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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.
Principles of Clinical Diagnosis
Published in Susan Bayliss Mallory, Alanna Bree, Peggy Chern, Illustrated Manual of Pediatric Dermatology, 2005
Susan Bayliss Mallory, Alanna Bree, Peggy Chern
Pachyonychia congenita Type I: Jadassohn–Lewandowsky syndromeMarked thickening of nails (subungual hyperkeratosis) (Figure 19.16)Recurrent nail sheddingPlantar and palmar keratosesAcral bullaeFollicular keratoses on buttocks and extremitiesHyperhidrosis of the palms and solesLeukoplakia that histologically resembles a white sponge nevus and shows no tendency toward malignant degenerationMutation of keratin gene: KRT6A, KRT16 (keratin 6a, keratin 16), gene locus: 17q12-q21, 12q13Type II: Jackson-Lawler syndrome 1. Clinical findings of Type I plus 2Bullae of palms and solesPalmar/plantar hyperhidrosis
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.