Long-term vitamin A supplementation in a preclinical mouse model for RhoD190N-associated retinitis pigmentosa.

Retinitis pigmentosa (RP) is caused by one of many possible gene mutations. The National Institutes of Health recommends high daily doses of vitamin A palmitate for RP patients. There is a critical knowledge gap surrounding the therapeutic applicability of vitamin A to patients with the different subtypes of the disease. Here, we present a case report of a patient with RP caused by a p.D190N mutation in Rhodopsin (RHO) associated with abnormally high quantitative autofluorescence values after long-term vitamin A supplementation. We investigated the effects of vitamin A treatment strategy on RP caused by the p.D190N mutation in RHO by exposing Rhodopsin p.D190N (RhoD190N/+) and wild-type (WT) mice to experimental vitamin A-supplemented and standard control diets. The patient's case suggests that the vitamin A treatment strategy should be further studied to determine its effect on RP caused by p.D190N mutation in RHO and other mutations. Our mouse experiments revealed that RhoD190N/+ mice on the vitamin A diet exhibited higher levels of autofluorescence and lipofuscin metabolites compared to WT mice on the same diet and isogenic controls on the standard control diet. Vitamin A supplementation diminished photoreceptor function in RhoD190N/+ mice while preserving cone response in WT mice. Our findings highlight the importance of more investigations into the efficacy of clinical treatments like vitamin A for patients with certain genetic subtypes of disease and of genotyping in the precision care of inherited retinal degenerations.

A Pearl for Pretibial and Forearm Repair Following Mohs Micrographic Surgery.

Wound repair of the pretibial and forearm regions presents a challenge during dermatologic surgery as these areas are under significant tension and exhibit increased skin fragility. Various methodologies have been proposed for the closure and repair of such wounds, however, the use of the bilayered suture technique may be simpler and more effective than other techniques such as the pinch stitch, pully stitch, slip-knot stitch, pulley set-back dermal suture, horizontal mattress suture, pully stitch, and tandem pulley stitch. Our objective was to describe a novel method for the repair of pretibial and forearm wounds following Mohs micrographic surgery utilizing bilayered closure followed by tissue adhesive application.  J Drugs Dermatol. 2024;23(5):380.     doi:10.36849/JDD.7139  .

Tinea pedis in underrepresented groups: All of Us database analysis.

BACKGROUND: Tinea pedis is the most common form of dermatophytosis resulting in interdigital infections. All of Us (AoU) is a National Institute of Health initiative with an emphasis on patient populations traditionally underrepresented in biomedical research. OBJECTIVES: Our objective was to evaluate the burden of tinea pedis in underrepresented groups in the United States, utilising the novel AoU research program. METHODS: We analysed AoU Registered Tier dataset version 5, which includes data collected between 30 May, 2017, and 1 April, 2021. We conducted a cross-sectional analysis linking survey and electronic health record (EHR) data to estimate the prevalence of tinea pedis in underrepresented groups. RESULTS: All of Us data release includes 329,038 participants. Of these, 251,597 (76.5%) had electronic health record data and 6932 had tinea pedis (overall prevalence, 2.76%; 95% CI, 2.69-2.82). Multivariate analyses revealed that compared with White participants, Black and Hispanic participants had a higher adjusted odds of tinea pedis (OR, 1.29; 95% CI, 1.20-1.38 and OR, 1.38; 95% CI, 1.28-1.48, respectively). Higher adjusted odds of tinea pedis were observed in underrepresented groups defined by: age > =75 years (OR, 1.45; 95% CI, 1.33-1.57), LGBTQ status (OR, 1.17; 95% CI, 1.09-1.27), less than a high school education (OR, 1.22; 95% CI, 1.11-1.34), income <$35,000 (OR, 1.09; 95% CI, 1.02-1.16) and physical disability (OR, 1.56; 95% CI, 1.08-1.24). CONCLUSIONS: Our findings are consistent with overall age, and gender-specific prevalence estimates from prior epidemiologic studies, validating the scientific consistency of the new AoU database. Additionally, there may be an increased burden of tinea pedis among Black and Hispanic individuals.

Racial Disparities in the Treatment of Hidradenitis Suppurativa: An Analysis of Data from the National Ambulatory Medical Care Survey.

Hidradenitis suppurativa (HS) is a painful, disfiguring, chronic inflammatory disease affecting the axillary, inframammary, and groin regions. Black Americans are disproportionately affected by HS. Structural barriers may be responsible for a lack of better prevention and management. This paper discusses possible reasons that may lead to a more severe presentation and barriers to treatment. Moseley I, Ragi SD, Handler MZ. racial disparities in the treatment of hidradenitis suppurativa: an analysis of data from the National Ambulatory Medical Care Survey. J Drugs Dermatol. 2023;22(7):692-694. doi:10.36849/JDD.6803.

"Kissing" basaloid follicular hamartomas of the eyelid.

Basaloid follicular hamartomas (BFHs) are rare, benign, cutaneous adnexal tumors characterized by branching cords and anastomosing strands of basaloid cells in a loose, fibrous stroma. BFHs exhibit variable clinical presentations although they are commonly observed as skin-colored papules and are diagnosed based on histopathological features. Common systemic diseases associated with BFH include alopecia, myasthenia gravis, and palmoplantar pitting. BFH of the eyelid is extremely rare with only five cases reported in the literature to date. Congenital "kissing" lesions have only previously been reported with nevi. Here, we present a novel case of congenital "kissing" BFH of the right upper and right lower eyelid, and histopathological examination revealed intradermal nodules of basaloid cells forming reticulated strands, pseudohorn cysts, mucinous stroma, and palisading with CD34 and Bcl-2 expression in the stromal fibroblasts and periphery, respectively.

CNGB1-related rod-cone dystrophy: A mutation review and update.

Cyclic nucleotide-gated channel ß1 (CNGB1) encodes the 240-kDa ß subunit of the rod photoreceptor cyclic nucleotide-gated ion channel. Disease-causing sequence variants in CNGB1 lead to autosomal recessive rod-cone dystrophy/retinitis pigmentosa (RP). We herein present a comprehensive review and analysis of all previously reported CNGB1 sequence variants, and add 22 novel variants, thereby enlarging the spectrum to 84 variants in total, including 24 missense variants (two of which may also affect splicing), 21 nonsense, 19 splicing defects (7 at noncanonical positions), 10 small deletions, 1 small insertion, 1 small insertion-deletion, 7 small duplications, and 1 gross deletion. According to the American College of Medical Genetics and Genomics classification criteria, 59 variants were considered pathogenic or likely pathogenic and 25 were variants of uncertain significance. In addition, we provide further phenotypic data from 34 CNGB1-related RP cases, which, overall, are in line with previous findings suggesting that this form of RP has long-term retention of useful central vision despite the early onset of night blindness, which is valuable for patient counseling, but also has implications for it being considered a priority target for gene therapy trials.

Therapy in Rhodopsin-Mediated Autosomal Dominant Retinitis Pigmentosa.

Rhodopsin-mediated autosomal dominant retinitis pigmentosa (RHO-adRP) is a hereditary degenerative disorder in which mutations in the gene encoding RHO, the light-sensitive G protein-coupled receptor involved in phototransduction in rods, lead to progressive loss of rods and subsequently cones in the retina. Clinical phenotypes are diverse, ranging from mild night blindness to severe visual impairments. There is currently no cure for RHO-adRP. Although there have been significant advances in gene therapy for inherited retinal diseases, treating RHO-adRP presents a unique challenge since it is an autosomal dominant disease caused by more than 150 gain-of-function mutations in the RHO gene, rendering the established gene supplementation strategy inadequate. This review provides an update on RNA therapeutics and therapeutic editing genome surgery strategies and ongoing clinical trials for RHO-adRP, discussing mechanisms of action, preclinical data, current state of development, as well as risk and benefit considerations. Potential outcome measures useful for future clinical trials are also addressed.

A case-control study: epigenetic age acceleration in psoriasis.

Psoriasis (PsO) is a chronic inflammatory skin condition, often accompanied by psoriatic arthritis (PsA) and linked to various comorbidities and increased mortality rates. This study aimed to explore the relationship between PsO and accelerated biological aging, specifically focusing on epigenetic DNA methylation clocks. Using a matched case-control design, 20 PsO cases were selected along with age, race, and sex-matched 20 controls without PsO from the Skin Disease Biorepository at Brown Dermatology, Inc, Providence, Rhode Island. Blood samples retrieved from both groups were analyzed for DNA methylation, and epigenetic ages were calculated using DNA methylation clocks, including Horvath, Hannum, Pheno, SkinBlood, and Grim ages. Generalized estimation equations were employed to test the differences in epigenetic and chronological ages between PsO cases and controls, as well as within various subgroups in comparison to their respective controls. There were no statistically significant differences in epigenetic ages between PsO cases and controls. However, notably, PsO cases with PsA demonstrated an accelerated PhenoAge, compared to their matched controls. This study represents a pioneering investigation into the potential link between PsO and epigenetic aging, shedding light on the possibility of accelerated epigenetic aging in PsA, possibly associated with heightened inflammatory burden. These findings emphasize the systemic impact of PsA on the aging process, prompting the need for deeper exploration into autoimmune pathways, inflammation, and epigenetic modifications underlying PsO pathogenesis and aging mechanisms. Larger-scale studies with diverse populations are imperative to discern PsO subgroups experiencing accelerated biological aging and decipher the intricate interplay between PsO, inflammation, and aging pathways.

Pedigree Analysis of Families and Patients Affected by Retinitis Pigmentosa.

Family pedigrees allow for a more thorough understanding of human genetic disorders. They are used to help establish patterns of inheritance and to identify individuals at risk of disease. Pedigree analysis can be helpful in identifying genetic disorders that demonstrate mechanisms such autosomal dominant or recessive inheritance, X-linked inheritance, and anticipation.

Tinea versicolour in underrepresented groups: An All of Us database analysis.

Tinea versicolour, used interchangeably with pityriasis versicolour (PV), is a superficial fungal infection of the stratum corneum caused by Malassezia furfur, a fungus of the normal flora of the skin. PV occurs when conditions favour proliferation of the organism's mycelial form, such as in environments with high temperatures/humidity, in immunodeficient/immunocompromised states, and during pregnancy. PV presents as numerous well- demarcated macules with a powdery scale. Prior epidemiologic studies have indicated that underrepresented groups defined by race experience a higher burden of PV as compared to White patients. However, the burden of PV in other underrepresented groups has not previously been examined, as underrepresented groups are frequently excluded from studies evaluating the impact of dermatologic disease. The new National Institute of Health All of Us Research Program (AoU) aims to build one of the world's largest and most diverse databases to promote elucidation of health disparities, particularly in communities that have been historically excluded from biomedical research.

Visual Function Tests.

Inherited retinal diseases (IRDs), including retinitis pigmentosa, have devastating consequences for the visual function of affected individuals. Chief among these are a gradual loss of visual field, visual acuity, and night vision (otherwise known as nyctalopia). These changes often occur slowly, over a course of decades. Objective modalities for assessing these many aspects of visual function are crucial, not only to the monitoring of disease progression but, in recent years, also to evaluating the efficacy or lack thereof of new therapeutic interventions in the setting of clinical trials. This chapter will provide descriptions of these valuable assessment modalities, alongside discussions of their advantages and limitations in the context of serving those afflicted by IRDs.

Use of the Medmont Dark-Adapted Chromatic Perimeter for Assessing Rod Function in Retinitis Pigmentosa.

Medmont Dark-Adapted Chromatic (DAC) Perimeter enables efficient and quantifiable evaluation of rod-mediated (scotopic) vision. DAC tests rod function at multiple retinal locations, creating a topographical map of rod-mediated vision. These dynamic rod responses can be used as a functional marker to monitor disease progression and functional alterations in inherited retinal dystrophies, such as retinitis pigmentosa, Stargardt disease, cone-rod dystrophy, and choroideremia. In this chapter, we describe a protocol for the operation and analysis of the Medmont DAC in monitoring and assessing various retinal disorders.

Ocular Injection Techniques for Retinitis Pigmentosa: Intravitreal, Subretinal, and Suprachoroidal.

Ocular gene therapy represents an emerging and promising therapeutic approach for the treatment of several of the inherited retinal diseases. Currently, the focus has been to investigate monogenic inherited retinal disorders. Genetic and cellular therapies can be delivered to the eye by various injection techniques, including those that are intravitreal, subretinal, and suprachoroidal. Each of these three delivery methods are discussed with regard to their historical background, indications, surgical steps, and follow-up.