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Item does not contain fulltext BACKGROUND: Skin manifestations are the most characteristic finding of psoriasis. However, nail involvement is also a clinical feature of disease although it is often overlooked. The documented prevalence of nail psoriasis varies between 10.0% and 81.1%. OBJECTIVES: The aim of this investigation is to gain knowledge about the prevalence and clinical manifestations of nail psoriasis and patient experiences of treatment of nail psoriasis. METHODS: A structured, self-administered questionnaire was distributed to all members (n = 5400) of the Dutch Psoriasis Association. The questionnaire enquired about sociodemographic patient characteristics, disease-related data and treatment of nail psoriasis. Patients reported their nail manifestations with photographs after instruction. Patients with nail psoriasis were compared with patients without nail psoriasis. RESULTS: A response rate of 27% was achieved. The prevalence of nail psoriasis was 66.0%. The most frequently observed psoriatic nail manifestation was pitting (65.4%), whereas red spots in the lunula were infrequently seen (6.5%). Patients with nail psoriasis more frequently stated psoriasis capitis (75.8% vs. 65.7%), genital psoriasis (32.7% vs. 20.3%) and psoriatic arthritis (46.4% vs. 30.6%) compared with patients with psoriasis without nail involvement. Only 16.0% of patients received treatment for nail psoriasis. Systemic therapies were most frequently stated as being effective for nail lesions. CONCLUSIONS: Nail manifestations seem to be more prevalent in patients with psoriasis than previously thought. In addition, nail psoriasis is shown to be associated with widespread and more severe forms of psoriasis, and different treatment options are experienced as being effective for nail psoriasis. Notwithstanding, nail psoriasis is still an often overlooked feature of the disease.

Summary Background Nail disorders can be diagnostically challenging to the dermatologist. Noninvasive methods might help to avoid nail biopsies. More knowledge of the typical features of healthy nails with these techniques is needed for comparison with nail diseases. Objectives To describe the typical morphology of healthy nails in optical coherence tomography (OCT) and confocal laser scanning microscopy (CLSM) and to examine the influence of exposure to water on OCT features, nail thickness as well as on transonychial water loss (TOWL) before and after a hand bath. Material and methods In the first part healthy nail plates were investigated with OCT and CLSM. The thickness of layers as well as structural details were defined. Secondly, in a prospective study 30 healthy volunteers conducted 10 hand baths with water within a 2-week period. Measurements of nail thickness and signal intensity by OCT as well as of the TOWL were performed over time. Results In OCT the unaffected nail plate appears as a band-like, layered structure, yet with some individual differences. In addition, CLSM is able to display single corneocytes and the integrity of their borders. Exposure to water led to a transient rise of TOWL and in nail thickness. Conclusions OCT, CLSM and TOWL offer valuable noninvasive diagnostic tools for the examination of nails. Using CLSM, microscopic features like integrity of single corneocytes can be investigated. OCT allows determination of nail plate thickness and both OCT and TOWL measurements are able to detect short-term effects after exposure to water.

Summary Background Topical therapy has recently been proposed for treating onychomycosis and other nail disturbances. However, the clinical outcome may be limited by the difficulty of active ingredients effectively penetrating the nail plate. Bovine hoof membranes have been widely used to predict in vitro efficacy of drug products in nail diseases. Many studies have compared bovine hooves with human healthy nails, considering the difference between healthy and unhealthy nails to be negligible. Objectives To validate bovine hoof slices as a model for human unhealthy nails by investigating the transungual permeation/retention of ciclopirox (CPX) through bovine hoof slices and excised infected human toenails after application of a new film-forming formulation (P-3051). To investigate the ability of CPX to achieve fungicidal concentrations in and through infected toenails. Methods A new experimental technique based on a permeation unit allowed analysis by high-performance liquid chromatography of the amounts of CPX permeating through and retained in the membranes. The efficacy index was evaluated as follows: amount of permeated CPX/Trichophyton rubrum minimum inhibiting concentration. Results Extrapolated CPX flux through bovine hoof slices was about 14-fold higher than through infected human toenails, the difference being mainly due to the fourfold higher thickness of the toenails. In toenails, the CPX efficacy index for T. rubrum was positive (> 1·0) soon after P-3051 application. Conclusions This study confirms the validity of bovine hoof slices as a model for infected human nails, and suggests a substantial equivalence between the two models. Following P-3051 application, CPX reaches fungicidal concentrations in and through human infected toenails.

Background Suspected toenail onychomycosis is a frequent problem. Clinical diagnosis has been considered inadequate. Objectives To assess the diagnostic accuracy of clinical findings for detecting fungi in toenails, and to develop and validate a clinical diagnostic rule aimed at improving dermatologists’ diagnosis of onychomycosis. Methods A cross-sectional diagnostic study was performed including a total of 277 patients seen by 12 dermatologists. The gold standard was the presence of dermatophytes on culture or a positive nail plate biopsy. For each sign we described prevalence, sensitivity, specificity, positive and negative predictive values, and likelihood ratios for positive and negative results. We developed a diagnostic clinical rule and validated it in a subsample. Results Helpful findings to predict the presence of fungi are: previous diagnosis of fungal disease; abnormal plantar desquamation (affecting > 25% of the sole); onychomycosis considered the most probable diagnosis by a dermatologist; and presence of interdigital tinea. When dermatologists considered onychomycosis the most probable diagnosis and plantar desquamation was present (13% of patients), the positive predictive value for presence of fungi was 81%. When both signs were absent (34% of patients), the positive predictive value for absence of fungi was 71%. In other situations, clinical diagnosis might not give enough information to decide on therapy. Conclusions In 13% of the patients (a large number in absolute terms), when dermatologists consider onychomycosis the most probable diagnosis and plantar desquamation is present, therapy should be started without any further test, as clinical diagnosis is at least as accurate as laboratory tests. In other situations, an optimal management strategy should be defined.

Background: Painful foot blistering is a common problem in patients with epidermolysis bullosa simplex (EBS) and pachyonychia congenita (PC). Hyperhidrosis, a condition which can be effectively blocked by plantar injections of botulinum toxin (Btx), often exacerbates the blistering. Objectives: A retrospective evaluation of the effects of Btx injections in 14 EBS and PC patients with foot blisters and painful callosities. Patients/methods: After informed consent, patients with EBS (n=6) and PC (n=8), aged 7-66 years, who had received Btx therapy at our centre since 2003, were included. The treatment consisted of multiple plantar injections of Btx A or Btx B after prior regional or general anaesthesia. Patients were interviewed about the treatment effect and were asked to score the improvement from 0-5, where 5 is 'excellent'. One PC patient with painful callosities was studied by magnetic resonance (MR) spectroscopic micro-imaging technique before and after Btx injections to disclose any underlying blisters. Results: A total of 76 treatments were evaluated (1-19 sessions/patient). Thirteen patients (92.8%) reported reduced plantar blistering and pain; the improvement score was >/=4 in 4/6 EBS patients and 6/8 PC patients. The mean effect duration was 3 months. No adverse events, apart from mild anti-cholinergic side-effects in 2 patients, were noted. MR spectroscopic micro-imaging showed disappearance of intraepidermal blistering after Btx therapy. Conclusions: Plantar injection of Btx is an efficient, long-lasting and safe treatment of painful blistering and callosities in EBS and PC that can be given repeatedly without loss of efficacy.

Summary Background Tests commonly used in the diagnosis of onychomycosis include potassium hydroxide (KOH) preparation, histopathological examination with periodic acid–Schiff stain (PAS) and culture. These tests are either time-consuming or require specially trained personnel. A recently developed polymerase chain reaction (PCR) assay has the potential to provide a quick, inexpensive, operator-independent diagnosis of onychomycosis. Objective To determine the range of fungal species detected by the PCR technique and to compare this technique with KOH, PAS and culture on patient specimens. Methods A total of 176 dermatophytic and nondermatophytic fungal culture isolates were tested by PCR. Five hundred and fifty nail specimens from 550 patients with suspected onychomycosis were split and tested concurrently with PCR, PAS, KOH and culture. Results PCR was positive in 65 out of 66 dermatophyte culture isolates and negative in all 110 nondermatophyte and yeast isolates. Overall, PAS, PCR, KOH and culture were positive in 54%, 37%, 40% and 22% of specimens, respectively. Fifty-two per cent were positive for KOH and PCR. Conclusion PCR is a specific, relatively sensitive test for onychomycosis. When used in conjunction with KOH, PCR can produce positivity rates similar to those with PAS alone.

Summary Background Although nail psoriasis affects a marked proportion of patients with psoriasis and causes significant psychological stress, only few epidemiological data characterizing patients with nail involvement are available. Objectives To gain robust data on the epidemiology and disease burden of nail psoriasis in Germany. Methods Two nationwide, noninterventional, cross-sectional studies on psoriasis health care were conducted in 2005 and 2007, involving 48 (2005) and 130 (2007) German office-based and clinic-based dermatological centres. Data of n = 3531 patients with psoriasis were collected using standardized questionnaires and physical examinations by trained dermatologists. Patients with nail psoriasis were compared with patients without any nail involvement concerning sex, age, disease duration, family history, disease severity, presence of psoriatic arthritis (PsA), health-related quality of life (HRQoL), number of inpatient therapies, and days off work. Results Nail psoriasis was diagnosed in 40·9% of the patients; prevalence was 11·2 percentage points higher in men than in women. Patients with nail involvement had a longer disease duration (21·9 vs. 18·1 years), higher disease severity (mean Psoriasis Area and Severity Index 12·7 vs. 9·3), higher frequency of PsA (26·0% vs. 12·7%), stronger impairment of HRQoL (mean Dermatology Life Quality Index 8·9 vs. 7·3), and a 2·5-fold higher rate of inpatient treatments. Conclusions Nail involvement is a relevant manifestation of psoriasis and is associated with a higher disease severity and quality of life impairment. Accordingly, management of psoriasis should include a special focus on nail involvement.

Summary Background Dermatophytes are the main cause of onychomycoses, but various nondermatophyte filamentous fungi are often isolated from abnormal nails. The correct identification of the aetiological agent of nail infections is necessary in order to recommend appropriate treatment. Objective To evaluate a rapid polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay based on 28S rDNA for fungal identification in nails on a large number of samples in comparison with cultures. Methods Infectious fungi were analysed using PCR-RFLP in 410 nail samples in which fungal elements were observed in situ by direct mycological examination (positive samples). The results were compared with those previously obtained by culture of fungi on Sabouraud agar from the same nail samples. Results PCR-RFLP identification of fungi in nails allowed validation of the results obtained in culture when Trichophyton spp. grew from infected samples. In addition, nondermatophyte filamentous fungi could be identified with certainty as the infectious agents in onychomycosis, and discriminated from dermatophytes as well as from transient contaminants. The specificity of the culture results relative to PCR-RFLP appeared to be 81%, 71%, 52% and 63% when Fusarium spp., Scopulariopsis brevicaulis, Aspergillus spp. and Candida spp., respectively, grew on Sabouraud agar. It was also possible to identify the infectious agent when direct nail mycological examination showed fungal elements, but negative results were obtained from fungal culture. Conclusions Improved sensitivity for the detection of fungi in nails was obtained using the PCR-RFLP assay. Rapid and reliable molecular identification of the infectious fungus can be used routinely and presents several important advantages compared with culture in expediting the choice of appropriate antifungal therapy.

Background Onychomycosis is a common disease; topical treatment is usually poorly effective, while systemic treatment is more effective but may be associated with side-effects. Iontophoretic drug delivery may improve drug penetration through the nail and lead to better therapeutic results. Objectives To evaluate the efficacy, safety and tolerability of topical treatments with terbinafine HCl delivered with or without an iontophoretic patch in patients with onychomycosis of the toenails. Methods Patients enrolled into the study were divided randomly into two groups. Group A was treated with terbinafine and an iontophoretic patch (at a constant current density of 100 microA cm(-2)). Group B was treated with terbinafine without iontophoresis. Treatment was overnight wear, every day, 5 days per week, for 4 weeks. Follow-up period was 8 weeks from the end of treatment. Results A significant clinical response was recorded in patients of group A (active group). The percentage of patients having healthy toenail growth of more than 1.5 mm at the end of treatment was 40% compared with 11% in patients treated with terbinafine without current (passive group). The percentage of patients having fungal elements (KOH) in nail specimens decreased significantly at 8 weeks following the completion of treatment: 16% in the active group vs. 53% in the passive group. Patients in the active group reported a tingling sensation that is expected when using an iontophoretic drug delivery treatment. Conclusions The delivery of terbinafine under an electrical current of 100 microA cm(-2) appears to be efficacious and safe and is well tolerated for the treatment of nail onychomycosis.

Onychomycosis is a fungal infection of the nail unit, most commonly caused by the anthropophilic dermatophyte fungi. It is generally accepted that this disease is increasing in prevalence despite the introduction of new and efficacious antifungal drugs. Several studies have documented health-related quality-of-life issues associated with onychomycosis and it is clear that patient treatment is both necessary and desirable. The aetiology and pathogenesis of onychomycosis is coming under increasing scrutiny and work in this field has grown substantially in recent years. This is reflected by the increased assurance with which clinicians can now prescribe treatment and be confident of improvement in a majority of their patients. However, a significant proportion of patients, perhaps as many as 25-40% of those encountered in clinical practice, are classified as treatment failures. Clinical indicators for poor prognosis include the development of residual foci of subungual fungal growth, onycholysis and severe disease. These observations have led to a resurgence of interest in combination treatments for use in patients at risk of failure/relapse. Several types of combination can be considered, including the use of oral or topical drugs and the concomitant use of surgical techniques, all of which have a place in the treatment of onychomycosis.

Objective In an open, randomized, clinical study of toenail onychomycosis with matrix area involvement, two alternative regimens of topical amorolfine/oral itraconazole therapy were compared with itraconazole monotherapy. Patients/Methods A total of 131 patients were randomized to treatment. Patients in the combination groups were treated with amorolfine 5% nail lacquer (Loceryl®, Galderma Laboratories) once weekly for 24 weeks and 200 mg itraconazole once daily for 6 weeks (Group AI-6) or 12 weeks (Group AI-12). A control group received itraconazole monotherapy for 12 weeks (Group I-12). Strict inclusion criteria specified that subjects had to have onychomycosis of the toenails with matrix area involvement and/or > 80% total nail surface involvement. Mycological evaluations using both microscopic examination and culture of nail samples were performed at weeks 12 and 24. A stringent assessment of outcome at study end combined the results of mycological and clinical outcomes into a global cure rate. Safety was also assessed. Results At week 12, mycological cure was attained in 42 of 45 patients (93·3%) in group AI-6, 29 of 35 patients (82·9%) in group AI-12, and 14 of 34 patients in group I-12. The difference between both combination groups and the control group were significant (P

Summary Background As Bowen’s disease of the nail apparatus is quite rare, there have been only a few reports on the prevalence of human papillomavirus (HPV) infection in this condition. Objectives The purpose of this study was to clarify the association of HPV with this disease involving the nail apparatus. Methods Five patients with Bowen’s disease of the nail apparatus were investigated clinically, virologically and histologically. Total DNAs extracted from excised skin lesions were analysed using polymerase chain reaction (PCR) for the presence of HPV DNA and the amplified products were subjected to DNA sequence analyses. Histological localization of HPV DNA was examined by in situ hybridization. Results In three of five patients, HPV was detected by PCR amplification, and subsequent sequence analyses of the PCR products showed the sequences of HPV type 56. A common clinical feature of the three HPV-positive patients was longitudinal melanonychia. In contrast, the two HPV-negative patients presented with a convex nail deformity and a periungual ulcerative lesion. In two of three positive cases, there was a silent point mutation in the L1 gene of each HPV. In the remaining one case, the nucleotide sequence was consistent with the consensus sequence of HPV 56. Sequence analyses of the E6 gene revealed the infection of different variants of HPV 56 among the three cases. The viral genomes were located in keratinocyte nuclei upon in situ hybridization. Conclusions HPV 56 may be involved in the carcinogenesis of Bowen’s disease affecting the nail matrix with longitudinal pigmentation.

Summary Background Nail diseases are often troubling to the patient and may present a diagnostic challenge to the dermatologist. Biopsies from the nail may be required although often perceived uncomfortable by the patient and potentially scarring. Noninvasive technologies are therefore of particular interest in the study of nails. Optical coherence tomography (OCT) is an optical imaging modality which may provide improved data. Objectives This study evaluates nail morphology and thickness in OCT images in comparison with high-frequency ultrasound (HFUS) imaging of the nail. Methods Ten healthy volunteers were recruited for imaging and nail measurements; OCT and HFUS images were compared qualitatively. Nail thickness measurements with four different techniques were compared: ultrasound, OCT, polarization-sensitive (PS) OCT and callipers. The OCT system was developed at Risoe National Laboratory, Denmark. A commercially available 20-MHz ultrasound system (Dermascan; Cortex Technology, Hadsund, Denmark) was used. Results In standard OCT the nail plate appeared as a layered structure containing a varying number of horizontal homogeneous bands of varying intensity and thickness. PS-OCT images of the nail plate also showed a layered structure. The refractive index of the nail was 1·47 ± 0·09. OCT and PS-OCT had low coefficients of variation, 6·31 and 6·53, respectively, compared with other methods: HFUS 12·70 and callipers 14·03. Conclusion PS-OCT has to our knowledge not been applied to OCT analysis of the nail, and offers some advantages in separation of the nail bed from the nail plate.

Summary Background Conventional therapy of onychomycosis is prolonged and often frustrating, which is why combination therapy involving topical, oral and surgical measures has been advocated as the treatment of choice. There are no controlled studies evaluating the efficacy of nail avulsion followed by topical antifungal therapy. Objectives To evaluate the efficacy of combined surgical and topical therapy for onychomycosis. Methods Forty patients with single nail onychomycosis [28 with distal and lateral subungual onychomycosis, seven with total dystrophic onychomycosis (TDO) and five with proximal subungual onychomycosis] were randomly assigned to four treatment groups. Each group received avulsion of the involved nail, followed by ketoconazole 2% cream without (group I) or with occlusion (group II), or oxiconazole 1% cream without (group III) or with occlusion (group IV). Topical therapies were applied twice daily. The patients were reviewed monthly and treatment was continued until the regrowth of completely normal nail (mycologically negative). In cured cases, further monthly review was carried out for at least 6 months, without any form of therapy. At each visit direct microscopic examination was repeated. Results There was a high dropout rate, with seven patients (group I), six patients (group II), six patients (group III) and eight patients (group IV) completing the treatment protocol. Out of these, mycological cure was achieved in three (43%) patients in group I, four (67%) in group II, two (33%) in group III and six (75%) in group IV. All the cases of TDO failed to respond to this therapy. Overall, 15 of 27 (56%) patients were cured with this approach. On further follow up, recurrence of onychomycosis was recorded in two patients in group I. No side-effects or long-term complications of the nail avulsion were encountered. Important limitations encountered in the present study included a small sample size, a high dropout rate (32%) and poor patient compliance. Conclusions Contrary to earlier reports, surgical nail avulsion with topical antifungal agents was not found to be a very encouraging modality for the treatment of onychomycosis. Both oxiconazole and ketoconazole delivered comparable results. Occlusion improved the treatment outcome, although the difference was not statistically significant. As a subtype, TDO showed poorest response. Surgical nail avulsion followed by topical antifungal therapy cannot be generally recommended for the treatment of onychomycosis.

Summary Background Onychomycosis is common, accounting for up to 50% of all nail disorders. Toenail onychomycosis can cause nail deformity, embarrassment, pain and walking difficulties. Some populations, such as individuals with diabetes, are at higher risk for developing secondary complications such as infections. Treatment takes many months and therapeutic choices can increase clinical effectiveness, lower toxicity and minimize healthcare costs. Objectives Based on the results of a previous pilot study, the objective of the present study was to show, in a larger population, the enhanced efficacy of a combination of amorolfine nail lacquer and oral terbinafine in the treatment of onychomycosis with matrix involvement. In addition, a cost-effectiveness analysis was performed. Methods In this multicentre, randomized, open-label, parallel group study, patients were randomized to receive either a combination of amorolfine hydrochloride 5% nail lacquer once weekly for 12 months plus terbinafine 250 mg once daily for 3 months (AT group) or terbinafine alone once daily for 3 months (T group). The study duration was 18 months including a 6-month treatment-free phase following the 12-month active treatment phase for the AT group and a 15-month treatment-free phase following the 3-month active treatment phase for the T group. The primary efficacy criterion was overall response, dichotomized into success or failure, success being the combination of clinical cure and negative mycology at month 18. This criterion was used as the effectiveness measure in the pharmacoeconomic analysis, conducted from a payer perspective. Results In total, 249 patients were included into the study: 120 in the AT group and 129 in the T group. A significantly higher success rate was observed for patients in the AT group relative to those in the T group at 18 months (59·2% vs. 45·0%; P = 0·03). Both treatment regimens were safe and well tolerated. Treatment cost per cured patient was lower for the combination than for terbinafine alone in all countries. Conclusions Study results confirmed that, in the treatment of dermatophytic toenail onychomycosis with matrix involvement, amorolfine nail lacquer in combination with oral terbinafine enhances clinical efficacy and is more cost-effective than terbinafine alone.

Summary Background Ectodermal dysplasias (EDs) describe a large and complex group of disorders characterized by abnormal development of the skin and appendages (hair, nails, teeth and sweat glands). Of the approximately 200 different EDs, about 30 have been studied at the molecular level. In an effort to understand the molecular bases of ED of hair and nail type, we studied a Pakistani consanguineous family with multiple affected individuals. Objectives To localize the gene responsible for the autosomal recessive form of ED of hair and nail type. Methods Genotyping of nine members of the family, including five affected and four normal individuals was performed using microsatellite markers mapping to candidate regions, harbouring genes involved in related phenotypes. Five epithelial keratin genes located in the candidate region were sequenced to identify the pathogenic mutation. Results We mapped the disease locus to a 24·2-cM interval flanked by markers D17S839 and D17S1299 on chromosome 17p12–q21.2 (Zmax = 4·4). DNA sequencing of five epithelial keratin candidate genes, present in the disease locus, did not reveal any pathogenic mutation in the affected individuals. Conclusions The gene for ED of hair and nail type has been mapped to chromosome 17p12–q21.2 in a Pakistani consanguineous family. Failure to detect mutations in epithelial keratin genes suggests that the mutation may lie either in regulatory regions of one of the epithelial keratin genes or in another unknown gene, located in the linkage interval, with a possible role in the development of ectodermal appendages.

Summary Background Involvement of the nail is quite common in psoriasis and at times may be the sole diagnostic clue. However, the histopathology of nail psoriasis has not been adequately evaluated. A confirmation of the diagnosis is required in cases suspected to have nail psoriasis in order to plan long-term therapy. Objectives To assess the diagnostic significance and safety profile of nail biopsy in cases with nail psoriasis. Methods Clinical and mycological features were studied in 42 patients with nail psoriasis. Of these, 22 patients gave consent for nail biopsies to be taken and the histopathological changes were assessed. Results Males were affected more commonly (57%) with a peak incidence in the age group of 10–20 years (29%). Distal onycholysis, discoloration of nail plate, subungual hyperkeratosis and fine nail pitting were the predominant clinical features. In the 22 biopsies done, hyperkeratosis with parakeratosis (91%) was found to be the most common and hypergranulosis was the least common histological finding (36%). Clinicohistological correlation was possible only in 55% cases. Periodic acid-Schiff (PAS) staining was done for all biopsies. Conclusions Histopathological examination of nails is a valuable diagnostic aid, especially in the absence of skin lesions. Examination of the PAS-stained sections is necessary before making a histological diagnosis of nail psoriasis because onychomycosis and psoriasis may show similar histology.

Congenital hyponychia and anonychia are rare malformations which may form part of syndromes such as nail-patella syndrome, ectodermal dysplasias and brachydactylies, or may occur as an isolated finding. Congenital hyponychia and anonychia are frequently accompanied by underlying skeletal abnormalities. A 20-year-old woman showed congenital bilateral hypoplasia or aplasia of the second, third and fourth toenails with corresponding phalanx dysplasia or aplasia of the affected toes. Malformations of the hands or other congenital defects were absent. The findings in this patient do not exactly fit any known entities. Our clinical observation prompted us to review the literature on congenital hyponychia/anonychia and to summarize recent advances in understanding molecular events in nail development. In conclusion, the association of nail anomalies with aplasia and/or hypoplasia of corresponding middle and/or distal phalanges supports the hypothesis of bone-dependent nail formation.

Onychomycosis is a common nail disease, responsible for up to 50% of diseases of the nail. The distribution of different pathogens is not uniform; it depends on various factors such as climate, geography and migration. However, studies have revealed that two dermatophytes, Trichophyton rubrum and Trichophyton mentagrophytes, account for more than 90% of onychomycoses. Onychomycosis can be divided into four major clinical presentations: distal subungal (the most common form of the disease), proximal subungal (the most common form found in patients with human immunodeficiency virus infection), and superficial and total dystrophic onychomycosis. Onychomycosis is a multifactorial disease. Age has a very important effect on the occurrence of onychomycosis, with a correlation between increasing age and infection. Genetics has also been identified as a factor governing the epidemiology of onychomycosis; T. rubrum infection shows a familial pattern of autosomal dominant inheritance. Disease and lifestyle may also play a role in the epidemiology of fungal nail infections. Studies have shown that diabetes, acquired immunodeficiency syndrome and peripheral arterial disease may be independent predictors of onychomycosis. Because of the multifactorial nature of the epidemiology, accurate diagnosis, pertinent treatment and patient education must be paramount when treating the disease.

Summary Background The reported frequency of recovery of fungi from infected nails varies according to the geographical area. Objectives To establish the nature of the causal agents in a sample of the Libyan population presenting with suspected onychomycosis. Methods Samples were taken from the infected fingernails of 648 patients attending the Tripoli Medical Centre. Results Samples from 500 patients proved positive for fungi following culturing, while 476 were potassium hydroxide and culture positive. Of the culture-positive samples, yeasts of the genus Candida (C. albicans, C. parapsilosis, C. glabrata, C. guillermondii and C. tropicalis) were the dominant cause of this condition in women (417 of 434, 96%) but were responsible for only a minority of cases in men (three of 66, 5%). In contrast, dermatophytes (Trichophyton violaceum, T. rubrum, T. mentagrophytes and Microsporum canis) were responsible for this condition in the majority of cases in men (53 of 66, 80%) but only 3% (15 of 434) of cases in women. The mould Aspergillus nidulans was isolated from the nails of 10 (15%) men and two (0·5%) women. Conclusions The data obtained in this study reveal an almost total separation of the aetiological agents responsible for onychomycosis based on gender.

Summary Background Previously, a double-blind, randomized, multicentre study (LION study) compared the efficacy of continuous terbinafine 250 mg daily for 3 or 4 months with itraconazole pulse therapy 400 mg daily for 3 or 4 months. At the end of the study at week 72 terbinafine proved to be more effective. Objectives To perform a 4-year follow-up of the Finnish participants in this study. Methods Patients were re-examined clinically and mycologically. Results Complete clinical and mycological cure with terbinafine for 4 months was 78% compared with 35% with terbinafine for 3 months, 24% with itraconazole for 4 months and 28% with itraconazole for 3 months. Conclusions These results suggest that the initial treatment for onychomycosis should be a 4-month continuous course of terbinafine.

Fungal infections of the nail are common in European populations. There are a number of clinical presentations usually resulting from an infection by one of the dermatophyte species, notably Trichophyton rubrum. A number of modern treatment strategies are available and are generally well tolerated and effective. However, a significant proportion of patients, 20-30%, can expect treatment failure and/or relapse following treatment. The search for new treatment modalities and drugs is hampered by our lack of understanding of the basic pathophysiological mechanisms that underlie these frequently encountered infections. A correct diagnosis is key to the implementation of successful treatment. Even then, some infections do appear to be more recalcitrant than others. This may be the result of a number of interacting factors: patient susceptibility, fungal growth patterns that resist treatment and the occurrence of dormant fungal spores (arthrospores) in the nail. Increasingly, research is turning towards the identification of clinical indicators of poor prognosis and the development of new treatment strategies to overcome them. The combination of drugs to produce synergistic activity is one possible advance towards achieving higher cure rates.

Background Pustular psoriasis of the nail apparatus is a common disease that greatly influences the quality of life because of its chronic course and poor response to treatment. Objectives To review the clinical and histopathological features, the response to treatment and the long-term follow-up of 46 patients with pustular psoriasis of the nail unit. Methods Treatments utilized included oral retinoids (n = 12), oral nimesulide (n = 13), topical calcipotriol (n = 15) and topical steroids (n = 18). Retinoids were utilized as first choice in seven patients with involvement of several digits and in five patients with severe relapses, whereas topical calcipotriol, oral nimesulide or topical steroids were utilized in patients with involvement of a single nail. Topical calcipotriol was also prescribed as maintenance therapy in patients who responded to oral treatment. Twenty-five patients were followed for more than 5 years. Results Improvement or regression of the lesions was obtained in 23 of 46 patients. Retinoids were effective in six of 12 patients, nimesulide in four of 13, topical calcipotriol in nine of 15 and topical steroids in four of 18. The long-term follow-up showed a complete remission of the disease in only two patients, both affected by pustular psoriasis involving multiple nails. All other patients experienced periodic relapses which were in most cases controlled by regular use of topical calcipotriol. Conclusions Severe cases of pustular psoriasis of the nail are best treated with systemic retinoids. Topical calcipotriol is effective in about 50% of patients with localized disorder and is also useful as maintenance therapy after retinoid treatment.

Background It is well known that nails can be involved in some diseases of the central nervous system; however, no systematic study has been carried out in order to evaluate the incidence and the possible mechanisms of these nail changes in hemiplegia. Objectives To study the presence of nail pathology specifically associated with hemiplegia and to evaluate its incidence and its temporal relationship with the onset of the neurological deficit. Methods In an open study, fingernails and toenails were examined by a dermatologist; 108 were patients with hemiplegia due to a stroke, consecutively admitted to our Department of Neurology between 1995 and 1998, and 121 were normal controls. Results Onychodystrophy of fingernails and onychomycosis of toenails were found in both patients with hemiplegia and normal controls. However, three conditions (longitudinal reddish striation, neapolitan nails and unilateral clubbing) were only observed in some patients, always affecting fingernails of the limb affected by hemiplegia. Neapolitan nails were present in three (3%) patients with hemiplegia which had its onset 3-14 months earlier, Hemiplegia had occurred approximately 40 months earlier, on average, in six patients (6%) with longitudinal reddish striation, and 60-120 months prior to unilateral clubbing in another two patients (2%). Conclusions In this study we were able to assess the presence of three different fingernail conditions that were characteristically associated with hemiplegia (longitudinal reddish striation, neapolitan nails and unilateral clubbing), to evaluate their incidence and to study the delay with which these changes occur after a stroke.

Changes in the microvasculature are considered to play an important part in the pathogenesis of psoriasis and its associated arthritis. The novel method of nailfold video capillaroscopy is an extension of the technique of widefield nailfold microscopy which has been of diagnostic and predictive use in the in vivo study of the microcirculation in systemic sclerosis and other connective tissue disorders. However, similar studies in patients with psoriasis and psoriatic arthritis and/or nail changes have produced conflicting results. We tested the hypothesis that any abnormalities in nailfold capillaries of either a quantitative or qualitative nature might be observed more readily in subjects with pathology adjacent to the nailfold, i.e. distal interphalangeal (DIP) joint changes and/or nail dystrophy, when using this technique. Forty-four patients with psoriasis were recruited (21 males, 23 females). Twelve patients had psoriasis alone, 13 had psoriasis and nail changes, six had DIP joint involvement with changes of psoriasis elsewhere, and 13 had psoriasis, DIP arthritis and nail changes. Capillary density and standard capillary dimensions were studied and compared with those of 44 age- and sex-matched control subjects. There was a significant (P < 0·05) decrease in capillary loop density in patients with either psoriasis plus nail disease (14·5 ± 5·7 capillaries per 3 mm field) or psoriasis plus nail and DIP joint disease (14·3 ± 5·0) when compared with controls (19·2 ± 3·8). In patients with psoriatic arthritis affecting the DIP joints, there was a statistically significant (P < 0·05) decrease in arterial and venous capillary limb diameters, and this was also seen in those with arthritis associated with nail changes. However, there was no difference in capillary dimensions between patients with psoriasis and/or nail changes when compared with normal controls. Morphological abnormalities previously described in the literature were not noted in any of our four patient groups. Our findings of diminution in both nailfold capillary bed density and dimensions of the arterial and venous capillary limbs suggest that vascular injury, previously noted in ultrastructural studies, may play a part in the pathogenesis of psoriatic arthritis. However, in contrast to previous studies, we found no specific pattern of a morphological nature of nailfold capillaries in patients with psoriasis with or without nail changes, when compared with normal controls.

We report a unique case of a congenital keratinocytic naevus associated with severe alopecia, onychodysplasia and palmoplantar involvement in a 13-year-old girl. The lesions, consisting of scaly, spinous and verrucous papules and plaques, mainly followed Blaschko's lines and have remained unchanged since birth. The predominant histopathological picture was that of a column of parakeratosis overlying the eccrine ostia and hair follicles. This is the first case of a systematized keratinocytic naevus characterized by histopathology of eccrine and hair follicle porokeratosis and a widespread bilateral involvement. This may be a distinct entity to be included in the differential diagnosis of linear, hyperkeratotic dermatoses. We suggest its classification as systematized porokeratotic eccrine and hair follicle naevus.

Four open, prospective, postmarketing studies with consistent protocols were undertaken, involving over 25,000 patients and nearly 3600 physicians in four European countries (UK, Netherlands, Germany and Austria). The purpose was to determine the tolerability of terbinafine when prescribed to a large, unselected patient population in general medical practice. Patients were recruited from dermatology departments and from general and family practitioners. All received at least one dose of terbinafine. No specific exclusion criteria were applied. The only treatment instructions provided were those contained in the manufacturer's product information. Patients were monitored for adverse events at baseline, during treatment, and at the end of treatment. Of the 25,884 patients entering the study, 38.6% (9991) had concomitant disease, 42.8% (11,078) were taking other medications, and 22.7% (5876) were older than 60 years. The predominant indication for prescribing terbinafine was onychomycosis. Mean duration of treatment was 13.2 weeks. No adverse events were reported in 89.5% (23,167) of patients. The remaining 10.5% (2717) reported one or more adverse events, primarily gastrointestinal (4.9%) or dermatological (2.3%). A total of 115 serious adverse events were recorded, but of these only four were probably and eight possibly related to terbinafine. There were no reported drug-drug interactions, even in patients receiving concomitant medications metabolized by cytochrome P-450 enzymes. There were also no clinically significant drug-disease interactions. In conclusion, terbinafine is well tolerated in an unselected general practice population. This confirms its good tolerability previously established during controlled clinical trials.

In this review, the current state of knowledge concerning nail melanoma is summarized. The pathogenesis, histological findings, clinical presentation, treatment and prognosis of this rare form of cutaneous melanoma are discussed. Important clinical clues to the early diagnosis of nail melanoma are highlighted and recommendations to improve the management of patients are suggested.

We report six HIV patients who developed painful periungual inflammation of several nails during treatment with the antiretroviral drugs indinavir and lamivudine. The lesions appeared 2-12 months after starting treatment. The occurrence of paronychia in HIV patients has recently been reported in two groups of patients receiving either indinavir or lamivudine. Dermatologists should be aware of this recently reported and probably not uncommon side-effect of antiretroviral treatment in order to avoid an invasive approach to the nail lesions.

Twenty-one patients (11 female, 10 male: mean age 21.3 years) with subungual exostoses were treated with elective surgery under local anaesthetic in a dermatology day case theatre over a period of 8 years. Fifteen (71%) tumours affected the great toe, four (19%) affected other toes and two (10%) affected fingers. All received local excision with great care to remove all tumour residue from the terminal phalanx. Wounds were allowed to heal by secondary intention. Attention was paid to preoperative antiseptic procedure and postoperative analgesia. During follow-up of between 6 and 36 months (mean 17 months), there were two relapses (10%) in the first 12 months, seen in two of the younger subjects aged 9 and 13 years. One required further surgery. One further case suffered long-term dystrophy due to perioperative damage to nail matrix. Conservative and thorough treatment of this pathology can be achieved using the appropriate tools in a dermatology day case theatre.

This new classification of onychomycosis is a development of previous schemes and depends on the recognition of different clinical patterns of nail plate involvement associated with fungal infection as well as histopathology. The main types are distal and lateral subungual onychomycosis, superficial onychomycosis, proximal subungual onychomycosis, endonyx onychomycosis and total dystrophic onychomycosis. In addition, patients may show different combinations of these patterns. The identification of clinical patterns of disease may be useful in defining differences in clinical behaviour, treatment response and associated disease.

The number of individuals diagnosed with diabetes mellitus is increasing. The diabetic may present with complications involving all systems of the body. While onychomycosis is often observed in diabetics, there have been no large studies on the prevalence of the condition in this patient group. We examined the prevalence of onychomycosis in diabetics attending diabetes and dermatology clinics in London, Ontario, Canada and Boston, MA, U.S.A. Diabetic subjects seen in dermatology offices were for unrelated dermatoses; those referred specifically for the management of onychomycosis were excluded from the sample. A total of 550 diabetic subjects was evaluated (283 males and 267 females), age 56.1 +/- 0.7 years (mean +/- SEM). Patients with type I diabetes constituted 34% of the sample. The racial origin was: 531 Caucasians, 17 Asians, one African-American and one American-Indian. Abnormal-appearing nails and mycological evidence of onychomycosis (mostly due to dermatophytes) were present in 253 (46%) and 144 (26%), respectively, of 550 subjects. The development of onychomycosis was significantly correlated with age (P < 0.0001) and male gender (P < 0.0001). Males were 2.99 times more likely to have onychomycosis compared with females (95% confidence interval, CI 1.94-4 61). After controlling for age and sex, the risk odds ratio for diabetic subjects to have toenail onychomycosis was 2.77 times compared with normal individuals (95% CI 2.15-3.57). After controlling for age and sex, a stepwise logistic regression demonstrated that significant predictors for onychomycosis included a family history of onychomycosis (P = 0.0001), concurrent intake of immunosuppressive therapy (P = 0.035) and peripheral vascular disease (P = 0.023). Toenail onychomycosis was present in 26% of the sample and is projected to affect approximately one-third of subjects with diabetes. Predisposing factors include increasing age, male gender, family history of onychomycosis, concurrent intake of immunosuppressive agents and peripheral vascular disease.

Our population-based study establishes epidemiological data on age-specific incidence rates, clinical presentation, Breslow microstaging, treatment and survival of nail apparatus melanoma (NAM) patients in England. Four cancer registries, covering a population of 10.6 million, recorded 105 cases of NAM during the period 1984-93. During the same decade there was a total of 7585 patients with cutaneous melanoma and NAM represents 1.4% of all cutaneous melanoma. The incidence rate of NAM in English patients is 0.1 per 100,000 of the population per annum. Amelanotic melanoma was the clinical presentation in 24 of our NAM cases. The overall prognosis is poor with an observed 5 year survival of only 51%. Patients with NAM less than 2.5 mm Breslow depth have a 5 year survival of 88% and are twice as likely to survive compared with those with tumours greater or equal to 2.5 mm in thickness (P < 0. 05). NAM patients are best managed by a multidisciplinary team approach in a few key skin cancer centres.

Alagille syndrome is a rare autosomal dominant developmental disorder, characterized by congenital paucity of interlobular bile ducts, peculiar facies, posterior embryotoxon, bone abnormalities, and peripheral pulmonary artery stenosis. Cutaneous involvement in this disorder is quite rare and the association of Alagille syndrome with multiple comedones and cysts has been described only once. Here, we report the clinical and histological findings of a 7-year-old patient affected by Alagille syndrome who presented multiple cystic lesions and comedones reminiscent of steatocystoma multiplex and a congenital total true leuconychia. Although unexplained, the association of this syndrome with a developmental disorder of the pilosebaceous unit may not be fortuitous.

Many nail abnormalities have traditionally been described in association with rheumatoid arthritis (RA), but their specificity has never been assessed in a controlled study. Our purpose was to evaluate the frequency and the specificity of nail changes associated with RA in a case-controlled study including 50 patients suffering from RA and 50 controls. For each patient, a general skin examination was performed and the 20 nails were examined. The nail features were noted and classified. A chi 2 test or a Fisher test was used to compare the two groups. The only nail abnormalities significantly associated with RA were longitudinal ridging on nine or 10 finger nails (29 patients in the RA group vs. three in the controls, chi 2: P < 0.001) and clubbing on at least one nail (24 patients vs. 10, chi 2: P < 0.01). Other nail changes were noticed but were not frequent enough to be significant. The presence of longitudinal ridging on the finger nails was significantly associated with RA.

Summary There is some controversy about the prevalence of onychomycosis in patients with psoriasis compared to non-psoriatics. We therefore measured the prevalence of toenail onychomycosis in psoriatics and non-psoriatics attending dermatologists'offices. None of the patients had a referring diagnosis of onychomycosis. The prevalence of pedal onychomycosis in psoriatics (n = 561) was 13%. The odds of patients with psoriasis having onychomycosis was 56% greater than non- psoriatics of the same age and sex (P= 0·02). In the psoriatics, when the toenails were clinically abnormal, the prevalence of onychomycosis was 27%. The odds of developing onychomycosis increased with age (P < 0·0001) and the odds of men developing onychomycosis was 2·5 times that of women (P= 0·0001). The duration of psoriasis did not significantly affect the odds of developing onychomycosis. The fungal organisms recovered from psoriasis subjects with onychomycosis were similar to those in the normal population with onychomycosis (P = 0·58).

Terbinafine (Lamisil) has been registered throughout the world for the treatment of finger and toenail onychomycosis. The recommended duration of treatment of toenail onychomycosis based on phase III studies is 12 weeks. This study was designed to determine: (i) if patients in whom the proximal part of the toenails was not affected respond as well after 6 weeks treatment as after 12 weeks treatment; (ii) to identify factors which may allow selection of patients for shorter treatment duration; and (iii) confirm that 6 weeks therapy is sufficient in fingernail mycosis. One hundred and forty-eight patients received 250 mg terbinafine daily for either 6 or 12 weeks in a double-blinded manner, and were allowed until 48 weeks after start of therapy. Cure of the nail infection was defined as negative mycological tests (mycological cure) and progressive growth of normal nail (clinical cure). Mycological cure was recorded in 43 of 72 (59.7%) in the 6-week group and 55 of 76 (72.4%) in the 12-week group. In those who completed the study per protocol in the 6-week group, 34 of 61 (55.7%) were cured mycologically corresponding to 46 of 56 (82.1%) in the 12-week group. The overall clinical and mycological cure rates for the two groups were 28 of 61 (45.9%) and 33 of 56 (58.9%), respectively. In the small number of patients with associated fingernail infection, all were improved and six of eight (75.0%) were cured after a duration of treatment of 6 weeks. A priori risk factors for failure of cure could not be identified in either group. However, shorter duration of disease prior to treatment and no involvement of the big toenail was associated with a trend toward better responses in both groups. It can be concluded from this study that, in toenail mycosis without visible matrix involvement, 6 weeks treatment of terbinafine is generally not sufficient, whereas fingernail infections respond well to this short therapy.

In this multicentre, double-blind, parallel group study, we evaluated the efficacy and safety of continuous treatment with itraconazole, 200 mg daily for 3 months, in comparison with itraconazole pulse therapy, 400 mg daily 1 week per month for 3 months, in the treatment of toe-nail onychomycosis. The study included 129 patients with distal subungual onychomycosis of the toe-nails, confirmed by microscopy and positive for dermatophyte culture; 65 received continuous treatment and 64 received pulse therapy. Patients were followed up for 9 months after treatment. After 12 months, there were 62 evaluable patients in the continuous group and 59 evaluable patients in the pulse group. The clinical response (i.e. the size of the affected area and the progress of the infection) and mycological cure (i.e. negative results on microscopy and culture) were the main outcome measures. A clinical response was defined as a cure or a marked improvement. Clinical response rates were 69%, in the continuous group, and 81% in the pulse group at month 12; the corresponding mycological cure rates were 66 and 69%. A better improvement in signs and symptoms was noted in the pulse group. Six patients were withdrawn from treatment because of adverse events, not all of which were thought to be drug-related. There were no clinically relevant laboratory abnormalities. We conclude that both regimens are effective, safe and well tolerated. The superiority of one treatment over the other was not established, but the results tended to favour pulse therapy. Equivalence testing confirmed that pulse therapy was at least equivalent to continuous treatment.

Fusarium infections in humans are usually opportunistic, but the fungus sometimes infects healthy persons, causing keratomycosis or onychomycosis. Onychomycosis is usually caused by F. solani or F. oxysporum. We report the first two cases of onychomycosis caused by F. proliferatum, and discuss methods of diagnosis and effective treatment. Nail samples from the two patients were examined by direct microscopy, cultured, and identified morphologically and genetically as F. proliferatum. Both patients were treated successfully with oral itraconazole, even though the minimum inhibitory concentration of itraconazole was relatively high in Patient 1. This is the first report of F. proliferatum as an agent of onychomycosis. Itraconazole may be effective in the treatment of onychomycosis caused by F. proliferatum.

Six cases of Scopulariopsis onychomycosis, including four patients with onychomycosis exclusively caused by Scopulariopsis brevicaulis and two patients with a mixed nail infection (S. brevicaulis + Tricophyton rubrum and S. brevicaulis + T. interdigitale), are reported. Four patients presented with a typical distal subungual onychomycosis characterized by subungual hyperkeratosis and onycholysis of the distal nail plate. In two patients, Scopulariopsis infection produced a total dystrophic onychomycosis associated with painful periungual inflammation. Three patients were treated with four pulses of itraconazole, 400 mg daily for 1 week a month, and three patients with terbinafine, 250 mg daily for 4 months. The mycological examination 8 months after discontinuation of treatment showed that one patient was mycologically cured whereas the remaining five patients still carried S. brevicaulis in their nails. The clinical examination at the end of the follow-up period showed a complete cure of the nail abnormalities in only one patient.

Abnormalities of the nail are not a well recognized feature of palmoplantar pustulosis (PPP). However, in a group of 50 patients with PPP, we found nail dystrophy in 15 (30%). The most frequent pattern was subungual pustulation, present in 10 patients, and progressing to nail destruction in two. Onycholysis and pitting of the nail were present in a few patients. In contrast to psoriasis vulgaris, the rate of linear nail growth in PPP was no greater than in matched normal controls. This is another clinical feature of PPP that separates it from psoriasis vulgaris.