Background: Few reports have described vitiligo developing in patients with cutaneous T-cell lymphoma (CTCL). Objective: We sought to identify possible factors that might predispose patients with CTCL to vitiligo. Methods: Patient demographics, CTCL disease characteristics and treatments were analyzed in 25 patients with CTCL who developed vitiligo. Cox proportional hazards modeling was used to identify associations of risk factors with the development of vitiligo. Results: Younger age, later CTCL disease stage (stages IIB-IV) and presence of a CD8+CD4- mycosis fungoides phenotype were associated with the development of vitiligo. After adjusting for disease stage, increased risk of vitiligo was associated with methotrexate and CD4 antibody therapies (although the total number of patients with these was small), while decreased risk was associated with nitrogen mustard and PUVA therapies. Conclusions: No single feature was common to all of our patients, suggesting that multiple factors may contribute to the development of vitiligo in a patient-specific fashion.

Keywords:
Cutaneous T-cell lymphoma, Cytokines, Leukoderma, Lymphoma, Mycosis fungoides, Vitiligo
1.
Rook AH, Heald P: The immunopathogenesis of cutaneous T-cell lymphoma. Hematol Oncol Clin North Am 1995;9:997-1010.
2.
Lutzner M, Edelson R, Schein P, et al: Cutaneous T-cell lymphomas: the Sézary syndrome, mycosis fungoides, and related disorders. Ann Intern Med 1975;83:534-552.
3.
Galper SL, Smith BD, Wilson LD: Diagnosis and management of mycosis fungoides. Oncology (Williston Park) 2010;24:491-501.
4.
Edelson RL: Cutaneous T cell lymphoma: mycosis fungoides, Sézary syndrome, and other variants. J Am Acad Dermatol 1980;2:89-106.
5.
Le Poole IC, Luiten RM: Autoimmune etiology of generalized vitiligo. Curr Dir Autoimmun 2008;10:227-243.
6.
Krüger C, Schallreuter K: A review of worldwide prevalence of vitiligo in children/adolescents and adults. Int J Dermatol 2012;51:1206-1212.
7.
Criscione VD, Weinstock MA: Incidence of cutaneous T-cell lymphoma in the United States. Arch Dermatol 2007;143:479-484.
8.
Alcalay J, David M, Shohat B, Sandbank M: Generalized vitiligo following Sézary syndrome. Br J Dermatol 1987;116:851-855.
9.
Bouloc A, Grange F, Delfau-Larue MH, et al: Leucoderma associated with flares of erythrodermic cutaneous T-cell lymphomas: four cases. The French Study Group of Cutaneous Lymphomas. Br J Dermatol 2000;143:832-836.
10.
Mimouni D, David M, Feinmesser M, et al: Vitiligo-like leucoderma during photochemotherapy for mycosis fungoides. Br J Dermatol 2001;145:1008-1014.
11.
Knol AC, Quereux G, Marques-Briand S, et al: Pathogenetic mechanisms of vitiligo in a patient with Sézary syndrome. Br J Dermatol 2005;153:1207-1212.
12.
Olsen E, Vonderheid E, Pimpinelli N, et al: Revisions to the staging and classification of mycosis fungoides and Sézary syndrome: a proposal of the International Society for Cutaneous Lymphomas (ISCL) and the cutaneous lymphoma task force of the European Organization of Research and Treatment of Cancer (EORTC). Blood 2007;110:1713-1722.
13.
Nordlund JJ, Abdel-Malek ZA: Mechanisms for post-inflammatory hyperpigmentation and hypopigmentation. Prog Clin Biol Res 1988;256:219-236.
14.
El-Darouti MA, Marzouk SA, Azzam O, et al: Vitiligo versus hypopigmented mycosis fungoides (histopathological and immunohistochemical study, univariate analysis). Eur J Dermatol 2006;16:17-22.
15.
Schallreuter KU, Wazir U, Kothari S, et al: Human phenylalanine hydroxylase is activated by H2O2: a novel mechanism for increasing the L-tyrosine supply for melanogenesis in melanocytes. Biochem Biophys Res Commun 2004;322:88-92.
16.
Lazarova R, Hristakieva E, Lazarov N, Shani J: Vitiligo-related neuropeptides in nerve fibers of the skin. Arch Physiol Biochem 2000;108:262-267.
17.
Glassman SJ: Vitiligo, reactive oxygen species and T-cells. Clin Sci (Lond) 2011;120:99-120.
18.
Gauthier Y, Cario Andre M, Taieb A: A critical appraisal of vitiligo etiologic theories. Is melanocyte loss a melanocytorrhagy? Pigment Cell Res 2003;16:322-332.
19.
Ongenae K, Van Geel N, Naeyaert JM: Evidence for an autoimmune pathogenesis of vitiligo. Pigment Cell Res 2003;16:90-100.
20.
Westerhof W, d'Ischia M: Vitiligo puzzle: the pieces fall in place. Pigment Cell Res 2007;20:345-359.
21.
Goodwin RG, Finlay AY, Anstey AV: Vitiligo following narrow-band TL-01 phototherapy for psoriasis. Br J Dermatol 2001;144:1264-1266.
22.
Halcin C, Hann SK, Kauh YC: Vitiligo following the resolution of psoriatic plaques during PUVA therapy. Int J Dermatol 1997;36:534-536.
23.
Smith DI, Heffernan MP: Vitiligo after the resolution of psoriatic plaques during treatment with adalimumab. J Am Acad Dermatol 2008;58(suppl 2):S50-S52.
24.
Larregue M, Martin J, Bressieux JM, et al: Vitiligoid achromias and severe atopic dermatitis. Apropos of 4 cases (in French). Ann Dermatol Venereol 1985;112:589-600.
25.
Quaglino P, Marenco F, Osella-Abate S, et al: Vitiligo is an independent favourable prognostic factor in stage III and IV metastatic melanoma patients: results from a single-institution hospital-based observational cohort study. Ann Oncol 2010;21:409-414.
26.
Todes-Taylor N, Abel EA, Cox AJ: The occurrence of vitiligo after psoralens and ultraviolet A therapy. J Am Acad Dermatol 1983;9:526-532.
27.
Falabella R, Escobar CE, Carrascal E, Arroyave JA: Leukoderma punctata. J Am Acad Dermatol 1988;18:485-494.
28.
Le Poole IC, van den Wijngaard RM, Westerhof W, Das PK: Presence of T cells and macrophages in inflammatory vitiligo skin parallels melanocyte disappearance. Am J Pathol 1996;148:1219-1228.
29.
Saed G, Fivenson DP, Naidu Y, Nickoloff BJ: Mycosis fungoides exhibits a Th1-type cell-mediated cytokine profile whereas Sézary syndrome expresses a Th2-type profile. J Invest Dermatol 1994;103:29-33.
30.
Yoo EK, Cassin M, Lessin SR, Rook AH: Complete molecular remission during biologic response modifier therapy for Sézary syndrome is associated with enhanced helper T type 1 cytokine production and natural killer cell activity. J Am Acad Dermatol 2001;45:208-216.
31.
Basak PY, Adiloglu AK, Ceyhan AM, Tas T, Akkaya VB: The role of helper and regulatory T cells in the pathogenesis of vitiligo. J Am Acad Dermatol 2009;60:256-260.
32.
Ciree A, Michel L, Camilleri-Broet S, et al: Expression and activity of IL-17 in cutaneous T-cell lymphomas (mycosis fungoides and Sézary syndrome). Int J Cancer 2004;112:113-120.
33.
Chong BF, Wilson AJ, Gibson HM, et al: Immune function abnormalities in peripheral blood mononuclear cell cytokine expression differentiates stages of cutaneous T-cell lymphoma/mycosis fungoides. Clin Cancer Res 2008;14:646-653.
34.
Bassiouny DA, Shaker O: Role of interleukin-17 in the pathogenesis of vitiligo. Clin Exp Dermatol 2010;36:292-297.
35.
Krejsgaard T, Odum N, Geisler C, et al: Regulatory T cells and immunodeficiency in mycosis fungoides and Sézary syndrome. Leukemia 2011;26:424-432.
36.
Klarquist J, Denman CJ, Hernandez C, et al: Reduced skin homing by functional Treg in vitiligo. Pigment Cell Melanoma Res 2010;23:276-286.
37.
Ahmed MB, Zaraa I, Rekik R, et al: Functional defects of peripheral regulatory T lymphocytes in patients with progressive vitiligo. Pigment Cell Melanoma Res 2011;25:99-109.
38.
Van Scott EJ, Yu RJ: Melanogenesis from topical mechlorethamine and analogues in skin of hairless mice and in vitiligo. J Invest Dermatol 1975;65:476-478.
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2015
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