RESUMEN
Primary cutaneous aggressive cytotoxic epidermotropic CD8+ T-cell lymphoma is an extremely rare, rapidly progressing, cutaneous lymphoma, with frequent systemic involvement and poor prognosis, that still represents a diagnostic and therapeutic challenge, especially in the early stage. Herein, we report a case of an elderly woman with a fulminant course, who at onset presented with clinical and pathological features mimicking erythema multiforme (EM) and treated with cyclosporine that led to rapid deterioration with fatal outcome 6 months after disease onset. Histopathology showed a lichenoid, epidermotropic and nodular, angiocentric, dermal and subcutaneous infiltrate of sF1, CD8+, CD45RA+ small to medium-sized atypical lymphoid cells, which strongly expressed cytotoxic markers. Monoclonal T-cell-γ receptor was clonally rearranged and array-CGH showed numerous chromosomal imbalances. This case evidences the clinical, pathological and therapeutic challenges involved in this tumor. The first biopsy showed an interface dermatitis-like pattern, revealing the deceptive features that early cutaneous infiltrates of this aggressive lymphoma may have. A high suspicion for aggressive CTCL and a low threshold for repeat biopsies should be maintained when faced with rapidly progressing and/or ulcerative EM-like lesions, especially if immunomodulatory therapy is being considered.
Asunto(s)
Linfocitos T CD8-positivos , Eritema Multiforme , Leucemia de Células T , Neoplasias Cutáneas , Anciano , Linfocitos T CD8-positivos/metabolismo , Linfocitos T CD8-positivos/patología , Eritema Multiforme/metabolismo , Eritema Multiforme/patología , Resultado Fatal , Femenino , Humanos , Leucemia de Células T/metabolismo , Leucemia de Células T/patología , Neoplasias Cutáneas/metabolismo , Neoplasias Cutáneas/patologíaRESUMEN
Increased dermal mucin is a feature of lupus erythematosus (LE); however, its amount and distribution have not been well characterized. The differentiation of LE from other forms of dermatitis can be challenging when other features of LE are subtle or equivocal. One hundred and thirty-five skin specimens showing LE, graft vs. host disease, erythema multiforme/fixed drug eruption, lichen planus, polymorphous light eruption (PMLE), urticaria, eczematous dermatitis and psoriasis and normal skin with and without photodamage were collected. The amounts of mucin in the papillary, superficial reticular and deep reticular dermis were scored from 0 to 3 on hematoxylin-eosin (H&E) and alcian blue (AB) stains, and compared between groups. The mean scores in the reticular dermis were significantly higher in LE than in other categories except PMLE and eczematous dermatitis. A combined H&E + AB score of ≥5 in the superficial reticular dermis gave an overall specificity of 85.7% for LE. Mucin in the papillary dermis failed to distinguish among entities. Normal photodamaged skin showed significantly more mucin in the superficial reticular dermis compared to non-photodamaged skin. While LE is associated with increased mucin deposition, scant to moderate amount of mucin alone has limited specificity and is common in other dermatitides or photodamaged skin.
Asunto(s)
Lupus Eritematoso Cutáneo/metabolismo , Lupus Eritematoso Sistémico/metabolismo , Mucinas/análisis , Piel/metabolismo , Colorantes/química , Dermis/metabolismo , Dermis/patología , Diagnóstico Diferencial , Erupciones por Medicamentos/metabolismo , Erupciones por Medicamentos/patología , Eccema/metabolismo , Eccema/patología , Eritema Multiforme/metabolismo , Eritema Multiforme/patología , Humanos , Liquen Plano/metabolismo , Liquen Plano/patología , Lupus Eritematoso Cutáneo/patología , Lupus Eritematoso Sistémico/patología , Mucinas/metabolismo , Trastornos por Fotosensibilidad/metabolismo , Trastornos por Fotosensibilidad/patología , Estudios Retrospectivos , Sensibilidad y Especificidad , Piel/patología , Rayos Ultravioleta/efectos adversosRESUMEN
Activating transcription factor 3 (ATF3) expression is increased in erythema multiforme and is regulated by IFN-gamma in human keratinocytes. Experimental Dermatology 2010; 19: e310-e313. Abstract: Activating transcription factor 3 (ATF3) is a member of the ATF/cyclic AMP responsive element-binding protein (CREB) family of transcription factors and is involved in the regulation of immune responses, apoptosis, DNA repair and oncogenesis. The epidermal expression of ATF3 in the setting of cutaneous inflammation has not been well characterized. To examine the expression of ATF3 in the setting of inflammatory skin disease, ATF3 protein expression was analysed by immunohistochemistry (IHC). We found diffuse epidermal ATF3 protein expression in skin biopsies of erythema multiforme (EM). Given the role of interferon (IFN)-gamma in erythema multiforme, we sought to examine the impact of IFN-gamma on ATF3 expression in human keratinocytes. IFN-gamma induced ATF3 mRNA and protein in primary human keratinocytes and HaCaT cells. Thus, epidermal ATF3 expression can be increased in the setting of inflammatory skin diseases and is regulated by IFN-gamma in human keratinocytes.
Asunto(s)
Factor de Transcripción Activador 3/metabolismo , Eritema Multiforme/metabolismo , Interferón gamma/metabolismo , Queratinocitos/metabolismo , Carcinoma Basocelular/metabolismo , Carcinoma Basocelular/patología , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patología , Eritema Multiforme/patología , Humanos , Queratinocitos/patología , Melanoma/metabolismo , Melanoma/patología , ARN Mensajero/metabolismo , Neoplasias Cutáneas/metabolismo , Neoplasias Cutáneas/patologíaRESUMEN
BACKGROUND: The clinical significance of scattered or grouped cytoid bodies seen on direct immunofluorescence (DIF) examination has not been systematically analyzed in a variety of disorders. METHODS: We prospectively studied skin biopsy specimens obtained from July 2002 to December 2005 for which DIF examination using immunoglobulin (Ig) A, IgG, IgM, C3 and fibrinogen had been performed. Slides with cytoid bodies were further reviewed to assess the number, intensity and location of the cytoid bodies and for other specific findings. These data were compared with both clinical records in the medical charts and pathologic findings from concurrent skin biopsies. RESULTS: Of 1080 DIF examinations performed during the study period, 117 (10.8%) had cytoid bodies. These specimens were from patients with 28 different cutaneous disorders, the most common of which were various forms of lupus erythematosus (29/117, 24.8%) and erythema multiforme (22/117, 18.8%). In 81 (69.2%) of these specimens, interface dermatitis was found histopathologically. CONCLUSION: Cytoid bodies are not infrequent on DIF examination and, in the absence of a clear diagnosis, might point toward several common disorders, particularly those involving interface dermatitis.
Asunto(s)
Epidermis/patología , Técnica del Anticuerpo Fluorescente Directa/métodos , Enfermedades de la Piel/patología , Biomarcadores/metabolismo , Biopsia , Dermatitis/metabolismo , Dermatitis/patología , Epidermis/metabolismo , Eritema Multiforme/metabolismo , Eritema Multiforme/patología , Humanos , Inmunoglobulinas/metabolismo , Queratinocitos/metabolismo , Queratinocitos/patología , Lupus Eritematoso Cutáneo/metabolismo , Lupus Eritematoso Cutáneo/patología , Estudios Prospectivos , Enfermedades de la Piel/metabolismoRESUMEN
The clinical spectrum of cutaneous eruptions comprises benign variants like maculopapular rashes (MPRs) and potentially life-threatening events such as toxic epidermal necrolysis (TEN). Apoptosis of keratinocytes is a common histopathological feature of all these drug eruptions. As in skin lesions of TEN and Stevens-Johnson syndrome patients, apoptosis of keratinocytes is often accompanied by an only sparse cellular infiltrate, a soluble fatty acid synthetase ligand (sFASL)-mediated mechanism of keratinocyte cell death is postulated. In MPR patients, evidence for the occurrence of a similar process could not be established so far. We therefore examined sera and lesional skin sections from patients with clinical variants of drug eruptions for FASL expression using a sandwich ELISA and immunohistochemistry, respectively. As controls, healthy persons and patients with other inflammatory skin diseases such as viral exanthema were analyzed. Elevated levels of FASL were detected not only in TEN patients but also in sera and lesional skin of patients with MPR. In contrast, sFASL was repeatedly negative in all viral exanthemas and healthy controls tested. Thus, determination of sFASL serum concentration may represent a discriminating tool between drug rashes and viral exanthemas.
Asunto(s)
Erupciones por Medicamentos/diagnóstico , Exantema/diagnóstico , Exantema/virología , Proteína Ligando Fas/metabolismo , Virosis/complicaciones , Enfermedad Aguda , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Dermatitis/metabolismo , Diagnóstico Diferencial , Erupciones por Medicamentos/sangre , Erupciones por Medicamentos/metabolismo , Eritema Multiforme/metabolismo , Exantema/sangre , Exantema/metabolismo , Proteína Ligando Fas/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Piel/metabolismo , Síndrome de Stevens-Johnson/metabolismo , Virosis/metabolismoRESUMEN
Herpes simplex virus (HSV)-associated erythema multiforme (HAEM) is a recurrent disease characterized by the presence and expression of HSV DNA fragments in lesional skin. Our studies examined the mechanism of viral DNA transport to the skin of HAEM patients. CD34+ cells were isolated from the blood of normal subjects and HSV and HAEM patients during acute lesions and at quiescence. They were cultured with cytokines that favor their differentiation into Langerhans cells (LC) precursors (CD1a+/CD14-) and examined for HSV replication, HSV-induced cellular alterations, viral DNA fragmentation, and clearance. CD34+ cells from all study groups were non-permissive for HSV replication but infection favored their differentiation into CD1a+/CD14- LC precursors and upregulated E-cadherin expression, thereby assisting LC targeting to the skin. Only HAEM patients had CD34+ cells that retained viral DNA fragments, notably polymerase DNA, for at least 7 d of in vitro culture. The percentages of circulating CD34+ (and CD34+/CLA+) cells were significantly higher in HAEM patients at the time of acute lesions. A similar increase was not seen for HSV patients. The data are the first report implicating CD34+ cells in HAEM pathogenesis, likely by transporting HSV DNA fragments to lesional skin.
Asunto(s)
Antígenos CD34/metabolismo , Células Sanguíneas/metabolismo , ADN Viral/metabolismo , Eritema Multiforme/metabolismo , Simplexvirus/genética , Piel/metabolismo , Adulto , Apoptosis , Transporte Biológico , Recuento de Células , Diferenciación Celular , Eritema Multiforme/genética , Eritema Multiforme/fisiopatología , Eritema Multiforme/virología , Genes pol , Herpes Simple/complicaciones , Herpes Simple/metabolismo , Herpes Simple/patología , Humanos , Células de Langerhans/patología , Células Madre/patologíaRESUMEN
Autoantibodies in patients with autoimmune bullous skin diseases, such as pemphigus or bullous pemphigoid are of diagnostic value and might play a part in the pathogenic scenario. In this study we present five patients with erythematous plaques, subepidermal blister formation of the skin, and the presence of circulating autoantibodies directed against a so far unrecognized 190 kDa antigen in human keratinocytes. Amino acid sequence analysis identified the protein as IQGAP1, a recently described human Ras GTPase-activating-like protein suspected to act as an effector molecule for Cdc42 and Rac1, members of the Rho small GTPase family and to play a key part in regulating E-cadherin-mediated cell adhesion. The protein is selectively recognized by a monoclonal anti-IQGAP1 antibody on western blots and immunoprecipitates from keratinocyte extracts. Indirect immunofluorescence locates IQGAP1 within individual keratinocytes in a cytoplasmic pattern and along the cell periphery at adhesive sites. Our results demonstrate IQGAP1, a newly described multifunctional protein, to be constitutively expressed in human keratinocytes where it may contribute to the integrity of the epidermal layer. Furthermore, we found autoantibodies reacting with IQGAP1 in patients with bullous skin eruptions most apparently belonging to the spectrum of bullous pemphigoid.
Asunto(s)
Autoanticuerpos/inmunología , Proteínas Portadoras/inmunología , Proteínas Portadoras/metabolismo , Queratinocitos/metabolismo , Enfermedades Cutáneas Vesiculoampollosas/inmunología , Enfermedades Cutáneas Vesiculoampollosas/metabolismo , Proteínas Activadoras de ras GTPasa , Adulto , Anciano , Anciano de 80 o más Años , Secuencia de Aminoácidos/genética , Autoanticuerpos/sangre , Proteínas Portadoras/genética , Células Cultivadas , Eritema Multiforme/inmunología , Eritema Multiforme/metabolismo , Femenino , Técnica del Anticuerpo Fluorescente , Humanos , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Penfigoide Ampolloso/inmunología , Penfigoide Ampolloso/metabolismo , Pénfigo/inmunología , Pénfigo/metabolismo , Valores de Referencia , Piel/inmunología , Enfermedades Cutáneas Vesiculoampollosas/patologíaRESUMEN
Nutritional support is important in critically ill patients, with variable energy and nitrogen requirements (e.g., sepsis, trauma, postsurgical state) in this population. This study investigates how age, severity of illness, and mechanical ventilation are related to resting energy expenditure (REE) and nitrogen balance. Nineteen critically ill children (mean age, 8 +/- 6 [SD] y and range 0.4-17.0 y) receiving total parenteral nutrition (TPN) were enrolled. We used indirect calorimetry to measure REE. Expected energy requirements (EER) were obtained from Talbot tables. Pediatric Risk of Mortality (PRISM) and Therapeutic Intervention Scoring System (TISS) score were calculated. Total urinary nitrogen was measured using the Kjeldahl method. PRISM and TISS scores were 9 +/- 5 and 31 +/- 6 points, respectively. REE was 62 +/- 25 kcal.kg-1.d-1, EER was 42 +/- 11 kcal.kg-1. d-1, and caloric intake was 49 +/- 22 kcal.kg-1.d-1. Nitrogen intake was 279 +/- 125 mg.kg-1.d-1, total urinary nitrogen was 324 +/- 133 mg.kg-1.d-1, and nitrogen balance was -120 +/- 153 mg.kg-1.d-1. The protein requirement in this population was approximately 2.8 g.kg-1.d-1. These critically ill children were hypermetabolic, with REE 48% higher (20 kcal.kg-1.d-1) than expected. Nitrogen balance significantly correlated with caloric and protein intake, urinary nitrogen, and age, but not with severity of illness scores or ventilatory parameters.
Asunto(s)
Enfermedad Crítica , Metabolismo Energético , Nitrógeno/metabolismo , Respiración Artificial , Adolescente , Niño , Preescolar , Cuidados Críticos , Proteínas en la Dieta/administración & dosificación , Ingestión de Energía , Eritema Multiforme/metabolismo , Femenino , Infecciones por VIH/metabolismo , Humanos , Lactante , Masculino , Nitrógeno/orina , Neumonía/metabolismo , Neumonía por Pneumocystis/metabolismo , Descanso , Sepsis/metabolismoRESUMEN
The differentiation of graft-verus-host disease (GVHD) from erythema multiforme (EM) presents a common diagnostic challenge in skin biopsy specimens from patients who have received patients allogeneic bone marrow transplants. The presence of gastrointestinal involvement might be the only way to make a diagnosis of GVHD in these cases. In the absence of liver function tests, gastrointestinal biopsy, or molecular techniques such as microsatellite DNA analysis, the presence of intraepidermal bile pigment might prove helpful in elucidating hyperbilirubinemia and allowing a pathologist to favor a diagnosis of GVHD over EM. Routinely processed archival tissue from 50 cases of GVHD (42 Caucasian and 8 of unknown race) and 50 cases of EM (31 Caucasian and 19 of unknown race) was examined for pigmentation. Intraepidermal pigmentation was stained for bile pigment and melanin. Among the intraepidermal EM lesions, 4 (8%) stained for intracorneal melanin, but none stained for bile pigment. Among the intraepidermal GVHD lesions, 8 (16%) stained for intracorneal melanin, but 3 (6%) stained for intracorneal bile pigment. In addition, 13 (26%) GVHD lesions and 9 (18%) EM lesions showed melanosis with melanin in all layers of the epidermis as well as within papillary dermal melanophages. Thus, when presented with a differential diagnosis of GVHD versus EM, the presence of intraepidermal bile pigment might suggest liver involvement and a diagnosis of GVHD.
Asunto(s)
Pigmentos Biliares/metabolismo , Eritema Multiforme/diagnóstico , Enfermedad Injerto contra Huésped/diagnóstico , Piel/metabolismo , Piel/patología , Biopsia , Colorantes , Diagnóstico Diferencial , Eritema Multiforme/metabolismo , Enfermedad Injerto contra Huésped/metabolismo , Humanos , Melaninas/metabolismo , Coloración y Etiquetado/métodosRESUMEN
Erythema multiforme (EM) is caused by various insults, frequently an infectious agent or a drug. It is current practice that histologic identification of the precipitating factor is not possible. We have observed a pattern of acrosyringeal concentration of keratinocyte necrosis in certain cases of EM and retrospectively studied 29 consecutive cases of EM to establish clinicopathologic correlation for this finding. Acrosyringeal concentration was observed in 10 of 29 specimens, all 10 clinically drug related (Group 1). Nineteen specimens lacked this pattern (Group 2) of which 3 cases were clinically drug related (sensitivity = 0.8, specificity = 1.0). Eosinophils were present in the dermal infiltrate of 6 specimens from Group 1 and 2 specimens from Group 2 (p = 0.025). Acrosyringeal concentration of keratinocyte necrosis in EM occurs in drug-related cases and is more likely to be accompanied by a dermal inflammatory infiltrate containing eosinophils. Drug concentration in sweat may explain this pattern with subsequent toxic and immunologic mechanisms leading to the fully evolved lesion.
Asunto(s)
Eritema Multiforme/patología , Queratinocitos/metabolismo , Queratinocitos/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Conjuntivitis/complicaciones , Conjuntivitis/patología , Eosinófilos/patología , Epidermis/patología , Eritema Multiforme/inducido químicamente , Eritema Multiforme/metabolismo , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Enfermedades de la Boca/complicaciones , Enfermedades de la Boca/metabolismo , Enfermedades de la Boca/patología , Mucosa Bucal/patología , Necrosis , Estudios RetrospectivosRESUMEN
The bcl-2 gene family plays a significant role in the propagation of cell survival and tissue modeling. Bcl-2 was originally described in follicular lymphomas and is associated with the suppresion of cellular apoptosis. Evaluation for this protein has been performed for a variety of benign and malignant cutaneous tumors but not to any significant extent on inflammatory disorders. Therefore, we stained biopsy specimens from diseases with interface inflammation (lichen planus, acute graft-versus-host disease, and erythema multiforme) for Bcl-2. Epidermal expression of this protein was minimal for all three diseases; however, lymphocytes stained prominently in lichen planus. The data suggest that Bcl-2 is not prominently involved in the epidermal changes in these diseases. The role of other members of this oncogene family in interface dermatitis still needs to be elucidated.
Asunto(s)
Eritema Multiforme/metabolismo , Enfermedad Injerto contra Huésped/metabolismo , Liquen Plano/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/biosíntesis , Genes bcl-2 , HumanosRESUMEN
Inflammation and ulceration at the epithelium-connective tissue interface, a characteristic of erythema multiforme (EM), may be associated with altered molecular attachment of basal keratinocytes. To determine the expression of basal keratinocyte-associated integrins and their basement membrane ligands in oral EM, specimens of clinically and microscopically confirmed EM (n = 12) and mucosal controls (n = 7) were stained immunohistochemically for the integrins alpha 3, beta 6, beta 1, and beta 4 and for extracellular matrix proteins laminin 1, laminin 5, collagen IV, and collagen VII using a standard avidin-biotin-peroxidase technique. In EM, results showed increased staining intensity for all integrins studied in basal and suprabasal keratinocytes. Basement membrane-associated staining of a6 and b4 was intense, but disrupted and fragmented. In EM, integrin staining was most marked at the summit of the connective tissue papillae. Laminin 5 staining was more intense than in controls, was frequently fragmented, and extended into the lamina propria. Laminin 1 staining was discontinuous and was frequently less intense than in controls. Collagen IV staining in EM was interrupted along the basement membrane. Collagen VII staining was fragmented but unchanged in intensity. These alterations in interface adhesion molecules suggest that hemidesmosome-associated molecules are important in the pathogenesis of EM. The staining intensities and patterns of expression of these adhesion molecules suggest that oral EM is initially focused in the connective tissue papillae.
Asunto(s)
Eritema Multiforme/metabolismo , Integrinas/biosíntesis , Enfermedades de la Boca/metabolismo , Receptores de Superficie Celular/biosíntesis , Proteínas de la Matriz Extracelular/biosíntesis , Humanos , Inmunohistoquímica , Integrinas/clasificación , Especificidad de ÓrganosRESUMEN
Erythema-multiforme-like reactions are a rare manifestation of allergic contact sensitivity, the pathomechanisms of which and their possible relationship to erythema multiforme remain unclear. We present our histopathological and immunohistochemical findings regarding the expression of several adhesion molecules and immunophenotypic markers of the infiltrate in skin biopsy specimens from 2 cases of erythema-multiforme-like reactions due to contact sensitizers and 3 cases of typical post-herpetic erythema multiforme. The histopathological pattern of erythema-multiforme-like reactions was characterized by an upper-dermal perivascular lymphoid infiltrate with exocytosis and keratinocyte necrosis; in 1 of the cases, there were foci of spongiosis and an admixture of eosinophils in the infiltrate. In comparison with biopsy specimens from cases of typical erythema multiforme, in both cases of erythema-multiforme-like reactions, the epidermal expression of ICAM-1 was more prominent, the % of CD4+ cells in the infiltrate was higher and the % of CD69+ cells was lower. There were no other significant differences in the cell phenotype of the infiltrate or in adhesion molecule expression in biopsy samples from both disorders.
Asunto(s)
Moléculas de Adhesión Celular/análisis , Dermatitis Alérgica por Contacto/etiología , Dermatitis Alérgica por Contacto/metabolismo , Eritema Multiforme/inducido químicamente , Eritema Multiforme/metabolismo , Adulto , Antígenos CD/análisis , Antígenos de Diferenciación de Linfocitos T/análisis , Linfocitos T CD4-Positivos/patología , Moléculas de Adhesión Celular/genética , Dermatitis Alérgica por Contacto/patología , Eosinófilos/patología , Eritema Multiforme/patología , Exocitosis , Femenino , Regulación de la Expresión Génica , Herpes Simple/metabolismo , Herpes Simple/patología , Humanos , Inmunofenotipificación , Integrinas/análisis , Integrinas/genética , Molécula 1 de Adhesión Intercelular/análisis , Molécula 1 de Adhesión Intercelular/genética , Queratinocitos/patología , Lectinas Tipo C , Ligandos , Linfocitos/patología , Persona de Mediana Edad , Necrosis , Piel/química , Piel/efectos de los fármacos , Piel/patologíaRESUMEN
We found distinct patterns of intercellular adhesion molecule-1 (ICAM-1) expression in three diseases characterized by interface dermatitis with mononuclear infiltrates and keratinocyte cytotoxicity: lichen planus (LP), subacute cutaneous lupus erythematosus (SCLE), and erythema multiforme (EM). In LP, basal keratinocytes show strong ICAM-1 expression associated with a dermal infiltrate, but ICAM-1 expression in the rest of the epidermis is minimal. In SCLE, there is diffuse epidermal ICAM-1 expression, sometimes with accentuation on the cell surface of basal cells. In EM, there is strong basal cell expression of ICAM-1 with evident cell surface accentuation, and also pockets of suprabasal expression with cell surface accentuation. These patterns are associated with different factors that trigger cytokine release in different locations. Both tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) produce greater relative ICAM-1 expression in basal keratinocytes than in more differentiated keratinocytes. In LP, the pure basal keratinocyte expression of ICAM-1 appears to be caused by cytokines, predominantly IFN-gamma, released by dermal lymphocytes. The pattern of ICAM-1 in SCLE corresponds to the pattern induced by ultraviolet radiation (UVR): diffuse epidermal ICAM-1 expression, sometimes with basal accentuation. Some individuals are "responders" to TNF-alpha or UVR, showing high levels of ICAM-1 expression following UVR or TNF-alpha stimulation in vitro or UVR stimulation in vivo. We propose that the pattern of ICAM-1 induction in SCLE is dependent on UVR-induced TNF-alpha release. EM is associated with apparent latent Herpes simplex virus, and Herpes simplex virus (HSV)-infected keratinocytes show enhanced ICAM-1 expression. We propose that in EM suprabasal ICAM-1 expression may be induced directly by HSV infection or indirectly through TNF-alpha release induced by HSV reactivation. Induction of ICAM-1 within the epidermis is stratified and individually variable. Basal keratinocytes show maximal induction of ICAM-1 expression due to innate sensitivity to TNF and IFN-gamma stimulation, and to location adjacent to dermal sources of cytokines. Suprabasal ICAM-1 can be induced by UVR and epidermal TNF-alpha release, and by factors such as viral infection. Different triggers of cytokine release and adhesion molecule induction may influence the different patterns of inflammation seen in diverse inflammatory skin diseases.
Asunto(s)
Eritema Multiforme/metabolismo , Molécula 1 de Adhesión Intercelular/metabolismo , Liquen Plano/metabolismo , Lupus Eritematoso Cutáneo/metabolismo , Eritema Multiforme/patología , Humanos , Interleucina-1/farmacología , Queratinocitos/metabolismo , Liquen Plano/patología , Lupus Eritematoso Cutáneo/patología , Simplexvirus/fisiología , Factor de Necrosis Tumoral alfa/farmacología , Rayos UltravioletaRESUMEN
BACKGROUND: Perforin (Pf), a pore-forming protein, is a cytolytic protein of killer cells. Its deposition in lesioned skin has not been studied. OBJECTIVE: The purpose of this study is to show Pf deposition in the lesioned skin and Pf expression in the dermal infiltrates of various inflammatory skin diseases. METHODS: Frozen specimens obtained from 29 patients with 5 different diseases were immunohistochemically stained. RESULTS: Granular deposition of Pf was found in the lesioned skin in 2 out of 5 cases of viral vesicles and in 3 out of 7 cases of erythema multiforme. In the cases with Pf deposition, the percentages of Pf+ cells in the dermis were higher than in those without deposition. CONCLUSION: Pf released from natural killer cells or cytotoxic T lymphocytes may play a role in tissue damage.
Asunto(s)
Eritema Multiforme/patología , Herpes Zóster/patología , Glicoproteínas de Membrana/análisis , Enfermedades Cutáneas Virales/patología , Linfocitos T Citotóxicos/patología , Adolescente , Adulto , Anciano , Relación CD4-CD8 , Niño , Dermatitis por Contacto/metabolismo , Dermatitis por Contacto/patología , Eritema Multiforme/metabolismo , Femenino , Herpes Zóster/metabolismo , Humanos , Células Asesinas Naturales/química , Células Asesinas Naturales/patología , Erupciones Liquenoides/metabolismo , Erupciones Liquenoides/patología , Masculino , Persona de Mediana Edad , Penfigoide Ampolloso/metabolismo , Penfigoide Ampolloso/patología , Perforina , Proteínas Citotóxicas Formadoras de Poros , Piel/química , Piel/patología , Enfermedades Cutáneas Virales/metabolismo , Coloración y Etiquetado , Linfocitos T Citotóxicos/químicaRESUMEN
Lymphocytes in formalin-fixed skin biopsies from patients with cutaneous acute graft-versus-host disease (aGVHD) were studied with HECA-452 (an antibody recognizing lymphocytes with skin-homing properties) and a panel of antibodies recognizing pan-B (L26 [CD20]), pan-T (L60 [CD43] and A6 [CD45RA]), and T-helper subset (OPD4) antigens in paraffin sections. Biopsies from patients with erythema multiforme (EM) were similarly studied for comparison. In both conditions, T lymphocytes stained by OPD4 were predominantly confined to the dermis, whereas those stained by HECA-452 were concentrated in the epidermis; however, there was considerable variation between cases, and overlap between findings in the dermis and epidermis. Lymphocytes similarly studied in paraffin sections of liver, salivary gland, and gut affected by aGVHD were essentially unreactive with HECA-452, although they were largely stained by pan-T markers and showed some comparable reactivity with OPD4. The findings suggest that aGVHD of the skin is mediated by a different set of lymphocytes than in gut organs, and may have a similar immunologic mechanism to EM.
Asunto(s)
Anticuerpos/inmunología , Eritema Multiforme/metabolismo , Enfermedad Injerto contra Huésped/inmunología , Enfermedades Intestinales/metabolismo , Enfermedades de la Piel/inmunología , Linfocitos T/inmunología , Enfermedad Aguda , Adolescente , Adulto , Anciano , Niño , Epítopos , Humanos , Técnicas Inmunológicas , Intestinos/inmunología , Microscopía Electrónica , Persona de Mediana Edad , Adhesión en Parafina , Piel/inmunología , Piel/patología , Coloración y EtiquetadoRESUMEN
The association between erythema multiforme (EM) and herpes simplex virus (HSV) infection has long been appreciated, although the exact role which HSV may play in the pathogenesis of this herpes-associated EM (HAEM), is unknown. Previous studies have suggested, but not definitively demonstrated, the presence of HSV in lesions of HAEM. The presence of HSV would support the hypothesis that an immune-mediated response directed against HSV-specific antigens in the skin is central to lesion development in HAEM. The purpose of this study was to examine lesions of EM for the presence of HSV DNA by using the polymerase chain reaction (PCR). In addition, in situ hybridization using an HSV-specific RNA probe was performed to further localize the HSV nucleic acids within the skin. DNA was extracted from formalin-fixed, paraffin-embedded specimens of cutaneous lesions of HAEM and also from EM for which no precipitating factor could be documented, otherwise known as idiopathic EM (IPEM). DNA from lesions of bullous pemphigoid served as a negative control. Using PCR to specifically amplify HSV sequences which might be present, and then performing Southern analysis, we demonstrated HSV DNA in 9/13 HAEM and 6/9 IPEM biopsies. No HSV was detected in six lesions of bullous pemphigoid. In situ hybridization of three cutaneous HAEM lesions using an 35S-labeled HSV-specific RNA probe localized the HSV nucleic acids predominantly to the epidermis. Three biopsies of chronic dermatitis, used as negative controls, did not demonstrate this specific hybridization. These findings confirm the presence of HSV in lesions of HAEM and are consistent with the concept of an HSV-specific immune-mediated pathogenesis for this disease. In addition, most cases of IPEM appear to be herpes associated despite the absence of clinically apparent HSV infection.
Asunto(s)
ADN Viral/metabolismo , Eritema Multiforme/metabolismo , Simplexvirus/genética , Piel/metabolismo , Eritema Multiforme/etiología , Herpes Simple/complicaciones , Humanos , Hibridación de Ácido Nucleico , Sondas ARNRESUMEN
The distribution of fibronectin in human oral mucosal vesiculo-bullous diseases was studied by indirect immunofluorescence. Subepithelial (benign mucous membrane pemphigoid and erythema multiforme) as well as intraepithelial (pemphigus vulgaris and dyskeratosis follicularis) lesions were selected. A marked accumulation of fibronectin was generally found in the lamina propria and basement membrane region, except in dyskeratosis follicularis. Intraepithelial staining occurred in erythema multiforme and dyskeratosis follicularis. In pemphigus vulgaris intercellular staining was seen in relation to acantholysis. Both mucous membrane pemphigoid and erythema multiforme showed a linear accumulation corresponding to the intact basement membrane. However, only pemphigoid lesions disclosed fibronectin on the epithelial side of the vesicles.