Schapowal A G, Simon H U, Schmitz-Schumann M
Hochgebirgsklinik Davos Wolfgang, Switzerland.
Acta Otorhinolaryngol Belg. 1995;49(3):235-50.
Aspirin-sensitive rhinosinusitis is a non-allergic, non-infectious perennial eosinophilic rhinitis starting in middle age and rarely seen in children. It may also been seen in atopic patients who have developed a mixed type rhinitis with recurrent airway infections. There is an intolerance to aspirin and most other NSAID. An intolerance to tartrazine, food additives, alcohol, narcotics and local anaesthetics can follow. Most aspirin-sensitive patients develop nasal polyps. Untreated, it can lead to asthma. The frequency of aspirin intolerance is 6.18% in patients with perennial rhinitis and 14.68% in patients with nasal polyps. Immunologic studies of the blood and the nasal polyps show a hyperreactive immune system with an activation of the eosinophil granulocytes due to a TH1-lymphocyte-activation. In atopic subjects with a mixed type rhinitis, we found a TH2- and B-lymphocyte-activation as well. Inhibition of eosinophil apoptosis might be a second remarkable change in the immune system of aspirin-sensitive patients. A key pathogenic event for aspirin sensitivity is the change of the leukotriene pathway for arachidonic acid metabolism releasing high amounts of leukotrienes LTC4, LTD4 and LTE4, effective chemoattractants and activators of inflammatory cells. For the diagnosis of aspirin intolerance, nasal, bronchial and oral challenge are available. The sensitivity of nasal challenge with lysine-aspirin for the diagnosis of aspirin-sensitive rhinitis is 0.93, the specificity 0.97. It is the safest test in aspirin-sensitive asthmatics causing bronchial side effects only in 0.45%. Therapy of aspirin-sensitive rhinosinusitis includes avoidance of aspirin and NSAID. A general down regulation of the immune response with glucocorticosteroids is an effective means. We prefer a maintenance dose of budesonid 400 micrograms a day. Systemic steroids for a reversibility test or in exacerbation due to viral infection are given in a dose of 50 mg a day for one week. If steroids don't work well enough, we combine them with aspirin desensitizations at a maintenance dose of 500 mg a day. Gastrointestinal side effects occur in 20% of the patients with a dose of 500 mg aspirin a day, in 46% with a mean dose of 1300 mg a day. The combined treatment of topical nasal steroids and aspirin-desensitization is effective in 65% of the patients with improvement in the symptoms of hyper-secretion, irritation and blockage, while 73% show improvement of polyps, hyposmia and anosmia. Endonasal endoscopic surgery of the ethmoids, turbinectoms and septoplasty should be done if necessary, especially in cases where conservative treatment fails. After surgery a further antiinflammatory treatment is absolutely necessary otherwise polyps reoccur in 90% of the cases after weeks or months. Unfortunately there is so far no curative treatment. New drugs like cytokine or leukotriene receptor antagonists give hope for better results in treatment of aspirin intolerance in the future.
阿司匹林敏感性鼻窦炎是一种非过敏性、非感染性的常年性嗜酸性粒细胞性鼻炎,起病于中年,儿童少见。在患有复发性气道感染的特应性患者中也可能出现混合型鼻炎。对阿司匹林和大多数其他非甾体抗炎药不耐受。随后可能对酒石黄、食品添加剂、酒精、麻醉剂和局部麻醉剂也不耐受。大多数阿司匹林敏感患者会出现鼻息肉。未经治疗,可导致哮喘。常年性鼻炎患者中阿司匹林不耐受的发生率为6.18%,鼻息肉患者中为14.68%。血液和鼻息肉的免疫学研究显示免疫系统反应过度,由于TH1淋巴细胞激活导致嗜酸性粒细胞活化。在患有混合型鼻炎的特应性受试者中,我们还发现了TH2和B淋巴细胞活化。嗜酸性粒细胞凋亡的抑制可能是阿司匹林敏感患者免疫系统的另一个显著变化。阿司匹林敏感性的一个关键致病事件是花生四烯酸代谢的白三烯途径发生改变,释放大量白三烯LTC4、LTD4和LTE4,它们是炎症细胞的有效趋化剂和激活剂。对于阿司匹林不耐受的诊断,可进行鼻、支气管和口服激发试验。赖氨酸阿司匹林鼻激发试验诊断阿司匹林敏感性鼻炎的敏感性为0.93,特异性为0.97。这是阿司匹林敏感哮喘患者中最安全的试验,仅0.45%的患者会出现支气管副作用。阿司匹林敏感性鼻窦炎的治疗包括避免使用阿司匹林和非甾体抗炎药。用糖皮质激素全面下调免疫反应是一种有效的方法。我们倾向于每天使用400微克布地奈德的维持剂量。用于可逆性试验或因病毒感染加重时的全身性激素剂量为每天50毫克,持续一周。如果激素效果不佳,我们将其与每天500毫克的阿司匹林脱敏疗法联合使用。每天服用500毫克阿司匹林的患者中20%会出现胃肠道副作用,平均每天服用1300毫克时这一比例为46%。局部鼻用激素和阿司匹林脱敏联合治疗对65%的患者有效,分泌物过多、刺激和阻塞症状有所改善,73%的患者鼻息肉、嗅觉减退和嗅觉丧失症状有所改善。如有必要,应进行筛窦、鼻甲切除术和鼻中隔成形术的鼻内镜手术,尤其是在保守治疗失败的情况下。手术后进一步的抗炎治疗绝对必要,否则数周或数月后90%的病例息肉会复发。不幸的是,迄今为止尚无治愈性治疗方法。细胞因子或白三烯受体拮抗剂等新药为未来更好地治疗阿司匹林不耐受带来了希望。