Technology has rapidly changed our capabilities in many fields, including medicine. Two of the most important developments have been immediate, on-demand, on-site access to information via the Internet and the ability to easily collect, organize, and analyze huge volumes of information with easy-to-use computerized databases. Our challenge is to best use our new access to information.
IT SEEMS too natural to me to suggest that medicine is rapidly changing. I went to medical school in the early 1980s and was impressed by the rapid progress in our supposed understanding of disease mechanisms. These advances were primarily advances in "wet lab [laboratory]" sciences, such as immunology and molecular biology. In the 1990s there has been a swift movement toward unlocking the genetic mechanism of disease. Therapeutically, there have even been attempts at altering the genetic makeup of an individual or their cells to cure or alter the progression of a disease. Yet, it seems to me as a clinician that no change has been as dramatic as the changing landscape of who is primarily responsible for patient care and who pays the bill.
During the last decades, management of intertriginous psoriasis (IP) has been unsatisfactory because of the adverse effects associated with long-term corticosteroid application and the lack of alternatives. Recently, both pimecrolimus and tacrolimus have been investigated for this indication and shown to be safe and effective. So far, to our knowledge, a comparison of one of these drugs with standard regimens for IP has not been performed.
A single-center, 4-week, double-blind, randomized, vehicle-controlled comparison study to assess the safety and efficacy of 1% pimecrolimus, 0.005% calcipotriol, and 0.1% betamethasone valerate in the treatment of IP.
Dermatologic hospital at Ruhr University of Bochum.
Eighty adults with IP.
Treatment of IP with 1% pimecrolimus, 0.005% calcipotriol, 0.1% betamethasone, or the vehicle once daily for 28 days.
Mean reduction of the Modified Psoriasis Area and Severity Index (M-PASI) score after 28 days of treatment was considered the primary outcome measure, which was analyzed on an intention-to-treat basis. The secondary outcome was a visual analog scale score for itching.
After 4 weeks of treatment, the 3 active compounds and the vehicle resulted in a significant decrease in mean M-PASI score (86.4% for 0.1% betamethasone, 62.4% for 0.005% calcipotriol, 39.7% for 1% pimecrolimus, and 21.1% for vehicle). The 0.1% betamethasone was significantly more effective than 1% pimecrolimus during the study period (P<.05). No significant difference was found between 0.005% calcipotriol and 0.1% betamethasone and between 0.005% calcipotriol and 1% pimecrolimus. The visual analog scale score for pruritus decreased by 78% for 0.1% betamethasone, 57% for 0.005% calcipotriol, 35% for 1% pimecrolimus, and 43% for the vehicle, again demonstrating a clear advantage for the corticosteroid (P<.05).
The 1% pimecrolimus was shown to be less potent than 0.1% betamethasone in the treatment of IP. Considering the adverse-effect profile of long-term application of corticosteroids, occasional or intermittent rescue therapy with short-term topical corticosteroids and maintenance with a less potent agent, such as 1% pimecrolimus or 0.005% calcipotriol, might be appropriate for patients with IP in general practice.
To assess the safety and efficacy of 4 concentrations of tazarotene cream in the treatment of facial photodamage.
Prospective weekly multicenter, investigator-masked, randomized, parallel-group study.
University hospitals and clinical research centers.
Three hundred forty-nine subjects with facial photodamage.
Daily topical application of tazarotene cream (0.01%, 0.025%, 0.05%, and 0.1%) compared with its vehicle and with 0.05% tretinoin emollient cream.
Tazarotene cream and tretinoin cream significantly improved mottled hyperpigmentation and fine wrinkles. At week 24, treatment success rates based on global responses were 67% (39 of 58 subjects) with 0.1% tazarotene, 52% (30 of 58 subjects) with 0.05% tazarotene, 36% (21 of 58 subjects) with 0.025% tazarotene, 41% (24 of 59 subjects) with 0.01% tazarotene, 55% (32 of 58 subjects) with 0.05% tretinoin, and 22% (13 of 58 subjects) with vehicle. Local adverse events, although more frequent with tazarotene at higher concentrations, were generally mild to moderate.
Tazarotene in a cream formulation is safe and is associated with positive changes in the treatment of photodamaged facial skin.
Objective To evaluate the efficacy and safety of a novel mechlorethamine hydrochloride, 0.02%, gel in mycosis fungoides.
Design Randomized, controlled, observer-blinded, multicenter trial comparing mechlorethamine, 0.02%, gel with mechlorethamine, 0.02%, compounded ointment. Mechlorethamine was applied once daily for up to 12 months. Tumor response and adverse events were assessed every month between months 1 and 6 and every 2 months between months 7 and 12. Serum drug levels were evaluated in a subset of patients.
Setting Academic medical or cancer centers.
Patients In total, 260 patients with stage IA to IIA mycosis fungoides who had not used topical mechlorethamine within 2 years and were naive to prior use of topical carmustine therapy.
Main Outcome Measures Response rates of all the patients based on a primary clinical end point (Composite Assessment of Index Lesion Severity) and secondary clinical end points (Modified Severity-Weighted Assessment Tool and time-to-response analyses).
Results Response rates for mechlorethamine gel vs ointment were 58.5% vs 47.7% by the Composite Assessment of Index Lesion Severity and 46.9% vs 46.2% by the Modified Severity-Weighted Assessment Tool. By the Composite Assessment of Index Lesion Severity, the ratio of gel response rate to ointment response rate was 1.23 (95% CI, 0.97-1.55), which met the prespecified criterion for noninferiority. Time-to-response analyses demonstrated superiority of mechlorethamine gel to ointment (P < .01). No drug-related serious adverse events were seen. Approximately 20.3% of enrolled patients in the gel treatment arm and 17.3% of enrolled patients in the ointment treatment arm withdrew because of drug-related skin irritation. No systemic absorption of the study medication was detected.
Conclusion The use of a novel mechlorethamine, 0.02%, gel in the treatment of patients with mycosis fungoides is effective and safe.
Trial Registration clinicaltrials.gov Identifier:NCT00168064
Actinic prurigo is a chronic familial photodermatosis that occurs mostly in Amerindians. Eight patients with actinic prurigo were given intermittent 3- to 14-day courses of topical 0.05% clobetasol 17-propionate cream or ointment in 1988 and 1989. Seven out of eight patients cleared or markedly improved. All of the patients had been resistant previously to milder topical corticosteroids. There have been no side effects. This therapy offers an effective alternative to systemic corticosteroids, oral psoralen with long-wave UV radiation in the A range, or thalidomide.
Desonide cream, 0.05%, is a new nonfluorinated topical steroid cream. A doubleblind clinical evaluation of 133 patients demonstrates it to be as effective as 0.025% fluocinolone acetonide cream in the treatment of steroid responsive dermatoses with no statistically significant preponderance for either steroid.
Favre-Racouchot disease (FRD) is a cutaneous condition characterized by multiple, large, open comedones and nodules in the periorbital areas. Underlying skin is solar damaged, often pale, yellowish, diffusely thickened, and furrowed.1 It affects mainly white elderly men and has been connected with the long-term and repeated exposure to the sun and smoking.2Application of topical retinoids seems to represent the mainstay of FRD treatment. Tazarotene is a synthetic retinoic acid receptor–specific retinoid used for the treatment of photodamaged skin and acne vulgaris. Although its efficiency in FRD treatment seems predictable, we found no relevant reports in the literature.
To assess the safety and efficacy of topical 0.1% tacrolimus vs 0.05% clobetasol propionate.
Randomized double-blind trial.
Department of Dermatology, Hospital Central Dr Ignacio Morones Prieto, San Luis Potosí, México.
From 20 children with vitiligo, 2 symmetrical lesions of about the same size and evolution time were selected. They were devoid of any topical or systemic therapy for 2 months prior to inclusion. Interventions Treatment with topical tacrolimus and clobetasol for a 2-month period.
The grade of repigmentation was evaluated by color slides at baseline and again at every 2-week visit. The slides were analyzed by 2 clinicians unrelated to the study and by a morphometric digitalized computer program. Characteristics of pigment, time of response, symptoms, telangiectasias, and atrophy were evaluated every 2 weeks.
Eighteen (90%) of the 20 patients experienced some repigmentation. The mean percentage of repigmentation was 49.3% for clobetasol and 41.3% for tacrolimus. Lesions in 3 patients using clobetasol presented atrophy, and 2 lesions incurred telangiectasias; tacrolimus caused a burning sensation in 2 lesions.
Tacrolimus proved almost as effective as clobetasol propionate to restore skin color in lesions of vitiligo in children. Because it does not produce atrophy or other adverse effects, tacrolimus may be very useful for younger patients and for sensitive areas of the skin such as eyelids, and it should be considered in other skin disorders currently treated with topical steroids for prolonged periods.
Effective topical drug therapy requires drug delivery into the skin to produce the desired pharmacodynamic response. For topical corticosteroids, the visual skin-blanching assay has been used to rank the potency of the corticosteroids and their overall efficacy. While vehicles have been shown to influence the resulting blanching response, the dose of drug applied has not always produced proportional differences in the blanching assay. The mechanism of the nonproportional pharmacodynamic response to the corticosteroid dose is unclear. We describe four methods for assessing the dose-response relationship of topical betamethasone dipropionate on the ventral forearm of six human subjects: duration, concentration, film thickness, and surface area. Drug uptake analysis in human stratum corneum and the resulting pharmacodynamic response, measured visually and with a chromameter, were performed with each method to quantify the dose-response relationship.
Only the concentration and duration methods demonstrated an increase in mean drug uptake with increasing dose. The maximal mean pharmacodynamic response reflected the mean drug uptake with all four methods. Application conditions for maximal pharmacodynamic activity of topical betamethasone dipropionate in the skin include short duration of treatment (< or = 2 hours), a lower concentration than commercially marketed, and thin film thicknesses (1 to 5 microns).
A dose response can be produced by increasing the drug concentration or the duration of application time. Achievement of steady-state betamethasone dipropionate uptake into the stratum corneum was not commensurate with the maximal pharmacodynamic response. Very small amounts of this potent corticosteroid within the skin appear to maximize the receptor response to drug.
The effect of topical steroids on patch test responsiveness was investigated in 15 subjects. A 0.1% triamcinolone acetonide ointment and a control preparation were applied three times daily to opposing sites on the upper part of the inner arms prior to patch testing. From a total of 18 pairs of patch tests applied to the 15 patients, substantial differences in the paired reactions were seen in only three patients after 96 hours. Of these, two had the more intense reaction on the control side, and the third had a greater reaction on the triamcinolone-pretreated side. Previously applied, intermediate-strength topical steroids are unlikely to prevent the detection of contact allergy by patch testing.
To determine the efficacy and safety of 0.1% tazarotene cream for the treatment of photodamage.
A 24-week multicenter, double-blind, randomized, vehicle-controlled intervention study followed by a 28-week open-label extension.
Ambulatory patients in private and institutional practice.
Of 563 patients with facial photodamage, 91% and 86% completed the double-blind and open-label phases, respectively. In the double-blind phase, 20 of 283 tazarotene-treated patients and 1 of 280 vehicle-treated patients discontinued treatment owing to adverse events.
Once-daily application of 0.1% tazarotene cream or nonmedicated vehicle cream to the face for 24 weeks. Then, all continuing patients received treatment with 0.1% tazarotene cream for another 28 weeks.
Primarily, fine wrinkling and mottled hyperpigmentation. Also, lentigines, elastosis, pore size, irregular depigmentation, tactile roughness, coarse wrinkling, telangiectasia, actinic keratoses, overall integrated assessment of photodamage, global response to treatment, patients' overall assessment of photodamage, and plasma levels of tazarotenic acid.
Compared with the vehicle, at week 24 tazarotene resulted in a significantly greater incidence of patients achieving treatment success (>or=50% global improvement) and at least a 1-grade improvement in fine wrinkling, mottled hyperpigmentation, lentigines, elastosis, pore size, irregular depigmentation, tactile roughness, coarse wrinkling, and the overall integrated assessment of photodamage (P<.01). Additional clinical improvement occurred with continued tazarotene treatment and had not plateaued by week 52. Plasma tazarotenic acid concentrations did not exceed 0.71 ng/mL.
Once-daily applications of 0.1% tazarotene cream significantly reduced multiple signs of photodamage. Plasma levels of tazarotenic acid remained below those of endogenous retinoids.
Short-contact application of 0.1% tazarotene gel for acne was devised to minimize local adverse effects. Its efficacy and safety are unknown.
To assess acne improvement and tolerability during 12 weeks of short-contact treatment with 0.1% tazarotene gel vs a nonmedicated gel control.
A randomized, masked, vehicle-controlled trial.
Outpatient facilities at an urban medical school and an affiliated suburban office practice.
Ninety-nine volunteers with facial acne were enrolled; 81 completed the study.
Thirty-three patients were randomly assigned to each of 3 groups: T + T applied 0.1% tazarotene gel twice daily, T + V applied 0.1% tazarotene gel once daily and vehicle gel once daily, and V + V applied vehicle gel twice daily. Patients adjusted the contact period as tolerated, between 30 seconds and 5 minutes per application.
Acne efficacy by reduction in acne lesions, treatment success (50%-100% improvement in global response to treatment) and improvement in overall disease severity. Local adverse effects, scored from none to severe.
By week 12, T + T and T + V achieved significantly greater improvement in acne than V + V based on mean percentage reduction in noninflammatory lesions (46% and 41% vs 2%; P =.002) and inflammatory lesions (38% and 34% vs 9%; P =.01), percentage of treatment successes (64% and 61% vs 15%; P<.001), and reduction in overall disease severity (30% and 29% vs 3%; P<.001). Local adverse effects did not differ significantly among the 3 groups after week 4.
Short-contact 0.1% tazarotene gel therapy is a safe and effective new method of acne treatment.
Discoid lupus erythematosus (DLE), which is an autoimmune inflammatory disorder of the skin, often leads to scarring and alopecia. Current treatment options include topical and systemic glucocorticoids, antimalarial agents, and thalidomide. These treatments are often limited by a lack of efficacy or by adverse effects.We conducted an open-label pilot study using 0.1% tacrolimus (Protopic) ointment for the treatment of 5 subjects with biopsy-proved DLE. All subjects were receiving stable doses of systemic DLE-directed therapies for at least 4 weeks before study entry and had not applied topical steroids to the treatment area for 4 weeks.
Intertrigo is a combination of infectious, mechanical, and inflammatory changes of the skin folds that can be recurrent and chronic. Friction between skin folds and increased moisture promote an irritated cutaneous environment that increases the chance of infection. The combination of these factors leads to an inflammatory process.Historically, medium- to mild-potency topical steroids were prescribed for quick resolution of these inflammatory changes, but continued long-term therapy is sometimes required. This is not optimal because of atrophy and striae formation, especially in the intertriginous areas, associated with long-term topical steroid use. Thus, we used a nonsteroidal topical ointment, 0.1% tacrolimus, for 6 weeks in 10 patients with intertrigo.
To determine if the complete response rates of lentigo maligna (LM) to imiquimod, 5%, cream can be improved by the addition of a topical retinoid.
Prospective randomized study of patients treated with imiquimod alone vs imiquimod plus a topical retinoid, followed by conservative staged excisions.
Mohs surgical clinic in an academic institution.
Ninety patients with biopsy-confirmed LM.
Ninety patients with 91 LMs were randomized into 2 groups. One group received imiquimod, 5%, cream 5 d/wk for 3 months, while the other group also received tazarotene, 0.1%, gel 2 d/wk for 3 months. Following topical therapy, all patients underwent staged excisions and frozen section analysis with Melan-A immunostaining to confirm negative margins.
The presence or absence of residual LM at the time of staged excision. Results: Forty-six patients with 47 LMs were randomized to receive monotherapy: 42 of 47 LMs reached the intended treatment duration, with 27 complete responses (64%). Forty-four patients with 44 LMs were randomized to receive combined therapy: 37 of 44 LMs reached the intended treatment duration, with 29 complete responses (78%). This difference did not reach statistical significance (P=.17). There have been no recurrences to date, with a mean follow-up period of 42 months.
Among patients who received topical imiquimod with vs without tazarotene, 22% (8 of 37) of lesions vs 36% (15 of 42) of lesions showed residual LM on staged excisions. Pretreating LM with imiquimod, 5%, cream may decrease surgical defect sizes; however, total reliance on topical imiquimod as an alternative to surgery may put the patient at increased risk of a local recurrence.
To assess the potential of a superhigh-potency 0.1% fluocinonide cream to suppress the hypothalamic-pituitary-adrenal (HPA) axis in pediatric patients with atopic dermatitis.
A multicenter, multiple-dose, open-label safety study in 4 age cohorts with 0.1% fluocinonide cream applied once or twice daily for 2 weeks.
Clinical outpatient setting.
Patients with moderate to severe atopic dermatitis with 20% or more of the body surface area involved were included in the study. Each cohort began only after evaluation of the preceding cohort: ages 12 to younger than 18 years (cohort 1); 6 to younger than 12 years (cohort 2); 2 to younger than 6 years (cohort 3); and 3 months to younger than 2 years (cohort 4).
Assessment of HPA axis suppression, local and systemic adverse events, and change in disease status from baseline.
Suppression of the HPA axis was not observed in any patient treated once daily for the 2 youngest cohorts. Suppression was observed in 1 (7%) of 15 and 2 (12%) of 16 patients in the fluocinonide twice-daily group in cohorts 1 and 2, respectively. In all 4 cohorts, more than 90% of patients in the fluocinonide once-daily and twice-daily groups showed improvement in their disease status.
Once-daily treatment with 0.1% fluocinonide cream for 2 weeks does not result in HPA axis suppression under the conditions of this study. Once-daily applications provided similar or better efficacy as twice-daily applications with a lower risk of HPA axis suppression. The frequency of HPA axis suppression is no greater in younger children than in older children.
isrctn.org Identifier: ISRCTN71227633.
To determine the safety and efficacy of a new gel formulation of podofilox in the treatment of anogenital warts.
Double-blind, randomized, multicenter, vehicle-controlled investigation.
Private dermatology practices, university clinics (dermatology, gynecology, and infectious diseases), and contract research organizations.
Three hundred twenty-six patients with anogenital warts.
Number of patients with clearing of all treated warts (treatment success).
The 0.5% podofilox gel was significantly better than vehicle gel for successfully eliminating and reducing the number and size of anogenital warts. In the intent-to-treat population, 62 (37.1%) of 167 patients treated with 0.5% podofilox gel had complete clearing of the treated areas (treatment successes) compared with 2 (2.3%) of 86 patients who had clearing of warts with the vehicle gel (P < .001) after 4 weeks. Nineteen additional patients treated with 0.5% podofilox gel and 2 patients treated with vehicle gel had clearing of warts with continued treatment up to 8 weeks. After 8 weeks, 35.9% of the baseline anogenital warts treated with 0.5% podofilox gel remained; this was significantly fewer than in the vehicle-treated group (88.4% of the baseline number) (P = .001). The 0.5% podofilox gel was generally well tolerated, with predominantly mild or moderate local adverse reactions occurring in the majority of patients. Only 7 patients (3.2%), all receiving 0.5% podofilox gel, discontinued study treatment because of drug-related local reactions.
The results demonstrated that 0.5% podofilox gel is safe and significantly more effective than vehicle gel in the treatment of anogenital warts.
Amitriptyline, a first-generation tricyclic antidepressant, works by inhibiting serotonin and noradrenaline reuptake; it also blocks sodium channels. Ketamine is an N-methyl-D-aspartate (NMDA) receptor antagonist. The NMDA receptors have a key role in the maintenance of chronic pain syndromes. Normally, after a single painful stimulus, only glutamatergic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors are activated. However, when a barrage of impulses reaches the dorsal horn, the neuron does not have time to repolarize properly. The NMDA receptors have a magnesium molecule that normally blocks the channel, but when the intracellular potential rises and the neuron remains depolarized for a prolonged period (as with rapid glutamatergic firing), the magnesium molecule is dislodged, thus opening the channel to the influx of calcium and further depolarizing the cell. The influx of calcium activates second messengers and promotes the transcription of various genes, resulting in the increased production of glutamate and other excitatory neurotransmitters and the expression of supersensitive subtypes of sodium channels in primary sensory neurons. This cascade of events leads to increased excitability of the neurons of the pain pathways; thus, painful stimulation continues (the wind-up phenomenon).
Author Contributions: Dr Feldman had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Feldman. Acquisition of data: Yentzer, Hick, Williams, Inabinet, and Wilson. Analysis and interpretation of data: Yentzer, Wilson, Camacho, Russell, and Feldman. Drafting of the manuscript: Yentzer, Hick, and Russell. Critical revision of the manuscript for important intellectual content: Yentzer, Williams, Inabinet, Wilson, Camacho, Russell, and Feldman. Statistical analysis: Camacho and Russell. Obtained funding: Feldman. Administrative, technical, and material support: Williams, Inabinet, and Feldman. Study supervision: Feldman.
No long-term randomized controlled clinical trial has compared the efficacy of cryosurgery alone vs cryosurgery following fluorouracil applications for the treatment of actinic keratosis.
To determine the 6-month outcome of a 1-week course of 0.5% fluorouracil followed by cryosurgery.
Prospective, multicenter, randomized, double-blind, vehicle-controlled clinical trial performed in community and academic outpatient clinics.
A total of 144 patients with 5 or more visible or palpable actinic keratoses on the face.
Topical 0.5% fluorouracil or vehicle once daily for 7 days. At the 4-week follow-up visit, residual lesions were treated with cryosurgery.
Reduction in facial actinic keratoses from baseline to 4 weeks and 6 months.
At 4 weeks, mean actinic keratosis lesion count was reduced by 62.4% in the 0.5% fluorouracil group vs 28.8% in the vehicle group (P<.001), and complete clearance was achieved in 16.7% of patients in the 0.5% fluorouracil group vs 0% of those in the vehicle group (P<.001). At 6 months, mean lesion count was reduced by 67.0% in the 0.5% fluorouracil plus cryosurgery group vs 45.6% in the vehicle plus cryosurgery group (P =.01), and significantly more patients in the 0.5% fluorouracil plus cryosurgery group than in the vehicle plus cryosurgery group had complete clearance (30% vs 7.7%; P<.001).
A 1-week course of topical 0.5% fluorouracil before cryosurgery is significantly more effective in reducing patients' numbers of actinic keratosis lesions 6 months after treatment than cryosurgery alone. The high occurrence rate of actinic keratosis lesions at 6 months suggests a need for follow-up.
To compare the efficacy and safety of a novel formulation of 15% azelaic acid gel (Finacea; Berlex Laboratories, Inc, Montville, NJ) with 0.75% metronidazole gel (MetroGel; Galderma Laboratories LP, Fort Worth, Tex) as topical therapy for moderate, papulopustular facial rosacea.
Multicenter, double-blind, randomized, parallel-group study.
Thirteen US centers.
A total of 251 patients with papulopustular rosacea with persistent erythema and telangiectasia.
Patients were randomized to receive azelaic acid gel or metronidazole gel twice daily for 15 weeks.
Nominal and percent change in inflammatory lesion count, change in erythema and telangiectasia severity ratings, investigator's global assessment of rosacea, and investigator's and patient's overall improvement ratings.
Azelaic acid gel was superior to metronidazole gel in reduction of mean nominal lesion count (-12.9 vs -10.7, respectively) (P =.003) and mean percent decrease in inflammatory lesions (-72.7% vs -55.8%, respectively) (P<.001). With respect to erythema severity, 56% of azelaic acid gel-treated patients were rated improved vs 42% of metronidazole gel-treated patients (P =.02). The effectiveness of metronidazole gel on these variables seemed to plateau after week 8, whereas azelaic acid gel demonstrated progressive improvement through week 15. Neither treatment had a clinically appreciable effect on telangiectasia. Both the investigator's global assessment (P =.02) and overall assessment of improvement (P =.005) showed a significant therapeutic advantage for azelaic acid gel. Azelaic acid gel also scored higher on the patient's overall assessment of efficacy. Both treatments were rated as having high cosmetic acceptability. No serious or systemic treatment-related adverse events were reported in either group.
Use of 15% azelaic acid gel twice daily for 15 weeks demonstrated significant superiority over using 0.75% metronidazole gel in improving principal signs of rosacea (inflammatory lesions and erythema).
In their recent article, Elewski et al1 conclude that the "use of 15% azelaic acid gel twice daily for 15 weeks demonstrated significant superiority over using 0.75% metronidazole gel in improving principal signs of rosacea (inflammatory lesions and erythema)." This conclusion was based on differences in mean inflammatory lesion count reductions at the last observation carried forward: 12.9 mean inflammatory lesion count reduction for azelaic acid vs a 10.7 reduction for metronidazole (Δ = 2.2). At week 15, the difference was 13.6 for azelaic acid vs 11.8 for metronidazole (Δ = 1.8). However, in the "Methods" section it is stated, "A difference of 5 lesions in mean lesion count for the 2 treatments was considered to be medically relevant" and the sample size was calculated to detect this difference of Δ = 5 with a power of 80%. Thus, the observed difference (Δ = 2.2) was statistically significant but power of the test was below 80%.
Although patch-stage mycosis fungoides (MF) has a generally good prognosis, and long-term survival rates with current therapies (UV-B, photochemotherapy, topical nitrogen mustards, electron-beam therapy) are similar, there is concern regarding their potential adverse effects. Narrowband or TL-01 UV-B phototherapy (311 nm), in use for more than 10 years, is more effective than broadband UV-B for the treatment of psoriasis, with an efficacy approaching that of psoralen UV-A. This open study assesses TL-01 as an alternative therapy for patch-stage MF.
Eight white patients (4 men, 4 women; age range, 66-83 years) with histologically proven patch-stage MF received TL-01 phototherapy 3 times weekly using a standard protocol. Complete clearance of MF was achieved in 6 cases in a mean of 9 weeks or 26 treatments (range, 20-37 weeks) and 4 patients have had prolonged remissions. Mean duration of clinical improvement has been 20 months (range, 11-40 months). Partial response to TL-01 or poor histologic improvement was associated with rapid relapse.
TL-01 is an effective, convenient therapy that may have less risk of long-term adverse effects than current alternatives. Although larger prospective studies are necessary, for some patients intermittent courses of TL-01 may offer effective long-term therapy.
(1) To determine the prevalence of allergen sensitivity in patients with past or present leg ulcers in 2 North American study centers vs European study findings and the North American Contact Dermatitis Group (NACDG) database and (2) to delineate a standard battery of allergens for patch testing in North American patients that is representative of the newer dressings and wound care products.
Fifty-four patients, with or without dermatitis, were prospectively entered in the study. The patients were patch tested to the NACDG standard series and a comprehensive supplemental series of 52 allergens.
Wound healing clinics at Boston University Roger Williams Medical Center and University of Ottawa.
Sixty-three percent (n = 34) of patients had 1 or multiple positive patch test results, and 37% (n = 20) had no positive patch test result. The most common allergens were Myroxylon pereirae (balsam of Peru) (30% [16/54]), bacitracin (24% [13/54]), fragrance mix (20% [11/54]), wood tar mix (20% [11/54]), propylene glycol (14% [7/52]), neomycin sulfate (13% [7/54]), benzalkonium chloride (13% [7/54]), carba mix (11% [6/54]), nickel sulfate (11% [6/54]), and control gel hydrocolloid (11% [6/54]).
Comparable to European study findings, there is a high incidence of positive patch test results in patients with past or present leg ulcerations. The incidences of the most common allergens in our patient population were higher than those seen in the NACDG, except for nickel. Using a modified leg ulcer series along with the standard NACDG series is important in evaluating patients with leg ulcers.
To determine gene frequencies of HLA-DR alleles in 22 Mexican patients with focal epithelial hyperplasia and compare them with those present in ethnically matched healthy subjects, as well as to determine the types of human papillomavirus present in the lesions.
Prospective and retrospective observational study.
Dermatology outpatient clinic in a general hospital.
Twenty-two patients with clinically and histologically confirmed focal epithelial hyperplasia seen within a 10-year period.
Results of high-resolution DNA typing for HLA-DR alleles and biopsy for viral typing.
HLA-DR4 (DRB1*0404) was significantly increased (P<.001; odds ratio, 3.9; 95% confidence interval, 1.86-8.03). Seventeen (85%) of 20 patients had human papillomavirus subtype 13. The data on human papillomavirus differed from reports elsewhere that described association with human papillomavirus type 32.
The HLA-DRB1*0404 allele suggests that Amerindian populations are at risk, and in this group, the Mexican population studied was affected only by human papillomavirus type 13.
Odontogenic keratocysts of the jaw are a central feature of basal cell nevus syndrome (BCNS) and arise from the basal cell layer of the surface epithelium. Although they are benign, they tend to be aggressive, with local invasion of bony structures, extensive growth, and potential for substantial disfigurement and speech dysfunction. Complete surgical resection is the current standard of care; however, the procedures are often technically challenging and are followed by high recurrence rates.
We report the case of a 55-year-old man with a long-standing history of BCNS. Over a 25-year period, this patient had been treated for many basal cell carcinomas (BCCs). He also had multiple large odontogenic keratocysts in the mandible that had previously been treated using surgical, chemotherapeutic, and radiation treatment techniques. He had also undergone a right inguinal lymph node dissection after BCC metastasis was diagnosed within a lymph node. Owing to the recalcitrant nature of his condition and his history of BCC metastasis, the patient was started on a daily regimen of a new oral drug, GDC-0449, which inhibits the hedgehog signaling pathway, a key genetic contributor in the oncogenesis of BCCs. In addition to complete resolution of all his BCCs at 12-week follow-up, nearly complete resolution of 3 odontogenic keratocysts was documented by serial dental radiographs after 2 years of therapy.
We report the nearly complete regression of multiple BCNS-associated odontogenic keratocysts following nonsurgical treatment with GDC-0449. This novel drug, useful for the treatment of BCC, also appears to be effective for treatment of odontogenic keratocysts.
Vitamin D is a hormone, not a vitamin. The skin is responsible for producing vitamin D. During exposure to sunlight, ultraviolet radiation penetrates into the epidermis and photolyzes provitamin D3 to previtamin D3. Previtamin D3 can either isomerize to vitamin D3 or be photolyzed to lymisterol and tachysterol. Vitamin D is also sensitive to sunlight and is photolyzed to 5,6-transvitamin D3, suprasterol I, and suprasterol II. In Boston, solar irradiation only produces previtamin D3 in the skin between the months of March and October. Aging, sunscreens, and melanin all diminish the capacity of the skin to produce previtamin D3. Once formed, vitamin D3 enters the circulation and is sequentially metabolized to 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 (1,25-[OH]2-D3). The epidermis possesses receptors for 1,25-(OH)2-D3. 1,25-(OH)2-D3 inhibits the proliferation of cultured keratinocytes and induces them to terminally differentiate. The topical or oral administration of 1,25-(OH)2-D3 has proved to be effective for the treatment of psoriasis. Therefore, the skin is the site for the synthesis of vitamin D and a target tissue for its active metabolite. The successful use of 1,25-(OH)2-D3 for the treatment of psoriasis heralds a new approach for the treatment of this enigmatic disorder.
A group of 1,250 patients with verrucae plantaris have been treated with low exposures of external x-radiation. Of 1,065 patients who were followed, the lesion was cured in 1,022 or 96%. No instance of any radiation damage was observed. This series indicates that a very high percentage of cures in plantar warts can be obtained by using low dosage x-radiation fractionated over two to four weeks.
Adult allergic contact dermatitis to the black ink of a felt-tip marker pen occurred in two adult subjects. In both subjects the cutaneous reaction did not require photoactivation. Patch testing with the ingredients in the black ink demonstrated cutaneous sensitivity to the black dye. Further patch testing with the components of the black dye revealed cutaneous sensitivity in both subjects to the blue component, 1,4-bis(isopropylamino)anthraquinone, commonly known as Colour Index Solvent Blue 36.
The article published on the Archives of Dermatology website on April 16, 2012, titled “Early Depth Assessment of Local Burns by Dermoscopy: A New Frontier of Dermoscopic Evaluation” by Mihara et al1 is hereby retracted. The article was removed from consideration of publication at the authors' request pending clarification of methodology that did not affect the outcome of the study. The article was posted online inadvertently.
To identify prognostic factors in primary cutaneous anaplastic large cell lymphoma (pcALCL), focusing on extensive limb disease (ELD), defined as initial presentation or progression to multiple skin tumors in 1 limb or contiguous body regions, and to study gene expression profiles of patients with pcALCL.
Retrospective cohort study.
The Stanford Comprehensive Cancer Center and dermatology ambulatory clinics.
A total of 48 patients with pcALCL evaluated from 1990 through 2005.
Hazard ratios (HRs) for prognostic factors for overall survival (OS) and disease-specific survival (DSS) and risk factors for progression to extracutaneous disease were identified using Cox regression. Gene expression profiles of 9 typical pcALCL and 3 ELD samples were investigated using complementary DNA microarrays.
Univariate analysis demonstrated age, ELD, and progression to extracutaneous disease as significant prognostic factors for OS, whereas ELD and progression to extracutaneous disease were significant for DSS. In multivariate analysis, age (HR, 1.83; 95% confidence interval [CI], 1.02-3.26) and progression to extracutaneous disease (HR, 6.42; 95% CI, 1.39-29.68) remained significant for OS, whereas ELD (HR, 29.31; 95% CI, 1.72-500.82) and progression to extracutaneous disease (HR, 13.12; 95% CI, 1.03-167.96) remained independent prognostic factors for DSS. Presentation with T3 disease was a risk factor for progression to extracutaneous disease (HR, 10.20; 95% CI, 1.84-56.72). Microarray data revealed that patients with ELD and typical pcALCL formed distinct clusters.
Patients with ELD have a more aggressive course associated with a differential gene expression profile. More aggressive treatments may be indicated for patients with ELD and those whose disease progresses to extracutaneous disease because they have poorer outcomes.
The advent of ablative fractional laser technology has introduced potential new therapeutic options for patients with skin conditions involving fibrosis and scarring. We describe our experience using ablative fractional laser therapy in a patient with a morphea-related contracture refractory to conventional treatment.Department of Dermatology, Naval Medical Center San Diego, San Diego, CaliforniaCorrespondence: Peter R. Shumaker, MD, Department of Dermatology, Naval Medical Center San Diego, 34520 Bob Wilson Dr, Ste 300, San Diego, CA 92134 (email@example.com).Accepted for Publication: May 5, 2011.Author Contributions: Drs Kineston, Kwan, Uebelhoer, and Shumaker had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Kineston, Uebelhoer, and Shumaker. Acquisition of data: Kineston, Uebelhoer, and Shumaker. Analysis and interpretation of data: Kineston, Kwan, Uebelhoer, and Shumaker. Drafting of the manuscript: Kineston, Kwan, and Shumaker. Critical revision of the manuscript for important intellectual content: Kineston, Kwan, Uebelhoer, and Shumaker.Financial Disclosure: None reported.Disclaimer: The views expressed in this article are those of the authors and do not reflect the official policy or position of the Department of the Navy, Department of Defense, or the US Government.
Light reflected from skin has two components: regular reflectance, or "glare" arising from the surface, and light backscattered from within the tissue. The regular reflectance contains the visual cues related to surface texture, whereas the backscattered component contains the cues related to pigmentation, erythema, infiltrates, vessels, and other intracutaneous structures. Unlike the backscattered component, regular reflectance preserves the plane of polarization of polarized incident light. Thus, viewing skin through a linear polarizer, under linearly polarized illumination, separates the two components of tissue reflectance. Thirty patients were examined and photographed in this manner. When the planes of polarization are parallel, images with enhanced surface detail are obtained. When the planes are orthogonal, wrinkles and surface detail disappear, and an enhanced view of vasculature and pigmented lesions is obtained. Simple, clinically useful techniques are presented.