Drug-induced CD30+ T cell pseudolymphoma

ARTICLE

Auteur(s) : Shoko Fukamachi, Kazunari Sugita, Yu Sawada, Toshinori Bito, Motonobu Nakamura, Yoshiki Tokura

Department of Dermatology, University of Occupational and Environmental Health, Japan, 1-1 Iseigaoka Yahatanishi-ku, Kitakyushu 807-8555, Japan

CD30 is a member of the tumor necrosis factor receptor (TNFR) superfamily, but the functional significance of the interaction of the CD30 ligand (CD30L: CD153) with CD30 remains unclear. CD30+ T lymphocytes are the hallmark of primary cutaneous anaplastic large cell lymphoma (ALCL) and lymphomatoid papulosis (LyP) as well as Hodgkin’s disease [1]. Over the past 10 years, accumulating evidence has suggested the presence of drug-induced cutaneous pseudolymphoma with infiltration of CD30+ large atypical cells. Here we report a case of this type of pseudolymphoma with a review of the literature.

A 70-year-old man was referred to our hospital with a 4-month history of a widespread pruritic erythematous eruption. He had a 10-year history of hypertension and began taking amlodipine besilate one year before. Eight months after the administration of amlodipine, an erythematous eruption appeared and gradually spread to the whole body.

Clinical examination revealed multiple, partly coalesced, scaly erythematous plaques present predominantly on the trunk and extremities without mucosal involvement (figure 1A). His temperature was 36.3° C. Blood examination showed slight leukocytosis, 9,600/μL (normal, 3,100-9,100/μL) with eosinophilia (1,440/μL, 15%; normal, 1-5%), slightly high IgE level (383 U/mL; normal < 170 U/mL), no atypical lymphocytes, and a normal biochemical profile. A skin biopsy specimen from the right chest exhibited mild hyperkeratosis and dense infiltration of lymphocytes intermingled with eosinophils, mainly around vessels in the upper to middle dermis (figure 1B). An immunohistochemical study showed that infiltrating lymphocytes were mostly positive for CD4 (figure 1C). Notably, there were large atypical cells positive for CD30 (figure 1D). By flowcytometry, the peripheral blood mononuclear cells contained a normal range of T cells (CD3, 59.9%; CD4, 33.6%; and CD8, 20.8%) and B cells (CD20, 24.4%) and CD30⁺ T cells were not detected. Lymphocyte stimulation test, performed as reported previously [2], was positive for amlodipine besilate, with a stimulation index of 190% at a final concentration of 4 ng/mL (figure 1E). Based on the clinical and laboratory findings, the diagnosis was drug-induced CD30+ pseudolymphoma, caused by amlodipine besilate. Amlodipine was discontinued, and he was treated with oral fexofenadine, 120 mg daily, and topical application of betamethasone butyrate propionate, resulting in clinical improvement within 3 weeks. This is the second case of amlodipine besilate induced CD30+ T cell peudolymphoma, the first case was also reported by us [3].

Drug-induced CD30+ ALCL has rarely been reported with monoclonal T-cell receptor γ chain gene rearrangement [4]. Drug-induced CD30+ T cell pseudolymphoma also appears to be rare, as only ten cases including ours have been reported to date (table 1). Although the mechanism underlying drug-induced CD30+ pseudolymphoma remains only partly elucidated, a T-cell-mediated delayed-type drug hypersensitivity reaction has been proposed, supported by the positive lymphocyte stimulation tests in our two cases [3]. In seven of ten reported cases, the eruptions occurred after more than several weeks of drug administration. Our patient further suggests that this disorder frequently develops after a long period of drug intake. In Cases 3 and 4, skin eruptions occurred after short periods, they might have been already sensitized to the drugs.

Nathan et al. [5] reported a case of carbamazepine-induced CD30+ T cell pseudolymphoma with clinical manifestations of drug-induced hypersensitivity syndrome (DIHS), including high fever, liver dysfunction, eosinophilia, and leukocytosis. However, our cases lacked the clinical features suggestive of DIHS, including high fever, leukocytosis, human herpes simplex 6 reactivation and resistance to strong intervention. Clinically, it should be kept in mind that amlodipine, a drug widely used for hypertension, is an important causative agent for CD30+ pseudolymphoma.

Acknowledgements

Références

2 Sugita K, Koga C, Yoshiki R, et al. Papuloerythroderma caused by aspirin. Arch Dermatol 2006; 142: 792-3.

3 Kabashima R, Orimo H, Hino R, et al. CD30-positive T-cell pseudolymphoma induced by amlodipine. J Eur Acad Dermatol Venereol 2008; 22: 1522.

4 Di Lernia V, Viglio A, Cattania M, Paulli M. Carbamazepine-induced, CD30+, primary, cutaneous, anaplastic large-cell lymphoma. Arch Dermatol 2001; 137: 675-6.

5 Nathan DL, Belsito DV. Carbamazepine-induced pseudolymphoma with CD-30 positive cells. J Am Acad Dermatol 1998; 38: 806-9.