Department of Dermatology, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
Acta Derm Venereol. 2010;90(1):18-22. doi: 10.2340/00015555-0759.
Eosinophilic pustular folliculitis is an inflammatory skin disease characterized by pruritic follicular papulopustules. It is usually resistant to topical and/or systemic corticosteroids, but it responds well to systemic indomethacin. We report here two patients with classical-type disease who were treated with systemic indomethacin. As indomethacin is an inhibitor of cyclo-oxygenases and a potent agonist of the prostaglandin D2 (PGD2) receptor, CRTH2 (chemoattractant receptor homologous molecule expressed on Th2 cells), we investigated the effects of indomethacin on CRTH2 expression by leukocytes. CRTH2 was expressed on blood eosinophils and lymphocytes. In vitro treatment with indomethacin suppressed the expression of CRTH2 on these cells. In addition, systemic treatment with indomethacin reduced eosinophil CRTH2 expression in another patient in association with improvement of skin lesions and blood eosinophilia. A number of inflammatory cells expressed haematopoietic PGD synthase, an essential enzyme for generating PGD2 in skin lesions of eosinophilic pustular folliculitis. A PGD2-CRTH2 interaction may be involved in the pathogenesis. Moreover, indomethacin may exert its therapeutic effect via reducing CRTH2 expression, as well as by inhibiting PGD2 synthesis.
嗜酸性脓疱性毛囊炎是一种以瘙痒性毛囊性丘疹脓疱为特征的炎症性皮肤病。它通常对局部和/或全身皮质类固醇有耐药性，但对全身吲哚美辛反应良好。我们在此报告两例接受全身用吲哚美辛治疗的经典型疾病患者。由于吲哚美辛是环氧化酶抑制剂和前列腺素 D2（PGD2）受体的有效激动剂，CRTH2（表达于 Th2 细胞上的趋化因子受体同源物），我们研究了吲哚美辛对白细胞中 CRTH2 表达的影响。CRTH2 表达于血液嗜酸性粒细胞和淋巴细胞上。体外用吲哚美辛处理可抑制这些细胞上 CRTH2 的表达。此外，全身用吲哚美辛治疗另一位患者可降低嗜酸性粒细胞 CRTH2 表达，同时改善皮肤病变和血液嗜酸性粒细胞增多。在嗜酸性脓疱性毛囊炎皮损中，许多炎症细胞表达了造血 PGD 合酶，这是生成 PGD2 的必需酶。PGD2-CRTH2 相互作用可能参与发病机制。此外，吲哚美辛可能通过降低 CRTH2 表达以及抑制 PGD2 合成发挥治疗作用。
