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Dermatology Reports Jun 2023Porokeratosis (PK) is a disorder of keratinization with a clinical presentation of an atrophic center surrounded by a hyperkeratotic border. Lesions of porokeratosis...
Porokeratosis (PK) is a disorder of keratinization with a clinical presentation of an atrophic center surrounded by a hyperkeratotic border. Lesions of porokeratosis carry a risk of malignant transformation with giant porokeratosis (GPK) being a high-risk variant. We report a case in which a single, large, erythematous, scaly plaque in an immunocompromised patient showed initial histopathological features consistent with psoriasis and subsequent histological features consistent with GPK. This plaque underwent malignant transformation to squamous cell carcinoma on three occasions. This case highlights that specimens taken from central portions of porokeratosis may resemble a variety of dermatoses histologically, including psoriasis, resulting in misdiagnosis as seen in our patient. When a patient presents with a diagnosis previously made that isn't responding to therapy as expected, repeat biopsy is appropriate.
PubMed: 37397406
DOI: 10.4081/dr.2023.9634 -
Human Heredity 2023Porokeratosis is a rare chronic progressive hypokeratotic skin disease, possibly related to the mevalonate pathway. Variations in four enzymes, including...
BACKGROUND
Porokeratosis is a rare chronic progressive hypokeratotic skin disease, possibly related to the mevalonate pathway. Variations in four enzymes, including phosphomevalonate kinase (PMVK) may alter this pathway, ultimately leading to porokeratosis.
OBJECTIVES
The aim of the study was to identify the causative gene variant of porokeratosis in a Chinese family and investigate its population frequency and pathogenicity.
METHOD
In this study, Sanger sequencing was used to identify the gene variant causative of porokeratosis; its population frequency was investigated by polymerase chain reaction-restriction fragment length polymorphism in 4 patients and three normal individuals as well as in 100 normal unrelated controls; finally, the pathogenicity of the mutation and the associated structural changes were predicted.
RESULTS
We identified a novel heterozygous missense variant, c.207G>T (p. Lys69Asn) in the PMVK gene. This variant was found in all patients but not in the normal individuals in this family or in the 100 controls. In silico analysis indicated that the variant was pathogenic; p.Lys69Asn changed the length of the α-helix and the hydrogen bond pattern compared with the wild-type protein.
CONCLUSIONS
The novel variant c.207G>T (p. Lys69Asn) in the PMVK gene was the causative variant in this porokeratosis family. This finding provides further evidence for the genetic basis of this disease.
Topics: Humans; Porokeratosis; Mutation; Phosphotransferases (Phosphate Group Acceptor); Mutation, Missense; Pedigree
PubMed: 37315547
DOI: 10.1159/000531120 -
Cureus May 2023Linear porokeratosis (LP) is an epidermal keratinization disorder manifesting in the form of annular plaques with an atrophic center and hyperkeratotic margins. Although...
Linear porokeratosis (LP) is an epidermal keratinization disorder manifesting in the form of annular plaques with an atrophic center and hyperkeratotic margins. Although rare, LP carries a significant risk of skin cancer. Histological examination usually reveals the cornoid lamella, a parakeratosis column visualized in the outer layer of the epidermis. First-line treatment of LP is retinoids. However, the effects of combination therapy of isotretinoin and topical statins on LP are not well-understood. Herein, we attempted treatment with both isotretinoin and 2% cholesterol/atorvastatin ointment, with considerable improvement observed using the former but not the latter. These findings suggest that 2% topical cholesterol/atorvastatin treatment may not carry any additional benefits, even if used alongside retinoids. Further studies are needed to assess the potential effects of statins on LP.
PubMed: 37303383
DOI: 10.7759/cureus.38873 -
Autosomal dominant genodermatoses in adults being heralded by superimposed skin lesions in children.American Journal of Medical Genetics.... Jun 2023In autosomal dominant skin disorders, pronounced mosaic involvement may sometimes occur in the neonate, originating in a heterozygous embryo from early loss of... (Review)
Review
In autosomal dominant skin disorders, pronounced mosaic involvement may sometimes occur in the neonate, originating in a heterozygous embryo from early loss of heterozygosity, probably during the first week after fertilization. In biallelic phenotypes, such overlaying mosaic involvement may coexist with disseminated mosaicism, for example, in neurofibromatosis or tuberous sclerosis. In other phenotypes, however, classical nonsegmental involvement tends to appear much later, which is why the superimposed mosaic is a heralding feature. In Brooke-Spiegler syndrome (eccrine cylindromatosis), a large pedigree documented a 5-year-old boy with multiple, congenital small eccrine cylindromas along the lines of Blaschko. Disseminated cylindromas were absent because they usually appear in adulthood. ̶ In Hornstein-Knickenberg syndrome, an affected woman had an 8-year-old son with a nevus comedonicus-like lesion exemplifying a forerunner of the syndrome. ("Birt-Hogg-Dubé syndrome" represents a nonsyndromic type of hereditary perifollicular fibromas.) In glomangiomatosis, neonatal superimposed mosaicism is a heralding feature because disseminated lesions appear during puberty or adulthood. Linear porokeratosis is a harbinger of disseminated porokeratosis that develops 30 or 40 years later. ̶ Cases of superimposed linear Darier disease were forerunners of nonsegmental manifestation. ̶ In a case of Hailey-Hailey disease, neonatal mosaic lesions heralded nonsegmental involvement that began 22 years later.
Topics: Humans; Child; Carcinoma, Adenoid Cystic; Mosaicism; Inheritance Patterns; Phenotype
PubMed: 37288730
DOI: 10.1002/ajmg.c.32055 -
Clinical, Cosmetic and Investigational... 2023Porokeratosis ptychotropica (PPt) is a rare type of porokeratosis (PK) characterized by pruritic, reddish-brownish verrucous papules, and plaques usually around genital...
Porokeratosis ptychotropica (PPt) is a rare type of porokeratosis (PK) characterized by pruritic, reddish-brownish verrucous papules, and plaques usually around genital area or buttocks. Here, a case of a 70-year-old woman who was diagnosed as PPt was reported. The patient suffered from severe pruritic papules and plaques in the buttock region and pubis for 4 years. The skin lesions were giant, well-defined brown plaques with many satellite papules scattered around. Both clinical manifestations and histopathological features supported the diagnosis of PPt. In review of the identified mutation was found in patients with disseminated superficial actinic porokeratosis (DSAP) combined with PPt, while its unclear in PPt. To investigate the hypothesis that the variant reported in the present case report may played as an independent "likely pathogenic factor" of PPt. Consequently, a de novo missense pathogenic mutation in the MVK gene was identified in this case. Unexpectedly, it is a first report of a novel MVK mutation in sporadic PPt. This rare case suggested an isogenetic background between PPt and DSAP, which may help to explore the underlying pathogenesis of PPt.
PubMed: 37250911
DOI: 10.2147/CCID.S408016 -
Inflammation Aug 2023The mevalonate-diphosphate decarboxylase (MVD) gene, a member of the mevalonate pathway, plays a critical role in regulating the biosynthesis of cholesterol, steroid...
The mevalonate-diphosphate decarboxylase (MVD) gene, a member of the mevalonate pathway, plays a critical role in regulating the biosynthesis of cholesterol, steroid hormones, and non-steroid isoprenoids. Previous studies have suggested that the MVD c.746 T > C mutation is a major pathogenic gene of porokeratosis (PK), an autoinflammatory keratinization disease (AIKD) with unclear pathogenesis, few effective treatments, and no suitable animal model. To investigate the function of Mvd mutation, we developed a novel Mvd mouse model carrying an equivalent point mutation to the most common genetic variation among Chinese PK patients (MVD) using CRISPR/Cas9 technology, which exhibited reduced cutaneous expression of Mvd protein. In the absence of external stimulation, Mvd mice did not display specific phenotypes. However, upon induction with imiquimod (IMQ), Mvd mice exhibited decreased susceptibility to skin acute inflammation compared to wild-type (WT) mice, as evidenced by reduced cutaneous proliferation and lower protein levels of IL-17a and IL-1β. Additionally, after IMQ induction, the Mvdmice exhibited downregulated collagen generation and upregulated expression of Fabp3 compared to WT mice, whereas no significant changes in the key genes related to cholesterol regulation were found. Furthermore, the Mvd mutation activated autophagy. Our findings provided insights into the biological function of MVD in the skin.
Topics: Mice; Animals; Imiquimod; Mevalonic Acid; Aminoquinolines; Psoriasis; Skin; Inflammation; Disease Models, Animal; Mice, Inbred BALB C
PubMed: 37227548
DOI: 10.1007/s10753-023-01828-z -
Dermatopathology (Basel, Switzerland) May 2023Spiny keratoderma (SK) was first described by Brown in 1871 and is characterized by numerous 1-2 mm spines of keratin on the palms and soles, usually sparing the dorsal...
Spiny keratoderma (SK) was first described by Brown in 1871 and is characterized by numerous 1-2 mm spines of keratin on the palms and soles, usually sparing the dorsal surfaces, or disseminated over the trunk. Histologically, the "spine" represents a column of hyperkeratosis. Several different forms are known, including familial, sporadic, post-inflammatory and paraneoplastic. Although an association of SK with melanoma has been reported, the significance of such co-occurrence remains unclear due to the limited number of cases. To increase the body of knowledge and shed further light on this rare condition, we present a case of SK in a patient with a recent history of melanoma in situ.
PubMed: 37218903
DOI: 10.3390/dermatopathology10020021 -
Current Medicinal Chemistry 2024Statins are HMG-CoA reductase inhibitors and decrease plasma low-density lipoprotein cholesterol (LDL-C) levels. They are well tolerated, and because of their... (Review)
Review
Statins are HMG-CoA reductase inhibitors and decrease plasma low-density lipoprotein cholesterol (LDL-C) levels. They are well tolerated, and because of their LDL-C-lowering effect, they are utilized to decrease the risk of atherosclerosis and cardiovascular disease. However, statins have pleiotropic effects, including immunomodulatory, anti-inflammatory, antioxidant, and anticancer. Currently, oral administration is the only Food and Drug Administration (FDA)-approved route of administration for statins. However, other administration routes have demonstrated promising results in different pre-clinical and clinical studies. For instance, statins also seem beneficial in dermatitis, psoriasis, vitiligo, hirsutism, uremic pruritus, and graft-versus-host disease. Topically applied statins have been studied to treat seborrhea, acne, rhinophyma, and rosacea. They also have beneficial effects in contact dermatitis and wound healing in animal studies, (HIV) infection, osseointegration, porokeratosis, and some ophthalmologic diseases. Topical and transdermal application of statins is a non-invasive drug administration method that has shown significant results in bypassing the first-pass metabolism in the liver, thereby reducing possible adverse effects. This study reviews the multifaceted molecular and cellular impacts of statins, their topical and transdermal application, novel delivery systems, such as nanosystems for topical and transdermal administration and the challenges concerning this approach.
Topics: Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Administration, Cutaneous; Animals; Administration, Topical
PubMed: 37157198
DOI: 10.2174/0929867330666230508141434 -
Actas Dermo-sifiliograficas Apr 2024
Topics: Humans; Porokeratosis; Biopsy
PubMed: 37150245
DOI: 10.1016/j.ad.2022.07.037