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Archives of Plastic Surgery Nov 2023Pachyonychia congenita is a rare genetic disorder characterized by hypertrophic nail plates, hyperkeratotic nail beds, and thickened hyponychium of the fingers and toes,...
Pachyonychia congenita is a rare genetic disorder characterized by hypertrophic nail plates, hyperkeratotic nail beds, and thickened hyponychium of the fingers and toes, impairing manual dexterity and resulting in poor aesthetics. The current body of literature describes various treatment modalities, but no singular approach has been defined as the gold standard. In this case, the authors employed different surgical techniques for treating pachyonychia congenita to evaluate the most effective approach. A 3-year-old boy presented with hypertrophic nail growth involving all digits of both hands and feet. Three surgical procedures were performed on the patient's fingers and toes using germinal matrix excision (GME) alone, GME plus partial sterile matrix excision (pSME), or GME plus complete sterile matrix excision (cSME). The digits treated with GME + cSME exhibited no recurrence of nail growth. Those treated with GME alone exhibited recurrence of hypertrophic nail growth, although their growth slowed. Excision of GME + cSME prevented recurrence of hypertrophic nails, while GME alone or with pSME led to slower-growing hypertrophic nails. Complete excision of the germinal and sterile matrices with skin graft closure may be a definitive treatment for pachyonychia congenita, but further studies are needed to validate these findings.
PubMed: 38143838
DOI: 10.1055/s-0043-1771520 -
The Journal of Investigative Dermatology Apr 2024Pachyonychia congenita (PC) is a dominantly inherited genetic disorder of cornification. PC stands out among other genodermatoses because despite its rarity, it has been... (Review)
Review
Pachyonychia congenita (PC) is a dominantly inherited genetic disorder of cornification. PC stands out among other genodermatoses because despite its rarity, it has been the focus of a very large number of pioneering translational research efforts over the past 2 decades, mostly driven by a patient support organization, the Pachyonychia Congenita Project. These efforts have laid the ground for innovative strategies that may broadly impact approaches to the management of other inherited cutaneous and noncutaneous diseases. This article outlines current avenues of research in PC, expected outcomes, and potential hurdles.
Topics: Humans; Pachyonychia Congenita; Keratoderma, Palmoplantar; Administration, Cutaneous; Apoptosis; Cell Differentiation; Mutation
PubMed: 38099888
DOI: 10.1016/j.jid.2023.10.030 -
International Journal of Dermatology Feb 2024
Topics: Humans; Keratin-16; Keratin-6; Mutation; Mutation, Missense; Pachyonychia Congenita
PubMed: 38093419
DOI: 10.1111/ijd.16975 -
The Keio Journal of Medicine Dec 2023Pachyonychia Congenita Project (PC Project) is an international patient advocacy organization dedicated to patients who suffer from pachyonychia congenita (PC). This...
Pachyonychia Congenita Project (PC Project) is an international patient advocacy organization dedicated to patients who suffer from pachyonychia congenita (PC). This condition is a painful and debilitating skin disorder caused by a mutation in one of five keratin genes: KRT6A, KRT6B, KRT6C, KRT16,or KRT17. Through two primary programs, namely the International Pachyonychia Congenita Consortium (IPCC) and the International Pachyonychia Congenita Research Registry (IPCRR), PC Project provides comprehensive patient support and diagnostics while uniting patients, researchers, physicians, and industry partners on a global level to advance research and drug development for meaningful treatments and, ultimately, a cure for PC.
PubMed: 38072449
DOI: 10.2302/kjm.2023-0015-IR -
Journal of the European Academy of... Apr 2024
Topics: Humans; Pachyonychia Congenita; Simvastatin
PubMed: 37994233
DOI: 10.1111/jdv.19630 -
Journal of the American Podiatric... 2023
Topics: Humans; Pachyonychia Congenita
PubMed: 37938900
DOI: 10.7547/22-078 -
Current Opinion in Cell Biology Dec 2023The keratin cytoskeleton protects epithelia against mechanical, nonmechanical, and physical stresses, and participates in multiple signaling pathways that regulate cell... (Review)
Review
The keratin cytoskeleton protects epithelia against mechanical, nonmechanical, and physical stresses, and participates in multiple signaling pathways that regulate cell integrity and resilience. Keratin gene mutations cause multiple rare monoallelic epithelial diseases termed keratinopathies, including the skin diseases Epidermolysis Bullosa Simplex (EBS) and Pachyonychia Congenita (PC), with limited available therapies. The disease-related keratin mutations trigger posttranslational modifications (PTMs) in keratins and their associated proteins that can aggravate the disease. Recent findings of drug high-throughput screening have led to the identification of compounds that may be repurposed, since they are used for other human diseases, to treat keratinopathies. These drugs target unique PTM pathways and sites, including phosphorylation and acetylation of keratins and their associated proteins, and have shed insights into keratin regulation and interactions. They also offer the prospect of testing the use of drug mixtures, with the long view of possible beneficial human use coupled with increased efficacy and lower side effects.
Topics: Humans; Keratins; Cytoskeleton; Epidermolysis Bullosa Simplex; Mutation; Protein Processing, Post-Translational
PubMed: 37925932
DOI: 10.1016/j.ceb.2023.102264 -
The Keio Journal of Medicine Sep 2023Pachyonychia congenita (PC) is a rare, autosomal dominant inherited disorder of keratinization that is characterized by a triad of focal palmoplantar keratoderma,...
Pachyonychia congenita (PC) is a rare, autosomal dominant inherited disorder of keratinization that is characterized by a triad of focal palmoplantar keratoderma, plantar pain, and hypertrophic nail dystrophy. It can be debilitating, causing significantly impaired mobility. PC is diagnosed clinically alongside identification of a heterozygous pathogenic mutation in one of five keratin genes: KRT6A, KRT6B, KRT6C, KRT16, or KRT17. Each keratin gene mutation is associated with a distinct clinical phenotype, with variable age of onset and additional features, which has allowed classification by genotype. Additional features include pilosebaceous cysts, follicular hyperkeratosis, natal teeth, oral leukokeratosis, hidradenitis suppurativa, itching, and neurovascular structures. Although classed as rare, the prevalence of PC is likely to be underestimated. There is no cure or specific treatment for PC at present. Current treatments are limited to conservative measures to reduce plantar friction and trauma, mechanical debridement, topical treatments, and treatments for associated features or complications, most commonly infection. However, through active research in collaboration with PC Project, a patient-advocacy group, and the International PC Research Registry, a global registry of PC patients, there are now many new potential therapeutic options on the horizon. This review summarizes the clinical features associated with PC and highlights the current and future treatment of its manifestations.
PubMed: 37766547
DOI: 10.2302/kjm.2023-0012-IR -
Indian Dermatology Online Journal 2023
PubMed: 37727554
DOI: 10.4103/idoj.idoj_533_22 -
Cureus Sep 2023Background and objective Nail disorders encompass a wide spectrum of conditions, spanning congenital, developmental, infectious, neoplastic, degenerative,...
Background and objective Nail disorders encompass a wide spectrum of conditions, spanning congenital, developmental, infectious, neoplastic, degenerative, dermatological, and systemic diseases. A comprehensive exploration of their clinical manifestations, incidence, and associations is crucial for precise diagnosis and effective management. Methods This observational cross-sectional study conducted at B.J. Medical College and Civil Hospital, Ahmedabad involved 300 consecutive patients with nail changes from July 2017 to June 2019 reporting diverse dermatological and systemic conditions. The inclusion criteria involved patients of both genders and all age groups displaying nail changes associated with dermatological and systemic diseases. Data collection entailed a comprehensive clinical history, systemic and dermatological examinations, nail assessment using Dermoscope (DermLite 3, 10x), and supplementary tests. Analyses were performed on Microsoft Excel 2007 software. The study was approved by the Institute Ethics Committee. Results Among the 300 cases, females had a higher prevalence of nail involvement (57%), with a female-to-male ratio of 1.3:1. The most affected age group was 21-40 years, with 6-10 nails typically affected. Notably, housewives showed a higher prevalence. The most frequent nail condition was onychomycosis (24.33%) followed by psoriatic nail changes (20%). Less frequent nail changes involved eczema (5.7%), paronychia (5%), drug-induced (4.3%), lichen planus (3.7%), trauma-induced (3%), twenty nail dystrophy (2.33%), Darier's disease (2%), pemphigus vulgaris (2%), alopecia areata (1.67%), median Heller dystrophy (1.33%), atopic dermatitis (1%), epidermolysis bullosa (1%), racquet nail (1%), leprosy (1%), pityriasis rubra pilaris (0.67%), vitiligo (0.67%), secondary syphilis (0.67%), pachyonychia congenita (0.67%), as well as a case each of total leukonychia, subungual warts, Koenen tumor, and periungual fibroma(0.33%). Systemic autoimmune connective tissue disorders (CTD) accounted for 9%; the most common nail finding observed was nail fold erythema (48.1%) followed by nail fold telangiectasis (44.4%). In systemic sclerosis (SS), the most common finding was nail fold telangiectasia, and in systemic lupus erythematosus (SLE), the most common was nail fold erythema. Scleroderma capillary pattern on nail fold capillaroscopy was found in seven patients with SS, two patients with dermatomyositis, and only one patient with SLE. Nail changes observed in systemic diseases include onychomycosis in diabetes mellitus and chronic renal failure patients, splinter hemorrhages in ischemic heart disease and hypertension, longitudinal melanonychia in HIV, and koilonychia and platynychia in iron deficiency anemia. Other systemic diseases, such as Addison's disease and renal failure, also exhibited various nail changes. Conclusions Beyond their cosmetic importance, nails hold a vital pathologic role. Proficiency in nail terminology and classification is key for skillful evaluation. Understanding normal and abnormal nail variants, along with their disease associations, benefits diagnosis and tailored management. Nails, often overlooked but accessible, serve as a window into patients' general health and should be an integral part of thorough examinations. This study highlights an intricate clinical panorama of nail disorders, highlighting their significant role in both dermatological and systemic contexts.
PubMed: 37701161
DOI: 10.7759/cureus.45007