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Postepy Dermatologii I Alergologii Feb 2021Keratinization means cytodifferentiation of keratinocytes turning into corneocytes in the stratum corneum. Disorders of keratinization (hyperkeratosis, parakeratosis and... (Review)
Review
Keratinization means cytodifferentiation of keratinocytes turning into corneocytes in the stratum corneum. Disorders of keratinization (hyperkeratosis, parakeratosis and dyskeratosis) are causing many dermatological diseases, including various types of ichthyoses, pachyonychia congenita, pityriasis rubra pilaris, all subtypes of psoriasis, pityriasis lichenoides, dyskeratosis congenita, leukoplakia and keratosis follicularis, which apart from skin lesions may affect the eye's adnexae causing ectropion, entropion, blepharitis, madarosis, and trichiasis, the ocular surface causing keratitis, conjunctivitis, corneal ulceration and episcleritis, which in turn cause uveitis and various fundoscopic changes (proliferative retinopathy, retinal vasculopathy, macular oedema and birdshot chorioretinopathy). Knowledge of ocular symtoms associated with pathological keratinization is crucial, preventing sight-threatening complications such as corneal perforation, lagophthalmus, phthisis bulbi, retinal neovascularization, retinal vasculopathy and optic nerve atrophy. This review encourages dermatologists to monitor patients for ocular symptoms and encourage ophthalmologists to monitor patients for dermatological symptoms.
PubMed: 34408561
DOI: 10.5114/ada.2021.104272 -
Advanced Drug Delivery Reviews Sep 2021Non-viral gene therapy for hereditary skin diseases is an attractive prospect. However, research efforts dedicated to this area are rare. Taking advantage of the... (Review)
Review
Non-viral gene therapy for hereditary skin diseases is an attractive prospect. However, research efforts dedicated to this area are rare. Taking advantage of the branched structural possibilities of polymeric vectors, we have developed a gene delivery platform for the treatment of an incurable monogenic skin disease - recessive dystrophic epidermolysis bullosa (RDEB) - based on highly branched poly(β-amino ester)s (HPAEs). The screening of HPAEs and optimization of therapeutic gene constructs, together with evaluation of the combined system for gene transfection, were comprehensively reviewed. The successful restoration of type VII collagen (C7) expression both in vitro and in vivo highlights HPAEs as a promising generation of polymeric vectors for RDEB gene therapy into the clinic. Considering that the treatment of patients with genetic cutaneous disorders, such as other subtypes of epidermolysis bullosa, pachyonychia congenita, ichthyosis and Netherton syndrome, remains challenging, the success of HPAEs in RDEB treatment indicates that the development of viable polymeric gene delivery vectors could potentially expedite the translation of gene therapy for these diseases from bench to bedside.
Topics: Animals; Epidermolysis Bullosa Dystrophica; Gene Transfer Techniques; Genetic Therapy; Humans; Polymers; Skin Diseases, Genetic; Translational Research, Biomedical
PubMed: 34293384
DOI: 10.1016/j.addr.2021.113842 -
The Journal of Investigative Dermatology Dec 2021Pachyonychia congenita (PC) is a genetic disorder of keratin that presents with nail dystrophy, painful palmoplantar keratoderma, and other clinical manifestations. We...
Pachyonychia congenita (PC) is a genetic disorder of keratin that presents with nail dystrophy, painful palmoplantar keratoderma, and other clinical manifestations. We investigated the genotype‒structurotype‒phenotype correlations seen with mutations in keratin genes (keratin [K]6A, K6B, K6C, K16, K17) and utilized protein structure modeling of high-frequency mutations to examine the functional importance of keratin structural domains in PC pathogenesis. Participants of the International PC Research Registry underwent genetic testing and completed a standardized survey on their symptoms. Our results support previous reports associating oral leukokeratosis with K6A mutations and cutaneous cysts, follicular hyperkeratosis, and natal teeth with K17 mutations. Painful keratoderma was prominent with K6A and K16 mutations. Nail involvement was most common in patients with K6A mutation and least common in those with K6C mutation. Across keratin subtypes, patients with coil 2B mutations had the greatest impairment in ambulation, and patients with coil 1A mutations reported more emotional issues. Molecular modeling demonstrated that hotspot missense mutations in PC largely disrupted hydrophobic interactions or surface charge. The former may destabilize keratin dimers/tetramers, whereas the latter likely interferes with higher-order keratin filament formation. Understanding the pathologic alterations in keratin structure improves our knowledge of how PC genotype correlates with clinical phenotype, advancing insight into disease pathogenesis and therapeutic development.
Topics: Genetic Association Studies; Humans; Keratin-16; Keratin-17; Keratin-6; Keratins; Models, Molecular; Mutation; Pachyonychia Congenita
PubMed: 34116063
DOI: 10.1016/j.jid.2021.03.035 -
Skin Appendage Disorders Apr 2021Pachyonychia congenita (PC) is a rare dermatosis that confers lifelong physical and emotional morbidities in affected patients. However, the clinical findings,...
INTRODUCTION
Pachyonychia congenita (PC) is a rare dermatosis that confers lifelong physical and emotional morbidities in affected patients. However, the clinical findings, treatments, and psychosocial impact of this disease have not been adequately described. The International PC Research Registry (IPCRR), a multinational initiative to collect data on PC patients, has allowed an opportunity to distinguish the salient features of this disease. We aimed to characterize the breadth and extent of nail disease, treatments, and quality of life in PC patients, and to describe any significant differences in clinical presentation or treatment of PC subtypes.
METHODS
The most recent IPCRR patient survey data consisting of an 857-response questionnaire and a 102-response addendum were analyzed in a retrospective analysis. The survey data were collected as part of a multinational, multicenter initiative and comprise the largest representative population of PC to date. Participants (survey respondents) were included in the study based on questionnaire responses and a genetic confirmation of having a PC subtype.
RESULTS
A total of 857 survey responses were collected. Genetic variations among PC subtypes influence nail disease onset and severity of symptoms. Nail disease negatively impacts patients' emotional health, especially during the adolescent and young adult years. Nail treatment tools vary little in terms of effectiveness and acquired infection rates.
CONCLUSION AND DISCUSSION
Patients with different PC subtypes have distinct clinical nail presentations and psychosocial impact. Genetic testing should be used to confirm PC diagnoses. Further characterization of PC, especially the rarer subtypes, may allow for more individualized patient education.
PubMed: 34055907
DOI: 10.1159/000513340 -
Journal of Cutaneous Medicine and... 2021Hidradenitis suppurativa and steatocystoma multiplex may coexist in the same patient. The overlap of these 2 conditions could be suggestive of an unrecognized defect in...
Hidradenitis suppurativa and steatocystoma multiplex may coexist in the same patient. The overlap of these 2 conditions could be suggestive of an unrecognized defect in follicular proliferation mutual in the pathogenesis of both conditions. Here we present 5 patients with both hidradenitis suppurativa and steatocystoma multiplex. Recognizing the overlap between these 2 conditions is important for accurate diagnosis, management, and identification of potential surgical candidates, as well as future basic science research.
Topics: Adult; Diagnosis, Differential; Female; Hidradenitis Suppurativa; Humans; Male; Steatocystoma Multiplex
PubMed: 33908804
DOI: 10.1177/12034754211010145 -
Clinical and Experimental Dermatology Aug 2021
Topics: Genes, Neurofibromatosis 1; Humans; Male; Mutation; Neurofibromatosis 1; Pedigree; Steatocystoma Multiplex; Exome Sequencing; Young Adult
PubMed: 33876461
DOI: 10.1111/ced.14618 -
International Journal of General... 2021Pachyonychia congenita (PC) is a rare, autosomal dominant genodermatosis characterized by palmoplantar keratoderma, nail dystrophy, cystic lesions, follicular...
BACKGROUND
Pachyonychia congenita (PC) is a rare, autosomal dominant genodermatosis characterized by palmoplantar keratoderma, nail dystrophy, cystic lesions, follicular hyperkeratosis, mucosal leukokeratoses, hyperhidrosis, hoarseness, and, rarely, natal teeth. Five keratin genes, and , have been found to be associated with PC.
METHODS
Using polymerase chain reaction and Sanger sequencing techniques, the purpose of the present study was to investigate the clinical features associated with PC and discover disease-associated variants. The , and exonic and flanking region sequences were amplified and directly sequenced to detect mutations.
RESULTS
Across two independent instances of PC, we identified a previously reported c.1393T>C (p.Tyr465His) mutation in exon 7 of , and a novel c.1237G>C (p.Glu413Gln) heterozygous missense mutation in exon 6 of the gene.
CONCLUSION
Through phenotype-genotype analysis among PC pedigrees, confirmed diagnoses of PC-K6a and PC-K16 were made in the two patients who presented with symptoms of PC. A new pathogenic mutation site in PC-K16 was potentially discovered.
PubMed: 33762842
DOI: 10.2147/IJGM.S280160 -
Dermatologic Clinics Apr 2021Many pediatric nail findings are normal variants and are no cause for alarm. Others represent congenital abnormalities or genetic syndromes for which there is no cure.... (Review)
Review
Many pediatric nail findings are normal variants and are no cause for alarm. Others represent congenital abnormalities or genetic syndromes for which there is no cure. Still others are inflammatory or infectious entities that require treatment. Pediatric nail disorders are reviewed, along with management.
Topics: Child; Humans; Nail Diseases
PubMed: 33745636
DOI: 10.1016/j.det.2020.12.005 -
Toxins Feb 2021Botulinum toxin is a superfamily of neurotoxins produced by the bacterium Clostridium Botulinum with well-established efficacy and safety profile in focal idiopathic...
Botulinum toxin is a superfamily of neurotoxins produced by the bacterium Clostridium Botulinum with well-established efficacy and safety profile in focal idiopathic hyperhidrosis. Recently, botulinum toxins have also been used in many other skin diseases, in off label regimen. The objective of this manuscript is to review and analyze the main therapeutic applications of botulinum toxins in skin diseases. A systematic review of the published data was conducted, following Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Botulinum toxins present several label and off-label indications of interest for dermatologists. The best-reported evidence concerns focal idiopathic hyperhidrosis, Raynaud phenomenon, suppurative hidradenitis, Hailey-Hailey disease, epidermolysis bullosa simplex Weber-Cockayne type, Darier's disease, pachyonychia congenita, aquagenic keratoderma, alopecia, psoriasis, notalgia paresthetica, facial erythema and flushing, and oily skin. Further clinical trials are still needed to better understand the real efficacy and safety of these applications and to standardize injection and doses protocols for off label applications.
Topics: Botulinum Toxins; Dermatologic Agents; Dermatology; Female; Humans; Male; Off-Label Use; Patient Safety; Risk Assessment; Risk Factors; Skin Diseases; Treatment Outcome
PubMed: 33562846
DOI: 10.3390/toxins13020120 -
The Breast Journal Apr 2021
Topics: Breast Neoplasms; Diagnosis, Differential; Epidermal Cyst; Female; Humans; Steatocystoma Multiplex
PubMed: 33527591
DOI: 10.1111/tbj.14179