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Notes: Summary Background Historically, there has been a general resistance to treating onychomycosis on the basis that such treatments were protracted and of uncertain outcome. However, modern treatments act more promptly and reliably. Objectives To carry out a meta-analysis to evaluate the efficacy and safety of terbinafine in comparison with placebo, itraconazole and griseofulvin. Methods The analysis used data from published trials, supplemented where necessary by reference to the original trial reports. Results Three trials were included in which terbinafine was compared with placebo. From four trials comparing terbinafine with itraconazole, a statistically significant advantage in favour of terbinafine was observed for negative culture and microscopy at the end of the trials. Furthermore, both patients and physicians reported terbinafine to be better tolerated than itraconazole. From two trials comparing terbinafine with griseofulvin, a significantly higher rate of negative microscopy and culture was observed with terbinafine. Conclusions A significant advantage in favour of treatment with terbinafine was observed.

Notes: Background  The prevalence of onychomycosis is higher in certain high-risk populations, such as the immunocompromised, diabetics and human immunodeficiency virus (HIV)-positive patients. These patients can also develop onychomycosis due to nondermatophyte fungi. Although the efficacy of terbinafine is well demonstrated in the treatment of conventional dermatophyte nail infection, there are few data on the efficacy of terbinafine in high-risk patient groups or in nondermatophyte fungi, which can be difficult to treat.Objectives  To review previously published data regarding the safety and efficacy of terbinafine in special patient populations, such as those with diabetes mellitus or HIV infection, those receiving immunosuppressive therapy, and patients with onychomycosis due to nondermatophyte fungi.Methods  A Medline literature search up to October 2002 was performed in order to identify relevant studies. Pertinent abstracts presented at international meetings were also included. Cure rates (per-protocol and intention-to-treat) were extracted or calculated. All available safety data were also collated.Results  Terbinafine was highly effective and well tolerated in patients with diabetes mellitus. Mycological cure rates of 62–78% were achieved in three studies, which is comparable with the efficacy in nondiabetic populations. Mycological cure rates of 64–91% were achieved in subsets of diabetic patients with Candida-positive nail cultures. The efficacy of terbinafine in patients receiving immunosuppressive therapy was also similar to that reported in immunocompetent patients. Levels of ciclosporin in the blood clearly decreased, with little clinical consequence; however, consideration should be given to the monitoring of ciclosporin levels in patients concomitantly receiving immunosuppressive therapy and terbinafine. Two small studies reported that terbinafine was also effective in treating onychomycosis in HIV-positive patients. Terbinafine was also effective and well tolerated in the treatment of nondermatophyte onychomycosis.Conclusions  This review suggests that terbinafine is a safe and effective treatment for onychomycosis in high-risk populations. However, the majority of these studies only included small numbers of patients and larger clinical trials are needed, especially in patients with HIV infection.

Notes: Congenital naevocellular naevi (CNN) have classical histological criteria that are thought to allow distinction from acquired naevi. These criteria are mainly the horizontal distribution of melanocytes, forming ‘Indian files’, and a prominent adnexotropism. In order to check whether the previously described criteria were reliable, we analysed 1349 unselected consecutive cases of naevocellular naevi excised in children under 16 years, during a 54-month period. The slides were analysed in order to determine by histological analysis only if they could be classified as CNN. These results were then compared with the clinical files, in which only the most reliable data from parental and/or medical observations were included. Of the 1349 naevi, 659 had the typical histological criteria of CNN, 32 of them being deep CNN, characterized by massive involvement of the lower dermis and hypodermis. The comparison with clinical data showed that 32 naevi with the histological criteria of congenital naevi were actually acquired, and that 179 naevi present at birth did not fulfil these criteria. This study shows that the classic histological criteria are not absolutely specific and are poorly sensitive as 36% of naevi present at birth lacked the classic criteria. The most specific criteria of true CNN were the involvement of eccrine glands and presence of melanocytes in the septae. In the case of deep CNN which corresponded to large or very large naevi, the clinicopathological correlation was 100%. Deep CNN could easily be distinguished from superficial CNN and often exhibited many histological changes consistent with a complex hamartoma, such as presence of brown fat tissue, abnormal vessels and numerous large terminal follicles. In conclusion, our study suggests that it is not possible to predict, by histological analysis alone, that a naevus was present at birth, except in deep CNN which are likely to be a separate entity among all congenital naevi. Studies dealing with congenital naevus-associated melanoma should take into account the lack of sensitivity of these criteria.

Notes: Background  Modern antifungal drugs achieve high mycological and clinical cure rates in onychomycosis of the toes, but little is known about the long-term evolution of the treated patients. Objectives  The aim of this review was to analyse the therapeutic results recorded more than 1 year after initiation of therapy. Methods  We used two endpoints for the analysis: EP1 (the number of patients with negative mycology after follow-up, divided by the number of patients included at day 0, including all patients lost to follow-up), and EP2 (the number of patients with negative mycology after follow-up divided by the number of patients with negative mycology at week 48). Clinical cure rate (EPclin) was the number of patients clinically cured or with minimal residual lesions divided by the number of patients included at day 0. Results  From a Medline search we identified 17 studies providing results beyond 48 weeks. Ketoconazole 200 mg d−1 up to 1 year resulted in EP1 of 11% at 18 months, and EP2 of 43%. Griseofulvin 1 g d−1 for 1 year allowed an EP1 of 43% at 18 months, and EP2 of 71%. The mean EP1 after fluconazole once weekly up to 1 year was 49% at 18 months, and EP2 was 91%. With itraconazole 200 mg d−1 or 400 mg d−1 for 1 week each month for 3–4 months, EP1 was 37% at 18 months, and 53% at 2 years; EP2 was 76% at 4 years. Terbinafine 250 mg d−1 for 12–16 weeks achieved an EP1 of 62% at 18 months, 72% at 2 years, and 60% at 4 years; EP2 was 80% at 18 months, 81% at 2 years, and 71% at 4 years. In the only study planned to compare the long-term efficacy of terbinafine and itraconazole, EP1 at 18 months was significantly higher with continuous terbinafine than with intermittent itraconazole (66% vs. 37%, P 〈 0·001). The clinical cure rates were 21% at 60 weeks and 37% at 72 weeks with fluconazole. EPclin was 27% at 18 months and 35% at 2 years with itraconazole. EPclin was 48% at 18 months, 69% at 2 years and 50% at 4 years with terbinafine. Conclusions  Considering the stringency of the criteria we used, this critical review suggests that the long-term efficacy achieved with terbinafine is superior to that obtained with griseofulvin, ketoconazole, fluconazole or itraconazole.