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Medicina 2024Bazex syndrome is a paraneoplastic disorder most commonly linked to squamous cell carcinomas of the upper aerodigestive tract, followed by lung cancer and other...
Bazex syndrome is a paraneoplastic disorder most commonly linked to squamous cell carcinomas of the upper aerodigestive tract, followed by lung cancer and other malignancies. It manifests through three stages of skin involvement that mirror the tumor's progression. Remarkably, skin lesions precede tumor symptoms or diagnosis in two-thirds of cases, underscoring the crucial role of suspecting this condition as it can promptly reveal an underlying neoplasm. Treatment primarily focuses on addressing the root neoplasm, with recurrent skin lesions potentially indicating tumor relapse. In this context, we present a clinical case involving a male patient whose manifestation of this syndrome facilitated the timely diagnosis of lung adenocarcinoma. This case underscores the significance of understanding this uncommon syndrome and its link to cancer, enabling early and accurate oncological diagnosis.
Topics: Humans; Male; Neoplasm Recurrence, Local; Skin Neoplasms; Carcinoma, Basal Cell; Paraneoplastic Syndromes; Lung Neoplasms; Hypotrichosis
PubMed: 38271945
DOI: No ID Found -
Theranostics 2024Macrophage-associated inflammation and keratinocytes excessive proliferation and inflammatory cytokines secretion induced by stimulation play an important role in the...
Macrophage-associated inflammation and keratinocytes excessive proliferation and inflammatory cytokines secretion induced by stimulation play an important role in the progression of psoriasiform dermatitis. However, how these two types of cells communicate remains obscure. We induced a mouse model with experimental psoriasiform dermatitis by Imiquimod (IMQ). To investigate whether damaged keratinocytes promote macrophage polarization and accelerate skin lesions by releasing extracellular vesicle (EV), purified EV were isolated from the primary epidermis of 5-day IMQ-induced psoriasiform dermatitis model mice, and then fluorescence-labeled the EV with PKH67. The EV was injected into the skin of mice treated with IMQ or vehicle 2 days . In addition, we established a co-culture system of the human monocytic cell line (THP-1) and HaCaT, and THP-1/HaCaT conditioned media culture model respectively. Subsequently, we evaluated the effect of Leucine-rich α-2-glycoprotein 1 (LRG1)-enriched EV on macrophage activation. We demonstrated macrophages can significantly promote keratinocyte inflammation and macrophage polarization may be mediated by intercellular communication with keratinocytes. Interestingly, IMQ-induced 5-day, keratinocyte-derived EV recruited macrophage and enhanced the progression of skin lesions. Similar to results , EV released from M5-treated HaCaT significantly promotes Interleukin 1β (IL-1β) and Tumor necrosis factor α (TNF-α) expression of THP-1 cells. Importantly, we found that LRG1-enriched EV regulates macrophages via TGF beta Receptor 1 (TGFβR1) dependent process. Our findings indicated a novel mechanism for promoting psoriasiform dermatitis, which could be a potential therapeutic target.
Topics: Humans; Animals; Mice; Keratinocytes; Macrophages; Extracellular Vesicles; Glycoproteins; Inflammation; Dermatitis
PubMed: 38250043
DOI: 10.7150/thno.89180 -
Journal of Clinical and Investigative... Jul 2023Seborrheic dermatitis (SD) is an inflammatory disease that has a papulosquamous morphology in areas rich in sebaceous glands such as the scalp, face, and body folds....
BACKGROUND
Seborrheic dermatitis (SD) is an inflammatory disease that has a papulosquamous morphology in areas rich in sebaceous glands such as the scalp, face, and body folds. Petaloid SD is an uncommon presentation found in patients with dark skin (Fitzpatrick Skin type V-VI). This form of SD can appear as pink or hypopigmented polycyclic coalescing rings or scaly macules and patches in the typical areas SD appears, which can mimic other conditions including lupus erythematosus. There is significant disproportion in the representation of darker skin types in dermatological textbooks and scarce literature on petaloid SD. This case demonstrates the presentation of the petaloid SD in an African American patient to contribute to the limited literature on dermatological conditions within this population.
CASE REPORT
A 25-year-old African American female with a history of mild hidradenitis suppurativa and asthma who presented with asymptomatic hypopigmented rashes throughout her face, scalp, and chest. She was diagnosed with the petaloid form SD and treated with ketoconazole shampoo once weekly, ketoconazole cream 1-2x daily, and hydrocortisone 2.5% ointment twice daily as needed. At six-week post-treatment follow-up, the patient's rashes significantly improved.
CONCLUSIONS
The petaloid form of SD is commonly experienced in dark-skinned patients. While common treatments for SD are effective in this form of SD, special consideration of skin types, skincare habits, and haircare in the African American population should be explored. This case report demonstrates how this uncommon skin condition presents in patients of Fitzpatrick skin type V-VI and a successful treatment course.
PubMed: 38249156
DOI: 10.13188/2373-1044.1000086 -
The Journal of Investigative Dermatology Jul 2024Psoriasis is a chronic and relapsing inflammatory skin disorder characterized by keratinocyte hyperproliferation and immune cell infiltration. LPCAT1 has been identified...
Psoriasis is a chronic and relapsing inflammatory skin disorder characterized by keratinocyte hyperproliferation and immune cell infiltration. LPCAT1 has been identified as a cancer promoter in cutaneous squamous cell carcinoma by us, yet its role in psoriasis remains elusive. In this study, we report that LPCAT1 is highly expressed in psoriatic skin lesions. LPCAT1 promotes keratinocyte hyperproliferation and enhances the secretion of IL-1β, IL-6, CXCL10, CCL20, S100A9, and platelet-activating factor. In psoriasiform keratinocytes, LPCAT1 promotes proliferation and inflammatory mediator production by activating protein kinase B/NF-κB and signal transducer and activator of transcription 3 signaling pathways. Furthermore, LPCAT1 inhibition attenuated epidermal hyperplasia and relieved skin inflammation in imiquimod-treated mice. Importantly, we identify the glucose transporter GLUT3, a recently reported promising target to mitigate T helper 17 cell-mediated inflammatory diseases, as a critical downstream effector of LPCAT1. GLUT3 deficiency impaired the proliferation and inflammation of psoriatic keratinocytes. LPCAT1 regulates GLUT3 in keratinocytes through NF-κB/signal transducer and activator of transcription 3 signaling, enhancing keratinocyte glycolysis and promoting proproliferative and proinflammatory effects. In addition, suppressing GLUT3 in mice alleviated imiquimod-induced dermatitis. Taken together, our study indicates the critical role of the LPCAT1-GLUT3 axis in psoriasis pathogenesis and proposes LPCAT1 or GLUT3 as a potential therapeutic target for psoriasis.
Topics: Psoriasis; Animals; Keratinocytes; Mice; Humans; Cell Proliferation; Glucose Transporter Type 3; Disease Models, Animal; Signal Transduction; Imiquimod; Male; STAT3 Transcription Factor; Female
PubMed: 38246582
DOI: 10.1016/j.jid.2024.01.004 -
BMJ Case Reports Jan 2024A wide range of inherited and acquired conditions can manifest as infantile erythroderma, among which -associated papulosquamous eruption (CAPE) is a rare cause. An...
A wide range of inherited and acquired conditions can manifest as infantile erythroderma, among which -associated papulosquamous eruption (CAPE) is a rare cause. An infant boy presented with a psoriasiform rash that progressed to erythroderma and was unresponsive to topical steroids and cyclosporine. The early onset of the disease, its severity and resistance to conventional treatment were suggestive of a genetic cause. Genetic evaluation revealed a homozygous variant of uncertain significance establishing the diagnosis of CAPE, and his parents were heterozygous carriers. There was only minimal improvement in the condition with supportive management and treatment with acitretin. Unfortunately, the child succumbed to sepsis and metabolic complications following a sudden worsening of skin disease. This case highlights the significance of genetic studies in diagnosing treatment-refractory cases of infantile erythroderma and emphasises the importance of early recognition of this rare condition.
Topics: Infant; Male; Child; Humans; Dermatitis, Exfoliative; Acitretin; Cyclosporine; Guanylate Cyclase; Membrane Proteins; CARD Signaling Adaptor Proteins
PubMed: 38233005
DOI: 10.1136/bcr-2022-254090 -
Journal of the European Academy of... May 2024Psoriasis is an inflammatory skin disease. The pathogenesis of psoriasis has not been fully elucidated. T-lymphokine-activated killer cell-originated protein kinase...
BACKGROUND
Psoriasis is an inflammatory skin disease. The pathogenesis of psoriasis has not been fully elucidated. T-lymphokine-activated killer cell-originated protein kinase (TOPK) activity increases in a proinflammatory environment, and inhibiting TOPK blocks inflammation. However, whether TOPK is involved in the pathogenesis of psoriasis remains to be identified.
OBJECTIVES
We aimed to study the role of TOPK in psoriasis and attempted to find a drug targeting TOPK for the prevention and treatment of psoriasis.
METHOD
Firstly, the expressions of TOPK in psoriatic patients, psoriatic cell and animal model were analysed by Gene Expression Omnibus database, immunohistochemistry (IHC) staining and western blot (WB). After inhibiting TOPK by chemical or gene knockout, the effect of TOPK on the development of psoriasis was verified in cell and animal model by WB, qRT-PCR, ELISA, haematoxylin-eosin (H&E) and IHC staining. Moreover, phosphoproteomic analysis was performed to explore the signalling pathways regulated by TOPK in the occurrence and development of psoriasis. Then, an in vitro kinase assay was performed to prove TOPK kinase activity was inhibited by worenine. Ultimately, WB, qRT-PCR, ELISA, H&E and IHC staining were used to verify the anti-psoriasis effect of worenine by inhibiting TOPK was in cell and animal model.
RESULTS
In this study, we found that TOPK was highly expressed in psoriasis patients, psoriatic cell and animal model, which suggests that TOPK might be associated with psoriasis pathogenesis. Interestingly, chemical or genetic inhibition of TOPK alleviated M5- and imiquimod (IMQ)-induced psoriasis-like dermatitis, which further confirmed the role of TOPK in promoting the development of psoriasis. Moreover, we determined that worenine inhibited TOPK kinase activity. In addition, worenine relieved M5- and IMQ-induced psoriasiform dermatitis by inhibiting TOPK activity.
CONCLUSIONS
T-lymphokine-activated killer cell-originated protein kinase promotes the development of psoriasis. Therefore, TOPK might be a promising drug target for the prevention and treatment of psoriasis. Worenine alleviates psoriasiform dermatitis by inhibiting TOPK activity, providing new strategies for clinical intervention.
Topics: Psoriasis; Humans; Animals; Mice; Disease Models, Animal; Signal Transduction; Mitogen-Activated Protein Kinase Kinases
PubMed: 38131517
DOI: 10.1111/jdv.19724 -
Proceedings of the National Academy of... Dec 2023Genetic medicines have the potential to treat various diseases; however, certain ailments including inflammatory diseases and cancer would benefit from control over...
Genetic medicines have the potential to treat various diseases; however, certain ailments including inflammatory diseases and cancer would benefit from control over extracellular localization of therapeutic proteins. A critical gap therefore remains the need to develop and incorporate methodologies that allow for posttranslational control over expression dynamics, localization, and stability of nucleic acid-generated protein therapeutics. To address this, we explored how the body's endogenous machinery controls protein localization through signal peptides (SPs), including how these motifs could be incorporated modularly into therapeutics. SPs serve as a virtual zip code for mRNA transcripts that direct the cell where to send completed proteins within the cell and the body. Utilizing this signaling biology, we incorporated secretory SP sequences upstream of mRNA transcripts coding for reporter, natural, and therapeutic proteins to induce secretion of the proteins into systemic circulation. SP sequences generated secretion of various engineered proteins into the bloodstream following intravenous, intramuscular, and subcutaneous SP mRNA delivery by lipid, polymer, and ionizable phospholipid delivery carriers. SP-engineered etanercept/TNF-α inhibitor proteins demonstrated therapeutic efficacy in an imiquimod-induced psoriasis model by reducing hyperkeratosis and inflammation. An SP-engineered anti-PD-L1 construct mediated mRNA encoded proteins with longer serum half-lives that reduced tumor burden and extended survival in MC38 and B16F10 cancer models. The modular nature of SP platform should enable intracellular and extracellular localization control of various functional proteins for diverse therapeutic applications.
Topics: Humans; Animals; Melanoma; Psoriasis; Inflammation; Protein Sorting Signals; Dermatitis; RNA, Messenger; Disease Models, Animal
PubMed: 38109533
DOI: 10.1073/pnas.2313009120 -
Cureus Nov 2023Bloch-Sulzberger Syndrome, also known as Incontinence Pigmentosa (IP), is a rare genodermatosis in which skin involvement occurs in almost all patients. Additionally,...
Bloch-Sulzberger Syndrome, also known as Incontinence Pigmentosa (IP), is a rare genodermatosis in which skin involvement occurs in almost all patients. Additionally, other ectodermal tissues like the central nervous system, eyes, hair, nails, and teeth may also be impacted. An X-linked dominant inheritance pattern characterizes the condition. But in our situation, IP caused a mutation in the body cells. There are four steps to the dermatological results. We describe the case of a 12-day-old female who had cutaneous features. It is crucial to make an early diagnosis using criteria like cutaneous symptoms so that quick diagnoses and interventions for other organs can be made to control more deadly complications in the future.
PubMed: 38106755
DOI: 10.7759/cureus.48823 -
Pediatric Dermatology 2024Dupilumab is an interleukin-4 receptor antagonist important in the treatment of refractory atopic dermatitis (AD), particularly among pediatric patients. Two boys with a...
Dupilumab is an interleukin-4 receptor antagonist important in the treatment of refractory atopic dermatitis (AD), particularly among pediatric patients. Two boys with a history of AD and cardiac transplant who developed psoriasiform dermatitis in response to dupilumab therapy are reported. These patients paradoxically developed an immune-mediated adverse drug reaction despite taking systemic immunosuppressive agents. While the literature suggests possible pathomechanisms for psoriasiform dermatitis despite immunosuppression, further research is necessary to better characterize this unique and unexpected phenomenon.
Topics: Humans; Antibodies, Monoclonal, Humanized; Heart Transplantation; Male; Dermatitis, Atopic; Psoriasis; Child; Immunosuppressive Agents
PubMed: 38097389
DOI: 10.1111/pde.15497 -
Pharmaceuticals (Basel, Switzerland) Nov 2023: Immune-related cutaneous adverse events (ircAEs) are frequent and may reduce quality of life and consistent dosing. IL12/23 has been implicated in psoriasis, which is...
: Immune-related cutaneous adverse events (ircAEs) are frequent and may reduce quality of life and consistent dosing. IL12/23 has been implicated in psoriasis, which is reminiscent of the psoriasiform/lichenoid ircAE phenotype. We report the use of ustekinumab as a therapeutic option. : Patients at Memorial Sloan Kettering Cancer Center, New York, who received immune checkpoint inhibitors and were treated with ustekinumab or had the keywords "ustekinumab" or "Stelara" in their clinical notes between 1 March 2017 and 1 December 2022 were retrospectively identified via a database query. Documentation from initial and follow-up visits was manually reviewed, and response to ustekinumab was categorized into complete cutaneous response (CcR, decrease to CTCAE grade 0), partial cutaneous response (PcR, any decrease in CTCAE grade exclusive of decrease to grade 0), and no cutaneous response (NcR, no change in CTCAE grade or worsening). Labs including complete blood count (CBC), cytokine panels, and IgE were obtained in a subset of patients as standard of care. Skin biopsies were reviewed by a dermatopathologist. : Fourteen patients with psoriasiform (85.7%), maculopapular (7.1%), and pyoderma gangrenosum (7.1%) ircAEs were identified. Ten (71.4%) receiving ustekinumab had a positive response to treatment. Among these 10 responders, 4 (40%) demonstrated partial cutaneous response and 6 (60%) demonstrated complete cutaneous resolution. Six patients (42.9%) experienced interruptions to their checkpoint inhibitor treatment as a result of intolerable ircAEs, and following ircAE management with ustekinumab, two (33.3%) were successfully rechallenged with their checkpoint inhibitors. On histopathology, patients primarily had findings of interface or psoriasiform dermatitis. No patients reported an adverse event related to ustekinumab. : Ustekinumab showed a benefit in a subset of patients with psoriasiform/lichenoid ircAEs. No safety signals were identified. However, further prospective randomized controlled trials are needed to confirm our findings.
PubMed: 38004414
DOI: 10.3390/ph16111548