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  • Voriconazole exposure and risk of cutaneous squamous cell carcinoma among lung or hematopoietic cell transplant patients: A systematic review and meta-analysis
    J. Am. Acad. Dermatol. (IF 6.898) Pub Date : 2018-08-18
    Huilin Tang, Weilong Shi, Yiqing Song, Jiali Han

    Background Current evidence about the association between voriconazole and risk of cutaneous squamous cell carcinoma (SCC) remains inconsistent. Objective To assess the association between voriconazole use and risk of SCC. Methods We systematically searched PubMed and Embase and performed a random effects model meta-analysis to calculate the pooled relative risk (RR) with 95% confidence interval (CI). Results Of the 8 studies involving 3,710 individuals with lung transplant (LT) or hematopoietic cell transplant (HCT) included in qualitative analysis, five studies were included in the meta-analysis. Use of voriconazole was significantly associated with increased risk of SCC (RR, 1.86; 95% CI, 1.36 – 2.55). The increased risk did not differ according to type of transplantation or adjustment for sun exposure. Longer duration of voriconazole was found to be positively associated with risk of SCC (RR, 1.72; 95% CI, 1.09 – 2.72). Voriconazole use was not associated with increased risk of basal cell carcinoma (RR, 0.84; 95% CI, 0.41 – 1.71). Limitations There were some heterogeneities in retrospective observational studies. Conclusions Our findings support an increased risk of SCC associated with voriconazole in individuals with LT or HCT. Routine dermatologic surveillance should be performed, especially among individuals at high risk of developing SCC.

  • Subcutaneous panniculitis-like T-cell lymphoma: Clinical features, therapeutic approach, and outcome in a case series of 16 patients
    J. Am. Acad. Dermatol. (IF 6.898) Pub Date : 2018-08-17
    Ingrid López-Lerma, Yeray Peñate, Fernando Gallardo, Rosa M. Martí, Josune Mitxelena, Isabel Bielsa, Virginia Velasco-Tamariz, Juan I. Yanguas-Bayona, Pedro Sánchez-Sambucety, Vicente García-Patos, Pablo L. Ortiz-Romero, Ramón M. Pujol, Teresa Estrach

    BackgroundSubcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare primary cutaneous lymphoma of mature cytotoxic T cells. Initially, patients with SPTCL were treated with doxorubicin-based polychemotherapy.ObjectiveTo analyze clinical, biologic, immunophenotypical, molecular, imaging, treatment, and outcome data reflecting the current state of knowledge.MethodsA retrospective multicenter study of 16 patients with SPTCL that was diagnosed between 1996 and 2016.ResultsThe female-to-male ratio was 1.7. The median age at diagnosis was 46.5 years. Patients presented with multiple nodular or plaque-like lesions preferentially affecting the legs and/or trunk. Histopathology typically showed a lobular panniculitis with individual adipocytes surrounded by atypical lymphocytes, usually with a CD3+, CD4–, CD8+, CD56–, TIA1 cytotoxic granule associated RNA binding protein 1–positive phenotype and high proliferation rate. SPTCL was associated with autoimmune diseases in 25% of patients, and with the development of hemophagocytic syndrome in 18% of patients. Oral steroids alone or in combination with low-dose methotrexate or cyclosporine A were the most common initial treatment, achieving a complete response in 85% of the treated patients. The median follow-up time was 14 months. The 5-year disease-specific survival rate was 85.7%.LimitationsThis was a retrospective study.ConclusionsSPTCL has an excellent prognosis. Immunosuppressive agents can be considered for first-line treatment.

  • Angioinvasive Fungal Infections Impacting the Skin: Background, Epidemiology, and Clinical Presentation (Part 1)
    J. Am. Acad. Dermatol. (IF 6.898) Pub Date : 2018-08-10
    Bridget E. Shields, Misha Rosenbach, Zoe Brown-Joel, Anthony Berger, Bradley A. Ford, Karolyn A. Wanat

    Angioinvasive fungal infections cause significant morbidity and mortality due to their propensity to invade blood vessel walls, resulting in catastrophic tissue ischemia, infarct, and necrosis. While occasionally seen in immunocompetent hosts, opportunistic fungi are emerging in immunosuppressed hosts, including patients with hematologic malignancy, acquired immunodeficiency syndrome (AIDS), organ transplant, and poorly controlled diabetes mellitus. The widespread use of antifungal prophylaxis has led to an “arms race” of emerging fungal resistance patterns. As the at-risk population expands and as new anti-fungal resistance patterns develop, it is critical for dermatologists to understand and recognize angioinvasive fungal pathogens, as they are often the first to encounter the cutaneous manifestations of these diseases. Rapid clinical recognition, histopathologic, and culture confirmation can help render a timely, accurate diagnosis to ensure immediate medical and surgical intervention. As superficial dermatophyte infections and deep fungal infections such as blastomycosis and histoplasmosis have been well characterized within the dermatologic literature, this article will focus on the severe infections acquired by angioinvasive fungal species, including an update on new and emerging pathogens. In part 1 of this series, we review the epidemiology and cutaneous manifestations, and part 2 will focus on diagnosis, treatment, and complications of these infections.

  • Angioinvasive Fungal Infections Impacting the Skin: Diagnosis, Management, and Complications (Part 2)
    J. Am. Acad. Dermatol. (IF 6.898) Pub Date : 2018-08-10
    Anthony P. Berger, Bradley A. Ford, Zoe Brown-Joel, Bridget E. Shields, Misha Rosenbach, Karolyn A. Wanat

    As discussed in Part I, angioinvasive fungal infections pose a significant risk to immunocompromised and immunocompetent patients alike,1 with potential for severe morbidity and high mortality. Part I of this CME focused on the epidemiology and clinical presentation of these infections; Part II will discuss diagnosis, management, and potential complications of these infections. The mainstay diagnostic tests (positive tissue culture with histologic confirmation) are often supplemented with serum biomarker assays and molecular testing (e.g., quantitative PCR analysis and MALDI-TOF mass spectrometry) to ensure proper speciation. When an angioinvasive fungal infection is suspected or diagnosed, further work-up for visceral involvement also is essential and may partially depend on the organism. Different fungal organisms demonstrate varied susceptibilities to antifungal agents, and knowledge on optimal treatment regimens is important to avoid potential complications associated with undertreated or untreated fungal infections.

  • Association of skin hyperpigmentation disorders with digital ulcers in systemic sclerosis: analysis of a cohort of 239 patients
    J. Am. Acad. Dermatol. (IF 6.898) Pub Date : 2018-08-07
    Vaianu Leroy, Pauline Henrot, Thomas Barnetche, Muriel Cario-André, Anne-Sophie Darrigade, Pauline Manicki, Marie-Sylvie Doutre, Estibaliz Lazaro, Joel Constans, Damien Barcat, Jean-Philippe Vernhes, Christophe Richez, Alain Taieb, Marie-Elise Truchetet, Julien Seneschal,

    BackgroundSkin pigmentation disorders in systemic sclerosis (SSc) have been sparsely described in the literature. Nevertheless, they could be a diagnostic and/or a severity marker.ObjectivesTo assess the association between pigmentation disorders and systemic involvement in SSc patients.MethodsFive patterns of skin pigmentation disorders were defined: diffuse hyperpigmentation, sun-exposed area hyperpigmentation, head/neck/upper chest hypopigmentation, acral hypopigmentation and diffuse hypopigmentation.Results239 patients were included, eighty-eight (36.8%) patients had skin pigmentation disorders as follows: diffuse and sun-exposed hyperpigmentation in 38.6% (n=34) and 27.3% (n=24) respectively, face/neck/chest hypopigmentation in 10.2% (n=9), diffuse hypopigmentation in 12.5% (n=11) and acral hypopigmentation in 17% (n=15). Diffuse hyperpigmentation, was associated with diffuse SSc (p= 0.001), increased modified Rodnan’s skin score (mRSS) (p= 0.001) and and shorter duration of Raynaud (p=0.002) in univariate analysis but not in multivariate analysis. Moreover, diffuse hyperpigmentation was associated with digital ulcers (p= 0.005) confirmed by multivariate analysis OR 2.96 [1.28-6.89].LimitationsThis was a single-center retrospective study on a cohort of SSc patients.ConclusionScreening for skin pigmentation disorders could be useful in the management of SSc patients to identify patients with a high risk of developing digital ulcers, a symptom of vascular involvement in SSc.

  • Immune checkpoint inhibitors and the development of granulomatous reactions
    J. Am. Acad. Dermatol. (IF 6.898) Pub Date : 2018-08-06
    Christine M. Cornejo, Paul Haun, Joseph English, Misha Rosenbach

    Immune checkpoint inhibitors (ICPis) have emerged as a frontline treatment for a growing list of malignancies. Disruption of the negative regulatory immune checkpoints by ICIs has been associated with many immune-related adverse events (irAEs). Granulomatous reactions, such as sarcoidosis-like, granulomatous panniculitis, granuloma annulare, and granulomatous dermatitis, are an uncommon, but increasingly recognized irAE seen in patients treated with ICIs. The frequency and significance of these eruptions, including the question of whether they portend treatment responsiveness, remains unclear. Additionally, understanding the role of immune checkpoint blockade in these reactions may provide mechanistic insight into the relevant signaling pathways involved in sarcoidosis and other granulomatous disorders.

  • Cutaneous Malignant Melanoma Incidence and Mortality Trends in Canada: A Comprehensive Population-based Study
    J. Am. Acad. Dermatol. (IF 6.898) Pub Date : 2018-08-06
    Feras M. Ghazawi, Janelle Cyr, Rami Darwich, Michelle Le, Elham Rahme, Linda Moreau, Elena Netchiporouk, Andrei Zubarev, Osama Roshdy, Steven J. Glassman, Denis Sasseville, Ivan V. Litvinov

    Background The incidence of cutaneous malignant melanoma (CMM) is on the rise in many parts of the world. However, there is limited knowledge on the epidemiology of CMM in Canada. Objective To conduct a comprehensive population-based study of CMM in Canada. Methods We examined patient clinical and pathological characteristics, incidence and mortality trends of CMM using 3 independent population-based registries. Results 72,565 Canadian patients were diagnosed with CMM during 1992-2010 of which 47.5% were females. Average age at the time of diagnosis was 56.5 years for females and 60.4 years for males. We report a steady increase in CMM incidence and mortality rates in both sexes. The overall incidence rate of CMM in Canada was 12.29 cases per 100,000 individuals per year. We also report important differences in the incidence and mortality rates between Canadian provinces and territories, where the highest incidence of this cancer was documented in Nova Scotia and Prince Edwards Island. Limitations Data on race, clinical disease stage and Breslow’s depth of CMM was not available. Conclusions This study, for the first time, defines the disease burden of CMM in Canada and highlights important longitudinal, geographic and spatial differences in the distribution of CMM in this country.

  • Psoriasis is not associated with cognition, brain imaging markers and risk of dementia: the Rotterdam Study
    J. Am. Acad. Dermatol. (IF 6.898) Pub Date : 2018-08-06
    Elena Pezzolo, Unal Mutlu, Meike W. Vernooij, Emmilia A. Dowlatshahi, Paolo Gisondi, Giampiero Girolomoni, Tamar Nijsten, M. Arfan Ikram, Marlies Wakkee

    Background Based on increased cardio-metabolic comorbidities, inflammation and an overlap in genetics with Alzheimer’s disease, psoriasis patients may be at risk for cognitive dysfunction and dementia. Objective To compare cognition, magnetic resonance imaging (MRI)-markers and dementia risk in psoriasis and non-psoriasis participants in the population-based Rotterdam Study. Methods We identified 318 psoriatic and 9678 non-psoriatic participants (mean age: 66.1 years, 58% women). The association of psoriasis with cognitive function, mild cognitive impairment (MCI) and MRI-markers of brain damage was examined by linear and logistic regression. Dementia risk was calculated using Cox regression. Models were adjusted for age, gender, education and cardio-vascular risk factors. Results Cognitive test scores and volumetric, microstructural, focal measures on brain MRI did not differ between psoriasis (28% systemic/UV treatment) and non-psoriasis participants and psoriasis was not associated with MCI (adjusted odd ratio 0.87, (95% Confidence Interval (CI): 0.53-1.43)). During 115.000 person-years of follow-up, 810 incident dementia cases (15 among psoriasis patients) occurred. After adjusting for confounders, psoriasis was associated with a lower risk of developing dementia (adjusted hazard ratio 0.50, (95% CI: 0.28-0.91)). Limitations Limited dementia cases among psoriasis patients. Conclusions In this population-based study, psoriasis was not associated with preclinical markers or higher dementia risk.

  • Dupilumab does not affect correlates of vaccine-induced immunity: a randomized, placebo-controlled trial in adults with moderate-to-severe atopic dermatitis
    J. Am. Acad. Dermatol. (IF 6.898) Pub Date : 2018-08-06
    Andrew Blauvelt, Eric L. Simpson, Stephen K. Tyring, Lisa A. Purcell, Brad Shumel, Christopher D. Petro, Bolanle Akinlade, Abhijit Gadkari, Laurent Eckert, Neil M.H. Graham, Gianluca Pirozzi, Robert Evans

    Background The impact of dupilumab, an anti-interleukin (IL)-4Rα antibody that inhibits IL-4/IL-13 signaling, on vaccine responses in atopic dermatitis (AD) patients is unknown. Objectives To assess T-cell-dependent and -independent humoral responses to tetanus and meningococcal vaccines, IgE seroconversion to tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccination, and dupilumab efficacy and safety. Methods In a randomized, double-blinded, placebo-controlled study (NCT02210780), adults with moderate-to-severe AD received dupilumab (300 mg) or placebo weekly for 16 weeks, and single doses of Tdap and quadrivalent meningococcal polysaccharide vaccines at Week 12. Primary endpoint was proportion of patients achieving satisfactory IgG response to tetanus toxoid at Week 16. Results 178 patients completed the study. Similar positive responses with dupilumab/placebo to tetanus (83.3%/83.7%) and meningococcal polysaccharide (86.7%/87.0%) were achieved. Dupilumab significantly decreased total serum IgE; most dupilumab-treated patients were Tdap IgE-seronegative at Week 32 (62.2%/34.8%; dupilumab/placebo). Dupilumab improved key AD efficacy endpoints (P<0.001). Injection-site reactions and conjunctivitis were more common with dupilumab; AD exacerbations more frequent with placebo. Limitation Patients’ prior vaccination status was not available before enrollment. Conclusions Dupilumab did not affect responses to the vaccines studied, significantly decreased IgE, and improved measures of AD severity versus placebo, with an acceptable safety profile.

  • Identification of patients at risk for metastasis using a prognostic 31-gene expression profile in subpopulations of melanoma patients with favorable outcomes by standard criteria
    J. Am. Acad. Dermatol. (IF 6.898) Pub Date : 2018-08-04
    Brian R. Gastman, Pedram Gerami, Sarah J. Kurley, Robert W. Cook, Sancy Leachman, John T. Vetto

    Background A substantial number of patients who relapse and die from cutaneous melanoma (CM) are categorized as low-risk by traditional staging factors. The 31-gene expression profile (31-GEP) test independently stratifies metastatic risk for CM patients as low (Class 1; 1A lowest risk) or high (Class 2; 2B highest risk). Objective To assess risk prediction by a 31-GEP test within three American Joint Committee on Cancer low-risk CM populations: sentinel lymph node (SLN)-negative, stage I-IIA, or thin (≤1mm, T1) tumors. Methods Three previous validation studies provided a non-overlapping cohort of 690 patients with 31-GEP results, staging information, and survival outcomes. Kaplan-Meier and Cox regression analysis were performed. Results Results included the identification of 70% of SLN-negative patients who metastasized as Class 2; reduced recurrence-free survival for patients with thin tumors and Class 2B biology compared to Class 1A biology (p<0.0001); and, determination of the 31-GEP test as an independent predictor of risk compared to traditional staging factors in stage I-IIA patients. Limitations Diagnoses spanned multiple versions of pathologic staging criteria. Conclusions The 31-GEP test identifies high-risk patients who are likely to recur or die from melanoma within low-risk groups with SLN negative disease, stage I-IIA, and thin tumor CM subpopulations.

  • Local radiation and phototherapy most cost-effective treatments for stage IA mycosis fungoides: a comparative decision-analysis model in the United States
    J. Am. Acad. Dermatol. (IF 6.898) Pub Date : 2018-08-03
    Fan Di Xia, Bart S. Ferket, Victor Huang, Robert S. Stern, Peggy A. Wu

    BackgroundTreatments for early stage mycosis fungoides (MF) include topical steroids, topical nitrogen mustard, topical bexarotene, narrowband UVB (NBUVB), psoralen UVA (PUVA), and local radiation. The relative cost-effectiveness of each treatment given differences in treatment failure, disease progression, and therapy escalation is not established.ObjectiveTo compare the cost-effectiveness (CE) of treatment options for stage IA MF.MethodsA state-transition model was constructed with health states of Stage IA-IV disease, no MF, and death. Treatment-specific remission and relapse rates were obtained from the literature. Lifetime costs were calculated accounting for medications, office visits, laboratory monitoring, related procedures, work absences, and travel.ResultsThe order of cost-effectiveness was: local radiation ($225,399 for 15.40 life-years, LYs), NBUVB ($344,728 for 15.17 LYs), PUVA ($371,741 for 15.07 LYs), topical corticosteroids ($469,354 for 14.65 LYs), topical nitrogen mustard ($951,662 for 14.29 LYs), and topical bexarotene ($11,892,496 for 13.55 LYs). Sensitivity analyses confirmed the CE rankings.LimitationsWe assumed constant probability of response, relapse rates, and 3-month treatment intervals.ConclusionLocal radiation is most cost effective for limited local disease while phototherapy (NBUVB or PUVA) is cost effective for generalized disease. Our findings can serve to inform future studies and recommendations regarding stage IA MF therapy selection.

  • The first 30 years of the American Academy of Dermatology skin cancer screening program: 1985-2014
    J. Am. Acad. Dermatol. (IF 6.898) Pub Date : 2018-07-26
    Jean-Phillip Okhovat, Derek Beaulieu, Hensin Tsao, Allan C. Halpern, Dominique S. Michaud, Shimon Shaykevich, Alan C. Geller

    BackgroundThe incidence of melanoma is rising faster than that of any other preventable cancer in the United States. The American Academy of Dermatology has sponsored free skin cancer education and screenings conducted by volunteer dermatologists in the United States since 1985.ObjectiveWe aimed to assess the American Academy of Dermatology's national skin cancer screening program from 1986 to 2014 by analyzing the risk factor profile, access to dermatologic services, and examination results.MethodsWe conducted several detailed statistical analyses of the screening population.ResultsFrom 1986 to 2014, records were available for 2,046,531 screenings, 1,963,141 (96%) of which were subjected to detailed analysis. Men comprised 38% of all participants. The number of annual screenings reached approximately 100,000 in 1990 and remained relatively stable thereafter. From 1991 to 2014 (data for 1995, 1996 and 2000 were unavailable), clinical diagnoses were rendered for 20,628 melanomas, 156,087 dysplastic nevi, 32,893 squamous cell carcinomas, and 129,848 basal cell carcinomas. Only 21% of screenees had a regular dermatologist. Those with a clinical diagnosis of skin cancer were more likely than the general screening population to be uninsured.LimitationsInability to verify clinical diagnoses histopathologically.ConclusionOur findings suggest that the SPOTme program has detected thousands of skin cancers that may have gone undetected or experienced a delay in detection.

  • Melanoma risk after in vitro fertilization: A review of the literature
    J. Am. Acad. Dermatol. (IF 6.898) Pub Date : 2018-07-25
    Juliana Berk-Krauss, Amy Kalowitz Bieber, Maressa C. Criscito, Jane M. Grant-Kels, Marcia S. Driscoll, Martin Keltz, Miriam Keltz Pomeranz, Kathryn J. Martires, Tracey N. Liebman, Jennifer A. Stein

    Background The role of female sex hormones in the pathogenesis of malignant melanoma (MM) remains controversial. While melanocytes appear to be hormonally responsive, the effect of estrogen on MM cells is less clear. Available clinical data does not consistently demonstrate that increased endogenous hormones from pregnancy, or increased exogenous hormones from oral contraceptive pills and hormone replacement, impact MM prevalence and outcome. Objective We sought to examine potential associations between in vitro fertilization (IVF) and melanoma. Methods A literature review was conducted. Primary outcomes were reported as associations between IVF and melanoma risk, as compared to the general population. Secondary outcomes included associations stratified by type of IVF regimen and subgroup, such as parous versus nulliparous patients. Results Eleven studies met our inclusion criteria. Five studies found no increased risk of MM among IVF users as compared to the general population. Two studies found an increase in MM in clomiphene users. Four studies found an increase in MM among patients who were gravid or parous either before or after IVF. Conclusions The reviewed studies do not reveal consistent patterns of association between IVF and MM among all infertile women. However, the data indicates that there may be an increased risk of MM in ever-parous patients treated with IVF. High-quality studies, which include a large number of MM cases and control for well-established MM risk factors, are needed to adequately assess the relationship between IVF and MM, particularly among ever-parous women.

  • Allergic Contact Dermatitis To Personal Care Products And Topical Medications In Adults With Atopic Dermatitis
    J. Am. Acad. Dermatol. (IF 6.898) Pub Date : 2018-07-25
    Supriya Rastogi, Kevin R. Patel, Vivek Singam, Jonathan I. Silverberg

    Background Atopic dermatitis (AD) is associated with skin-barrier disruption, immune dysregulation, and application of emollients and topical medications, which may predispose towards developing allergic contact dermatitis (ACD). Objective(s) To determine the predictors of ACD and relevant allergens in AD. Methods A retrospective chart review was performed of 502 adults (age ≥18 years) who were patch-tested to an expanded allergen series from 2014-2017. Results Overall, 108 (21.5%) had current AD and 109 (21.7%) had past AD. Patients with vs. without current AD had similar proportions of any positive (+/++/+++: 80 [74.1%] vs. 254 [64.5%]; Chi-square, P=0.06), stronger (++/+++: 34 [31.5%] vs. 102 [25.9%], P=0.25) and irritant (56 [51.9%] vs. 188 [47.7%], P=0.45) patch test reactions. AD patients had significantly higher rates of positive reactions to ingredients in personal care products and topical medications, including fragrance mix II (P=0.04), lanolin (P=0.03), bacitracin (P=0.04), cinnamal (P=0.02), budesonide (P=0.01), tixocortol (P=0.02), and chlorhexidine (P=0.001); relevance was established in >90% of these reactions. Polysensitization occurred more commonly in patients with vs. without AD (35 [32.4%] vs. 75 [19.0%], P=0.01). Limitations Study performed at a single center. Conclusion AD patients had more positive patch test reactions to ingredients in personal care products, topical steroids and antibiotics.

  • Journal of the American Academy of Dermatology: Original article Comorbidities in alopecia areata: A systematic review and meta-analysis
    J. Am. Acad. Dermatol. (IF 6.898) Pub Date : 2018-07-18
    Solam Lee, Hanil Lee, Chung Hyeok Lee, Won-Soo Lee

    Background Alopecia areata (AA) may be associated with various systemic diseases according to several studies. Objective To identify prevalent and incident diseases in AA patients and quantify their prevalence and odds and hazard ratio compared with those in non-AA controls. Methods A systematic review of the studies published before February 28, 2018 was performed using MEDLINE, Embase, Web of Science and Cochrane Library databases. Observational studies on prevalent or incident diseases in AA patients were included, whereas studies limited to pediatrics or providing only laboratory results or continuous data were excluded. Inverse variance method with random-effects model was used for meta-analyses. Results Eighty-seven studies were analyzed. Atopic diseases, metabolic syndrome, Helicobacter pylori infection, lupus erythematosus, iron deficiency anemia, thyroid diseases, psychiatric diseases, vitamin D deficiency, and audiologic and ophthalmic abnormalities were more prevalent in AA patients. AA patients had a higher risk of developing autoimmune diseases. Limitations Some diseases were investigated by an insufficient number of studies to be meta-analyzed. Meta-analysis on incident diseases was not performed owing to the limited availability on cohort studies. Conclusion AA is associated with various systemic and psychiatric diseases. Physicians are encouraged to evaluate and manage potential comorbid conditions to achieve better outcomes.

  • Bullous disorders associated with anti-PD-1 and anti-PD-L1 therapy: A retrospective analysis evaluating the clinical and histopathologic features, frequency, and impact on cancer therapy
    J. Am. Acad. Dermatol. (IF 6.898) Pub Date : 2018-07-17
    Jacob Siegel, Mariam Totonchy, William Damsky, Juliana Berk-Krauss, Frank Castiglione, Mario Sznol, Daniel P. Petrylak, Neal Fischbach, Sarah B. Goldberg, Roy H. Decker, Angeliki M. Stamatouli, Navid Hafez, Earl J. Glusac, Mary M. Tomayko, Jonathan S. Leventhal

    Background Bullous disorders associated with anti-PD-1/PD-L1 therapy are increasingly reported and may pose distinct therapeutic challenges. Their frequency and impact on cancer therapy are not well established. Objective To evaluate the clinical and histopathologic findings, frequency, and impact on cancer therapy of bullous eruptions due to anti-PD-1/PD-L1 therapy. Methods We retrospectively reviewed the medical records of patients evaluated by the onco-dermatology clinic and consultative service of Yale New Haven Hospital from 2016 to 2018. Results We identified 9 patients who developed bullous eruptions of 853 patients (∼1%) treated with anti-PD-1/PD-L1 therapy at our institution during the study period: 7 presented with bullous pemphigoid, 1 presented with bullous lichenoid dermatitis, and 1 presented with linear IgA bullous dermatosis in the context of vancomycin therapy. 8 patients required systemic steroids, 5 required maintenance therapy, and 8 required interruption of immunotherapy. All 9 patients had an initial positive tumor response or stable disease, but 4 went on to develop disease progression. Limitations This was a retrospective study from a single tertiary care center. Conclusion Bullous disorders developed in approximately 1% of patients treated with anti-PD-1/PD-L1 therapy at our institution and frequently resulted in interruption of immune therapy and management with systemic corticosteroids and occasionally steroid-sparing agents.

  • Antiandrogen therapy with spironolactone for the treatment of hidradenitis suppurativa
    J. Am. Acad. Dermatol. (IF 6.898) Pub Date : 2018-07-10
    Nicole M. Golbari, Martina L. Porter, Alexa B. Kimball

    Background Hormonal therapy is a potential treatment for hidradenitis suppurativa (HS). However, little data exists describing the efficacy of spironolactone in HS treatment. Objective To assess whether spironolactone treatment improves HS disease severity and patient reported pain. Methods We performed a single center chart review of female HS patients treated with spironolactone between 2000 and 2017. Primary outcome measurements included the HS Physician Global Assessment (HSPGA), Hurley Staging, inflammatory lesion count, fistula count, and a numeric rating scale for pain. Results Subjects on average were exposed to 75mg of spironolactone daily over a 7.1-month follow-up period. Patients achieved significant disease improvement with regards to pain (Δ-1.5, P=.01), inflammatory lesions (Δ-1.3, P=.02), and HSPGA (Δ-0.6, P<.001). As expected, no change was found for Hurley stage (Δ0, P=.32) or fistulas (Δ0, P=.73). There was no difference in improvement between subjects who received less than 75mg daily (n= 25, average 45mg/day) and those who received greater than 100mg daily (n=21, average 112mg/day). Limitations Retrospective nature, limited sample size, and variations in severity measures documented were limiting factors. Conclusions Management of HS with spironolactone reduces lesion count, HSPGA and pain. Lower doses appear to be effective and may be an appropriate option for patients with tolerability concerns.

  • Topical Glycopyrronium Tosylate for the Treatment of Primary Axillary Hyperhidrosis: Results from the ATMOS-1 and ATMOS-2 Phase 3 Randomized Controlled Trials
    J. Am. Acad. Dermatol. (IF 6.898) Pub Date : 2018-07-10
    Dee Anna Glaser, Adelaide A. Hebert, Alexander Nast, William P. Werschler, Lawrence Green, Richard Mamelok, Janice Drew, John Quiring, David M. Pariser

    Background Glycopyrronium tosylate (GT) is a topical anticholinergic developed for once-daily treatment of primary axillary hyperhidrosis. Objective Assess the efficacy and safety of GT for primary axillary hyperhidrosis. Methods ATMOS-1 and ATMOS-2 were replicate randomized, double-blind, vehicle-controlled, 4-week phase 3 trials. Patients were randomized 2:1 to GT 3.75% or vehicle applied once daily to each axilla for 4 weeks. Coprimary endpoints were responder rate (≥4-point improvement from Baseline) on Item 2 (sweating severity) of the Axillary Sweating Daily Diary (ASDD), a newly developed patient-reported outcome, and absolute change from Baseline in axillary gravimetric sweat production at Week 4. Safety evaluation included treatment-emergent adverse events (TEAEs). Results Pooled data, consistent with individual trial results show significantly more GT-treated patients achieved ASDD Item 2 response versus vehicle (59.5% vs 27.6%) and had reduced sweat production from Baseline (-107.6mg/5min vs -92.1mg/5min) at Week 4 (P<0.001 for both coprimary endpoints). Most TEAEs were mild or moderate and infrequently led to discontinuation. Limitations Short trial duration and inherent challenges in gravimetrically assessing sweat production. Conclusions Daily, topically-applied GT over 4 weeks reduced sweating severity as measured by ASDD-Item 2, reduced sweat production as measured gravimetrically, and was generally well tolerated in primary axillary hyperhidrosis patients.

  • Efficacy, Safety, and Comparison of Sonic Hedgehog Inhibitors in Basal Cell Carcinomas: A Systematic Review and Meta-Analysis
    J. Am. Acad. Dermatol. (IF 6.898) Pub Date : 2018-07-10
    Pingxing Xie, Philippe Lefrançois

    Background Sonic Hedgehog Inhibitors (SHHi) provide an additional treatment option for basal cell carcinomas (BCC), especially for metastatic or locally advanced BCC. However, studies have been heterogeneous and lacking direct comparisons between molecules. Objective To determine the efficacy and safety of SHHi, as a class of molecules, for treating BCC, and to compare them individually. Methods We performed a PRISMA-compliant systematic review of studies followed by a meta-analysis. Results Eighteen articles were included in our meta-analysis; sixteen articles were combined for efficacy and sixteen for safety. In locally advanced BCC, Overall Response Rates (ORR) were similar for vismodegib and sonidegib (69% vs. 57%), but not Complete Response Rates (31% vs. 3%). In metastatic disease, the ORR of vismodegib was 2.7-fold higher than the ORR of sonidegib (39% vs. 15%). For side effects affecting a majority of patients, combined prevalences were 67.1%, 54.1% and 57.7% for muscle spasms, dysgeusia, and alopecia, respectively, in similar proportions for sonidegib and vismodegib. Patients receiving sonidegib experienced more upper GI distress than patients receiving vismodegib. Conclusions SHHi as a class lead to partial responses for locally advanced BCC disease. Side effects are similar across molecules, common, associated with high discontinuation rates, and warrant discussion beforehand.

  • Intralesional Immunotherapy for the Treatment of Warts: A Network Meta-analysis
    J. Am. Acad. Dermatol. (IF 6.898) Pub Date : 2018-07-10
    Samar Salman, Mohamed Shehata Ahmed, Ahmed Mohamed Ibrahim, Omar Mohamed Mattar, Hassan El-Shirbiny, Sameh Sarsik, Ahmed M. Afifi, Ruba Marwan Anis, Nadim Aiman Yakoub Agha, Abdelrahman Ibrahim Abushouk

    Background Without clear evidence, selecting among the existing immunotherapeutic options for warts remains challenging. Objective Through network meta-analyses, we aimed to evaluate the comparative efficacy of different intralesional immunotherapeutic modalities. Methods We included randomized controlled trials (RCTs) comparing intralesional immunotherapeutic modalities to cryotherapy, placebo or imiquimod. All outcomes were presented as odds ratio (OR) with 95% confidence-interval. Both conventional and network meta-analyses (with a frequentist approach) were conducted on R software. The P-score was used to rank different treatments. Results Network meta-analysis of 17 RCTs (1676 patients) showed that PPD (OR=39.56), MMR (OR=17.46) and INF-β (OR=15.55) had the highest efficacy in terms of complete recovery at the primary site, compared to placebo. Regarding complete recovery at the distant site, autoinoculation (OR=79.95), PPD (OR=42.95) and MMR (OR=15.39) were all statistically superior to placebo. According to the P-score, MMR was more effective than other modalities in reducing recurrence rate at the same site. Limitations Relatively-small sample size in some comparisons and variability in baseline characteristics. Conclusion PPD and MMR were the most effective in achieving complete primary and distant recovery (along with autoinoculation for distant recovery) and reducing the recurrence rate at the same site, compared to cryotherapy and other immunotherapeutic modalities.

  • Mohs micrographic surgery (MMS) with MART-1 immunostaining for atypical intraepidermal melanocytic proliferation (AIMP)
    J. Am. Acad. Dermatol. (IF 6.898) Pub Date : 2018-07-10
    Jeremy R. Etzkorn, Olivia S. Jew, Thuzar M. Shin, Joseph F. Sobanko, Donald E. Neal, Christopher J. Miller

    Background The efficacy of Mohs micrographic surgery (MMS) for atypical intraepidermal melanocytic proliferation (AIMP) is unknown. Objective To ascertain the frequency of diagnostic change to melanoma (upstaging) and the frequency of local recurrence after MMS for AIMP. A secondary outcome was the frequency of subclinical spread (defined as the requirement for greater than one stage of MMS to achieve tumor-free margins). Methods Retrospective, cross-sectional study of 223 AIMP (with 92.4% located on the head, neck, hand, foot, or pretibial leg) treated with MMS with MART-1 immunostaining. Results Upstaging to unequivocal MIS or invasive melanoma was identified in 18.8% (42/223) of all AIMP. The local recurrence rate was 0% (0/223) with a mean follow-up time of 2.7 years (998 days). Subclinical spread was present in 23.8% (53/223) of AIMP. Limitations Single site, retrospective design, observational study, lack of objective criteria to diagnose AIMP Conclusion MMS with MART-1 immunostaining achieves excellent local control of specialty-site AIMP and permits definitive removal of subclinical spread prior to reconstruction. The central debulking excision should be evaluated with formalin-fixed paraffin-embedded sections, since a significant percentage of AIMP are reclassified as MIS or invasive melanoma.

  • The ALT-70 Predictive Model Outperforms Thermal Imaging for the Diagnosis of Lower Extremity Cellulitis: A Prospective Evaluation
    J. Am. Acad. Dermatol. (IF 6.898) Pub Date : 2018-07-10
    David G. Li, Anna K. Dewan, Fan Di Xia, Hasan Khosravi, Cara Joyce, Arash Mostaghimi

    Background We previously demonstrated dermatology consultation to substantially reduce cellulitis misdiagnosis rates; however, broad implementation is impractical due to existing practice patterns and reimbursement systems. Meanwhile, efforts to improve diagnostic accuracy have culminated in point-of-care tools, including the ALT-70 predictive model for lower extremity cellulitis and thermal imaging. Objective To prospectively evaluate the performance of ALT-70 and thermal imaging in diagnosing lower extremity cellulitis in a head-to-head comparison. Methods We collected ALT-70 and thermal imaging data from patients with presumed lower extremity cellulitis and compared classification measures and accuracy for ALT-70, thermal imaging, and combination testing (ALT-70 plus thermal imaging). Results We enrolled 67 patients with ALT-70 and thermal imaging data. ALT-70 conferred the highest sensitivity (97.8%) and negative predictive value (90.9%), while combination testing had the highest specificity (71.4%) and positive predictive value (86.6%). ALT-70 had improved classification measures compared to thermal imaging. Combination testing conferred a marginal benefit to ALT-70 alone. Limitations Single-center design may limit generalizability. Conclusion ALT-70 outperformed thermal imaging in diagnosing lower extremity cellulitis. The accuracy of the ALT-70 was high and consistent with previously published reports. Broad implementation of ALT-70 into clinical practice may decrease misdiagnosis rates of lower extremity cellulitis.

  • Drug-Induced Phototoxicity: A Systematic Review
    J. Am. Acad. Dermatol. (IF 6.898) Pub Date : 2018-07-10
    Whan B. Kim, A.J. Shelley, K. Novice, J. Joo, H.W. Lim, S.J. Glassman

    Background Phototoxicity has been attributed to numerous oral drugs over the past 60 years. Objective Determine the quality of evidence supporting suspected phototoxicity from oral drugs Methods MEDLINE and EMBASE databases were searched for all studies containing original data for drug-induced phototoxicity published between May 1959 and December 2016. Study quality was assessed using a modified GRADE scale. Results The review included 240 eligible studies with a total of 2466 subjects. There were 1134 cases of suspected phototoxicity associated with 129 drugs. Most associations were supported by either very low-quality or low-quality evidence (89.1% of the studies). Medications supported by stronger evidence were vemurafenib, non-steroidal anti-inflammatory drugs (NSAIDs), and antibiotics, specifically fluoroquinolones and tetracyclines. The most frequently reported drugs were: vemurafenib, voriconazole, doxycycline, hydrochlorothiazide, amiodarone, and chlorpromazine. Photobiologic evaluation was performed in only 56 studies (23.3%), while challenge-rechallenge was done in 10% of cases. Limitations Only English-language publications were reviewed. Phototoxicity cases incorrectly termed photoallergy would not have been included. Conclusions Most purported associations between oral drugs and phototoxicity are not supported by high-quality evidence. Despite the variable quality of data, clinicians should be aware of the possible consequences of chronic use of culprit drugs.

  • “Comparing the eighth and the seventh editions of the ajcc staging system and the brigham and women’s hospital alternative staging system for cutaneous squamous cell carcinoma: implications for clinical practice”
    J. Am. Acad. Dermatol. (IF 6.898) Pub Date : 2018-07-10
    J. Cañueto, J. Burguillo, D. Moyano-Bueno, A. Viñolas-Cuadros, A. Conde-Ferreirós, Luis Antonio Corchete-Sánchez, J. Pérez-Losada, C. Román-Curto

    Background The new 8th edition of the American Joint Committee on Cancer (AJCC) staging system incorporates changes regarding cutaneous squamous cell carcinoma (CSCC). Objectives We aimed to compare the 8th edition of the AJCC (AJCC-8) staging system with the previous 7th edition (AJCC-7) and the Brigham and Women’s Hospital alternative staging system, to identify their usefulness and the utility of their risk factors in defining prognostic groups in CSCC. Methods A series of 186 CSCCs of the head and neck was retrospectively collected. All three staging systems were compared in their ability to predict poor prognosis. Binary logistic regression models were built to determine which risk factors were most relevant. Results Poor prognosis was mainly associated with T2-AJCC-7, with T2b/T3-BWH’s and with T3-AJCC-8. The AJCC-8 and the BWH’s staging systems displayed overlap between each other in predicting poor prognosis and both were superior to the AJCC-7. The new risk factors incorporated into the AJCC-8 and the poor degree of differentiation were independently associated with poor outcome. Limitations Retrospective study and few cases with bone invasion. Conclusions The AJCC-8 is more distinctive, monotonous and homogeneous than the AJCC-7 and shows some overlap in the stratification of tumors with the BWH’s system.

  • Methotrexate for alopecia areata: a systematic review and meta-analysis
    J. Am. Acad. Dermatol. (IF 6.898) Pub Date : 2018-07-10
    Kevin Phan, Vignesh Ramachandran, Deshan Frank Sebaratnam

    Background Methotrexate has been used both as an adjunct for low-risk maintenance therapy after initiation with corticosteroids for alopecia areata (AA) and as standalone therapy in some investigations, based on a lack of definitive evidence/guidelines. Objective To (1) determine the efficacy and risks associated with methotrexate therapy for AA (2) determine differences efficacy of combination with corticosteroids versus standalone treatment, and (3) determine relative efficacy of methotrexate in adult versus pediatric populations. Methods A systematic review and meta-analysis was performed according to recommended PRISMA guidelines. Results Methotrexate has reasonable effectiveness in patients with severe AA, and that adults appear to be more responsive to methotrexate treatment compared to pediatric cases. Methotrexate in conjunction with corticosteroids result in higher good/complete response rates compared to those treated with methotrexate alone. A large proportion of recurrence rates occurred in the setting of tapering treatment. Complication rates were acceptable and similar between adults and pediatric cases. Limitations Studies reviewed were retrospective observational studies with heterogeneity between centers in terms of dosages/protocols for methotrexate use in AA, and adjunctive treatments with a lack of data beyond one year. Conclusion Methotrexate is an effective monotherapy or adjunct to corticosteroid in the treatment of severe AA.

  • CME Part I Psoriasis: Which Therapy for Which Patient Psoriasis comorbidities and preferred systemic agents
    J. Am. Acad. Dermatol. (IF 6.898) Pub Date : 2018-07-11
    Shivani B. Kaushik, Mark G. Lebwohl

    Psoriasis is a systemic inflammatory disease associated with increased risk of comorbidities such as psoriatic arthritis, Crohn disease, malignancy, obesity and cardiovascular diseases. All these factors have a significant impact on the decision to use one therapy over another. The past decade has seen a paradigm shift in our understanding of the pathogenesis of psoriasis which has led to identification of new therapeutic targets. Several new drugs have gained FDA approval, expanding the psoriasis armamentarium but still a large number of patients continue to be untreated or undertreated. Treatment regimens for psoriasis patients should be tailored to meet specific needs based on disease severity, impact on quality of life, response to previous therapies and presence of comorbidities. Part 1 of this CME article will focus on specific comorbidities and provide insights to choose appropriate systemic treatment in patients with moderate to severe psoriasis.

  • CME Part II Psoriasis: Which Therapy for Which Patient Focus on special populations and chronic infections
    J. Am. Acad. Dermatol. (IF 6.898) Pub Date : 2018-07-11
    Shivani B. Kaushik, Mark G. Lebwohl

    Despite the availability of several new systemic agents for psoriasis treatment, it can be challenging to choose the right therapy in certain patient populations. There are few up-to-date reviews on systemic drugs for moderate to severe psoriasis in pregnant and pediatric patients and in patients with concomitant chronic infections such as hepatitis, HIV and latent tuberculosis. These groups are usually excluded from clinical trials and much of the available evidence is based on anecdotal case reports and case series. Being a chronic disease, psoriasis requires long-term treatment and there are concerns of adverse maternal-fetal outcomes, long term side-effects in children and reactivation of latent infections with use of systemic agents in these patients. Part 2 of this CME article will provide insights for choosing appropriate systemic agents for treating moderate-to-severe psoriasis in pregnant and pediatric patients and in the setting of chronic infections such as hepatitis, HIV and latent tuberculosis.

  • Drug Utilization Patterns and Adherence in Patients on Systemic Medications for the Treatment of Psoriasis: A Retrospective Comparative Cohort Study
    J. Am. Acad. Dermatol. (IF 6.898) Pub Date : 2018-07-05
    Erica D. Dommasch, Moa P. Lee, Cara J. Joyce, Elizabeth M. Garry, Joshua J. Gagne

    BackgroundNon-adherence to systemic treatments for psoriasis leads to treatment failure and increased healthcare utilization.ObjectiveExamine drug utilization patterns and adherence for new users of systemic medications for psoriasis.MethodsWe conducted a retrospective comparative cohort study using a large US health insurance claims database including psoriasis patients who were new users of acitretin, adalimumab, etanercept, methotrexate, and ustekinumab. Adherence was measured using proportion of days covered (PDC) dichotomized as adherent (≥0.80) or non-adherent (<0.80). Odds ratios (ORs) and 95% confidence intervals (CIs) comparing adherence to each exposure (acitretin, adalimumab, etanercept, and ustekinumab) to the referent (methotrexate) were estimated via logistic regression, with pairwise 1:1 propensity score (PS) matching to adjust for potential confounders.Results22,742 patients were new users of systemic medications. Compared to methotrexate, we report greater adherence among users of adalimumab, etanercept, and ustekinumab [PS-matched OR (95% CI) = 2.24 (2.05, 2.45), 1.77 (1.63, 1.92), and 2.54 (2.24, 2.87), respectively], and lower adherence among new users of acitretin [0.57 (0.50, 0.63)].LimitationsUnable to evaluate reasons for discontinuation.ConclusionsWe report greater adherence in new users of biologics when compared to methotrexate. Further research is needed to understand overall low adherence to systemic medications for psoriasis.

  • Atypical Fibroxanthoma: Systematic Review and Meta-analysis of Treatment with Mohs Micrographic Surgery or Excision
    J. Am. Acad. Dermatol. (IF 6.898) Pub Date : 2018-07-05
    Stanislav N. Tolkachjov, Benjamin F. Kelley, Fares Alahdab, Patricia J. Erwin, Jerry D. Brewer

    BackgroundAtypical fibroxanthoma (AFX) is a fibrohistiocytic tumor with relatively high local recurrence rates, but low metastatic potential. Wide local excision (WLE) and Mohs micrographic surgery (MMS) are common treatments, although no consensus exists regarding optimal therapy.ObjectiveTo systematically review evidence of AFX recurrence and metastatic rates following different surgical modalities.MethodsData Sources: Comprehensive search from 1946 or database inception to March 20, 2017.Study SelectionIncluded studies had 5 or more patients with atypical fibroxanthoma treated surgically.Data Extraction and SynthesisTwo reviewers independently abstracted the data. Risk of bias was assessed with Newcastle-Ottawa Scale.Main Outcomes and MeasuresRecurrence and metastasis.Results23 studies were selected (907 patients and 914tumors). 175 cases were treated with MMS (recurrence rate, 2.0% [95% CI, 0%-4.1%]; metastatic rate, 1.9% [95% CI, 0.1%-3.8%]). 732 were treated with WLE (recurrence rate, 8.7% [95% CI,5%-12.3%]; metastasis rate, 1% [95% CI, 0.2%-1.9%]). Among immunocompromised patients, no recurrence or metastases developed in the MMS subgroup, whereas 4/10 recurred and 1/10 metastasized in the WLE subgroup.Limitationslow quality of published studiesConclusionMMS for atypical fibroxanthoma is associated with a lower recurrence rate than wide local excision.

  • A Phase 2, Randomized Dose-Finding Study of Tapinarof (GSK2894512 Cream) for the Treatment of Atopic Dermatitis
    J. Am. Acad. Dermatol. (IF 6.898) Pub Date : 2018-07-03
    Johnny Peppers, Amy S. Paller, Tomoko Maeda-Chubachi, Sterling Wu, Kevin Robbins, Kelly Gallagher, John E. Kraus

    Background Safe and efficacious topical treatments are needed for atopic dermatitis (AD). Objective We assessed the safety and efficacy of tapinarof cream (2 concentrations; 2 application frequencies) in patients with AD. Methods Double-blind, vehicle-controlled, randomized, 6-arm trial (1:1:1:1:1:1) in patients aged 12-65 years, with body surface area (BSA) involvement ≥5% and ≤35% and Investigator Global Assessment (IGA) ≥3 (moderate-severe) at Baseline. Primary endpoint included IGA score of clear or almost clear (0 or 1), and minimum 2-grade improvement (“treatment success”) at Week 12. Secondary analyses: ≥ 75% improvement in Eczema Area Severity Index (EASI 75), reduction of numeric rating scale (NRS) Itch from Baseline, and other prespecified endpoints. Results Treatment success rates at Week 12 were: 53% [1% BID]; 46% [1% QD]; 37% [0.5% BID]; 34% [0.5% QD]; 24% [vehicle BID]; 28% [vehicle QD]. The rate (53%) of 1% BID was statistically significantly higher than (24%) vehicle BID. Treatment success was maintained for 4 weeks after end of tapinarof treatment. Treatment-emergent adverse events (TEAE) were higher with tapinarof (93/165; 56%) vs. vehicle (34/82; 41%) and mild-to-moderate in intensity. Limitations Large confirmation trials are needed. Conclusions Tapinarof cream is efficacious and well tolerated in adolescent and adult patients with AD.

  • Apremilast for moderate hidradenitis suppurativa: results of a randomized controlled trial
    J. Am. Acad. Dermatol. (IF 6.898) Pub Date : 2018-07-03
    Allard R.J.V. Vossen, M.B.A. van Doorn, Hessel H. van der Zee, Errol P. Prens

    Background Effective anti-inflammatory treatments for hidradenitis suppurativa (HS) are limited. Objective To evaluate the efficacy and short-term safety of apremilast in patients with moderate HS. Methods Twenty patients with moderate HS were randomised in a 3 : 1 ratio, to receive blinded treatment with apremilast 30 mg twice daily or placebo for 16 weeks. The primary outcome was the Hidradenitis Suppurativa Clinical Response (HiSCR) at week 16. Linear mixed effects modeling (ANCOVA) was used to assess secondary clinical outcomes between treatment groups. Results The HiSCR was met in 8 of 15 (53.3%) patients in the apremilast group and none of 5 patients (0%) in the placebo group (P=0.055) at week 16. Moreover, apremilast-treated patients showed a significantly lower abscess and nodule count (mean difference -2.6; 95% confidence interval -6.0, -0.9; P=0.011), NRS for pain (-2.7; -4.5, -0.9; P=0.009) and itch (-2.8; -5.0, -0.6; P=0.015) over 16 weeks compared with placebo-treated patients. There was no significant difference in the DLQI over time between the two treatment groups (-3.4; -9.0, 2.3; P=0.230). The most frequently reported adverse events in the apremilast-treated patients were mild to moderate headache and gastro-intestinal symptoms, which have not resulted in drop-outs. Limitations Small number of patients, relatively short study duration. Conclusion Apremilast at a dose of 30 mg twice daily demonstrated clinically meaningful efficacy and was generally well tolerated in patients with moderate HS.

  • A Comparison of Skin Cancer Screening and Treatment Costs at a Massachusetts Cancer Center, 2008 versus 2013
    J. Am. Acad. Dermatol. (IF 6.898) Pub Date : 2018-07-03
    Frederick C. Morgan, Juanita Duran, Belen Fraile, Pritesh S. Karia, Jennifer Y. Lin, Patrick A. Ott, Emily Stamell Ruiz, David M. Wang, Yichen Zhang, Chrysalyne D. Schmults

    Background Temporal analyses of skin cancer costs are needed to examine how expenditure differences between diagnoses are changing. Objective To tabulate the costs of skin cancer-related care (SCRC), including both screening and treatment, at an academic cancer center at two time points. Methods Cost data (insurance and patient payments) at an academic cancer center from 2008 and 2013 were queried for International Classification of Diseases, Ninth Revision (ICD-9) codes pertaining to skin cancer. Screening costs were separated from treatment costs through associated Current Procedure Terminology (CPT) codes. Results The total annual cost of SCRC increased by 64%, the number of patients receiving SCRC increased by 45%, and the mean cost per patient treated increased by 13%. Screening accounted for 17% and 16% of total annual costs in 2008 and 2013, respectively. The mean cost per melanoma patient increased by 84%, which was the largest increase among skin cancer diagnoses. In 2013, the few melanoma patients treated with ipilimumab (n=48, 4% of melanoma patients) accounted for 42% of melanoma treatment costs and 20% of SCRC costs. Limitations Prescription costs were unavailable Conclusion Melanoma costs increased due to the introduction of ipilimumab. Ongoing studies are needed to monitor SCRC cost-effectiveness at a national level.

  • Natural History of Disease Activity and Damage in Patients with Cutaneous Lupus Erythematosus
    J. Am. Acad. Dermatol. (IF 6.898) Pub Date : 2018-06-30
    Khor Jia Ker, Noelle M. Teske, Rui Feng, Benjamin F. Chong, Victoria P. Werth

    BackgroundLong-term studies characterizing disease course of cutaneous lupus erythematosus (CLE) patients on standard-of-care treatments are lacking.ObjectiveWe characterized and compared disease course of CLE patients using Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI).Methods83 patients with CLASI scores collected from ≥3 study visits within 2 years had disease activity and damage trends calculated by average change scores (ACS). Trends were classified as “improved” (ACS ≤-3), “worsened” (ACS ≥+3), or “stable” (-3< ACS<+3). Linear regression models compared CLASI trends between groups.Results72.73% with initial CLASI activity (CLASI-A) >9 (N=33) had improved disease activity versus 14.00% with initial CLASI-A ≤9 (N=50). Linear regression analyses showed significant improvement in CLASI-A scores in patients with baseline CLASI-A >9 (p<0.0001), baseline CLASI damage (CLASI-D) ≥10 (p=0.0001), minority races (p<0.05), and CLE disease duration ≤1 year (p=0.01). 35.71% with baseline CLASI-D ≥10 (N=28) had improving disease damage versus 5.26% with initial CLASI-D=5-9 (N=19) and 0% with initial CLASI-D <5 (N=36) (p=0.0005).LimitationsLimitations include small sample size.ConclusionBaseline CLASI-A >9, minority race, and shorter disease duration predict CLE disease activity improvement. Baseline CLASI-D ≥10 is associated with disease damage improvement.

  • Ixekizumab provides superior efficacy compared to ustekinumab over 52-weeks of treatment: results from IXORA-S, a phase 3 study
    J. Am. Acad. Dermatol. (IF 6.898) Pub Date : 2018-06-30
    Carle Paul, Christopher E.M. Griffiths, Peter C.M. van de Kerkhof, Lluís Puig, Yves Dutronc, Carsten Henneges, Martin Dossenbach, Kristin Hollister, Kristian Reich

    BackgroundBiologics targeting interleukin (IL)-17A allow for rapid clearance of psoriatic plaques, with a clinically favorable safety profile.ObjectivesTo compare the safety and efficacy of ixekizumab, an IL-17A antagonist, versus the IL-12/23 inhibitor, ustekinumab, through 52 weeks of treatment in the head-to-head trial, IXORA-S.MethodsPatients were randomized to ixekizumab (N=136) or ustekinumab (N=166) and dosed per approved labels. After one year, efficacy was assessed via improvements in Psoriasis Area and Severity Index (PASI; 90% improvement=PASI 90), and static physician global assessment (sPGA) responses of (0) or (0,1), counting drop-outs as non-responders. Safety analyses included treatment-emergent adverse events (TEAEs).ResultsAt Week 52, significantly more ixekizumab-treated patients (p<0.01) reported PASI 90 (104, 76.5%), sPGA (0) (72, 52.9%), and sPGA (0,1) (110, 82.1%) responses, compared to ustekinumab-treated patients (PASI 90: 98, 59.0%; sPGA (0): 60, 36.1%; sPGA (0,1): 108, 65.1%). TEAE, serious AEs, and discontinuation rates were not different between the treatment groups. Injection site reactions occurred more frequently in the ixekizumab treatment group (IXE: 22, 16.3%, UST: 2, 1.2%; p<0.001).LimitationsThis study was not designed to compare safety endpoints related to rare events.ConclusionsIxekizumab showed superior efficacy and comparable safety outcomes versus ustekinumab through 52 weeks of treatment.

  • Part II: Onychomycosis: Treatment and Prevention of Recurrence
    J. Am. Acad. Dermatol. (IF 6.898) Pub Date : 2018-06-28
    Shari R. Lipner, Richard K. Scher

    Onychomycosis is a fungal nail infection caused by dermatophytes, non-dermatophytes, and yeast and is the most common nail disorder seen in clinical practice. It is an important problem, as it may cause local pain, paresthesias, difficulties performing activities of daily life, and impair social interactions. The epidemiology, risk factors, and clinical presentation and diagnosis of onychomycosis were discussed in the first article in this continuing medical education series. In this article, we review the prognosis and response to onychomycosis treatment, Food and Drug Administration approved medications for onychomycosis, as well as, off-label therapies and devices. Methods to prevent onychomycosis recurrences and emerging therapies are also described.

  • Part I: Onychomycosis: Clinical Overview and Diagnosis
    J. Am. Acad. Dermatol. (IF 6.898) Pub Date : 2018-06-28
    Shari R. Lipner, Richard K. Scher

    Onychomycosis is a fungal nail infection caused by dermatophytes, non-dermatophytes, and yeast and is the most common nail disorder seen in clinical practice. It is an important problem, as it may cause local pain, paresthesias, difficulties performing activities of daily life, and impair social interactions. In the following continuing medical education manuscript, we review the epidemiology, risk factors, and clinical presentation of onychomycosis and demonstrate current and emerging diagnostic strategies.

  • Prevalence of psoriatic arthritis in patients with psoriasis: A systematic review and meta-analysis of observational and clinical studies
    J. Am. Acad. Dermatol. (IF 6.898) Pub Date : 2018-06-19
    Farzad Alinaghi, Monika Calov, Lars Erik Kristensen, Dafna D. Gladman, Laura C. Coates, Denis Jullien, Alice B. Gottlieb, Paolo Gisondi, Jashin J. Wu, Jacob P. Thyssen, Alexander Egeberg

    Background Wide-ranging prevalence estimates of psoriatic arthritis (PsA) in patients with psoriasis have been reported. Objectives To assess the prevalence and incidence of PsA in patients with psoriasis. Methods Two authors independently searched three databases for studies reporting on the prevalence or incidence of PsA in patients with psoriasis. A proportion meta-analysis was performed to calculate the pooled proportion estimates of PsA in patients with psoriasis. Results A total of 266 studies were included, examining 976,408 patients with psoriasis. Overall, the pooled proportion (95% confidence interval) of PsA among patients with psoriasis was 19.7% (18.5%-20.9%). In children and adolescents (<18 years), the pooled prevalence was 3.3% (2.1%-4.9%). The PsA prevalence was 22.7% (20.6%-25.0%) in European, 21.5% (15.4%-28.2%) South American, 19.5% (17.1%-22.1%) North American, 15.5% (0.009%-51.5%) African, and 14.0% (11.7%-16.3%) in Asian psoriasis patients. The prevalence of PsA was 23.8% (20.1%-27.6%) in studies where the ClASsification criteria for Psoriatic ARthritis (CASPAR) was applied. The incidence of PsA among psoriasis patients ranged from 0.27 to 2.7 per 100 person-years. Limitations Between-study heterogeneity may have affected the estimates. Conclusions We found that one in five patients with psoriasis have PsA. With the growing recognition of CASPAR, more homogenous and comparable prevalence estimates are expected to be reported.

  • CADM1 is a diagnostic marker in early-stage mycosis fungoides: Multicenter study of 58 cases
    J. Am. Acad. Dermatol. (IF 6.898) Pub Date : 2018-06-19
    Akihiko Yuki, Satoru Shinkuma, Ryota Hayashi, Hiroki Fujikawa, Taisuke Kato, Erina Homma, Yohei Hamade, Osamu Onodera, Masao Matsuoka, Hiroshi Shimizu, Hiroaki Iwata, Riichiro Abe

    Background Mycosis fungoides (MF) is the most common cutaneous T-cell lymphoma (CTCL). Early-stage MF patches or plaques often resemble inflammatory skin disorders (ISDs), including psoriasis and atopic dermatitis. Cell adhesion molecule 1 (CADM1), initially identified as a tumor suppressor gene in human non-small-cell lung cancer, has been reported as a diagnostic marker for adult T-cell leukemia/lymphoma (ATLL). Objective We investigated CADM1 expression in MF neoplastic cells, especially during early stages, and evaluated its usefulness as a diagnostic marker for MF. Methods We conducted a retrospective study using immunohistochemical staining and confirmed the expression of CADM1 in MF. In addition, we compared CADM1 mRNA expression in microdissected MF samples and ISD samples. Results In the overall study period, 55 of 58 (94.8 %) MF samples stained positive for CADM1. None of the 50 ISD samples showed positive reactivity (P < 0.0001). We found CADM1 mRNA expression in the intradermal lymphocytes of MF cases, but not in those of ISD cases. Limitations We did not conduct a validation study for MF cases in other institutions. Conclusion CADM1 positive cells can be identified in early cases with less infiltrating cells and may be useful as a diagnostic marker for early-stage MF.

  • Association between Breslow Thickness and Dermoscopic Findings in Acral Melanoma
    J. Am. Acad. Dermatol. (IF 6.898) Pub Date : 2018-06-13
    Je-Ho Mun, Gwanghyun Jo, Claudia C. Darmawan, Jin Park, Jung Min Bae, HyunJu Jin, Woo-Il Kim, Hoon-Soo Kim, Hyun-Chang Ko, Byung-Soo Kim, Moon-Bum Kim

    Background Dermoscopy is a useful tool for the diagnosis of acral melanomas (AM). However, little is known about the influence of tumor thickness on the dermoscopic findings of AM. Objective To investigate the impact of Breslow thickness (BT) on the dermoscopic patterns of AM. Methods Data on cases of AM on the glabrous skin were collected from four university hospitals. We investigated the frequency of each dermoscopic feature of AM according to the BT. Statistical analysis was performed to investigate the association between the specific dermoscopic patterns and BT. Results Multivariable analysis revealed that red (odds ratio [OR] 16.482, 95% confidence interval [CI] 3.605-99.016), blue (OR 7.092; 95% CI 1.707-37.435), and white colors (OR 5.048, 95% CI 1.152-22.897) were more common in AM with BT >2 mm. Regarding patterns, atypical vascular patterns (OR 34.589, 95% CI 6.458-305.852), blue-white veil (OR 9.605, 95% CI 1.971-72.062), and ulcers (OR 5.084, 95% CI 1.145-24.152) were more frequently detected in cases with BT >2 mm. Limitations A retrospective study design and small sample size Conclusion This study showed an association between dermoscopic patterns and tumor thickness among patients with AM. Dermoscopy can be a useful adjuvant tool in predicting BT in AM.

  • Systematic Review of the Therapeutic Roles of Adipose Tissue in Dermatology
    J. Am. Acad. Dermatol. (IF 6.898) Pub Date : 2018-06-11
    Frances M. Walocko, Ariel E. Eber, Robert S. Kirsner, Evangelos Badiavas, Keyvan Nouri

    Background Adipose tissue has classically functioned as a filler in restoring facial volume. Adipose tissue is also rich in stem cells, which may have a role in regenerative medicine. Objective To summarize the literature on the clinical uses of adipose tissue in scarring, wound healing, and hair growth and determine if evidence exists for clinical practice changes in dermatology. Methods We utilized the Preferred Reporting Items for Systemic Reviews and Meta-Analysis (PRISMA) to conduct the review. The PubMed search engine was used to assess the available literature on adipose tissue in scarring, wound healing, and hair growth. Results Thirteen studies matched our inclusion criteria. Six of seven studies on scar treatment, all three studies on wound healing, and all three studies on hair growth demonstrated improved outcomes with adipose tissue treatments. Limitations The literature supporting the use of adipose tissue is limited to case series, cohort studies, and small randomized controlled trials, which have an overall low level of evidence. Conclusion The existing evidence for adipose tissue as a treatment option in scarring, wound healing, and hair growth is not strong enough to justify changes to current clinical practice. The literature does provide evidence for future large randomized clinical trials.

  • Review: Surgical Smoke: Risks Assessment and Mitigation Strategies
    J. Am. Acad. Dermatol. (IF 6.898) Pub Date : 2018-06-11
    Corey Georgesen, Shari R. Lipner

    Background Although many dermatologic surgeons are aware of the risks of surgical smoke, many do not employ hazard reduction strategies. Objective To identify the infectious, inhalational, chemical, and mutagenic risks of surgical smoke in dermatologic procedures and suggest evidence based hazard reduction strategies. Methods A review of articles indexed for MEDLINE on PubMed using keywords “surgical smoke”, “dermatology”, “surgical mask”, “respirator”, “smoke evacuator”, and “guidelines” was performed in 13 combinations using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocols. This review includes data from 45 manuscripts from the dermatology, surgery, infectious disease, obstetrics, and cancer biology literature. Results There are risks associated with surgical smoke, and although some dermatologists are aware of these risks, many are not using hazard reduction strategies such as smoke evacuators and surgical masks. Limitations Most of the data regarding surgical smoke hazards and methods for smoke safety is derived from in vitro and non-human in vivo studies, in addition to resources outside of the dermatology literature. Conclusion Standardized guidelines for surgical smoke safety should be implemented in the dermatology community and residency curriculum.

  • Pain, psychiatric comorbidities, and psychosocial stressors associated with Klippel-Trenaunay Syndrome
    J. Am. Acad. Dermatol. (IF 6.898) Pub Date : 2018-06-05
    Jamison A. Harvey, Henry Nguyen, Katelyn R. Anderson, Jennifer J. Schoch, Emily C. Bendel, David J. Driscoll, Brian A. Palmer, Megha M. Tollefson

    Background Klippel-Trenaunay syndrome (KTS) is characterized by the triad of capillary malformation (CM), venous malformation (VM) +/- lymphatic malformation, and limb overgrowth. Patients with KTS have lower scores in general and mental health, physical function, and quality of life than the general population. Objective To determine the prevalence of pain and psychiatric comorbidity in patients with KTS. Methods A retrospective review of 410 patients with KTS evaluated between 1976 and 2012 was conducted to identify the presence of pain, psychiatric comorbidities, and psychosocial stressors. Results Pain was reported by 260 patients (63.4%) and was associated with any KTS complication (p<0.0001) and VMs of the lower extremities (p=0.0008) and feet (p=0.0007). Ninety-five patients had a diagnosed psychiatric condition (23.2%), most commonly depression (15.1%) and anxiety (5.1%). Pain (p=0.0016), superficial thrombosis (p=0.0269), deep embolic/thrombotic events (p=0.0005), gastrointestinal complications (p=0.0085), genitourinary complications (p=0.0163), and CM of the hands (p=0.0040) were associated with having a psychiatric diagnosis. Limitations Retrospective study that relied on physician detection and reporting of variables. Conclusions Pain and psychiatric conditions, particularly depression and anxiety, are common in patients with KTS. Awareness of the psychosocial impact of KTS and appropriate screening are important.

  • A systematic review and meta-analysis of the prevalence and phenotype of adult-onset atopic dermatitis
    J. Am. Acad. Dermatol. (IF 6.898) Pub Date : 2018-06-02
    Harrison H. Lee, Kevin R. Patel, Vivek Singam, Supriya Rastogi, Jonathan I. Silverberg

    Background Previous studies found conflicting results about whether atopic dermatitis (AD) begins in adulthood. Objective To determine rates, predictors and phenotypical differences of adult-onset AD. Methods A systematic review was performed of all published observational studies in MEDLINE, EMBASE, GREAT, LILACS, Cochrane Library, and Scopus that analyzed the age of AD onset beyond 10 years of age. Two reviewers performed study title/abstract review and data abstraction. Pooled meta-analysis of the proportion of adult-onset AD was performed using random-effects weighting (I2=99.3%). Results Overall, 25 studies met inclusion criteria. Seventeen studies reported age of AD-onset past 16 years and had sufficient data for meta-analysis. The pooled proportion (95% CI) of adult-onset AD was 26.1% (16.5-37.2%). Similar results were found in sensitivity analyses by diagnostic method for AD, study region, and gender. Phenotypical differences were observed across studies for adult vs. child onset AD, including higher rates of foot dermatitis and personal history of atopy, but lower rates of flexural lesions and other signs and symptoms. Limitations Characteristics of adult- vs. child-onset AD were not commonly reported. Conclusions AD is not only a disease of childhood. One in 4 adults with AD report adult-onset disease. Adult-onset AD was associated with distinct clinical characteristics.

  • Long-term adalimumab efficacy in patients with moderate-to-severe hidradenitis suppurativa/acne inversa: 3-year results of a phase 3 open-label extension study
    J. Am. Acad. Dermatol. (IF 6.898) Pub Date : 2018-06-01
    Christos C. Zouboulis, Martin M. Okun, Errol P. Prens, Robert Gniadecki, Peter A. Foley, Charles Lynde, Jamie Weisman, Yihua Gu, David A. Williams, Gregor B.E. Jemec

    Background The long-term optimal dosing strategy for adalimumab in hidradenitis suppurativa/acne inversa (HS) was evaluated by pooling the results of the PIONEER phase 3 trials and an open-label extension (OLE) study. Objective To assess response and tolerability of long-term adalimumab in HS. Methods The durations of PIONEER I/II periods A, B, and OLE were 12, 24, and ≥ 52 weeks, respectively. Patients who entered the OLE and received adalimumab 40 mg every week continuously (ADAew) and responders plus partial responders (PRR) were evaluated. Primary efficacy assessments included HS Clinical Response (HiSCR) measure, lesion counts, skin pain, and Dermatology Life Quality Index (DLQI). Treatment-emergent adverse events were assessed. Results At week 12, 52.3% (ADAew) and 73.0% (PRR) of patients achieved HiSCR. Achievement of HiSCR was maintained through week 168 in 52.3% of ADAew patients and 57.1% of PRR patients. Sustained improvement in lesion counts, skin pain, and DLQI were also observed. The safety profile throughout the OLE was similar to the profiles observed in the PIONEER studies. Limitations The OLE was uncontrolled. Conclusion Continuous weekly dosing with adalimumab 40 mg is a reasonable treatment option for long-term control of moderate-to-severe HS.

  • Association of family structure with atopic dermatitis in United States children
    J. Am. Acad. Dermatol. (IF 6.898) Pub Date : 2018-06-01
    Costner McKenzie, Jonathan I. Silverberg

    Background Children from families without two married, biological parents have increased risk of poverty and poor health. The relationship between family structure and atopic dermatitis (AD) has not been elucidated. Objectives To determine the prevalence of AD and related outcomes in children from different family structures. Methods Data were analyzed from 13,275 children (≤17 years) and their parents from the 2012 National Health Interview Survey. Results In multivariable logistic regression models adjusting for socio-demographics, children from single adult households (adjusted odds ratio [95% confidence interval]: 1.272 [1.050–1.542]), families with ≤2 members (1.413 [1.079–1.852]), families with a mother, but no father present (1.402 [1.179–1.667]), non-biological fathers (1.464 [1.089–1.969]), or unmarried mothers (1.508 [1.017–2.237]) had increased odds of AD. Among children with AD, there were significantly increased odds of having only good/fair/poor vs. very good/excellent overall health (1.545 [1.262–1.893]), greater odds of depression (2.287 [1.523–3.434]), anxiety (2.001 [1.543–2.595]), and stress (2.013 [1.499–2.704]). Limitations Cross-sectional study. Conclusions US children from families with single adults, single mothers, non-biological fathers, or unmarried mothers may have increased odds of AD. Family structures were associated with poorer overall health, depression, anxiety, and stress in children with AD.

  • Characterization of dermatitis after PD-1/PD-L1 inhibitor therapy and association with multiple oncologic outcomes: a retrospective case-control study
    J. Am. Acad. Dermatol. (IF 6.898) Pub Date : 2018-05-29
    Charles Kyung Min Lee, Shufeng Li, Duy Cong Tran, Gefei Alex Zhu, Jinah Kim, Bernice Y. Kwong, Anne Lynn S. Chang

    Background Cutaneous adverse events are common with Programmed Death (PD)-1/ PD-Ligand (L)1 inhibitors. However, the nature of the specific cutaneous adverse event of dermatitis has not been investigated across various PD-1/PD-L1 inhibitors. Oncologic outcomes potentially associated with dermatitis are not well characterized. Objective (s): To assess the nature of dermatitis after PD-1/PD-L1 inhibitor exposure and oncologic outcomes associated with dermatitis. Methods Retrospective, matched, case-control study conducted at a single academic center. Results The most common histologic patterns were lichenoid dermatitis (50%) and spongiotic dermatitis (40%). Overall tumor response rate was 65.0% for cases and 17.0% for controls (p=0.0007), odds ratio: 7.3 (95% CI 2.3-23.1). Progression Free Survival (PFS) and Overall Survival (OS) times were significantly longer for cases than controls by Kaplan-Meier analysis (p<0.0001 and 0.0203, respectively). Limitations Retrospective design and relatively small sample size precluded matching on all cancer types. Conclusion Lichenoid and spongiotic dermatitis associated with PD-1/PD-L1 inhibitors could be a sign of robust immune response and improved oncologic outcomes. The predictive value of PD-1/PD-L1 related dermatitis on cancer outcomes awaits investigation through prospective multicenter studies for specific cancer types.

  • Ablative fractional laser-assisted photodynamic therapy provides superior long-term efficacy compared to standard methyl aminolevulinate photodynamic therapy for lower extremity Bowen’s disease
    J. Am. Acad. Dermatol. (IF 6.898) Pub Date : 2018-05-29
    Ho-Jin Kim, Ki-Hoon Song

    Background Ablative fractional laser-assisted methyl aminolevulinate photodynamic therapy (AFL-MAL-PDT) has shown significantly higher efficacy and lower recurrence rates at 12 months than conventional methyl aminolevulinate photodynamic therapy (MAL-PDT) for the treatment of Bowen’s disease (BD). However, long-term follow-up data are not available. Objective To compare the 5-year efficacy and recurrence rates of AFL-MAL-PDT and conventional MAL-PDT for the treatment of lower extremity BD. Methods Sixty patients with 84 BD lesions were randomly assigned to a single session of AFL-MAL-PDT or two sessions of MAL-PDT with a 1-week interval between sessions. Patients were followed-up at 3, 12, 24, 36, 48, and 60 months post-treatment. Efficacy, recurrence rates, and risk factors for unsuccessful treatments were assessed. Results After 5 years, the overall clearance rate of AFL-MAL-PDT (84.78%) was significantly better than that of MAL-PDT (44.74%) for BD lesions. The recurrence rate was significantly lower for AFL-MAL-PDT (9.3%) than for MAL-PDT (41.38%). Diameters larger than 20 mm and lesions with a history of previous treatment were independent factors for treatment failure. Limitations The small sample-size and single-center study design were limitations. Conclusions For patients with lower extremity BD lesions, AFL-MAL-PDT showed significantly higher long-term efficacy and lower recurrence rates than standard MAL-PDT.

  • Oral diabetes medications other than dipeptidyl peptidase-4 inhibitors are not associated with bullous pemphigoid: a Finnish nationwide case control study
    J. Am. Acad. Dermatol. (IF 6.898) Pub Date : 2018-05-25
    O. Varpuluoma, A.-K. Försti, J. Jokelainen, M. Turpeinen, M. Timonen, K. Tasanen, L. Huilaja

    Background Dipeptidyl peptidase-4 inhibitors (DPP-4i) used to treat diabetes have been reported to be associated with an increased risk of bullous pemphigoid (BP). There are no previous reports analyzing the risk of BP in patients using other diabetes medications. Objective To evaluate the association between diabetes medications other than DPP-4i and development of BP. Methods We investigated prevalence of diabetes among BP patients, and the association between the use of diabetes drugs (excluding DPP-4i, metformin and insulin) and BP, by analyzing national Finnish registry data for 3397 BP patients and 12941 basal cell carcinoma patients as controls. Results Our results show that 19.6% of BP patients have type 2 diabetes. The use of none of the investigated medications was associated with an increased risk for BP. Limitations Since this was a registry-based study, it was not possible to verify the accuracy of the diagnoses. The risk of BP in users of glucagon-like peptide-1 receptor agonists could not be analyzed. Conclusion Our study shows that the investigated diabetes drugs are not associated with increased risk of BP in a Finnish patient-base, indicating they can be safely used in this population. Generalization of these results to other populations will require further study.

  • Maintenance of Skin Clearance With Ixekizumab Treatment of Psoriasis: Three-Year Results From the UNCOVER-3 Study
    J. Am. Acad. Dermatol. (IF 6.898) Pub Date : 2018-05-25
    Craig Leonardi, Catherine Maari, Sandra Philipp, Orin Goldblum, Lu Zhang, Nicole Burkhardt, Susan Ball, Lotus Mallbris, Pablo Gonzalez, Pablo Fernández-Peñas, Lluis Puig

    Background Psoriasis, a chronic disease, may require long-term treatment. Ixekizumab, a high-affinity monoclonal antibody that selectively targets interleukin-17A, is an approved therapy for patients with moderate-to-severe plaque psoriasis. Objective To evaluate efficacy and safety of ixekizumab through 156 weeks from the UNCOVER-3 study in patients who received the recommended dose regimen [160 mg at Week 0, 80 mg every 2 weeks (IXE Q2W) to Week 12, and 80 mg every 4 weeks (IXE Q4W) thereafter. Methods Patients randomized to IXE Q2W, IXE Q4W, etanercept twice weekly, or placebo were switched to IXE Q4W during long-term extension period. Efficacy data were summarized using as-observed, multiple imputation (MI), and modified nonresponder imputation (mNRI) methods. Results At Week 156, response rates were 80.5%, 66.0%, and 45.1% for PASI 75, 90 and 100 using mNRI method, respectively, and 97.2% and 86.2 for PASI 75 using as-observed and MI methods, respectively.. Similar response rates were observed in patients with baseline scalp, nail, or palmoplantar involvement. No new safety signals were identified through Year 3. Limitations No placebo or active comparison after Week 12. Conclusion Ixekizumab sustained high responses with clearance of skin and nail lesions, with no new safety concerns through 3 years.

  • The Potential of Narrow Band UVB to Induce Sustained Durable Complete Remission off-Therapy in Stage I Mycosis Fungoides
    J. Am. Acad. Dermatol. (IF 6.898) Pub Date : 2018-05-23
    Pavlotsky Felix, Dawood Marwan, Barzilai Aviv

    Background Narrow Band UVB (NB UVB) is a first line therapy for stage I Mycosis Fungoides (MF) with complete response (CR) in 75%-85% of patients. However, long-term, off-therapy disease free survival (DFS) data are scarce. Objective To assess the long-term DFS following NB UVB treatment stage I MF. Methods An historic cohort of all stage I MF patients achieving CR with NB UVB and discontinuing any treatment prior to 2011. Age at the beginning of phototherapy, gender, stage, skin phototype, number of treatments, total dose and the length of DFS was collected. Results Of the 117 patients who started NB UVB, 93 patients (80%) had CR and 56 of them (60%) were disease free as of March 2017. In a multivariate analysis only age and disease stage independently affected DFS. The DFS was longer for patients younger than 50 years old (124 and 91 months respectively, p=0.01); and for stage IA patients (131 and 87.6 months respectively, p=0.001). Limitations The study was retrospective in nature Conclusions Following a single course of NB UVB, over a half of stage I MF patients achieve more than 5 years DFS period and potentially cured. Thus NB UVB can be considered as a disease modifying therapy.

  • Financial burden of emergency department visits for atopic dermatitis in the United States
    J. Am. Acad. Dermatol. (IF 6.898) Pub Date : 2018-05-23
    Lauren Kwa, Jonathan I. Silverberg

    Background Little is known about the utilization and financial-burden of emergency care visits for atopic dermatitis or eczema (AD-E) in the US. Objective To determine the prevalence, risk factors and cost of emergency care for AD-E in the US Methods Cross-sectional study of the 2006–2012 National Emergency Department Sample (NEDS), including a 20% sample of ED visits throughout the US (n=198,102,435). Results The mean annual incidence of ED visits with a primary diagnosis of AD-E was 3368.4 to 3553.0 per-million persons. The prevalence of ED visits for AD-E increased significantly from 2006 to 2012 (survey logistic regression; P<0.05). ED visits with vs. without a primary diagnosis of AD-E were associated with younger patient age, Medicaid or no insurance, lower household income-quartiles, and more likely to occur during weekends and summer months. The geometric mean and total costs of ED visits for AD-E significantly increased from $369.07 and $127,275,080 in 2006 to $642.10 and $265,541,084 in 2012, respectively Limitations NEDS did not include data on AD severity, recurrent ED visits, race/ethnicity or treatments provided. Conclusion There is a substantial and increasing financial-burden of ED visits for AD-E in the US. Interventions are needed to decrease ED visits for AD.

  • Basal Cell Carcinoma, PART II: Contemporary Approaches to Diagnosis, Treatment, and Prevention
    J. Am. Acad. Dermatol. (IF 6.898) Pub Date : 2018-05-19
    Michael C. Cameron, Erica Lee, Brian Hibler, Cerrene N. Giordano, Christopher A. Barker, Shoko Mori, Miguel Cordova, Kishwer S. Nehal, Anthony M. Rossi

    As the most common human cancer worldwide and continuing to increase in incidence, basal cell carcinoma is associated with significant morbidity and cost. Continued advances in research have refined both our insight and approach to this seemingly ubiquitous disease. This 2-part continuing medical education article will provide a comprehensive and contemporary review of basal cell carcinoma. Part II of this series will present both standard of care and newly developed approaches to diagnosis, treatment, and prevention of this disease.

  • Basal Cell Carcinoma: Part 1
    J. Am. Acad. Dermatol. (IF 6.898) Pub Date : 2018-05-18
    Michael C. Cameron, Erica Lee, Brian Hibler, Christopher A. Barker, Shoko Mori, Miguel Cordova, Kishwer S. Nehal, Anthony M. Rossi

    As the most common human cancer worldwide and continuing to increase in incidence, basal cell carcinoma is associated with significant morbidity and cost. Continued advances in research have refined both our insight and approach to this seemingly ubiquitous disease. This 2-part continuing medical education article will provide a comprehensive and contemporary review of basal cell carcinoma. Part I of this series will describe our current understanding of this disease in regards to epidemiology, cost, clinical and histopathologic presentations, carcinogenesis, natural history, and disease associations.

  • Psoriatic patients with chronic viral hepatitis do not have an increased risk of liver cirrhosis despite long-term methotrexate use: real-world data from a nationwide cohort study in Taiwan.
    J. Am. Acad. Dermatol. (IF 6.898) Pub Date : 2018-05-10
    Kuo-Tung Tang, Yi-Ming Chen, Shih-Ni Chang, Ching-Heng Lin, Der-Yuan Chen

    Background Methotrexate (MTX) is commonly used in the treatment of patients with moderate to severe psoriasis. Objective We conducted a nationwide population-based cohort study to investigate the impact of long-term MTX use on the risk of chronic viral hepatitis-related cirrhosis among psoriatic patients in Taiwan. Methods This study obtained data from the National Health Insurance Research Database in Taiwan. We identified 2417 psoriatic patients with chronic hepatitis B (CHB) (370 MTX users and 2047 MTX non-users) and 1127 psoriatic patients with chronic hepatitis C (CHC) (174 MTX users and 953 MTX non-users) from January 1, 2000 to December 31, 2010. Results After a mean follow-up of more than 9 years since the diagnosis of chronic viral hepatitis, a total of 125 (5%) CHB patients and 120 (11%) CHC patients developed liver cirrhosis. A comparable proportion of MTX users and MTX non-users developed liver cirrhosis (4% vs. 5% in CHB patients and 11% and vs. 11% in CHC patients, both p < 0.05). Limitations There is possibly selection bias and medication nonadherence. Conclusion Our real-world data show that long-term MTX use may not be associated with an increased risk of liver cirrhosis among psoriatic patients with chronic viral hepatitis.

  • Ethnic differences and comorbidities of 909 Prurigo Nodularis patients
    J. Am. Acad. Dermatol. (IF 6.898) Pub Date : 2018-05-04
    Emily Boozalis, Olive Tang, Shivani Patel, Yevgeniy R. Semenov, Manuel P. Pereira, Sonja Stander, Sewon Kang, Shawn G. Kwatra

    Background Prurigo Nodularis (PN) is a poorly understood, understudied pruritic dermatosis that reduces quality of life. Objective To characterize the demographics and comorbidities associated with PN. Methods Cross-sectional study of patients ≥ 18 years old seen at the Johns Hopkins Health System (JHHS) between 12/6/2012-12/6/2017. Results Over the last five years, 909 patients with PN were seen at JHHS. African-American patients were 3.4 times more likely to have PN than white patients (OR 3.4, 95% CI 2.9-3.9, p < 0.001). PN was significantly associated with a variety of systemic, cardiovascular, and psychiatric comorbidities when compared to race-matched controls, including: chronic kidney disease, chronic hepatitis C, chronic obstructive pulmonary disease, congestive heart failure, depression, and atopic dermatitis. Black patients with PN were 10.5 times more likely (OR 10.5, CI 7.9-13.9, p < 0.001) to have HIV than race-matched controls with atopic dermatitis, and eight times more likely (OR 8.0, 95% CI 5.7-11.1, p < 0.001) to have HIV than African-American patients with psoriasis. Limitations Our data describes patients seen by one hospital system. Our data identifies associated conditions and comorbidities, but is unable to support a causal relationship. Conclusion PN disproportionately affects African-Americans and is associated with several systemic conditions including HIV, chronic kidney disease, and diabetes.

  • Certolizumab Pegol for the Treatment of Chronic Plaque Psoriasis: Results through 48 Weeks from Two Phase 3, Multicenter, Randomized, Double-Blinded, Placebo-Controlled Studies (CIMPASI-1 and CIMPASI-2)
    J. Am. Acad. Dermatol. (IF 6.898) Pub Date : 2018-04-13
    Alice B. Gottlieb, Andrew Blauvelt, Diamant Thaçi, Craig L. Leonardi, Yves Poulin, Janice Drew, Luke Peterson, Catherine Arendt, Daniel Burge, Kristian Reich

    Background Certolizumab pegol, the only Fc-Free, PEGylated anti-tumor necrosis factor biologic, demonstrated clinically meaningful improvements and suggested a positive risk-benefit balance in phase 2 studies in adults with moderate-to-severe chronic plaque psoriasis. Objective Assess certolizumab efficacy and safety versus placebo in phase 3 studies. Methods Patients with moderate-to-severe chronic plaque psoriasis were randomized 2:2:1 to certolizumab 400 mg, 200 mg, or placebo every 2 weeks. At Week 16, certolizumab-treated patients achieving 50% reduction in psoriasis area and severity index continued treatment through Week 48. Coprimary endpoints were Week 16 responder rates, defined as 75% reduction in psoriasis area and severity index and physician’s global assessment 0/1 (‘clear’/‘almost clear’ and ≥2-point improvement). Safety was assessed by treatment-emergent adverse events. Results Week 16 endpoints were significantly greater for both doses of certolizumab versus placebo, and responses maintained through Week 48. For most measures, improvement was numerically greater for certolizumab 400 mg. No unexpected safety signals were identified. Limitations No active comparator. Conclusions Treatment with either certolizumab 400 mg or 200 mg every 2 weeks was associated with significant, clinically meaningful improvements in moderate-to-severe psoriasis. The 400 mg dose may provide additional clinical benefit. The safety profile was consistent with the therapeutic class.

  • Subcutaneous Infiltration of Carbon Dioxide (Carboxytherapy) for Abdominal Fat Reduction: A Randomized Clinical Trial
    J. Am. Acad. Dermatol. (IF 6.898) Pub Date : 2018-04-24
    Murad Alam, Divya Sadhwani, Amelia Geisler, Imran Aslam, Inder Raj S. Makin, Daniel I. Schlessinger, Wareeporn Disphanurat, Marisa Pongprutthipan, Nataya Voravutinon, Alexandra Weil, Brian R. Chen, Dennis P. West, Emir Veledar, Emily Poon

    Background Non-invasive fat removal is preferred because of decreased downtime and lower perceived risk. It is important to seek new non-invasive fat removal treatments that are both safe and efficacious. Objective To assess the extent to which carboxytherapy, the insufflation of carbon dioxide gas into subcutaneous fat, results in reduction of fat volume. Methods Randomized, sham-controlled, split-body study. Adults (BMI 22-29) were randomized to receive five weekly infusions of 1000 cc CO2 to one side of the abdomen, and five sham treatments to the contralateral side. Primary outcome measures were ultrasound measurement of fat layer thickness, as well as total circumference before and after treatment. Results Sixteen participants completed the study. Ultrasound measurement indicated less fat volume on the sides treated with carboxytherapy one week after the last treatment, (p=0.011), but was not maintained at 28 weeks. Total circumference decreased nominally but not significantly at Week 5 compared to baseline (p=0.0697). Participant body weights did not change over the entire course of the study (p=1.00) Limitations Limitations included modest sample size and some sources of error in circumference and fat layer measurements. Conclusion Carboxytherapy provides a transient decrease in subcutaneous fat that may not persist. Treatment is well-tolerated.

  • Red meat and processed meat intake and risk of cutaneous melanoma in white women and men: Two prospective cohort studies
    J. Am. Acad. Dermatol. (IF 6.898) Pub Date : 2018-04-24
    Hsi Yen, Wen-Qing Li, Ashar Dhana, Tricia Li, Abrar Qureshi, Eunyoung Cho

    Background Red and processed meat consumption has been associated with increased risk of several cancers, but association with cutaneous melanoma risk has been inconclusive. Objective To investigate the association between red and processed meat intake and melanoma risk. Methods Dietary information was assessed using food frequency questionnaires in two prospective cohorts – 75,263 women from the Nurses’ Health Study (1984 – 2010) and 48,523 men from the Health Professionals Follow-up Study (1986 – 2010). Melanoma cases were confirmed by review of pathological records. Pooled multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models. Results A total of 679 female and 639 male melanoma cases were documented during follow-up. Red and processed meat intake was inversely associated with melanoma risk (P for trend = 0.002); the pooled HRs (95% CIs) of the two cohorts were 1.00 (reference), 1.00 (0.87 – 1.14), 0.98 (0.86 – 1.13), 0.89 (0.77 – 1.02), and 0.81 (0.70 – 0.95) for increasing quintiles of intake. Limitations Findings may have limited generalizability, as the cohorts were limited to white health professionals. Conclusion Red and processed meat intake was inversely associated with melanoma risk in these two cohorts.

  • Analysis of Spin in the Reporting of Studies of Topical Treatments of Photoaged Skin
    J. Am. Acad. Dermatol. (IF 6.898) Pub Date : 2018-04-22
    Catherine C. Motosko, Anna K. Ault, Laura L. Kimberly, M David Gothard, Roger S. Ho, Alexes Hazen

    Background Spin—reporting that distorts the interpretation of results—is not unusual within scientific literature. Objective To appraise strategies of spin among placebo-controlled double-blind clinical trials of topical treatments for photoaged skin. Methods A systematic review of literature was performed to identify placebo-controlled double-blind clinical trials of topical treatments for photoaged skin. A survey of spin strategies was developed and applied to the cohort of identified studies. Results Systematic review identified 20 studies, all of which employed various spin strategies, broadly classified as either inappropriate statistical analysis or inappropriate interpretation of results. Most commonly used strategies included use of multiple primary outcomes (95%), inappropriate extrapolation of the results from specific outcome to global improvement (95%), focus on within-group comparison (75%), and focus on interim analyses to give more weight to nonsignificant findings (65%).Limitations: Classification of spin strategies is subjective and may not encompass all methods used by studies in the published literature. Conclusions Findings in this study may inform efforts to reduce spin in the dermatologic literature.

  • Topical Janus Kinase Inhibitors: A Review of Applications in Dermatology
    J. Am. Acad. Dermatol. (IF 6.898) Pub Date : 2018-04-16
    Anna-Marie Hosking, Margit Juhasz, Natasha Atanaskova Mesinkovska

    Background Janus kinase inhibitors (JAKi) have attracted attention for their role in treating inflammatory disorders. This new class of biologics has the potential to significantly impact the field of dermatology, especially with the development of topical formulations. Objective To summarize published evidence on the efficacy, safety, and tolerability of topical JAKi in the treatment of inflammatory skin conditions. Methods This is a review of PubMed and Cochrane Library up until November 2017. Results Fifty-five potential articles were identified; 11 articles were included for review, comprising an aggregate 924 patients. In randomized clinical trials (RCTs), topical JAKi demonstrate modest improvements in psoriasis and atopic dermatitis disease scores, patient-reported outcomes, and quality of life. Results for vitiligo are conflicting, with improvements seen only in facial vitiligo. Conclusive efficacy data for alopecia areata is lacking. Limitations It was not possible to perform a meta-analysis due to lack of standardization and low number of RCTs. Conclusions Topical JAKi provide an attractive treatment option for patients with psoriasis, atopic dermatitis, alopecia areata, and vitiligo. Although early phase clinical studies of this novel drug class are promising, large phase 3 and 4 studies are needed to further define the role of topical JAKi in dermatology.

Some contents have been Reproduced with permission of the American Chemical Society.
Some contents have been Reproduced by permission of The Royal Society of Chemistry.
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