Serlopitant for the treatment of chronic pruritus: results of a randomized, multicenter, placebo-controlled phase 2 clinical trial J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2018-02-17 Gil Yosipovitch, Sonja Ständer, Matthew B. Kerby, James W. Larrick, Andrew J. Perlman, Edward F. Schnipper, Xiaoming Zhang, Jean Y. Tang, Thomas Luger, Martin Steinhoff
Background The substance P/neurokinin 1 receptor (NK1R) pathway is critical in chronic pruritus; anecdotal evidence suggests antagonism of this pathway can reduce chronic itch. Objective To assess the safety and efficacy of the NK1R antagonist serlopitant in treating chronic pruritus. Methods Eligible patients with severe chronic pruritus who were refractory to antihistamines or topical steroids were randomized to serlopitant 0.25, 1, or 5 mg, or placebo, administered once daily for 6 weeks as monotherapy or with midpotency steroids and emollients. The primary efficacy end point was percentage change in Visual Analog Scale (VAS) pruritus score from baseline. Results Serlopitant treatment resulted in a dose-dependent decrease in pruritus. Mean percentage decreases from baseline VAS pruritus scores were statistically significantly larger for the 1- and 5-mg doses of serlopitant (P = .022 and P = .013) versus placebo at week 6. No significant safety or tolerability differences were detected among the groups. Limitations The sample size was insufficient for subgroup analyses of the efficacy of serlopitant for chronic pruritus based on underlying conditions. Conclusions Serlopitant 1 mg and 5 mg daily was associated with a statistically significant reduction in chronic pruritus and was well tolerated [NCT01951274].
Diagnosis and Management of Pemphigus: recommendations by an International Panel of Experts J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2018-02-10 Dedee F. Murrell, Sandra Peña, Pascal Joly, Branka Marinovic, Takashi Hashimoto, Luis A. Diaz, Animesh A. Sinha, Aimee S. Payne, Maryam Daneshpazhooh, Rüdiger Eming, Marcel F. Jonkman, Daniel Mimouni, Luca Borradori, Soo-Chan Kim, Jun Yamagami, Julia S. Lehman, Marwah Adly Saleh, Donna A. Culton, Annette Czernik, John J. Zone, David Fivenson, Hideyuki Ujiie, Katarzyna Wozniak, Ayşe Akman-Karakaş, Philippe Bernard, Neil J. Korman, Frédéric Caux, Kossara Drenovska, Catherine Prost-Squarcioni, Snejina Vassileva, Ron J. Feldman, Adela Rambi Cardones, Johann Bauer, Dimitrios Ioannides, Hana Jedlickova, Francis Palisson, Aikaterini Patsatsi, Soner Uzun, Savas Yayli, Detlef Zillikens, Masayuki Amagai, Michael Hertl, Enno Schmidt, Valeria Aoki, Sergei A. Grando, Hiroshi Shimizu, Sharon Baum, Guiseppe Cianchini, Claudio Feliciani, Pilar Iranzo
Background Several European countries recently developed international diagnostic and management guidelines for pemphigus, which have been instrumental in the standardization of pemphigus management, Objective We now present results from a subsequent Delphi consensus to broaden the generalizability of recommendations. Methods A preliminary survey, based on the European Dermatology Forum (EDF) and the European Academy of Dermatology and Venereology (EADV) guidelines, was sent to a panel of international experts to determine the level of consensus. The results were discussed at the International Bullous Diseases Consensus Group in March 2016 during the annual American Academy of Dermatology (AAD) conference. A second survey was sent following the meeting to more experts to achieve greater international consensus. Results The 39 experts participated in the first round of the Delphi-survey while 54 from 21 countries completed the second round. The number of statements in the survey was reduced from 175 topics in Delphi I to 24 topics in Delphi II based on Delphi results and meeting discussion. Limitations Each recommendation represents the majority opinion and therefore may not reflect all possible treatment options available. Conclusions We present here the recommendations resulting from this Delphi process. This international consensus includes intravenous CD20 inhibitors as a first line therapy option for moderate to severe pemphigus.
The impact of underlying disease state on outcomes in patients with pyoderma gangrenosum: A national survey J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2018-02-10 Benjamin H. Kaffenberger, Alice Hinton, Somashekar Krishna
Background It is unclear if the underlying disease affects the outcomes in pyoderma gangrenosum. Objectives To determine the impact of comorbid disease associations and concomitant procedural treatments on patient outcomes in PG patient-hospitalizations. Methods A cross-sectional analysis of the Nationwide Inpatient Sample (NIS) for PG patient-hospitalizations from years 2002-2011, analyzing in-hospital mortality rate and health care resource utilization. Results Inflammatory bowel disease was the most frequent comorbid association, followed by inflammatory arthritis, hematologic malignancies/dyscrasias, and vasculitis. Multivariable modeling showed that vasculitis and hematologic malignancy/dyscrasia, when compared to subjects with IBD, were associated with a 4-6 fold increased risk of in-hospital mortality while increasing healthcare resource utilization. Inpatient procedural interventions including skin grafts, biopsies, and debridement did not impact mortality and were associated with an increased length of stay. Limitations The database does not account for outpatient follow-up, additionally there was a low rate of coded comorbid conditions. Conclusions Comprehensive evaluation to determine the underlying comorbidity for patients with PG is important for patient risk stratification.
Comparative Effectiveness of Targeted Immunomodulators for the Treatment of Moderate-to-Severe Plaque Psoriasis: A Systematic Review and Network Meta-Analysis J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2018-02-10 Anne M. Loos, Shanshan Liu, Celia Segel, Daniel A. Ollendorf, Steven D. Pearson, Jeffrey A. Linder
Background The comparative effectiveness of available targeted immunomodulators for moderate-to-severe psoriasis has not been evaluated. Objective To evaluate the comparative effectiveness of targeted immunomodulators for adults with moderate-to-severe plaque psoriasis. Methods Systematic literature review of placebo-controlled and head-to-head randomized trials of eight targeted immunomodulators that evaluated clinical benefits or harms. The primary outcome was a 75% improvement on the Psoriasis Area and Severity Index (“PASI 75”). We also conducted a network meta-analysis (NMA) adjusted for placebo response to perform indirect comparisons between agents. Results In the NMA, the targeted immunomodulators ordered by an increasing relative risk (demonstrating greater likelihood) of achieving PASI 75 relative to placebo were: apremilast (6.2), etanercept (9.6), adalimumab (13.0), ustekinumab (14.0), secukinumab (15.4), infliximab (16.2), brodalumab (17.3), and ixekizumab (17.9). Ixekizumab, brodalumab, and infliximab were all statistically superior to ustekinumab, adalimumab, etanercept, and apremilast; results were similar to head-to-head studies where data were available. Limitations Much of the evidence is short-term (10-16 weeks); limited direct comparisons. Conclusions The Interleukin-17A inhibitors are more effective in achieving clearance than ustekinumab, which are, in turn, generally more effective than etanercept, adalimumab, and apremilast.
Estimating the health care costs associated with recurrent cellulitis managed in the outpatient setting J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2018-02-07 Jessica St. John, Lauren Strazzula, Priyanka Vedak, Daniela Kroshinsky
Background Recurrent cellulitis is diagnosed in 22% to 49% of all cellulitis cases, but little is known about the costs associated with these cases. Objective To characterize patients with recurrent cellulitis in the outpatient setting and estimate the associated costs. Methods A retrospective chart review was conducted for adult patients who presented to the outpatient facilities at our institution from January 1, 2007, to December 31, 2011, with recurrent cellulitis. Data provided by the Centers for Medicare and Medicaid Services were used. Results A total of 157 patients were identified; 56% were male, with a mean age of 62.7 years. The mean number of episodes of cellulitis per patient was 3. Antibiotics were prescribed for all patients with a diagnosis of recurrent cellulitis, with 93% treated with oral antibiotics and 17.6% treated with intravenous antibiotics. A total of 1081 laboratory and 175 radiologic imaging tests were ordered. The minimum average cost per cellulitis episode was $586.91; the average cost per visit was $292.50. Limitations Retrospective study; use of a single, large academic institution; and utilization of cost estimates that may not adequately reflect the variation of costs across closed-system sites or geographic regions. There was no accounting for the nonfinancial or opportunity costs associated with hospitalization, such as lost days of employment or child care and any long-term morbidities, among others. Conclusions Recurrent cellulitis in the outpatient setting costs about $586.91 per episode. Although there is no criterion standard for diagnosis or treatment of cellulitis, our analysis demonstrates the need for more evidence-based management to achieve better outcomes and reduce the significant health care costs.
Demographics and Outcomes of Stage I-II Merkel Cell Carcinoma Treated with Mohs Micrographic Surgery Compared with Wide Local Excision in the National Cancer Data Base J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2018-02-03 Babu Singh, Muhammad M. Qureshi, Minh Tam Truong, Debjani Sahni
Background The optimal surgical approach (wide local excision (WLE) vs. Mohs micrographic surgery (MOHS)) for treating Merkel cell carcinoma (MCC) is yet to be determined. Objective To compare survival outcomes in patients with early stage MCC treated with MOHS versus WLE. Methods A retrospective review of all cases in the National Cancer Data Base (NCDB) of MCC of clinical Stage I-II MCC treated with WLE or MOHS was performed. Results 1,795 cases of Stage I-II MCC were identified who underwent WLE (N=1,685) or MOHS (N=110). There was no difference in residual tumor on surgical margins between the two treatment groups (p=0.588). On multivariate analysis, there was no difference in overall survival between the treatment modalities (adjusted HR 1.02; 95% CI 0.72-1.45, p=0.897). There was no difference in overall survival between the two groups on propensity score matched analysis. Limitations Disease specific survival was not reported as this data in not available in the NCDB. Conclusions MOHS appears to be as effective as WLE in treating early stage MCC.
Baricitinib in adult patients with moderate-to-severe atopic dermatitis: a phase 2 parallel, double-blinded, randomized placebo-controlled multiple-dose study J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2018-02-02 Emma Guttman-Yassky, Jonathan I. Silverberg, Osamu Nemoto, Seth B. Forman, August Wilke, Randy Prescilla, Amparo de la Peña, Fabio P. Nunes, Jonathan Janes, Margaret Gamalo, David Donley, Jim Paik, Amy M. DeLozier, Brian J. Nickoloff, Eric L. Simpson
Background Baricitinib, an oral selective inhibitor of Janus kinase (JAK)1 and JAK2, modulates pro-inflammatory cytokine signaling. Objectives The efficacy and safety of baricitinib were evaluated in patients with moderate-to-severe atopic dermatitis (AD). Methods In this phase 2, randomized, double-blind, placebo-controlled study, 124 patients with moderate-to-severe AD applied topical corticosteroids (TCS) for 4 weeks before randomization to once daily placebo, baricitinib 2 mg, or baricitinib 4 mg for 16 weeks. Use of TCS was permitted during the study. Primary outcome was the proportion of patients achieving ≥50% reduction in the Eczema Area and Severity Index (EASI-50) compared to placebo. Results Significantly more baricitinib 4-mg patients achieved EASI-50 compared to placebo (61% vs 37%; P=0.027) at 16 weeks. The proportion of baricitinib 2- and 4-mg patients achieving EASI-50 compared to placebo was significant as early as week 4. Baricitinib also improved pruritus and sleep loss. Treatment-emergent adverse events were reported in 24 (49%) placebo, 17 (46%) baricitinib 2-mg, and 27 (71%) baricitinib 4-mg patients. Limitations A TCS standardization period prior to randomization reduced disease severity, limiting the ability to compare results to baricitinib monotherapy. Longer studies are required to confirm baricitinib efficacy and safety in AD patients. Conclusions Baricitinib used with TCS reduced inflammation and pruritus in patients with moderate-to-severe atopic dermatitis (AD).
Diacerein Orphan Drug Development for Epidermolysis Bullosa Simplex: A Phase 2/3 Randomized, Placebo-Controlled, Double-Blind Clinical Trial J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2018-02-02 Verena Wally, Alain Hovnanian, Juliette Ly, Hana Buckova, Victoria Brunner, Thomas Lettner, Michael Ablinger, Thomas K. Felder, Peter Hofbauer, Martin Wolkersdorfer, Florian B. Lagler, Wolfgang Hitzl, Martin Laimer, Sophie Kitzmüller, Anja Diem, Johann W. Bauer
Prognostic value of sentinel lymph node biopsy according to Breslow thickness for cutaneous melanoma J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2018-01-31 Evan Stiegel, David Xiong, Jason Ya, Pauline Funchain, Raymond Isakov, Brian Gastman, Alok Vij
Background Sentinel lymph node biopsy (SLNB) is widely performed for melanoma of certain histologic parameters and offers important prognostic and staging information. Breslow thickness (BT) by itself also provides meaningful prognostic information. Objective To evaluate whether sentinel lymph node (SLN) status provides independent prognostic information than that which is already provided by BT. Methods We conducted a retrospective cohort study of 896 patients who underwent SLNB for primary cutaneous melanoma. Stratified analysis of the impact of SLN status within BT groups (0.01-1mm, 1.01-2.00mm, 2.01-4.00mm, and >4.00mm) was performed. In addition, a Cox proportional hazard model was fit to evaluate the interaction between BT unadjusted and then adjusted for SLN status to determine if predictive ability is improved. Results Having a negative SLN did not confer a statistically significant survival advantage for any BT subgroup (P= 0.54, 0.075, 0.17, and 0.95 for subgroups 0.01-1mm, 1.01-2.00mm, 2.01-4.00mm, and >4.00mm, respectively). In multivariate analysis, SLN status did not demonstrate independent prognostic ability over BT alone (P=0.067). Limitations Retrospective study, single institution. Conclusion Our data suggest that SLN status does not offer better prognostic information for patients compared to BT alone.
Horizontal and vertical sections of scalp biopsy specimens from dermatomyositis patients with scalp involvement J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2018-01-31 Julio Jasso-Olivares, José Manuel Diaz-Gonzalez, Mariya Miteva
Background The histologic findings of scalp involvement in dermatomyositis are not well characterized due to lack of large series. Objective To systematize the histologic features of scalp involvement in dermatomyositis on horizontal and vertical sections. Materials and methods A descriptive, prospective, cross-sectional study recruited 31 patients with pathologically and serologically confirmed dermatomyositis in Mexico City from June 2014 to June 2015. Thirty six scalp biopsies from 20 patients with scalp involvement in dermatomyositis were processed as 20 vertical and 16 horizontal sections. Results Dilated capillaries and diffuse mucin deposition were detected in all biopsies, followed by interface dermatitis. Partial or segmental thickening of the basement membrane, hyperkeratosis, atrophic epidermis, and acrosyringeal hypergranulosis with hyperkeratosis were other very common findings. Preserved follicular architecture, with intact or slightly atrophic sebaceous glands, was present in most horizontal sections. There was decreased follicular density with terminal:vellus ratio of 4:1 and telogen count of 10.3%. Eosinophils were present in 15% and 25% of horizontal and vertical sections respectively. Limitations No special stains performed. Conclusion Scalp involvement in dermatomyositis shows non-scarring pattern on horizontal sections, consistent with chronic telogen effluvium. Telangiectasia and mucin are universal histologic features; eosinophils and acrosyringeal hypergranulosis with hyperkeratosis are new findings.
Efficacy and Safety of Topical Oxymetazoline Cream 1.0% for Treatment of Persistent Facial Erythema Associated With Rosacea: Findings From the Two Phase 3, 29-Day, Randomized, Controlled REVEAL Trials J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2018-01-31 Linda Stein-Gold, Leon H. Kircik, Zoe Diane Draelos, Philip Werschler, Janet DuBois, Edward Lain, Leslie Baumann, David J. Goldberg, Joely Kaufman, Emil A. Tanghetti, Nancy Alvandi, Emily Weng, David R. Berk, Gurpreet Ahluwalia
Background Rosacea is a chronic dermatologic condition with limited treatment options. Objective To evaluate topical oxymetazoline cream 1.0% in patients with moderate to severe persistent erythema of rosacea. Methods Data were pooled from two identically designed phase 3 trials. Patients were randomized to receive oxymetazoline or vehicle once daily for 29 days and were followed for 28 days posttreatment. The primary efficacy outcome was the proportion of patients with ≥2-grade improvement from baseline on both Clinician Erythema Assessment (CEA) and Subject Self-Assessment (SSA) at 3, 6, 9, and 12 hours postdose, day 29. Results The pooled population included 885 patients (78.8% female); 85.8% and 91.2% had moderate erythema based on CEA and SSA, respectively. The primary outcome was achieved by significantly more patients in the oxymetazoline than vehicle group (P<0.001). Individual CEA and SSA scores and reduction in facial erythema (digital image analysis) favored oxymetazoline over vehicle (P<0.001). The incidence of treatment-emergent adverse events was low (oxymetazoline, 16.4%; vehicle, 11.8%). No clinically relevant erythema worsening (based on CEA and SSA) was observed during the 28-day posttreatment follow-up period (oxymetazoline, 1.7%; vehicle, 0.6%). Limitations Short-term treatment period. Conclusion Oxymetazoline effectively reduced moderate to severe persistent facial erythema of rosacea and was well tolerated.
A prospective study comparing patients with early and late relapsing pemphigus treated with rituximab J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2018-01-31 Marwah Adly Saleh
Background Rituximab (RTX) is an effective therapy for patients with pemphigus. However it does not prevent relapse. Objectives To compare early relapsing patients (before 12 months) and late relapsing patients (after 24 months) following RTX therapy. Methods In this prospective study, 19 patients were enrolled (14 pemphigus vulgaris and 5 pemphigus foliaceus). The baseline disease score, autoantibodies, and percentage of CD20+ cells of pemphigus patients were measured. Patients received 1 cycle of RTX and were followed for 26 months. Results Among early relapsing patients (5), the time to relapse was 6 -11 months. Among late relapsing patients (6), the time to relapse was 24-26 months. A significant difference was observed in the mean baseline anti-desmoglein (Dsg)1 index between early relapsing (705.72) and late relapsing patients (210.4), p =0.0014. A significant negative correlation was found between the baseline anti-Dsg1 index and time to relapse, r=-0.777, p= 0.00009. Limitations A small number of pemphigus foliaceus patients. Conclusion Since patients with high baseline anti-Dsg1 indices, relapsed earlier, it may be important to follow these patients closely for the initial 12 months after RTX therapy. These patients may require a maintenance RTX dose during the first 12 months after RTX therapy.
Efficacy and Safety of Oxymetazoline Cream 1.0% for Treatment of Persistent Facial Erythema Associated With Rosacea: Findings From the 52-Week Open Label REVEAL Trial J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2018-01-31 Zoe Diana Draelos, Michael H. Gold, Robert A. Weiss, Leslie Baumann, Steven K. Grekin, Deanne Mraz Robinson, Steven E. Kempers, Nancy Alvandi, Emily Weng, David R. Berk, Gurpreet Ahluwalia
Background Limited treatments are available for persistent erythema of rosacea. Objective To examine long-term safety and efficacy of oxymetazoline cream 1.0% in rosacea patients with moderate to severe persistent erythema. Methods Patients applied oxymetazoline once daily for 52 weeks. Safety assessments included treatment-emergent adverse events (TEAEs), skin blanching, inflammatory lesion counts, telangiectasia, disease severity, and rebound effect. Efficacy was assessed by the Clinician Erythema Assessment (CEA) and Subject Self-Assessment (SSA) composite score at 3 and 6 hours postdose on day 1 and weeks 4, 26, and 52. Results Among 440 patients, 8.2% reported treatment-related TEAEs; most common were application-site dermatitis, paresthesia, pain, and pruritus. The discontinuation rate due to adverse events (mostly application-site TEAEs) was 3.2%. No clinically meaningful changes were observed in skin blanching, inflammatory lesions, or telangiectasia. At week 52, 36.7% and 43.4% of patients achieved ≥2-grade composite improvement from baseline in both CEA and SSA at 3 and 6 hours postdose, respectively. Less than 1% of patients experienced rebound effect following treatment cessation. Limitations A vehicle-control group was not included. Conclusion This long-term study demonstrated sustained safety, tolerability, and efficacy of oxymetazoline for moderate to severe persistent erythema of rosacea.
Efficacy and safety of fezakinumab (an anti-IL-22 monoclonal antibody) in adults with moderate-to-severe atopic dermatitis inadequately controlled by conventional treatments - A randomized, double-blind, phase 2a trial J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2018-01-17 Emma Guttman-Yassky, Patrick M. Brunner, Avidan U. Neumann, Saakshi Khattri, Ana B. Pavel, Kunal Malik, Giselle K. Singer, Danielle Baum, Patricia Gilleaudeau, Mary Sullivan-Whalen, Sharon Rose, Shelbi Jim On, Xuan Li, Judilyn Fuentes-Duculan, Yeriel Estrada, Sandra Garcet, Claudia Traidl-Hoffmann, James G. Krueger, Mark G. Lebwohl
Background IL-22 promotes epidermal hyperplasia and inhibits skin barrier function. Objective Evaluate IL-22 blockade in adults with moderate-to-severe atopic dermatitis (AD). Methods Randomized, double-blind, placebo-controlled trial with intravenous fezakinumab monotherapy every 2wks for 10wks, with follow-up assessments until 20wks. SCORAD change from baseline at 12wks served as primary endpoint. Results At 12wks, mean SCORAD decline was 13·8±2·7 (fezakinumab) vs. 8·0±3·1 (placebo) for the entire population (p=0·134). In severe patients (baseline SCORAD≥50), SCORAD decline was significantly stronger in drug vs. placebo at 12wks (21·6±3·8 vs. 9·6±4·2, p=0.029) and 20wks (27·4±3·9 vs. 11·5±5·1, p=0·010). At 12wks, improvements were significantly stronger in drug vs. placebo (12·4%±2·4 vs. 6·2%±2·7; p=0·009) for BSA in the entire population, and for IGA in severe patients (0·7±0·2 vs. 0·3±0·1; p=0·034). All scores showed progressive improvements after last dosing (10wks) until end of study (20wks). Common adverse events were upper respiratory tract infections. Limitations Limited sample size, lack of EASI and numerical rating scale (NRS) pruritus assessments; significance primarily obtained in severe AD. Conclusion Fezakinumab was well-tolerated, with sustained clinical improvements after last drug dosing.
Efficacy and safety of lebrikizumab (an anti-IL-13 monoclonal antibody) in adults with moderate-to-severe atopic dermatitis inadequately controlled by topical corticosteroids: A randomized, placebo-controlled phase II trial (TREBLE) J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2018-01-17 Eric L. Simpson, Carsten Flohr, Lawrence F. Eichenfield, Thomas Bieber, Howard Sofen, Alain Taïeb, Ryan Owen, Wendy Putnam, Marcela Castro, Kendra DeBusk, Chin-Yu Lin, Athina Voulgari, Karl Yen, Theodore A. Omachi
Background Interleukin (IL)-13 plays a key role in type 2 inflammation and is an emerging pathogenic mediator in atopic dermatitis. Objective We investigated the efficacy and safety of lebrikizumab, an anti-IL-13 monoclonal antibody, as add-on to topical corticosteroid (TCS). Methods A randomized, placebo-controlled, double-blind, phase II study. Adults with moderate-to-severe AD were required to use twice-daily TCS, and randomized (1:1:1:1) to lebrikizumab 125 mg single dose (SD), 250 mg SD, 125 mg once every 4 weeks (Q4W), or placebo Q4W for 12 weeks, after 2-week TCS run-in. Primary endpoint was percentage of patients achieving Eczema Area and Severity Index (EASI)-50 at Week 12. Results 209 patients received study drug. At Week 12, significantly more patients achieved EASI-50 with lebrikizumab 125 mg Q4W (82.4%; p=0.026) versus placebo (62.3%); patients receiving lebrikizumab SD showed no statistically significant improvements in EASI-50 versus placebo. Adverse events were similar between groups (66.7% all lebrikizumab vs 66.0% placebo), mostly mild or moderate. Limitations Protocol-mandated twice-daily TCS limits understanding of lebrikizumab efficacy as monotherapy. Short study duration did not allow long-term efficacy or safety evaluation. Conclusions Lebrikizumab 125 mg Q4W led to significant improvement in patients with moderate-to-severe AD, when added to TCS, and was well tolerated.
Prevalence of Type II Diabetes Mellitus Among Patients with Hidradenitis Suppurativa in the United States J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2018-01-12 Amit Garg, Morgan Birabaharan, Andrew Strunk
Background Few studies have evaluated the relationship between hidradenitis suppurativa (HS) and diabetes mellitus (DM), and the existing data show conflicting results. Objective To determine prevalence of DM among HS patients, and identify at risk demographic subgroups. Methods Cross-sectional analysis identifying DM among HS and non-HS patients from a demographically heterogeneous population-based sample of over 50 million patients in the United States. Results Overall prevalence of DM among HS patients was 24.8% (10,705/43,105), compared to 15.6% (1,993,320/12,527,570) among patients without HS. Prevalence was greatest among HS patients who were male (3,045/10,785; 28.2%), older (1,945/3,950; 49.2%), non-white (4,665/17,495; 26.7%), obese (9,065/30,855; 29.4%), tobacco smokers (6,880/25,005; 27.5%), hypertensive (8,595/19,610; 43.8%), and hyperlipidemic (7,965/17,190; 46.3%). In univariable and multivariable analyses, HS patients had 1.75 [95% CI 1.71-1.79] and 1.58 [95% CI 1.54-1.62] times the odds, respectively, of having DM. HS was associated with DM across all demographic subgroups. The association was stronger for younger patients (OR 1.67, 95% CI 1.60-1.72 for ages 18-44 years, vs OR 1.50, 95% CI 1.41-1.61 for ages > 65 years). Limitations We lacked information on HS disease severity. Conclusion HS patients with risk factors, signs or symptoms of DM should be screened.
Assessing the Outcomes, Risks, and Costs of Local vs. General Anesthesia: A Review with Implications for Cutaneous Surgery J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2018-01-12 Maren C. Locke, Jeremy C. Davis, Ross Joseph Brothers, W.Elliot Love
Background There is a paucity of data providing direct comparison of outcomes, complications and costs between general and local anesthesia in cutaneous surgery. Objective Analyze the literature from dermatologic and other specialties to compare outcomes, risks and costs of general and local anesthesia. Methods A retrospective analysis of case comparison studies from other specialties comparing outcomes, risks, and/or costs in local vs. general anesthesia is performed. A review of the literature from dermatology and other specialties is included. Results 51 studies were selected. 41 studies directly examined outcomes in procedures performed under local and general anesthesia and none found a significant difference in outcomes. 41 studies measured adverse effects. Of these, 15 (36.6%) studies report significantly better outcomes between the two techniques. Only 2 studies (4.9%) report significantly improved outcomes using general anesthesia. 15 of 36 studies (41.7%) report fewer adverse events in local anesthesia. Of the 13 studies that examined costs, all (100%) found significantly decreased costs using local anesthesia. Limitations These data cannot be seamlessly applied to all cases of cutaneous surgery. Conclusion Local anesthetic techniques provide outcomes equal to or better than general anesthesia and with significantly lower costs.
Guidelines of care for the management of basal cell carcinoma J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2018-01-10 Christian Baum, Jeremy S. Bordeaux, Marc Brown, Klaus J. Busam, Daniel B. Eisen, Vivek Iyengar, Clifford Lober, David J. Margolis, Jane Messina, Alexander Miller, Stanley Miller, Eliot Mostow, Christen Mowad, Kishwer Nehal, Kristi Schmitt-Burr, Aleksandar Sekulic, Paul Storrs, Joyce Teng, Siegrid Yu, Conway Huang, Kevin Boyer, Wendy Smith Begolka, Murad Alam, John Y.S. Kim, Jeffrey H. Kozlow, Bharat Mittal, Jeffrey Moyer, Thomas Olencki, Phillip Rodgers
Basal cell carcinoma (BCC) is the most common form of human cancer, with a continually increasing annual incidence in the United States. When diagnosed early, the majority of BCCs are readily treated with office-based therapy, which is highly curative. In these evidence-based guidelines of care, we provide recommendations for the management of patients with BCC, as well as an in-depth review of the best available literature in support of these recommendations. We discuss biopsy techniques for a clinically suspicious lesion and offer recommendations for the histopathologic interpretation of BCC. In the absence of a formal staging system, the best available stratification based on risk for recurrence is reviewed. With regard to treatment, we provide recommendations on treatment modalities along a broad therapeutic spectrum, ranging from topical agents and superficially destructive modalities to surgical techniques and systemic therapy. Finally, we review the available literature and provide recommendations on prevention and the most appropriate follow-up for patients in whom BCC has been diagnosed.
Guidelines of care for the management of cutaneous squamous cell carcinoma J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2018-01-10
Cutaneous squamous cell carcinoma (cSCC) is the second most common form of human cancer and has an increasing annual incidence. Although most cSCC is cured with office-based therapy, advanced cSCC poses a significant risk for morbidity, impact on quality of life, and death. This document provides evidence-based recommendations for the management of patients with cSCC. Topics addressed include biopsy techniques and histopathologic assessment, tumor staging, surgical and nonsurgical management, follow-up and prevention of recurrence, and management of advanced disease. The primary focus of these recommendations is on evaluation and management of primary cSCC and localized disease, but where relevant, applicability to recurrent cSCC is noted, as is general information on the management of patients with metastatic disease.
An assessment of the use of antihistamines in the management of atopic dermatitis J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2018-01-06 Alice He, Steven R. Feldman, Alan B. Fleischer Jr.
Background Antihistamines are often used to treat pruritus associated with atopic dermatitis (AD) despite lack of evidence for their efficacy. The American Academy of Dermatology does not recommend the general use of antihistamines in the management of AD, although the value of short-term sedating antihistamine use for insomnia secondary to itch is recognized. Objective To assess the use of sedating and non-sedating antihistamines for AD from 2003-2012. Methods The National Ambulatory Medical Care Survey (NAMCS) provided data on physician visits from 2003-2012. Sedating and non-sedating antihistamine use was identified at AD visits. Results There were 990,000 annual visits for AD. Antihistamines were prescribed for AD in a significant proportion of visits across physician specialties (16-44%). Dermatologists and pediatricians primarily used sedating antihistamines (58-70%), while the majority of family/general practitioners, internists, and other specialists prescribed non-sedating antihistamines for AD (55-100%) Limitations We were limited by the accuracy of AD diagnosis and medication recording. Conclusions Antihistamines are widely used for the treatment of AD. There is no high-level evidence to suggest that non-sedating antihistamines reduce itch in patients with AD, or that sedating antihistamines provide benefit in controlling AD symptoms (except perhaps sleep and AD co-morbidities, such as allergic rhinitis).
Personal History of Keratinocyte Carcinoma is Associated with Reduced Risk of Death from Invasive Melanoma in Men J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2018-01-06 Fengju Song, Steven T. Chen, Xin Li, Jiali Han
Background Previous studies have found an increased risk of invasive cutaneous melanoma (CM) among those with a history of keratinocyte carcinoma (KC). Objective The aim of this study is to evaluate the risk of CM death after KC. Methods The study was based on the Health Professionals Follow-up Study (HPFS). Cox proportional hazards model was used to examine the hazard ratio (HR) of CM death associated with personal history of KC, among the entire study population (primary analysis) and invasive CM cases (secondary analysis) respectively. Results We documented a total of 908 invasive CM cases over a total of 0.7 million person-years of follow-up. Among all participants, the risk of developing either lethal or non-lethal invasive CM increased for those with KC history. The risk of melanoma death based on KC history was non-significantly increased, with HR (95% CI) of 1.53 (0.95 – 2.46). In the case-only analysis, those with KC history had a significantly lower risk of melanoma death compared with those with no such history, HR=0.60 (0.35-0.94). Limitations Because HPFS consists exclusively of male health professionals, the results of this study may not be extended to the entire population. Conclusion Personal history of KC is associated with a decreased risk of melanoma-specific death among male patients with invasive CM.
Post-diagnosis aspirin use and overall survival in patients with melanoma J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2018-01-06 Saleh Rachidi, Kristin Wallace, Hong Li, Tim Lautenschlaeger, Zihai Li
Background Mouse studies show that tumor-derived prostaglandins and platelets promote melanoma progression and immune-evasion. Objective Determine if aspirin confers longer survival in patients with melanoma. Methsods A retrospective cohort study of 1,522 patients at Indiana University Health (IUH) diagnosed with melanoma between 2000 and 2014 and followed up through September, 2016. Results Aspirin use was associated with longer overall survival in univariate analysis and after controlling for age, sex, stage, and treatment modalities (HR 0.58, 95% CI [0.45-0.75]). Aspirin use was not associated with survival in patients with in situ and stage I melanoma, but was associated with better survival in stages II (HR 0.45, 95% CI [0.24-0.82]) and III (HR 0.57, 95% CI [0.34-0.96]). No statistical significance was observed in stage IV patients (HR 0.55, 95% CI [0.27-1.13]). In turn, patients using aspirin before diagnosis were less likely to be diagnosed in stages III or IV disease. Limitations Observational study. Conclusions Aspirin could provide a survival advantage in melanoma. Clinical trials investigating the therapeutic potential of aspirin are warranted.
Fluorescence microscopy for the evaluation of elastic tissue patterns within fibrous proliferations of the skin on hematoxylin-eosin-stained slides J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2018-01-05 Robert Borucki, David M. Perry, Dan R. Lopez-Garcia, Viktoryia Kazlouskaya, Dirk M. Elston
Background Diagnosis of fibrous tumors can be challenging and expensive due to the use of special stains. Objective Determine the usefulness of fluorescence microscopy in the evaluation of elastic pattern on H&E stained slides. Methods A total of 228 slides were evaluated by fluorescence microscopy for elastic tissue patterns and sensitivity and specificity determined for relevant comparisons. Results Fluorescence microscopy was found to be useful especially in the case of distinguishing dermatofibroma (DF) vs dermatofibrosarcoma protuberans (DFSP) and also dermatomyofibroma (DMF) vs other fibrous tumors. Limitations In some cases, excessive background staining made it difficult to interpret. Conclusion Evaluation of elastic tissue patterns by fluorescence microscopy in fibrous tumors is a cheap and efficient means to further delineate these often challenging tumors.
Progression of undiagnosed cutaneous lymphoma after anti-tumor necrosis factor alpha therapy J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2018-01-04 Maria Estela Martinez-Escala, Alba L. Posligua, Heather Wickless, Audrey Rutherford, Kimberly A. Sable, Belen Rubio-Gonzalez, Xiaolong A. Zhou, Jason B. Kaplan, Barbara Pro, Jaehyuk Choi, Christiane Querfeld, Steven T. Rosen, Joan Guitart
Background Cutaneous lymphoma (CL) diagnosed after anti-tumor necrosis factor (TNF)α therapy has been reported in the literature, yet a clear link between both events remains elusive. Objective To review our experience with CL diagnosed during or after the use of anti-TNFα therapies. Methods This is a multicenter retrospective study and a literature review. Results Twenty-two cases, including 20 cutaneous T-cell lymphomas (CTCL) and 2 cutaneous B-cell lymphomas (CBCL), were identified. In the CTCL group, 75% of the patients received an anti-TNFα agent for a presumed inflammatory skin condition. Mycosis fungoides and Sézary syndrome were the most common subtypes of CTCL diagnosed. Advanced disease (IIB – IVA) was commonly seen at time of diagnosis requiring aggressive therapy, including stem cell transplant in three patients. Two patients diagnosed with CBCL had an indolent course. A total of 31 cases were gathered from a literature search. Limitations This is a retrospective study. Conclusions Our findings suggest that most of the identified patients were misdiagnosed as having psoriasis or eczema; therefore, a comprehensive morphological and molecular review of skin biopsies and peripheral blood should be considered prior to initiation of anti-TNFα therapy in patients with poorly defined dermatitis or atypical presentations of “psoriasis”.
Predictive value of basal cell carcinoma biopsies with negative margins: A retrospective cohort study J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2018-01-04 Hal Bret Willardson, Jamie Lombardo, Matt Raines, Tina Nguyen, Jisuk Park, Scott Dalton, Simon Ritchie
Background Pathology reports of basal cell carcinoma (BCC) biopsies often contain comments of positive or negative margins, with only 1-2% of the margin evaluated. The negative predictive value (NPV) of biopsy margin status on residual BCC is unknown. Objective The purpose of this study was to determine the NPV of BCC biopsy margin status on the absence of residual BCC in the corresponding excision. Methods From our institution’s archives, we collected BCC biopsies with negative margin readings that had subsequent excisions. For excisions read as negative for residual BCC, the excision blocks were sectioned at 150 μm intervals until exhausted. Results We collected 143 cases that met criteria. 34 (24%) were found to contain residual BCC in the corresponding excision leading to a NPV of 76%; in 31/34 (91%) of the cases the residual histologic subtype was superficial. Limitations Our sectioning technique did not evaluate 100% of the excision specimens. Conclusions Negative margins in a BCC biopsy are a poor predictor of residual disease in the patient. We recommend that clinicians treat these lesions, and that pathologists who comment on margin status of BCC biopsies consider adding a caveat to reflect these findings.
Subsequent non-melanoma skin cancers and impact of immunosuppression in liver transplant recipients J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2018-01-04 Pamela Funk-Debleds, Emilie Ducroux, Olivier Guillaud, José Ursic-Bedoya, Evelyne Decullier, Mélanie Vallin, Sylvie Euvrard, Georges-Philippe Pageaux, Olivier Boillot, Jérôme Dumortier
Background Non-melanoma skin cancers (NMSC) are the most frequent cancers in solid organ transplant recipients, with a high rate of subsequent tumors. Objectives To describe subsequent NMSC in a large cohort of liver transplant recipients (LTR) with long follow-up, and to analyze the factors influencing it, including immunosuppressive regimen. Methods Ninety-eight LTR (76 male) with a personal post-transplant history of squamous-cell carcinoma (SCC), basal-cell carcinoma (BCC) or Bowen’s disease were included, with a median follow-up of 12.4 years (range: 1.5-27.8) after liver transplantation. Results Median follow-up after first NMSC was 6.4 years (range: 0.17-22.1). Fifty-two (53.1%) patients developed 141 subsequent NMSC with a BCC/SCC ratio of 1.8:1. The actuarial risk of developing a second NMSC was 13.7% at 1 year, 28.4% at 2 years, 49.4% at 5 years, 65.7% at 10 years, and 88.4% at 15-years. Multivariate analysis found that phototype I-II (vs. III-IV) was a significant risk factor for second NMSC (HR: 2.556, 95%CI [1.45; 4.48], p=0.001), whereas withdrawal of calcineurin inhibitors (CNI) was significantly protective (HR: 0.358, 95%CI [0.142; 0.902], p=0.029). Limitations Retrospective analysis. Conclusions Subsequent NMSC are very frequent in LTR and conversion from CNI-based immunosuppressive regimen to mTORi/antimetabolite-based immunosuppressive regimen can reduce subsequent NMSC.
The association between dermoscopic features and BRAF mutational status in cutaneous melanoma: significance of the blue-white veil J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2018-01-04 M. Armengot-Carbó, E. Nagore, Z. García-Casado, R. Botella-Estrada
Background The genetic basis of melanoma affects its clinicopathological characteristics and increasingly influences its management. BRAF-mutated melanoma may present with specific dermoscopic features. Objectives To identify the dermoscopic features associated with BRAF mutation in cutaneous melanoma and to evaluate a model capable of predicting BRAF mutations based on dermoscopic and clinicopathological features easily accessible in normal clinical practice. Methods A prospective, cross-sectional, observational, and descriptive study was performed. Ninety-three cutaneous melanomas with dermoscopic images from 93 patients were included. BRAF mutational status was determined by genetic analysis using two methods: cobas 4800 BRAF V600 Mutation Test and Sanger sequencing. Clinicopathological data were collected; dermoscopic images were analyzed by two independent blind observers. Results Blue-white veil in dermoscopy was significantly associated with BRAF mutations (OR: 4.3; 95% CI: 1.6-11.5; p=0.003). Patients with BRAF-mutated melanomas were significantly younger than those with wild-type melanomas (OR: 0.96; 95% CI: 0.93-0.99; p=0.008). Based on these two variables, it was possible to predict BRAF mutational status in melanoma with 73% accuracy. Limitations Histological data were obtained from pathology reports. The accuracy of the predictive model has not been tested with a new dataset. Conclusions Blue-white veil in dermoscopy is associated with BRAF mutations in cutaneous melanoma.
Skin cancer in the military: a systematic review of melanoma and non-melanoma skin cancer incidence, prevention, and screening among active duty and veteran personnel J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2017-12-30 Kelsie Riemenschneider, Jesse Liu, Jennifer G. Powers
Background Occupational sun exposure is a well-studied risk factor for skin cancer development, but more work is needed to assess melanoma and non-melanoma skin cancer risk among U.S. military personnel to improve education and screening efforts in this population. Objective To conduct an extensive review of skin cancer risks for U.S. military personnel to inform preventative education, diagnosis, and treatment efforts to better protect these individuals from future skin cancer development. Methods A systematic review of published studies on the subject of melanoma and non-melanoma skin cancer in military personnel was conducted. Results Nine studies describing skin cancer incidence in the United States military were identified, with four studies specific to melanoma. The study findings reveal an increased risk of melanoma associated with service in the military or prisoner of war status. Service in tropical environments was associated with an increased incidence of both melanoma and non-melanoma skin cancer among World War II soldiers. Two studies found that increased melanoma risk was also branch-dependent, with the highest rates among the United States Air Force (USAF) branch. Several of the reviewed studies implicated increased sun exposure during military service and lack of sufficient sun protection as the causes of higher rates of skin cancer among U.S. military and veteran populations as compared to the non-military population in the US. Limitations The reviewed articles have variable results; a prospective randomized controlled trial would be helpful to develop interventions that mitigate skin cancer risk in the U.S. military. Conclusion This review identifies an abundance of evidence for an increased risk of skin cancer development among U.S. active duty and veteran populations.
Applicability of EULAR/ACR Classification Criteria for Dermatomyositis to Amyopathic Disease J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2017-12-29 Basil Patel, Neelam Khan, Victoria P. Werth
Background Existing classification systems for idiopathic inflammatory myopathies (IIM) fail to classify and/or diagnose patients with amyopathic dermatomyositis (ADM). Objective In light of the new EULAR/ACR classification criteria for IIM, we evaluated the likelihood of the skin variables included in the EULAR/ACR criteria (Gottron’s sign, Gottron’s papules, and heliotrope rash) to give a high probability of classifying patients with ADM. Methods This retrospective study evaluated 211 adult patients with dermatomyositis at the University of Pennsylvania. The EULAR/ACR criteria were used to determine the probability of classification for patients with ADM. Results 73.7% of patients with ADM would be classified as having a reasonable probability of DM based on the new EULAR/ACR criteria. 26.3% of patients with ADM would not meet the suggested 55% minimum probability cutoff to be classified based on the EULAR/ACR criteria. Limitations This study was conducted with retrospective design at a tertiary academic medical center. Conclusions The three skin variables included in the EULAR/ACR classification criteria for IIM improve on previous criteria but miss classifying some with ADM. It is important to consider additional variables such as skin biopsy to encompass more of these patients and prevent the inclusion of any skin diseases mimicking ADM.
SPF 100+ sunscreen is more protective against sunburn than SPF 50+ in actual-use: Results of a randomized, double-blind, split-face, natural sunlight exposure, clinical trial J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2017-12-29 Joshua D. Williams, Prithwiraj Maitra, Evren Atillasoy, Mei-Miau Wu, Aaron S. Farberg, Darrell S. Rigel
Background The value of additional photoprotection provided by use of high SPF sunscreens is controversial and limited clinical evidence exists. Objective To compare the sunburn protection provided by SPF100+ and SPF50+ sunscreen in conditions of actual use. Methods 199 healthy men and women (≥18 years) participated in a natural sunlight, single exposure, split face, randomized, double blind study in Vail, Colorado. Each participant wore both sunscreens simultaneously during activities with no usage restrictions other than treatment area designation. Erythema was clinically assessed the day following exposure. Comparative efficacy was evaluated through bilateral comparison of sunburn between treatment areas and erythema score as evaluated separately for each treatment area. Results Following an average 6.1 ± 1.3 hours of sun exposure, investigator blinded evaluation identified 55.3% (110/199) of the participants as more sunburned on the SPF50+ and 5% (10/199) on the SPF100+ protected side. Post exposure, 40.7% (81/199) of the participants exhibited increased erythema scores ≥ 1 on the SPF50+ protected side as compared to 13.6% (27/199) on the SPF100+. Limitations Single day exposure may not extrapolate to benefits of longer-term protection. Conclusion SPF100+ sunscreen was significantly more effective in protecting against sunburn than SPF50+ sunscreen in actual-use conditions. Trial Registration ClinicalTrials.gov(NCT02952235).
A Split-Face, Single-Blinded, Randomized Controlled Comparison of Alexandrite 755 nm Picosecond Laser vs. Alexandrite 755 nm Nanosecond Laser in the Treatment of Acquired Bilateral Nevus of Ota-like Macules (ABNOM) J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2017-12-27 Wenyou Yu, Jiafang Zhu, Wenxin Yu, Dongze Lyu, Xiaoxi Lin, Zhen Zhang
Background Q-switched alexandrite lasers (QSAL) have been used for the treatment of acquired bilateral nevus of Ota-like macules (ABNOM). Currently, picosecond alexandrite laser (PSAL) pulses have become available for pigmentary disorders. However, no studies have compared PSAL and QSAL in the treatment of ABNOM. Objective To compare the efficacy and safety of a PSAL and a QSAL in the treatment of ABNOM. Methods Each patient (n = 30) received three treatments at six-month intervals. Matching areas were delimitated on the face of each patient (left/right comparison); one side was treated with PSAL, and the other side was treated with QSAL. The safety and efficacy of the two lasers were determined by visual assessment and self-report from patients, six months after the final treatment. Results The PSAL-treated area achieved significantly better clearance (3.73 vs. 2.4) with less severe pain (4.47 vs. 5.16). The incidence rate of post-inflammatory hyperpigmentation (PIH) was 27.77% and 54.44% for the PSAL and QSAL treatments, respectively, and the duration of PIH was 1.32 and 1.74 months, respectively (P < .001). Limitations Small sample size, without objective evaluations. Conclusion Compared with QSAL, PSAL therapy afforded significantly better clinical outcomes and fewer side-effects in the treatment of ABNOM.
Diagnosis and management of peristomal pyoderma gangrenosum: A systematic review J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2017-12-27 Ladan Afifi, Isabelle M. Sanchez, Matthew M. Wallace, Sara F. Braswell, Alex G. Ortega-Loayza, Kanade Shinkai
Background Peristomal pyoderma gangrenosum (PPG) is an uncommon subtype of pyoderma gangrenosum. PPG is a challenging condition to diagnose and treat; no evidence-based guidelines exist. Objective To identify important clinical features of PPG and effective treatments available for its management. Methods A systematic literature review of PPG was performed using PubMed, Medline, and Embase databases. Results We describe 335 patients with PPG from 79 studies. Clinical features include a painful, rapidly progressing ulcer with undermined, violaceous borders with a history of ostomy leakage and local skin irritation or trauma. Systemic steroids are first line therapy; infliximab and adalimumab provide concomitant control of active IBD. Combination local and systemic therapy was commonly utilized. Wound dressings, vehicle selection, and appropriate ostomy devices to minimize leakage, irritation, and pressure-induced ischemia can improve healing. Distinct from classic ulcerative PG, surgical approaches, such as stoma closure and resection of active IBD, have an effective role in PPG management. Limitations PPG is a rare disease lacking randomized trials or diagnostic guidelines. Treatment length and follow-up time among studies are variable. Conclusion Key clinical characteristics of PPG are highlighted. Several treatments – including a more prominent role for surgical intervention – may be effective for PPG treatment.
Comorbidity scores associated with limited life expectancy in the very elderly with nonmelanoma skin cancer J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2017-12-27 Emma M. Rogers, Karen L. Connolly, Kishwer S. Nehal, Stephen W. Dusza, Anthony M. Rossi, Erica Lee
Background There is controversy regarding nonmelanoma skin cancer (NMSC) treatment in the very elderly, with some suggesting that this population may not live long enough to benefit from invasive treatments. Tools to assess limited life expectancy (LLE) exist, but performance in the very elderly NMSC population has not been well-defined. Objective Define comorbidity scores associated with LLE in the very elderly presenting for management of NMSC. Methods A retrospective review of 488 patients aged 85 or older presenting for NMSC management between July 1999 through December 2014 was performed. Comorbidities were scored using Adult Comorbidity Evaluation-27 (ACE-27) and age-adjusted Charlson Comorbidity Index (ACCI). Dates of death, follow-up, and overall survival were determined. Results ACE-27 and ACCI scores were associated with overall survival: scores of 3 and 7+, respectively, were associated with <50% survival at 4 years. Mohs surgery patients survived a median of 20 months longer than non-Mohs patients. Limitations Retrospective study design. Referral bias. Conclusions ACE-27 and ACCI predicted LLE. The cohort presenting for MMS had improved survival, despite similar inter-cohort comorbidity. This suggests that additional factors contributed to survival, and that age and comorbidities alone are inadequate for making NMSC treatment decisions in the very elderly.
A real-world, community-based cohort study comparing the effectiveness of topical fluoruracil vs. topical imiquimod for the treatment of actinic keratosis J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2017-12-24 Romain Neugebauer, Katherine A. Levandoski, Zheng Zhu, Monica Sokil, Mary-Margaret Chren, Gary D. Friedman, Maryam M. Asgari
Background The most widely used topical agents for the field-based treatment of multiple actinic keratoses (AKs) are 5-fluorouracil and imiquimod, but their comparative effectiveness has not been assessed in a real-world setting. Objective We compared the effectiveness of 5-fluorouracil and imiquimod in reducing risk of subsequent AKs in a large, integrated healthcare delivery system in Northern California. Methods In this cohort study, we identified adult health plan members that had an AK diagnosed in 2007 and subsequently filled a prescription for 5-fluorouracil or imiquimod (n=5,700). We followed subjects for subsequent AKs identified by International Classification of Diseases codes and estimated the 2-year (“short-term”) and 5-year (“long-term”) differences in cumulative risk while controlling for potential confounding by pre-treatment variables. Results 5-Fluorouracil reduced the short-term incidence of subsequent AKs (cumulative risk difference -4.54% [95% CI: -7.91% to -1.17%]), but there was no statistically significant evidence of a long-term decreased risk (cumulative risk difference -1.43% [95% CI: -3.43% to 0.05%]) compared to imiquimod. Limitations This is a retrospective study. Generalizability to other healthcare settings may be limited. Conclusion We found that 5-fluorouracil appeared to be significantly more effective than imiquimod in the short-term, but not long-term, prevention of subsequent AKs.
Evaluation of mapping biopsies for extramammary Paget’s disease: a retrospective study J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2017-12-23 Yumiko Kaku-Ito, Takamichi Ito, Gaku Tsuji, Takeshi Nakahara, Akihito Hagihara, Masutaka Furue, Hiroshi Uchi
Background Extramammary Paget’s disease (EMPD) sometimes shows an ill-defined border and an unexpectedly extended tumor spread beyond the clinical borders. Mapping biopsy is one approach for complete surgical removal, but its efficacy has remained controversial. Objective We sought to evaluate the mapping biopsy for EMPD. Methods We performed a retrospective review of 133 patients with 150 primary EMPD lesions. We histopathologically examined 1182 skin biopsy specimens (975 from mapping biopsy and 207 from lesional biopsy). Results Only 1.6% (13/810) of mapping biopsy specimens from well-defined EMPD were positive. Moreover, 4.6% (8/165) of mapping biopsy specimens from ill-defined EMPD were positive, while all specimens taken from sites ≥ 2 cm from the clinical border were negative. For both well-defined and ill-defined EMPD, there was no significant difference in the margin status of surgical resection regardless of mapping biopsy. Limitations This was a retrospective study. Conclusions Mapping biopsies are unnecessary for well-defined EMPD or when 2 cm margins can be achieved, while surgical removal with predetermined margins (1 cm for well-defined EMPD and 2 cm for ill-defined EMPD) appears to be safe. Mapping biopsy can be considered when shortening of the safe surgical margin to <2 cm is required in ill-defined EMPD.
Dipeptidyl peptidase-IV inhibitors, a risk factor for bullous pemphigoid. Retrospective multicenter case-control study in France and Switzerland J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2017-12-21 Michael Benzaquen, Luca Borradori, Philippe Berbis, Simone Cazzaniga, René Valero, Marie-Aleth Richard, Laurence Feldmeyer
Background Case reports have suggested an association between dipeptidyl peptidase-IV inhibitors (DPP4i) and development of bullous pemphigoid (BP). Objective To evaluate the association between DPP4i treatment and development of BP. Methods We conducted a retrospective 1:2 case-control study, comparing diabetic BP cases to age and sex-matched diabetic controls, issued from Swiss (Bern) and French (Marseille) dermatological departments, from January 1st 2014 to July 31st 2016. Results We collected 61 diabetic BP patients and 122 controls. DPP4i were associated with an increased risk of developing BP (adjusted OR=2.64; 95% CI: 1.19-5.85; p=0.02), with vildagliptin showing the highest adjusted OR (3.57; 95% CI: 1.07-11.84; p=0.04). Stratified analysis showed a stronger association in males and patients aged 80 years or older. DPP4i withdrawal and the institution of first-line treatments led to clinical remission in 95% of cases. Limitations This was a retrospective study in tertiary referral hospitals. We focused the analysis on DPP4i intake, without analyzing the potential isolated effect of metformin. Conclusions DPP4i, especially vildagliptin, are associated with an increased risk of developing BP. Their use needs to be carefully evaluated, particularly in high-risk patients, such as males and those aged 80 years or older.
Merkel cell carcinomas infiltrated with CD33+ myeloid cells and CD8+ T cells are associated with improved outcome J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2017-12-19 Thibault Kervarrec, Pauline Gaboriaud, Patricia Berthon, Julia Zaragoza, David Schrama, Roland Houben, Yannick Le Corre, Eva Hainaut-Wierzbicka, Francois Aubin, Guido Bens, Jorge Domenech, Serge Guyétant, Antoine Touzé, Mahtab Samimi
Background Merkel cell carcinoma (MCC) is a rare tumor of the skin with an aggressive behavior. Immunity is the main regulator of MCC development, and many interactions between lymphocytes and tumor cells have been proven. However, the impact of tumor-infiltrating myeloid cells (TIMs) needs better characterization. Objective To characterize TIMs in MCC and their association with other immune effectors and patient outcome. Methods MCC cases were reviewed from a historical/prospective cohort. In all, 103 triplicate tumor samples were included in a tissue microarray. Macrophages, neutrophils and myeloid-derived suppressor cells were characterized by the following markers: CD68, CD33, CD163, CD15, and CD33+/HLA-DR-. The association between these populations and PD-L1 expression, CD8 infiltrates and vascular density was assessed. Impact on survival was analyzed by log-rank tests and a Cox multivariate model. Results The median density of macrophages was 216/mm2. CD68+ and CD33+ macrophage densities were associated with CD8 infiltrates and PD-L1 expression. In addition, MCC harboring infiltration of CD8 T cells and brisk CD33 myeloid-cell infiltrates was significantly and independently associated with improved outcome (MCC recurrence and death). Limitations Sampling bias and retrospective design. Conclusion Infiltration of CD33 myeloid cells and CD8 lymphocytes defines a subset of MCC associated with improved outcome.
Repeated Amblyomma testudinarium tick bites are associated with elevated anti-galactose-α-1,3- galactose carbohydrate IgE antibody levels: A retrospective cohort study in a single institute J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2017-12-19 Hideo Hashizume, Toshiharu Fujiyama, Takatsune Umayahara, Reiko Kageyama, Andrew F. Walls, Takahiro Satoh
Background Alpha gal syndrome is a hypersensitivity reaction to red meat mediated by specific IgE antibody to galactose-α-1,3-galactose carbohydrate (alpha gal). Amblyomma tick bites are associated with this condition although the pathophysiology is not understood. Objective To clarify the mechanism of development of alpha gal syndrome after tick bites. Methods We compared alpha gal antibodies between patients with and without a history of tick bites and examined the histology of tick bite lesions between patients with and without detectable anti-alpha-gal IgE antibody. Results Patients who had ≥ 2 tick bites had higher levels of anti-alpha-gal IgE antibody compared with those with 1 tick bite or healthy individuals. On histological investigation, greater numbers of infiltrating basophils and eosinophils, but not mast cells, were observed in the lesions of patients with ≥ 2 tick bites compared with those with 1 tick bite. Type 2 cytokine-producing T cell infiltration was also predominantly observed in such patients. Limitation The study was conducted at a single institution in Japan. Conclusions In Amblyomma tick bites, basophils, eosinophils and type 2 cytokine-producing T cells infiltrate the skin, and anti-alpha gal IgE antibodies are produced, which provides a potential mechanistic connection to red meat hypersensitivity.
Inflammatory dermatoses, infections and drug eruptions are the most common skin conditions in hospitalized cancer patients J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2017-12-19 Gregory S. Phillips, Azael Freites-Martinez, Meier Hsu, Anna Skripnik Lucas, Dulce M. Barrios, Kathryn Ciccolini, Michael A. Marchetti, Liang Deng, Patricia L. Myskowski, Erica H. Lee, Alina Markova, Mario E. Lacouture
Background Dermatologic conditions cause morbidity and mortality among hospitalized cancer patients. An improved understanding is critical for implementing clinical and research programs in inpatient oncodermatology. Objective To characterize inpatient dermatology consultations at a large comprehensive cancer center. Methods Retrospective database query of new admissions and medical record review of initial inpatient dermatology consultations comparing consulted inpatients with non-consulted inpatients from January-December 2015. Results In total, 412 of 11,533 inpatients received 471 dermatology consultations (54% male, median age 59.5). Patients with hematologic cancers were six times more likely to receive dermatologic consultations compared to non-hematologic cancers (OR 6.56, 95%CI (5.35, 8.05), p<.0001). Patients consulted by dermatology had significantly longer length of stay (median 11 vs 5 days, p<.0001). Among the 645 dermatologic conditions diagnosed, the most common categories were inflammatory diseases, infections, and drug reactions; the most frequent conditions were contact dermatitis, herpes zoster, and chemotherapy-induced drug eruptions. Limitations The study’s retrospective nature and single-institutional setting are potential limitations. Conclusion Hematologic malignancies are a significant risk factor for dermatology inpatient consultations. A significantly longer length of stay was associated with dermatology consultations, suggesting high comorbidities in these patients. Increased dermatologic care of these inpatients may improve quality of life, dermatologic health, and ability to receive anticancer agents.
Fibrous Cephalic Plaques in Tuberous Sclerosis Complex J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2017-12-16 Oyetewa Oyerinde, Danielle Buccine, Alison Treichel, Claire Hong, Chyi-Chia Richard Lee, Joel Moss, Thomas N. Darling
Background Fibrous cephalic plaques (FCPs) stereotypically develop on the forehead of tuberous sclerosis complex (TSC) patients. They constitute a major feature for TSC diagnosis, and may present before other TSC-related cutaneous hamartomas. Objective To describe the clinical characteristics of FCPs in TSC. Methods 113 patients with TSC were enrolled in an observational cohort study. Retrospective analysis of medical records and skin photography was performed. FCPs were categorized per anatomic location and size. Results FCPs were observed in 36% (41/113) of patients. Of 62 total lesions, 58% were 1 to <5 cm, 13% ≥5 cm, and 29% unknown size mostly due to prior excision. The distribution of lesions was 39% forehead, 27% face (non-forehead), 3% neck, and 31% scalp. Fourteen patients had similar lesions less than 1cm in diameter. Histopathologically, FCPs displayed dermal collagenosis, decreased elastic fibers, and features of angiofibromas or fibrofolliculomas. Limitations Men were underrepresented since the cohort was enriched for TSC patients with lymphangioleiomyomatosis, which occurs in adult women. Conclusion Two-fifths of FCPs presented on the forehead, with most of the remainder in other locations on the face and scalp. Better recognition of these lesions may lead to earlier diagnosis of TSC.
Emerging Therapies for Atopic Dermatitis: Jak Inhibitors J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2017-12-15 David G. Cotter, David Schairer, Lawrence Eichenfield
The Janus Kinase-Signal Transducer and Activator of Transcription (JAK-STAT) pathway is a conserved master regulator of immunity and myeloproliferation. Advanced understanding of this pathway has led to development of targeted inhibitors of Janus Kinases (Jakinibs). As a class, Jakinibs effectively treat a multitude of hematologic and inflammatory diseases. Given such success, use of Jakinibs for mitigation of atopic dermatitis is under active investigation. Herein, we review the evolving data on the safety and efficacy of Jakinibs in treatment of atopic dermatitis. While it is still early in the study of Jakinibs for atopic dermatitis, evidence identifies Jakinibs as effective alternatives to conventional therapies. Nonetheless, multiple large safety and efficacy trials are needed before widespread use of Jakinibs can be advocated for atopic dermatitis.
Emerging Therapies for Atopic Dermatitis: TRPV1 Antagonists J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2017-12-15 Jonathan G. Bonchak, Robert A. Swerlick
Transient receptor potential (TRP) ion channels are important mediators of somatosensory signaling throughout the body. Our understanding of the contribution of TRPs to a multitude of cutaneous physiologic processes has grown substantially in the past decade. TRPV1, one of the better-understood members of this large family of ion channels, impacts multiple pathways involved in pruritus. Further, TRPV1 appears to play a role in maintaining skin barrier function. Together, these properties make TRPV1 a ripe target for new therapies in atopic dermatitis. Neurokinin antagonists may affect similar pathways and have been studied to this effect. Early trials data suggest these therapies are safe, but assessment of their efficacy in atopic dermatitis is pending as we await publication of phase II and III clinical trials data.
Phosphodiesterase 4 (PDE4) Inhibitors J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2017-12-15 Rema Zebda, Amy S. Paller
Historically, drugs available for treating atopic dermatitis (AD) have been limited to topical corticosteroids (TCS) and topical calcineurin inhibitors (TCI), with systemic immunosuppressants and phototherapy reserved for severe AD. Despite their efficacy, with long term use, these agents have associated safety concerns and limitations. More targeted options with fewer systemic and cutaneous side effects are needed for treating atopic dermatitis. Phosphodiesterase 4 is involved in the regulation of proinflammatory cytokines via the degradation of cAMP. Phosphodiesterase 4 (PDE4) activity is increased in the inflammatory cells of patients with AD, leading to increased production of proinflammatory cytokines and chemokines. Targeting PDE4 reduces the production of these proinflammatory mediators in AD. Both topical and oral PDE4 inhibitors have a favorable safety profile. Crisaborole 2% ointment, a topical PDE4, is now FDA-approved for children >2yrs of age and adults in the treatment of AD. Crisaborole 2% ointment shows early and sustained improvement in disease severity and pruritus/ other AD symptoms, with burning/stinging upon application as the only related adverse event. Other PDE4 inhibitors are currently in trials with promising efficacy and safety.
T-Cell Inhibitors for Atopic Dermatitis J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2017-12-15 W. James Tidwell, Joseph F. Fowler Jr.
The management of atopic dermatitis is changing with the development of novel biological agents to target specific molecules in the inflammatory cascade. Dupilumab has proven its ability to act on the IL-4 receptor in treating atopic dermatitis. Thymic stromal lymphopoietin (TSLP) monoclonal antibody (AMG157/ MEDI9929) and OX40 blocking antibody (GBR 830) were developed by target the same pathway as dupilumab. The clinical data on the efficacy for these drugs is not yet known. There is some early evidence that AMG157/ MEDI9929 attenuates most measures of allergen-induced asthmatic responses. However, there is no public data on its ability to treat atopic dermatitis. In a Phase 2a study, GBR 830 showed at least a 50% reduction in patient’s Eczema Area and Severity Index (EASI) scores in 17 out of 23 patients, but it was not powered enough for statistical differences between GBR 830 versus placebo. Although there is potential for these two drugs to greatly improve the management of severe atopic dermatitis, there is not yet any available phase 3 clinical trials which are needed to truly evaluate their efficacy in affecting T-cells.
Emerging Therapies for Atopic Dermatitis: The Prostaglandin/Leukotriene Pathway J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2017-12-15 Daniel A. Yanes, Joy L. Mosser-Goldfarb
The role of leukotrienes and prostaglandins in development of atopy has been prototypically established in studies of asthma pathogenesis. Likewise, both in vitro and in vivo studies of atopic dermatitis have demonstrated that these molecules maintain important pathophysiologic roles. Thus, it follows that targeted therapies against these molecules may be promising in management of atopic dermatitis. Montelukast has had questionable efficacy in patients with atopic dermatitis, while small pilots using zileuton did have some clinically significant improvement. There are several agents in development that target leukotrienes and/or prostaglandins as well, including OC000459, Q301, and ZPL-521. In atopic dermatitis, OC000459 did not demonstrate efficacy in clinical trials, and the efficacy of the other two agents remains to be seen. Should these medications prove promising, these topical agents may play a future role in chronic maintenance therapy and flare prophylaxis in atopic dermatitis, as anti-leukotriene therapy does in asthma.
Monoclonal Antibodies Against IL-13 and IL-31RA in Development for Atopic Dermatitis J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2017-12-15 Carsten R. Hamann, Jacob P. Thyssen
The IL-13 and IL-31 cytokines and inflammatory pathways have been identified as important for atopic dermatitis (AD) pathophysiology. Monoclonal antibodies against IL-13 have been studied for the treatment of asthma since 2011. More recently, two phase two trials have been completed with these antibodies in atopic dermatitis treatment. In both trials, significant reductions of Eczema Area and Severity Index (EASI) scores were seen. IL-31 is thought to play a role transmitting itch sensation to the central nervous system, and blocking IL-31 activity reduces itch in atopic dermatitis patients. One phase two trial has been completed for a humanized antibody against IL-31 receptor alpha, one subunit of the IL-31 receptor complex. This study showed significant dose-dependent reductions in pruritus, EASI scores, and markers of sleep quality. Initial clinical trials for monoclonal antibodies against IL-13 and IL-31 receptor A all show promise, although long term safety and efficacy data are lacking. Nevertheless, these medications will likely play a role in the treatment of moderate-to-severe atopic dermatitis.
New Therapies for Atopic Dermatitis: Additional Treatment Classes J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2017-12-14 Paras P. Vakharia, Jonathan I. Silverberg
Background A wide array of miscellaneous agents is being studied for the treatment of atopic dermatitis (AD), including targeted topical, oral systemic and biologic agents. Objective To review the known efficacy and safety to-date for such agents being studied for the treatment of AD. Methods A non-systematic review of the literature was performed. PubMed and ClinicalTrials.gov were searched for studies assessing agents not described in previous chapters for the treatment of AD. Randomized controlled trials (RCTs) were primarily sought, but other study types were also included if they contained pertinent data. Agents are presented by mechanism of action, with analysis of mechanism of action and data regarding efficacy and safety in AD patients. Results Data regarding the following agents are presented: omiganan (antimicrobial peptide), tapinarof (non-steroidal anti-inflammatory agent), PR022 (hypochlorous acid), asimadoline (kappa opioid agonist), DS107 (dihomo-gamma-linolenic acid), ZPL-389 (histamine H4 receptor antagonist), secukinumab (interleukin 17A inhibitor), fezakinumab (interleukin 22 inhibitor). Limitations Limited clinical data exists for many of the described agents. Conclusions As recent research has improved our understanding of AD pathogenesis, various agents with unique mechanisms of action have been studied for the treatment of AD. Many of these hold great therapeutic promise for AD, and continued research and development is warranted.
Mohs micrographic surgery and dermatopathology concordance; An analysis of 1421 Mohs cases over 17 years J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2017-12-13 Katarina Kesty, Omar P. Sangueza, Barry Leshin, John G. Albertini
Background The success of Mohs micrographic surgery depends on the surgeon’s ability to correctly interpret intraoperative frozen sections. Objective This retrospective study analyzed the rate of concordance between Mohs surgeons and dermatopathologists in reading slides from Mohs surgery cases. Methods A dermatopathologist reviewed all the frozen sections and the corresponding Mohs map for every 30th Mohs case at a practice employing 6 different Mohs surgeons from 2001-2017. Cases in which the dermatopathologist and the Mohs surgeon disagreed on the interpretation were noted. Results The concordance rate between Mohs surgeons and dermatopathologists was 99.79%. The three discordant cases included one case each of squamous cell carcinoma, superficial basal cell carcinoma, and hypertrophic squamous cell carcinoma in situ. Limitations This analysis is limited to fellowship-trained Mohs surgeons and therefore may not be applicable to all physicians who perform Mohs. Conclusions Fellowship-trained Mohs surgeons show very high concordance with board-certified dermatopathologists in the accurate and precise interpretation of histology slides in the setting of Mohs micrographic surgery.
Metformin and skin cancer risk in Taiwanese patients with type 2 diabetes J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2017-12-13 Chin-Hsiao Tseng
Background Metformin, an antidiabetic drug, is associated with decreased cancer risk, but its effect on skin cancer is unknown. Objective To evaluate skin cancer risk associated with metformin use. Methods Matched pairs of 16237 ever and never metformin users were retrospectively enrolled from patients with new-onset type 2 diabetes diagnosed between 1999 and 2005 from Taiwan’s National Health Insurance database, and followed until December 31, 2011. Hazard ratios (HRs) were estimated using Cox regression weighted for propensity scores. Results Skin cancer incidence was 45.59 and 83.90 per 100,000 person-years in ever and never users, respectively (HR 0.540, 95% confidence interval: 0.357–0.819). In ever users, the HRs (95% confidence intervals) for the first (<21.00 months), second (21.00–45.83 months), and third (>45.83 months) cumulative duration tertiles were 0.817 (0.448–1.489), 0.844 (0.504–1.412), and 0.114 (0.036–0.364), respectively; and 1.006 (0.579–1.748), 0.578 (0.317–1.051), and 0.229 (0.099–0.530), respectively, for the first, second, and third cumulative dose tertiles. HRs were 0.523 (0.175–1.562) for melanoma and 0.496 (0.319–0.772) for non-melanoma skin cancer. Limitations Few patients with skin cancer and lack of information on ultraviolet exposure and tumor histopathology. Conclusion Metformin use is associated with decreased skin cancer risk.
Association of Very Preterm Birth with Decreased Risk of Eczema: A Systematic Review and Meta-analysis J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2017-12-12 Tingting Zhu, Jing Zhao, Yi Qu, Li Zhang, Dezhi Mu.
Background Accumulating studies suggest that an association exists between preterm birth and eczema. Objective We performed a meta-analysis of the available evidence to determine whether the risk of developing eczema is affected by preterm birth. Methods We searched for observational studies using PubMed, Cochrane Library, Web of Science, and EMBASE databases from inception to February 1, 2017. Studies that met the inclusion criteria were included. Unadjusted and adjusted effect estimates were pooled using a random-effects model. Subgroup analysis and sensitivity analysis were performed to assess the robustness of associations. Results Eighteen studies were included in this study. Compared to full term birth, very preterm birth had a lower risk of eczema in unadjusted (relative risk 0.78, 95% confidence interval 0.72–0.85) and adjusted analyses (relative risk 0.76, 95% confidence interval 0.68–0.86). The risk became insignificant among children born moderate preterm (unadjusted: relative risk 0.88, 95% confidence interval 0.77–1.00; adjusted: relative risk 0.86, 95% confidence interval 0.73–1.01). Limitations Included studies used different assessments of eczema, and gestational age varied among studies. Conclusions The available evidence suggests an association between very preterm birth and a decreased risk of eczema.
Anti-melanoma differentiation-associated gene 5 (MDA5) dermatomyositis: a concise review with an emphasis on distinctive clinical features J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2017-12-09 Drew JB. Kurtzman, Ruth Ann Vleugels
Melanoma differentiation-associated gene 5 (MDA5) is a recently described autoantigen target in a subset of patients with dermatomyositis (DM). Anti-MDA5 DM is characterized by a unique mucocutaneous and systemic phenotype that includes cutaneous and oral ulceration, painful palmar papules, alopecia, panniculitis, arthritis, a lower incidence of myositis, and, importantly, an elevated risk of interstitial lung disease, with a potentially fatal course. Because the clinical features may differ substantially from those typically observed in cutaneous DM, the diagnosis is often overlooked, which may negatively affect patient outcomes. This review aims to familiarize the clinician with the distinctive clinical features of anti-MDA5 DM in order to enhance its recognition and to facilitate an appropriate screening and management strategy.
Merkel Cell Carcinoma: An Update and Review. Part II: Current and Future Therapy J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2017-12-09 Tiffany L. Tello, Kathleen Coggshall, Sue S. Yom, Siegrid S. Yu
Merkel cell carcinoma (MCC) is a rare neuroendocrine tumor of the skin associated with a high risk of local recurrence and distant metastases. It most commonly occurs on sun-exposed areas of Caucasian patients over the age of 65.1,2 The Merkel cell polyomavirus (MCV) is thought to be responsible for malignant transformation in approximately 80% of cases in the northern hemisphere,3 while ultraviolet radiation induced DNA damage is implicated in MCV-negative tumors.4 The overall incidence of MCC is low, with approximately 1600 cases diagnosed annually in the United States. The rate is much higher in patients with lymphoproliferative malignancies, solid organ transplants, and HIV infection.5–9 The low overall incidence of this tumor makes it challenging to conduct prospective clinical trials with sufficient power.10 As a result, most management recommendations are based on case series, retrospective reviews, and expert opinion. The pathogenesis, diagnosis, and staging of MCC are discussed in Part I of this review. Part II focuses on current management guidelines and promising new therapies in development. Due to the complexity, aggressive nature, and individuality of each case, MCC is best treated by a multidisciplinary team.
Merkel Cell Carcinoma: an Update and Review Part 1. Pathogenesis, Diagnosis, and Staging J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2017-12-09 Kathleen Coggshall, Tiffany L. Tello, Jeffrey P. North, Siegrid S. Yu
Merkel cell carcinoma (MCC) is an uncommon primary cutaneous neuroendocrine cancer. It most commonly presents as an indurated plaque or nodule on sun-damaged skin in elderly patients and is characterized by high rates of local recurrence and nodal metastasis. Survival at five years is 51% for local disease and as low as 14% for distant disease, which underscores the aggressive nature of this tumor and challenges in management. Advances in immunology and molecular genetics have broadened our understanding of the pathophysiology of MCC and expanded our therapeutic arsenal. With this comprehensive review, we provide an update of MCC epidemiology, pathogenesis, clinical presentation, diagnostic evaluation and prognostic markers. Part II of this review will explore the evolving landscape in MCC management.
A systematic review of safety and efficacy of systemic corticosteroids in atopic dermatitis J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2017-12-06 Sherry Yu, Aaron M. Drucker, Mark Lebwohl, Jonathan I. Silverberg
Background Systemic corticosteroids are often used to treat atopic dermatitis (AD). However, few studies have assessed the safety and efficacy of systemic corticosteroids in AD. Objective To systematically review the literature on efficacy and safety of systemic corticosteroid use (oral, intramuscular, and intravenous) in AD. Methods PubMed, Embase, Medline, Scopus, Web of Science, and Cochrane Library were searched. We included systematic reviews, guidelines, and treatment reviews of systemic corticosteroid use among patients of all ages with a diagnosis of AD (52 reviews and 12 studies). Results There was general consensus in the literature to limit the use of systemic steroids to short courses as a bridge to steroid-sparing therapies. Systemic side effects include growth suppression in children, osteoporosis, osteonecrosis, adrenal insufficiency, Cushing syndrome, hypertension, glucose intolerance, diabetes, gastritis, gastroesophageal reflux, peptic ulcer disease, weight gain, emotional lability, behavioral changes, opportunistic infections, cataracts, glaucoma, myopathy, myalgia, dysaesthesia, pseudotumor cerebri, hyperlipidemia, malignancy, thrombosis, skin atrophy, sleep disturbance, and rebound flaring. Limitations Baseline clinical severity, corticosteroid delivery and dose, and treatment response were reported incompletely and heterogeneously across studies. Conclusions Evidence is not strong enough to determine optimal delivery or duration of systemic corticosteroids in AD.
Statin Use and Risk of Skin Cancer J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2017-12-05 Brian M. Lin, Wen-Qing Li, Eunyoung Cho, Gary C. Curhan, Abrar A. Qureshi
Background Statins are among the most commonly used medications in the United States, and statin use is associated with increased risk of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). However, previous studies are limited by lack of adjustment for important confounders. Objective Examine the relation between statins and skin cancer risk in the Nurses’ Health Study and Health Professionals Follow-up Study. Methods Cox proportional hazards regression was used to evaluate associations. Results During follow-up (2000-2010), we documented 10,201 BCC, 1,393 SCC, and 333 melanoma cases. History of high cholesterol was not associated with risk of BCC (pooled multivariable-adjusted Hazard ratio (HR)=1.04 [1.00, 1.09], SCC (HR=0.95 [0.85, 1.06]), or melanoma (HR=0.87 [0.64, 1.19]). Statin use was not associated with risk of BCC (HR=1.04 [0.99, 1.09]), SCC (HR=1.08 [0.94, 1.24]), or melanoma (HR=1.04 [0.78, 1.38]). There was a trend towards higher BCC risk with longer duration of statin use in men (P-trend=0.003), but not in women (P-trend=0.86). Limitations Lack of treatment data. Conclusion History of high cholesterol was not associated with skin cancer risk. Longer duration of statin use was associated with a trend towards higher BCC risk in men.
Hydrochlorothiazide use and risk of non-melanoma skin cancer: A nationwide case-control study from Denmark J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2017-12-04 Sidsel Arnspang, David Gaist, Sigrun Alba Johannesdottir Schmidt, Lisbet Rosenkrantz Hölmich, Søren Friis, Anton Pottegård
Background Hydrochlorothiazide, one of the most frequently used diuretic and antihypertensive drugs in the United States and Western Europe, is photosensitizing and has previously been linked to lip cancer. Objective To examine the association between hydrochlorothiazide use and the risk of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Methods From the Danish Cancer Registry, we identified patients (cases) with NMSC during 2004-2012. Controls were matched 1:20 by age and sex. Cumulative hydrochlorothiazide use (1995-2012) was assessed from the Danish Prescription Registry. Using conditional logistic regression, we calculated odds ratios (ORs) for BCC and SCC associated with hydrochlorothiazide use. Results High use of hydrochlorothiazide (≥50,000 mg) was associated with ORs of 1.29 (95% confidence interval [CI] 1.23-1.35) for BCC and 3.98 (95% CI 3.68-4.31) for SCC. We found clear dose-response relationships between hydrochlorothiazide use and both BCC and SCC; the highest cumulative dose category (≥200,000 mg HCTZ) had ORs of 1.54 (95% CI 1.38-1.71) and 7.38 (95% CI 6.32-8.60) for BCC and SCC, respectively. Use of other diuretics and antihypertensives was not associated with NMSC. Limitations No data on sun exposure was available. Conclusions Hydrochlorothiazide use is associated with a substantially increased risk of NMSC, especially SCC.
An age-dependent interaction between sex and geographical UV index in melanoma risk J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2017-12-02 Feng Liu-Smith, Argyrios Ziogas
Background UV exposure may not equally impact melanoma development in different sexes and ages. Whether and how these factors interact with each other in melanoma risk is unknown. Objective This study attempts to estimate interactions among UVI, sex and age in melanoma risk. Methods Melanoma incidence data was collected from 42 cancer registries. Geographical UV index (UVI) was collected from local satellite stations. Negative binomial regression models were used to estimate the impact of each risk factor and their interactions. Results Sex, UVI and age, as well as interactions between any two of these factors were significantly associated with melanoma risk. In younger age groups, the female sex is an independent risk factor for melanoma that is not impacted by ambient UV exposure. In older age groups, however, the female sex interacts with UV exposure as a risk factor, exhibiting a protective effect. The switching age category is 45-49, which correlates with dramatic hormonal changes. Limitations the interaction between sex and UVI is measured at an ecological level. Conclusion The interaction between sex and UVI is age-dependent. The female sex is an independent risk factor for early onset melanoma, but the female sex also protects against UV-associated melanoma in older age groups.
Pemphigus and hematologic malignancies: A population-based study of 11,859 patients J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2017-12-02 Khalaf Kridin, Shira Zelber-Sagi, Doron Comaneshter, Erez Batat, Arnon D. Cohen
Background The association of non-paraneoplastic pemphigus with comorbid hematologic malignancies is yet to be established. Objective To estimate the association between pemphigus and the common types of hematologic malignancies. Methods A cross-sectional study was conducted comparing pemphigus patients with age-, sex- and ethnicity-matched control subjects regarding the prevalence of 6 comorbid hematologic malignancies. The study was performed utilizing the computerized database of Clalit Health Services ensuring 4.5 million subjects. Results The study included 1985 pemphigus patients and 9874 control subjects. The prevalence of chronic leukemia (0.9% vs. 0.4%; OR, 2.1; 95% CI, 1.2-3.6), multiple myeloma (0.8% vs. 0.4%; OR, 2.2; 95% CI, 1.2-3.9), and non-Hodgkin lymphoma (1.8% vs. 1.2%; OR, 1.5; 95% CI, 1.0-2.2) was greater in patients with pemphigus than in controls. The association with chronic leukemia remained significant following the adjustment for immunosuppressive therapy (adjusted OR, 2.0; 95% CI, 1.1-3.7). No significant associations between pemphigus and acute leukemia, Hodgkin lymphoma, myelodysplastic syndrome, and polycythemia vera were observed. Limitations Lack of immunopathological validation of the diagnosis of pemphigus. Conclusions Significant association was observed between pemphigus and chronic leukemia, multiple myeloma, and non-Hodgkin lymphoma. Further research is warranted to establish this observation in other cohorts.
Mitotic Rate is Associated with Positive Lymph Nodes in Thin Melanomas J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2017-12-01 Lee Wheless, Chelsea A. Isom, Mary A. Hooks, Rondi M. Kauffmann.
Background The American Joint Commission on Cancer will remove mitotic rate from its staging guidelines in 2018. Objective Using a large nationally-representative cohort, we examined the association between mitotic rate and lymph node positivity among thin melanomas. Methods 149,273 thin melanomas in the National Cancer Database were examined for their association between high-risk features of mitotic rate, ulceration, and Breslow depth, with lymph node status. Results Among 17,204 thin melanomas with data on Breslow depth, ulceration, and mitotic rate who underwent a lymph node biopsy, there was a strong linear relationship between odds of having a positive lymph node and mitotic rate (R2 = 0.96, p <0.0001, β = 3.31). The odds of having a positive node increased by 19% with each 1-point increase in mitotic rate (Odds ratio 1.19, 95% confidence interval 1.17 – 1.21). Cases with negative nodes had a mean mitotic rate of 1.54 + 2.07 mitoses/mm2, compared to 3.30 + 3.54 mitoses/mm2 for those with positive nodes (p < 0.0001 Limitations The data collected do not allow for survival analyses Conclusion Mitotic rate was strongly associated with the odds of having a positive lymph node and should continue to be reported on pathology.
Some contents have been Reproduced by permission of The Royal Society of Chemistry.
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