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Abstract：
BACKGROUND: Lymphangioleiomyomatosis (LAM) is common in tuberous sclerosis complex (TSC) yet under recognised with management mostly based upon evidence obtained from patients with sporadic LAM. We performed a prospective audit of patients with TSC-LAM attending a national referral centre to inform management guidelines.
METHODS: The UK LAM Centre was established in 2011 and conducts a prospective audit of pre-defined quality outcomes for all subjects. Audit data are reported on all patients with TSC-LAM and a comparator population of patients with sporadic LAM.
RESULTS: Between 2011 and 2022, 73 patients were seen with TSC-LAM. All were women with a mean (SD) age of 39 (12) years. Referral rates were similar over the study period including after the introduction of CT screening. Median age of diagnosis with TSC was 11 years (range 0-70) with one third diagnosed with TSC as adults. Compared with all TSC patients in the \'TOSCA\' registry, TSC-LAM patients tended to have been diagnosed with TSC at an older age, had fewer neuro-cognitive manifestations and were more likely to have angiomyolipoma. The most common presentations of TSC-LAM were following workup for angiomyolipoma, pneumothorax or dyspnoea with only one fifth detected after CT screening. Baseline FEV1 and DLCO at first assessment were reduced to 77 and 63% predicted respectively and were similar to patients with sporadic LAM. During follow-up, FEV1 fell by a mean of 81 ml/year and DLCO fell by 0.309 mmol/ml/kPa/year in patients not being treated with an mTOR inhibitor. 55% required treatment with either sirolimus or Everolimus for LAM or angiomyolipoma respectively. For those treated with an mTOR inhibitor, mean FEV1 fell by 3 ml/year and DLCO increased by 0.032 mmol/ml/kPa/year and was similar to sporadic LAM. Risk of death due to LAM or need for lung transplant in patients with TSC-LAM was 0.67%/year.
CONCLUSIONS: Despite screening recommendations, LAM is often diagnosed in TSC after symptoms develop which may delay treatment. Complications including pneumothorax and loss of lung function are significant and similar to sporadic LAM. Work is needed to implement the recommended CT screening for LAM and improve respiratory care for TSC-LAM.
METHODS: The UK LAM Centre was established in 2011 and conducts a prospective audit of pre-defined quality outcomes for all subjects. Audit data are reported on all patients with TSC-LAM and a comparator population of patients with sporadic LAM.
RESULTS: Between 2011 and 2022, 73 patients were seen with TSC-LAM. All were women with a mean (SD) age of 39 (12) years. Referral rates were similar over the study period including after the introduction of CT screening. Median age of diagnosis with TSC was 11 years (range 0-70) with one third diagnosed with TSC as adults. Compared with all TSC patients in the \'TOSCA\' registry, TSC-LAM patients tended to have been diagnosed with TSC at an older age, had fewer neuro-cognitive manifestations and were more likely to have angiomyolipoma. The most common presentations of TSC-LAM were following workup for angiomyolipoma, pneumothorax or dyspnoea with only one fifth detected after CT screening. Baseline FEV1 and DLCO at first assessment were reduced to 77 and 63% predicted respectively and were similar to patients with sporadic LAM. During follow-up, FEV1 fell by a mean of 81 ml/year and DLCO fell by 0.309 mmol/ml/kPa/year in patients not being treated with an mTOR inhibitor. 55% required treatment with either sirolimus or Everolimus for LAM or angiomyolipoma respectively. For those treated with an mTOR inhibitor, mean FEV1 fell by 3 ml/year and DLCO increased by 0.032 mmol/ml/kPa/year and was similar to sporadic LAM. Risk of death due to LAM or need for lung transplant in patients with TSC-LAM was 0.67%/year.
CONCLUSIONS: Despite screening recommendations, LAM is often diagnosed in TSC after symptoms develop which may delay treatment. Complications including pneumothorax and loss of lung function are significant and similar to sporadic LAM. Work is needed to implement the recommended CT screening for LAM and improve respiratory care for TSC-LAM.
摘要：
背景：淋巴管平滑肌瘤病（LAM）在结节性硬化症（TSC）中很常见，但主要基于从散发性LAM患者获得的证据，目前仍未被认识到。我们对在国家转诊中心就诊的TSC-LAM患者进行了前瞻性审核，以告知管理指南。
方法：英国LAM中心成立于2011年，对所有受试者的预定义质量结果进行前瞻性审核。报告了所有TSC-LAM患者和散发性LAM患者的比较人群的审核数据。
结果：在2011年至2022年之间，有73例患者出现TSC-LAM。全部为平均(SD)年龄为39(12)岁的女性。在研究期间，包括引入CT筛查后的转诊率相似。诊断为TSC的中位年龄为11岁（范围0-70岁），其中三分之一被诊断为成人TSC。与“TOSCA”注册表中的所有TSC患者相比，TSC-LAM患者往往在年龄较大时被诊断为TSC，有较少的神经认知表现和更可能有血管平滑肌脂肪瘤。TSC-LAM最常见的表现是血管平滑肌脂肪瘤的后续检查，CT筛查后仅发现五分之一的气胸或呼吸困难。首次评估时的基线FEV1和DLCO分别降低至预测的77％和63％，与散发性LAM患者相似。随访期间,在未使用mTOR抑制剂治疗的患者中，FEV1平均下降81ml/年，DLCO下降0.309mmol/ml/kPa/年。55％的人分别需要西罗莫司或依维莫司治疗LAM或血管平滑肌脂肪瘤。对于那些用mTOR抑制剂治疗的患者，平均FEV1下降3ml/年,DLCO增加0.032mmol/ml/kPa/年,与散发性LAM相似.TSC-LAM患者因LAM或需要肺移植而死亡的风险为0.67％/年。
结论：尽管有筛查建议，LAM通常在症状发展后在TSC中诊断，这可能会延迟治疗。包括气胸和肺功能丧失的并发症是显著的并且与散发性LAM相似。需要进行建议的LAMCT筛查并改善TSC-LAM的呼吸道护理。
方法：英国LAM中心成立于2011年，对所有受试者的预定义质量结果进行前瞻性审核。报告了所有TSC-LAM患者和散发性LAM患者的比较人群的审核数据。
结果：在2011年至2022年之间，有73例患者出现TSC-LAM。全部为平均(SD)年龄为39(12)岁的女性。在研究期间，包括引入CT筛查后的转诊率相似。诊断为TSC的中位年龄为11岁（范围0-70岁），其中三分之一被诊断为成人TSC。与“TOSCA”注册表中的所有TSC患者相比，TSC-LAM患者往往在年龄较大时被诊断为TSC，有较少的神经认知表现和更可能有血管平滑肌脂肪瘤。TSC-LAM最常见的表现是血管平滑肌脂肪瘤的后续检查，CT筛查后仅发现五分之一的气胸或呼吸困难。首次评估时的基线FEV1和DLCO分别降低至预测的77％和63％，与散发性LAM患者相似。随访期间,在未使用mTOR抑制剂治疗的患者中，FEV1平均下降81ml/年，DLCO下降0.309mmol/ml/kPa/年。55％的人分别需要西罗莫司或依维莫司治疗LAM或血管平滑肌脂肪瘤。对于那些用mTOR抑制剂治疗的患者，平均FEV1下降3ml/年,DLCO增加0.032mmol/ml/kPa/年,与散发性LAM相似.TSC-LAM患者因LAM或需要肺移植而死亡的风险为0.67％/年。
结论：尽管有筛查建议，LAM通常在症状发展后在TSC中诊断，这可能会延迟治疗。包括气胸和肺功能丧失的并发症是显著的并且与散发性LAM相似。需要进行建议的LAMCT筛查并改善TSC-LAM的呼吸道护理。
