Indomethacin-induced reduction in CRTH2 in eosinophilic pustular folliculitis (Ofuji's disease): a proposed mechanism of action.
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.
Satoh
Takahiro
T
Department of Dermatology, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan. tasa-1688.derm@tmd.ac.jp
Shimura
Chieko
C
Miyagishi
Chiyako
C
Yokozeki
Hiroo
H
D000284:Administration, Oral; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000627:therapeutic use*; D015536:Down-Regulation; D004802:Eosinophilia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004804:Eosinophils / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D005499:Folliculitis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007213:Indomethacin / Q000008:administration & dosage / Q000627:therapeutic use*; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D015230:Prostaglandin D2 / Q000096:biosynthesis; D011971:Receptors, Immunologic / Q000378:metabolism*; D011982:Receptors, Prostaglandin / Q000378:metabolism*; D012008:Recurrence; D013492:Suppuration; D016896:Treatment Outcome; D055815:Young Adult
D000894:Anti-Inflammatory Agents, Non-Steroidal; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; D015230:Prostaglandin D2; D007213:Indomethacin; C036293:prostaglandin D2 receptor