Knockdown of sodium channel Nax reduces dermatitis symptoms in rabbit skin.

The skin plays a critical role in maintenance of water homeostasis. Dysfunction of the skin barrier causes not only delayed wound healing and hypertrophic scarring, but it also contributes to the development of various skin diseases. Dermatitis is a chronic inflammatory skin disorder that has several different subtypes. Skin of contact dermatitis and atopic dermatitis (AD) show epidermal barrier dysfunction. Nax is a sodium channel that regulates inflammatory gene expression in response to perturbation of barrier function of the skin. We found that in vivo knockdown of Nax using RNAi reduced hyperkeratosis and keratinocyte hyperproliferation in rabbit ear dermatitic skin. Increased infiltration of inflammatory cells (mast cells, eosinophils, T cells, and macrophages), a characteristic of dermatitis, was reduced by Nax knockdown. Upregulation of PAR-2 and thymic stromal lymphopoietin (TSLP), which induce Th2-mediated allergic responses, was inhibited by Nax knockdown. In addition, expression of COX-2, IL-1ß, IL-8, and S100A9, which are downstream genes of Nax and are involved in dermatitis pathogenesis, were also decreased by Nax knockdown. Our data show that knockdown of Nax relieved dermatitis symptoms in vivo and indicate that Nax is a novel therapeutic target for dermatitis, which currently has limited therapeutic options.

Pigmented skin lesions displaying regression features: Dermoscopy and reflectance confocal microscopy criteria for diagnosis.

Melanomas and nevi displaying regression features can be difficult to differentiate. To describe reflectance confocal microscopy features in benign and malignant pigmented skin lesions characterized by regression features in dermoscopy. Observational retrospective study. Inclusion criteria were presence of dermoscopic features of regression; availability of clinical, dermoscopic and RCM imaging; definite histopathologic diagnosis. The study sample comprised 217 lesions; 108 (49.8%) melanomas and 109 were benign lesions, of which 102 (47.0%) nevi and 7 (3.2%) lichen planus-like keratosis (lplk). Patients with melanoma were significantly older than those with benign lesions (61.9 ± 15.4 vs 46.1 ± 14.8; P < 0.001) and a higher proportion of melanomas displayed dermoscopic regression structures in more than 50% of lesion surface (n = 83/108; 76.9%; P < 0.001). On RCM examination, pagetoid cells were significantly more reported in melanoma group, than in benign lesions (86.1% vs 59.6%; P < 0.001) and were more frequently widespread distributed (65.6% vs 20.0%; P < 0.001) and both dendritic and roundish (36.6% vs 15.4%; P < 0.001) in shape. Aspecific architecture at the dermo-epidermal junction (DEJ) was more commonly seen among melanomas than benign lesions (23.1% vs 11.9%; P = 0.002) with higher presence of dendritic and both dendritic and roundish atypical cells at the DEJ (28.7% vs 18.3% and 19.4% vs 3.7%; P < 0.001, respectively). Focal pagetoid infiltration and ringed or clod patterns were more commonly seen in benign lesion. In conclusion, the correct interpretation of regressing lesions remains a challenge, assessing carefully the extent and characteristics of architectural and cytologic atypia on RCM is an additional piece of the complex puzzle of melanoma diagnosis.

Impact of the mechanical hyperkeratotic lesions and its association with quality of life: An observational case-control study.

BACKGROUND: Mechanical hyperkeratotic lesions (MHL) are common condition amongst population of all ages. Such problems may be associated with pain, reduction in mobility, changes of gait and risk of falls and is believed to affect the quality of life (QoL), general health and optimal foot health. OBJECTIVE: The main aim of this study was to describe and compare both foot and general health-related QoL in two groups of participants: (i) with MHL and (ii) healthy controls. METHOD: A total sample of 150 patients, mean age 49.50 ± 36.50 years, was recruited from an outpatient clinic. Demographic data, medical history and clinical characteristics of overall health were determined, and the obtained values were compared by the Foot Health Status Questionnaire (FHSQ). RESULTS: The FHSQ scores of the sample with MHL showed lower scores than control subjects in sections one and two for footwear, general and foot health, foot pain, foot function and physical activity (P < 0.01), but not for social capacity and vigour (P > 0.01). CONCLUSIONS: People with MHL showed a decrease in QoL, based on FHSQ scores, regardless of gender.

Pachydermodactyly: An Unknown Entity.

Pachydermodactyly is a rare benign disease that usually affects the dorsal skin and subcutaneous tissue of the proximal interphalangeal joints of the index, middle, ring, and little fingers; the thumb is usually spared. Hyperkeratosis on the dorsal side of the affected areas is common. We present a case of a 19-year-old man who was diagnosed with pachydermodactyly after evaluation of a painless, progressive swelling and hyperkeratosis at the proximal interphalangeal and distal interphalangeal joints of all fingers, bilaterally, for 6 years before presentation. Conservative treatment was prescribed and the patient remains asymptomatic. Given the benign and nonprogressive course of the disease, symptomatic treatment alone is all that is usually required.

Correlation of periodontal parameters to various types of smokeless tobacco in tobacco pouch keratosis patients: A cross-sectional study.

BACKGROUND: Tobacco practice in relation with oral diseases is a foremost cause for the global oral disease burden and is accountable for up to 50% of all periodontitis cases among adults. The present cross-sectional study was undertaken to evaluate the local effects of various types of smokeless tobacco on periodontal health in tobacco pouch keratosis (TPK) patients in Mangalore city in the state of Karnataka. MATERIALS AND METHODS: A total of 345 TPK patients were evaluated of which all were smokeless tobacco users. All the patients were clinically examined for different clinical periodontal parameters such as stains, gingival recession (GR), periodontal pocket, furcation involvement, and mobility and local effects of various types of smokeless tobacco on periodontal health in TPK sites were recorded. RESULTS: The prevalence of GR was of 87.5%. Haathichaap was the most common smokeless tobacco used (35.9%) closely followed by nonpackaged type (loose tobacco) (19.4%). This was followed by Madhu (14.2%). Likewise, periodontal parameters were observed more in these patients in decreasing order. CONCLUSION: The results of the present study agree strongly with other smokeless tobacco user studies in terms of the strong association between GR and smokeless tobacco placement. The present cross-sectional study indicates that TPK lesions are positively associated with periodontal diseases. It is important to raise awareness of both oral cancer and periodontal risks and inform about its possible health consequences thereby working towards an improvement of oral and general health and related quality of life in these patients.

Common benign and malignant oral mucosal disease.

BACKGROUND: Mucosal diseases of the oral cavity are relatively common, and patients often seek initial assessment from their general practitioner. OBJECTIVE: The aim of this article is to provide an overview of common oral mucosal diseases to help with formulating a differential diagnosis and stratifying the urgency of referral. DISCUSSION: Pathological mucosal conditions of the oral cavity and jaws commonly present as a mucosal ulcer or a white, red or pigmented lesion. In this review, the authors outline the most common conditions organised according to their clinical presentation and describe their typical appearance and management.

Crusted nipple and areola: A new aetiology of secondary hyperkeratosis of the nipple and areola.

Hyperkeratosis of the nipple and areola is a rare condition first described by Tauber in 1923. Less than 100 cases have been reported in the literature. Hyperkeratosis of the nipple and areola presents as hyperkeratotic, hyperpigmented plaques on the nipple and areola. It is more common in females. An 18-year-old female patient presented with hyperkeratotic, plaque-like, hard crusts on both nipples and areolas. The examining physician could successfully remove this crust using his finger. The crust had accumulated as a result of the patient's reluctance to touch or clean the breast area due to psychological issues. A crusted nipple and areola may occur as a secondary condition due to a patient's reluctance to touch or clean their breasts.

Pharmacoeconomic analysis of the treatment of multiple actinic keratoses.

Actinic keratosis (AK) is common and lesions may progress to squamous cell carcinoma. The choice of therapy depends mainly on 2 factors: the efficacy of therapeutic options and the number of lesions present. Cryotherapy alone is suitable for treating a few lesions, whereas topical medications, photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA), or either in combination with cryotherapy are appropriate for treating multiple (>15) lesions. When combinations are necessary, the total cost to treat multiple AKs to 100% clearance becomes important. This report provides a simple pharmacoeconomic analysis of 4 FDA-cleared therapies (imiquimod, diclofenac, 5-fluorouacil [5-FU], and ALA PDT) for AK given in combination with cryotherapy. This analysis assumes standard costs of procedures and office visits (based on April 2007 reimbursement data) and 2 treatment courses (medications: imiquimod, diclofenac, 5-FU) or sessions (ALA PDT) of each modality followed by cryotherapy to 100% clearance. The total cost of each combination is $725.17 for ALA PDT, $845.07 for diclofenac, $942.13 for 5-FU, and $1,473.39 for imiquimod. When phase III trial efficacies of the 4 modalities are considered, the actual cost of using imiquimod or diclofenac increases because additional treatments may be required. Among these 4 FDA-cleared therapies for multiple AK lesions, ALA PDT is the least expensive treatment and imiquimod is the most expensive treatment under the stated assumptions.

Treatments Improving Skin Barrier Function.

Moisturizers affect the stratum corneum architecture and barrier homeostasis, i.e. topically applied ingredients are not as inert to the skin as one might expect. A number of different mechanisms behind the barrier-influencing effects of moisturizers have been suggested, such as simple deposition of lipid material outside the skin. Ingredients in the moisturizers may also change the lamellar organization and the packing of the lipid matrix and thereby skin permeability. Topically applied substances may also penetrate deeper into the skin and interfere with the production of barrier lipids and the maturation of corneocytes. Furthermore, moisturizing creams may influence the desquamatory proteases and alter the thickness of the stratum corneum.

Frequency of metabolic syndrome in patients with knuckle pads.

Knuckle pads are hyperkeratotic, benign skin lesions that we commonly observe in obese patients. There is no study that investigates the association between metabolic syndrome (MetS) and knuckle pads. We aimed to investigate the frequency of MetS in patients with knuckle pads. Forty-seven patients with knuckle pads and 46 age- and sex-matched controls were enrolled. The presence of MetS was evaluated according to National Cholesterol Education Program-Adult Treatment Panel III criteria. In the patient group, waist circumference (P < 0.01), body mass index (BMI; P < 0.01), and systolic (P < 0.01) and diastolic blood pressure (P < 0.01) were higher than controls, and most of the patients had a history of hypertension (P < 0.01). The presence of MetS was found in 66% of the patients with knuckle pads and in 52.2% of the controls (P = 0.25). In the patient group, compared with controls, more patients had blood pressure above reference values or were on antihypertensive therapy (70.2% and 43.5%, P = 0.017, respectively), and had greater waist circumference value (93.6% and 76.1%, P = 0.038, respectively). The presence of the other three criteria were similar in both groups. Although we found similar MetS frequency in both groups, patients with knuckle pads should be examined for the presence of MetS components, especially abdominal obesity and hypertension.

High incidence and regression rates of solar keratoses in a queensland community.

The presence of solar keratoses on the skin is one of the major risk factors for basal cell and squamous cell carcinomas, which constitute a growing public health problem in today's white populations. In spite of this, little is known of the natural history of solar keratoses. We conducted follow-up studies to monitor the incidence, regression, and recurrence rates of solar keratoses in a random sample (N = 96) of the Nambour community in Queensland. At baseline, 43 participants (46%) were diagnosed with at least one solar keratosis [26 men (55%), 17 women (37%)] with a total count of 494 prevalent solar keratoses. The distribution of lesions per person was highly skewed, with 11 individuals (12%) having 65% of the total number of solar keratoses. During 12 mo of follow-up, 614 incident solar keratoses were diagnosed (549 in men and 65 in women); 526 solar keratoses regressed and 53 prevalent solar keratoses recurred, giving a net 45% increase in solar keratosis numbers in men (from 354 to 512 solar keratoses) and a net 44% reduction in women (from 114 to 64). Regression rates were higher in prevalent (74%) than incident (29%) solar keratoses. Solar keratosis prevalence increased with age in both sexes, and individuals with solar keratoses at baseline were over seven times more likely to develop additional solar keratoses in the next 12 mo than those without prevalent solar keratoses at baseline. These results show that the natural history of solar keratoses in the community is one of high turnover and that a small percentage of susceptible individuals carry the major burden of solar keratoses in the community.

DNA repair in cells from patients with actinic keratosis.

UV-induced DNA repair was studied in peripheral blood lymphocytes from patients with multiple actinic keratoses (AK) requiring surgical therapy and from age-matched normal control individuals. The DNA repair activity in lymphocytes from AK patients at 4 h after UV-irradiation was 50% of that in control lymphocytes, but at 21 h the extent of DNA repair synthesis was similar to that in control cells.

The permeability of epidermis lacking normal membrane-coating granules: an ultrastructural tracer study of Kyrle-Flegel disease.

Skin lesions from patients with Flegel's disease have been reported to be without membrane-coating granules (Odland bodies). Biopsies of the hyperkeratinized papules of Kyrle-Flegel disease were incubated in vitro with the intercellular tracer, horseradish peroxidase, and the extent of penetration of this substance examined in the light and electron microscopes. The peroxidase was present throughout the corium and extended through the intercellular spaces of the epidermis to a level close to the junction of the granular and keratinized layers; it did not enter the bulk of the thickened stratum corneum of the lesion. Ultrastructural examination revealed the presence of small vesicles in the granular layer, similar in size and shape to membrane-coating granules but lacking a lamellate internal structure; these were occasionally seen fusing with the plasma membrane of the cells. It is suggested that the intercellular permeability barrier to horseradish peroxidase demonstrated in the Kyrle-Flegel lesion may arise from material contributed by these granules to the intercellular space.

Expression of activated MEK1 in differentiating epidermal cells is sufficient to generate hyperproliferative and inflammatory skin lesions.

Epidermal activation of Erk MAPK is observed in human psoriatic lesions and in a mouse model of psoriasis in which beta1 integrins are expressed in the suprabasal epidermal layers. Constitutive activation of the upstream kinase MEK1 causes hyperproliferation and perturbed differentiation of human keratinocytes in culture. It is not known, however, whether Erk activation in differentiating keratinocytes is sufficient to trigger hyperproliferation of basal keratinocytes and a skin inflammatory infiltrate. To investigate this, we expressed constitutively active MEK1 in the suprabasal epidermal layers of transgenic mice. Proliferation in the epidermal basal layer was stimulated and epidermal terminal differentiation was perturbed. Some older mice also developed papillomas. There was a large increase in T lymphocytes, dendritic cells, and neutrophils in the skin. The effects of suprabasal MEK1 on basal keratinocytes and leukocytes, cells that were transgene negative, suggested that MEK1 activity might stimulate cytokine release. Transgenic keratinocytes expressed elevated IL-1alpha and crossing the mice with mice overexpressing the IL-1 receptor in the epidermal basal layer led to exacerbated hyperproliferation and inflammation. These data suggest that activation of MEK1 downstream of beta1 integrins plays an important role in epidermal hyperproliferation and skin inflammation.