Basophils infiltrate into skin lesions more commonly than previously thought, and thus they may play important roles in a variety of inflammatory skin diseases.
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.
The Student's t-test was used to assess the statistical significance of differences between mean values of healthy subjects and patients. *P < 0.05.Abbreviations: CRTH2, chemoattractant receptor-homologous molecule expressed on Th2 cells; PGD2 prostaglandin D2.
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DEAR EDITOR, We appreciate the interest from and comments by Dr Naldi about our work recently published in the BJD, 1 which suggested that preservation of the deep fascia in melanomas thicker than 2 mm (excised with a 1-cm excision margin) is safe and results in a similar outcome to fascia excision. 2 Balancing function, morbidity and cosmetics with oncological outcomes in melanoma management requires careful decision making with respect to determining the appropriate method of excision. 3 Inadequate excision might lead residual tumour cells to a local recurrence of metastases, a life-threatening process (60-80% of such patients eventually die as a result of their disease). 4,5 However, unnecessary tissue excisions are associated with greater morbidity and might lead to bad functional and cosmetic results. 6,7 Unfortunately, the optimal depth of excision remains unknown, and the current melanoma guidelines do not make direct recommendations on the depth of excision. 8 Therefore, this lack of evidence-based data causes significant heterogeneity among surgeons, even in a single centre, with regard to the removal or preservation of the deep muscular fascia at the time of wide local excision for primary cutaneous thick melanomas. 8-10 It is obvious that randomized controlled trials (RCTs) are the reference standard to assess efficacy. Furthermore, the establishment of new protocols and dramatic modification of currently approved melanoma guidelines should only be performed carefully after the implementation of prospective randomized multicentric clinical trials. However, despite several limitations (being retrospective, nonrandomized, and having limited statistical power and a relatively short follow-up), the results of our study addressed this neglected issue and highlighted possible hope for the future, and may provoke the melanoma centres to set up new, large-scale RCTs with longer follow-ups in order to overcome the controversial issue of the correct depth of melanoma excision.
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