Journal of the American Academy of Dermatology - Articles in Press

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.

A 20-year analysis of previous and emerging allergens that elicit photoallergic contact dermatitis - Corrected Proof

Frank C. Victor, David E. Cohen, Nicholas A. Soter — 2010-02-17

Background: Retrospective chart reviews are periodically needed to update allergen series to detect changes in photoallergic contact dermatitis (PACD) over time.Objective: We sought to evaluate photopatch test results during a 13-year period and extend the observations to 20 years.Methods: A retrospective chart review was conducted in patients who were photopatch tested.Results: In all, 76 patients were evaluated. A total of 69 positive photopatch and 45 positive patch test reactions were detected in 30 and 23 patients, respectively. The frequencies of the positive photopatch test reactions were sunscreens 23.2%, antimicrobial agents 23.2%, medications 20.3%, fragrances 13%, plants and plant derivatives 11.6%, and pesticides 8.7%. Of the positive photopatch reactions to antimicrobial agents, 60% were caused by Fentichlor.Limitations: This study was a retrospective chart analysis, and the number of patients was small.Conclusions: Sunscreens and antimicrobial agents were the most frequent allergens eliciting PACD, and there was a decrease in PACD caused by fragrances. The number of reactions to medications increased. This study also demonstrated that pesticides can be a cause of PACD. The detection of reactions to Fentichlor was unexpected and, although they have been attributed in some studies to cross-reactions to sulfanilamides and bithionol, such a robust association was not observed in this study. This study extends our experience of the changes in the allergens that elicit PACD to 20 years.

Bisphosphonate-related osteonecrosis of the jaw presenting as a cutaneous dental sinus tract: A case report and review of the literature - Corrected Proof

Sam V. Truong, Linda C. Chang, Timothy G. Berger — 2010-02-12

Bisphosphonates are endogenous pyrophosphate analogs that work to inhibit osteoclast activity. They are commonly used in the treatment of patients with bone related diseases, such as solid tumor metastasis and osteoporosis. One of the infrequent but not rare side effects, especially with high doses of bisphosphonates, is osteonecrosis of the jaw. Although predominantly recognized by dentists because of the bony and intraoral manifestations of the disease, it may also present on the skin. We present a case of osteonecrosis of the jaw resembling two flesh-colored papules associated with dental sinus tracts to highlight the clinical manifestations that dermatologists may encounter, and review the literature on this rare but morbid condition.

Periorbital mucinosis: A variant of cutaneous lupus erythematosus? - Corrected Proof

2010-02-12

Lupus erythematosus has a wide spectrum of cutaneous manifestations, including periorbital mucinosis. We report 3 cases of periorbital mucinosis occurring in association with other cutaneous signs of lupus erythematosus. Based on a review of the literature, periorbital mucinosis is a rare and not widely recognized clinical manifestation of the disease. Although unusual, familiarity with periorbital mucinosis as a manifestation of lupus erythematosus broadens our understanding of these entities and expands the spectrum of cutaneous lupus erythematosus.

Comparison of advertising strategies between the indoor tanning and tobacco industries - Corrected Proof

Jennifer Greenman, David A. Jones — 2010-02-08

The indoor tanning industry is large and continues to grow, with 2007 domestic sales in excess of $5 billion. Advertising is central to shaping the consumer's perception of indoor tanning as well as driving industry demand. This article aims to identify key drivers of consumer appeal by comparing tanning advertising strategies to those used by tobacco marketers. Tobacco advertising was selected as a reference framework because it is both well documented and designed to promote a product with known health hazards. Two thousand advertisements from 4 large tobacco advertisement databases were analyzed for type of advertisement strategy used, and 4 advertising method categories were devised to incorporate the maximum number of advertisements reviewed. Subsequently, contemporary tanning advertisements were collected from industry magazines and salon websites and evaluated relative to the identified strategy profiles. Both industries have relied on similar advertising strategies, including mitigating health concerns, appealing to a sense of social acceptance, emphasizing psychotropic effects, and targeting specific population segments. This examination is a small observational study, which was conducted without rigorous statistical analysis, and which is limited both by the number of advertisements and by advertising strategies examined. Given the strong parallels between tobacco and tanning advertising methodologies, further consumer education and investigation into the public health risks of indoor tanning is needed.

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.

Orofacial granulomatosis: Clinical features and long-term outcome of therapy - Corrected Proof

2010-02-05

Background: Orofacial granulomatosis (OFG) is a chronic inflammatory disorder characterized by persistent or recurrent soft tissue enlargement, oral ulceration, and a variety of other orofacial features. There remain few detailed reports of the clinical features and long-term response to therapy of substantial groups of patients with OFG.Objective: The aim of this study was to determine retrospectively the clinical, hematologic, and histopathological features of a large case series of patients with OFG. In addition the long-term response to therapy was examined.Methods: Clinically relevant data of 49 patients with OFG who attended a single oral medicine unit in the United Kingdom were retrospectively examined. The analyzed parameters included diagnostic features, clinical manifestations, and outcomes and adverse side effects of therapy.Results: Labial swelling was the most common presenting clinical feature at diagnosis (75.5%), followed by intraoral mucosal features other than ulceration such as cobblestoning and gingival enlargement (73.5%). Mucosal ulceration was observed in 36.7% of patients whereas extraoral facial manifestations such as cutaneous erythema and swelling were present in 40.8% of patients. Of the 45 patients who required treatment, 24 (53.3%) were treated with topical corticosteroids/immunosuppressants only, whereas 21 (46.7%) received a combined therapy (topical plus systemic corticosteroids/immunosuppressants and/or intralesional corticosteroids). The long-term outcome analysis showed complete/partial resolution of tissue swelling and oral ulceration in 78.8% and 70% of patients, respectively.Limitations: The main limitation of the current study was its retrospective design and methodology including differences in reporting clinical features and outcome.Conclusions: OFG can show multiple facial and mucosal clinical features. Long-term treatment with topical and/or combined therapy is needed in the majority of patients. Response to therapy is highly variable even though in the long-term complete/partial disease resolution can be obtained in the majority of patients. Mucosal ulceration tends to be more recalcitrant than orofacial swelling. Adverse side effects of therapy are rare.

Imiquimod 2.5% and 3.75% for the treatment of actinic keratoses: Results of two placebo-controlled studies of daily application to the face and balding scalp for two 3-week cycles - Corrected Proof

2010-02-04

Background: Imiquimod 5% cream is approved as a 16-week regimen for the treatment of actinic keratoses involving a 25-cm2 area of skin.Objective: We sought to evaluate imiquimod 2.5% and 3.75% creams for short-course treatment of the entire face and scalp.Methods: In two identical studies, adults with 5 to 20 lesions were randomized to placebo, or imiquimod 2.5% or 3.75% cream (1:1:1). Up to two packets (250 mg each) were applied per dose once daily for two 3-week treatment cycles, with a 3-week, no-treatment interval. Efficacy was assessed at 8 weeks posttreatment.Results: In all, 490 subjects were randomized to placebo, or imiquimod 2.5% or 3.75% cream. Median baseline lesion counts for the treatment groups were 9 to 10. Complete and partial clearance rates were 5.5% and 12.8% for placebo, 25.0% and 42.7% for imiquimod 2.5%, and 34.0% and 53.7% for imiquimod 3.75% (P < .001, each imiquimod vs placebo; P = .034, 3.75% vs 2.5% for partial clearance). Median reductions from baseline in lesion count were 23.6%, 66.7%, and 80.0% for the placebo, imiquimod 2.5%, and imiquimod 3.75% groups, respectively (P < .001 each imiquimod vs placebo). There were few treatment-related discontinuations. Temporary treatment interruption (rest) rates were 0%, 17.1%, and 27.2% for the placebo, imiquimod 2.5%, and imiquimod 3.75%, respectively.Limitations: Local effects of imiquimod, including erythema, may have led to investigator and subject bias.Conclusions: Both imiquimod 2.5% and 3.75% creams were more effective than placebo and had an acceptable safety profile when administered daily as a 3-week on/off/on regimen.

Imiquimod 2.5% and 3.75% for the treatment of actinic keratoses: Results of two placebo-controlled studies of daily application to the face and balding scalp for two 2-week cycles - Corrected Proof

2010-02-04

Background: The approved imiquimod 5% cream regimen for treating actinic keratoses requires a long treatment time and is limited to a small area of skin.Objective: We sought to evaluate imiquimod 2.5% and 3.75% for short-course treatment of the full face or balding scalp.Methods: In two identical studies, adults with 5 to 20 lesions were randomized to placebo, imiquimod 2.5%, or imiquimod 3.75% (1:1:1). Up to two packets (250 mg each) were applied per dose once daily for two 2-week treatment cycles, with a 2-week, no-treatment interval between cycles. Efficacy was assessed at 8 weeks posttreatment.Results: A total of 479 patients were randomized to placebo, or imiquimod 2.5% or 3.75%. Complete and partial clearance (≥75% lesion reduction) rates were 6.3% and 22.6% for placebo, 30.6% and 48.1% for imiquimod 2.5%, and 35.6% and 59.4% for imiquimod 3.75%, respectively (P < .001 vs placebo, each; P = .047, 3.75% vs 2.5% for partial clearance). Median reductions from baseline in lesion counts were 25.0% for placebo, 71.8% for imiquimod 2.5%, and 81.8% for imiquimod 3.75% (P < .001, each active vs placebo; P = .048 3.75% vs 2.5%). There were few treatment-related discontinuations. Patient rest period rates were 0% for placebo, 6.9% for imiquimod 2.5%, and 10.6% for imiquimod 3.75%.Limitations: Local pharmacologic effects of imiquimod, including erythema, may have limited concealment of treatment assignment in some patients.Conclusions: Both imiquimod 2.5% and 3.75% creams were more effective than placebo and were well tolerated when administered daily as a 2-week on/off/on regimen to treat actinic keratoses.

Systematic review of the safety of topical corticosteroids in pregnancy - Corrected Proof

Ching-Chi Chi, Shu-Hui Wang, Gudula Kirtschig, Fenella Wojnarowska — 2010-02-01

Background: Pregnant women may have skin conditions that require topical corticosteroids. However, little is known about their safety in pregnancy.Objective: We sought to evaluate the available evidence concerning the safety of topical corticosteroids in pregnancy.Methods: We systematically searched 17 databases and trial registers, and contacted pharmaceutical companies. Randomized controlled trials and cohort studies of topical corticosteroids in pregnant women, and case-control studies comparing maternal exposure to topical corticosteroids between patients and control subjects were included. The Newcastle-Ottawa Scale was used for quality assessment of included studies.Results: Seven studies, including two cohort and five case-control studies, were included. Most studies did not find significant associations of topical corticosteroids with congenital abnormality, preterm delivery stillbirth, and mode of delivery. One study found a significant association between first-trimester use of topical corticosteroids and orofacial cleft, and another study found a significant association between very potent topical corticosteroids and low birthweight.Limitations: The available data were limited and mainly on orofacial cleft. The quality of evidence was generally low.Conclusions: Currently limited and inconclusive data are unable to detect an association between topical corticosteroids and congenital abnormality, preterm delivery, or stillbirth. The current evidence shows no statistically significant difference between pregnant women who use and those who do not use topical corticosteroids. However, there does appear to be an association of very potent topical corticosteroids with low birthweight. Further cohort studies with comprehensive outcome measures, consideration of corticosteroid potency, dosage and indications, and a large sample size are needed.

Dermatoscopy of pigmented Bowen's disease - Corrected Proof

Alan Cameron, Cliff Rosendahl, Philipp Tschandl, Elisabeth Riedl, Harald Kittler — 2010-01-18

Background: Pigmented Bowen's disease is not well characterized.Objective: To characterize the clinical and dermatoscopic appearance of pigmented Bowen's disease.Methods: We performed a retrospective analysis of 52 consecutive cases of pigmented Bowen's disease.Results: Of 951 histopathologically verified cases of Bowen's disease that underwent biopsy during the study period, 52 (5.5%) were pigmented. Dermatoscopically pigmented Bowen's disease is typified by a pattern of dots and/or structureless zones. In 21.2% (n=11), we observed brown or gray dots arranged in a linear fashion. Vessels were identified in 67.3% of lesions with a predomination of coiled vessels. A linear arrangement of vessels was seen in 11.5%.Limitations: Conclusions are limited by the fact that this was a retrospective, uncontrolled study.Conclusions: Pigmented Bowen's disease has a characteristic dermatoscopic pattern. Linear arrangement of brown and/or gray dots and/or coiled vessels is a specific clue to pigmented Bowen's disease.

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.

Low rates of clinical recurrence after biopsy of benign to moderately dysplastic melanocytic nevi - Corrected Proof

Agnessa Gadeliya Goodson, Scott R. Florell, Kenneth M. Boucher, Douglas Grossman — 2009-12-17

Background: Little is known about the recurrence/persistence rates of dysplastic nevi (DN) after biopsy, and whether incompletely removed DN should be re-excised to prevent recurrence.Objective: Our purpose was to determine the recurrence rates of previously biopsied DN, and to assess whether biopsy method, margin involvement, congenital features, epidermal location, and degree of dysplasia are associated with recurrence.Methods: Patients having a history of a “nevus biopsy” at least 2 years earlier were assessed for clinical recurrence. Slides of original lesions were re-reviewed by a dermatopathologist.Results: A total of 271 nevus biopsy sites were assessed in 115 patients. Of 195 DN with greater than 2 years of follow-up, 7 (3.6%) demonstrated recurrence on clinical examination. In all, 98 DN had a follow-up period of at least 4 years with no clinical recurrence. Of 61 benign nevus biopsy sites examined, clinical recurrence was observed in two (3.3%). For all nevi, recurrence was significantly associated with shave biopsy technique but not with nevus dysplasia or subtype, or the presence of positive margin or congenital features.Limitations: Most biopsies were performed in a pigmented lesion clinic at a single tertiary referral center. Determinations of nevus recurrence were made on clinical rather than histologic grounds, and follow-up times were limited in some cases.Conclusion: In this cohort, rates of clinical recurrence after biopsy of DN and benign nevi were extremely low. Re-excision of nevi, including mildly to moderately DN with a positive margin, may not be necessary.

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.

Platelet activation in patients with psoriasis: Increased plasma levels of platelet-derived microparticles and soluble P-selectin - Corrected Proof

Risa Tamagawa-Mineoka, Norito Katoh, Saburo Kishimoto — 2009-12-07

Background: It has recently been established that platelets have an important role in increasing inflammation, in addition to their main role in hemostasis and thrombosis. An increased incidence of occlusive vascular disease has been reported in patients with psoriasis and the pathomechanism of psoriasis may involve platelet activation.Objective: The goal of the study was to establish a clearer explanation of the association between platelet activation and psoriasis activity by investigating the levels of markers of platelet activation in patients with psoriasis and examining the relationship between the marker levels and a severity score for psoriasis.Methods: Plasma levels of platelet-derived microparticles (PDMPs) and soluble P-selectin were measured by enzyme-linked immunosorbent assay as markers of platelet activation in 21 patients with psoriasis and 22 healthy control subjects. The relationships between the platelet activation markers and the Psoriasis Area and Severity Index score were investigated.Results: Plasma PDMPs and soluble P-selectin levels were markedly higher in patients with psoriasis compared with those in healthy control subjects. There was a significant correlation between the PDMPs levels and the Psoriasis Area and Severity Index score, and the increased plasma PDMPs and soluble P-selectin levels were markedly reduced after clinical improvement occurred.Limitations: The number of people evaluated was relatively small.Conclusions: Our results show that blood platelets are activated in patients with psoriasis, especially in those with extensive disease, and suggest a close association between platelet activation and psoriasis activity. Plasma PDMPs level may be a useful indicator of the severity of psoriasis.

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 erythrodermic psoriasis: From the medical board of the National Psoriasis Foundation - Corrected Proof

2009-08-10

Background: Erythrodermic psoriasis is a severe form of psoriasis that can arise acutely or follow a chronic course. There are a number of treatment options, but overall there are few evidence-based data to guide clinicians in managing these challenging cases.Objective: Our aim was to create treatment recommendations to help dermatologists treat patients with erythrodermic psoriasis.Methods: A task force of the National Psoriasis Foundation Medical Board was convened to evaluate treatment options for erythrodermic or exfoliative psoriasis. Meetings were held by teleconference and were coordinated and funded by the National Psoriasis Foundation. Consensus on treatment of erythrodermic psoriasis was achieved. A literature review was conducted to examine treatment options for erythrodermic psoriasis and the strength of the evidence for each option.Results: There is no high-quality scientific evidence on which to base treatment recommendations. Treatment should be dictated by the severity of disease at time of presentation and the patient's comorbidities. Cyclosporine and infliximab appear to be the most rapidly acting agents for the treatment of erythrodermic psoriasis. Acitretin and methotrexate are also appropriate first-line choices, although they usually work more slowly. Treating physicians can consider a number of second-line agents, including etanercept or combination therapy, in the treatment of patients with erythrodermic psoriasis. Combination therapy may be more effective than a single-agent approach; there is a paucity of scientific data in this area. All patients should be evaluated for underlying infection. Supportive care can help control disease and patient symptoms if instituted appropriately. Physicians should avoid potential exacerbating agents when managing this challenging disease.Limitations: There are few high-quality studies examining treatment options for erythrodermic psoriasis.Conclusion: Treatment of patients with erythrodermic psoriasis demands a thorough understanding of the treatment options available. Therapy should be based on acuity of disease and the patient's underlying comorbidities. There are limited data available to compare treatment options for erythrodermic psoriasis. Further studies are necessary to explore the optimal treatment algorithm for these patients. (J Am Acad Dermatol doi:10.1016/j.jaad.2009.05.048.)

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.