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Frontiers in Immunology 2020
Topics: Animals; Autoimmune Diseases; Autoimmunity; Humans; Inflammation; Inflammation Mediators; Keratins; Signal Transduction; Skin; Skin Diseases
PubMed: 32849625
DOI: 10.3389/fimmu.2020.01753 -
Indian Journal of Dermatology,... 2022Porokeratosis is a keratinization disorder with unclear etiopathogenesis, varied clinical presentation and characteristic histopathology, and is usually unresponsive to... (Review)
Review
Porokeratosis is a keratinization disorder with unclear etiopathogenesis, varied clinical presentation and characteristic histopathology, and is usually unresponsive to current therapeutic options. Until now, it was considered to be a clonal disorder with immunity, ultra violet radiation and other factors playing important roles in etiopathogenesis. It is now known that abnormalities in the mevalonate pathway are responsible for this clonal keratinization abnormality. New variants of porokeratosis like eruptive bullous, pruriginous, lichen planus like, follicular variants and porokeratoma have been described. While the cornoid lamella is the classical histopathologic feature, dermoscopy and reflectance confocal microscopy make the diagnosis clearer. Development of malignancy in a few variants is a concern. Linear, disseminated superficial actinic and giant lesions are most prone to developing malignancies. Bowen's disease, squamous cell carcinoma, basal cell carcinoma and even melanoma have been reported in cases of long-standing porokeratosis. Newer modalities of therapy such as photodynamic therapy, ingenol mebutate and HMGCoA inhibitors may play a role in the future.
Topics: Bowen's Disease; Carcinoma, Squamous Cell; Humans; Porokeratosis; Skin Neoplasms; Ultraviolet Rays
PubMed: 34877845
DOI: 10.25259/IJDVL_806_20 -
Clinical Reviews in Allergy & Immunology Dec 2023Recent advances in medical genetics elucidated the background of diseases characterized by superficial dermal and epidermal inflammation with resultant aberrant... (Review)
Review
Recent advances in medical genetics elucidated the background of diseases characterized by superficial dermal and epidermal inflammation with resultant aberrant keratosis. This led to introducing the term autoinflammatory keratinization diseases encompassing entities in which monogenic mutations cause spontaneous activation of the innate immunity and subsequent disruption of the keratinization process. Originally, autoinflammatory keratinization diseases were attributed to pathogenic variants of CARD14 (generalized pustular psoriasis with concomitant psoriasis vulgaris, palmoplantar pustulosis, type V pityriasis rubra pilaris), IL36RN (generalized pustular psoriasis without concomitant psoriasis vulgaris, impetigo herpetiformis, acrodermatitis continua of Hallopeau), NLRP1 (familial forms of keratosis lichenoides chronica), and genes of the mevalonate pathway, i.e., MVK, PMVK, MVD, and FDPS (porokeratosis). Since then, endotypes underlying novel entities matching the concept of autoinflammatory keratinization diseases have been discovered (mutations of JAK1, POMP, and EGFR). This review describes the concept and pathophysiology of autoinflammatory keratinization diseases and outlines the characteristic clinical features of the associated entities. Furthermore, a novel term for NLRP1-associated autoinflammatory disease with epithelial dyskeratosis (NADED) describing the spectrum of autoinflammatory keratinization diseases secondary to NLRP1 mutations is proposed.
Topics: Humans; Psoriasis; Inflammation; Mutation; Immunity, Innate; Keratosis; Guanylate Cyclase; Membrane Proteins; CARD Signaling Adaptor Proteins; Interleukins
PubMed: 38103162
DOI: 10.1007/s12016-023-08971-3 -
The Journal of Clinical and Aesthetic... Apr 2023No known studies have attempted to describe the pathophysiological relationship between patients who develop both porokeratosis and hidradenitis suppurativa (HS). The...
OBJECTIVE
No known studies have attempted to describe the pathophysiological relationship between patients who develop both porokeratosis and hidradenitis suppurativa (HS). The purpose of this report is to present possible immunological mechanisms that predispose patients to developing both porokeratosis and HS.
METHODS
In this case series, patients were identified during routine clinical encounters and data was extracted from the electronic medical record from October 2010 until April 2021. This study is a single center case series including patients from the department of dermatology at the UNC School of Medicine in Chapel Hill, North Carolina. Patients were selected via digital chart review if they had simultaneous diagnoses of disseminated porokeratosis and HS. Two eligible patients were identified as actively receiving care. One patient is a Black female and the other a White male. No primary study outcomes were planned. This investigation utilized chart review to identify disease time course, which was subsequently used to elucidate study outcomes.
RESULTS
Patient A is a 54-year-old Black female and Patient B is a 65-year-old White male. Both patients developed porokeratosis after multiple years of living with HS. Immunosuppression with adalimumab, corticosteroids, or other medications did not clearly precede porokeratosis development in either patient.
LIMITATIONS
Limitations include that this study was conducted at a single center and prevalence of patients with concomitance of both conditions is low.
CONCLUSION
In patients who demonstrate simultaneous HS and porokeratosis, activation of the innate immune system and associated IL-1 production may lead to autoinflammation and a phenotype of hyperkeratinization. Mutations in genes such as mevalonate kinase may predispose subjects to the development of porokeratoses and HS.
PubMed: 37077926
DOI: No ID Found -
Australian Journal of General Practice Nov 2019Disseminated superficial actinic porokeratosis (DSAP) is a precancerous skin condition often seen by dermatologists that is characterised by multiple annular... (Review)
Review
BACKGROUND
Disseminated superficial actinic porokeratosis (DSAP) is a precancerous skin condition often seen by dermatologists that is characterised by multiple annular hyperkeratotic lesions on sun-exposed areas. In Australia, DSAP is not a rare condition, possibly owing to Australia's high levels of sun exposure, and patients with DSAP often initially present to general practitioners (GPs). A lack of awareness about DSAP may result in misdiagnosis and inappropriate management of the condition.
OBJECTIVE
The aim of this article is to provide an overview of DSAP relevant to GPs to better facilitate diagnosis, management and referral to a dermatologist.
DISCUSSION
The underlying pathophysiological mechanism of DSAP is unknown. Although there is currently no effective standardised treatment, ongoing management is warranted, given the potential for malignant transformation. Suggested strategies include frequent full skin checks, patient education about sun protection and ablative treatment (such as cryotherapy) if indicated. Suspicious lesions require excision and histopathology.
Topics: Diagnostic Errors; Humans; Porokeratosis; Precancerous Conditions; Skin
PubMed: 31722456
DOI: 10.31128/AJGP-04-19-4914 -
Frontiers in Oncology 2023Lynch syndrome (LS)-associated glioblastoma (GBM) is rare in clinical practice, and simultaneous occurrence with cutaneous porokeratosis is even rarer. In this study, we...
BACKGROUND
Lynch syndrome (LS)-associated glioblastoma (GBM) is rare in clinical practice, and simultaneous occurrence with cutaneous porokeratosis is even rarer. In this study, we analyzed the clinicopathological and genetic characteristics of LS-associated GBMs and concurrent porokeratosis, as well as evaluated the tumor immune microenvironment (TIME) of LS-associated GBMs.
METHODS
Immunohistochemical staining was used to confirm the histopathological diagnosis, assess MMR and PD-1/PD-L1 status, and identify immune cell subsets. FISH was used to detect amplification of EGFR and PDGFRA, and deletion of 1p/19q and CDKN2A. Targeted NGS assay analyzed somatic variants, MSI, and TMB status, while whole-exome sequencing and Sanger sequencing were carried out to analyze the germline mutations.
RESULTS
In the LS family, three members (I:1, II:1 and II:4) were affected by GBM. GBMs with loss of MSH2 and MSH6 expression displayed giant and multinucleated bizarre cells, along with mutations in , , , and genes. All GBMs had TMB-H but not MSI-H. CD8+ T cells and CD163+ macrophages were abundant in each GBM tissue. The primary and recurrent GBMs of II:1 showed mesenchymal characteristics with high PD-L1 expression. The family members harbored a novel heterozygous germline mutation in and genes, confirming the diagnosis of LS and disseminated superficial actinic porokeratosis.
CONCLUSION
LS-associated GBM exhibits heterogeneity in clinicopathologic and molecular genetic features, as well as a suppressive TIME. The presence of MMR deficiency and TMB-H may serve as predictive factors for the response to immune checkpoint inhibitor therapy in GBMs. The identification of LS-associated GBM can provide significant benefits to both patients and their family members, including accurate diagnosis, genetic counseling, and appropriate screening or surveillance protocols. Our study serves as a reminder to clinicians and pathologists to consider the possibility of concurrent genetic syndromes in individuals or families.
PubMed: 37529690
DOI: 10.3389/fonc.2023.1194232 -
Dermatology Practical & Conceptual Oct 2020
PubMed: 33150040
DOI: 10.5826/dpc.1004a112 -
Dermatology Online Journal Oct 2007Linear porokeratosis is a rare variant. It can be present at birth or can develop in adult life. Lesions of linear porokeratosis are grouped and linearly arranged along...
Linear porokeratosis is a rare variant. It can be present at birth or can develop in adult life. Lesions of linear porokeratosis are grouped and linearly arranged along the lines of Blaschko. On the extremities it affects the distal portion more than the proximal areas. On the trunk these can be zosteriform in distribution. Lesions of linear porokeratosis probably result from an abnormal clone of epidermal precursors. A 20 year old male presented with annular plaques in linear pattern following the lines of Blaschko over the left upper limb extending up to the axilla present since childhood. The lesions had atrophic centre and raised hyperkeratotic borders. The lesions were more proximal than distal. Few scattered lesions were present on left side of trunk. There was no family history of such lesions. Systemic examination of patient was normal. On histopathological examination there was hyperkeratosis and parakeratosis. A coronoid lamella was present. At the base of coronoid lamella thinned out granular layer and necrotic keratinocytes were also seen. In the dermis pigment incontinence and perivascular lymphocytic infiltrate were present. This case is being reported because of its rarity. It is an atypical presentation because the lesions were disposed more over proximal than distal area of upper limb. Linear porokeratosis is associated with an increased risk of malignant transformation.
Topics: Adult; Arm; Humans; Male; Porokeratosis; Skin
PubMed: 18319012
DOI: No ID Found -
Proceedings (Baylor University. Medical... Jul 2020Porokeratosis is an uncommon cutaneous condition with multiple clinical variants that is defined by round patches with a raised, fine scaling border. Punctate...
Porokeratosis is an uncommon cutaneous condition with multiple clinical variants that is defined by round patches with a raised, fine scaling border. Punctate porokeratosis is a rare variant of porokeratosis that is characterized by elevated, seed-like lesions of the palms and soles. While variants of porokeratosis may be associated with an increased risk of squamous cell carcinoma within the lesion, punctate porokeratosis does not increase the risk of squamous cell carcinoma. However, punctate porokeratosis may mimic other dermatoses affecting the palms and soles including spiny keratoderma, arsenical keratosis, and nevus comedonicus. Distinguishing punctate porokeratosis and spiny keratoderma is important, as spiny keratoderma may be associated with underlying solid organ malignancy or chronic medical conditions, including chronic kidney disease. Here, we present a case of punctate porokeratosis mimicking spiny keratoderma in order to distinguish the two conditions and aid in their differentiation from other dermatologic conditions involving the palms and soles.
PubMed: 32675969
DOI: 10.1080/08998280.2020.1755212