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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.

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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.

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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.

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OBJECTIVE: The aim of this study was to analyze the temporal evolution of melanoma incidence in the department of the Bas-Rhin, France, and to study the evolution of tumor thickness. DESIGN: Retrospective study including all histologically proven melanomas recorded at the cancer registry of the department of the Bas-Rhin between January 1980 and December 1992 and at the Cutaneous Histopathology Department of the University Hospitals, Strasbourg, between January 1980 and December 1997. SETTING: Population-based cancer registry and academic cutaneous histopathology department. PATIENTS: A total of 1254 patients with histologically proven melanomas. INTERVENTION: None. MAIN OUTCOME MEASURES: Temporal evolution of melanoma incidence and tumor thickness. RESULTS: The mean (SD) and median tumor thicknesses were 1.48 (1.59) mm and 0.87 mm, respectively, and they decreased during the study period. The increase in the number of melanomas was mainly related to an increase of superficial spreading melanomas in both sexes. The number of intermediate melanomas (1-2 mm) in both sexes and the number of melanomas with a Breslow index between 2 and 4 mm in women increased only slightly. The number of melanomas with a Breslow index greater than 2 mm in men and greater than 4 mm in women remained stable during the reference period. CONCLUSION: A striking increase in incidence of thin melanomas contrasts with a stable incidence of thick melanomas.

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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.

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OBJECTIVE: To study the prevalence of hepatitis C virus (HCV) and hepatitis G virus (HGV) infection in patients with chronic urticaria. DESIGN: Prospective case-control study and literature review. SETTING: Dermatology department of an academic medical center in Strasbourg, France. PATIENTS: One hundred ten consecutive patients with typical urticaria lasting longer than 2 months were seen between March 1, 1997, and August 31, 1998. None had a history of viral hepatitis. Age- and sex-matched patients (n = 110) seen in the same department and during the same period were included for controls. None of the controls had a history of urticaria, pruritic dermatosis, or hepatitis. MAIN OUTCOME MEASURES: The detection of HCV antibodies through a third-generation enzyme-linked immunosorbent assay. To detect early HCV infection without plasmatic antibodies, genomic amplification of HCV RNA was carried out in all patients using 2 different methods. Hepatitis G virus RNA was detected only by genomic amplification. All measures were planned before data collection. RESULTS: Antibodies to HCV were found in 1 patient with urticaria and in 1 of the control group (0.9% of each group). None had circulating HCV RNA, and liver function test results were within the reference range. Genomic amplification without HCV antibodies was not observed. Two patients with urticaria and 2 of the control group (1.8% of each group) had circulating HGV RNA, but they had neither coinfection with HCV nor changes in their liver function test results. CONCLUSIONS: Systematic HCV screening in patients with chronic urticaria is not cost-effective, at least in Europe, because hepatitis C rates were similar to those of the general population. We could not confirm the hypothesis that urticaria occurs in an early phase of HCV infection-ie, before evidence of HCV can be detected by serologic testing. Hepatitis C virus is unlikely to be the cause of urticaria in the infected patient detected in this study because of the absence of HCV RNA and changes on liver function tests. Hepatitis G virus is also unlikely to be a cause of urticaria, as the rate of HGV positivity in this study was even lower than that in the general French population.

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The arylpropionic acid derivatives (APADs) ketoprofen and tiaprofenic acid can provoke photoallergic dermatitis. Possible cross-reactivity between APADs is of importance in patients using nonsteroidal anti-inflammatory drugs. Because of the similarities in chemical structures, we investigated patients with photoallergy to ketoprofen or tiaprofenic acid, in order to study cross-reactivity between APADs and a possible pattern of cross-reactivity between benzophenone-containing molecules, so as to determine the molecular basis of photoallergy to ketoprofen or tiaprofenic acid. 10 patients with photoallergy to topical ketoprofen, 2 with photoallergy to oral tiaprofenic acid, and 15 control subjects with no history of contact dermatitis from APADs, nor from benzophenone-containing molecules, were photopatch tested in triplicate with ketoprofen, tiaprofenic acid, other APADs (alminoprofen, fenoprofen, flurbiprofen, ibuprofen and naproxen), benzophenone-containing molecules (fenofibrate, oxybenzone, sulisobenzone), and unsubstituted benzophenone. 1 set was irradiated with UVA light, 1 with solar-simulated irradiation and 1 dark control. Tests were read at 2, 3 and 4 days. Patients reacted to both ketoprofen and tiaprofenic acid (12/12), fenofibrate (8/12), oxybenzone (3/12) and unsubstituted benzophenone (11/12), but not to other APADs, nor to sulisobenzone. Tests remained negative in control patients. Photoallergy is due to the benzophenone moiety of ketoprofen, or to the very similar thiophene-phenylketone of tiaprofenic acid, but not to their arylpropionic function. This induces cross-reactivity to fenofibrate and oxybenzone but not to APADs without a benzophenone moiety, which may therefore probably be used in such patients. Unsubstituted benzophenone should be added to standard phototesting series.

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