Leukotriene-Receptor Inhibition for the Treatment of Systemic Mastocytosis
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《新英格兰医药杂志》
To the Editor: Systemic mastocytosis is an uncommon and potentially misdiagnosed condition. Its hallmark is the accumulation and abnormal proliferation of mast cells in various tissues.
A two-month-old boy was referred to our facility with numerous bullae on the skin and unilateral periorbital cellulitis. The child was inconsolable, and his skin lesions, which had been present since birth, progressed into subcutaneous nodules, plaques, and tumors, which were excoriated. He had hepatomegaly and wheezing. Findings on examination of biopsy specimens of the skin and bone marrow were consistent with the diagnosis of systemic mastocytosis. There were no bony lesions, and there was no evidence of associated hematologic cancer. He was treated with oral prednisone (1 mg per kilogram of body weight, given twice daily); the dose was slowly tapered, and therapy was discontinued 16 months after the diagnosis had been made. The infant had also been treated with inhibitors of mast-cell degranulation (cromolyn), of histamine H1 and H2 receptors (hydroxyzine and ranitidine, respectively), and of the cysteinyl leukotriene receptor (montelukast, given orally at a dose of 0.25 mg per kilogram twice daily). On two occasions, when the montelukast was not given, the wheezing and skin vesicles reappeared, only to subside when the montelukast was resumed.
Systemic mastocytosis has been treated with inhibitors of various mast-cell mediators, including corticosteroids, antihistamines, methoxypsoralen plus ultraviolet A photochemotherapy, nonsteroidal antiinflammatory agents, cromolyn,1 and interferon.2 Marone et al.1 recently suggested treatment with c-kit inhibitors (since, in some instances, mastocytosis is associated with mutations in the gene encoding the stem-cell factor receptor, c-kit) and leukotriene antagonists. Oxygenated derivatives of arachidonic acid are potent mast-cell mediators, and competitive leukotriene-receptor antagonists have been used for the treatment of bronchial asthma, with favorable therapeutic results. In addition, montelukast has been successfully used for the treatment of interstitial cystitis and detrusor mastocytosis.3
Our case report supports the possibility that leukotriene inhibitors, in combination with mast-cell degranulation inhibitors and histamine-receptor blockers, can be used as corticosteroid-sparing agents in the long-term management of extensive cutaneous or systemic mast-cell disease in childhood.
Jakub Tolar, M.D., Ph.D.
Whitney D. Tope, M.D.
Joseph P. Neglia, M.D., M.P.H.
University of Minnesota
Minneapolis, MN 55455
tolar@lenti.med.umn.edu
References
Marone G, Spadaro G, Granata F, Triggiani M. Treatment of mastocytosis: pharmacologic basis and current concepts. Leuk Res 2001;25:583-594
Casassus P, Caillat-Vigneron N, Martin A, et al. Treatment of adult systemic mastocytosis with interferon-alpha: results of a multicentre phase II trial on 20 patients. Br J Haematol 2002;119:1090-1097.
Bouchelouche K, Nordling J, Hald T, Bouchelouche P. The cysteinyl leukotriene D4 receptor antagonist montelukast for the treatment of interstitial cystitis. J Urol 2001;166:1734-1737.
A two-month-old boy was referred to our facility with numerous bullae on the skin and unilateral periorbital cellulitis. The child was inconsolable, and his skin lesions, which had been present since birth, progressed into subcutaneous nodules, plaques, and tumors, which were excoriated. He had hepatomegaly and wheezing. Findings on examination of biopsy specimens of the skin and bone marrow were consistent with the diagnosis of systemic mastocytosis. There were no bony lesions, and there was no evidence of associated hematologic cancer. He was treated with oral prednisone (1 mg per kilogram of body weight, given twice daily); the dose was slowly tapered, and therapy was discontinued 16 months after the diagnosis had been made. The infant had also been treated with inhibitors of mast-cell degranulation (cromolyn), of histamine H1 and H2 receptors (hydroxyzine and ranitidine, respectively), and of the cysteinyl leukotriene receptor (montelukast, given orally at a dose of 0.25 mg per kilogram twice daily). On two occasions, when the montelukast was not given, the wheezing and skin vesicles reappeared, only to subside when the montelukast was resumed.
Systemic mastocytosis has been treated with inhibitors of various mast-cell mediators, including corticosteroids, antihistamines, methoxypsoralen plus ultraviolet A photochemotherapy, nonsteroidal antiinflammatory agents, cromolyn,1 and interferon.2 Marone et al.1 recently suggested treatment with c-kit inhibitors (since, in some instances, mastocytosis is associated with mutations in the gene encoding the stem-cell factor receptor, c-kit) and leukotriene antagonists. Oxygenated derivatives of arachidonic acid are potent mast-cell mediators, and competitive leukotriene-receptor antagonists have been used for the treatment of bronchial asthma, with favorable therapeutic results. In addition, montelukast has been successfully used for the treatment of interstitial cystitis and detrusor mastocytosis.3
Our case report supports the possibility that leukotriene inhibitors, in combination with mast-cell degranulation inhibitors and histamine-receptor blockers, can be used as corticosteroid-sparing agents in the long-term management of extensive cutaneous or systemic mast-cell disease in childhood.
Jakub Tolar, M.D., Ph.D.
Whitney D. Tope, M.D.
Joseph P. Neglia, M.D., M.P.H.
University of Minnesota
Minneapolis, MN 55455
tolar@lenti.med.umn.edu
References
Marone G, Spadaro G, Granata F, Triggiani M. Treatment of mastocytosis: pharmacologic basis and current concepts. Leuk Res 2001;25:583-594
Casassus P, Caillat-Vigneron N, Martin A, et al. Treatment of adult systemic mastocytosis with interferon-alpha: results of a multicentre phase II trial on 20 patients. Br J Haematol 2002;119:1090-1097.
Bouchelouche K, Nordling J, Hald T, Bouchelouche P. The cysteinyl leukotriene D4 receptor antagonist montelukast for the treatment of interstitial cystitis. J Urol 2001;166:1734-1737.