Psoriasiform Dermatitis Research Articles

Electrophilic nitro-fatty acids suppress psoriasiform dermatitis through the inhibition of STAT3

Abstract Psoriasis is a systemic, immune-mediated disorder, characterized by chronic inflammatory skin and joint manifestations. Electrophilic nitro-fatty acids (NO2-FAs) have been reported to exert potent anti-inflammatory effects in several in vivo murine models of inflammatory diseases, such as chronic kidney disease and cardiovascular disease. To study the therapeutic potential of NO2-FAs on psoriasis, we employed both acute and chronic murine experimental models of psoriasis. Our studies demonstrate that oral treatments of nitro-oleic acid (OA-NO2), prior to imiquimod (IMQ) or rIL-23 treatments, significantly inhibited the induction of psoriasis-like inflammation and inflammatory cytokine production in the skin. Moreover, utilizing transgenic murine models of psoriasis, we determined that OA-NO2 had both a preventative and therapeutic effect on psoriasiform inflammation. Mechanistic in vitro experiments demonstrated that OA-NO2 decreased IL-17A-induced IL-6 expression in normal human dermal fibroblasts through the inhibition of NF-κB phosphorylation. Importantly, OA-NO2 also impaired signal transducers and activators of transcription 3 (STAT3) phosphorylation and translocation to the nucleus. Further mechanistic results indicated that OA-NO2 regulates STAT3 activation by post-translational modification of STAT3 via nitroalkylation. Overall, our results confirm the critical role of STAT3 in psoriasiform dermatitis and highlight the potential of NO2-FAs as therapeutic agents for the treatment of cutaneous inflammatory diseases, such as psoriasis.

Differential Requirement for CCR6 in IL-23–Mediated Skin and Joint Inflammation

CCR6 is important for the trafficking of IL-17A-producing γδ T cells and required for the development of psoriasiform dermatitis in an IL-23 intradermal injection model. The role of CCR6, however, in IL-23-mediated joint inflammation is unclear. We herein hydrodynamically delivered IL-23 minicircle DNA into wild-type and CCR6-deficient (CCR6-knockout) mice to induce overexpression of IL-23 systemically. After IL-23 gene transfer, wild-type mice exhibited concurrent skin and joint changes that recapitulate some features found in human psoriatic skin and joints. CCR6-knockout mice were resistant to IL-23-induced skin inflammation but exhibited no changes in joint inflammation compared with wild-type mice. Depletion of neutrophils protected wild-type mice from skin and joint disease without suppressing T helper type 17 cytokine expression. In contrast, mice lacking γδ T cells showed a partial reduction in neutrophilic recruitment and a significant decrease in IL-17A expression in skin and paw tissue. Thus, in an IL-23-mediated model that allows concurrent assessment of both skin and joint disease, we showed that CCR6 is critical for inflammation in the skin but not in the joint. Furthermore, our data suggest that neutrophils and γδ T cells are key effector cells in IL-23-mediated skin and joint inflammation in mice.

A toxic palmitoylation of Cdc42 enhances NF-κB signaling and drives a severe autoinflammatory syndrome

CDC42 gene mutations arise in large clinical spectra. The de novo R186C variant results in Cdc42 palmitoylation, retention in the Golgi apparatus, and NF-κB hyperactivation, leading to a severe psoriasiform dermatitis, hematological abnormalities and autoinflammation.

Clinicomorphological correlation of psoriasis and psoriasiform dermatitis

Introduction: Psoriasis is a chronic inflammatory skin disorder. Psoriasiform dermatitis on other hand is a frequently encountered terminology in a variety of inflammatory dermatoses. It often poses challenges to both dermatologists and pathologists alike. Clinical features when considered alone may not be reliable to differentiate psoriasis from psoriasiform dermatitis. Aims: (a)To correlate the clinicomorphological features of psoriasis and psoriasiform dermatitis. (b)To identify determinants that may contribute to the diagnosis of psoriasis and psoriasiform dermatitis. Methods: This is a prospective study of 40 cases. Cases clinically diagnosed as psoriasis and psoriasiform dermatitis were screened microscopically and as per morphological criterias 20 cases from each entity were selected and included in the study. Detailed histopathological analysis and correlation was done. Results: The clinical features of typical scales (p= 0.0012) and Auspitz's sign (p = 0.058) morphological evidence of regular acanthosis (p= 0.0005), absent granular layer (p = 0.0001) and presence of micromunros abscess (p=0.0001) were found to be statistically highly significant contributors to the diagnosis of psoriasis in comparison to psoriasiform hyperplasia. Other morphological features like suprapapillary thinning (p= 0.051) was also found to be morphologically significant. Vertical orientation of collagen bundles (p = 0.002) was found to be significantly associated with diagnosis of psoriasiform hyperplasia when compared to psoriasis. Conclusion: The present study reconfirms the diagnostic accuracy of scales, Auspitz’s sign as clinically reliable signs of psoriasis. However, in their absence, morphological presence of regular acanthosis, absent granular layer and Munro microabscess may contribute to the diagnosis of psoriasis. Similarly, vertical orientation of collagen bundles points toward a diagnosis of psoriasiform dermatitis. This may help clinicians not to miss the diagnosis of clinically insignificant psoriasis in order to start early treatment and prevent the poor prognosis in these patients.

Short-Term Exposure to a Western Diet Induces Psoriasiform Dermatitis by Promoting Accumulation of IL-17A–Producing γδ T Cells

A Western diet (WD)-characterized by its high fat and simple sugar content-is thought to predispose individuals to inflammatory skin diseases such as psoriasis through the development of obesity. This scenario, however, is being challenged by emerging data suggesting that dietary components, rather than obesity itself, may exacerbate psoriasis. We herein show that short-term feeding with a diet analogous to the WD in mice leads to T helper type 1-/T helper type 17-biased skin inflammation before significant body weight gain. Feeding for as little as 4 weeks with a WD promoted mild dermatitis and accumulation of IL-17A-producing γδ T cells in the skin. Strikingly, γδ T cells from WD-fed mice exhibited enriched IL-23 receptor expression and increased the potential to produce IL-17A after IL-23 stimulation. In contrast to wild-type mice, WD-fed TCRδ-deficient and CCR6-deficient mice had reduced skin inflammation and IL-17A expression. Supplementation with a bile acid sequestrant, cholestyramine, prevented WD-induced skin inflammation along with a reduction in the infiltration of γδ T cells and the expression of proinflammatory mediators. In summary, our data revealed dietary influences in inflammatory signaling in the skin. The dysregulation of IL-23 pathways and bile acid pathways may be key to the development of WD-associated psoriasiform dermatitis.

Yaws in the Philippines: first reported cases since the 1970s

BackgroundYaws is a chronic, highly contagious skin and bone infection affecting children living in impoverished, remote communities and caused by Treponema pallidum subspecies pertenue. The Philippines was thought to be free of yaws following the 1950s eradication campaign but it has been reported in the Liguasan Marsh area, Central Mindanao. This is the first documentation of yaws cases in the Philippines since the 1970s. We describe active and latent yaws recently detected in the Southern Philippines.Case presentationCross-sectional surveys and screening of skin diseases were conducted in one randomly selected public elementary school per selected municipality in Liguasan Marsh, covering three municipalities per province. Yaws suspects underwent screening and confirmatory serologic tests for Treponema pallidum using Dual Path Platform Syphilis Screen and Confirm Assay (DPP) and Treponema pallidum Particle Agglutination (TPPA). Children with yaws skin lesions and reactive confirmatory tests for T. pallidum and non-treponemal antibodies were considered confirmed yaws cases. Four children aged 5–10 years old had confirmed secondary yaws in Tulunan Municipality, Cotabato Province and in Lambayong Municipality, Sultan Kudarat Province. All had secondary yaws lesions such as moist, cauliflower-like papillomas, thick yellow crusts on pink papules and nodules, whitish, papulosquamous papules and plaques, or hypopigmented patches with small papules on the periphery. Yaws papillomas and erosions were also found on the soles of the feet of one child. The index case had a skin punch biopsy of a partially treated papilloma on his axilla. Histopathological findings showed lichenoid psoriasiform dermatitis with plasma cells, consistent with yaws.ConclusionsThe clinical, serological, and histopathological confirmation of four yaws cases among children has made the Philippines the 14th country endemic for yaws. This report can help health personnel recognize hidden cases of yaws based on skin signs and serological tests. Yaws remained unrecognized and unreported in the Philippines and in countries previously endemic for yaws probably due to the unsustained integration of the yaws program in the general health services and complacency after the 1950s eradication campaign. Our findings have provided the necessary evidence and stimulus to develop a yaws control and eradication program as one of the country’s neglected tropical diseases.

Dupilumab-Induced Psoriasiform Dermatitis

Atopic dermatitis (AD) is a common inflammatory skin condition. The newly FDA approved biologic dupilumab has demonstrated significant improvement in the signs and symptoms of AD, including pruritus as well as those of anxiety and depression1. The most frequently reported adverse effects of dupilumab include injection site reactions, nasopharyngitis, upper respiratory infections, and conjunctivitis 1-5. We report a case of dupilumab-induced psoriasiform dermatitis. To our knowledge, there have been no reports to date of a dupilumab-induced psoriasiform dermatitis. There has been one report of an erythrodermic presentation of psoriasis in a patient treated with dupilumab8. As novel immunotherapy treatments are developed and employed in the treatment of common conditions such as AD, it is important to better understand and be aware of the potential side effects and immune-based sequelae that may arise in addition to available treatment options for these adverse reaction.

Diet-induced obesity exacerbates imiquimod-mediated psoriasiform dermatitis in anti-PD-1 antibody-treated mice: Implications for patients being treated with checkpoint inhibitors for cancer

BackgroundAn ever-increasing number of cancer patients are being treated with checkpoint inhibitors such as anti-PD-1 antibodies, and a small percentage of these patients develop a psoriasis-like skin eruption or severe flares of prior psoriasis. ObjectiveWe investigated the role of obesity in immune checkpoint inhibitors-exacerbated psoriasiform eruption. MethodsWe fed female C57BL/6 mice a so-called Western diet (WD) or a control diet (CD). Imiquimod (IMQ) was applied topically on ears for 5 consecutive days to induce psoriasiform dermatitis (PsD). Psoriasis-related markers were examined by quantitative real-time PCR. Then we induced PsD in WD- and CD-fed mice in the presence or absence of systemic treatment of anti-PD-1 antibodies to examine if obese mice are more susceptible to anti-PD-1 related PsD than lean mice. ResultsWD-fed mice showed higher baseline mRNA expression levels of psoriasis-associated cytokines such as IL-17, S100A8, and S100A9 compared to mice fed with CD. Furthermore, WD-fed mice had more γδ low (GDL) T cells in the whole skin and higher expression of PD-1 on GDL T cells than CD-fed mice. WD-fed mice receiving anti-PD-1 had more prominent ear swelling than lean mice receiving anti-PD-1 during the 5-day IMQ course (2-fold increase, P < 0.0001 on day 5). ConclusionWD-induced obesity enhances IMQ-induced psoriasiform inflammation. The finding that WD-fed mice have a more dramatic response to anti-PD-1 than lean mice in terms of IMQ-induced ear swelling suggests that obesity could be a risk factor in the development of psoriasiform eruption during anti-PD-1 therapy.

Excessive skin toxicity in a patient receiving pegylated liposomal doxorubicin, associated with Nicolau syndrome, exacerbated by morbid obesity

Pegylated liposomal doxorubicin (PLD) is an anthracycline anticancer agent used in ovarian cancer and a form of doxorubicin enclosed in pegylated liposomes. Although it causes less cardiotoxicity than doxorubicin, it is frequently associated with cutaneous toxicity, mainly palmoplantar erythrodysesthesia. Other forms of skin toxicity – such as maculopapular rash, intertrigo-like dermatitis, psoriasiform dermatitis and radiation recall dermatitis – have also been described. Nicolau syndrome is a rare complication fol­lowing the intramuscular administration of several agents, mainly injection of nonsteroidal anti-inflammatory drugs. Obesity is not only an established risk factor for developing cancer, but can also adversely influence the course of the disease in the advanced or metastatic set­ting. In this article, we present the case of a 44-year-old mor­bidly obese woman diagnosed with platinum-resistant stage IV ovarian cancer treated with pegylated liposomal do­xo­ru­bi­cin in a second-line setting. The patient developed severe skin toxicity caused by pegylated liposomal do­xo­ru­bicin, manifested by paronychia, intertrigo-like der­ma­ti­tis with ulcerations, bleeding, infection, and pso­ria­si­form dermatitis. She also presented with associated Nicolau syndrome, due to injection of antalgics into the subcutaneous fat instead of intramuscular. These skin toxicities caused further complications, such as severe anemia and acute renal failure. We hypothesize that the morbid obesity was the main contributing factor to all of these complications. With this presentation, we want to underline the importance of maintaining a healthy body weight in cancer patients.

Widespread pustular eruption following probiotic use

A 26-year-old woman with Crohn disease and palmoplantar psoriasis on ustekinumab presented with a diffuse and intensely pruritic rash with a few pin-point pustules within days after initiation of an over-the-counter Align brand probiotic. Biopsy revealed psoriasiform and spongiotic dermatitis with spongiform subcorneal pustules and scattered eosinophils, consistent with acute generalized exanthematous pustulosis. Our case highlights a unique presentation of acute generalized exanthematous pustulosis following probiotic exposure with fewer than usual pustular lesions. IL23 suppression by ustekinumab may have contributed to the patient's reduced pustular presentation.

Psoriasiform Dermatitis Related with T-Cell Immunoreceptor with Immunoglobulin and Immunoreceptor Tyrosine-Based Inhibitory Motif Domains Inhibitor in a Patient with Non-Small-Cell Lung Cancer

Psoriasiform Dermatitis Related with T-Cell Immunoreceptor with Immunoglobulin and Immunoreceptor Tyrosine-Based Inhibitory Motif Domains Inhibitor in a Patient with Non-Small-Cell Lung Cancer

A case of resistant pityriasis ribra pilaris responsive to combination acitrentin and ustekinumab

Pityriasis rubra pilaris is a rare psoriasiform dermatitis. Treatment has been adopted from psoriasis protocols, with topical corticosteroids and systemic retinoids as first-line agents, followed by escalation to biologics for recalcitrant disease. We report a patient with resistant pityriasis rubra pilaris who dramatically improved with acitretin and ustekinumab, a combination not well documented in the literature. The purpose of this letter is to emphasize the potential benefit of dual therapy in patients who fail traditional pityriasis rubra pilaris treatment regimens.

β-Hydroxybutyrate Reduces Psoriasiform Dermatitis

β-Hydroxybutyrate Reduces Psoriasiform Dermatitis

Possible Role of Lysine Demethylase 2A in the Pathophysiology of Psoriasis.

BackgroundPsoriasis is a common chronic inflammatory skin disease. The development of psoriasis is dependent on many intercellular events such as innate immunity and T cell-mediated inflammation. Furthermore, genetic factors are strongly implicated in the pathophysiology of psoriasis. Although a variety of susceptible genes are identified, it is likely that many important genes remain undisclosed.ObjectiveThe aim of this study is to investigate the possible role of lysine demethylase 2A (KDM2A) in the pathophysiology of psoriasis.MethodsWe examined the expression of KDM2A using a well established imiquimod-induced psoriasiform dermatitis model.ResultsImmunohistochemistry analysis showed that expression of KDM2A was increased in imiquimod-induced psoriasiform dermatitis. Consistent with this result, KDM2A level was markedly increased in the epidermis of psoriatic patient. When keratinocytes were stimulated with TLR3 agonist poly(I:C), KDM2A was increased at both the mRNA and protein levels. Poly(I:C) increased the expression of psoriasis-related cytokines including tumor necrosis factor-α, interleukin-8, and CCL20, and KDM2A inhibitor daminozide enhanced the poly(I:C)-induced cytokine expression. Finally, topical co-application of imiquimod and daminozide exacerbated the imiquimod-induced psoriasiform dermatitis.ConclusionTogether, these results suggest that KDM2A is increased to negatively regulate the inflammatory reaction of epidermal keratinocytes in psoriasis.

FOLLICULAR MUCINOSIS IN A PATIENT WITH PARAPSORIASIS

We present the case of a young patient, without comorbidities, who developed an erythematous-squamous, disseminated, discrete itchy rash, associated with scarring alopecia at the level of the scalp and the external third of the eyebrows, in 3-year evolution, in which two skin biopsies showed: subacute spongiotic dermatitis and psoriasiform dermatitis. As new lesions continued to appear despite treatment with phototherapy, systemic, local corticosteroids, it was decided to perform another skin biopsy: loose areas, granular appearance that color blue with Alcian Blue staining, thus supporting the diagnosis of follicular mucinosis. The treatment consisted of Acitretin 30 mg / day, with favorable evolution. Follicular mucinosis is a rare inflammatory disease, characterized by mucin deposits located in the follicular epithelium and sebaceous glands. There are two clinical forms: a primary, benign, limited to the skin, and a secondary form, commonly associated with cutaneous T-cell lymphoma. The evolution of both forms of follicular mucinosis is a chronic one, and the correct therapeutic attitude consists primarily in the periodic surveillance of the patient, with possible repeat biopsy, to exclude the form associated with a mycosis fungoides. The management of such patients is extremely difficult, as a number of conditions must be evaluated, such as: screening for collagenosis, diabetes, inflammatory bowel disease, evaluation of thyroid function, tumor markers.

Increased Expression of Interleukin-12 in Lesional Skin of Atopic Dermatitis Patients with Psoriasiform Features on Histopathology: An Immunohistochemical Study.

BackgroundBased on clinical and genetic differences, atopic dermatitis (AD) and psoriasis have been classified in two different diseases, but recently, some authors regarded them as in one spectrum. The histological similarities including epidermal hyperplasia between chronic stages of AD and psoriasis supports the presence of two diseases in one spectrum.ObjectiveWe investigated clinical and immunohistopathological characteristics of adult Korean patients with AD showing psoriasiform chronic dermatitis on histopathology.MethodsIn total, 59 Korean patients with chronic AD were enrolled. Clinical, laboratory, and histopathological features were compared between AD patients with psoriasiform features and those with non-psoriasiform chronic dermatitis features on histology. In addition, immunohistopathological characteristics were analyzed using antibodies for key regulatory and effector cytokines in psoriasis.ResultsFifteen patients (25.4%) showed a more “psoriasiform” histological appearance. The lesions in patients with psoriasiform features often showed clearer boundaries and noticeable scaling. The interleukin (IL)-23 expression in the psoriasiform chronic dermatitis group was not different from that in the psoriasis group, but the IL-17 expression was less than that in the psoriasis group. In the case of IL-12, multiple dermal inflammatory cells with dendrites were stained in the psoriasiform chronic dermatitis group compared with the 2 other non-psoriasiform subgroups.ConclusionThe results suggest that IL-12 secreted from dermal inflammatory cells might be one of the important factors associated with the formation of psoriasiform features in chronic AD. However, further studies are required to better define the specific role of IL-12.

Clinicopathologic overlap of psoriasis, eczema, and psoriasiform dermatoses: A retrospective study of T helper type 2 and 17 subsets, interleukin 36, and β-defensin 2 in spongiotic psoriasiform dermatitis, sebopsoriasis, and tumor necrosis factor α inhibitor–associated dermatitis

T helper (Th) type 17 and Th2 cells mediate psoriasis and eczema, respectively. Some dermatoses exhibit overlapping clinicopathologic features, and their immunopathology is relatively unexplored. To determine whether Th17 and Th2 subsets and interleukin (IL) 36 and β-defensin 2 (BD-2) markers of IL-17 signaling expression can discriminate between biopsy samples of psoriasis and eczematous/spongiotic dermatitis and to use those markers to immunophenotype cases with clinicopathologic overlap. A retrospective study was performed on biopsy samples of psoriasis, eczema/spongiotic dermatitis, sebopsoriasis, tumor necrosis factor α inhibitor-associated psoriasiform dermatitis, and ambiguous cases diagnosed as spongiotic psoriasiform dermatitis. Dual CD4/GATA3 and CD4/RORC, IL-36, and BD-2 immunohistochemistry was performed. IL-36 and BD-2 were strongly expressed in biopsy samples of psoriasis compared with eczema/spongiotic dermatitis. No significant differences were observed in the percentages of Th2 and Th17cells between disease types. Strong expression of IL-36 and BD-2 was observed in a subset of spongiotic psoriasiform dermatitis, sebopsoriasis, and tumor necrosis factor α inhibitor-associated psoriasiform dermatitis biopsy samples. This was an exploratory study with a small sample size. No multiple testing adjustment was done. Clinical follow-up was limited. In cases with clinicopathologic overlap between psoriasis and spongiotic dermatitis, IL-36, and to a lesser extent BD-2, may be used to assess for a psoriasis-like/IL-17 phenotype, which could inform therapeutic clinical decisions.

Systemic Psoriasiform Dermatitis Appeared after the Administration of Pembrolizumab.

Systemic Psoriasiform Dermatitis Appeared after the Administration of Pembrolizumab.

IL-23 induces regulatory T cell plasticity with implications for inflammatory skin diseases

Foxp3+ regulatory T cells (Tregs) represent a major fraction of skin resident T cells. Although normally protective, Tregs have been shown to produce pro-inflammatory cytokines in human diseases, including psoriasis. A significant hurdle in the Treg field has been the identification, or development, of model systems to study this Treg plasticity. To overcome this gap, we analyzed skin resident Tregs in a mouse model of IL-23 mediated psoriasiform dermatitis. Our results demonstrate that IL-23 drove the accumulation of Tregs; including a subpopulation that co-expressed RORγt and produced IL-17A. Genesis of this population was attenuated by a RORγt inverse agonist compound and clinically relevant therapeutics. In vitro, IL-23 drove the generation of CD4+Foxp3+RORγt+IL-17A+ cells from Treg cells. Collectively, our data shows that IL-23 drives Treg plasticity by inducing a population of CD4+Foxp3+RORγt+IL-17A+ cells that could play a role in the disease pathogenesis. Through this work, we define an in vitro system and a pre-clinical in vivo mouse model that can be used to further study Treg homeostasis and plasticity in the context of psoriasis.

Calcipotriol and betamethasone dipropionate exhibit different immunomodulatory effects on imiquimod-induced murine psoriasiform dermatitis.

Psoriasis is a T-helper (Th)1/Th17-mediated, chronic inflammatory dermatitis that is commonly treated with topical corticosteroids and vitamin D3 analogs. The combination of a topical corticosteroid and vitamin D3 analog showed superior efficacy to each alone in clinical trials; however, the mechanisms by which the topical corticosteroid and vitamin D3 analog exert their effects on lesional skin in combination and each alone remain unknown. In this study, we examined the effects of combined calcipotriol (Cal)/betamethasone dipropionate (BD) ointment on psoriasis in vivo, utilizing imiquimod (IMQ)-induced murine psoriasiform skin inflammation, compared with each alone. Vehicle, Cal/BD, Cal or BD was applied on the shaved back skin for 3 consecutive days. Then, IMQ was applied for 6 consecutive days. Twenty-four hours after the last IMQ treatment, the murine skin was evaluated clinically and pathologically. mRNA expressions were examined by quantitative polymerase chain reaction. All ointments alleviated IMQ-induced psoriasiform skin inflammation clinically in comparison with vehicle application. Cal/BD suppressed mRNA expressions of cytokines involved in psoriasis pathogenesis such as interleukin (IL)-17A and IL-22 efficiently. Cal alone induced IL-10 expression, whereas BD alone reduced IL-6 mRNA expression and the number of phosphorylated signal transducer and activator of transcription 3-positive cells in lesional skin. Our study revealed that Cal and BD have different effects on IMQ-induced psoriasiform skin. Some of the immune effects of Cal and BD may be additive or synergistic, which may account for the superior clinical efficacy of their combination.