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.

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

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.

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.

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.

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.

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.

Determining the Number of Ischemic Strokes Potentially Eligible for Endovascular Thrombectomy: A Population-Based Study.

BACKGROUND AND PURPOSE: Endovascular thrombectomy (ET) is standard-of-care for ischemic stroke patients with large vessel occlusion, but estimates of potentially eligible patients from population-based studies have not been published. Such data are urgently needed to rationally plan hyperacute services. Retrospective analysis determined the incidence of ET-eligible ischemic strokes in a comprehensive population-based stroke study (Adelaide, Australia 2009-2010). METHODS: Stroke patients were stratified via a prespecified eligibility algorithm derived from recent ET trials comprising stroke subtype, pathogenesis, severity, premorbid modified Rankin Score, presentation delay, large vessel occlusion, and target mismatch penumbra. Recognizing centers may interpret recent ET trials either loosely or rigidly; 2 eligibility algorithms were applied: restrictive (key criteria modified Rankin Scale score 0-1, presentation delay <3.5 hours, and target mismatch penumbra) and permissive (modified Rankin Scale score 0-3 and presentation delay <5 hours). RESULTS: In a population of 148 027 people, 318 strokes occurred in the 1-year study period (crude attack rate 215 [192-240] per 100 000 person-years). The number of ischemic strokes eligible by restrictive criteria was 17/258 (7%; 95% confidence intervals 4%-10%) and by permissive criteria, an additional 16 were identified, total 33/258 (13%; 95% confidence intervals 9%-18%). Two of 17 patients (and 6/33 permissive patients) had thrombolysis contraindications. Using the restrictive algorithm, there were 11 (95% confidence intervals 4-18) potential ET cases per 100 000 person-years or 22 (95% confidence intervals 13-31) using the permissive algorithm. CONCLUSIONS: In this cohort, ≈7% of ischemic strokes were potentially eligible for ET (13% with permissive criteria). In similar populations, the permissive criteria predict that ≤22 strokes per 100 000 person-years may be eligible for ET.

Guidelines of care for the management of acne vulgaris.

Acne is one of the most common disorders treated by dermatologists and other health care providers. While it most often affects adolescents, it is not uncommon in adults and can also be seen in children. This evidence-based guideline addresses important clinical questions that arise in its management. Issues from grading of acne to the topical and systemic management of the disease are reviewed. Suggestions on use are provided based on available evidence.

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.

Development and Evaluation of a Rosacea Screening Instrument (Rosascreen).

BACKGROUND: There are no current instruments to facilitate population screening for rosacea. OBJECTIVE: To develop and evaluate a screening instrument for rosacea applicable for population surveys. METHODS: A rosacea-specific screening instrument (Rosascreen), consisting of a subject-completed questionnaire and screening algorithm, was developed based on current diagnostic criteria for rosacea. Three iterations were pilot tested and refined for clarity and sensitivity in adult outpatients with and without rosacea. RESULTS: Three subject groups were consecutively evaluated with iterations of the questionnaire at each centre (overall N = 121). The final version had a sensitivity of 93% to 100% for key diagnostic criteria, and use of the algorithm had a sensitivity of 100% for detection of rosacea and specificity of 63% to 71%. Most subjects found the questionnaire easy to understand and complete. CONCLUSION: Rosascreen, a subject-completed questionnaire and diagnostic algorithm, is a highly sensitive screening instrument that may facilitate estimation of rosacea prevalence in general populations.

Incidence and associations of hemiplegic shoulder pain poststroke: prospective population-based study.

OBJECTIVE: To provide an epidemiological perspective of the clinical profile, frequency, and determinants of poststroke hemiplegic shoulder pain. DESIGN: A prospective population-based study of an inception cohort of participants with a 12-month follow-up period. SETTING: General community and hospital within a geographically defined metropolitan region. PARTICIPANTS: Multiple ascertainment techniques were used to identify 318 confirmed stroke events in 301 individuals. Among adults with stroke, data on shoulder pain were available for 198 (83% of the survivors) at baseline and for 156 and 148 at 4 and 12 months, respectively. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Subjective reports of onset, severity, and aggravating factors for pain and 3 passive range-of-motion measures were collected at baseline and at 4- and 12-month follow-up. RESULTS: A total of 10% of the participants reported shoulder pain at baseline, whereas 21% reported pain at each follow-up assessment. Overall, 29% of all assessed participants reported shoulder pain during 12-month follow-up, with the median pain score (visual analog scale score=40) highest at 4 months and more often associated with movement at later time points. Objective passive range-of-motion tests elicited higher frequencies of pain than did self-report and predicted later subjective shoulder pain (crude relative risk of 3.22 [95% confidence interval, 1.01-10.27]). CONCLUSIONS: The frequency of poststroke shoulder pain is almost 30%. Peak onset and severity of hemiplegic shoulder pain in this study was at 4 months, outside of rehabilitation admission time frames. Systematic use of objective assessment tools may aid in early identification and management of stroke survivors at risk of this common complication of stroke.

One-year topical stabilized retinol treatment improves photodamaged skin in a double-blind, vehicle-controlled trial.

BACKGROUND: Retinol, a precursor of retinoic acid, has great potentials as a topical anti-aging molecule; however, only a handful of clinical investigations have been published to date. OBJECTIVE: This study aimed to assess the efficacy and safety of 0.1% stabilized retinol on photodamaged skin during a one-year treatment. METHODS: The investigation included two 52-week, double-blind, vehicle-controlled studies. In the main study, 62 subjects applied either a stabilized retinol formulation or its vehicle to the full face. A second exploratory study evaluated histological/histochemical markers in 12 subjects after 52 weeks of either retinol or vehicle use on contralateral dorsal forearms. RESULTS: The retinol group showed significant photodamage improvement over vehicle at all timepoints during the study. After 52 weeks, retinol had improved crow's feet fine lines by 44%, and mottled pigmentation by 84%, with over 50% of subjects showing +2 grades of improvement in many parameters. Additionally, at week 52, histochemical data confirmed the clinical results, showing increased expression of type I procollagen, hyaluronan, and Ki67 as compared to vehicle. CONCLUSION: This study confirms that a stabilized retinol (0.1%) formulation can significantly improve the signs of photoaging, and improvements in photodamage continue with prolonged use.

Understanding and Reducing the Risk for Acne Scarring.

Scarring is a lifelong, physically disfiguring and often emotionally debilitating sequela resulting from acne vulgaris. Nearly 80% of patients have some scarring and 50% have clinically relevant scarring. Although the extent, duration, and intensity of inflammation are important risk factors, scarring also can develop in patients with relatively mild inflammation. Assessment of scarring should be part of the evaluation in all patients with acne and should be a consideration in determining treatment. Semin Cutan Med Surg 34(supp5):S89-S91 © 2015 published by Frontline Medical Communications.

Clinical associations and causes of convexity subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: It has been previously found noted that ≈15% to 20% of subarachnoid hemorrhage (SAH) is nonaneurysmal. Nontraumatic convexity SAH (cSAH) is increasingly recognized. Data concerning incidence and associations are scant. METHODS: We identified all SAH-coded cases from South Australian public hospitals between January 2005 and July 2011. Electronic discharge summaries were reviewed, and cases of cSAH were ascertained. Clinical and radiological features were recorded, and pathogenesis was assigned. RESULTS: Of 742 cases with SAH, 41 (6%) cases were cSAH, giving a minimum population annual incidence of 5.1 per million (95% confidence interval, 3.7-7.0). Median age was 70 years (interquartile range, 48-79). Commonest causes were cerebral amyloid angiopathy (39%), reversible cerebral vasoconstriction syndrome (17%), cerebral venous sinus thrombosis (10%), large-vessel stenotic atherosclerosis (10%), and posterior reversible encephalopathy syndrome (5%). No cause was identified in 20% (mostly elderly patients with incomplete evaluation). Most (63%) presented with transient neurological symptoms. Many (49%) were misdiagnosed as transient ischemic attacks and treated inappropriately with antithrombotics. CONCLUSIONS: cSAH comprises a significant proportion of SAH. Commonest causes are cerebral amyloid angiopathy in the elderly and reversible cerebral vasoconstriction syndrome in the young, but differential diagnosis is broad. Misdiagnosis is common and leads to potentially harmful treatments.

Reliability of Clinician Erythema Assessment grading scale.

BACKGROUND: Facial erythema is a clinical hallmark of rosacea and often causes social and psychological distress. Although facial erythema assessments are a common endpoint in rosacea clinical trials, their reliability has not been evaluated. OBJECTIVE: The objective of this study was to evaluate the inter- and intrarater reliability of the Clinician's Erythema Assessment (CEA), a 5-point grading scale of facial erythema severity. METHODS: Twelve board-certified dermatologists, previously trained on use of the scale, rated erythema of 28 rosacea subjects twice on the same day. Interrater and intrarater agreement was assessed with the intraclass correlation and κ statistic. RESULTS: The CEA had high interrater reliability and good intrarater reliability with an overall intraclass correlation coefficient (ICC) for session 1 and session 2 of 0.601 and 0.576, respectively; the overall weighted κ statistic for session 1 and session 2 was 0.692. LIMITATIONS: Raters were experienced dermatologists and there may be a risk of recall bias. CONCLUSION: When used by trained raters, CEA is a reliable scale for measuring the facial erythema of rosacea.

Randomized, phase 2, dose-ranging study in the treatment of rosacea with encapsulated benzoyl peroxide gel.

OBJECTIVE: Compare the safety and efficacy of 1% and 5% silica encapsulated benzoyl peroxide (E-BPO) in patients with papulopustular rosacea. DESIGN: Multi-centered randomized, double blind, vehicle controlled parallel group, 12 week treatment in 92 patients with papulopustular rosacea. Primary endpoints were dichotomized IGA with success defined as clear/near clear and reduction in inflammatory lesions. PATIENTS: 92 patients: 74% graded as moderate IGA, 14% severe and 12% mild. The mean inflammatory lesion count was 24. INTERVENTION: Once daily treatment for 12 weeks with vehicle, 1% or 5% E-BPO. RESULTS: 1% and 5% E-BPO were superior to vehicle in reducing papulopustular lesions P =0.01 and P =0.02. 5% E-BPO was superior to vehicle for IGA P =0.0013.