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Journal of Inflammation Research 2022As a multifunctional cytokine, lipocalin 2 is weakly expressed in skin and serum under normal conditions. However, it is over-expressed by neutrophils and keratinocytes... (Review)
Review
As a multifunctional cytokine, lipocalin 2 is weakly expressed in skin and serum under normal conditions. However, it is over-expressed by neutrophils and keratinocytes in the skin lesions and sera in several skin diseases. Recent studies demonstrated that lipocalin 2 participates in the pathogenesis of psoriasis by exerting versatile effects on skin resident cells and infiltrating immune cells. Lipocalin 2 inhibits the synthesis of keratin, involucrin, and loricrin in keratinocytes, leading to epidermal parakeratosis via the Tcf7l1-lipocalin 2 signaling axis. It also recruits inflammatory cells such as T cells and neutrophils into skin lesions via the IL-23/IL17, p38-MAPK, and ERK-1/2 signaling pathways. Additionally, lipocalin 2 and other cytokines such as IL-17 have the synergetic effects on skin cells. The neutralization of lipocalin 2 or relevant cytokines can alleviate psoriasis, verifying that lipocalin 2 is an effective interfering target for psoriasis. In this review, we summarize the roles of lipocalin 2 in the processes of psoriatic inflammation and the promising therapeutic strategies based on lipocalin 2-related molecules.
PubMed: 35386225
DOI: 10.2147/JIR.S358492 -
Journal of Clinical Medicine Jan 2023Psoriasis is a common chronic, inflammatory skin disease characterised by keratinocyte hyperproliferation, parakeratosis, and T-cell infiltration. Adipose tissue has an...
Psoriasis is a common chronic, inflammatory skin disease characterised by keratinocyte hyperproliferation, parakeratosis, and T-cell infiltration. Adipose tissue has an endocrine function, producing an abundance of cytokines and adipokines. It has also been described that the major adipokines, leptin, resistin, and adiponectin, may be involved in the pathogenesis of psoriasis. The aim of the study was to examine the plasma levels of adiponectin, leptin, and resistin in patients with psoriasis and their correlations with disease activity parameters: Psoriasis Activity Severity Index (PASI), Dermatology Life Quality Index (DLQI), and Body Surface Area (BSA) index, as well as selected clinical parameters. The study included 53 patients with the plaque type and 31 healthy controls. The plasma concentrations of adiponectin were significantly lower in patients with psoriasis (p < 0.001) than in the control group. The plasma concentrations of leptin were higher in patients with psoriasis, however, due to high intra-patient variability of leptin plasma concentrations these differences did not reach statistical significance (p = 0.2). The plasma concentrations of resistin were significantly increased in patients with psoriasis compared to healthy controls (p = 0.02). There were no statistically significant correlations between adiponectin and leptin plasma concentrations and values of PASI, DLQI, and BSA. The resistin plasma concentrations correlated significantly with DLQI values. Additionally, we examined the correlations between adiponectin, leptin, and resistin plasma concentrations, and selected clinical parameters. Plasma concentrations of adiponectin correlated significantly with CRP values and ALT values. Leptin plasma concentrations correlated significantly with creatinine values. The results of our study confirm the role of adiponectin, leptin, and resistin in the pathogenesis of psoriasis.
PubMed: 36675592
DOI: 10.3390/jcm12020663 -
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 -
Dermatology Online Journal Feb 2021Epidermolytic ichthyosis (EI, OMIM 113800) is a rare autosomal dominant keratinization disorder that is caused by keratin 1 or 10 gene mutation. It can be classified...
Epidermolytic ichthyosis (EI, OMIM 113800) is a rare autosomal dominant keratinization disorder that is caused by keratin 1 or 10 gene mutation. It can be classified clinically based on the presence of palmoplantar hyperkeratosis involvement and extent of skin involvement. The diagnosis is made by clinical and histopathological examinations that can be confirmed by genetic testing. We present a 2-year-old girl who presented with erythematous and thick scaling skin. Her condition began at birth as multiple flaccid blisters that would easily break into erosions. There was no history of similar condition nor consanguinity within her family. Skin examination revealed diffuse erythematous skin covered with thick scales and erosion, predominantly on her face, extremities, palms, and soles. The skin histopathology examination showed diffuse parakeratosis with vacuolar and granular degeneration within granular and spinous layers along the epidermis. She was diagnosed with generalized EI with palmoplantar hyperkeratosis based on the clinical and histopathological examinations. Clinical improvement was observed after a one-month treatment with mupirocin cream, sodium bicarbonate bath, and moisturizer after bathing.
Topics: Child, Preschool; Female; Humans; Hyperkeratosis, Epidermolytic; Keratoderma, Palmoplantar
PubMed: 33818988
DOI: No ID Found -
Frontiers in Immunology 2024Psoriasis is a chronic inflammatory disease affecting skin and joints characterized by a chronically altered immune and inflammatory response. Several factors occur from... (Review)
Review
Psoriasis is a chronic inflammatory disease affecting skin and joints characterized by a chronically altered immune and inflammatory response. Several factors occur from the onset to the development of this disease due to different types of cells spatially and temporally localized in the affected area, such as, keratinocytes, macrophages, neutrophils and T helper lymphocytes. This scenario leads to the chronic release of high levels of inflammatory mediators (, IL-17, IL-23, IL-22, TNF-α, S100 proteins, Defensins) and lastly parakeratosis and thickening of the stratum spinosum. Extracellular vesicles (EVs) are small double membraned biological nanoparticles that are secreted by all cell types and classified, based on dimension and biogenesis, into exosomes, microvesicles and apoptotic bodies. Their role as vessels for long range molecular signals renders them key elements in the pathogenesis of psoriasis, as well as innovative platforms for potential biomarker discovery and delivery of fine-tuned anti-inflammatory therapies. In this review, the role of EVs in the pathogenesis of psoriasis and the modulation of cellular microenvironment has been summarized. The biotechnological implementation of EVs for therapy and research for new biomarkers has been also discussed.
Topics: Humans; Psoriasis; Extracellular Vesicles; Biomarkers; Animals; Skin; Cellular Microenvironment
PubMed: 38827737
DOI: 10.3389/fimmu.2024.1360618 -
Journal of Cosmetic Dermatology Aug 2021Baboon syndrome is a rare, type IV hypersensitivity reaction causing a maculopapular rash. Tamoxifen is an antineoplastic agent, working as an estrogen receptor...
BACKGROUND
Baboon syndrome is a rare, type IV hypersensitivity reaction causing a maculopapular rash. Tamoxifen is an antineoplastic agent, working as an estrogen receptor antagonist, also called a selective estrogen receptor modulator. A variety of rashes were reported with Tamoxifen use to-date except baboon syndrome. The Tamoxifen-induced baboon syndrome seems to be reversible, as discontinuation of the drug improves clinical outcomes.
AIM
Herein, we present the first case of Tamoxifen-induced baboon syndrome which occurred 8 years after initiation of Tamoxifen use.
PATIENTS
A 44-year-old woman presented with papulovesicular eruption on her body and erythema on her face for a duration of 6 months. There was no evidence of ocular or mucosal involvement. She was diagnosed with breast cancer and treated with tamoxifen 10 mg twice daily over the past 8 years. She was not taking other medications or over-the-counter supplements at the time of presentation. The patient underwent urgent skin biopsies of two lesions on her buttock and thigh. No organisms were seen on Gram stain. The patient's skin biopsy revealed extensive hyperorthokeratosis, minimal parakeratosis, hypergranulosis, and lichenoid interface dermatitis in the irregularly acanthotic epidermis supporting diagnosis of fixed drug eruption. Following a multidisciplinary discussion, the patient was diagnosed with baboon syndrome or symmetrical drug-related intertriginous and flexural exanthema (SDRIFE) associated with Tamoxifen.
RESULTS
Hence, Tamoxifen was immediately discontinued and treated with oral steroid along with topical agents. She showed improvement of clinical abnormalities within days after discontinuation of Tamoxifen.
CONCLUSIONS
Given the widespread use of Tamoxifen in the management of patients with breast cancer, it is important that healthcare professionals monitor for rare, however clinically significant, and potentially life-threatening dermatological manifestations of Tamoxifen use, such as baboon syndrome.
Topics: Adult; Animals; Drug Eruptions; Exanthema; Female; Humans; Papio; Syndrome; Tamoxifen
PubMed: 33253493
DOI: 10.1111/jocd.13863 -
Inflammation Apr 2024The mouse model of 2,4-dinitrochlorbenzene (DNCB)-induced human-like atopic dermatitis (hlAD) has been widely used to test novel treatment strategies and compounds....
The mouse model of 2,4-dinitrochlorbenzene (DNCB)-induced human-like atopic dermatitis (hlAD) has been widely used to test novel treatment strategies and compounds. However, the study designs and methods are highly diverse, presenting different hlAD disease patterns that occur after sensitization and repeated challenge with DNCB on dorsal skin. In addition, there is a lack of information about the progression of the disease during the experiment and the achieved pheno- and endotypes, especially at the timepoint when therapeutic treatment is initiated. We here examine hlAD in a DNCB-induced BALB/cJRj model at different timepoints: (i) before starting treatment with dexamethasone, representing a standard drug control (day 12) and (ii) at the end of the experiment (day 22). Both timepoints display typical AD-associated characteristics: skin thickening, spongiosis, hyper- and parakeratosis, altered cytokine and gene expression, increased lipid mediator formation, barrier protein and antimicrobial peptide abnormalities, as well as lymphoid organ hypertrophy. Increased mast cell infiltration into the skin and elevated immunoglobulin E plasma concentrations indicate a type I allergy response. The DNCB-treated skin showed an extrinsic moderate sub-acute hlAD lesion at day 12 and an extrinsic mild sub-acute to chronic pheno- and endotype at day 22 with a dominating Th2 response. A dependency of the filaggrin formation and expression in correlation to the disease severity in the DNCB-treated skin was found. In conclusion, our study reveals a detailed classification of a hlAD at two timepoints with different inflammatory skin conditions and pheno- and endotypes, thereby providing a better understanding of the DNCB-induced hlAD model in BALB/cJRj mice.
Topics: Dermatitis, Atopic; Animals; Dinitrochlorobenzene; Mice; Filaggrin Proteins; Disease Models, Animal; Mice, Inbred BALB C; Skin; Cytokines; Dexamethasone; Inflammation; Female
PubMed: 38150167
DOI: 10.1007/s10753-023-01943-x -
Pharmaceutics Jun 2022Recently, various types of in vitro-reconstructed 3D skin models have been developed for drug testing and disease modeling. Herein, we structurally and functionally...
Recently, various types of in vitro-reconstructed 3D skin models have been developed for drug testing and disease modeling. Herein, we structurally and functionally validated a self-assembled reconstructed skin equivalent (RSE) and developed an IL-17a-induced in vitro psoriasis-like model using a self-assembled RSE. The tissue engineering approach was used to construct the self-assembled RSE. The dermal layer was generated using fibroblasts secreting their own ECM, and the epidermal layer was reconstructed by seeding keratinocytes on the dermal layer. To generate the psoriatic model, IL-17A was added to the culture medium during the air-liquid interface culture period. Self-assembled RSE resulted in a fully differentiated epidermal layer, a well-established basement membrane, and dermal collagen deposition. In addition, self-assembled RSE was tested for 20 reference chemicals according to the Performance Standard of OECD TG439 and showed overall sensitivity, specificity, and accuracy of 100%, 90%, and 95%, respectively. The IL-17a-treated psoriatic RSE model exhibited psoriatic epidermal characteristics, such as epidermal hyperproliferation, parakeratosis, and increased expression of KRT6, KRT17, hBD2, and S100A9. Thus, our results suggest that a self-assembled RSE that structurally and functionally mimics the human skin has a great potential for testing various drugs or cosmetic ingredients and modeling inflammatory skin diseases.
PubMed: 35745784
DOI: 10.3390/pharmaceutics14061211 -
Cureus Aug 2023Esophagitis dissecans superficialis (EDS) is a rare esophageal lesion characterized by sloughing of the esophageal mucosa. Typically asymptomatic and histopathologically...
Esophagitis dissecans superficialis (EDS) is a rare esophageal lesion characterized by sloughing of the esophageal mucosa. Typically asymptomatic and histopathologically nonspecific, diagnosis relies on endoscopic appearance. We report a case of an 81-year-old female who presented with an 8-pound weight loss in two weeks. Upper endoscopy showed severe mucosal changes with sloughing in the lower esophagus, consistent with EDS. Histopathology confirmed the diagnosis. No offending agents were identified, and high-dose proton pump inhibitors (PPIs) were initiated, resulting in symptom improvement. EDS remains poorly understood; it is associated with medication use, esophageal motility disorders, and autoimmune conditions. EDS should be considered in unexplained weight loss cases, with treatment focused on the discontinuation of culprits and PPI therapy.
PubMed: 37779763
DOI: 10.7759/cureus.44372 -
Frontiers in Pharmacology 2022Psoriasis is a chronic inflammatory skin disorder characterized by keratinocyte hyperproliferation and differentiation with increased immune cell infiltration. The...
Psoriasis is a chronic inflammatory skin disorder characterized by keratinocyte hyperproliferation and differentiation with increased immune cell infiltration. The anti-psoriatic effect of lavender oil has been reported. However, its phytoconstituents, linalool (L) and linalyl acetate (LA), showed a distinctive affinity with psoriasis targets. This investigation was aimed to determine the combined effect of L and LA in ameliorating psoriasis-like skin inflammation and its safety in long-term topical uses. The combined effect of L and LA was compared with their individual effects. The anti-psoriatic activity was performed using imiquimod (IMQ)-induced psoriasis in BALB/c mice and evaluated to reduce PASI and CosCam scores and Th-1 and Th-17 cell-specific cytokine levels. The acute and repeated dose dermal toxicities were investigated as per the OECD guidelines. L and LA combination (LLA) in the 1:1 w/w ratio at 2% concentration showed a synergistic effect. The combination showed 76.31% and 71.29% recovery in PASI and CosCam Scores; however, L2% and LA2% showed 64.28% and 47.61% recovery in PASI and 64.75 and 56.76% recovery in CosCam scores, respectively. It showed >90% and >100% recovery in Th-17 and Th-1 cell-specific cytokines, respectively, and restored epidermal hyperplasia and parakeratosis toward normal compared with psoriatic mice. A marked reduction in NF-κB, cck6, and the IL-17 expression was also observed in the LLA-treated group. This combination was safe in a therapeutically effective dose for 28 days as no significant changes were observed in organ and body weights, liver and kidney parameters, and differential leukocyte counts. This study proves the synergy between L and LA in a 1:1 w/w ratio at 2% in the treatment of psoriasis-like skin inflammation and provides strong scientific evidence for its safe topical use.
PubMed: 35991888
DOI: 10.3389/fphar.2022.913174