Atypical form of transient reactive papulotranslucent acrokeratoderma in a cystic fibrosis carrier.

We report the first documented case of an atypical form of transient reactive papulotranslucent acrokeratoderma (TRPA) in a patient heterozygous for the ΔF508 CFTR(cystic fibrosis transmembrane conductance regulator) mutation. TRPA represents a condition that classically presents with translucent to white plaques that become evident after water exposure. An atypical form with persistent lesions has also been described. Our patient is a 16-year-old girl with small, white papules coalescing into pebbly plaques on the palms. This condition is exacerbated after 5-10 min of water exposure and is associated with discomfort. The skin biopsy showed expanded stratum corneum, orthohyperkeratosis and dilation of eccrine ducts consisting with TRPA. A cystic fibrosis carrier state, barrier function defect, hyperhidrosis and the intake of cyclooxygenase inhibitors may have been pathogenic factors in our patient.

Treatment Modelling of a 3D Tumour in Brain by Laser-Induced Interstitial Thermotherapy.

Introduction: There are some ways to examine heat transfer in tumor tissue, which is an important issue in bioengineering. One of these ways uses the bioheat equation, proposed by Pennes, in a continuous medium. Another one uses a porous medium to model heat transfer in living tissues. The objective of this paper was to study an approach to modelling the temperature distribution and tumour ablation in brain tissue and compare results to Pennes' approach. Methods: This approach presents and uses a porous medium as the tissue instead of a continuous medium. In addition, the two approaches (simulation in continuous and porous medium) are compared in terms of temperature simulation and amount of cell ablation. The density, heat conduction factor, and blood perfusion rate are considered functions of temperature. Results: In these approaches, after an 85-second treatment, the temperature increases to about 90°C. The temperature increase of the porous medium is relatively the same as that of the continuous medium and for this reason, the amount of cancerous cells that are ablated in a porous medium is approximately the same as that in a continuous medium. The volume of cell ablation is about 6500 mm3 for two ideas. In addition, the degree of damage, computed from the Arrhenius integral method, and the ablated volume of the tumour endorse equality at the end of treatment. According to the results, similar to the continuous approach, the porous approach predicts the temperature and amount of volume of damaged cells. Conclusion: Therefore, it is possible to use the porous approach instead of the Pennes approach for tumour treatment.

What is the role of field-directed therapy in the treatment of actinic keratosis? Part 1: overview and investigational topical agents.

Actinic keratosis (AK) constitutes the initial epidermal lesion in a disease continuum that may progress to invasive squamous cell carcinoma (SCC). A number of treatment options are available to clear lesions, and thus reduce the risk for progression. Field-directed approaches are primarily used to clear multiple AKs and subclinical lesions. Current field-directed approaches still have a number of unmet needs, and a number of investigational agents are being evaluated. Topical therapy can be improved by shortening treatment periods; enhancing tolerability, compliance, and patient satisfaction; reducing recurrence rates; and lowering cost. This 2-part review will explain the role of field-directed therapy in the treatment of AK. Part 1 focuses mainly on investigational agents that are being studied for topical patient-administered, field-directed therapy.

What is the role of field-directed therapy in the treatment of actinic keratosis? Part 2: Commonly used field-directed and lesion-directed therapies.

Actinic keratosis (AK) constitutes the initial epidermal lesion in a disease continuum that may potentially progress to invasive squamous cell carcinoma (SCC). A number of treatment options are available to clear lesions and thus reduce the risk for progression to SCC. Field-directed therapies are primarily used to clear multiple AKs and subclinical lesions. Part 1 of this review explaining the role of field-directed therapy for the treatment of AK discussed the unmet needs with current therapies and the investigational agents that are being developed to fill treatment gaps. Part 2 will mainly focus on field-directed therapies that currently are available for AK, such as resurfacing procedures, patient-administered topical therapy, and photodynamic therapy (PDT), as well as lesion-directed therapy, which is used to clear discrete lesions in relatively small numbers.

New approach of controlling the area affected in brain tumour treatment by LITT.

There are some techniques to ablate tumours of brain, breast and liver. One of them is laser irradiation. The most important problem of this technique is to injure noncancerous tissues. It is a challenging work to control the domain of laser effects. In other words, it is hard to ablate cancerous tissue without ablating noncancerous. To gain this goal, some researchers have been proposed some ways, such as using two or three applicators or moving applicator. The objective of this paper is to present an approach to control the temperature distribution and heat affected zone in brain tumours when irradiated by shielded laser beam, 1064 nm ND-YAG. The effects of laser beam, resulting in tissue temperature increasing, follows the border of tumour by defining of a dual intensity distribution. This is included two distinct intensity distributions of laser on the applicator by shielding. Treatment of an arbitrary topology of tumour will be simulated irradiation of laser by two different distributions through numerical method. Results show when dual distribution on the tumour border is used, the pattern of photon distribution is coincident by the tumour and the affected zone and temperature increasing follows the borderline of tumour, qualitatively. It shows that the ablated volume of tumour will be 53% more than when the unique distribution is used and the treatment time is shorter, resultantly.

A comparative study evaluating the tolerability and efficacy of two topical therapies for the treatment of keloids and hypertrophic scars.

BACKGROUND: Onion extract gel (OE) and 0.5% hydrocortisone, silicone and vitamin E lotion (HSE) are two over-the-counter preparations used to enhance the cosmesis of keloids and hypertrophic scars. OBJECTIVE: To determine the tolerability and efficacy of OE versus HSE versus placebo in subjects with keloids and hypertrophic scars. METHODS: Thirty subjects (> or =18 years) with keloids or hypertrophic scars were randomly assigned to one of three study preparations for 16 weeks. Scar volume was measured at baseline and weeks 4, 8, 12 and 16. Subjects and blinded investigators assessed scar parameters (induration, erythema, pigmentation alteration, pain, itching, tenderness and cosmetic appearance) and patient satisfaction at each visit using a visual analog scale (VAS). Data analysis included: mean percentage change (MPC) for subjects completing the study (n = 15); the mixed model test to determine differences between the groups over time; and the Kruskal-Wallis test for the analysis of differences in subjects' satisfaction within the three groups over 16 weeks for subjects who completed at least one follow-up visit (n = 21). RESULTS: All three preparations were well tolerated with the exception of a mild acneiform-like eruption in one OE patient. Significant improvements were obtained with OE in volume, length, width and induration and with HSE in volume, length, induration, erythema and pigmentation alteration. There was a trend showing that a higher percentage of subjects were satisfied with OE than with HSE or placebo. The Mix Model Analysis (MMA) showed significant improvements with OE over placebo in investigator cosmetic assessment, lesion induration, pigmentation and tenderness and with HSE over placebo in investigator cosmetic assessment, lesion induration, pigmentation and erythema. Improvements in erythema and pigmentation were significantly greater in HSE than in OE. CONCLUSION: Both OE and HSE were more effective than placebo in the management of hypertrophic scars and keloids.

Newer technologies/techniques and tools in the diagnosis of melanoma.

A number of non-invasive approaches have been developed over the years to provide an objective means of evaluating and diagnosing skin melanoma. However, the current gold-standard in melanoma diagnosis is the examination of a skin lesion by the trained eye of a physician followed by histological examination of an invasive excisional biopsy of the skin specimen. Diagnosis of melanoma by simple visual examination is incorrect in almost 1 out of every 3 melanoma diagnoses. Therefore, the diagnosis of early stage in-depth melanoma by non-invasive methods remains an active area of research. Recent advancements in computer and digital technology have provided several sensitive tools to evaluate the different characteristics of a melanoma lesion including its contour, edge, color, size, depth, and/or elevation. These tools include (1) digital imaging systems and computer analysis instruments such as MoleMax, SIAscope, SolarScan, MelaFind; (2) tape stripping mRNA; (3) laser-based technology such as Confocal scanning laser microscopy (CSLM), optical coherence tomography (OCT), laser Doppler perfusion imaging (LDPI), (4) Ultrasonography, and (5) other imaging tools such as electrical bio-impedance, MRI and PET scan. The ultimate goal of all investigational instrumentation is the prevention of unnecessary biopsies and a decrease in the prevalence and morbidity associated with malignant melanoma.

Evaluating the tolerability and efficacy of etanercept compared to triamcinolone acetonide for the intralesional treatment of keloids.

BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) is a proinflammatory and profibrotic cytokine that inhibits degradation of collagen and glycosaminoglycans. Etanercept, a recombinant TNF-alpha receptor fusion protein, may decrease excessive fibrous tissue in keloids. OBJECTIVE: To evaluate the tolerability and efficacy of etanercept as compared to triamcinolone acetonide (TAC) for the treatment of keloids. METHODS: Twenty subjects were randomly assigned to receive monthly intralesional injections of either 25 mg of etanercept or 20 mg of TAC for 2 months. Keloids were evaluated at baseline, week 4, and week 8 by subjects and investigators in a blinded fashion using physical, clinical, and cosmetic parameters. Photographs were taken and adverse events were noted during each evaluation. RESULTS: Etanercept improved 5/12 parameters including significant pruritus reduction, while TAC improved 11/12 parameters at week 8, although no statistical difference was observed as compared to baseline. There was no significant difference between the 2 treatment groups. Both treatments were safe and well tolerated. CONCLUSION: Etanercept was safe, well tolerated, improved several keloid parameters, and reduced pruritus to a greater degree than TAC therapy. However, further studies are required before it can be recommended for the treatment of keloids.

Prevention and management of hypertrophic scars and keloids after burns in children.

Hypertrophic scars and keloids are challenging to manage, particularly as sequelae of burns in children in whom the psychologic burden and skin characteristics differ substantially from adults. Prevention of hypertrophic scars and keloids after burns is currently the best strategy in their management to avoid permanent functional and aesthetical alterations. Several actions can be taken to prevent their occurrence, including parental and children education regarding handling sources of fire and flammable materials, among others. Combination of therapies is the mainstay of current burn scar management, including surgical reconstruction, pressure therapy, silicon gels and sheets, and temporary garments. Other adjuvant therapies such as topical imiquimod, tacrolimus, and retinoids, as well as intralesional corticosteroids, 5-fluorouracil, interferons, and bleomycin, have been used with relative success. Cryosurgery and lasers have also been reported as alternatives. Newer treatments aimed at molecular targets such as cytokines, growth factors, and gene therapy, currently in developing stages, are considered the future of the treatment of postburn hypertrophic scars and keloids in children.

Pharmacotherapy of actinic keratosis: an update.

INTRODUCTION: Actinic keratosis (AK) represents the initial intraepidermal manifestation of abnormal keratinocyte proliferation, with the potential of progression to squamous cell carcinoma (SCC). Few visible AKs lead to the use of lesion-directed treatments, including ablative and/or surgical procedures. Multiple and/or the suspicion of subclinical (non-visible) AKs lead to the use of field-directed therapies, including topical and ablative treatments. Predicting which AK will progress to SCC is difficult, and so all are treated. The goals of treatment are to eliminate visible AKs and to treat subclinical (non-visible) AKs, minimizing their risk of progression to invasive SCC, while pursuing good cosmesis. AREAS COVERED: This review discusses the prevention of AKs (such as ultraviolet light avoidance, sunscreen use, protective clothing, and frequent self-examinations, in addition to chemoprevention with retinoids, eflornithine, silymarin, and others). It also covers lesion-directed treatments (e.g., cryotherapy, electrodessication and curettage, and surgery). Field-directed treatments are also mentioned (including laser resurfacing, dermabrasion, chemical peels, topical immunomodulators (imiquimod and diclofenac), topical chemotherapeutic agents (5-fluorouracil and retinoids), and photodynamic therapy). Finally, newer and investigational treatments are discussed (including ingenol mebutate). EXPERT OPINION: There is no panacea in the treatment of AKs. The current best approach is the sequential treatment with a lesion-directed and a field-directed therapy. Several combinations seem to work well; they just need to be selected based on the evidence and adjusted to patient needs, preferences and dermatologist expertise.

Alteration in hair texture following regrowth in alopecia areata: a case report.

BACKGROUND: Alopecia areata is a common cause of hair loss seen in 3.8% of patients in dermatology clinics and in 0.2% to 2.0% of the general US population. The pathology of the disease remains poorly understood. Hair loss in alopecia areata can range from a single patch to 100% loss of body hair. When hair regrowth occurs in alopecia areata, the new hair may demonstrate pigment alterations, but a change in hair texture (ie, curly or straight) has rarely been reported as a consequence of alopecia areata. OBSERVATIONS: We report a case of a 13-year-old African American boy who experienced an alteration of hair shape following regrowth after alopecia areata. The new hair recapitulated his hair shape from early childhood. CONCLUSIONS: The precipitating factor for a change in hair texture in alopecia areata may be a result of treatment, pathophysiologic changes, or a combination of both. Whether the change is triggered at the level of stem cell differentiation, by cytokine or hormonal influences, gene expression during hair follicle development, a combination of all of these, or an unknown cause is a question that remains to be answered.

The Expression of Toll-like Receptors in Dermatological Diseases and the Therapeutic Effect of Current and Newer Topical Toll-like Receptor Modulators.

Toll-like receptors are a group of glycoproteins located mostly in cellular membranes, capable of recognizing certain molecules in exogenous microorganisms and initiating immune responses against them through the activation of several intracellular signaling pathways. Toll-like receptors can be stimulated when an inflammatory reaction is needed for the treatment of conditions, such as viral infections or skin cancer, or can be inhibited when a reduction of inflammation is necessary for the treatment of conditions, such as rheumatoid arthritis, systemic lupus erythematosus, and septic shock. In the human skin, keratinocytes and Langerhans cells are known to express these receptors. Skin conditions where Toll-like receptors are known to be upregulated include acne, psoriasis, atopic dermatitis, syphilis, leprosy, Staphylococcus aureus infections, candidiasis, and herpes simplex and varicella zoster infections. Besides imiquimod, which is the most successful and more studied topical Toll-like receptor-modulating agent to date, other topical agents, such as nicotinamide, all-trans retinoic acid, adapalene, zinc, and sodium tosylchloramide, have also been found to exert some of their action through Toll-like receptors. Recent topical agents, including CBT-SL5 and CpG-ODN, are being evaluated for the treatment of inflammatory acne and skin cancer, respectively, and have demonstrated to be effective in the treatment of those conditions.

Nonsurgical innovations in the treatment of nonmelanoma skin cancer.

Basal cell carcinoma and squamous cell carcinoma are the most frequent types of cancer in the United States and represent 75 percent and 20 percent, respectively, of all nonmelanoma skin cancers. Since ultraviolet radiation is implicated in their development, photoprotection is fundamental in their prevention. Additional preventive measures include identifying high-risk individuals for early detection along with using agents, such as retinoids, that are effective in decreasing the risk of premalignant cells further developing into carcinomas. Newer agents achieving this goal include perillyl alcohol, T4 endonuclease 5, DL-alpha-tocopherol, and alpha-difluoromethylornithine. Procedural modalities are currently the standard of treatment, but recent evidence has consistently shown that newer (nonsurgical) therapies, such as interferon, imiquimod, retinoids, and 5-fluorouracil, can be used effectively either as monotherapies or as adjuvants to those surgical modalities for the treatment of superficial nonmelanoma skin cancers and premalignant lesions. These newer therapies have achieved significant reductions in morbidity and mortality. Procedural modalities that have been evolving into important tools for the treatment of actinic keratosis and nonmelanoma skin cancers include photodynamic therapy and lasers. Nonsurgical therapies currently proving to be effective in clinical trials include ingenol mebutate and cyclooxygenase-2 inhibitors. Agents that are showing promising results in early phases of clinical trials include betulinic acid; hedgehog signaling pathway inhibitors, such as cyclopamine and GDC-0449; alpha-melanocyte-stimulating hormone analogs, such as afamelanotide; epidermal growth factor receptor inhibitors, such as gefitinib and erlotinib; anti-epidermal growth factor receptor monoclonal antibodies, such as cetuximab and panitumumab; and the 5-fluorouracil prodrug capecitabine.

Innovative therapies in the treatment of keloids and hypertrophic scars.

Keloids and hypertrophic scars are benign fibrous overgrowths of scar tissue, which results from an abnormal response to trauma. Several therapeutic modalities have been described for the treatment and prevention of these conditions, but the optimal management approach has not yet been defined. This article reviews the most recent, innovative, therapeutic strategies for the management of hypertrophic scars and keloids, including mitomycin-C, tamoxifen citrate, methotrexate, imidazolaquinolines, retinoids, calcineurin inhibitors, phenylakylamine calcium channel blockers, botulinum toxin, vascular endothelial growth factor inhibitors, hepatocyte growth factor, basic fibroblast growth factor, interleukin-10, manosa-6-phosphate, transforming growth factor beta, antihistamines, and prostaglandin E2. No consensus in treatment regimens has been reached due to the limited evidence-based information found in the literature. Most therapeutic options have potential effectiveness as both monotherapy and as combination therapy. However, recent reports offer novel modalities that may approach scarring from different angles.

Herpes simplex virus and human papillomavirus genital infections: new and investigational therapeutic options.

Human papillomavirus and Herpes simplex virus are the most common genital viral infections encountered in clinical practice worldwide. We reviewed the literature focusing on new and experimental treatment modalities for both conditions, based on to the evidence-based data available. The modalities evaluated include topical agents such as immune response modifiers (imiquimod, resiquimod, and interferon), antivirals (penciclovir, cidofovir, and foscarnet), sinecatechins, microbiocidals (SPL7013 gel, and PRO 2000 gel), along with experimental (oligodeoxynucleotides), immunoprophylactic, and immunotherapeutic vaccines.

Pharmacotherapy of actinic keratosis.

Actinic keratosis (AK) represents the initial intraepidermal manifestation of abnormal keratinocyte proliferation with the potential of progression to squamous cell carcinoma (SCC). When in limited numbers, clinically visible AKs are treated individually with ablative and/or surgical procedures (lesion-directed treatment), while multiple and sublinical AKs are treated with field-directed therapies that use ablative, nonablating and other topically applied treatment modalities. Owing to difficulties in predicting which AK will progress to SCC, the general rule is to treat all AKs. The goals of treatment are to eliminate the AKs, minimizing their risk of progression to invasive SCC, while pursuing good cosmetic outcomes. Prevention is the most important treatment modality for AKs. Avoidance of sun and artificial sources of ultraviolet light, applying sunscreen and self-examination are among the most effective preventive measures. Chemopreventive modalities such as retinoids, 2-(Difluoromethyl)-dl-ornithine (DFMO), perillyl alcohol, T4 endonuclease V, and dl-alpha-tocopherol are described. Lesion-directed treatment modalities include cryotherapy, surgery and electrodessication with or without curettage. Field-directed treatment modalities include nonablative and ablative laser resurfacing, dermabrasion, chemical peels, topical immunomodulators (imiquimod, 5-fluorouracil and diclofenac) and photodynamic therapy. And, finally, newer and investigational treatment modalities such as ingenol mebutate, resiquimod and betulinic acid are also being discussed.

Cocamidopropyl betaine.

Cocamidopropyl betaine (CAPB) is an amphoteric synthetic detergent that has been increasingly used in cosmetics and personal hygiene products (eg, shampoos, contact lens solutions, toothpaste detergents, makeup removers, bath gels, skin care products, cleansers, liquid soaps, antiseptics, and gynecologic and anal hygiene products) because it induces relatively mild skin irritation. Delayed T-cell-mediated type IV hypersensitivity reactions to CAPB have been reported, and contact sensitization prevalence is estimated at between 3.0 and 7.2%. The increasing rates of sensitization led to CAPB's being named Allergen of the Year in 2004. Related impurities rendered during the manufacturing process (such as amidoamine and dimethylaminopropylamine) are thought to play a role in sensitization.