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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