Matrix metalloproteinases (MMPs) are zinc-containing endopeptidases with an extensive range of substrate specificities. Collectively, these enzymes are able to degrade various components of extracellular matrix (ECM) proteins. Based on their structure and substrate specificity, they can be categorized into five main subgroups, namely (1) collagenases (MMP-1, MMP-8 and MMP-13); (2) gelatinases (MMP-2 and MMP-9); (3) stromelysins (MMP-3, MMP-10 and MMP-11); (4) matrilysins (MMP-7 and MMP-26); and (5) membrane-type (MT) MMPs (MMP-14, MMP-15, and MMP-16). The alterations made to the ECM by MMPs might contribute in skin wrinkling, a characteristic of premature skin aging. In photocarcinogenesis, degradation of ECM is the initial step towards tumor cell invasion, to invade both the basement membrane and the surrounding stroma that mainly comprises fibrillar collagens. Additionally, MMPs are involved in angiogenesis, which promotes cancer cell growth and migration. In this review, we focus on the present knowledge about premature skin aging and skin cancers such as basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma, with our main focus on members of the MMP family and their functions.

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.

In wound healing and many pathologic conditions, keratinocytes become activated: they turn into migratory, hyperproliferative cells that produce and secrete extracellular matrix components and signaling polypeptides. At the same time, their cytoskeleton is also altered by the production of specific keratin proteins. These changes are orchestrated by growth factors, chemokines, and cytokines produced by keratinocytes and other cutaneous cell types. The responding intracellular signaling pathways activate transcription factors that regulate expression of keratin genes. Analysis of these processes led us to propose the existence of a keratinocyte activation cycle, in which the cells first become activated by the release of IL-1. Subsequently, they maintain the activated state by autocrine production of proinflammatory and proliferative signals. Keratins K6 and K16 are markers of the active state. Signals from the lymphocytes, in the form of Interferon-gamma, induce the expression of K17 and make keratinocytes contractile. This enables the keratinocytes to shrink the provisional fibronectin-rich basement membrane. Signals from the fibroblasts, in the form of TGF-beta, induce the expression of K5 and K14, revert the keratinocytes to the healthy basal phenotype, and thus complete the activation cycle.

Psoriasis is an immune-mediated genetic skin disease. The underlying pathomechanisms involve complex interaction between the innate and adaptive immune system. T cells interact with dendritic cells, macrophages, and keratinocytes, which can be mediated by their secreted cytokines. In the past decade, biologics targeting tumor necrosis factor-α, interleukin (IL)-23, and IL-17 have been developed and approved for the treatment of psoriasis. These biologics have dramatically changed the treatment and management of psoriasis. In contrast, various triggering factors can elicit the disease in genetically predisposed individuals. Recent studies suggest that the exacerbation of psoriasis can lead to systemic inflammation and cardiovascular comorbidity. In addition, psoriasis may be associated with other auto-inflammatory and auto-immune diseases. In this review, we summarize the risk factors, which can be divided into two groups (namely, extrinsic and intrinsic risk factors), responsible for the onset and exacerbation of psoriasis in order to facilitate its prevention.

Generalized pustular psoriasis (GPP) is a severe inflammatory skin disease characterized by the presence of sterile pustules covering almost the entire body and systemic symptoms such as fever. Secukinumab, a fully human-recombinant anti-interleukin-17A monoclonal antibody was indicated for psoriasis vulgaris and psoriatic arthritis in Japan but is not yet investigated for GPP. In this phase III, open-label multicenter single arm study, the efficacy and safety of secukinumab as monotherapy or with co-medication was evaluated in 12 Japanese patients with GPP. All the patients received secukinumab 150 mg s.c. at baseline, week 1, 2, 3 and 4, and then every 4 weeks. Two non-responders were up-titrated to 300 mg. Change in GPP severity from baseline was evaluated by clinical global impression (CGI) categorized as "worsened", "no change", "minimally improved", "much improved" or "very much improved". Treatment success was achieved by 83.3% (n = 10) of patients at week 16 (primary end-point) with CGI evaluated as "very much improved" (n = 9) and "much improved" (n = 1). Moreover, the area of erythema with pustules improved as early as week 1 and resolved by week 16 in most of the patients. The improvements were sustained throughout 52 weeks. Over the 52-week treatment period, secukinumab was well tolerated with no unexpected safety signals. Nasopharyngitis, urticaria, diabetes mellitus and arthralgia were the frequent adverse events reported. The data from this study shows that secukinumab can become one of the potent treatment options for GPP.