-
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 -
Clinical, Cosmetic and Investigational... 2023Epidermal keratinocytes with an abnormal glucose metabolism have been identified in psoriasis. Hexokinase 2 (HK2) is a crucial enzyme involved in glycolytic metabolic...
PURPOSE
Epidermal keratinocytes with an abnormal glucose metabolism have been identified in psoriasis. Hexokinase 2 (HK2) is a crucial enzyme involved in glycolytic metabolic pathways. However, the expression of HK2 and its potential therapeutic effects in psoriasis remains unclear. This study aimed to investigate the expression pattern of HK2 and evaluate its therapeutic effects in psoriasis.
PATIENTS AND METHODS
A gene expression dataset (GSE121212) downloaded from the Gene Expression Omnibus (GEO) database was used to examine the expression of HK2 in psoriasis. HK2 RNA and protein expression were investigated in psoriasis vulgaris (n=5) and healthy (n=5) samples. Immunohistochemistry for HK2 was performed on psoriasis vulgaris (n=22) and healthy skin (n=10) samples. Additionally, HaCaT cells were treated with M5 (interleukin [IL]-17A, tumor necrosis factor-α, IL-1α, IL-22, and Oncostatin-M) to induce a psoriatic inflammation cell model. A mouse model of psoriatic inflammation was established using topical 5% imiquimod cream. Psoriasis-like cells and mouse models were treated with the HK2 inhibitor 3-bromopyruvate (3-BrPA). Cell proliferation, glucose consumption, and lactate production were assessed. Furthermore, the activation of nuclear factor-kappa B (NF-Kb) and NOD-like receptor thermal protein domain associated protein 3 (NLRP3) was investigated using Western blot analysis.
RESULTS
According to the GEO dataset, HK2 expression was significantly elevated in psoriasis. Upregulation of HK2 in psoriatic tissues was confirmed by quantitative real-time polymerase chain reaction and Western blotting. The immunohistochemistry score for HK2 was higher in psoriatic lesions than in healthy skin. 3-BrPA inhibited the proliferation and glycolysis of M5-stimulated HaCaT cells. Topical 3-BrPA ameliorated imiquimod-induced psoriasis-like dermatitis. Activation of NF-kB and NLRP3 was downregulated by 3-BrPA treatment.
CONCLUSION
Our study revealed that the glycolytic enzyme HK2 was upregulated in psoriasis and that the HK2 inhibitor 3-BrPA exhibited therapeutic effects in psoriasis cell and mouse models.
PubMed: 37965102
DOI: 10.2147/CCID.S435624 -
Dermatitis : Contact, Atopic,... Nov 2023
PubMed: 37934278
DOI: 10.1089/derm.2023.0208 -
Journal of Taibah University Medical... Feb 2024Psoriasis is an uncontrolled, long-lasting inflammatory dermatosis distinguished by thickened, erythematous, and flaky skin lesions. Massive amounts of inflammatory...
UNLABELLED
Psoriasis is an uncontrolled, long-lasting inflammatory dermatosis distinguished by thickened, erythematous, and flaky skin lesions. Massive amounts of inflammatory cytokines are produced when immune system imbalances are driven by genetic and environmental triggers. Vinpocetine (VNP), a man-made analogue of the compound vincamine found in the dwarf periwinkle herb, has robust anti-inflammatory, immunomodulatory, and anti-oxidative effects; alleviates the epidermal penetration of immune cells, such as eosinophils and neutrophils; and abolishes the generation of pro-inflammatory molecules.
OBJECTIVE
This study was aimed at exploring the effects of long-term topical VNP, both alone and co-administered with clobetasol propionate, in an imiquimod-induced mouse model of psoriasiform dermatitis.
METHODS
The study protocol consisted of 48 Swiss albino mice, randomly divided into six groups of eight mice each. In group I, petroleum jelly was administered daily for 8 days. In group II, imiquimod was administered topically at 62.5 mg daily for 8 days. In groups III, VI, V, and VI, 0.05% clobetasol propionate, 1% VNP, 3% VNP, and 3% VNP plus 0.05% clobetasol were administered topically for an additional 8 days after the induction, thus resulting in a total trial length of 16 days.
RESULTS
Topical VNP at various doses alleviated the severity of imiquimod-induced psoriatic lesions-including erythema, silvery-white scaling, and thickening-and reversed the histopathological abnormalities. Moreover, imiquimod-exposed animals treated with VNP showed markedly diminished concentrations of inflammatory biomarkers, including tumour necrosis factor-α, interleukin (IL)-8, IL-17A, IL-23, IL-37, nuclear factor-kappa B (NF-κB), and transforming growth factor-β1.
CONCLUSION
This research provides new evidence that VNP, alone and in combination with clobetasol, may serve as a potential adjuvant for long-term management of autoimmune and autoinflammatory skin diseases, particularly psoriasis, by attenuating psoriatic lesion severity, suppressing cytokine generation, and limiting NF-κB-mediated inflammation.
PubMed: 37868105
DOI: 10.1016/j.jtumed.2023.09.002 -
The Journal of Investigative Dermatology Apr 2024Psoriasis is characterized by excessive keratinocyte proliferation and immunocyte infiltration, but the underlying pathogenesis remains unclear. Aminoacyl-tRNA...
Psoriasis is characterized by excessive keratinocyte proliferation and immunocyte infiltration, but the underlying pathogenesis remains unclear. Aminoacyl-tRNA synthetases are universally expressed enzymes that catalyze the first step of protein synthesis. Glycyl-tRNA synthetase (GARS) is a member of the aminoacyl-tRNA synthetase family. In addition to its canonical function, we found that GARS was overexpressed in the serum and skin lesions of patients with psoriasis. Moreover, GARS was highly expressed in human skin keratinocytes, and GARS knockdown in keratinocytes suppressed cell proliferation and promoted apoptosis through NF-κB/MAPK signaling pathway. Moreover, intradermal injection of recombinant GARS protein caused skin thickening, angiogenesis, and IFN/TNF-driven skin inflammation. Intriguingly, the reported functional receptor for GARS, cadherin 6 (CDH6), was specifically expressed in vascular endothelial cells, and we found that keratinocyte-derived GARS promotes inflammation and angiogenesis of vascular endothelial cells through CDH6. In addition, intradermal injection of GARS aggravated the phenotype and angiogenesis in imiquimod-induced psoriasiform dermatitis models, whereas the psoriatic phenotype and angiogenesis were relieved after knockdown of GARS by adeno-associated virus. Taken together, the results of this study identify the critical role of GARS in the pathogenesis of psoriasis and suggest that blocking GARS may be a therapeutic approach for alleviating psoriasis.
Topics: Humans; Angiogenesis; Dermatitis; Endothelial Cells; Glycine-tRNA Ligase; Inflammation; Keratinocytes; Psoriasis; Skin
PubMed: 37827278
DOI: 10.1016/j.jid.2023.09.270 -
Australian Journal of General Practice Oct 2023It is important to be able to manage patients regardless of ethnicities. The understanding of skin diseases, including atopic dermatitis, in patients with skin of colour...
BACKGROUND
It is important to be able to manage patients regardless of ethnicities. The understanding of skin diseases, including atopic dermatitis, in patients with skin of colour (SOC) is lagging compared with that in patients with lighter skin and has been identified as an educational gap among medical practitioners.
OBJECTIVE
This paper synthesises the latest literature on the diagnosis, assessment, treatment outcomes and cultural considerations for managing atopic dermatitis in children with SOC in the general practice setting.
DISCUSSION
Atopic dermatitis in children with SOC can vary from traditional descriptions and appear psoriasiform, lichenoid, scaly, papular, hypopigmented or violaceous. It can be misdiagnosed and its severity underestimated. Complications from atopic dermatitis, as well as the treatments provided, might result in inadequate treatment unless the treating doctor is aware of specific nuances in children with SOC.
Topics: Humans; Child; Dermatitis, Atopic; Skin Pigmentation; Skin; Treatment Outcome; Psoriasis
PubMed: 37788687
DOI: 10.31128/AJGP-01-23-6684 -
Di-(2-ethylhexyl) phthalate aggravates psoriasis-like skin lesions: In vitro and in vivo evaluation.Toxicology and Applied Pharmacology Nov 2023Di-(2-ethylhexyl) phthalate (DEHP), which is a widely used phthalate (PAE), has recently received public attention owing to it causing health problems. The aim of this...
Di-(2-ethylhexyl) phthalate (DEHP), which is a widely used phthalate (PAE), has recently received public attention owing to it causing health problems. The aim of this study was to elucidate the aggravating effects of DEHP on psoriasis and skin toxicity. Human keratinocyte (HaCaT) cells were treated with gradient concentrations of DEHP, and mice with imiquimod (IMQ)-induced psoriasiform dermatitis were hypodermically injected with 40 μg/kg/day of DEHP for seven consecutive days. The skin condition was assessed based on the psoriasis area and severity index score, which indicated the deterioration of IMQ-induced psoriasis-like skin lesions after DEHP exposure. To further analyze the effect of DEHP on psoriasis, the proliferation, inflammation, and tight junction (TJ) damage were examined, which correlated with the development and severity of psoriasis. The results showed that DEHP promoted proliferation both in vivo and in vitro, which manifested as epidermal thickening; an increase in cell viability; upregulation of Ki67, CDK2, cyclinD1, and proliferating cell nuclear antigen; and downregulation of p21. An excessive inflammatory response is an important factor that exacerbates psoriasis, and our results showed that DEHP can trigger the release of inflammatory cytokines as well as the infiltration of T cells. TJ disorders were found in mice and cells after DEHP treatment. Additionally, p38 mitogen-activated protein kinase (MAPK) was strongly activated during this process, which may have contributed to skin toxicity caused by DEHP. In conclusion, DEHP treatment promotes proliferation, inflammation, TJ disruption, and p38 MAPK activation in HaCaT cells and psoriasis-like skin lesions.
Topics: Mice; Animals; Humans; Diethylhexyl Phthalate; Psoriasis; Skin Diseases; Imiquimod; Inflammation; p38 Mitogen-Activated Protein Kinases; Skin
PubMed: 37783235
DOI: 10.1016/j.taap.2023.116707 -
World Journal of Clinical Cases Sep 2023Atopic dermatitis and asthma are two diseases whose pathogenesis is largely attributable to the activation, at least in the initial stages, of T helper (Th)-2...
BACKGROUND
Atopic dermatitis and asthma are two diseases whose pathogenesis is largely attributable to the activation, at least in the initial stages, of T helper (Th)-2 Lymphocytes, the related cytokine axis, and B lymphocytes with antibody production. Psoriasis is conversely a pathology resulting from a recruitment of Th-17 and Th-1 lymphocytes, after an initial role of innate immunity. Mepolizumab is a humanized monoclonal antibody directed against interleukin (IL)-5, a central cytokine in the Th-2 axis, therefore involved in the pathogenesis of asthma. Several authors have described the appearance of psoriatic lesions in patients with asthma or atopic dermatitis following the therapy with dupilumab, a monoclonal antibody that blocks the interleukin (IL)-4, another Th-2 cytokine.
CASE SUMMARY
We present the case of a 59-year-old patient who developed psoriasiform lesions on the palms after mepolizumab therapy for asthma, for the activation of the parallel cytokine cascade after the blockade of IL-5. We successfully treated the patient with a topical calcipotriol and betamethasone ointment.
CONCLUSION
We should investigate with further attention the possible impact on the human immunological ecosystem put in place by the inhibition of the activity of individual inflammatory mediators, so as to be able to recognize the initial adverse effects early.
PubMed: 37731552
DOI: 10.12998/wjcc.v11.i26.6154 -
The Journal of Dermatological Treatment Dec 2023Although psoriasis and atopic dermatitis (AD) were for decades considered to be opposing diseases, it is now known that these skin conditions can coexist or even...
Although psoriasis and atopic dermatitis (AD) were for decades considered to be opposing diseases, it is now known that these skin conditions can coexist or even overlap in the same individual. Especially when using modern drugs with targeted IL inhibition, the balance between Th1 and Th2 immunity can be disturbed. In line with it, numerous clinical cases of AD have been induced by antipsoriatic biologics (e.g., TNF-alpha, IL-23, or IL-17 inhibitors), and IL-4-/IL-13 inhibition by dupilumab also resulted in paradoxical psoriasis in patients with AD. Herein, we describe a case of psoriasis vulgaris in a patient with intrinsic AD after systemic treatment with the anti-IL-13 antibody tralokinumab. We present a 36-years-old male patient with a severe course of an intrinsic atopic dermatitis and dyshidrotic hand eczema. He responded well to the therapy with tralokinumab. However, about 7 months after the start of anti-IL-13 treatment the patient developed psoriasiform lesions. The drug was then discontinued. Currently, the patient is receiving topical therapy with topical corticosteroids and calcineurin inhibitors with stable course of psoriasis and AD. This case suggests, that not only a dual IL-4-/IL-13-blockade, but also a selective IL-13-inhibition is able to skew immune responses toward IL-17 cytokine pathway-related disease. However, no clinical scores exist to predict the development of paradoxical psoriasis in patients with AD during therapy with biologics.
Topics: Humans; Male; Adult; Interleukin-17; Dermatitis, Atopic; Interleukin-4; Psoriasis; Interleukin-13; Biological Products
PubMed: 37705378
DOI: 10.1080/09546634.2023.2258240