Showing papers in "Journal of The American Academy of Dermatology in 2009"

New insights into the management of acne: An update from the Global Alliance to Improve Outcomes in Acne Group

Abstract: The Global Alliance to Improve Outcomes in Acne published recommendations for the management of acne as a supplement to the Journal of the American Academy of Dermatology in 2003. The recommendations incorporated evidence-based strategies when possible and the collective clinical experience of the group when evidence was lacking. This update reviews new information about acne pathophysiology and treatment–such as lasers and light therapy–and relevant topics where published data were sparse in 2003 but are now available including combination therapy, revision of acne scarring, and maintenance therapy. The update also includes a new way of looking at acne as a chronic disease, a discussion of the changing role of antibiotics in acne management as a result of concerns about microbial resistance, and factors that affect adherence to acne treatments. Summary statements and recommendations are provided throughout the update along with an indication of the level of evidence that currently supports each finding. As in the original supplement, the authors have based recommendations on published evidence as much as possible.

Hidradenitis suppurativa: A comprehensive review

Abstract: Hidradenitis suppurativa, also known as acne inversa, is a chronic, often debilitating disease primarily affecting the axillae, perineum, and inframammary regions. Prevalence rates of up to 4% have been estimated. Our understanding of the disease has changed over time. It is now considered a disease of follicular occlusion rather than an inflammatory or infectious process of the apocrine glands. Clinically, the disease often presents with tender subcutaneous nodules beginning around puberty. The nodules may spontaneously rupture or coalesce, forming painful, deep dermal abscesses. Eventually, fibrosis and the formation of extensive sinus tracts may result. The location of the lesions may lead to social embarrassment and the failure to seek medical treatment. Therapies in the past have consisted of long-term antibiotics, antiandrogens, and surgery. New treatments like tumor necrosis factor-alfa inhibitors have given clinicians more options against this difficult disease.

Guidelines of care for the management of psoriasis and psoriatic arthritis: section 4. Guidelines of care for the management and treatment of psoriasis with traditional systemic agents.

Abstract: Psoriasis is a common, chronic, inflammatory, multisystem disease with predominantly skin and joint manifestations affecting approximately 2% of the population. In this fourth of 6 sections of the guidelines of care for psoriasis, we discuss the use of traditional systemic medications for the treatment of patients with psoriasis. Treatment should be tailored to meet individual patients' needs. We will discuss in detail the efficacy and safety, and offer recommendations for the use of the 3 most commonly used, and approved, traditional systemic agents: methotrexate, cyclosporine, and acitretin. We will also briefly discuss the available data for the use of azathioprine, fumaric acid esters, hydroxyurea, leflunomide, mycophenolate mofetil, sulfasalazine, tacrolimus, and 6-thioguanine in psoriasis.

The prevalence of previously diagnosed and undiagnosed psoriasis in US adults: Results from NHANES 2003–2004

Abstract: Background Psoriasis is a predictor of morbidity. It is important to determine the extent to which psoriasis remains undiagnosed. Objective To determine the prevalence of psoriasis. Methods We conducted a cross-sectional study using the National Health and Nutrition Examination Survey 2003-2004. Results The prevalence of diagnosed psoriasis was 3.15% (95% confidence interval [CI], 2.18-4.53), corresponding to 5 million adults. Approximately 17% of these patients have moderate to severe psoriasis based on body surface area report and 25% rate psoriasis a large problem in everyday life. The prevalence of undiagnosed active psoriasis by conservative estimate was 0.4% (95% CI, 0.19-0.82), corresponding to approximately 600,000 US adults, and 2.28% (95% CI, 1.47-3.50) by a broader definition, corresponding to 3.6 million US adults. Undiagnosed patients had a trend toward being more likely to be male, nonwhite, less educated, and unmarried compared with patients who had received a diagnosis. Limitations The method for determining the presence of psoriasis had limited ability to detect mild disease and only fair interrater agreement. Conclusion More than 5 million adults have been diagnosed with psoriasis. A large number have undiagnosed psoriasis and there are important disparities which may be associated with not receiving medical attention.

The safety of nanosized particles in titanium dioxide– and zinc oxide–based sunscreens

Abstract: Given the increasing incidence and prevalence of skin cancer, dermatologists are more frequently recommending sunscreens to their patients. However, the safety of titanium dioxide and zinc oxide nanosized particles in the majority of sunscreens has come under scrutiny from governments and the general public. We sought to characterize the use, safety, and regulatory state of nanosized particles in titanium dioxide and zinc oxide in sunscreens based on studies and position statements from 1980 to 2008. Although we found no evidence of significant penetration of titanium dioxide and zinc oxide nanosized particles beyond the stratum corneum, further studies must be done to simulate real-world conditions particularly in sunburned skin and under ultraviolet exposure.

Neurofibromatosis Type 1

Abstract: Neurofibromatosis type 1 (NF1) is an autosomal dominant, multisystem disorder affecting approximately 1 in 3500 people. Significant advances in the understanding of the pathophysiology of NF1 have been made in the last decade. While no medical therapies for NF1 are currently available, trials are ongoing to discover and test medical treatments for the various manifestations of NF1, primarily plexiform neurofibromas, learning disabilities, and optic pathway gliomas. In addition, mutational analysis has become available on a clinical basis and is useful for diagnostic confirmation in individuals who do not fulfill diagnostic criteria or when a prenatal diagnosis is desired. There are several disorders that may share overlapping features with NF1; in 2007, a disorder with cutaneous findings similar to NF1 was described. This paper addresses the dermatologist's role in diagnosis and management of NF1 and describes the variety of cutaneous and extracutaneous findings in NF1 to which the dermatologist may be exposed. Learning objectives After completing this learning activity, participants should be able to discuss the indications and limitations of genetic testing in neurofibromatosis type 1, distinguish common and uncommon cutaneous findings, and recognize the dermatologist's role in diagnosis and management.

Guidelines of Care for the Management of Psoriasis and Psoriatic Arthritis. Section 3. Guidelines of Care for the Management and Treatment of Psoriasis With Topical Therapies

Abstract: Psoriasis is a common, chronic, inflammatory, multi-system disease with predominantly skin and joint manifestations affecting approximately 2% of the population. In this third of 6 sections of the guidelines of care for psoriasis, we discuss the use of topical medications for the treatment of psoriasis. The majority of patients with psoriasis have limited disease (<5% body surface area involvement) and can be treated with topical agents, which generally provide a high efficacy-to-safety ratio. Topical agents may also be used adjunctively for patients with more extensive psoriasis undergoing therapy with either ultraviolet light, systemic or biologic medications. However, the use of topical agents as monotherapy in the setting of extensive disease or in the setting of limited, but recalcitrant, disease is not routinely recommended. Treatment should be tailored to meet individual patients' needs. We will discuss the efficacy and safety of as well as offer recommendations for the use of topical corticosteroids, vitamin D analogues, tazarotene, tacrolimus, pimecrolimus, emollients, salicylic acid, anthralin, coal tar, as well as combination therapy.

Epidermolysis bullosa and the risk of life-threatening cancers: the National EB Registry experience, 1986-2006.

Abstract: Background Case series have demonstrated that potentially lethal cutaneous squamous cell carcinomas arise in patients with recessive dystrophic epidermolysis bullosa (RDEB), although the magnitude of this risk is undefined. Methods Systematic case finding and data collection were performed throughout the continental United States (1986-2002) by the National EB Registry on 3280 EB patients to determine cumulative and conditional risks for squamous cell carcinoma (SCC), basal cell carcinoma (BCC), and malignant melanoma (MM) within each major EB subtype, as well as the cumulative risk of death from each tumor. Study design was cross-sectional, with a nested randomly sampled longitudinal subcohort (N = 450). Results SCCs arose primarily in RDEB, especially the Hallopeau-Siemens subtype (RDEB-HS), first beginning in adolescence. Less frequently, SCCs occurred in junctional EB (JEB). Cumulative risks rose steeply in RDEB-HS, from 7.5% by age 20 to 67.8%, 80.2%, and 90.1% by ages 35, 45, and 55, respectively. In Herlitz JEB, the risk was 18.2% by age 25. SCC deaths occurred only in RDEB, with cumulative risks in RDEB-HS of 38.7%, 70.0%, and 78.7% by ages 35, 45, and 55, respectively. MM arose in RDEB-HS, with a cumulative risk of 2.5% by age 12. BCCs arose almost exclusively in the most severe EB simplex subtype (Dowling-Meara) (cumulative risk=43.6% by age 55). Limitations Mutational analyses were performed on only a minority of enrollees in the National EB Registry, preventing evaluation of the possible influence of specific genotypes on the risk of developing or dying from cutaneous SCCs. Conclusions SCC is the most serious complication of EB within adults, especially those with RDEB-HS. By mid-adulthood, nearly all will have had at least one SCC, and nearly 80% will have died of metastatic SCC despite aggressive surgical resection. When compared with SCCs arising within the normal population, the remarkably high risk of occurrence of and then death from SCCs among RDEB patients suggests likely differences in pathogenesis. Additional studies of EB-derived tumors and SCC cell lines may not only provide new insights into the mechanisms of carcinogenesis but also means whereby these particular tumors may be prevented or more effectively treated.

Methotrexate and psoriasis: 2009 National Psoriasis Foundation Consensus Conference

Abstract: Background Methotrexate remains a valuable option for the treatment of psoriasis. This report will summarize studies regarding the use of methotrexate 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 methotrexate in the treatment of psoriasis. Methods Reports in the literature were reviewed regarding methotrexate therapy. Results A consensus was achieved on use of methotrexate in psoriasis including specific recommendations on dosing and monitoring. The consensus received unanimous approval from members of the Medical Board of the National Psoriasis Foundation. Limitations There are few evidence-based studies on the treatment of psoriasis with methotrexate. Many of the reviewed reports are for the treatment of rheumatoid arthritis. Conclusions Methotrexate is a safe and effective drug for the treatment of psoriasis. Appropriate patient selection and monitoring will significantly decrease the risks of side effects. In patients without risk factors for hepatic fibrosis, liver biopsies may not be indicated or the frequency of liver biopsies may be markedly reduced.

Extracutaneous manifestations and complications of inherited epidermolysis bullosa: part I. Epithelial associated tissues.

Abstract: Based upon case reports and small case series, it has been known for many years that some types and subtypes of inherited epidermolysis bullosa (EB) may be at risk for developing one or more extracutaneous complications. Many of these are associated with considerable morbidity; some may result in death. Only over the past few years have there been data generated from large, well characterized cohorts. However, these data, to date, have been published almost exclusively in the nondermatologic literature. Our objective is to provide dermatologists with a comprehensive review of each major extracutaneous complication with a summary of the pertinent literature and recommendations for evaluation and optimal management. Part I highlights epithelial associated tissues, and part II addresses other organs. Based on these reviews, the readership should gain a greater understanding of the types of complications that may occur, when they are most likely to develop, and the range of medical and surgical interventions that are currently available. It should also be possible for the reader to develop surveillance strategies based on an understanding of the published evidence-based data. The breadth and range of severity of complications that arise in some EB types and subtypes within the external eye, ear, nose, upper airway, and gastrointestinal and genitourinary tracts suggest that optimal management must be multidisciplinary. Given the unique knowledge that dermatologists have of this disease, we believe that the care of the EB patient should be under the direction of his or her dermatologist, who can best assist in timely referrals to those specialists who are most experienced in the care of specific extracutaneous problems.

Clinical characteristics of a series of 302 French patients with hidradenitis suppurativa, with an analysis of factors associated with disease severity.

Abstract: Background Factors associated with the severity of hidradenitis suppurativa (HS) are not known. Objective We sought to identify factors associated with the severity of HS. Methodology The severity of disease in a series of 302 consecutive patients with HS was assessed using the Sartorius score. Results Atypical locations were more common in men than in women (47.1% vs 14.8%; P Limitations The referral center base of the study may have biased recruitment. Conclusion Our data showed a significant association between the severity of HS and several clinical and behavioral factors. Prospective studies are needed to confirm the prognostic role of these factors.

Trends in incidence of adult-onset psoriasis over three decades: A population-based study

Abstract: Background Incidence studies of psoriasis are rare, mainly due to lack of established epidemiological criteria and the variable disease course. The objective of this study is to determine time trends in incidence and survival of psoriasis patients over three decades. Methods We identified a population-based incidence cohort of 1633 subjects aged ≥18 years first diagnosed with psoriasis between January 1, 1970 and January 1, 2000. The complete medical records for each potential psoriasis subject were reviewed and diagnosis was validated by either 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 the 2000 US white population. Results The overall age- and sex-adjusted annual incidence of psoriasis was 78.9 per 100,000 (95% confidence interval [CI]: 75.0-82.9). When psoriasis diagnosis was restricted to dermatologist-confirmed subjects, the incidence was 62.3 per 100,000 (95% CI: 58.8-65.8). Incidence of psoriasis increased significantly over time from 50.8 in the period 1970-1974 to reach 100.5 per 100,000 in the 1995-1999 time period ( P = .001). Although the overall incidence was higher in males than in females ( P = .003), incidence in females was highest in the sixth decade of life (90.7 per 100,000). Survival was similar to that found in the general population ( P = .36). Limitations The study population was mostly white and limited to adult psoriasis patients. Conclusion The annual incidence of psoriasis almost doubled between the 1970s and 2000. The reasons for this increase in incidence are currently unknown, but could include a variety of factors, including a true change in incidence or changes in the diagnosing patterns over time.

Extracutaneous manifestations and complications of inherited epidermolysis bullosa: part II. Other organs.

Abstract: It is well known, primarily via case reports and limited case series, that nonepithelial tissues may become injured in patients with epidermolysis bullosa. Only recently, however, have there been data generated from large, well characterized cohorts. Our objective is to provide dermatologists with a comprehensive review of each of these major extracutaneous complications, with a summary of the pertinent literature and evidence-based recommendations for surveillance, evaluation, and management. Some epidermolysis bullosa subtypes are at risk for severe injury of the bone marrow, musculoskeletal system, heart, kidney, and teeth, and for the development of squamous cell carcinoma, basal cell carcinoma, or malignant melanoma. If untreated, significant morbidity or mortality may result.

A randomized double-blind trial of intravenous immunoglobulin for pemphigus

Abstract: Background Pemphigus is a rare life-threatening intractable autoimmune blistering disease caused by IgG autoantibodies to desmogleins. It has been difficult to conduct a double-blind clinical study for pemphigus partly because, in a placebo group, appropriate treatment often must be provided when the disease flares. Objective A multicenter, randomized, placebo-controlled, double-blind trial was conducted to investigate the therapeutic effect of a single cycle of high-dose intravenous immunoglobulin (400, 200, or 0 mg/kg/d) administered over 5 consecutive days in patients relatively resistant to systemic steroids. Methods We evaluated efficacy with time to escape from the protocol as a novel primary end point, and pemphigus activity score, antidesmoglein enzyme-linked immunosorbent assay scores, and safety as secondary end points. Results We enrolled 61 patients with pemphigus vulgaris or pemphigus foliaceus who did not respond to prednisolone (≥20 mg/d). Time to escape from the protocol was significantly prolonged in the 400-mg group compared with the placebo group ( P P P P Limitation Prednisolone at 20 mg/d or more may not be high enough to define steroid resistance. Conclusion Intravenous immunoglobulin (400 mg/kg/d for 5 d) in a single cycle is an effective and safe treatment for patients with pemphigus who are relatively resistant to systemic steroids. Time to escape from the protocol is a useful indicator for evaluation in randomized, placebo-controlled, double-blind studies of rare and serious diseases.

Treatments for psoriasis and the risk of malignancy

Abstract: Background There are multiple therapeutic options for the treatment of moderate to severe psoriasis. The process of choosing among potential treatment options requires both the physician and the patient to weigh the benefits of individual modalities against their potential risks. Traditional systemic therapies for psoriasis, including methotrexate (MTX) and cyclosporine (CsA), have a well-documented array of toxicities, particularly end-organ toxicities. Over the past several years, the use of biologic therapies for the treatment of moderate to severe psoriasis has been a major clinical and research focus. With the advent of these novel immunosuppressive therapies, one of the central safety issues surrounding these agents is their potential to increase the risk of malignancy. Objective Our objective was to review the risk of malignancy associated with therapies for moderate to severe psoriasis, including phototherapy, traditional systemic therapies, and biologic therapies. We reviewed the existing body of literature in order to define the known incidence of malignancy associated with psoralen and ultraviolet A (PUVA), narrowband and broadband ultraviolet B (UVB), MTX, CsA, mycophenolate mofetil (MMF), and biologic therapies, including alefacept, efalizumab, infliximab, etanercept, adalimumab, and ustekinumab. Results PUVA, when given long term, is associated with increased risks of cutaneous squamous cell carcinoma and malignant melanoma. Reviews of studies on UVB, both narrowband and broadband, do not indicate any increased risk of nonmelanoma skin cancer or melanoma. The traditional systemic psoriasis therapies—MTX, CsA, and MMF—may be associated with an increased risk of lymphoproliferative disorders during treatment, demonstrated in clinical trials in patients with rheumatoid arthritis and documented in case reports concerning psoriasis patients. The risk of malignancy with biologic therapy is still unclear. However, the majority of studies examining this carcinogenic risk suggest that tumor necrosis factor–α inhibitors may cause a slightly increased risk of cancer, including nonmelanoma skin cancer and hematologic malignancies. Limitations The majority of studies cited in this review lack the power and randomization of large clinical trials, as well as the long-term follow-up periods which would further substantiate the hypothetical link between these antipsoriatic treatment regimens and the potential for malignancy. Because of the substantial lack of clinical data, the majority of studies evaluated focus on the treatment of patients with rheumatoid arthritis, which is a systemic inflammatory disorder comparable to psoriasis. Additionally, the increased risk of malignancy associated with psoriasis itself is a confounding factor. Conclusion Many of the therapies for moderate to severe psoriasis, including PUVA, traditional systemic therapies, and some biologic therapies, may increase the risk of malignancy. Appropriate patient counseling and selection, as well as clinical follow-up, are necessary to maximize safety with these agents. Further long-term study is necessary to more precisely quantify the risks associated with biologic therapies.

Rates of cutaneous metastases from different internal malignancies: experience from a Taiwanese medical center.

Abstract: Background Previous reports regarding the rates at which various internal tumors metastasize to the skin have been limited and have only included the Caucasian population. Moreover, the mechanisms that predispose certain internal malignancies to metastasize to the skin have rarely been discussed in the scientific literature. Objectives We determined the frequencies with which various internal malignancies metastasize to the skin in patients from a Taiwanese medical center. We also evaluated whether expressions of chemokine receptors CCR10 and CXCR4 by tumor cells correlate with cutaneous metastatic ability. Methods Clinical records from Kaohsiung Medical University Hospital, Kaohsiung, Taiwan, during 20 years (1986-2006) were reviewed and cases of biopsy-proven primary internal malignancies and cutaneous metastases were identified. Immunohistochemical staining with antibodies to CCR10 and CXCR4 was performed on a selected number of internal malignancies with and without skin metastases. Results From 12,146 patients with internal malignancies, we found 124 cases (1.02%) with cutaneous metastases. The highest rates of skin metastases were found to occur from carcinoma of the breast, followed by the lung, oral mucosa, colon and rectum, stomach, and esophagus. However, the rate of cutaneous metastasis from breast cancer was much lower compared with previous studies involving Caucasians. In general, adenocarcinomas gave rise to cutaneous metastases at a higher frequency compared with other histologic subtypes. In addition, the expressions of CCR10 and CXCR4 by tumor cells did not correlate well with the presence or absence of skin metastases. Limitation This study is retrospective in nature. Conclusions Different internal malignancies metastasize to the skin with different frequencies, and the rates at which different malignancies metastasize to cutaneous sites differ between the Taiwanese and Caucasian populations. The mechanisms responsible for the cutaneous metastatic ability of certain malignancies likely involve factors other than chemokine receptors CCR10 and CXCR4, because their expressions by tumor cells are neither necessary nor sufficient for the formation of skin metastases.

Cutaneous side effects of anti-tumor necrosis factor biologic therapy: a clinical review.

Abstract: Background Anti-tumor necrosis factor (anti-TNF) biologic agents have been associated with a number of adverse events. Objective To review the cutaneous reactions that have been reported in patients receiving anti-TNF therapy. Methods We performed a systematic MEDLINE search of relevant publications, including case reports and case series. Results Reported cutaneous events included infusion and injection site reactions, psoriasiform eruptions, lupus-like disorders, vasculitis, granulomatous reactions, cutaneous infections, and cutaneous neoplasms. Infusion reactions and injection site reactions were definitely associated with anti-TNF administration, whereas all other events had a varying strength of association and severity, not necessarily requiring drug discontinuation. Limitations Most information was derived from spontaneous case reports, where ascertainment biases and frequency of reporting may impair detection methodology and causal relationships. Conclusions As anti-TNF biologic agents are progressively being used in clinical practice, cutaneous adverse events will be encountered more frequently. Until more data are accumulated with respect to their pathogenesis and potential association with anti-TNF therapy, dermatologists should become more familiar with the clinical presentation and management of such events.

Strategies for early melanoma detection: Approaches to the patient with nevi

Abstract: Given its propensity to metastasize and the lack of effective therapies for most patients with advanced disease, early detection of melanoma is a clinical imperative. Although there are no noninvasive techniques for the definitive diagnosis of melanoma, and the "gold standard" remains biopsy with histologic examination, a variety of modalities may facilitate early melanoma diagnosis and the detection of new and changing nevi. This article reviews the general clinical principles of early melanoma detection and various modalities that are currently available or on the horizon, providing the clinician with an up to date understanding of management strategies for their patients with numerous or atypical nevi. Learning objective After completing this learning activity, participants should understand the clinical importance of early melanoma detection, appreciate the challenges of early melanoma diagnosis and which patients are at highest risk, know the general principles of early melanoma detection, be familiar with current and emerging modalities that may facilitate early melanoma diagnosis and the detection of new and changing nevi, know the advantages and limitations of each modality, and be able to practice a combined approach to the patient with numerous or clinically atypical nevi.

Development of a two-step method for the diagnosis of melanoma by reflectance confocal microscopy

Abstract: Background Reflectance confocal microscopy (RCM) has been shown to improve accuracy in the differentiation of nevus from melanoma, but only a few studies have evaluated both melanocytic lesions (ML) and non-ML. Objective We sought to develop an algorithm for the in vivo diagnosis of skin tumors by RCM. Methods In 143 patients we evaluated 154 skin tumors (100 melanocytic, 54 nonmelanocytic) by RCM before their excision. We analyzed RCM features on stored images and performed univariate and multivariate analyses to determine the association of RCM features with tumor types. Results Four confocal features differentiated ML from non-ML: cobblestone pattern of epidermal layers, pagetoid spread, mesh appearance of the dermoepidermal junction, and the presence of dermal nests. Within ML, the presence of roundish suprabasal cells and atypical nucleated cells in the dermis was associated with melanoma, and the presence of edged papillae and typical basal cells was associated with nevi. Based on the correlation of RCM features with dermatoscopy and histology, we developed a two-step algorithm for the diagnosis of skin tumors by RCM. Limitations This is a preliminary study, and the results must be validated in further studies with a larger number of cases. Conclusion RCM appears to be helpful in improving the presurgical diagnosis of difficult skin tumors.

Lichen planus–like eruptions: An emerging side effect of tumor necrosis factor-α antagonists

Abstract: As tumor necrosis factor (TNF)-α inhibitors gain wider use in clinical practice, it is becoming increasingly evident that these potent immunosuppressants can also induce inflammatory reactions. We present two cases of lichen planus–like eruptions after infliximab and adalimumab therapy for psoriasis, and review the literature on this phenomenon. Eleven cases of lichen planus or lichenoid drug eruptions have been previously reported in patients taking TNF-α inhibitors, in addition to several cases of psoriasiform eruptions with a lichenoid histology. Because TNF-α has been implicated in the pathogenesis of lichen planus, induction of lichenoid reactions by TNF-α inhibition is somewhat unexpected. We consider potential immunologic mechanisms, and suggest that TNF-α inhibition may precipitate lichenoid reactions through disruption of a delicate balance between TNF-α and interferon-α in susceptible patients.

Selection criteria for genetic assessment of patients with familial melanoma

Abstract: Approximately 5% to 10% of melanoma may be hereditary in nature, and about 2% of melanoma can be specifically attributed to pathogenic germline mutations in cyclin-dependent kinase inhibitor 2A (CDKN2A). To appropriately identify the small proportion of patients who benefit most from referral to a genetics specialist for consideration of genetic testing for CDKN2A, we have reviewed available published studies of CDKN2A mutation analysis in cohorts with invasive, cutaneous melanoma and found variability in the rate of CDKN2A mutations based on geography, ethnicity, and the type of study and eligibility criteria used. Except in regions of high melanoma incidence, such as Australia, we found higher rates of CDKN2A positivity in individuals with 3 or more primary invasive melanomas and/or families with at least one invasive melanoma and two or more other diagnoses of invasive melanoma and/or pancreatic cancer among first- or second-degree relatives on the same side of the family. The work summarized in this review should help identify individuals who are appropriate candidates for referral for genetic consultation and possible testing.

History of atopy or autoimmunity increases risk of alopecia areata.

Abstract: Background The association between a history of atopy or autoimmune diseases and risk of alopecia areata (AA) is not well established. Objective The purpose of this study was to use the National AA Registry database to further investigate the association between history of atopy or autoimmune diseases and risk of AA. Methods A total of 2613 self-registered sporadic cases (n = 2055) and controls (n = 558) were included in this analysis. Results Possessing a history of any atopic (odds ratio=2.00; 95% confidence interval 1.50-2.54) or autoimmune (odds ratio=1.73; 95% confidence interval 1.10-2.72) disease was associated with an increased risk of AA. There was no trend for possessing a history of more than one atopic or autoimmune disease and increasing risk of AA. Limitations Recall, reporting, and recruiting bias are potential sources of limitations in this analysis. Conclusion This analysis revealed that a history of atopy and autoimmune disease was associated with an increased risk of AA and that the results were consistent for both the severe subtype of AA (ie, alopecia totalis and alopecia universalis) and the localized subtype (ie, AA persistent).

Dermatologic symptoms associated with the multikinase inhibitor sorafenib.

Abstract: Background The multikinase inhibitor sorafenib (Nexavar) is associated with a relatively high incidence of dermatologic symptoms. Objective We sought to evaluate and provide guidance on the diagnosis and clinical management of dermatologic symptoms associated with sorafenib in patients with advanced solid tumors. Methods English-language studies representative of a patient population with a variety of tumor types, who received single-agent sorafenib, were selected. Particular emphasis was placed on the phase III Treatment Approaches in Renal Cancer Global Evaluation Trial (TARGETs). Results Frequently observed dermatologic side effects (any grade in TARGETs) of sorafenib include rash/desquamation (40%), hand–foot skin reaction (30%), alopecia (27%), and pruritus (19%). Generally, dermatologic symptoms resolve with appropriate management, including topical treatments, dose interruptions, dose reductions, or a combination of these. Limitations The results presented here are based on a limited number of studies. Conclusion Although sorafenib is associated with dermatologic symptoms, these are usually resolved with appropriate intervention, patient-led practical treatment, and preventative measures.

Accuracy of teledermatology for pigmented neoplasms

Abstract: Background Studies of teledermatology utilizing the standard reference of histopathology are lacking. Objective To compare accuracy of store-and-forward teledermatology for non-pigmented neoplasms with in-person dermatology. Methods This study was a repeated-measures equivalence trial involving veterans with non-pigmented skin neoplasms. Each lesion was evaluated by an in-person dermatologist and a teledermatologist; both generated a primary diagnosis, up to two differential diagnoses, and management plan. The primary outcome was aggregated diagnostic accuracy (percent correct matches of any chosen diagnosis with histopathology). Secondary outcomes included management plan accuracy (percent correct matches with expert panel management plan). Additional analyses included evaluation of the incremental effect of using polarized light dermatoscopy in addition to standard macro images, and evaluating benign and malignant lesion subgroups separately. Results Most of the 728 participants were male (97.8%) and Caucasian (98.9%). The aggregated diagnostic accuracy (primary outcome) of teledermatology (macro images) was not equivalent (95% confidence interval [CI] for difference within +/−10%) and was inferior (95% CI lower bound P = .0017). The addition of polarized light dermatoscopy showed the same pattern for malignant lesions, but not for benign lesions. Most interestingly, for malignant lesions, the addition of polarized light dermatoscopy yielded equivalent aggregated diagnostic accuracy rates. Limitations Non-diverse study population. Conclusions Using macro images, the diagnostic accuracy of teledermatology was inferior to in-person dermatology, but accuracy of management plans was equivalent. The addition of polarized light dermatoscopy yielded significantly better aggregated diagnostic accuracy, but management plan accuracy was not significantly improved. For the important subgroup of malignant lesions, the addition of polarized light dermatoscopy yielded equivalent diagnostic accuracy between teledermatologists and clinic dermatologists.

Pityriasis rosea: an update with a critical appraisal of its possible herpesviral etiology.

Abstract: Pityriasis rosea is an acute, self-healing exanthem characterized by oval erythematous-squamous lesions of the trunk and limbs, that usually spares face, scalp, palms, and soles. Constitutional symptoms, which have the character of true prodromes; clinical features, which resemble those of the known exanthems; and many epidemiologic data all suggest an infectious origin. A host of infectious agents have been incriminated, but, recently, human herpesvirus 6 and 7 have been extensively studied. The goal of this review is to outline the epidemiologic, clinical, histologic, and ultrastructural features of pityriasis rosea, but mainly to stress its possible human herpesvirus nature. In addition, clues have been added to help the reader to go through the complex subtleties of the virologic investigation.

The role of Malassezia in atopic dermatitis affecting the head and neck of adults.

Abstract: Atopic dermatitis is a common chronic skin condition. A subset of patients with head and neck dermatitis may have a reaction to Malassezia flora fueling their disease. Although there are no documented differences in Malassezia species colonization, patients with head and neck atopic dermatitis are more likely to have positive skin prick test results and Malassezia-specific IgE compared with healthy control subjects and patients with atopy without head and neck dermatitis. There is no clear relationship with atopy patch testing. The reaction to Malassezia is likely related to both humoral- and cell-mediated immunity. Clinically, Malassezia allergy may be suspected in patients with atopic dermatitis and: (1) head and neck lesions; (2) exacerbations during adolescence or young adulthood; (3) severe lesions recalcitrant to conventional therapy; and (4) other atopic diseases. There is literature to suggest that these patients will benefit from a 1- to 2-month course of daily itraconazole or ketoconazole followed by long-term weekly treatment.

The burden of vitiligo: Patient characteristics associated with quality of life

Abstract: Background Vitiligo is commonly regarded as a harmless cosmetic skin problem in Western societies, and the importance of treating patients with vitiligo is often underestimated. Objective We sought to determine the clinical and sociodemographic variables that adversely affect the quality of life in adult patients with generalized vitiligo so that these variables can be considered in the treatment and care. Methods A total of 245 adult patients with generalized vitiligo completed two quality-of-life questionnaires (the Medical Outcomes Study 36-Item Short-form General Health Survey and the Skindex-29). Physicians assessed sociodemographic and clinical characteristics of these patients. Results Dark skin type, vitiligo located on the chest, and treatment in the past appeared to have an adverse impact on the psychosocial domains of quality of life. Moreover, itch was reported by 20% of the patients in this study. Limitations Psychiatric comorbidity was not evaluated in the analyses. Conclusion Generalized vitiligo is a serious skin disorder with an adverse impact on the emotional state, comparable with that of other major skin diseases.

Sentinel node biopsy and standard of care for melanoma

Abstract: An international panel was convened by the organizing committee of the International Sentinel Node (SN) Society (ISNS) at their meeting in Sydney, Australia, on February 21, 2008, to address questions about SN biopsy (SNB) for melanoma. The panelists subsequently wrote this consensus statement, based on their interpretation of current evidence, as a guide to clinical treatment of patients with clinically localized melanoma. The panel comprised a cross section of expert melanoma surgeons who have contributed data and leadership to investigations of SNB.

Sebaceous lesions and their associated syndromes: Part II

Abstract: Sebaceous lesions are associated with two syndromes with widespread multisystem disorders and tumors. Linear sebaceous nevus syndrome has been traditionally known as the triad of sebaceous nevus of Jadassohn, seizures, and mental retardation. This syndrome encompasses a much broader spectrum of multisystem disorders, which is explored below. Muir–Torre syndrome is described as the presence of sebaceous tumors or keratoacanthomas with an underlying visceral malignancy. It is caused by mutations in DNA mismatch repair genes. We discuss its relationship with Lynch syndrome and suggest a comprehensive algorithm on how to screen patients with sebaceous neoplasms for Muire–Torre syndrome. We also provide suggested intensive cancer screening guidelines based on recommendations for patients with Lynch syndrome that may also be of value for patients with Muir–Torre syndrome. Learning objectives After completing this learning activity, participants should be able to discuss the characteristics of Lynch and Muir–Torre syndromes, both of which are associated with sebaceous lesions, evaluate a patient who might have epidermal nevus syndrome, formulate an approach to identify patients at risk for Muir–Torre syndrome who have a newly diagnosed sebaceous neoplasm, and discuss screening recommendations for patients who are identified as having Muir–Torre syndrome.