Epidemiologic and clinicomycologic profile of onychomycosis from north India

Background  Onychomycosis is an important public health problem because of the increase in immunosuppressive states. Large-scale studies in India are scarce, and so the baseline incidence of onychomycosis is not firmly established.
Methods  Three hundred and two clinically suspected cases of onychomycosis were included in this study. Nail samples were collected for direct microscopic examination and culture. Clinical patterns and associated relevant factors were noted according to a predetermined protocol.
Results  The associated predisposing conditions included diabetes mellitus (3.9%) and systemic lupus erythematosus (2.3%). Distal and lateral subungual onychomycosis was the most common clinical pattern (62%), followed by total dystrophic onychomycosis (20.2%). The most common fungal isolates were dermatophytes (49.5%), followed by Candida spp. (40.4%) and nondermatophyte molds (10.1%). Of the dermatophytes, Trichophyton rubrum (47%) was the most common isolate, followed by Trichophyton tonsurans (20.4%). Of the Candida spp., Candida albicans was the most common (60%).
Conclusions  Until recently, yeasts and nondermatophyte molds were regarded as contaminants, but their emergence as a significant cause of onychomycosis in immunocompromised patients calls for mycologic diagnosis and antifungal susceptibility testing in onychomycosis. The recognition of the changing patterns of onychomycosis will aid in the therapeutic approach and the implementation of control measures.     

Amorolfine and itraconazole combination for severe toenail onychomycosis; results of an open randomized trial in Spain

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  < 0·001). The global cure rate at week 24 was 83·7% (36 patients) in group AI-6, 93·9% (31 patients) in group AI-12, and 68·8% (22 patients) in group I-12. The difference between the AI-12 group and itraconazole monotherapy was significant ( P  < 0·05).
Conclusions These results indicate that amorolfine combination therapy represents an improved treatment strategy for patients with severe onychomycosis.     

Comparison of direct smear, culture and histology for the diagnosis of onychomycosis

A sensitive and efficient diagnostic strategy is needed to confirm the clinical suspicion of onychomycosis. The purpose of this study was to compare the sensitivity of three most commonly used diagnostic methods for onychomycosis. Nail specimens of 96 patients with clinically suspected onychomycosis were evaluated using potassium hydroxide smear, culture and histology. A positive result of any of these tests was considered confirmatory for fungal infection and the sensitivity of each test as well as various combinations of them was calculated. The diagnosis of onychomycosis was confirmed in 47 patients (48.9%). Histology was the most sensitive single test for the diagnosis of onychomycosis, although its sensitivity (80.8%) was not statistically different from smear (76.5%). Both histology and smear were significantly more sensitive than culture (53.2%). The most sensitive combination of tests, smear plus histology, was 97.8% sensitive with 98% negative predictive value. In conclusion, direct smear combined with histological examination is the most sensitive diagnostic approach for onychomycosis.     

Contact sensitivity in patients with venous leg ulcers in Serbia: comparison with contact dermatitis patients and relationship to ulcer duration

Background: Contact hypersensitivity is a common occurrence in patients with chronic venous leg ulcers (CVLU) with allergen profiles depending upon the local treatment policies.
Objective: This study was to determine the frequency of contact sensitivity, prevalence of individual allergens, polyvalent sensitization, and/or their relationship to ulcers duration in the population of CVLU and contact dermatitis patients in Serbia.
Patients: 75 patients with CVLU and 82 patients with clinically suspected contact dermatitis were prospectively included in the study. The patients were patch tested with a series of 21 standard and 22 supplemental allergens.
Results: 73% ( n  = 55) of CVLU and 52% ( n  = 43) of control subjects had 1 or more positive patch test results ( P  < 0.01). Polysensitization was found in 53% of patients and 21% of controls ( P  < 0.01). CVLU patients run 2.5 and 4.3 higher risk for contact sensitization and polysensitization, respectively. The most common allergens were Balsam of Peru (21.3%), carba mix (18.7%), fusidic acid (17.3%), colophony (13.3%), paraben mix (12%), chloramphenicol (12%), silver nitrate (12%), and neomycin (10.7%). Polivalent sensitization and higher mean number of allergens were associated with ulcer duration >5 years.
Conclusions: The results confirm a high rate of contact (poly)sensitization in patients with CVLU and local variability in allergen prevalence.     

GMS is superior to PAS for diagnosis of onychomycosis

Background:  Onychomycosis is a common cause of deformed nails. Periodic acid-Schiff (PAS) stains are more sensitive than fungal cultures for diagnosing onychomycosis. We performed a retrospective study comparing the use of PAS and Gomori methenamine silver (GMS) stains for histopathologic diagnosis of onychomycosis.
Methods:  GMS stains were performed on 20 PAS-positive and 51 PAS-negative cases from nail biopsies with a clinical diagnosis of onychomycosis. The PAS stained slides and GMS stained slides were evaluated for the presence of fungal hyphae. The results were analyzed with McNemar's test.
Results:  All 20 PAS-positive cases were also positive with GMS stains. Of the 51 PAS-negative cases, GMS stains detected an additional five cases with fungal hyphae. GMS stains were quantitatively superior (p < 0.0253). GMS stains were also qualitatively superior. More fungal hyphae were highlighted and fungal hyphae were more easily recognized on low or medium power magnification.
Conclusions:  GMS stains are superior to PAS stains for the routine diagnosis of onychomycosis.     

Onychomycosis infections in the Middle Black Sea Region, Turkey

Background  Onychomycosis, a fungal infection of the nail, is caused by dermatophytes, yeasts, and nondermatophyte molds. The causative pathogen and incidence of onychomycosis depend on age, gender, geographic and climatic conditions, living habits, and immune status of the host.
Aim  To determine the incidence and etiologic agents of onychomycosis in the Middle Black Sea Region, Turkey.
Methods  Two hundred and seventy-six specimens were collected from patients with suspected onychomycosis during January 2004 to May 2008.
Results  Culture positivity was obtained in 240 of the 276 samples. Dermatophytes were isolated in 225 samples. The most common causative agent of onychomycosis was Trichophyton rubrum (91) (38%), followed by Trichophyton mentagrophytes (49) (20.4%), Epidermophyton floccosum (41) (17%), and Trichophyton verrucosum (34) (14.2%). Seven isolates were identified as yeasts (2.9%). Nondermatophyte molds were isolated from eight samples (3.3%).
Conclusions  This survey reveals that the etiologic agents of onychomycosis in our area show large discrepancies from those in other regions of Turkey and Europe.     

Molecular detection of dermatophytes and nondermatophytes in onychomycosis by nested polymerase chain reaction based on 28S ribosomal RNA gene sequences

Background  Onychomycosis is often caused by dermatophytes, but the role of nondermatophytes is underestimated due to the difficulty of identifying them by conventional direct microscopy and culture.
Objectives  This study aims to detect nondermatophytes, as well as dermatophytes, in the nail samples of patients with onychomycosis using a polymerase chain reaction (PCR)-based culture-independent method.
Materials and methods  The nested PCR assay targeting the sequence of the 28S ribosomal RNA gene was used to amplify fungal DNAs from 50 microscopy-positive nail specimens. Newly designed primer sets for dermatophyte universal, Trichophyton rubrum , T. mentagrophytes , Aspergillus spp., Scopulariopsis brevicaulis , Fusarium solani , F. oxysporum , F. verticillioides , Candida albicans and C. tropicalis were used after confirmation of their specificity.
Results  Forty-seven cases (94%) were positive for fungal DNA, among which dermatophytes were detected in 39 cases (83·0%): T. rubrum in 35 cases (74·5%) and T. mentagrophytes in eight cases (17·0%). Surprisingly, nondermatophytes were detected in 18 cases (38·3%), both dermatophytes and nondermatophytes in 10 cases (21·3%) and nondermatophytes alone in eight cases (17·0%). Aspergillus spp. alone was observed in five cases (10·6%).
Conclusions  This study indicates that most of the affected nail plates of patients with onychomycosis were positive for specific fungal DNAs, and suggests that nondermatophytes detected at high rates may be involved in the pathogenesis of onychomycosis.     

Matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry: a new tool in diagnostic investigation of nail disorders?

Abstract:  The incidence and prevalence of onychomycosis are rising worldwide. Common diagnostic techniques often lack sensitivity or specificity. Differentiation between non-infectious nail disorders is frequently not possible. The aim of this study was to establish a better diagnostic routine procedure based on modern mass spectrometric peptide analysis techniques. One hundred and fifty-five nail samples from 145 patients with clinically suspected onychomycosis ( n  = 96, 62%) and without onychomycosis [e.g. nail psoriasis or nail dystrophy resulting from eczema ( n  = 59, 38%)] were investigated using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) peptide mass fingerprinting in comparison with standard techniques. We demonstrated that MALDI-TOF MS represents a precise, robust and fast tool in diagnostic investigation of nail disorders, which is superior to common standard methods.     

Metabolic syndrome associated with toenail onychomycosis in Taiwanese with diabetes mellitus

Background Onychomycosis is a complication of diabetes mellitus (DM), which has a deleterious impact on the quality of life. Aim To explore the prevalence of onychomycosis amongst Taiwanese diabetics, and to analyze the factors associated with onychomycosis after adjusting for age and sex. Methods A total of 1245 Taiwanese diabetics were enrolled, and a nested case–control study was performed by onychomycosis outcome and the exposures were compared. Results The overall prevalence of onychomycosis among DM patients was 30.76% (383/1245), with a significantly higher prevalence in men than in women (P = 0.024). The factors associated with onychomycosis in matched pairs by gender and age were analyzed in 375 pairs. It was found that metabolic syndrome, obesity, triglyceride (TG) levels, and glycosylated hemoglobin (HbA1c) were associated with onychomycosis (P < 0.05). Conclusion Higher prevalence rates of onychomycosis were found in men and older DM patients. Metabolic syndrome, obesity, high TG levels, and poor glycemic control were associated with onychomycosis.     

Brain-derived neurotrophic factor gene polymorphisms and serum levels in Chinese atopic dermatitis patients

Background  Brain-derived neurotrophic factor (BDNF) plays an important role in the pathogenesis of atopic dermatitis (AD). Whether BDNF gene polymorphisms are associated with Chinese AD remains totally unknown.
Objective  The aim is to determine if BDNF gene C270T and G196A polymorphisms are associated with Chinese AD, and analyse the clinical relevance of BDNF gene polymorphisms and BDNF serum levels.
Methods  We conducted a case-control association analysis (160 patients and 169 controls) in Northern Chinese subjects. Genotyping was performed by restriction fragment length polymorphism, and serum levels of BDNF were measured using enzyme-linked immunosorbent assay.
Results  For C270T, there were significant differences in C/T genotype distribution ( P  = 0.003) and T allele frequencies ( P  = 0.004) between AD patients and controls in the whole dataset. Higher C/T genotype frequencies were found in male AD (10.6% vs. 1.1%, P  = 0.018) and in intrinsic AD (IAD; 15.79% vs. 2.91%, P  = 0.008). No association between G196A polymorphism and AD was observed in the whole cohort, while A allele was much more frequent in AD patients with atopy in first-degree relatives (65.8% vs. 34.2%, P  = 0.038). Serum BDNF levels were correlated with IAD severity as measured by Scoring Atopic Dermatitis index ( r  = 0.576, P  < 0.001).
Conclusion  T allele in C270T may be a risk factor for AD, especially in IAD and male AD. A allele in G196A may be a risk factor in AD patients with atopy in first-degree relatives. Serum BDNF levels were correlated with the severity of IAD.     

An innovative water-soluble biopolymer improves efficacy of ciclopirox nail lacquer in the management of onychomycosis

Background  A new 8% ciclopirox-medicated nail lacquer (P-3051), based on a new technology, revealed superior properties in terms of affinity to keratin, nail permeation, and ease of use.
Objective  This study aims to assess the efficacy and safety of P-3051 vs. the market 8% ciclopirox nail lacquer.
Methods  This is a multicentre, randomized, three-arm, placebo-controlled, parallel groups, evaluator-blinded study. Overall, 467 patients with onychomycosis of at least one big toenail were randomized to receive P-3051, the reference drug or placebo in a 2 : 2 : 1 ratio for a 48-week treatment by daily application, followed by a 12-week follow-up.
Results  The study satisfied its objective by demonstrating that P-3051 was both superior to placebo and non-inferior to reference in the complete cure rate after a 48-week active treatment period. Switching the non-inferiority to superiority hypothesis, the superiority of P-3051 vs. reference was nearly significant at week 48 (confirmed at week 52), and it was significant at week 60 (cure rate for P-3051 is 119% higher than reference; P  < 0.05). Altogether, the results on primary endpoint exceed expectations; superiority test was performed also on secondary endpoints to confirm the superiority trend of the study. At the end of follow-up, percentages of patients who achieved the endpoint 'responder' in the P-3051 group were 66% higher than reference ( P  < 0.05), and those who achieved the endpoint 'decrease of diseased nail' were 40% higher ( P  < 0.05).
Conclusion  Ciclopirox 8% hydrolacquer is more active than reference ciclopirox nail lacquer in the treatment of onychomycosis.

Conflicts of interest

None declared.     

Atopic dermatitis and risk factors in poor children from Great Buenos Aires, Argentina

Background.  In recent decades, the prevalence of atopic dermatitis (AD) has risen steadily, and risk factors for AD are currently being investigated worldwide. In Argentina, there are no available data on risk factors of AD.
Aim.  To determine the prevalence of and any gender predilection for AD, and to identify familial and environmental factors that are associated with increased AD risk.
Methods.  In this case–control cross sectional study, 603 children aged 12–60 months old from a poor urban community in Buenos Aires were recruited. AD was defined following UK Working Party Diagnostic Criteria. We evaluated the relationship between AD and the presence of family history of atopy, > 5 family members, wearing synthetic clothes, having a carpeted room, eating ≥ 3 eggs/week, tobacco smoking indoors by family members, and living< 300 m from a main road, polluted stream or industry.
Results.  The prevalence of AD was 41.1% (95% CI 37.2–45.2%). Logistic regression analysis showed that AD was significantly associated only with a family history of atopy (OR = 5.7; 95% CI 3.7–8.8%; P  = 0.0000), wearing synthetic clothes (OR = 2.2; 95% CI 1.4–3.5; P  = 0.0009), having a carpeted room OR = 1.9; 95% CI 1.2–3.0%; P  = 0.009) and living < 300 m from an industry (OR = 1.93; 95% CI 1.2–3.1%; P  = 0.0051).
Conclusion.  We found a high prevalence of AD in our study population. Not all the investigated risk factors for AD had a significant association with the disease.     

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.     

Impact of pruritus on quality of life in sulfur mustard-exposed Iranian veterans

Background  Sulfur mustard, a chemical warfare agent, has various verified chronic effects on the skin. One of the foremost negative impacts of this agent is chronic pruritus, which plagues chemically injured veterans for life and can downgrade their quality of life.
Aim  To assess the association between the quality of life and pruritus severity in chemically injured veterans.
Methods  One hundred and twenty-five consecutive chemically injured veterans suffering from pruritus were assessed via the Dermatology Life Quality Index (DLQI) and pruritus score. Pruritus scores less than 15, between 16 and 30, and more than 30 were considered as mild, moderate, and severe pruritus, respectively. Patients with different levels of pruritus were compared with respect to their DLQI and its subscores.
Results  All subjects were male with a mean age of 44.3 ± 8.0 years; 11.2% had mild, 35.2% moderate, and 53.6% severe itching. The DLQI median scores in the mild, moderate, and severe cases were 16, 20, and 21, respectively ( P  = 0.014). The DLQI subscores of symptoms and feelings ( P  = 0.015), personal relationships ( P  = 0.002), and daily activities ( P  = 0.036) were worst in patients with severe itching.
Conclusion  Chemically injured veterans suffering from severe itching have a significantly poorer quality of life than do patients with milder symptoms.     

Prognostic factors for the response to treatment in males with genital warts

Background  Factors predicting an unfavourable course of genital warts to treatment have not been determined.
Materials and methods  Behavioural and baseline disease characteristics were recorded from 246 males with anogenital warts. Urethral swabs were obtained and examined using the Hybrid Capture 2 Microplate assay. Patients were treated for their anogenital warts with cryotherapy, imiquimod cream 5% or podophyllotoxin. They were followed up every 3 months for 1 year.
Results  Patients with a negative or low-risk initial test tended to respond earlier to treatment than those with a high/intermediate-risk human papillomavirus (HPV) or with a dual infection ( P  = 0.028). The response rate was unrelated ( P  > 0.05) to the duration, number and anatomical location of the lesions and to the patient's age and sexual orientation, and only marginally to the initial extent of the lesion ( P  = 0.046). However, the type of treatment predicted a favourable response (P ≤ 0.001), with patients who received both imiquimod and crotherapy responding worse. Considering all factors simultaneously in logistic regression, only the type of treatment and extent of the disease were found to influence the response rate.
Conclusion  The type of treatment and extent of the disease were the only factors found critical for patients' response.     

Expression of minichromosome maintenance proteins in Merkel cell carcinoma

Objective  Minichromosome maintenance (MCM) nuclear proteins have barely been employed in the diagnosis of skin malignancies. We aimed to assess whether MCM immunohistochemistry can be utilized to examine tumour proliferation in Merkel cell carcinoma (MCC).
Methods  In this pilot study, we studied skin specimens of eight patients with MCC. As a control, eight patients with cutaneous malignant melanoma (MM) were included. Immunohistochemistry was performed for MCM4, MCM6, MCM7, Ki-67, p53, and p21.
Results  Protein expression of MCM4 (66.0 ± 26.5% vs. 33.9 ± 22.4%; P  = 0.017), MCM6 (70.9 ± 11.9 vs. 31.7 ± 22.7; P  = 0.0031), and MCM7 (76.5 ± 16.4% vs. 34.9 ± 25.5%; P  = 0.0013) was significantly increased in tumour cells of MCC when compared to tumour cells of MM. Ki-67 immunoreactivity was also significantly higher in MCC than in MM (28.7 ± 7.9 vs. 11.0 ± 9.2; P  = 0.0012). Immunolabelling of p53 (68.6 ± 26.2 vs. 58.4 ± 28.8; P  = 0.46) and p21 (40.1 ± 38.8 vs. 25.8 ± 16.1; P  = 0.35) was relatively high but not significantly increased in MCC when compared to MM.
Conclusion  Our preliminary data indicate that MCM immunohistochemistry may be a useful tool for the determination of tumour cell proliferation in MCC.     

Efficacy of dioic acid compared with hydroquinone in the treatment of melasma

Background  Melasma is a common disorder of pigmentation characterized by relatively symmetric, brown or gray–brown patches on sun-exposed facial areas. Hydroquinone, the most effective agent in melasma, is known to irritate the skin, and so new alternatives in the treatment of melasma are required. We sought to assess the clinical response of a new depigmenting agent in melasma.
Methods  Ninety-six Mexican female patients with melasma were enrolled in this open, comparative, 12-week study. The patients received 1% dioic acid cream (twice daily) or 2% hydroquinone cream (twice daily).
Results  There was a significant difference in the Melasma Area Severity Index (MASI) scores from baseline to the end of the study using treatment with dioic acid (baseline, 14.52 3.4; after 12 weeks of treatment, 6.05 ± 1.2; P  = 0.001) and hydroquinone (baseline, 15.22 ± 2.4; after 12 weeks of treatment, 6.34 ± 1.3; P  = 0.001); however, there were no significant differences between treatments (baseline, P  = 0.311; after 12 weeks of treatment, P  = 0.287). The side-effects were similar with both medications; however, pruritus was more common in patients using hydroquinone.
Conclusions  Dioic acid is an effective and highly tolerated skin product, although further controlled, blind, multicenter studies are required to support these results.     

Clinical characteristics and outcome measures in hidradenitis suppurativa research

Introduction:  Outcome measures for medical treatment of HS are needed.
Patients and methods:  One hundred and sixty-four consecutive patients were prospectively evaluated. A new score was evaluated: HSPAIN = pain intensity on a visual analog scale (VAS 1-10) × number of painful days/month.
Results:  Mean age was 34 years (± 11), sex ratio F/M 2.8:1. Forty-two per cent were over weighted; 82% were smokers, 30% had a family history of HS. Age at onset was 23 years. Hurley's class was I = 72%; II = 25 %; III = 3%. Mean Sartorius' score ( 1 ) was 22 (range: 3–72). Pain on VAS was 4.1 for lower localizations, and its duration was >15 days/month for 25% of patients. Patients with a Sartorius' score > median were older ( P  = 0.003), more frequently overweighted (0.02). The mean HSPAIN scored 7.9 (0–30). It was highly correlated to Sartorius' score ( P  < 10-3). This new score has been used in therapeutic trials of dalacine – rifadin combination and of zinc gluconate. Quality of life study of 61 patients emphasizes the strong impact of HS compared with other dermatological diseases; patients with an early onset, long duration and continuous evolution are particularly affected.
Conclusion:  Surgery is not the only treatment for HS; we need outcome measures that are more adapted to medical treatment, i.e. integrating pain which is the major burden of this disease.     

Proliferation, DNA repair and apoptosis in androgenetic alopecia

Background   Androgenetic alopecia is a common hair disorder, resulting from interplay of genetic, endocrine and ageing factors. Meanwhile, it is unclear if an altered degree of proliferation or increased apoptosis could contribute to its pathogenesis.
Objective   To evaluate the role of proliferation, DNA damage and apoptosis in the pathogenesis of androgenetic alopecia.
Methods   Thirty biopsies were taken from the frontal (bald) area and occipital (hairy) area of 15 male patients with androgenetic alopecia, as well as five specimens from frontal area of five age-matched controls. These specimens were used for immunohistochemical staining of cell proliferation [proliferating cell nuclear antigen (PCNA)] and DNA repair markers (XRCC1, APE1, PARP-1) as well as apoptosis regulatory protein p53.
Results   The frontal bald area of patients showed significantly higher levels of X-ray Cross Complementing-1 (XRCC1; P  < 0.001) and p53 ( P  < 0.001) expression when compared with occipital hairy area of patients and frontal area of controls ( P  = 0.003 and 0.04, respectively). On the other hand, there were significantly lower expression of PCNA ( P  < 0.001) and apurinic/apyridinic endonuclease 1 (APE1; P  = 0.001 and 0.02) when compared with the frontal area of controls and occipital area of patients, respectively. Meanwhile, APE1 showed significant inverse correlation with p53 overexpression ( P  = 0.03).
Conclusion   The frontal bald area of patients with androgenetic alopecia has lower proliferation rate that result in follicular miniaturization. There is increased DNA damage that would be beyond the capacity of cells to repair in advanced cases. An alternative pathway would take place in order to eliminate the damaged cells through apoptosis.     

Filaggrin mutations may confer susceptibility to chronic hand eczema characterized by combined allergic and irritant contact dermatitis

Background  The pathogenesis of chronic hand eczema (CHE) is multifactorial and involves both endogenous predisposition and environmental triggers.
Objectives  Filaggrin is a structural protein of the cornified envelope and important for the formation of the epidermal skin barrier. The aim of this investigation was to evaluate the role of mutations in the filaggrin gene ( FLG ) in the development of CHE.
Methods  In total, 122 German patients with clearly defined CHE subtypes were screened for the FLG variants R501X and 2282del4 by polymerase chain reaction and restriction enzyme digest analysis. The prevalence of these variants in CHE patients was compared with that in 95 healthy individuals.
Results  Overall, allele frequency and the number of mutation carriers were similar in both the CHE and control groups. When classified according to clearly defined CHE subtypes, however, the nonfunctional FLG variants showed an association with CHE involving an aetiological combination of contact allergy and irritant factors [ P  = 0·04; P (exact test) = 0·06; P (difference in rates) = 0·09; 95% confidence interval (CI) 0–56·8)], or with excessive daily exposure to water and irritants [ P  = 0·003; P (difference in rates) < 0·001; 95% CI 29·3–67·9].
Conclusion  Heterozygosity for nonfunctional mutations in the FLG gene may contribute to the manifestation and maintenance of a particular CHE subtype that is characterized by the combination of allergic and irritant contact dermatitis.