plete response of cutaneous LCH with PIH and mild irritation at 6-month and 2-year follow-up, respectively. In the first case, the patient eventually became intolerant to all topical therapies, including petrolatum in all affected areas even in areas not treated with topical nitrogen mustard. She also developed CMML. Interestingly, patients with cutaneous LCH have been observed to develop secondary hematologic malignancies in small cohort studies.3 In the second case, our patient experienced complete response and remission.
The literature on the short-term effects of topical nitrogen mustard therapy is inconsistent, ranging from mild hypopigmentation or hyperpigmentation to urticarial, bullous reactions, and severe allergic contact dermatitis in treated adults.6,8,12,13 Long-term side effects have not been well-studied. There is concern regarding increased incidence of epithelial skin cancer in patients treated with topical nitrogen mustard for mycosis fungoides.12 Moreover, a possible carcinogenic effect has been observed in animal models.14 Long-term outcomes remain to be studied. The literature is scant regarding mitigation of allergic or irritant contact dermatitis from topical nitrogen mustard, but dilution with water, concomitant use of topical corticosteroids, and desensitization may help minimize side effects.5,6 In conclusion, our cases support the use of topical nitrogen mustard as a possible treatment for primary cutaneous LCH with positive responses that may spare patients from requiring systemic immunosuppressive treatments.
The literature on the short-term effects of topical nitrogen mustard therapy is inconsistent, ranging from mild hypopigmentation or hyperpigmentation to urticarial, bullous reactions, and severe allergic contact dermatitis in treated adults.6,8,12,13 Long-term side effects have not been well-studied. There is concern regarding increased incidence of epithelial skin cancer in patients treated with topical nitrogen mustard for mycosis fungoides.12 Moreover, a possible carcinogenic effect has been observed in animal models.14 Long-term outcomes remain to be studied. The literature is scant regarding mitigation of allergic or irritant contact dermatitis from topical nitrogen mustard, but dilution with water, concomitant use of topical corticosteroids, and desensitization may help minimize side effects.5,6 In conclusion, our cases support the use of topical nitrogen mustard as a possible treatment for primary cutaneous LCH with positive responses that may spare patients from requiring systemic immunosuppressive treatments.
DISCLOSURES
The authors have no conflicts of interest to report.
REFERENCES
1. Abla O, Egeler RM, Weitzman S. Langerhans cell histiocytosis: Current concepts and treatments. Cancer Treat Rev. 2010;36(4):354-359.
2. Titgemeyer C, Grois N, Minkov M, Flucher-Wolfram B, Gatterer-Menz I, Gadner H. Pattern and course of single-system disease in Langerhans cell histiocytosis data from the DAL-HX 83- and 90-study. Med Pediatr Oncol. 2001;37(2):108-114.
3. Edelbroek JR, Vermeer MH, Jansen PM, et al. Langerhans cell histiocytosis first presenting in the skin in adults: frequent association with a second haematological malignancy. Br J Dermatol. 2012;167(6):1287-1294.
4. Failla V, Wauters O, Caucanas M, Nikkels-Tassoudji N, Nikkels AF. Photodynamic therapy for multi-resistant cutaneous Langerhans cell histiocytosis. Rare Tumors. 2010;2(2):e34.
5. Lindahl LM, Fenger-Grøn M, Iversen L. Topical nitrogen mustard therapy in patients with Langerhans cell histiocytosis. Br J Dermatol. 2012;166(3):642- 645.
6. Sheehan MP, Atherton DJ, Broadbent V, Pritchard J. Topical nitrogen mustard: an effective treatment for cutaneous Langerhans cell histiocytosis. J Pediatr. 1991;119(2):317-321.
7. Taverna JA, Stefanato CM, Wax FD, Demierre MF. Adult cutaneous Langerhans cell histiocytosis responsive to topical imiquimod. J Am Acad Dermatol. 2006;54(5):911-913.
8. Schlinsog AS, Kreft B, Marsch WC. Cutaneous Langerhans cell histiocytosis - an indication for dermatological pharmacotherapy with topical nitrogen mustard. J Dtsch Dermatol Ges. 2018;16(9):1133-1135.
9. Treat JR, Suchin KR, James WD. Topical nitrogen mustard ointment with occlusion for Langerhans' cell histiocytosis of the scalp. J Dermatolog Treat. 2003;14(1):46-47.
10. Berman B, Chang DL, Shupack JL. Histiocytosis X: treatment with topical nitrogen mustard. J Am Acad Dermatol. 1980;3(1):23-29.
11. Nethercott JR, Murray AH, Medwidsky W, Chalvardjian A. Histiocytosis X in two adults. Treatment with topical mechlorethamine. Arch Dermatol. 1983;119(2):157-161.
12. Hoeger PH, Nanduri VR, Harper JI, Atherton DA, Pritchard J. Long term follow up of topical mustine treatment for cutaneous langerhans cell histiocytosis. Arch Dis Child. 2000;82(6):483-487.
13. Goday JJ, Aguirre A, Ratón JA, DÃaz-Pérez JL. Local bullous reaction to topical mechlorethamine (mustine). Contact Dermatitis. 1990;22(5):306-307.
14. Epstein JH. Effects of mechlorethamine (HN2, nitrogen mustard) on UV-induced carcinogenesis in hairless mouse skin. J Natl Cancer Inst. 1984;72(2):383-385.
2. Titgemeyer C, Grois N, Minkov M, Flucher-Wolfram B, Gatterer-Menz I, Gadner H. Pattern and course of single-system disease in Langerhans cell histiocytosis data from the DAL-HX 83- and 90-study. Med Pediatr Oncol. 2001;37(2):108-114.
3. Edelbroek JR, Vermeer MH, Jansen PM, et al. Langerhans cell histiocytosis first presenting in the skin in adults: frequent association with a second haematological malignancy. Br J Dermatol. 2012;167(6):1287-1294.
4. Failla V, Wauters O, Caucanas M, Nikkels-Tassoudji N, Nikkels AF. Photodynamic therapy for multi-resistant cutaneous Langerhans cell histiocytosis. Rare Tumors. 2010;2(2):e34.
5. Lindahl LM, Fenger-Grøn M, Iversen L. Topical nitrogen mustard therapy in patients with Langerhans cell histiocytosis. Br J Dermatol. 2012;166(3):642- 645.
6. Sheehan MP, Atherton DJ, Broadbent V, Pritchard J. Topical nitrogen mustard: an effective treatment for cutaneous Langerhans cell histiocytosis. J Pediatr. 1991;119(2):317-321.
7. Taverna JA, Stefanato CM, Wax FD, Demierre MF. Adult cutaneous Langerhans cell histiocytosis responsive to topical imiquimod. J Am Acad Dermatol. 2006;54(5):911-913.
8. Schlinsog AS, Kreft B, Marsch WC. Cutaneous Langerhans cell histiocytosis - an indication for dermatological pharmacotherapy with topical nitrogen mustard. J Dtsch Dermatol Ges. 2018;16(9):1133-1135.
9. Treat JR, Suchin KR, James WD. Topical nitrogen mustard ointment with occlusion for Langerhans' cell histiocytosis of the scalp. J Dermatolog Treat. 2003;14(1):46-47.
10. Berman B, Chang DL, Shupack JL. Histiocytosis X: treatment with topical nitrogen mustard. J Am Acad Dermatol. 1980;3(1):23-29.
11. Nethercott JR, Murray AH, Medwidsky W, Chalvardjian A. Histiocytosis X in two adults. Treatment with topical mechlorethamine. Arch Dermatol. 1983;119(2):157-161.
12. Hoeger PH, Nanduri VR, Harper JI, Atherton DA, Pritchard J. Long term follow up of topical mustine treatment for cutaneous langerhans cell histiocytosis. Arch Dis Child. 2000;82(6):483-487.
13. Goday JJ, Aguirre A, Ratón JA, DÃaz-Pérez JL. Local bullous reaction to topical mechlorethamine (mustine). Contact Dermatitis. 1990;22(5):306-307.
14. Epstein JH. Effects of mechlorethamine (HN2, nitrogen mustard) on UV-induced carcinogenesis in hairless mouse skin. J Natl Cancer Inst. 1984;72(2):383-385.
AUTHOR CORRESPONDENCE
Nicole R. LeBoeuf MD MPH nleboeuf@bwh.harvard.edu
