Annoying Psoriasis and Atopic Dermatitis: A Narrative Review.

Skin is an important organ that mainly functions as a barrier. Skin diseases can damage a person's self-confidence and reduce their willingness to socialize, as well as their social behavior and willingness. When the skin appearance is abnormal, in addition to affecting the quality of life, it often leads to personal, social, and psychological dysfunction and even induces depression. Psoriasis and atopic dermatitis are common chronic skin diseases. Their prevalence in the world is 3-10%, and there is an increasing trend year by year. These congenital or acquired factors cause the dysfunction of the immune system and then destroy the barrier function of the skin. Because these patients are flooded with a variety of inflammatory mediators, this causes skin cells to be in chronic inflammation. Therefore, psoriasis and atopic dermatitis are also considered systemic chronic inflammatory diseases. In the healthcare systems of developed countries, it is unavoidable to spend high costs to relieve symptoms of psoriasis and atopic dermatitis patients, because psoriasis and atopic dermatitis have a great influence on individuals and society. Giving a lot of attention and developing effective treatment methods are the topics that the medical community must work on together. Therefore, we used a narrative review manuscript to discuss pathogenesis, clinical classification, incidence, and treatment options, including topical medication, systemic therapeutics, immunosuppressive medication for psoriasis, and atopic dermatitis, as well as also comparing the differences between these two diseases. We look forward to providing readers with comprehensive information on psoriasis and atopic dermatitis through this review article.

The Roles of Lipoprotein in Psoriasis.

The association between psoriasis and cardiovascular disease risk has been supported by recent epidemiological data. Patients with psoriasis have an increased adjusted relative risk for myocardial infarction. As such, the cardiovascular risk conferred by severe psoriasis may be comparable to what is seen with other well-established risk factors, such as diabetes mellitus. Previous studies demonstrated that low-density lipoprotein (LDL) plays critical roles during atherogenesis. It may be caused by the accumulation of macrophages and lipoprotein in the vessel wall. Oxidized LDL (ox-LDL) stimulates the expression of adhesion molecules, such as ICAM-1 and VCAM-1, on endothelial cells and increases the attachment of mononuclear cells and the endothelium. Even though previous evidence demonstrated that psoriasis patients have tortuous and dilated blood vessels in the dermis, which results in the leakage of ox-LDL, the leaked ox-LDL may increase the expression of adhesion molecules and cytokines, and disturb the static balance of osmosis. Therefore, exploration of the relationship between hyperlipidemia and psoriasis may be another novel treatment option for psoriasis and may represent the most promising strategy.

A dipeptidyl peptidase-4 inhibitor promotes wound healing in normoglycemic mice by modulating keratinocyte activity.

Dipeptidyl peptidase-4 (DPP-4) inhibitors are a well-known and novel class of oral antihyperglycaemic drugs. DPP-4 inhibition facilitates ulcer healing in patients with diabetes. However, the actual mechanisms, which are independent of lower blood glucose levels, are still unknown. Therefore, the aim of this study was to analyse the effect of the DPP-4 inhibitor sitagliptin on wound healing through a glucose-independent pathway. In this study, DPP-4 inhibitors facilitate keratinocyte differentiation and the proliferation, increase blood flow in the cutaneous of wounds in healthy C57BL/6 mice. Additionally, the administration of the DPP-4 inhibitor ameliorates wound healing and enhances adiponectin expression in healthy C57BL/6 mice. Taken together, our results reveal a protective role for the DPP-4 inhibitor sitagliptin in wound healing by regulating adiponectin and phospho-eNOS levels in keratinocytes. Based on these results, the DPP-4 inhibitor may have therapeutic potential for healing wounds through a diabetes-independent mechanism.

Oxidized Low-Density Lipoprotein-Deteriorated Psoriasis Is Associated with the Upregulation of Lox-1 Receptor and Il-23 Expression In Vivo and In Vitro.

Psoriasis is a chronic inflammatory skin disease. Even though scientists predict that abnormalities in lipid metabolism play an important role in the pathogenesis of psoriasis, the actual underlying mechanisms are still unclear. Therefore, understanding the possible relationship between mechanisms of the occurrence of psoriasis and dyslipidemia is an important issue that may lead to the development of effective therapies. Under this principle, we investigated the influences of hyperlipidemia in imiquimod (IMQ)-induced psoriasis-like B6.129S2-Apoetm1Unc/J mice and oxidized low-density lipoprotein (oxLDL) in tumor necrosis factor (TNF)-α-stimulated Hacat cells. In our study, we showed that a high-cholesterol diet aggravated psoriasis-like phenomena in IMQ-treated B6.129S2-Apoetm1Unc/J mice. In vitro analysis showed that oxLDL increased keratinocyte migration and lectin-type oxLDL receptor 1 (LOX-1) expression. Evidence suggested that interleukin (IL)-23 was a main cytokine in the pathogenesis of psoriasis. High-cholesterol diet aggravated IL-23 expression in IMQ-treated B6.129S2-Apoetm1Unc/J mice, and oxLDL induced IL-23 expression mediated by LOX-1 in TNF-α-stimulated Hacat cells. Therefore, it will be interesting to investigate the factors for the oxLDL induction of LOX-1 in psoriasis. LOX-1 receptor expression may be another novel treatment option for psoriasis and might represent the most promising strategy.

Methotrexate-induced epidermal necrosis: A case series of 24 patients.

BACKGROUND: Methotrexate-induced epidermal necrosis (MEN) is a rare but life-threatening cutaneous reaction that mimics Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). OBJECTIVES: To investigate the clinicopathology, risk factors, and prognostic factors of MEN. METHODS: We enrolled 24 patients with MEN and 150 controls and analyzed the demographics, pathology, and plasma concentrations of methotrexate (MTX). RESULTS: Patients with MEN showed extensive skin necrosis (mean, 33.2% total body surface area) but no target lesions. The histopathology displayed keratinocyte dystrophy. Early signs of MEN included painful skin erosions, oral ulcers, and leukopenia/thrombocytopenia. Although 79.2% patients received leucovorin treatment, there was 16.7% mortality. Risk factors for MEN included older age (>60 years), chronic kidney disease, and high initial dosage of MTX without folic acid supplementation. Renal insufficiency delayed MTX clearance. Severe renal disease and leukopenia predicted poor prognosis in MEN, but none of the SCORe of Toxic Epidermal Necrosis criteria were associated with mortality of MEN. LIMITATIONS: The study was limited by the small sample size. CONCLUSION: MEN exhibited distinct clinicopathologic features from SJS/TEN. Recognition of the early signs and prognostic factors is important, because the rapid institution of leucovorin may be helpful. To reduce the risk of MEN, physicians should avoid prescribing MTX to high-risk patients and titrate the dosage slowly upward with folic acid supplementation.

Psoriasis is associated with an increased risk of parkinsonism: a population-based 5-year follow-up study.

BACKGROUND: Few studies have examined the association between autoimmune diseases and parkinsonism. OBJECTIVE: We sought to investigate the risk for parkinsonism during a 5-year follow-up period after a diagnosis of psoriasis using a population-based data set in Taiwan. METHODS: We identified 4885 patients with psoriasis for the study cohort and randomly selected 24,425 patients as a control cohort. Each subject was individually followed up for a 5-year period to identify those who subsequently developed parkinsonism. RESULTS: Stratified Cox proportional hazards regression showed that the adjusted hazard ratio for parkinsonism during the 5-year follow-up period for patients with psoriasis was 1.74 (95% confidence interval 1.35-2.20) that of control patients. Furthermore, the adjusted hazard ratios for parkinsonism within the 5-year follow-up period after the index date for subjects with psoriasis were similar between both sexes (1.78 and 1.66 for men and women, respectively). LIMITATION: Our data set did not provide detailed information on the severity of psoriasis, or individual factors such as cigarette smoking, alcohol consumption, body mass index, and dietary patterns. CONCLUSION: Patients with psoriasis were found to be at a significant risk of parkinsonism during a 5-year follow-up.

Hesperetin, a Selective Phosphodiesterase 4 Inhibitor, Effectively Suppresses Ovalbumin-Induced Airway Hyperresponsiveness without Influencing Xylazine/Ketamine-Induced Anesthesia.

Hesperetin, a selective phosphodiesterase (PDE)4 inhibitor, is present in the traditional Chinese medicine, "Chen Pi." Therefore, we were interested in investigating its effects on ovalbumin- (OVA-) induced airway hyperresponsiveness, and clarifying its rationale for ameliorating asthma and chronic obstructive pulmonary disease (COPD). Hesperetin was revealed to have a therapeutic (PDE4(H)/PDE4(L)) ratio of >11. Hesperetin (10 ~ 30 µmol/kg, intraperitoneally (i.p.)) dose-dependently and significantly attenuated the airway hyperresponsiveness induced by methacholine. It also significantly suppressed the increases in total inflammatory cells, macrophages, lymphocytes, neutrophils, and eosinophils, and levels of cytokines, including interleukin (IL)-2, IL-4, IL-5, interferon-γ, and tumor necrosis factor-α in bronchoalveolar lavage fluid (BALF). It dose-dependently and significantly suppressed total and OVA-specific immunoglobulin E levels in the BALF and serum. However, hesperetin did not influence xylazine/ketamine-induced anesthesia, suggesting that hesperetin has few or no emetic effects. In conclusion, the rationales for ameliorating allergic asthma and COPD by hesperetin are anti-inflammation, immunoregulation, and bronchodilation.

Hesperidin-3'-o-methylether is more potent than hesperidin in phosphodiesterase inhibition and suppression of ovalbumin-induced airway hyperresponsiveness.

Hesperidin is present in the traditional Chinese medicine, "Chen Pi," and recently was reported to have anti-inflammatory effects. Therefore, we were interested in comparing the effects of hesperidin and hesperidin-3'-O-methylether on phosphodiesterase inhibition and airway hyperresponsiveness (AHR) in a murine model of asthma. In the present results, hesperidin-3'-O-methylether, but not hesperidin, at 30 µmol/kg (p.o.) significantly attenuated the enhanced pause (P(enh)) value, suppressed the increases in numbers of total inflammatory cells, macrophages, lymphocytes, neutrophils, and eosinophils, suppressed total and OVA-specific immunoglobulin (Ig)E levels in the serum and BALF, and enhanced the level of total IgG(2a) in the serum of sensitized and challenged mice, suggesting that hesperidin-3'-O-methylether is more potent than hesperidin in suppression of AHR and immunoregulation. The different potency between them may be due to their aglycons, because these two flavanone glycosides should be hydrolyzed by ß-glucosidase after oral administration. Neither influenced xylazine/ketamine-induced anesthesia, suggesting that they may have few or no adverse effects, such as nausea, vomiting, and gastric hypersecretion. In conclusion, hesperidin-3'-O-methylether is more potent in phosphodiesterase inhibition and suppression of AHR and has higher therapeutic (PDE4(H)/PDE4(L)) ratio than hesperidin. Thus, hesperidin-3'-O-methylether may have more potential for use in treating allergic asthma and chronic obstructive pulmonary disease.

Hesperetin-7,3'-O-dimethylether selectively inhibits phosphodiesterase 4 and effectively suppresses ovalbumin-induced airway hyperresponsiveness with a high therapeutic ratio.

BACKGROUND: Hesperetin was reported to selectively inhibit phosphodiesterase 4 (PDE4). While hesperetin-7,3'-O-dimethylether (HDME) is a synthetic liposoluble hesperetin. Therefore, we were interested in investigating its selectivity on PDE4 and binding ability on high-affinity rolipram-binding sites (HARBs) in vitro, and its effects on ovalbumin-induced airway hyperresponsiveness in vivo, and clarifying its potential for treating asthma and chronic obstructive pulmonary disease (COPD). METHODS: PDE1~5 activities were measured using a two-step procedure. The binding of HDME on high-affinity rolipram-binding sites was determined by replacing 2 nM [3H]-rolipram. AHR was assessed using the FlexiVent system and barometric plethysmography. Inflammatory cells were counted using a hemocytometer. Cytokines were determined using mouse T helper (Th)1/Th2 cytokine CBA kits, and total immunoglobulin (Ig)E or IgG2a levels were done using ELISA method. Xylazine (10 mg/kg)/ketamine (70 mg/kg)-induced anesthesia was performed. RESULTS: HDME revealed selective phosphodiesterase 4 (PDE4) inhibition with a therapeutic (PDE4H/PDE4L) ratio of 35.5 in vitro. In vivo, HDME (3~30 µmol/kg, orally (p.o.)) dose-dependently and significantly attenuated the airway resistance (RL) and increased lung dynamic compliance (Cdyn), and decreased enhanced pause (Penh) values induced by methacholine in sensitized and challenged mice. It also significantly suppressed the increases in the numbers of total inflammatory cells, macrophages, lymphocytes, neutrophils, and eosinophils, and levels of cytokines, including interleukin (IL)-2, IL-4, IL-5, interferon-γ, and tumor necrosis factor-α in bronchoalveolar lavage fluid (BALF) of these mice. In addition, HDME (3~30 µmol/kg, p.o.) dose-dependently and significantly suppressed total and ovalbumin-specific immunoglobulin (Ig)E levels in the BALF and serum, and enhanced IgG2a level in the serum of these mice. CONCLUSIONS: HDME exerted anti-inflammatory effects, including suppression of AHR, and reduced expressions of inflammatory cells and cytokines in this murine model, which appears to be suitable for studying the effects of drugs on atypical asthma and COPD, and for screening those on typical asthma. However, HDME did not influnce xylazine/ketamine-induced anesthesia. Thus HDME may have the potential for use in treating typical and atypical asthma, and COPD.

Risk of herpes zoster among patients with chronic obstructive pulmonary disease: a population-based study.

Background Systemic inflammation and dysregulated immune function in chronic obstructive pulmonary disease (COPD) is hypothesized to predispose patients to development of herpes zoster. However, the risk of herpes zoster among patients with COPD is undocumented. We therefore aimed to investigate the risk of herpes zoster among patients with COPD. Methods We conducted a cohort study using data from the Taiwan Longitudinal Health Insurance Database. We performed Cox regressions to compare the hazard ratio (HR) of herpes zoster in the COPD cohort and in an age- and sex-matched comparison cohort. We divided the patients with COPD into three groups according to use of steroid medications and performed a further analysis to examine the risk of herpes zoster. Results The study included 8486 patients with COPD and 33 944 matched control patients. After adjustment for potential confounding factors, patients with COPD were more likely to have incidents of herpes zoster (adjusted HR 1.68, 95% confidence interval [CI] 1.45-1.95). When compared with the comparison cohort, the adjusted HR of herpes zoster was 1.67 (95% CI 1.43-1.96) for patients with COPD not taking steroid medications. The adjusted HR of herpes zoster was slightly greater for patients with COPD using inhaled corticosteroids only (adjusted HR 2.09, 95% CI 1.38-3.16) and was greatest for patients with COPD using oral steroids (adjusted HR 3.00, 95% CI 2.40-3.75). Interpretation Patients with COPD were at increased risk of herpes zoster relative to the general population. The relative risk of herpes zoster was greatest for patients with COPD using oral steroids.

Increased risk of acute myocardial infarction in patients with psoriasis: a 5-year population-based study in Taiwan.

BACKGROUND: No previous study has investigated the incidence or risk of acute myocardial infarction (AMI) developing after the diagnosis of psoriasis in Asian populations. OBJECTIVE: We sought to evaluate the association between psoriasis and subsequent AMI during a 5-year follow-up period, using a nationwide Taiwanese population-based claims database, and taking clinical and demographic characteristics into consideration. METHODS: Our study cohort consisted of all patients with a first recorded diagnosis of psoriasis (N = 4752) between 1999 and 2001 and of patients without a diagnosis of psoriasis (N = 23,760) who were matched by age and sex (1:5) to the patients with psoriasis. Each patient was tracked using hospitalization data from 2001 until the end of 2006. Stratified Cox proportional hazard regressions (stratified by age and sex) were performed as a means of computing the 5-year AMI-free survivals after adjusting for possible confounding factors. RESULTS: Of the total sample, 70 patients (0.2%) had AMIs during the 5-year follow-up period: 22 (0.5% of the patients with psoriasis) from the study cohort and 48 (0.2%) from the comparison cohort. After adjusting for other factors, the hazard of AMI during the 5-year follow-up period was 2.10 times greater (95% confidence interval 1.27-3.43, P = .004) for patients with psoriasis than for comparison patients. LIMITATIONS: We could not take into account some known risk factors for AMI, such as smoking and body mass index. CONCLUSIONS: Psoriasis may confer an independent risk of AMI in Asian populations. We suggest that patients with psoriasis be made aware of the increased risk of AMI.

Cutaneous reactive angiomatosis associated with cholesterol embolism.

Cholesterol embolism (CE) is characterized by emboli containing cholesterol crystal in the arterioles, most commonly found in the skin and the kidney. The skin presentations of CE include livedo reticularis, blue toe syndrome, ulceration and gangrene. Cutaneous reactive angiomatosis (CRA) is a recently proposed term to describe a group of reactive vascular proliferation in skin caused by various diseases. Its occurrence in association with CE is extremely uncommon. An 82-year-old man with a history of cerebral infarction and on long-term warfarin therapy developed progressive, multiple violaceous papules and nodules on the dorsal feet, soles and toes, simulating Kaposi's sarcoma. Skin biopsy showed marked vascular endothelial cell proliferations characteristic of CRA affecting the full thickness of dermis. In addition, cholesterol crystal emboli were found in dermal arterioles. The skin lesions improved after the warfarin dose was reduced. We emphasize the possible presence of CE in a patient presented with CRA, especially in those with a pre-existing atherosclerotic disease, on anticoagulation therapy, or having a prior history of invasive vascular procedure.

Lycopene Inhibit IMQ-Induced Psoriasis-Like Inflammation by Inhibiting ICAM-1 Production in Mice.

Lycopene is the most abundant carotenoid in tomatoes, which has been identified to have the properties of anti-inflammation in addition to the capability to inhibit the expression of adhesion molecules. Intercellular adhesion molecules play a critical role in the pathogenesis of psoriasis. Here, we report that the topical use of a lycopene decreased imiquimod (IMQ)-induced psoriasis-like inflammatory responses, the progress of which was based on adhesion molecules. In vitro analysis showed that lycopene decreased keratinocyte and monocyte adhesion. Evidence suggests that intercellular adhesion molecule-1 (ICAM-1) is a main mediator of psoriasis pathogenesis. Therefore, it will be interesting to investigate the factors that contribute to the lycopene-mediated inhibition of ICAM-1 expression in psoriasis. We expect that lycopene will with potential value in the treatment of psoriasis.

Clear cell fibrous papule: report of a case mimicking a balloon cell nevus.

Clear cell fibrous papule (FP) is a rare variant of FP. We report a 39-year-old female patient who presented with a dome-shaped papule on the nose. The diagnosis of clear cell FP was made based on histological and immunohistochemical studies. Interestingly, scattered S-100 cells were admixed within the lesion, a finding hitherto not reported. The S-100 positivity may be misleading and should be cautiously interpreted.

Atypical angioma serpiginosum.

Angioma serpiginosum is an uncommon, acquired vascular nevoid disorder with capillary dilation and proliferation in the papillary dermis. The eruptions are asymptomatic and characterized by grouped, erythematous to violaceous, serpiginous and punctate macules. The condition usually appears in females during adolescence on unilateral lower extremities and the buttocks. We report a rare case with a late onset and atypical distribution of lesions in a 48-year-old female patient who had groups of punctate lesions on her left foot for four to five years. Histopathological examination showed hyperkeratosis and multiple dilated and proliferated capillaries in the papillary dermis. Inflammation and extravasation of red blood cells were not found. According to the clinical and pathological findings, we established a diagnosis of angioma serpiginosum. She was treated with a pulsed dye laser, and the angiomatous lesions subsequently improved.

Disseminated cutaneous Mycobacterium kansasii infection presenting with Rosai-Dorfman disease-like histological features in a patient carrying anti-interferon-γ autoantibodies.

Typical cutaneous non-tuberculous mycobacteria (NTM) infections show a histopathology pattern of granulomas with admixed Langhans giant cells, and abscesses may be observed in acute lesions. Herein, we describe a patient carrying a high titer of autoantibodies to interferon (IFN)-γ with disseminated Mycobacterium kansasii infection presenting with emperipolesis and Rosai-Dorfman disease (RDD)-like histopathological features characterized by remarkable, large, pale-staining "RD cells", which were CD68 and S100 positive and CD1a negative. The patient was misdiagnosed with RDD initially, but exhibited a poor response to all interventions. A re-biopsy revealed Langhans-type multinucleated giant cells; multiple definite acid-fast bacilli were also found. M. kansasii was isolated from cultured tissues. Anti-NTM treatment was initiated. After treatment, all lesions resolved almost completely within the following month. High-titer anti-IFN-γ autoantibodies were detected during follow up, leading to the diagnosis of adult-onset immunodeficiency syndrome. In conclusion, patients carrying high-titer autoantibodies to IFN-γ who also have a disseminated cutaneous M. kansasii infection may present with RDD-like histopathological features, which may be a pitfall in the diagnosis of disseminated cutaneous NTM infections.