Impact of Clinical Specialty Setting and Geographic Regions on Disease Management in Patients with Psoriatic Arthritis in the United States: A Multicenter Observational Study Abstract Background Information on the factors that influence treatment management decisions for psoriatic arthritis (PsA) is limited. Objective Our objective was to evaluate the impact of clinical specialty setting and geographic region on the management of patients with PsA in the USA. Methods LOOP was a multicenter, cross-sectional, observational study conducted across 44 sites in the USA. Patients were aged ≥ 18 years with a suspected or established diagnosis of PsA and were routinely visiting a rheumatologist or dermatologist. All patients enrolled in the study were assessed by both a rheumatologist and a dermatologist. Primary outcomes were the times from symptom onset to PsA diagnosis; PsA diagnosis to first conventional synthetic disease-modifying antirheumatic drug (csDMARD); PsA diagnosis to first biologic DMARD (bDMARD); and first csDMARD to first bDMARD. Results Of 681 patients enrolled in the study, 513 had a confirmed diagnosis of PsA and were included in this analysis. More patients were recruited by rheumatologists (71.3%) than by dermatologists (28.7%). The median time from symptom onset to diagnosis of PsA was significantly shorter for patients enrolled by rheumatologists than for those enrolled by dermatologists (1.0 vs. 2.6 years; p < 0.001). Disease activity and burden were generally similar across enrolling specialties. However, patients in western areas of the USA had less severe disease than those in central or eastern areas, including measures of joint involvement, enthesitis, and dactylitis. Conclusions There was a substantial delay in the time from symptom onset to diagnosis in this study population, and this was significantly longer for patients enrolled in the dermatology versus the rheumatology setting. This supports the need for collaboration across specialties to ensure faster recognition and treatment of PsA.

Efficacy, Safety, and Patient-Reported Outcomes in Patients with Moderate-to-Severe Plaque Psoriasis Treated with Brodalumab for 5 Years in a Long-Term, Open-Label, Phase II Study Abstract Background Chronic inflammatory diseases such as psoriasis require treatment options that maintain efficacy and tolerability during extended treatment. Objective The aim of the study was to assess the long-term efficacy and safety of brodalumab, a fully human anti-interleukin-17 receptor A monoclonal antibody, in patients with moderate-to-severe plaque psoriasis. Methods Patients who completed a 12-week, phase II, dose-ranging clinical trial received brodalumab 210 mg every 2 weeks in an open-label extension study. Efficacy was assessed by static physician’s global assessment (sPGA) and psoriasis area and severity index (PASI). Quality of life, assessed by dermatology life quality index (DLQI), and safety were also evaluated. Results Overall, 181 patients received brodalumab for a median of 264 weeks. Brodalumab treatment resulted in rapid improvements in sPGA, PASI, and DLQI that were maintained through week 264. Achieving PASI 90 to < 100 or PASI 100 at weeks 12, 240, and 264 was associated with greater likelihood for DLQI 0 or 1 compared with achieving PASI 75 to < 90. Over 5 years, one adverse event of suicidal ideation was reported, no suicides occurred, and no new safety signals emerged. Conclusions Brodalumab demonstrated skin clearance and improved quality of life, with an acceptable safety profile, throughout 5 years of treatment. ClinicalTrials.gov Identifier NCT01101100.

Oral Lesions in Autoimmune Bullous Diseases: An Overview of Clinical Characteristics and Diagnostic Algorithm Abstract Autoimmune bullous diseases are a group of chronic inflammatory disorders caused by autoantibodies targeted against structural proteins of the desmosomal and hemidesmosomal plaques in the skin and mucosa, leading to intra-epithelial or subepithelial blistering. The oral mucosa is frequently affected in these diseases, in particular, in mucous membrane pemphigoid, pemphigus vulgaris, and paraneoplastic pemphigus. The clinical symptoms are heterogeneous and may present with erythema, blisters, erosions, and ulcers localized anywhere on the oral mucosa, and lead to severe complaints for the patients including pain, dysphagia, and foetor. Therefore, a quick and proper diagnosis with adequate treatment is needed. Clinical presentations of autoimmune bullous diseases often overlap and diagnosis cannot be made based on clinical features alone. Immunodiagnostic tests are of great importance in differentiating between the different diseases. Direct immunofluorescence microscopy shows depositions of autoantibodies along the epithelial basement membrane zone in mucous membrane pemphigoid subtypes, or depositions on the epithelial cell surface in pemphigus variants. Additional immunoserological tests are useful to discriminate between the different subtypes of pemphigoid, and are essential to differentiate between pemphigus and paraneoplastic pemphigus. This review gives an overview of the clinical characteristics of oral lesions and the diagnostic procedures in autoimmune blistering diseases, and provides a diagnostic algorithm for daily practice.

Managing Psoriasis in Patients with HBV or HCV Infection: Practical Considerations Abstract Considered more efficacious and safer than traditional systemic drugs, biologic therapies have dramatically improved the quality of life of patients with psoriasis. Recently, there has been a proliferation of new targeted treatment options, including anti-interleukin-17, anti-interleukin-12/23, as well as small-molecule drugs such as apremilast. There are nevertheless some concerns regarding their use, especially in patients with chronic infections such as hepatitis B virus (HBV) and hepatitis C virus (HCV). It has been estimated that two billion individuals are infected with HBV worldwide and approximately 240 million have chronic HBV infection. Moreover, there are approximately 71 million individuals with chronic HCV infection worldwide, with a high percentage of them unaware of being infected. As patients with HBV and HCV infections are excluded from controlled clinical trials investigating new drugs, data regarding their safety in patients with psoriasis are based almost exclusively on case reports and small retrospective cohort studies and need to be constantly updated. The risk of HBV reactivation can be defined as: high risk (≥ 10%), moderate risk (1–10%), and low risk (< 1%) depending on the type of immunosuppressive therapy stratified by the presence or absence of hepatitis B surface antigen but positivity to anti-hepatitis B core antigen. Hepatitis B surface antigen-positive patients treated with tumor necrosis factor-α inhibitors, ustekinumab, or cyclosporine carry a high or moderate risk of HBV reactivation and should be considered candidates for prophylactic anti-HBV therapy. Once therapy is commenced, it is important to check HBV DNA levels every 3 months. Hepatitis B virus reactivation typically occurs with immune reconstitution and therefore antiviral therapy should continue for 6–12 months after stopping immunosuppression. Hepatitis B surface antigen-positive patients who are prescribed methotrexate, acitretin, or apremilast have a low risk and need to be monitored for viral reactivation by determining alanine aminotransferase and HBV DNA levels every 3 months. No conclusive data are available for interleukin-17 and interleukin-23 inhibitors. Anti-hepatitis B core antigen-positive patients treated with tumor necrosis factor-α inhibitors, ustekinumab, and cyclosporine are linked to a moderate risk of reactivation, and they should preferably undergo HBV DNA or hepatitis B surface antigen and alanine aminotransferase testing rather than be subjected to routine pre-emptive therapy. Anti-hepatitis B core antigen-positive patients receiving methotrexate, acitretin, or apremilast have a low risk of reactivation and do not require anti-HBV therapy, nor should monitoring be considered mandatory. No conclusive data are available for interleukin-17 and interleukin-23 inhibitors.

Level of Evidence Review for a Gene Expression Profile Test for Cutaneous Melanoma Abstract Background The advent of molecular medicine may allow for individualized cancer prognostication, which should enable better clinical management and, hopefully, improve patient outcomes. A 31-gene expression profile (31-GEP) test is currently available for patients diagnosed with cutaneous melanoma; this test helps inform patients’ individual treatment plans, especially when combined with traditional biomarkers. Objective The objective of this study was to review the current literature and establish the level of evidence for a cutaneous melanoma 31-GEP test. Methods A review of seven development and validation studies for the 31-GEP test was conducted. The respective strengths and weaknesses of each study were applied to the level of evidence criteria from major organizations that publish guidelines for melanoma management: American Joint Committee on Cancer, National Comprehensive Cancer Network, and American Academy of Dermatology. Results Evaluating each study led to classifying the 31-GEP test as level I/II, I–IIIB, and IIA according to American Joint Committee on Cancer, National Comprehensive Cancer Network, and American Academy of Dermatology criteria, respectively. This stands in contrast to the official unrated status conferred by the American Joint Committee on Cancer and National Comprehensive Cancer Network and the II/IIIC rating designated by the American Academy of Dermatology. Conclusions Differences between the authors’ findings and official published ratings may be attributed to chronological issues, as many of the studies were not yet published when the aforementioned organizations conducted their reviews. There was also difficulty in applying the National Comprehensive Cancer Network criteria to this prognostic test, as their guidelines were intended for evaluation of predictive markers. Nevertheless, based upon the most current data available, integration of the 31-GEP test into clinical practice may be warranted in certain clinical situations.

Intratumoral and Combination Therapy in Melanoma and Other Skin Cancers Abstract Skin cancer, as the most physically accessible malignancy, allows for the greatest variety in treatment innovation. The last 2 decades have seen striking increases in the life expectancies of those diagnosed with malignant melanoma. However, many cases remain in which disease prevails against standard treatment, and those patients rely on continuing ingenuity. Drugs that can be injected directly into patients’ tumors have become increasingly promising, not least for the reduction in side effects observed. Intratumoral therapy encompasses a wide array of agents, from chemotherapeutic drugs to cancer vaccines. While each show some efficacy, those agents which regulate the immune system likely have the greatest potential for preventing disease progression or recurrence. Recent research has highlighted the importance of the presence of cytotoxic T cells and of keeping regulatory T cells in check. Thus, manipulating the tumor microenvironment is a need in skin cancer therapy, which intratumoral delivery can potentially address. In order to find the best approach to each person’s disease, more studies are needed to test intralesional agents in combination with currently approved therapies and with each other.

The Microbiome and Atopic Dermatitis: A Review Abstract The microbiome is defined as the sum of microbes, their genomes, and interactions in a given ecological niche. Atopic dermatitis is a multifactorial chronic inflammatory skin disease leading to dryness and itchiness of the skin. It is often associated with comorbidities such as allergic rhinoconjunctivitis and asthma. Today, culture-free techniques have been established to define microbes and their genomes that may be both detrimental and beneficial for their host. There are signs that microbes, both on skin and in the gut, may influence the course of atopic dermatitis. Antiseptic treatment has been used for decades, however now, with the help of traditional culture-based methods and modern metagenomics, we are beginning to understand that targeted treatment of dysbiosis may possibly become part of an integrated therapy plan in the future.

Ocular Co-Morbidities of Atopic Dermatitis. Part I: Associated Ocular Diseases Abstract Ocular diseases associated with atopic dermatitis (AD) may be sight-threatening. A general understanding of the pathophysiology, diagnosis, and treatment of atopic eye disease may assist dermatologists in knowing when to refer to ophthalmology and in co-managing these diseases with ophthalmologists. Ocular diseases associated with AD include eyelid dermatitis, keratoconjunctivitis, keratoconus, cataract, and retinal detachment. AD patients are also at higher risk for bacterial and viral ocular infections. The objective of this article is to provide a current review of ocular diseases that commonly affect AD patients. The pathogenesis, clinical manifestations, diagnosis, and treatment of ocular co-morbidities of AD will be discussed.

Ocular Co-Morbidities of Atopic Dermatitis. Part II: Ocular Disease Secondary to Treatments Abstract Treatments used for managing atopic dermatitis (AD) may have adverse ocular effects that permanently affect vision. The objective of this review is to raise awareness among dermatologists regarding the potential ocular adverse effects of various AD therapies, including corticosteroids, calcineurin inhibitors, an interleukin-4 receptor α (IL-4Rα) antagonist, and phototherapy. Pertinent potential short- and long-term risks of these therapies include elevations in intraocular pressure from use of topical corticosteroids and conjunctivitis from use of dupilumab. Since some of these adverse effects may not exhibit symptomatology until permanent vision impairment occurs, it is important for dermatologists to understand these risks and proactively ensure their patients are receiving appropriate measures to prevent them.