar/tratamiento farmacológico , Acné Vulgar/patología , Acné Vulgar/sangre , Adolescente , Adulto , Antibacterianos/uso terapéutico , Antiinflamatorios no Esteroideos/administración & dosificación , Antiinflamatorios no Esteroideos/uso terapéutico , Sedimentación Sanguínea , Dermatitis Atópica/complicaciones , Femenino , Fiebre , Glucocorticoides/uso terapéutico , Humanos , Isotretinoína/administración & dosificación , Isotretinoína/uso terapéutico , Articulaciones/patología , Leucocitosis/patología , Masculino , Músculos/patología , Osteólisis/patología , Dolor , Estudios Retrospectivos , Tetraciclina/administración & dosificación , Tetraciclina/uso terapéutico , Úlcera/patologíaRESUMEN
Prednisolone combined with erythromycin was given to 6 patients with cystic acne. The treatment responses were compared to those in 6 patients with cystic acne receiving isotretinoin and erythromycin and also to those in 3 patients with acne fulminans treated with prednisolone and erythromycin. During the first 4 weeks cystic acne showed a clear improvement in 5 out of 6 patients in both treatment groups. A similar improvement occurred in all 3 patients with acne fulminans. When corticosteroid was stopped, 2 out of 5 patients with cystic acne had a relapse and needed isotretinoin for complete control. In the isotretinoin-treated group, one patient with cystic acne needed prednisolone because the acne worsened to an ulcerative form. Slightly elevated liver enzymes, possibly due to erythromycin treatment, were observed in 2 patients with cystic acne and in one patient with acne fulminans. The present results show that prednisolone combined with erythromycin is an effective treatment during the early stages of cystic and febrile acne, but isotretinoin is needed for long-term control.
Asunto(s)
Acné Vulgar/tratamiento farmacológico , Isotretinoína/administración & dosificación , Prednisolona/administración & dosificación , Adolescente , Quistes/tratamiento farmacológico , Quimioterapia Combinada , Eritromicina/administración & dosificación , Eritromicina/efectos adversos , Humanos , Isotretinoína/efectos adversos , Masculino , Prednisolona/efectos adversosRESUMEN
OBJECTIVE: Acne fulminans is an uncommon form of ulcerative acne with acute onset. It usually affects adolescent boys who have associated musculoskeletal pain and septic fever. Osteolytic bone lesions have been reported in these patients. Severe cystic acne occurs almost equally in both sexes, but it has a less dramatic clinical course than acne fulminans and rarely causes ulcerative skin lesions and systemic symptoms. In this study we investigated the imaging features of bone lesions associated with acne fulminans and determined if patients with severe cystic acne have similar bone lesions. SUBJECTS AND METHODS: From 1970 through 1991, 24 patients with acne fulminans were treated in the dermatologic departments of Finnish hospitals. Radiologic (plain radiographs or conventional tomograms) or scintigraphic data were available for 21 patients and analyzed retrospectively. For comparison, 20 consecutive patients with severe cystic acne were examined prospectively with scintigraphy. RESULTS: Ten patients (48%) with acne fulminans had lytic bone lesions on the radiographs, and the bone scans showed increased uptake in 14 patients (67%). Destructive lesions resembling osteomyelitis were seen in seven patients. The bones of the anterior chest wall were predominantly involved: sternum in four patients, clavicle in three patients, and acromion scapulae in one patient. Sternoclavicular hyperostosis was seen in six patients. Four patients had small lytic lesions in the epiphyseal growth plate or a periosteal reaction. Follow-up was performed in eight patients with acne fulminans and in seven revealed either normal findings or sclerosis and hyperostosis in the previously affected areas of the sternum and clavicles. Slightly increased uptake of radionuclide, usually in the sternum or around the sternoclavicular joints, was seen in nine patients with severe cystic acne, but these findings were regarded as normal and radiographs were not obtained. CONCLUSION: Lytic lesions in the bones of the anterior chest wall and in the epiphyseal growth plates are common in patients with acne fulminans, but do not seem to occur in patients with severe cystic acne. The prognosis of bone disease associated with acne fulminans appears to be good, and the chronic sequelae, if any, are mild sclerosis and hyperostosis of the affected bones. Acne fulminans should be added to the list of dermatoses associated with bone lesions detectable by radiologic and scintigraphic methods.
Asunto(s)
Acné Vulgar/complicaciones , Huesos/diagnóstico por imagen , Osteólisis/complicaciones , Adolescente , Difosfonatos , Femenino , Humanos , Masculino , Osteólisis/diagnóstico por imagen , Radiografía , Cintigrafía , Compuestos de TecnecioRESUMEN
BACKGROUND: Molecular characterization of tight junction proteins during the past few years has provided novel methods for studying these specialized junctions. Tight junctions have recently been characterized in the granular cell layer of human epidermis, and the role of these junctions in the epidermal barrier is now being re-evaluated. OBJECTIVES: To investigate the expression of tight junction components during the re-epithelialization of suction blisters and the regeneration of the corneal layer after tape stripping. METHODS: Suction blisters were induced in eight healthy volunteers, and skin biopsies were taken 4 or 6 days afterwards. The restoration of epidermal barrier function was evaluated by measuring water evaporation (WE) from the wound area. Tape stripping was performed on three volunteers to remove the corneal layer. The tissues were immunolabelled using indirect immunofluorescence or the avidin-biotin method. RESULTS: Prior to the biopsies, WE from the blister wounds was markedly elevated in comparison with normal skin. In the epidermis surrounding the blister, occludin and ZO-1 were expressed in the granular cell layer only. In the hyperproliferative zone adjacent to the border of the blister, the expression of ZO-1 was redistributed into several spinous cell layers, while occludin expression was restricted to the upper epidermis. In the leading edge of migrating keratinocytes, both proteins were expressed exclusively in the most superficial layer of keratinocytes. Double labelling for ZO-1 and involucrin showed expression of both proteins in the same layers of hyperproliferative keratinocytes, while the expression patterns were clearly different in the migrating keratinocytes. CONCLUSIONS: Tight junctions of regenerating epidermis may provide a functional barrier prior to regeneration of the corneal layer.
Asunto(s)
Epidermis/metabolismo , Proteínas de la Membrana/metabolismo , Fosfoproteínas/metabolismo , Uniones Estrechas/metabolismo , Cicatrización de Heridas/fisiología , Adulto , Epidermis/lesiones , Epidermis/fisiología , Femenino , Técnica del Anticuerpo Fluorescente Indirecta , Humanos , Técnicas para Inmunoenzimas , Queratinocitos/metabolismo , Masculino , Ocludina , Precursores de Proteínas/metabolismo , Pérdida Insensible de Agua/fisiología , Proteína de la Zonula Occludens-1RESUMEN
We examined all babies born live (4346) at two Finnish hospitals in the course of one year to determine the frequency of birthmarks, specially pigmented lesions, among Finnish newborns. All birthmarks excluding common salmon patches on the forehead and neck were recorded and photographed at birth. The babies were re-examined at the age of three months. Various birthmarks were recorded for 241 of 4346 babies, i.e. for 5.5% of all newborns. Ninety-one (2.1%) infants had congenital pigmented skin lesions, 167 (3.8%) had various vascular lesions and 21 (0.5%) had other birthmarks. The frequency of congenital melanocytic naevi was 1.5%. Most of the naevi were less than 20 mm in diameter. Only one child had a giant naevus. The frequency of congenital naevi in our study was the same or somewhat higher than previously described (1-8) but fewer other pigmented skin lesions were found than in previous studies perhaps due to racial differences.
Asunto(s)
Hemangioma/epidemiología , Nevo Pigmentado/epidemiología , Trastornos de la Pigmentación/epidemiología , Neoplasias Cutáneas/epidemiología , Femenino , Finlandia/epidemiología , Hemangioma/congénito , Hemangioma/patología , Humanos , Recién Nacido , Masculino , Nevo Pigmentado/congénito , Nevo Pigmentado/patología , Trastornos de la Pigmentación/congénito , Trastornos de la Pigmentación/patología , Neoplasias Cutáneas/congénito , Neoplasias Cutáneas/patologíaRESUMEN
To investigate the inflammatory and immunological aspects of severe acne, we examined the luminol-enhanced chemiluminescence of whole blood, T-cell subsets and natural killer cell functions in 11 patients with severe nodular acne and 4 patients with acne fulminans. In patients with severe nodular acne, the active phase of the disease, compared to the values in remission (means 47 mV, SD 24.8 and 32 mV, SD 8.3, p < 0.05). The patients with acne fulminans also showed high values in the active phase of the disease (mean mV 68.3, SD3.5) compared to remission (mean 30.5 mV, SD 15.3). No marked alterations were seen in the percentages of T-helper cells, T-suppressor cells or DR-positive lymphocytes or in the levels of soluble interleukin 2 receptor. The percentages and activities of natural killer cells did not show any significant changes either. Five patients (4 with severe nodular acne and one with acne fulminans, accounting for 33% of all patients) carried HLA Cw6 antigen, which is a significantly increased frequency compared to health controls (pc = 0.015). The present chemiluminescence results suggest that peripheral blood neutrophils are activated in patients with severe acne.
Asunto(s)
Acné Vulgar/sangre , Subgrupos de Linfocitos T/inmunología , Acné Vulgar/tratamiento farmacológico , Acné Vulgar/inmunología , Adolescente , Adulto , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Femenino , Antígenos HLA-C/análisis , Antígenos HLA-DR/análisis , Humanos , Células Asesinas Naturales/inmunología , Mediciones Luminiscentes , Luminol , Masculino , Neutrófilos/inmunología , Receptores de IgG/análisis , Receptores de Interleucina-2/análisis , Inducción de Remisión , Linfocitos T Colaboradores-Inductores/inmunología , Linfocitos T Reguladores/inmunologíaRESUMEN
Acne fulminans is a rare, severe type of acne with unknown etiology. Ulcerative acne lesions, fever and musculoskeletal pain are typical symptoms. In addition, osteolytic or even destructive osteomyelitis-like bone lesions occur in many patients with acne fulminans. In the present study the degradation product (ICTP) of type I collagen, the most abundant collagen of the skeleton, was measured from the sera of patients suffering from acne fulminans. In 3 of 4 acne fulminans patients with active disease, the ICTP concentrations were clearly higher than the range of concentrations in age-matched controls. The mean concentration of ICTP in the acne fulminans patients was 17.6 +/- 6.0 micrograms/I, whereas the corresponding concentration in 6 patients with severe nodular acne was 6.9 +/- 2.1 micrograms/I. Increased uptake of radionuclide in bone scans was observed in all of the 4 patients with acne fulminans. The present results suggest that ICTP is increased in acne fulminans, due to the destruction of bone collagen matrix. ICTP could thus be used for monitoring the activity of acne fulminans affecting the skeleton.
Asunto(s)
Acné Vulgar/metabolismo , Enfermedades Óseas/etiología , Colágeno/sangre , Acné Vulgar/complicaciones , Acné Vulgar/diagnóstico por imagen , Adolescente , Adulto , Biomarcadores/sangre , Enfermedades Óseas/sangre , Enfermedades Óseas/diagnóstico por imagen , Estudios de Casos y Controles , Colágeno/metabolismo , Humanos , Masculino , Pronóstico , Cintigrafía , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: Increased hypersensitivity reactions to Propionibacterium acnes may be involved in the pathogenesis of severe acne. OBJECTIVE: To study delayed and immediate hypersensitivity reactions to P. acnes in patients with severe nodular acne (SNA) and acne fulminans (AF). METHODS: We performed lymphocyte stimulation and skin tests for P. acnes antigens on 11 patients with SNA and 7 patients with AF. RESULTS: The patients with SNA had similar mean lymphocyte stimulation indices (mean 13.96, SD 8.6) to P. acnes during active disease as had healthy controls (12.63, SD 6.46). After the treatment the mean stimulation index was significantly elevated (23.47, SD 13.84, p = 0.006). A similar increase occurred in the patients with AF (mean 17.04, SD 5.74, and 33.42, SD 27.17, respectively). Two of 7 patients with SNA and 3 of the 7 patients with AF but none of the 10 control subjects showed positive 48-hour intradermal tests to P. acnes. CONCLUSION: Specific cell-mediated immunity to P. acnes increases during the course of severe inflammatory acne.
Asunto(s)
Acné Vulgar/inmunología , Acné Vulgar/microbiología , Hipersensibilidad Tardía/inmunología , Propionibacterium acnes/inmunología , Acné Vulgar/fisiopatología , Adolescente , Adulto , Antígenos Bacterianos/inmunología , Femenino , Estudios de Seguimiento , Humanos , Hipersensibilidad Inmediata/inmunología , Inmunidad Celular/inmunología , Activación de Linfocitos/inmunología , Masculino , Pruebas CutáneasRESUMEN
BACKGROUND: Neurofibromatosis type 1 (NF1) protein (neurofibromin) accelerates the inactivation of Ras-GTP in various cell types. Somatic mutations of the NF1 gene may lead to malignant transformation and uncontrolled proliferation. We have previously shown that NF1 protein expression is downregulated in psoriasis in vivo. OBJECTIVES: To study the functional expression and distribution of NF1 mRNA and protein in vivo and in psoriatic and normal keratinocyte cultures. METHODS: Immunohistochemistry and in situ hybridization were used to study NF1 gene and protein expression in psoriasis in vivo. Furthermore, Northern and in situ hybridizations, immunoblot and localization analyses were utilized to study NF1 mRNA and protein in vitro in keratinocyte cultures. RESULTS: NF1 tumour suppressor gene expression was reduced in lesional psoriatic skin compared with perilesional and normal skin in vivo. The in vitro results showed that the levels of NF1 mRNA and protein were reduced in cultured psoriatic keratinocytes during cellular differentiation even after multiple passaging of the cells. Moreover, cultured nonlesional psoriatic keratinocytes were almost equally defective as lesional cells with respect to NF1 expression. CONCLUSIONS: Our findings demonstrate that psoriatic keratinocytes maintain an altered phenotype and gene expression profile even when isolated from interaction with lymphocytes and fibroblasts, which are known to increase proliferation of keratinocytes. As NF1 protein is regarded as a Ras proto-oncogene regulator, the aberrant expression and distribution of NF1 protein and mRNA found in the present study may be causative to the previously described increased activation of Ras in psoriatic lesions, and relate to altered cellular behaviour.
Asunto(s)
Genes de Neurofibromatosis 1 , Genes ras/genética , Neurofibromina 1/análisis , Psoriasis/genética , Northern Blotting , Western Blotting , Células Cultivadas , Expresión Génica , Humanos , Inmunohistoquímica , Queratinocitos , Neurofibromina 1/genética , Proto-Oncogenes Mas , ARN Mensajero/análisisRESUMEN
The MELAS syndrome (mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes) belongs to the category of mitochondrial disorders. The most common molecular aetiology of the syndrome is a mutation at base pair (bp) 3243 in the mitochondrial genome (mtDNA). The phenotype is varied and, apart from central nervous system involvement, the patients with this mutation may present with neurosensory hearing loss, diabetes mellitus and cardiomyopathy. These phenotypes suggest that organs dependent on aerobic metabolism suffer most. We investigated the possible clinical and physiological manifestations of impaired energy metabolism in the skin of 28 patients with the bp 3243 mutation in mtDNA. Non-invasive sonography and laser Doppler flowmetry were used to measure skin thickness and the blood flow of the skin. Skin collagen synthesis was assayed from suction blister fluid. Evaporimetry was used to assess the re-epithelialization rate of suction blister wounds. Histochemistry and immunohistochemistry were used to evaluate the melanocytes and pigment in the skin. Vitiligo was found in three of the 28 patients (11%), which was markedly more than in the general population. Histological findings showed an absence of pigment, but an apparently normal distribution of melanocytes in the dermoepidermal junction. Seborrhoeic eczema and atopy were also somewhat more frequent. No features of premature ageing, such as a marked decrease in skin thickness, blood flow, collagen synthesis or re-epithelialization rate, were demonstrated.