Sylvia L. Brice

Detection of herpes simplex virus DNA in the peripheral blood during acute recurrent herpes labialis

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.

Examination of non‐involved skin, previously involved skin, and peripheral blood for herpes simplex virus DNA in patients with recurrent herpes‐associated erythema multiforme

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 lo 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. I ISV 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 pal inns with HAEM appears lo 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 hemalogenous spread of viral DNA may bean important factor in the development of HAEM.

Clinical evaluation of the use of low-intensity ultrasound in the treatment of recurrent aphthous stomatitis

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 Students 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.

Examination of cutaneous T‐cell lymphoma for human herpesviruses by using the polymerase chain reaction

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 β 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.

Paraneoplastic Pemphigus Herpetiformis With IgG Antibodies to Desmoglein 3 and Without Mucosal Lesions

BACKGROUND Pemphigus herpetiformis (PH) is a rare clinical entity that combines the clinical features of dermatitis herpetiformis and the immunopathologic features of pemphigus. The target antigen is usually desmoglein 1, with exceptional cases manifesting autoantibodies against desmoglein 3. More recently, it has been found that many patients with PH also demonstrate autoantibodies against desmocollin. The association of PH with a malignant neoplasm is rare. OBSERVATIONS We describe a patient with PH and a lung neoplasm. Immunologic studies demonstrated IgG antibodies to desmoglein 3 and to an unknown 178-kDa protein but no antibodies to desmocollin. CONCLUSIONS The association of PH with a thoracic malignant neoplasm has been reported in only 4 previous cases, and the neoplasm could be responsible for the unusual immunologic profile in the patient described herein. To our knowledge, this is the first report of PH with an associated neoplasm in which only anti-desmoglein 3 antibody was detected.

The herpes-specific immune response of individuals with herpes-associated erythema multiforme compared with that of individuals with recurrent herpes labialis.

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.

Atypical forms of herpes simplex-associated erythema multiforme.

Erythema multiforme (EM) is an uncommon condition mostly observed in otherwise healthy young adults. von Hebra l is credited with the first detailed description of EM, namely, a recurrent condition characterized by the abrupt appearance of self-limited, symmetrically distributed round, red papules some of which evolved into target lesions. More recently, it has been found that in the majority of occurrences both in children and adults, EM is precipitated by herpes simplex virus.2,3 This type of EM is also known as herpesassociated EM (HAEM), and herpes simplex virus (HSV) DNA has been demonstrated in the involved skin of HAEM,4 further evidence of a causal association. We describe four women with atypical presentations of HAEM.

Dermatology information on the Internet: An appraisal by dermatologists and dermatology residents

To the Editor: Patients increasingly seek health information on the World Wide Web both for personal knowledge and to facilitate patientephysician discussion at the timeofmedical consultation. In January 2008, approximately 44% of all health-related Web site traffic was on pages found via search engines, an increase of 3% in health-related traffic share from the previous year. Google.com received the greatest portion of this Internet traffic. The Internet provides an easily accessible forum through which health information, with varying accuracy, can be spread. This holds especially true with the development of Web 2.0, which is comprised of Web sites that are geared toward the facilitation of communication between Internet users (Wikipedia, blogs, etc). We sought to assess the content, accuracy, and quality of dermatologic health information on the Internet. The top three Web sites found through a query of the top eight dermatologic diagnoses using Google were analyzed by six board-certified dermatologists and three dermatology residents for accuracy, content, and completeness. Each Web site was given a positive, neutral, or negative rating according to the evaluators’ overall impression of the Web site, the accuracy of its disease description, treatment description, and photographic depiction, and its user-friendliness. Web sites were also categorized according to target audience, sponsorship or affiliation, number of languages, presence of reliability certification (ie, Health on the Net Foundation), and types and extent of consumer advertising. FlescheKincaid grade levels for readability were calculated for all Web sites using Microsoft Office Word software (Microsoft; Redmond, WA). Twenty-four Web sites were found by searching for the top eight dermatologic diagnoses on the search engine Google. There were no duplicate Web sites or broken links among the returned search results. Common Internet domains included: Wikipedia.org (8 Web sites), MayoClinic.com (2), and MedicineNet.com (2). Six additional Web sites were represented by dermatology-specific organizations (one each from AOCD.org, SkinCarePhysicians.com, SkinCancer.org, Psoriasis.org, Acne.org, and Acne.com), and five additional Web sites were represented by organizations with a general medical focus (one each from WebMD.com, eMedicine.com, Medline [NIH.gov], FamilyDoctor.org, andMerck.com). One Web site (About.com) was not specifically healthrelated. No Web sites were excluded. Dermatologists and dermatology residents rated dermatology Web sites found through Google as generally accurate (Table I). Importantly, Web 2.0 Web sites that were evaluated were found to be generally equal in accuracy and completeness to their noneWeb 2.0 counterparts. Furthermore, each Web site was categorized according to the various criteria mentioned above (Table II). Web sites found through Google are generally targeted for a lay patient audience, represent a wide variety of types of sponsorships and affiliations (Web 2.0 developments being the most common), have a number of language translations, possess some version of health reliability certification, and contain a fair amount of advertising. In general, however, Web sites had a FlescheKincaid grade level well above the recommended sixth grade level. While Internet resources regarding health information are subject to misinformation, dermatologic Web sites are relatively accurate and complete according to dermatologists and dermatology residents. However, our findings also suggest that Internet-based information may be too difficult for comprehension by a substantial portion of the patient population. Patients who want to know more about specific dermatologic conditions may benefit seeking information from reliable Web sites found through Google.com.

Recurrent aphthous stomatitis

Abstract Recurrent aphthous stomatitis (RAS), also known as “canker sores,” is one of the most common diseases of the oral mucosa. It is characterized by the recurrent development of one to several discrete, painful ulcers in the mouth, often leading to difficulty in eating, drinking, and talking. RAS is world-wide in distribution and afflicts approximately 20% of the population. This disorder generally begins during adolescence, increases into adulthood, and then decreases with advancing age. Most patients are otherwise healthy. Although self-limited in nature, some individuals experience frequent and severe episodes, so that RAS may be associated with significant morbidity. Two disorders that are potentially related to RAS are “complex aphthosis” (CA) and Behcets Disease (BD). In CA, recurrent oral and genital ulcers, or almost continuous oral ulcers (more than three), are seen. BD was originally described as the triad of oral ulcers, genital ulcers, and uveitis. However, it is now appreciated that BD is a complex multisystem disease. In both CA and BD, the mucosal ulcers are clinically and histologically indistinguishable from those that occur in RAS. For this reason, it has been suggested that these three processes present a continuum along the same disease spectrum, ranging from RAS, to CA, to BD. RAS has been divided into two forms, minor aphthous ulcers (MiAU), and major aphthous ulcers (MjAU). MiAU and MJAU, as the names imply, differ in the severity and frequency of active episodes. In both cases the clinical presentation of the oral ulcers typically progresses through four stages: premonitory, preulcerative, ulcerative, and healing. Histologic findings in RAS depend on the stage at which the biopsy was performed. Necrosis of individual epithelial cells evolves to more generalized destruction of the epithelial surface. A predominantly mononuclear inflammatory cell infiltrate is present, but vasculitis is not seen. Results of direct immunofluorescence studies have been variable and are generally considered nonspecific. The pathogenesis of RAS is unknown, despite multiple investigative studies. Possible etiologies that have been considered include genetic, nutritional, hormonal, allergic, psychological, traumatic, infectious, and autoimmune. An infectious agent and/or alteration in host immune function are considered most likely. Other disorders that may be associated with oral ulceration, and must be differentiated from RAS, include various infections (herpes simplex virus, coxsackie virus, yeast), mucocutaneous syndromes (erythema multiforme, cicatricial pemphigoid, pemphigus vulgaris, lichen planus), and certain systemic diseases (lupus erythematosus, inflammatory bowel disease, hematologic disorders). Some systemic, as well as topical, medications may also result in the development of RAS-like lesions. Unfortunately, there is currently no cure for RAS and no uniformly effective treatment. However, multiple therapeutic regimens exist that may provide significant symptomatic relief to the individuals with frequently recurrent or severe disease.