Morphological Alterations of the Eccrine Sweat Apparatus in Amputated Feet from Diabetes Mellitus Patients

Several physiological studies have demonstrated decreased or absent thermoregulatory sweating in the distal legs and feet of diabetes patients. Such hypohidrosis in diabetes patients is believed to be a clinical symptom of autonomic neuropathy. Thus, the present study sought to clarify the pathogenesis of structural alterations of the eccrine sweat apparatus in diabetes patients. For this study, we enrolled 17 patients with diabetic ulcers/gangrene who underwent amputation of the foot. Specimens were obtained 30mm from the ulcer/gangrene after amputation using a 6-mm trepan, with 12 normal human skin samples obtained from areas adjacent to pigmented nevi or benign skin tumors on the legs or feet to serve as controls. Numbers and morphological abnormalities of eccrine sweat glands and ducts were assessed by light microscopy. The pathogenesis of morphological alterations was examined by electron microscopy and immunoelectron microscopy of type IV collagen. Rates of disappearance of the lumen, shrunken morphology, and irregular outlines of eccrine sweat glands and ducts were significantly higher or more abundant in diabetes patients than in controls (P = 0.0002〜0.0001). Ultrastructurally, we observed prominent thickening of the basement membranes in eccrine sweat glands, admixed cell debris, and narrowing of the lumenal space. The thickened basement membranes resulted in the shrunken morphology and irregular outlines in eccrine sweat glands and ducts. Immunoelectron microscopy showed immunogold labeling for type IV collagen throughout the thickened basement membrane zone. These morphological alterations of the eccrine sweat apparatus in amputated feet from diabetes patients could be caused by diabetic and/or uremic neuropathy, and at least in part by angiopathy

CCR6+ MCAM+ Th17 Cell Numbers Increase in Patients with Psoriasis and Correlate with Disease Severity

Psoriasis is a chronic immune-mediated disease in which the interleukin (IL)-23/IL-17 axis plays a key role in the inflammatory cascade. We recently reported that co-expression of CCR6 and melanoma cell adhesion molecule (MCAM) in effector memory CD4 T cells (TEM) of peripheral blood might be a useful marker for T helper (Th) 17 cells. In this study, we monitored changes in TEM expressing CCR6 and MCAM using the Psoriasis Area and Severity Index (PASI) score during anti-tumor necrosis factor (TNF) therapy. We also studied CCR6+ MCAM+ Th17 cells histologically in skin biopsy samples from psoriasis patients. In psoriasis patients treated with anti-TNF therapy, the PASI score and the percentage of CCR6+ MCAM+ TEM cells in the blood changed almost in parallel. In immunohistochemical analyses, the proportions of IL-17+ T cells and MCAM+ T cells in the lesional skin of severely psoriatic patients were significantly higher than in mildly psoriatic patients (P<0.05), and the number of IL17+ T cells correlated with the PASI score (r=0.400, P<0.05). Taken together, these results indicate that CCR6+ MCAM+ Th17 cells in peripheral blood and lesional skin might play an important role in the pathology of psoriasis

血清TARC/CCL17値は薬剤性過敏症症候群(DIHS) の早期診断および病勢の指標となりうる。

BACKGROUND:Drug-induced hypersensitivity syndrome (DIHS)/drug rash with eosinophilia and systemic symptoms (DRESS) is a serious acute drug reaction with fever, cutaneous eruption, lymphadenopathy, and several visceral dysfunctions. Eosinophilia is a common hematological abnormality in DIHS/DRESS suggesting that the Th2-type immune response is involved. Thymus and activation-regulated chemokine (TARC/CCL17) is a family of CC chemokines known to play an important role in Th2-mediated immune-inflammatory processes. OBJECTIVE:We investigated the pathogenic role of TARC in patients with DIHS. METHODS:Sera were obtained from 8 patients with DIHS, 7 patients with Stevens-Johnson syndrome/Toxic epidermal necrolysis (SJS/TEN), and 14 patients with drug-induced maculopapular exanthema (MPE). Serum TARC levels were measured by ELISA. TARC levels were then compared with clinical symptoms and various hematological parameters. In addition, a biopsy was taken from the lesional skin of patients with DIHS and stained with anti-TARC Ab and anti-CD11c Ab. RESULTS:Serum TARC levels in patients with DIHS were significantly higher than those in patients with SJS/TEN and MPE during the acute phase. Serum TARC levels in DIHS patients correlated with skin eruptions, serum sIL-2R levels, eosinophil counts, and serum IL-5 levels. Immunohistochemical staining revealed that TARC was mainly expressed on CD11c+ dermal dendritic cells in patients with DIHS. CONCLUSION:Serum TARC levels may be associated with the initial presentation of DIHS as well as disease activity during the course. Thus, they could be useful as an indicator for early diagnosis and assessment of disease activity in DIHS. CD11c+ dendritic cells may be the main source of TARC in patients with DIHS.博士（医学）・甲第597号・平成25年3月15日Copyright © 2012 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved

CD14 and CD16 expression in noninfectious granulomatous skin diseases

Abstract Objectives Peripheral blood monocytes are categorized as classical (CD14++/CD16−) or nonclassical (CD14−/CD16+ and CD14+/CD16+) based on their CD14 expression and CD16 expression. Maturation of classical monocytes produces CD14+/CD16+ macrophages. Our aim was to clarify the in vivo distribution of CD14 and C16 monocytes/macrophages in three granulomatous skin diseases—sarcoidosis, granuloma annulare, and lupus miliaris disseminatus faciei. Methods CD14 and CD16 immunohistochemistry, and CD14/CD16, CD16/CD11c, CD16/CD68, and CD16/factor XIIIa dual labeling were performed in tissues sampled from three cases of sarcoidosis, four cases of granuloma annulare, and three cases of lupus miliaris disseminatus faciei. Results The main infiltrating cell types were CD14+/CD16+ and CD14−/CD16++ macrophages. A small number of CD14+/CD16− macrophages localized along the granuloma periphery. Dual immunofluorescence showed that CD16+ overlapped the most with CD68+ cells, partially overlapped with CD11c+ cells, and did not overlap with FXIIIa+ cells. Conclusions Inflammatory granulomatous skin diseases are characterized by CD16+, mature and inflammatory macrophages; some of which are in the process of maturation