Raffaele Filotico

The E6 and E7 Proteins of the Cutaneous Human Papillomavirus Type 38 Display Transforming Properties

ABSTRACT Several studies have suggested the involvement of cutaneous human papillomaviruses (HPVs) in the development of nonmelanoma skin cancers. Here we have characterized the in vitro properties of E7 proteins of three cutaneous HPV types, 10, 20, and 38, which are frequently detected in skin specimens. We show that HPV38 E7 is able to inactivate the tumor suppressor pRb and induces loss of G1/S transition control, a key event in carcinogenesis. In contrast, HPV10 and HPV20 E7 proteins do not display these in vitro transforming activities. We also show that the two early proteins E6 and E7 of HPV38 are sufficient to corrupt the cell cycle and senescence programs in primary cells, inducing active and long-lasting proliferation of primary human keratinocytes, the natural host cells. Our study shows that E6 and E7 of this cutaneous HPV type have transforming activity in primary human cells, suggesting a role for HPV38 infection in skin carcinogenesis. In further support of such a role, we detected HPV38 DNA in approximately 50% of nonmelanoma skin cancers, but only in 10% of healthy skin specimens (P < 0.001).

Accuracy in melanoma detection: A 10-year multicenter survey

BACKGROUND Early excision is the only strategy to reduce melanoma mortality, but unnecessary excision of benign lesions increases morbidity and healthcare costs. OBJECTIVE To assess accuracy in melanoma detection based on number-needed-to-excise (NNE) values over a 10-year period. METHODS Information was retrieved on all histopathologically confirmed cutaneous melanomas or melanocytic nevi that were excised between 1998 and 2007 at participating clinics. NNE values were calculated by dividing the total number of excised lesions by the number of melanomas. Analyses included changes in NNE over time, differences in NNE between specialized clinical settings (SCS) versus non-specialized clinical settings (NSCS), and patient factors influencing NNE. RESULTS The participating clinics contributed a total of 300,215 cases, including 17,172 melanomas and 283,043 melanocytic nevi. The overall NNE values achieved in SCS and NSCS in the 10-year period were 8.7 and 29.4, respectively. The NNE improved over time in SCS (from 12.8 to 6.8), but appeared unchanged in NSCS. Most of the effect on NNE in SCS was due to a greater number of excised melanomas. Higher NNE values were observed in patients younger than 40 years and for lesions located on the trunk. LIMITATIONS No data concerning the use of dermatoscopy and digital monitoring procedures were collected from the participating centers. CONCLUSION Over the 10-year study period, accuracy in melanoma detection improved only in specialized clinics maybe because of a larger use of new diagnostic techniques such as dermatoscopy.

Low-dose dapsone in chronic idiopathic urticaria: preliminary results of an open study.

Sir, Chronic idiopathic urticaria (CIU) is defined as the occurrence of wheals on most days for more than 6 weeks in the absence of any known causative or triggering agents (1). Most cases of chronic urticaria are classified as ‘idiopathic’, despite intense efforts to determine any aetiological factor, and require long-term treatment with H1-receptor antagonists, which are the first-line approach to uncomplicated forms (2). Here we present our cumulative experience with dapsone in some cases of severe refractory CIU.

Evaluation of a New ELISA Assay for Detection of BP230 Autoantibodies in Bullous Pemphigoid

The diagnosis of bullous pemphigoid is based on clinical observations and on the presence of autoantibodies directed against proteins of the dermoepidermal junction. Human recombinant BP180 and BP230 peptides have been used to develop new quantitative enzyme immunoassays (EIA) for the detection of specific antibodies. This study evaluated the sensitivity and specificity of a new immunoassay for the detection of BP230 autoantibodies and clinical correlations. Serum samples were tested from patients with bullous pemphigoid, other skin diseases, and from healthy donors. Autoantibodies anti‐BP230 and anti‐BP180 were assayed using the EIA method. Diagnostic specificity for both tests was over 98%; diagnostic sensitivity was 90% and 60% for anti‐BP180 and anti‐BP230, respectively. IgG anti‐BP180 titers exhibited a significant correlation with disease activity. No patient in remission was positive for anti‐BP230. In conclusion, anti‐BP180 and anti‐BP230 assays are useful in the diagnosis of bullous pemphigoid and provide information on disease activity.

Cyclosporine in the treatment of generalized granuloma annulare.

A 56-year-old man had numerous small papules, some in an annular pattern, on the trunk, upper and lower extremities , and neck that had appeared gradually during the last 6 months. Histologic examination showed a palisading granuloma of the papillary dermis with a predominantly lymphohistiocytic infiltrate; there was no fragmentation of elastic fibersor elastophagocytosis. Direct immunofluorescence testing results were negative. GGA was diagnosed. Blood glucose, cholesterol, uric acid, immunoglobulin, and complement levelswere normal. Treatment with diaminodiphenylsulfone (DDS), 100 mg/day, was started. After 12 weeks the eruption was unchanged and treatment was stopped. With the informed consent of the patient , treatment with cyclosporine, 6 mgjkgjday, was started. Cyclosporine trough levels and serum creatinine levels were monitored twice monthly throughout treatment. After 2 weeks the papules began to flatten, and the erythema was reduced. The lesions had virtually disappeared after 30 days. The dose of cyclosporine was decreased to 3 mg/kg /day, and therapy was continued for another 90 days, at the end of which time complete clearing was obtained (Figs. I and 2). During the following year no recurrence was noted.

Prevalence of beta and gamma human papillomaviruses in the anal canal of men who have sex with men is influenced by HIV status

BACKGROUND Mucosal high-risk human papillomavirus (HPV) types benefit differently from the immunocompromised status of the host. So far it is not known whether a similar scenario holds for the large group of the β and γ cutaneous HPV types that appear to be present at several anatomical sites. METHODS The presence of β (n=43) and γ (n=30) HPVs in the anal samples of 66 HIV-positive and 153 HIV-negative anonymized men who have sex with men (MSM) was determined by multiplex PCR, using type-specific primers and bead-based hybridization (Luminex technology). RESULTS The prevalence of β and γ HPV infection was 65.6% and 68.2%, respectively, among HIV-positive MSM and 59.1% and 57.7%, respectively, among HIV-negative MSM. β-2 and γ-10 were found to be the most prevalent species in both groups. The prevalence of infection with HPV types of the species β-1 (P=0.02), β-3 (P=0.002), γ-6 (P=0.002), and γ-7 (P=0.02) was higher in HIV-positive than HIV-negative men. In contrast, the β-2 species was equally distributed in the two groups, while the γ-10 species was slightly affected by HIV status. CONCLUSIONS These findings provide evidence that impairment of the hosts immune surveillance impacts β and γ HPV infections differently.

Influence of desloratadine on oxidative stress markers in patients with chronic idiopathic urticaria

Background  Recent findings suggest the involvement of oxidative stress in the pathogenesis of chronic idiopathic urticaria (CIU). It has been demonstrated that desloratadine has an antioxidant activity in vitro. We evaluated the effects of desloratadine on markers of oxidative stress in patients with CIU.

Purpuric clothing dermatitis due to Disperse Yellow 27

Comment Contact sensitization to bufexamac is not rare, though often unknown or forgotten by the patient, but seems to be less frequent in our series than in previous reports (2, 3). Bufexamac (4-butoxy-N-hydroxy-benzeneacetamide) and diclofenac (2[(2,6-dichlorophenyl)amino]-benzeneacetic acid) both have a benzene ring, with an acetamide (bufexamac) or an acetic acid group (diclofenac) on the alkyl chain. This difference might explain the absence

Evaluation of inflammatory parameters in physical urticarias and effects of an anti‐inflammatory/antiallergic treatment

Background  Physical urticaria (PU) includes a heterogeneous group of urticarias whose etiopathogenic aspects are still obscure and whose therapeutical management is often difficult. We have previously demonstrated the efficacy of a sequential treatment with nimesulide, a unique nonsteroidal anti‐inflammatory drug, and ketotifen in various forms of PU.

Pubic and vulvar inflammatory tinea due to Trichophyton mentagrophytes

immunofluorescence and immunoprecipitation studies were not performed. The presence of bronchiolitis obliterans has been reported as a cause of respiratory failure in PNP. The association of PNP and soft tissue sarcomas is uncommon and has only a few reports. Malignant fibrous histiocytoma is the most common soft tissue sarcoma of late adult life, but as a cause of PNP it is rare. It arises most commonly in the extremities (70–75% of cases), followed by the retroperitoneum. The tumor is sometimes observed in patients younger than 20 years of age. The possible explanation for the concomitant occurrence of malignant fibrous histiocytoma and PNP is difficult. The real relationship of the two conditions has yet to be studied. Association may be just coincidental, but a possible explanation is that primitive mesenchymal cell, which is believed to be a cell of origin for malignant fibrous histiocytoma, does not have desmosomes, but shows an intimate relationship with lymphatic capillaries and endothelial cells, which are rich in intercellular connections and desmosomal proteins, although they are not able to form typical desmosomes. It may be speculated that some soluble glycoproteins, secreted by many soft tissue tumors, may act on adjacent capillaries inducing changes on desmosomal proteins, which may acquire immunogenic properties and produce PNP.