Showing papers in "Journal of The American Academy of Dermatology in 2018"
TL;DR: The incidence, recurrence rates, mortality rates, and risk factors associated with cSCC are discussed and the staging systems used to stratify patients into high- and low-risk groups are reviewed.
Abstract: Cutaneous squamous cell carcinoma (cSCC), a malignant proliferation of cutaneous epithelium, represents 20% to 50% of skin cancers. Although the majority of cSCCs are successfully eradicated by surgical excision, a subset of cSCC possesses features associated with a higher likelihood of recurrence, metastasis, and death. The proper identification of these aggressive cSCCs can guide additional work-up and management. In the first article in this continuing medical education series, we discuss the incidence, recurrence rates, mortality rates, and risk factors associated with cSCC and review the staging systems used to stratify patients into high- and low-risk groups. The second article in this series reviews the treatment options for cSCC, with focused attention on the management of high-stage tumors.
437 citations
Northwestern University1, University of Colorado Denver2, Mayo Clinic3, Case Western Reserve University4, University of Rochester5, Memorial Sloan Kettering Cancer Center6, University of California, Davis7, University of Pennsylvania8, University of South Florida9, Geisinger Medical Center10, Burton Snowboards11, Stanford University12, University of California, San Francisco13, University of Alabama at Birmingham14, American Academy of Dermatology15, University of Michigan16, Ohio State University17
TL;DR: The primary focus of these recommendations is on evaluation and management of primary cSCC and localized disease, but where relevant, applicability to recurrent cS CC is noted, as is general information on the management of patients with metastatic disease.
Abstract: Cutaneous squamous cell carcinoma (cSCC) is the second most common form of human cancer and has an increasing annual incidence. Although most cSCC is cured with office-based therapy, advanced cSCC poses a significant risk for morbidity, impact on quality of life, and death. This document provides evidence-based recommendations for the management of patients with cSCC. Topics addressed include biopsy techniques and histopathologic assessment, tumor staging, surgical and nonsurgical management, follow-up and prevention of recurrence, and management of advanced disease. The primary focus of these recommendations is on evaluation and management of primary cSCC and localized disease, but where relevant, applicability to recurrent cSCC is noted, as is general information on the management of patients with metastatic disease.
282 citations
TL;DR: Recommendations for the management of patients with BCC and recommendations on treatment modalities along a broad therapeutic spectrum, ranging from topical agents and superficially destructive modalities to surgical techniques and systemic therapy are provided.
Abstract: Basal cell carcinoma (BCC) is the most common form of human cancer, with a continually increasing annual incidence in the United States. When diagnosed early, the majority of BCCs are readily treated with office-based therapy, which is highly curative. In these evidence-based guidelines of care, we provide recommendations for the management of patients with BCC, as well as an in-depth review of the best available literature in support of these recommendations. We discuss biopsy techniques for a clinically suspicious lesion and offer recommendations for the histopathologic interpretation of BCC. In the absence of a formal staging system, the best available stratification based on risk for recurrence is reviewed. With regard to treatment, we provide recommendations on treatment modalities along a broad therapeutic spectrum, ranging from topical agents and superficially destructive modalities to surgical techniques and systemic therapy. Finally, we review the available literature and provide recommendations on prevention and the most appropriate follow-up for patients in whom BCC has been diagnosed.
262 citations
TL;DR: Patients with AA frequently experience marked impairment in psychological well-being, self-esteem, and may be more likely to suffer from psychiatric comorbidities.
Abstract: Alopecia areata (AA) is a common, inflammatory, nonscarring type of hair loss. Significant variations in the clinical presentation of AA have been observed, ranging from small, well-circumscribed patches of hair loss to a complete absence of body and scalp hair. Patients affected by AA encompass all age groups, sexes, and ethnicities, and may experience frustration with the unpredictable nature of their disease for which there is currently no definitive treatment. The cause of AA remains incompletely understood, though it is believed to result—at least in part—from a loss of immune privilege in the hair follicle, autoimmune-mediated hair follicle destruction, and the upregulation of inflammatory pathways. Patients with AA frequently experience marked impairment in psychological well-being, self-esteem, and may be more likely to suffer from psychiatric comorbidities. Part one of this two-part continuing medical education series describes the epidemiology, clinical evaluation, prognosis, and recent advancements in the understanding of the pathogenesis of AA.
247 citations
TL;DR: In this article, the efficacy and safety of lebrikizumab, an IL-13 monoclonal antibody, as an add-on to topical corticosteroid (TCS) treatment was investigated.
Abstract: Background Interleukin (IL)-13 plays a key role in type 2 inflammation and is an emerging pathogenic mediator in atopic dermatitis (AD). Objective We investigated the efficacy and safety of lebrikizumab, an IL-13 monoclonal antibody, as an add-on to topical corticosteroid (TCS) treatment. Methods A randomized, placebo-controlled, double-blind, phase 2 study. Adults with moderate-to-severe AD were required to use TCS twice daily and then randomized (1:1:1:1) to lebrikizumab 125 mg single dose, lebrikizumab 250 mg single dose, lebrikizumab 125 mg every 4 weeks for 12 weeks, or placebo every 4 weeks for 12 weeks, after a 2-week TCS run-in. The primary endpoint was percentage of patients achieving Eczema Area and Severity Index (EASI)-50 at week 12. Results In total, 209 patients received the study drug. At week 12, significantly more patients achieved EASI-50 with lebrikizumab 125 mg every 4 weeks (82.4%; P = .026) than placebo every 4 weeks (62.3%); patients receiving a single dose of lebrikizumab showed no statistically significant improvements in EASI-50 compared with placebo. Adverse events were similar between groups (66.7% all lebrikizumab vs 66.0% placebo) and mostly mild or moderate. Limitations Protocol-mandated twice daily TCS treatment limits our understanding of the efficacy of lebrikizumab as a monotherapy. The short study duration did not enable long-term efficacy or safety evaluations. Conclusion When combined with TCS, lebrikizumab 125 mg taken every 4 weeks led to a significant improvement and was well tolerated in patients with moderate-to-severe AD.
242 citations
TL;DR: Baricitinib used with TCSs reduced inflammation and pruritus in patients with moderate‐to‐severe atopic dermatitis and improvedPruritus and sleep loss.
Abstract: Background Baricitinib, an oral selective inhibitor of Janus kinase 1 and Janus kinase 2, modulates proinflammatory cytokine signaling. Objectives The efficacy and safety of baricitinib were evaluated in patients with moderate-to-severe atopic dermatitis (AD). Methods In this phase 2, randomized, double-blind, placebo-controlled study, 124 patients with moderate-to-severe AD applied topical corticosteroids (TCSs) for 4 weeks before randomization to once-daily placebo, 2 mg of baricitinib, or 4 mg of baricitinib for 16 weeks. Use of TCSs was permitted during the study. The primary outcome was the proportion of patients achieving at least a 50% reduction in the Eczema Area and Severity Index (EASI-50) compared with placebo. Results Significantly more patients who received baricitinib, 4 mg, achieved EASI-50 than did patients receiving placebo (61% vs 37% [P = .027]) at 16 weeks. The difference between the proportion of patients receiving baricitinib, 2 or 4 mg, who achieved EASI-50 and the proportion of patients receiving placebo and achieving EASI-50 was significant as early as week 4. Baricitinib also improved pruritus and sleep loss. Treatment-emergent adverse events were reported in 24 of the patients receiving placebo (49%), 17 of those receiving 2 mg of baricitinib (46%), and 27 of those receiving 4 mg of baricitinib (71%). Limitations A TCS standardization period before randomization reduced disease severity, limiting the ability to compare results with those of baricitinib monotherapy. Longer studies are required to confirm baricitinib's efficacy and safety in patients with AD. Conclusions Baricitinib used with TCSs reduced inflammation and pruritus in patients with moderate-to-severe AD.
242 citations
TL;DR: In 2002, the National Rosacea Society assembled an expert committee to develop the first standard classification of rosacea, which was intended to provide clearer parameters to conduct investigations, guide diagnosis, and improve treatment.
Abstract: In 2002, the National Rosacea Society assembled an expert committee to develop the first standard classification of rosacea. This original classification was intended to be updated as scientific knowledge and clinical experience increased. Over the last 15 years, significant new insights into rosacea's pathogenesis and pathophysiology have emerged, and the disorder is now widely addressed in clinical practice. Growing knowledge of rosacea's pathophysiology has established that a consistent multivariate disease process underlies the various clinical manifestations of this disorder, and the clinical significance of each of these elements is increasing as more is understood. This review proposes an updated standard classification of rosacea that is based on phenotypes linked to our increased understanding of disease pathophysiology. This updated classification is intended to provide clearer parameters to conduct investigations, guide diagnosis, and improve treatment.
238 citations
TL;DR: Fezakinumab was well‐tolerated, with sustained clinical improvements after last drug dosing, andSignificance was primarily obtained in severe AD.
Abstract: Background Interleukin 22 promotes epidermal hyperplasia and inhibits skin barrier function. Objective Evaluate interleukin 22 blockade in adults with moderate-to-severe atopic dermatitis (AD). Methods We performed a randomized, double-blind, placebo-controlled trial with intravenous fezakinumab monotherapy every 2 weeks for 10 weeks, with follow-up assessments until 20 weeks. The change in SCOring AD (SCORAD) score from baseline at 12 weeks served as the primary end point. Results At 12 weeks, the mean declines in SCORAD for the entire study population were 13.8 ± 2.7 in the fezakinumab arm and 8.0 ± 3.1 in the placebo arm (P = .134). In the severe AD patient subset (with a baseline SCORAD of ≥50), SCORAD decline was significantly stronger in the drug-treated patients than placebo-treated patients at 12 weeks (21.6 ± 3.8 vs 9.6 ± 4.2, P = .029) and 20 weeks (27.4 ± 3.9 vs 11.5 ± 5.1, P = .010). At 12 weeks, improvements in body surface area involvement in the entire population were significantly stronger in the drug-treated than placebo-treated patients (12.4% ± 2.4 vs 6.2% ± 2.7; P = .009), and in the severe AD subset, the decline in Investigator Global Assessment was significantly higher in the drug-treated than placebo-treated patients (0.7 ± 0.2 vs 0.3 ± 0.1; P = .034). All scores showed progressive improvements after last dosing (10 weeks) until end of study (20 weeks). Common adverse events were upper respiratory tract infections. Limitations The limited sample size and lack of assessment with Eczema Area and Severity Index and a pruritus numerical rating scale were limiting factors. Significance was primarily obtained in severe AD. Conclusion Fezakinumab was well-tolerated, with sustained clinical improvements after last drug dosing.
231 citations
TL;DR: Deep learning computer vision systems classified melanoma dermoscopy images with accuracy that exceeded some but not all dermatologists, as well as combining individual automated predictions into “fusion” algorithms.
Abstract: Background Computer vision may aid in melanoma detection Objective We sought to compare melanoma diagnostic accuracy of computer algorithms to dermatologists using dermoscopic images Methods We conducted a cross-sectional study using 100 randomly selected dermoscopic images (50 melanomas, 44 nevi, and 6 lentigines) from an international computer vision melanoma challenge dataset (n = 379), along with individual algorithm results from 25 teams We used 5 methods (nonlearned and machine learning) to combine individual automated predictions into "fusion" algorithms In a companion study, 8 dermatologists classified the lesions in the 100 images as either benign or malignant Results The average sensitivity and specificity of dermatologists in classification was 82% and 59% At 82% sensitivity, dermatologist specificity was similar to the top challenge algorithm (59% vs 62%, P = 68) but lower than the best-performing fusion algorithm (59% vs 76%, P = 02) Receiver operating characteristic area of the top fusion algorithm was greater than the mean receiver operating characteristic area of dermatologists (086 vs 071, P = 001) Limitations The dataset lacked the full spectrum of skin lesions encountered in clinical practice, particularly banal lesions Readers and algorithms were not provided clinical data (eg, age or lesion history/symptoms) Results obtained using our study design cannot be extrapolated to clinical practice Conclusion Deep learning computer vision systems classified melanoma dermoscopy images with accuracy that exceeded some but not all dermatologists
226 citations
University of New South Wales1, University of Pennsylvania2, Veterans Health Administration3, University of Zagreb4, Kurume University5, University of North Carolina at Chapel Hill6, University at Buffalo7, Tehran University of Medical Sciences8, University of Marburg9, University Medical Center Groningen10, Rabin Medical Center11, University Hospital of Bern12, Yonsei University13, Keio University14, Mayo Clinic15, Cairo University16, Icahn School of Medicine at Mount Sinai17, University of Utah18, Mercy Health19, Hokkaido University20, Medical University of Warsaw21, Akdeniz University22, Reims University23, Emory University24, Duke University25, Paracelsus Private Medical University of Salzburg26, Aristotle University of Thessaloniki27, Masaryk University28, Clínica Alemana29, Karadeniz Technical University30, University of Lübeck31, University of São Paulo32, University of California, Irvine33, Sheba Medical Center34, University of Parma35, University of Barcelona36, St. John's University37, Leicester Royal Infirmary38, Stanford University39, United States Department of Veterans Affairs40, University of California, Davis41
TL;DR: Recommendations from a subsequent Delphi consensus to broaden the generalizability of recommendations includes intravenous CD20 inhibitors as a first line therapy option for moderate to severe pemphigus.
Abstract: Background Several European countries recently developed international diagnostic and management guidelines for pemphigus, which have been instrumental in the standardization of pemphigus management. Objective We now present results from a subsequent Delphi consensus to broaden the generalizability of the recommendations. Methods A preliminary survey, based on the European Dermatology Forum and the European Academy of Dermatology and Venereology guidelines, was sent to a panel of international experts to determine the level of consensus. The results were discussed at the International Bullous Diseases Consensus Group in March 2016 during the annual American Academy of Dermatology conference. Following the meeting, a second survey was sent to more experts to achieve greater international consensus. Results The 39 experts participated in the first round of the Delphi survey, and 54 experts from 21 countries completed the second round. The number of statements in the survey was reduced from 175 topics in Delphi I to 24 topics in Delphi II on the basis of Delphi results and meeting discussion. Limitations Each recommendation represents the majority opinion and therefore may not reflect all possible treatment options available. Conclusions We present here the recommendations resulting from this Delphi process. This international consensus includes intravenous CD20 inhibitors as a first-line therapy option for moderate-to-severe pemphigus.
207 citations
TL;DR: Clinical trials have shown that adults with moderate‐to‐severe AD who receive weekly or biweekly dupilumab injections have significantly improved clinical and patient‐reported outcomes, including Eczema Area Severity Index, SCORing Atopic Dermatitis, Dermatology Life Quality Index, and itch Numeric Rating Scale scores.
Abstract: Atopic dermatitis (AD) is a chronic, pruritic immune-mediated inflammatory dermatosis characterized by a T helper 2 (Th2) immune response phenotype and may be associated with systemic inflammation. Dupilumab is an interleukin 4 (IL-4) receptor α-antagonist that inhibits IL-4 and IL-13 signaling through blockade of the shared IL-4α subunit. Blockade of IL-4/13 is effective in reducing Th2 response. Dupilumab has recently been approved in the United States and Europe for the treatment of adult patients with moderate-to-severe AD. Clinical trials have shown that adults with moderate-to-severe AD who receive weekly or biweekly dupilumab injections have significantly improved clinical and patient-reported outcomes, including Eczema Area Severity Index, SCORing Atopic Dermatitis, Dermatology Life Quality Index, and itch Numeric Rating Scale scores. Concomitant use of topical corticosteroids along with dupilumab results in a greater improvement in signs and symptoms of AD than with use of dupilumab alone. Biomarker analyses show that dupilumab modulates the AD molecular signature and other Th2-associated biomarkers. Common adverse events reported in the clinical trials were nasopharyngitis, upper respiratory tract infection, injection site reactions, skin infections, and conjunctivitis. These were mild-to-moderate in nature, and overall rates of adverse events occurred with similar frequency between the treatment and placebo groups. There were no significant serious safety concerns identified in phase III clinical trials. Dupilumab, as monotherapy or with concomitant use of topical corticosteroids, can significantly improve clinical outcomes and quality of life in patients suffering from moderate-to-severe AD. Ongoing studies of dupilumab will help determine the clinical efficacy and safety profile of its long-term use.
Penn State Milton S. Hershey Medical Center1, Mount Sinai Hospital2, First Pavlov State Medical University of St. Peterburg3, University of Ferrara4, Memorial Medical Center5, Hospital Kuala Lumpur6, National Skin Centre7, Otto-von-Guericke University Magdeburg8, Universidad Autónoma de Nuevo León9, University of Chile10, Johns Hopkins University11, University of Szeged12, University of Antwerp13, University of Pennsylvania14, Chulalongkorn University15, Bumrungrad International Hospital16, Karolinska University Hospital17, Central University of Venezuela18, New Generation University College19, University of Western Ontario20, University of Buenos Aires21, Fudan University22
TL;DR: This supplement focuses on providing relevant clinical guidance to health care practitioners managing patients with acne, with an emphasis on areas where the evidence base may be sparse or need interpretation for daily practice.
Abstract: Scientific advances are continually improving the knowledge of acne and contributing to the refinement of treatment options; it is important for clinicians to regularly update their practice patterns to reflect current standards. The Global Alliance to Improve Outcomes in Acne is an international group of dermatologists with an interest in acne research and education that has been meeting regularly since 2001. As a group, we have continuously evaluated the literature on acne. This supplement focuses on providing relevant clinical guidance to health care practitioners managing patients with acne, with an emphasis on areas where the evidence base may be sparse or need interpretation for daily practice.
TL;DR: Depression, anxiety, and suicidal ideation should be considered by doctors when treating patients with AD because AD disease improvement appears to reduce these risks, this should be a priority.
Abstract: Background Atopic dermatitis (AD) has been associated with anxiety and depression, but the magnitude of the alleged association is unknown. Objective To perform a systematic review and meta-analysis of the association between AD in children and adults and, respectively, depression, anxiety, and suicidal behavior. Methods The medical databases PubMed, Embase, and PsychINFO were searched. Results There was a significant association between adult AD and, respectively, depression (pooled odds ratio [OR], 2.19; 95% confidence interval [CI], 1.87-2.57) and anxiety (pooled OR, 2.19; 95% CI, 1.75-2.73). AD was also associated with depression in children (pooled OR, 1.27; 95% CI, 1.12-1.45); few data were available for anxiety. A positive association was found between AD in adults and adolescents and suicidal ideation (pooled OR, 4.32; 95% CI, 1.93-9.66). Only a few studies examined the risk of completed suicide, but the majority showed a positive association between completed suicide and AD. Limitations Included studies used different definitions of depression and anxiety, and few studies examined the severity of AD. Conclusion Depression, anxiety, and suicidal ideation should be considered by doctors when treating patients with AD. Because AD disease improvement appears to reduce these risks, this should be a priority.
TL;DR: The evidence supporting new treatment methods, among them Janus kinase inhibitors, are described and an overview of conventional therapy is provided with new insights gleaned from recent studies.
Abstract: Many therapies are available for the treatment of alopecia areata, including topical, systemic, and injectable modalities. However, these treatment methods produce variable clinical outcomes and there are no currently available treatments that induce and sustain remission. When making management decisions, clinicians must first stratify patients into pediatric versus adult populations. Disease severity should then be determined (limited vs extensive) before deciding the final course of therapy. The second article in this continuing medical education series describes the evidence supporting new treatment methods, among them Janus kinase inhibitors. We evaluate the evidence concerning the efficacy, side effects, and durability of these medications. An overview of conventional therapy is also provided with new insights gleaned from recent studies. Finally, future promising therapeutic options that have not yet been fully evaluated will also be presented.
TL;DR: Dual neutralization of IL‐ 17A and IL‐17F with bimekizumab provided rapid and substantial clinical improvements in patients with psoriasis, with no unexpected or dose‐related safety findings.
Abstract: Background Neutralizing interleukin (IL) 17F in addition to IL-17A might provide a more complete and specific approach to inhibiting inflammation. Objective Assess the efficacy and safety of bimekizumab, a monoclonal antibody that potently and selectively neutralizes IL-17A and IL-17F, in patients with moderate-to-severe plaque psoriasis. Methods Double-blinded, placebo-controlled phase 2b study (NCT02905006). Patients (randomized 1:1:1:1:1:1) received subcutaneous bimekizumab every 4 weeks at doses of 64 mg, 160 mg, 160 mg with 320 mg loading dose, 320 mg, 480 mg, or placebo. Primary endpoint was ≥90% reduction in Psoriasis Area Severity Index (PASI90) at week 12. Results There was a significant (P Limitations No active comparator. Conclusion Dual neutralization of IL-17A and IL-17F with bimekizumab provided rapid and substantial clinical improvements in patients with psoriasis, with no unexpected or dose-related safety findings.
TL;DR: In this paper, the authors evaluate the clinical and histopathologic findings, frequency, and impact on cancer therapy of bullous eruptions due to anti-programmed cell death 1 (PD-1)/programmed Cell death ligand 1(PD-L1) therapy.
Abstract: Background Bullous disorders associated with anti–programmed cell death 1 (PD-1)/programmed cell death ligand 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 oncodermatology clinic and consultative service of Yale New Haven Hospital from 2016 to 2018. Results We identified 9 of 853 patients who developed bullous eruptions (∼1%) that were 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. In all, 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. Conclusions 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.
TL;DR: Comparison with controls and the timing of events do not indicate a causal relationship between SIB and brodalumab treatment.
Abstract: Background Individuals with psoriasis are at increased risk for psychiatric comorbidities, including suicidal ideation and behavior (SIB). Objective To distinguish between the underlying risk and potential for treatment-induced psychiatric adverse events in patients with psoriasis being treated with brodalumab, a fully human anti–interleukin 17 receptor A monoclonal antibody. Methods Data were evaluated from a placebo-controlled, phase 2 clinical trial; the open-label, long-term extension of the phase 2 clinical trial; and three phase 3, randomized, double-blind, controlled clinical trials (AMAGINE-1, AMAGINE-2, and AMAGINE-3) and their open-label, long-term extensions of patients with moderate-to-severe psoriasis. Results The analysis included 4464 patients with 9161.8 patient-years of brodalumab exposure. The follow-up time–adjusted incidence rates of SIB events were comparable between the brodalumab and ustekinumab groups throughout the 52-week controlled phases (0.20 vs 0.60 per 100 patient-years). In the brodalumab group, 4 completed suicides were reported, 1 of which was later adjudicated as indeterminate; all patients had underlying psychiatric disorders or stressors. Limitations There was no comparator arm past week 52. Controlled study periods were not powered to detect differences in rare events such as suicide. Conclusions Comparison with controls and the timing of events do not indicate a causal relationship between SIB and brodalumab treatment.
TL;DR: Treatment with either certolizumab 400 mg or 200 mg every 2 weeks was associated with significant and clinically meaningful improvements in moderate‐to‐severe psoriasis, and the 400‐mg dose could provide additional clinical benefit.
Abstract: Background Certolizumab pegol, the only Fc-free, PEGylated anti–tumor necrosis factor biologic, demonstrated clinically meaningful improvements suggestive of 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, certolizumab 200 mg, or placebo every 2 weeks. At week 16, certolizumab-treated patients achieving a 50% reduction in Psoriasis Area and Severity Index continued treatment through week 48. Coprimary endpoints were week 16 responder rates, defined as a 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 the responses were maintained through week 48. For most measures, improvement was numerically greater for certolizumab 400 mg. No unexpected safety signals were identified. Limitation There was no active comparator. Conclusion Treatment with either certolizumab 400 mg or 200 mg every 2 weeks was associated with significant and clinically meaningful improvements in moderate-to-severe psoriasis. The 400-mg dose could provide additional clinical benefit. The safety profile was consistent with the therapeutic class.
TL;DR: Systemic treatment incorporating steroids and cytostatic drugs for at least one year has improved prognosis of multisystem LCH and represents the current standard of care.
Abstract: Langerhans cell histiocytosis (LCH) is an inflammatory neoplasia of myeloid precursor cells driven by mutations in the mitogen-activated protein kinase pathway. When disease involves the skin, LCH most commonly presents as a seborrheic dermatitis or eczematous eruption on the scalp and trunk. Evaluation for involvement of other organ systems is essential, because 9 of 10 patients presenting with cutaneous disease also have multisystem involvement. Clinical manifestations range from isolated disease with spontaneous resolution to life-threatening multisystem disease. Prognosis depends on involvement of risk organs (liver, spleen, and bone marrow) at diagnosis, particularly on presence of organ dysfunction, and response to initial therapy. Systemic treatment incorporating steroids and cytostatic drugs for at least one year has improved prognosis of multisystem LCH and represents the current standard of care.
TL;DR: The first article in this continuing medical education series explores the pathogenesis of neutrophilic dermatoses and reviews the epidemiology, clinical and histopathologic features, diagnosis, and management of Sweet syndrome, neutrophobic eccrine hidradenitis, and Behçet disease.
Abstract: Neutrophilic dermatoses are a heterogeneous group of inflammatory skin disorders that present with unique clinical features but are unified by the presence of a sterile, predominantly neutrophilic infiltrate on histopathology. The morphology of cutaneous lesions associated with these disorders is heterogeneous, which renders diagnosis challenging. Moreover, a thorough evaluation is required to exclude diseases that mimic these disorders and to diagnose potential associated infectious, inflammatory, and neoplastic processes. While some neutrophilic dermatoses may resolve spontaneously, most require treatment to achieve remission. Delays in diagnosis and treatment can lead to significant patient morbidity and even mortality. Therapeutic modalities range from systemic corticosteroids to novel biologic agents, and the treatment literature is rapidly expanding. The first article in this continuing medical education series explores the pathogenesis of neutrophilic dermatoses and reviews the epidemiology, clinical and histopathologic features, diagnosis, and management of Sweet syndrome, neutrophilic eccrine hidradenitis, and Behcet disease.
TL;DR: Both certolizumab regimens improved psoriasis symptoms, with a greater response seen with the higher dose, and no new safety signals were observed.
Abstract: Background Phase 2 psoriasis studies with the Fc-free, PEGylated, anti–tumor necrosis factor biologic certolizumab pegol demonstrated meaningful clinical activity. Objective Assess safety and efficacy of certolizumab in adults with moderate-to-severe chronic plaque psoriasis. Methods Patients were randomized 3:3:1:3 to certolizumab 400 mg, certolizumab 200 mg, or placebo every 2 weeks for 16 weeks or etanercept 50 mg twice weekly for 12 weeks. Certolizumab-treated patients achieving a ≥75% reduction in Psoriasis Area and Severity Index (PASI) at week 16 from baseline PASI were rerandomized to certolizumab or placebo for 32 weeks. The primary endpoint was responder rate (≥75% reduction in PASI from baseline PASI) versus placebo (primary analysis) and etanercept (secondary analysis) at week 12; secondary endpoints included responder rates on various measures versus placebo at weeks 12, 16, and 48. Safety was assessed by treatment-emergent adverse events. Results All endpoints were significantly greater for certolizumab versus placebo with the greatest response seen with 400 mg. Certolizumab 400 mg was superior to and 200 mg was noninferior to etanercept. Adverse events were consistent with the anti–tumor necrosis factor class of drugs. Limitations Etanercept was administered by unblinded study staff or self-administered, but efficacy assessments were performed by a blinded assessor. Conclusion Both certolizumab regimens improved psoriasis symptoms, with a greater response seen with the higher dose. No new safety signals were observed.
TL;DR: The second article in this continuing medical education series addresses in question and answer format the most common questions related to advanced and high-stage cutaneous squamous cell carcinomas, with a simplified flowchart as mentioned in this paper.
Abstract: While the majority of cutaneous squamous cell carcinomas (cSCCs) can be treated surgically, the additional work-up and treatments indicated for high-risk cSCC remain undefined. In recent years, improvements in tumor staging systems have allowed for the more accurate stratification of tumors into high- and low-risk categories. This insight, along with the publication of cSCC guidelines, brings us closer to the development of a consensus approach. The second article in this continuing medical education series addresses in question and answer format the most common questions related to advanced and high-stage cSCCs, with a simplified flowchart. The questions include the following: 1) Does my patient have high-risk cSCC?; 2) What is the next step for patients with cSCC and palpable lymphadenopathy?; 3) In patients with no clinically evident lymphadenopathy, who are candidates for lymph node staging?; 4) What forms of radiologic imaging can help detect subclinical lymph node metastases?; 5) What is the role of sentinel lymph node biopsy in cSCC?; 6) Which patients with cSCC need adjuvant radiation therapy?; 7) Is adjuvant chemotherapy an option for patients with high-stage cSCC after surgery?; 8) Are targeted and immunologic therapies an option for advanced cSCC?; 9) How often should I follow up with my patient after he/she has been diagnosed with a high-risk cSCC?; 10) What are the options for chemoprophylaxis in a patient with an increased risk of cSCC?; and 11) What chemopreventive measures can be started in coordination with medical oncology or transplant physicians?
TL;DR: Adequate follow-up to monitor for disease progression, relapse, and sequelae is recommended in all patients, and positive immunohistochemistry staining for CD1a and CD207 (langerin) are required for a definitive diagnosis.
Abstract: A definitive diagnosis of Langerhans cell histiocytosis (LCH) requires a combination of clinical presentation, histology, and immunohistochemistry. The inflammatory infiltrate contains various proportions of LCH cells, the disease hallmark, which are round and have characteristic "coffee-bean" cleaved nuclei and eosinophilic cytoplasm. Positive immunohistochemistry staining for CD1a and CD207 (langerin) are required for a definitive diagnosis. Isolated cutaneous disease should only be treated when symptomatic, because spontaneous resolution is common. Topical steroids are first-line treatment for localized disease of skin and bone. For multifocal single-system or multisystem disease, systemic treatment with steroids and vinblastine for 12 months is the standard first-line regimen. Current research is seeking more effective regimens because recurrence rates, which increase the risk of sequelae, are still high (30-50%) in patients with multisystem disease. An active area of research is the use of targeted therapy directed at the mitogen-activated protein kinase pathway. Adequate follow-up to monitor for disease progression, relapse, and sequelae is recommended in all patients.
TL;DR: The first article in this 2-part continuing medical education series provides a comprehensive overview of the clinical and pathologic characteristics of cutaneous lichenoid dermatoses and links these manifestations to recent advances in the understanding of the underlying pathobiology of such diseases.
Abstract: Deriving from the Greek word λeιχήν for "tree moss" and the Latin word planus for "planar," lichen planus is a relatively uncommon and heterogeneous cutaneous disorder that typically develops in middle-aged adults. Despite the significant clinical burden associated with the disorder, little well-conducted molecular research has been undertaken, possibly because of heterogeneity impeding consistent and confident phenotyping. The multiple variants of lichenoid disease bear overlapping clinical and pathologic features despite manifesting as distinct clinical disorders. The first article in this 2-part continuing medical education series provides a comprehensive overview of the clinical and pathologic characteristics of cutaneous lichenoid dermatoses and links these manifestations to recent advances in our understanding of the underlying pathobiology of such diseases.
TL;DR: Dupilumab is associated with a decreased incidence of skin infections and eczema herpeticum in adults with moderate‐to‐severe AD, and the mechanism underlying this association is uncertain but is likely related to improvement in AD severity.
Abstract: Background Atopic dermatitis (AD) is characterized by skin barrier defects, T helper type 2 cell activation, and increased risk for cutaneous and extracutaneous infections. In clinical trials, dupilumab appeared to decrease rates of skin infections in AD. Objective We aimed to determine the impact of dupilumab on rates of skin and other infections in patients with moderate-to-severe AD. Methods We conducted a systematic review and meta-analysis of randomized controlled trials of dupilumab for AD. We searched the PubMed database for relevant studies. Risk ratios (RRs) and 95% confidence intervals (CIs) for skin infections, herpesvirus infections, and overall infections and infestations were calculated for dupilumab compared with for placebo by using binary random effects meta-analysis. For the analysis of eczema herpeticum, Peto odds ratios were calculated. Results Eight randomized controlled trials in 4 publications with 2706 participants were included, with follow-up time ranging from 4 to 52 weeks. Meta-analysis including all dosing schedules and follow-up times showed a RR of skin infection of 0.54 (95% CI, 0.42-0.70) and an odds ratio of eczema herpeticum of 0.34 (95% CI, 0.14-0.84) for dupilumab compared with placebo. No significant association was found for dupilumab with overall herpesvirus infections (RR, 1.16; 95% CI, 0.78-1.74) and overall infections (RR, 0.98; 95% CI, 0.83-1.16). Limitations Our analysis is limited by the short follow-up time in most trials and the relatively low number of patients treated with dupilumab to date. Conclusions Dupilumab is associated with a decreased incidence of skin infections and eczema herpeticum in adults with moderate-to-severe AD. The mechanism underlying this association is uncertain but is likely related to improvement in AD severity. Dupilumab, a monoclonal antibody targeting interleukin 4 and interleukin 13, appears to significantly decrease the risk for skin infections and eczema herpeticum in adults with moderate-to-severe AD.
TL;DR: Lichenoid and spongiotic dermatitis associated with PD‐1/PD‐L1 inhibitors could be a sign of robust immune response and improved oncologic outcomes and await investigation through prospective multicenter studies for specific cancer types.
Abstract: Background Cutaneous adverse events are common with programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) 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 To assess the nature of dermatitis after exposure to a PD-1/PD-L1 inhibitor 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%). The overall tumor response rate was 65.0% for the case patients and 17.0% for the controls (P = .0007) (odds ratio, 7.3; 95% confidence interval, 2.3-23.1). The progression-free survival and overall survival times were significantly longer for the case patients than for the controls by Kaplan-Meier analysis (P Limitations The retrospective design and relatively small sample size precluded matching for all cancer types. Conclusions Lichenoid and spongiotic dermatitis associated with PD-1/PD-L1 inhibitors could be a sign of robust immune response and improved oncologic outcomes. The value of PD-1/PD-L1–related dermatitis in predicting cancer outcomes awaits investigation through prospective multicenter studies for specific cancer types.
TL;DR: Serlopitant, 1 mg and 5 mg daily, was associated with a statistically significant reduction in chronic pruritus and was well tolerated (NCT01951274).
Abstract: Background The substance P/neurokinin 1 receptor pathway is critical in chronic pruritus; anecdotal evidence suggests that antagonism of this pathway can reduce chronic itch Objective To assess the safety and efficacy of the substance P/neurokinin 1 receptor antagonist serlopitant in treating chronic pruritus Methods Eligible patients with severe chronic pruritus who were refractory to antihistamines or topical steroids were randomized to serlopitant, 025, 1, or 5 mg, or to placebo, administered once daily for 6 weeks as monotherapy or with midpotency steroids and emollients The primary efficacy end point was percentage change in visual analog scale pruritus score from baseline Results Serlopitant treatment resulted in a dose-dependent decrease in pruritus The mean percentage decreases from baseline visual analog scale pruritus scores were statistically significantly larger with the 1- and 5-mg doses of serlopitant ( P = 022 and P = 013, respectively) than with placebo at week 6 No significant safety or tolerability differences were detected among the groups Limitations The sample size was insufficient for subgroup analyses of the efficacy of serlopitant for chronic pruritus on the basis of underlying conditions Conclusions Serlopitant, 1 mg and 5 mg daily, was associated with a statistically significant reduction in chronic pruritus and was well tolerated (NCT01951274)
TL;DR: Exeditious treatment of stage I melanoma is associated with improved outcomes, and surgical timing did not affect survival in stages II and III.
Abstract: Background The ideal timing for melanoma treatment, predominantly surgery, remains undetermined. Patient concern for receiving immediate treatment often exceeds surgeon or hospital availability, requiring establishment of a safe window for melanoma surgery. Objective To assess the impact of time to definitive melanoma surgery on overall survival. Methods Patients with stage I to III cutaneous melanoma and with available time to definitive surgery and overall survival were identified by using the National Cancer Database (N = 153,218). The t test and chi-square test were used to compare variables. Cox regression was used for multivariate analysis. Results In a multivariate analysis of patients in all stages who were treated between 90 and 119 days after biopsy (hazard ratio [HR], 1.09; 95% confidence interval [CI], 1.01-1.18) and more than 119 days (HR, 1.12; 95% CI, 1.02-1.22) had a higher risk for mortality compared with those treated within 30 days of biopsy. In a subgroup analysis of stage I, higher mortality risk was found in patients treated within 30 to 59 days (HR, 1.05; 95% CI, 1.01-1.1), 60 to 89 days (HR, 1.16; 95% CI, 1.07-1.25), 90 to 119 days (HR, 1.29; 95% CI, 1.12-1.48), and more than 119 days after biopsy (HR, 1.41; 95% CI, 1.21-1.65). Surgical timing did not affect survival in stages II and III. Limitations Melanoma-specific survival was not available. Conclusion Expeditious treatment of stage I melanoma is associated with improved outcomes.
TL;DR: A comparison of the study patients and race‐matched controls revealed that PN was significantly associated with a variety of systemic, cardiovascular, and psychiatric comorbidities, including chronic kidney disease, chronic hepatitis C, chronic obstructive pulmonary disease, congestive heart failure, depression, and atopic dermatitis.
Abstract: 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 and older who were seen at the Johns Hopkins Health System between December 6, 2012, and December 6, 2017. Results Over the past 5 years, 909 patients with PN were seen at Johns Hopkins Health System. African American patients were 3.4 times more likely to have PN than white patients were (odds ratio [OR], 3.4; 95% confidence interval [CI], 2.9-3.9; P Limitations Our data describe patients seen by 1 hospital system. Our data identify associated conditions and comorbidities but are 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.
TL;DR: Clinicians may measure BSA affected by psoriasis to target diabetes prevention efforts for patients with Psoriasis, and Worldwide, it is estimated an additional 125,650 new diagnoses of type 2 diabetes mellitus per year in patients with ps oriasis as compared with in those without psOriasis.
Abstract: Background Data evaluating the impact of objectively measured psoriasis severity on type 2 diabetes mellitus (T2DM) risk are lacking. Objective To determine the risk for T2DM in patients with psoriasis compared with that in adults without psoriasis, stratified by categories of directly assessed body surface area (BSA) affected by psoriasis. Methods A prospective, population-based, cohort study from the United Kingdom in which 8124 adults with psoriasis and 76,599 adults without psoriasis were followed prospectively for approximately 4 years. Results There were 280 incident cases of diabetes in the psoriasis group (3.44%) and 1867 incident cases of diabetes in those without psoriasis (2.44%). After adjustment for age, sex and body mass index, the hazard ratios for development of incident diabetes were 1.21 (95% confidence interval [CI], 1.01-1.44), 1.01 (95% CI, 0.81-1.26), and 1.64 (95% CI, 1.23-2.18) in the groups with 2% or less of their BSA affected, 3% to 10% of their BSA affected, and 10% or more of their BSA affected compared with in the groups without psoriasis, respectively ( P = .004 for trend). Worldwide, we estimate an additional 125,650 new diagnoses of T2DM per year in patients with psoriasis as compared with in those without psoriasis. Limitations Relatively short-term follow-up and exclusion of prevalence cases, which may have masked associations in patients with less extensive psoriasis. Conclusion Clinicians may measure BSA affected by psoriasis to target diabetes prevention efforts for patients with psoriasis.