蕈样肉芽肿的治疗和预后研究进展

蕈样肉芽肿的进程、患者的年龄及外周血乳酸脱氢酶的水平与患者的预后密切相关。单独或联合应用UVA或UVB光疗、光化学疗法和注射干扰素、白介素 2等免疫疗法已经成功用于各期蕈样肉芽肿的治疗。外用氮芥或卡莫司汀化学治疗对于早期蕈样肉芽肿疗效较好 ;而对于进展期和红皮病型蕈样肉芽肿 ,全身皮肤电子束照射及低剂量的化学药物如甲氨蝶呤、羟基脲、苯丁酸氮芥和阿霉素等系统应用安全有效。上述提示 ,应根据不同的病情选择适宜的疗法     

皮肤T细胞淋巴瘤的治疗进展

皮肤T细胞淋巴瘤(CTCL)是一组原发于皮肤的非霍奇金淋巴瘤。蕈样肉芽肿是最常见的CTCL类型,多数患者处于疾病早期,发展缓慢,以局部治疗为主。但进展期(ⅡB期～Ⅳ期)患者可累及淋巴结、血液和内脏器官,尚缺少有效的治疗方法,进展期患者预后不佳,5年生存率仅为47%。近年随着对肿瘤发病机制的认识加深,出现多种新型疗法,如单克隆抗体和抗体偶联药物、表观遗传学修饰药物、免疫检查点抑制剂等。该文对CTCL的发病机制及治疗进展作一综述。     

蕈样肉芽肿的发病机制及治疗进展

蕈样肉芽肿的发病机制目前仍不清楚,近年来对蕈样肉芽肿皮肤淋巴细胞归巢机制、淋巴细胞凋亡异常以及基因异常的研究,为揭示蕈样肉芽肿发病以及治疗提供了一些新的观点。除传统的光化学疗法、放疗、化疗、体外光化学疗法外,维A酸类、干扰素、白介素2融合蛋白、重组白介素12、人源化单克隆抗体等免疫调节剂对早期蕈样肉芽肿有较好的疗效。     

血清胸腺活化调节因子水平与蕈样肉芽肿病程进展的关系

蕈样肉芽肿属皮肤T细胞淋巴瘤，临床分为3期，即斑片期、斑块期和肿瘤期。以往对蕈样肉芽肿病程的评估主要以肿瘤浸润的深度、血清乳酸脱氢酶、可溶性白介素-2受体(sIL-2R)水平作为指标，并认为蕈样肉芽肿主要是以Th2型细胞因子如干扰素-γ的表达为主。但早期蕈样肉芽肿中的T     

PUVA联合α-干扰素及氮芥外用治疗斑块期蕈样肉芽肿1例

患者女,45岁。全身浸润斑块、瘙痒18年,诊断为蕈样肉芽肿斑块期。采用ＰＵＶＡ联合α 干扰素肌注及氮芥外用治疗4周,皮损消退,留有较重色素沉着。     

微小RNA在蕈样肉芽肿中的研究进展

蕈样肉芽肿是一种原发性皮肤T细胞淋巴瘤,临床表现多种多样,极易误诊.微小RNA(miRNA)是一种长约22个核苷酸的非编码小RNA,参与细胞分化、增殖、代谢、凋亡等生命活动,miRNA的功能失调对肿瘤的发生起作用.目前发现,一些miRNA在蕈样肉芽肿的发病、辅助诊断、判断预后起作用,并对蕈样肉芽肿的治疗具有潜在价值.如miR-155、miR-22、miR-150能促进蕈样肉芽肿的发病,miR-233、miR-200c则抑制蕈样肉芽肿.一组miRNA,miR-155、miR-203和miR-205,有助于鉴别诊断皮肤T细胞淋巴瘤和良性皮肤病.     

血清胸腺活化调节因子水平与蕈样肉芽肿病程进展的关系

蕈样肉芽肿属皮肤T细胞淋巴瘤,临床分为3期,即斑片期、斑块期和肿瘤期。以往对蕈样肉芽肿病程的评估主要以肿瘤浸润的深度、血清乳酸脱氢酶、可溶性白介素- 2受体(sIL - 2R)水平作为指标,并认为蕈样肉芽肿主要是以Th2型细胞因子如干扰素-γ的表达为主。但早期蕈样肉芽肿中的T细胞克隆并不表达Th1 /Th2型细胞因子。因此,目前尚不清楚在各期蕈样肉芽肿中是否有Th1 /Th2型细胞因子的表达。作者研究了2 0例经临床和病理证实的蕈样肉芽肿患者(男1 0例,女1 0例)。其中斑片期8例、斑块期7例、肿瘤期5例。对照组为寻常型银屑病1 0例、健康人1 0…     

蕈样肉芽肿的治疗

(一)现时对于蕈样肉芽肿治疗的原则是:在肿瘤前期(即Ⅰ期湿疹样、鳞屑性红斑等的多型初期发疹期和Ⅱ期扁平隆起浸润性红斑的扁平浸润期)应尽可能施以姑息疗法以求控制,而在Ⅲ期肿瘤期特别当皮肤以外其他内脏也受到侵袭时则应施行象对恶性淋巴瘤那样的强力的全身疗法。为了控制Ⅰ和Ⅱ期患者的皮疹,又不损害患者的健康,在皮肤科局部疗法占很大的比重。当然,局部疗法对于蕈样肉芽肿的全期都是必要的,而在占蕈样肉芽肿病期最长时间的Ⅰ和Ⅱ期则局部疗法是其主要治疗手段。     

肉芽肿性蕈样肉芽肿

肉芽肿性蕈样肉芽肿是蕈样肉芽肿的一种罕见的组织学变异。复习文献闹述肉芽肿性蕈样肉芽肿的临床表现、组织病理变化、免疫组化染色、发病机制、诊断和鉴别诊断与预后。     

蕈样肉芽肿:致癌物质与中枢神经受累

本文报道了3例蕈样肉芽肿,患者均长期从事火箭固体燃料生产,在制作过程中接触致癌物质,其中2例发生中枢神经系统肿瘤.典型病例,男,56岁,1970年发生皮肤瘙痒性红斑,外用类固醇激素软膏,紫外线及浅层X线照射均无效,1973年皮肤病理证实为蕈样肉芽肿(MF),在4年内局部外用盐酸氮芥效果良好.1978年皮损扩展,并发生结节及斑块,应用电子束全身照射,1980年双肺门浸润,经胸腔穿刺证实为MF,应用环磷酰胺,阿霉素,长春碱,氨甲喋呤及强的松治疗后,症状缓解,1981年5月皮损播散,发生多处溃疡,经胞嘧啶治疗后,皮损及肺部病变明显改善,同年6月发现虚弱、乏力、迟钝.家属回忆2年前即     

Mycosis fungoides and Sezary syndrome: therapeutic approach and outcome in 113 patients

BACKGROUND: Mycosis fungoides (MF) and Sezary syndrome (SS) are the most common forms of cutaneous T-cell lymphoma (CTCL). Various topical and systemic therapeutic alternatives are available, but there is no standard or definite curative treatment regimen. When making a decision about the appropriate treatment modality, the age and compliance of the patient, stage of the disease, treatment accessibility, and previous treatment history should be considered. AIM: To determine the therapeutic response of patients with MF and SS to different treatment modalities. Patients were evaluated with respect to their clinical and demographic features. METHODS: One hundred and thirteen patients diagnosed clinically and dermatopathologically with MF and SS between March 1984 and June 2001 were included in the study. RESULTS: Of the 113 patients studied, 110 had a diagnosis of MF and three had a diagnosis of SS; 101 patients (89.4%) were diagnosed with early stage (IA, IB, IIA) and 12 (10.6%) with late stage (IIB, III, IVA, IVB) disease. The age at diagnosis varied between 12 and 81 years (mean, 45.6+/-15.8 years). Fifty-five (48.7%) patients were male and 58 (51.3%) were female. The duration of the skin lesions varied between 1.5 months and 32 years (mean, 6.1 years). Psoralen plus UVA (PUVA) was the most commonly used initial treatment modality in early stage disease (91%), with a complete remission (CR) rate of 80.4%. With PUVA+interferon-alpha (INF-alpha) treatment, CR was 57% in the early stages and 33.3% in the late stages. For late stage disease, systemic therapies, such as pentostatin, gemcitabine, and fludarabine, alone or in combination with INF-alpha, were preferred. Of the 113 patients, eight (7% of the total and 57.1% of the advanced stage cases) died of MF; 21.4% of the late stage patients showed partial remission and 14.2% showed CR. None of the patients diagnosed with early stage disease died of MF, but two (1.9%) progressed to late stage disease. CONCLUSIONS: PUVA and PUVA+INF-alpha are effective treatment modalities, especially for early stage MF. Once the disease has progressed, both MF and SS are very resistant to treatment regimens, including chemotherapeutic agents. It is important to diagnose and treat these diseases, especially MF, in the early stages for lasting remission.     

Topical nitrogen mustard therapy in patients with mycosis fungoides or parapsoriasis

Background Topical nitrogen mustard is a chemotherapeutic agent used in treatment of mycosis fungoides (MF). Objective To evaluate the response and side effects in patients with MF and parapsoriasis treated with topical nitrogen mustard. Methods A retrospective study of treatment response in 116 patients diagnosed with MF and 71 patients with parapsoriasis and treated with topical nitrogen mustard from 1991 to 2009. Results Overall response rate and complete response (CR) rate was 91.4% and 53.4% in patients with MF and 90.1% and 40.8% in patients with parapsoriasis, respectively. Relapse following CR was observed in 67.7% in patients with MF and 62.1% in patients with parapsoriasis. Freedom‐from‐relapse was higher in patients with T1‐T2 than in T3 disease (P < 0.01). Progressive disease (PD) occurred in 25.0% and 26.8% in patients with MF and parapsoriasis, respectively. Progression‐free survival was similar in patients with T1‐T2 compared with T3 (P = 0.79) and T4 disease (P = 0.22) and lower in patients with parapsoriasis with <10% than >10% skin involvement (P = 0.05). Conclusion The present study confirms that topical nitrogen mustard is a safe and effective therapy. The treatment response in patients with parapsoriasis was not statistically different from the response in patients with MF. This supports, that parapsoriasis is not a distinct entity, but an early stage of MF. Nitrogen mustard should therefore still be considered as an important treatment modality in patients with early stages (parapsoriasis) and later stages of MF either as monotherapy or in combination with other topical or systemic therapies.     

皮肤T细胞淋巴瘤的治疗选择

皮肤T细胞淋巴瘤是一种少见的淋巴细胞增生性疾病,依据疾病的分类及分期不同,治疗选择有很大差异性。多数的皮肤T细胞淋巴瘤病程进展缓慢,诸如早期的蕈样肉芽肿和淋巴瘤样丘疹病,只需要选择皮肤局部治疗的方案。侵袭性或顽固性如Sézary综合征、复发性CTCL等,则需系统治疗,包括化疗。本文对国内现有药物及最新治疗方法进行综述。     

Safety and Efficacy of Low-Dose Bexarotene and PUVA in the Treatment of Patients with Mycosis Fungoides

Background:The new rexinoid bexarotene is a retinoid X receptor antagonist and immune response modifier. Although combinations of oral bexarotene and psoralen plus UVA (PUVA) have been tried in patients with all stages of mycosis fungoides (MF), the dosage of bexarotene used in these combination regimens has been variable. Objective: To assess the efficacy and safety of low-dose oral bexarotene and PUVA in patients with relapsed or treatment-refractory MF following monotherapy with multiple agents including PUVA, narrow-band UVB, interferon-?, oral bexarotene, and topical corticosteroids. Method: Combination therapy with PUVA three times weekly and low-dose oral bexarotene (150 or 300 mg/day, depending on physicians’ preference) was administered to 14 patients, seven men and seven women (median age 49.5 years, range 30-75 years), with relapsed or refractory MF stages I-III. All responders received maintenance treatment at the same bexarotene dose that induced remission until progression or unacceptable toxicity. Results: Low-dose oral bexarotene combined with PUVA was associated with an overall response rate (complete response or partial response) in 67% of the nine patients with refractory MF who completed the treatment course. Of these nine patients, four had a complete response, two had a partial response, one had stable disease, and two had progressive disease. Five patients withdrew because of hyperlipidemia. Oral bexarotene was continued as maintenance therapy in three of the four complete responders (one refused); two of these patients relapsed 2-10 months after PUVA discontinuation. Patients with partial response or stable disease received the combination for 3-5 months and were switched to another treatment regimen because of lack of further response. Therapy was fairly well tolerated. Conclusion: In a select population of patients who had not responded to at least one monotherapy for early-stage MF, a combination of low-dose oral bexarotene and PUVA was successful in achieving a satisfactory overall response rate in 67% of patients who completed the treatment course and was fairly well tolerated. Limitations of the study include the small number of patients evaluated, its retrospective nature, and the fact that patients were commenced on different bexarotene starting doses (150 or 300 mg/day), depending on physicians’ preference.     

Early-stage mycosis fungoides, parapsoriasis en plaque, and pregnancy

BACKGROUND: Non-Hodgkin's lymphoma (NHL) coincident with pregnancy is rare, and the literature regarding mycosis fungoides (MF), the most common primary cutaneous NHL, and pregnancy is strikingly sparse. The effect of pregnancy on MF, or on parapsoriasis en plaque (PPP), and the effect of these diseases on pregnancy, are still unknown. OBJECTIVE: To study the effect of pregnancy on MF and PPP and the impact of these diseases on pregnancy. METHODS: The files of the MF and PPP patients seen during the past 12 years in our department were reviewed to search for patients who had been pregnant during the course of their disease. RESULTS: Nine women who met the study criteria were identified, seven with early-stage MF and two with PPP. A total of 12 pregnancies was recorded: nine in patients with MF and three in patients with PPP. In none of the patients was there any indication that pregnancy changed the course of MF or PPP. Of the 12 pregnancies, 11 were normal; one was naturally aborted. Two of the patients were treated with topical steroids during pregnancy. One patient was treated with narrow-band ultraviolet-B combined with topical steroids. The rest preferred to avoid any therapy. CONCLUSIONS: Pregnancy appeared to have no impact on the course of early MF or PPP, and no adverse effect was noted on pregnancy. Further studies are needed to clarify the interplay between pregnancy and MF or PPP.     

Treatment of mycosis fungoides using a 308-nm excimer laser: two case studies

Early-stage mycosis fungoides (MF) is most commonly treated with skin-directed therapies such as topical steroids, phototherapy (broadband or narrowband UVB), photochemotherapy (psoralen plus UVA), topical nitrogen mustard, and total skin electron-beam irradiation. Recently, several small studies have demonstrated the efficacy of the 308-nm excimer laser in the treatment of early-stage MF. This xenon-chloride laser, which emits monochromatic excimer light at the 308-nm wavelength, has been approved by the Food and Drug Administration to treat psoriasis since 1997 and to treat vitiligo since 2001. We report two patients in which patch-stage MF was treated with a 308-nm excimer laser. Our findings confirm previous observations that the 308-nm excimer laser is a safe, effective, and well-tolerated therapy for early stage MF.     

Narrowband UVB and psoralen-UVA in the treatment of early-stage mycosis fungoides: a retrospective study

BACKGROUND: Treatment of early-stage mycosis fungoides (MF) consists of topical steroids, phototherapy (UVB), photochemotherapy (psoralen plus UVA [PUVA]), topical nitrogen mustard, or total skin electron-beam irradiation. It has been reported that the same effective UVB dose is safer than PUVA regarding carcinogenicity and produces fewer side effects. Narrowband UVB (311 nm) results in less irritation and erythema and is more effective compared with broadband UVB. OBJECTIVE: Our purpose in this retrospective study was to analyze the response to treatment, relapse-free interval, and irradiation dose in 56 patients with early-stage MF (stage Ia and Ib). A total of 21 patients were treated with narrowband UVB (311 nm); 35 patients were treated with PUVA. RESULTS: Narrowband UVB treatment led to complete remission in 17 of 21 patients (81%), partial remission in 4 of 21 (19%), and none showed progressive disease. PUVA treatment led to complete remission in 25 of 35 patients (71%), partial remission in 10 of 35 (29%), and none showed progressive disease. The mean relapse-free interval for patients treated with UVB was 24.5 months (range, 2-66 months) and for patients treated with PUVA, 22.8 months (range, 1-43 months). CONCLUSION: Narrowband UVB therapy for patients with early-stage MF is an effective treatment modality. It has several advantages over treatment with broadband UVB and PUVA. When treating patients with early-stage MF it may be beneficial to start with narrowband UVB therapy and, if there is progression or no response, switch to PUVA therapy.     

Pediatric Follicular Mucinosis: Presentation,Histopathology, Molecular Genetics,Treatment, and Outcomes over an 11‐Year Period at the Mayo Clinic

Follicular mucinosis (FM) and folliculotropic mycosis fungoides (MF) are rare in children, and data regarding long‐term outcomes are limited. We sought to describe clinical and histopathologic findings of children with FM with and without MF, as well as treatments administered and clinical outcomes. We conducted a retrospective chart review of patients younger than 22 years (at time of diagnosis) with a biopsy demonstrating FM who were seen in the Dermatology Department at the Mayo Clinic from September 1, 1999, to September 1, 2010. Eleven patients (six male, five female) ages 11 to 19 years at the time of diagnosis met the inclusion criteria. Follow‐up data were available for 10 patients, with a mean duration of 4.9 years. The head, neck, and extremities were the most common sites of involvement, and lesions were follicular‐based papules (18%), scaly alopecic patches and plaques (45%), or a combination of the two (36%). Overall, three patients were confirmed to have MF. T‐cell receptor gene rearrangement demonstrated clonality in two cases and was equivocal in one case. Treatments included topical corticosteroids, topical retinoids, oral minocycline, and, in patients with MF, ultraviolet light and topical bexarotene. Lesions resolved completely in seven patients, partially in one, and not at all in two (no follow‐up data on one patient). Of the three patients with MF, two had complete resolution, and one has intermittent flares. To our knowledge, no patients developed other lymphoproliferative disorders. FM in children is rare. A histopathologic diagnosis of FM does not equate to folliculotropic MF in all cases. Most patients responded to treatment with topical steroids, topical retinoids, or phototherapy. In our series of patients, the disease ran a benign course.     

Durable remission of folliculotropic mycosis fungoides achieved with a combined topical treatment with cytarabine and carmustine

Folliculotropic mycosis fungoides (MF) is an uncommon subtype of MF which has a more aggressive natural history and is more resistant to treatment than other forms of MF. In this article, an innovative method of treatment is presented. We describe a successful use of topical cytarabine combined with topical carmustine in a patient with a folliculotropic MF. Based on our patient history we suggest this method as an effective therapy option for patients with folliculotropic MF unresponsive to other forms of treatment.