Correlation of basal cell carcinoma subtype with histologically confirmed subclinical extension during Mohs micrographic surgery: A prospective multicenter study.

BACKGROUND: Traditionally "aggressive" histologic subtypes (HSs) of basal cell carcinoma (BCC) are more likely to quantitatively exhibit subclinical extension (SCE), requiring more stages during Mohs micrographic surgery (MMS) and, therefore, larger margins upon excision. However, the tendency for SCE has never been compared between HSs of BCC in a prospective manner. OBJECTIVE: To prospectively correlate the HS of BCC with the likelihood of SCE as defined by the number of MMS stages required to clear the tumor. METHODS: In a prospective, multicenter study involving 17 Mohs surgeons in 16 different practices across the United States, data regarding 1686 cases of BCC undergoing MMS were collected. Patient demographics, tumor characteristics, number of MMS stages required for tumor clearance, and specific BCC subtypes noted on both index biopsy and the final MMS stage were recorded. RESULTS: Analysis of the average number of MMS stages for each HS required to clear tumor revealed 2 distinct degrees of SCE (P < .0001): high (higher than average) risk of SCE (1.9 stages, 1.0 SD) and low (lower than average) risk of SCE (1.6 stages, 0.9 SD). Subtypes of BCC within the high category were morpheaform (2.1), infiltrative (1.9), metatypical (1.9), mixed (1.8), and superficial (1.8). The low category included BCC subtypes of basosquamous (1.6), micronodular (1.6), nodular (1.6), and unspecified (1.5). Three hundred twenty-four cases (22.0%) manifested HS drift or a change in subtype from index biopsy to the final MMS stage. Superficial BCC was the only subtype that showed an increase in prevalence from index biopsy to the final MMS stage (from 16.0% to 25.8%; P < .0002). LIMITATIONS: HSs from index biopsy may not be representative of all HSs present, resulting in sampling bias. CONCLUSION: SCE of superficial BCC was as likely as SCE of BCC subtypes that are considered "aggressive" and are deemed "appropriate" for MMS by the appropriate use criteria. Our study also found that when HS drift occurs, the most likely subtype to extend subclinically is superficial BCC.

Successful treatment of perniosis with hydroxychloroquine.

BACKGROUND: The current medical therapies for perniosis are diverse. The agents used have produced variable results and lack evidence-based data. OBJECTIVE: To determine outcomes of patients with perniosis treated with hydroxychloroquine. METHODS: In this retrospective study, patients with a diagnosis of perniosis treated with hydroxychloroquine were analyzed for dosage required, subjective improvement in signs and symptoms, and adverse drug reactions. RESULTS: Hydroxychloroquine resulted in improvement of symptoms in four of five patients. Review of the literature has revealed 12 out of 51 cases have responded to hydroxychloroquine alone or in combination with other therapies. CONCLUSION: Hydroxychloroquine is a relatively safe, well tolerated alternative therapy for the treatment of perniosis and should be considered as part of the initial management. Additional data are needed to further evaluate this drug in a prospective manner and in a larger population of patients.

Phenytoin-associated hypersensitivity syndrome with features of DRESS and TEN/SJS.

Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome, toxic epidermal necrolysis (TEN), and Stevens-Johnson syndrome (SJS) are rare and life-threatening conditions that may be precipitated by anticonvulsive agents. We describe a patient with overlapping features of these hypersensitivity syndromes.

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.

Novel therapies for pemphigus vulgaris: an overview.

Pemphigus comprises a group of autoimmune, mucocutaneous blistering disorders. Its principal cause may be a group of antibodies directed against proteins present on the surface of keratinocytes that provide mechanical structure to the epidermis. In the case of pemphigus vulgaris, the characteristic blistering noted just above the basal layer may be triggered by autoantibodies directed against desmoglein 3 (Dsg3). The process by which the binding of these antibodies leads to acantholysis, apoptosis and eventual loss of epidermal function is not completely understood. Current therapies are primarily directed against the formation of these antibodies by suppression of the immune system, and are associated with significant adverse events. As our understanding of the pathophysiology of pemphigus increases, newer therapies have been proposed and evaluated. These novel therapies include intravenous immunoglobulin, plasmapheresis, immunoadsorption, extracorporeal photochemotherapy, biological agents, as well as experimental therapies such as cholinergic receptor agonists, Dsg3 peptides and a p38 mitogen-activated protein kinase inhibitor. Current limitations to the widespread use of these therapies include cost, a lack of consistent data regarding their benefit, limited availability, and the experimental nature of some of the treatments. This review highlights the latest case reports and studies that employ established as well as new therapeutics in a novel way to treat this rare, but serious, disorder.

Treatment of keloid scars post-shave excision with imiquimod 5% cream: A prospective, double-blind, placebo-controlled pilot study.

BACKGROUND: No effective treatment exists for permanent keloid removal. When applied to excised-sites, imiquimod 5% cream reduces keloid recurrence. Case series suggest the tolerability and efficacy of imiquimod 5% application to sites of shaved keloids; however, this has not been verified in placebo-controlled studies. OBJECTIVE: To determine the tolerability and compare the efficacy of imiquimod 5% and vehicle cream in lowering keloid recurrence after shaving. METHODS: Twenty randomized, shaved keloids were administered imiquimod 5% or vehicle cream nightly for two weeks, and then given three times a week under occlusion for one month. Pain, tenderness, pruritus and keloid recurrence were evaluated at baseline, week 2, week 6 and 6 months. TOLERABILITY: Tenderness and pain were significantly (p = 0. 02 and p = 0. 02, respectively) higher at week 2 in the imiquimod group than for those treated with vehicle cream. Pruritus did not attain statistical difference between the groups. EFFICACY: At 6 months, keloid recurrence rates were 37.5% (3/8) in the imiquimod group and 75% (3/4) in the vehicle group, p = 0.54. CONCLUSION: Imiquimod was well tolerated. There was not enough statistical power to detect a significant difference in six-month keloid recurrence rates between the two treated groups.

Ecthyma gangrenosum caused by Escherichia coli bacteremia: a case report and review of the literature.

Ecthyma gangrenosum (EG) is a serious and well-recognized cutaneous condition. Development of EG is most commonly associated with Pseudomonas aeruginosa septicemia. Other organisms, such as Escherichia coli, have been identified less often as the cause of EG. We describe a 50-year-old man previously diagnosed with acute myelogenous leukemia (AML) who developed an E coli-colonized EG lesion secondary to E coli bacteremia. This case represents the seventh of its kind in the literature and the first case in a patient with AML. In addition, a brief review of the etiopathology and management of EG is presented.

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.

A review of the biologic effects, clinical efficacy, and safety of silicone elastomer sheeting for hypertrophic and keloid scar treatment and management.

Silicone elastomer sheeting is a medical device used to prevent the development of and improve the appearance and feel of hypertrophic and keloid scars. The precise mechanism of action of silicone elastomer sheeting has not been defined, but clinical trials report that this device is safe and effective for the treatment and prevention of hypertrophic and keloid scars if worn over the scar for 12 to 24 hours per day for at least 2 to 3 months. Some of the silicone elastomer sheeting products currently on the market are durable and adhere well to the skin. These products are an attractive treatment option because of their ease of use and low risk of adverse effects compared to other treatments, such as surgical excision, intralesional corticosteroid injections, pressure therapy, radiation, laser treatment, and cryotherapy. Additional controlled clinical trials with large patient populations may provide further evidence for the efficacy of silicone elastomer sheeting in the treatment and prevention of hypertrophic and keloid scars. The purpose of this article is to review the literature on silicone elastomer sheeting products and to discuss their clinical application in the treatment and prevention of hypertrophic and keloid scars.

Update on rosacea and anti-inflammatory-dose doxycycline.

Approximately 13 million individuals in the United Sates suffer from rosacea, a recurrent disease that may require long-term therapy. Topical and oral antibiotics have been used to treat rosacea; however, high-dose antibiotics or long-term, low-dose antibiotics commonly used for the treatment of rosacea flares or for rosacea maintenance therapy, respectively, can lead to the development of antibiotic-resistant organisms. The first oral medication approved by the U.S. Food and Drug Administration for the treatment of rosacea in the United States is Oracea (CollaGenex Pharmaceuticals Inc., Newtown, PA, USA). Oracea is a 40 mg capsule of doxycycline monohydrate, containing 30 mg immediate-release and 10 mg delayed-release doxycycline beads ("anti-inflammatory-dose doxycycline"). Anti-inflammatory-dose doxycycline is not an antibiotic and does not lead to the development of antibiotic-resistant organisms. Each capsule of anti-inflammatory-dose doxycycline contains a total of 40 mg of anhydrous doxycycline as 30 mg of immediate-release and 10 mg of delayed-release beads. In contrast to other oral therapies, anti-inflammatory-dose doxycycline is taken once daily, which may increase treatment compliance. The results of two phase III trials have been encouraging, leading to the recent release (summer 2006) of Oracea for the treatment of rosacea in the United States. Anti-inflammatory-dose doxycycline should not be used by individuals with known hypersensitivity to tetracyclines or increased photosensitivity, or by pregnant or nursing women (anti-inflammatory-dose doxycycline is a pregnancy category-D medication). The risk of permanent teeth discoloration and decreased bone growth rate make anti-inflammatory-dose doxycycline contraindicated in infants and children. However, when used appropriately in patients with rosacea, anti-inflammatory-dose doxycycline may help prolong the effectiveness and life span of our most precious antibiotics.

Bacterial derived proteoliposome as ideal delivery system and cellular adjuvant.

We explored the potential of a proteoliposome (PL) from the outer membrane of N. meningitidis B, as an immunopotentiator and as a vector for antigen delivery to dendritic cells (DC). DC were incubated with PL resulting in up-regulation of MHC-II, CD40, CD80, and CD86 expression and production of TNFalpha and IL12(p70). Ovoalbumin (OVA) was incorporated within PL (PL-OVA). PL-OVA presented OVA-specific peptides to CD4+ and CD8+ OVA-specific T-cell hybridomas. PL exerts an immunomodulatory effect on DC and is a general system to deliver antigens for presentation to CD4+ and CD8+ T-cells possibly implicated in the induction CD8+ cytotoxic T lymphocytes (CTLs) responses.

New method for obtaining conjugated vaccines.

We describe a new method to obtain conjugates against Neisseria meningitidis serogroups A, B, C, Vibrio cholera, and Salmonella typhi and their immunogenicity in Balb/c mice. The saccharides were activated by basic hydrolysis with the generation of amine groups in the saccharidic chain, and these groups were linked to carboxyl groups of tetanus toxoid by via carbodiimida-mediated reaction. The resultant conjugates were administered to mice for the immunogenicity studies. The pirogenicity of LPS was measured by LAL assay. The anti-saccharide IgG, IgG1, and IgG2a antibodies were evaluated. A significant decrease in the pirogenicity of LPS after basic hydrolysis treatment was observed. The conjugates elicited higher titers of anti-polysaccharides or anti-LPS IgG, IgG1, and IgG2a in conjugates than in unconjugated saccharides. The results indicate that we have a new method for obtaining conjugated vaccines and we have demonstrated that after conjugation there was a change in the responses for all saccharides, from thymus-independent to thymus-dependent responses.