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International Journal of Clinical and... 2022Porokeratosis is a disorder of keratinization with many clinical variants. The histological hallmark feature of porokeratosis is a cornoid lamella. Other accompanying...
Porokeratosis is a disorder of keratinization with many clinical variants. The histological hallmark feature of porokeratosis is a cornoid lamella. Other accompanying features include lichenoid inflammation, atrophy towards the centre of the lesion, dermal cytoid bodies, and adjacent lichenoid changes. Lichenoid keratosis is a benign cutaneous condition, thought to largely represent a degenerating seborrheic keratosis or solar lentigo. The classical histologic appearances are characterized by parakeratosis, epidermal acanthosis, and a dense band of lichenoid lymphocytic infiltrate. Since a lichenoid inflammatory reaction pattern can be seen in porokeratosis it has the potential to be misdiagnosed as a lichenoid keratosis if the cornoid lamella is not identified or missed due to sampling selection. We critically review 104 cases of benign lichenoid keratosis to establish whether any of these cases had features to support a diagnosis of porokeratosis. With 9.6% of cases considered for re-classification, we review clues to reaching this histologic diagnosis.
PubMed: 35265253
DOI: No ID Found -
Frontiers in Medicine 2022Actinic cheilitis or solar cheilosis is considered a precursor of malignancy or even an squamous cell carcinoma (SCC) of the lip, located most frequently on the lower... (Review)
Review
Actinic cheilitis or solar cheilosis is considered a precursor of malignancy or even an squamous cell carcinoma (SCC) of the lip, located most frequently on the lower lip. Actinic cheilitis (AC) has a higher likelihood of developing into invasive SCC of the lip, which is one of the deadliest non-melanoma skin cancers. Risk factors include chronic UV exposure, increasing age, male gender, fair phototypes, chronic scarring, immunosuppressive therapy, and tobacco use. From a clinical point of view, AC is characterized by dryness, scaling, atrophy, indistinct borders, and erosions. Ulceration and the appearance of a nodule often suggest the progression to invasive SCC. Dermoscopic examination reveals white structureless areas, scales, erosions, and white halos of the vermilion. Reflectance confocal microscopy shows disruption of the stratum corneum, parakeratosis, an atypical honeycomb pattern, solar elastosis, and dilated and tortuous blood vessels with increased blood flow. The rate of malignant transformation ranges from 10 to 30% and early diagnoses and treatment are essential in preventing the development of invasive SCC. Optimal treatment has not been established yet, but invasive and topical treatments can be tried. The present paper aims to review the existing data regarding epidemiology, risk factors, clinical picture, non-invasive imaging, diagnosis, and therapy in AC.
PubMed: 35242781
DOI: 10.3389/fmed.2022.805425 -
Cureus Jan 2022Esophagitis dissecans superficialis (EDS) is a rare esophageal disease with a wide spectrum of presentations from asymptomatic to debilitating symptoms. There is a...
Esophagitis dissecans superficialis (EDS) is a rare esophageal disease with a wide spectrum of presentations from asymptomatic to debilitating symptoms. There is a strong association of EDS with autoimmune diseases, smoking, and medications, but it can also be idiopathic. Due to the sporadic occurrence of EDS, identification requires a high index of suspicion to avoid frequent misdiagnoses. Herein, we present a case of EDS associated with the long-standing use of oral diclofenac with a favorable outcome after therapy with a proton pump inhibitor (PPI).
PubMed: 35233324
DOI: 10.7759/cureus.21647 -
Experimental Dermatology Jul 2022Psoriasis vulgaris is an inflammatory skin disease that affects 2%-3% of the population worldwide. One of the major challenges in discovering novel therapies is the poor...
Psoriasis vulgaris is an inflammatory skin disease that affects 2%-3% of the population worldwide. One of the major challenges in discovering novel therapies is the poor translatability of animal models to human disease. Therefore, it is imperative to develop human preclinical models of psoriasis that are amenable to pharmacological intervention. Here, we report a 3-D reconstituted human epidermis (RHE) culture system treated with cytokines commonly associated with psoriasis (TNFα, IL-17A and IL-22) that reproduced some key features of the human disease. The effects on epidermal morphology, gene transcription and cytokine production, which are dysregulated in psoriasis were assessed. Certain morphological features of psoriatic epidermis were evident in cytokine-stimulated RHEs, including hypogranulosis and parakeratosis. In addition, RHEs responded to a cytokine mix in a dose-dependent manner by expressing genes and proteins associated with impaired keratinocyte differentiation (keratin 10/K10, loricrin), innate immune responses (S100A7, DEFB4, elafin) and inflammation (IL-1α, IL-6, IL-8, IL-10, IL-12/23p40, IL-36γ, GM-CSF and IFNγ) typical of psoriasis. These disease-relevant changes in morphology, gene transcription and cytokine production were robustly attenuated by pharmacologically blocking TNFα/IL-17A-induced NF-κB activation with IKK-2 inhibitor IV. Conversely, inhibition of IL-22-induced JAK1 signalling with ABT-317 strongly attenuated morphological features of the disease but had no effect on NFκB-dependent cytokine production, suggesting distinct mechanisms of action by the cytokines driving psoriasis. These data support the use of cytokine-induced RHE models for identifying and targeting keratinocyte signalling pathways important for disease progression and may provide translational insights into novel keratinocyte mechanisms for novel psoriasis therapies.
Topics: Animals; Humans; Interleukin-17; Keratinocytes; NF-kappa B; Psoriasis; Skin; Tumor Necrosis Factor-alpha
PubMed: 35213752
DOI: 10.1111/exd.14551 -
Modern Pathology : An Official Journal... Aug 2022The aim of this multicenter retrospective study is to characterize the histopathologic features of initial/early biopsies of proliferative leukoplakia (PL; also known as...
The aim of this multicenter retrospective study is to characterize the histopathologic features of initial/early biopsies of proliferative leukoplakia (PL; also known as proliferative verrucous leukoplakia), and to analyze the correlation between histopathologic features and malignant transformation (MT). Patients with a clinical diagnosis of PL who have at least one biopsy and one follow-up visit were included in this study. Initial/early biopsy specimens were reviewed. The biopsies were evaluated for the presence of squamous cell carcinoma (SCCa), oral epithelial dysplasia (OED), and atypical verrucous hyperplasia (AVH). Cases that lacked unequivocal features of dysplasia were termed "hyperkeratosis/parakeratosis not reactive (HkNR)". Pearson chi-square test and Wilcoxon test were used for statistical analysis. There were 86 early/initial biopsies from 59 patients; 74.6% were females. Most of the cases had a smooth/homogenous (34.8%) or fissured appearance (32.6%), and only 13.0% had a verrucous appearance. The most common biopsy site was the gingiva/alveolar mucosa (40.8%) and buccal mucosa (25.0%). The most common histologic diagnosis was OED (53.5%) followed by HkNR (31.4%). Of note, two-thirds of HkNR cases showed only hyperkeratosis and epithelial atrophy. A lymphocytic band was seen in 34.8% of OED cases and 29.6% of HkNR cases, mostly associated with epithelial atrophy. Twenty-eight patients (47.5%) developed carcinoma and 28.9% of early/initial biopsy sites underwent MT. The mortality rate was 11.9%. Our findings show that one-third of cases of PL do not show OED with most exhibiting hyperkeratosis and epithelial atrophy, but MT nevertheless occurred at such sites in 3.7% of cases.
Topics: Atrophy; Cell Transformation, Neoplastic; Female; Humans; Hyperplasia; Leukoplakia, Oral; Male; Mouth Neoplasms; Precancerous Conditions; Retrospective Studies
PubMed: 35184151
DOI: 10.1038/s41379-022-01021-x -
Clinical features, histology, and treatment outcomes of granular parakeratosis: a systematic review.International Journal of Dermatology Aug 2022Granular parakeratosis is a rare disorder characterized by erythematous-brown hyperkeratotic papules and erythematous patches with scaling, occurring predominantly in...
BACKGROUND
Granular parakeratosis is a rare disorder characterized by erythematous-brown hyperkeratotic papules and erythematous patches with scaling, occurring predominantly in the flexures and sites of occlusion. While the exact underlying pathogenesis remains unknown, there has been a wide variety of precipitating factors and treatment options reported in the literature.
OBJECTIVE
We systematically reviewed and identified precipitants of granular parakeratosis, as well as its clinical and histologic features and treatment outcomes.
METHOD
A comprehensive literature search was conducted using MEDLINE and Embase in March 2021.
RESULTS
A total of 60 studies with 129 patients were included for analysis. An inciting factor was identified in 53.4%, the most common being topical agents including zinc oxide (17.1%), deodorant/antiperspirant (15.5%), and those containing benzalkonium chloride (7.0%). The majority presented with bilateral (68.2%) eruption of hyperkeratotic papules or erythematous patches and plaques, most frequently involving the axilla (56.5%). The prevailing histologic feature was retained keratohyalin granules within the stratum corneum in punch biopsy (97.2%) and curette (100%) specimens. Treatment options with reported success ranged from topical corticosteroids and systemic antibiotics to surgical interventions.
CONCLUSION
We provide a systematic review of reported precipitants, clinical features, and treatment options that clinicians should consider when granular parakeratosis is considered.
Topics: Dermatologic Agents; Humans; Keratosis; Parakeratosis; Skin; Treatment Outcome
PubMed: 35094385
DOI: 10.1111/ijd.16107 -
Romanian Journal of Morphology and... 2021Condyloma acuminatum (CA) is a pathology caused by the human papillomavirus (HPV). It is manifested by the appearance of warts in the vulvar, pubic, and anorectal... (Review)
Review
Condyloma acuminatum (CA) is a pathology caused by the human papillomavirus (HPV). It is manifested by the appearance of warts in the vulvar, pubic, and anorectal regions, but can occur in other areas. It is a common disease that can be prevented by using measures such as condoms or vaccine. Topical, local, pharmacological, surgical, and excisional therapy options are available for this pathology. Macroscopically, it appears as a vegetative tumor, with a single implantation base that branches towards the periphery, with a cauliflower appearance. CA is defined microscopically by acanthosis, parakeratosis, papillomatosis and koilocytosis. Immunohistochemical studies can detect the presence of various HPV strains or viral antigens and can emphasize certain specific characteristics; e.g., in the case presented in this study, we observed that the tumor had a fulminant evolution due to a strong vascular base identified with anti-cluster of differentiation (CD) 34 antibody, by the existence of epithelial cells with a high degree of cell proliferation, as evidenced by the anti-Ki67 antibody, the inactivation of the tumor suppressor gene and the appearance of immunolabeling for the anti-p53 antibody, by the strong immunoreactivity for p63 which reveals the existence of cells with dysplastic and neoplastic transformation potential, but also by detecting the immunolabeling for p16INK4a that is associated with the existence of HPV. Also, the tumor was immunoreactive for cytokeratin (CK) AE1∕AE3, partially immunoreactive for CK5∕6 in the basal layer and negative for CK7, which demonstrates the squamous epithelial origin of the described tumor. Subepithelial cells of the inflammatory system have been identified, such as macrophages immunolabeled with anti-CD68 antibody, T-lymphocytes immunolabeled with anti-CD3 antibody and rare B-lymphocytes immunolabeled with anti-CD20 antibody, which demonstrates the strong cellular response to remove the virus from the structure. Surgical and excisional treatment was helpful for the patient, because she was able to resume normal sexual activity and defecation, and on the other hand, microscopic studies showed the potential for malignant transformation of CA.
Topics: Condylomata Acuminata; Cyclin-Dependent Kinase Inhibitor p16; Female; Humans; Immunohistochemistry; Papillomaviridae
PubMed: 35024725
DOI: 10.47162/RJME.62.2.03 -
Effect of Total Glucosides of Paeony on Imiquimod-Induced Psoriatic Skin Lesions by Regulating VEGF.Clinical, Cosmetic and Investigational... 2021The purpose of this study was to use a murine model of psoriasis to examine the effect of total glycosides of paeony (TGP) on psoriatic skin lesions and on the...
PURPOSE
The purpose of this study was to use a murine model of psoriasis to examine the effect of total glycosides of paeony (TGP) on psoriatic skin lesions and on the expression of vascular endothelial growth factor (VEGF) in skin lesions and blood.
METHODS
A murine model of psoriasis was produced by shaving the backs of the mice and applying 5% imiquimod cream, 50 mg, to the backs of the mice once a day. Mice were killed on day 8, and skin and blood samples were obtained for histopathological examination and analysis of VEGF mRNA expression.
RESULTS
By day 8 of the application of imiquimod cream, skin lesions characteristic of psoriasis were evident, and histopathological examination of skin sections showed changes consistent with psoriasis (corneum thickening and parakeratosis, attenuation of the stratum granulosum, thickening of the stratum spinosum, and lengthening of the epidermal ridge). In the treatment group, 7 days of treatment with TGP resulted in resolution of the skin lesions, and histopathological examination showed the epidermis and dermis are approximately normal, without corneum thickening, hyperkeratosis, and parakeratosis. On day 7 of treatment, skin expression of VEGF mRNA was significantly lower in the treatment group than in the group that did not receive treatment (p < 0.05). Blood VEGF mRNA expression was not different between the groups.
CONCLUSION
TGP is effective for the treatment of psoriasis and may act by decreasing lesion VEGF mRNA expression.
PubMed: 34992404
DOI: 10.2147/CCID.S339627 -
Nanomaterials (Basel, Switzerland) Dec 2021Methotrexate (MTX), the gold standard against psoriasis, poses severe problems when administered systemically viz increased toxicity, poor solubility and adverse...
Methotrexate (MTX), the gold standard against psoriasis, poses severe problems when administered systemically viz increased toxicity, poor solubility and adverse reactions. Hence, a topical formulation of MTX for the management of psoriasis can be an effective approach. The present study aimed to develop an MTX based nanoparticle-loaded chitosan hydrogel for evaluating its potential efficacy in an imiquimod-induced psoriatic mice model. MTX-NPs loaded hydrogel was prepared and optimized using the o/w emulsion solvent evaporation method. Particle size, zeta potential, entrapment efficiency, in vitro drug release, ex vivo permeation, skin irritation and deposition studies were performed. Psoriatic Area and Severity Index (PASI) score/histopathological examinations were conducted to check the antipsoriatic potential of MTX-NPs loaded hydrogel using an imiquimod (IMQ)-induced psoriatic model. Optimized MTX-NPs showed a particle size of 256.4 ± 2.17 nm and encapsulation efficiency of 86 ± 0.03%. MTX-NPs loaded hydrogel displayed a 73 ± 1.21% sustained drug release in 48 h. Ex vivo permeation study showed only 19.95 ± 1.04 µg/cm of drug permeated though skin in 24 h, while epidermis retained 81.33% of the drug. A significant decrease in PASI score with improvement to normalcy of mice skin was observed. The developed MTX-NPs hydrogel displayed negligible signs of mild hyperkeratosis and parakeratosis, while histopathological studies showed healing signs of mice skin. So, the MTX-NPs loaded hydrogel can be a promising delivery system against psoriasis.
PubMed: 34947782
DOI: 10.3390/nano11123433 -
The International Journal of... 2022The epidermis is a stratified epithelium that forms the barrier between the organism and its environment. It is mainly composed of keratinocytes at various stages of...
The epidermis is a stratified epithelium that forms the barrier between the organism and its environment. It is mainly composed of keratinocytes at various stages of differentiation. The stratum corneum is the outermost layer of the epidermis and is formed of multiple layers of anucleated keratinocytes called corneocytes. We aim to highlight the roles of epidermal differentiation and proteolysis in skin diseases. Skin biopsies isolated from mice, the established model of Netherton syndrome (NS), and from patients with NS, seborrheic dermatitis (SD) and psoriasis, as well as healthy controls, were analyzed by histology and immunohistochemistry. Our results showed that NS, SD, and psoriasis are all characterized by abnormal epidermal differentiation, manifested by hyperplasia, hyperkeratosis, and parakeratosis. At the molecular level, abnormal differentiation is accompanied by increased expression of involucrin and decreased expression of loricrin in NS and psoriasis. Increased epidermal proteolysis associated with increased kallikrein-related peptidases (KLKs) expression is also observed in both NS and psoriatic epidermis. Furthermore, reduced expression of desmosomal proteins is observed in NS, but increased in psoriasis. Since desmosomal proteins are proteolytic substrates and control keratinocyte differentiation, their altered expression directly links epidermal proteolysis to differentiation. In conclusion, abnormal cellular differentiation and proteolysis are interconnected and underlie the pathology of NS, SD and psoriasis.
Topics: Animals; Cell Differentiation; Epidermis; Humans; Keratinocytes; Mice; Peptide Hydrolases; Proteolysis; Psoriasis
PubMed: 34881788
DOI: 10.1387/ijdb.210161gs