Journal of the American Academy of Dermatology - Articles in Press

Rural-urban differences in behaviors to prevent skin cancer: An analysis of the Health Information National Trends Survey - Corrected Proof

Whitney E. Zahnd, Jonathan Goldfarb, Steven L. Scaife, Mark L. Francis — 2010-03-17

Background: There is concern that rural residents may be less likely to engage in behaviors to reduce their risk for skin cancer compared with urban residents.Objectives: First, we sought to determine whether rural residents are less likely to use sunscreen and engage in other skin cancer preventive measures. Second, we sought to determine whether such actions are sufficiently explained by factors known to affect these behaviors or whether such actions are affected by rurality.Methods: We analyzed the 2005 Health Information National Trends Survey, a survey of the noninstitutionalized, adult population performed by the National Cancer Institute. We used logistic regression analysis to adjust for confounding by age, race, income, education, health insurance, smoking, sex, marital status, and region.Results: Compared with urban residents, rural residents were 33% less likely (odds ratio = 0.67; 95% confidence interval, 0.57-0.80) to wear sunscreen when exposed to the sun for more than 1 hour. After adjusting for the above confounding variables, however, rural individuals were just as likely as urban individuals to use sunscreen with sun exposure.Limitations: Inability to adjust for unmeasured confounding variables, such as occupational sun exposure, is a limitation.Conclusion: Rural residents were less likely to use sunscreen. This decreased use of sunscreen, however, was explained by differences in age, race, income, education, and other confounding factors that negatively influence the use of sunscreen.

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.

Seven-point checklist for dermatoscopy: Performance during 10 years of prospective surveillance of patients at increased melanoma risk - Corrected Proof

2010-03-12

Background: The retrospectively developed 7-point checklist is one of the most applicable dermatoscopic algorithms for clinical use. However, until today no prospective data on the diagnostic performance of this algorithm were reported.Objective: Our aim was to assess the sensitivity, specificity, and diagnostic accuracy of the 7-point checklist in the setting of a prospective long-term study.Methods: Patients at increased melanoma risk (n = 688) were screened at regular intervals by naked-eye examination, the dermatoscopic 7-point checklist, and digital dermatoscopy follow-up (10-year study interval).Results: We detected 127 melanomas including 50 melanomas in situ. The mean Breslow thickness of invasive melanomas was 0.57 mm. A total of 79 melanomas displayed the 7-point checklist melanoma threshold of 3 or more points (62% sensitivity, compared with 78%-95% in retrospective settings). In all, 48 melanomas scored fewer than 3 points and were excised because of complementary information (eg, lesional history, dynamic changes detected by digital dermatoscopy). The specificity of the 7-point checklist was 97% (compared with 65%-87% in retrospective settings). Regression patterns, atypical vascular patterns, and radial streaming were associated with the highest relative risk for melanoma (odds ratio 3.26, 95% confidence interval 2.05-5.16; odds ratio 3.04, 95% confidence interval 1.70-5.46; odds ratio 2.91, 95% confidence interval 1.64-5.15; P < .0003, respectively). Melanomas thicker than 0.5 mm exhibited significantly more regression patterns and atypical vascular patterns (P < .02). The malignant versus benign ratio for all excised lesions was 1:8.6 (127 melanomas, 1092 nonmelanomas).Limitations: Calculation of the specificity was a limitation. True negative lesions were defined by a score less than 3 points and either the histopathological diagnosis of nonmelanoma or the absence of dynamic changes during digital dermatoscopy follow-up (nonexcised, nonsuspicious, no change).Conclusions: The 7-point checklist for dermatoscopy was less sensitive but highly specific in this prospective clinical setting. Complementary information clearly increased the sensitivity. Regression patterns or radial streaming in nevi of patients at high risk should raise a higher melanoma suspicion than might be concluded from retrospective studies.

Enacting legislation to restrict youth access to tanning beds: A survey of advocates and sponsoring legislators - Corrected Proof

Busayo Obayan, Alan C. Geller, Elissa A. Resnick, Marie-France Demierre — 2010-03-12

Background: Passing tanning bed legislation restricting underage use has remained challenging.Objective: We sought to determine the resources required to pass tanning bed legislation restricting use to children and identify key barriers to its passage.Methods: A total of 15 states sought to pass tanning bed legislation in 2006; in-depth surveys were completed with advocates in 10 states and legislators in 5 states.Results: Advocates sought advice from the sponsoring legislator or legislators (n = 9), held discussions with other organizations (n = 8), and used a lobbyist (n = 5). The 3 major barriers were strong lobbying efforts by the tanning bed industry (n = 10), proceedings after the bill was filed (n = 5), and obtaining support from other organizations (n = 4). For legislators, the most significant barrier was making colleagues aware of the health effects of tanning bed use.Limitations: Five of 10 legislators and 10 of 15 advocates responded to the survey.Conclusion: Barriers to passage of tanning bed legislation can potentially be surmounted with advice to advocates and coordinated efforts by multiple organizations.

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.

Four novel ATP2A2 mutations in Slovenian patients with Darier disease - Corrected Proof

Aleksandar Godic, Branka Korošec, Jovan Miljković, Aleksej Kansky, Damjan Glavač — 2010-03-11

Background: Darier disease (DD) is an autosomal dominant genodermatosis caused by mutations in the ATP2A2 gene. It has been reported that depletion of Ca2+ stores within the endoplasmic reticulum of keratinocytes is associated with impaired cell cycle regulation and terminal differentiation. Mechanical stress, heat, or UV irradiation might delay cell cycle exit and permit progression into the quiescent stage without repair. When there is associated DNA damage, this can lead to an accumulation of secondary somatic mutations and possible clonal proliferation of damaged keratinocyes within keratotic papules and plaques.Objective: We sought to present clinical, demographic, and genetic analysis of the cohort of Slovenian patients with DD, which represents 52% of DD patients in the country.Methods: We examined 28 Slovenians with DD and screened genomic DNA for ATP2A2 mutations and RNA for splice site mutations.Results: The estimated prevalence of the disease in Slovenia is 2.7/100.000. We identified 7 different ATP2A2 mutations, 4 of which are novel: A516P, R559G, 463-6del6, and 1762-6del18. We also found two previously described polymorphisms in intron XVIII (2741 + 54 G>A) and in exon 15 (2172 G>A; A724A), with allele frequencies of 64.15% and 11.32%, respectively. There was a history of perceptive deafness in two DD patients from two families.Limitations: Analysis of SERCA2 expression, measurements of Ca2+ uptake and their influence on desmosomal assembly in vitro would add additional value to the study. Although single-stranded conformational analysis (SSCP) is a common and accepted method for screening for the presence of mutations, it does miss 10% to 20% of mutations.Conclusions: We identified 4 novel ATP2A2 mutations in Slovenian patients with DD. Deafness seems to be a new phenotypic characteristic of DD patients.

Risk of second primary malignancies following cutaneous melanoma diagnosis: A population-based study - Corrected Proof

Joshua P. Spanogle, Christina A. Clarke, Sarah Aroner, Susan M. Swetter — 2010-03-11

Background: Understanding risk patterns for developing a second primary malignancy (SPM) after cutaneous melanoma (CM) has implications for both research and clinical practice, including cancer screening.Objective: We sought to describe incidence patterns of SPMs occurring after CM.Methods: We calculated incidence rates and relative risks for the development of 65 different SPMs occurring in 16,591 CM survivors during 1.3 million person-years of observation in the Surveillance, Epidemiology, and End Results program data from 1973 to 2003.Results: Compared with the general population, CM survivors had a 32% higher risk of developing any SPM and demonstrated significantly elevated risks for 13 cancers: melanoma of the skin (standardized incidence ratio [SIR] 8.99), soft tissue (SIR 2.80), melanoma of the eye and orbit (SIR 2.64), nonepithelial skin (SIR 2.31), salivary gland (SIR 2.18), bone and joint (SIR 1.70), thyroid (SIR 1.90), kidney (SIR 1.29), chronic lymphocytic leukemia (SIR 1.29), brain and nervous system (SIR 1.31), non-Hodgkin lymphoma (SIR 1.25), prostate (SIR 1.13), and female breast (SIR 1.07). Risks of second primary melanoma of the skin, melanoma of the eye and orbit, and cancers of the prostate, soft tissue, salivary gland, and bone and joint were elevated throughout the study period, implying no surveillance bias.Limitations: Possible underreporting of CM incidence in cancer registries is a limitation. In addition, the lack of individual-level data in cancer registry data precludes detailed examination of coincident risk factors.Conclusion: Risks of particular SPMs after CM may be explained by surveillance bias or shared risk factors. However, these probably do not explain the increased risks observed for prostate, soft tissue, salivary gland, and bone and joint cancers years after CM diagnosis. Further investigation into genetic or environmental commonalities between CM and these cancers is warranted.

Use of and beliefs about total body photography and dermatoscopy among US dermatology training programs: An update - Corrected Proof

Vitaly Terushkin, Susan A. Oliveria, Ashfaq A. Marghoob, Allan C. Halpern — 2010-03-11

Background: Total body photography (TBP) and dermatoscopy are imaging techniques used to treat patients with pigmented lesions.Objective: We sought to describe use, training, logistics, and beliefs about these tools among residency programs and to assess changes during a 10-year period.Methods: Surveys were sent to all directors (n = 111) and chief residents (n = 109) of US dermatology training programs.Results: A total of 83 (74.8%) attendings answered the questionnaire. In all, 59 (71.1%) reported using TBP, an 11.9% increase (P = .2484) over the past decade. Reasons for using TBP included: reduces patient anxiety (81.4%), helps detect early melanoma (78.0%), and leads to fewer biopsies (66.1%). Logistical (79.2%) and financial (45.8%) constraints were reasons for not using TBP. Seventy respondents (84.3%) reported using dermatoscopy, a 40.0% increase (P = .0001) over the 10-year period. Reasons for dermatoscopy use were consistent over time: helps find melanoma in curable stage (75.7%), reduces patient anxiety (61.4%), and leads to fewer biopsies (57.1%). The most common reason for not using dermatoscopy remained lack of training (38.5%). A total of 92 (84.4%) residents completed their survey, of which 41 (44.6%) and 81 (88.0%) reported using TBP and dermatoscopy, respectively. In all, 62 (67.4%) and 79 (85.9%) respondents would prefer additional training in TBP and dermatoscopy, respectively.Limitations: Results may not be applicable to the general dermatology community.Conclusions: Use of dermatoscopy among residency programs has increased significantly during the last decade. A more modest increase in the use of TBP was observed. Barriers to diffusion of these technologies into practice persist, including insufficient logistics and training.

The effect of adalimumab on reducing depression symptoms in patients with moderate to severe psoriasis: A randomized clinical trial - Corrected Proof

2010-03-10

Background: Psoriasis is associated with health-related quality-of-life impairment and depression.Objective: We sought to determine the effect of adalimumab on depression symptoms in patients with psoriasis.Methods: Patients with moderate to severe psoriasis in a randomized, placebo-controlled, double-blind clinical trial were assessed for depression symptoms at baseline and week 12 or early termination (ET) using the Zung Self-rating Depression Scale (ZDS). The effects of adalimumab (40 mg every other week) versus placebo on ZDS score at week 12/ET were assessed using analysis of covariance. Relationships between ZDS and the Psoriasis Area and Severity Index (PASI), the Dermatology Life Quality Index, and the Short Form 36 Health Survey were assessed using Pearson correlations. Changes in ZDS score were compared for patients with and without a 75% or greater reduction in baseline PASI score.Results: Compared with the placebo group (n = 52), the adalimumab group (n = 44) experienced an additional 6-point reduction in ZDS score (95% confidence interval: 2.5-9.5; P < .001) by week 12/ET. Depression improvement was correlated with improvement in PASI (r = 0.5; P < .0001) and Dermatology Life Quality Index (r = 0.5; P < .0001). Greater ZDS score improvement was observed at week 12/ET in responders with a 75% or greater reduction in baseline PASI score than in nonresponders (10.6 [SD = 9.4] vs 1.4 [SD = 9.6]; P < .001).Limitations: This analysis cannot distinguish whether adalimumab has a direct or indirect effect on depression.Conclusions: Adalimumab treatment reduced psoriasis symptoms, reduced depression symptoms, and improved health-related quality of life in patients with moderate to severe psoriasis.

Effectiveness of a knowledge-based intervention for melanoma among those with ethnic skin - Corrected Proof

2010-03-10

Background: Among patients with melanoma, ethnic minorities are 1.96 to 3.01 times as likely to die from melanoma as Caucasians of the same age and sex.Objective: We sought to assess the effectiveness of a melanoma early detection educational intervention among those with ethnic skin.Methods: A consecutive convenience sample of patients received instruction on the ABCDEs of melanoma and skin self-examination. Self-report questionnaires assessing knowledge, attitudes, and behaviors were completed before, and immediately and 3 months after, the intervention.Results: Among the 71 participants, 21% reported a skin phenotype with at least sometimes burning. Knowledge that melanoma is a skin cancer and of the warning signs of melanoma significantly increased after the intervention and was retained at 3 months. The perception of being at risk to develop a melanoma significantly increased after the intervention and was retained at 3 months (P < .001). Monthly checking of the skin, especially acral sites (palms, soles, periungual), increased significantly immediately after the intervention.Limitations: A limitation is accrual from dermatology patients, who may be more inclined to perform skin self-examination compared with the general minority population.Conclusions: People of color benefit from specific physician recommendations explaining their risk to develop melanoma and which anatomic sites to check. Acral lentiginous melanoma among ethnic minorities tends to present in non-sun-exposed but visible areas, particularly volar and subungual sites; therefore, skin self-examination educational materials for minority populations should incorporate these anatomic sites.

Differences in melanoma outcomes among Hispanic Medicare enrollees - Corrected Proof

Panta Rouhani, Kristopher L. Arheart, Robert S. Kirsner — 2010-03-10

Background: Hispanics are given the diagnosis of melanoma at later stages and have reduced survival.Objective: We sought to evaluate the effect of Hispanic ethnicity and different health care delivery systems (fee-for-service [FFS] and health maintenance organizations) on melanoma stage at diagnosis and survival.Methods: We studied a retrospective cohort of 40,633 patients, with at least 3 years of follow-up, who were given the diagnosis of incident melanoma from 1991 to 2002 and were 65 years or older using data from the Surveillance, Epidemiology, and End Results–Medicare linked database. The analytic sample consisted of 39,962 non-Hispanic whites (NHW) and 671 Hispanics. Logistic regression models examined the roles of the health care delivery system and race/ethnicity in stage at diagnosis and survival.Results: For FFS patients, Hispanics were more likely to be given a diagnosis at an advanced stage (distant vs earlier stages [odds ratio {OR} = 2.07; 95% confidence interval {CI} = 1.36-3.16]; regional vs earlier stages [OR = 2.31; 95% CI = 1.75-3.03]) compared with NHW. Among Hispanic patients, those enrolled in health maintenance organizations were less likely to be given a diagnosis at later stage (regional vs earlier stages [OR = 0.50; 95% CI = 0.31-0.81]) than FFS patients; however, the earlier stage at diagnosis did not improve survival. For patients with a previous cancer before their melanoma diagnoses, NHW enrolled in health maintenance organizations from 1991 to 2002 were given a diagnosis at earlier stages compared with NHW FFS patients (OR = 0.72; 95% CI = 0.52-0.99); this was not found among Hispanics.Limitations: These results reflect findings in a Medicare-aged population and it is not clear if they are generalizable to younger patients.Conclusions: Differences in melanoma outcomes among different ethnic groups are, in part, dependent on the health care setting in which patients are enrolled.

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.

Characterization of Staphylococcus aureus cutaneous infections in a pediatric dermatology tertiary health care outpatient facility - Corrected Proof

Alex G. Ortega-Loayza, Stephanie A. Diamantis, Peter Gilligan, Dean S. Morrell — 2010-02-22

Background: Epidemiology and patterns of antibiotic resistance for Staphylococcus aureus are changing in the United States.Objective: We sought to determine the epidemiology and antibiotic susceptibility profiles in S aureus cutaneous infections in a pediatric dermatology tertiary health care facility in North Carolina.Methods: We conducted a prospective observational study involving pediatric patients (n = 93, age<18 years) with signs of skin and soft tissue infections seen at a pediatric dermatology clinic between 2005 and 2007.Results: We analyzed 141 cultures from 93 pediatric dermatology patients. S aureus was recovered from 97 cultures, of which 32% were methicillin-resistant S aureus (MRSA). In the pediatric dermatology clinic, children with atopic dermatitis accounted for 66% of the cultures; however, the presence of atopy did not represent a risk factor to acquire MRSA infection (P = .190; odds ratio = 1.643 [95% confidence interval: 0.672-4.014]). In all, 97 cultures were tested for antibiotic susceptibility and demonstrated the following resistance patterns: penicillin (86%), erythromycin (46%), methicillin (32%), clindamycin (22%), gentamicin (3%), vancomycin (0%), and trimethoprim-sulfamethoxazole (0%). Of the pediatric dermatology outpatient MRSA infections, the resistance patterns were as follows: erythromycin (71%), clindamycin (16%), gentamicin (2%), and trimethoprim-sulfamethoxazole (0%).Limitations: This study addressed a select population of children in North Carolina and may not generalize to different clinical settings or regions.Conclusion: Cutaneous S aureus infections in an outpatient pediatric dermatology tertiary health care facility demonstrated less resistance than previously reported from inpatient and emergency department settings. In our population, clindamycin and tetracyclines are still effective antibiotic choices in the majority of MRSA infections. Local prevalence and susceptibility of community-acquired MRSA as well as individual risk factors should be considered for diagnosis and treatment.

Disseminated Strongyloides stercoralis: Hyperinfection during medical immunosuppression - Corrected Proof

2010-02-22

Hyperinfection caused by Strongyloides stercoralis in iatrogenically immunosuppressed patients is becoming more frequently observed. Here, we review the relevant literature and present a recent case of hyperinfection syndrome of S stercoralis in a patient chronically treated with systemic corticosteroids and methotrexate for dermatomyositis. The patient was born in Guatemala but no history of Strongyloides infection was documented. Disseminated Strongyloides is often associated with the immunocompromised state and is commonly seen with cutaneous lesions, respiratory failure, and sepsis. In this patient, a protracted course of progressive muscle weakness and multiple hospital stays for respiratory distress led to acute respiratory failure, septic shock, and rapid physical decline. A few days preceding his death, the patient developed petechiae and multiple purpuric macules and patches over the abdomen and thighs. Histologic review of skin biopsy specimens demonstrated multiple intravascular and interstitial filariform larvae. Dermatologists should be aware of patient populations at risk for infection with S stercoralis and be able to make this diagnosis to initiate earlier treatment of hyperinfection and dissemination.

Drug samples in dermatology: Special considerations and recommendations for the future - Corrected Proof

Ali Alikhan, Mary Sockolov, Robert T. Brodell, Steven R. Feldman — 2010-02-22

Background: The use of drug samples is a controversial issue in medicine.Objective: We sought to determine the pros and cons of drug sampling, and how drug sampling in general medicine differs from dermatology.Methods: Literature searches were conducted on PubMed, Google, and Yahoo!. Articles were found pertaining to drug sampling in general, and for dermatology specifically.Results: Numerous pros and cons for drug sampling were found in the literature search. We divided these by cost-related issues, such as the industry-wide cost of sampling and the use of sampling to assist the underinsured and poor, and quality of care issues, such as adherence, patient education, and safety considerations. Articles also suggested that dermatology may differ from general medicine as topical treatments have fewer side effects, are more complicated to use, and come in different vehicles.Limitations: We identified few studies specifically focused on issues relevant to sampling in dermatology.Conclusion: There are strong arguments for and against drug sampling involving both cost and quality of care issues. Dermatology-specific medications clearly differ from oral medications in several regards. We ultimately conclude that the benefits of drug sampling outweigh the risks, but give recommendations on how drug sampling can be done ethically and effectively, including limiting personal use, not selling samples, properly documenting sample release, teaching patients about proper use, teaching students and residents ethical use of samples, working with pharmaceutical representatives in an ethical manner, prescribing the drug that is best for the patient, and securing samples appropriately to prevent theft and misuse.

Individual drug sampling does not supplant the need for head-to-head trials in dermatology - Corrected Proof

Jack S. Resneck, Marta VanBeek — 2010-02-22

A growing body of evidence has highlighted several risks and benefits associated with in-office sampling of prescription medications. While use-testing dermatologic medications from a sample closet may benefit some patients, it seems that the stunning lack of head-to-head trials comparing therapeutic options is a much larger and more important impediment to our determination of when the increased cost of newer agents is justified by superior efficacy, safety, or tolerability. If physicians are to retain the critical autonomy to make independent prescribing decisions in concert with our individual patients, we must take responsibility to call for and generate the comparative data we need to evaluate therapeutic options.

Atypical vascular lesion of the breast - Corrected Proof

Joshua Mandrell, Sheetal Mehta, Stacy McClure — 2010-02-08

Atypical vascular lesions (AVLs) are vascular proliferations that develop after surgery and radiation for breast carcinoma and may represent precursors to angiosarcoma. AVLs are not well-known entities and currently lack official prognostic factors and guidelines for surgical treatment. We report the case of a patient who developed an AVL, vascular type, 4 years after lumpectomy and radiation therapy for ductal carcinoma in situ of the breast. The patient underwent wide local excision with 1-cm margins with subsequent pathologic examination confirming complete excision of the residual atypical vascular proliferation. This case highlights the importance of close cutaneous surveillance in patients with a history of surgery and radiation for breast carcinoma, and a low threshold for biopsy. More studies are needed to further delineate the risk of AVLs progressing to angiosarcoma and to identify histologic features or immunophenotypic markers, which may be predictive of this risk. Furthermore, formal treatment recommendations for these enigmatic entities would be helpful.

Malignant melanoma transformation within a nevus of Ito - Corrected Proof

Sean R. Wise, Gregory Capra, Peter Martin, Donna Wallace, Charles Miller — 2010-01-14

The mongolian spot, nevus of Ota, and nevus of Ito are the most common morphologic forms of the dermal melanocytoses, a group of benign pigmented lesions histologically characterized by the presence of melanocytes within the dermis. Nevus of Ito is clinically distinct, presenting with unilateral, bluish gray, patchy discolorations in the skin within the distributions of the posterior supraclavicular and lateral cutaneous brachial nerves. Although all dermal melanocytoses are generally considered benign, rare cases of malignant transformation associated with nevus of Ota have been described. Only one case of malignant melanoma transformation in association with nevus of Ito has previously been reported. We present the second description of malignant melanoma transformation within a nevus of Ito and provide comment on the malignant potential of the dermal melanocytoses.

Expression of proliferative biomarkers in anal intraepithelial neoplasia of HIV-positive men - Corrected Proof

2009-12-14

Background: Anal intraepithelial neoplasia (AIN), a human papillomavirus (HPV)–associated precursor lesion of anal carcinoma, is highly prevalent among HIV-infected individuals, especially in men having sex with men (MSM). Early diagnosis and treatment of AIN might prevent development of anal cancer.Objectives: We aimed to evaluate the expression of 8 promising proliferative biomarkers in anal dysplasia and to compare the efficacy of these markers in diagnosing high-grade AIN.Methods: Immunohistochemical analysis of minichromosome maintenance proteins (MCM3, MCM4, MCM6, and MCM7), p21, Ki-67, p16, and proliferating cell nuclear antigen (PCNA) was performed in a total of 49 specimens of normal anal mucosa and high- and low-grade anal dysplasia. HPV typing for 36 high- and low-risk HPVs was performed, and high-risk HPV-DNA loads were determined by real-time polymerase chain reaction (PCR) for HPV-types 16, 18, 31, and 33.Results: A total of 392 immunohistochemical slides were analyzed in this study. In the progression from normal epithelium to high-grade dysplasia, we found significant differences in the expression of all biomarkers. A cutoff of 25% or 50% lesional immunopositivity for the 4 MCMs, Ki-67, and p16 resulted in 100% sensitivity and 100% specificity to diagnose high-grade AIN. Sensitivity and specificity of PCNA and p21 for a high-grade AIN diagnosis were lower. HPV-DNA was detectable in 100% of high-grade AIN and 87.5% of low-grade AIN lesions. All MCMs, p16, Ki-67, and PCNA, but not p21 correlated with cumulative lesional high-grade HPV-DNA loads.Limitations: The relatively small number of samples is a limitation, especially for adequate subgroup analyses.Conclusions: MCMs, Ki67, and p16 are reliable immunohistochemical adjuncts for diagnosing high-grade AIN.

Incidence of psoriasis in children: A population-based study - Corrected Proof

Megha M. Tollefson, Cynthia S. Crowson, Marian T. McEvoy, Hilal Maradit Kremers — 2009-12-07

Background: Although psoriasis is considered to have a dual peak in age of onset, currently no studies exist regarding the incidence of psoriasis in children.Objective: The objective of this study was to determine the incidence of psoriasis in childhood.Methods: A population-based incidence cohort of patients aged younger than 18 years first given the diagnosis of psoriasis between January 1, 1970, and December 31, 1999, was assembled. The complete medical record of each child was reviewed and psoriasis diagnosis was validated by a confirmatory diagnosis in the medical record by a dermatologist or medical record review by a dermatologist. Age- and sex-specific incidence rates were calculated and were age and sex adjusted to 2000 US white population.Results: The overall age- and sex-adjusted annual incidence of pediatric psoriasis was 40.8 per 100,000 (95% confidence interval: 36.6-45.1). When psoriasis diagnosis was restricted to dermatologist-confirmed subjects in the medical record, the incidence was 33.2 per 100,000 (95% confidence interval: 29.3-37.0). Incidence of psoriasis in children increased significantly over time from 29.6 per 100,000 in 1970 through 1974 to 62.7 per 100,000 in 1995 through 1999 (P < .001). Chronic plaque psoriasis was the most common type (73.7%), and the most commonly involved sites were the extremities (59.9%) and the scalp (46.8%).Limitations: The population studied was a mostly white population in the upper Midwest.Conclusion: The incidence of pediatric psoriasis increases with increasing age. There is no apparent dual peak in incidence. The incidence of pediatric psoriasis increased in recent years in both boys and girls.

Factors affecting sleep quality in patients with psoriasis - Corrected Proof

Smitha Gowda, Orin M. Goldblum, W. Vaughn McCall, Steven R. Feldman — 2009-11-30

Poor sleep quality adversely affects quality of life in patients with psoriasis. However, the factors impairing sleep in these patients have not been well described. We reviewed the available literature linking sleep quality and psoriasis to elucidate factors that interfere with sleep. Pruritus, depression, pain, and obstructive sleep apnea may be likely sources of sleep impairment in patients with psoriasis. Fatigue resulting from sleep interference may also be implicated in this relationship. Pruritus, depression, and pain interfere with sleep quality by increasing nocturnal awakenings and sleep fragmentation. Obstructive sleep apnea may occur in a greater percentage of patients with psoriasis than control populations. Factors associated with psoriasis appear to have similarities in their cytokine and neuropeptide profiles. Moreover, these variables are complex and interconnected. Further study and awareness of potential factors impacting sleep in patients with psoriasis may provide new avenues for treatment of recalcitrant disease.

Cyclosporine and psoriasis: 2008 National Psoriasis Foundation∗ Consensus Conference - Corrected Proof

David M. Rosmarin, Mark Lebwohl, Boni E. Elewski, Alice B. Gottlieb — 2009-11-25

Background: Cyclosporine is a valuable option for the treatment of psoriasis. This report summarizes studies regarding the use of cyclosporine since the last guidelines were published in 1998.Objective: A task force of the National Psoriasis Foundation Medical Board was convened to evaluate treatment options. Our aim was to achieve a consensus on new updated guidelines for the use of cyclosporine in the treatment of psoriasis.Methods: Reports in the literature were reviewed regarding cyclosporine therapy.Limitations: There are few evidence-based studies on the treatment of psoriasis with cyclosporine.Results: A consensus was achieved on the use of cyclosporine in psoriasis including specific recommendations on dosing, monitoring, and use of cyclosporine in special situations. The consensus received approval from members of the National Psoriasis Foundation Medical Board.Conclusions: Cyclosporine is a safe and effective drug for the treatment of psoriasis. It has a particularly useful role in managing psoriatic crises, treating psoriasis unresponsive to other modalities, bridging to other therapies, and treating psoriasis within a rotational scheme of other medications. Appropriate patient selection and monitoring will significantly decrease the risks of side effects.

Erythema multiforme during anti–tumor necrosis factor treatment for plaque psoriasis - Corrected Proof

Jennifer Ahdout, Jennifer C. Haley, Melvin W. Chiu — 2009-11-16

Tumor necrosis factor alpha (TNF-α) inhibitors constitute a class of biologic treatments utilized in the management of psoriasis. We report a case of a patient treated for chronic plaque psoriasis with the anti-TNF-α monoclonal antibody adalimumab, who developed erythema multiforme (EM). The patient had previously developed EM on two occasions while taking the TNF-α inhibitor etanercept. EM has previously been reported in connection with other TNF-α inhibitors, including etanercept and infliximab. To our knowledge, this is the first case reported in the literature documenting EM occurring subsequent to adalimumab treatment for psoriasis. The recurrent development of EM in our patient while being treated with distinct TNF-α inhibitors may suggest that EM is the consequence of a class effect with TNF-α inhibitors.

Efficacy and safety of treatments for childhood psoriasis: A systematic literature review - Corrected Proof

2009-11-09

Background: Evidence-based recommendations for therapeutic decision making in childhood psoriasis are lacking.Objectives: We sought to systematically review all available literature concerning treatment efficacy and safety in childhood psoriasis and to propose a recommendation for topical and systemic treatment of childhood psoriasis.Methods: Databases searched were PubMed, EMBASE, and the Cochrane Controlled Clinical Trial Register. All studies reporting on efficacy and safety of all treatment options in childhood psoriasis were obtained and a level of evidence was determined.Results: Literature search revealed 2649 studies, of which 64 studies met the inclusion criteria. The majority of topical and systemic therapies given in childhood psoriasis are efficacious. Short-term side effects were usually mild; long-term side effects were not described.Limitations: Most conclusions formulated are not based on randomized controlled trials.Conclusions: A rough summary of the proposed algorithm is as follows: first, calcipotriene with/without topical corticosteroids, followed by dithranol. Methotrexate is considered to be the systemic treatment of choice.

Spatiotemporal expression pattern of neuroepithelial stem cell marker nestin suggests a role in dermal homeostasis, neovasculogenesis, and tumor stroma development: A study on embryonic and adult human skin - Corrected Proof

Klaus Sellheyer, Dieter Krahl — 2009-10-28

Background: Whereas keratinocytic bulge stem cells are well characterized, comparably little is known about cutaneous mesenchymal stem cells. The follicular connective tissue sheath is proposed as a niche for dermal stem cells.Objective: Because the neuroepithelial stem cell marker nestin represents a marker for mesenchymal stem cells in various tissues, our aim was to characterize its spatiotemporal expression pattern in the skin with special reference to the follicular mesenchyme.Methods: We studied immunohistochemically nestin expression over the course of human cutaneous embryogenesis, in postnatal skin, in scalp wounds, and in the peritumoral stroma of basal cell carcinomas and compared its expression with that of other known mesenchymal markers.Results: Nestin is expressed throughout the entire early embryonic dermis but confined later during development to the follicular connective tissue sheath, where it can also be found in postnatal human hair follicles. Its expression is up-regulated in scalp wounds and the nestin-positive cells seem to originate from the follicular mesenchyme. Nestin is also expressed in a thin layer of fibroblasts in the immediate vicinity of basal cell carcinomas.Limitations: The examination for nestin expression of scalp wounds is considered preliminary, because we examined scalp wounds representing re-excisions of previously diagnosed neoplasms from which we had no exact time table available as to when the original excision took place.Conclusion: We propose that nestin functions as a stem cell marker of the follicular mesenchyme and has a major regulatory role in dermal homeostasis, cutaneous neovasculogenesis, and tumor stroma development.

Development of Pneumocystis carinii pneumonia in patients with immunobullous and connective tissue disease receiving immunosuppressive medications - Corrected Proof

Jacqueline L. Gerhart, Amer N. Kalaaji — 2009-10-14

Background: Pneumocystis carinii pneumonia (PCP) causes morbidity and mortality in immunocompromised hosts. Data describing use of PCP prophylaxis in immunosuppressed dermatologic patients are lacking.Objective: We sought to describe the frequency of PCP among dermatologic patients receiving immunosuppression for immunobullous disease or connective tissue disease.Methods: We retrospectively reviewed the cases of patients with immunobullous and connective tissue disease at our department of dermatology between 1980 and 2006 who received immunosuppression and had subsequent development of pneumonia. We recorded patient characteristics, use of PCP prophylaxis, whether PCP developed, and if so, their morbidity and mortality.Results: Of 334 patients identified, 7 (2.1%) were given the diagnosis of PCP during immunosuppressive treatment. Of these 7 patients, 3 (43%) died within 1 month of diagnosis, and none received PCP prophylaxis.Limitations: Retrospective study design and limited patient group are limitations.Conclusions: PCP prophylaxis may improve outcomes for some patients with immunobullous or connective tissue disease receiving immunosuppressive therapy.

Amelanotic lentigo maligna: A report of three cases and review of the literature - Corrected Proof

Farah Rukhsana Abdulla, Mary Jo Kerns, Diya F. Mutasim — 2009-09-22

Background: Amelanotic lentigo maligna is not clinically suspected and is often mistaken for a basal cell carcinoma, squamous cell carcinoma, or dermatitis.Objective: Our objective was to review previously reported cases of amelanotic lentigo maligna and compare them with our 3 cases.Methods: The clinical presentation and histologic findings of 3 new cases are described and compared with those in the literature.Results: The index of suspicion for amelanotic lentigo maligna is extremely low. No reported cases have been diagnosed clinically. None of our 3 cases was suspected.Limitations: Only three cases were reviewed.Conclusion: A high degree of clinical and histologic suspicion is required to make the diagnosis of this clinically nondescript neoplasm.

Treatment of acne conglobata with modern external beam radiation - Corrected Proof

Joseph N. Myers, Ashley R. Mason, Lori K. Gillespie, Kimberly S. Salkey — 2009-08-10

Like other diseases of the follicular occlusion tetrad, acne conglobata can be difficult to treat. We describe the successful use of modern external beam radiation for acne conglobata in the case of a 53-year-old man with long-standing and disfiguring acne conglobata and hidradenitis suppurativa. For patients with severe acne conglobata resistant to more accepted therapies, modern external beam radiation may be a viable alternative on the therapeutic ladder.