Porokeratosis Research Articles

Penile and Scrotal Porokeratosis: A Single-Institution Experience.

There is a paucity of data regarding porokeratosis confined to the penis and scrotum. We evaluated our single-institutional experience regarding this entity. We interrogated our pathology archive for all specimens from the penis or scrotum, signed out as porokeratosis between 2000 and 2022. Clinical and histopathological features were reviewed, including the number of cornoid lamella(e) per tissue profile and squamous dysplasia. Nine patients were included in the study. The median age at the time of diagnosis was 51 years. Multiple lesions were present in 3 patients. Six patients had exclusively penile involvement, whereas 2 patients had exclusively scrotal involvement. One patient had multiple lesions consistent with porokeratosis ptychotropica, extending from the scrotum to the buttocks and perineum. Clinically, a collarette of scale was noted in 3 patients and diagnosis of porokeratosis was considered in 1 patient before biopsy. Histopathologically, 2 patients exhibited multiple cornoid lamellae in the same profile and 1 patient had follicular cornoid lamellae. Focal squamous dysplasia was only present in 1 patient. Follow-up was available for 5 patients (median duration: 35 months). In 4 patients, the lesions were removed completely during the shave biopsy procedure. At the past follow-up, there were no signs of recurrence or malignant transformation to squamous cell carcinoma in any patient. Porokeratosis involving the penis and/or scrotum may be elusive to diagnosis based on clinical features alone, emphasizing the role of histopathological examination. Increased awareness of this entity may help better delineate its clinicopathological presentation and appropriate classification.

Establishment of a Mouse Model for Porokeratosis Due to Mevalonate Diphosphate Decarboxylase Deficiency.

Porokeratosis (PK) is an autoinflammatory keratinization disease (AIKD) characterized by circular or annular skin lesions with a hyperkeratotic rim, pathologically shown as the cornoid lamella. Four genes that cause PK are associated with the mevalonate (MV) pathway. In Chinese PK patients, mevalonate diphosphate decarboxylase (MVD) is the most common causative gene. The lack of an animal model has greatly limited research on PK pathogenesis. In this research, we constructed K14-CreERT2-Mvdfl/fl mice using the Cre-LoxP system to create a mouse model for in-depth studies of PK. The Epidermal Mvd gene was knocked out by intraperitoneal injection of Tamoxifen (TAM). Pathology, immunohistochemistry, RNA-seq, and Western Blot analysis were performed. Skin lesions appeared following Mvd deficiency, and pathological examination revealed the characteristic cornoid lamella, as well as cutaneous inflammation. Furthermore, we observed elevated levels of IL-17A and IL-1β, and a decreased Loricrin level in epidermal Mvd-deficient mice. Compared with the wild-type (WT) group, Mvd deficiency activated the expression of lipid metabolism-related proteins. We developed the first mouse model for PK research, enabling further studies on disease development and treatment approaches.

Porokeratoses: an update on pathogenesis and treatment.

Porokeratoses (PK) are a group of uncommon dermatoses characterized by abnormal epidermal differentiation due to a disorder of the mevalonate metabolic pathway. Several clinical subtypes exist that can be associated with the same patient or affect different patients within a family and could, therefore, be different expressions of one disease. All PK subtypes share a common histopathologic finding, the cornoid lamella, a vertical stack of parakeratotic corneocytes embedded in an orthokeratotic horny layer. PK often affects immunosuppressed patients, in whom the course may parallel the level of immunosuppression. The pathogenesis of PK, which had long remained mysterious, has been recently unraveled after discovering pathogenic variants of genes involved in the mevalonate metabolic pathway. The disease is due to germline pathogenic variants of genes of this pathway but requires a second-hit event to manifest; therefore, PK is considered a dominantly inherited but recessively expressed condition. The prognosis of PK is usually favorable, even though the lesions progress to keratinocyte carcinomas in 7%-16% of patients. The treatment of PK was based on physical (ablative) procedures and various (topical or systemic) treatments, whose efficacy is nevertheless inconsistent and often temporary. The discovery of the metabolic pathway involved in the pathogenesis of PK paved the way for the elaboration of new topical treatments (combination of statins and cholesterol), which are more regularly efficacious compared with older treatments, even though the management of some patients with PK may still be challenging.

Line-field confocal optical coherence tomography for the differential diagnosis of porokeratosis from clinical simulators: a preliminary study.

Porokeratosis variants are relatively rare and can be clinically misdiagnosed with several common papulo-keratosic simulators. Line-field confocal optical coherence tomography (LC-OCT) is a new technology able to explore the skin in vivo up to 500µm depth. In this preliminary study we aimed to investigate the role of LC-OCT in the diagnosis of many porokeratosis variants. A total of 54 patients (28 was affected by one among 13 porokeratosis variants, 26 had a simulator condition) were examined at lesional and perilesional sites in vertical and horizontal view. We found an almost perfect interobserver agreement in LC-OCT images interpretation and a perfect correspondence with histologic slides. In addition, a series of morphologic in vivo and 3D features related to the cornoid lamella were detected by LC-OCT, not visible under histology. This device can be proposed for rapid bed-side non-invasive differentiation of porokeratosis variants from their simulators, possibly sparing incisional biopsy in doubtful cases.

Rapid Progression of Linear Porokeratosis Following COVID-19 Vaccination: A Case Report

Rapid Progression of Linear Porokeratosis Following COVID-19 Vaccination: A Case Report

Conventional and Novel Treatment Strategies for Porokeratoses: A Narrative Review.

Porokeratoses are a heterogenous group of autoinflammatory keratinization disorders all characterized by the presence of a cornoid lamella. In addition to gene mutations affecting the mevalonate pathway, environmental factors such as UV radiation, immunosuppression, trauma, and infection are also thought to contribute to porokeratoses. To date, there are no management guidelines or levels of evidence for commonly used pharmacologic and non-pharmacologic treatment options for porokeratoses. Conventional treatment strategies encompass topical and systemic drugs (e.g., salicylic acid, topical glucocorticoids, and retinoids), phototherapy, laser, and surgical interventions. Better insights into the pathogenesis of porokeratoses have paved the way for the development of novel therapeutic approaches, such as topical statins or the use of monoclonal antibodies. This narrative review aims to summarize both conventional and novel treatment options, including their level of evidence, advantages, and disadvantages.

A Review of Therapeutic Options for Linear Porokeratosis

Linear porokeratosis (LP) is a rare and uncommon variant of porokeratosis presenting as linear annular papules or plaques along Blaschko’s lines. It may arise spontaneously, although evidence of genetic predisposition exists via point mutations in the mevalonate pathway of cholesterol biosynthesis. Malignant transformation is the most serious complication of this chronic, progressive dyskeratosis. We review the currently available treatment options for LP, including topical, systemic, laser, photodynamic, and surgical therapies.

Malignant Transformation in a Genitocrural Porokeratosis : A Case Report

Porokeratosis is a rare heterogenous group of keratinization disorder with an unclear pathogenesis, and has varied clinical presentations. It may present with annular papules or plaques with central atrophy and clinically and histologically distinct ridge-like border called 'cornoid lamella'. Common variants include porokeratosis of Mibelli (PM), disseminated superficial actinic porokeratosis (DSAP), linear porokeratosis, punctate porokeratosis and porokeratosis palmaris et plantaris disseminata (PPPD). Here we report the case of a 79 year old female, who developed malignancy of porokeratosis over the groin region which had been mismanaged as eczema for many months and has been eventually diagnosed as Squamous cell carcinoma.

A Clinico-Epidemiological Study on Porokeratosis.

Porokeratosis (PK) is a chronic progressive disorder of keratinization characterized clinically by hyperkeratotic papules or plaques surrounded by a threadlike, elevated border that expands centrifugally. Pathogenesis involves heterozygous mutations in mevalonate kinase enzyme. The most common variants are disseminated superficial actinic porokeratosis (DSAP) and PK of Mibelli. All forms show a thin column of parakeratosis, the cornoid lamella, representing the active border. Dermoscopy reveals central brownish discoloration surrounded by a single hypopigmented band and a peripheral 'white track'. Long-standing cases of PK may undergo malignant transformation. UV-protection and topical agents, such as 5-fluorouracil, imiquimod, calcipotriol, tretinoin and oral retinoids are helpful. To study the clinical and epidemiological pattern of PK and the clinico-dermoscopic and histopathological correlation of PK. A prospective cross-sectional study was conducted on the patients attending the dermatology outpatient department (OPD) over 9 months with suspected features of PK. These patients were evaluated clinically and subjected to dermoscopy and histopathology. Statistical Package for the Social Sciences (SPSS) Of 11 patients, there were four (36.36%) males and seven (63.66%) females. The youngest was 18-year-old boy, and the eldest was 63-year-old man. The clinically most common type was PK of Mibelli with five (45.45%) cases. The most common dermoscopic feature observed was double-marginated, white peripheral border. The most common histopathological feature noted was cornoid lamella. PK is a rare skin disorder with a wide spectrum of clinical variants. Dermoscopy and histopathology aid in diagnosis, whereas dermoscopy plays a pivotal role in early and non-invasive diagnosis. Regular follow-up is mandatory to watch for the development of malignancies in a few variants.

Disseminated superficial actinic porokeratosis in an elderly patient undergoing androgen deprivation therapy for advanced prostate cancer: exploring the potential association

Porokeratosis is a group of chronic dermatoses characterized by the presence of cornoid lamellae. Disseminated superficial actinic porokeratosis (DSAP) is a common subtype, presenting as multiple small annular scaly lesions primarily in sun-exposed areas. While previous studies have documented DSAP in prostate cancer patients, the association with androgen deprivation therapy (ADT) has not been reported. In this report, we describe an elderly patient with advanced prostate cancer, who developed DSAP subsequent to undergoing ADT. We present the clinical, dermoscopic, and histopathological evaluations, and discuss the potential role of ADT in the pathogenesis of DSAP.

Porokeratoses-A Comprehensive Review on the Genetics and Metabolomics, Imaging Methods and Management of Common Clinical Variants.

Porokeratosis is a heterogeneous group of keratinising disorders characterised by the presence of particular microscopic structural changes, namely the presence of the cornoid lamella. This structure develops as a consequence of a defective isoprenoid pathway, critical for cholesterol synthesis. Commonly recognised variants include disseminated superficial actinic porokeratosis, disseminated superficial porokeratosis, porokeratosis of Mibelli, palmoplantar porokeratosis (including porokeratosis palmaris et plantaris disseminata and punctate porokeratosis), linear porokeratosis, verrucous porokeratosis (also known as genitogluteal porokeratosis), follicular porokeratosis and porokeratoma. Apart from the clinical presentation and epidemiology of each variant listed, this review aims at providing up-to-date information on the precise genetic background, introduces imaging methods facilitating the diagnosis (conventional and ultraviolet-induced fluorescence dermatoscopy, reflectance confocal microscopy and pathology), discusses their oncogenic potential and reviews the literature data on the efficacy of the treatment used, including the drugs directly targeting the isoprenoid-mevalonate pathway.

Verrucous Linear Porokeratosis with Dermal Amyloid Deposits – A Rare Presentation

Verrucous Linear Porokeratosis with Dermal Amyloid Deposits – A Rare Presentation

Porokeratosis of Mibelli- By dermoscopic lens. A rare case report

Porokeratosis is a benign, rare genetically determined autosomal dominant disorder. It is a disorder of epidermal keratinization characterized by hyperkeratotic papules or plaques surrounded by elevated border. It expands centrifugally. There is a clonal proliferation of keratinocytes, may be associated and chronic sun exposure, viral illness like HBV, HCV, HIV and immune-suppression.

Targeted anti-interleukin-17 therapy for linear porokeratosis.

We report a case involving a 12-year-old female patient with linear porokeratosis (LP) associated with the PMVK pathogenic variant c.329C>A, p.R110Q (monoallelic in DNA from blood and biallelic in DNA from LP). Therapeutic measures, which included a statin/cholesterol cream, did not ameliorate the patient’s skin lesions. Our findings demonstrate a strong interleukin (IL)-17A-positive inflammatory infiltrate, upregulation of IL-17-responsive genes and a significant clinical response to anti-IL-17A therapy in LP.

P06 Porokeratosis ptychotropica: a rare and recalcitrant genitogluteal eruption

Abstract A 45-year-old man with a history of psoriasis presented to our male genital dermatology clinic with a several-year history of pruritic, painful, hyperkeratotic red–brown plaques on both buttocks. He had previously been treated unsuccessfully with cryotherapy and topical imiquimod and podophyllotoxin for suspected condyloma acuminata. A 4-mm punch biopsy from the left buttock showed hyperkeratosis, hypergranulosis, papillomatosis and multiple columns of parakeratin with underlying agranulosis and dyskeratosis, consistent with cornoid lamella formation. A diagnosis of porokeratosis ptychotropica was made. He was treated with Dovobet® ointment and Trimovate® cream, with little improvement. He underwent four cycles of topical photodynamic therapy to his right buttock and two cycles to his left buttock, with minimal improvement. Oral isotretinoin was also trialled, but this led to lipid derangement prior to any observed benefit, so it was stopped. Porokeratosis ptychotropica is a rare and under-recognized variant of porokeratosis, characterized by epidermal keratinization that manifests as keratotic papules in the genitogluteal region. It is often misdiagnosed as psoriasis, tinea cruris or condyloma acuminata, as in our case. Typically, multiple cornoid lamellae are seen on histology (Lucker GP, Happle R, Steijlen PM. An unusual case of porokeratosis involving the natal cleft: porokeratosis ptychotropica? Br J Dermatol 1995; 132:150–1). The aetiology of porokeratosis ptychotropica is unknown, but there is potential for malignant transformation (Mazori DR, Shvartsbeyn M, Meehan SA et al. Transformation of porokeratosis ptychotropica into invasive squamous cell carcinoma. Int J Dermatol 2017; 56:679–80). It is commonly recalcitrant to treatment, with varying reports of success with topical retinoids, keratolytics, tacrolimus, calcipotriol, topical 5-fluorouracil, imiquimod, systemic retinoids, psoralen ultraviolet A, intralesional bleomycin, cryotherapy, photodynamic therapy, excision, dermabrasion and CO2 laser.

Decreased Imiquimod-Induced Psoriasis-Like Skin Inflammation in a Novel MvdF250S/+ Knock-In Mouse Model.

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.746T > 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 MvdF250S/+ mutation, we developed a novel MvdF250S/+ mouse model carrying an equivalent point mutation to the most common genetic variation among Chinese PK patients (MVDF249S/+) using CRISPR/Cas9 technology, which exhibited reduced cutaneous expression of Mvd protein. In the absence of external stimulation, MvdF250S/+ mice did not display specific phenotypes. However, upon induction with imiquimod (IMQ), MvdF250S/+ 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 MvdF250S/+mice 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 MvdF250S/+ mutation activated autophagy. Our findings provided insights into the biological function of MVD in the skin.

Photo gallery. Rare dermatoses. Part I

Orphan dermatoses are caused by both genetic causes and a number of autoimmune, inflammatory and infectious processes in the body. Congenital giant nevus is associated with serious complications: malignant melanoma, CNS lesions (neurocutaneous melanosis). Multiple epidermoid cysts are often a component of Gardner's syndrome. Angiolymphoid hyperplasia with eosinophilia, a vascular tumor formation with proliferation of histiocytoid endothelial cells, with severe lymphocytic and eosinophilic infiltration, recurs in 1/3 of cases. Morbigan's disease is persistent erythema and swelling of the middle third and upper part of the face. Skin mastocytosis in children is prone to spontaneous resolution during puberty. Squamous cell skin cancer accounts for 20% of all skin cancers and has a high risk of recurrence, metastasis, and death. Buschke's scleroderma is a scleroderma-like disease that causes progressive fibrous-mucinous thickening of the skin affecting the neck, shoulders, proximal upper extremities, and face. Fulminant (lightning) acne is a sharply exacerbated form of acne vulgaris, characterized by an acute onset and the appearance of confluent abscesses. Cases of acne fulminans have been observed during treatment with isotretinoin. Norwegian (crustose) scabies is associated with a compromised immune response, which allows the mites to multiply and can number in the millions. Pretibial myxedema (thyroid dermopathy) is a rare extrathyroid manifestation of Graves' disease along with thyrotoxicosis, thyroid hypertrophy, ophthalmopathy, and acropachy. Porokeratosis Mibelli predisposing factors of development are immunosuppressive conditions, malignancy is possible. Osteomas are formations from bone tissue in the dermis or subcutaneous fat as a result of metaplasia of fibroblasts into osteoblasts, or differentiation of primitive mesenchymal cells into osteoblasts and their migration to an ectopic site. Sarcoidosis of the skin is characterized by a variety of clinical forms, rarely observed before 40 years. Xanthomas with histiocytosis X ― a violation of lipid metabolism. The rural type of leishmaniasis (acute necrotizing) has a short incubation period, a significant spread of rashes and healing with the formation of scar tissue. The giant condyloma of BuschkeLevenshtein is characterized by progressive growth, large size and recurrent course, it can transform into squamous cell carcinoma. Degos disease ― malignant atrophic papulosis ― a rare disease caused by blockage of the arteries and veins.

Porokeratosis plantaris palmaris et disseminata with pruritic inflammatory changes

AbstractPorokeratosis plantaris palmaris et disseminata (PPPD) is a rare variant of porokeratosis that begins on the palms and soles and subsequently spreads to the trunk and extremities. We report a case of PPPD with pruritic inflammatory changes in a 48‐year‐old man, presenting with a 3‐year history of pruritic papules that initially appeared on his soles and palms and later spread to his limbs as hyperkeratotic erythematous papules and confluent thick plaques. Skin biopsies revealed cornoid lamellae, along with an inflammatory infiltrate consisting of lymphocytes and histocytes in the upper dermis.

Porokeratotic variant of lichen planus or lichen planus with porokeratosis: report of a challenging case

Annular lichenoid diseases have many differential diagnoses. Lichen planus (LP) and porokeratosis could show annular-shaped lesions with a lichenoid tissue pattern infiltration, but typical cornoid lamella formation is mainly in favor of porokeratosis. We present a 57-year-old man with papulovesicular and annular lesions on the shins with an exophytic lesion of left great toe nail. Papular lesions showed classic histopathology of LP, but annular lesions revealed imperfect cornoid lamella formation that could be seen in the porokeratotic variant of LP. Nail bed biopsy showed in-situ squamous cell carcinoma and so distal phalangeal amputation was performed. Our patient had no good response to topical and systemic steroid, but he had moderate improvement with oral retinoid. We think that our case had different types of LP including classic, bullous and porokeratotic variants which is a rare association.

A Case of Linear Porokeratosis.

A Case of Linear Porokeratosis.