Journal of the American Academy of Dermatology - Articles in Press

Current leadership training in dermatology residency programs: A survey - Corrected Proof

David S. Baird, Magdalena Soldanska, Bryan Anderson, Jeffrey J. Miller — 2012-01-30

Background: Residents and physicians frequently find themselves in leadership roles. Current residency curricula focus on the development of clinical knowledge and technical skills. A previous survey of Penn State Dermatology graduates demonstrated the perceived need and benefit of a formalized leadership curriculum in this selected group.Objectives: We sought to identify and measure the perceived need and benefit of formalized leadership training and investigate opinions regarding leadership theory from the perspective of dermatology residency program directors and chief residents nationally.Methods: A survey containing 26 questions related to leadership theory and training were mailed to all US dermatology residency programs.Results: In all, 91% of program directors and chief residents agreed that leadership skills could be taught through observation and training. A total of 78% of respondents agreed that leadership training is important during dermatology residency training. In all, 66% agreed that a formalized leadership curriculum would help residents become better resident supervisors and physicians. Only 13% reported having a formalized leadership curriculum. Participants most frequently reported learning leadership through observation and modeled behavior. A total of 15% of chief residents believed their faculty did not effectively model leadership, whereas only 2% of the program directors believed the same (P = .01).Limitations: In all, 62% (68/109) of programs surveyed returned at least one response from the program director or chief resident. A total of 39% (42/109) had responses from both the program director and the chief resident. Because of the voluntary nature of the survey, response bias could not be excluded.Conclusion: Most program directors and chief residents believe leadership skills can be cultivated through observation and training. Leadership curriculum is not part of most residency programs.

The histopathological characteristics of male melasma: Comparison with female melasma and lentigo - Corrected Proof

Yong Hyun Jang, Ji Hyun Sim, Hee Young Kang, You Chan Kim, Eun-So Lee — 2012-01-30

Background: Knowledge of the histopathology of melasma is a prerequisite for understanding its pathogenesis. However, the histopathological characteristics of male melasma are not well characterized.Objective: We sought to investigate the histopathological characteristics of melasma in men compared with those of women with melasma and solar lentigo.Methods: Biopsy specimens were obtained from both the lesional skin and the adjacent nonlesional skin in 8 men with melasma, 10 women with melasma, and 5 men and women each with solar lentigo. The samples were stained using Fontana-Masson and Verhoeff-van Gieson. Immunohistochemistry for melanocytes, the estrogen receptor, progesterone receptor, factor VIIIa–related antigen, stem cell factor, and c-kit was performed.Results: Increased vascularity was found in the lesion of male melasma. The lesion to nonlesion ratio of the vessel area was increased in male melasma compared with lentigo groups. In the lesion of male melasma, there was a significant increase of stem cell factor and c-kit expression. In addition, the lesion to nonlesion ratio of stem cell factor was increased in male melasma compared with female melasma and lentigo groups. The lesion to nonlesion ratio of c-kit was also increased in male melasma compared with lentigo groups.Limitations: This study did not include clinical data regarding social habits and was not confirmed by other molecular techniques.Conclusion: The results suggest that chronic ultraviolet radiation associated with signaling of paracrine cytokines plays an important role in the mechanism associated with hyperpigmentation in male melasma.

Aberrant expression of HMB-45 in traumatized melanocytic nevi - Corrected Proof

Todd M. Leleux, Victor G. Prieto, A. Hafeez Diwan — 2012-01-30

Background: Assessment of histologic and immunohistochemical maturation (with HMB-45 and anti-Ki-67) may be helpful in differentiating benign melanocytic nevi (BMN) from malignant melanoma. Recently, we reported loss of maturation and aberrant immunohistochemical findings in melanocytic nevi after liquid nitrogen cryotherapy (Adeniran et al, J Am Acad Dermatol 2009;61:341-5). Herein we report a similar phenomenon identified in traumatized melanocytic nevi (TMN).Objective: We sought to evaluate the histologic and immunohistochemical findings in early and late stages of traumatized nevi.Methods: Twenty-four cases of TMN were retrieved from the pathology archives. These were then assessed by two pathologists (T.L. and A.H.D.) using HMB-45 and MIB-1 (for Ki-67) antibodies.Results: TMN showed some of the following findings: epidermal changes (parakeratosis, ulceration, serum crust, flattening of the epidermis) and dermal changes including fibrosis and the presence of melanophages. In some cases, there was architectural disorder of the overlying melanocytes, with crowding in the basal layer, but without significant pagetoid spread. Occasionally, the dermal scar contained larger, more epithelioid-appearing melanocytes than those beneath the scar. Fifty-four percent of TMN lacked obvious immunohistochemical maturation with HMB-45, since nevus cells within the scar or directly beneath it were strongly labeled. None of the TMN showed appreciable labeling for Ki-67.Limitations: The exact clinical duration between trauma and biopsy could not be determined.Conclusion: Loss of maturation with HMB-45 in TMN can be a diagnostic pitfall in challenging cases. Concurrent evaluation of MIB-1 expression, along with the characteristic histologic features of trauma, should allow the correct diagnosis to be reached.

Toxic epidermal necrolysis: Five years of treatment experience from a burn unit - Corrected Proof

Bahar F. Firoz, Jeffrey Scott Henning, Lee Ann Zarzabal, Brad H. Pollock — 2012-01-30

Background: Toxic epidermal necrolysis (TEN) is a serious drug eruption that results in death in approximately 25% to 50% of patients. There is controversy over whether SCORTEN accurately predicts mortality or if treatment interventions such as intravenous immunoglobulin (IVIg) can alter mortality.Objectives: We sought to determine whether SCORTEN accurately predicts mortality in this cohort, whether IVIg improved survival, and which drugs and medical comorbidities impacted mortality.Methods: We summarize our experience prospectively over 5 years and 82 patients. Patients either received supportive care, intravenous immunoglobulin, or cyclosporine as treatment. All patients had a SCORTEN on admission, an offending drug on record, and a list of medical comorbidities.Results: Of the 82 patients, 29% died from TEN. SCORTEN accurately predicted mortality in this cohort with an area under the curve (AUC) of 0.83 in a receiver operator curve (ROC) analysis. A Kaplan-Meier curve did not show improved mortality if patients received IVIg versus supportive care (P = .9). Medications most often responsible for TEN were trimethoprim/sulfamethoxazole, followed by anticonvulsants, nonsteroidal anti-inflammatories, and allopurinol.Limitations: This prospective cohort study design is not as ideal as patients presenting for a randomized controlled trial.Conclusions: SCORTEN was an accurate predictor of mortality in this cohort. Age older than 40 years, the presence of metabolic syndrome and/or gout, higher body surface area involvement, higher SCORTEN, and higher number of medical comorbidities statistically significantly increased risk of death. IVIg did not significantly alter mortality. Although the highest number of cases was due to trimethoprim/sulfamethoxazole, the greatest proportion of deaths was due to allopurinol.

Ultrasound in dermatology: Principles and applications - Corrected Proof

Rebecca Kleinerman, Talley B. Whang, Robert L. Bard, Ellen S. Marmur — 2012-01-30

Ultrasonic imaging has been used in the field of dermatology for nearly 30 years. In this review, we seek to explain the basic principles of ultrasound as they relate to the skin. Based on differences in keratin, collagen, and water content, ultrasonic waves are reflected back to a transducer and translated into a gray-scale image for interpretation. The technicalities of the process and its variations (power, continuous wave Doppler ultrasound, ultrasound elastography) are briefly reviewed, and we further highlight many of the applications for ultrasound in the treatment and diagnosis of dermatologic conditions, including melanoma and nonmelanoma skin cancer, benign tumors, inflammatory diseases, and lipoablation. Each of these entities is uniquely characterized using ultrasonic techniques. Based on published sources, we contend that although ultrasound is still being fine-tuned for application in dermatology and largely remains in experimental phases, it has potential for use in many arenas of our specialty.

Pruritus in cutaneous T-cell lymphoma: A review - Corrected Proof

Kristen Ahern, Elaine S. Gilmore, Brian Poligone — 2012-01-30

Background: Pruritus can be a distressing and even debilitating symptom for patients with cutaneous T-cell lymphoma (CTCL). To date, few studies have evaluated the pathophysiology of this symptom. Because of this, therapy for pruritus in CTCL has mainly relied on those therapies that target and treat the lymphoma. For patients living with CTCL that relapses or becomes refractory to treatment, and who continue to experience severe itch, this lymphoma-targeted treatment may not be enough to combat their pruritus. Therefore, other itch-targeted therapies are needed for use in this disease.Objective: We sought to evaluate the current evidence regarding the mechanism of action and treatments for pruritus associated with CTCL.Methods: An explicit and thorough search was restricted to all peer-reviewed literature available through MEDLINE (1950 to September 2011) and PubMed. Search terms used were “pruritus,” “cutaneous T-cell lymphoma,” “CTCL,” “mycosis fungoides,” “MF,” and “Sézary syndrome.” All studies that involved pruritus in CTCL, mycosis fungoides, or Sézary syndrome were evaluated by all 3 authors.Results: The current literature helps to identify therapies and possible mechanisms for treating patients with CTCL-associated pruritus.Limitation: Most studies were preclinical. Only studies involving mechanisms of action or treatment were included.Conclusion: A guideline is necessary to assist in the treatment of pruritus in CTCL and additional studies are necessary to uncover the exact mechanism or mechanisms of action.

Incidence of spontaneous remission in patients with CD25-positive mycosis fungoides/Sézary syndrome receiving placebo - Corrected Proof

2012-01-30

Background: Spontaneous remission is recognized in mycosis fungoides (MF) and Sézary syndrome (SS).Objective: We analyzed the outcome of 44 patients with previously treated CD25-positive (CD25+), recurrent/persistent MF/SS randomly assigned to receive placebo as part of a phase III trial.Methods: This trial investigated the efficacy and safety of two doses of denileukin diftitox in patients with MF/SS who had received up to 3 prior therapies. The primary end point was overall response rate. Multivariate regression analyses were used to assess the relationship between baseline covariates and clinical outcomes.Results: The overall response rate was 15.9% for placebo recipients (complete response: 2.3%; partial response: 13.6%), reflecting the baseline rate of disease remission that can be expected in a clinical trial. The median progression-free survival (PFS) in the placebo arm was moderately short at 4.4 months compared with the active-agent arm but important to consider in the context of recent single-arm phase II studies of other therapies for MF/SS that report PFS of approximately 6 months. Multivariate analyses identified no significant effects of any baseline factors on either overall response rate or PFS, although there was a trend toward poorer PFS with advanced age. Because sepsis occurred significantly more often in the placebo arm versus the active-treatment arm, the role of antibiotics in causing remission cannot be discounted (6.8% vs 0%; P < .05).Limitations: This study had a relatively small sample size, yielding a wide 95% confidence interval.Conclusion: The results may serve as a useful comparator for other active-treatment studies of MF/SS that lack a placebo-control arm.

The 7th edition AJCC staging system for cutaneous squamous cell carcinoma accurately predicts risk of recurrence for heart and lung transplant recipients - Corrected Proof

2012-01-30

Background: Cutaneous squamous cell carcinoma (cSCC) is the most common malignancy after solid organ transplantation, with an increased risk of recurrence and metastasis over the general population. The newly updated 7th edition American Joint Committee on Cancer (AJCC) staging system for cSCC is based on consensus expert opinion and requires validation in large cohort studies and in specific patient subpopulations.Objective: Our objective was to evaluate the risk of cSCC recurrence in a high-risk population of heart and lung transplant recipients, based on the 7th edition AJCC staging system.Methods: We performed a 10-year retrospective cohort study of all primary cSCC diagnosed in heart and lung transplant recipients at a tertiary care academic dermatology center.Results: The cumulative incidence of local recurrence was 4% for cSCC in situ and 19% for stage I cSCC at 5 years, and 54% for stage II cSCC at 3 years. Stage II tumors had a 10-fold greater risk of recurrence than stage I, and a 43-fold greater risk of recurrence than in situ tumors.Limitations: This study is limited to a specific patient subgroup at a tertiary care center, and may not be generalizable to all populations.Conclusions: Heart and lung transplant recipients are at high risk for local recurrence of cSCC. These data substantiate the prognostic accuracy of the newly updated 7th edition AJCC staging system for stage 0, I, and II cSCC in this population and demonstrate the aggressive behavior of this cancer in immunosuppressed patients.

Recognition of melanoma: A dermatologic clinical competency in medical student education - Corrected Proof

2012-01-27

Background: Non-dermatologist physicians are well positioned for opportunistic melanoma detection; however, education in the skin cancer examination is limited during medical school and traditionally lecture-based. Simulating melanoma cases provides a means to demonstrate whether proficiency in knowledge and recognition of melanoma images translates into improved clinical skill.Objective: To evaluate medical student recognition and appropriate response to a prosthetic melanoma placed on a standardized patient (SP) during a simulated clinical encounter.Methods: In this pilot study, prosthetic mimics of melanoma were placed on the backs of SPs unbeknownst to a convenience sample of 59 second-year medical students. The study took place during clinical skills practice sessions with SPs conducted from February to April 2010 at Mount Sinai School of Medicine (New York, NY). SPs presented with non-dermatologic chief complaints typical for an acute office visit. All students had the opportunity to attend a lecture on the clinical signs of melanoma 2 to 4 months earlier, for which pre-test and post-test data were collected.Results: Recognition and evaluation of a prosthetic melanoma as determined by querying the SPs and reviewing the students’ examination notes. During the SP encounter, 37 students (63%) asked about the melanoma moulage; of those, 25 (68%) made recommendations for further evaluation. The moulage was documented in 17 examination notes (43%). Thirty-three students (56%) asked about the skin on review of systems, although this did not predict moulage detection.Conclusions: Prosthetic mimics of melanoma are useful tools for assessing skin cancer awareness and detection skills among medical students.

Preliminary clinical activity of a topical JAK1/2 inhibitor in the treatment of psoriasis - Corrected Proof

2012-01-27

Background: Janus-associated kinases (JAKs) are involved in signal transduction from a variety of cytokines implicated in the pathogenesis of psoriasis, including interleukin (IL)-12, IL-23, and interferon-γ. INCB018424, a small molecule inhibitor of JAK1 and JAK2, inhibits cytokine-induced JAK/signal transducers and activators of transcription signaling and the resultant production of inflammatory proteins (eg, IL-17).Objective: We sought to demonstrate proof of concept in patients with stable plaque psoriasis.Methods: Patients were dosed with vehicle, 0.5% or 1.0% INCB018424 phosphate cream once a day or 1.5% twice a day for 28 days. Additional groups included two active comparators (calcipotriene 0.005% cream or betamethasone dipropionate 0.05% cream).Results: Both the 1% and the 1.5% cream improved lesion thickness, erythema, and scaling and reduced lesion area compared with placebo. A composite lesion score decreased by greater than 50% with the efficacious doses of INCB018424 compared with 32% for vehicle controls. Topical application of INCB018424 was well tolerated with few mild adverse events noted. Mean plasma concentrations of INCB018424 after topical application of 0.5% to 1.5% cream were in the low nanomolar range, representing a fraction (<1%) of the half maximal inhibitory concentration (IC50) in whole blood for inhibition of cytokine-stimulated signal transducers and activators of transcription-3 phosphorylation.Limitations: This study was limited by the relatively short study duration and small sample size.Conclusion: Topical INCB018424 is safe, is well tolerated, and exhibits clinical activity in the topical treatment of psoriasis.

A review of the clinical phenotype of 254 patients with genetically confirmed pachyonychia congenita - Corrected Proof

2012-01-24

Background: Pachyonychia congenita (PC) is a group of autosomal dominant keratinizing disorders caused by a mutation in one of 4 keratin genes. Previous classification schemes have relied on data from case series and case reports. Most patients in these reports were not genetically tested for PC.Objective: We sought to clarify the prevalence of clinical features associated with PC.Methods: We surveyed 254 individuals with confirmed keratin mutations regarding their experience with clinical findings associated with PC. Statistical comparison of the groups by keratin mutation was performed using logistic regression analysis.Results: Although the onset of clinical symptoms varied considerably among our patients, a diagnostic triad of toenail thickening, plantar keratoderma, and plantar pain was reported by 97% of patients with PC by age 10 years. Plantar pain had the most profound impact on quality of life. Other clinical findings reported by our patients included fingernail dystrophy, oral leukokeratosis, palmar keratoderma, follicular hyperkeratosis, hyperhidrosis, cysts, hoarseness, and natal teeth. We observed a higher likelihood of oral leukokeratosis in individuals harboring KRT6A mutations, and a strong association of natal teeth and cysts in carriers of a KRT17 mutation. Most keratin subgroups expressed a mixed constellation of findings historically reported as PC-1 and PC-2.Limitations: Data were obtained through questionnaires, not by direct examination. Patients were self- or physician-referred.Conclusions: We propose a new classification for PC based on the specific keratin gene affected to help clinicians improve their diagnostic and prognostic accuracy, correct spurious associations, and improve therapeutic development.

Delusional infestation: Clinical presentation in 147 patients seen at Mayo Clinic - Corrected Proof

2012-01-24

Background: Delusional infestation is the conviction that one’s skin is infested with foreign organisms or materials despite contradictory objective evidence.Objective: To delineate clinical characteristics of patients presenting with delusional infestation.Methods: We performed a retrospective study of patients meeting delusional infestation criteria who were seen for diagnosis and treatment in our tertiary care academic medical center (2001–2007). Medical records were reviewed to abstract demographic, historical, and physical findings and treatment.Results: Over 7 years, 147 patients presented with delusional infestation; 87% (123/142) for another opinion. Mean age was 57 years; female-to-male ratio was 2.89 to 1; 82 (56%) were married. Mean duration of symptoms was 31 months. Employment data were available for 145 patients: 48 (33%) were self-described as disabled, 16 of whom cited delusions as their disability; 41 (28%) were retired; and 38 (26%) were employed. Reported infestations included multiple materials (45% [64/143]), not limited to insects (79% [113/143]), worms (27% [39/143]), and fibers (20% [29/143]). Most patients presented initially to dermatology or other specialties; only 3 presented to psychiatry. A high proportion (81%) had prior psychiatric conditions. Thirty-eight (26%) of the 147 patients had a shared psychotic disorder.Limitations: The retrospective nature of the study and the incompleteness of some data because not all the characteristics that were analyzed were documented for every patient.Conclusion: Patients were predominantly female, had a long history of symptoms, and had been seen previously at many medical centers. A large proportion were disabled or retired. Patients reported skin infestation with both animate and inanimate objects.

The risk of squamous cell and basal cell cancer associated with psoralen and ultraviolet A therapy: A 30-year prospective study - Corrected Proof

Robert S. Stern, PUVA Follow-Up Study — 2012-01-20

Background: By 1977, psoralen and ultraviolet A (PUVA) was established as a highly effective therapy for psoriasis. Because of concerns about potential long-term adverse effects, particularly cancer, the PUVA Follow-Up Study was established to assess long-term risk and benefits of PUVA.Objective: We sought to determine the association of certain squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) risk with exposure to PUVA.Methods: For nearly 30 years, this prospective cohort study of 1380 patients with psoriasis first treated with PUVA in 1975 to 1976 documented exposures and incident events including biopsy-proven skin cancers.Results: From 1975 to 2005, 351 of 1380 (25%) cohort patients developed 2973 biopsy-proven SCC and 330 (24%) developed 1729 BCCs. After adjusting for age, gender, and significant confounders, the risk of developing one or more SCC in a year was strongly associated with total number of PUVA treatments (350-450 vs <50 treatments, incidence rate ratio [IRR] = 6.01, 95% confidence interval [CI] = 4.41-8.20). When all tumors are included this risk is significantly higher (IRR = 20.92, 95% CI = 14.08-31.08). Corresponding risks for BCC were much lower (person counts IRR = 3.09, 95% CI = 2.36-4.06; tumor counts IRR = 2.12, 95% CI = 1.47-3.05).Limitations: This was an observational prospective study of a cohort with severe psoriasis. An unknown factor associated with higher dose exposure to PUVA in our cohort that was not included in our analysis could account for the observed associations.Conclusion: Exposure to more than 350 PUVA treatments greatly increases the risk of SCC. Exposure to fewer than 150 PUVA treatments has, at most, modest effects on SCC risk. Even high-dose exposure to PUVA does not greatly increase BCC risk. The risks of SCC in long-term PUVA-treated patients should be considered in determining the risk of this therapy relative to other treatments for severe psoriasis.

Recognizing large-cell transformation of mycosis fungoides - Corrected Proof

Jennifer L. Herrmann, Lauren C. Hughey — 2012-01-20

Background: Although patients with mycosis fungoides (MF) typically experience an indolent disease course, a minority undergo a process of large-cell transformation (LCT), which often heralds more aggressive disease and shortened survival. Regrettably, most dermatologists are unfamiliar with LCT, and even fewer understand how to recognize it clinically. Because a diagnosis of LCT typically triggers more aggressive therapy and/or referral to cutaneous T-cell lymphoma (CTCL) centers, it is paramount for clinicians to be able to recognize suspect lesions visually.Objective: LCT is diagnosed histologically; however, diagnostic biopsy is performed only if transformed lesions are suspected clinically. Because the literature provides little information on what clinical features should lead to suspicion of LCT, we sought to identify and categorize the presentations of LCT to aid in its recognition.Methods: We identified 14 patients with biopsy-proven LCT confirmed by a board-certified dermatopathologist experienced with this diagnosis. The clinical presentations of LCT, timing of its evolution, and treatment regimens were evaluated by chart and photograph review.Results: We devised 3 categories that clinically represent LCT: (1) LCT occurring as a new, solitary nodule within a classic MF patch or plaque, (2) LCT occurring as abrupt onset of multiple scattered papules and/or nodules without spontaneous resolution, and (3) LCT occurring within new or enlarging tumors.Limitations: A larger number of reviewed cases might reveal additional clinical presentations of LCT.Conclusions: Dermatologists may use our categories of clinical indicators to recognize and diagnose LCT earlier, allowing implementation of more aggressive treatment regimens when appropriate.

Rituximab treatment of severe pemphigus: Long-term results including immunologic follow-up - Corrected Proof

Ziad Reguiai, Thierry Tabary, Michael Maizières, Philippe Bernard — 2012-01-20

Background: Rituximab (RTX) has been shown to be effective and safe for short-term treatment of severe pemphigus. Its long-term results remain unknown.Objective: We sought to evaluate long-term RTX efficacy and safety in comparison with classic immunosuppressants for the treatment of severe pemphigus.Methods: This retrospective study included, from 1997 to 2010, 24 consecutive patients with severe pemphigus, treated with RTX (n = 13) or systemic corticosteroids alone or combined with immunosuppressants (n = 11 control subjects). Anti-desmoglein antibodies were titered by enzyme-linked immunosorbent assay, every 3 months the first year, then at least annually.Results: Among the 13 patients treated with RTX, 9 achieved complete remission 3 months after a first RTX cycle. Thereafter, 7 patients (4 with maintenance therapy) relapsed within a mean of 18 months after the last RTX cycle and received 1 or 2 additional RTX cycles. With mean follow-up at 41 months after the first RTX cycle and 28 months after the last one, all 13 patients remained in complete remission (5 patients off therapy). No severe RTX side effects occurred. Anti-desmoglein-3 autoantibodies remained positive in 7 patients, despite long-term complete remission. Long-term remission rates and immunologic profiles did not differ between patients with pemphigus according to RTX status.Limitations: This was a single-center, retrospective study.Conclusions: RTX appeared to be an effective and well-tolerated treatment for severe pemphigus at long term. However, the long-term remission rate without maintenance therapy did not differ significantly from that of control subjects. Anti-desmoglein-1 autoantibody titers were more reliable than anti-desmoglein-3 titers for long-term follow-up.

Fungal melanonychia - Corrected Proof

Justin Finch, Roberto Arenas, Robert Baran — 2012-01-18

Fungal melanonychia is a relatively rare nail disorder caused by nail infection that produces brown-to-black pigmentation of the nail unit. The number of organisms implicated as etiologic agents of fungal melanonychia is increasing, and the list currently tops 21 species of dematiaceous fungi and at least 8 species of nondematiaceous fungi. These superficial infections may clinically mimic subungual melanoma and are often not responsive to traditional antifungal therapy. This article reviews the literature on fungal melanonychia and the role of fungal melanin in infection.

Therapy with rituximab for autoimmune pemphigus: Results from a single-center observational study on 42 cases with long-term follow-up - Corrected Proof

2012-01-16

Background: Rituximab induces depletion of B cells and has shown efficacy in antibody-mediated autoimmune disorders. In studies on small series of patients with pemphigus, rituximab administration results in significant improvement. However, differences in inclusion criteria, treatment protocols, and follow-up make it difficult to derive uniform conclusions.Objectives: We sought to test the efficacy and tolerability of rituximab as adjuvant therapy to corticosteroids in the treatment of pemphigus.Methods: In all, 42 patients with pemphigus were treated with rituximab and followed up for up to 5 years. No additional immunosuppressive agents were used. Steroids were rapidly tapered. Outcomes were the proportion of patients who achieved a complete response on or off therapy, the rate of discontinuation of corticosteroid within 6 months, length of remission, time to relapses, and occurrence of adverse events.Results: In all, 36 of 42 patients (86%; 95% confidence interval 75%-96%) achieved a complete response on or off therapy and discontinued steroids within 6 months from induction therapy. Six patients had a complete response off therapy with an additional infusion of rituximab 6 months after initial treatment. Twenty patients experienced a total of 34 relapses; the time to relapse was 8 to 64 months. Every relapse was treated with rituximab (500 mg) without corticosteroids, which induced a new complete response. No serious adverse events were observed.Limitations: Lack of a control group is a limitation.Conclusions: Rituximab therapy induces prolonged clinical remission in patients with pemphigus. Coadministration of other immunosuppressive agents is not necessary. Relapses can be managed with additional infusions administered on demand.

Clinicopathologic study of 85 cases of melanoma of the female genitalia - Corrected Proof

2012-01-16

Background: Melanoma of the female genitalia has poor overall prognosis.Objective and methods: To examine prognostic factors influencing survival, the Duke Melanoma and Tumor Registry Databases were queried for patients who had received their clinical care at Duke University Medical Center, with a diagnosis of melanoma of the female genitalia, including vulva, vagina, and cervix, between 1970 and 2009. From this group, any available histopathologic specimens were procured for further review.Results: Eighty-five patients were identified. The median follow-up time was 8.8 years with 60% of the patients experiencing melanoma-related mortality at last follow-up. Survival rates at 1, 5, and 10 years were 85%, 51%, and 30%, respectively. The available histopathologic specimens from 36 cases were reviewed by a dermatopathologist (M.A.S.). Fifteen of 36 cases were notable for the presence of atypical melanocytic hyperplasia adjacent to the primary melanoma. Breslow depth, lymph node status, systemic therapy, and surgery were also examined for differences in survival distributions using the log-rank test. In general, survival was inversely correlated with Breslow depth, extent of nodal involvement, and provision of systemic therapy. A higher survival rate was observed among those who received wide local excision. Log-rank test demonstrated that survival between different decades of diagnosis was not significantly different.Limitations: Because of its small sample size, this study may be underpowered.Conclusion: Despite new treatments developed and attempted, there is no evidence that survival has improved over the past 40 years. In summary, patients with thinner melanomas amenable to surgical resection had a better prognosis than those with more extensive, metastatic disease at presentation.

Correlates of systemic disease in adult Henoch-Schönlein purpura: A retrospective study of direct immunofluorescence and skin lesion distribution in 87 patients at Mayo Clinic - Corrected Proof

2012-01-16

Background: Detection of IgM in lesional skin of adult patients with Henoch-Schönlein purpura via direct immunofluorescence (DIF) has been associated with the presence of renal disease.Objective: We sought to examine whether DIF findings of skin biopsy specimens and distribution of skin lesions were associated with the presence of systemic disease, including renal, gastrointestinal tract, and joint involvement.Methods: We performed a retrospective review of adult patients with Henoch-Schönlein purpura seen at Mayo Clinic between 1992 and 2011.Results: Of the 87 patients (mean age, 46.1 years), 51 (59%) were male. A total of 39 patients (45%) had renal disease; 32 (37%), gastrointestinal tract involvement; 39 (45%), joint involvement; and 65 (75%), some systemic involvement. In all, 61 patients (70%) had cutaneous lesions above the waist. The DIF findings showed the presence of IgA in all 87 patients (100%). In addition, findings were positive for IgM in 32 patients (37%); IgG in 3 patients (3%); C3 in 75 patients (87%); and fibrinogen in 78 patients (92%). IgM was not found to be significantly associated with renal disease (P = .10); however, absence of fibrinogen was correlated with presence of renal involvement (P = .04). No other correlations were detected between DIF findings and systemic disease. Lesions above the waist were not significantly associated with renal (P = .12) or any (P = .76) systemic involvement.Limitations: This study is retrospective.Conclusions: Neither IgM in lesional skin nor distribution of skin lesions above the waist was a reliable indicator of renal or systemic disease in adults with Henoch-Schönlein purpura.

Risks of developing psychiatric disorders in pediatric patients with psoriasis - Corrected Proof

2012-01-16

Background: Symptoms of psoriasis can be embarrassing and distressing, and may increase risk of developing psychiatric disorders in young people.Objective: We sought to compare incidences of psychiatric disorders between pediatric patients with psoriasis and psoriasis-free control subjects.Methods: Patients (<18 years) with continuous health plan enrollment 6 months before and after first psoriasis diagnosis (index date) were selected (Thomson Reuters MarketScan database, 2000-2006 [Thomson Reuters, New York, NY]). Patients with psoriasis (N = 7404) were matched 1:5 on age and sex to psoriasis-free control subjects (N = 37,020). Patients were followed from index date to first diagnosis of a psychiatric disorder (ie, alcohol/drug abuse, depression, anxiety disorder, bipolar disorder, suicidal ideation, eating disorder), end of data availability, or disenrollment. Patients with psychiatric diagnoses or psychotropic medication use before the index date were excluded. Cox proportional hazard models controlling for age, sex, and comorbidities were used to estimate the effect of psoriasis on risks of developing psychiatric disorders.Results: Patients with psoriasis were significantly more at risk of developing psychiatric disorders versus control subjects (5.13% vs 4.07%; P = .0001; hazard ratio = 1.25; P = .0001), especially depression (3.01% vs 2.42%; P = .0036; hazard ratio = 1.25; P = .0053) and anxiety (1.81% vs 1.35%; P = .0048; hazard ratio = 1.32; P = .0045).Limitations: Retrospective, observational studies of medical claims data are typically limited by overall quality and completeness of data and accuracy of coding for diagnoses and procedures.Conclusions: Pediatric patients with psoriasis had an increased risk of developing psychiatric disorders, including depression and anxiety, compared with psoriasis-free control subjects.

Application of mobile teledermatology for skin cancer screening - Corrected Proof

2012-01-16

Background: With advancements in mobile technology, cellular phone–based store-and-forward teledermatology may be applied to skin cancer screening.Objective: We sought to determine diagnostic and management concordance between in-person and teledermatology evaluations for patients at skin cancer screening whose clinical images and history were transmitted through mobile phones.Methods: A total of 86 patients with 137 skin lesions presented to a skin cancer screening event in California. These patients’ clinical history and skin images were captured by a software-enabled mobile phone. Patients were assessed separately by an in-person dermatologist and a teledermatologist, who evaluated the mobile phone–transmitted history and images. Diagnostic and management concordance was determined between the in-person and teledermatology evaluations.Results: The primary categorical diagnostic concordance was 82% between the in-person dermatologist and the teledermatologist (95% confidence interval 0.73-0.89), with a Kappa coefficient of 0.62 indicating good agreement. The aggregated diagnostic concordance between the in-person dermatologist and the teledermatologist was 62% (95% confidence interval 0.51-0.71), with Kappa coefficient of 0.60 indicating good agreement. Management concordance between the in-person dermatologist and the teledermatologist was 81% (95% confidence interval 0.72-0.88), with a Kappa coefficient of 0.57, which indicates moderate agreement between the dermatologists. Multivariate analysis showed that older age and presentation of atypical nevus were significantly associated with disagreement in diagnosis between the teledermatologist and in-person dermatologist, after adjusting for other factors.Limitations: Dermatoscopic images were not captured via mobile phones, which might improve diagnostic accuracy.Conclusion: Mobile teledermatology using cellular phones is an innovative and convenient modality of providing dermatologic consultations for skin cancer screening.

The effect of different pulse durations in the treatment of nail psoriasis with 595-nm pulsed dye laser: A randomized, double-blind, intrapatient left-to-right study - Corrected Proof

2012-01-16

Background: Several studies have proven the efficacy of pulsed dye laser (PDL) in the treatment of plaque type psoriasis. However, only two published studies indicate the effectiveness of PDL on nail psoriasis.Objective: We sought to study the effect of different pulse durations in the treatment of nail psoriasis with the 595-nm PDL to determine the optimal pulse duration.Methods: Twenty patients with bilateral fingernail psoriasis were recruited and completed a 6-month trial. PDL was applied on the proximal and lateral nailfolds based on random assignment. Forty nails were treated with 6-millisecond pulse duration and 9 J/cm2 whereas 39 nails were treated with 0.45-millisecond pulse duration and 6 J/cm2. Patients were blinded to pulse durations. One blinded dermatologist used the Nail Psoriasis Severity Index (NAPSI) to assess the clinical outcome from pretreatment and posttreatment photographs. Patients were monitored for adverse events. Pain was evaluated after the procedure using a visual analog scale assessed by the patient.Results: After 6 months of first treatment, there was a significant reduction in overall NAPSI, nail matrix NAPSI, and nail bed NAPSI scores from baseline in both groups; however, no significant difference was found between the two pulse duration groups. Side effects were mild including transient petechiae and hyperpigmentation.Limitations: There was no placebo group.Conclusions: PDL was found to be an effective and well-tolerated option in the treatment of nail psoriasis. No significant difference in terms of efficacy was found between the longer and shorter pulse duration treatment groups.

Enhanced port-wine stain lightening achieved with combined treatment of selective photothermolysis and imiquimod - Corrected Proof

2012-01-16

Background: Pulsed dye laser (PDL) is the gold standard for treatment of port-wine stain (PWS) birthmarks but multiple treatments are required and complete resolution is often not achieved. Posttreatment vessel recurrence is thought to be a factor that limits efficacy of PDL treatment of PWS. Imiquimod 5% cream is an immunomodulator with antiangiogenic effects.Objective: We sought to determine if application of imiquimod 5% cream after PDL improves treatment outcome.Methods: Healthy individuals with PWS (n = 24) were treated with PDL and then randomized to apply posttreatment placebo or imiquimod 5% cream for 8 weeks. Chromameter measurements (Commission Internationale de l’Eclairage L∗a∗b∗ colorspace) for 57 PWS sites (multiple sites per patient) were taken at baseline and compared with measurements taken 8 weeks posttreatment. The Δa∗ (change in erythema) and ΔE (difference in color between normal-appearing skin and PWS skin) were measured to quantify treatment outcome.Results: Two patients developed minor skin irritation. Other adverse effects were not noted. Average ∆a∗ was 0.43 for PDL + placebo sites (n = 25) and 1.27 for PDL + imiquimod sites (n = 32) (P value = .0294) indicating a greater reduction in erythema with imiquimod. Average ∆E was 2.59 for PDL + placebo and 4.08 for PDL + imiquimod (P value = .0363), again indicating a greater color improvement with imiquimod.Limitations: Effects were evaluated after a single treatment and duration of effect is unknown.Conclusion: Combined selective photothermolysis and antiangiogenic therapy may enhance PWS treatment efficacy.

Correction - Corrected Proof

2012-01-16

Chen Y-J, Wu C-Y, Chen T-J, Shen J-L, Chu S-Y, Wang C-B, Chang Y-T. The risk of cancer in patients with psoriasis: A population-based cohort study in Taiwan. J Am Acad Dermatol 2011;65:84-91.

A profile of skin cancer prevention media coverage in 2009 - Corrected Proof

2012-01-11

Background: Little is known about the coverage of skin cancer prevention messages in news print media.Objective: To perform a content analysis of mass-media articles from newspaper and magazines pertaining to skin cancer prevention in 4 specific months (January, May, July, and October) in 2009 and assess the extent of coverage of skin cancer prevention messages.Methods: We conducted a content analysis of 144 articles related to skin cancer prevention extracted from strategic media scans of selected months in 2009. We sought to provide the frequency of mass-media content categorized by theme and focus related to ultraviolet radiation (UVR) protection and risk-reducing behaviors.Results: The audience for the vast majority (78%) of the articles was the general public. Among the assessed articles, more were published in May (49%) and July (35%) than in the remaining other months. The two most frequent themes focused on ‘protection of the skin’ (32%) and on ‘skin cancer prevention’ (23%) via risk reduction behavioral practices. Analysis of message content regarding UVR reduction practices showed that many mentioned ‘use of sunscreen’ (65% of messages) with the least-often mentioned behaviors being ‘seek shade’ (6.3%) and ‘do not burn’ (1.4%). In addition, a quarter of the articles lacked any content mentioning recommended UVR reduction behaviors.Limitations: This study was limited to the narrow scope of articles published in 2009 and for selected months.Conclusions: This profile of mass-media content regarding skin cancer prevention revealed gaps in coverage of UVR reduction behaviors with possible room for improvement. Strategies for improving and comprehensiveness of coverage of recommended skin cancer prevention behaviors in the media are discussed.

Orodental manifestations of facial port-wine stains - Corrected Proof

Megan B. Dowling, Yueqin Zhao, David H. Darrow — 2012-01-10

Background: Patients with facial port-wine stains (PWS) often demonstrate oral manifestations of their disorder; however, the spectrum and prevalence of such findings among a cohort of patients with PWS has not been established. As a result, dermatologists and oral health specialists may be uncertain how to counsel their patients with PWS regarding oral hypervascularity, bony oral changes, and oral hygiene.Objectives: We sought to identify physical findings and complications involving the teeth, oral cavity, and perioral structures in individuals with facial PWS.Methods: This was a cross-sectional study of 30 patients with facial PWS. Descriptive data were collected through anonymous paired surveys completed by patients and their dentists, and analyzed (Fisher exact test) for trends based on physical findings and stage of the PWS.Results: The most common orodental manifestations according to patients were enlargement of the lip (53.3%), stained gums (46.7%), abnormal bite (30%), and spontaneous bleeding of the gums (26.7%). Staining of the gingiva correlated significantly with gingival hyperplasia (P = .006), maxillary hyperplasia (P = .014), and widened interdental spaces (P = .002), and in all cases gingival staining predated these findings. Lip hyperplasia was reported more frequently by patients than by their dentists (50% vs 18.2%, P = .008). Orodental manifestations were more common among patients with darker and thicker PWS. Hemorrhage after dental procedures was rare (4.5%).Limitations: Modest sample size and difficulty recruiting control subjects are limitations.Conclusions: Facial PWS commonly affect the orodental structures, and intraoral staining may predict future complications.

Melanoma in situ in a private practice setting 2005 through 2009: Location, lesion size, lack of concern - Corrected Proof

2012-01-10

Background: Studies have shown that the incidence of melanoma in situ (MIS) is increasing significantly.Objective: This study analyzes selected clinical and demographic characteristics of MIS cases observed in private dermatology practices in the United States.Methods: This study collected 257 MIS cases from 4 private dermatology practices in the United States from January 2005 through December 2009, recording age, gender, anatomic location, lesion size, patient-reported change in lesion, and concern about lesion. Case totals for invasive melanoma during the same period were recorded.Results: The data collected showed a higher incidence of MIS in sun-exposed areas of older patients, especially men. The median age of patients at the time of MIS detection was 69 years. The most common site for MIS was the head-neck region. The number of MIS cases collected exceeded the number of invasive malignant melanoma cases during the study period, with an observed ratio of 1.35:1.Limitations: For 136 patients, data were collected retrospectively for lesion size, location, gender, and age. For these patients, patient-reported change in lesion and concern about lesion were not collected. Patients often did not consent to a full body examination, therefore, it is possible that MIS lesions may have been missed in double-clothed areas.Conclusion: Careful attention to pigmented lesions, even lesions less than 4 mm, on sun-exposed areas, including scalp, trunk, and feet, will facilitate earlier diagnosis of MIS. As only 30.4% of male patients and 50% of female patients had concern about these lesions, it still falls to the dermatologist to discover MIS.

Topical eflornithine hydrochloride improves the effectiveness of standard laser hair removal for treating pseudofolliculitis barbae: A randomized, double-blinded, placebo-controlled trial - Corrected Proof

Yang Xia, Sunghun Cho, Robin S. Howard, Kurt L. Maggio — 2012-01-09

Background: Pseudofolliculitis barbae (PFB) significantly impacts the military population, especially deployed personnel.Objective: This study was designed to determine whether the addition of topical eflornithine to hair laser treatment would improve efficacy in treating PFB.Methods: This was a randomized, double-blinded, placebo-controlled, paired (right and left neck) comparison study examining a combination of eflornithine and hair laser versus placebo and hair laser for the treatment of PFB. In all, 27 male patients with clinical PFB were treated with a long-pulsed neodymium:yttrium-aluminum-garnet laser with an energy fluence of 25 to 30 J/cm2, a pulse duration of 20 to 30 milliseconds, and a 10-mm spot size to the entire bearded neck region. The laser treatment was performed every 4 weeks for a total of 16 weeks. Between laser treatments, patients applied eflornithine and placebo creams twice daily to opposite sides of the bearded neck region. The number of hairs and inflammatory papules were counted bilaterally at each visit.Results: The eflornithine side had a statistically significant decrease in the number of hairs and inflammatory papules compared with the placebo side. At 16 weeks, the eflornithine side had a median hair reduction of 99.5% from baseline (range 48.5%-100.0%), whereas the placebo side had an 85.0% median hair reduction from baseline (range 50.5%-94.5%), P less than .001.Limitations: Patients were not followed up beyond 16 weeks.Conclusion: The addition of topical eflornithine to hair laser treatment decreased hairs and inflammatory papules faster when compared with hair laser therapy alone in the treatment of PFB.

A randomized pilot comparative study of topical methyl aminolevulinate photodynamic therapy versus imiquimod 5% versus sequential application of both therapies in immunocompetent patients with actinic keratosis: Clinical and histologic outcomes - Corrected Proof

2012-01-09

Background: Photodynamic therapy (PDT) and imiquimod are the treatments of choice for actinic keratosis (AK). As they have different mechanisms of action, it seems reasonable to assume that applying both treatments sequentially would be efficacious.Objectives: We sought to determine which of these therapeutic modalities provides a better clinical and histologic response in patients with AK and whether sequential use of both was more efficacious than each separately.Methods: Patients were randomly assigned to one treatment group: group 1, PDT only; group 2, imiquimod only; or group 3, sequential use of PDT and imiquimod. The primary outcome measure was complete clinical response. Partial clinical response was defined as a reduction of more than 75% in the initial number of lesions. A complete clinicopathologic response was defined as lack of evidence of AK in the biopsy specimen.Results: In all, 105 patients completed the study (group 1, 40 patients; group 2, 33 patients; group 3, 32 patients). Sequential application of PDT and imiquimod was more efficacious in all the outcome measures. More patients were satisfied with PDT than with the other two modalities (P = .003). No significant differences were observed among the 3 modalities and tolerance to treatment.Limitations: Only one cycle of imiquimod was administered. The follow-up period was brief.Conclusions: Sequential application of PDT and imiquimod provides a significantly better clinical and histologic response in the treatment of AK than PDT or imiquimod monotherapy. It also produces less intense local reactions and better tolerance and satisfaction than imiquimod monotherapy.

Primary cutaneous aggressive epidermotropic CD8+ T-cell lymphoma: Proposed diagnostic criteria and therapeutic evaluation - Corrected Proof

Ahmad Nofal, M. Yousry Abdel-Mawla, Magda Assaf, Eman Salah — 2012-01-09

Primary cutaneous aggressive epidermotropic CD8+ T-cell lymphoma is a rare cytotoxic lymphoma characterized clinically by aggressive behavior and histologically by prominent epidermotropism of atypical CD8+ lymphocytes. Despite the continuous addition of new case reports, no definite diagnostic criteria have been established, and an optimum treatment is still awaiting. Herein, we study and analyze the different clinical, histopathological, and immunohistochemical features described in the reported cases. Different therapeutic modalities and their impact on the prognosis of the tumor are also evaluated and presented. We propose two sets of diagnostic criteria. The first comprises constant clinical, histopathological, and immunohistochemical features that are always present in every case, and the combination of which is necessary for the diagnosis. The second set helps to avoid missing cases and includes variable features that may be present in some cases, and to which any emerging finding could be added. Although different therapeutic options have been used, either as single agents or in combinations, there is no standard therapy for primary cutaneous aggressive epidermotropic CD8+ T-cell lymphoma and the tumor still represents a therapeutic challenge with very poor prognosis.

Open-label, pilot study examining sequential therapy with oral tacrolimus and topical tacrolimus for severe atopic dermatitis - Corrected Proof

2012-01-06

Background: Systemic treatment options for generalized atopic dermatitis (AD) are limited. To our knowledge, there have been no prospective trials examining the use of oral tacrolimus, a calcineurin inhibitor, in AD.Objectives: We assessed the safety and efficacy of sequential therapy with oral tacrolimus and topical tacrolimus in the treatment of generalized AD using the Eczema Area and Severity Index and the Physician Global Assessment scores as the primary end points.Methods: Twelve patients with AD covering at least 50% body surface area were enrolled. Patients in both phases of the study received sequential therapy with oral and topical tacrolimus over a 14-week treatment period. Eczema Area and Severity Index, Physician Global Assessment, and pruritus scores were calculated at each study visit.Results: Patients recorded a 67% improvement in the Eczema Area and Severity Index score, a 45% improvement in the Physician Global Assessment score, and a 69% reduction in the pruritus score.Limitations: This investigator-initiated, open-label, single-center, proof-of-concept study lacks a large sample size and placebo control group.Conclusion: Sequential therapy with oral tacrolimus and topical tacrolimus may be an effective treatment for AD. A large, randomized control study is warranted.

Surgical margins for melanoma in situ - Corrected Proof

Joy H. Kunishige, David G. Brodland, John A. Zitelli — 2011-12-26

Background: A controversy in the treatment of melanoma in situ is the required width of surgical margin. The currently accepted 5-mm margin is based on a 1992 consensus opinion, despite data since then showing this is inadequate.Objective: We sought to develop guidelines for predetermined surgical margins for excision of melanoma in situ.Methods: A prospectively collected series of 1072 patients with 1120 melanoma in situs was studied. All lesions were excised by Mohs micrographic surgery with frozen-section examination of the margin. The minimal surgical margin was 6 mm, and the total margin was calculated by adding an additional 3 mm for each subsequent stage required. The minimum surgical margin that would successfully remove 97% of all tumors was calculated. Local recurrence was also tabulated.Results: In all, 86% of melanoma in situs were successfully excised with a 6-mm margin; 9 mm removed 98.9% of melanoma in situs. The superiority of 9-mm to 6-mm margins was significant (P < .001). Gender, location, and diameter did not affect results. Recurrence rate for this set of patients treated with Mohs micrographic surgery was 0.3% (n = 3).Limitations: Margins less than 6 mm were not studied. This is a referral center for melanoma in situ and 10% of tumors were previously treated before presentation to our clinic.Conclusion: The frequently recommended 5-mm margin for melanoma is inadequate. Standard surgical excision of melanoma in situ should include 9 mm of normal-appearing skin, similar to that recommended for early invasive melanoma.

Assessing students’ ability to detect melanomas using standardized patients and moulage - Corrected Proof

Claudia Hernandez, Robin Mermelstein, June K. Robinson, Rachel Yudkowsky — 2011-12-26

Background: Detection of melanoma by physicians via opportunistic surveillance during focused physical examinations may reduce mortality. Medical students may not encounter a clinical case of melanoma during a dermatology clerkship.Objective: This study examined the proficiency of fourth-year University of Illinois at Chicago medical students at detecting melanomas.Methods: Melanoma moulages were applied to the second digit of the left hand of standardized patients (SPs) participating in a wrist pain scenario during a required clinical skills examination. An observer reviewed videotapes of the examination, written SP checklists, and student notes for evidence that the student noticed the moulage, obtained a history, or provided counseling.Results: Among the 190 fourth-year medical students, 56 students were observed noticing the lesion; however, 13 failed to write it in their notes or advise the patient. The detection rate was 22.6% (43 of 190 students). Students who detected the probable melanoma consistently inquired about changes in the lesion and symptoms, but did not examine the rest of the skin or regularly palpate for adenopathy.Limitations: Testing one class of students from a single medical school with a time-restricted SP encounter while focusing the students’ attention toward a different presenting symptom may hinder exploration of medical issues.Conclusion: The low detection rate and failure of students who noticed the moulage to identify the lesion as atypical represents a lost opportunity to provide a patient intervention. Use of SP examinations may help physicians in training build confidence and competence in cutaneous malignancy screening.

Chemotherapy-induced alopecia - Corrected Proof

Susan Y. Chon, Rachel W. Champion, Elizabeth R. Geddes, Rashid M. Rashid — 2011-12-19

Chemotherapy-induced alopecia is a distressing side effect common to certain treatment regimens in oncology. Unfortunately, chemotherapy-induced alopecia is an often overlooked or minor factor among our current research priorities and thus advances in amelioration have been minimal. This review offers a comprehensive examination of the clinically relevant basic science, clinical research, and current management options for chemotherapy-induced alopecia. We emphasize that hair loss secondary to chemotherapy is not as random or nonspecific in patterns or extent of disease, as one would initially perceive. Patient support and education information and templates are provided to facilitate patient treatment.

Profound disturbances of sexual health in patients with acne inversa - Corrected Proof

2011-12-19

Background: Acne inversa (AI) leads chronically to painful eruptions and extensive scarring in predominantly intimate areas. We hypothesized an impairment of sexual life caused by the disease.Objectives: By means of validated questionnaires, sexual health and quality of life were assessed in patients with AI and in healthy control subjects.Methods: A self-administered questionnaire was given to 85 voluntary study participants. In all, 45 women (24 patients vs 21 control subjects) and 40 men (20 patients vs 20 control subjects) were enrolled in the study. The Female Sexual Function Index, the International Index of Erectile Function, and the Frankfurt Self-Concept Scale for Sexuality were used to assess sexual health. Quality of life was measured with the Dermatology Life Quality Index.Results: This study demonstrated, for the first time to our knowledge, that patients with AI have sexual dysfunctions and sexual distress in comparison with matched control subjects. Sexual distress was particularly higher in female than in male patients with AI. Surprisingly, severity of cutaneous alterations correlated neither with sexual dysfunctions nor with sexual distress. However, the sexual dysfunction and sexual distress negatively correlated with the quality of life in female patients with AI who had a lower quality of life compared with gender-matched control subjects and male patients.Limitations: Small sample size is the main limitation of this study.Conclusions: Sexual health is diminished in patients with AI. We underscore the need for physicians to implement attention on the impact of AI on sexual health and quality of life when treating patients for this disease.

A critical reappraisal of the current data on drug-induced linear immuglobulin A bullous dermatosis: A real and separate nosological entity? - Corrected Proof

Giulio Fortuna, Julio Cesar Salas-Alanis, Eugenio Guidetti, M. Peter Marinkovich — 2011-12-12

Background: Linear IgA disease (LAD) has been associated with a variety of drugs over the past 30 years.Objective: To review current literature on all available cases of drug-induced LAD, in order to ascertain whether a close relationship is justified, so that it constitutes a real and separate nosological entity.Methods: The PubMed database was searched for all articles written in English related to drug-induced LAD published between January 1980 and December 2010.Results: The literature review shows that at least 84 articles were published, describing a total of 103 patients. Of these articles, only 46, from 13 countries, were included in this analysis, with a total of 52 patients: 24 (46.2%) were believed to be induced by vancomycin and 28 (53.8%) by drugs other than vancomycin. Challenge-dechallenge-rechallenge testing protocol was performed on only 6 (11.5%) of 52 patients, of which only 5 showed a positive result, while the Naranjo algorithm was performed on only 2 of them (0.3%).Limitations: The evidence of this review analysis is based only on case reports. No study on large samples of drug-induced LAD is currently available.Conclusions: The literature analysis reveals no strong scientific evidence to support the notion that some drugs have induced LAD; therefore in many reviewed cases, we must question whether drug-induced LAD is really the underlying entity. Further and thorough investigations using one of the available algorithms for adverse drug reaction are warranted.

Toxic epidermal necrolysis: Review of pathogenesis and management - Corrected Proof

Andrew Downey, Chris Jackson, Nadia Harun, Alan Cooper — 2011-12-12

Toxic epidermal necrolysis (TEN) is a severe cutaneous drug reaction with a mortality rate of approximately 30%. The hallmark of TEN is widespread epidermal sloughing due to keratinocyte apoptosis. Multiple genetic associations between TEN and specific ethnic populations have been determined. The pathophysiology of TEN has yet to be fully elucidated; however, current pathogenic models implicate Fas ligand, granulysin, and reactive oxygen species. The value of current therapies, such as intravenous immunoglobulin and corticosteroids, remains under evaluation.

Vulvo-cervico-vaginal manifestations and evaluation of Papanicolaou smears in pemphigus vulgaris and pemphigus foliaceus - Corrected Proof

2011-12-12

Background: Vulvo-cervico-vaginal involvement has rarely been reported in pemphigus vulgaris (PV) and has not been reported in pemphigus foliaceus (PF).Objectives: We sought to evaluate genital lesions and Papanicolaou (Pap) smears in female patients with PV and PF.Methods: This prospective study includes all consecutive cases of female patients with PV and PF seen from May 2009 to February 2010. Gynecologic examination was performed and Pap smears were collected for cytologic analysis from each patient.Results: A total of 56 patients were given a diagnosis of pemphigus (41 PV and 15 PF). Genital involvement was observed in 9 patients with PV (22%) and the vulva was the most common genital site of involvement. Of these 9 patients, 8 presented with active skin/mucous lesions. Four of 15 patients with PF had genital lesions and vulva was the exclusive site of involvement. Three of 4 patients with PF and genital involvement also showed active cutaneous lesions. Six of 56 patients (5 PV and 1 PF) presented with atypical squamous cells of undetermined significance in Pap smear analysis. Upon further pathologic review, acantholytic cells were seen, confirming the diagnosis of pemphigus.Limitations: A small number of PF cases were studied.Conclusions: Vulvar lesions were the second most frequent site of mucous membrane PV. Herein we report the first case to our knowledge of symptomatic genital lesions in a patient with PF. Moreover, acantholytic cells in Pap smears were found in a patient with PF who was in complete remission off therapy with no clinical genital lesions and no circulating anti-desmoglein-1 and anti-desmoglein-3 autoantibodies. Gynecologic evaluation in patients with pemphigus, including a careful evaluation of Pap smears, should be recommended.

The efficacy and safety of infliximab in patients with plaque psoriasis who had an inadequate response to etanercept: Results of a prospective, multicenter, open-label study - Corrected Proof

2011-12-12

Background: In patients with psoriasis and inadequate response (IR) to tumor necrosis factor-α antagonist treatment, the incremental benefit of switching to another tumor necrosis factor-α antagonist is unknown.Objective: We sought to evaluate the clinical response to an etanercept-to-infliximab switch in patients with psoriasis and IR to etanercept.Methods: Adults with moderate-to-severe plaque psoriasis and IR to etanercept (≥4 months) were eligible for this open-label study (called PSUNRISE). Patients had a Physician Global Assessment (PGA) score of at least 2 (mild) on a 5-point scale with etanercept, with or without concomitant oral systemic methotrexate or cyclosporine at baseline and during the study. Patients received intravenous infusions of infliximab 5 mg/kg at weeks 0, 2, 6, 14, and 22. PGA was used to evaluate efficacy at week 10 (primary end point) and week 26 (durability). Safety was evaluated through the end of the study.Results: Of 215 patients, only 10 received concomitant immunomodulators. At week 10, 65.4% of patients (138 of 211; 95% confidence interval 58.6%-71.8%) achieved a PGA score of clear (0) or minimal (1) (primary end point). This response was durable through week 26, at which time 61.3% (122 of 199; 95% confidence interval 54.2%-68.1%) achieved a PGA score of clear (0) or minimal (1). There were no unexpected side effects or safety concerns.Limitations: This was an open-label, 26-week study; an incremental change of 1 PGA point, even mild to minimal, was considered clinically significant, as most psoriasis practitioners seek to achieve minimal psoriasis or clear skin.Conclusion: After switching to infliximab, a substantial proportion of patients with psoriasis and IR to etanercept experienced rapid and durable improvement.

Increased diagnosis of thin superficial spreading melanomas: A 20-year study - Corrected Proof

2011-12-12

Background: Diagnostic practice by dermatopathologists evaluating pigmented lesions may have evolved over time.Objectives: We sought to investigate diagnostic drift among a group of dermatopathologists asked to re-evaluate cases initially diagnosed 20 years ago.Methods: Twenty nine cases of dysplastic nevi with severe atypia and 11 cases of thin radial growth–phase melanoma from 1988 through 1990 were retrieved from the pathology files of the Massachusetts General Hospital. All dermatopathologists who had rendered an original diagnosis for any of the 40 slides and the current faculty in the Massachusetts General Hospital Dermatopathology Unit were invited to evaluate the slide set in 2008 through 2009.Results: The mean number of melanoma diagnoses by the 9 study participants was 18, an increase from the original 11 melanoma diagnoses. A majority agreed with the original diagnosis of melanoma in all 11 cases. In contrast, a majority of current raters diagnosed melanoma in 4 of the 29 cases originally reported as dysplastic nevus with severe atypia. Interrater agreement over time was excellent (kappa 0.88) and fair (kappa 0.47) for cases originally diagnosed as melanoma and severely atypical dysplastic nevus, respectively.Limitations: The unbalanced composition of the slide set, lack of access to clinical or demographic information, access to only one diagnostic slide, and imposed dichotomous categorization of tumors were limitations.Conclusions: A selected cohort of dermatopathologists demonstrated a general trend toward the reclassification of prior nonmalignant diagnoses of severely atypical dysplastic nevi as malignant but did not tend to revise prior diagnoses of cutaneous melanoma as benign.

Indoor tanning and risk of early-onset basal cell carcinoma - Corrected Proof

2011-12-12

Background: Despite an increase in incidence of basal cell carcinoma (BCC) among young people and the ubiquity of indoor tanning in this population, few epidemiologic studies have investigated this exposure-disease relationship.Objective: We sought to evaluate the association between indoor tanning and early-onset BCC.Methods: Patients with BCC (n = 376) and control subjects with minor benign skin conditions (n = 390) who were younger than 40 years of age were identified through Yale Dermatopathology. Participants provided information on ever indoor tanning, age of initiation, frequency, duration, burns while tanning, and type of tanning device during an in-person interview. We calculated odds ratios (OR) and 95% confidence intervals (CI) using multivariate logistic regression with never indoor tanners as the referent group.Results: Ever indoor tanning was associated with a 69% increased risk of early-onset BCC (95% CI 1.15-2.48). This association was stronger among females (OR 2.14, 95% CI 1.31-3.47), for multiple BCCs (OR 2.16, 95% CI 1.26-3.70), and for BCCs on the trunk and extremities (OR 2.81, 95% CI 1.57-5.02). Risk increased dose dependently with years using regular indoor tanning devices (P trend = .003), number of overall burns (P trend < .001), and burns to biopsy site (P trend < .001) from indoor tanning. Approximately one quarter (27%) of early-onset BCCs (or 43% among women) could be prevented if individuals never tanned indoors.Limitations: Potential recall bias of indoor tanning by patients and generalizability of the control population suggest replication in other studies is warranted.Conclusions: Indoor tanning was a strong risk factor for early-onset BCC, particularly among females. Indoor tanning should continue to be targeted by both policy-based and behavioral interventions, as the impact on BCC-associated morbidity may be substantial.

Clinicopathological consistency in skin disorders: A retrospective study of 3949 pathological reports - Corrected Proof

2011-12-06

Background: Although the clinicopathological approach plays an important role in skin disorder diagnoses, few studies have evaluated the consistency between clinical and histopathological diagnoses of skin disorders.Objective: We sought to investigate the consistency, and factors affecting consistency, between clinical diagnoses and pathological diagnoses in patients with skin disorders referred for biopsy by dermatologists.Methods: We retrospectively examined 3949 pathological reports of biopsy specimens, between 1999 and 2008. The relationships between clinical and pathological diagnoses were studied in 4 groups, namely: (1) definite pathological diagnoses consistent with the clinical diagnoses, (2) descriptive pathological diagnoses consistent with the clinical diagnoses, (3) definite pathological diagnoses inconsistent with the clinical diagnoses, and (4) descriptive pathological diagnoses inconsistent with the clinical diagnoses. The first two groups show consistency, whereas the latter two groups show inconsistency between the diagnoses.Results: The pathological diagnoses were consistent with the clinical diagnoses in 3034 biopsy reports (76.8%), and they were inconsistent in 915 reports (23.2%). In all types of skin disorders, clinicopathological consistency was higher in patients with sufficient clinical descriptive information. No correlation was observed between clinicopathological consistency and biopsy type, number of clinical diagnoses, or specifying the location of disease. Disease duration was shorter in the biopsy reports showing clinicopathological consistency. Moreover, a statistically significant increase was found in clinicopathological consistency for inflammatory dermatoses, when pathologists evaluated the specimens with clinical diagnoses, in comparison with blind evaluation.Limitations: The retrospective nature of the study might have resulted in a loss of data.Conclusion: In a dermatology clinic setting, providing sufficient clinical descriptive information for pathology requisition forms increases the probability of making an accurate diagnosis.

Single-blind, randomized controlled trial evaluating the treatment of facial seborrheic dermatitis with hydrocortisone 1% ointment compared with tacrolimus 0.1% ointment in adults - Corrected Proof

Kim A. Papp, Alexine Papp, Betty Dahmer, Christina S. Clark — 2011-11-21

Background: Tacrolimus is a topical calcineurin inhibitor with immunomodulatory, anti-inflammatory, and fungicidal properties that may be beneficial in the treatment of facial seborrheic dermatitis.Objectives: We sought to compare the efficacy and safety of tacrolimus with standard corticosteroid treatment in adults with facial seborrheic dermatitis in a phase II, single-blind, randomized controlled trial.Methods: Adult patients were enrolled in a 12-week study. Subjects were randomized to tacrolimus 0.1% ointment (n = 16) or hydrocortisone 1% ointment (n = 14) applied twice daily to symptomatic regions of the face. The primary efficacy measure was the severity of facial seborrhea at the end of treatment (day 84) as measured by the Seborrhea Area and Severity Index–Face. Secondary efficacy measures included physician and patient assessment of seborrhea, the frequency of medication application, and adverse events.Results: The severity of facial seborrhea was similarly improved in both treatment groups (P = .86). Tacrolimus 0.1% ointment was used on significantly fewer days than 1% hydrocortisone ointment (mean missed doses per patient at first visit: 15.6 vs 7.6, P < .05; at last visit: 13.5 vs 7.7, P = .08). The majority of doses were missed because of lack of symptoms. The adverse event profile for both agents was similar; however, there was a numerically higher incidence of adverse events in the hydrocortisone group.Limitations: This was a small, open-label study.Conclusion: Tacrolimus 0.1% ointment required significantly fewer applications compared with hydrocortisone 1% ointment to achieve a comparable clinical response in adults with facial seborrheic dermatitis. Tacrolimus was generally well tolerated.

Erythema multiforme and Stevens-Johnson syndrome/toxic epidermal necrolysis associated with lupus erythematosus - Corrected Proof

Daniele Torchia, Paolo Romanelli, Francisco A. Kerdel — 2011-11-21

Background: The occurrence of erythema multiforme (EM)-like lesions in association with lupus erythematosus (LE) is often referred to as “Rowell syndrome” (RS). However, the existence of RS, or at least its nosographic independence from LE, is questioned. The association of Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) with LE is also controversial.Objective: We sought to define the features of EM and SJS/TEN in the setting of LE.Methods: The worldwide literature on the topic was systematically collected and reviewed.Results: A total of 132 citations were found, from which 95 cases of EM-like lesions and 47 of SJS/TEN associated with LE were retrieved. Our analysis identified a subgroup defined as “subacute cutaneous LE (CLE)/acute CLE with EM-like lesions” and highlighted that this and subacute CLE/acute CLE with TEN-like lesions are variants of already known CLE subpatterns. On the other hand, RS can be considered an independent chronic CLE subtype characterized by the distinctive co-occurrence of chronic CLE and EM-like lesions and frequent, albeit mild, systemic involvement.Limitations: The study was based on retrospective data and the number of reported cases identified was relatively small.Conclusion: RS might be included as a chronic CLE subtype within the spectrum of LE-specific skin disease.

Prognostic value of histologic features of toxic epidermal necrolysis - Corrected Proof

2011-11-17

Background: The prognosis of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome (SJS), and SJS/TEN overlap syndrome has been assessed using a disease-specific severity score (SCORTEN) based on clinical and laboratory data. Histologic data may improve outcome prediction.Objective: We sought to evaluate whether dermal mononuclear infiltration and epidermal necrosis predict survival of patients with TEN, SJS, or SJS/TEN.Methods: We conducted a retrospective review of clinical records and skin biopsy specimens read without knowledge of clinical data.Results: We identified 108 patients (SJS, n = 42; SJS/TEN, n = 36; TEN, n = 30). Overall mortality was 21.3%. Dermal infiltration and epidermal necrosis were not associated with time from disease onset to biopsy. Extensive dermal infiltrates were seen in 19 (18.5%) patients and full-thickness epidermal necrosis in 56 (52%) patients. Dermal infiltrate severity was not associated with day-1 (D1) SCORTEN or hospital death. Epidermal necrosis severity showed trends toward associations with D1 SCORTEN (P = .11) and hospital death (P = .06). In univariate analyses, full-thickness epidermal necrosis was significantly associated with hospital death (32.1% vs 11.4%, P = .017) and worse D1 SCORTEN values (1.98 ± 1.29 vs 1.55 ± 1.21; P = .04). In the bivariate analysis, however, D1 SCORTEN remained significantly associated with hospital death (odds ratio = 3.07, 95% confidence interval 1.83-5.16) but the association with full-thickness epidermal necrosis was no longer significant (odds ratio = 2.02, 95% confidence interval 0.65-7.12).Limitations: Retrospective study design and indirect assessment of progression are limitations.Conclusion: Full-thickness epidermal necrosis was associated with mortality but did not independently predict hospital death after adjustment based on the SCORTEN value. Dermal infiltrate severity was not associated with hospital death.

The risk of nail changes with epidermal growth factor receptor inhibitors: A systematic review of the literature and meta-analysis - Corrected Proof

Benjamin C. Garden, Shenhong Wu, Mario E. Lacouture — 2011-11-17

Background: The overall incidence and risk of nail changes associated with the use of epidermal growth factor receptor inhibitors (EGFRIs) varies widely across the literature.Objective: We conducted a systematic review of the literature and performed a meta-analysis to determine the risk of developing nail toxicity among patients receiving EGFRIs.Methods: Databases from Pubmed and Web of Science from January 1998 until July 2011 and abstracts presented at the American Society of Clinical Oncology annual meetings from 2004 through July 2011 were searched to identify relevant studies. The incidence and relative risk (RR) of nail toxicity were calculated using random-effects or fixed-effects model depending on the heterogeneity of the included studies.Results: A total of 2107 patients from 22 clinical trials were included in this analysis. The overall incidence of all-grade nail toxicity was 17.2% (95% confidence interval [CI]: 13.8%-21.3%), with an RR of 76.94 (95% CI: 40.76-145.22, P < .001). The overall incidence of high-grade nail toxicity was 1.4% (95% CI: 0.9%-2.1%), with an RR of 13.11 (95% CI: 3.73-46.03, P < .001).Limitations: The ability to detect and grade nail changes may vary among institutions.Conclusion: There is a significant risk of developing nail toxicity in cancer patients receiving EGFRIs. The risk is independent of the underlying agent. Adequate monitoring and early intervention are recommended to prevent debilitating toxicity and suboptimal dosing of EGFRI.

Predictive value of margins in diagnostic biopsies of nonmelanoma skin cancers - Corrected Proof

Julie E. Jackson, Brent Kelly, Matthew Petitt, Tatsuo Uchida, Richard F. Wagner — 2011-11-16

Background: With geographic regional variation, nonmelanoma skin cancer biopsy reports include assessment of margins. When margins are reported as negative, clinical dilemmas may emerge concerning the necessity of additional treatment.Objective: To evaluate the predictive value of biopsy margins with regard to residual tumor present in subsequent excisions of nonmelanoma skin cancers.Methods: This is a retrospective review of 235 diagnostic nonmelanoma skin cancer biopsies and their corresponding excisions for margin status at biopsy, and the presence of residual tumor in subsequent excisions.Results: Twelve of 148 squamous cell carcinomas (8.1%) had negative biopsy margins and all of the subsequent excisions were free of residual tumor. The squamous cell carcinomas with negative biopsy margins consisted predominantly of nonfacial, superficial tumors of the well-differentiated and keratoacanthoma subtype. Nine of 87 basal cell carcinomas (10.3%) had negative biopsy margins. Seven of those 9 (77.8%) had residual tumor present in subsequent excisions.Limitations: Statistical analysis performed reached significance, but with small sample size as only 21 of the biopsy specimens had negative margins. Also, residual tumor was determined via standard bread-loafing technique on excisions, which is known to examine only a proportion of the tissue and can lead to false-negative results.Conclusions: The results of this small pilot study suggest that negative-margin diagnostic biopsies may be therapeutic for well-differentiated or keratoacanthoma subtypes of squamous cell carcinoma because all subsequent excisions were devoid of tumor. Negative biopsy margins from basal cell carcinomas were not predictive of tumor removal.

A follow-up survey of the integrity of the dermatology National Resident Matching Program - Corrected Proof

Jennifer A. Sbicca, Emily S. Gorell, David H. Peng, Alfred T. Lane — 2011-11-16

Background: Our group’s 2009 study of the integrity of the dermatology match revealed that some dermatology program directors violated National Resident Matching Program (NRMP) policy during their communications with applicants. Our group’s article concluded with recommendations to change this behavior.Objective: We repeated a survey of dermatology applicants to understand if dermatology program personnel behavior has changed since our group’s 2009 study of the dermatology match.Methods: We surveyed 2011 applicants to Department of Dermatology, Stanford University, Palo Alto, CA. The survey was anonymous and available online.Results: Of applicants, 14% were asked to reveal how they intended to rank a program before match day. Of applicants, 32% felt pressured to reveal how they intended to rank programs. Of applicants, 90% were asked about interviews at other programs. Of applicants, 44% were asked about their marital status and 19% were asked if they had children or intended to have children.Limitations: The response rate for applicants was 53%.Conclusion: Although our previous study increased knowledge about the problems within the dermatology match, dermatology program personnel continue to violate NRMP policy. The most widespread violations are asking applicants where they will interview, asking applicants if they are married, and pressuring applicants to reveal how they intend to rank programs. We continue to recommend that programs avoid postinterview contact, and recommend that the NRMP create training videos for applicants and interviewers.

Are patients with psoriasis being screened for cardiovascular risk factors? A study of screening practices and awareness among primary care physicians and cardiologists - Corrected Proof

2011-11-14

Introduction: Increasing literature suggests that patients with psoriasis who have severe disease appear to have increased frequency of cardiovascular (CV) diseases. The National Psoriasis Foundation recommends screening for CV risk factors as early as 20 years of age. The extent to which these screening guidelines are implemented in practice is unclear.Objective: We sought to assess CV risk factor screening practices in patients with psoriasis and to assess primary care physician (PCP) and cardiologist awareness of worse CV outcomes in patients with psoriasis.Methods: We distributed 1200 questionnaires to PCPs and cardiologists between October 1, 2010, and April 15, 2011. A representative national sample of physicians was obtained by random selection from professional medical societies.Results: A total of 251 PCPs and cardiologists responded to the questionnaire. Among these physicians, 108 (43%) screened for hypertension, 27 (11%) screened for dyslipidemia, 75 (30%) screened for obesity, and 67 (27%) screened for diabetes. Physicians who cared for a greater number of patients with psoriasis were significantly more likely to screen for CV risk factors (hypertension P = .0041, dyslipidemia P = .0143, and diabetes P = .0065). Compared with PCPs, cardiologists were 3.5 times more likely to screen for dyslipidemia (95% confidence interval 1.32-9.29, P = .012). A total of 113 (45%) physicians were aware that psoriasis was associated with worse CV outcomes.Limitations: The questionnaire response rate was modest.Conclusions: Most PCPs and cardiologists did not routinely screen patients with psoriasis for CV risk factors. Educating physicians regarding potentially increased CV risk in psoriasis and adopting a multidisciplinary approach in the care of patients with psoriasis will likely lead to improved patient outcomes.

Erosive pustular dermatosis of the scalp: A review with a focus on dapsone therapy - Corrected Proof

Karen Chen Broussard, Timothy G. Berger, Michael Rosenblum, Jenny E. Murase — 2011-11-10

Background: Erosive pustular dermatosis of the scalp (EPDS) is an inflammatory disorder of unknown origin characterized by pustules, erosions, and crusting in areas of alopecia that tend to be atrophic, actinically damaged, or both. The most common treatments reported include antibiotics and topical anti-inflammatories, which can be ineffective. In the search for effective treatment for EPDS, we share our experience with topical dapsone 5% gel.Observations: We present 4 patients with EPDS, all with classic clinical presentations and histologic findings of EPDS, who had failed a variety of treatments including oral, intralesional, or topical steroids, tacrolimus, and antibiotics. All patients demonstrated rapid improvement or resolution with topical dapsone 5% gel.Limitations: Our experience and success with topical dapsone for EPDS is observational and not the result of a randomized controlled trial.Conclusion: Our observations demonstrate topical dapsone 5% gel to be a novel, safe, and efficacious therapeutic alternative for mild to moderate EPDS.