Sweet's syndrome associated with propylthiouracil-induced antineutrophil cytoplasmic antibody

Abstract

A 44-year-old woman had tender erythematous nodules in both the upper and lower extremities, headache, and fever during the course of propylthiouracil therapy for Graves' disease. Serologic tests showed high titers of antineutrophil cytoplasmic antibody (ANCA) against myeloperoxidase (MPO). A skin biopsy showed neutrophilic dermatitis consistent with Sweet's syndrome. After the cessation of propylthiouracil therapy and the administration of steroids, all her symptoms disappeared and the titer of antineutrophil cytoplasmic antibody against myeloperoxidase decreased. A causal relationship between propylthiouracil (PTU) therapy and Sweet's syndrome is suggested.     

丙基硫氧嘧啶和甲巯咪唑治疗Graves病的免疫学作用

目的 观察丙基硫氧嘧啶(PTU)和甲巯咪唑(MMI)治疗Graves病(GD)患者促甲状腺素受体抗体(TRAb)、可溶性细胞间黏附分子1(sICAM-1)水平的变化。方法 106例临床确诊的GD患者分为PTU和MMI组,每组53例,两组在治疗量期、减量期、维持期均予规律用药,共36个月。TRAb和sICAM-1均以酶联免疫吸附法(ELISA)测定。结果 (1)两组治疗前一般情况比较差异无统计学意义(P＞0.05)。(2)PTU组与MMI组治疗前TRAb阳性率分别为94.33％、98.11％,两组间无显著差异;治疗36个月后临床缓解率两组间无显著差异（83.02％对88.68％）,临床治愈率MMI组明显高于PTU组（58.49％对37.74％,P＜0.05）。(3)两组TRAb水平治疗前及治疗后6、12、24、30和36个月均有显著差异（均P＜0.01）,随时间增加逐渐下降( F=275.48,P＜0.01);两药物组治疗后TRAb水平存在显著差异(F=5.86,P＜0.05)。(4)两组sICAM-1水平在用药36个月后与用药前相比差异有统计学意义(P＜0.01),而两药物组间sICAM-1无显著差异。结论 PTU和MMI均能够改善GD患者的自身免疫状态,而MMI的免疫抑制作用较为明显。     

丙基硫氧嘧啶与甲巯咪唑对Graves病患者细胞因子的影响

将64例Graves病(GD)患者分为甲巯咪唑组(MMI,n=30)和丙基硫氧嘧啶组(PTU,n=34),20名健康志愿者作为对照组.采集各组患者治疗前、治疗后3、6个月血清,分别用酶标记免疫吸附法检测血浆白细胞介素(IL)-2、IL-6及促甲状腺素受体抗体(TRAb)的水平.结果显示,2组治疗前一般情况比较差异无统计学意义.2组用药后6个月IL-2、IL-6水平较治疗前差异均有明显统计学意义(P＜0.05),随时间延长IL-2逐渐升高,IL-6逐渐降低;用药6个月后MMI组IL-6水平较PTU组明显降低(P＜0.05).2组治疗前TRAb水平无显著差异,2组治疗后3和6个月TRAb差异均有统计学意义(均P＜0.01),随时问增加逐渐下降.IL-2/IL-6比值在同一组治疗3、6个月后均较治疗前明显升高(P＜0.05).治疗6个月后MMI组较PTU组更高(P＜0.05).GD治疗前血清中IL-6水平与FT3、FT4呈正相关,IL-2水平与FT3、FT4和TRAb呈负相关;治疗3、6个月后,IL-2、IL-6与FT3、FT4无明显相关性;MMI组治疗前后IL-2、IL-6水平均与TRAb相关.这些结果提示,MMI较PTU更具有改善GD患者自身免疫的作用.     

丙硫氧嘧啶相关性小血管炎和原发性小血管炎血清髓过氧化物酶抗体抗原决定簇结合谱的比较

目的比较丙硫氧嘧啶(PTU)相关性小血管炎和原发性小血管炎髓过氧化物酶(MPO)抗体的抗原决定簇结合谱.方法以人MPO制备的MPO亲和层析柱,分别从1例PTU相关性小血管炎和1例显微镜下型多血管炎(MPA)患者的血浆置换液中分离纯化MPO抗体(Pab1和Pab2),并经辣根过氧化物酶标记(Pab1-HRP和Pab2-HRP). 以Pab1-HRP和Pab2-HRP以及两种鼠抗人MPO单克隆抗体(3D8和6B9)分别作为识别MPO分子上不同抗原决定簇的探针,应用竞争性ELISA对10例PTU引起的抗中性粒细胞胞浆抗体(ANCA)阳性小血管炎患者和10例MPA患者血清中MPO抗体的抗原决定簇结合谱进行比较研究.结果 PTU组10例标本均可抑制3D8,平均抑制率为44.7%, 9/10例标本可抑制6B9, 平均抑制率为35.6%; MPA组10例标本均可抑制3D8和6B9, 平均抑制率分别为68.4%和62.2%, 与PTU组相比差异具有显著性(P<0.01).两组标本对Pab1-HRP的平均抑制率均达80%以上,MPA组标本对Pab2-HRP的抑制率均值显著大于PTU组(76.3% 比 58.9%, P<0.01).结论丙硫氧嘧啶相关性小血管炎和MPA患者血清中的MPO抗体均可识别MPO分子上多个抗原决定簇,二者识别的抗原决定簇有一定程度的交叉,但PTU组识别的抗原决定簇可能较局限.抗原决定簇结合谱的不同可能与临床表现的不同有关.     

知柏地黄口服液联合丙硫氧嘧啶辅治甲状腺功能亢进症的效果及对甲状腺激素、抗氧化指标的影响

目的观察知柏地黄口服液联合丙硫氧嘧啶辅治甲状腺功能亢进症(甲亢)的效果及对甲状腺激素、抗氧化指标的影响。方法选取2017年3月-2018年4月我院收治82例甲亢患者作为研究对象,根据治疗方案的不同均分为观察组和对照组。对照组给予丙硫氧嘧啶、普萘洛尔片治疗,观察组在对照组治疗基础上加用知柏地黄口服液治疗。比较两组治疗12周后临床效果,治疗前及治疗12周后游离三碘甲状腺原氨酸(FT3)、游离甲状腺素(FT4)和抗氧化指标[超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GPX)、丙二醛(MDA)]水平,以及治疗过程中不良反应发生情况。结果观察组临床总有效率为97.56%显著高于对照组总有效率的82.93%(P<0.05)。两组治疗后FT3、FT4水平较治疗前显著下降,且观察组FT3、FT4降低程度显著大于对照组,差异均有统计学意义(P<0.05或P<0.01)。治疗后,两组SOD、GPX水平明显高于治疗前,MDA水平明显低于治疗前,且治疗后观察组SOD、GPX水平显著高于对照组,MDA水平明显低于对照组,差异均有统计学意义(P<0.05或P<0.01)。观察组皮疹发生率低于对照组(P<0.05)。结论知柏地黄口服液联合丙硫氧嘧啶辅治甲亢效果显著,能明显改善患者的临床症状,促进甲状腺功能和血清抗氧化指标恢复正常,并能有效减少不良反应的发生。     

Occurrence of antineutrophil cytoplasmic antibodies and associated vasculitis in patients with hyperthyroidism treated with antithyroid drugs: A long‐term followup study

Objective

To test whether antineutrophil cytoplasmic antibodies (ANCA) and ANCA‐associated vasculitis (AAV) are not only induced during treatment with antithyroid drugs, but can also become evident when medication has been ceased, possibly after years.

Methods

Patients who visited our hospital for the treatment of hyperthyroidism were included (n = 207). Treatment consisted of antithyroid medications, radioactive iodide, thyroidectomy, or a combination of these treatment options. Patients were retested 3–6 years later to evaluate long‐term effects of antithyroid drugs. Patients were tested for the presence of ANCA and, if positive, evaluated for the presence of AAV.

Results

Of 209 patients with hyperthyroidism, 12 patients (6%) were positive for myeloperoxidase‐ (MPO‐), proteinase 3‐, or human leukocyte elastase‐ANCA. Seventy‐seven of 209 patients were retested; 1 patient who had not been treated with antithyroid drugs had developed MPO‐ANCA. In 3 of 6 patients previously positive, ANCA could still be detected. The presence of ANCA was highly associated with treatment with antithyroid drugs (odds ratio 11.8 [95% confidence interval 1.5–93.3]). Of 13 patients with a positive ANCA result on enzyme‐linked immunosorbent assay, AAV with glomerulonephritis was diagnosed in 4 (31%).

Conclusion

The presence of ANCA with or without vasculitis is associated with previous treatment with antithyroid drugs, possibly after years.

     

丙基硫氧嘧啶诱导的ANCA相关性系统性小血管炎与IgA肾病

抗甲状腺药物丙基硫氧嘧啶(PTU)可引起针对多种靶抗原的抗中性粒细胞胞浆抗体(ANCA)阳性,进而导致系统性小血管炎(AASV),最常累及肾脏,多表现为寡免疫复合物型急进性肾小球肾炎.IgA肾病以肾小球系膜区IgA沉积为特点,ANCA阳性可能是其预后不良的一个指标,但目前尚无证据表明PTU致ANCA阳性可引起IgA肾病,多数学者仍认为两者是并存的关系.     

Two decades of supertasting: where do we stand?

Oral chemosensation can vary greatly across individuals, both in terms of the lowest concentration that can be detected (threshold) and in the magnitude of perceived intensity for stimuli at higher concentrations (suprathreshold response). Individuals who experience greater taste intensity are often termed supertasters, and this phenotype has typically been measured via the suprathreshold bitterness of the tastant propylthiouracil (PROP). Notably, supertasting extends beyond bitterness and other tastants to include oral somatosensation and retronasal olfaction, and it may also include finer acuity as well. Here, we describe the evolution of the supertasting concept over the last 20 years, and summarize the current state of the field. Alternative phenotyping approaches that are not dependent on PROP are reviewed, and the molecular genetics of broadly tuned heightened taste and orosensory response are discussed. We conclude by initiating a conversation on nomenclature as we look toward the next 20 years of chemosensory research.     

丙基硫氧嘧啶联合地塞米松治疗甲状腺功能亢进的临床效果观察

目的：探讨丙基硫氧嘧啶联合地塞米松治疗甲状腺功能亢进的临床效果。方法回顾性分析2012年1月~2013年12月在本院治疗的甲状腺功能亢进患者48例的临床资料,其中23例采用丙基硫氧嘧啶联合地塞米松治疗,为研究组,25例患者采用丙基硫氧嘧啶治疗,为对照组。治疗8周后,比较两组的临床疗效。结果治疗后,研究组的甲状腺体积显著小于对照组,症状消失时间、指标恢复正常时间均短于对照组(P<0.01)。治疗后,两组的FT3、FT4、TT3、TT4水平与治疗前比较均显著下降(P<0.01);研究组治疗后的FT3、FT4、TT3、TT4水平均显著低于对照组(P<0.05)。结论丙基硫氧嘧啶联合地塞米松治疗甲状腺功能亢进具有较好的临床效果,值得临床推广。     

The Kinetics of Propylthiouracil in Hyperthyroidism

Abstract: The kinetics of propylthiouracil have been estimated in 10 hyperthyroid subjects according to a two-compartment model by giving the drug initially by the intravenous and subsequently by the oral route. The apparent half-life was 77 ± 34 min. (mean ± S.D.). This value and other pharmacokinetic parameters were compared with the corresponding values obtained in a previous study in normal subjects. No significant differences were found. A table showing studies in humans correlating drug metabolism and thyroid status is presented.