Report of terbinafine resistant Trichophyton spp. in Italy: Clinical presentations, molecular identification, antifungal susceptibility testing and mutations in the squalene epoxidase gene.

BACKGROUND: Numerous reports of resistance to terbinafine in Trichophyton spp. from all over the world are arousing justified attention and concern. Point mutations in the gene that encodes the squalene epoxidase (SQLE) enzyme are responsible for these therapeutic resistances. OBJECTIVES: Primary objective of the study was to describe first isolates of Trichophyton spp. resistant to terbinafine among the patients treated between September 2019 and June 2022 at the Dermatology Units of Ospedale Maggiore Policlinico and San Bortolo Hospital. Secondary objective was to study the resistance mechanism. METHODS: Patients with confirmed Trichophyton spp. infection has been treated with systemic and topical terbinafine. Patients were then re-evaluated 12 weeks after the therapy. Patients with incomplete or absent response to terbinafine underwent a new skin scraping for direct mycological examination, new identification of dermatophyte species from culture and MALDI-TOF, molecular species identification, antifungal susceptibility testing and molecular analysis of SQLE gene. RESULTS: We identified five patients without clinical response to treatment with terbinafine. The DNA sequencing of the ITS region identified one Trichophyton rubrum and four Trichophyton indotineae. The T. rubrum strain showed minimum inhibitory concentration (MIC) (90% growth inhibition) of 4 mg/L for terbinafine. The four T. indotineae strains showed a MICs range of 0.25-4 mg/L for terbinafine. The analysis of the SQLE gene in the T. rubrum strain showed a nucleotide substitution generating a missense mutation (L393F). The SQLE gene sequencing in the T. indotineae strains showed a nucleotide substitution generating a missense mutation (F397L) in two strains, a nucleotide substitution L393S in one strain and a nucleotide substitution F415C in another strain. CONCLUSIONS: We report the first cases of terbinafine-resistant Trichophyton isolates in the Italian population. Solid antifungal management programs will be needed to promote more responsible use of antimycotics and preserve their therapeutic efficacy to control antifungal resistance.

Intralesional vincristine as first-line therapy for nodular lesions in classic Kaposi sarcoma: a prospective study in 151 patients.

BACKGROUND: Classic Kaposi sarcoma is a rare angioproliferative neoplasm with varying biological behaviour. Depending on the clinical stage, local or systemic therapy can be used. Vincristine has proven to be effective as systemic chemotherapy and in very few reports as intralesional treatment. OBJECTIVES: Our aim was to determine the efficacy and safety of intralesional vincristine in the treatment of classic Kaposi sarcoma nodular lesions. METHODS: We conducted a prospective, open-label, single-centre clinical trial in 151 patients with stage IB classic Kaposi sarcoma. Vincristine was injected in a single nodule (0.3-0.8 mm) on the lower limb. Another similar lesion on the same limb, at a distance of >or= 10 cm, or on the contralateral limb, was kept under clinical observation as control. Adverse effects were evaluated after 1 week, and efficacy after 4 and 12 weeks. RESULTS: One hundred and fifty-one patients were enrolled. At final evaluation, 115 patients presented complete response (76.1%), 28 had partial response (18.5%), six had improvement (4%), one had stable disease (0.7%) and only one patient had tumour progression (0.7%). Therefore the total response rate was 98.7% (149 patients). Therapy was generally well tolerated. The most frequently registered adverse events, observed in 21 patients (13.9%), were erythema and itching. CONCLUSIONS: Intralesional vincristine is an effective and safe treatment for nodular lesions in classic Kaposi sarcoma and can be recommended as first-line therapy in initial stages and as support therapy in advanced stages.

Lymphogranuloma venereum: the Italian experience.

An epidemic of lymphogranuloma venereum (LGV) has been described in men who have sex with men (MSM) in the western world, particularly in western Europe. The first Italian case was reported by the authors in 2006, and up to March 2008 there have been 13 symptomatic cases, all in MSM. Ten cases had LGV proctitis and three cases had inguinal adenopathy as their clinical presentation. The initial three cases reported receptive anal intercourse in metropolitan areas of northern Europe, Turkey and eastern Europe, whereas the later cases were infections acquired locally. Diagnosis was by LGV-specific real-time PCR in nine cases, by symptoms and PCR for Chlamydia trachomatis in three cases, and in one case clinically and epidemiologically.

Weekly paclitaxel for advanced aggressive classic Kaposi sarcoma: experience in 17 cases.

BACKGROUND: Paclitaxel has proved to be highly effective in the treatment of severe AIDS-related Kaposi sarcoma (KS), for which it is now considered as a second-line monotherapy. Taxanes were recently shown to be active also in classic, endemic and post-transplantation KS. OBJECTIVES: To evaluate the clinical efficacy and tolerability of standardized paclitaxel treatment (100 mg weekly, intravenously) in a homogeneous group of 17 patients with advanced aggressive and refractory classic KS (cKS). METHODS: Seventeen patients with aggressive refractory cKS (stage IIIBc-IVBcv) were treated with intravenous paclitaxel 100 mg weekly. The response to the therapy was evaluated after 12 weeks. A maintenance treatment every 2 weeks was introduced for most of the patients and a final evaluation was made. RESULTS: A partial/complete response was achieved in 14 of 17 patients. Two patients had allergic reactions, for which treatment was discontinued. One patient had progression of disease despite initial improvement. Patients received a mean of 16.8 courses. The treatment was generally well tolerated. Mean time to recurrence was 4.5 months from the end of the therapy and 7.35 months from the 12th course. In four of 10 patients who relapsed at follow-up, the recurrence was mild and responsive to local treatment, while the other six relapsing patients repeated paclitaxel with good response in five of them. CONCLUSIONS: This study shows that low-dose paclitaxel proved to be effective and well tolerated in patients with aggressive refractory cKS, controlling the aggressiveness of the disease. The treatment can be repeated with good response.

Treatment of classic Kaposi sarcoma with a nicotine dermal patch: a phase II clinical trial.

BACKGROUND: Kaposi sarcoma (KS), a malignancy of dermal endothelial cells that is caused by human herpesvirus 8 (HHV8) infection, is sensitive to perturbations of immunity. Nicotine might be effective against KS because of its immunologic and vascular effects and because smoking is associated with a low risk of KS. OBJECTIVE AND STUDY DESIGN: We conducted a masked, randomized phase 2 clinical trial of transdermal nicotine and placebo patches to assess the safety and efficacy of nicotine against classic KS (cKS). SUBJECTS AND METHODS: Three cKS lesions, predominantly nodules, in each of 24 non-smoking patients were randomly assigned to 15 weeks continuous treatment with nicotine patch (escalated to 7 mg), identical masked placebo patch or no patch. Changes in lesion area and elevation from baseline through six follow-up visits, by direct measurement and by two independent readers using digital photographs of the lesions, were compared using non-parametric and regression methods. Changes in longitudinal levels of HHV8 antibodies and DNA in blood cells were similarly assessed. RESULTS: There were no systemic or serious adverse events, and compliance was good. One patient resumed smoking and discontinued patches, and two patients withdrew at week 12 for unrelated indications. Six (29%) of the remaining 21 suspended use of patches to relieve local skin irritation; four of these six completed the trial at reduced dose. Treatment assignment was not associated with significant or consistent changes in cKS lesion area or elevation, HHV8 viral load or antibodies. CONCLUSION: Transdermal nicotine and placebo patches caused no serious toxicities but had no demonstrable effect on nodular cKS lesions or HHV8 levels.

Ano-rectal lymphogranuloma venereum: the first case in Italy.

Lymphogranuloma venereum (LGV) is a sexually transmitted infection endemic in Central Africa, South-East Asia and in some countries of Central and South America. In Italy LGV has been sporadically reported in patients coming from abroad. The etiological agent of LGV is Chlamydia trachomatis serovars L1, L2, L3, differentiating by pathogenetic action. The clinical course of LGV can be divided into three stages with a initial small papule, which may ulcerate, at the site of inoculation, followed by massive lymphadenopathy, which is usually unilateral, and eventually by lymphatic obstruction, causing elephantiasis. During 2004 a LGV ano-rectal clinical variant has been described as an erosive proctitis among homosexual HIV-positive men in some countries of Western Europe, not coming from endemic areas. Until now this syndrome has been often explained as chronic intestinal inflammatory disease. This report describes a case of proctitis caused by CT serovar L2; to Authors' knowledge this is the first case reported in Italy.

Posttransplantation cutaneous B-cell lymphoma with monoclonal Epstein-Barr virus infection, responding to acyclovir and reduction in immunosuppression.

Posttransplantation lymphoproliferative disorders (PTLDs) represent an important complication of solid organ transplantation. The main causative factor of PTLDs seems to be the intensity and type of immunosuppressive therapy and the frequent occurrence of Epstein-Barr virus infection. PTLDs that are disseminated at diagnosis or present late after transplantation generally share an unfavorable prognosis and are unlikely to regress in response to reduction in immunosuppressive therapy. We describe a case of cutaneous B-cell lymphoma occurring 4 years after heart transplantation in which molecular analysis revealed a monoclonal pattern of Epstein-Barr virus infection and immunoglobulin gene rearrangement. In spite of its monoclonal nature and late occurrence, the lymphomatous lesions regressed completely after antiviral treatment and a reduction in immunosuppressive therapy.

Immunohistological evaluation of basal cell carcinoma immunoinfiltrate during intralesional treatment with alpha 2-interferon.

We investigated the peritumoral and intratumoral immune infiltrate in 6 basal cell carcinomas (BCCs) treated with recombinant alpha 2b-interferon. Each BCC was injected intralesionally three times a week for 3 weeks with 1.5 x 10(6) IU of interferon per injection (total dose 13.5 x 10(6) IU). The immunohistological study was done before the start of interferon therapy and 15 days afterwards, using a series of monoclonal antibodies and an immunocytochemical technique. Before therapy the infiltrate consisted mainly of CD3+ (T) cells, with prevalence of CD4+ (helper/inducer) T cells. The percentage of T cells expressing interleukin-2 receptor (CD25+ cells) was higher in the tumor nests than in the peritumoral infiltrate (20% and 11% respectively). CD1+ (Langerhans) cells and CD14b+ cells (monocytes/macrophages) were present in the peritumoral infiltrate in all cases (9% +/- 5% and 14% +/- 7% respectively). Very few CD56+ (natural killer), CD15+ (granulocytes) and CD20+ (B) cells were observed in the peritumoral infiltrate and none at all in tumor nests. After 15 days of interferon therapy, we observed an increase in peritumoral and intratumoral CD4+ cells. There was a decrease in the number of CD25+ cells and of CD1+ cells in the peritumoral infiltrate. The number of intratumoral CD25+ increased. No variations were seen in CD14b, CD15, CD20, and CD56 positive cells. Eight weeks after completion of therapy, two BCCs were cleared and the remaining four showed clinical and histological improvement. These results may indicate a direct effect of interferon against BCC; in addition the immunohistological findings suggest that intralesional interferon enhances T cell mediated immune response, especially in tumor nests.(ABSTRACT TRUNCATED AT 250 WORDS)

[Cytofluorimetric evaluation of peripheral blood dendritic cells in patients with Mediterranean Kaposi's sarcoma]. / Valutazione citofluorimetrica di cellule dendritiche circolanti in pazienti affetti da sarcoma di Kaposi mediterraneo.

AIM: Kaposi's sarcoma (KS) is a lympho-angioproliferative disorder characterized by angiomatous nodules and plaques that mainly affect the skin. The disease is consistently associated with human herpesvirus-8 (HHV8) and with a state of preexistent immunosuppression. Dendritic cells (DCs) have an instrumental role in the activation and function of both innate and adaptative immune responses. At least 2 distinct subsets have been characterized in peripheral blood based on phenotypic markers: myeloid DCs (CD11c+), associated with Ag uptake, T cell activation and ability to secrete IL-12, and plasmacytoid DCs, high virus-induced IFN-alpha producing cells. Because of the role of both DC subtypes in antiviral and antitumor induced responses, we hypothesized that DCs could be involved in the onset and evolution of KS. METHODS: Thirty-five patients with mediterranean KS assigned to different clinical stages were compared with 51 healthy control subjects. Peripheral blood DCs were quantified and functionally characterised by flow cytometry directly on whole blood samples. The production of the regulatory cytokines, IL-12 and IL-10, was assessed as intracellular accumulation after incubation with or without lipopolysaccharide (LPS). RESULTS: Myeloid DCs identified as lineage-/HLA-DR+/CD11c+ cells were significantly lower in KS patients than in controls (0.54+/-0.25 vs 0.69 +/-0.26% of the peripheral blood mononuclear cells; p<0.017). Furthermore, CD11c+ DCs were lower in patients with more diffuse disease. Plasmacytoid DCs, identified as lineage-/HLA-DR+/CD123+ cells, were lower in KS patients (0.23+/-0.19 vs 0.36+/-0.17; p<0.001). DCs from KS patients were more mature, as assessed by expression of the maturation marker CD83, and showed an impaired ability to produce IL-12 upon LPS stimulation, as compared with controls. CONCLUSION: The numerical and functional alterations of peripheral blood DCs observed in KS patients suggest an involvement of these cells in the onset and evolution of the disease.

[Late secondary syphilis]. / Lue secondaria tardiva.

A case of late secondary syphilis characterized by morphologically and topographically typical papulo-nodular and nodulo-ulcerative lesions is described. In the course of the late secondary stage nodular and ulcerous lesions arise as precursors of the tertiary stage. Therapy with penicillin caused the rapid regression of the disease with slight residual atrophy and dyschromia.

[Structural and ultrastructural study of an isolated case of pili annulati]. / Studio strutturale e ultrastrutturale in un caso isolato di pili annulati.

A case of pili annulati in an eighteen year old woman is described. The hairs show bright spots along hair shafts when viewed in daylight. The transmission and scanning electron microscopy confirmed that the bright spots are due to small cavities into the cortex. The plasmatic measurement of copper, zinc and of the most important hormone, such as the dosage of plasmatic, urinary and hair aminoacids, allowed the Authors to exclude any influence of metabolic systemic alterations on the pathogenesis of pili annulati. Neither cutaneous nor internal anomalies were detected.

Continuous exposure to Kaposi sarcoma-associated herpesvirus (KSHV) in healthcare workers does not result in KSHV infection.

Kaposi sarcoma (KS)-associated herpesvirus (KSHV or HHV-8) infection routes and risk of occupational exposure are still ill-defined. We analysed the risk for occupational acquisition of KSHV infection in healthcare workers (HCWs) with prolonged professional exposure to patients with classic KS, comparing the results to those obtained in healthy relatives of KS patients. Serum and/or saliva KSHV-specific antibodies and DNA were detected in five out of 35 healthy relatives of KS patients but in none of the eight HCWs, suggesting that, outside strict family contacts, horizontal transmission of KSHV is highly inefficient even for HCWs with prolonged contact with KS patients.