Journal of the American Academy of Dermatology - Articles in Press

Germline melanoma susceptibility and prognostic genes: A review of the literature - Corrected Proof

Katherine A. Ward, DeAnn Lazovich, Maria K. Hordinsky — 2012-05-14

In recent years, there have been increasing efforts to identify germline genetic variants that may alter melanoma susceptibility and prognosis. The findings of these studies have indicated the presence of rare, high-penetrance alleles with large effects, such as CDKN2A and CDK4, more common, moderately penetrant genes like MC1R, and very common, low-penetrance polymorphisms with small effects that are related to pigmentation, nevus count, immune responses, DNA repair, metabolism, and the vitamin D receptor. The study of these low-penetrance single nucleotide polymorphisms is relatively new; thus many of them are termed ‘candidate melanoma susceptibility or prognostic genes.’ This review summarizes the research on germline polymorphisms that have been implicated in melanoma susceptibility and prognosis in order to provide a framework for additional studies to meet the ultimate goal of predicting a patient's risk of, and prognosis in, cutaneous malignant melanoma.

Clinical and histopathologic spectrum of alopecia mucinosa/follicular mucinosis and its natural history in children - Corrected Proof

Alex Zvulunov, Vered Shkalim, Dan Ben-Amitai, Meora Feinmesser — 2012-05-14

Background: Some authorities consider alopecia mucinosa (AM)/follicular mucinosis (FM) to invariably represent mycosis fungoides (MF). This understanding of AM/FM derives from observations in adults.Objectives: We sought to explore the clinicopathologic features and natural history of pediatric AM/FM.Methods: Medical records were searched for children given the diagnosis of AM/FM from 1998 through 2009. Diagnosis of AM/FM was defined as the presence of well-demarcated hairless plaques with follicular prominence plus an abundance of mucin on histopathologic examination.Results: Forty children with a clinical diagnosis of AM/FM were identified. Nine did not meet the inclusion criteria. In the 31 remaining cases (16 boys, 15 girls) the mean age at onset was 9 ± 3.5 years. Histopathologic examination showed folliculotropism in 28 patients (90%) and epidermotropism in 15 (48%). Twelve cases fulfilled the International Society of Cutaneous Lymphomas (ISCL) diagnostic criteria for early MF. The histopathologic findings were typical of MF in only in two of these cases. T-cell receptor gene rearrangement was positive in 3 of 6 (50%) of tested samples, one in a patient who fulfilled the ISCL criteria for early MF. Mean duration of follow-up was 6.2 ± 3.7 years. All skin lesions resolved and none persisted or recurred. Hodgkin lymphoma was diagnosed 6 months after diagnosis of AM/FM in one patient.Limitations: This was a retrospective study.Conclusions: Although some pediatric cases meet the diagnostic criteria for MF, AM/FM cannot be regarded unequivocally as early follicular MF in this age group. We suggest the current diagnostic criteria for early MF should exclude children with AM/FM. Long-term follow-up of children with AM/FM is nevertheless warranted.

Hair loss in pityriasis versicolor lesions: A descriptive clinicopathological study - Corrected Proof

2012-05-10

Background: We have observed that hair thinning and/or loss occur at times as a presenting symptom or sign in patients with pityriasis versicolor (PV).Objective: Our objective was to verify and explore this clinical observation and depict its underlying pathology.Methods: A total of 39 patients with PV were examined during a period of 11 months and skin biopsy specimens were taken from lesional and nonlesional skin. Hematoxylin-eosin– and periodic acid–Schiff–stained sections were examined and described. Results were statistically analyzed.Results: Hair loss and/or thinning within PV lesions was shown in 61.5% of patients (P value < .0005), appearing most commonly on forearms, abdomen, and neck as well as the beard area (only in male participants). Histopathologically, in addition to the classically described features of PV, basal hydropic degeneration, follicular degeneration, miniaturization, atrophy, plugging, and/or hair shaft absence occurred in 46% of lesional versus 20.5% of nonlesional biopsy specimens (P value < .05); these changes appeared to be directly or indirectly related to the presence of Malassezia organisms in hair follicles and/or stratum corneum.Limitations: Some patients with PV lesions on the face did not approve facial biopsy.Conclusion: This study provides clinical and histopathological evidence that PV lesions may be associated with hair thinning and/or loss.

Epidermolysis Bullosa Oropharyngeal Severity (EBOS) score: A multicenter development and reliability assessment - Corrected Proof

2012-05-10

Background: Epidermolysis bullosa (EB) is a genetic mucocutaneous disorder characterized by blister formation upon mild trauma. All 4 EB types may show oropharyngeal lesions involving either hard or soft tissues. Currently, there are very few data on EB scoring that include the oropharyngeal cavity.Objectives: We sought to develop an oropharyngeal severity score that was objective, valid, reliable, reproducible, easy to perform, and appropriate for all EB types.Methods: In this study, oral medicine specialists developed a new score, the EB Oropharyngeal Severity (EBOS) score. This measured oropharyngeal disease activity (erythema, atrophy, blisters, erosion/ulceration) and structural damage (microstomia, ankyloglossia, scarring phenotype beyond microstomia and ankyloglossia, enamel hypoplasia). It was tested on 92 patients with different types/subtypes of EB, and interobserver and intraobserver reliability were assessed.Results: The EBOS mean total score was 12.9 ± 10.9 (range: 0-34). Both interobserver and intraobserver reliability for total score on all patients with EB were considered excellent (intraclass correlation coefficient 0.94; 95% confidence interval 0.90-0.96 and intraclass correlation coefficient 0.90; 95% confidence interval 0.84-0.94, respectively). Even analyzing each single parameter of the disease activity and structural damage, a substantial to excellent correlation was found in the interobserver (except for 4 sites) and intraobserver reliability. A significant correlation was found between EB types/subtypes and the EBOS median score (P < .001), but not between age and the EBOS mean total score in each group.Limitations: The sample size was small and the number of EB subtypes was limited.Conclusions: The EBOS score seems to represent an instrument capable of truly quantifying the oropharyngeal severity in different types/subtypes of EB, demonstrating excellent interobserver and intraobserver reliability.

Site identification challenges in dermatologic surgery: A physician survey - Corrected Proof

Shari A. Nemeth, Naomi Lawrence — 2012-05-07

Background: Previous single-institution studies have shown that patients and physicians struggle to identify biopsy sites requiring surgery on the day of treatment. To date no studies have been done to assess if this is a widespread challenge faced by many dermatologic surgeons.Objective: We sought to determine if site identification is an issue among Mohs surgeons, and to determine which practice environments have the best supplementary data available to surgeons for site localization.Methods: We conducted an online survey of 722 members of the American College of Mohs Surgery inquiring about site identification and documentation typically received from referring physicians.Results: Of 325 surveys completed (45% response rate), 71% reported that more than 5% of their patients have difficulty identifying their surgery site. The majority (89%) responded that a photograph is most useful for identifying biopsy sites. Surgeons in academic centers and multispecialty group practices were more likely to receive a photograph versus those in private practice.Limitations: Individual survey responses may be subject to recall bias.Conclusion: Difficulty identifying biopsy sites needing surgery is a common challenge faced by Mohs surgeons. The majority of Mohs surgeons surveyed find photographs the most useful documentation for decreasing the risk of wrong-site dermatologic surgery.

The predictive value of imaging studies in evaluating regional lymph node involvement in Merkel cell carcinoma - Corrected Proof

2012-05-02

Background: Merkel cell carcinoma (MCC) is a rare cutaneous neuroendocrine malignancy with high potential for nodal or distant metastatic spread. Little information exists on sensitivity and specificity of various imaging techniques when compared with the gold standard of histopathologic evaluation of the lymph node basin.Objective: We sought to further understand the value of various imaging modalities in the staging and initial workup of patients with MCC.Methods: Of 240 patients with primary MCC evaluated between 1981 and 2008, 99 had diagnostic imaging at initial presentation with biopsy-proven cutaneous MCC and had histopathologic nodal evaluation within 4 weeks of the initial scan. We conducted a retrospective chart review of these identified patients.Results: Computed tomography (n = 69) demonstrated a sensitivity of 47%, specificity of 97%, positive predictive value of 94%, and negative predictive value of 68% in detecting nodal basin involvement. Fluorine-18-fluorodeoxyglucose positron emission tomography scan (n = 33) demonstrated a sensitivity of 83%, specificity of 95%, positive predictive value of 91%, and negative predictive value of 91% in detecting nodal basin involvement. Magnetic resonance imaging (n = 10) demonstrated a sensitivity of 0%, specificity of 86%, positive predictive value of 0%, and negative predictive value of 67% in detecting nodal basin involvement.Limitations: This was a retrospective study with small sample size.Conclusion: Use of fluorine-18-fluorodeoxyglucose positron emission tomography in the evaluation of a regional lymph node basin in primary MCC is significantly more sensitive and equally specific when compared with traditional computed tomography. Both fluorine-18-fluorodeoxyglucose positron emission tomography and computed tomography are more sensitive than clinical examination alone.

Sebaceous neoplasms with mismatch repair protein expressions and the frequency of co-existing visceral tumors - Corrected Proof

Bonnie A. Lee, Limin Yu, Linglei Ma, Anne C. Lind, Dongsi Lu — 2012-05-02

Background: Visceral malignancy has been associated with sebaceous neoplasms in patients with Muir-Torre syndrome. However, no large studies have been done to evaluate the frequency of visceral tumors in patients with sebaceous neoplasms and mismatch repair (MMR) protein expression of the sebaceous tumors.Objective: We sought to determine the frequency of visceral tumors in patients with sebaceous neoplasms, MMR protein expression of the sebaceous tumors, and the related surveillance practices of physicians.Methods: We identified 85 patients with sebaceous neoplasms. Relevant clinical information was obtained via chart review and database searches. MMR protein expression was examined by immunohistochemistry.Results: Nineteen of the 85 patients had a total of 22 visceral malignancies, of which 41% were genitourinary in origin. Ten of the 17 patients (59%) with visceral malignancy had loss of MMR expression in their sebaceous neoplasms or somatic MMR mutation. Thirty patients had other findings such as colonic adenomas and polyps. Of the 23 patients who had a family history of visceral malignancy, 9 had a personal history of visceral malignancy.Limitations: Only one sebaceous tumor from each patient (except one) was tested for MMR, which might reduce the sensitivity.Conclusion: Our findings demonstrate an increased frequency of internal malignancy in patients with sebaceous neoplasms compared with the general population, and highlight the heterogeneous nature of the visceral tumors. A majority of the sebaceous tumors show loss of MMR expression. The study reminds us to strive toward a consistent and comprehensive approach to screening for internal malignancy when a patient is given a diagnosis of a sebaceous neoplasm.

Giant angiofibromas in tuberous sclerosis complex: A possible role for localized lymphedema in their pathogenesis - Corrected Proof

2012-05-02

Background: Giant angiofibromas in patients with tuberous sclerosis complex (TSC) are rare.Objective: We sought to report two patients who had TSC with unusually large and disfiguring facial angiofibromas and to identify underlying histopathologic changes that may possibly explain the clinical features.Methods: We performed a clinicopathologic, immunohistochemical, and molecular biologic study using 42 lesional specimens and peripheral blood from one of the two patients. The immunohistochemical investigations were mainly focused on the vascular moiety of the lesions. TSC1 and TSC2 alterations were studied using multiplex ligation-dependent probe amplification for large deletion/duplication mutations, whereas screening for small mutations was performed using polymerase chain reaction amplification of individual coding exons and exon-intron junctions of both genes followed by an analysis on denaturation gradient gel electrophoresis.Results: Histopathologic examination revealed, in addition to findings typical of angiofibroma, several unusual features including multinucleated giant cells containing multiple intracytoplasmic vacuoles, Touton-like cells, emperipolesis, pagetoid dyskeratosis, vacuolar alteration at the dermoepidermal junction, Civatte bodies, and melanophages in the subjacent dermis. Numerous dilated lymphatic vessels were detected indicating localized lymphostasis, probably caused by secondary lymphedema. The lymphatic nature of the vessels was confirmed by immunohistochemical study. Genetic testing for TSC1 and TSC2 gene mutations revealed a substitution on position c.2251C>T resulting in a nonsense mutation R751X in fragment 20.2.Limitations: Histopathologic specimens and peripheral blood were available from only one patient.Conclusion: Localized lymphedema may contribute to the formation of large disfiguring angiofibromas in patients with TSC.

Difficulty with surgical site identification: What role does it play in dermatology? - Corrected Proof

Kathleen M. Rossy, Naomi Lawrence — 2012-04-27

Background: The potential for wrong-site surgery is a growing concern in dermatology.Objective: The purpose of this study was to determine the incidence of difficulty with surgical site identification and possible confounding factors.Methods: This was a prospective study on 333 Mohs cases performed between April 1, 2009, and February 9, 2010. Data collection forms were used on the day of surgery to record the difficulty associated with surgical site identification and potential confounding factors.Results: Of the 333 patients evaluated, 9% were unable to identify their surgical sites. The majority of cases (88.5%) were located on the head and neck. When comparing patients who were able to identify their site and those who were not, there was a statistically significant difference (P = .035) in the percentage of lesions residing in a location visible to the patient. Those who were able to see their biopsy sites were 3.5 times more likely to identify their surgical site. Of the 47.6% of patients with chart notes, only 5% of these cases were photographs and 23% had high-quality diagrams. Although a delay in treatment of greater than 3 months from the original biopsy site was higher among those with difficulty in identifying their surgical site, this was not found to be statistically significant.Limitations: We believe our sample size was not large enough to show a significant link between difficulty with surgical site identification and several likely confounding factors.Conclusion: We have shown that at least 9% of patients presenting for Mohs micrographic surgery are unable to confidently identify their surgical sites.

Mohs frozen tissue sections in comparison to similar paraffin-embedded tissue sections in identifying perineural tumor invasion in cutaneous squamous cell carcinoma - Corrected Proof

2012-04-26

Background: Perineural invasion (PNInv) in cutaneous squamous cell carcinoma (cSCC) increases the risk of recurrence, possibly because of suboptimal identification on frozen or paraffin-embedded tissue sections. Perineural inflammation (PNInf) may portend PNInv.Objective: We sought to correlate identification of PNInv and PNInf in hematoxylin-eosin–stained Mohs frozen sections with PNInv and PNInf identified in similarly oriented paraffin-embedded sections obtained in cases of cSCC.Methods: We reviewed same patient Mohs frozen and paraffin-embedded tissue sections for all patients presenting within a 2-year period to our Mohs micrographic surgical unit for removal of cSCC with PNInv or PNInf identified on either type of tissue section.Results: Of 537 patients undergoing surgical resection of cSCC, 21 (3.9%) had either PNInv (n = 11) or PNInf (n = 10) on frozen sections. PNInv on Mohs frozen sections was identified in 11 cases and confirmed on paraffin-embedded sections in 9 cases (82%). Paraffin-embedded sections failed to identify PNInv present in Mohs frozen sections in two (2/11), or 18% of cases. PNInf on Mohs frozen sections was confirmed on paraffin-embedded sections in 3 cases (30%), but PNInv was identified in 5 cases (50%).Limitations: Our results are a retrospective case review from a specific time period by one institution. Furthermore, it is impossible to compare identical tissue specimens using two sequential tissue processing techniques.Conclusion: PNInv can be accurately identified with Mohs frozen sections. PNInf on Mohs frozen sections suggests the presence of PNInv and requires further histologic investigation.

Solitary mycosis fungoides: A distinct clinicopathologic entity with a good prognosis: A series of 15 cases and literature review - Corrected Proof

2012-04-26

Background: Mycosis fungoides (MF) is the most common cutaneous T-cell lymphoma (CTCL), accounting for almost 50% of all primary cutaneous lymphomas. The occurrence of solitary lesions, which are clinically and histopathologically indistinguishable from classic MF has been described.Objective: We describe 15 cases of solitary MF and discuss the relationship to classic MF, “reactive” processes and to other, rarer forms of CTCL that may present with solitary lesions.Methods: We conducted a retrospective chart review and a PubMed search to identify all reported cases of solitary MF to date, as well as information about other CTCLs presenting as a solitary lesion.Results: Fifteen patients were identified. Follow-up data were available on 10 patients with a median follow-up of 10 months (range, 1 to 48 months). Clinical, pathological, immunocytochemical, and molecular-genetic features were analyzed. Five cases were diagnosed as folliculotropic MF (FMF). Of the 10 cases with follow-up, 2 were treated with topical steroids, 2 were completely excised, 5 received radiotherapy, and 1 received tacrolimus. One hundred twenty-eight cases of solitary MF were identified in the literature and reviewed for commonalities to and differences with our cases and other CTCLs.Limitations: This study was retrospective; follow-up data were not available in some cases and were only short term in others.Conclusions: Solitary MF appears to have a good prognosis. In lesions that are not completely excised, curative radiotherapy can be used. Long-term follow up is advised.

Coexistence of lichen sclerosus and morphea: A retrospective analysis of 472 patients with localized scleroderma from a German tertiary referral center - Corrected Proof

2012-04-26

Background: The coexistence of lichen sclerosus (LiS) and localized scleroderma (LoS) has sporadically been reported in the literature. Recently, a prospective multicenter study demonstrated a surprisingly high percentage of genital LiS in patients with morphea.Objective: The aim of this study was to determine the prevalence of LiS in a cohort of patients with LoS who presented at a tertiary referral medical center for connective tissue diseases in Germany.Methods: We retrospectively evaluated the prevalence of genital and extragenital LiS in adult and pediatric patients with different subtypes of LoS. Secondary outcome measures included demographic characteristics and prevalence of other concomitant autoimmune diseases.Results: Of the 472 patients (381 adults, 91 children; mean age: 46 years; range, 4-88 years; female to male ratio: 3.5:1 in adults and 8:1 in children) with LoS, 27 (5.7%) also presented with LiS (19 extragenital and 8 genital lesions). LiS exclusively occurred in patients with plaque-type (morphea) and generalized LoS. Twenty-six of the 27 (96.2%) patients with concomitant LoS and LiS were adults. Compared with LiS in the general population, LiS was significantly more frequent in LoS as indicated by an odds ratio of 18.1 (95% confidence interval 2.6-134.2; P < .0001). In all, 38 (8.1%) patients with LoS had other autoimmune disorders (most frequently Hashimoto thyroiditis, rheumatoid arthritis, and alopecia areata).Limitations: This was a retrospective study.Conclusions: This large retrospective analysis confirms recent reports of a high prevalence of LiS in patients with LoS. Based on these findings, patients with LoS, especially those with morphea, should be carefully screened for concomitant LiS, including inspection of the anogenital region.

Pruritic papular eruption and eosinophilic folliculitis associated with human immunodeficiency virus (HIV) infection: A histopathological and immunohistochemical comparative study - Corrected Proof

2012-04-23

Background: Among the papular-pruriginous dermatoses related to human immunodeficiency (HIV) infection, two entities remain poorly differentiated leading to confusion in their diagnosis: HIV-related pruritic papular eruption (HIV-PPE or prurigo) and eosinophilic folliculitis (HIV-EF).Objective: To establish histopathological and immunohistochemical parameters to differentiate between two conditions associated with HIV infection, the pruritic papular eruption (HIV-PPE) and eosinophilic folliculitis (HIV-EF).Methods: Clinically typical HIV-PPE (18 cases) and HIV-EF (10 cases) cases were compared with each other in terms of the following topics: clinical and laboratory features (gender, age, CD4+ cell and eosinophil count), histopathological features (hematoxylin-eosin and toluidine blue staining) and immunohistochemical features (anti-CD1a, anti-CD4, anti-CD7, anti-CD8, anti-CD15, anti-CD20, anti-CD30, anti-CD68/macrophage and anti-S-100 reactions).Results: Among the HIV-EF patients, we found an intense perivascular and diffuse inflammatory infiltration compared with those patients with HIV-PPE. The tissue mast cell count by toluidine staining was higher in the HIV-EF patients, who also presented higher expression levels of CD15 (for eosinophils), CD4 (T helper), and CD7 (pan-T lymphocytes) than the HIV-PPE patients.Limitations: Only quantitative differences and not qualitative differences were found.Conclusions: These data indicate that HIV-related PPE and EF could possibly be differentiated by histopathological and immunohistochemical findings in addition to clinical characteristics. In fact, these two inflammatory manifestations could be within the spectrum of the same disease because only quantitative, and not qualitative, differences were found.

Characterization of 1152 lesions excised over 10 years using total-body photography and digital dermatoscopy in the surveillance of patients at high risk for melanoma - Corrected Proof

2012-04-23

Background: The combined use of total-body photography and digital dermatoscopy, named “two-step method of digital follow-up,” allowed the detection of incipient melanoma as a result of dermatoscopic or macroscopic changes during follow-up.Objective: We sought to assess dermatoscopic features and dynamic changes leading to excision of melanocytic lesions during our 10-year experience of monitoring patients at high risk for melanoma.Methods: We analyzed 1152 lesions excised during the surveillance of 618 patients at high risk for melanoma from 1999 to 2008.Results: A total of 779 excised lesions had been previously recorded: 728 were removed because of dermatoscopic changes during follow-up and 51 were removed even though no significant change was noted. The remaining 373 excised lesions were new or undetected on previous total-body photography. A total of 98 melanomas were detected, 60 in the monitored lesions, and 38 among the “new” lesions. The most frequent dermatoscopic changes detected were asymmetric enlargement in almost 60% (n = 418), focal changes in structure in 197 (27%) and in pigmentation in 122 (17%), the latter two being more frequently seen in melanomas than in nevi (both P < .001). No significant differences were detected between dermatoscopic or histopathological characteristics of the melanomas in each group, with a considerable proportion of melanomas misclassified as benign in both groups (26.3% and 38.3%, respectively).Limitations: The dermatoscopy pattern of stable lesions and the histopathology of lesions not removed were not included in the study.Conclusion: The most frequent dermatoscopic features associated with melanoma were focal change in pigmentation or structure. Melanomas detected by dermatoscopic changes were remarkably similar to those detected in total-body photography. Almost 40% of melanomas diagnosed in individuals at high risk corresponded to lesions that were not under dermatoscopic surveillance.

Do automated text messages increase adherence to acne therapy? Results of a randomized, controlled trial - Corrected Proof

Andreas Boker, H. Jill Feetham, April Armstrong, Patricia Purcell, Heidi Jacobe — 2012-04-23

Background: Acne is a common skin condition often requiring complex therapeutic regimens. Patient nonadherence to prescribed medication regimens is a factor in treatment failure.Objective: The goal of this study was to determine if daily automated text messages would result in increased adherence to recommended use of topical acne medication and consequently greater improvement in acne.Methods: Forty patients with mild to moderate acne were prescribed clindamycin/benzoyl peroxide 1%/5% gel in the mornings and adapalene 0.3% gel in the evenings for 12 weeks. Each medication tube was fitted with an electronic Medication Event Monitoring System cap (MEMS, Aardex Group, Sion, Switzerland) (to record the date and time of every opening/closing of the tube). Twenty patients were randomly assigned to receive customized twice-daily text messages instructing them to apply their morning and evening medication. The remainder of patients (N = 20), who did not receive text messages, served as control subjects.Results: Mean adherence rates for the correct application of both medications on a daily basis over 12 weeks was 33.9% for patients in the reminder group and 36.5% for patients in the control group (P = .75). Patients in both groups had similar clinical improvement of their acne.Limitations: The small sample size may limit the ability to detect differences between the study groups.Conclusions: Electronic reminders in the form of daily, customized text messages were not associated with significant differences in adherence to topical medications in patients with mild to moderate acne and had no significant effect on therapeutic response.

World Health Organization–European Organization for Research and Treatment of Cancer classification of cutaneous lymphoma in Korea: A retrospective study at a single tertiary institution - Corrected Proof

2012-04-23

Background: The relative frequency and the clinicopathological characteristics of lymphoma may vary according to geography and ethnicity. Data are limited regarding the features of cutaneous lymphoma (CL) presented according to the World Health Organization (WHO) and the European Organization for Research and Treatment of Cancer (EORTC) classification (2005) in Korea.Objective: The study determined the relative frequency of CL in Korea and presented the clinical relevance of CL based on the WHO–EORTC classification.Methods: We reclassified the cases of CL collected over a 16-year period in a tertiary institution–based dermatologic setting in Korea.Results: In all, 164 cases were divided into 96 primary and 68 secondary CL. The group of primary CL consisted of T- and natural killer–cell lymphomas (84.3%), B-cell lymphomas (13.5%), and immature hematopoietic malignancies (2%). The Korean population presented with a higher rate of T-cell and natural killer–/T-cell CL and a lower rate of cutaneous B-cell lymphoma than Western countries. Compared with 2003 Korean data, the rate of mycosis fungoides was lower and the rate of nasal and nasal-type natural killer–/T-cell lymphomas was higher.Limitations: This study was retrospective and based on a single-center experience.Conclusion: As the relative frequency of lymphomas differs widely with geography and ethnicity, there is a need to collect more data to describe the epidemiologic characteristics in the Far East.

Histologically challenging melanocytic tumors referred to a tertiary care pigmented lesion clinic - Corrected Proof

2012-04-23

Background: The histopathologic diagnosis of some melanocytic tumors is extraordinarily difficult. With this in mind, melanocytic tumors from patients referred to the Massachusetts General Hospital (MGH) Pigmented Lesion Clinic (PLC) are routinely reviewed in the MGH Dermatopathology Unit.Objective: We sought to determine the frequency of diagnostically challenging cases from patients treated at the MGH PLC, as measured by a change in the diagnosis upon review of the referral materials.Methods: We retrospectively reviewed the MGH and referral pathology reports for 478 consecutive cutaneous melanocytic tumors: 126 from 1996-1997 and 352 from 2010-2011. Differences in diagnosis and in therapeutic impact were evaluated.Results: Changes in diagnosis occurred in 168 of 478 cases (35%), more frequently when the original diagnostician was a general pathologist (P = .003). A similar fraction of diagnoses were changed from malignant to benign or vice versa, in both historic and contemporary cohorts. In 64 patients (13%), changes in diagnosis led to a change in therapy. Changes in stage or grading led to the most changes in therapy (78%; 50/64) versus changes from benign to malignant or vice versa (22%; 14/64).Limitations: This is a retrospective study with the bias of a tertiary-care referral center.Conclusions: These findings demonstrate the diagnostic difficulty of a subset of melanocytic tumors and highlight the utility of review by more than one pathologist; patient treatment is affected in more than 10% of cases. Identification of melanoma prognostic factors and melanocytic nevus grading led to clinically significant changes in diagnosis leading to a change in patient management.

Keratoacanthoma: Clinical and histopathologic features of regression - Corrected Proof

Christine J. Ko, Jennifer M. McNiff, Marcus Bosenberg, Keith A. Choate — 2012-04-23

Background: The clinical and histopathologic features of regressing keratoacanthomas have not been adequately described in the literature.Objective: “True” keratoacanthomas (ie, squamous tumors with evidence of spontaneous resolution) were studied clinically and histopathologically.Methods: Nineteen crateriform tumors with a partial biopsy histopathologically compatible with keratoacanthoma were followed over time for correlation with biologic behavior (ie, regression). Tumors displaying spontaneous resolution, arbitrarily defined as a decrease in size of at least 25%, were categorized as keratoacanthomas.Results: Seven regressing keratoacanthomas tended to show flattening before a decrease in diameter. Histopathologically, there was variable epidermal hyperplasia with generally prominent hyperkeratosis, retained crateriform architecture, and dermal fibrosis.Limitations: This study has a small sample size.Conclusions: Regressing keratoacanthomas show persistent crateriform architecture, clinically and histopathologically. Lesions become flatter before decreasing in diameter, and keratinocytes appear banal and lack glassy pink cytoplasm during regression.

D2-40 immunohistochemical overexpression in cutaneous squamous cell carcinomas: A marker of metastatic risk - Corrected Proof

2012-04-23

Background: Approximately 4% of cutaneous squamous cell carcinomas (cSCCs) develop lymphatic metastases. The value of lymphatic endothelial markers to enhance the detection of lymphatic tumor invasion in cSCC has not been assessed previously.Objective: We sought to evaluate the use of the antibody D2-40, a podoplanin immunohistochemical marker, to identify tumor lymph vessel invasion in cSCC and to assess its expression in tumor cells.Methods: This was a retrospective case-control study. A series of 101 cSCC, including 51 cases that developed lymphatic metastatic spread (metastasizing cSCC [MSCC]) and 50 cases that resolved definitely after surgical excision (non-MSCC) were included in the study. Lymph vessel invasion using D2-40 was evaluated on all primary biopsy specimens. The percentage of tumor cells showing D2-40 positivity and intensity scoring were recorded. All the immunohistochemical findings were correlated with the clinicopathological features.Results: Lymph vessel invasion was observed in 8% of non-MSCCs and in 25.5% of MSCCs (P = .031). D2-40 expression was significantly increased, both in intensity (odds ratio 4.42 for intensity ++/+++) and in area (odds ratio 2.29 for area >10%), in MSCC when compared with non-MSCC. Interestingly, almost half (49%) of the MSCC had moderate to intense D2-40 positivity compared with 16% of non-MSCC. D2-40 immunohistochemical expression was increased in tumors with an infiltrative pattern of extension. In the multivariate analysis, histologically poorly differentiated tumors, recurrent lesions, and cSCC showing D2-40 overexpression (in intensity) were significantly associated with lymphatic metastases development (odds ratios 15.67, 14.72, and 6.07, respectively).Limitations: This was a retrospective study.Conclusion: The expression of podoplanin associates with high metastatic risk in cSCC.

Topical propranolol for treatment of superficial infantile hemangiomas - Corrected Proof

Guangqi Xu, Renrong Lv, Zhongfang Zhao, Ran Huo — 2012-04-20

Background: “Wait-and-see” is a common principle for most superficial infantile hemangiomas (IHs) because of their expected involution. Topical propranolol has recently been reported to be an effective treatment for superficial IHs.Objective: The aim of this study was to evaluate the efficacy and safety of 1% propranolol ointment in the treatment of superficial IHs.Methods: A retrospective chart review was performed on 25 children (21 female and 4 male) with a median age of 4 months (range, 1-10 months). A total of 28 lesions were treated with 1% propranolol ointment. Topical propranolol was applied thrice daily for a mean duration of 21 weeks (range, 5-59 weeks). Changes in the size, texture, and color of the tumor were monitored and recorded at regular intervals. The treatment response was evaluated using a 3-point scale system: good, partial, and no response. Adverse effects after medication were evaluated and managed accordingly.Results: Of the 28 hemangiomas, 16 (57%) demonstrated good response, 9 (33%) showed a partial response, and 3 (10%) had no response. Among all the IHs, 90% showed either good or partial responses to topical 1% propranolol ointment treatment. No systemic complication was observed in any of the patients.Limitations: This report is a retrospective uncontrolled study.Conclusions: Topical therapy with 1% propranolol ointment may be a safe and effective method for the treatment of superficial IHs and can be used as an adjuvant treatment measure during the wait-and-see period.

Basal cell carcinoma characteristics as predictors of depth of invasion - Corrected Proof

2012-04-16

Background: Pretreatment risk stratification of basal cell carcinoma (BCC) is largely based on histologic subtype reported from biopsy specimens.Objective: We sought to determine the degree of concordance between characteristics identified on biopsy specimen and excision and to determine if histologic characteristics other than subtype correlated with depth of invasion.Methods: Histologic specimens of 100 BCC biopsy specimens and corresponding excisions were reviewed. Anatomic site, histologic subtype, maximum depth of extension, contour of the lobules at the leading edge, elastosis characteristics, presence of necrosis, calcification, and ulceration were recorded. Concordance between biopsy specimens and their excisions with relation to depth of tumor lobules was analyzed.Results: The concordance between the subtype of biopsy specimen and excision was 62%. Micronodular tumors had the greatest mean depth, followed by infiltrative, nodular, and superficial subtypes. Subtype reported from biopsy specimen (P = .0002) and excision (P < .0001) correlated to depth and was superior to age, contours of excision specimens, the presence of necrosis, and the extent of excisional solar elastosis. Gender, anatomic site, contours of biopsy specimens, elastosis color, elastosis type, the presence of ulceration, and calcification did not correlate with depth.Limitations: Selection bias is present as only standard excisions were included; BCCs treated by other methods were not examined.Conclusions: BCC subtype identified on biopsy specimen may not correlate with subtype identified on excision. Morphologic subtype has the highest correlation with depth and reporting should reflect the highest risk growth pattern if a biopsy specimen contains more than one pattern. Consideration should be given to reporting necrosis and degree of solar elastosis.

Frontal fibrosing alopecia: A review of 60 cases - Corrected Proof

Alison MacDonald, Colin Clark, Susan Holmes — 2012-04-16

Background: Frontal fibrosing alopecia (FFA) is a variant of lichen planopilaris primarily affecting postmenopausal women, with a predilection for the frontotemporal hairline.Objectives: We sought to examine possible causal associations and review the clinical features, natural history, and response to treatment of patients with FFA attending a specialist hair clinic.Methods: This was a case note review of 60 patients with FFA.Results: The number of patients with FFA seen has increased over the last decade. All were Caucasian women, with significantly above-average affluence scores and were less likely to be smokers. The mean age at presentation was 64 years and average disease duration was 3.4 years (range: 6 months-30 years). Three patients were premenopausal. All patients had frontotemporal involvement, with follicular hyperkeratosis, scarring, and variable perifollicular erythema. Several patients had more unusual patterns: 8 had extensive parietal involvement, 4 had occipital involvement, 1 had asymmetric frontal involvement, and 5 had typical FFA associated with diffuse scalp lichen planopilaris. Eyebrow loss was documented in 73%, eyelash loss in 3%, and body hair loss in 25%. Almost all patients had been treated with superpotent topical steroids. Other treatments included topical calcineurin inhibitors; intralesional triamcinolone acetate; phototherapy; hydroxychloroquine; lymecycline; and prednisolone. Although some treatments may reduce inflammation, their efficacy in controlling the progress of the alopecia was uncertain.Limitations: This is a retrospective review.Conclusions: FFA is a clinically distinctive condition, the prevalence of which appears to be increasing. It has a generally poor response to treatment. The origin remains uncertain.

Grading dermatologic adverse events of cancer treatments: The Common Terminology Criteria for Adverse Events Version 4.0 - Corrected Proof

2012-04-13

Dermatologic adverse events to cancer therapies have become more prevalent and may to lead to dose modifications or discontinuation of life-saving or prolonging treatments. This has resulted in a new collaboration between oncologists and dermatologists, which requires accurate cataloging and grading of side effects. The Common Terminology Criteria for Adverse Events Version 4.0 is a descriptive terminology and grading system that can be used for uniform reporting of adverse events. A proper understanding of this standardized classification system is essential for dermatologists to properly communicate with all physicians caring for patients with cancer.

Systematic review and meta-analysis of randomized controlled trials on topical interventions for genital lichen sclerosus - Corrected Proof

2012-04-09

Background: Lichen sclerosus (LS) is a chronic inflammatory dermatosis that occurs mainly in the anogenital area and causes itching and soreness. Progressive destructive scarring may result in burying of the clitoris in females and phimosis in males. Affected people have an increased risk of genital cancers.Objective: We sought to assess the effects of topical interventions for genital LS.Methods: We undertook a systematic review and meta-analysis using the methodology of the Cochrane Collaboration.Results: We included 7 randomized controlled trials with a total of 249 participants covering 6 treatments. Clobetasol propionate 0.05% was better than placebo in treating genital LS (participant-rated improvement/remission of symptoms: risk ratio 2.85 [95% confidence interval {CI} 1.45-5.61]; investigator-rated global degree of improvement: standardized mean difference [SMD] 5.74 [95% CI 4.26-7.23]) as was mometasone furoate 0.05% (change in clinical grade of phimosis: SMD −1.04 [95% CI −1.77 to −0.31]). We found no evidence supporting the efficacy of topical androgens and progesterone. There were no differences between pimecrolimus and clobetasol propionate in relieving symptoms through change in pruritus (SMD −0.33 [95% CI −0.99 to 0.33]) and burning/pain (SMD 0.03 [95% CI −0.62 to 0.69]). However, pimecrolimus was less effective than clobetasol propionate in improving gross appearance (investigator-rated global degree of improvement: SMD −1.64 [95% CI −2.40 to −0.87]).Limitations: Most of the included studies were small.Conclusions: The current limited evidence supports the efficacy of clobetasol propionate, mometasone furoate, and pimecrolimus in treating genital LS. Further randomized controlled trials are needed.

High-SPF sunscreens (SPF ≥ 70) may provide ultraviolet protection above minimal recommended levels by adequately compensating for lower sunscreen user application amounts - Corrected Proof

Hao Ou-Yang, Joseph Stanfield, Curtis Cole, Yohini Appa, Darrell Rigel — 2012-04-01

Background: The manner in which consumers apply sunscreens is often inadequate for ultraviolet protection according to the labeled sun protection factor (SPF). Although sunscreen SPFs are labeled by testing at an application density of 2 mg/cm2, the actual protection received is often substantially less because of consumer application densities ranging from 0.5 to 1 mg/cm2. High-SPF sunscreens may provide more adequate protection even when applied by consumers at inadequate amounts.Objective: We sought to measure the actual SPF values of various sunscreens (labeled SPF 30-100) applied in amounts typical of those used by consumers.Methods: Actual SPF values were measured on human volunteers for 6 sunscreen products with labeled SPF values ranging from 30 to 100, applied at 0.5, 1.0, 1.5, and 2.0 mg/cm2.Results: There was a linear relationship between application density and the actual SPF; sunscreens with labeled SPF values of 70 and above provided significant protection, even at the low application densities typically applied by consumers. Sunscreens labeled SPF 70 and 100 applied at 0.5 mg/cm2 provided an actual SPF value of, respectively, 19 and 27.Limitations: The study was conducted in a laboratory setting under standardized conditions and results are extrapolated to actual in-use situations.Conclusion: Sunscreens with SPF 70 and above add additional clinical benefits when applied by consumers at typically used amounts, by delivering an actual SPF that meets the minimum SPF levels recommended for skin cancer and photodamage prevention. In contrast, sunscreens with SPF 30 or 50 may not produce sufficient protection at actual consumer usage levels.

Molecular biology of melanoma - Corrected Proof

Julie M. Swick, John C. Maize — 2012-03-29

Dermatologists and dermatopathologists face the difficulties of accurately diagnosing and treating atypical melanocytic lesions and melanomas. Despite huge advances in medicine, our management of melanoma has not significantly changed in many years. The biggest gains made recently have been in the identification of common mutations in melanoma and the use of these mutations to aid in the diagnosis and treatment of melanoma. To understand these gains one must first be familiar with the regulatory pathways of melanoma and the most common mutations found there. This article will review the function and significance of the most studied mutations in melanoma and briefly discuss new and planned treatment options.

State of teledermatology programs in the United States - Corrected Proof

2012-03-29

Background: Teledermatology programs in the United States have evolved over the past several decades. No systematic survey of teledermatology programs in the United States is available in peer-reviewed literature.Objective: To provide up-to-date information regarding the state of teledermatology programs in the United States.Methods: Active U.S. teledermatology programs were surveyed in 2011 with regards to practice models, clinical volume, and payment methods. These findings were compared with those from 2003.Results: By January 2012, 37 teledermatology programs were active in the United States. Store-and-forward teledermatology was the most frequent delivery modality offered by 30 (81%) of the programs. The majority of the programs were based at academic institutions (49%), followed by Veterans Administration hospitals (27%), private practice (16%), and health maintenance organizations (HMOs) (8%). The majority of programs (67%) provided services to their home state only, whereas the rest also served additional U.S. states or abroad. The median number of consultations per program was 309 (range, 5-6500) in 2011. The most frequent payer sources were private payers, followed by self-pay, Medicaid, Medicare, and HMOs. Since 2003, with the confirmed discontinuation of 24 previously active programs, the total number of active teledermatology programs in 2011 was 60% of that in 2003. However, the annual consult volume per program nearly doubled for the sustainable programs in 2011.Limitations: Itemized billing information was not uniformly available from all programs.Conclusion: The turnover in teledermatology programs is relatively constant, with an increase in consult volume for sustainable programs. Store-and-forward is the dominant modality of delivery, while hybrid technology model is emerging.

Hypopigmented parapsoriasis en plaque, a new overlooked member of the parapsoriasis family: A report of 34 patients and a 7-year experience - Corrected Proof

Mohammad A. El-Darouti, Marwa M. Fawzy, Rehab A. Hegazy, Rania M. Abdel Hay — 2012-03-29

Background: In the past 7 years we have extensively studied an uncommon hypopigmented disorder that, apart from hypopigmentation, showed many common features with parapsoriasis en plaque (PSEP), both clinically and histopathologically.Objective: We sought to verify whether this disorder should be considered a hypopigmented variant of PSEP and thus be referred to as hypopigmented PSEP.Methods: A total of 34 patients presenting with this peculiar hypopigmented disorder were included (2003-2010). Patients were subjected to a predesigned algorithm excluding all possible differential diagnoses of hypopigmented lesions.Results: Our findings indicated that this disorder can be diagnosed as hypopigmented PSEP. These findings included: (1) exclusion of all other disorders causing similar hypopigmented lesions; (2) shape and size of the lesions being very similar to those of classic small PSEP (small-plaque parapsoriasis [SPP]); (3) similar distribution of the lesions (trunk, proximal upper and lower limbs) to the classic PSEP; (4) digitiform extensions of most the lesions (70.5% of our patients) as in SPP; (5) absence of itching as in PSEP (SPP type); (6) good response to narrowband ultraviolet B in 76.4% of the patients (n = 26); and (7) during follow-up 5 patients (14.7%) converted into hypopigmentd mycosis fungoides.Limitations: A limitation in our study is that we did not perform clonal T-cell receptor gene rearrangement because of limited resources.Conclusion: Based on our findings we believe that this hypopigmented disorder is a well-defined new variant of the PSEP family that shows, apart from the hypopigmentation, all the features of PSEP, particularly the SPP variant, and accordingly could be referred to as hypopigmented PSEP.

A retrospective analysis of the Dermatology Foundation's Career Development Award Program - Corrected Proof

Chris Boris, Stuart R. Lessin, Bruce U. Wintroub, Kim B. Yancey — 2012-03-29

Background: To provide research support that develops and retains leaders, educators, and investigators in dermatology and cutaneous biology, the Dermatology Foundation (DF) has designed and implemented a comprehensive Career Development Award (CDA) Program.Objective: To assess the impact of the DF's 3-year CDA, a comprehensive survey of recipients who received this mechanism of support between 1990 and 2007 was performed.Methods: Of 196 individuals receiving a DF CDA, 181 were identified and asked to complete a comprehensive questionnaire concerning their career status, employment history, professional rank, and record of independent research funding (private foundation, federal, other). A personal assessment of the impact of this funding on these individuals' career trajectory was also requested.Results: Eighty percent of 181 CDA recipients identified currently hold full- or part-time positions in academic medicine. The faculty rank of 112 survey respondents included 46 assistant professors (41%), 41 associate professors (37%), 18 professors (16%), and 7 division or departmental chairs (6%). Of respondents, 84% reported that they have received subsequent independent research funding; 95 of these individuals (86%) have received funding from a federal agency (235 federal grants awarded to date with funding >$318M).Limitations: The study was retrospective and self-reported; some awardees did not respond to the survey.Conclusions: The DF's CDA Program has succeeded in supporting the early career development of talented investigators, educators, and leaders; fostered the promotion and retention of these individuals in academic medicine; and nucleated numerous investigative careers that have successfully acquired independent research funding.

Necrotizing Sweet syndrome: A new variant of neutrophilic dermatosis mimicking necrotizing fasciitis - Corrected Proof

2012-03-27

Background: We report a series of patients initially given the diagnosis of necrotizing fasciitis whose course progressed despite surgical debridement, antibiotic therapy, or both, but who responded rapidly to systemic corticosteroids.Objective: We sought to evaluate the clinical data, histopathologic and microbiology information, and treatment course of this unusual entity.Methods: This was a descriptive study/case series.Results: Three immunocompromised patients who presented with signs and symptoms of necrotizing fasciitis were included. They appeared septic, failed multiple courses of antibiotics, demonstrated pathergy, and two of them underwent extensive surgical debridement. None of the cases yielded a microbial source. Dermatologic consultation and histopathology confirmed deep Sweet syndrome in all cases, with marked necrosis of the soft tissue–including myonecrosis–in the two patients with debridement. All patients responded rapidly to high-dose systemic corticosteroids.Limitations: To our knowledge, this is the first report of this unusual presentation; there are a limited number of cases.Conclusion: We propose that these cases represent a new variant of neutrophilic dermatosis: “necrotizing Sweet syndrome,” an acute necrotizing neutrophilic dermatosis. This subtype is also characterized by the rapid onset of progressive erythematous, warm, edematous cutaneous lesions with deep-tissue neutrophilic infiltration and soft-tissue necrosis, in the absence of infectious cause. Awareness of this entity and early dermatologic consultation is critical as debridement results in expansion of the process, resulting in additional and aggressive resection–a vicious cycle with significant possible morbidity.

Sun damage in ultraviolet photographs correlates with phenotypic melanoma risk factors in 12-year-old children - Corrected Proof

2012-03-12

Background: Ultraviolet (UV) photography has been used to motivate sun safety in behavioral interventions. The relationship between sun damage shown in UV photographs and melanoma risk has not been systematically investigated.Objective: To examine the relationship between severity of sun damage in UV photographs and phenotypic melanoma risk factors in children.Methods: UV, standard visible and cross-polarized photographs were recorded for 585 children. Computer software quantified sun damage. Full-body nevus counts, skin color by colorimetry, facial freckling, hair and eye color were collected in skin examinations. Demographic data were collected in telephone interviews of parents.Results: Among 12-year-old children, sun damage shown in UV photographs correlated with phenotypic melanoma risk factors. Sun damage was greatest for children who were non-Hispanic white and those who had red hair, blue eyes, increased facial freckling, light skin and greater number of nevi (all P values < .001). Results were similar for standard visible and cross-polarized photographs. Freckling was the strongest predictor of sun damage in visible and UV photographs. All other phenotypic melanoma risk factors were also predictors for the UV photographs.Limitations: Differences in software algorithms used to score the photographs could produce different results.Conclusion: UV photographs portray more sun damage in children with higher risk for melanoma based on phenotype. Therefore sun protection interventions targeting those with greater sun damage on UV photographs will target those at higher melanoma risk. This study establishes reference ranges dermatologists can use to assess sun damage in their pediatric patients.

The role of antioxidants in photoprotection: A critical review - Corrected Proof

Lucy Chen, Judy Y. Hu, Steven Q. Wang — 2012-03-12

Free radicals have long been studied as a contributor to aging and disease processes. Endogenous production of radicals from cellular metabolism and exogenous sources from ultraviolet radiation and pollution can damage the skin on the cellular and tissue levels. Although the body possesses an elegant defense system to prevent radical damage, this innate system can be overwhelmed and lead to a state of oxidative stress or immunosuppression, and can even trigger carcinogenesis. Topical supplementation of antioxidants can provide additional protection to neutralize reactive oxygen species from both endogenous and exogenous sources. This review will discuss our current understanding of the mechanisms of free radical damage and evaluate the potential benefit of topical antioxidants in sunscreens and skin care products.

Hair and scalp dermatoscopy - Corrected Proof

Mariya Miteva, Antonella Tosti — 2012-03-12

Dermatoscopy is a noninvasive diagnostic tool that allows the recognition of morphologic structures not visible by the naked eye. Trichoscopy (scalp dermatoscopy and videodermatoscopy) is useful for the diagnosis and follow-up of hair and scalp disorders. However, it is not widely used in the management of hair disorders. This review provides updated information from the literature and our experience on the dermoscopic features of the most common hair and scalp disorders. This will enable dermatologists to make fast diagnoses of tinea capitis and alopecia areata, distinguish early androgenetic alopecia from telogen effluvium, and differentiate scarring from nonscarring alopecia.

Ultraviolet photography as a skin cancer risk assessment and intervention tool - Corrected Proof

Robin L. Hornung, Victor J. Strecher — 2012-03-12

In the Gamble et al study in this issue, the authors conducted a comprehensive study assessing the relationship between severity of sun damage in ultraviolet (UV) photographs with phenotypic melanoma risk factors in a large population of 12-year-old children. They found that indeed the severity of sun damage in UV photography correlates closely with phenotypic melanoma risk factors such as freckling and skin color, yet standard visible light photography did not.

A review of Parry-Romberg syndrome - Corrected Proof

Jessica El-Kehdy, Ossama Abbas, Nelly Rubeiz — 2012-03-09

Parry-Romberg syndrome, also known as progressive hemifacial atrophy, is a rare disorder characterized by unilateral facial atrophy affecting the skin, subcutaneous tissue, muscles, and sometimes extending to the osteocartilaginous structures. It has been associated with various systemic manifestations, particularly neurologic, ophthalmologic and maxillofacial. In this article, we review Parry-Romberg syndrome with its associated findings (neurologic, ophthalmologic, cardiac, rheumatologic, endocrinologic, infectious, orthodontic and maxillofacial, and autoimmune), underlying cause, differential diagnoses (en coup de sabre, scleroderma, and Rasmussen encephalitis), and therapeutic options.

Oral glycopyrrolate as second-line treatment for primary pediatric hyperhidrosis - Corrected Proof

2012-03-09

Background: Primary focal hyperhidrosis not uncommonly begins during the first two decades of life, and can have a profound effect on quality of life. Few treatment options have been studied in children.Objective: We sought to evaluate the response to oral glycopyrrolate in pediatric patients.Methods: Records of pediatric patients with hyperhidrosis seen at a pediatric hospital in a 10-year period were reviewed retrospectively and, if possible, parents and patients were also interviewed. The efficacy and adverse effects of oral glycopyrrolate were assessed.Results: In all, 31 children took at least one dose of oral glycopyrrolate. All had daily hyperhidrosis that affected their quality of life and were resistant or intolerant of aluminum salts. The mean age of hyperhidrosis onset was 10.3 years, and mean age of initiation of glycopyrrolate was 14.8 years. At a mean dosage of 2 mg daily, 90% of patients experienced improvement, which was major in 71% of responders. Improvement occurred within hours of administration and disappeared within a day of discontinuation. Duration of treatment averaged 2.1 years (range to 10 years). Side effects were noted by 29% of children, most commonly dry mouth (26%) and eyes (10%), and were dose-related. One patient developed blurred vision, which resolved with dosing below 5 mg/d; one patient experienced palpitations and discontinued the medication.Limitations: This was a retrospective analysis of a limited number of pediatric patients.Conclusion: Oral glycopyrrolate is a cost-effective, painless second-line therapy for children and adolescents with primary focal hyperhidrosis that impacts their quality of life.

The natural history of halo nevi: A retrospective case series - Corrected Proof

Mouhammad Aouthmany, Mara Weinstein, Matthew J. Zirwas, Robert T. Brodell — 2012-03-05

Background: The time period between onset of depigmentation around the halo nevus (HN) to complete resolution of the nevus and halo has not been well studied.Objective: We sought to better understand the natural history of the HN.Methods: A retrospective chart review of patients with a clinical diagnosis of HN selected from a private practice database (1994-2010) was performed. In all, 52 patients with 80 HN were identified. The current stage of the HN was determined by a follow-up questionnaire and physical examination of 36 patients with 56 HN.Results: Seven HN were excised. Of the remaining 49 HN, 51% (25) demonstrated no change in the halo or nevus after an average of 4.2 years; 14.3% (7) demonstrated partial nevus regression with persistence of the halo after an average of 6.7 years; 4.1% (2) demonstrated complete involution of the nevus with persistent halo depigmentation after an average of 7.7 years; 8.2% (4) demonstrated complete nevus involution with some repigmentation of the halo after an average of 11.8 years; 22.4% (11) demonstrated complete resolution of the nevus with complete repigmentation of the halo after an average of 7.8 years.Limitation: Some subjects were lost to follow-up. The time of initial HN onset was dependent on patient recall.Conclusion: These results demonstrate that HN typically persist for a decade or longer. A subgroup may progress through stages of involution with a return to normal-appearing skin, but even these lesions persisted for an average of 7.8 years. Education about the prolonged natural history of HN may reassure patients and avoid unnecessary excision.

A consensus approach to wound care in epidermolysis bullosa - Corrected Proof

2012-03-05

Background: Wound care is the cornerstone of treatment for patients with epidermolysis bullosa (EB); however, there are currently no guidelines to help practitioners care for these patients.Objectives: The objective of this study was to generate a list of recommendations that will enable practitioners to better care for patients with EB.Methods: An expert panel generated a list of recommendations based on the best evidence available. The recommendations were translated into a survey, and sent to other EB experts to generate consensus using an online-based modified Delphi method. The list was refined and grouped into themes and specific recommendations.Results: There were 15 respondents (45% response rate), with significant experience in the EB field (>10 years [67%]). Respondents included physicians (67%), nurses (17%), and allied health professionals (7%). There was more than 85% agreement for all the proposed items. These were further refined and grouped into 5 main themes (assessment and management of factors that impair healing, patient-centered concerns, local wound care, development of an individualized care plan, and organizational support) and 17 specific recommendations.Limitations: There is a paucity of scientific evidence with most recommendations based on expert opinion.Conclusions: These recommendations will provide practitioners with a framework for caring for these patients. Additional scientific research including effectiveness studies for everyday practice and expert consensus, may further refine these recommendations.

Multidisciplinary approach to the management of dermatofibrosarcoma protuberans - Corrected Proof

2012-03-05

Background: Dermatofibrosarcoma protuberans (DFSP) is the most common cutaneous sarcoma. Tentacle-like extensions of neoplastic cells create a high incidence of local recurrence and pose challenges to resection and reconstruction.Objective: Here we present a multidisciplinary approach to the management of DFSP incorporating the expertise of a Mohs micrographic surgeon, surgical oncologist, dermatopathologist, and plastic surgeon.Methods: This was a single-institution, retrospective review of a prospectively maintained database of 19 consecutive patients who underwent resection and reconstruction of a DFSP from 1998 to 2010. All patients underwent Mohs micrographic surgery for mapping of peripheral margins (stage I excision), followed by wide local excision for delineation of the deep margin (stage II excision). Procedures were performed in consultation with a dermatopathologist who confirmed tumor-free margins, and a plastic surgeon who performed immediate reconstruction after the wide local excision (stage II reconstruction).Results: Nineteen patients were included in this study. The average number of Mohs stages required for clearance of peripheral margins was 2.7 ± 0.7. The mean time between stage I and II procedures was 16 ± 11 days. The average defect size after the stage II operation was 87.3 cm2 (range, 9-300 cm2). There were no cases of tumor recurrence. Mean follow-up time was 17 months (range, 1-53 months).Limitations: This is a retrospective review of a single-institution experience.Conclusion: A multidisciplinary approach to the management of DFSP optimizes both oncologic and reconstructive outcomes, minimizing the risk for local recurrence and limiting the functional and cosmetic morbidity associated with surgical resection.

Deficiency of serum concentration of 25-hydroxyvitamin D in psoriatic patients: A case-control study - Corrected Proof

2012-03-05

Background: Some autoimmune conditions have been associated with reduced vitamin D levels, including systemic lupus erythematosus, rheumatoid arthritis, diabetes mellitus, and multiple sclerosis.Objective: The main objective of this study was to analyze the 25-hydroxyvitamin D (OHD) status of patients with psoriasis in comparison with control subjects without this disease.Methods: This case-control study included 86 patients (43 with psoriasis and 43 age- and sex-matched control subjects) from the outpatient clinic of our hospital dermatology department in Granada, Spain. All patients and control subjects were studied during one 4-week period to avoid seasonal variations in vitamin D levels.Results: Serum 25-OHD levels were significantly lower in psoriatic patients than in control subjects even after adjusting for confounding factors in a multivariate analysis (odds ratio 2.89, 95% confidence interval 1.02-7.64, P < .03 for vitamin D insufficiency). Low 25-OHD levels were negatively associated with C-reactive protein (inflammatory activation marker) and body mass index in multiple linear regression analysis. Psoriatic patients with body mass index greater than or equal to 27 kg/m2 had a higher risk of 25-OHD insufficiency (sensitivity of 82.3% and specificity of 51.7%).Limitations: Further studies with larger numbers of patients are required to analyze the pathogenic mechanisms underlying the relationship between 25-OHD deficiency and psoriasis.Conclusions: The 25-OHD values are significantly lower in psoriatic patients than in control subjects. Low 25-OHD levels are negatively associated with C-reactive protein, an inflammatory activation marker, and with obesity. Psoriatic patients with a body mass index of 27 or more are likely to have vitamin D insufficiency.

Multicenter clinical trial of a home-use nonablative fractional laser device for wrinkle reduction - Corrected Proof

James Leyden, Thomas J. Stephens, James H. Herndon — 2012-03-02

Background: Until now, nonablative fractional treatments could only be delivered in an office setting by trained professionals.Objective: The goal of this work was to perform clinical testing of a nonablative fractional laser device designed for home-use.Methods: This multicenter trial consisted of two clinical studies with slightly varying treatment protocols in which subjects performed at-home treatments of periorbital wrinkles using a handheld nonablative fractional laser. Both studies included an active treatment phase (daily treatments) and a maintenance phase (twice-weekly treatments). In all, 36 subjects were followed up for as long as 5 months after completion of the maintenance phase and 90 subjects were followed up until the completion of the maintenance phase. Evaluations included in-person investigator assessment, independent blinded review of high-resolution images using the Fitzpatrick Wrinkle Scale, and subject self-assessment.Results: All 124 subjects who completed the study were able to use the device following written instructions for use. Treatments were well tolerated with good protocol compliance. Independent blinded evaluations by a panel of physicians showed Fitzpatrick Wrinkle Scale score improvement by one or more grades in 90% of subjects at the completion of the active phase and in 79% of subjects at the completion of the maintenance phase. The most prevalent side effect was transient posttreatment erythema.Limitations: Lack of a control group and single-blinded study groups were limitations.Conclusion: Safety testing with self-applications by users demonstrated the utility of the device for home use. Independent blinded review of clinical images confirmed the device’s proficiency for improving periorbital wrinkles.

Family history, body mass index, selected dietary factors, menstrual history, and risk of moderate to severe acne in adolescents and young adults - Corrected Proof

2012-03-02

Background: Genetic and environmental components may contribute to acne causation.Objective: We sought to assess the impact of family history, personal habits, dietary factors, and menstrual history on a new diagnosis of moderate to severe acne.Methods: We conducted a case-control study in dermatologic outpatient clinics in Italy. Cases (205) were consecutive those receiving a new diagnosis of moderate to severe acne. Control subjects (358) were people with no or mild acne, coming for a dermatologic consultation other than for acne.Results: Moderate to severe acne was strongly associated with a family history of acne in first-degree relatives (odds ratio 3.41, 95% confidence interval 2.31-5.05). The risk was reduced in people with lower body mass index with a more pronounced effect in male compared with female individuals. No association with smoking emerged. The risk increased with increased milk consumption (odds ratio 1.78, 95% confidence interval 1.22-2.59) in those consuming more than 3 portions per week. The association was more marked for skim than for whole milk. Consumption of fish was associated with a protective effect (odds ratio 0.68, 95% confidence interval 0.47-0.99). No association emerged between menstrual variables and acne risk.Limitations: Some degree of overmatching may arise from choosing dermatologic control subjects and from inclusion of mild acne in the control group.Conclusions: Family history, body mass index, and diet may influence the risk of moderate to severe acne. The influence of environmental and dietetic factors in acne should be further explored.

Morphea in adults and children cohort II: Patients with morphea experience delay in diagnosis and large variation in treatment - Corrected Proof

Weilan Johnson, Heidi Jacobe — 2012-03-01

Background: Little is known about the diagnosis, evaluation, and therapy of morphea (localized scleroderma) in the United States. Delays in diagnosis and initiation of appropriate therapy, if present, may negatively affect patient care. Further, this gap in knowledge hinders planning for clinical trials and therapeutic guidelines. The morphea in adults and children (MAC) cohort is designed to address this gap.Objective: We sought to determine the duration between morphea onset and diagnosis, specialty of the diagnosing provider, and initial evaluation and therapy in the MAC cohort.Methods: This was a cross-sectional survey of the inception cohort of the MAC study.Results: In all, 63% (n = 141 of 224) of patients were given the diagnosis more than 6 months after onset. Dermatologists diagnosed and treated the majority of patients (83.5%, n = 187). Rheumatologists diagnosed and treated the more severe forms of morphea (linear and generalized). The most commonly prescribed therapy was topical corticosteroids (63%). Dermatologists predominantly prescribed topical treatments or phototherapy (P < .0001, P = .0018, respectively), even to patients with linear and generalized morphea. In contrast, rheumatologists predominantly prescribed systemic immunosuppressives and physical therapy (P < .0001, P = .0021, respectively).Limitations: Referral bias and recall bias may affect patterns of evaluation/therapy and ascertainment of disease duration before diagnosis.Conclusions: Patients with morphea experience delay in diagnosis, which likely impacts outcome. Therapeutic decision making is largely determined by the specialty of the provider rather than disease characteristics and many treatments with little or no proven efficacy are used, whereas others with proven efficacy are underused. This underscores the need for a collaborative, multispecialty approach in designing therapeutic trials and guidelines.

Influence of sporting activity and smoking on peripheral lymph nodes in patients with melanoma analyzed by high-resolution ultrasound - Corrected Proof

2012-02-29

Background: The sonographic examination of peripheral lymph nodes (LNs) plays an important role in the preoperative treatment and in the follow-up of patients with melanoma.Objective: A prospective study including 200 consecutive patients with a history of invasive cutaneous melanoma was performed at the Department of Dermatology and Allergy, University of Bonn, Germany, to examine the influence of sporting activity, physical workload, interferon alfa therapy, smoking habits, and infections of the upper respiratory tract on morphology and number of LNs analyzed by high-resolution ultrasound.Methods: Between May 2010 and June 2011, 106 men and 94 women (mean age 51.1 ± 12.8 years) were included in this study. During their follow-up visits for cutaneous melanoma, high-resolution ultrasound examination of cervical, axillary, and inguinal LN regions were performed. LN diameters and volumes were measured and correlated with the above given factors.Results: Sports-active patients had more LNs in inguinal regions, a higher volume and a larger LN diameter, and a higher maximum width of the hypoechoic LN margin in comparison with the nonactive patients. Patients with a hard physical workload in their occupations had a significantly higher volume of the biggest LN. Compared with nonsmoking patients smokers presented higher values in the total quantity of the LNs, in the greatest volume of LN, and in the greatest diameter of LN in the cervical regions. The other factors had no significant influence on the LN parameters.Limitations: Our study population was too small to comment on influencing factors in more detail especially the influences of different sporting activities or smoking habits.Conclusion: Sporting activity, physical workload, and smoking habits as associated cofactors influencing sonomorphologic aspects in patients with cutaneous melanoma should always be considered.

Development and validation of a vitiligo-specific quality-of-life instrument (VitiQoL) - Corrected Proof

2012-02-27

Background: Vitiligo significantly affects a person’s health-related quality of life (HRQL). Although a small number of generic, and disease-specific, dermatologic HRQL measures exist, currently no vitiligo-specific instrument is available to capture disease-targeted concerns and issues.Objective: We sought to develop and validate a vitiligo-specific self-report instrument for HRQL.Methods: A pool of vitiligo-specific items was created based on in-depth interviews with patients with vitiligo (n = 16) and their responses to items in several previously validated HRQL measures. These items comprising our new instrument, VitiQoL, along with Skindex-16 and Dermatology Life Quality Index were administered to patients with vitiligo (n = 90) at two academic centers. This new instrument was validated using psychometric analysis.Results: The VitiQoL items showed high internal consistency (Cronbach alpha = 0.935). Exploratory factor analysis demonstrated 3 factors: participation limitation, stigma, and behavior. Concurrent validity was evidenced by large correlations between self-reported severity and VitiQoL scores (r = 0.51). Known groups validity was demonstrated for the VitiQoL behavior subscale between individuals with exposed and unexposed patches (P = .01). Convergent validity was shown by strong correlations between VitiQoL and outside dermatology scales measuring similar constructs (Skindex-16, r = 0.82; Dermatology Life Quality Index, r = 0.83).Limitations: Potential selection bias was a limitation as most patients were recruited from academic centers. Reliability of the instrument was tested only with internal consistency and not reproducibility. Responsiveness of the instrument was not tested because of the prolonged time course necessary to observe clinically significant change in vitiligo.Conclusion: VitiQoL is a reliable and valid HRQL instrument.

Sensitive and specific assays for routine serological diagnosis of epidermolysis bullosa acquisita - Corrected Proof

2012-02-20

Background: Epidermolysis bullosa acquisita (EBA) is a severe autoimmune subepidermal blistering disease characterized by autoantibodies against the N-terminal collagenous domain (NC1) of type VII collagen (Col VII).Objective: Development of reliable assays for the detection of anti-Col VII-NC1 antibodies.Methods: NC1 was expressed in human HEK293 cells and used as target antigen in an enzyme-linked immunosorbent assay (ELISA) and in an immunofluorescence assay (IFA). These two assays were probed in a large cohort of patients with EBA (n = 73), bullous pemphigoid (BP, n = 72), anti-p200 pemphigoid (n = 24), anti-laminin 332 mucous membrane pemphigoid (MMP, n = 15), pemphigus vulgaris (PV, n = 24), and healthy control subjects (n = 254).Results: The cut-off for the ELISA was optimized for accuracy by receiver-operating characteristics (area under the curve [AUC] = 0.9952). IgG reactivity against NC1 was detected in 69 of 73 EBA (94.5%) and 5 control sera (2 healthy controls and 3 BP patients), resulting in a specificity of 98.7%. The IFA showed a sensitivity of 91.8% and specificity of 99.8%. Reproducibility of the ELISA was demonstrated by an intra-class correlation coefficient of 0.97. IgG subclass analyses by ELISA revealed IgG1, IgG2, IgG3, and IgG4 anti-NC1 reactivity in 83.6%, 85.3%, 37.7%, and 83.6% of EBA sera, respectively.Limitations: The novel assays were not evaluated prospectively and their use in monitoring serum levels during the disease course was not tested.Conclusion: The two assays are highly specific and sensitive to diagnose EBA. Their diagnostic competence was demonstrated in a large cohort of well-characterized EBA sera.

A static-image telepathology system for dermatopathology consultation in East Africa: The Massachusetts General Hospital Experience - Corrected Proof

2012-02-20

Background: The histologic diagnosis of skin lesions in the developing world is complicated by the shortage of pathologists with subspecialty training in dermatopathology, limited access to ancillary diagnostic testing, and costly referrals for expert glass slide consultation in challenging cases.Objective: In this study we evaluate the feasibility of a static-image telepathology platform in Africa for performing accurate dermatopathology consultations.Methods: A static-image telepathology platform using the iPath server was utilized by referring pathologists in 4 African hospitals. Diagnostic interpretations were provided by Massachusetts General Hospital dermatopathologists at no cost. The diagnostic accuracy and interobserver correlation was evaluated.Results: The static histopathologic images were diagnostic in 22 of 29 (76%) cases. Diagnostic accuracy between static image and glass slide diagnosis in 22 cases was 91%, ranging from 86% to 95% according to years of dermatopathology subspecialty expertise. Comparison with the glass slides showed that the telepathology diagnosis was limited by inappropriate field selection in only one case. Interobserver concordance between two pathologists was high (K = 0.86) suggesting that this platform is easy to use with minimal training of both referring and consulting pathologists.Limitations: Concordance between conventional microscopy and static image telepathology was performed in 22 of 29 cases for which glass slides were received. Interobserver concordance was performed for two pathologists.Conclusion: Static-image telepathology is a feasible means of rendering diagnoses on dermatopathology cases and is a cost-effective technology for obtaining much-needed second opinions in resource-poor settings.

Investigation into optimal treatment intervals of facial port-wine stains using the pulsed dye laser - Corrected Proof

2012-02-20

Background: Port-wine stains (PWS) affect 0.3% to 0.5% of newborns and pulsed dye laser (PDL) remains the treatment of choice. Optimal treatment intervals have not been established.Objective: We sought to validate the optimal treatment intervals for the management of facial PWS with PDL.Methods: In all, 24 infants with facial PWS who received at least 5 treatments with the PDL at 2-, 3-, and 4-week intervals at a private laser and skin surgery center from 2009 to 2010 were identified by a retrospective chart review. Safety and efficacy were compared by blinded investigators.Results: Side effects were equivalent in all interval groups and included only expected short-term erythema, edema, purpura, and mild postinflammatory hyperpigmentation. No patient developed hypopigmentation, scarring, or infection. All interval groups showed 50% to 100% clearance of their PWS after 5 treatments. Complete or near-complete clearance was seen in 6 of 8 (75%) and 7 of 8 (87.5%) patients in the 2- and 3-week interval groups, respectively, as compared with 3 of 8 (37.5%) patients in the 4-week interval group.Limitations: This was a retrospective chart review from a single institution. Long-term side effects and recurrence rates were not assessed.Conclusion: We conclude that PDL treatments at 2-, 3-, and 4-week intervals are effective for the management of facial PWS in infants with minimal short-term side effects. Shorter treatment intervals may allow for relatively more rapid and more effective treatment.

Skin cancer after pancreas transplantation - Corrected Proof

2012-02-17

Background: Skin cancer in patients who have undergone pancreas transplantation (PT) has not been extensively characterized.Objective: We sought to describe the incidence, tumor burden, and risk factors for skin cancer in PT recipients at Mayo Clinic from 1998 through 2006.Methods: A retrospective study was performed by analyzing outcomes among a cohort of pancreas allograft recipients at Mayo Clinic between 1998 and 2006.Results: Among 216 allogeneic PT recipients at 2, 5, and 10 years posttransplantation, the cumulative incidence of any skin cancer was 4.7%, 12.7%, and 19.6%; the cumulative incidence of squamous cell carcinoma was 2.8%, 10.3%, and 16.7%; and the cumulative incidence of basal cell carcinoma was 2.4%, 7.8%, and 17.4%, respectively. The cumulative incidence of a second squamous cell carcinoma developing was 56% at 2 years; the cumulative incidence of a second basal cell carcinoma developing was 36% at 2 years. Of the risk factors examined, only age and having a skin cancer before transplantation were predictive of skin cancer development.Limitations: This was a retrospective study. Results from a large tertiary center may not be generalizable.Conclusions: Nonmelanoma skin cancers commonly occur in recipients of PT, and those patients who have a history of nonmelanoma skin cancer have a very high likelihood of further skin cancer development.

Diffuse neonatal hemangiomatosis: An evidence-based review of case reports in the literature - Corrected Proof

2012-02-17

Background: The term “diffuse neonatal hemangiomatosis” has been used historically to describe multifocal vascular lesions affecting the skin and viscera in infants.Objective: We hypothesized that many cases reported as diffuse neonatal hemangiomatosis did not have infantile hemangiomas (IH), but represented more recently described neonatal vascular diseases.Methods: A literature search was performed using PubMed database (1950-2009) with the terms “neonatal hemangiomatosis,” “benign hemangiomatosis,” and “diffuse hemangiomatosis.” A total of 180 articles were identified. Exclusion criteria included disease onset later than 3 years of age and absence of multifocal skin involvement. In all, 73 cases were selected and categorized into 3 groups: IH/probable IH; multifocal lymphangioendotheliomatosis with thrombocytopenia (MLT)/probable MLT; and multifocal vascular lesions, not otherwise specified.Results: Of the 73 cases, 43 had IH/probable IH, 17 had MLT/probable MLT, and 13 had multifocal vascular lesions, not otherwise specified. The clinical outcomes of these groups differed in that two of 43 (5%) patients with IH died whereas 11 of 17 (65%) patients with MLT died (odds ratio 37.6, confidence interval 5.6-387.6, P value < .0001).Limitations: This was a literature-based meta-analysis, which inherently has limitations of incomplete and inconsistently presented information.Conclusions: Many cases reported in the literature as diffuse neonatal hemangiomatosis represent newly described multifocal vascular anomalies such as MLT, which has a strikingly higher mortality than IH. We propose the term “multifocal infantile hemangioma–with or without extracutaneous disease” instead of “diffuse neonatal hemangiomatosis” for multiple cutaneous IH. Accurate diagnosis of multifocal neonatal vascular lesions is imperative to facilitate appropriate evaluation, treatment, and prognosis.