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Cureus Aug 2022Immune checkpoint inhibitors (ICIs), a class of anticancer agents that upregulate T-cell response to tumor cells, are associated with immune-related adverse events...
Immune checkpoint inhibitors (ICIs), a class of anticancer agents that upregulate T-cell response to tumor cells, are associated with immune-related adverse events (irAEs), and the skin is one of the most commonly affected organs. We report the first two cases of a unique ICI-induced clinicopathological entity. A psoriasiform-appearing eruption with psoriasiform, spongiotic, and lichenoid dermatitis pattern on histopathology. A 73-year-old male with stage IV melanoma treated with nivolumab and a 63-year-old female with stage IV colorectal cancer treated with pembrolizumab and TAK-981 separately presented to our clinic with a psoriasiform rash. In both patients, punch biopsy revealed an unusual combination of psoriasiform, spongiotic, and lichenoid dermatitis. Treatment with apremilast in the first patient yielded some improvement, while treatment with ixekizumab in the second patient yielded a complete resolution of the eruption. Our cases add to the growing body of reported immune toxicities related to ICI use and illustrate the utility of targeted immune suppression of pathways in disease phenotype to allow for ICI continuation and optimization of cancer treatment.
PubMed: 36134105
DOI: 10.7759/cureus.28010 -
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 -
The Journal of Dermatology Oct 2023Phospholipase D2 (PLD2), a major isoform of the PLD family, has been reported to regulate inflammatory responses. Thus far, the relevance of PLD2 in psoriasis, an...
Phospholipase D2 (PLD2), a major isoform of the PLD family, has been reported to regulate inflammatory responses. Thus far, the relevance of PLD2 in psoriasis, an inflammatory skin disease, has not been explored. In the current study, we examined PLD2 expression in the skin of psoriasis patients and the role of PLD2 in an interleukin (IL)-23-induced mouse model of psoriasiform dermatitis. Both in situ hybridization and bulk RNA sequencing showed PLD2 gene expression is significantly higher in lesional relative to non-lesional skin of psoriasis patients or the skin of healthy subjects. PLD2 expression is also enriched in residual lesions from patients on biologic therapies. Murine in vivo studies showed that PLD2 deficiency significantly reduced psoriasiform inflammation in IL-23-injected ears, as reflected by decreases in ear thickness, expression of defensin beta 4A and the S100 calcium binding protein A7A, macrophage infiltrate, and expression of CXCL10 and IL-6. However, the expression of type 17 cytokines, IL-17A and IL-17F, were not reduced. Dual knockout of PLD1 and PLD2 offered little additional protection compared to PLD2 knockout alone in the IL-23 model. In addition, pharmacological inhibition with a pan-PLD1/PLD2 inhibitor also suppressed IL-23-induced psoriasiform dermatitis. Bone-marrow-derived macrophages from wild type (WT) and PLD2 knockout (KO) mice exhibited little difference in viability and sensitivity to lipopolysaccharide and/or interferon gamma, or resiquimod (R848). PLD2 deficiency did not alter the differentiation and function of Th17 cells in an ex vivo study with splenocytes isolated from WT and PLD2 KO mice. Overall, these data suggest that PLD2 may play a role in the pathophysiology of psoriasis. Reducing macrophage infiltrate and cytokine/chemokine production might contribute to an anti-inflammatory effect observed in PLD2 knockout mice. Further studies are required to better understand the mechanisms by which PLD2 contributes to skin lesions in psoriasis patients and psoriasiform dermatitis models.
PubMed: 37455419
DOI: 10.1111/1346-8138.16899 -
Journal of Dermatological Science May 2021The involvement of the nerve in psoriasis development was suggested by sporadic case reports.
BACKGROUND
The involvement of the nerve in psoriasis development was suggested by sporadic case reports.
OBJECTIVES
To provide multiple evidence for the nerve in psoriasis development with a retrospective case review, a literature review and a mouse-based experimental experiment.
METHODS
Psoriatic patients who had concomitant nerve injuries and such cases from literatures were reviewed. And, on wild-type mouse level, unilateral denervation surgery was performed on the dorsal skin before and after the induction of psoriasiform dermatitis, respectively. Lesion visual scores were calculated, and biopsies were taken for hematoxylin-eosin (HE) staining, immunofluorescence analysis, and RNA sequencing & bioinformatics analysis before denervation surgery and the 2, 4, 6, 8 day after the surgery.
RESULTS
All clinical cases (20/20) showed that local lesions under the control of injured nerves relieved spontaneously or even cleared/spared, and only about 1/3 experienced partial recurrence. Next, mouse psoriasiform experiments demonstrated that unilateral denervation prior to imiquimod application attenuated the enhancement of inflammatory reactions (e.g. adaptive immune response and Th17 cell differentiation pathway) and the induction of ipsilateral psoriasiform dermatitis. On the other hand, unilateral denervation after psoriasiform dermatitis induction promoted the regression of inflammatory reactions (e.g. T cell activation, TNF signaling, and Th17 cell differentiation pathway) and ipsilateral dermatitis recovery.
CONCLUSION
Our study based on both retrospective clinical case review and wild-type mouse experiments provides multiple evidence for the involvement of the nerve in psoriasis development. Regulation of immune events, including TNF signaling and Th17 cell differentiation, may be the mechanisms of the nerve in psoriasis.
Topics: Adult; Aged; Aged, 80 and over; Animals; Denervation; Disease Models, Animal; Female; Gene Expression Regulation; Humans; Imiquimod; Male; Mice; Middle Aged; Neuroimmunomodulation; Peripheral Nerve Injuries; Psoriasis; Retrospective Studies; Skin
PubMed: 33676787
DOI: 10.1016/j.jdermsci.2021.02.006 -
Lasers in Surgery and Medicine Aug 2021Technological advances in medicine have brought about many novel skin imaging devices. This review aims to evaluate the scientific evidence supporting the use of... (Review)
Review
BACKGROUND AND OBJECTIVES
Technological advances in medicine have brought about many novel skin imaging devices. This review aims to evaluate the scientific evidence supporting the use of noninvasive optical imaging techniques to aid in the diagnosis and prognosis of inflammatory skin diseases.
STUDY DESIGN/MATERIALS AND METHODS
PubMed and Scopus were searched in September 2020 according to PRISMA guidelines for articles using reflectance confocal microscopy (RCM), optical coherence tomography (OCT), and multiphoton microscopy (MPM) in inflammatory skin diseases, excluding studies monitoring treatment efficacy.
RESULTS
At the time of the study, there were 66 articles that addressed the utilization of noninvasive imaging in interface, spongiotic, psoriasiform, vesiculobullous, and fibrosing/sclerosing inflammatory skin dermatoses: RCM was utilized in 46, OCT in 16, and MPM in 5 articles. RCM was most investigated in psoriasiform dermatoses, whereas OCT and MPM were both most investigated in spongiotic dermatoses, including atopic dermatitis and allergic contact dermatitis.
CONCLUSIONS
There is preliminary evidence to support the diagnostic potential of noninvasive optical imaging techniques in inflammatory skin diseases. Improvements in the devices and further correlation with histology will help broaden their utility. Additional studies are needed to determine the parameters for diagnostic features, disease differentiation, and staging of inflammatory skin conditions. Lasers Surg. Med. © 2021 Wiley Periodicals LLC.
Topics: Dermatitis, Atopic; Humans; Microscopy, Confocal; Skin; Skin Diseases; Tomography, Optical Coherence
PubMed: 33527483
DOI: 10.1002/lsm.23386 -
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 -
Biomaterials Science Jan 2023Psoriasis is a refractory and difficult-to-treat skin disorder. The neutrophil-targeting approach represents a promising option for psoriasis therapy. This study...
Psoriasis is a refractory and difficult-to-treat skin disorder. The neutrophil-targeting approach represents a promising option for psoriasis therapy. This study developed and examined NIMP-R14-conjugated immunonanoparticles for specific targeting to neutrophils associated with psoriasiform dermatitis. In the process, roflumilast (RFL), as a phosphodiesterase (PDE) 4 inhibitor, was encapsulated in the nanocarriers to assess the anti-inflammatory capability against primary neutrophil activation and murine psoriasiform lesion. The average size and surface charge of the immunonanocarriers were 305 ± 36 nm and -18 ± 6 mV, respectively. The monovalent antibody-conjugated nanoparticles offered precise uptake by both human and mouse neutrophils but failed to exhibit this effect in monocytes and lymphocytes. The intracellular RFL concentration of the immunonanocarriers was five-fold superior to that of the passive counterparts. The immunonanocarriers specifically recognized the neutrophils through the Ly6 antigen with no apparent cytotoxicity. The antibody-conjugated nanoparticles mitigated superoxide anion production and migration of the activated human neutrophils. The biodistribution in the psoriasiform mice, found using an imaging system (IVIS) and liquid chromatography (LC)-mass-mass analysis, showed that the antibody conjugation increased the nanoparticle residence in systemic circulation after intravenous administration. On the other hand, most of the nanoparticles were accumulated in the lesional skin after subcutaneous injection. The actively-targeted nanocarriers were better than the free RFL and unfunctionalized nanoparticles in suppressing psoriasiform inflammation. The immunonanocarriers reduced neutrophil recruitment and epidermal hyperplasia in the plaque. Intravenous and subcutaneous treatments with the immunonanocarriers significantly reduced the overexpressed cytokines and chemokines in the inflamed skin, demonstrating that the nanosystems could both systematically and locally alleviate inflammation. The results indicated that the NIMP-R14-conjugated RFL-loaded nanoparticles have potential as an anti-autoimmune disease delivery system for neutrophil targeting.
Topics: Animals; Humans; Mice; Anti-Inflammatory Agents; Dermatitis; Disease Models, Animal; Inflammation; Neutrophils; Psoriasis; Tissue Distribution; Antigens, Ly
PubMed: 36515218
DOI: 10.1039/d2bm01521h -
International Journal of Molecular... May 2024Psoriasis is a systemic autoimmune/autoinflammatory disease that can be well studied in established mouse models. Skin-resident macrophages are classified into epidermal... (Review)
Review
Psoriasis is a systemic autoimmune/autoinflammatory disease that can be well studied in established mouse models. Skin-resident macrophages are classified into epidermal Langerhans cells and dermal macrophages and are involved in innate immunity, orchestration of adaptive immunity, and maintenance of tissue homeostasis due to their ability to constantly shift their phenotype and adapt to the current microenvironment. Consequently, both macrophage populations play dual roles in psoriasis. In some circumstances, pro-inflammatory activated macrophages and Langerhans cells trigger psoriatic inflammation, while in other cases their anti-inflammatory stimulation results in amelioration of the disease. These features make macrophages interesting candidates for modern therapeutic strategies. Owing to the significant progress in knowledge, our review article summarizes current achievements and indicates future research directions to better understand the function of macrophages in psoriasis.
Topics: Psoriasis; Animals; Macrophages; Disease Models, Animal; Mice; Humans; Langerhans Cells; Immunity, Innate; Skin
PubMed: 38791342
DOI: 10.3390/ijms25105306 -
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 -
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