Ryuhei Uchiyama

Nivolumab-induced organizing pneumonia in a melanoma patient

We report the case of a 70-year-old woman with vaginal melanoma and multiple metastases in the lung. After the third dose of nivolumab, decreased room-air resting arterial oxygen saturation with bilateral basal fine crackles on auscultation developed despite the absence of respiratory symptoms. Computed tomography showed ground-glass opacities with airspace consolidations scattered with a peculiar distribution, and most were observed around the existing metastatic tumors in the lung. From the 42nd day to the 56th day after the last administration of nivolumab, she received dexamethasone 1-2 mg/body for the prevention of adverse events after stereotactic radiation for brain metastasis. At 3 months after the last administration of nivolumab, a computed tomography scan revealed improvement of the pneumonia and a decreased size and number of metastatic lesions in the lung, although some lesions showed enlargement. Further examination is needed to clarify the relationship between the pattern of pneumonia after Nivo therapy and clinical effects.

IgA/IgG pemphigus with infiltration of neutrophils and eosinophils in an ulcerative colitis patient.

© 2014 The Authors. doi: 10.2340/00015555-1836 Journal Compilation

Varicella zoster virus–associated generalized pustular psoriasis in a baby with heterozygous IL36RN mutation

Fig 1. Varicella zoster viruseinduced generalized pustular psoriasis in an infant. Pustulosis and crusts on the face, trunk, and limbs are seen. REFERENCES 1. Nassif A, Bensussan A, Doroth ee G, Mami-Chouaib F, Bachot N, Bagot M, et al. Drug-specific cytotoxic T cells in the skin lesions of a patient with toxic epidermal necrolysis. J Invest Dermatol 2002;118:728-33. 2. Pereira FA, Mudgil AV, Rosmarin DM. Toxic epidermal necrolysis. J Am Acad Dermatol 2007;56:181-200. 3. Clark RA, Chong B, Mirchandani N, Brinster NK, Yamanaka K, Dowgiert RK, et al. The vast majority of CLA T cells are resident in normal skin. J Immunol 2006;176:4431-9. 4. Sathaliyawala T, Kubota M, Yudanin N, Turner D, Camp P, Thome JJ, et al. Distribution and compartmentalization of human circulating and tissue-resident memory T cell subsets. Immunity 2013;38:187-97. 5. Ostrov DA, Grant BJ, Pompeu YA, Sidney J, Harndahl M, Southwood S, et al. Drug hypersensitivity caused by alteration of the MHC-presented self-peptide repertoire. Proc Natl Acad Sci U S A 2012;109:9959-64.

Notch down-regulation in regenerated epidermis contributes to enhanced expression of interleukin-36α and suppression of keratinocyte differentiation during wound healing

BACKGROUND Notch signaling controls a number of cellular processes, including cell fate decisions, proliferation, differentiation, and survival/apoptosis, in multiple tissues. In the epidermis, Notch1 functions as a molecular switch that controls the transition of cells from an undifferentiated state into a differentiated state. OBJECTIVE To clarify the functions of Notch in the regenerated epidermis during wound healing. METHODS Wounds on mouse skin were immunostained. To investigate the functions of Notch, Notch was inhibited in primary keratinocytes by treatment with a γ-secretase inhibitor and by small interfering RNA-mediated knockdown, and was activated by a recombinant adenovirus approach. RESULTS Notch1 and Notch2 were down-regulated in the regenerated epidermis during wound healing. To clarify the significance of this down-regulation, we examined its effect on expression of the interleukin (IL)-1 family of proinflammatory cytokines because wounds are exposed to pathogens from the outside world. Among the IL-1 family, IL-36α expression was induced by Notch inhibition. This was consistent with the decreased IL-36α expression in Notch-overexpressing keratinocytes. Notch down-regulation in the regenerated epidermis may reinforce defense against stress from the outside world by inducing IL-36α expression. Next, we examined the effects of Notch down-regulation on keratinocyte growth and differentiation. Notch down-regulation did not alter keratinocyte proliferation. On the other hand, Notch1 down-regulation suppressed induction of spinous layer-specific keratins (keratin1 and keratin10) in keratinocytes, which was consistent with the decreased expression of these keratins in the regenerated epidermis. The reduced levels of these keratins would increase cellular flexibility. CONCLUSION Notch down-regulation in the epidermis appears to contribute to tissue regeneration during wound healing.

5-Hydroxymethylcytosine is a useful marker to differentiate between dermatofibrosarcoma protuberans and dermatofibroma

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