RESUMEN

OBJECTIVE: The purpose of this study was to exam the oral mucosa and peripheral blood cells of patients with recurrent aph-thous ulceration (RAU) for the presence of the following human herpesviruses: herpes simplex viruses 1 and 2, varicella zoster virus, Epstein-Barr virus, cytomegalovirus, human herpesvirus-6, and human herpesvirus-7. STUDY DESIGN: Fifty-eight subjects with RAU and 10 control subjects were recruited at an academic referral center and enrolled in this prospective, nonrandomized, case-controlled study. Each of the subjects with RAU was seen during an acute episode, and swab specimens from lesional (RAU-acute/lesion) and clinically normal (RAU-acute/normal) oral mucosa were obtained. Each of 2 subjects with RAU was evaluated during more than one acute episode. Three subjects with RAU were seen between active episodes, and swab specimens were taken from clinically normal (RAU-convalescent) oral mucosa. Swab specimens from clinically normal (control/normal) oral mucosa were obtained from the control subjects. Peripheral blood specimens were obtained from subjects with RAU and control subjects at the time the swab specimens were performed. Through use of polymerase chain reaction, all swab and peripheral blood specimens were examined for the presence of human herpesvirus DNA. Statistical significance was determined by means of chi(2) analysis. RESULTS: Herpes simplex virus and human herpesvirus-6 were found in a higher percentage of mucosal specimens from the control subjects (herpes simplex virus, 4/10; human herpesvirus-6, 5/9) than from the subjects with RAU (RAU-acute/lesion: 3/45 herpes simplex virus, 13/53 human herpesvirus-6; RAU-acute/normal: 7/48 herpes simplex virus, 9/53 human herpesvirus-6). No difference was demonstrated between RAU-acute/lesion, RAU-acute/normal, and RAU-convalescent mucosal specimens for any of the human herpesviruses. Different human herpesviruses were identified from individual subjects with RAU during subsequent episodes of disease. Epstein-Barr virus (6/35), human herpesvirus-6 (3/40), and human herpesvirus-7 (7/43) were detected in the peripheral blood mononuclear cells during acute RAU but not in RAU-convalescent or control peripheral blood mononuclear cells. CONCLUSIONS: The detection of human herpesvirus DNA from the oral mucosa and peripheral blood mononuclear cells of patients with RAU appears to represent normal viral shedding rather than a direct causal mechanism in this disorder.

Asunto(s)

Herpesviridae/aislamiento & purificación , Mucosa Bucal/virología , Estomatitis Aftosa/virología , Adulto , Estudios de Casos y Controles , Distribución de Chi-Cuadrado , ADN Viral/análisis , Femenino , Herpesviridae/patogenicidad , Humanos , Leucocitos Mononucleares/virología , Masculino , Reacción en Cadena de la Polimerasa , Estudios Prospectivos , Viremia/diagnóstico

RESUMEN

OBJECTIVE: To investigate our hypothesis that recurrent aphthous stomatitis (RAS), an inflammatory disease of the oral mucosa, is the result of an abnormal oral mucosal cytokine cascade leading to an enhanced cell-mediated immune response directed toward focal areas of the oral mucosa. DESIGN: Prospective nonrandomized case-control study. SETTING: Academic referral center PATIENTS: For part 1, 21 patients with RAS and 7 control patients; for part 2, 6 patients with RAS and 6 control patients. INTERVENTION: For study part 1, lesional and clinically normal oral mucosal biopsy specimens were obtained during an acute episode (within 72 hours of onset of ulcer) from 21 patients with RAS. Normal oral mucosal biopsy specimens were obtained from 7 healthy individuals, who served as controls. In study part 2, oral mucosal biopsy specimens were obtained from 6 RAS and 6 control patients at 24 and 48 hours after surgical trauma to those sites. MAIN OUTCOME MEASURES: Detection of the following messenger RNA (mRNA) types by use of semiquantitative reverse transcriptase polymerase chain reaction. For part 1, interleukins (IL) 2, 4, 5, and 10, interferon gamma, and tumor necrosis factor alpha were measured. For study part 2, IL-10 and interferon gamma were measured. RESULTS: In part 1, elevated levels of IL-2, interferon gamma, and tumor necrosis factor alpha mRNAs were detected in RAS lesions, consistent with a cell-mediated immune response. The IL-10 mRNA was not increased in RAS lesions. In addition, lower resting levels of IL-10 mRNA were detected in the clinically normal mucosa from patients with RAS, as compared with levels seen in the healthy controls. In part 2, at both 24 and 48 hours following trauma to the oral mucosa, the levels of mucosal IL-10 mRNA remained lower in patients with RAS than those observed in healthy controls, while interferon gamma mRNA levels were higher. CONCLUSION: Failure to suppress the inflammatory reaction initiated by trauma or other external stimuli, likely involving a functional deficiency of IL- 10 in the oral mucosa, appears to be important in the pathogenesis of RAS.

Asunto(s)

Interferón gamma/metabolismo , Interleucinas/metabolismo , Estomatitis Aftosa/metabolismo , Estomatitis Aftosa/patología , Factor de Necrosis Tumoral alfa/metabolismo , Biopsia , Estudios de Casos y Controles , Femenino , Humanos , Interferón gamma/genética , Interleucina-10/genética , Interleucina-10/metabolismo , Interleucina-2/genética , Interleucina-2/metabolismo , Interleucina-4/genética , Interleucina-4/metabolismo , Interleucina-5/genética , Interleucina-5/metabolismo , Interleucinas/genética , Masculino , Mucosa Bucal/química , Mucosa Bucal/metabolismo , Mucosa Bucal/patología , Estudios Prospectivos , ARN Mensajero/metabolismo , Recurrencia , Estomatitis Aftosa/complicaciones , Factor de Necrosis Tumoral alfa/genética , Úlcera/complicaciones

Asunto(s)

Eritema Multiforme/virología , Herpes Simple/diagnóstico , Aciclovir/uso terapéutico , Adolescente , Adulto , Antivirales/uso terapéutico , ADN Viral/análisis , Eritema Multiforme/patología , Femenino , Estudios de Seguimiento , Herpes Labial/complicaciones , Herpes Simple/patología , Humanos , Simplexvirus/genética , Simplexvirus/aislamiento & purificación

RESUMEN

OBJECTIVE: The purpose of this study was to assess the efficacy of low-intensity ultrasound in the treatment of recurrent aphthous stomatitis. STUDY DESIGN: Fifty patients with recurrent aphthous stomatitis were enrolled, and 35 patients completed this randomized crossover trial. The ultrasound was self-administered by twice daily use of an ultrasonic toothbrush. The level of aphthous ulcer activity was first observed for each patient with the use of either an ultrasonic or placebo toothbrush over a 6 month period. Patients were then observed for a 2 to 4 month period while using the alternate toothbrush. The level of ulcer activity was calculated as a numeric index: the total duration of sores divided by the period of observation. Statistical analysis was performed with the Student's t test. RESULTS: During the initial study period, the level of aphthous ulcer activity was lower for patients in the ultrasonic toothbrush group than for those in the placebo group (0.58 versus 0.78). This difference was not statistically significant. However, when the patients who used the placebo switched to the ultrasonic toothbrush, the level of aphthous ulcer activity dropped by 46% (O.81 to 0.44; p < 0.05). Those patients who started with the ultrasonic toothbrush worsened slightly after switching to the placebo. CONCLUSION: Routine use of low intensity ultrasound appears to have a modest beneficial effect on recurrent aphthous stomatitis.

Asunto(s)

Estomatitis Aftosa/terapia , Terapia por Ultrasonido , Adulto , Estudios Cruzados , Femenino , Humanos , Masculino , Cepillado Dental/instrumentación , Resultado del Tratamiento

RESUMEN

The association between infection with HSV and the subsequent development of erythema multiforme is well established, although the role that the virus plays in the pathogenesis of this disorder is not known. HSV DNA has been detected in cutaneous lesions of herpes-associated erythema multiforme (HAEM), and it has been suggested that the tissue damage seen in these lesions is virus-specific. In the current, prospective study, we examined biopsies of lesional, non-involved, and previously involved but healed skin, in addition to specimens of peripheral blood, from patients with HAEM, for HSV DNA by using the polymerase chain reaction. HSV DNA was detected in lesional skin of 10 of 11 patients compared to 2 of 11 non-involved skin biopsies obtained at the same time. HSV was present in 4 of 6 blood specimens obtained during the acute episode. Five patients returned 3 months after the acute episode resolved for biopsies of previously involved skin. HSV was detected in 4 of these 5 biopsies. Thus, the presence of HSV DNA in the skin of patients with HAEM appears to be predominantly in areas of clinical involvement; the virus remains in those cutaneous sites for up to 3 months without evidence of clinical disease; and HSV DNA may be detected in the peripheral blood cells during acute HAEM. Based on these findings, we suggest that the virus plays a role in lesion development, that the skin may function as a site of viral persistence, and that hematogenous spread of viral DNA may be an important factor in the development of HAEM.

Asunto(s)

ADN Viral/análisis , Eritema Multiforme/virología , Simplexvirus/aislamiento & purificación , Piel/virología , Sangre/virología , Eritema Multiforme/sangre , Herpes Simple/virología , Humanos , Reacción en Cadena de la Polimerasa , Estudios Prospectivos , Recurrencia

RESUMEN

Langerhans cell histiocytosis (LCH) is a disease characterized by Langerhans cell infiltration of skin and bone, with its most severe form manifested by multifocal infiltration of many organs. The etiology is unknown, although viral infection has been proposed as a potential pathogenic factor. Human herpesvirus 6 (HHV-6), a recently described member of the human herpesvirus family, has been associated with atypical or malignant lymphocytic processes, and immune disorders. Based on these observations, we suspected that HHV-6 may play a role in the pathogenesis of LCH. Lesional tissue of 30 patients with LCH was retrospectively examined for the presence of HHV-6 by using the polymerase chain reaction. Tissue specimens from 63 patients with other benign and malignant histiocytic and lymphocytic diseases served as controls. In addition, all specimens were examined with control primers specific for herpes simplex virus (HSV). HHV-6 DNA was detected in lesions of 14 of 30 patients with LCH (47%). On clinical subgroup analysis, HHV-6 DNA was found in 10 of 16 patients with extraosseous disease (63%) and in four of 14 patients with disease limited to bone (29%). In each case, the prevalence of HHV-6 in LCH lesions was statistically significant, when compared to the control population. HSV DNA was not found in any of the LCH or control specimens. Although the presence of a virus alone does not establish a causal role in the disease, it supports the possibility of an etiologic relationship. From this study, we emphasize the need for further investigation of the potential HHV-6-mediated pathogenesis of LCH.

Asunto(s)

Herpesvirus Humano 6/aislamiento & purificación , Histiocitosis de Células de Langerhans/microbiología , Adolescente , Adulto , Preescolar , ADN Viral/análisis , Infecciones por Herpesviridae/complicaciones , Herpesvirus Humano 6/genética , Histiocitosis de Células de Langerhans/etiología , Humanos , Lactante , Reacción en Cadena de la Polimerasa

RESUMEN

The etiology of cutaneous T-cell lymphoma remains unknown, although an association with viral infection, in particular certain retroviruses and human herpesviruses, has been suggested. The purpose of this study was to examine skin biopsies of cutaneous T-cell lymphoma for the presence of Epstein-Barr virus, herpes simplex virus type 1 and type 2, and human herpesvirus-6 by using the polymerase chain reaction. Lesional skin biopsies from 30 patients with cutaneous T-cell lymphoma were studied. Control specimens included biopsies from 9 patients with lymphomatoid papulosis and 10 patients with pityriasis lichenoides et varioliformis acuta. DNA extracted from each specimen, as well as from a known positive control for each virus, was examined by using the polymerase chain reaction with viral-specific primers. Each DNA specimen was also amplified with control primers for human beta globin. The specificity of the amplified products was confirmed by Southern analysis. Neither Epstein-Barr virus nor herpes simplex virus was detected in any of the patient specimens examined. Human herpesvirus-6 was detected in one specimen of cutaneous T-cell lymphoma and one specimen of lymphomatoid papulosis. These results do not support a role for any of these herpesviruses in the pathogenesis of cutaneous T-cell lymphoma.

Asunto(s)

ADN Viral/análisis , Herpesviridae/genética , Linfoma Cutáneo de Células T/química , Neoplasias Cutáneas/química , Biopsia , ADN Viral/genética , Herpesviridae/fisiología , Herpesvirus Humano 1/genética , Herpesvirus Humano 1/fisiología , Herpesvirus Humano 2/genética , Herpesvirus Humano 2/fisiología , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/fisiología , Herpesvirus Humano 6/genética , Herpesvirus Humano 6/fisiología , Humanos , Linfoma Cutáneo de Células T/microbiología , Piel/química , Piel/patología , Neoplasias Cutáneas/microbiología

RESUMEN

Infection with herpes simplex virus (HSV) is the most common precipitating factor in the development of erythema multiforme (EM). It is not known why only a few of the many individuals who experience recurrent HSV infection also develop herpes-associated EM (HAEM), although a difference in the HSV-specific immune response has been postulated. The purpose of this study was to compare the HSV-specific immune response of individuals with HSV infection alone with that of individuals with HAEM. There were 21 patients in each of the two groups. Four parameters of the HSV-specific immune response were examined: (1) anti-HSV IgG titers were measured by ELISA; (2) antibody neutralization was assessed using a plaque assay; and (3) antibody-dependent complement-mediated cytotoxicity, and (4) antibody-dependent cellular cytotoxicity were investigated using a previously described in vitro HSV-specific cytotoxicity assay. No statistically significant differences were detected between the two patient groups. Thus, a difference in these HSV-specific immune mechanisms does not explain the development of HAEM in some individuals with recurrent HSV infection.

Asunto(s)

Eritema Multiforme/inmunología , Herpes Labial/inmunología , Herpes Simple/inmunología , Inmunoglobulina G/sangre , Formación de Anticuerpos , Especificidad de Anticuerpos , Proteínas del Sistema Complemento/inmunología , Pruebas Inmunológicas de Citotoxicidad , Ensayo de Inmunoadsorción Enzimática , Eritema Multiforme/complicaciones , Herpes Simple/complicaciones , Humanos , Recurrencia

RESUMEN

BACKGROUND: Although herpes simplex virus (HSV) has been detected in the peripheral blood of immunocompromised patients and in neonates with disseminated disease, the extent to which this virus may be present in the blood during a localized infection in otherwise healthy adults is unknown. OBJECTIVE: The purpose of this study was to determine whether HSV may be detected in the peripheral blood during acute recurrent herpes labialis. METHODS: Peripheral blood mononuclear cells (PBMCs) were obtained from otherwise healthy adults with recurrent herpes labialis, both during an acute episode and several weeks after the lesions had healed. The PBMCs were examined for the presence of HSV with the polymerase chain reaction (PCR) and viral culture. RESULTS: By PCR, HSV DNA was detected in 7 of 34 specimens from an acute episode but in none of 24 specimens in the convalescent stage (p less than 0.004). PBMCs from seven donors, who were seronegative for HSV, were also negative for HSV by PCR. Viral cultures of 22 PBMC specimens were negative (including four specimens that were positive by PCR). CONCLUSION: The presence of HSV DNA in the blood is a transient phenomenon limited to the period of active infection in a minority of patients with herpes labialis, although it may be important in the development of disseminated disease as well as in the pathogenesis of herpes-associated cutaneous processes such as erythema multiforme.

Asunto(s)

ADN Viral/sangre , Herpes Labial/sangre , Leucocitos Mononucleares/microbiología , Simplexvirus/aislamiento & purificación , Enfermedad Aguda , Adulto , Femenino , Herpes Labial/microbiología , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Recurrencia , Simplexvirus/genética

RESUMEN

Although an association between herpes simplex virus (HSV) infection and erythema multiforme (EM) minor has been documented in adults, this has not been reported in the pediatric population. This study assessed the potential role of HSV infection in the pathogenesis of EM minor in children. Erythema multiforme skin lesions from 20 children, aged 1 to 16 years, were examined for the presence of HSV by using the polymerase chain reaction. The children included all fit strict clinical criteria for EM minor. Ten had a clinical history of an antecedent herpes infection ("herpes-associated EM"), and 10 did not ("idiopathic EM"). Herpes simplex virus DNA was detected in skin lesions of 8 of 10 children with herpes-associated EM and in 8 of 10 with idiopathic EM. Control skin biopsies from children with other bullous inflammatory diseases were negative. In addition, no HSV could be detected in a biopsy of normal uninvolved skin of a child in whom HSV was present in lesional skin. In situ hybridization on selected biopsies by means of an HSV-specific riboprobe confirmed the presence of HSV and localized it to the epidermis. It is concluded that HSV is a significant precipitating factor for EM minor in children, as it is in adults, and that clinicians should maintain a high index of suspicion of HSV even in the absence of a known history of herpes infection.

Asunto(s)

Eritema Multiforme/microbiología , Herpes Simple/diagnóstico , Simplexvirus/aislamiento & purificación , Adolescente , Causalidad , Niño , Preescolar , Sondas de ADN , ADN Viral/análisis , Humanos , Lactante , Hibridación de Ácido Nucleico , Reacción en Cadena de la Polimerasa

RESUMEN

Erythema multiforme minor is an acute, self-limited cutaneous or mucocutaneous disorder. Although it most commonly afflicts young adults, it is also frequently seen in children. An antecedent infection with herpes simplex virus is often the precipitating factor. Recent studies detailing the usual clinical course and histologic features of erythema multiforme minor, together with investigative studies examining potential pathomechanisms, have begun to provide a clearer picture of this disease process such that a more rational approach to therapy is now possible.

Asunto(s)

Eritema Multiforme , Aciclovir/uso terapéutico , Adolescente , Adulto , Factores de Edad , Niño , Preescolar , Diagnóstico Diferencial , Eritema Multiforme/clasificación , Eritema Multiforme/diagnóstico , Eritema Multiforme/epidemiología , Eritema Multiforme/etiología , Eritema Multiforme/terapia , Herpes Simple/complicaciones , Humanos , Lactante

RESUMEN

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 ARN

RESUMEN

Herpes simplex virus (HSV) specific immune mediated cytotoxicity may be involved in control of HSV infections and in the tissue damage induced by HSV infection or HSV related skin disease such as herpes associated erythema multiforme. Developing an in vitro model to study this process has proved difficult due to the lack of an appropriate target cell that will express HSV antigens but is not simultaneously subject to viral induced cell death. The purpose of this study was to develop a model in which keratinocytes express cell surface HSV specific antigens but at the same time are protected from death due to viral infection. We found that keratinocytes infected with HSV in the presence of acyclovir (ACV) expressed such antigens yet remained viable for a period of time after the onset of antigen expression such that cytotoxicity studies could be successfully performed. Rabbit skin cells, a transformed keratinocyte line, or second passage human neonatal foreskin keratinocytes were grown in culture medium with or without 200 microM ACV and were infected with HSV. Examination by direct immunofluorescence with anti-HSV antibody revealed uniform HSV antigen expression by cells both with and without ACV by 8 h after infection. Cells infected without ACV exhibited marked structural abnormalities including formation of multinucleated giant cells, while cells with ACV showed fewer such changes throughout a 24-h period. An Ethidium Bromide-Acridine Orange cytotoxicity assay demonstrated significant increases in the cytotoxicity of infected cells not protected by ACV compared to that of cells with ACV (p less than .001). This in vitro model should prove useful in the investigation of HSV specific immune mediated cytotoxicity.

Asunto(s)

Citotoxicidad Inmunológica , Células Epidérmicas , Epítopos , Queratinas , Simplexvirus/inmunología , Naranja de Acridina , Aciclovir/farmacología , Animales , Antígenos Virales/inmunología , Células Cultivadas , Pruebas Inmunológicas de Citotoxicidad , Epidermis/inmunología , Etidio , Herpes Simple/inmunología , Herpes Simple/patología , Queratinas/inmunología

Asunto(s)

Pitiriasis Rubra Pilaris/tratamiento farmacológico , Estanozolol/uso terapéutico , Administración Oral , Humanos , Proteínas de Unión al Retinol/metabolismo , Estanozolol/administración & dosificación

RESUMEN

Diffuse lichen planus, a rare disorder in children, was observed in an 8-year-old boy. Effective therapy in this disease remains a problem and currently relies predominantly on the use of the corticosteroids. The complications attendant with corticosteroid administration in children are discussed and a review of alternate modes of therapy for lichen planus is presented.

Asunto(s)

Corticoesteroides/uso terapéutico , Liquen Plano/tratamiento farmacológico , Corticoesteroides/administración & dosificación , Corticoesteroides/efectos adversos , Insuficiencia Suprarrenal/inducido químicamente , Niño , Griseofulvina/uso terapéutico , Trastornos del Crecimiento/inducido químicamente , Humanos , Masculino , Terapia PUVA , Prurito/inducido químicamente , Tretinoina/uso terapéutico , Vitamina A/uso terapéutico