Shinjita Das

Depletion of GGA3 stabilizes BACE and enhances β-secretase activity

Summary β-site APP-cleaving enzyme (BACE) is required for production of the Alzheimers disease (AD)-associated Aβ protein. BACE levels are elevated in AD brain, and increasing evidence reveals BACE as a stress-related protease that is upregulated following cerebral ischemia. However, the molecular mechanism responsible is unknown. We show that increases in BACE and β-secretase activity are due to posttranslational stabilization following caspase activation. We also found that during cerebral ischemia, levels of GGA3, an adaptor protein involved in BACE trafficking, are reduced, while BACE levels are increased. RNAi silencing of GGA3 also elevated levels of BACE and Aβ. Finally, in AD brain samples, GGA3 protein levels were significantly decreased and inversely correlated with increased levels of BACE. In summary, we have elucidated a GGA3-dependent mechanism regulating BACE levels and β-secretase activity. This mechanism may explain increased cerebral levels of BACE and Aβ following cerebral ischemia and existing in AD.

Correlates of self-reported quality of life in adults and children with morphea

BACKGROUND Determining a diseases impact on life quality is important in clinical decision making, research, and resource allocation. Determinants of quality of life (QOL) in morphea are poorly understood. OBJECTIVE We sought to ascertain demographic and clinical variables correlated with negative impact on self-reported QOL in morphea. METHODS We conducted a cross-sectional survey of the Morphea in Adults and Children cohort. RESULTS Symptoms (pruritus and pain) and functional impairment were correlated with decreased QOL in children and adults. This was true in both sexes and was independent of subtype and age. Patient-reported QOL correlated with physician-based measures of disease severity in adults, but not in children. Patients with linear and generalized morphea had the greatest impact on QOL. LIMITATIONS Small sample size is a limitation. CONCLUSION Symptoms and functional impairment were determinants of impaired life quality in both children and adults independent of morphea subtype. These results suggest that clinicians should consider suppressing the accumulation of new lesions (when rapidly accumulating) and symptoms (pain and pruritus) in the treatment of patients with morphea.

Reliability assessment and validation of the postacne hyperpigmentation index (PAHPI), a new instrument to measure postinflammatory hyperpigmentation from acne vulgaris

BACKGROUND There are no validated outcome measures for postinflammatory hyperpigmentation (PIH). OBJECTIVE We sought to determine the reliability and validity of an outcome measure for PIH after acne in patients with skin of color. METHODS A postacne hyperpigmentation index (PAHPI) was developed. Six raters scored 21 patients with PIH twice. Reliability was determined within and between raters, whereas validity was evaluated by comparing scores with severity ranking by an independent dermatologist. The pigment intensity scores were compared with the melanin index of each patient using a narrowband reflectance spectrophotometer. A quality-of-life score (Skindex-29) was also compared with PAHPI scores. RESULTS Total PAHPI scores showed good reliability within and between raters and were valid when compared with clinical severity and melanin indices. Good correlation was achieved between the total PAHPI score and the emotion subscale of the Skindex-29. LIMITATIONS Generalizability of results is limited to African American females. CONCLUSION The PAHPI shows good reliability and validity when scored on patients with PIH from acne vulgaris. The PAHPI also correlates well with the emotional impact of PIH as measured by the Skindex-29. Future studies should assess the ability of the PAHPI to change with improvement of PIH from acne after treatment.

Cheilitis and urticaria associated with stannous fluoride in toothpaste

patients are mentioned. This reputation of harmlessness has favored the development of this technique, not only among dermatologists but also among other specialists. Its use today extends beyond the medical field, and several beauty salons also offer LED therapy. Solar urticaria is a rare form of physical urticaria induced by sun exposure and must be distinguished from other photodermatoses. The condition can be disabling and remains difficult to manage. Our case suggests that solar urticaria is a previously unrecognized side effect of LED therapy that physicians should be aware of. This case also pleads for clinical studies with robust methodologic quality to explore the efficacy and side effects of LEDs in dermatologic indications. Our gratitude to Jane Esdaile for revising the letter.

Generational Influence on Patient Learning Preferences in Dermatology

REFERENCES 1. Kampf G, Kramer A. Epidemiologic background of hand hygiene and evaluation of the most important agents for scrubs and rubs. Clin Microbiol Rev. 2004;17:863-893. 2. Storr J, Twyman A, Zingg W, et al. Core components for effective infection prevention and control programmes: new WHO evidence-based recommendations. Antimicrob Resist Infect Control. 2017;6:6. 3. Hoarau G, Mukherjee PK, Gower-Rousseau C, et al. Bacteriome and mycobiome interactions underscore microbial dysbiosis in familial Crohn’s disease. MBio. 2016;7. 4. Berardesca E, European Group for Efficacy Measurements on Cosmetics and Other Topical Products. EEMCO guidance for the assessment of stratum corneum hydration: electrical methods. Skin Res Technol. 1997;3:126-132. 5. Zapka C, Leff J, Henley J, et al. Comparison of standard culture-based method to culture-independent method for evaluation of hygiene effects on the hand microbiome. MBio. 2017;8.

Pigment Changes and Drug Reactions

Medications have long been known to cause pigmentary changes of the skin. While this frequently occurs as post-inflammatory changes of a resolving drug-induced rash, medications can also directly promote dyspigmentation through stimulation of melanin production and/or deposition of drug (or drug metabolite) within the skin. Medications can also cause hypo- or depigmentation. Drug-induced pigmentary changes depend on factors such as the particular drug (or heavy metal) and level of deposition or melanocyte stimulation (or inhibition of melanogenesis). Drug-induced dyschromias have historically been categorized in a medication-class based manner. Because the clinician is generally faced with a patient whose chief complaint is dyspigmentation (which comes in varying shades), we propose a color-based approach for understanding drug-induced dyschromias.

Fingertip Purpura in a Dental Student: An Unusual Manifestation of Methyl Methacrylate Dermatitis

Discussion | The term pseudolymphoma designates a group of reactive lymphocytic disorders that involve an inflammatory response to known or unknown stimuli simulating malignant lymphomas both clinically and histologically.2 To our knowledge only 2 cases of cutaneous multiple pseudolymphomas induced by H medicinalis have been reported.3,4 Smolle et al3 described multiple pseudolymphomas on the lower legs of a woman receiving leech therapy for venous insufficiency. More recently, Choi and Kim4 reported a similar case on the lower eyelids of a Japanese man who had infraorbital dark circles treated with H medicinalis. Medicinal leeches have historically been used as a nonconventional treatment for chronic venous insufficiency and are now frequently used in plastic surgery.5,6 In addition, less common applications such as osteoarthritis, muscular pains, or injuries have been reported.6 In conclusion, with the increasing popularity of traditional and alternative medicine, H medicinalis therapy is becoming increasingly popular, and we all need to be aware that pseudolymphoma represents a possible complication in this type of treatment.

Factors Influencing Patient Decisions Regarding Treatments for Skin Growths: A Cross-Sectional Study

Variations in treatment modalities for skin growths contribute substantially to overall healthcare spending within dermatology. However, little is known regarding factors impacting patient decision-making when choosing a treatment modality. In this survey-based, cross-sectional study (n = 375, 81.9% response rate), we asked patients to rate the importance of different treatment parameters for a nonfacial skin growth, further classified into five domains: efficacy, appearance, financial impact, visit duration, and productivity. Although patients generally prioritized treatment efficacy when selecting a treatment modality, they emphasized different aspects of the treatment experience as a function of age, gender, race, insurance status, and history of malignancy. Patients over age 50 were less likely to consider treatment impact on finances as being “important”, but more so efficacy and visit duration. Women were more likely to value efficacy and appearance. Patients without private insurance were more likely to cite efficacy and impact on productivity as being “important”. While the underlying reasons for these variations differ across patients, these findings help explain variations in treatment selection among patients choosing between treatments for skin growths and may ultimately lead to improved shared decision-making.

A 71-Year-Old Female with Myocardial Infarction and Long-Standing Ulcers on the Thigh

Calciphylaxis is most commonly encountered in patients with end-stage renal disease; however, it is increasingly observed in nonuremic patients as well. It is important to consider and diagnose nonuremic calciphylaxis early, as prompt treatment and mitigation of associated risk factors is essential to improve long-term outcomes for these patients. Here, we present the case of a 71-year-old woman with atrial fibrillation on warfarin, but without renal disease, who presented with two long-standing ulcers on her thigh and was diagnosed with the aid of biopsy with calciphylaxis. We review the existing literature on the subject and offer this case as a representative report of a clinicopathologic correlation for this disorder.