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Immune checkpoint inhibitors (ICI), including monoclonal antibodies to programmed death 1, programmed death ligand 1, and cytotoxic T lymphocyte-associated antigen 4, have provided great therapeutic benefits for cancer patients at advanced stages. However, the introduction of ICI frequently results in the development of immune-related adverse events (irAE) through activation of autoreactive T cells. Here, we present three cases of cancer patients with cutaneous irAE, including development of de novo psoriasis and exacerbation of pre-existing psoriasis. Interestingly, these patients shared an altered histological feature characterized by loss of epidermal CD1a

We experienced a rare case of drug-induced hypersensitivity syndrome (DIHS) in which salazosulfapyridine (SASP) reactivated human herpesvirus 6 (HHV-6) and cytomegalovirus (CMV), which resulted in a relapse of skin symptoms after changing to mizoribine. At the time of recurrence of skin erythema after the initiation of mizoribine, the serum DNA titers of not HHV-6 but CMV were elevated. A drug-induced lymphocyte stimulation test was negative for mizoribine but positive for SASP. In this case, DIHS developed with SASP in association with HHV-6 and CMV reactivation. The immunocompromised state induced by herpes virus reactivation and mizoribine might have caused the relapse of skin erythema.

Pediatric cutaneous mastocytosis (CM) is mainly attributed to gain-of-function mutations in KIT in mast cells. On the other hand, growing evidence suggests that CM patients exist without KIT mutations. To date, the association between the KIT mutation status and clinical phenotype has not been elucidated in pediatric CM, especially in patients with wild-type KIT. Nevertheless, genetic analysis has yet to be performed with whole KIT sequence of mast cells in Japanese patients with pediatric CM. In the present study, 11 Japanese patients with pediatric CM were analyzed to determine whether they had KIT mutations in their skin, and their clinical phenotypes were observed. The approximate frequency of patients with KIT mutation and that of wild-type KIT was almost consistent with the European analysis. The distribution of overall macules was similar between the patients with and without KIT mutations.

Bone homeostasis is maintained by a balance in activity between bone-resorbing osteoclasts and bone-forming osteoblasts. Shifting the balance toward bone resorption causes osteolytic bone diseases such as rheumatoid arthritis and periodontitis. Osteoclast differentiation is regulated by receptor activator of nuclear factor κB ligand (RANKL), which, under some pathological conditions, is produced by T and B lymphocytes and synoviocytes. However, the mechanism underlying bone destruction in other diseases is little understood. Bone destruction caused by cholesteatoma, an epidermal cyst in the middle ear resulting from hyperproliferation of keratinizing squamous epithelium, can lead to lethal complications. In this study, we succeeded in generating a model for cholesteatoma, epidermal cyst-like tissue, which has the potential for inducing osteoclastogenesis in mice. Furthermore, an in vitro coculture system composed of keratinocytes, fibroblasts, and osteoclast precursors was used to demonstrate that keratinocytes stimulate osteoclast differentiation through the induction of RANKL in fibroblasts. Thus, this study demonstrates that intercellular communication between keratinocytes and fibroblasts is involved in the differentiation and function of osteoclasts, which may provide the molecular basis of a new therapeutic strategy for cholesteatoma-induced bone destruction.

Keratinocytes are known to synthesize cortisol through activation of the enzyme 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1). To confirm the function of 11β-HSD1 in keratinocytes during inflammation in vivo, we created keratinocyte-specific-11β-HSD1 knockout mice (K5-Hsd11b1-KO mice) and analyzed the response to narrow-band ultraviolet B (NB-UVB) irradiation. Firstly, we measured the mRNA and protein levels of 11β-HSD1 following NB-UVB irradiation and found that the expression of 11β-HSD1 in keratinocytes of mouse ear skin was enhanced at 3 and 24 hours after 250 mJ/cm(2), 500 mJ/cm(2), 1 J/cm(2), and 2 J/cm(2) NB-UVB irradiation. Next, we determined that 24 hours after exposure to 1 J/cm(2) NB-UVB irradiation, the numbers of F4/80-, CD45-, and Gr-1-positive cells were increased in K5-Hsd11b1-KO mice compared to wild type (WT) mice. Furthermore, the expression of the chemokine (C-X-C-motif) ligand 1 (CXCL1) and interleukin (IL)-6 was also significantly enhanced in NB-UVB-irradiated K5-Hsd11b1-KO mice compared with WT mice. In addition, activation of nuclear factor-kappa B (NF-κB) after NB-UVB irradiation was enhanced in K5-Hsd11b1-KO mice compared to that in WT mice. Thus, NB-UVB-induced inflammation is augmented in K5-Hsd11b1-KO mice compared with WT mice. These results indicate that 11β-HSD1 may suppress NB-UVB-induced inflammation via inhibition of NF-κB activation.