Systemic sclerosis (SSc) is a chronic multisystem disorder characterized by fibrosis and autoimmunity. Interleukin (IL)-31 has been implicated in fibrosis and T helper (Th) 2 immune responses, both of which are characteristics of SSc. The exact role of IL-31 in SSc pathogenesis is unclear. Here we show the overexpression of IL-31 and IL-31 receptor A (IL-31RA) in dermal fibroblasts (DFs) from SSc patients. We elucidate the dual role of IL-31 in SSc, where IL-31 directly promotes collagen production in DFs and indirectly enhances Th2 immune responses by increasing pro-Th2 cytokine expression in DFs. Furthermore, blockade of IL-31 with anti-IL-31RA antibody significantly ameliorates fibrosis and Th2 polarization in a mouse model of SSc. Therefore, in addition to defining IL-31 as a mediator of fibrosis and Th2 immune responses in SSc, our study provides a rationale for targeting the IL-31/IL-31RA axis in the treatment of SSc.

Cellulitis is a skin and soft tissue infection that is accompanied by symptoms, such as swelling, flushing, and pain [1]. The main causative bacterial species are group A β-Streptococcus and Staphylococcus aureus [2]. Some patients, especially those with chronic swelling (lymphedema), obesity, and diabetes, are at an increased risk of cellulitis [1,3]. Previous studies have reported that 41% to 45.3% of cellulitis cases eventually recur [4].A recurrence prediction score for the cellulitis of the lower limbs has been developed, and patients with lymphedema, chronic venous insufficiency, peripheral circulatory disturbance, and deep vein thrombosis are considered to be at risk [4]. While this score is expected to be applied clinically, it has limited usefulness because it

Aim: Systemic sclerosis (SSc) is a chronic autoimmune disease resulting in vasculopathy and fibrosis of the skin and major internal organs. Especially, interstitial lung disease and pulmonary arterial hypertension are the leading causes of mortality. C-C motif ligand 20 (CCL20) is known as a homeostatic and inflammatory chemokine, which is associated with fibrosis and angiogenesis and constantly expressed in organs involved in SSc. Therefore, we investigated the potential contribution of CCL20 to the development of SSc. Method:We conducted cross-sectional analyses of 67 SSc patients and 20 healthy controls recruited in a single center for 9 years. Serum CCL20 levels were measured by enzyme-linked immunosorbent assay. Statistical analyses were performed with the Mann-Whitney U test, the Kruskal-Wallis test followed by Dunn's multiple comparison test, Fisher's exact probability test and the Spearman's rank correlation coefficient.Results: SSc patients had significantly higher serum CCL20 levels than healthy controls. In SSc patients, serum CCL20 levels correlated inversely with the percentage of predicated diffusion lung capacity for carbon monoxide and positively with mean pulmonary artery pressure (mPAP). In addition, SSc patients with increased serum CCL20 levels had anti-mitochondrial antibody M2 titer significantly elevated relative to those with normal levels, and SSc patients with asymptomatic primary biliary cholangitis (PBC) possessed higher serum CCL20 levels than those without. Importantly, serum CCL20 levels were associated positively with mPAP values and PBC presence by multivariate regression analysis. Conclusion:Serum CCL20 levels may be involved in the development of pulmonary vascular involvement leading to pulmonary arterial hypertension and asymptomatic PBC in SSc patients.

Vasohibin‐1 (VASH‐1) is a potent anti‐angiogenic factor mainly produced by endothelial cells. In addition, VASH‐1 prevents TGF‐β–dependent activation of renal fibroblasts. Since systemic sclerosis (SSc) is an autoimmune disease characterized by vasculopathy and fibrosis of multiple organs, VASH‐1 may be involved in the development of this disease. In this study, we investigated the potential role of VASH‐1 in SSc by evaluating the clinical correlation between serum VASH‐1 levels and the expression of VASH‐1 in SSc‐involved skin. Serum VASH‐1 levels were higher in SSc patients, especially those with diffuse cutaneous involvement, than in healthy controls and positively correlated with skin score. Furthermore, SSc patients with interstitial lung disease had significantly elevated levels of serum VASH‐1 as compared to those without. Importantly, serum VASH‐1 levels correlated inversely with both the percentage of predicted vital capacity and the percentage of predicted diffusion lung capacity for carbon monoxide and positively with serum KL‐6 levels, but not serum surfactant protein D levels. In SSc‐involved skin, VASH1 mRNA was remarkably upregulated compared with healthy control skin, but the major source of VASH‐1 was not clear. Fli1 deficiency, a predisposing factor inducing SSc‐like endothelial properties, did not affect VASH‐1 expression in human dermal microvascular endothelial cells. Collectively, these results suggest that VASH‐1 upregulation in the skin and sera is linked to dermal and pulmonary fibrotic changes in SSc, while the contribution of VASH‐1 to SSc vasculopathy seems to be limited.

We describe a case of breakthrough Candida parapsilosis fungemia in an 80-year-old woman with pyoderma gangrenosum and rheumatoid arthritis. C. parapsilosis was detected in blood culture while the patient was treated with micafungin for a Candida glabrata bloodstream infection. The breakthrough infection was successfully treated with liposomal amphotericin B.

Background: Infections caused by Prevotella bivia, a gram-negative anaerobic bacillus, are rare, with no reported cases in Japan. We present a novel case of scrotal abscess in a Japanese patient co-infected with Prevotella bivia and Streptococcus agalactiae. Case Presentation: A 41-year-old uncontrolled diabetic man complained of swelling and pain in the scrotum. On examination, computed tomography revealed an abscess of 5-cm diameter in the scrotum. Then, the abscess was incised and drained. He was treated with cefazolin empirically. Prevotella bivia and Streptococcus agalactiae were identified in the pus cultures obtained from the abscess. However, the susceptibility tests for Prevotella bivia could not be submitted. Seven days following admission, the pain reduced, and the drainage slowed. The patient was discharged on day 14 when cefazolin was discontinued and oral amoxicillin (750 mg/day) was started. Amoxicillin was continued until day 42; improvement was confirmed. Conclusion:To the best of our knowledge, this case is the first report of Prevotella bivia in Japan. We suggest that cephem antibiotics such as cefazolin may be effective against Prevotella bivia in Japan.

Objectives Psoriatic arthritis (PsA) is one of the most serious comorbidities associated with psoriasis. While the early intervention in PsA is demanded, risk factors of PsA development are not well-known. This is the first prospective study to evaluate the clinical significance of nailfold capillary (NFC) changes in patients with psoriasis. Methods We conducted a prospective cohort study in a population of 449 psoriasis patients who had not been treated with systemic therapy or topical finger therapy. NFCs were observed by dermoscopy and capillaroscopy, and the correlation of NFC abnormalities, including nailfold bleeding (NFB) and enlarged capillaries, with the prevalence of PsA, incidence of new PsA, and serum levels of TNF-a, IL-17A, and IL-23 were analyzed. Results Detailed examination at the time of inclusion revealed that of 449 patients, 236 had Psoriasis vulgaris (PsV) and 213 had PsA. Both NFB and enlarged capillaries were significantly more frequent in patients with PsA (34.7% vs. 84.5%, p< 0.0001; 25.4% vs. 100%, p< 0.0001). In addition, PsV patients were prospectively observed before they developed PsA (mean 21 months, 95%CI 2–77 months). Multivariate analysis suggested that the appearance of NFB and enlarged capillaries was a predictor of PsA development (HR 2.75, 95%CI 1.38–5.47 and HR 4.49, 95%CI 2.25–8.96, respectively). The degree of NFC abnormalities also correlated with the severity of PsA and serum cytokine levels. Conclusions NFC abnormalities were suggested to be a predictor of PsA in psoriasis patients, and at the same time, its degree could be an indicator of disease severity.

Systemic sclerosis (SSc) is a multisystem autoimmune and vascular disease resulting in multiple organ fibrosis with unknown aetiology. 1 It is generally accepted that an orchestrated complex network of signalling pathways drives a common SSc-specific pathological cascade across multiple organs, 2 which can be affected by organ-specific disease modifiers. 3-5 Recently, damage-associated molecular patterns (DAMPs) have drawn attention as molecules underlying SSc development. 6-9 DAMPs are evolutionally conserved endogenous molecules normally localized inside cells. Upon cellular stress or injury, DAMPs are released into the extracellular space from damaged cells, subsequently activating innate immune cells. The S100A protein family, a