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Nails
Published in Richard Ashton, Barbara Leppard, Differential Diagnosis in Dermatology, 2021
Richard Ashton, Barbara Leppard
Pachyonychia congenita is a rare genetic abnormality present from birth. The nail grows both vertically and horizontally causing a thick wedge-shaped nail, which is unsightly on the fingers and causes pain from pressure of shoes on the toes.
An approach to nail examination
Published in Archana Singal, Shekhar Neema, Piyush Kumar, Nail Disorders, 2019
Examine the toenails and feet for traumatic nail dystrophy, calluses, signs of inflammation, traumatic onycholysis, ankle edema, or pedal edema. Onychogryphosis is characterized by thickening and curving of the nails in the finger or toe due to injuries or infection (Figure 4.8). Palmoplantar keratoderma is present in cases of pachyonychia congenita along with typical nail findings.
Genodermatoses affecting the nail
Published in Eckart Haneke, Histopathology of the NailOnychopathology, 2017
There are surprisingly few histologic examinations of the nails in pachyonychia congenita. Most histopathologic studies including immunohistochemistry of different keratins comprise the palmo-plantar hyperkeratoses,53,54 which probably, but not necessarily, are similar to what one might expect to see in the nail bed.
Laser ablation and topical drug delivery: a review of recent advances
Published in Expert Opinion on Drug Delivery, 2019
Chien-Yu Hsiao, Shih-Chun Yang, Ahmed Alalaiwe, Jia-You Fang
The CO2 laser is also capable of inducing the skin permeation of macromolecules such as siRNA, vaccine, and protein. RNA interference is a therapy of siRNA delivery for silencing specific genes. Some evidences show that RNA interference has the potential to treat some skin diseases, including neoplasm, pachyonychia congenital, psoriasis, atopic dermatitis, and epidermolysis bullosa [74]. The clinical translation of siRNA therapy for cutaneous disorder management is always difficult due to the SC barrier [75] Lee et al. [76] compared the skin permeation of siRNA mediated by fractional CO2 and Er:YAG lasers. The CO2 and Er:YAG lasers created MTZs with diameters of 120 and 250 μm, respectively. The TJ marker claudin-1 was absent in and around the micropores, suggesting a loss of epidermal barrier function. The respective siRNA flux mediated by CO2 and Er:YAG lasers was 12- and 11-fold superior to the passive control. There was a broad distribution of fluorescein-conjugated siRNA throughout the epidermis by the irradiation of both lasers. Appendageal pathway is vital as a delivery route for topically applied macromolecules [77]. The fluorescence microscopy illustrated that hair follicles were important accumulation regions for laser-mediated siRNA delivery.
Small interfering RNA-based nanotherapeutics for treating skin-related diseases
Published in Expert Opinion on Drug Delivery, 2023
Yen-Tzu Chang, Tse-Hung Huang, Ahmed Alalaiwe, Erica Hwang, Jia-You Fang
Owing to compelling and specific gene silencing, siRNAs have been investigated as an effective approach for treating cardiovascular, oncological, infectious, and neurodegenerative diseases [30]. Patisiran, marketed by Alnylam Pharmaceuticals, is the first siRNA-based drug approved by the USFDA in 2018. This RNAi therapy is employed for the management of polyneuropathy induced by hereditary transthyretin-mediated amyloidosis [31]. One of the symptoms of this disease is the skin thickening and bruising. The other four siRNA drugs approved for clinical application are givosiran, lumasiran, inclisiran, and vutrisiran. Givosiran is used for the treatment of acute hepatic porphyria, whereas lumasiran is approved to treat a rare disease of primary hyperoxaluria type 1 [32]. Inclisiran, developed by Novartis, is used for treating lower low density lipoprotein (LDL) cholesterol. Similar to patisiran, vutrisiran is approved for amyloid polyneuropathy treatment. There are approximately 50 clinical trials currently underway, with the liver being the most studied target organ since foreign materials are easily tracked toward this organ [14]. Among these, five clinical trials at phase I and phase II are conducted to treat skin-associated diseases such as pachyonychia congenita and hypertrophic scar. A search using the keyword ‘siRNA’ in the clinical trials in the US National Library of Medicine (www.clinicaltrials.gov) shows a list of 118 clinical studies currently being performed (before 14 March 2023). This suggests an increasing trend of siRNA application in clinical medicine. Topical siRNAs can be an effective therapy for skin disorders, as proven in some cell-, animal-, and human-based studies. Topical approaches to deliver siRNA can target skin tissue to potentially modulate local gene expression while evading the adverse effects in systemic circulation. This strategy is successful for treating psoriasis, AD, melanoma, skin wounds, alopecia, and pachyonychia congenita [29]. RXI-109 is a self-delivering siRNA targeting connective tissue growth factor (CTGF), a regulator of molecular events occurring in wound healing processes such as scar and fibrosis. A phase II clinical trial showed that topical RXI-109 is well absorbed in the wound site to improve the appearance of revised scars [30]. Cotsiranib is designed to include two siRNAs targeting transforming growth factor (TGF)-β1 and cyclooxygenase (COX)-2 to regulate fibrosis and inflammatory response, respectively. Intradermal injection of cotsiranib in a clinical trial is applied to treat hypertrophic scars.