Generalized pustular psoriasis (GPP) is a rare disease characterized by recurrent fever and systemic flushing accompanied by extensive sterile pustules. The committee of the guidelines was founded as a collaborative project between the Japanese Dermatological Association and the Study Group for Rare Intractable Skin Diseases under the Ministry of Health, Labour, and Welfare Research Project on Overcoming Intractable Diseases. The aim of the guidelines was to provide current information to aid in the treatment of patients with GPP in Japan. Its contents include the diagnostic and severity classification criteria for GPP, its pathogenesis, and recommendations for the treatment of GPP. Since there are few clinical trial data with high levels of evidence for this rare disease, recommendations by the committee are described in the present guidelines.

Background Atopic dermatitis (AD) is a common inflammatory skin disease exhibiting a predominantly Th2/“T22” immune activation and a defective epidermal barrier. Narrow-band UVB (NB-UVB) is considered an efficient treatment for moderate-to-severe AD. In psoriasis, NB-UVB has been found to suppress the Th1/Th17-polarization with subsequent reversal of epidermal hyperplasia. The immunomodulatory effects of this treatment are largely unknown in AD. Objective To evaluate the effects of NB-UVB on immune and barrier abnormalities in AD, aiming to establish reversibility of disease and biomarkers of therapeutic response. Methods 12 moderate-to-severe chronic AD patients received NB-UVB phototherapy 3 times weekly for up to 12 weeks. Lesional and non-lesional skin biopsies were obtained before and after treatment and evaluated by gene-expression and immunohistochemistry studies. Results All patients had at least a 50% reduction in SCORing of AD (SCORAD) index with NB-UVB phototherapy. The Th2, “T22,” and Th1 immune pathways were suppressed and measures of epidermal hyperplasia and differentiation normalized. The reversal of disease activity was associated with elimination of inflammatory leukocytes, Th2/“T22”- associated cytokines and chemokines, and normalized expression of barrier proteins. Conclusions Our study shows that resolution of clinical disease in patients with chronic AD is accompanied by reversal of both the epidermal defects and the underlying immune activation. We have defined a set of biomarkers of disease response that associate resolved Th2 and “T22” inflammation in chronic AD patients with reversal of barrier pathology. By showing reversal of the AD epidermal phenotype with a broad immune-targeted therapy, our data argues against a fixed genetic phenotype.

IL-22 is a cytokine that acts mainly on epithelial cells. In the skin, it mediates keratinocyte proliferation and epidermal hyperplasia and is thought to play a central role in inflammatory diseases with marked epidermal acanthosis, such as psoriasis. Although IL-22 was initially considered a Th17 cytokine, increasing evidence suggests that T helper cells can produce IL-22 even without IL-17 expression. In addition, we have shown the existence of this unique IL-22-producing T cell in normal skin and in the skin of psoriasis and atopic dermatitis patients. In the present study, we investigated the ability of cutaneous resident dendritic cells (

Objective-C-reactive protein (CRP), a predictor of cardiovascular events, localizes in atherosclerotic arteries and exerts proinflammatory effects on vascular cells. Reactive oxygen species (ROS) have been implicated in atherogenesis and plaque instability. Methods and Results-Expressional pattern of CRP in directional coronary atherectomy specimens from 39 patients was examined. Characteristics of histological plaque instability and higher levels of serum CRP and fibrinogen were associated with the CRP immunoreactivity. In situ hybridization revealed the presence of CRP mRNA in coronary vasculature. Furthermore, the expression of CRP mRNA and protein was detected in cultured human coronary artery smooth muscle cells (CASMCs) by reverse transcriptase-polymerase chain reaction and Western blotting. In addition, CRP was frequently colocalized with p22 phox , an essential component of NADH/NADPH oxidase, which is an important source of ROS in vasculature. Moreover, the incubation of cultured CASMCs with CRP resulted in the enhanced p22 phox protein expression and in the generation of intracellular ROS. Conclusions-The expression of CRP in coronary arteries was associated with histological and clinical features of vulnerable plaque, and it had a prooxidative effect on cultured CASMCs, suggesting that it might play a crucial role in plaque instability and in the pathogenesis of acute coronary syndrome via its prooxidative effect. Key Words: C-reactive protein Ⅲ inflammation Ⅲ oxidative stress Ⅲ free radicals Ⅲ coronary artery diseases A therosclerosis is a chronic inflammatory disease. This concept is supported by recent findings where systemic inflammatory markers such as C-reactive protein (CRP) and fibrinogen are regarded as strong predictors of cardiovascular complications in various clinical settings. [1][2][3] Fibrinogen, a key coagulation factor, is considered to contribute atherogenesis by promoting platelet aggregation, fibrin formation, and plasma viscosity. 4 However, the role of CRP in the pathogenesis of atherosclerotic vascular diseases remains unknown. Recent histological investigations have demonstrated that CRP is present in the human arterial intima at atherosclerotic lesions and is frequently colocalized with the terminal complement complex. 5 Moreover, in vitro studies have shown that the stimulation of human endothelial cells with CRP induces the expression of adhesion molecules and monocyte chemoattractant protein-1 (MCP-1). 6,7 These data suggest that CRP might have direct proinflammatory effects on vascular cells which might, in part, explain the involvement of inflammation in atherogenesis.Reactive oxygen species (ROS) have been implicated in the pathogenesis of a variety of vascular diseases, including atherosclerosis. To date, many types of cells in vasculature have been shown to generate ROS. There are various potential sources that generate ROS in vascular cells: the mitochondrial electron transport chain, cyclooxygenase, lipoxygenase, xanthine oxidase, and NADH/NADPH oxidase. 8,9 Recent ...

Objective-NADH/NADPH oxidase is an important source of reactive oxygen species (ROS) in the vasculature. Recently, we demonstrated that p22 phox , an essential component of this oxidase, was expressed in human coronary arteries and that its expression was enhanced with the progression of atherosclerosis. The present study was undertaken to investigate its functional importance in the pathogenesis of coronary artery disease. For this aim, the expression of p22 phox , the distribution of oxidized low density lipoprotein (LDL), and the generation of ROS in directional coronary atherectomy (DCA) specimens were examined. Methods and Results-DCA specimens were obtained from patients with stable or unstable angina pectoris. The distribution of p22 phox and of oxidized LDL was examined by immunohistochemistry. The generation of superoxide in DCA specimens was assessed by the dihydroethidium method and lucigenin-enhanced chemiluminescence. ROS were closely associated with the distribution of p22 phox and oxidized LDL. Not only inflammatory cells but also smooth muscle cells and fibroblasts generated ROS. There was a correlation between ROS and the expression of p22 phox or oxidized LDL. The generation of ROS was significantly higher in unstable angina pectoris compared with stable angina pectoris. Conclusions-ROS generated by p22phox -based NADH/NADPH oxidase likely mediate the oxidative modification of LDL and might play a major role in pathogenesis of atherosclerotic coronary artery disease. (Arterioscler Thromb Vasc Biol.

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