Department of Pediatric Immunology and Hematology, Assistance Publique-Hôpitaux de Paris, Hôpital Necker Enfants-Malades, Paris, France.
J Allergy Clin Immunol. 2011 Oct;128(4):847-53. doi: 10.1016/j.jaci.2011.05.024. Epub 2011 Jun 28.
Cartilage-hair hypoplasia (CHH) is a rare autosomal recessive disorder characterized by short-limbed skeletal dysplasia. Some patients also have defects in cell-mediated immunity and antibody production. Granulomatous inflammation has been described in patients with various forms of primary immunodeficiencies but has not been reported in patients with CHH.
We sought to describe granulomatous inflammation as a novel feature in patients with CHH, assess associated immunodeficiency, and evaluate treatment options.
In a retrospective observational study we collected clinical data on 21 patients with CHH to identify and further characterize patients with granulomatous inflammation.
Four unrelated patients with CHH (with variable degrees of combined immunodeficiency) had epithelioid cell granulomatous inflammation in the skin and visceral organs. Anti-TNF-α mAb therapy in 3 of these patients led to significant regression of granulomas. However, 1 treated patient had fatal progressive multifocal leukoencephalopathy caused by the JC polyomavirus. In 2 patients immune reconstitution after allogeneic hematopoietic stem cell transplantation led to the complete disappearance of granulomas.
To the best of our knowledge, this is the first report of granulomatous inflammation in patients with CHH. Although TNF-α antagonists can effectively suppress granulomas, the risk of severe infectious complications limits their use in immunodeficient patients.
软骨-毛发发育不全（CHH）是一种罕见的常染色体隐性遗传疾病，其特征为短肢骨骼发育不良。一些患者还存在细胞介导的免疫和抗体产生缺陷。在各种形式的原发性免疫缺陷患者中已经描述了肉芽肿性炎症，但在 CHH 患者中尚未报道。
我们旨在描述 CHH 患者中作为一种新特征的肉芽肿性炎症，评估相关免疫缺陷，并评估治疗选择。
在一项回顾性观察研究中，我们收集了 21 例 CHH 患者的临床数据，以确定和进一步描述具有肉芽肿性炎症的患者。
4 名无关的 CHH 患者（具有不同程度的联合免疫缺陷）在皮肤和内脏器官中存在上皮样细胞肉芽肿性炎症。在这 3 名患者中使用抗 TNF-α mAb 治疗导致了肉芽肿的显著消退。然而，1 名接受治疗的患者因 JC 多瘤病毒引起了致命的进行性多灶性白质脑病。在 2 名患者中，异基因造血干细胞移植后的免疫重建导致了肉芽肿的完全消失。
据我们所知，这是首例 CHH 患者发生肉芽肿性炎症的报告。尽管 TNF-α 拮抗剂可以有效地抑制肉芽肿，但严重感染并发症的风险限制了其在免疫缺陷患者中的使用。
