The association between severe long-term atopic dermatitis (AD) and the risk of skin lymphoma is still a matter of debate, since epidemiological studies have shown contradictory results. We report 2 cases of patients with a documented history of severe longstanding atopic disease, who had never been treated with topical or systemic calcineurin inhibitors, and who developed a cytotoxic cutaneous T cell lymphoma (CTCL). For these 2 patients, clinical manifestations preceded the diagnosis of CTCL. The diagnosis was based on histological findings and molecular analysis of the T cell receptor (TCR) clonality. These cases illustrate the difficulty in diagnosing CTCL in patients with severe AD and extensive inflammatory skin lesions. The transition between severe AD and CTCL is progressive; histological findings and molecular evidence of TCR clonality are detected after the clinical changes. These 2 cases lend further support to the hypothesis of an association between severe long-term AD and CTCL.

Keywords:
Atopic dermatitis, Calcineurin inhibitors, CD30-positive lymphocytes, Cutaneous T cell lymphoma
1.
McWhorter WP: Allergy and risk of cancer: a prospective study using NHANESI follow up data. Cancer 1988;62:451–455.
2.
Söderberg KC, Hagmar L, Schwartzbaum J, Feychting M: Allergic conditions and risk of hematological malignancies in adults: a cohort study. BMC Public Health 2004;4:51.
3.
Eriksson NE, Holmen A, Hogstedt B, Mikoczy Z, Hagmar L: A prospective study of cancer incidence in a prospective cohort examined for allergy. Allergy 1995;50:718–722.
4.
Talbot-Smith A, Fritschi L, Divitini ML, Mallon DF, Knuiman MW: Allergy, atopy and cancer: a prospective study of the 1981 Busselton cohort. Am J Epidemiol 2003;157:606–612.
5.
Cartwright RA, McKinney PA, O’Brien C, Richards ID, Roberts B, et al: Non-Hodgkin’s lymphoma: case control epidemiological study in Yorkshire. Leuk Res 1988;12:81–88.
6.
Mehrany K, El-Azhary RA, Bouwhuis SA, Pittelkow MR: Cutaneous T-cell lymphoma and atopy: is there an association? Br J Dermatol 2003;149:1013–1017.
7.
McGregor JM, Crook T, Fraser-Andrews EA, Rozycka M, Crossland S, Brooks L, et al: Spectrum of p53 gene mutations suggests a possible role for ultraviolet radiation in the pathogenesis of advanced cutaneous lymphomas. J Invest Dermatol 1999;112:317–321.
8.
Li G, Chooback L, Wolfe JT, Rook AH, Felix CA, Lessin SR, et al: Overexpression of p53 protein in cutaneous T cell lymphoma. J Invest Dermatol 1998;110:767–770.
9.
Mougel FR, Dalle S, Balme B, Houot R, Thomas L: Aggressive CD30 large cell lymphoma after cyclosporine given for putative atopic dermatitis. Dermatology 2006;213:239–241.
10.
Laube S, Stephens M, Smith AG, Whittaker SJ, Tan BB: Lymphomatoid papulosis in a patient with atopic eczema on long-term ciclosporin therapy. Br J Dermatol 2005;152:1346–1348.
11.
Fletcher CL, Orchard GE, Hubbard V, Whittaker SJ, Edelson RL, Russell-Jones R: CD30(+) cutaneous lymphoma in association with atopic eczema. Arch Dermatol 2004;140:449–454.
12.
Kirby B, Owen CM, Blewitt RW, Yates VM: Cutaneous T-cell lymphoma developing in a patient on cyclosporin therapy. J Am Acad Dermatol 2002;47:S165–S167.
13.
Pielop JA, Jones D, Duvic M: Transient CD30+ nodal transformation of cutaneous T-cell lymphoma associated with cyclosporine treatment. Int J Dermatol 2001;40:505–511.
14.
Van Haselen CW, Toonstra J, Preesman AH, Van Der Putte SC, Bruijnzeel-Koomen CA, Van Vloten WA: Sézary syndrome in a young man with severe atopic dermatitis. Br J Dermatol 1999;140:704–707.
15.
Rajka G, Winkelmann RK: Atopic dermatitis and Sézary syndrome. Arch Dermatol 1984;120:83–84.
16.
Abel EA, Nickoloff BJ, Shelby DM, Watson W, Wood GS: Tumor stage mycosis fungoides in a patient treated with long-term corticosteroids for asthma and atopic-like dermatitis. J Dermatol Surg Oncol 1986; 12:1089–1093.
17.
Lange-Vejlsgaard G, Ralfkiaer E, Larsen JK, O’Connor N, Thomsen K: Fatal cutaneous T cell lymphoma in a child with atopic dermatitis. J Am Acad Dermatol 1989;20:954–958.
18.
Fischer M, Harvima IT, Carvalho RF, Möller C, Naukkarinen A, Enblad G, et al: Mast cell CD30 ligand is upregulated in cutaneous inflammation and mediates degranulation-independent chemokine secretion. J Clin Invest 2006;116:2748–2756.
19.
US Food and Drug Administration: FDA Public Health Advisory: elidel (pimecrolimus) cream and protopic (tacrolimus) ointment. 2005. http://www.fda.gov/cder/drug/advisory/elidel_protopic.htm (accessed October 31, 2008).
20.
Ormerod AD: Topical tacrolimus and pimecrolimus and the risk of cancer: how much cause for concern? Br J Dermatol 2005;153:701–705.
21.
Arellano FM, Wentworth CE, Arana A, Fernadez C, Paul CF: Risk of lymphoma following exposure to calcineurin inhibitors and topical steroids in patients with atopic dermatitis. J Invest Dermatol 2007;127:808–816.
22.
Jackow CM, Cather JC, Hearne V, Asano AT, Musser JM, Duvic M: Association of erythrodermic CTCL, superantigen-positive Staphylococcus aureus, and oligoclonal T-cell receptor V gene expansion. Blood 1997;89:32–40.
© 2008 S. Karger AG, Basel
2008
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