Asymmetric proptosis in thyroid eye disease.

PURPOSE: Patients with thyroid eye disease (TED) can present with asymmetric disease. The purpose of this study was to evaluate the prevalence of asymmetric TED in an Australian cohort and investigate clinical, biochemical, and radiological associations of asymmetric TED. METHODS: This was a retrospective study of patients with TED who underwent Hertel exophthalmometry and orbital computed tomography (CT) scans. Asymmetry was defined as a difference in the globe protrusion of ≥ 3 mm using Hertel exophthalmometry. Data was collected on patient demographics, clinical disease presentation, thyroid function tests and antibody levels. Muscles volumes were determined by manually segmenting the extraocular muscles on CT scans using a commercially available software. RESULTS: 172 orbits from 86 patients were included in the study. 28 (33%) patients had asymmetric TED. No significant differences were observed in age, gender, thyroid hormone status, anti-thyroid peroxidase levels, thyroid stimulating hormone receptor antibodies, disease activity status, or dysthyroid optic neuropathy between the asymmetric and non-asymmetric groups. The extraocular muscle volumes were significantly higher in the asymmetric orbit compared to its contralateral orbit. CONCLUSION: Asymmetric TED is a reasonably common occurrence in the course of TED. It is associated with higher extraocular muscle volumes, suggesting muscle enlargement as one of the underlying contributors to asymmetric proptosis. Thyroid eye disease should be considered in the differential of asymmetric orbital inflammatory disease.

Optic nerve sheath infiltration in dysthyroid optic neuropathy.

PURPOSE: To assess the association of optic nerve sheath (ONS) infiltration, fat infiltration, and scleral enhancement with active thyroid eye disease (TED) and dysthyroid optic neuropathy (DON). METHODS: Thyroid eye disease patients who had axial and coronal fat-suppressed contrast enhanced T1-weighted magnetic resonance imaging (MRI) imaging performed were included. Optic nerve sheath infiltration was defined by the presence of thickening and circumferential enhancement of the optic nerve sheath. Clinical assessments were performed by orbital surgeons or neuro-ophthalmologists and the disease activity (active/inactive) and presence or absence of dysthyroid optic neuropathy were recorded. RESULTS: The study population consisted of 76 orbits from 38 patients with a mean age of 53 ± 15 years, with 25 (66%) being female. Optic nerve sheath infiltration was present in 28 (37%) orbits, fat infiltration in 37 (49%) and scleral enhancement in 14 (18%) orbits. ONS infiltration (OR 19.8, p < 0.01), fat infiltration (OR 5.2, p < 0.01) and scleral enhancement (OR 12.2, p = 0.01) were all significantly associated with active clinical disease. Patients with ONS infiltration had a significantly higher odds of dysthyroid optic neuropathy (OR 3.4, p < 0.05). Fat infiltration (OR 2.8, p = 0.1) and scleral enhancement (OR 2.3, p = 0.23) were not significantly associated with DON. CONCLUSIONS: Optic nerve sheath infiltration may be a predictor of dysthyroid optic neuropathy. Intraorbital fat infiltration and scleral enhancement may be used to detect active TED. These radiological findings may serve as useful diagnostic and stratification tools in evaluating TED patients.

Tretinoin Review With Newer Formulations: Providing Effective and Tolerable Solutions in Clinical Practice.

Topical tretinoin has historically been limited by poor tolerability and molecular instability. Research advances have enhanced its efficacy and tolerability, along with reducing oxidation and photodegradation. By overcoming historical limitations, tretinoin use can be extended to patient populations and clinical situations previously not suitable. This review discusses historical limitations of tretinoin, methods employed to overcome those limitations, use within clinical practice, and new formulations of tretinoin for the treatment of acne. J Drugs Dermatol. 2023;22(1):35-40. doi:10.36849/JDD.7146.

Update: Mechanisms of Topical Retinoids in Acne.

Topical retinoids are the cornerstone of current acne management due to their actions on multiple facets of acne pathophysiology. Retinoids are a family of compounds that structurally and functionally resemble vitamin A, an essential nutrient with a key role in cellular growth and differentiation. In the skin, retinoids exert their effects by binding retinoic acid receptors (RARs) in the cell nucleus with subsequent regulation of gene transcription. There are three subtypes of RARs, and the topical retinoids currently approved for acne have differing receptor binding profiles which may translate to clinical differences, since the specific RAR subtypes activated dictate the biological response of target cells. The activity of a retinoid depends on cellular transport, receptor-binding pattern and affinity, and the genes activated. This review discusses physiologic pathways in skin that are affected by topical retinoids during acne therapy, with a focus on new data from trifarotene, a retinoid which is highly selective for the RAR-γ receptor. Recently, bioinformatic data comparing gene expression in acne lesions treated with trifarotene versus spontaneously resolving acne lesions showed that trifarotene significantly modulates 67 genes that do not appear in the spontaneously resolving lesion. These genes are involved in cellular migration, activation of adaptive immunity, inflammation, and matrix reorganization. Expression of these trifarotene-regulated genes after treatment and in an active lesion occurred in opposite directions, providing clues to the molecular and genetic response to trifarotene in resolving acne. J Drugs Dermatol. 2022;21(7):734-740. doi:10.36849/JDD.6890.

Recent Advances in Mild and Moisturizing Cleansers

Mild and moisturizing cleanser technologies, and the science underpinning them, have progressed significantly over the past decade. This includes introduction of amino-acid based milder surfactants into the cleansing arena, a deeper understanding of the roles of stratum corneum lipids and proteins in their interaction with cleanser surfactants, the role of pH in skin cleansing, and the development of improved methodologies for predicting skin irritation and drying potential of cleansers. In this paper, the recent advances in these areas as well as newer technologies are reviewed, and the future directions are outlined. J Drugs Dermatol. 2019;18(1 Suppl):s80-88

Transient Ischaemic Attack Rarely Precedes Stroke in a Cohort with Low Proportions of Large Artery Atherosclerosis: A Population-Based Study.

BACKGROUND: Ischaemic stroke is reportedly preceded by transient ischaemic attack (TIA) in 15-30% of all cases. The risk of stroke following TIA is highest in the presence of unstable atherosclerotic plaques in large arteries. The recent population-based Adelaide Stroke Incidence Study describes a population with a low proportion (16%) of stroke attributable to large artery atherosclerosis (LAA). We hypothesized that this population-based ischaemic stroke cohort would have a lower rate of preceding TIA than previously reported. METHODS: This paper is a prospective ascertainment of all suspected TIAs and strokes in a 12-month period from 2009 to 2010. Ischaemic stroke pathogenesis was classified by the TOAST criteria. Details of preceding TIA events were scrutinised. RESULTS: In this 12-month period, 318 stroke events in 301 individuals were recorded. Of the total 258 ischaemic strokes, 16% (95% confidence interval [CI] 12-22) were from LAA. Of 258 ischaemic stroke patients, only 11 (4%; 95% CI 2-7) reported symptoms in the preceding 90 days consistent with TIA. Nine (82%) sought medical attention. The median ABCD2 score in this group was 4.5 (IQR: 3-7), and the median time of event prior to stroke was 20 days (IQR: 4-32). CONCLUSION: In our population-based cohort, rates of TIA preceding ischaemic stroke were much lower than previously reported, probably reflective of effective secondary prevention (active TIA clinics) and primary prevention (limiting LAA prevalence). In our population, further enhancements in TIA care will be of limited yield.

Excess stroke incidence in young Aboriginal people in South Australia: Pooled results from two population-based studies.

Background Retrospective data indicate increased stroke incidence in Aboriginal/Torres Strait Islander (Indigenous) Australians, possibly with poorer outcomes. We present the first prospective population-based stroke incidence study in Indigenous Australians. Methods We pooled data from ASCEND and SEARCH, two prospective "ideal" South Australian stroke incidence studies, ASCEND conducted in urban Northwestern Adelaide (2009-2010) and SEARCH in five South Australian rural centers (2009-2011). We calculated age-standardized incidence for Aboriginal and non-Aboriginal people. Results The study population comprised 261,403 inhabitants. Among 432 first-ever strokes, 13 were in Aboriginal people (median age 51 vs. 78 years for non-Aboriginal people, p < 0.001). Age-standardized stroke incidence per 100,000 in Aboriginal patients (116, 95% CI: 95-137) was nearly two-fold that of non-Aboriginal patients (67, 95% CI: 51-84). Age-stratified excess incidence in Aboriginal people was restricted to those aged < 55 years (incidence rate ratio (IRR) 3.5, 95% CI: 2-7), particularly for intracerebral hemorrhage (IRR: 16, 95% CI: 4-61). Conclusion The excess stroke incidence in Aboriginal South Australians appears substantial, especially in those aged <55 years. Further work is required to delineate and address disparities.

Efficacy and Safety of Sarecycline, a Novel, Once-Daily, Narrow Spectrum Antibiotic for the Treatment of Moderate to Severe Facial Acne Vulgaris: Results of a Phase 2, Dose-Ranging Study.

BACKGROUND: There is a need for new oral antibiotics for acne with improved safety profiles and targeted antibacterial spectra. Sarecycline is a novel, tetracycline-class antibiotic specifically designed for acne, offering a narrow spectrum of activity compared with currently available tetracyclines, including less activity against enteric Gram-negative bacteria. This phase 2 study evaluated the efficacy and safety of three doses of sarecycline for moderate to severe facial acne vulgaris. METHODS: In this multicenter, double-blind, placebo-controlled study, patients aged 12 to 45 years were randomized to once-daily sarecycline 0.75 mg/kg, 1.5 mg/kg, 3.0 mg/kg, or placebo. Efficacy analyses included change from baseline in inflammatory and noninflammatory lesion counts at week 12, with between-group comparisons using analysis of covariance. Safety assessments included adverse events (AEs), clinical laboratories, vital signs, electrocardiograms, and physical examinations. RESULTS: Overall, 285 randomized patients received at least one dose of study drug. At week 12, sarecycline 1.5 mg/kg and 3.0 mg/kg groups demonstrated significantly reduced inflammatory lesions from baseline (52.7% and 51.8%, respectively) versus placebo (38.3%; P=0.02 and P=0.03, respectively). Sarecycline was safe and well tolerated, with similar gastrointestinal AE rates in sarecycline and placebo groups. Vertigo and photosensitivity AEs occurred in less than 1% of patients when pooling sarecycline groups; no vulvovaginal candidiasis AEs occurred. Discontinuation rates due to AEs were low. No serious AEs occurred. CONCLUSION: Once-daily sarecycline 1.5 mg/kg significantly reduced inflammatory lesions versus placebo and was safe and well tolerated with low rates of AEs, including gastrointestinal AEs. Sarecycline 3.0 mg/kg did not result in additional efficacy versus 1.5 mg/kg. Sarecycline may represent a novel, once-daily treatment for patients with moderate to severe acne. It offers a narrow antibacterial spectrum relative to other tetracycline options, which may lead to less selective pressure on enteric Gram-negative bacteria, resulting in less disruption of commensal organisms and less potential for antibiotic resistance.

J Drugs Dermatol. 2018;17(3):333-338.

Practical management of acne for clinicians: An international consensus from the Global Alliance to Improve Outcomes in Acne.

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.

Evidence-based recommendations for the management of acne fulminans and its variants.

BACKGROUND: Acne fulminans (AF) is a severe variant of inflammatory acne. It typically manifests as an explosive worsening and ulceration of skin lesions, and can be associated with systemic symptoms. However, there is a paucity of evidence-based information and no clear guidelines concerning the classification and treatment of AF. OBJECTIVE: To better define the spectrum of AF and its variants, devise optimal therapeutic approaches, and identify areas of future research. METHODS: A panel of physicians with expertise in severe acne vulgaris was convened after a comprehensive literature review of severe acne variants. Priority topics were reviewed and presented by each panelist at a 5-hour conference. Following review of the audiotape and scribed notes from the conference, surveys were utilized to address points of controversy and to clarify consensus recommendations. RESULTS: Appropriate clinical case presentations and consensus survey questions were utilized to create final recommendations based on both the literature and the expert consensus. LIMITATIONS: Limited evidenced-based data and prospective studies in the literature concerning the treatment of AF is available. CONCLUSION: These guidelines better characterize AF and provide health care practitioners approaches to the classification, treatment, and prevention of AF and its variants.

Why Topical Retinoids Are Mainstay of Therapy for Acne.

Acne-focused dermatology expert groups have consistently recommended that most patients with acne be treated with a combination of topical retinoid and antimicrobial therapy. This is based on clinical data as well as evidence that these drug classes have different and complementary mechanisms of action that target multiple aspects of acne's complex pathophysiology. Recent evidence-based guidelines for acne, including those from the American Academy of Dermatology (AAD) and the European Dermatology Forum (EDF), have agreed that retinoids have an essential role in this widespread disease. The AAD states "retinoids are the core of topical therapy for acne because they are comedolytic, resolve the precursor microcomedone lesion, and are anti-inflammatory;" further, they "allow for maintenance of clearance." Despite uniform recommendation for use of topical retinoids, a recent study of prescribing practices from 2012 to 2014 indicated that dermatologists prescribed retinoids just 58.8% of the time while non-dermatologists prescribed them for only 32.4% of cases. In this article, we review the reasons supporting retinoids as the mainstay of acne therapy and discuss some of the perceived barriers that may be limiting use of this important drug class. Further, we discuss how and when titrating retinoid concentrations may be utilized in clinical practice. FUNDING: Galderma International.

Isotretinoin and Timing of Procedural Interventions: A Systematic Review With Consensus Recommendations.

Importance: The notion that systemic isotretinoin taken within 6 to 12 months of cutaneous surgery contributes to abnormal scarring or delayed wound healing is widely taught and practiced; however, it is based on 3 small case series from the mid-1980s. Objective: To evaluate the body of literature to provide evidence-based recommendations regarding the safety of procedural interventions performed either concurrently with, or immediately following the cessation of systemic isotretinoin therapy. Evidence Review: A panel of national experts in pediatric dermatology, procedural/cosmetic dermatology, plastic surgery, scars, wound healing, acne, and isotretinoin was convened. A systematic PubMed review of English-language articles published from 1982 to 2017 was performed using the following search terms: isotretinoin, 13-cis-retinoic acid, Accutane, retinoids, acitretin, surgery, surgical, laser, ablative laser, nonablative laser, laser hair removal, chemical peel, dermabrasion, wound healing, safety, scarring, hypertrophic scar, and keloid. Evidence was graded, and expert consensus was obtained. Findings: Thirty-two relevant publications reported 1485 procedures. There was insufficient evidence to support delaying manual dermabrasion, superficial chemical peels, cutaneous surgery, laser hair removal, and fractional ablative and nonablative laser procedures for patients currently receiving or having recently completed isotretinoin therapy. Based on the available literature, mechanical dermabrasion and fully ablative laser are not recommended in the setting of systemic isotretinoin treatment. Conclusions and Relevance: Physicians and patients may have an evidence-based discussion regarding the known risk of cutaneous surgical procedures in the setting of systemic isotretinoin therapy. For some patients and some conditions, an informed decision may lead to earlier and potentially more effective interventions.

Prevalence and Risk Factors of Acne Scarring Among Patients Consulting Dermatologists in the USA

Although there have been few formal studies, scarring is a known bothersome companion of acne vulgaris. We performed a prospective study of subjects consulting a dermatologist for active acne to assess the frequency of acne scarring. Investigators performed a short questionnaire on all acne patients seen at their office for one consecutive 5-day work week to assess scar frequency. Additionally, the first four subjects with acne scars identified were enrolled for a second phase (scar cohort) of the study during which the investigator collected further medical history and performed a clinical evaluation and the patient completed a self-administered questionnaire about scar perceptions and impact on quality of life. A total of 1,972 subjects were evaluated by 120 investigators. Among these, 43 percent (n=843) had acne scarring. Subjects with acne scars were significantly more likely to have severe or very severe acne (P less than .01); however, 69% of the subjects with acne scars had mild or moderate acne at the time of the study visit. Risk factors correlated with increased likelihood of scarring were acne severity, time between acne onset and first effective treatment, relapsing acne, and male gender. Treatments that can completely resolve acne scars are not yet available - prevention and early treatment remain a primary strategy against scars. It is vital for clinicians who manage individuals with acne to institute effective therapy as early as possible, since treatment delay is a key modifiable risk factor for scarring.

Stroke Epidemiology in an Australian Rural Cohort (SEARCH).

Background Stroke rates in Australia and New Zealand have been declining since 1990 but all studies have been completed in large urban centers. Aim We report the first Australasian stroke incidence study in a rural population. Methods The authors applied the principle of complete ascertainment, used the WHO standard definition of stroke and classified ischemic stroke by the TOAST criteria. Data were collected from five rural centers defined by postcode of residence, over a 2-year period with 12 months of follow up of all cases. Results There were 217 strokes in 215 individuals in a population of 96,036 people, over 2 years, giving a crude attack rate of 113 per 100,000 per year. The 181 first-ever strokes (83% of total), standardized to the WHO world population, occurred at a rate of 50/100,000 (95% CI: 43-58). The 28-day fatality for first-ever strokes was 24% (95% CI: 18-31) and 77% (95% CI: 71-83) were classified as ischemic (140/181), 15% (95% CI: 10-21) intracerebral hemorrhage, 3% (95% CI: 1-6) due to subarachnoid hemorrhage and 5% (95% CI: 2-9) were unknown. A high proportion of first-ever ischemic strokes (44%) were cardioembolic, mostly (77%) due to atrial arrhythmias. Of the 38 with known atrial arrhythmias prior to stroke, only six (16%) were therapeutically anticoagulated. Conclusions This rural companion study of a recent Australian urban stroke incidence study confirms the downward trend of stroke incidence in Australia, and reiterates that inadequate anticoagulation of atrial arrhythmia remains a preventable cause of ischemic stroke.

Daily Use of a Facial Broad Spectrum Sunscreen Over One-Year Significantly Improves Clinical Evaluation of Photoaging.

BACKGROUND: Sunscreens are known to protect from sun damage; however, their effects on the reversal of photodamage have been minimally investigated. OBJECTIVE: The aim of the prospective study was to evaluate the efficacy of a facial sun protection factor (SPF) 30 formulation for the improvement of photodamage during a 1-year use. METHODS: Thirty-two subjects applied a broad spectrum photostable sunscreen (SPF 30) for 52 weeks to the entire face. Assessments were conducted through dermatologist evaluations and subjects' self-assessment at baseline and then at Weeks 12, 24, 36, and 52. RESULTS: Clinical evaluations showed that all photoaging parameters improved significantly from baseline as early as Week 12 and the amelioration continued until Week 52. Skin texture, clarity, and mottled and discrete pigmentation were the most improved parameters by the end of the study (40% to 52% improvement from baseline), with 100% of subjects showing improvement in skin clarity and texture. CONCLUSION: The daily use of a facial broad-spectrum photostable sunscreen may visibly reverse the signs of existing photodamage, in addition to preventing additional sun damage.

Status Report from the Scientific Panel on Antibiotic Use in Dermatology of the American Acne and Rosacea Society: Part 1: Antibiotic Prescribing Patterns, Sources of Antibiotic Exposure, Antibiotic Consumption and Emergence of Antibiotic Resistance, Impact of Alterations in Antibiotic Prescribing, and Clinical Sequelae of Antibiotic Use.

Oral and topical antibiotics are commonly prescribed in dermatologie practice, often for noninfectious disorders, such as acne vulgaris and rosacea. Concerns related to antibiotic exposure from both medical and nonmedical sources require that clinicians consider in each case why and how antibiotics are being used and to make appropriate adjustments to limit antibiotic exposure whenever possible. This first article of a three-part series discusses prescribing patterns in dermatology, provides an overview of sources of antibiotic exposure, reviews the relative correlations between the magnitude of antibiotic consumption and emergence of antibiotic resistance patterns, evaluates the impact of alterations in antibiotic prescribing, and discusses the potential relevance and clinical sequelae of antibiotic use, with emphasis on how antibiotics are used in dermatology.

Status Report from the Scientific Panel on Antibiotic Use in Dermatology of the American Acne and Rosacea Society: Part 3: Current Perspectives on Skin and Soft Tissue Infections with Emphasis on Methicillin-resistant Staphylococcus aureus, Commonly Encountered Scenarios when Antibiotic Use May Not Be Needed, and Concluding Remarks on Rational Use of Antibiotics in Dermatology.

In this third article of the three-part series, management of skin and soft tissue infections is reviewed with emphasis on new information on methicillin-resistant Staphylococcus aureus. Due to changes in the evolution of methicillin-resistant Staphylococcus aureus clones, previous distinctions between healthcare-acquired methicillin-resistant Staphylococcus aureus and community-acquired methicillin-resistant Staphylococcus aureus are currently much less clinically relevant. Many nosocomial cases of methicillin-resistant Staphylococcus aureus infection are now caused by community-acquired methicillin-resistant Staphylococcus aureus, with changing patterns of antibiotic susceptibility and resistance. Also reviewed are clinical scenarios where antibiotics may not be needed and suggestions for optimal use of antibiotic therapy for dermatologie conditions, including recommendations on perioperative antibiotic use.

Cerebral Venous Sinus Thrombosis Incidence Is Higher Than Previously Thought: A Retrospective Population-Based Study.

BACKGROUND AND PURPOSE: The incidence of cerebral venous thrombosis (CVT) varies between studies, but it is estimated to be between 2 and 5 per million per year. A recent study in the Netherlands with comprehensive ascertainment suggested a much higher incidence. It is uncertain whether these differing estimates reflect the quality of ascertainment or true variation. The purpose of this study was to determine the incidence of CVT in Adelaide, using a novel clinical and radiological methodology. METHODS: We retrospectively identified CVT International Classification of Diseases-coded cases from all Adelaide public hospitals from 2005 to 2011. We also searched all neuroimaging studies (259 101) from these hospitals for text variations containing venous thromb. All potential cases were reviewed, and cases of incident CVT ascertained. Associations and outcomes were determined. RESULTS: Of 169 possible cases, 105 cases of CVT were confirmed (59 cases by both coding and neuroimaging, 40 from neuroimaging alone, and 6 from coding alone). In our population of 953 390 adults, this represented an incidence of 15.7 million per year (95% confidence interval, 12.9-19.0), the highest incidence reported. Of these cases, a possible procoagulant predisposition was identified in 48%. Fifty-five of 105 cases occurred in females. Relative risk of CVT in females of reproductive age was insignificantly higher than in males (1.18 [95% confidence interval, 0.94-1.48]). CONCLUSIONS: Cerebral venous sinus thrombosis in our study was more common than previously reported, perhaps because of more complete ascertainment. Future CVT incidence studies should include comprehensive capture and review of neuroimaging.

How does our increased understanding of the role of inflammation and innate immunity in acne impact treatment approaches?

A supplement article recently published in the Journal of the European Academy of Dermatology and Venereology by Dréno et al., members of the Global Alliance to Improve Outcomes in Acne group, summarized the data for the emerging concept that inflammation in general and the innate immune system specifically play a central role in the pathogenesis of acne. This review, entitled "Understanding innate immunity and inflammation in acne: implications for management", also discusses the impact of different treatment options on the innate immune response and inflammation. The aim of the present summary is to provide a synopsis of the key points made in the paper, from the members of the Global Alliance, as relevant to the main article within this supplement: "Recent advances in the use of adapalene 0.1%/benzoyl peroxide 2.5% to treat acne patients with moderate to severe acne".