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Mediators of Inflammation 2022Itch is one of the major clinical manifestations of psoriasis, which is closely related with neurogenic inflammation and difficult to control. Colquhounia Root (CR) is a...
Itch is one of the major clinical manifestations of psoriasis, which is closely related with neurogenic inflammation and difficult to control. Colquhounia Root (CR) is a Chinese herb exhibiting broad bioactivities on anti-inflammation. This study was designed to explore the antipsoriatic and anti-itch potential of CR and its underlying mechanisms. Mice in a model of imiquimod-induced psoriasiform dermatitis were treated topically with CR for 7 days, and the severity of skin lesions and itch was significantly ameliorated. CR reduced the inflammatory cell infiltration, as well as mast cells in skins. Particularly, the expression of inflammatory cytokines and chemokine including , , and and itch-related molecules such as , , and in lesions were decreased in diseased mice upon application with CR. The normal human epidermal keratinocytes were stimulated with the M5 cytokine cocktail, the mixture of IL-17A, IL-22, Oncostatin M, IL-1, and TNF-, and cell viability and mRNA expression levels of inflammatory factors and itch-related molecules were measured after being treated with CR. We found that CR inhibited both cell hyperproliferation and overexpression of inflammatory cytokines and itch-related molecules . Altogether, we conclude that CR relieves psoriatic lesions and itch via controlling immunological and neurogenic inflammation.
Topics: Animals; Disease Models, Animal; Eczema; Imiquimod; Inflammation; Mice; Psoriasis; Skin
PubMed: 35069008
DOI: 10.1155/2022/5782922 -
JID Innovations : Skin Science From... Dec 2021Dimethyl fumarate (DMF) is an effective oral treatment for psoriasis administered in Europe for nearly 60 years. However, its potential has been limited by contact...
Dimethyl fumarate (DMF) is an effective oral treatment for psoriasis administered in Europe for nearly 60 years. However, its potential has been limited by contact dermatitis that prohibits topical application. This paper characterizes a DMF derivative, isosorbide DMF (IDMF), which was designed to have antipsoriatic effects without skin-sensitizing properties. We show that IDMF exhibits neither genotoxicity nor radiation sensitivity in skin fibroblasts and is nonirritating and nonsensitizing in animal models (rat, rabbit, guinea pig). Microarray analysis of cytokine-stimulated keratinocytes showed that IDMF represses the expression of genes specifically upregulated in psoriatic skin lesions but not those of other skin diseases. IDMF also downregulated genes induced by IL-17A and TNF in keratinocytes as well as predicted targets of NF-κB and the antidifferentiation noncoding RNA (i.e., ). IDMF further stimulated the transcription of oxidative stress response genes (, , ) with stronger NRF2/ARE activation compared to DMF. Finally, IDMF reduced erythema and scaling while repressing the expression of immune response genes in psoriasiform lesions elicited by topical application of imiquimod in mice. These data show that IDMF exhibits antipsoriatic activity that is similar or improved compared with that exhibited by DMF, without the harsh skin-sensitizing effects that have prevented topical delivery of the parent molecule.
PubMed: 34909741
DOI: 10.1016/j.xjidi.2021.100040 -
Cureus Nov 2021Lichen planus is a chronic papulosquamous eruption of the skin, scalp, nails, and mucous membranes. "Pruritic, purple, polygonal, planar, papules, plaques" are the...
Lichen planus is a chronic papulosquamous eruption of the skin, scalp, nails, and mucous membranes. "Pruritic, purple, polygonal, planar, papules, plaques" are the traditional six "P's" of lichen planus. We describe an unusual case of lichen planus presenting as cellulitis. A 64-year-old lady with a past medical history of pyoderma gangrenosum, inclusion body myositis, and chronic kidney disease presented with a two-week history of swelling, erythema, tenderness, hyperkeratotic plaques, and blisters on the medial aspect of both thighs. She had a previous history of pyoderma gangrenosum exacerbations with similar presentations; however, current lesions were different from prior presentations. We considered the differential diagnoses of bacterial cellulitis versus pyoderma gangrenosum exacerbation. Due to the difference in these lesions from previous episodes, the patient was empirically treated for bacterial cellulitis with intravenous cefepime and linezolid. The infectious diseases team was consulted and valacyclovir was added to cover for possible herpes infection, with no improvement in symptomatology. Dermatology was then consulted, and a clinical diagnosis of psoriasiform dermatitis was made. A skin biopsy was obtained and the patient was started on prednisone. There was an immediate improvement in the papules within 24 hours. The papules cleared, leaving behind violaceous flat plaques, clinically diagnosed as lichen planus. The affected area was shrinking as compared to previous examinations. The skin biopsy was reported as chronic psoriasiform dermatitis with the main differential of lichen planus. The patient was discharged home on a tapering dose of oral prednisone, topical clobetasol, and oral moxifloxacin. This case demonstrates the importance of familiarity with rare clinical subtypes as a suspicion for lichen planus. The vesiculobullous subtype of lichen planus, as seen in this patient, tends to present as blisters and cellulitis from infection of the bullae. Treatment of the infection alone is not enough and steroids are essential. This knowledge helps change management, allows for earlier improvement and better patient outcomes.
PubMed: 34900481
DOI: 10.7759/cureus.19304 -
Frontiers in Nutrition 2021Psoriasis is a common chronic recurrent dermatitis. Accumulating observations show gut microbiota dysbiosis in psoriasis. We intend to further investigate the...
Psoriasis is a common chronic recurrent dermatitis. Accumulating observations show gut microbiota dysbiosis in psoriasis. We intend to further investigate the relationship between intestinal microbiota and psoriasis development. We first performed an epidemiological investigation on differences of gastrointestinal discomfort symptoms between patients with psoriasis and general population. Then variation of gut microbiota in patients with psoriasis (un)treated with acitretin plus narrow-band ultraviolet B (NB-UVB) was analyzed by 16S rRNA sequencing. We last compared recovery status and vital cytokines (lesion and intestine) of mouse psoriasiform models, which were transplanted with fecal microbiota from patients with psoriasis or healthy controls. (1) About 85.5% of patients with psoriasis vs. 58.1% of healthy controls presented with at least one gastrointestinal symptom. The prevalence of investigated symptoms (e.g., abdominal distension and constipation) were significantly higher in patients, compared with controls ( < 0.05). Passing flatus and constipation were significantly correlated with psoriasis ( < 0.05 in both cases). (2) The abundance of Ruminococcaceae family, genus, and genus were decreased with psoriasis improvement ( < 0.05, respectively), which had been demonstrated significantly increased in psoriasis. (3) Mice receiving psoriatic microbes transplantation showed delayed recovery of psoriasiform dermatitis and less reduction of interleukin (IL)-17A than those receiving healthy microbiota or blank control ( < 0.05 and < 0.01, respectively). Multiple evidence we provided here preliminarily demonstrates the involvement of gut microbiota in the different degree of psoriasis activity. The strategy based on overall microbial communities is expected to be a promising supplementary for long-term management of psoriasis.
PubMed: 34881280
DOI: 10.3389/fnut.2021.761978 -
Journal Der Deutschen Dermatologischen... Nov 2021Given the increasing use of novel targeted therapies, dermatologists are constantly confronted with novel cutaneous side effects of these agents. A rapid diagnosis and...
Given the increasing use of novel targeted therapies, dermatologists are constantly confronted with novel cutaneous side effects of these agents. A rapid diagnosis and appropriate management of these side effects are crucial to prevent impairment of the patients' quality of life and interruptions of essential cancer treatments. Immune checkpoint and EGFR inhibitors are frequently used targeted therapies for various malignancies and are associated with a distinct spectrum of cutaneous adverse events. Exanthematous drug eruptions represent a particular diagnostic challenge in these patients. Immune checkpoint inhibitors can elicit a plethora of immune-related exanthemas, most commonly maculopapular, lichenoid, and psoriasiform eruptions. Additionally, autoimmune bullous dermatoses and exanthemas associated with connective tissue diseases may arise. In cases of severe, atypical or therapy-resistant presentations an extensive dermatological investigation including a skin biopsy is recommended. Topical and systemic steroids are the mainstay of treatment. Papulopustular eruptions represent the major cutaneous adverse effect of EGFR inhibitor therapy, occurring in up to 90 % of patients within the first two weeks of therapy, depending on the agent. Besides topical antibiotics and steroids, oral tetracyclines are the first choice in systemic treatment and can also be used as prophylaxis.
Topics: Drug Eruptions; ErbB Receptors; Humans; Immunotherapy; Neoplasms; Quality of Life
PubMed: 34811916
DOI: 10.1111/ddg.14641 -
The Journal of Investigative Dermatology May 2022Bile acids (BAs), produced in the liver and further transformed in the gut, are cholesterol-derived molecules involved in essential physiological processes. Recent...
Bile acids (BAs), produced in the liver and further transformed in the gut, are cholesterol-derived molecules involved in essential physiological processes. Recent studies suggest that BAs regulate T helper 17 cell function, but the underlying mechanism of this action and their therapeutic value in disease models remains unclear. Using an IL-23 minicircle DNA-based murine model of psoriasiform dermatitis, we showed that oral administration of secondary BAs, including lithocholic acid (LCA), deoxycholic acid, and 3-oxoLCA, significantly improved psoriasiform dermatitis without inducing apparent hepatotoxicity. Of the BAs tested, LCA possessed the greatest potency in treating psoriasiform dermatitis. Intravenous administration of LCA at a much lower dosage (compared with oral treatment) showed a comparable antipsoriatic effect and markedly suppressed the IL-17A response. Ex vivo experiments revealed that LCA reduced IL-17A production in IL-23-stimulated murine T cells in the absence of BA receptors TGR5 or FXR. Strikingly, BAs inhibited CCL20 expression in keratinocytes, which led to reduced migration of CCR6-expressing Jurkat cells cultured in the conditioned medium of stimulated keratinocytes. Thus, BAs improve psoriasiform dermatitis with minimal toxicity via direct inhibition of IL-17A production and blockade of CCL20-mediated trafficking, supporting the potential use of BAs in psoriasis.
Topics: Animals; Bile Acids and Salts; Chemokine CCL20; Eczema; Humans; Interleukin-17; Interleukin-23; Mice; Psoriasis; Receptors, CCR6
PubMed: 34808237
DOI: 10.1016/j.jid.2021.10.027 -
Therapeutic Advances in Gastroenterology 2021Skin eruptions are prevalent among patients with inflammatory bowel diseases (IBD), often associated with therapies and frequently leading to dermatological consults and...
BACKGROUND AND AIMS
Skin eruptions are prevalent among patients with inflammatory bowel diseases (IBD), often associated with therapies and frequently leading to dermatological consults and treatment interruptions. We aimed to assess the impact of joint shared decision-making in a multidisciplinary (MDT) IBD-DERMA clinic.
METHODS
This retrospective cohort study assessed a consecutive group of patients with IBD who were referred for consultation in an MDT clinic at a tertiary referral center in Israel.
RESULTS
Over 1 year, 118 patients were evaluated in the MDT-IBD-DERMA clinic: 68 (57.6%) males; age - 35.2 ± 13.5 years, disease duration - 7.1 (interquartile range: 3.7-13.9) years; Crohn's disease - 94/118 (79.6%). Skin eruption induced by an anti-tumor necrosis factor (TNF) were the most common diagnoses [46/118 (39%)], including psoriasiform dermatitis (PD) - 31/46 (67.4%) and inflammatory alopecia (IA) - 15/46 (32.6%). Of these, 18 patients (39.1%) continued the anti-TNF agent concomitantly with a topical or systemic anti-inflammatory agent to control the eruption. The remaining 28 patients (60.9%) discontinued the anti-TNF, of whom 16/28 (57.1%) switched to ustekinumab. These strategies effectively treated the majority [38/46 (82.6%)] of patients. Continuation of the anti-TNF was possible in a significantly higher proportion of patients with PD: 12/31 (38.7%) than only one in the IA group, = 0.035. There was a higher switch to ustekinumab among the IA 7/15 (46.6%) compared with the PD 7/31 (22.6%) group, = .09. Following IBD-DERMA advised intervention, IBD deteriorated in 9/4 6(19.5%) patients, 5/9 on ustekinumab (PD IA, = NS).
CONCLUSION
Shared decision-making in an integrated IBD-DERMA clinic allowed successful control of skin eruptions while preserving control of the underlying IBD in more than 80% of cases. Patients with IA profited from a switch to ustekinumab.
PubMed: 34777576
DOI: 10.1177/17562848211053112 -
Archive of Clinical Cases 2019Psoriasiform dermatoses represent a wide spectrum of inflammatory conditions, with several major forms represented by psoriasis, as the prototype of this category,... (Review)
Review
Psoriasiform dermatoses represent a wide spectrum of inflammatory conditions, with several major forms represented by psoriasis, as the prototype of this category, followed by pustular psoriasis, Reiter's syndrome, pityriasis rubra pilaris, lichen simplex chronicus and large-plaques parapsoriasis. They create a diagnostic challenge, both clinical and histopathological, because of their complexity and frequent overlapping of the microscopical features. The characteristic histopathological features of psoriasiform reaction comprise extensive hyperkeratosis, with horizontally confluent but vertically intermittent parakeratosis, which alternate with orthokeratosis, thin granular layer, with relative frequent mitoses, uniform elongated and fused rete ridges, edematous superficial papillary dermis, with dilated capillaries, perivascular lymphocytic infiltrate, Munro's microabscesses, and spongiform pustules of Kogoj. Our paper aims to review the histopathology of major form of psoriasiform dermatoses and to emphasize the characteristic microscopical differences between them, for a better approach of the diagnosis as an important key for clinical and therapeutical management. Using the clinicopathological correlations, a thoroughly evaluation of the microscopical features and compartments distribution or special stainings and techniques, the range of differential diagnosis can be decreased and a more accurate diagnostic can be usually achieved. The insights into the pathogenic mechanisms can lead to new therapeutic opportunities targeted to the specific type of inflammatory lesion.
PubMed: 34754910
DOI: 10.22551/2019.24.0603.10155 -
Frontiers in Immunology 2021Neuroimmunity is involved in the pathogenesis of psoriasis, but the mechanism underlying the interaction between the nervous system and the interleukin (IL)-23/IL-17...
Neuroimmunity is involved in the pathogenesis of psoriasis, but the mechanism underlying the interaction between the nervous system and the interleukin (IL)-23/IL-17 immune axis is yet unclear. This study reveals the essential role of the sensory neuron-derived calcitonin gene-related peptide (CGRP) in imiquimod (IMQ)-induced expression of IL-23. First, we show that the increased nociceptive behavior was consistent with the development of psoriasiform dermatitis, which requires intact sensory innervation. Systemic ultrapotent Transient receptor potential vanilloid 1 (TRPV1) agonist (resiniferatoxin, RTX) treatment-induced sensory denervation resulted in a significant decrease in IL-23 expression in this model, while the recombinant IL-23 treatment induced IL-17A expression was intact after RTX treatment. In addition, IMQ exposure induced a transient increase in CGRP expression in the dorsal root ganglion. The neuron-derived CGRP expression was completely abolished by sensory denervation, thereby downregulating IL-23 expression, which could be reversed through the introduction of CGRP into the denervated dorsal skin. Our results suggest that nociceptive sensory neurons may drive the production of IL-23, resulting in IL-17A production from γδ T cells the neuropeptide CGRP in the pathology of psoriasis.
Topics: Animals; Calcitonin Gene-Related Peptide; Disease Models, Animal; Interleukin-23; Male; Mice; Mice, Inbred BALB C; Neuroimmunomodulation; Nociceptors; Psoriasis; Receptors, Antigen, T-Cell, gamma-delta
PubMed: 34745116
DOI: 10.3389/fimmu.2021.743675 -
Cell Death & Disease Oct 2021Psoriasis is a common, chronic, and recurrent inflammatory disease. It is characterized by hyperproliferation and abnormal differentiation of keratinocytes. Keratinocyte...
Psoriasis is a common, chronic, and recurrent inflammatory disease. It is characterized by hyperproliferation and abnormal differentiation of keratinocytes. Keratinocyte death is also involved in many pathophysiological conditions and amplifies the inflammatory cascade. As a newly recognized form of cell death, ferroptosis is involved in several inflammatory diseases. In this study, we aimed to investigate a previously unrecognized role for ferroptosis in psoriasis. Ferroptosis is mediated by lipid peroxidation and iron overload. Compared with normal lesions, the mRNA expression of acyl-CoA synthetase long-chain family member 4 (ACSL4), prostaglandin-endoperoxide synthase 2 (PTGS2), and transferrin receptor (TFRC) were highly expressed in psoriatic lesions, with decreased levels of glutathione peroxidase 4 (GPX4), ferritin light chain (FTL), and ferritin heavy chain 1 (FTH1). The protein levels of ACSL4 and GPX4 were consistent with their mRNA levels. A similar tendency of ferroptosis was also observed in erastin-treated human primary keratinocytes and the Imiquimod (IMQ)-induced model of psoriasis. To investigate the correlation between inflammation and peroxidation, we analyzed single-cell RNA-sequencing data and identified 15 cell types. There was a high correlation between the activity of the lipid oxidation and the Th22/Th17 response in keratinocytes at a single-cell level. Moreover, ferrostatin-1 (Fer-1), a potent inhibitor of lipid peroxidation, suppressed ferroptosis-related changes in erastin-treated keratinocytes and alleviated psoriasiform dermatitis of IMQ-induced models. Additionally, Fer-1 blocked inflammatory responses in vitro and in vivo, reducing the production of cytokines including TNF-α, IL-6, IL-1α, IL-1β, IL-17, IL-22, and IL-23. This study revealed an expression pattern of ferroptosis in which specific molecules enhance inflammatory reactions in psoriasis.
Topics: Animals; Case-Control Studies; Ferroptosis; Humans; Inflammation; Keratinocytes; Mice; Psoriasis
PubMed: 34707088
DOI: 10.1038/s41419-021-04284-5