Ken Washio

Pressure Bandage as an Effective Treatment for Intralymphatic Histiocytosis Associated with Rheumatoid Arthritis

The patient is a 71-year-old male who has been suffering from rheumatoid arthritis for over 20 years. He first noticed the erythema on his right forearm in 2008, which got worse in 2009. Topical corticosteroids were not effective, and a skin biopsy was performed. Histopathologic examination showed aggregation of the inflammatory cells in the dermal vessels. Those cells were positive for CD68 and CD31 and all the surrounding vessels expressed D2–40 and CD31. We diagnosed him with intralymphatic histiocytosis. One week after the skin was biopsied, only the part of the erythematous lesion covered by skin tape had improved, suggesting that pressure on the lesion might improve the erythematous eruption. We therefore used a pressure bandage elbow supporter in addition to topical treatment. The lesion improved 3 months later and was totally diminished after 9 months. Combined with previously reported cases, our case suggested that intralymphatic histiocytosis is closely related to lymphostasis.

Anti-SIRP alpha antibodies as a potential new tool for cancer immunotherapy

Tumor cells are thought to evade immune surveillance through interaction with immune cells. Much recent attention has focused on the modification of immune responses as a basis for new cancer treatments. SIRPα is an Ig superfamily protein that inhibits phagocytosis in macrophages upon interaction with its ligand CD47 expressed on the surface of target cells. Here, we show that SIRPα is highly expressed in human renal cell carcinoma and melanoma. Furthermore, an anti-SIRPα Ab that blocks the interaction with CD47 markedly suppressed tumor formation by renal cell carcinoma or melanoma cells in immunocompetent syngeneic mice. This inhibitory effect of the Ab appeared to be mediated by dual mechanisms: direct induction of Ab-dependent cellular phagocytosis of tumor cells by macrophages and blockade of CD47-SIRPα signaling that negatively regulates such phagocytosis. The antitumor effect of the Ab was greatly attenuated by selective depletion not only of macrophages but also of NK cells or CD8+ T cells. In addition, the anti-SIRPα Ab also enhances the inhibitory effects of Abs against CD20 and programmed cell death 1 (PD-1) on tumor formation in mice injected with SIRPα-nonexpressing tumor cells. Anti-SIRPα Abs thus warrant further study as a potential new therapy for a broad range of cancers.

Anti-Inflammatory Role of Langerhans Cells and Apoptotic Keratinocytes in Ultraviolet-B–Induced Cutaneous Inflammation

UV radiation, particularly UVB, is the major risk factor for the induction of skin cancer, and it induces skin inflammation and immunosuppression. Although reports documented that Langerhans cells (LCs) play various roles in photobiology, little is known about whether they contribute to UVB-induced cutaneous inflammation. Recently, the anti-inflammatory effect of apoptotic cells was noted. This study focuses on the roles of LCs and apoptotic cells in UVB-induced cutaneous inflammation. We show that LCs are essential for resolution of UVB-induced cutaneous inflammation. Administration of quinolyl-valyl-O-methylaspartyl-[2,6-difluophenoxy]-methyl ketone, a broad-spectrum caspase inhibitor with potent antiapoptotic properties, inhibited the formation of UVB-induced apoptotic cells and aggravated UVB-induced cutaneous inflammation in wild-type mice. In contrast, exacerbation of UVB-induced cutaneous inflammation following quinolyl-valyl-O-methylaspartyl-[2,6-difluophenoxy]-methyl ketone administration was not observed in LC-depleted mice. These results suggest that the interaction between LCs and apoptotic cells is critical for resolution of UVB-induced cutaneous inflammation. Interestingly, UVB-induced apoptotic keratinocytes were increased in LC-depleted mice. In addition, we revealed that UVB-induced apoptotic keratinocytes were phagocytosed by LCs ex vivo and that prolongation of UVB-induced cutaneous inflammation following treatment with Cytochalasin D, an inhibitor of phagocytosis, was partially attenuated in LC-depleted mice. Collectively, our findings demonstrate that the interaction between LCs and apoptotic cells, possibly via LC-mediated phagocytosis of apoptotic keratinocytes, has an essential anti-inflammatory role in the resolution of UVB-induced cutaneous inflammation.

A Case of Lichen Planus Pemphigoides Successfully Treated with a Combination of Cyclosporine A and Prednisolone

Lichen planus pemphigoides (LPP) is a rare clinical variant of bullous pemphigoid (BP). A 35-year-old female patient presented to our hospital complaining of pruritic violaceous-colored plaques or papules on the extremities. Tense vesicles were also seen on the soles. Skin biopsies from the papules and vesicles demonstrated lichen planus and BP, respectively. Direct immunofluorescence demonstrated linear IgG and C3 deposition on the basement membrane zone. Indirect immunofluorescence on 1 M NaCl split skin detected IgG reactivity with the epidermal side. Enzyme-linked immunosorbent assay also detected anti-BP180 antibodies. After treatment with oral prednisolone alone had failed, low-dose cyclosporine A (CyA) was added. The clinical symptoms immediately improved and the titer of the anti-BP180 antibodies decreased. Although there is little information about the treatment of recalcitrant LPP, additional CyA appeared to be beneficial.

Case of recurrent Sweet's syndrome in a patient with relapsing polychondritis and myelodysplastic syndrome.

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UVB Exposure Prevents Atherosclerosis by Regulating Immunoinflammatory Responses

Objective— UVB irradiation is an established treatment for immunoinflammatory cutaneous disorders and has been shown to suppress cutaneous and systemic inflammatory diseases through modulation of the adaptive immune response. However, it remains unknown whether UVB irradiation prevents an immunoinflammatory disease of arteries such as atherosclerosis. Approach and Results— Here, we show that UVB exposure inhibits the development and progression of atherosclerosis in atherosclerosis-prone mice by expanding and enhancing the functional capacity of CD4+ forkhead box P3+ regulatory T cells and regulating proatherogenic T-cell responses. Experimental studies in Langerhans cell–depleted mice revealed that epidermal Langerhans cells play a critical role in UVB-dependent induction of CD4+ forkhead box P3+ regulatory T cells, suppression of proatherogenic T-cell responses, and prevention of atherosclerotic plaque development. Conclusions— Our findings suggest the skin immune system as a novel therapeutic target for atherosclerosis and provide a novel strategy for the treatment and prevention of atherosclerosis.

Steroid treatment can improve the impaired quality of life of patients with acquired idiopathic generalized anhidrosis

DEAR EDITOR, Acquired idiopathic generalized anhidrosis (AIGA) is characterized by systemic anhidrosis or hypohidrosis with no identified cause or other autonomic or neurological abnormalities. AIGA is sometimes accompanied by cholinergic urticaria with symptoms of tingling, unpleasant sensation and severe pruritus. Treatment options for AIGA are limited. Most reported cases responded to high-dose systemic corticosteroids including intravenous steroid pulse therapy. AIGA can lead to discomfort, hyperthermia and heat stroke, which may affect the quality of life (QoL) of patients. However, the relationship between the QoL of patients with AIGA and effectiveness of therapy has not been examined. The aim of this study was to examine the impact of AIGA on QoL and the relationship between therapeutic effectiveness and improvement in QoL. Eight male patients and one female patient with AIGA were enrolled in this study. The patient characteristics are described in Table 1. The diagnosis of anhidrosis and the treatment efficacy were assessed by a systemic thermoregulatory sweating test and local sweating test involving intradermal injection of acetylcholine and the starch–iodine test (Minor test). Other diseases with hypohidrosis such as Sj€ ogren syndrome and Fabry disease were excluded. Cholinergic urticaria was observed in seven patients. Histological findings revealed that morphological abnormalities of sweat glands and sweat ducts were absent in all patients, and slight infiltration of lymphocytes around the sweat glands was found in five patients. The mean interval between disease onset and treatment was 27 8 months. Histamine release test with the sweat or skin test using autologous sweat revealed sweat allergy in two of eight tested patients. One course of methylprednisolone pulse therapy (3 days, 1000 mg per day) was given to six patients, two courses were given to one patient and three courses were given to one patient. Sweating improved in all patients after therapy. Adverse effects and recurrence of symptoms were not observed for > 1 year after therapy. In the absence of therapy, anhidrosis remained unchanged in one patient who declined treatment. Skindex-16 inquires about the effect of skin conditions on QoL. Patients respond to questions by choosing one of seven possible response choices, which range from ‘never bothered’ to ‘always bothered’. Skindex responses are reported in three subscales (symptoms, emotions and functioning), which address three domains: symptoms, emotional effects, and effects on social and physical functioning. Scores vary from 0 (minimal effect on QoL) to 100 (significant effect on QoL). The mean Skindex-16 subscale scores before and after therapy are shown in Figure 1. Skindex-16 questions before therapy were carried out from spring to autumn (from May to November). Skindex-16 questions after therapy were performed in September (autumn in Japan). The average September temperature of our facility is 20–30 °C. Sweating tests were also performed alongside the Skindex-16 questionnaire before and after therapy.

Cholinergic urticaria: epidemiology, physiopathology, new categorization, and management

PurposeThe aim of this study was to review the evidence on the epidemiology, physiopathology, categorization, and management of cholinergic urticaria. We specifically focused on several subtypes of cholinergic urticaria and investigated the relationship between cholinergic urticaria and idiopathic anhidrosis.MethodsUsing an integrative approach, we reviewed publications addressing the epidemiology, clinical features, diagnostic approach, physiopathology, subtype classification, and therapeutic approach to cholinergic urticaria.ResultsMultiple mechanisms were found to contribute to the development of cholinergic urticaria. This disorder should be classified based on the pathogenesis and clinical characteristics of each subtype. Such a classification system would lead to better management of this resistant condition. In particular, sweating function should be given more attention when examining patients with cholinergic urticaria.ConclusionsBecause cholinergic urticaria is not a homogeneous disease, its subtype classification is essential for selection of the most suitable therapeutic method.

Addition of lafutidine can improve disease activity and lead to better quality of life in refractory cholinergic urticaria unresponsive to histamine H1 antagonists

Abbreviations: CU, cholinergic urticaria; H1RA, H1 receptor antagonists; H2RA, H2 receptor antagonists; QoL, quality of life; DLQI-J, Dermatology Life Quality Index. * Corresponding author at: Department of Dermatology, Kurume University School of Medicine, and Kurume University Institute of Cutaneous Cell Biology, 67 Asahimachi, Kurume, Fukuoka 8300011, Japan. Fax: +81 942 31 7853. E-mail address: hashimot@med.kurume-u.ac.jp (T. Hashimoto).

Dendritic cell SIRPα regulates homeostasis of dendritic cells in lymphoid organs

Signal regulatory protein α (SIRPα), an immunoglobulin superfamily protein that is expressed predominantly in myeloid lineage cells such as dendritic cells (DCs) or macrophages, mediates cell–cell signaling. In the immune system, SIRPα is thought to be important for homeostasis of DCs, but it remains unclear whether SIRPα intrinsic to DCs is indeed indispensable for such functional role. Thus, we here generated the mice, in which SIRPα was specifically ablated in CD11c+ DCs (SirpaΔDC). SirpaΔDC mice manifested a marked reduction of CD4+ CD8α– conventional DCs (cDCs) in the secondary lymphoid organs, as well as of Langerhans cells in the epidermis. Such reduction of cDCs in SirpaΔDC mice was comparable to that apparent with the mice, in which SIRPα was systemically ablated. Expression of SIRPα in DCs was well correlated with that of either endothelial cell‐selective adhesion molecule (ESAM) or Epstein–Barr virus‐induced molecule 2 (EBI2), both of which were also implicated in the regulation of DC homeostasis. Indeed, ESAM+ or EBI2+ cDCs were markedly reduced in the spleen of SirpaΔDC mice. Thus, our results suggest that SIRPα intrinsic to CD11c+ DCs is essential for homeostasis of cDCs in the secondary lymphoid organs and skin.