Lane Thirusha, Loeffler Jutta M, Rowczenio Dorota M, Gilbertson Janet A, Bybee Alison, Russell Tonia L, Gillmore Julian D, Wechalekar Ashutosh D, Hawkins Philip N, Lachmann Helen J
National Amyloidosis Centre, University College London Medical School, Royal Free Campus, Rowland Hill Street, London NW3 2PF, UK.
Arthritis Rheum. 2013 Apr;65(4):1116-21. doi: 10.1002/art.37827.
AA amyloidosis is a life-threatening complication of the hereditary periodic fever syndromes (HPFS), which are otherwise often compatible with normal life expectancy. This study was undertaken to determine the characteristics, presentation, natural history, and response to treatment in 46 patients who had been referred for evaluation at the UK National Amyloidosis Centre.
Disease activity was monitored by serial measurement of serum amyloid A. Renal function was assessed by measurement of serum creatinine and albumin levels, the estimated glomerular filtration rate, and proteinuria from 24-hour urine collections. The amyloid load was measured by serum amyloid P scintigraphy.
Twenty-four patients had familial Mediterranean fever, 12 patients had tumor necrosis factor receptor-associated periodic syndrome, 6 patients had cryopyrin-associated periodic syndromes, and 4 patients had mevalonate kinase deficiency. The median age at onset of HPFS was 5 years; median age at presentation with AA amyloidosis was 38 years. Diagnosis of an HPFS had not been considered prior to presentation with AA amyloidosis in 23 patients (50%). Eleven patients (24%) had end-stage renal failure (ESRF) at presentation; of these, 3 had received transplants prior to referral. A further 13 patients developed ESRF over the followup period, with 10 undergoing renal transplantation. The median time to progression to ESRF from onset of AA amyloidosis was 3.3 years (interquartile range [IQR] 2-8), with a median time to transplant of 4 years (IQR 3-6). Eleven patients (24%) died. The median survival in the entire cohort was 19 years from diagnosis of AA amyloidosis. Of the 37 patients who were treated successfully, or in whom at least partial suppression of the underlying HPFS was achieved, 17 (46%) showed amyloid regression, 14 (38%) showed a stable amyloid load, and 2 (5%) showed increased amyloid deposition over the followup period.
AA amyloidosis remains a challenging and serious late complication of HPFS; however, outcomes are excellent when HPFS is diagnosed early enough to allow effective treatment, thus preventing or retarding further amyloid deposition and organ damage.
AA 淀粉样变性是遗传性周期性发热综合征（HPFS）的一种危及生命的并发症，而 HPFS 在其他方面通常与正常预期寿命相符。本研究旨在确定 46 例转诊至英国国家淀粉样变性中心进行评估的患者的特征、临床表现、自然病史及治疗反应。
通过连续测量血清淀粉样蛋白 A 监测疾病活动。通过测量血清肌酐和白蛋白水平、估算肾小球滤过率以及 24 小时尿蛋白定量评估肾功能。通过血清淀粉样蛋白 P 闪烁扫描测量淀粉样蛋白负荷。
24 例患者患有家族性地中海热，12 例患者患有肿瘤坏死因子受体相关周期性综合征，6 例患者患有冷吡啉相关周期性综合征，4 例患者患有甲羟戊酸激酶缺乏症。HPFS 发病的中位年龄为 5 岁；出现 AA 淀粉样变性时的中位年龄为 38 岁。23 例患者（50%）在出现 AA 淀粉样变性之前未考虑过 HPFS 的诊断。11 例患者（24%）就诊时已处于终末期肾衰竭（ESRF）；其中 3 例在转诊前已接受移植。在随访期间，另有 13 例患者发展为 ESRF，其中 10 例接受了肾移植。从 AA 淀粉样变性发病到进展为 ESRF 的中位时间为 3.3 年（四分位间距[IQR]2 - 8），移植的中位时间为 4 年（IQR 3 - 6）。11 例患者（24%）死亡。整个队列从诊断 AA 淀粉样变性起的中位生存期为 19 年。在 37 例得到成功治疗或至少部分抑制了潜在 HPFS 的患者中，17 例（46%）在随访期间淀粉样蛋白出现消退，14 例（38%）淀粉样蛋白负荷稳定，2 例（5%）淀粉样蛋白沉积增加。
AA 淀粉样变性仍然是 HPFS 具有挑战性且严重的晚期并发症；然而，如果能足够早地诊断 HPFS 以进行有效治疗，从而预防或延缓进一步的淀粉样蛋白沉积和器官损害，预后会很好。
