A combined assay of hTERT and E6 oncoprotein to identify virus-infected keratinocytes with higher telomerase activity in human papillomaviruses 16 and 18-related bowenoid papulosis.

In the present study, we aim to evaluate the application potential of a combined assay of human telomerase reverse transcriptase (hTERT) and E6 oncoprotein in screening the virus-infected keratinocytes with higher telomerase activity in human papillomaviruses (HPV) 16- and 18-related bowenoid papulosis (BP). HPV16/18 DNA in BP (n = 123) was identified by in situ hybridization, the expression of hTERT and E6 in HPV16/18-related BP (n = 68) was determined by immunohistochemistry. We demonstrated that the expression of hTERT correlated well with that of E6 oncoprotein in HPV16/18-related BP lesions (Spearman rho = 0.868, P < 0.01). Furthermore, the majority of keratinocytes with positive nuclear staining for hTERT or E6 in the consecutive sections of each HPV16/18-related BP lesion showed nuclear paleomorphism or nuclear mitosis. In conclusion, we suggested that a combined assay of hTERT and E6 oncoprotein can be used to screen the HPV-infected keratinocytes with higher telomerase activity in HPV16-related and HPV18-related BP lesions.

Pruritic papular eruption and eosinophilic folliculitis associated with human immunodeficiency virus (HIV) infection: a histopathological and immunohistochemical comparative study.

BACKGROUND: Among the papular-pruriginous dermatoses related to human immunodeficiency (HIV) infection, two entities remain poorly differentiated leading to confusion in their diagnosis: HIV-related pruritic papular eruption (HIV-PPE or prurigo) and eosinophilic folliculitis (HIV-EF). OBJECTIVE: To establish histopathological and immunohistochemical parameters to differentiate between two conditions associated with HIV infection, the pruritic papular eruption (HIV-PPE) and eosinophilic folliculitis (HIV-EF). METHODS: Clinically typical HIV-PPE (18 cases) and HIV-EF (10 cases) cases were compared with each other in terms of the following topics: clinical and laboratory features (gender, age, CD4+ cell and eosinophil count), histopathological features (hematoxylin-eosin and toluidine blue staining) and immunohistochemical features (anti-CD1a, anti-CD4, anti-CD7, anti-CD8, anti-CD15, anti-CD20, anti-CD30, anti-CD68/macrophage and anti-S-100 reactions). RESULTS: Among the HIV-EF patients, we found an intense perivascular and diffuse inflammatory infiltration compared with those patients with HIV-PPE. The tissue mast cell count by toluidine staining was higher in the HIV-EF patients, who also presented higher expression levels of CD15 (for eosinophils), CD4 (T helper), and CD7 (pan-T lymphocytes) than the HIV-PPE patients. LIMITATIONS: Only quantitative differences and not qualitative differences were found. CONCLUSIONS: These data indicate that HIV-related PPE and EF could possibly be differentiated by histopathological and immunohistochemical findings in addition to clinical characteristics. In fact, these two inflammatory manifestations could be within the spectrum of the same disease because only quantitative, and not qualitative, differences were found.

Papular purpuric gloves and socks syndrome. Presentation of a clinical case.

Papular-Purpuric Glove-and-Sock Syndrome is a rare, infectious disease, of viral etiology, characterized by the presence of pruritus, edema and symmetrical erythema, very well defined at the wrists and ankles with a gloves-and-socks distribution. Other areas can be affected, with a moderate erythema appearing in cheeks, elbows, knees, armpits, abdomen, groin, external genitalia, internal face of the thighs and the buttocks. Erosions, small ulcers, enanthema and blisters can be observed in the oral cavity and lips, and less frequently in other mucous membranes. Complications are rare, although they can be severe, 50% of the published cases are related with the Parvovirus B19. Due to its oral involvement stomatologists should be aware of this syndrome in order to carry out a correct diagnosis of the disease.

The juvenile variant of papular-purpuric gloves and socks syndrome and its association with viral infections.

BACKGROUND: Papular-purpuric gloves and socks syndrome (PPGSS) occurs mostly in adults and has been shown to be related to several possible viral infections. However, childhood-onset PPGSS seems to be not so rare as previously thought in our clinical experience. OBJECTIVES: To survey the general characteristics of childhood-onset PPGSS and to determine the possible association between this juvenile variant of PPGSS and various viral infections. PATIENTS AND METHODS: Thirty-three children with erythematopurpuric papular eruptions on the hands and/or feet were enrolled. Detailed history-taking and physical examination were performed on all of them. Blood samples were obtained from 25 patients about 1-5 weeks after the appearance of cutaneous eruptions to check complete blood counts, differential white blood cell counts, and IgM and IgG antibodies to parvovirus B19, cytomegalovirus (CMV), viral capsid antigen of Epstein-Barr virus (EBV) and measles. RESULTS: The median age of these 33 patients was 23 months. The mean duration of the skin eruption was 4.8 weeks (SD 2.7, 95% CI 3.9-5.0). Lymphocytosis was present in 13 patients (52%) while mild eosinophilia occurred in only three patients (12%). Five patients (20%) were positive for IgM antibodies against CMV and seven (28%) were positive for IgM antibodies against EBV. Only one patient (4%) was detected to have IgM antibodies against parvovirus B19. CONCLUSIONS: Childhood-onset PPGSS shows somewhat different clinical features from the adult type. It may represent a nonspecific manifestation of several viral infections, including CMV, EBV and parvovirus B19 infections.

Response to smallpox vaccine in persons immunized in the distant past.

CONTEXT: There is renewed interest in use of smallpox vaccine due to the potential for a bioterrorist attack. This would involve vaccinating health care workers who were previously vaccinated. OBJECTIVE: To evaluate the use of diluted vaccinia virus in vaccination of previously vaccinated (non-naive) participants. DESIGN, SETTING, AND PARTICIPANTS: Eighty non-naive participants, aged 32 to 60 years, were randomized in a single-blinded study to receive either undiluted or diluted (1:3.2, 1:10, or 1:32) doses of smallpox vaccine. A comparison group, aged 18 to 31 years, of 10 vaccinia-naive participants received undiluted vaccine. Participants were enrolled between April 1 and May 15, 2002, at the National Institute of Allergy and Infectious Diseases Vaccine and Treatment Evaluation Unit at Saint Louis University, St Louis, Mo. INTERVENTION: Smallpox vaccine was administered by scarification using 15 skin punctures in the deltoid region of the arm. MAIN OUTCOME MEASURES: Presence of a major reaction, defined as a vesicular or pustular lesion or area of palpable induration surrounding a central lesion following vaccination, and measures of viral shedding and antibody titers. RESULTS: Initial vaccination resulted in a major reaction in 64 of 80 non-naive participants. Ninety-five percent of non-naive participants had major reactions in the undiluted group, 90% in the 1:3.2 dilution group, 81% in the 1:10 dilution group, and 52.6% in the 1:32 dilution group. All (n = 10) of the vaccinia-naive participants had major reactions. Compared with vaccinia-naive participants, non-naive participants had significantly smaller skin lesions (P =.04) and significantly less incidence of fever (P =.02). Preexisting antibody was present in 76 of 80 non-naive participants. Antibody responses were significantly higher and occurred more rapidly in the non-naive participants compared with the vaccinia-naive participants (P =.002 for day 28 and P =.003 for 6 months). Vaccinia-naive participants shed virus from the vaccination site 2 to 6 days longer and had significantly higher peak mean viral titers when compared with the non-naive participants (P =.002). CONCLUSIONS: Previously vaccinated persons can be successfully revaccinated with diluted (

Evaluation and treatment of itching in HIV-infected patients.

Itching is a common complaint among patients infected with HIV and may cause significant morbidity and embarrassment. Although idiopathic HIV-pruritus has been described, it is probably less common than was previously thought. In most patients, a careful history and physical examination will show that a dermatosis accounts for their pruritus. Dry skin, seborrheic dermatitis, eczema, psoriasis, pruritic papular eruption, staphylococcal folliculitis and prurigo nodularis are frequently encountered in these patients. These common dermatoses, drug eruptions, several rarer conditions and systemic causes of itching should be excluded before diagnosing idiopathic HIV-pruritus. Treatment should be directed to the underlying skin problem and may be supplemented with sedating antihistamines. Phototherapy is a safe and effective therapeutic modality for many pruritic dermatoses as well as for idiopathic pruritus.

Oral bowenoid lesions: differential diagnosis and pathogenetic insights.

OBJECTIVE: To determine if oral lesions exhibiting bowenoid features reflect the diverse microscopic appearance and biologic behaviour of Bowen's disease and bowenoid papulosis of the skin and genitalia. STUDY DESIGN: Seven cases of oral bowenoid lesions (6 with follow-up data) were assessed for differences in histologic features, human papillomavirus (HPV) viral status, and selected immunohistochemically detectable cell cycling proteins (p53, WAF-1, Cyclin D1, Bcl-2) and were correlated with available follow-up data. RESULTS: Two histologic subsets were identified. One, which was believed to correspond to Bowen's disease, exhibited large numbers of transepithelial apoptotic bodies, dyskeratotic cells and mitoses (bowenoid elements), poor differentiation of background epithelial cells, and consistent HPV-16/18 positivity. The other, believed to correspond to bowenoid papulosis, exhibited few bowenoid elements, good background differentiation, and inconsistent HPV-16/18 positivity. One of the aggressive cases exhibited repeated recurrences despite apparent total clinical excision, whereas none of the other group recurred. CONCLUSION: Although a small number of cases are in this study, results suggest that oral bowenoid lesions may exhibit histopathologic and behavioral variations ranging from oral Bowen's disease to oral bowenoid papulosis. Studies on more cases are needed to confirm this initial impression.

Heterogeneity of human papillomavirus DNA in a patient with Bowenoid papulosis that progressed to squamous cell carcinoma.

Bowenoid papulosis (BP) of the genitalia, characterized by the histological findings of a squamous cell carcinoma, follows a largely benign clinical course. The detection of oncogenic human papilloma viruses (HPV) from BP points to an aetiological role of these viral infections. A 47-year-old man with multiple genital skin lesions was seen over a 10-year period with the diagnosis of BP. Recently, he attended again with a recurrent genital tumour that was diagnosed as squamous cell carcinoma. His genital lesions progressed and became polymorphic in appearance, from a wart-like tumour to a reddish invasive plaque. To screen for the presence of different HPV sequences from different skin lesions and to correlate each HPV type with distinct clinical manifestations, polymerase chain reaction and single-strand conformational polymorphism (PCR-SSCP) were performed. PCR-SSCP revealed the presence of several types of HPV from different genital lesions. Sequencing results disclosed that he had a mixed infection of HPV6b, HPV16, HPV18 and HPV33, respectively. Interestingly, the clinical findings were fairly well correlated with the oncogenic potential of HPV found from each lesion.

No evidence of KSHV/HHV-8 in mycosis fungoides or associated disorders.

The recently discovered human virus known as Kaposi's sarcoma-associated herpesvirus (KSHV) or human herpesvirus-8 (HHV-8) has been associated with body-cavity-based lymphomas in AIDS patients. It is most closely related to two other herpesviruses, the Epstein-Barr virus and herpesvirus saimiri, which are known to be associated with lymphomas in humans and nonhuman primates, respectively. To determine whether KSHV/HHV-8 is involved in the pathogenesis of mycosis fungoides (MF) and related disorders, we used a genomic PCR assay followed by confirmatory Southern blot analysis with a nested oligonucleotide probe to analyze cases for the presence of this virus. The specimens studied included fresh-frozen lesional tissues obtained from 16 patients with MF, seven with lymphomatoid papulosis, seven with primary cutaneous CD30+ large cell lymphoma of T-cell lineage, and five with Hodgkin's disease. Two T-cell tumor lines were also studied: MT4 (derived from a patient with adult T-cell leukemia/lymphoma) and Jurkat (derived from a patient with T-cell acute lymphoblastic leukemia). All cases were uniformly negative for KSHV/HHV-8, whereas Kaposi's sarcoma-positive controls and human beta-globin DNA integrity controls were appropriately positive. These findings provide strong evidence against a role for KSHV/HHV-8 in the pathogenesis of MF or associated lymphoproliferative disorders.

Multiple pigmented cutaneous papules associated with a novel canine papillomavirus in an immunosuppressed dog.

Cutaneous papillomavirus infection was diagnosed in a 6-year-old female Boxer dog that was under long-term corticosteroid therapy for atopic dermatitis. Multiple black, rounded papules were present on the ventral skin. Spontaneous regression occurred within 3 weeks after cessation of corticosteroids. Histologically, the lesions consisted of well-demarcated cup-shaped foci of epidermal endophytic hyperplasia with marked parakeratosis. In the upper stratum spinosum and in the stratum granulosum, solitary or small collections of enlarged keratinocytes were observed with basophilic intranuclear inclusion bodies and a single eosinophilic fibrillar cytoplasmic inclusion. Ultrastructurally, viruslike particles (40-45 nm in diameter) were observed within the nucleus, free or aggregated in crystalline arrays. Undulating fibrillar material, thought to be a modified keratin protein, was observed in the cytoplasmic inclusion. Immunohistochemistry, restriction enzyme analysis, and molecular hybridization experiments indicated that these distinctive clinical, histologic, and cytologic features were associated with a novel canine papillomavirus.