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Advances in dermatology and venereology Acta Dermato-Venereologica
CD8 + T-cell-mediated Interface Dermatitis after CCR4 + T-cell Depletion by Mogamulizumab Treatment of Adult T-cell Leukaemia / lymphoma
Ayako ITO 1, Kazunari SUGITA 1 *, Koji ADACHI 1, Yuzuru HOSODA 2, Toru MOTOKURA 2 and Osamu YAMAMOTO 1
1
Division of Dermatology, Department of Medicine of Sensory and Motor Organs and 2 Division of Clinical Laboratory Medicine, Department of Pathophysiological and Therapeutic Science, Tottori University Faculty of Medicine, 86 Nishi-cho, Yonago 683-8504, Japan. * E-mail: sugita @ med. tottori-u. ac. jp Accepted Oct 26, 2016; Epub ahead of print Oct 27, 2016
Adult T-cell leukaemia / lymphoma( ATLL), a malignancy of CD4 + T cells with poor prognosis, is caused by human T-cell lymphotropic virus type 1( HTLV-1). Based on the organ involvement and severity, ATLL is divided into 4 clinical categories: acute, chronic, lymphoma and smouldering types( 1). ATLL neo plastic cells are usually present with the phenotype of CD4 + CD25 + CCR4 + cells( 2, 3). CCR4 is a 7-transmembrane domain, G-proteincoupled receptor that is specific for the CC chemokines CCL17 and CCL22. Among the various T-cell subsets, CCR4 is also expressed on activated Th2 cells and regulatory T cells( Treg)( 4 – 7). A novel defucosylated humanized anti-CCR4 monoclonal antibody, mogamulizumab, has been approved for treatment of ATLL in Japan( 8). Mogamulizumab exerts highly cytotoxic for ATLL cells via antibody-dependent cellular cytotoxicity. Here, we show that vacuolar type of interface dermatitis induced by CD8 + T cells may occur in association with the elevated immunity after mogamulizumab treatment.
CASE REPORT
An 85-year-old Japanese man with chronic heart failure was diagnosed with acute-type ATLL. Peripheral blood examination showed an elevated leukocyte count of 24,300 / μl with 79 % abnormal lymphocytes; approximately 94 % of the lymphocytes were positive for CD4, CD25 and CCR4. The level of soluble interleukin-2 receptor was 4,811 IU / ml. At that time, he did not report having any skin symptoms. Since there was strong expression of CCR4 on ATLL cells in peripheral blood, he was treated with mogamulizumab. One month after the completion of treatment with 8 doses of mogamulizumab, a skin lesion appeared and he was referred to our department. Prior to the development of the eruption, he had been treated for hypertension, prostatomegaly, arrhythmia, bronchitis, and hypokalaemia with spironolactone, tamsulosin, bisoprolol fumarate, carbocisteine, and potassium chloride, respectively.
Physical examination revealed widespread erythema with papules predominantly on the trunk and extremities( Fig. 1a, b). A skin biopsy specimen from the left forearm showed vacuolar interface dermatitis with exocytosis of lymphocytes and perivascular infiltration of lymphocytes in the dermis( Fig. 1c). These lymphocytes did not exhibit significant atypia. A lymphocyte stimulation test was negative for spironolactone, tamsulosin, bisoprolol fumarate, carbocisteine and potassium chloride. Thus, we suspected drug reaction due to mogamulizumab. He was treated with topical application of 0.05 % clobetasol propionate and oral levocetirizine hydrochloride( 5 mg) every day for 2 months, resulting in partial clinical improvement.
Three months after the skin lesion first appeared, despite the discontinuation of mogamulizumab administration, the erythematous eruptions deteriorated. Physical examination revealed widespread erythema with solid papules predominantly on the trunk and extremities and palmoplantar hyperkeratosis( Fig. 1d, e). A skin biopsy from the right lower leg disclosed hyperkeratosis with exocytosis of small lymphocytes without any atypia, vacuolar alteration in the junctional zone and marked perivascular lymphocytic infiltrates in the dermis( Fig. 1f). A peripheral blood sample showed no reactivation of varicella zoster virus, cytomegalovirus, Epstein-Barr virus or human herpes virus 6. Anti-nuclear(× 40, normal < 40), anti-double-stranded DNA(< 0.5, 10 IU / ml) and anti-phospholipid
Fig. 1. Clinical pictures at( a, b) the first and( d, e) the second eruption phases, and histology at( c) the first and( f) the second eruption phases.( Haematoxylin-eosin, original magnification × 100).
This is an open access article under the CC BY-NC license. www. medicaljournals. se / acta Journal Compilation © 2017 Acta Dermato-Venereologica. doi: 10.2340 / 00015555-2555 Acta Derm Venereol 2017; 97: 377 – 378