皮肤衰老与微小RNA

皮肤衰老是机体衰老的表现之一,由于表皮和真皮内细胞结构、功能以及细胞外基质组分的变化所致.微小RNA是一组内源性非编码小分子RNA,研究表明,微小RNA与表皮、真皮的衰老以及紫外线诱导的皮肤衰老相关.在真皮中,微小RNA可以靶向作用于细胞外基质组分和细胞黏附分子,或调控细胞周期、端粒酶活性、细胞内信号通路及氧化应激等影响成纤维细胞的衰老.在表皮中,微小RNA可通过染色质重塑和p63途径参与角质形成细胞的衰老,或靶向作用于转化生长因子β依赖或非依赖的途径影响朗格汉斯细胞的衰老.而在紫外线诱导的皮肤衰老中,微小RNA在组蛋白甲基化、细胞周期调控因子以及转录激活因子等层面参与皮肤衰老过程.此外,有一些微小RNA如微小RNA 125b参与皮肤衰老的机制可能与表皮干细胞相关.     

成人朗格汉斯细胞组织细胞增生症1例

患者男,48岁,肛周皮肤增生性斑块半年。皮肤科情况:肛周见裙边样增生性斑块,边缘游离,表面光滑。皮损组织病理示:表皮基本正常,真皮乳头水肿,可见大量浆细胞浸润,中下层可见大量增生单个核细胞成结节状浸润,胞质丰富淡染,核椭圆形或肾形,部分可见核沟,并可见大量的嗜酸性粒细胞及淋巴细胞浸润。免疫组织化学示:CD1a(+)、S-100(+)、CD68(+),Ki-67(40%+)。诊断:朗格汉斯细胞组织细胞增生症。治疗:给予口服沙利度胺50 mg,2次/d治疗,3个月后肛周皮损明显消退。     

Congenital “self‐healing” Langerhans cell histiocytosis (Hashimoto‐Pritzker disease): A report of two cases with the same cutaneous manifestations but different clinical course

Congenital self‐healing Langerhans cell histiocytosis or Hashimoto‐Pritzker disease is a rare condition present at birth or in the neonatal period characterized by small reddish‐brown crusted papulonodular lesions. In most cases these lesions are not accompanied by systemic findings and tend to involute spontaneously within weeks or months, but in other cases there may be extracutaneous involvement and/or recurrence of the disease. This emphasizes that the clinical course is variable and a long‐term follow‐up is mandatory in order to reveal possible systemic involvement. We describe two cases of congenital self‐healing Langerhans cell histiocytosis with widespread and very similar cutaneous manifestations but different clinical course. The first patient had multisystemic disease (with lymph nodes, bones, liver and lungs affected) that required systemic therapy. The second patient had cutaneous and bony lesions that resolved spontaneously. We think that the adjective “self‐healing” is misleading and should be abandoned. We stress the importance of a complete systemic evaluation and the necessity of a long‐term follow‐up.     

Langerhans cell sarcoma in a patient with hairy cell leukemia: common clonal origin indicated by identical immunoglobulin gene rearrangements

Histiocytic/dendritic cell sarcomas are rare tumors, a few of which have been reported in association with B-cell lymphoma/leukemia. Isolated reports have documented identical immunoglobulin gene rearrangements suggesting a common clonal origin for both the sarcoma and the B-cell neoplasm from individual patients. We report a case of a 75-year-old male with hairy cell leukemia who subsequently developed Langerhans cell sarcoma 1 year after his primary diagnosis of leukemia. The bone marrow biopsy containing hairy cell leukemia and skin biopsies of Langerhans cell sarcoma were evaluated by routine histology, immunohistochemistry, flow cytometric immunophenotyping and PCR-based gene rearrangement studies of the immunoglobulin heavy chain and kappa genes. The hairy cell leukemia showed characteristic morphologic, immunohistochemical and flow cytometric features. The Langerhans cell sarcoma showed pleomorphic cytology, a high mitotic rate and characteristic immunohistochemical staining for Langerin, S100 and CD1a. There was no evidence of B-cell differentiation or a background B-cell infiltrate based on the absence of immunoreactivity with antibodies to multiple B-cell markers. Identical immunoglobulin gene rearrangements were identified in both the hairy cell leukemia and Langerhans cell sarcoma specimens. Despite the phenotypic dissimilarity of the two neoplasms, identical immunoglobulin gene rearrangements indicate a common origin.     

RADIOLOGICAL EVALUATION OF PATIENTS WITH PITUITARY LANGERHANS CELL HISTIOCYTOSIS AT DIAGNOSIS AND AT FOLLOW-UP

This study evaluated pituitary imaging findings in 13 patients with Langerhans cell histiocytosis (LCH) with diabetes insipidus. Nine patients were evaluated with pituitary magnetic resonance imaging (MRI), 3 with brain computed tomography, and 1 with brain MRI. The infundibulum was thickened in 11 (84.6%) patients, thread-like in 1 (7.7%), and normal in 1 (7.7%). Posterior pituitary intensity was absent in 10 patients (76.9%); in 4 patients, the pituitary gland was small in size, and 2 patients had atrophic pituitary. Three had a small sella. Infundibular thickening and absence of posterior pituitary intensity were the most common radiological findings. MRI imaging should be used to follow up patients with pituitary histiocytosis, and patients with LCH and diabetes insipidus should be followed for pituitary atrophy.     

LANGERHANS CELL HISTIOCYTOSIS: Retrospective Evaluation of 123 Patients at a Single Institution

The aim of this study was to retrospectively evaluate clinical characteristics at diagnosis and outcome of patients with Langerhans cell histiocytosis (LCH). From October 1987 to March 1996, 133 patients with confirmed LCH were admitted to Hospital JP Garrahan in Buenos Aires (123 evaluable). Median age was 5 years (range 15 days to 18 years). Initial organ involvement included bone 114 patients, ear 34, skin 30, liver 18, lung 14, lymph nodes 14, spleen 12, diabetes insipidus 9, and bone marrow 2. Nineteen patients had organ dysfunction, pulmonary 14, hematological 14, and hepatic 12. Two groups were defined: Group A included patients with single system disease (unior multifocal) and group B multisystem (with or without organ dysfunction). In group A (n = 82), 24 patients were treated with chemotherapy (prednisone and vinblastine), 21 with surgery, 15 received radiotherapy, and 22 were only observed. Patients of group B ( n = 41) were treated with chemotherapy consisting of prednisone and vinblastine, DALHX 83, or LCH1-based chemotherapy. At a median follow-up of 3 years (range 1 month-8 5/12 years) 93% of patients of group A and 39% of group B survive free of reactivation. In group B, 22% had a reactivation and 39% died of progressive disease. Sequelae were detected in 35 patients (28%), which included diabetes insipidus in 17, hearing loss in 13, bony sequelae in 11, sclerosing cholangitis in 6, and lung fibrosis with bullae in 6. Two patients had a subsequent malignant disease. A total of 17 (14%) patients died and 16 of them belonged to the group B: 13 died of progressive disease, 2 due to sclerosing cholangitis (with sepsis in one case and encephalitis in the other one), 1 with progressive disease and associated myelofibrosis, and 1 patient of group A with active disease and brain stem tumor. Patients who had organ dysfunction had a reactivation free survival of 32%. All these patients survived with sequelae. Logistic regression analysis showed that organ dysfunction and hematological involvement had significant predictive values in relation to death. Patients of group A had an excellent survival rate, whereas in those of group B a high mortality was found, especially in the subgroup of patients with organ dysfunction. Lahey's criteria should be revised. Sequelae were also more common in this group.     

Langerhans cell histiocytosis in non‐twin siblings

Langerhans cell histiocytosis (LCH), which has unknown pathogenesis, can manifest as many kinds of signs and symptoms at any age. Although its genetic background has not been exactly identified, the familial clustering of this disease has been described in some reports. It is very uncommon, however, in siblings who are not monozygotic or dizygotic twins. Reported herein is a case of LCH in non‐twin siblings (younger sister and elder brother) who were diagnosed at 3.3 and 14.5 years of age, respectively, and successfully treated with chemotherapy, with BRAF V600E mutation status, and a brief review of the literature.     

Regulation of the cutaneous allergic reaction by humidity

Humidity is 1 of the environmental factors which regulate skin conditions. Effects of humidity on the cutaneous immune reaction were examined. Contact hypersensitivity to 2,4,6-trinitrochlorobenzene was elicited in C57BL/6 mice. The reaction was greater in mice housed under low humidity conditions (about 10%) for 2 days, at either the induction or elicitation phase, than in mice housed under rather high humidity conditions (80%). After housing under controlled humidity for 2 days, the number of I-A positive cells was 16% higher in the epidermis exposed to the dry condition. The increased population of FITC-positive cells were in regional lymph nodes after painting of FITC during housing under lower humidity. Our study demonstrated that the cutaneous immune reaction is regulated by environmental humidity and suggested 2 possible mechanisms, i.e., increase in Langerhans cells and increased penetration of allergen with low humidity.