BackgroundCholesterol management drugs known as statins are widely used and often well tolerated; however, a variety of muscle-related side effects can arise. These adverse events (AEs) can have serious impact, and form a significant barrier to therapy adherence. Surveillance of post-marketing AEs is of vital importance to understand real-world AEs and reporting differences between individual statin drugs. We conducted a review of post-approval muscle and tendon AE reports in association with statin use, to assess differences within the drug class.MethodsWe analyzed all case reports from the FDA AE Reporting System (AERS) database linking muscle-related AEs to statin use (07/01/2005–03/31/2011). Drugs examined were: atorvastatin, simvastatin, lovastatin, pravastatin, rosuvastatin, and fluvastatin.ResultsRelative risk rates for rosuvastatin were consistently higher than other statins. Atorvastatin and simvastatin showed intermediate risks, while pravastatin and lovastatin appeared to have the lowest risk rates. Relative risk of muscle-related AEs, therefore, approximately tracked with per milligram LDL-lowering potency, with fluvastatin an apparent exception. Incorporating all muscle categories, rates for atorvastatin, simvastatin, pravastatin, and lovastatin were, respectively, 55%, 26%, 17%, and 7.5% as high, as rosuvastatin, approximately tracking per milligram potency (Rosuvastatin>Atorvastatin>Simvastatin>Pravastatin≈Lovastatin) and comporting with findings of other studies. Relative potency, therefore, appears to be a fundamental predictor of muscle-related AE risk, with fluvastatin, the least potent statin, an apparent exception (risk 74% vs rosuvastatin).InterpretationAE reporting rates differed strikingly for drugs within the statin class, with relative reporting aligning substantially with potency. The data presented in this report offer important reference points for the selection of statins for cholesterol management in general and, especially, for the rechallenge of patients who have experienced muscle-related AEs (for whom agents of lower expected potency should be preferred).

BackgroundClinical trial data for dupilumab, a monoclonal antibody against the interleukin‐4 receptor (IL‐4Rα), have shown that it is safe and effective for the treatment of moderate to severe atopic dermatitis in patients whose disease is resistant to other therapies. However, little real‐world experience with dupilumab use has been reported thus far. The aim of this retrospective study was to assess overall outcomes in adult patients with atopic dermatitis (AD) treated with dupilumab.MethodsA retrospective review of electronic medical records was conducted for patients treated with dupilumab in the Department of Dermatology at the University of California, Irvine.ResultsWe analyzed the medical records of 77 AD patients who received dupilumab according to standard dosing and had at least one documented follow‐up visit. In 66 patients (86%), dupilumab improved clinical disease severity, with 23 patients (30%) experiencing complete clearance on dupilumab. Dupilumab was generally well‐tolerated and caused no serious adverse events. The most common side effects included dry eyes, conjunctivitis, and keratitis. The most common reason for discontinuation of treatment was lack of substantial clinical improvement or progression of disease severity, followed by ophthalmologic side effects.ConclusionsOverall, dupilumab was well‐tolerated and resulted in clinical improvement in our patient population. These results provide additional important information on the safety and utility of dupilumab treatment for moderate to severe atopic dermatitis in the real‐world clinical setting.

The cAMP response element-binding protein (CREB) is a nuclear transcription factor that is critical for normal and neoplastic hematopoiesis. Previous studies have demonstrated that CREB is a proto-oncogene whose overexpression promotes cellular proliferation in hematopoietic cells. Transgenic mice that overexpress CREB in myeloid cells develop a myeloproliferative disease with splenomegaly and aberrant myelopoiesis. However, CREB overexpressing mice do not spontaneously develop acute myeloid leukemia. In this study, we used retroviral insertional mutagenesis to identify genes that accelerate leukemia in CREB transgenic mice. Our mutagenesis screen identified several integration sites, including oncogenes Gfi1, Myb, and Ras. The Sox4 transcription factor was identified by our screen as a gene that cooperates with CREB in myeloid leukemogenesis. We show that the transduction of CREB transgenic mouse bone marrow cells with a Sox4 retrovirus increases survival and self-renewal of cells in vitro. Furthermore, leukemic blasts from the majority of acute myeloid leukemia patients have higher CREB, phosphorylated CREB, and Sox 4 protein expression. Sox4 transduction of mouse bone marrow cells results in increased expression of CREB target genes. We also demonstrate that CREB is a direct target of Sox4 by chromatin immunoprecipitation assays. These results indicate that Sox4 and CREB cooperate and contribute to increased proliferation of hematopoietic progenitor cells.

Background Plasma cell vulvitis (PCV) is an inflammatory vulvar dermatosis that is not well characterized. Diagnosis is often delayed, and the condition can be refractory to treatment. To date, there are no systematic reviews on this topic. Objective This study aimed to provide a systematic review of PCV, including epidemiologic, clinical, and histopathologic findings, as well as associated comorbidities and treatment options. Methods A primary literature search was conducted using the PubMed, Ovid Medline, Cochrane, and CINAHL databases. Results Fifty-three publications with 196 patients (mean age: 55.3 ± 14.5 years) were included. The majority of studies were case reports and case series. Common symptoms included burning/stinging (52%), dyspareunia (44%), and pruritus (41%). Common findings included erythema (84%), glistening/shiny appearance (29%), well-demarcated lesions (25%), and erosions (22%). Common anatomic sites were the labia minora (45%), introitus (31%), and periurethral (19%). Fifty-three percent of patients had a solitary lesion. Common histologic findings were a predominant plasma cell infiltrate (88%), presence of other inflammatory cells (55%), hemosiderin/siderophages (46%), and epidermal atrophy (43%). Topical corticosteroids (64%) and tacrolimus ointment (13%) were the most frequent treatment modalities. In most reports, previous treatments were tried, and there was a diagnostic delay. Conclusion PCV is likely underrecognized and should be considered in patients with erythema of the mucous and modified mucous membranes, symptoms of burning or stinging, and a predominant plasma cell infiltrate on histopathology. First-line therapy should begin with high-potency topical corticosteroids, with the most evidence for clobetasol 0.05% or tacrolimus 0.1% ointment. Prospective studies are needed to further characterize this condition and to develop treatment guidelines.

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SUMMARYBackground: All over the world, refractive errors are among the most frequently occuring treatable disturbances of visual function. Ametropias have a prevalence of nearly 70% among adults in Germany and are thus of great epidemiologic and socio-economic relevance.

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ImportanceErosive pustular dermatosis (EPD) is a rare chronic inflammatory condition of the scalp and legs that is often difficult to manage. Currently, there are no treatment guidelines.ObjectiveTo systematically assess the existing literature on various treatment modalities and their efficacies when used in the management of EPD.Evidence reviewWe searched PubMed, Cochrane Libraries, Scopus, and clicnialtrial.gov databases for articles in the English language with no limited time frame. Emphasis was placed on articles that reported on treatment for EPD.FindingsOf the 168 articles identified by the literature search, 92 met eligibility criteria and were included for qualitative analysis. Efficacious topical treatments included clobetasol, betamethasone, and tacrolimus. Ninety‐three and 88% of cases utilizing clobetasol and betamethasone respectively demonstrated improvement or resolution. All 32 cases utilizing tacrolimus reported improvement. Efficacious systemic treatments included oral steroids such as prednisone, methylprednisolone, and dexamethasone. Topical dapsone, photodynamic therapy, systemic steroids, cyclosporine, and oral zinc derivatives were also described with some success.Conclusions and relevanceAccording to available data, limited solely to case reports and case series, potent topical steroids are an effective treatment option for EPD. Topical tacrolimus may also be considered in cases that require long‐term use or maintenance. Other treatment modalities shown to be successful based on high reported efficacy and low rates of recurrence after treatment include topical dapsone, systemic steroids, zinc derivatives, and cyclosporine. Further studies are needed to compare treatment modalities and to establish treatment protocols.