Hauck Fabian, Koletzko Sibylle, Walz Christoph, von Bernuth Horst, Klenk Anne, Schmid Irene, Belohradsky Bernd H, Klein Christoph, Bufler Philip, Albert Michael H
Pediatric Hematology/Oncology/Immunology/Stem Cell Transplantation, Dr von Hauner Children's Hospital, Ludwig-Maximilians University, Munich, Germany Immunological Diagnostics Laboratory, Dr von Hauner Children's Hospital, Ludwig-Maximilians University, Munich, Germany
Pediatric Gastroenterology/Hepatology, Dr. von Hauner Children's Hospital, Ludwig-Maximilians University, Munich, Germany.
J Crohns Colitis. 2016 Jan;10(1):112-5. doi: 10.1093/ecco-jcc/jjv186. Epub 2015 Oct 13.
X-linked chronic granulomatous disease [X-CGD] due to hemizygous mutations in CYBB is characterised by invasive bacterial and fungal infections and granulomatous inflammation. Inflammatory bowel disease [IBD] is an additional or isolated manifestation. Allogeneic haematopoietic stem cell transplantation [alloHSCT] is the standard curative treatment. X-CGD carriers are usually healthy but those with non-random X-chromosome inactivation [XCI] may develop infectious or autoinflammatory manifestations.
We report on two female patients with severe treatment-refractory Crohn-like IBD manifesting at age 23 and 8 years, respectively. NADPH-oxidase activity testing and molecular genetics proved X-CGD carrier status with non-random XCI. As in CGD, histopathology from colonic biopsies disclosed pigment-laden macrophages and reduced CD68(+) macrophages. Following submyelo-ablative conditioning, the younger patient was treated with alloHSCT at age 20 years. She came into remission within 3 months after transplantation and shows complete mucosal healing after 16 months off all medications.
We suggest that children and young adults with refractory IBD should mandatorily be tested for CGD. AlloHSCT should be considered as curative therapy in severely diseased female carriers of X-CGD with non-random XCI.
由于CYBB基因半合子突变导致的X连锁慢性肉芽肿病[X-CGD]的特征为侵袭性细菌和真菌感染以及肉芽肿性炎症。炎症性肠病[IBD]是一种额外的或孤立的表现。异基因造血干细胞移植[alloHSCT]是标准的治愈性治疗方法。X-CGD携带者通常健康，但那些具有非随机X染色体失活[XCI]的携带者可能会出现感染性或自身炎症性表现。
我们报告了两名分别在23岁和8岁时出现严重的难治性克罗恩样IBD的女性患者。NADPH氧化酶活性检测和分子遗传学证实了她们为具有非随机XCI的X-CGD携带者状态。与慢性肉芽肿病一样，结肠活检的组织病理学显示有含色素的巨噬细胞和CD68(+)巨噬细胞减少。在进行亚清髓预处理后，较年轻的患者在20岁时接受了alloHSCT治疗。她在移植后3个月内进入缓解期，在停用所有药物16个月后显示完全黏膜愈合。
我们建议，对于难治性IBD的儿童和年轻人应强制检测慢性肉芽肿病。对于患有严重疾病且具有非随机XCI的X-CGD女性携带者，应考虑将alloHSCT作为治愈性疗法。
