特应性皮炎样移植物抗宿主病的临床特点与诊疗策略

移植物抗宿主病（graft-versus-host disease, GVHD）常见于异基因造血干细胞移植术后的一种累及多器官的免疫性疾病［１］。少数实质器官移植也可能产生GVHD,如肝移植等。皮肤是GVHD最易受累且最易发现的器官,对全身其他器官的排异反应有重要的预警作用［2］。随着移植术的广泛开展,累及皮肤的移植物抗宿主病不断增多并呈多样化,常见的皮肤表现如扁平苔藓样,硬皮病样和皮肤异色症样GVHD［3-5］。近年来陆续报道了一些罕见皮肤表现的GVHD,包括红斑狼疮样［6］,皮肌炎样［7］,银屑病样［8］,鱼鳞病样［9］,大疱性类天疱疮样［１0］,以及多形红斑样［1１］等表现的移植物抗宿主病。1999年,Tanasescu等［１2］报道了1例湿疹样GVHD。2007年Creamer等［１3］将10例湿疹样GVHD的临床特征及其对UVA治疗的疗效观察进行了研究报道。我国报道了一种特应性皮炎样移植物抗宿主病（atopic dermatitis-like GVHD）［１4-15］,并且发现具有这种皮肤表现的GVHD逐渐增多,现将特应性皮炎（AD）样移植物抗宿主病概述如下……     

慢性移植物抗宿主病患者的足底鳞状细胞癌

慢性移植物抗宿主病(GVHD)是一种骨髓移植后常见的、严重并发症,常导致皮肤硬皮病样改变伴慢性复发性皮肤溃疡。作者报道了1例慢性GVHD 患者表现为足底溃疡的皮肤鳞状细胞癌。患者女,20岁。因左足底溃疡保守治疗9个月未愈而住院治疗。局部无外伤史,溃疡面细菌培养为假单胞菌类。患者13年前因再生障碍性贫血而接受骨髓移植。因急性 GVHD 用氨甲喋呤治疗,4个月后发生进行性硬度病样改变伴有足趾挛缩和复发性皮肤溃疡。皮肤活检证实为慢性 GVHD。体检示广泛的皮肤硬化,瘢痕性秃发、角膜混浊及所有指趾屈曲挛缩。口腔粘膜正常。右前臂有3×4cm 溃疡。左足底内侧有6×7cm 溃疡,后者中央和边缘角化过度。全血细胞计数示轻度红细胞减少。肝     

表现为特应性皮炎的移植物抗宿主病11例临床分析

目的:初步探讨特应性皮炎(AD)样移植物抗宿主病(GVHD)的临床特点、实验室检查异常和治疗反应.方法:对2007年1月-2010年12月期间就诊的11例AD样GVHD患者进行观察和临床资料分析.结果:11例患者原发病为:慢性粒细胞性白血病(慢粒)4例、急性粒细胞性白血病(急粒)3例、急性淋巴细胞性白血病(急淋)2例、再生障碍性贫血1例、骨髓增生异常综合征1例.与供者有血缘关系者8例,无血缘关系者3例;11例中1例移植后8周发病,其余10例发病均在移植后12周后,表现为皮肤干燥、湿疹样皮疹、瘙痒、IgE和(或)外周血嗜酸性粒细胞升高.大部分患者同时伴有其他器官的受累.经过治疗3例患者症状得到迅速控制,7例患者症状好转后间断反复发作,1例患者于移植术后1年半出现硬斑病样皮损.结论:AD样GVHD是GVHD的特殊皮肤表现,治疗应早期应用糖皮质激素和免疫抑制剂,并辅以局部治疗.该病预后良好.     

急性皮肤型移植物抗宿主病8例临床分析并文献复习

目的:初步探讨异基因造血干细胞移植(allo-HSCT)后急性皮肤型移植物抗宿主病(GVHD)的临床特征,为早期诊断和治疗提供临床依据。方法:对2012年12月—2013年12月期间就诊的8例急性皮肤型GVHD患者进行观察和临床资料分析,并结合文献讨论其早期诊断和治疗方法、发病危险因素和预防措施。结果:8例患者原发病分别为:急性单核细胞白血病(2例),急性混合细胞白血病(1例),慢性粒细胞白血病(2例),急性重型再生障碍性贫血(2例),非霍奇金淋巴瘤(1例)。血缘人类白细胞抗原(HLA)全相合者5例,半相合者3例。8例患者中女4例,男4例,移植后GVHD发生时间为15 d~3个月,临床表现大多为弥漫性红斑、斑丘疹,1例表现为特征性的毛囊周围丘疹,结合皮损组织病理检查明确诊断,给予糖皮质激素联合免疫抑制剂治疗,8例患者病情均得到有效控制。结论:allo-HSCT后急性皮肤型GVHD临床表现大多无特异性,需结合病史和组织病理检查明确诊断,早期治疗预后良好。     

硬皮病用中西医结合治疗前后甲皱微循环检查分析

硬皮病属于结缔组织疾病 ,是以局限性或弥漫性皮肤及内脏器官结缔组织纤维化或硬化 ,以及小血管痉挛最后发生萎缩为特征的疾病。本病中医学归属“皮痹疽范畴”。活血化瘀是相应的治疗方法。近几年来 ,临床及实验研究证实 ,血瘀患者可有全身或局部微循环障碍。本文以硬皮病患者为对象 ,观察其甲皱循环指标变化结果如下。1　临床资料一般情况　本组 40例硬皮病患者 ,年龄 8～ 5 6岁 ,其中 8～ 18岁 10例 ,19～48岁 2 2例 ,49～ 5 6岁 8例。系统性硬皮病 8例 ,局限性硬皮病 32例 ,男 9例 ,女31例 ,男女之比为 1:3.4。发病年龄 ,局限性硬皮病多…     

系统性硬皮病并发皮肤结节病

患者女,54岁。发现四肢皮下结节1个月,系统性硬皮病病史20余年。皮肤科检查见"假面具脸",双手呈鹰爪样改变,四肢串珠状排列和散在分布大小不等的皮下结节,边界清楚,质硬,活动不明显,皮肤表观正常。皮损组织病理:皮下脂肪间隔多数结核样结构,大部分呈"裸结节",未见典型干酪样坏死,周围淋巴细胞很少。诊断:系统性硬皮病并发皮肤结节病。     

复方甘草酸苷联合益脉康滴丸治疗局限型硬皮病疗效观察

<正>硬皮病是一种累及皮肤和黏膜组织的纤维化和硬化性结缔组织病,局限于皮肤者为局限性硬皮病,又称为硬斑病。硬皮病的病因复杂,治疗方法较多,疗效不一。我科于2010年1月至2013年6月应用复方甘草酸苷联合益脉康滴丸治疗局限型硬皮病,取得较好的疗效,现报道如下。1资料与方法 1.1一般资料46例患者均来自我科门诊(其中有6例作病理活检),诊断根据《中国临床皮肤病学》中有关硬皮病的诊断标准[1]:①皮肤有局限性象牙     

硬化性粘液水肿

硬化性粘液水肿(Scleromyxedema)是粘液水肿性苔藓的一种特殊类型,是临床上以局限性或全身性苔藓样丘疹及硬皮病样改变、组织病理上以皮肤内成纤维细胞增生和酸性粘多糖过多沉积为特征的少见病.国外报道已逾百例,国内资料少有介绍.本文就有关文献复习如下.     

系统性硬皮病112例临床分析

目的　探讨皮肤硬化及内脏损害在系统性硬皮病中的意义及两者的关联。方法　回顾分析 112例系统性硬皮病患者的Rodnan修定皮肤评分、Furst’s内脏评分、首发症状、加重因素、病程、免疫学指标。结果　 83例 (74.1% )以雷诺现象为首发症状 ,加重因素为感染 ,弥漫型脏器损害发生率明显高于局限型 ,并且弥漫型更易发生肾损害。弥漫型Rodnan修定皮肤评分、Furst’s内脏评分均较高 ,分别为 (19.7± 14 .2 ) ,(2 9.7± 2 0 .5 ) ,与局限型相比差异均有显著性 (P均 <0 .0 5 ) ,且二者呈正相关 (b =3 .3 8)。结论　系统性硬皮病最常见的首发症状是雷诺现象 ,其最常见加重因素为感染。弥漫型硬皮病皮肤及内脏评分均较高 ,且二者呈正相关 ,提示广泛皮肤损害的患者常有较重的内脏损害。     

系统性硬皮病患者血清中I型原胶原羧基末端前肽的浓度

已有人报告过系统性硬皮病(SSc)患者血清Ⅲ型原胶原氨基末端前肽(P3NP)水平升高,但正常皮肤和硬皮病皮肤中主要胶原成分是Ⅰ型胶原。因此作者研究了SSc患者中血清Ⅰ型原胶原羧基末端前肽(P_1CP)水平,以了解后者与临床特征间的关系。血标本采自61例SSc患     

Bullous scleroderma-like changes in chronic graft-versus-host disease

Cutaneous graft-versus-host disease (GVHD) is the most common clinical setting for GVHD after bone marrow transplantation. Chronic cutaneous GVHD is categorized according to the type of skin lesions into lichenoid and sclerodermoid variants, but bullous scleroderma-like changes are exceptional. Recently, we studied a patient with these alterations. This is the second case described in the literature.     

Risk factors and clinical characteristics of acute and chronic cutaneous graft-versus-host disease in pediatric patients undergoing hematopoietic stem cell transplantation

Acute and chronic cutaneous graft-versus-host disease (GVHD) are common complications following hematopoietic stem cell transplantation (HSCT) in pediatric patients. In this retrospective study, we explored the risk factors and clinical characteristics of acute and chronic cutaneous GVHD in a case series of children undergoing HSCT at a tertiary referral hospital. We found that 36% of acute cutaneous GVHD was severe and these patients were more likely to have an unrelated donor, and that children with acute cutaneous GVHD who progressed to chronic cutaneous GVHD had a higher proportion of malignant diseases, total body irradiation, and bronchiolitis obliterans compared to those who did not progress to chronic cutaneous GVHD. Our study highlights the importance of identifying and monitoring these high-risk patients to improve the clinical management and outcomes of cutaneous GVHD in pediatric HSCT recipients.     

Clinical manifestations of cutaneous graft-versus-host disease after allogeneic haematopoietic cell transplantation: long-term follow-up results in a single Turkish centre

The aim of this study was to evaluate the clinical manifestations of cutaneous graft-versus-host disease (GVHD) developed after allogeneic haematopoietic cell transplantation. In all, 67 patients were evaluated: 49 patients developed acute GVHD, 17 patients developed de novo chronic GVHD and 29 developed secondary chronic (15 limited, 14 progressive) GVHD following acute cutaneous GVHD. Of the 46 patients with chronic GVHD, lichenoid lesions were observed in 32 and sclerodermoid lesions were observed in 12. In four patients with sclerodermoid cutaneous GVHD, these lesions occurred after a lichenoid phase. Oral lesions were present in 61% of the patients and six of them had only oral mucosal involvement without any skin lesions. Nail lesions were observed in 31% of the patients. During the follow-up period 15 patients with GVHD died and in 7 of them the cause of death was related to chronic GVHD. In conclusion, GVHD has a wide spectrum of cutaneous manifestations, which can be used as an important tool for the early diagnosis of the disease.     

Naevi in allogeneic bone marrow transplantation recipients: the effect of graft-versus-host disease on naevi

BACKGROUND: Non-melanoma skin carcinoma is more common in transplant recipients, probably because of immunosuppression. An increased risk of developing melanoma could be a late effect of transplantation. The number of naevi, which is a risk marker for melanoma, is increased in renal transplant recipients of all ages and may be related to immunosuppression. The risk of melanoma has been suspected to be particularly high after bone marrow transplantation. Cutaneous graft-versus-host disease (GVHD) might be an interesting model for the study of interactions between naevi and the immune system. OBJECTIVE: To assess whether aBMT exposes an individual to a particularly high risk of melanoma, using naevi as a surrogate measure of the risk. To improve our knowledge of the effect of the immune system on naevi, using GVHD as a model. METHODS: We carried out an epidemiological case-control study with two age-, sex- and hair colour-matched controls for each case. The results were analysed with analysis of variance, a general linear model analysis and multivariate analysis. RESULTS: The number of naevi was not significantly increased in aBMT patients, as compared with controls, although there was a significant excess on the palms and legs. In exploratory subgroup case-control comparisons and with the general linear model, patients who were conditioned with a combination of two alkylating drugs at high doses, and patients who had an aBMT before the age of 20 years tended to have a higher count of naevi (P = 0.002 and P = 0.06, respectively). Conversely, there was a trend in favour of a lower count of naevi in patients with diffuse skin lesions of chronic GVHD (P = 0.01). These data were corroborated by multivariate analysis, which showed that conditioning with high-dose chemotherapy, the absence of severe chronic cutaneous GVHD and a young age at transplantation were the main variables that independently predicted an excess of naevi. CONCLUSIONS: This study of aBMT patients confirms that chemotherapy stimulates naevus growth. It also suggests for the first time that diffuse lesions of chronic cutaneous GVHD are associated with a decreased number of naevi. Whether allo-immunity, chronic skin inflammation or the masking of naevi by pigmentation and fibrosis is responsible for the decreased number of naevi requires further investigation. With respect to the long-term risk of melanoma in aBMT recipients, our results support an increased risk particularly when aBMT is performed at a young age, and when conditioning is with high doses of alkylating drugs.     

Annular plaques: An unusual manifestation of graft-versus-host disease

Chronic cutaneous graft-versus-host disease (GVHD) classically presents with lichenoid papules or sclerotic plaques. This case highlights an unusual clinical manifestation of chronic GVHD and demonstrates that the skin morphology of chronic GVHD and cutaneous lymphoma may be similar. We report for the first time a case of annular scleroderma-like graft-versus-host disease in a patient following allogeneic stem cell transplant for CD30+ anaplastic large cell lymphoma. Treatment of these skin lesions with ultraviolet A1 (UVA1) phototherapy resulted in significant improvement.     

Eczematoid graft-vs-host disease: a novel form of chronic cutaneous graft-vs-host disease and its response to psoralen UV-A therapy

BACKGROUND: Chronic cutaneous graft-vs-host disease (GVHD) is generally classified by whether lesions have a lichenoid or sclerodermatous morphology. Other unusual clinical forms have been reported that exhibit the features of dermatomyositis and lupus erythematosus. Within a large population of individuals who underwent allogeneic stem cell transplantation because of hematologic malignancy, a group of patients was identified in whom severe and persistent eczema developed. OBSERVATIONS: We prospectively evaluated 10 adult patients with unexplained eczematous dermatosis after allogeneic hematopoietic stem cell transplantation. The dermatosis developed between 2 and 18 months (mean, 7.5 months) after receipt of the transplant, exhibited the typical clinical features of dermatitis, and became erythrodermic in each case. The patient group had strong risk factors for chronic cutaneous GVHD: 8 had received a transplant from an unrelated donor, 7 had evidence of extracutaneous GVHD, and 7 had a history of acute cutaneous GVHD. Sampling of lesional skin revealed the histologic features of GVHD coexisting with the changes of dermatitis. The patients were treated with topical corticosteroid and systemic immunosuppressive agents. Six patients also received psoralen-UV-A. Four patients achieved prolonged remission. Six patients died, 5 of infective complications and 1 of relapsed leukemia. CONCLUSIONS: The eczematous dermatosis observed represents a novel form of chronic cutaneous GVHD that we named eczematoid GVHD. Eczematoid GVHD is an aggressive, chronic dermatosis that requires substantial immunosuppression therapy to achieve control. It is associated with a poor prognosis. Although atopy can be transmitted to an individual from a hematopoietic stem cell transplant, none of the donors in this series gave a history of an atopic disorder. Therefore, other factors must be implicated in provoking the expression of an eczematous phenotype in individuals with underlying chronic graft-vs-host activity.     

PUVA therapy for chronic cutaneous graft-vs-host disease

Chronic graft-vs-host disease (GVHD) is an immunologic disorder frequently occurring as a late sequelae of allogeneic bone marrow transplantation and characterized in the skin with lichenoid or sclerodermoid lesions. Systemic immunosuppressive agents such as corticosteroids or cyclosporine are usually required to control the disease. Therapy with psoralen and UVA (PUVA) has recently been shown to be effective for skin and oral mucosa in a few cases of GVHD. We present our experience with PUVA in six patients, five with lichenoid and one with sclerodermoid GVHD. None of these patients had significant systemic involvement. All five patients with lichenoid GVHD showed clinical improvement after PUVA therapy. Three of these patients had complete clearance of skin lesions. Clinical clearance of the disease was accompanied by microscopic clearance. The patient with sclerodermoid GVHD did not respond to therapy. No significant complications or exacerbation of systemic disease occurred. We confirm that PUVA is an effective and safe therapy for the cutaneous manifestations of lichenoid chronic GVHD. We postulate that PUVA therapy clears chronic lichenoid GVHD by selective cytotoxicity for the activated lymphoid cells in the inflammatory infiltrate.     

银屑病样表现的移植物抗宿主病1例

患儿男,5岁。躯干、四肢皮疹伴瘙痒1周。7个月前,因患"急性B淋巴细胞白血病"行异基因造血干细胞移植术,术后发生两次急性移植物抗宿主病,临床表现为绿豆大鲜红色丘疹,压之退色,疹间皮肤正常,曾予糖皮质激素或免疫抑制剂治疗,丘疹可消退。皮肤科情况:面、颈、躯干及四肢伸侧可见散在分布大小不一的圆形或椭圆形干燥性红斑,上覆白色鳞屑,指/趾甲无受累,Auspitz’s征阴性。皮损组织病理示:表皮不规则增厚,浆痂形成,灶性海绵水肿,灶性基底细胞液化,表皮内可见个别坏死角质形成细胞,真皮浅中层血管周围可见稀疏的单一核细胞浸润。诊断:银屑病样表现的慢性移植物抗宿主病。     

Histochemical and ultrastructural study of diffuse melanoderma after bone marrow transplantation

Summary Hyperpigmentation is a well-recognized feature of cutaneous graft-versus-host disease (GVHU). and is usually restricted to sites where lichenoid or sclerodermiform lesions have occurred. Since 1975, two of 745 patients treated by allogeneic bone marrow transplantation in our institution have developed diffuse melanoderma which differed considerably from the classic presentations. They both developed acute GVHD. then lichen planus-like chronic lesions and diffuse melanoderma. Histology of biopsies of the pigmented skin showed intense pigment deposition in the basal and suprabasal layers, and in dermal macrophages. On split-dopa, melanocyte counts were 98 and 93 per Held, respectively. Electron microscopy showed melanocytes protruding into the dermis, and dark melanosomes in all epidermal layers and in macrophages. These findings were suggestive of post-inflammatory hyperpigmentation. In bone marrow recipients, de nova melanoderma is a rare event which could represent a feature of cutaneous GVHD in pigmented subjects.     

183例儿童皮肤型肥大细胞增生症临床及预后分析

目的 探讨儿童皮肤型肥大细胞增生症的临床特征及预后。 方法 回顾分析183例儿童皮肤型肥大细胞增生症患者的临床资料,并随访部分患者。 结果 183例患者中,色素性荨麻疹136例（74.3%）,肥大细胞瘤43例（23.5%）,弥漫性肥大细胞增生症4例（2.2%）;生后2岁内发病者179例（97.8%）。43例肥大细胞瘤患者中出生即发病者21例（48.8%）,出生后至6个月发病者17例（39.5%）,136例色素性荨麻疹患者中出生即发病者35例（25.7%）,出生至6个月发病者78例（57.3%）。伴随症状记录详细的33例患者中,10例出现伴随症状,其中9例为潮红发作。对45例患者随访3 ~ 6年（平均4年）,色素性荨麻疹患者1例于11岁时皮损完全消退,18例皮损部分消退;肥大细胞瘤患者1例皮损于8岁时完全消退,7例行皮肤活检后1年内皮损消退。口服抗组胺药可控制患者潮红、风团及水疱等症状;口服糖皮质激素可有效控制弥漫性肥大细胞增生症患儿反复发生的泛发水疱、大疱。 结论 儿童皮肤型肥大细胞增生症以色素性荨麻疹最常见,其次为肥大细胞瘤。肥大细胞瘤多于出生即发病,而色素性荨麻疹以出生后至6个月发病多见。口服抗组胺药可控制介质释放相关症状。严重的弥漫性肥大细胞增生症患者可口服糖皮质激素控制症状。