Fulminant molluscum contagiosum infection and concomitant leukaemia cutis after bone marrow transplantation for chronic myeloid leukaemia
Fulminant molluscum contagiosum infection and concomitant leukaemia cutis after bone marrow transplantation for chronic myeloid leukaemia
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慢性粒细胞白血病骨髓移植后暴发性传染性软疣感染及并发皮肤白血病
DOI：
10.1046/j.1365-2133.2000.03859.x
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发表时间：
2000
影响因子：
10.3
通讯作者：
T. Shek
中科院分区：
文献类型：
--
作者：
W. Au;A. Lie;T. Shek
主席先生，传染性软疣是一种痘病毒皮肤感染，常使后天或医源性免疫抑制的病人病情复杂化。这些病例的临床和组织学特征可能是不典型的。我们报告了一例慢性粒细胞白血病（CML）异基因骨髓移植（BMT）后复发的暴发性MC感染伴皮肤白血病的独特临床和组织学特征。一位49岁的中国女性接受了来自HLA完全相同的姐妹的骨髓移植（预处理：白消安、环磷酰胺、全身照射）治疗加速期Ph阳性CML。她顺利移植，没有慢性移植物vs。宿主病（GVHD）。骨髓移植后18个月内，通过聚合酶链反应和细胞遗传学进行的一系列骨髓再评估均为阴性。在36个月时，她被发现有血液学复发的慢性粒细胞白血病，细胞遗传学亚克隆进化。她接受了羟基脲和供体淋巴细胞输注（DLI）（分三次输注6 - 1 10 kg细胞）治疗，以增强移植物对白血病（GVL）效应。外周血细胞计数控制良好，无GVHD证据。40个月时的重复骨髓活检显示异常克隆抑制至分析中期的3%。不幸的是，在46个月时，疾病再次进展，中性粒细胞计数增加（52 × 10 L），皮肤活检证实皮肤白血病（图1a，1b）。这是治疗与联合化疗（阿糖胞苷150毫克5，硫鸟嘌呤160毫克5），导致正常化的细胞计数和所有皮肤病变的决议。BMT后49个月进行第二个疗程的DLI（4 '2 10 kg细胞）。然而，在DLI后三周，患者在整个面部、上肢和上躯干出现密集的丘疹性丘疹病变。病变的摄影被拒绝。一个病灶的活检显示异常表皮细胞小叶，胞浆内充满嗜酸性病毒包涵体（图2a）。电子显微镜显示异常表皮细胞内有大量胞浆内痘病毒颗粒（大小为240 - 95 nm），与MC一致（图2b）。此外，观察到早幼粒细胞和未成熟髓样母细胞浸润，与复发性皮肤白血病一致。1周后，患者死于颅内出血，可能与脑内疾病相关。DLI的使用是骨髓移植后CML复发的治疗选择。主要的副作用是严重的骨髓和免疫抑制，伴有或不伴有急性和慢性GVHD。休眠DNA病毒如巨细胞病毒、水痘带状疱疹和B型肝炎病毒的重新激活是DLI引起的免疫抑制的潜在并发症。这是第一次报告严重MC并发DLI。在免疫抑制的宿主中，由于痘病毒的暴发性复制，MC的临床和病理特征可以高度可变，并且通常需要积极的治疗。甚至在HIV感染患者MC病变附近的组织学正常皮肤表皮中也发现了病毒颗粒。先前有两份报告称MC的皮肤变化与涉及皮肤的血液恶性肿瘤相似。在我们的病例中，临床背景和病理特征高度支持真正的双重病理。人们认识到，骨髓移植后患者髓外部位（包括皮肤）白血病累及的发生率增加。由于骨髓外GVL效应较弱，DLI挽救患者的发生率可能更高。MC复制和白血病浸润在皮损中的精确共定位可能是由于高浓度的趋化性
Sir, Molluscum contagiosum (MC) is a poxvirus skin infection that often complicates the course of patients with acquired or iatrogenic immunosuppression. Both the clinical and histological features of disease in these cases may be atypical. We report the unique clinical and histological features of a case of fulminant MC infection with concomitant leukaemia cutis in a patient with relapse of chronic myeloid leukaemia (CML) after allogeneic bone marrow transplantation (BMT). A 49-year-old Chinese woman underwent BMT (conditioning: busulphan, cyclophosphamide, total body irradiation) from an HLA identical sister for Ph positive CML in accelerated phase. She engrafted uneventfully with no chronic graft-vs.-host disease (GVHD). Serial bone marrow reassessments, up to 18 months post-BMT, were negative for residual disease by polymerase chain reaction and cytogenetics. At 36 months, she was found to have haematological relapse of CML, with cytogenetic subclonal evolution. She was treated with hydroxyurea and donor lymphocyte infusions (DLI) (6 ́1 10 kg cells infused in three doses) to enhance the graft-vs.-leukaemia (GVL) effect. There was good control of the peripheral cell counts and no evidence of GVHD. A repeat marrow biopsy at 40 months showed suppression of the abnormal clone to 3% of analysed metaphases. Unfortunately, at 46 months the disease progressed again with increased neutrophil counts (52 10 L), and leukaemia cutis documented by skin biopsy (Figs 1a, 1b). This was treated with combination chemotherapy (cytosine arabinoside 150 mg 5, thioguanine 160 mg 5) resulting in normalization of cell count and resolution of all skin lesions. A second course of DLI (4 ́2 10 kg cells) was administered at 49 months post-BMT. Three weeks after DLI, however, the patient presented with a dense eruption of erythematous papular lesions over the entire face, upper limbs and upper trunk. Photography of the lesions was refused. A biopsy of one lesion showed lobules of abnormal epidermal cells with cytoplasm packed with eosinophilic viral inclusion bodies (Fig. 2a). Electron microscopy showed numerous intracytoplasmic poxvirus particles (240 95 nm in size) within the abnormal epidermal cells, consistent with MC (Fig. 2b). In addition, an infiltrate of promyelocytes and immature myeloid blast cells was seen, consistent with recurrent leukaemia cutis. She died 1 week later of an intracranial haemorrhage, probably related to intracerebral disease. The use of DLI is the treatment of choice for relapse of CML after BMT. The main side-effects are profound marrow and immune suppression, with or without acute and chronic GVHD. Reactivation of dormant DNA viruses like cytomegalovirus, varicella zoster and hepatitis B viruses are potential complications of immunosuppression caused by DLI. This is the first report of severe MC complicating DLI. In immunosuppressed hosts, due to the fulminant replication of the poxvirus, the clinical and pathological features of MC can be highly variable, and aggressive treatment is often needed. Viral particles have even been found in the histologically normal skin epidermis adjacent to MC lesions in patients infected with HIV. There have been two previous reports of skin changes in MC mimicking haematological malignancy involving the skin. In our case, the clinical setting and pathological features are highly supportive of a genuine double pathology. It is recognized that post-BMT patients have an increased incidence of leukaemic involvement of extramedullary sites, including the skin. The incidence may be even higher in patients salvaged with DLI, due to a weaker GVL effect outside the marrow. The precise colocalization of MC replication and leukaemic infiltration in the skin lesions may have been due to a high concentration of chemotactic
假性甲状旁腺功能减退症 I 型成纤维细胞缺陷：受体环化酶偶联蛋白活性降低。
DOI：
10.1210/jcem-53-3-636
发表时间：
1981
期刊：
The Journal of clinical endocrinology and metabolism
影响因子：
--
作者：
Bourne,HR;Kaslow,HR;Brickman,AS;Farfel,Z
通讯作者：
Farfel,Z