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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.

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. Na x 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 Na x 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 Na x knockdown. Upregulation of PAR-2 and thymic stromal lymphopoietin (TSLP), which induce Th2-mediated allergic responses, was inhibited by Na x knockdown. In addition, expression of COX-2, IL-1β, IL-8, and S100A9, which are downstream genes of Na x and are involved in dermatitis pathogenesis, were also decreased by Na x knockdown. Our data show that knockdown of Na x relieved dermatitis symptoms in vivo and indicate that Na x is a novel therapeutic target for dermatitis, which currently has limited therapeutic options.

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., Competing Interests: None

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., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

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., (© 2018 European Academy of Dermatology and Venereology.)

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., (Copyright © 2016 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)

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., (© 2016 S. Karger AG, Basel.)

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., (© 2015 Japanese Dermatological Association.)

Background: Olmsted syndrome is a rare congenital skin disorder presenting with periorifical hyperkeratotic lesions and mutilating palmoplantar keratoderma, which is often associated with infections of the keratotic area. A recent study identified de novo mutations causing constitutive activation of TRPV3 as a cause of the keratotic manifestations of Olmsted syndrome., Methods: Genetic, clinical and immunological profiling was performed on a case study patient with the clinical diagnosis of Olmsted syndrome., Results: The patient was found to harbour a previously undescribed 1718G-C transversion in TRPV3, causing a G573A point mutation. In depth clinical and immunological analysis found multiple indicators of immune dysregulation, including frequent dermal infections, inflammatory infiltrate in the affected skin, hyper IgE production and elevated follicular T cells and eosinophils in the peripheral blood., Conclusions: These results provide the first comprehensive assessment of the immunological features of Olmsted syndrome. The systemic phenotype of hyper IgE and persistent eosinophilia suggest a primary or secondary role of immunological processes in the pathogenesis of Olmsted syndrome, and have important clinical consequences with regard to the treatment of Olmsted syndrome patients.

Objective: To examine the association between magnetic resonance imaging (MRI) features of distal phalanx (DP) disease and the progression of nail pathology in psoriatic arthritis (PsA)., Methods: Clinical nail assessment and hand MRI scans were done on 34 patients with PsA. Twenty patients had repeat nail assessments after 1 year., Results: Nails with onycholysis and hyperkeratosis at baseline were more likely to have corresponding DP bone erosion and proliferation on MRI. DP bone edema on baseline MRI was associated with development of onycholysis and hyperkeratosis in corresponding nails., Conclusion: Our data suggest that DP inflammation is central in the development of psoriatic nail disease.

A case is presented of a female Caucasian patient with chronic peripheral blood eosinophilia and unusual skin manifestations. Within a couple of years, the patient developed multiple hyperkeratotic and hyperpigmented papules and plaques all over the body, palmoplantar keratoderma, pachydermia of acral parts of the body, and generalized pruritus. Generalized lymphadenopathy appeared. Other relevant symptoms were persistent peripheral blood hypereosinophilia and increased level of total IgE. The patient was diagnosed with a very rare condition, pachydermatous eosinophilic dermatitis, and was administered combined therapy with dapsone, oral methylprednisolone and fexophenadine. After one month of treatment, the skin changes markedly improved.

Background: The histological findings associated with idiopathic guttate hypomelanosis (IGH) are hyperkeratosis, an atrophic epidermis, and flattened rete ridges. In addition, a decreased melanin content and reduced numbers of melanocytes are reported features. However, there are few recent studies that have been published on the histopathology of IGH and no comparative studies are available on the skin lesions and perilesional skin of patients with IGH., Objectives: The goals of this study were to identify the clinical and histopathological features of IGH and determine their correlation. We evaluated the clinical features and the histopathological differences between the skin lesions and the perilesional skin in patients with IGH., Methods: A clinical survey was carried out on 47 patients with IGH. Specimens from skin lesions and perilesional skin were stained with hematoxylin-eosin, Fontana-Masson, MART-1, and NKI/beteb. We also studied the ultrastructure of four cases., Results: About 30% of the patients had their initial lesions prior to 20 years of age. The arm was the most commonly affected site (53%). Histologically, we found hyperkeratosis in 18 cases (38.3%), but epidermal atrophy was present in only five cases (10.6%), and flattened rete ridges in seven cases (14.9%) compared to the normal skin. Epidermal atrophy was more frequently found at nonsun-exposed areas. The IGH lesions demonstrated decreased melanin pigment and reduced numbers of melanocytes by NKI/beteb and MART-1. The ultrastructural evaluation showed degenerative melanocytes and decreased melanosomes. One specimen had normal melanocytes with decreased melanosomes., Conclusions: Idiopathic guttate hypomelanosis is a disorder with multifactorial etiology; its pathogenesis may depend on various factors such as patient age and sun-exposure. Histopathologically, hyperkeratosis was frequently found; however, the other characteristic findings such as epidermal atrophy and flattened rete ridges were relatively rare.

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.

Computer-assisted image analysis is useful for quantifying the histologic and molecular changes of sun-induced squamous cell carcinoma progression. We used the CAS 200 image analysis system to measure nuclear morphometric parameters, p53 expression, and proliferation markers in actinic keratosis (AK), sun-exposed, and normal skin in 51 patients. Nuclear morphometry revealed significant increases in nuclear absorbance, irregularity of nuclear shape, and nuclear size in AK compared with normal and sun-damaged skin. These parameters showed significantly greater variability in AK nuclei. Argyrophyllic nucleolar organizer area and number were also significantly greater in AK compared with sun-damaged skin and normal skin. Ki67 and p53 expressions were both increased in sun-damaged skin relative to normal and greater still in AK. These data are evidence that sun damage induces proliferation and p53 abnormalities before the appearance of nuclear abnormalities and their associated DNA instability. Following these changes during a skin cancer chemopreventative trial can then help assess the efficacy of the agent and help determine where in the progression of neoplastic changes it exerts its biological effects.

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.

Skin aging is the result of intrinsic and extrinsic factors. Extrinsic aging, also called photoaging, is mainly caused by ultraviolet radiation from the sun and leads to a state which has been termed dermatoheliosis. The aim of this article is to provide an overview of photoaged skin addressing actinic keratoses (AKs) in particular. This review will describe the clinical features of photoaged skin and briefly summarize the underlying histological, photobiochemical and molecular mechanisms responsible for photoaging. The concept of the disease continuum from AK to squamous cell carcinoma will also be presented. A special focus will be on established and new therapeutic approaches to undo photoinduced skin damage., (Copyright 2004 S. Karger AG, Basel)

Photodynamic therapy (PDT) is proposed as an effective therapy with a good safety profile for patients with actinic keratoses. PDT involves the application of a photosensitizer to dysplastic or neoplastic tissue such that when exposed to light of an appropriate wavelength, the target tissue undergoes a cytotoxic reaction. Studies to date have demonstrated that PDT for the treatment of patients with actinic keratoses achieves clearance of lesions with minimal morbidity, maintenance of functional integrity of underlying tissues, and excellent cosmetic results. We present a review of the treatment of patients with actinic keratoses and the role of PDT in this context.

In this report, a case is presented of a child, descendent from parents originating in the Virgin Islands, with symmetric and progressive hyperpigmented, hyperkeratotic plaques consistent with progressive symmetric erythrokeratoderma (PSEK). Additional family members were also affected in an autosomal dominant pattern of inheritance. Erythrokeratodermas are rare genodermatoses that have characteristic clinical presentations of well-demarcated, hyperkeratotic, and erythematous plaques. Three types exist, differentiated by their clinical presentation. In this report, a case of progressive symmetric erythrokeratoderma (PSEK) is presented. The clinical features, pathogenesis, and treatment options for erythrokeratodermas are discussed.

Objective: To examine the potential of the two tumour necrosis factor (TNF) inhibitors infliximab and etanercept as remission-inducing agents in chronic therapy-resistant inflammatory disorders of immune or non-immune pathogenesis., Methods: 14 patients with adult Still's disease/macrophage activation syndrome (4), Wegener's disease (3), Behçet's disease (3), keratoscleritis (1), lymphomatous tracheo-bronchitis (1) Cogan's syndrome (1), and rapidly destructive crystal arthropathy (1) were treated with infliximab (n = 10) and etanercept (n = 4). All patients showed organ-threatening progression of their diseases with resistance to conventional immunosuppressive medication. Therapeutic benefit was assessed clinically and by documenting organ-specific functional and morphological alterations. Side effects were compared with the data of our clinic's rheumatoid arthritis (RA) patients treated by TNF inhibitors., Results: A rapid and dramatic beneficial effect was documented in 9 patients and a moderate one in 5. Best responses (clinical and laboratory parameters) were seen in patients with macrophage activation syndrome/adult Still's disease and Behçet's disease, while the results were less impressive in those with Wegener's disease, Cogan's syndrome, idiopathic cerato-scleritis and lymphomatous tracheobronchitis. In all cases immunosuppressive agents and systemic glucocorticoids could be reduced or discontinued., Conclusions: TNF inhibition may be highly effective in patients with severe, therapy-resistant chronic inflammatory disorders.

Long-term ultraviolet light exposure of human skin epidermis in Caucasians is associated with an increased risk for the development of melanoma and nonmelanoma skin cancers. Ultraviolet radiation not only induces DNA damage in epidermal cells, it also interferes with skin homeostasis, which is maintained by a unique distribution pattern of apoptosis-inducing and apoptosis-preventing molecules. We demonstrate that, beside CD95 ligand, TRAIL and TRAIL receptors also function as important sensors in the human epidermis preserving skin integrity and preventing cell transformation. Ultraviolet irradiation extensively changes the expression pattern of some of these molecules, diminishing their sensor function. In particular, CD95 ligand and to a somewhat lesser extent TRAIL receptors are downregulated upon ultraviolet light exposure. CD95 ligand downregulation is not due to protein degradation as in situ hybridization experiments strongly support a transcriptional regulation. The downregulation of these molecules with sensor function increases the risk that aberrant cells are less efficiently eliminated. This concept is supported by the fact that the expression of these molecules is also low or absent in actinic keratosis, a precancerous state that has developed as the consequence of long-term ultraviolet exposure. Progression to invasive neoplasms is then accompanied by an upregulation of CD95 ligand and a downregulation of CD95 and of the TRAIL receptors. The high expression of CD95 ligand, TRAIL, and FLIP in squamous cell carcinoma may then contribute to the immune escape of the tumor, whereas the lack of expression of CD95 and TRAIL receptors prevents autolysis of the tumor.

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.

The terminal differentiation of epidermal keratinocytes has been regarded as an example of programmed cell death. Among the proteins specifically expressed in this process is profilaggrin, which consists offilaggrin repeats and N- and C-terminal domains. Profilaggrin is proteolytically processed into individual domains during the terminal differentiation. Filaggrin released from profilaggrin aggregates keratin filaments to form compacted cornified cells with a keratin pattern. A recent transfection experiment has indicated initiation of cell death by filaggrin expression constructs. The transitional cells between the granular and cornified cells show morphologic characteristics of apoptotic cells, and their nuclei contain fragmented DNA and profilaggrin N-terminal domains. This suggests that the N-terminus of profilaggrin may participate in nuclear events accompanying programmed cell death. Among inherited skin disorders with abnormal keratinization, progressive symmetric erythrokeratoderma is caused by loricrin mutation (loricrin keratoderma). In this disease, profilaggrin N-terminal domains are aggregated with mutant loricrin within condensed nuclei. These nuclei persist in the cornified layer as parakeratosis. Loricrin keratoderma could therefore be regarded as a representative form of disrupted cell death.

Trichostasis spinulosa (TSS) is a relatively common follicular disorder that can occur on the face and trunk, especially in the interscapular area. Its cause remains unclear. We examined clinically 30 patients with TSS and follicular materials extracted from each patient were examined microscopically. Bacterial culture and skin biopsy were done in 12 and 10 patients, respectively. Periodic acid Schiff (PAS) and Brown-Brenn Gram stain were used for detection of pityrosporum (malassezia) and bacteria. The interscapular area (14/30), nose (8/30), and cheek (4/30) were common sites of TSS. Pityrosporum and bacteria in the extracted follicular material were found at the rates of 82.6% and 73.3%, respectively. In histologic examination, follicular hyperkeratosis and numerous vellus hairs enveloped within keratotic sheath were common features. Pityrosporum and bacteria were found at the rate of 70% in biopsied specimens on PAS and Brown-Brenn Gram stain. In bacterial culture, Propionibacterium acne was most commonly identified in 75% (9 out of 12 patients). Pityrosporum and bacteria, especially Propionibacterium acne, were commonly found in the extracted follicular material and biopsied specimens. Thus, they may be related to the induction of follicular hyperkeratosis with retention of vellus hairs, and we suggest that these microorganisms may be one of the possible etiologic factors of TSS.

Photodynamic therapy with 5-aminolevulinic acid (ALA-PDT) is based on photosensitization by endogenous synthesis of protoporphyrin IX and its transient accumulation especially in malignant epithelially derived tissues. Recent studies have indicated that ALA-PDT is effective for the treatment of solar keratoses (SK), but there has been a lack of long-term clinical follow-up. The goal of the present study was to investigate the immediate and long-term effect of ALA-PDT on SK. Twenty-eight patients with a total of 251 SK were enrolled in the study. Standard treatment involved the topical application of 20% ALA, under occlusive and light-shielding dressing for 4 hours before exposure to UVA and/or different wave bands or wave band combinations of polychromatic visible light (full-spectrum visible light, and/or different wave bands of filtered visible light > 515, > 530, > 570, or > 610 nm) in one or two treatment sessions. The primary complete response rate of SK to ALA-PDT was 64% after one treatment, but 85% when the responses to a second treatment were included. Taken all treatments together, the complete response rate for lesions on face, scalp and neck was 93% for full-spectrum visible light, 96% for the combination of full-spectrum visible light and filtered light, 91% for different wave bands of filtered visible light, and 100% for the combination of long wave UVA and full-spectrum visible light, respectively. The complete response rate for lesions on forearms and hands was 51% for full-spectrum visible light and 33% for the combination of full-spectrum visible light and filtered light. The greater response rate for SK on the face, scalp, and neck was associated with a higher surface fluorescence and immediate response rate after ALA photosensitization at these sites (chi 2; p = 0.0001). However, due to the treatment protocol the mean light dose applied to lesions on the face, scalp and neck (50 J cm-2) was substantially higher than that for lesions on forearms and hands (35 J cm-2). In the long term follow-up of SK on face scalp and neck, the projected disease-free rate at 36 months after therapy was 71% for lesions treated with full-spectrum visible light versus 23% for lesions treated with different wave bands of filtered light (Log rank-Mantel Cox; p = 0.0001). These results indicate that treatment with full-spectrum visible light at higher light doses may be the most effective and promising form of light exposure in ALA-PDT of SK.

To elucidate the pathogenesis of impaired barrier function and the influence of surfactant on the stratum corneum in hyperkeratosis, we investigated morphological alterations of the corneocytes with soap solution. Groups of five patients each with psoriasis vulgaris (PV), ichthyosis vulgaris (IV), atopic dermatitis (AD), and normal controls were examined. Four samples of the horny layer were obtained from the same site by cyanoacrylate adhesive biopsy. The first sample was used for the superficial layer, and the fourth, for the basal horny layers. Each sample was agitated in 1% stirred soap solution at 60 degrees C. The number and size of isolated corneocytes and the morphologic changes were investigated. The release of corneocytes was greater and the swelling and morphological changes of corneocytes exposed to soap solutions were less in PV and AD than in IV or in healthy subjects. In IV, the release was markedly less than in controls. The release and swelling were greater in the superficial than in the basal horny layers. It was concluded that the cohesiveness of corneocytes was probably less in PV and AD and greater in IV than in normals. It was also suggested that the cohesion of corneocytes from the superficial horny layer was less than that from the deep layer. The permeability of the cornified envelope in PV and AD patients was less than in IV or healthy subjects. It was confirmed that highly potent soaps induce loss of many corneocytes and reduce the barrier function of the stratum corneum.

Phonomicrosurgery is optimized by maximally preserving the vocal fold's layered microstructure (laminae propriae). The technique of submucosal infusion of saline and epinephrine into the superficial lamina propria (SLP) was examined to delineate how, when, and why it was helpful toward this surgical goal. A retrospective review revealed that the submucosal infusion technique was used to enhance the surgery in 75 of 152 vocal fold procedures that were performed over the last 2 years. The vocal fold epithelium was noted to be adherent to the vocal ligament in 29 of the 75 cases: 19 from previous surgical scarring, 4 from cancer, 3 from sulcus vocalis, 2 from chronic hemorrhage, and 1 from radiotherapy. The submucosal infusion technique was most helpful when the vocal fold epithelium required resection and/or when extensive dissection in the SLP was necessary. The infusion enhanced the surgery by vasoconstriction of the microvasculature in the SLP, which improved visualization during cold-instrument tangential dissection. Improved visualization facilitated maximal preservation of the SLP, which is necessary for optimal pliability of the overlying epithelium. The infusion also improved the placement of incisions at the perimeter of benign, premalignant, and malignant lesions, and thereby helped preserve epithelium uninvolved by the disorder.

Hyperkeratosis of the laryngeal epithelium is considered a clinically premalignant lesion that develops into invasive carcinoma in about 7-20% of cases. We reviewed 125 cases of patients with laryngeal keratosis in biopsy obtained by direct laryngocopy over a 10-year period. The evolution of these lesions to malignancy was conditioned by age, the presence of atypias in the initial lesions, and smoking; smoking is a modifiable factor. Surgery is the treatment of choice, with periodic follow-up for three to five years. The literature was reviewed.

Background: Some workers in paraquat manufacturing, exposed to bipyridines, have developed pigmentation and keratosis on sun-exposed skin. This condition has been described as skin-malignancy or premalignancy. This study was designed to clarify the pathologic features of these lesions and to explore the etiologic role played by bipyridine., Methods: Twenty-three biopsy specimens, obtained from the affected skin of 10 workers, were scrutinized by a dermatopathologist. A total of 242 exposed workers from 28 paraquat factories were examined and interviewed during the period from 1983 to 1991. The severity of the characteristic skin lesions was graded from the lowest to the highest response to analyze the data by Mantel extension for a trend that focused on the heavy exposure to bipyridines as risk factor., Results: All pathology specimens showed various degrees of solar damage: early actinic change, solar lentigo, actinic keratosis (AK), AK coexisting with squamous cell carcinoma (scc), and scc. Six specimens from four workers were scc or scc in situ. Three of six scc showed the coexistence of AK. Of the workers, 133 had skin lesions ranging in severity from grade 1 to grade 3 on sun-exposed areas. The severity of skin changes is strongly associated with heavy exposure to bipyridines (P < 0.0001)., Conclusion: This pathologic study proves that all the lesions showed either photodamage or skin cancer. The strong trend in the correlation between severity of photodamage and exposure to bipyridine leads to the speculation about the synergistic role of bipyridine exposure and the solar effect in causing these malignant and premalignant skin lesions.

Pachyonychia congenita is a genetic syndrome of epithelial dysplasia. In infants and young children, laryngeal involvement can present a life threatening complication: obstruction of the patient's airway due to leukokeratosis can lead to severe respiratory distress. This report concentrates on the diagnosis and successful microsurgical management of laryngeal obstruction in the first female case, a 19-month-old girl with pachyonychia congenita.

The Acrokeratosis paraneoplastica is a skin pathology sometimes linked with malignancies of the upper respiratory or digestive ways. We report a case of a 71-year-old man enduring and dedifferenciated carcinoma of the parotid gland and metastatic cervical lymph nodes. Perusal of the literature about Bazex's syndrome.

The clinical course of condylomas of the cervix, and more generally of all cervical dysplasias whether associated with koilocytosis or not, remains unpredictable. Based on a series of earlier publications, we undertook a routine typing for human papillomaviruses in intraepithelial malpighian lesions of the cervix. We examined the real usefulness of such typing to determine prognosis of the lesions and correct clinical management. We determined the correlations between human papillomaviruses, as detected by the in situ hybridization method, with the histological grade of 125 cervical lesions (in 106 patients) and the clinical course (mean follow-up = 24 months) in 56% of them. Viruses 16/18 and/or 31/33/55, considered to be potential oncogenes, predominated, whatever the grade, in in situ hybridization positive intraepithelial malpighian lesions (57 out of 59 cases; 97%). In the follow-up cases, there was no difference in the clinical course of the lesions in terms of grade (simple condyloma mild or moderate dysplasia) based on the hybridization results (detection and typing). These findings suggest that routine viral typing cannot be proposed to determine the therapeutic attitude (abstention, destruction) for the management of intraepithelial lesions of the cervix.

In this study, we characterized the stratum corneum barrier function in 39 patients with various keratinization disorders (autosomal dominant ichthyosis vulgaris [ADI] [n = 7], X-linked recessive ichthyosis [XRI] [n = 6], autosomal recessive congenital ichthyosis [CI] [n = 10], dyskeratosis follicularis [Darier's disease; DD] [n = 8], erythrokeratoderma variabilis [EKV] [n = 8]), and 21 healthy volunteers, using two non-invasive methods: transepidermal water loss (TEWL) measuring outward transport of water through the skin by evaporimetry, and the vascular response to hexyl nicotinate (HN) penetration into the skin as determined by laser-Doppler flowmetry. Significantly increased TEWL values were found on the volar forearm in all three forms of ichthyosis, compared with the healthy control group, with the highest TEWL values in the CI group. The penetration of HN on the volar forearm was accelerated in patients with ADI, XRI and CI, as indicated by a shorter lag time (t0) between HN application and initial vascular response. However, differentiation between CI and the other ichthyoses was not possible by this method. When using both methods in DD and EKV, no differences compared with the healthy controls could be detected on the volar forearm, where the skin was principally unaffected; only the measurements from the affected skin on alternative sites demonstrated significantly increased TEWL values. In ADI and CI, however, normal-appearing skin also showed impaired values. We conclude that both TEWL and the vascular response to penetration of HN are suitable methods to monitor the skin barrier function in keratinization disorders, and are helpful in discriminating between these disorders.

We have previously described the pathways of movement of epithelium on the tympanic membrane, showing that there are two discrete and separate zones. Four cases of keratosis of the tympanic membrane and deep external auditory canal are here reported. All patients complained of tinnitus and other aural symptoms. Sequences of otoscopic photography of daubs of dye placed on the tympanic membrane showed an abnormal anterior movement over the whole tympanic membrane in two cases and complete paralysis of movement in the two others. These findings suggest that the disorder arises from damage to basal epidermal cells caused by inflammation, which is probably due to infection. Treatment is by suction-stripping of keratin from the eardrum. Careful examination of the eardrum under magnification is required in all cases of tinnitus so as to detect this condition.

Background and Design: Psoriatic scale extracts contain a unique chemotactic peptide fraction that is likely to be involved in the induction of rhythmic transepidermal leukocyte chemotaxis. Recent studies have identified the presence of two unrelated chemotactic peptides in this fraction, ie, C5a/C5a des Arg and interleukin 8 (IL-8), and its related cytokines. To investigate their relative contribution to the transepidermal leukocyte migration as well as their interrelationship in psoriatic lesions, we have quantified concentrations of immunoreactive C5a/C5a des Arg and IL-8 in psoriatic lesional scale extracts and those from related sterile pustular dermatoses such as subcorneal pustular dermatosis and pustulosis palmaris et plantaris., Results: The concentrations of C5a/C5a des Arg and IL-8 were more significantly increased in the horny-tissue extracts from lesional skin than in those from noninflammatory orthokeratotic skin (P < .01). The increase of C5a/C5a des Arg concentration was specific to the lesional scale extracts, but showed a rather wide range of variation. By contrast, IL-8 concentration, although consistently increased in the lesional scale extracts, was also moderately increased even in noninflammatory scale extracts prepared from ichthyosis vulgaris. The elevation of IL-8 levels in psoriatic lesions was also confirmed by measuring their levels in cutaneous tissue fluid samples collected from suction blisters. However, unexpectedly, some control samples obtained from normal skin also showed a moderate increase in the IL-8 level. Neutrophil chemotactic activity correlated significantly only with the levels of C5a/C5a des Arg in the scales (P < .05). No such significant correlation was found between chemotactic activity and IL-8 or between C5a/C5a des Arg and IL-8., Conclusion: Based on these results, we speculate that, although IL-8 may exert a synergistic effect with C5a/C5a des Arg in the induction of transepidermal leukocyte chemotaxis, it constitutes a proinflammatory cytokine that is involved in the production of the persistent inflammatory changes characterized by a T-lymphocyte infiltration. In contrast, C5a/C5a des Arg seems to be generated only in the inflammatory lesional skin under specific circumstances that preferentially favor complement activation and also seems to play a major role in the induction of cyclic transepidermal leukocyte chemotaxis from "squirting papillae."

Laryngeal keratosis (LK) is a precancerous mucosal change with great similarity to oral leukoplakia. Its malignant transformation rate varies from 1% to 40%, with the highest rates being found in patients microscopically diagnosed as "keratosis with atypia" (KWA). Recent evidence indicates that even cases with only mild or moderate epithelial dysplasias are at increased risk for malignant transformation, with the highest rates occurring in patients with more severe dysplasia or carcinoma in situ. Approximately 81% of LK patients are men and the average age at diagnosis is 50 years, a decade younger than that for laryngeal carcinoma patients. A high proportion of LK patients are tobacco smokers (84%) and alcohol abusers (at least 35%). LK is almost always found on the true vocal cords and is usually bilateral (67%). Clinical signs of high risk include, in decreasing order of importance: erythroplakia, surface granularity, increased keratin thickness, increased size, recurrence after conservative removal, and long duration. The annual incidence of LK in the United States is 10.2 and 2.1 lesions per 100,000 males and females, respectively.

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.