Keratosis pilaris: an update and approach to management.

Keratosis pilaris (KP) is a common, hyperkeratotic skin condition characterized by small, folliculocentric papules with variable perifollicular erythema. We provide an updated review on the pathogenesis, clinical manifestations, and management of this common, and often annoying, finding. KP represents a family of follicular disorders, of which KP simplex is by far the most common. Other variants and rare subtypes include keratosis pilaris rubra, erythromelanosis follicularis faciei et colli, and the spectrum of keratosis pilaris atrophicans. Inherited mutations of the FLG gene and ABCA12 gene have been implicated etiologically. KP may be associated with ichthyosis vulgaris and palmar hyperlinearity, but less likely atopic dermatitis. Some potential differential diagnoses for KP include lichen spinulosus, phrynoderma, ichthyosis vulgaris, and trichostasis spinulosa. General cutaneous measures such as hydrating skin, avoiding long baths or showers, and using mild soaps or cleansers should be recommended. Topical keratolytic agents are first-line therapy, followed by topical retinoids and corticosteroids. Recent options include a variety of lasers and microdermabrasion if the patient is refractory to topical therapy.

Life-threatening hemoptysis in patients with metastatic kidney cancer.

Hemoptysis is a complication of intrathoracic tumors, both primary and metastatic, and the risk may be increased by procedural interventions as well as Stereotactic Ablative Radiation (SAbR). The risk of hemoptysis with SAbR for lung cancer is well characterized, but there is a paucity of data about intrathoracic metastases. Here, we sought to evaluate the incidence of life-threatening/fatal hemoptysis (LTH) in patients with renal cell carcinoma (RCC) chest metastases with a focus on SAbR. We systematically evaluated patients with RCC at UT Southwestern Medical Center (UTSW) Kidney Cancer Program (KCP) from July 2005 to March 2020. We queried Kidney Cancer Explorer (KCE), a data portal with clinical, pathological, and experimental genomic data. Patients were included in the study based on mention of "hemoptysis" in clinical documentation, if they had a previous bronchoscopy, or had undergone SAbR to any site within the chest. Two hundred and thirty four patients met query criteria and their records were individually reviewed. We identified 10 patients who developed LTH. Of these, 4 had LTH as an immediate procedural complication whilst the remaining 6 had prior SAbR to ultra-central (UC; abutting the central bronchial tree) metastases. These 6 patients had a total of 10 lung lesions irradiated (UC, 8; central 1, peripheral 1), with a median total cumulative SAbR dose of 38 Gray (Gy/ lesion) (range: 25-50 Gy). Other risk factors included intrathoracic disease progression (n = 4, 67%), concurrent anticoagulant therapy (n = 1, 17%) and concurrent systemic therapy (n = 4, 67%). Median time to LTH from first SAbR was 26 months (range: 8-61 months). Considering that 130 patients received SAbR to a chest lesion during the study period, the overall incidence of LTH following SAbR was 4.6% (6/130). The patient population that received SAbR (n = 130) was at particularly high risk for complications, with 67 (52%) having two or more chest metastaes treated, and 29 (22%) receiving SAbR to three or more lesions. Overall, the risk of LTH following SAbR to a central or UC lesion was 10.5% (6/57). In conclusion, SAbR of RCC metastases located near the central bronchial tree may increase the risk of LTH.

Hailey-Hailey disease: a diagnostic challenge.

Hailey-Hailey disease (HHD) is an autosomal-dominant genodermatosis characterized by crusted macerated erosions, as well as velvety, dry, fissured plaques in the intertriginous areas. No predilection for sex or ethnic group has been reported. The typical age of onset is in the third decade of life. Diagnosis of HHD is suggested based on clinical morphology, location of lesions, family history, and histology demonstrating a characteristic dilapidated brick wall appearance of the epidermis. However, HHD often is misdiagnosed due to lack of knowledge of this uncommon disorder and its resemblance to other dermatoses. We describe an unusual presentation of HHD with a late age of onset and involvement of nonintertriginous regions.

Topical antibiotics in pregnancy: A review of safety profiles.

Medications should be used with caution in women of childbearing age who are pregnant, or are contemplating pregnancy. Although topical medications are considered safer than oral or parenteral agents, their safety data in pregnancy must be assessed carefully. The available information on medication use in pregnancy is limited, and not always aided by the FDA pregnancy letter category system. Thus, in this article, we aggregate human studies, animal studies, and pharmacokinetics data to provide recommendations on utilizing topical antibiotics in pregnancy.

Effects of AM80 compared to AC261066 in a high fat diet mouse model of liver disease.

The roles of retinoids in nonalcoholic fatty liver disease (NAFLD) remain unclear and a better understanding may lead to therapies that prevent or limit NAFLD progression. We examined the actions of retinoic acid receptor (RAR) agonists- AM80 for RARα and AC261066 for RARß2- in a murine model of NAFLD. We fed wild type C57Bl/6 mice a chow or a 45% high fat diet (HFD) for 12 weeks, followed by 4 additional weeks with the HFD+AM80; HFD+AC261066; or HFD. The HFD+AM80 group showed greater hyperglycemia and glucose intolerance compared to other groups. Histopathological evaluation of the livers showed the highest degree of steatosis, triglycerides levels, and inflammation, assessed by F4/80 staining, in the HFD+AM80-treated compared to the HFD, the HFD+AC261066, and chow-fed mice. Liver vitamin A (retinol (ROL)) and retinyl palmitate levels were markedly lower in all HFD groups compared to chow-fed controls. HFD+AC261066-treated mice showed higher levels of a key intracellular ROL transporter, retinol-binding protein-1 (RBP1) compared to the HFD and HFD+AM80 groups. In conclusion, these data demonstrate that the selective RARα agonist AM80 exacerbates HFD-induced NAFLD and hyperglycemia. These findings should inform future studies examining the therapeutic potential of RAR agonists in HFD-related disorders.

Hereditary leiomyomatosis and renal cell cancer syndrome: An update and review.

Hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome is a rare genetic disorder that predisposes individuals to multiple cutaneous leiomyomas, renal cell carcinomas, and in women, uterine leiomyomas. Also known as Reed syndrome, it is caused by a germline heterozygous mutation of the fumarate hydratase tumor suppressor gene. HLRCC is associated with significant morbidity because of pain from cutaneous and uterine leiomyomas, the cutaneous pain often of unique character. Although genetic testing is currently considered the criterion standard to diagnose HLRCC, newer immunohistochemistry markers may provide rapid and cost effective alternatives to genetic testing. Because of the potentially aggressive nature of renal cell carcinomas that develop as early as in childhood, close annual cancer surveillance is desirable in individuals with HLRCC. In this review, we offer an update and an approach to the diagnosis, management, and renal cancer surveillance in HLRCC.

Outcomes of Vestibular Schwannoma Surgery among the Elderly.

Objective To compare comorbidities and in-hospital complications between elderly and nonelderly patients undergoing vestibular schwannoma (VS) surgery. To examine average length of stay (LOS) and hospital charges among elderly patients. Study Design Population-based inpatient registry analysis. Setting Academic medical center. Subjects and Methods Retrospective analysis of the National Inpatient Sample for patients undergoing VS surgery from 2002 to 2010: 4137 patients met inclusion criteria, with 519 (12.5%) in the elderly cohort (≥65 years). Outcomes of elderly and nonelderly (<65 years) patient cohorts were compared. Results Compared with the nonelderly cohort, the elderly cohort had more comorbidities, including diabetes mellitus, hypertension, and pulmonary disease (all P < .001). Elderly patients had longer LOS (6.5 vs 5.4 days; P = .001) but did not incur significantly greater hospital charges. Rates of cerebrospinal fluid leak, meningitis, and facial nerve injury did not vary significantly between groups. The elderly cohort experienced higher rates of in-hospital complications, including acute cardiac events, iatrogenic cerebrovascular infarction/hemorrhage, postoperative bleeding (hemorrhage/hematoma), and in-hospital mortality (all P < .05). In binary logistic regression, correcting for patient demographics and presence of comorbidities, elderly status was associated with 1.848 (95% confidence interval, 1.167-2.927; P = .009) greater odds of medical complications and 13.188 (95% confidence interval, 1.829-95.113; P = .011) greater odds of in-hospital mortality. Conclusion Elderly patients undergoing VS surgery have more comorbidities, in-hospital complications, and longer LOS than nonelderly patients. The elderly cohort had a greater rate of in-hospital mortality, though rare. Interestingly, elderly patients did not have a higher rate of many known complications associated with VS surgery and did not incur more hospital charges.

Malignant otitis externa hospitalizations: Analysis of patient characteristics.

OBJECTIVES/HYPOTHESIS: Malignant otitis externa (MOE) is a rare disorder that is not well studied in the inpatient setting. The Nationwide Inpatient Sample (NIS) database was utilized to analyze characteristics and predischarge outcomes of hospitalized MOE patients. METHODS: MOE hospitalizations were identified in the 2002 to 2013 NIS. Patient demographics, length of hospital stay, hospital charges, concomitant diagnoses, treatment-related procedures, complications, and in-hospital mortality rates were examined, with comparisons made among age cohorts and between diabetes mellitus (DM) and non-DM groups. RESULTS: A total of 8,300 cases of inpatient MOE were identified, with elderly DM patients compromising 22.7% of cases. Compared to adults, elderly patients had more inpatient procedures, longer hospitalizations (6.0 vs. 4.3 days), higher hospital charges ($26,712 vs. $19,047) (all P < 0.001), greater odds of in-hospital complications, and in-hospital mortality (odds ratio 14.435, 95% confidence interval 5.313-39.220). Adult/elderly patients with DM had more comorbidities, longer hospital stays (5.5 vs. 4.0 days), and higher hospital charges ($25,118 vs. $17,039) (all P < 0.001) than non-DM patients. However, DM was not associated with greater in-hospital mortality rates (0.6% vs. 0.5%; P = 0.640). Compared to the adult/elderly cohort, pediatric patients had higher rates of nonelective admissions (19.8% vs. 14.5%), shorter hospital stays (2.9 vs. 4.9 days), and lower hospital charges ($8,876 vs. $21,672) (all P < 0.05). CONCLUSION: Elderly diabetic patients made up a smaller fraction of hospitalized MOE cases than anticipated. Elderly patients had greater in-hospital complications and mortality. Diabetes mellitus in adult/elderly patients was not associated with increased mortality. Pediatric patients fared well with low complications rates and no instances of in-hospital mortality. LEVEL OF EVIDENCE: 2C. Laryngoscope, 127:2328-2336, 2017.

Safety of Topical Medications for Scabies and Lice in Pregnancy.

Medications should be employed with caution in women of childbearing age. Topical medications have little systemic absorption. Therefore, they are considered safer than oral or parenteral agents and less likely to be embryotoxic or fetotoxic. However, their safety profile must be assessed cautiously as the available data are limited. In this article, we aggregate human and animal studies to provide recommendations on using topical anti-scabies and anti-lice therapy in pregnancy.

Safety of Topical Dermatologic Medications in Pregnancy.

Dermatologic drugs should be employed with caution in women of childbearing age who are pregnant or considering pregnancy. Topical drugs have little systemic absorption. Therefore, they are deemed safer than oral or parenteral agents and less likely to harm the fetus. However, their safety profile must be assessed cautiously, as there is limited available data. In this article, we aggregate human and animal studies and provide recommendations on using topical dermatologic medications in pregnancy.

J Drugs Dermatol. 2016;15(7):830-834.

Using Drosophila melanogaster as a Model for Genotoxic Chemical Mutational Studies with a New Program, SnpSift.

This paper describes a new program SnpSift for filtering differential DNA sequence variants between two or more experimental genomes after genotoxic chemical exposure. Here, we illustrate how SnpSift can be used to identify candidate phenotype-relevant variants including single nucleotide polymorphisms, multiple nucleotide polymorphisms, insertions, and deletions (InDels) in mutant strains isolated from genome-wide chemical mutagenesis of Drosophila melanogaster. First, the genomes of two independently isolated mutant fly strains that are allelic for a novel recessive male-sterile locus generated by genotoxic chemical exposure were sequenced using the Illumina next-generation DNA sequencer to obtain 20- to 29-fold coverage of the euchromatic sequences. The sequencing reads were processed and variants were called using standard bioinformatic tools. Next, SnpEff was used to annotate all sequence variants and their potential mutational effects on associated genes. Then, SnpSift was used to filter and select differential variants that potentially disrupt a common gene in the two allelic mutant strains. The potential causative DNA lesions were partially validated by capillary sequencing of polymerase chain reaction-amplified DNA in the genetic interval as defined by meiotic mapping and deletions that remove defined regions of the chromosome. Of the five candidate genes located in the genetic interval, the Pka-like gene CG12069 was found to carry a separate pre-mature stop codon mutation in each of the two allelic mutants whereas the other four candidate genes within the interval have wild-type sequences. The Pka-like gene is therefore a strong candidate gene for the male-sterile locus. These results demonstrate that combining SnpEff and SnpSift can expedite the identification of candidate phenotype-causative mutations in chemically mutagenized Drosophila strains. This technique can also be used to characterize the variety of mutations generated by genotoxic chemicals.