An open comparative study of nail drilling as adjunctive treatment for toenail onychomycosis (.).

Introduction Novel treatment regimens are being developed to improve drug penetration through the nail plate. This study investigated the efficacy of nail drilling regimens for the treatment of onychomycosis. Methods Participants were assigned to holes with combination (oral plus topical terbinafine) therapy (Group 1), holes with topical terbinafine (Group 2) or topical terbinafine only (Group 3). Measurement of clear nail and mycology was performed at baseline and at weeks 4, 10, 16, 22 and 28. Mixed linear models were used to compare mean percent clear nail. Mycological cure rates were also tabulated for each group. Tolerability and adverse events were documented. Results Ninety-eight participants were enrolled (106 nails). Both groups with holes had significantly higher percentage of clear nail compared with topical terbinafine alone. Although no significant difference between the two groups where holes were drilled in the nail plate, Group 1 demonstrated improvement over Group 3 earlier than Group 2 (visit 2 versus visit 4). Group 1 also had the highest mycological cure rates. Conclusion Treatment with holes plus topical terbinafine produces significantly greater improvement in toenails' appearance and higher mycological cure rates compared to treating the dorsal aspect of the nail plate with topical terbinafine alone.

Darier disease in Israel: combined evaluation of genetic and neuropsychiatric aspects.

BACKGROUND: Darier disease (DD) is a rare genodermatosis caused by heterozygous mutations in the ATP2A2 gene. It has been associated with neuropsychiatric manifestations. OBJECTIVES: To investigate the genetic basis of Israeli patients with DD, and its association with the neuropsychiatric phenotype. METHODS: A cohort of 32 families comprising 74 affected individuals and 13 unaffected family members was recruited from the Haemek Dermatology Department and other dermatology clinics in Israel. The individuals were evaluated by detailed questionnaires, physical examination and genetic analysis. The main outcome measures were genetic mutations, psychiatric profile and their association. RESULTS: Twenty-three mutations in ATP2A2 were scattered over the entire gene, 14 of them novel. Two families shared the same mutation. Twenty-one patients (28%) had a history of psychiatric disorders, most of them mood disorders. Another seven patients (9%) were highly suspected of having a psychiatric disorder; 21 (28%) reported suicidal thoughts and five (7%) had attempted suicide. The psychiatric phenotype demonstrated inter- and intrafamilial variability, and was not associated with disease severity, family history of psychiatric disease or mutation location. CONCLUSIONS: The cohort demonstrated genetic heterogeneity with no mutation cluster along the gene, and a high prevalence of psychiatric disorders. Although no clear genotype-phenotype correlation was found, the results point to a major effect of genetic background on psychiatric phenotype, together with other modifiers.

Clinical comparison and complete cure rates of Terbinafine efficacy in affected onychomycotic toenails.

BACKGROUND: Clinical studies regarding complete cure rate of onychomycosis using oral Terbinafine have a very broad range (14-90%) based solely on response to treatment on the big toenail. OBJECTIVE: To evaluate the efficacy of Terbinafine in all affected onychomycotic toenails and, furthermore, to evaluate differences in mycological, clinical and complete cure rate between affected onychomycotic toenails. PATIENTS AND METHODS: Inclusion criteria are as follows: distolateralsubungual onychomycotic involvement of the hallux and additional involvement of at least two more toenails of the same foot. Exclusion criteria are as follows: patients with nail traumata and hypersensitivity to Terbinafine. Patients were treated with oral Terbinafine 250 mg/day for 16 weeks. Mycological analysis was performed using direct microscopy and culture. Clinical improvement was assessed using digital photography. RESULTS: Statistically significant difference was found in clinical improvement between the great toenail and all other involved toenails. The rate of complete cure (100% clinical cure and mycological cure) of the big toenail was lower (23%) as compared to the second (65%), third (51%) and the fourth toenail (67%). LIMITATIONS: This is a case series study that was based on a single-centre cohort. CONCLUSIONS: Our results support findings that efficacy of Terbinafine should be based on all involved onychomycotic toenails; the big toenail is not superior in response compared to other affected toenails.

When is onychomycosis onychomycosis? A cross-sectional study of fungi in normal-appearing nails.

BACKGROUND: The presence of fungal organisms in healthy-looking toenails has previously been reported in individuals with a known dermatophyte infection and in those with onycholysis, but has not been extensively studied in individuals who do not present with foot pathology. OBJECTIVES: To determine the prevalence of fungal organisms in the toenails and on the soles of normal-appearing feet. METHODS: Adults who visited a dermatology clinic between June 2012 and February 2013 for concerns unrelated to fungal infection of the nails and feet participated in this study. Participants' feet were clinically examined, and skin and nail samples were collected and sent for potassium hydroxide (KOH) light microscopy and culture. RESULTS: Five hundred and eighty-five individuals with normal-appearing feet and toenails participated in this study. Fungal organisms were detected in 9·2%, 3·9% and 3·1% of participants' toenails by KOH, culture, and a combination of KOH and culture, respectively, while fungal organisms were present on the soles of the feet of 7·0%, 2·9% and 1·4% of participants by KOH, culture and both these methods combined, respectively. A significant association between the presence of fungal organisms in toenails and on the soles of the feet was found (P < 0·01). CONCLUSIONS: The presence of fungal organisms in the nail, even in the absence of clinical signs, may be termed 'subclinical' onychomycosis. The normal-appearing nail plate may act as a reservoir for infectious dermatophyte and nondermatophyte organisms. When left unimpeded by the host's immune system, these organisms are inclined to proliferate to produce clinically apparent disease.

A case series of 46 patients with lichen planopilaris: Demographics, clinical evaluation, and treatment experience.

BACKGROUND: Lichen planopilaris (LPP) is as a lymphocytic variant of primary cicatricial alopecia. OBJECTIVE: To evaluate the demographics, clinical findings, natural history, and response to various treatments of LPP. METHODS: A retrospective review of medical records of all patients with clinical and histopathological diagnoses of LPP. RESULTS: Out of 46 patients, there were 38 (82.6%) women and 8 (17.4%) men. There was no clear association of specific medical background and medications with disease onset. The most frequent complaint was itching scalp. Asymptomatic hair loss was observed in 39.2%. LPP involved the entire scalp in 39.1%, vertex in 28.3%, anterior scalp and vertex in 17.4%, fronto-temporal scalp in 6.5%, and posterior and parietal scalp in 6.5%. The topical treatment that caused the highest rate of symptomatic improvement was intralesional injection of corticosteroids. The treatment that led to the highest rate of remission was hydroxychloroquine combined with topical corticosteroid application. The remission rate was 6.5% after 3 months and 33% after 18 months. Of patients who achieved remission, 50% need continuous treatment to maintain remission. No patient had any visible hair regrowth on any treatment. CONCLUSION: The range of empiric topical and systemic treatments used gives unsatisfactory results, in LPP patients.

Learning disabilities in Darier's disease patients.

BACKGROUND: Neuropsychiatric features and intellectual difficulties have been reported in studies of Darier's disease. Learning disabilities have never been reported or evaluated systematically in these patients. OBJECTIVE: To assess the prevalence of learning disabilities in 76 patients with Darier's disease, and cognitive functioning in 19 of them. METHODS: The data were collected by two methods: a questionnaire, as part of a larger study on the clinical characteristics of 76 patients; and neuropsychological measures for the assessment of learning disabilities in 19 of them. RESULTS: Thirty-one of the 76 patients reported learning disabilities (41%) and 56 (74%) reported a family history of learning disabilities. Significant differences were found between the 19 patients evaluated on cognitive tasks and a control group of 42 skilled learners on subtraction and multiplication tasks. Six (32%) of the 19 were identified as having reading difficulties and five (26%) exhibited low performance on the Concentration Performance Test. All patients had general cognitive ability in the average range. CONCLUSIONS: Findings suggest an association between Darier's disease and learning disabilities, a heretofore unreported association, pointing to the need to obtain personal and family history of such disabilities in order to refer cases of clinical concern for further study.

Bacteriological aspects of Darier's disease.

BACKGROUND: There are no established data on the prevalence of bacterial colonization of lesional skin, nares and perineum in Darier's disease (DD), or its contribution to the clinical manifestations of the disease. OBJECTIVE: To determine the prevalence of bacterial colonization of lesional skin and Staphylococcus aureus (S. aureus) in nares and perineum in 75 patients with DD, the association of these parameters with disease and patient characteristics, and the features of the bacterial skin infection in this group. METHODS: Medical interviews and physical examinations were performed. Bacteria were isolated from swabs taken from lesional skin, nares and perineum. RESULTS: S. aureus was isolated in 68%, 47% and 22% of lesional skin, nares and perineum cultures respectively. Subjects with positive S. aureus culture from lesional skin and/or nares had a statistically significant higher percentage of skin area affected and a more severe disease than patients with negative culture. Thirty of the 75 patients (40%) recalled bacterial skin infection, most often on the chest. CONCLUSIONS: Patients with DD have high prevalence of S. aureus colonization in lesional skin and nares, with a correlation between disease severity and extent of the colonization. Further studies examining the consequences of S. aureus eradication in those sites may establish the need for S. aureus lesional skin and nares colonization screening and eradication as part of the treatment of DD exacerbations.

Health-related quality of life among Darier's disease patients.

BACKGROUND: Darier's disease (DD) is an autosomal dominant skin disorder characterized by persistent eruption of hyperkeratotic papules. The effect of DD on quality of life (QOL) has been assessed in only one study, which found no correlation between the Dermatology Life Quality Index (DLQI) score and clinical severity of the disease. The correlation between health-related quality of life (HRQL) and other diseases and patient characteristics has not been studied. OBJECTIVES: To examine the HRQL of patients with DD and to evaluate the association between HRQL scores and disease and patient characteristics. METHODS: A total of 74 DD patients completed three QOL questionnaires: DLQI, EQ-5D, and one specially designed for the study. The data reported in this study were collected as part of a larger study on the clinical characteristics of DD; the socio-demographic and clinical data were used in the statistical analysis of the current study. RESULTS: Mean DLQI was 5.41 ± 5.57 and the mean EQ-Visual Analogue Scale (VAS), was 70.84 ± 19.25. DLQI and EQ-VAS were significantly associated with skin area affected, disease severity, age at onset of DD and a seborrhoeic distribution pattern of DD. Stepwise linear regression showed skin area affected to be the most significant variable in the predication of DLQI (beta = 0.183; SE = 0.04; P < 0.001), and disease severity the most significant variable in the predication of EQ-VAS (beta = -9.15; SE = 3.21; P < 0.006). CONCLUSIONS: Darier's disease has a negative impact on HRQL of patients and the HRQL is associated with various disease characteristics, mainly skin area affected and clinical severity.

A rationale for systemic treatment in onychomycosis with negative results on fungal examination.

BACKGROUND: Fungal infection of the nail affects millions of people worldwide, and has an estimated prevalence of about 10% of the general population. Laboratory confirmation of fungal infection is currently accepted as a requirement before initiation of antifungal treatment in clinical practice. AIM: To examine the rationale for systemic treatment in cases of clinical onychomycosis with negative results on fungal examination (potassium hydroxide test and fungal culture). METHODS: In total, 147 patients with suspected clinical toenail onychomycosis but with negative results on fungal examination underwent up to three consecutive fungal examinations of the affected nails. Patients who were negative after these examinations underwent a fourth set of investigations, including PCR. RESULTS: Of the 147 cases initially thought to be negative, 138 (94%) were rated as positive after up to four consecutive sets of laboratory mycological investigations including PCR. Trichophyton rubrum was by far the commonest dermatophyte cultured from all samples. CONCLUSIONS: In the majority of cases of initially negative examinations, consecutive laboratory fungal tests will eventually produce positive results. These findings suggest that systemic antifungal treatment should be started in patients with suspected fungal infections, even if they have negative laboratory fungal examinations.

A novel two-step kit for topical treatment of tinea pedis--an open study.

BACKGROUND: Tinea pedis is a common skin disease affecting most of the population during their lifetime. Topical and systemic treatments give only temporary relief. OBJECTIVE: To evaluate the efficacy and safety of a new topical treatment for moderate-to-severe tinea pedis. METHODS: Fifty patients suffering from tinea pedis were treated in two stages: the active stage--single use of the novel topical solution for 45 min and novel cream twice weekly for 4 weeks; the preventive stage--cream application once weekly for 10 months. RESULTS: Forty-five patients completed the active stage and achieved 76% cure rate. The medication was well tolerated; one patient dropped from the study because of very mild irritation. No other topical or systemic side effects were noted. Another five patients were lost to follow-up during the preventive stage. The total cure rate after the preventive stage was 70%. CONCLUSIONS: This novel treatment was found to be effective, well tolerated and safe in the treatment of moderate and severe tinea pedis during the active and the preventive stages.

Low-dose methotrexate treatment for moderate-to-severe atopic dermatitis in adults.

BACKGROUND: Atopic dermatitis (AD) is a common inflammatory skin disease. Methotrexate (MTX) was suggested as an effective treatment option in cases of moderate-to-severe atopic dermatitis. This study assessed the efficacy and safety of treatment with low weekly doses of methotrexate for moderate-to-severe AD in adults. METHODS: Twenty adult patients with moderate-to-severe AD were included in this retrospective study. Those patients were unresponsive to topical treatments, antihistamines and at least one of the second-line treatments. MTX in low weekly doses of 10-25 mg was administered orally or intramuscularly with folic acid supplementation 5 mg per week for at least 8-12 weeks. The response to treatment was evaluated by change in SCORAD (SCORing Atopic Dermatitis), DLQI (Dermatology Quality of Life Index) and the global assessment of the clinical response score. RESULTS: After 8-12 weeks of treatment, we observed an objective response in most patients. There were 16 responders and 4 non-responders. The mean SCORAD and DLQI decreased by 28.65 units (44.3%) and 10.15 units (43.5%), respectively. The first improvement was observed after a period ranging from 2 weeks to 3 months (mean 9.95 w +/- 3.17). Treatment was more effective in adult onset AD than in childhood onset. Tolerance of treatment was good. However, nausea and an increase of liver enzymes were observed in 5 patients and 3 of them required a transient discontinuation of MTX. One patient developed peripheral neuropathy, which was resolved several weeks after the discontinuation of MTX. CONCLUSION: MTX seems to be an effective and safe second-line treatment for patients with moderate-to-severe atopic dermatitis. A randomized, controlled study is warranted.

Iontophoretic delivery of terbinafine in onychomycosis: a preliminary study.

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.

A randomized, double-blind, placebo-controlled study to evaluate the efficacy in AD of liquid soap containing 12% ammonium lactate + 20% urea.

Atopic dermatitis (AD) is a common chronic skin disease, which mainly affects children. Xerosis is one of the most troublesome signs of the disease. The aim of this study was to evaluate the efficacy of liquid soap containing 12% ammonium lactate + 20% urea in patients with AD. In a randomized, double-blind study, 36 patients (both male and female patients; age range 3-40 years) with mild to moderate AD were enrolled. Patients were divided randomly into two groups, in a ratio of 2:1 (active:placebo). The prescribed soap was used on a daily basis during a shower for 3 weeks. All patients continued all other systemic or topical medication but avoided any other soap or emollients. After 3 weeks of treatment, efficacy was assessed both by clinician and patient. There were significant improvements in scaling (P < 0.0001), skin dryness (P < 0.0001) and redness (P = 0.03) as rated by the investigator, and subjective patient assessment of itch also improved (P < 0.001) in the study group compared with the control group. The liquid soap was found to be effective in patients with AD, as use of this soap in patients with stable mild to moderate AD improved the parameters studied.

New criteria for the laboratory diagnosis of nondermatophyte moulds in onychomycosis.

BACKGROUND: Nondermatophyte moulds (NDM) may be found as aetiological agents or as contaminants in onychomycosis. The classic and most used criteria for the diagnosis of NDM are those established by English in 1976. OBJECTIVES: The aim of this article is to re-evaluate the laboratory criteria for the diagnosis of NDM in onychomycosis. PATIENTS AND METHODS: Patients with suspected NDM of the nail underwent five consecutive examinations by both KOH and mycological culture; at the first visit, three samples from the affected nail were taken and were examined separately. Later those patients underwent four consecutive examinations; during this stage only a single sample for both KOH and culture was taken. We compared the culture results obtained from the three nail samples obtained at the first visit with the results from the four consecutive visits. RESULTS: We noted a clear trend showing that as the number of positive cultures increases (one to three cultures) during the first examination, the percentage of subsequent positive cultures, taken during the four consecutive visits, also increased. CONCLUSIONS: We suggest that when NDM infection is found in the first culture, the patient should be re-examined in a subsequent visit in which three separate samples are taken from the affected nail. If NDM is confirmed in all three cultures, the diagnosis of NDM is established. Treatment should be recommended in patients who show positive results in all three cultures.

Pancreatic panniculitis and carcinoma of the pancreas.

Pancreatic panniculitis is a rare complication of carcinoma of the pancreas, most often accompanying the rare acinar cystadenocarcinoma. It presents with painful erythematous subcutaneous nodules typically located on the leg. We present a case of a 79-year-old man with neuroendocrine carcinoma of the pancreas and liver metastasis, who developed painful subcutaneous nodules on his shins. Laboratory values included a raised lipase level with normal amylase level and peripheral eosinophilia. The patient was treated with nonsteroidal anti-inflammatory drugs, dexamethasone and antibiotics, with resolution of the dermatological symptoms.

Onycomycosis due to artificial nails.

BACKGROUND: The use of artificial nails (ANs) as part of nail-care cosmetics is very popular. Several side effects and complications, such as contact dermatitis and bacterial and fungal infections, have been reported in patients using ANs. Objective The purpose of this study was to identify the fungal pathogens in nail abnormalities appearing in patients with ANs. METHODS: We evaluated 68 patients suffering from nail changes and paronychia, which appear after removal of ANs. Mycological samples were obtained from two sites: distal parts of the involved nail and the proximal nail fold. KOH examination and fungal culture were used for detection and identification of fungal infection. RESULTS: Mycological results from the distal part of the nail showed positive KOH test in 57 cases (83.8%), and culture was positive in 67 patients (98.5%). Mycological results obtained from the proximal nail fold showed positive KOH test in 36 patients (52.9%); in 36 of the cases, culture was positive. Candida spp. were the most common pathogen. Both KOH and culture results were significantly better while sampling from the distal part of the nail compared with sampling from the proximal nail fold (P = 0.0001). CONCLUSION: Onychomycosis was found to be very common in nail changes due to ANs, leading to an increased risk of transmitting microbial infections. Therefore, health care personnel and workers in the food industry should avoid using ANs.