Vascular anomalies include various diseases, which are classified into two types according to the International Society for the Study of Vascular Anomalies (ISSVA) classification: vascular tumors with proliferative changes of endothelial cells, and vascular malformations primarily consisting of structural vascular abnormalities. The most recent ISSVA classifications, published in 2018, detail the causative genes involved in many lesions. Here, we summarize the latest findings on genetic abnormalities, with the presentation of the molecular pathology of vascular anomalies.

The objective was to prepare guidelines to perform the current optimum treatment by organizing effective and efficient treatments of hemangiomas and vascular malformations, confirming the safety, and systematizing treatment, employing evidence-based medicine (EBM) techniques and aimed at improvement of the outcomes. Clinical questions (CQs) were decided based on the important clinical issues. For document retrieval, key words for literature searches were set for each CQ and literature published from 1980 to the end of September 2014 was searched in Pubmed, Cochrane Library, and Japana Centra Revuo Medicina (JCRM). The strengths of evidence and recommendations acquired by systematic reviews were determined following the Medical Information Network Distribution System (MINDS) technique. A total of 33 CQs were used to compile recommendations and the subjects included efficacy of resection, sclerotherapy/embolization, drug therapy, laser therapy, radiotherapy, and other conservative treatment, differences in appropriate treatment due to the location of lesions and among symptoms, appropriate timing of treatment and tests, and pathological diagnosis deciding the diagnosis. Thus, the Japanese Clinical Practice Guidelines for Vascular Anomalies 2017 have been prepared as the evidence-based guidelines for the management of vascular anomalies.

Systemic sclerosis (SSc) is characterized by excessive collagen deposition in the skin and internal organs. Activated fibroblasts are the key effector cells for the overproduction of type I collagen, which comprises the α1(I) and α2(I) chains encoded by COL1A1 and COL1A2, respectively. In this study, we examined the expression patterns of α1(I) and α2(I) collagen in SSc fibroblasts, as well as their co-regulation with each other. The relative expression ratio of COL1A1 to COL1A2 in SSc fibroblasts was significantly higher than that in control fibroblasts. The same result was observed for type I collagen protein levels, indicating that α2(I) collagen is more elevated than α2(I) collagen. Inhibition or overexpression of α1(I) collagen in control fibroblasts affected the α2(I) collagen levels, suggesting that α1(I) collagen might act as an upstream regulator of α2(I) collagen. The local injection of COL1A1 small interfering RNA in a bleomycin-induced SSc mouse model was found to attenuate skin fibrosis. Overall, our data indicate that α2(I) collagen is a potent regulator of type I collagen in SSc; further investigations of the overall regulatory mechanisms of type I collagen may help understand the aberrant collagen metabolism in SSc.

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Systemic sclerosis (SSc) induces skin thickening and numerous symptoms involving the entire body. Collagen deposition, immune disorder, and vascular abnormalities is currently estimated to be three major causal factors involved in the respective conditions. Vascular abnormalities usually develop in the initial phase of this disease, and may exist in all phases; therefore, they markedly influence the patient’s quality of life. This article reviews recent findings about ‘narrow-sense’ vascular lesions (including Raynaud’s phenomenon, skin ulcers, nailfold bleedings, pitting scars, telangiectasia, and pulmonary hypertension) and ‘broad-sense’ vascular lesions (such as calcinosis or erectile dysfunction). Affected blood vessels can be classified into arteriole/small artery and capillary blood vessels. Furthermore, pathological changes include the proliferation of the vascular endothelial or smooth muscle cells, lumen stenosis by collagen accumulation of the vascular intima, vasodilation or fragility, and apoptosis. There may be interaction between vascular lesions, autoimmune disorder, and collagen deposition. Thus, various symptoms of this disease may be controlled through the treatment of vascular lesions.

Infantile hemangioma sometimes grows rapidly to a significant size around the first 2 months of life, which can be problematic and even destroy normal tissue. However, it is very difficult to predict the tumor growth at the first visit and to decide necessity of treatment. Therefore the identification of the biomarkers that can indicate a tendency to grow is clinically very important. In the present study, we evaluated the possibility that serum cytokine levels are available as the marker of hemangioma growth. Progressive hemangioma was defined as a lesion showing increased tumor size and/or coloration two weeks before and after the serum sampling, and we used membrane array to compare the twenty cytokine profiles between the sera of 3 progressive hemangioma patients and sex-/age-matched non-progressive hemangioma patients. As a result, many of the 20 cytokines were detected in the patients' sera. When a 2-fold difference in the mean levels of each group was considered meaningful, 6 of the 20 cytokines (IGF-1, IL-6, IL-8, PIGF, RANTES, TGF-β1) were down-regulated in the progressive hemangioma group compared to the non- progressive hemangioma group, and there were statistically significant difference (p < 0.05): especially, IGF-1, IL-6, IL-8, PIGF, and TGF-β1 did not expressed in all 3 progressive hemangioma patients. Accordingly, complicated cytokine network by these multiple cytokines may control the pathogenesis, and these cytokine levels may become clinically useful tumor markers. Furthermore, immunotherapy against them will be novel therapeutic approach.