IL36RN encodes interleukin-36 receptor antagonist (IL-36Ra) . The majority of generalized pustular psoriasis (GPP) that is not accompanied by psoriasis vulgaris is caused by IL-36Ra deficiency. Recently, it was reported that acute generalized exanthematous pustulosis is partly related to IL36RN mutation, and that neutrophil-derived proteases process and activate IL-36 cytokines. Thus, it is likely that new therapies for GPP will target activation of IL-36 cytokines through reduction of neutrophils in skin lesions.

　Skin barrier defects are an important causative factor in atopic dermatitis (AD) . It is well known that AD may be associated with ichthyosis vulgaris. Recently, it was revealed that filaggrin gene mutations cause ichthyosis vulgaris, and increase the risk of developing AD, food allergy, asthma and allergic rhinitis. In addition to ichthyosis vulgaris, there are several other hereditary skin barrier defects associated with atopic conditions such as Netherton syndrome, inflammatory peeling skin syndrome, SAM syndrome and ichthyosis prematurity syndrome. In these conditions, dermatitis, and increased serum levels of total IgE and IgE against various food allergens are typically seen. Although these diseases, excluding ichthyosis vulgaris, are rare, they are monogenic diseases and their pathological mechanisms are relatively easy to understand. Therefore, it is possible to obtain insights regarding the pathogenesis of AD and other atopic conditions by studying these monogenic skin diseases.

　Allergic diseases do not occur when the causative allergens are controlled so that they will not infect the patients. This procedure is known as allergen control. Historically, pigmented cosmetic dermatitis (PCD) , a bizarre dark facial pigmentation had been incurable in the 1950s to 1970s, but were found to be completely curable by the exclusive usage of allergen-free soaps and cosmetics. Many causative allergens of PCD were discovered by a group study in the 1970s using patch testing. The studies showed that Yellow No.11 provoked chemical-induced SLE, and consequently it was banned by the government. Enough evidence has been accumulated that dermatophagoides mites were the main causation of atopic dermatitis (AD) . As the mites were invisible, a new technique called the MBA method was invented to analyze the mite fauna of the patients' homes. It enabled the elimination of mite numbers to less than 50/m², resulting to cure of intractable cases of AD and retaining normal skin conditions thereafter. Metal ions have been common sensitizers, and were reported as the causation of not only contact dermatitis but also lichen planus, pustulosis palmaris and plantaris, and recently, of severe cases of alopecia areata as well. Therefore it is essential that a patch test using a series of water-based metal allergens is performed. The elimination of causative metal allergens from patients' oral cavities and pans, based on a metal analysis, assisted in hair regrowth and prevented the relapse of severe defluvium, for a follow-up average of 4 years and 4 months.

　This article examines issues related with contact dermatitis caused by products used in daily life. Although new products often contain unrecorded allergens that can cause contact dermatitis, safety evaluation or imported products is insufficient in Japan, and it is difficult to obtain information about the raw materials used in such products. Among occupational skin disorders, contact dermatitis accounts for the largest proportion, and patients may be forced to abandon work without confirming the allergens that are responsible. Patch testing is very useful for protecting individuals and improving the safety of products.

　Allergic diseases, including atopic dermatitis (AD) , are characterized by abundant production of Th2 cytokines. It was recently reported that IL-17A in the acute phase and IFNγ and IL-22 in the chronic phase both increased in the skin of AD. These cytokines were produced by immune cells that infiltrated into the lesional skin, resulting in the modification of structural protein expressions in the epidermis. This review summarizes (1) the effects of cytokines that are involved in development of AD on expression of structural proteins produced by epidermal keratinocytes and (2) the significance of keratin or desmosomal cadherin deficiency in increased expression of inflammatory cytokines and decreased expression of other structural proteins produced by epidermal keratinocytes. Challenges for the future will be to clarify the pathophysiology in AD based on changes in structural molecules and cytokines produced and cascades of molecular interactions causing different phases of pathophysiological changes in AD.

　The recent growth and development of cancer care (surgery, radiotherapy, and chemotherapy) have been remarkable. The five-year survival rate for all types of cancer has increased, and there are 32.5 million outpatients who continue care with employment (2010) . Patients going through cancer treatment while actively engaging in society have increased awareness of their change in appearance due to treatment. A study conducted using 638 cancer patients in 2013 found high distress due to change in appearance among other physical side effects from treatment. Most patients expressed the need for hospitals to provide information and care for change in appearance.

　As shown above, distress due to appearance change, such as skin issues and hair loss, is significant. Medical professionals likely recognize the absence of a relationship between severity of symptoms and levels of distress that patients experience. Based on recent studies, we examined what types of distress patients experience and how medical professionals can support their needs.

　Background: Potential allergens in plastic spectacle frames concern plasticizers, anti-oxidants, UV inhibitors, and dyes. Among the latter, Solvent Orange 60 (SO 60) has been recognized as an important allergen, both in Japan and Scandinavian countries.

　Objectives: To report on 4 patients with allergic contact dermatitis from SO 60 in spectacle frames observed between 2009 and 2016, and to provide a summary regarding the 8 Japanese cases reported until 2004.

　Methods: Patch tests were performed with scrapings of plastic parts of the spectacle frames and with SO 60 diluted in petrolatum. Gas chromatography/mass spectrometry (GC/MS) of an extract from a plastic temple was performed for one of the causative spectacles.

　Results: All 4 patients reacted strongly positive to the scrapings as well as to SO 60, indeed detected by GC/MS in the spectacle frame examined. One patient cross-reacted to Solvent Red 179 (SR 179) .

　Conclusions: SO 60 should be patch tested in all suspected cases of dermatitis from plastic spectacle frames, eventually together with SR 179 to check for cross-sensitivity. The patch-test concentration should be lower than 1%, but needs further specification.

　Case 1 : A 70-year-old man with recurrent rectal cancer after surgery and multiple pelvic lymph node metastases started treatment with mFOLFOX6 panitumumab. Two months after treatment, punched-out skin ulcers appeared on the dorsum of the hands, knees and elbows. Histopathological findings revealed perivascular infiltration of neutrophils with nuclear dust and extravasation of erythrocytes, corresponding to leukocytoclastic vasculitis (LCV) in the upper dermis. At 7 weeks after withdrawal of the treatment, all skin ulcers became epithelialized. Case 2 : A 67-year-old man with colon cancer and multiple liver and lung metastases started treatment with panitumumab. 2.5 months after treatment, punched-out skin ulcers appeared on the knees and elbows. All skin ulcers healed 4 weeks after discontinuation of the treatment. Case 3 : A 68-year-old man with peritoneal dissemination after surgery for rectal cancer started treatment with CPT11 cetuximab. 6 months after treatment, punched-out skin ulcers appeared on the knees. By 2 weeks after withdrawal of the treatment, all skin ulcers had disappeared. Recently, many cases of LCV during treatment with EGFR-tyrosine kinase inhibitors have been reported in the literature, and we suspect that our cases of punched-out skin ulcers were due to LCV caused by treatment with anti-EGFR monoclonal antibodies.