Primary Cutaneous Langerhans Cell Histiocytosis Treated with Photochemotherapy

A 23-year-old man with Langerhans cell histiocytosis presented with asymptomatic, purplish, slightly scaly, confluent papules of one year's duration. Histological studies of biopsy specimens revealed a dense infiltrate of histiocytic mononuclear cells beneath the epidermis; these cells reacted strongly with anti-S-100 antibodies. Extensive investigations failed to detect systemic involvement. He was treated with repeated oral 8-methoxypsoralen (8-MOP) plus ultraviolet A (PUVA) therapy three times a week for two months and then once or twice with maintenance phototherapy. The lesions did not recur during the four-month follow-up period.     

即时型PUVA对郎格罕细胞和接触过敏的影响

在实验动物中研究了即时型光化学疗法对表皮郎格单细胞数量和形态的影响及对接触过敏反应的抑制，并与常规使用的光化学疗法进行了对比，结果表明二种方法间无差异，３Ｊ/ｃｍ２的即时型光化学疗法无红斑反应并能引起郎格罕细胞数量和形态的变化，并且通过诱导抑制性淋巴细胞抑制接触过敏反应。还探讨了有关致癌的可能性。     

The inhibitory effect of PUVA on the immunity of experimental dermatophytosis in guinea pigs

Summary The effect of topical PUVA on the disease course and immunity of T. mentagrophytes dermatophytosis was investigated in guinea pigs. Animals which had been inoculated on nontreated skin showed mild erythematous lesions with scaling in a few days and then developed the most intense reaction between days 10 and 14. The lesions resolved completely by the third week. On the other hand, animals which had been inoculated on the PUVA-treated sites showed only mild squamous, erythematous lesions until the fourth postinfective week, when the intense reaction began to appear. Complete regression was observed by the fifth week in these animals. Trichophytin tests performed on the 14th day were positive in the guinea pigs of nontreated group, while negative in the PUVA-treated animals. The latter group revealed a positive reaction on the fifth week. PUVA did not show inhibitory effect on the sensitization by intracutaneous injection of trichophytin antigen. The PUVA treatment depleted the ATPase-positive Langerhans' cells. These results indicate that PUVA treatment suppresses the immunity of dermatophytosis and delays the spontaneous resolution of the lesions, and suggest that the Langerhans' cell is involved in the development of cell-mediated immunity in experimental dermatophytosis.     

表现为结节性损害的老年皮肤朗格汉斯细胞组织细胞增生症1例

患者男,63岁。头皮、额部、双耳前至面颊部、两下颌部和胸背部暗红色浸润性丘疹、结节、斑块6年余,伴严重瘙痒。浅表淋巴结和胸部CT和腹部彩超均未见异常。皮损组织病理示:真皮大量单个核细胞弥漫浸润,部分细胞体积较大,胞质淡,核椭圆形,可见核沟。免疫组织化学检查示:CD1a及S-100染色阳性。诊断:皮肤朗格汉斯细胞组织细胞增生症。     

老人皮肤朗格汉斯细胞组织细胞增生症1例

朗格汉斯细胞组织细胞增多症（LCH）是以朗格汉斯细胞增生为特征的多系统侵犯的反应性增生性疾病,小儿多见,成人少见,老人罕见,对1例62岁老人的红皮病样损害伴明显瘙痒患者行临床,皮肤和淋巴结病理及免疫组化等检查,诊断LCH,该患者经合理治疗,取得满意疗效。     

Electron-microscopic Observation of a Human Epidermal Langerhans Cell in Mitosis

Langerhans cells are dendritic cells of the epidermis originating from bone marrow precursors which may exceptionally undergo mitosis within the skin. We report herein an electron-microscopic observation of a dividing LC within a seemingly hyperproliferative human epidermis. This observation further underlines the self-reproducing capacity of LC in situ and suggests that LC may respond to the same mitogenic stimuli as keratinocytes.     

Langerhans cell migration is modulated by N-sulfated glucosamine moieties in heparin

Dendritic cell (DC) migration into and out of tissues is important for the generation of primary immune responses to antigens encountered in tissues. In order to study the mechanisms involved in DC migration we used a skin explant system and quantitated the number of Langerhans cells (LC), which are immature precursors of DC in skin-draining lymph nodes, remaining in the epidermis in response to incubation with various biomolecules. This paper shows that LC trafficking in epidermis is a metabolically active process that is modulated by heparin, specifically by N-sulfated glucosamine moieties in heparin. This is the first demonstration of structural specificity in the biochemical requirements for DC migration in a tissue and therefore is important to understanding DC migration in general.     

Extensive cutaneous Langerhans cell histiocytosis in an elderly woman

Langerhans cell histiocytosis (LCH), especially with involvement limited to the skin in adults is a rare entity. Primary cutaneous LCH in older patients usually follows a benign course and can regress spontaneously. We report a fatal case of disseminated cutaneous LCH in an elderly woman. A 64‐year‐old woman presented with confluenced erythematous macule and diffuse papuloscaling and papulocrusted lesions on the trunk that became erosive on the area of axillae and groins. Histopathological study of skin specimens showed extensive epidermotropic and folliculotropic, lichenoid infiltration of Langerhans' cells. Positive immunohistochemical staining for CD1a and S‐100 protein in Langerhans' cells, and numerous typical Birbeck granules in the cytoplasm of Langerhans' cells by electron microscopy study confirmed the diagnosis of LCH. Chest X‐rays and computed tomography scans showed mild interstitial pneumonia without a honeycomb appearance. The patient was diagnosed with LCH. Her general condition worsened rapidly and she died 1 month after diagnosis. Because extracutaneous involvement of LCH had been ruled out by laboratory and imaging investigations, we would like to believe this case should be classified as “malignant” LCH based on the clinical course.     

Morphological identification of Langerhans cells in mouse epidermal cell suspension by scanning electron microscopy

The distribution of Ia^k antigens on suspended epidermal cells prepared from C3H/He mice by trypsinizing their ear skin was examined by the scanning immunoelectron microscopic method using antibody against the antigen and antibody bacteriophage T4 conjugates as a visual marker. Ia^k antigens were found to be distributed diffusely over a cell type with a relatively flat shape and a number of microvilli and ruffles. These cells are considered to be Langerhans cells. Significance of these findings is discussed.     

中波紫外线照射对表皮朗格汉斯细胞p53蛋白磷酸化表达的影响

目的：研究皮肤朗格汉斯（Langerhans）细胞（LC）在不同剂量中波紫外线（UVB）照射前、后p53蛋白磷酸化水平的差异。方法：联合采用密度梯度离心和免疫磁珠的方法分离纯化LC,将LC分为实验组和对照组,实验组分别接受30、60和90mJ／cm^2 UVB辐射,辐射后4h提取总蛋白,采用Western—blotting法检测各组细胞中p53蛋白及磷酸化p53蛋白的表达量,并比较两者之间的差异。结果：接受UVB辐射后,皮肤LC中p53蛋白表达基本无变化,而p53蛋白磷酸化水平显著升高,差异具有统计学意义,并呈剂量依赖性。结论：UVB辐射可刺激p53蛋白磷酸化,并呈剂量依赖性,进而诱导p53蛋白活化,发挥其下游功能。     

Stat3 activation in epidermal keratinocytes induces Langerhans cell activation to form an essential circuit for psoriasis via IL-23 production

Background

Psoriasis is an inflammatory disease associated with aberrant crosstalk between the epidermis and immune system. However, the role of Langerhans cells (LCs) in psoriasis remains controversial.

Modulation of Ia+ Langerhans cell numbers in vivo by cultured epidermis derived supernatants and by GM-CSF

Abstract This paper demonstrates that epidermal cells in culture produce an activity which can increase the frequency of Ia⁺ epidermal Langerhans cells (LC). This was achieved by treating mice topically with a mixture containing supernatant derived from primary culture of murine epidermis (ES) and a synthetic corticosteroid, triamcinolone acetonide (TAG). The presence of the supernatant in the mixture partially protected the Ia⁺ LC from depletion by the steroid. The Ia⁺ LC frequency increasing activity was measured as the difference between the Ia⁺ LC frequency due to treatment with steroid mixed with supernatant and the Ia⁺ LC frequency due to treatment with steroid mixed with negative control medium. The mean frequency of Ia⁺ LC in epidermis treated with TAC mixed with ES was 606(SD 43) cells/mm², as compared with 486 (SD 68) cells/mm² in the epidermis treated with TAC mixed with control medium. The activity appeared to be caused by (a) proteinaceous factor(s). A fraction of ES which was retained above a ≥10 KDa molecular weight cut-off membrane was capable of partially protecting Ia⁺ LC frequency from TAC depletion. Supernatants from cultured lymph nodes, dermis as well as the squamous cell carcinoma lines T7 and T79, but not the human osteosarcoma cell-line 143B, also contained similar activities. We demonstrate that GM-CSF also increased the number of Ia⁺ epidermal LC when applied topically to mouse skin in this system. Therefore, using this Ia⁺ LC frequency modulation system, we propose that GM-CSF is one example of a cytokine which may be involved in the regulation of Ia⁺ LC numbers in epidermis and that epidermal cells produce factors which can increase the number of Ia⁺ LC.     

Ultraviolet B radiation suppresses Langerhans cell migration in the dermis by down-regulation of alpha4 integrin

Background/Purpose: Ultraviolet B (UVB) radiation affects the migration and function of epidermal Langerhans cells (LC) and causes immunosuppression of contact hypersensitivity. It is known that LC leaves the epidermis after exposure to UVB. To know the behavior of LC in the dermis after UVB radiation, we studied the effect of UVB radiation on the expression of integrin families on freshly isolated or cultured murine LC. We also examined whether UVB radiation affects the migration of LC to secondary lymphoid tissue chemokine (SLC/6Ckine).
Methods: Integrin expressions of murine LC cultured in epidermal cell suspension were analyzed using flowcytometry. We used murine LC sorted flowcytometrically for binding assay to extracellular matrix and for migration assay to chemokine. Skin explant assay and immnohistochemical staining for 'cords formation' were performed as previously described.
Results: Twenty and 40 mJ/cm² of UVB radiation down-regulated the expression of α4 integrin on 24 h-cultured LC, but not that of α6, β1, or β4 integrin. The number of cultured LC adhered to fibronectin, a ligand for α4 integrin, was decreased after UVB irradiation, while that to laminin, a ligand for α6 integrin, was not influenced. UVB radiation reduced the number of migrating LC to SLC. Furthermore, skin sheet explant experiments showed that UVB radiation inhibited the 'cords' formation in dermal vessels of the 48 h-cultured skin.
Conclusions: These data suggest that UVB radiation may suppress the migration of LC from the dermis to lymphatic vessels. UVB radiation may downregulate the adherence of LC to dermal fibronectin and migration to SLC, and consequently suppress the migration of LC from the UVB-irradiated dermis to lymphatics.     

Combination therapy with extracorporeal photopheresis,interferon‐α, PUVA and topical corticosteroids in the management of Sézary syndrome

Background: Extracorporeal photopheresis (ECP) is recommended for the treatment of Sézary syndrome (SS), the leukemic variant of cutaneous T‐cell lymphoma (CTCL). Several combination therapies are used to increase response rates to ECP. Patients and Methods: We report our experience with the combination therapy of ECP, interferon‐α, PUVA and topical corticosteroids in SS. Results: The treatment outcome in 12 SS patients was retrospectively analyzed and showed an overall response rate to this combination treatment of 42 % with 4/12 patients achieving a partial remission and 1/12 patients a stable disease. The median overall survival time was 42 months. We investigated several clinical and laboratory parameters as an indicator for a response to treatment in our patient cohort. A combined analysis of the erythroderma assessment scale, WBC, LDH, CD4/CD8 ratio and the number of Sézary cells revealed that a reduction of several parameters significantly correlated with response to treatment. The parameters which correlated best with response were number of Sézary cells, CD4/CD8 ratio and WBC. Conclusions: The investigated combination therapy was effective and well‐tolerated in a subgroup of SS patients but needs to be evaluated in a larger patient population.     

Modulation of MHC class II+ Langerhans cell numbers in corticosteroid treated epidermis by GM-CSF in combination with TNF-α

Abstract It is important to understand how dendritic cells (DC) are recruited, maintained and stimulated to migrate from tissues to lymph nodes. This is because DC are potent initiators of primary immune responses and candidates for vaccine development. Identification of factors which could lead to increased numbers of DC in tissues could affect immune responses by modulating their interaction with antigen which penetrates the tissue. To identify cytokines which could increase DC in tissues we tested the ability of GM-CSF, TNF-α and IL-6 to partially prevent steroid depletion of Langerhans cells (LC) from the epidermis. Cytokines diluted in serum-containing medium were compared with cytokines diluted in albumin-containing, serum-free medium in order to determine a minimum combination of cytokines required to increase LC and the effect of serum on the LC-increasing activity of cytokines. In the presence of serum, GM-CSF or TNF-α could increase LC frequency compared to the control; but in the absence of serum neither of these cytokines were effective unless they were combined with each other. In the presence of serum the combination of GM-CSF with TNF-α was ineffective. The data support the hypotheses that GM-CSF and TNF-α are both important in regulating LC numbers in the epidermis in vivo. Serum may modulate how each of these cytokines, separately or in combination, affect LC frequency in the epidermis–GM-CSF and TNF-α separately probably interact with other factors present in serum to increase LC frequency, whereas in combination it is possible that these separate effects are cancelled in the presence of serum. TNF-α and GM-CSF together, in the absence of serum, form one combination of a minimum number of cytokines which can regulate LC frequency in the epidermis; and IL-6 alone, or in combination with GM-CSF, does not increase LC frequency.     

Lymphomatoid Papulosis Followed by Anaplastic Large Cell Lymphoma in a Pediatric Patient

Lymphomatoid papulosis (LyP) is a benign, self-healing, papular eruption that can wax and wane over time. Transformation to T-cell lymphoma has been well documented in 10% to 20% of adults with LyP. However, this transformation rarely occurs in patients younger than 20 years of age. Here, we present the first known pediatric patient in Korea, a 12-year-old boy who developed a subcutaneous nodule on the scrotum 13 months after papulonecrotic lesions of LyP were identified on both lower extremities and face. Histological and immunohistochemical examination of the subcutaneous nodule revealed anaplastic large cell lymphoma (ALCL). A T-cell receptor gene rearrangement analysis demonstrated an identical rearranged pattern in the two specimens, indicating that a common T-cell clone had proliferated over time in both the LyP and ALCL lesions.