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. 2000 Jun;82(6):483–487. doi: 10.1136/adc.82.6.483

Long term follow up of topical mustine treatment for cutaneous Langerhans cell histiocytosis

P Hoeger 1, V Nanduri 1, J Harper 1, D Atherton 1, J Pritchard 1
PMCID: PMC1718363  PMID: 10833183

Abstract

BACKGROUND AND OBJECTIVES—Skin lesions in Langerhans cell histiocytosis (LCH) are often painful and difficult to treat. Topical application of nitrogen mustard (0.02% mechlorethamine hydrochloride, mustine), an alkylating cytostatic agent, has been shown to be effective. There is, however, concern about potentially harmful long term side effects.
STUDY DESIGN—In a retrospective study 20 children with LCH (average extent of initial skin involvement: 16.4% body surface) were followed up for an average of 8.3 years after completion of topical mustine therapy. They had received a total of 34 courses (mean duration 14.2 weeks) of topical mustine. Disease status on follow up was assessed according to the Histiocyte Society classification.
RESULTS—After mustine was introduced, 16 patients were able to discontinue systemic steroids and/or chemotherapy. Topical mustine was well tolerated in 18 patients, but two developed irritant dermatitis. On follow up, the disease was inactive in 10 patients. Among the children with active disease, six had mild skin disease and four had progressive disease, two of them with skin lesions unresponsive to mustine treatment. Scars confined to areas of formerly active skin disease were found in six patients. There was no evidence of premalignant or malignant skin disease in the treated areas.
CONCLUSION—Topical mustine is an effective and safe treatment for skin disease in most children with LCH. Residual scarring was probably a result of the disease itself rather than to mustine. Although no evidence of skin cancer was found in this study, continued long term follow up is advisable.



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Selected References

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  1. Abel E. A., Sendagorta E., Hoppe R. T. Cutaneous malignancies and metastatic squamous cell carcinoma following topical therapies for mycosis fungoides. J Am Acad Dermatol. 1986 Jun;14(6):1029–1038. doi: 10.1016/s0190-9622(86)70128-x. [DOI] [PubMed] [Google Scholar]
  2. Avril M. F. La Caryolysine locale. Ann Dermatol Venereol. 1987;114(1):133–141. [PubMed] [Google Scholar]
  3. Broadbent V., Gadner H., Komp D. M., Ladisch S. Histiocytosis syndromes in children: II. Approach to the clinical and laboratory evaluation of children with Langerhans cell histiocytosis. Clinical Writing Group of the Histiocyte Society. Med Pediatr Oncol. 1989;17(6):492–495. doi: 10.1002/mpo.2950170527. [DOI] [PubMed] [Google Scholar]
  4. Daughters D., Zackheim H., Maibach H. Urticaria and anaphylactoid reactions after topical application of mechlorethamine. Arch Dermatol. 1973 Mar;107(3):429–430. [PubMed] [Google Scholar]
  5. Du Vivier A., Vonderheid E. C., Van Scott E. J., Urbach F. Mycosis fungoides, nitrogen mustard and skin cancer. Br J Dermatol. 1978 Jul;99(1):61–63. doi: 10.1111/j.1365-2133.1978.tb01962.x. [DOI] [PubMed] [Google Scholar]
  6. Egeler R. M., D'Angio G. J. Langerhans cell histiocytosis. J Pediatr. 1995 Jul;127(1):1–11. doi: 10.1016/s0022-3476(95)70248-2. [DOI] [PubMed] [Google Scholar]
  7. Epstein J. H. Nitrogen mustard (mechlorethamine) and UVB photocarcinogenesis: a dose response effect. J Invest Dermatol. 1984 Nov;83(5):320–322. doi: 10.1111/1523-1747.ep12264105. [DOI] [PubMed] [Google Scholar]
  8. Esterly N. B., Maurer H. S., Gonzalez-Crussi F. Histiocytosis X: a seven-year experience at a children's hospital. J Am Acad Dermatol. 1985 Sep;13(3):481–496. doi: 10.1016/s0190-9622(85)70192-2. [DOI] [PubMed] [Google Scholar]
  9. Ganor S. Skin cancer in psoriatics treated with nitrogen mustard. J Am Acad Dermatol. 1983 Jul;9(1):164–165. doi: 10.1016/s0190-9622(83)80111-x. [DOI] [PubMed] [Google Scholar]
  10. Goday J. J., Aguirre A., Ratón J. A., Díaz-Pérez J. L. Local bullous reaction to topical mechlorethamine (mustine). Contact Dermatitis. 1990 May;22(5):306–307. doi: 10.1111/j.1600-0536.1990.tb01614.x. [DOI] [PubMed] [Google Scholar]
  11. Grunnet E. Contact urticaria and anaphylactoid reaction induced by topical application of nitrogen mustard. Br J Dermatol. 1976 Jan;94(1):101–103. doi: 10.1111/j.1365-2133.1976.tb04350.x. [DOI] [PubMed] [Google Scholar]
  12. Halprin K. M., Comerford M., Taylor J. R. Cancer in patients with psoriasis. J Am Acad Dermatol. 1982 Nov;7(5):633–638. doi: 10.1016/s0190-9622(82)70144-6. [DOI] [PubMed] [Google Scholar]
  13. Hancock B. W., Vaughan Hudson G., Vaughan Hudson B., Haybittle J. L., Bennett M. H., MacLennan K. A., Jelliffe A. M. British National Lymphoma Investigation randomised study of MOPP (mustine, Oncovin, procarbazine, prednisolone) against LOPP (Leukeran substituted for mustine) in advanced Hodgkin's disease--long term results. Br J Cancer. 1991 Apr;63(4):579–582. doi: 10.1038/bjc.1991.134. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hoeger P. H., Janka-Schaub G., Mensing H. Late manifestation of diabetes insipidus in "pure" cutaneous Langerhans cell histiocytosis. Eur J Pediatr. 1997 Jul;156(7):524–527. doi: 10.1007/s004310050653. [DOI] [PubMed] [Google Scholar]
  15. Irving R. M., Broadbent V., Jones N. S. Langerhans' cell histiocytosis in childhood: management of head and neck manifestations. Laryngoscope. 1994 Jan;104(1 Pt 1):64–70. doi: 10.1288/00005537-199401000-00011. [DOI] [PubMed] [Google Scholar]
  16. Kravitz P. H., McDonald C. J. Topical nitrogen mustard induced carcinogenesis. Acta Derm Venereol. 1978;58(5):421–425. [PubMed] [Google Scholar]
  17. Lee C. W., Park M. H., Lee H. Recurrent cutaneous Langerhans cell histiocytosis in infancy. Br J Dermatol. 1988 Aug;119(2):259–265. doi: 10.1111/j.1365-2133.1988.tb03210.x. [DOI] [PubMed] [Google Scholar]
  18. Lee L. A., Fritz K. A., Golitz L., Fritz T. J., Weston W. L. Second cutaneous malignancies in patients with mycosis fungoides treated with topical nitrogen mustard. J Am Acad Dermatol. 1982 Nov;7(5):590–598. doi: 10.1016/s0190-9622(82)70138-0. [DOI] [PubMed] [Google Scholar]
  19. Mandy S., Taylor J. R., Halprin K. Topically applied mechlorethamine in the treatment of psoriasis. Arch Dermatol. 1971 Mar;103(3):272–276. [PubMed] [Google Scholar]
  20. McLelland J., Broadbent V., Yeomans E., Malone M., Pritchard J. Langerhans cell histiocytosis: the case for conservative treatment. Arch Dis Child. 1990 Mar;65(3):301–303. doi: 10.1136/adc.65.3.301. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Munn S., Chu A. C. Langerhans cell histiocytosis of the skin. Hematol Oncol Clin North Am. 1998 Apr;12(2):269–286. doi: 10.1016/s0889-8588(05)70510-4. [DOI] [PubMed] [Google Scholar]
  22. Nielsen M., Rasmussen K., Knudsen N., Thestrup-Pedersen K. Long-term topical nitrogen mustard treatment does not induce pulmonary fibrosis in MF patients. Acta Derm Venereol. 1994 Jan;74(1):70–71. doi: 10.2340/00015555747071. [DOI] [PubMed] [Google Scholar]
  23. Sheehan M. P., Atherton D. J., Broadbent V., Pritchard J. Topical nitrogen mustard: an effective treatment for cutaneous Langerhans cell histiocytosis. J Pediatr. 1991 Aug;119(2):317–321. doi: 10.1016/s0022-3476(05)80752-8. [DOI] [PubMed] [Google Scholar]
  24. Stern R. S., Nichols K. T., Väkevä L. H. Malignant melanoma in patients treated for psoriasis with methoxsalen (psoralen) and ultraviolet A radiation (PUVA). The PUVA Follow-Up Study. N Engl J Med. 1997 Apr 10;336(15):1041–1045. doi: 10.1056/NEJM199704103361501. [DOI] [PubMed] [Google Scholar]
  25. Studstrup L., Beck H. I., Bjerring P., Wulf H. C., Lundgren K. No detectable increase in sister chromatid exchanges in lymphocytes from mycosis fungoides patients after topical treatment with nitrogen mustard. Br J Dermatol. 1988 Dec;119(6):711–715. doi: 10.1111/j.1365-2133.1988.tb03492.x. [DOI] [PubMed] [Google Scholar]
  26. Van Vloten W. A., Cooijmans A. C., Poel J., Meulenbelt J. Concentrations of nitrogen mustard in the air during topical treatment of patients with mycosis fungoides. Br J Dermatol. 1993 Apr;128(4):404–406. doi: 10.1111/j.1365-2133.1993.tb00199.x. [DOI] [PubMed] [Google Scholar]
  27. Vonderheid E. C., Tan E. T., Kantor A. F., Shrager L., Micaily B., Van Scott E. J. Long-term efficacy, curative potential, and carcinogenicity of topical mechlorethamine chemotherapy in cutaneous T cell lymphoma. J Am Acad Dermatol. 1989 Mar;20(3):416–428. doi: 10.1016/s0190-9622(89)70051-7. [DOI] [PubMed] [Google Scholar]
  28. Vonderheid E. C. Topical mechlorethamine chemotherapy. Considerations on its use in mycosis fungoides. Int J Dermatol. 1984 Apr;23(3):180–186. doi: 10.1111/j.1365-4362.1984.tb04507.x. [DOI] [PubMed] [Google Scholar]
  29. Whitlock J. A., Greer J. P., Lukens J. N. Epipodophyllotoxin-related leukemia. Identification of a new subset of secondary leukemia. Cancer. 1991 Aug 1;68(3):600–604. doi: 10.1002/1097-0142(19910801)68:3<600::aid-cncr2820680326>3.0.co;2-f. [DOI] [PubMed] [Google Scholar]
  30. Zachariae H. Histiocytosis X in two infants--treated with topical nitrogen mustard. Br J Dermatol. 1979 Apr;100(4):433–438. doi: 10.1111/j.1365-2133.1979.tb01645.x. [DOI] [PubMed] [Google Scholar]
  31. Zachariae H., Thestrup-Pedersen K., Søgaard H. Topical nitrogen mustard in early mycosis fungoides. A 12-year experience. Acta Derm Venereol. 1985;65(1):53–58. [PubMed] [Google Scholar]

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