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Turk Patoloji Dergisi 2023Pediatric skin diseases may show various manifestations, occasionally affecting the patients' quality of life. Histopathological examination may be required for the...
OBJECTIVE
Pediatric skin diseases may show various manifestations, occasionally affecting the patients' quality of life. Histopathological examination may be required for the diagnosis. The aim of this study was to evaluate the spectrum of clinicopathological features in pediatric skin lesions.
MATERIAL AND METHOD
A total of 368 biopsies of 359 consecutive patients were included. The clinicopathological findings were retrospectively evaluated. Non-neoplastic (inflammatory) lesions (ILs) (n=186) were grouped per their origin, while neoplastic/proliferative lesions (NPLs) (n=182) were grouped based on their pattern. The clinical and histopathological characteristics were statistically analyzed.
RESULTS
51% were male and the median age was 10.4±4.9 years (range 0-17). ILs mainly involved the head and neck, and NPLs were mostly located in the lower extremity (p < 0.001). The most common NPLs were benign nevus (18%, n=33) and pilomatrixoma (15%, n=27), while the most frequent IL was spongiotic/psoriasiform dermatitis (38%). Skin appendage/connective tissue tumors were the largest among NPLs (p=0.02). NPLs were more frequently seen in children > 12 years old compared to ILs (p=0.03). The discordance rate between clinical and histopathological diagnoses was higher for NPLs (27% vs. 15%).
CONCLUSION
Although the spectrum of skin lesions is broad in pediatric patients, most are benign in nature. The higher frequency of melanocytic and/or cystic lesions among children > 12 years old may be attributed to increased self-care during puberty. Neoplastic/proliferative lesions of childhood seem to be less commonly recognized by clinicians, and a multidisciplinary approach remains the optimal method, considering the relatively high rate of discordance between the clinical and histopathological diagnoses.
Topics: Humans; Child; Male; Infant, Newborn; Infant; Child, Preschool; Adolescent; Female; Retrospective Studies; Quality of Life; Skin Neoplasms; Skin; Biopsy
PubMed: 36779578
DOI: 10.5146/tjpath.2023.01599 -
Frontiers in Immunology 2022Psoriasis is a common inflammatory skin disease recognized by the World Health Organization as "an incurable chronic, noninfectious, painful, disfiguring and disabling...
INTRODUCTION
Psoriasis is a common inflammatory skin disease recognized by the World Health Organization as "an incurable chronic, noninfectious, painful, disfiguring and disabling disease." The fact that metabolic syndrome (MetS) is the most common and important comorbidities of psoriasis suggests an important role of lipid metabolism in the pathogenesis of psoriasis. Narciclasine (Ncs) is an alkaloid isolated from the Amaryllidaceae plants. Its biological activities include antitumor, antibacterial, antiinflammatory, anti-angiogenic and promoting energy expenditure to improve dietinduced obesity. Here, we report that Ncs may be a potential candidate for psoriasis, acting at both the organismal and cellular levels.
METHODS
The therapeutic effect of Ncs was assessed in IMQ-induced psoriasis-like mouse model. Then, through in vitro experiments, we explored the inhibitory effect of Ncs on HaCaT cell proliferation and Th17 cell polarization; Transcriptomics and lipidomics were used to analyze the major targets of Ncs; Single-cell sequencing data was used to identify the target cells of Ncs action.
RESULTS
Ncs can inhibit keratinocyte proliferation and reduce the recruitment of immune cells in the skin by inhibiting psoriasis-associated inflammatory mediators. In addition, it showed a direct repression effect on Th17 cell polarization. Transcriptomic and lipidomic data further revealed that Ncs extensively regulated lipid metabolismrelated genes, especially the Phospholipase A2 (PLA2) family, and increased antiinflammatory lipid molecules. Combined with single-cell data analysis, we confirmed that keratinocytes are the main cells in which Ncs functions.
DISCUSSION
Taken together, our findings indicate that Ncs alleviates psoriasiform skin inflammation in mice, which is associated with inhibition of PLA2 in keratinocytes and improved phospholipid metabolism. Ncs has the potential for further development as a novel anti-psoriasis drug.
Topics: Animals; Mice; Anti-Inflammatory Agents; Dermatitis; Group IV Phospholipases A2; Imiquimod; Lipid Metabolism; Phospholipids; Psoriasis
PubMed: 36700214
DOI: 10.3389/fimmu.2022.1094375 -
The Malaysian Journal of Pathology Dec 2022Less biopsies were expected when large scale social restrictions were enforced during COVID-19 pandemic.
INTRODUCTION
Less biopsies were expected when large scale social restrictions were enforced during COVID-19 pandemic.
AIM
To compare the skin diseases prompting biopsy before and during the COVID-19 pandemic.
MATERIALS AND METHODS
A retrospective study of skin diseases was performed; the skin problems were then grouped into major histopathological reactions.
RESULTS
A total of 229 biopsies were performed before the COVID-19 outbreak, whereas only 160 biopsies were done during the pandemic. Before versus during the outbreak, the proportion of major reactions were granulomatous 20.52% vs 21.88%, neoplasms 17.47% vs 20%, psoriasiform 14.85% vs 10%, vesiculobullous 9.61% vs 8.75%, others 10.92% vs 7.50%, interface dermatitis 6.99% vs 10%, vasculopathy 6.99% vs 5.63%, spongiotic 6.55% vs 8.13%, panniculitis 3.49% vs 3.75%, and superficial and deep dermal infiltrate 2.62% vs 4.38%.
CONCLUSION
A decreased total number of patients prompting less biopsies were reported during the COVID-19 outbreak. However, the three largest percentages of major histopathological reactions were still similar, namely granulomatous, neoplasms, and psoriasiform.
Topics: Humans; Pandemics; Indonesia; Retrospective Studies; COVID-19; Skin Diseases; Biopsy
PubMed: 36591716
DOI: No ID Found -
Case Reports in Dermatological Medicine 2022Psoriasis is a chronic inflammatory papulosquamous disorder which affects around 2% of the world's population. A peak exacerbation in psoriatic symptoms was noted during...
Psoriasis is a chronic inflammatory papulosquamous disorder which affects around 2% of the world's population. A peak exacerbation in psoriatic symptoms was noted during COVID-19 due to lack of access to dermatological care mixed with heightened emotional stress during the pandemic. This case report describes a 52-year-old admitted male patient who sustained a diffuse rash on multiple areas of his body a week prior to testing positive for COVID-19. We explore plausible causes for the occurrence of the rash, discuss our treatment plan, include relevant clinical pictures, and review published literature to examine conditions that present similarly to the rash seen in our patient. It is crucial for dermatologists to be able to discern various systemic manifestations associated with cutaneous lesions, such as the one seen in this patient, in order to make an accurate and prompt diagnosis. A better understanding of the association between COVID-19 infection and psoriasiform lesions is needed for improving the prognostic and therapeutic outcomes in patients.
PubMed: 36567752
DOI: 10.1155/2022/1820673 -
Schweizer Archiv Fur Tierheilkunde Jan 2023Cyclosporine is a potent immunosuppressive agent used in veterinary medicine to treat a variety of inflammatory or immune mediated conditions. Many adverse effects are...
Cyclosporine is a potent immunosuppressive agent used in veterinary medicine to treat a variety of inflammatory or immune mediated conditions. Many adverse effects are associated with this medication, however most of them rarely occur. A 5-year-old, female intact French bulldog was presented with multiple, multifocally distributed, severe hyperkeratotic and papillomatous/verrucous plaques. The dog was on long-term immunosuppressive treatment with cyclosporine for meningoencephalitis of unknown origin (MUO). It had an history of atopic dermatitis and calcinosis cutis. A papillomavirus infection was excluded by polymerase chain reaction (PCR), and histopathologic analysis revealed a chronic lymphoplasmacytic non-specific dermatitis, perifolliculitis and periadnexitis and focal folliculitis with papillomatous epidermal hyperplasia and orthokeratotic hyperkeratosis. The diagnosis of "cyclosporine-induced epidermal hyperplasia with secondary pyoderma" was made. Cyclosporine was discontinued and as an alternative mycophenolate mofetil was started to control the MUO. An antimicrobial treatment was prescribed for three weeks. After four months, the skin lesions had healed completely. To date after 2 years, the dog is still in remission. The occurrence of hyperplastic lesions associated with cyclosporine therapy have already been described in previous reports. Most of them resemble those of psoriasiform lichenoid dermatitis, although papilloma virus may be detected in some instances. The dog of the present case showed some peculiarities in the histopathological findings, and a papillomavirus involvement was ruled out with PCR. Like observed in a previous report, there was no correlation between cyclosporine blood level and the severity of dermatological changes. A discontinuation of cyclosporine resulted in complete healing in 4 months. This case highlights the importance of regular monitoring and follow-ups in patients on immunosuppressive therapy. Even rare side effects should always be considered in these cases.
Topics: Dogs; Female; Animals; Cyclosporine; Hyperplasia; Immunosuppressive Agents; Papilloma; Dermatitis, Atopic; Chronic Disease; Dog Diseases
PubMed: 36562746
DOI: 10.17236/sat00382 -
Life (Basel, Switzerland) Dec 2022Isorhamnetin (IRh), which has a wide range of pharmacological effects, is one of the most significant active components in the fruits of L. and the leaves of L. It...
Isorhamnetin (IRh), which has a wide range of pharmacological effects, is one of the most significant active components in the fruits of L. and the leaves of L. It protects the heart and brain, in addition to possessing anti-tumor, anti-inflammatory, antioxidant, organ protection, and anti-obesity properties. We sought to assess IRh's anti-psoriatic activity, explore its immunomodulatory properties in reducing the severity of psoriatic symptoms, and evaluate its potential immunotherapeutic effects. We used IRh to treat imiquimod (IMQ)-induced psoriasis in BALB/C mice and examined the underlying mechanisms. The outcomes demonstrated that IRh reduced epidermal hyperplasia, lowered PASI scores, and improved histopathological psoriasiform lesions in IMQ-induced mice. IRh attenuated the accumulation of malondialdehyde (MDA), and also reversed the reduction caused by IMQ of superoxide dismutase (SOD) and catalase (CAT) in skin tissues. Additionally, IRh effectively inhibited IMQ's ability to increase proinflammatory cytokines such as TNF-α, IL-6, IL-17A, and transcription factor NF-κB. Furthermore, IRh significantly reduced the percentage of Th1 and Th17 in the spleens of mice treated with IMQ and suppressed the maturation of splenic dendritic cells. Overall, our research suggests that IRh protects against oxidative stress and inflammation in the pathogenesis of psoriasis, with potential for the development of new and potent medication for the treatment of psoriasis.
PubMed: 36556472
DOI: 10.3390/life12122107 -
Diagnostics (Basel, Switzerland) Dec 2022Palmoplantar psoriasis (PP) is a relatively uncommon variant of psoriasis that affects palms and soles, and that frequently shares both clinical and histologic features...
Palmoplantar psoriasis (PP) is a relatively uncommon variant of psoriasis that affects palms and soles, and that frequently shares both clinical and histologic features with chronic eczema, hyperkeratotic hand dermatitis and allergic contact dermatitis. The present study aims to characterize the histologic features of PP on a series of 21 cases. The following morphological features and their distribution were included: parakeratosis, dilated vessels in papillary dermis, psoriasiform acanthosis with elongation of rete ridges, perivascular lymphocytic infiltrate, decrease/loss of granular layer, Munro's microabscesses, spongiform pustules of Kogoj, spongiosis and lymphocytic exocytosis. The main diagnostic clues and histologic differential diagnoses are also discussed.
PubMed: 36553078
DOI: 10.3390/diagnostics12123071 -
Frontiers in Immunology 2022Psoriasis is a chronic skin disease associated with deregulated interplays between immune cells and keratinocytes. Neutrophil accumulation in the skin is a histological...
BACKGROUND
Psoriasis is a chronic skin disease associated with deregulated interplays between immune cells and keratinocytes. Neutrophil accumulation in the skin is a histological feature that characterizes psoriasis. However, the role of neutrophils in psoriasis onset and development remains poorly understood.
METHODS
In this study, we utilized the model of psoriasiform dermatitis, caused by the repeated topical application of an imiquimod containing cream, in neutrophil-depleted mice or in mice carrying impairment in neutrophil functions, including p47phox -/- mice (lacking a cytosolic subunit of the phagocyte nicotinamide adenine dinucleotide phosphate - NADPH - oxidase) and Sykfl/fl MRP8-cre+ mice (carrying the specific deletion of the Syk kinase in neutrophils only), to elucidate the specific contribution of neutrophils to psoriasis development.
RESULTS
By analyzing disease development/progression in neutrophil-depleted mice, we now report that neutrophils act as negative modulators of disease propagation and exacerbation by inhibiting gammadelta T cell effector functions via nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-mediated reactive oxygen species (ROS) production. We also report that Syk functions as a crucial molecule in determining the outcome of neutrophil and γδ T cell interactions. Accordingly, we uncover that a selective impairment of Syk-dependent signaling in neutrophils is sufficient to reproduce the enhancement of skin inflammation and γδ T cell infiltration observed in neutrophil-depleted mice.
CONCLUSIONS
Overall, our findings add new insights into the specific contribution of neutrophils to disease progression in the IMQ-induced mouse model of psoriasis, namely as negative regulatory cells.
Topics: Mice; Animals; Imiquimod; Neutrophils; NADP; Psoriasis; Disease Models, Animal; Eczema; NADPH Oxidases; Disease Progression
PubMed: 36466913
DOI: 10.3389/fimmu.2022.1049079 -
Clinical, Cosmetic and Investigational... 2022Urea as an ingredient in topical skin applications can aid skin integrity and hydration and have keratolytic, anti-fungal, anti-bacterial, and anti-pruritic effects....
PURPOSE
Urea as an ingredient in topical skin applications can aid skin integrity and hydration and have keratolytic, anti-fungal, anti-bacterial, and anti-pruritic effects. Skin conditions that urea-containing formulations have been utilized to treat include hand eczema/dermatitis, seborrheic dermatitis and psoriasiform dermatoses of the scalp. Two monocentric, simple blind, observational studies were carried out in healthy participants to examine the efficacy and safety of two urea-containing products in these skin conditions.
PATIENTS AND METHODS
Study 1 tested the actions of a commercially available 30% urea topical cream on hand eczema. The product was applied ≥2/day for 28 ±2 days. Transepidermal water loss, skin redness, skin hydration, and participant ratings of efficacy and qualities were assessed prior to first product application and on days 14 and 29. Study 2 tested the actions of a commercially available foaming product containing 10% urea on seborrheic dermatitis and scalp psoriasiform dermatoses. The product was applied ≥2/day for 28 ±2 days. Desquamation index and surface occupied by squames, analysis of extracted squames, microscopic assessment of scalp photos and participant ratings of product efficacy and qualities was carried out prior to first product application and on days 14 and 29.
RESULTS
In Study 1 (n = 20 females), results showed a significant (p < 0.05) decrease in transepidermal water loss, with an increase in hydration level of the upper skin layers, and a decrease in skin redness. In Study 2 (n = 13 females, 7 males), product use led to significant (p < 0.05) decreases in desquamation measures and dryness. In both studies, the majority of participants "agreed" or "slightly agreed" that the product had good efficacy and was easy to apply. No adverse reactions were reported.
CONCLUSION
These findings point to the utility of urea in topically applied vehicles for hand eczema, seborrheic dermatitis, and psoriasiform dermatoses.
PubMed: 36387960
DOI: 10.2147/CCID.S377718 -
Frontiers in Immunology 2022Transient receptor potential melastatin 4 (TRPM4) is a Ca-activated, monovalent cation channel that is expressed in a wide range of cells. We previously reported two...
Transient receptor potential melastatin 4 (TRPM4) is a Ca-activated, monovalent cation channel that is expressed in a wide range of cells. We previously reported two gain-of-function (GoF) mutations of TRPM4 as the cause of progressive symmetric erythrokeratodermia (PSEK), which shares similar clinical and histopathological features with psoriasis. Using CRISPR/Cas9 technology, we generated TRPM4 mice that have the equivalent mutation to one of the two genetic mutations found in human PSEK (equivalent to human TRPM4). Using this mutant mice, we examined the effects of TRPM4 GoF at the cellular and phenotypic levels to elucidate the pathological mechanisms underlying PSEK. In the absence of experimental stimulation, TRPM4 mice did not show a phenotype. When treated with imiquimod (IMQ), however, TRPM4 mice were predisposed to more severe psoriasiform dermatitis (PsD) than wild-type (WT), which was characterized by greater accumulation of CCR6-expressing γδ T cells and higher mRNA levels of . In TRPM4 mice, dendritic cells showed enhanced migration and keratinocytes exhibited increased proliferation. Moreover, a TRPM4 inhibitor, glibenclamide, ameliorated PsD in WT and TRPM4 mice. Our results indicate elevated TRPM4 activities boosted susceptibility to cutaneous stimuli, likely through elevation of membrane potential and alteration of downstream cellular signaling, resulting in enhanced inflammation. Our results further suggest a possible therapeutic application of TRPM4 inhibitors in psoriasis.
Topics: Mice; Humans; Animals; Gain of Function Mutation; Imiquimod; Psoriasis; Skin; Eczema; TRPM Cation Channels
PubMed: 36341417
DOI: 10.3389/fimmu.2022.1025499