1 Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic, Rochester, Minnesota.
2 Division of Metabolism, Endocrinology, and Diabetes, University of Michigan, Ann Arbor, Michigan.
Thyroid. 2019 May;29(5):692-699. doi: 10.1089/thy.2018.0706. Epub 2019 Apr 8.
Severe pretibial myxedema (PTM) can be difficult to manage, highlighting the need to investigate newer therapies. Rituximab (RTX) and intravenous immunoglobulin (IVIg) have been tried in Graves' orbitopathy. Since PTM and orbitopathy share a similar underlying pathophysiology, this study aimed to explore these therapies for progressive PTM. The electronic database was screened for PTM patients evaluated at the Mayo Clinic, Rochester, from 2002 to 2016, and three patients who received IVIg and five who received RTX are reported. PTM pattern was classified as non-pitting edema, plaque and induration, nodular/nummular, and elephantiasis. PTM was confirmed by biopsy in six patients. The patients' median age was 53.8 years, 75% were female, and all but one patient were either active or former smokers. All patients were euthyroid and had progressed despite various therapies prior to starting these agents. Six patients had a plaque and induration pattern, and two had a nodular pattern with elephantiasis. After therapy, six (75%) patients had PTM stability or improvement both subjectively and objectively (80% with RTX and 66% with IVIg). The three patients (one in the IVIg group and two in the RTX group) who had subjective improvement had a plaque pattern. One patient with elephantiasis had a transient response to IVIg and another had stability after RTX. Thyrotropin receptor antibody values and orbitopathy also improved in patients who demonstrated PTM improvement. No serious adverse events were reported, but one patient each had transient hypertension and injection-site thrombophlebitis after IVIg. Immunomodulation therapy was followed by PTM improvement or stability in most patients, with a slightly better response after RTX compared to IVIg. A validated response assessment instrument and larger series of patients are required to determine if the underlying disease process could be curtailed with these agents.
严重的胫前黏液性水肿（PTM）难以治疗，这突出表明需要探索新的治疗方法。利妥昔单抗（RTX）和静脉注射免疫球蛋白（IVIg）已在格雷夫斯眼病中进行了尝试。由于 PTM 和眼病具有相似的潜在病理生理学基础，因此本研究旨在探索这些治疗方法对进行性 PTM 的疗效。通过电子数据库筛选了 2002 年至 2016 年在罗切斯特梅奥诊所接受评估的 PTM 患者，报告了 3 名接受 IVIg 治疗的患者和 5 名接受 RTX 治疗的患者。PTM 模式分为非凹陷性水肿、斑块和硬结、结节/小结节和象皮肿。6 名患者通过活检证实为 PTM。患者的中位年龄为 53.8 岁，75%为女性，除 1 名患者外，其余均为现吸烟者或曾吸烟者。所有患者均为甲状腺功能正常，尽管在开始使用这些药物之前已接受了各种治疗，但仍有进展。6 名患者存在斑块和硬结模式，2 名患者存在结节模式伴象皮肿。治疗后，6 名（75%）患者的 PTM 无论是主观上还是客观上均稳定或改善（RTX 组为 80%，IVIg 组为 66%）。3 名（IVIg 组 1 名，RTX 组 2 名）主观改善的患者存在斑块模式。1 名伴象皮肿的患者接受 IVIg 治疗后出现短暂缓解，另 1 名患者接受 RTX 治疗后病情稳定。接受治疗后，PTM 改善的患者甲状腺刺激素受体抗体值和眼病也有所改善。未报告严重不良事件，但各有 1 名患者在接受 IVIg 治疗后出现短暂高血压和注射部位血栓性静脉炎。免疫调节治疗后，大多数患者的 PTM 得到改善或稳定，与 IVIg 相比，RTX 的反应略好。需要使用验证后的反应评估工具和更大系列的患者来确定这些药物是否能控制潜在的疾病进程。
