New approaches to therapy for mastocytosis - A case for treatment with kit kinase inhibitors
New approaches to therapy for mastocytosis - A case for treatment with kit kinase inhibitors
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DOI：
10.1016/s0889-8588(05)70302-6
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发表时间：
2000-06-01
影响因子：
2.4
通讯作者：
McMahon, G
中科院分区：
文献类型：
--
作者：
Longley, BJ;Ma, YS;McMahon, G
目前尚无治疗肥大细胞增多症的方法。肥大细胞增多症的治疗通常是保守的和有症状的，目的是防止或改善肥大细胞介质的有害作用，而不是消除产生和释放肥大细胞介质的肥大细胞。(9)因此，肥大细胞增多症的管理始于教育患者避免可能导致肥大细胞介质释放的特定因素及其症状反应。直接治疗干预是针对个别患者的症状，主要由阻断组胺受体的药物组成。阻断H-1受体在控制皮肤症状如潮红和瘙痒方面有一定疗效，H-2拮抗剂用于预防和治疗组胺诱导的消化性溃疡疾病、痉挛和腹泻。甘糖酸二钠稳定肥大细胞膜，减少介质释放，似乎有助于缓解某些患者的痉挛和腹泻，但其使用存在争议。除了这些极其严重的症状，可使肥大细胞增多症患者的生活痛苦，严重的问题，如危及生命的过敏反应可能与肥大细胞介质的释放有关。肾上腺素和充分的支持护理可能是必要的过敏性反应或血管塌陷引起的大量肥大细胞脱颗粒。此外，尽管肥大细胞及其介质在与肥大细胞增多症相关的骨髓纤维化和骨髓增生异常骨髓疾病、严重贫血和血液恶性肿瘤的发病机制中的作用尚未确定，但肥大细胞有可能直接导致这些危及生命的疾病。显然，通过减少或消除肿瘤肥大细胞的数量来治疗肥大细胞增多症是可取的。几种形式的治疗已被用于暂时减少肥大细胞数量，但这些治疗与显著的不良副作用相关。补骨脂素-紫外线A疗法（PUVA）能减少皮肤肥大细胞的数量，抑制瘙痒。补骨脂素-紫外线A疗法对皮肤肥大细胞增多症患者也有美容效果，但长期使用会增加患皮肤癌的风险，而其治疗效果只是暂时的。同样，局部或全身使用皮质类固醇可能会短暂地减少肥大细胞负荷并缓解症状，但它们与长期皮肤萎缩、肾上腺皮质抑制、骨质疏松和股骨头无菌性坏死等副作用有关。这些疗法都不是针对肥大细胞增多症的特定原因。
There is currently no cure for mastocytosis. The treatment of mastocytosis is generally conservative and symptomatic and is designed to prevent or ameliorate the deleterious effects of mast cell mediators rather than to eliminate the mast cells which produce and release them.(9) Thus, management of mastocytosis begins with educating the patient to avoid specific factors that can cause the release of mast cell mediators and the symptomatic responses to them. Direct therapeutic intervention is tailored to the symptom complex of individual patients and consists mainly of drugs that block histamine receptors. Blockage of H-1 receptors has some efficacy in controlling cutaneous symptoms such as flushing and itching, and H-2 antagonists are used to prevent and treat histamine-induced peptic ulcer disease, cramping, and diarrhea. Disodium cromoglycate stabilizes mast cell membranes, decreases mediator release, and seems to be helpful in relieving cramping and diarrhea in some patients, but its use is controversial. Besides these extremely aggravating symptoms, which can make life miserable for mastocytosis patients, serious problems such as life-threatening anaphylaxis may be associated with the release of mast cell mediators. Adrenaline and full supportive care may be necessary for anaphylaxis or vascular collapse induced by massive mast cell degranulation. Furthermore, although the contribution of mast cells and their mediators to the pathogenesis of the myelofibrotic and myelodysplastic bone marrow disease, severe anemia, and hematologic malignancy associated with mastocytosis has not been determined, it is possible that the mast cells directly contribute to these life-threatening conditions. Obviously, it would be preferable to treat mastocytosis by decreasing or eliminating the number of neoplastic mast cells. Several forms of therapy have been used to decrease mast cell numbers temporarily, but these therapies are associated with significant adverse side effects. Psoralen-ultraviolet A therapy (PUVA) can decrease the number of cutaneous mast cells and suppress pruritus. Psoralen-ultraviolet A therapy may also have cosmetic benefits for patients with cutaneous mastocytosis, but its long-term use is associated with an increased risk of skin cancer, whereas its therapeutic benefits are only temporary. Likewise, topical or systemic corticosteroids may transiently decrease the mast cell burden and provide symptomatic relief, but they are associated with long-term cutaneous atrophy, adrenocortical suppression, osteoporosis, and aseptic necrosis of the femoral head, among other side effects. None of these therapies is directed against a specific cause of mastocytosis.