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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 British Journal of Dermatology Sep 2022The coexistence of pachyonychia congenita (PC) and hidradenitis suppurativa (HS) has been described in case reports. However, the pathomechanism underlying this...
BACKGROUND
The coexistence of pachyonychia congenita (PC) and hidradenitis suppurativa (HS) has been described in case reports. However, the pathomechanism underlying this association and its true prevalence are unknown.
OBJECTIVES
To determine the genetic defect underlying the coexistence of PC and HS in a large kindred, to delineate a pathophysiological signalling defect jointly leading to both phenotypes, and to estimate the prevalence of HS in PC.
METHODS
We used direct sequencing and a NOTCH luciferase reporter assay to characterize the pathophysiological basis of the familial coexistence of HS and PC. A questionnaire was distributed to patients with PC registered with the International Pachyonychia Congenita Research Registry (IPCRR) to assess the prevalence of HS among patients with PC.
RESULTS
Direct sequencing of DNA samples obtained from family members displaying both PC and HS demonstrated a missense variant (c.275A>G) in KRT17, encoding keratin 17. Abnormal NOTCH signalling has been suggested to contribute to HS pathogenesis. Accordingly, the KRT17 c.275A>G variant resulted in a significant decrease in NOTCH activity. To ascertain the clinical importance of the association of HS with PC, we distributed a questionnaire to all patients with PC registered with the IPCRR. Seventy-two of 278 responders reported HS-associated clinical features (25·9%). Disease-causing mutations in KRT17 were most prevalent among patients with a dual phenotype of PC and HS (43%).
CONCLUSIONS
The coexistence of HS and KRT17-associated PC is more common than previously thought. Impaired NOTCH signalling as a result of KRT17 mutations may predispose patients with PC to HS. What is already known about this topic? The coexistence of pachyonychia congenita (PC) and hidradenitis suppurativa (HS) has been described in case reports. However, the pathomechanism underlying this association and its true prevalence are unknown. What does this study add? A dual phenotype consisting of PC and HS was found to be associated with a pathogenic variant in KRT17. This variant was found to affect NOTCH signalling, which has been previously implicated in HS pathogenesis. HS was found to be associated with PC in a large cohort of patients with PC, especially in patients carrying KRT17 variants, suggesting that KRT17 variants causing PC may also predispose to HS. What is the translational message? These findings suggest that patients with PC have a higher prevalence of HS than previously thought, and hence physicians should have a higher level of suspicion of HS diagnosis in patients with PC.
Topics: Hidradenitis Suppurativa; Humans; Keratin-17; Mutation; Pachyonychia Congenita; Phenotype
PubMed: 35606927
DOI: 10.1111/bjd.21674 -
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 -
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 -
Dermatology Online Journal Dec 2013Steatocystoma multiplex is a rare condition that is characterized by cutaneous cysts and may be inherited in an autosomal dominant manner or may occur sporadically. The...
Steatocystoma multiplex is a rare condition that is characterized by cutaneous cysts and may be inherited in an autosomal dominant manner or may occur sporadically. The pathogenesis is hypothesized to involve mutations in the keratin 17 gene. There are no internal manifestations. The lesions are usually asymptomatic. However, a suppurative variant exists in which the lesions become inflamed and suppurative after minor trauma. Treatments include cryosurgery, aspiration, surgical excision, laser therapy, and modified surgical incision techniques. This report presents a case of steatocystoma multiplex, the suppurative variant, in a 26-year-old woman with involvement of rare locations on the buttocks, groin, and extremities.
Topics: Adult; Cryosurgery; Drainage; Female; Humans; Laser Therapy; Steatocystoma Multiplex
PubMed: 24365012
DOI: No ID Found -
BioMed Research International 2014Many advances in dermatology have been made in recent years. In the present review article, newly described disorders from the last six years are presented in detail. We... (Review)
Review
Many advances in dermatology have been made in recent years. In the present review article, newly described disorders from the last six years are presented in detail. We divided these reports into different sections, including syndromes, autoinflammatory diseases, tumors, and unclassified disease. Syndromes included are "circumferential skin creases Kunze type" and "unusual type of pachyonychia congenita or a new syndrome"; autoinflammatory diseases include "chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) syndrome," "pyoderma gangrenosum, acne, and hidradenitis suppurativa (PASH) syndrome," and "pyogenic arthritis, pyoderma gangrenosum, acne, and hidradenitis suppurativa (PAPASH) syndrome"; tumors include "acquired reactive digital fibroma," "onychocytic matricoma and onychocytic carcinoma," "infundibulocystic nail bed squamous cell carcinoma," and "acral histiocytic nodules"; unclassified disorders include "saurian papulosis," "symmetrical acrokeratoderma," "confetti-like macular atrophy," and "skin spicules," "erythema papulosa semicircularis recidivans."
Topics: Autoimmune Diseases; Humans; Skin Diseases; Skin Neoplasms; Syndrome
PubMed: 25243162
DOI: 10.1155/2014/616973 -
Case Reports in Pathology 2012A 5-year-old female, known case of pachyonychia congenita, presented with diffuse hair loss; remaining hairs were easily plucked kinky hairs. Hair samples from patient...
A 5-year-old female, known case of pachyonychia congenita, presented with diffuse hair loss; remaining hairs were easily plucked kinky hairs. Hair samples from patient were investigated using a light microscope. The hairs of the patients were mainly anagen hairs and unlike normal plucked anagen hairs, showed keratinization and cornification of their hair bulbs. No specific hair shaft abnormality was found.
PubMed: 23056978
DOI: 10.1155/2012/850658 -
The Journal of Investigative... Oct 2005There are currently no specific treatments for pachyonychia congenita (PC). Available treatments generally are directed at specific manifestations of the disorder, and... (Review)
Review
There are currently no specific treatments for pachyonychia congenita (PC). Available treatments generally are directed at specific manifestations of the disorder, and an effective treatment plan must recognize that different patients are more or less troubled by different manifestations of the disease. Treatment for all aspects of PC has been less than completely satisfactory. Very few studies have compared different approaches to treatment, and fewer still have given longitudinal follow-up of efficacy and patient acceptance. This review is essentially a compilation of anecdotes. It was collected from physicians' reports in the literature, from direct communication with physicians currently following patients with PC and from patients who answered a questionnaire on the Pachyonychia Congenita Project web page (http://www.pachyonychia.org/Registry.html).
Topics: Darier Disease; Ectodermal Dysplasia; Female; Humans; Keratins; Keratoderma, Palmoplantar; Male; Mutation; Nails, Malformed
PubMed: 16250205
DOI: 10.1111/j.1087-0024.2005.10203.x -
The British Journal of Dermatology Mar 2020Pachyonychia congenita (PC), a rare genodermatosis, primarily affects ectoderm-derived epithelial appendages and typically includes oral leukokeratosis, nail dystrophy... (Review)
Review
BACKGROUND
Pachyonychia congenita (PC), a rare genodermatosis, primarily affects ectoderm-derived epithelial appendages and typically includes oral leukokeratosis, nail dystrophy and very painful palmoplantar keratoderma (PPK). PC dramatically impacts quality of life although it does not affect lifespan. PC can arise from mutations in any of the wound-repair-associated keratin genes KRT6A, KRT6B, KRT6C, KRT16 or KRT17. There is no cure for this condition, and current treatment options for PC symptoms are limited and palliative in nature.
OBJECTIVES
This review focuses on recent progress made towards understanding the pathophysiology of PPK lesions, the most prevalent and debilitating of all PC symptoms.
METHODS
We reviewed the relevant literature with a particular focus on the Krt16 null mouse, which spontaneously develops footpad lesions that mimic several aspects of PC-associated PPK.
RESULTS
There are three main stages of progression of PPK-like lesions in Krt16 null mice. Ahead of lesion onset, keratinocytes in the palmoplantar (footpad) skin exhibit specific defects in terminal differentiation, including loss of Krt9 expression. At the time of PPK onset, there is elevated oxidative stress and hypoactive Keap1-Nrf2 signalling. During active PPK, there is a profound defect in the ability of the epidermis to maintain or return to normal homeostasis.
CONCLUSIONS
The progress made suggests new avenues to explore for the treatment of PC-based PPK and deepens our understanding of the mechanisms controlling skin tissue homeostasis. What's already known about this topic? Pachyonychia congenita (PC) is a rare genodermatosis caused by mutations in KRT6A, KRT6B, KRT6C, KRT16 and KRT17, which are normally expressed in skin appendages and induced following injury. Individuals with PC present with multiple clinical symptoms that usually include thickened and dystrophic nails, palmoplantar keratoderma (PPK), glandular cysts and oral leukokeratosis. The study of PC pathophysiology is made challenging because of its low incidence and high complexity. There is no cure or effective treatment for PC. What does this study add? This text reviews recent progress made when studying the pathophysiology of PPK associated with PC. This recent progress points to new possibilities for devising effective therapeutics that may complement current palliative strategies.
Topics: Animals; Homeostasis; Kelch-Like ECH-Associated Protein 1; Keratin-16; Keratoderma, Palmoplantar; Mice; Mutation; NF-E2-Related Factor 2; Pachyonychia Congenita; Quality of Life
PubMed: 31021398
DOI: 10.1111/bjd.18033