Skin cancer: preventive photodynamic therapy in patients with face and scalp cancerization. A randomized placebo-controlled study.

Background Patients with a previous medical history of nonmelanoma skin cancers (NMSCs) often develop multiple or recurrent malignant lesions around the site of the primary tumour. This finding led to the field cancerization theory, which suggests that the entire epithelial surface of the regional skin has an increased risk for the development of malignant lesions. Management of field change is challenging, taking into account the high impact of NMSCs on public health and healthcare costs. Objectives We sought to investigate whether field-photodynamic therapy (PDT) of extreme photodamaged skin would prevent new NMSCs, in comparison with a control area receiving placebo-PDT, in patients with clinical and histological signs of field cancerization. Methods Forty-five patients, previously diagnosed as having NMSCs of the face or scalp, with actinic keratoses symmetrically distributed over the same regions, were randomized for field treatment with 20% aminolaevulinic acid (ALA)-PDT on one side and placebo-PDT on the other. During the next 12-month period of follow up, patients were clinically evaluated for new NMSCs. Results A significant delay in the mean time of appearance and a reduction in the total number of new lesions were observed in the field-PDT protocol, when compared with the control. Conclusions The results obtained showed that field therapy with ALA-PDT confers a significant preventive potential against the formation of new NMSCs in patients with field changes.

Photodynamic therapy with 5-aminolevulinic acid in actinic cheilitis: an 18-month clinical and histological follow-up.

BACKGROUND: Actinic cheilitis (AC) may bear the initial and superficial changes of actinically induced squamous cell carcinoma (SCC) and may progress into fully developed SCCs. Early and effective treatment is important. OBJECTIVE: To assess the clinical and histological long-term outcome in AC after two ALA-PDT sessions. METHODS: Patients with histologically proven grade 1 and 2 AC received two ALA-PDT sessions at 2 weeks interval. Subjects with complete clinical response at 3 months were evaluated further clinically and histologically at months 6, 12 and 18. Long-term study outcome was defined as clinical and histological AC recurrence among patients with complete clinical response 3 months after treatment. Cosmetic outcome was assessed by the investigators at the final follow-up visit at 18 months. RESULTS: Of the 40 patients enrolled, 38 completed the study. Complete clinical response at 3 months was achieved in 26 patients. At 6 months, clinical and histological recurrence occurred in three patients and at 12 months, one more patient showed clinical and histological recurrence. At 18 months, overall clinical recurrence rate was 15.38% (4/26), while overall histological recurrence rate was 34.61% (9/26). Cosmetic outcome was rated as excellent in more than 80% of evaluated cases. CONCLUSION: PDT represents a moderately effective treatment modality in AC. Optimization of treatment procedure and protocols is still needed for higher response rates to be achieved. Moreover, the high treatment cost should be given consideration. Further long-term follow-up studies are needed for assessment of clinical and histological very late recurrences that could be expected after PDT.

Angiolymphoid hyperplasia with eosinophilia: good response to photodynamic therapy.

Angiolymphoid hyperplasia with eosinophilia (ALHE) is an uncommon benign vascular disease of unknown pathogenesis, that occurs as solitary or multiple nodules or papules. Lesions are located mainly on the head, forehead and neck, and may be persistent and difficult to eradicate. We report a case of ALHE treated with aminolaevulinic acid photodynamic therapy (ALA-PDT). Treatment consisted of two ALA-PDT sessions with a 2-week interval. Clinical evaluation, 8 weeks after treatment, showed marked improvement though not complete regression. The treatment was well tolerated. At follow-up 4 months after treatment, the lesions were stable. We believe that PDT could be an alternative therapeutic approach for ALHE or could be used as a neoadjuvant treatment to reduce lesion size especially where size or site of lesions limits the efficacy or acceptability of other treatments. The lack of cumulative effects allows repeated treatments with ALA-PDT, but long-term follow-up is advised for assessment of recurrence.

Intraindividual, right-left comparison of topical 5-aminolevulinic acid photodynamic therapy vs. 5% imiquimod cream for actinic keratoses on the upper extremities.

BACKGROUND: Actinic keratoses (AKs) are considered as in situ squamous cell carcinoma. Early and effective treatment is important. Objective To compare the efficacy, cosmetic outcome and patient preference of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) with that of 5% imiquimod (IMIQ) cream in patients with AKs on the dorsa of hands and forearms. METHODS: Subjects received two ALA-PDT treatment sessions and one or two courses of imiquimod (three times per week for 4 weeks each). Treatments were randomly allocated to alternate upper extremities. Assessments included lesion response one and six months after treatment, cosmetic outcome evaluated by the investigators and patients' preference 6 months after treatment. Efficacy end point included the individual AK lesion clearance rate. RESULTS: Thirty patients with 256 lesions were included in the study. At the first follow-up, treatment with ALA-PDT resulted in significantly larger rate of cured lesions relative to 5% IMIQ cream (70.16% vs. 18.26%). At the second follow-up both treatments showed a high rate of cured lesions (65.32% for PDT vs. 55.65% for IMIQ cream). Response rates obtained in grade I lesions were higher for both treatments (71.64% for PDT vs. 72.13% for IMIQ), while treatment with PDT resulted in a significant larger rate of cured grade II lesions (57.89% for PDT vs. 37.03 for IMIQ). Difference in cosmetic outcome was not statistically significant. Results for subject preference favoured ALA-PDT. CONCLUSIONS: Our study shows that ALA-PDT and 5% IMIQ cream are both attractive treatment options for upper extremities AKs with comparable efficacy and cosmetic outcomes.

Pemphigus vulgaris affecting 19 nails.

A 60-year-old woman presented with painful erosions in the oral mucosa, pharynx, perineum and perianal area, and multiple plaques with thick adherent crusts on the scalp. Most (nine) of the patient's fingernails had alterations in colour, affecting more than half of the nail plate, and all the toenails had severe inflammation of the nail folds, haemorrhagic paronychia and subungual or intraungual haemorrhage. A diagnosis of pemphigus vulgaris (PV) was made based on histology and on direct and indirect immunofluorescence findings. Groups of acantholytic cells were also observed in a Tzanck smear obtained from a subungual lesion. Onychomadesis in most of the fingernails and in all the toenails developed gradually. The patient was hospitalized and treated with oral corticosteroids. Complete recovery without residual damage to the nails and persistent remission was achieved. Nail involvement in PV is rarely described and is always of interest, as its presentation varies widely.

Detection of anti-BP180NC16a and anti-BP230 autoantibodies in blister fluid of patients with bullous pemphigoid: the first survey in Greece.

Bullous pemphigoid (BP) is an acquired bullous disease with an increasing prevalence among elderly people worldwide, including in Greece. Blister formation in most patients with BP is caused by autoantibodies against structural components of the basement membrane zone of the skin, predominantly BP180NC16a and BP230 antigens on the hemidesmosome adhesion complex. Routine diagnostic methods such as histological examination and direct and indirect immunofluorescence are combined to determine diagnosis. In this study, an ELISA was used to measure levels of both anti-BP180NC16A and anti-BP230 autoantibodies in the blister fluid of 13 patients with newly diagnosed BP, before starting treatment. The aim of the study was to evaluate this method as a diagnostic tool in BP. Our results indicate that blister-fluid examination by ELISA can be a useful tool to diagnose bullous pemphigoid, especially in elderly patients who refuse biopsy or have poor venous access.

Forty-eight-hour diagnosis of onychomycosis with subtyping of Trichophyton rubrum strains.

A novel strategy for the molecular identification of fungal agents of onychomycosis (including Trichophyton rubrum) has been designed based on the use of species-specific and universal primers in conjunction with a commercial kit that allows the extraction of DNA directly from the nail specimens. The microsatellite marker T1, which is based on a (GT)n repeat, was applied for the species-specific identification of Trichophyton rubrum. To evaluate how often Scopulariopsis spp. are detected in nail specimens, a second primer pair was designed to amplify specifically a 336-bp DNA fragment of the 28S region of the nuclear rRNA gene of S. brevicaulis and closely related species. Other fungal species were identified using amplification of the internal transcribed spacer (ITS) region of the rRNA gene, followed by restriction fragment length polymorphism analysis or sequencing. In addition, polyacrylamide gel separation of the T1-PCR product allowed subtyping of T. rubrum strains. We studied 195 nail specimens (the "nail sample") and 66 previously collected etiologic strains (the "strain sample") from 261 onychomycosis patients from Bulgaria and Greece. Of the etiologic agents obtained from both samples, T. rubrum was the most common organism, confirmed to be present in 76% of all cases and serving as the sole or (rarely) mixed etiologic agent in 199 of 218 cases (91%) where the identity of the causal organism(s) was confirmed. Other agents seen included molds (6% of cases with identified etiologic agents; mainly S. brevicaulis) and other dermatophyte species (4%; most frequently Trichophyton interdigitale). Simultaneous infections with two fungal species were confirmed in a small percentage of cases (below 1%). The proportion of morphologically identified cultures revealed by molecular study to have been misidentified was 6%. Subtyping revealed that all but five T. rubrum isolates were of the common type B that is prevalent in Europe. In comparison to microscopy and culture, the molecular approach was superior. The PCR was more sensitive (84%) than culture (22%) in the nail sample and was more frequently correct in specifically identifying etiologic agents (100%) than microscopy plus routine culture in either the nail or the strain samples (correct culture identifications in 96% and 94% of cases, respectively). Using the molecular approach, the time for diagnosing the identity of fungi causing onychomycosis could be reduced to 48 h, whereas culture techniques generally require 2 to 4 weeks. The early detection and identification of the infecting species in nails will facilitate prompt and appropriate treatment and may be an aid for the development of new antifungal agents.

Is itraconazole the treatment of choice in Microsporum canis tinea capitis?

Mycotic scalp infection caused by Microsporum canis is the most dominant cause of tinea capitis in Greece. Griseofulvin has been the gold standard for the treatment of tinea capitis, but it is unavailable in our country. In this study, we evaluated 111 children with M. canis tinea capitis that were treated with itraconazole. Eighty-one of them were treated with itraconazole capsule pulse therapy (group A) and 30 (group B) were treated with oral suspension administered in continuous regimen. Twenty-one patients, all from group A, were lost to follow-up, probably due to the length of this regimen. In all patients that made up the study protocol, complete cure was achieved within seven pulses for group A and 12 weeks for group B. No significant side effects to lead to the cessation of therapy were recorded. Laboratory investigations were performed in 32 randomly chosen patients and were within normal ranges. The response to therapy did not appear to depend upon the formulation administered (capsules versus suspension). Using the pulse regimen, we also believe that it is necessary to individualize the number of pulses administered according to the clinical response. In conclusion, itraconazole proved safe and effective in our study, providing an ideal alternative to griseofulvin.

Efficacy and tolerability of 8 weeks' treatment with terbinafine in children with tinea capitis caused by Microsporum canis: a comparison of three doses.

BACKGROUND: Tinea capitis caused by Microsporum canis is the most common mycosis of the scalp in preschool and school-aged children in Greece. OBJECTIVE: To compare the efficacy, safety and tolerability of an 8-week course of oral terbinafine at different doses. METHODS: Patients received oral terbinafine at doses ranging from 3.3 to 12.5 mg/kg/day for 8 weeks, as follows: group A, terbinafine 3.3 to 6.0 to 7.0 mg/kg/day (23 patients); group C, terbinafine > 7.0 to 12.5 mg/kg/day (37 patients). Fungal microscopy and cultures were performed 4 weeks before the start of the treatment, at the end of the treatment (week 8) and at a follow-up visit at week 16. RESULTS: At week 8 mycological cure was achieved in one patient (2.7%) in group A, in 21 patients (91.3%) in group B and in 34 patients (97.1%) in group C. At week 16 mycological cure was achieved in one patient (2.7%) in group A, in 22 patients (95.7%) in group B and in 35 patients (100%) in group C. There was a statistically significant difference (P < 0.0005) between dose level and efficacy of terbinafine at the end of the treatment period and also at the follow-up visit at week 16. Five patients (three in group A and two in group C) discontinued treatment because of adverse events. CONCLUSIONS: The administration of terbinafine at a dose of either 6-7 or 7-12.5 mg/kg/day for 8 weeks is safe and effective for the treatment in children of tinea capitis caused by M. canis.

Onychomycosis in Northern Greece during 1994-1998.

In the 5-year period 1994-1998, 13957 patients were examined in the Mycological Laboratory of the State Hospital for Skin and Venereal Diseases, in Thessaloniki, Greece. Of the 2766 patients presenting with onychomycoses (20%), 67% were women and 33% were men. In the toenail infections, dermatophytes were most often isolated (72.3%), especially in women, followed by moulds (9.6%) and yeasts (2%); 16.1% of the infections were mixed. In the fingernail infections mostly yeasts were isolated (72%), especially in women, followed by dermatophytes (10%) and moulds (5.6%); 12.4% of the infections were mixed.

Tinea capitis in children in northern Greece during the period 1981-1995.

In our 15 years of investigation in northern Greece, the predominant organism producing tinea capitis in children was found to be the zoophilic Microsporum canis (494 strains) which is a common saprophyte of the hair of pets, especially cats. The high percentage of cases with M. canis (97%), in contrast to zoophilic fungi (3%), is probably due to the increased contact of children with pets. The small number of infections with anthropophilic fungi (41 strains) is attributed to good hygienic conditions. The fluorescence of infected hair under Wood's light seems to be a major diagnostic criterion in the hands of dermatologists who are not served by a mycological laboratory.

Cutaneous alternariosis in an immunocompromised patient.

A case of cutaneous alternariosis in a 68-year-old male farmer is presented. The patient had been treated with prednisone and azathioprine for thrombocytopenic purpura, and two months later he noted multiple ulcerated and slightly infiltrated granulomatous lesions on exposed areas. The diagnosis was confirmed by results of direct examination, culture of biopsy material, and histologic examination. A concurrent herpetic infection healed without sequelae. The protracted course of our patient's condition and a review of the literature suggest the tapering or stopping of steroids as the first step in the successful and permanent treatment of cutaneous alternariosis.