Journal of the American Academy of Dermatology - Articles in Press

Marie Unna hereditary hypotrichosis: Identification of a U2HR mutation in the family from the original 1925 report - Corrected Proof

2010-07-26

Background: In 1925, Dr Marie Unna described a rare form of hereditary hypotrichosis in a German multigenerational family. This was later termed “Marie Unna hereditary hypotrichosis” (MUHH). MUHH is an autosomal dominant disorder that is characterized by the absence or scarcity of scalp hair, eyebrows, and eyelashes at birth; coarse and wiry hair during childhood; and progressive hair loss beginning around puberty. Causal mutations in U2HR, an inhibitory upstream open reading frame in the 5'-untranslated region of the human hairless (HR) gene, were recently identified in several unrelated MUHH families from various ethnic backgrounds.Objective: Although there have been several clinical reports of descendants of the originally described family, the molecular cause of disease in this particular family has not been established. The aim of this study was to investigate descendants of this family and to analyze their DNA for the presence of U2HR mutations.Methods: Descendants of the family (including one affected individual) were examined clinically. Direct sequencing of U2HR was performed. Enzymatic digestion using the restriction enzyme NcoI was performed to confirm the sequencing results.Results: The index patient displayed the typical MUHH pattern of hair loss and was found to carry the disease-causing c.3G>A (p.M1I) U2HR mutation. This mutation was not detected in unaffected family members.Limitations: Only one affected family member was investigated.Conclusions: Eighty-five years after the first description of this rare form of alopecia, the disease-causing mutation in the originally reported family has been identified.

Radiotherapy for extramammary Paget disease of the anogenital region - Corrected Proof

2010-07-23

Extramammary Paget disease is a rare condition that most commonly affects the anogenital region in the elderly. The treatment of choice has been surgical excision of the affected area with adequate depth and lateral margins, criteria that cannot always be fulfilled, especially when the vulva, anal canal, or penis are involved. More recently radiotherapy has been suggested as a suitable treatment when surgical excision or other modalities are not appropriate. We report a case of anogenital extramammary Paget disease and the clinical response to treatment with radiotherapy. The aim of this article is to review relevant aspects of radiotherapy as a first-choice curative treatment in specific situations of anogenital extramammary Paget disease in situ.

Gastric bypass surgery improves psoriasis - Corrected Proof

Eric W. Hossler, Michele S. Maroon, Chris M. Mowad — 2010-07-23

Recent studies have found that psoriasis is linked to a higher rate of obesity, and that obesity itself is a risk factor for the development of psoriasis. There are two recent reports of chronic severe psoriasis improving with weight loss after Roux-en-Y gastric bypass surgery. We have observed two patients with body mass indices greater than 50 kg/m2 who had marked improvement in their psoriasis after gastric bypass surgery. The common link between psoriasis and obesity may be a state of chronic inflammation, including elevated levels of T helper 1 (TH-1) cytokines such as tumor necrosis factor. More recent research has shown that the appetite suppressant leptin is also elevated in patients with psoriasis and obesity, and that levels decrease with weight loss. We conclude that weight loss may be a useful adjunctive therapy for obese patients with psoriasis.

Revised nomenclature and classification of inherited ichthyoses: Results of the First Ichthyosis Consensus Conference in Sorèze 2009 - Corrected Proof

2010-07-20

Background: Inherited ichthyoses belong to a large, clinically and etiologically heterogeneous group of mendelian disorders of cornification, typically involving the entire integument. Over the recent years, much progress has been made defining their molecular causes. However, there is no internationally accepted classification and terminology.Objective: We sought to establish a consensus for the nomenclature and classification of inherited ichthyoses.Methods: The classification project started at the First World Conference on Ichthyosis in 2007. A large international network of expert clinicians, skin pathologists, and geneticists entertained an interactive dialogue over 2 years, eventually leading to the First Ichthyosis Consensus Conference held in Sorèze, France, on January 23 and 24, 2009, where subcommittees on different issues proposed terminology that was debated until consensus was reached.Results: It was agreed that currently the nosology should remain clinically based. “Syndromic” versus “nonsyndromic” forms provide a useful major subdivision. Several clinical terms and controversial disease names have been redefined: eg, the group caused by keratin mutations is referred to by the umbrella term, “keratinopathic ichthyosis”–under which are included epidermolytic ichthyosis, superficial epidermolytic ichthyosis, and ichthyosis Curth-Macklin. “Autosomal recessive congenital ichthyosis” is proposed as an umbrella term for the harlequin ichthyosis, lamellar ichthyosis, and the congenital ichthyosiform erythroderma group.Limitations: As more becomes known about these diseases in the future, modifications will be needed.Conclusion: We have achieved an international consensus for the classification of inherited ichthyosis that should be useful for all clinicians and can serve as reference point for future research.

Results of patch testing to personal care product allergens in a standard series and a supplemental cosmetic series: An analysis of 945 patients from the Mayo Clinic Contact Dermatitis Group, 2000-2007 - Corrected Proof

2010-07-20

Background: Patch testing to a standard screening series of allergens in combination with supplemental cosmetic allergens is often used to diagnose allergic contact dermatitis due to personal care products.Objective: To report results of patch testing to skin care product allergens contained in a standard series and a supplemental cosmetic series and to compare efficacy of this combined series in detecting positive reactions to personal care product allergens with the efficacy of various standard screening series.Methods: Positive reaction rates to skin care product allergens were tabulated for patients who underwent patch testing to both standard and cosmetic series allergens at Mayo Clinic between 2000 and 2007. Data were compared with skin care allergens detected on standard screening series, including the thin-layer rapid use epicutaneous (TRUE) test.Results: Of 945 patch-tested patients, 68.4% had at least one positive reaction and 47.3% had at least two positive reactions. Also, 49.4% of patients reacted to at least one preservative; 31.2% reacted to at least one fragrance/botanical additive. Compared with use of our standard series and cosmetic series, use of the TRUE test would have missed 22.5% of patients with preservative allergy, 11.3% with fragrance/botanical allergy, and 17.3% with vehicle allergy.Limitations: Various allergens tested over time, patch test reading by residents, and lack of confirmation of allergen in personal care products.Conclusion: Standard patch-test screening series miss a substantial number of patients with skin care product ingredient allergy.

Role of primary prophylaxis for pneumocystis pneumonia in patients treated with systemic corticosteroids or other immunosuppressive agents for immune-mediated dermatologic conditions - Corrected Proof

Julia S. Lehman, Amer N. Kalaaji — 2010-07-20

Background: The incidence of pneumocystis pneumonia (PCP), an opportunistic infection caused by Pneumocystis jiroveci, in patients taking immunosuppressive medications for dermatologic indications is unknown.Objective: We sought to define the incidence of PCP in patients with dermatologic conditions, to characterize risk factors for PCP development in these patients, to examine PCP prophylaxis practices among dermatologists, and to document adverse effects of PCP prophylaxis medications.Methods: We reviewed the medical records of patients taking immunosuppressive medications for longer than 1 month who were treated for dermatologic conditions between 1998 and 2007 at Mayo Clinic, Rochester, MN.Results: Of 198 patients meeting inclusion criteria (150 [75.8%] of whom received no PCP prophylaxis), one patient (0.5% and 0.7%, respectively) had PCP that developed during the follow-up period. In this patient, a 94-year-old woman with bullous pemphigoid, severe interstitial pulmonary fibrosis, aortic stenosis, and hypoalbuminemia, PCP developed within 7 months of diagnosis and was treated with methotrexate and prednisone. She had not received PCP prophylaxis. Only 6 patients (3%) with dermatology as their primary service received PCP prophylaxis. Overall, rates of adverse effects with PCP prophylaxis were low.Limitations: The study design was retrospective. Low rates of PCP precluded our development of concrete PCP prophylaxis guidelines.Conclusions: Results did not support routine administration of PCP prophylaxis in all patients taking immunosuppressive medications. When prescribing immunosuppressive medications for dermatologic indications, physicians should consider PCP prophylaxis on a case-by-case basis.

Palmar fasciitis and polyarthritis syndrome associated with transitional cell carcinoma of the bladder - Corrected Proof

Lynsey L. Clarke, Cameron T.C. Kennedy, Peter Hollingworth — 2010-07-20

Palmar fasciitis and polyarthritis syndrome is a rare, disabling, paraneoplastic condition of unknown pathogenesis. There is no known effective treatment, although the condition may be halted by control of the cancer. Previously reported cases have mostly been in patients with advanced ovarian malignancies. We present the case of a 69-year-old woman with this condition in association with bladder carcinoma, together with a review of the literature and discussion of possible therapeutic options.

Acute respiratory distress syndrome complicating generalized pustular psoriasis (psoriasis-associated aseptic pneumonitis) - Corrected Proof

Nicolas Kluger, Didier Bessis, Bernard Guillot, Céline Girard — 2010-07-16

Generalized pustular and/or erythrodermic psoriasis may have severe or even lethal complications. A peculiar noninfectious acute respiratory distress syndrome (so-called "sterile pneumonitis") has been described in generalized pustular psoriasis and/or erythrodermic psoriasis. We report a new case in a 14-year-old girl with a long history of pustular psoriasis and review the published work on this complication. The girl developed sterile pneumonitis during a disease flare-up, and high-dose corticosteroid therapy was quickly initiated. Within a few days, her clinical and radiological status was dramatically improved. The pathogenesis of aseptic pneumonitis is unknown, but various proinflammatory cytokines have been implicated, especially tumor necrosis factor-alpha, which could play a role in the recruitment of leukocytes to the lung. This complication has rarely been reported but should be more widely known as the differential diagnoses include congestive heart failure, acute lung infection related or unrelated to immunosuppressive therapy, and drug hypersensitivity reaction. Early recognition would avoid delays in the correct management of this potentially lethal complication, which requires high-dose systemic corticosteroid therapy.

Therapeutic ladder for pemphigus vulgaris: Emphasis on achieving complete remission - Corrected Proof

Lindsay C. Strowd, Sarah L. Taylor, Joseph L. Jorizzo, Mohammad R. Namazi — 2010-07-15

Background: Pemphigus vulgaris (PV) is a blistering autoimmune bullous disease that is usually fatal without proper treatment. There are no clear treatment guidelines for PV at this time.Purpose: We suggest a standard treatment regimen for patients with PV based on the success of our treatment.Methods: A retrospective chart review of 18 patients with PV was conducted to assess response to a similar approach using mycophenolate mofetil (MMF) and prednisone. Diagnosis was confirmed through routine histology, direct immunofluorescence, and indirect immunofluorescence, and patients were followed up for a total average of 35.2 months.Results: We achieved complete disease control in 89% of patients using our treatment algorithm. Fourteen of 18 patients achieved complete disease control on therapy with prednisone and MMF. Three of the 4 patients who did not achieve control on MMF and prednisone went on to receive rituximab therapy, and two of those patients achieved disease control on rituximab. The average length of time from initiating therapy to 75% clearance of lesions was 4.5 months. Three of 18 patients were able to discontinue therapy after an average of 3 years and have remained in complete remission for more than 1 year.Limitations: This was a retrospective chart review with a small patient sample size.Conclusions: The combination therapy of MMF and prednisone is an effective treatment regimen to achieve rapid and complete control of PV. For those patients who fail treatment with MMF and prednisone, rituximab is an efficacious alternative therapy.

Androgenetic alopecia and cardiovascular risk factors in men and women: A comparative study - Corrected Proof

2010-07-09

Background: Numerous studies in recent decades have associated male androgenetic alopecia (AGA) with the risk of cardiovascular disease. However, only 3 studies have addressed this association in female patients. Most studies considered the risk of myocardial infarction or mortality as a result of heart disease, without analyzing cardiovascular risk factors.Objectives: The objectives of this study were to analyze the presence of cardiovascular risk factors included in the Adult Treatment Panel-III criteria for metabolic syndrome, the prevalence of carotid atheromatosis, hormonal (aldosterone, insulin, testosterone, and sex hormone–binding globulin) factors, and acute phase reactant (C-reactive protein, fibrinogen, D-dimers, erythrocyte sedimentation rate) variables in male and female patients with AGA and in a control group, and to analyze differences among the groups.Methods: This case-control study included 154 participants, 77 with early-onset AGA (40 male and 37 female) and 77 healthy control subjects (40 male and 37 female) from the dermatology department at a university hospital in Granada, Spain.Results: Metabolic syndrome was diagnosed in 60% of male patients with AGA (odds ratio [OR] = 10.5, 95% confidence interval [CI] 3.3-32.5), 48.6% of female patients with AGA (OR = 10.73, 95% CI 2.7-41.2), 12.5% of male control subjects, and 8.1% of female control subjects (P < .0001). Atheromatous plaques were observed in 32.5% of male patients with AGA (OR = 5.93, 95% CI 1.5-22.9) versus 7.5% of male control subjects (P = .005) and 27% of female patients with AGA (OR = 4.19, 95% CI 1.05-16.7) versus 8.1% of female control subjects (P = .032). Aldosterone and insulin levels were significantly higher in the male and female patients with AGA versus their respective control subjects. Mean values of fibrinogen were significantly higher in male patients with AGA, whereas values of fibrogen, C-reactive protein, and D-dimers were significantly higher in female patients with AGA versus their respective control subjects.Limitations: The study of a wider sample of patients with AGA would confirm these findings and allow a detailed analysis of the above factors as a function of the degree of alopecia or between menopausal and premenopausal women.Conclusion: The determination of metabolic syndrome and ultrasound study of the carotid arteries may be useful screening methods to detect risk of developing cardiovascular disease in male and female patients with early-onset AGA and signal a potential opportunity for early preventive treatment.

Dermatoscopy use by US dermatologists: A cross-sectional survey - Corrected Proof

Holly C. Engasser, Erin M. Warshaw — 2010-07-09

Background: Although dermatoscopy is widely used in Europe and Australia, little is known about dermatoscopy use by US dermatologists.Objective: We sought to estimate the prevalence of dermatoscopy use by US dermatologists and examine associations with practice characteristics.Methods: We conducted a cross-sectional survey of all US fellows of the American Academy of Dermatology.Results: Of 8501 eligible recipients, 3238 (38.1%) surveys were completed and returned. Of respondents, 48% used dermatoscopy (n = 1555). Dermatoscopy use was associated with the following characteristics: age younger than 50 years (P < .0001), female sex (P = .0001), practice location in the Northeast (P < .0001), involvement in resident teaching (P < .0001), and dermatoscopy training (P < .0001). The main reasons for not using dermatoscopy included: lack of training (39.7%), lack of interest (32.5%), time required for dermatoscopic examination (27.6%), and belief dermatoscopy would not affect clinical decisions (15.2%).Limitations: Low response rate and potential response bias were limitations.Conclusions: Approximately half of respondents used dermatoscopy in their practice. Not surprisingly, dermatoscopy users were more likely to be younger, involved in resident teaching, or have training in dermatoscopy.

Revisiting nephrogenic systemic fibrosis in 6 kidney transplant recipients: A single-center experience - Corrected Proof

2010-07-09

Background: Nephrogenic systemic fibrosis (NSF) is a fibrotic disorder occurring in patients with renal dysfunction. Exposure to gadolinium (Gd)-based contrast agents (GBCAs) during renal impairment is associated with development of NSF.Methods: A cross-referenced search of kidney transplantation and radiology databases at a single institution revealed the prevalence of NSF in the transplant population. Clinical records and skin biopsy specimens from 6 patients with kidney transplant given a diagnosis of NSF were reviewed to identify contributing factors.Results: Between January 1999 and December 2006, NSF was diagnosed in 6 of 705 patients with kidney transplant (0.9%). Renal function was impaired in all patients. Of 33 patients with kidney transplant exposed to GBCAs, 5 (15.2%) developed NSF. Disease onset ranged from 7 days to 11 months after exposure to GBCAs. All 5 patients exposed to GBCAs who developed NSF were also treated with a β-blocker and clinical improvement was observed with discontinuation. The sixth case NSF appeared unrelated to Gd, without a known exposure, and testing of tissue via mass spectrometry revealed no Gd. Symptoms of NSF in this patient disappeared after administration of darbepoetin was switched from subcutaneous to intravenous injection. One patient with NSF who manifested the highest Gd level in tissue died 22 months after disease onset.Limitations: The study represents the retrospective experience of only a single center.Conclusions: NSF can develop in kidney transplant recipients with altered graft function. In these patients, exposure to GBCAs appears associated with development of NSF. The role of β-blockers in the course of the disease merits further investigation.

The immigration delay disease: Adermatoglyphia–inherited absence of epidermal ridges - Corrected Proof

Bettina Burger, Dana Fuchs, Eli Sprecher, Peter Itin — 2010-07-09

In the digital age, personal identification by fingerprints (epidermal ridges) has become more frequent and is often required for biometric passports. The more fingerprints are analyzed, the more variants in their formation are documented. Individuals completely missing fingerprints as an isolated finding are extremely rare. Only 4 kindreds have been described to date, with additional clinical features in most cases. We describe a female patient with missing epidermal ridges on the fingers, palms, toes, and soles as an isolated feature. Absent fingerprints, or adermatoglyphia, were inherited over 4 generations of her family in an autosomal dominant fashion. We present the clinical features of the index patient, and compare the case with previous reports in the literature. Because of problems in personal identification, this embryologic malformation caused the patient significant difficulties when traveling to other countries, which is why we name it the immigration delay disease.

Underestimated clinical features of postadolescent acne - Corrected Proof

2010-07-09

Background: Postadolescent acne is usually described as an inflammatory, mild-to-moderate dermatosis, frequently involving the lower third of the face, the jawline, and the neck. However, we have also frequently observed a clinical form predominantly characterized by retention lesions (microcomedones and macrocomedones), with few inflammatory lesions (comedonal postadolescent acne [CPAA]), which appears significantly correlated with cigarette smoking.Objective: We sought to investigate the clinical features of postadolescent acne in a group of female patients affected by acne and its relationship with cigarette smoking.Methods: A total of 226 women with acne (25-50 years) attending our department were examined by a team of 3 dermatologists, to assess the age of onset of the disease, and the number, type, and distribution of acne lesions.Results: In all, 192 of 226 patients (85.0%) were classified as having CPAA and 34 as having papulopustular postadolescent acne. A smoking habit was confirmed in 150 of 226 (66.3%). Remarkably, 72.9% of patients with CPAA were smokers as compared with only 29.4% of those with papulopustular postadolescent acne (P < .0001).Limitations: Possible limitations are related to geographic area or to the prevalence of darker skin types (III and IV) (data about skin types have not been collected). Other possible aggravating factors (ie, stress and diet) have not been investigated.Conclusions: According to our results, CPAA appears as the most frequent clinical form of postadolescent acne and seems to be strictly correlated with cigarette smoking.

Patient-reported outcomes in pediatric patients with psoriasis undergoing etanercept treatment: 12-week results from a phase III randomized controlled trial - Corrected Proof

2010-07-09

Background: Psoriasis adversely affects health-related quality of life (HRQoL) in adults; however, little information exists about its impact on children and adolescents.Objective: The effect of etanercept therapy on HRQoL compared with placebo was evaluated in children and adolescents with moderate to severe plaque psoriasis.Methods: HRQoL data were collected from patients 4 to 17 years of age in a randomized, double-blind, placebo-controlled, North American, phase III study of etanercept. Instruments for assessing HRQoL included the Children's Dermatology Life Quality Index (CDLQI), Pediatric Quality of Life Inventory (PedsQL), Stein Impact on Family Scale, and Harter Self-Perception Profile for Children.Results: Baseline CDLQI and PedsQL scores revealed reduced HRQoL in patients with psoriasis relative to comparative populations. Patients treated with etanercept demonstrated significantly higher mean percentage improvement in total CDLQI scores from baseline to week 12 compared with those treated with placebo (52.3% etanercept vs 17.5% placebo [P = .0001]). At week 12, patients who achieved 75% improvement in their Psoriasis Area and Severity Index score had higher percentage improvements from baseline in total CDLQI scores than those who did not have 75% improvement in Psoriasis Area and Severity Index score.Limitations: The PedsQL, Stein scale, and Harter profile demonstrated limited improvement in patients' HRQoL, suggesting that these scales may not be sensitive to issues that are relevant to children with psoriasis and their families.Conclusion: Etanercept therapy had a clinically and statistically meaningful impact on disease-specific quality of life (CDLQI) and a clinically meaningful impact on general quality of life (PedsQL) in children and adolescents with moderate to severe plaque psoriasis.

Pilot, multicenter, double-blind, randomized placebo-controlled bilateral comparative study of a combination of calcipotriene and nicotinamide for the treatment of psoriasis - Corrected Proof

2010-07-05

Background: Calcipotriene has limited efficacy in treating psoriasis. By inhibiting proinflammatory cytokines such as interleukin-12, interleukin-23, and tumor necrosis factor-alfa, nicotinamide may enhance the efficacy of calcipotriene therapy when used in combination.Objective: We sought to determine if the combination of nicotinamide with calcipotriene is more effective than either component alone.Methods: In this randomized, double-blinded, multicenter 7-arm bilateral comparison-controlled trial, patients were randomized to two of 7 treatments–placebo, calcipotriene 0.005% alone, nicotinamide 1.4% alone, calcipotriene plus nicotinamide 0.05%, calcipotriene plus nicotinamide 0.1%, calcipotriene plus nicotinamide 0.7%, or calcipotriene plus nicotinamide 1.4%–each administered to lesions on one side of the body or to one of two lesions at least 5 cm apart, for 12 weeks. Efficacy was measured using a clear to almost clear outcome.Results: In all, 50.0% of patients in the calcipotriene and nicotinamide 1.4% combination group achieved a clear to almost clear outcome at week 12, compared with only 18.8% of patients treated with placebo (P = .002), 25% of patients treated with nicotinamide 1.4% alone (P = .02), and 31.5% of patients treated with calcipotriene alone (P = .096). A dose-response trend existed for increasing concentrations of nicotinamide, but it was not significant.Limitations: The relatively small patient numbers, relatively high placebo effect, and maximum in-life portion of only 12 weeks of dosing are weaknesses of the study.Conclusion: This study provides evidence that using the combination nicotinamide and calcipotriene may provide additional benefit in the topical treatment for patients with psoriasis and may be an adequate steroid-sparing substitute treatment.

Validation and response to treatment of a pruritus self-assessment tool in patients with moderate to severe psoriasis - Corrected Proof

Alice Gottlieb, JingYuan Feng, David J. Harrison, Denise Globe — 2010-07-05

Background: Pruritus is a common symptom of psoriasis. In many clinical trials of psoriasis treatments, severity of pruritus is a patient-reported outcome.Objective: We sought to evaluate a patient-reported pruritus self-assessment tool using data from clinical trials of a tumor necrosis factor blocker.Methods: The validity of the patient-reported 6-point pruritus assessment tool (0 = none to 5 = severe) was determined using data from a phase III trial of etanercept, a tumor necrosis factor blocker. The performance of the pruritus assessment tool was then evaluated using data from two large etanercept trials.Results: The pruritus assessment tool was validated and deemed to have good test-retest reliability (kappa coefficient = 0.71; 95% confidence interval = 0.62-0.80) and responsiveness (standardized response mean = 1.28; effect size = 1.63, responsiveness statistic = 1.54). Improvements in pruritus scores correlated with improvements in Psoriasis Area and Severity Index after 8 weeks of etanercept therapy in two phase III trials.Limitations: The pruritus assessment is validated only for patients with moderate to severe plaque psoriasis, and may not be applicable to other patient populations.Conclusions: The pruritus assessment tool is a valid measurement of pruritus intensity in patients with moderate to severe plaque psoriasis and can discriminate between patients on and off treatment.

The integrity of the dermatology National Resident Matching Program: Results of a national study - Corrected Proof

Jennifer A. Sbicca, Emily S. Gorell, Matthew H. Kanzler, Alfred T. Lane — 2010-07-05

Background: National Resident Matching Program (NRMP) policy outlines the conduct expected by both program directors and residency applicants. However, recent studies and personal experiences have introduced the possibility that NRMP policy is violated during the residency application process.Objective: To investigate the communications that occur between dermatology applicants and dermatology programs during the residency application process.Methods: From April to July 2009, we surveyed 2009 Stanford dermatology applicants, current US dermatology residents, and US dermatology program directors. The survey was anonymous and available online. The main outcome measures were the frequency and incidence of dermatology NRMP policy violations.Results: Thirty-one percent of Stanford applicants and 19% of US dermatology residents felt pressured to reveal to programs how they ranked them before match day. Seventeen percent of Stanford applicants and 14% of US dermatology residents witnessed behavior that made them feel uncomfortable or that they thought was a possible ethical infraction of NRMP policy.Limitations: Response rates were as follows: 43% of Stanford applicants, 46% of residents, and 61% of program directors.Conclusions: Our data suggest that some dermatology program directors violate NRMP policy during their communications with applicants. The most widespread violation is pressuring applicants into revealing how they intend to rank programs. Other violations include apparent sexual discrimination and reserving NRMP positions for preselected applicants. Additional studies should be done in order to determine the incidence of dermatology applicants violating NRMP policy.

Impact of weight on the efficacy and safety of ustekinumab in patients with moderate to severe psoriasis: Rationale for dosing recommendations - Corrected Proof

2010-07-05

Background: Patients with psoriasis tend to be overweight, and the efficacy of fixed-dose biologics may be compromised by high body weight.Objective: We sought to determine whether the optimal dose of ustekinumab is affected by weight in patients with psoriasis.Methods: Patients were randomized in two phase III trials (PHOENIX 1 and 2) to receive 45 mg or 90 mg of ustekinumab every 12 weeks (n = 1331) or placebo with crossover to ustekinumab at week 12 (n = 665). Efficacy and serum ustekinumab concentrations were to be evaluated by 10-kg increments of body weight at week 28 (steady-state trough level).Results: Mean baseline weight was 93.9 and 91.0 kg in PHOENIX 1 and 2, respectively. Based on the analyses by 10-kg increments, a cutoff of 100 kg was determined to best differentiate the dose response. The proportion of patients with at least 75% improvement from baseline in Psoriasis Area and Severity Index score was 74.2% for 90 mg and 54.6% for 45 mg in heavier patients (>100 kg), but the proportion with a response of at least 75% improvement from baseline in Psoriasis Area and Severity Index score was similar between doses (80.8% vs 76.9%) in lighter patients (≤100 kg). Serum ustekinumab concentrations were also affected by weight, with lower serum concentrations observed in heavier patients at each dose. Safety was not affected by weight.Limitations: Low numbers of patients at the extremes of body weight may limit the analyses of these subgroups.Conclusion: Results of weight-based analyses of clinical and pharmacokinetic data indicate that fixed dosing of ustekinumab based on weight is appropriate for the treatment of patients with psoriasis.

Giant fibrous hamartoma of infancy: A report of two cases and review of the literature - Corrected Proof

Joseph McGowan, Charles D. Smith, John Maize, Joel Cook — 2010-07-02

We present two unique cases of fibrous hamartoma of infancy defined by giant-sized and/or multicentric cutaneous and subcuticular lesions—features not, to our knowledge, reported to coexist. We review the nature of such tumors and examine the clinical implications of tumor size and multicentricity on risk for recurrence and likelihood of visceral involvement.

Factors associated with large cutaneous squamous cell carcinomas - Corrected Proof

2010-07-02

Background: Large cutaneous squamous cell carcinoma (SCC) is associated with a higher risk of disfigurement, local recurrence, and metastasis; however, little is known about factors associated with tumor size at diagnosis.Objectives: We sought to evaluate factors associated with SCC size, including diagnostic/treatment delay and patient and tumor characteristics.Methods: We studied a stratified sample of 308 patients with SCC recently treated at a dermatologic referral center in Italy. Medical records were reviewed and telephone interviews conducted. Multiple logistic regression was used to examine factors associated with SCC size.Results: With univariate analyses, among both invasive and in situ cases, SCC greater than 2cm was significantly associated with male gender, tumors arising in chronic lesions, and tumors located on not easily visible sites. Long delay before surgical removal was significantly associated with large SCC size only for invasive SCC (P < .001). Among patients with invasive SCC, when controlling for age and gender, multivariate analysis showed a significantly higher likelihood of SCC greater than 2cm with a total delay longer than 18 months before surgical removal (odds ratio=4.18; 95% confidence interval 2.45-7.13) and for tumors arising in chronic lesions (odds ratio=6.42; 95% confidence interval 3.13-13.2).Limitations: The study was cross-sectional and based on a single center.Conclusions: Long total delay in removal significantly increased the likelihood of invasive SCC greater than 2cm. Our findings highlight the importance of early detection and treatment to prevent large invasive SCCs, which are associated with a higher risk of disfigurement, recurrence, and metastasis. Particular attention should be paid to chronic skin lesions and not easily visible body sites during physician- and patient-performed examinations.

Effect of hair color and sun sensitivity on nevus counts in white children in Colorado - Corrected Proof

2010-06-28

Background: It has been widely reported that individuals with a light phenotype (ie, light hair color, light base skin color, and propensity to burn) have more nevi and are at greater risk for developing skin cancer. No studies have systematically investigated how phenotypic traits may interact in relation to nevus development.Objective: We sought to systematically examine whether any combinations of phenotype are associated with a greater or lesser risk for nevus development in white children.Methods: In the summer of 2007, 654 children were examined to determine full body nevus counts, skin color by colorimetry, and hair and eye color by comparison with charts. Interviews of parents were conducted to capture sun sensitivity, sun exposure, and sun protection practices.Results: Among 9-year-old children with sun sensitivity rating type II (painful burn/light tan), those with light hair had lower nevus counts than did those with dark hair (P value for interaction = .03). This relationship was independent of eye color, presence of freckling, sex, usual daily sun exposure, sunburn in 2004 to 2007, sun protection index, and waterside vacation sun exposure. The difference in nevus counts was further determined to be specific to small nevi (<2 mm) and nevi in intermittently exposed body sites.Limitations: Geographic and genetic differences in other study populations may produce different results.Conclusion: The standard acceptance that dark phenotype is a marker for low melanoma risk and light phenotype a marker for high risk may need to be reevaluated. In non-Hispanic white children, dark-haired individuals who burn readily and then tan slightly are more prone to nevus development, and may therefore be a previously underrecognized high-risk group for melanoma.

Lack of evidence for basal or squamous cell carcinoma infection with Merkel cell polyomavirus in immunocompetent patients with Merkel cell carcinoma - Corrected Proof

2010-06-28

Background: Merkel cell polyomavirus (MCV) was discovered by digital transcriptome subtraction as a monoclonal infection of Merkel cell carcinoma (MCC) tumors. Subsequent studies have repeatedly confirmed that MCV is the likely cause for most MCC. Polymerase chain reaction–based detection of the virus in other nonmelanoma skin cancers, however, has been inconsistent and controversial.Objective: We sought to directly assay for MCV infection in squamous cell carcinoma (SCC) or basal cell carcinoma (BCC) tumor cells by immunostaining for viral antigen.Methods: CM2B4, a monoclonal antibody to exon 2 peptides of MCV T antigen, was used to examine tumors from 20 patients with MCC with and without secondary SCC or BCC tumors.Results: MCV T antigen was readily detected in 15 (75%) of 20 MCC tumors including 11 MCC tumors from patients with secondary SCC or BCC. In contrast to MCC, none of these secondary BCC or SCC was MCV T-antigen positive.Limitations: A limitation was the small study size with antigen detection including only the MCV large T and 57kT proteins.Conclusions: MCV T antigen is generally not expressed in BCC or SCC tumors from a population favored to have MCV infection, ie, those persons already given the diagnosis of MCV-positive MCC. This suggests that episodic polymerase chain reaction detection of MCV genome in BCC or SCC tumors may represent coincidental rather than causal infection, and that these tumors share other noninfectious risk factors.

Digital squamous cell carcinoma and association with diverse high-risk human papillomavirus types - Corrected Proof

Rachel H. Gormley, Caroline M. Groft, Christopher J. Miller, Carrie L. Kovarik — 2010-06-28

Digital squamous cell carcinoma (SCC) presents a diagnostic challenge because of its relatively rare occurrence and mimicry of benign conditions. Although low-risk human papillomavirus (HPV) subtypes are commonly associated with benign digital verrucae, digital SCC can be associated with high-risk, oncogenic HPV subtypes. We report 7 patients, including 4 HIV-positive patients, who presented with 10 lesions of digital SCC in situ. Six of 10 lesions were typed for HPV by immunostain or polymerase chain reaction. Multiple high-risk oncogenic subtypes were found, including HPV-16, -33, -51, and -73. The majority of reports linking HPV and digital SCCs have implicated the HPV-16 subtype. This case series highlights the diversity of oncogenic HPV types that may be associated with digital SCCs. Because the high rate of recurrence of digital SCCs may be a result of persistence of oncogenic HPV at the margins of resection, aggressive treatment of individual lesions and of genital reservoirs for HPV on patients and their sexual partners is warranted.

Tyrosine kinases in inflammatory dermatologic disease - Corrected Proof

Ricardo T. Paniagua, David F. Fiorentino, Lorinda Chung, William H. Robinson — 2010-06-28

Tyrosine kinases (TKs) are enzymes that catalyze the phosphorylation of tyrosine residues on protein substrates. They are key components of signaling pathways that drive an array of cellular responses including proliferation, differentiation, migration, and survival. Specific TKs have recently been identified as critical to the pathogenesis of several autoimmune and inflammatory diseases. Small-molecule inhibitors of TKs are emerging as a novel class of therapy that may provide benefit in certain patient subsets. In this review, we highlight TK signaling implicated in inflammatory dermatologic diseases, evaluate strategies aimed at inhibiting these aberrant signaling pathways, and discuss prospects for future drug development.

Wound healing in the 21st century - Corrected Proof

2010-06-24

Delayed wound healing is one of the major therapeutic and economic issues in medicine today. Cutaneous wound healing is an extremely well-regulated and complex process basically divided into 3 phases: inflammation, proliferation, and tissue remodeling. Unfortunately, we still do not understand this process precisely enough to give direction effectively to impaired healing processes. There have been many new developments in wound healing that provide fascinating insights and may improve our ability to manage clinical problems. Our goal is to acquaint the reader with selected major novel findings about cutaneous wound healing that have been published since the beginning of the new millennium. We discuss advances in areas such as genetics, proteases, cytokines, chemokines, and regulatory peptides, as well as therapeutic strategies, all set in the framework of the different phases of wound healing.

Pathologic nodal evaluation improves prognostic accuracy in Merkel cell carcinoma: Analysis of 5823 cases as the basis of the first consensus staging system - Corrected Proof

2010-06-21

Background: The management of Merkel cell carcinoma (MCC) has been complicated by a lack of detailed prognostic data and by the presence of conflicting staging systems.Objective: We sought to determine the prognostic significance of tumor size, clinical versus pathologic nodal evaluation, and extent of disease at presentation and thereby derive the first consensus staging/prognostic system for MCC.Methods: A total of 5823 prospectively enrolled MCC cases from the National Cancer Data Base had follow-up data (median 64 months) and were used for prognostic analyses.Results: At 5 years, overall survival was 40% and relative survival (compared with age- and sex-matched population data) was 54%. Among all MCC cases, 66% presented with local, 27% with nodal, and 7% with distant metastatic disease. For cases presenting with local disease only, smaller tumor size was associated with better survival (stage I, ≤2 cm, 66% relative survival at 5 years; stage II, >2 cm, 51%; P < .0001). Patients with clinically local-only disease and pathologically proven negative nodes had better outcome (76% at 5 years) than those who only underwent clinical nodal evaluation (59%, P < .0001).Limitations: The National Cancer Data Base does not capture disease-specific survival. Overall survival for patients with MCC was therefore used to calculate relative survival based on matched population data.Conclusion: Although the majority (68%) of patients with MCC in this nationwide cohort did not undergo pathologic nodal evaluation, this procedure may be indicated in many cases as it improves prognostic accuracy and has important treatment implications for those found to have microscopic nodal involvement.

Treatment of angiotensin-converting enzyme inhibitor–related angioedema with the bradykinin B2 receptor antagonist icatibant - Corrected Proof

Peter W. Schmidt, Michael M. Hirschl, Franz Trautinger — 2010-06-16

To the Editor: Angiotensin-converting enzyme (ACE) inhibitor–induced angioedema (AE) occurs with a reported incidence of 0.1% to 0.2% and may be life threatening in up to 20% of patients. Its pathomechanism is not entirely clear, but is likely related to the accumulation of bradykinin because of its reduced degradation under ACE inhibition. Although around 50% of the reactions occur within the first week of treatment, delayed onset is common and may occur at any time during therapy. Emergency treatment usually is as for other acute forms of acquired AE. The synthetic decapeptide icatibant, a selective competitive antagonist at the bradykinin B2 receptor, is authorized in Europe but not yet by the US Food and Drug Administration for the treatment of acute attacks of hereditary AE. Its mechanism of action makes icatibant a promising drug for severe ACE inhibitor–induced AE, and we describe here for the first time its successful use in this condition.

Efficacy and safety of adalimumab across subgroups of patients with moderate to severe psoriasis - Corrected Proof

Alan Menter, Kenneth B. Gordon, Craig L. Leonardi, Yihua Gu, Orin M. Goldblum — 2010-06-04

Background: The phase III randomized controlled evaluation of adalimumab every other week dosing in moderate to severe psoriasis trial (REVEAL) demonstrated adalimumab induced significant improvements and was well tolerated for patients with moderate to severe psoriasis.Objective: We sought to determine the efficacy and safety of adalimumab for various subgroups of patients in REVEAL with moderate to severe psoriasis and to determine whether these profiles were consistent with the overall results.Methods: Patients (N = 1212) with moderate to severe psoriasis were randomized to adalimumab or placebo during the first 16 weeks of the trial. The primary efficacy endpoint was percentage of patients achieving at least 75% improvement in the Psoriasis Area and Severity Index (PASI) score at week 16. Post hoc subgroup analyses were conducted to determine relationships between adalimumab efficacy and/or safety and age group, sex, race, baseline weight intervals, baseline body mass index, disease duration, baseline severity, prior treatments, and comorbidities.Results: Consistent 75% or greater improvement in the PASI score responses were observed across all patient subgroups, with moderately reduced responses noted for patients in the greater weight and body mass index categories. A multivariate analysis identified treatment received, weight, and age as the most influential factors for mean percentage change in PASI score at week 16. No significant differences in the risk of serious adverse events in adalimumab- versus placebo-treated patients were observed across weight categories or for patients with baseline comorbidities.Limitations: These subanalyses are limited by their relatively short, 16-week duration.Conclusion: Treatment of moderate to severe psoriasis with adalimumab led to consistent 75% or greater improvement in PASI score response rates across the majority of patient subgroups, with no significant differences in serious adverse events.

Phenotypic variability among café-au-lait macules in neurofibromatosis type 1 - Corrected Proof

2010-06-04

Background: Café-au-lait macules (CALMs) in neurofibromatosis type 1 (NF1) are an early and accessible phenotype in NF1, but have not been extensively studied.Objective: We sought to more fully characterize the phenotype of CALMs in patients with NF1.Methods: In all, 24 patients with a diagnosis of NF1 confirmed through clinical diagnosis or molecular genetic testing were recruited from patients seen in the genetics department at the University of Alabama at Birmingham. CALM locations were mapped using standard digital photography. Pigment intensity was measured with a narrowband spectrophotometer, which estimates the relative amount of melanin based on its absorption of visible light. The major response was defined as the difference between the mean melanin from the CALM and the mean melanin from the surrounding skin. The major response for each spot was compared with spots within an individual and across individuals in the study population.Results: There was significant variability of the major response, primarily attributable to intrapersonal variability (48.4%, P < .0001) and secondly to interpersonal variability (33.0%, P < .0094). Subsequent analysis based on genetic mutation type showed significantly darker spots in individuals with germline mutations leading to haploinsufficiency.Limitations: The study was performed on a small population of patients and the method has not yet been used extensively for this purpose.Conclusions: CALMs vary in pigment intensity not only across individuals, but also within individuals and this variability was unrelated to sun exposure. Further studies may help elucidate the molecular basis of this finding, leading to an increased understanding of the pathogenesis of CALMs in NF1.

Long-term etanercept in pediatric patients with plaque psoriasis - Corrected Proof

2010-06-04

Background: No systemic therapies are approved by the US Food and Drug Administration for the treatment of psoriasis in children and adolescents.Objective: We sought to evaluate the long-term safety and efficacy of etanercept in pediatric patients (aged 4-17 years) with moderate to severe plaque psoriasis.Methods: Patients who completed or received substantial treatment benefit in a 48-week, randomized, double-blind, placebo-controlled study (N = 211) evaluating the efficacy and safety of once-weekly etanercept (0.8 mg/kg) were enrolled in this 264-week open-label extension study. The primary end point was the occurrence of adverse events. Secondary end points included Psoriasis Area and Severity Index 50%, 75%, and 90% responses compared with baseline; static Physician Global Assessment; and clear and clear/almost clear static Physician Global Assessment status. Results from a 96-week interim analysis are presented.Results: Of 182 enrolled patients, 181 received treatment and 140 (76.9%) completed week 96. A total of 145 patients (80.1%) reported adverse events; 5 serious adverse events occurred in 3 patients, none of which were treatment related. Observed Psoriasis Area and Severity Index 50% (89%), 75% (61%), and 90% (30%) responses compared with baseline at week 96 were similar to those observed in the double-blind trial. The static Physician Global Assessment was maintained through week 96, when 47% of patients achieved clear/almost clear status.Limitations: This is an interim analysis from an open-label study.Conclusion: Extended treatment with etanercept in pediatric patients with moderate to severe plaque psoriasis was generally well tolerated, and efficacy was maintained through 96 weeks.

Intralesional chemotherapy for nonmelanoma skin cancer: A practical review - Corrected Proof

Joslyn S. Kirby, Christopher J. Miller — 2010-06-01

Intralesional chemotherapy for nonmelanoma skin cancer has existed for more than 5 decades. However, it is used so infrequently that recent consensus guidelines for the treatment of basal cell and squamous cell carcinoma do not include intralesional chemotherapy. Barriers to the use of intralesional chemotherapy include the off-label use of these agents, absence of therapeutic guidelines, a relatively small number of patients treated, and a lack of large, well-designed trials with long-term follow-up. Surgical intervention remains the gold standard for the treatment of nonmelanoma skin cancer; however, intralesional chemotherapy remains an option for well-selected patients who cannot or will not undergo surgery. The objectives of this article are to determine response rates and suggest reasonable treatment guidelines for the treatment of squamous cell carcinoma, keratoacanthoma, and basal cell carcinoma with the most widely available intralesional agents (methotrexate, 5-fluorouracil, bleomycin, and interferon).

New World cutaneous leishmaniasis: Current challenges in diagnosis and parenteral treatment - Corrected Proof

2010-05-24

Many physicians in the United States and other nonendemic countries lack familiarity with New World cutaneous leishmaniasis (CL) and fail to include it in their differential diagnosis when seeing patients with suggestive lesions and recent high-risk travel. Moreover, even when the diagnosis of New World CL is considered and confirmed, physicians in the United States still face obstacles in obtaining appropriate treatment. In this report, we present 3 cases of New World CL that were either initially misdiagnosed or faced significant delays in therapy. We also discuss the optimal approach by which to confirm New World CL and to collaborate with professional colleagues at the Centers for Disease Control and Prevention in treating individual patients. In particular, when pentavalent antimonial treatment is needed for treatment, physicians must obtain appropriate diagnostic studies, communicate with experts at the Centers for Disease Control and Prevention, complete necessary paperwork, and obtain approval from their local institutional review board to administer it.

Hansen's disease (leprosy) complicated by secondary mycobacterial infection - Corrected Proof

2010-05-24

A patient with Hansen's disease received corticosteroids for a type 1 leprosy reaction and subsequently developed a new cutaneous lesion at the original biopsy site from which Mycobacterium fortuitum was cultured. A review of the literature found only two other cases of coinfection with atypical mycobacteria and Mycobacterium leprae, although there are many reports of pulmonary tuberculosis in patients with leprosy. This case highlights the diagnostic difficulties encountered when a patient has two different mycobacterial infections of the skin. The published experience emphasizes that such coinfection is remarkably uncommon in leprosy, despite the frequent use of high doses of corticosteroids for leprosy reactions.

Sustained clinical response to rituximab in a case of life-threatening overlap subepidermal autoimmune blistering disease - Corrected Proof

Yaohan Li, J.B. Foshee, Richard D. Sontheimer — 2010-05-24

The conventional treatment for the autoimmune bullous skin diseases is broad-spectrum immunosuppressive regimen typically combining systemic corticosteroids with adjuvant immunosuppressive therapeutic agents. Orphan diseases in the pemphigus, pemphigoid, and epidermolysis bullosa acquisita groups of clinical disorders are often clinically severe, requiring long-term treatment with such drugs or drug combinations. Rituximab, a chimeric recombinant monoclonal antibody targeting CD20(+) B cells, has recently been suggested to be effective in the treatment of pemphigus with relatively few adverse effects. The clinical value of rituximab in other immune-mediated blistering diseases has been less thoroughly examined. We report a case of a woman who presented initially with the Brunsting-Perry phenotype of cicatricial pemphigoid who subsequently developed severe generalized subepidermal blisters healing with scarring and milia formation thought to be clinically compatible with epidermolysis bullosa acquisita, although type VII collagen autoantibodies were never identified. Treatment with a number of conventional systemic agents was unsuccessful and complicated by methicillin-resistant Staphylococcus aureus–induced cutaneous ulcers and near-fatal gram-negative sepsis. This woman has enjoyed an 18-month complete clinical remission after a single inductive 4-week cycle of intravenous rituximab. This outcome supports the idea that systemic memory B-cell depletion with drugs such as rituximab should be considered for therapeutically refractory subepidermal autoimmune blistering diseases in addition to intraepidermal autoimmune blistering diseases. A potential role for the immunologic phenomenon of epitope spreading in the generation of overlapping features of autoimmune blistering diseases, and its contribution to therapeutic refractoriness (“hardening”), is discussed.

Short anagen syndrome in an African American woman - Corrected Proof

Nidhi Avashia, Heather Woolery-Lloyd, Antonella Tosti, Paolo Romanelli — 2010-05-24

Short anagen syndrome is an uncommon condition characterized by the inability to grow long hair and an increase in the number of hairs in telogen. The incidence of short anagen syndrome is poorly documented in the medical literature. In all reports, patients are Caucasian and usually have fine blond hair. We report a case of a 38-year-old African American woman with short anagen syndrome.

Silver treatments and silver-impregnated dressings for the healing of leg wounds and ulcers: A systematic review and meta-analysis - Corrected Proof

Marissa J. Carter, Kimberly Tingley-Kelley, Robert A. Warriner — 2010-05-14

Previous systematic reviews of silver-impregnated dressings have been contradictory regarding the healing of leg wounds/ulcers. Our systematic review was restricted to randomized controlled trials. Cochrane Library, Scopus, and MEDLINE databases were searched using the term “silver” in combination with “wound” or “ulcer” (and plural versions) without date/language restriction. Study quality was assessed and meta-analysis conducted for complete wound healing, wound size reduction, and healing rates. Overall study quality was fair with most studies having some bias. Evidence for wound healing using individual studies was poor. Meta-analyses found strong evidence for wound healing based on wound size reduction but no evidence based on complete wound-healing or healing rates. Although our results provide some evidence that silver-impregnated dressings improve the short-term healing of wounds and ulcers, long-term effects remain unclear. Clinical trial data with longer follow-up times are needed to address these issues.

Skin mesenchymal stem cells: Prospects for clinical dermatology - Corrected Proof

Klaus Sellheyer, Dieter Krahl — 2010-05-14

Stem cell–based therapies are expected to have a great impact on the medicine of the 21st century. The focus of dermatologic stem cell research is on the epidermis and the hair follicle. In contrast, the characterization of stem cells in the mesenchymal compartments of the skin has largely escaped the attention of the dermatologic community. This is surprising because the dermis may represent a larger reservoir for adult stem cells than the epidermis and the hair follicle together. In 2001, mesenchymal stem cells residing within the dermis were first isolated. They have the capacity to differentiate into adipocytes, smooth muscle cells, osteocytes, chondrocytes, and even neurons and glia as well as hematopoietic cells of myeloid and erythroid lineage. The perifollicular connective tissue sheath and the papilla crystallize as the likely anatomic niche for these multipotent dermal cells. These previously unidentified mesenchymal stem cells have the potential to function as an easily accessible, autologous source for future stem cell transplantation. Potential therapeutic applications include the treatment of acute and steroid-refractory graft-versus-host disease, systemic lupus erythematosus resistant to currently available therapies, or idiopathic pulmonary fibrosis. The neuronal differentiation potential of cutaneous mesenchymal stem cells may also be exploited in the treatment of neurodegenerative disorders. The most immediate impact can be expected in the field of wound healing. In line with the cancer stem cell hypothesis, the potential contributions to dermatopathology include a conceptual understanding of mesenchymal skin-based neoplasms as evolving from a genetically altered dermal stem cell clone.

Ustekinumab significantly improves symptoms of anxiety, depression, and skin-related quality of life in patients with moderate-to-severe psoriasis: Results from a randomized, double-blind, placebo-controlled phase III trial - Corrected Proof

2010-05-12

Background: Anxiety, depression, and impaired health-related quality of life (HRQoL) are common in patients with psoriasis.Objective: We sought to analyze the effect of ustekinumab on these conditions in patients with moderate-to-severe psoriasis.Methods: Patients with moderate-to-severe psoriasis (n = 1230) were randomized 1:1:1 to receive 45 mg of ustekinumab, 90 mg of ustekinumab, or placebo. The Hospital Anxiety and Depression Scale was used to measure anxiety and depression, and the Dermatology Life Quality Index to measure HRQoL.Results: At baseline, 40.3% and 26.7% of patients reported symptoms of anxiety and depression, respectively, and 54.6% reported Dermatology Life Quality Index scores greater than 10, indicating a very high impact of disease on HRQoL. Greater improvements at week 12 in mean Hospital Anxiety and Depression Scale-Anxiety (13.9%), Hospital Anxiety and Depression Scale-Depression (29.3%), and Dermatology Life Quality Index (76.2%) scores were reported in ustekinumab groups compared with placebo (P < .001 each).Limitations: Results for these measures are reported only through 24 weeks.Conclusion: Patients receiving ustekinumab reported significant improvements in symptoms of anxiety, depression, and HRQoL.

Antipruritic treatment with systemic μ-opioid receptor antagonists: A review - Corrected Proof

Ngoc Quan Phan, Jeffrey D. Bernhard, Thomas A. Luger, Sonja Ständer — 2010-05-12

During the past two decades, systemic μ-opioid receptor antagonists (MORA) have been used in the treatment of various forms of chronic pruritus. In a number of case reports, case series, and controlled trials, treatment with MORA has demonstrated considerable antipruritic effects. In double-blind controlled studies, significant antipruritic relief has been achieved by MORA in cholestatic pruritus, chronic urticaria, and atopic dermatitis. In case reports and case series, antipruritic efficacy of MORA has been reported in prurigo nodularis, mycosis fungoides, postburn pruritus, aquagenic pruritus, hydroxyethyl starch-induced pruritus, and pruritus of unknown origin. However, most of the evidence remains anecdotal, the design of these trials varies, and comparison of results is difficult. In this review we aim to present an overview of these reports and to assess the evidence for the antipruritic action of the drugs naloxone, nalmefene, and naltrexone, which are currently in use for the treatment of chronic pruritus of different origins. We will also evaluate recommendations for the use of MORA in daily medical practice.

Cutaneous collagenous vasculopathy with generalized telangiectasia in two female patients - Corrected Proof

2010-05-07

Cutaneous collagenous vasculopathy is characterized by generalized cutaneous telangiectasia and unique microscopic and ultrastructural vascular changes, consisting of marked collagen deposition within the vascular walls of the post-capillary venules in the superficial dermis. There are only 4 previous cases described in the medical literature, all in males, mostly middle-aged. We have recently seen two female patients with clinical and histopathologic features diagnostic of cutaneous collagenous vasculopathy, indicating that it is not restricted to males. As cutaneous collagenous vasculopathy can be clinically indistinguishable from generalized essential telangiectasia, and histopathologic studies are rarely performed for this condition, it is likely that cutaneous collagenous vasculopathy frequently passes unrecognized, but it may be more common than previously thought.

Disseminated superficial actinic porokeratosis co-existing with linear and verrucous porokeratosis in an elderly woman: Update on the genetics and clinical expression of porokeratosis - Corrected Proof

Jenny Murase, Anita C. Gilliam — 2010-05-07

Disseminated superficial actinic porokeratosis (DSAP) is the most common form of porokeratosis, occurring mainly in women on the extremities as atrophic patches rimmed by a ridge of keratin (the cornoid lamella that is diagnostic of porokeratosis histologically and is thought to be a clonal keratinocyte proliferation). DSAP can sometimes coexist with other forms of porokeratosis (Mibelli, linear porokeratosis, porokeratosis palmaris et plantaris disseminata, and punctate porokeratosis). Rare variants of linear porokeratosis are the hyperkeratotic and verrucous forms which usually occur on the buttocks or perianal area. We present clinical and histopathologic findings from biopsy specimens of a 73-year-old woman with DSAP on the distal extremities, linear/segmental porokeratosis on thighs, and verrucous porokeratosis on buttocks and mons pubis. The verrucous lesions had been present for 30+ years, the DSAP and linear lesions for 10+ years. Biopsy specimens from distal extremity showed classic features of DSAP with infrequent cornoid lamellae separated by atrophic epidermis. Biopsy specimens from the mons pubis and thigh showed epidermal hyperplasia with multiple, almost contiguous, broad cornoid lamellae. Coexisting variants of porokeratosis are rare and our conclusions are drawn from a few cases in the literature. The rare variants of porokeratosis are of interest because the clinical morphology correlates with the histopathology.

Reliability assessment and validation of the Melasma Area and Severity Index (MASI) and a new modified MASI scoring method - Corrected Proof

2010-04-16

Background: The Melasma Area and Severity Index (MASI), the most commonly used outcome measure for melasma, has not been validated.Objective: We sought to determine the reliability and validity of the MASI.Methods: After standardized training, 6 raters independently rated 21 patients with mild to severe melasma once daily over a period of 2 days to determine intrarater and interrater reliability. Validation was performed by comparing the MASI with the melasma severity scale. The darkness component of the MASI was validated by comparing it with the difference between mexameter scores for affected versus adjacent normal-appearing skin. The area component of the MASI was validated by comparing it with the area of each section of the face determined by computer-based measurement software.Results: The MASI score showed good reliability within and between raters and was found to be valid when compared with the melasma severity scale, mexameter scores, and area measurements. Homogeneity assessment by raters showed the least agreement and can be removed from the MASI score without any loss of reliability.Limitations: Patients were limited to Hispanic, African, and Asian backgrounds.Conclusion: The MASI is a reliable measure of melasma severity. Area of involvement and darkness are sufficient for accurate measurement of the severity of melasma and homogeneity can be eliminated.

Spreading pigmented actinic keratosis: A review - Corrected Proof

Elizabeth E. Uhlenhake, Omar P. Sangueza, Andrew D. Lee, Joseph L. Jorizzo — 2010-03-24

Introduction: Spreading pigmented actinic keratosis (SPAK) is a common, but uncommonly reported or appreciated, variant of classic actinic keratosis (AK). It can mimic different pigmented lesions, which may be benign (eg, solar lentigo) or malignant (eg, lentigo maligna).Objective: We sought to review current data and identify areas needing further research to establish diagnostic guidelines for SPAK and to increase awareness of this common entity.Methods: A literature search was performed in both PubMed and MEDLINE databases using the search terms “spreading pigmented actinic keratosis,” “pigmented solar keratosis,” “pigmented actinic,” and “pigmented solar.” Each article was retrieved, reviewed, and summarized.Results: SPAK is a rarely reported lesion that can be difficult to distinguish from other benign and malignant pigmented lesions, including seborrheic keratosis, melanoma in situ (lentigo maligna type), and lentigo maligna melanoma. Located mainly on sun-exposed areas and with a size greater than 1.5 cm, the lesion typically spreads laterally. Pathologically, the lesion resembles classic AK with increased basal melanization. The malignancy potential has not yet been elucidated but destructive therapies such as cryotherapy are recommended.Limitations: Reports not yet published or not included in the comprehensive databases we used may exist that were not analyzed.Conclusions: SPAK can be associated with adjacent melanoma in situ; therefore, its diagnosis merits increased suspicion for coexisting melanoma.

Intralesional agents in the management of cutaneous malignancy: A review - Corrected Proof

Laurie M. Good, Misha D. Miller, Whitney A. High — 2010-03-24

Intralesional agents have a role in the management of cutaneous malignancies. In this article, the efficacy, side effects, strengths, limitations, costs, and practical considerations regarding the use of intralesional agents to treat basal cell carcinoma, squamous cell carcinoma, selected cutaneous lymphomas, and even metastatic melanoma are reviewed. Intralesional administration of 5-fluorouracil, interferon, interleukin-2, bleomycin with electrochemotherapy, and aminolevulinic acid with photodynamic therapy are discussed as treatment modalities in basal cell carcinoma. Interferon (∼1.5 M IU, 3 times weekly × 3 weeks) is perhaps the most widely used regimen for basal cell carcinoma. With regard to squamous cell carcinoma, treatment with 5-fluorouracil, methotrexate, interferon, and bleomycin are reviewed. Methotrexate (∼0.3-2.0 mL of 12.5 or 25 mg/mL, two injections ∼2 weeks apart) was perhaps the most widely used agent. Interferon (3 M IU × 3 times weekly for ∼8.5 weeks) and rituximab (10-30 mg per lesion, 3 times weekly for 1 week, possibly repeated 4 weeks later) are sometimes used in the management of primary cutaneous B-cell lymphomas, whereas in primary cutaneous CD30+ lymphoma intralesional methotrexate (0.4-0.5 mL of 50 mg/mL weekly for 2 weeks) has been used. Finally, the roles of BCG vaccine, cidofovir, rose bengal, and bleomycin with electrochemotherapy for the palliation of metastatic melanoma are reviewed. Intralesional management appears most useful when surgical intervention is not a viable option, for cases in which the cosmetic outcome may be superior, or for situations in which the side effects from systemic chemotherapeutic agents are to be minimized.

Cigarette smoking and malignant melanoma: A case-control study - Corrected Proof

2010-03-24

Background: Several previous studies have reported inverse associations between cigarette smoking and melanoma. Often these studies have not adjusted for ultraviolet (UV) exposure history, skin type, or number of blistering sunburns, which could confound the observed associations between cigarette smoking and melanoma.Objective: We sought to assess whether this reported inverse association persists after adjusting for UV exposure, skin type, and number of blistering sunburns.Methods: We conducted a population-based case-control study (82 patients with melanoma, 164 control subjects). Two control subjects were matched to each patient by age, sex, race, and skin type. Conditional logistic regression models were fit to assess the association between cigarette smoking history and melanoma, with additional adjustments for UV exposure and sunburns.Results: Compared with never smoking, both former (odds ratio 0.43, 95% confidence interval 0.18-1.04) and current (odds ratio 0.65, 95% confidence interval 0.19-2.24) smoking were inversely associated with melanoma, but the associations were not statistically significant.Limitations: The number of cutaneous nevi was not assessed in this study. In addition, the relatively small number of patients limits the statistical precision of the observed associations.Conclusions: After matching for age, sex, race, and skin type, and further adjusting for UV exposure and number of sunburns, cigarette smoking was not statistically significantly associated with melanoma risk, but the results were consistent with previous observations of an inverse association.

Cocaine-associated retiform purpura and neutropenia: Is levamisole the culprit? - Corrected Proof

2010-03-22

To the Editor: We describe two patients with neutropenia and retiform purpura associated with cocaine use and alert clinicians to the possible emerging public health threat of levamisole-contaminated cocaine.

Epidermotropic metastasis from vulvar squamous cell carcinoma: A rare cutaneous manifestation - Corrected Proof

Annie R. Wang, Meghan O'Brien, Rustin Ross, Thomas Long, Leslie Robinson-Bostom — 2010-03-12

Cutaneous metastases occur in 0.7% to 9% of all malignancies. In women, cutaneous metastases occur most often in breast cancer, followed in order by colorectal carcinoma, melanoma and ovarian carcinoma. Of the squamous cell carcinomas (SCC) that do metastasize, many are exceedingly difficult to differentiate from primary SCC of the skin and are often found in the advanced stages with well-established primary tumor and lymph node involvement. This is an important distinction because metastatic cutaneous SCC is associated with a much poorer prognosis than primary SCC. Cutaneous metastases from vulvar cancers are even less common and have been reported in only 8 cases. We report a rare case of epidermotropic metastatic squamous cell vulvar cancer in a 77-year-old woman.

Increased prevalence of left-sided skin cancers - Corrected Proof

Susan T. Butler, Scott W. Fosko — 2010-03-12

Background: Previous research has shown an increase in photodamage and precancers on the left side of the face.Objective: We sought to determine whether there is a higher frequency of skin cancer development on the left side of the body than the right.Methods: The study was a retrospective review of patients with skin cancer referred to our Mohs micrographic surgery and cutaneous oncology unit in 2004.Results: When including all types of skin cancers and both sexes, more cancers occurred on the left (52.6%) than the right (47.4%) (P = .059), with a stronger trend in men (P = .042). There were significantly more malignant melanoma in situ on the left (31/42, 74%) than the right (11/42, 26%) (P = .002).Limitations: Population was comprised of patients referred to an academic medical center and often for Mohs micrographic surgery.Conclusions: There were significantly more skin cancers on the left than the right side in men. This discrepancy was even more profound in malignant melanoma in situ.

Vitamins and photoaging: Do scientific data support their use? - Corrected Proof

Jamie Zussman, Jennifer Ahdout, Jenny Kim — 2010-03-02

With the rise of the cosmeceutical industry, numerous formulations have surfaced with claims of reducing the clinical manifestations of photoaging. Many of these products capitalize on the positive connection the public makes with vitamins, especially with respect to their antioxidant capabilities. An impressive amount of basic science and clinical research has been conducted in both an attempt to discover novel strategies for preventing detrimental sun damage and to validate the addition of vitamins to skin care products. As dermatologists, it will be essential to provide our patients with substantiated counseling regarding the efficacy of commercial assertions. In this review, we will systematically examine the evidence supporting the use of vitamins in oral and topical formulations and provide a brief summary of the pathogenesis of photoaging. Limitations of this study include that there may be unpublished data or additional studies that may have been overlooked in our comprehensive review of this topic.