A 71-year old woman was admitted due to elevation of her lymphocyte count. She had been diagnosed as suffering from acute-type ATL nearly 5 months prior to admission. She had received VCAP-AMP-VECP chemotherapy followed by oral sobuzoxane in another hospital, and achieved a transient partial remission. We started mogamulizumab to treat the flare-up of ATL disease (Fig. 1). Grade 1 skin eruptions appeared around her neck after three antibody infusions. Because we were also giving her antibacterial (ciprofloxacin hydrochloride), fungal (itraconazole), pneumocystic (sulfamethoxazole-trimethoprim) and viral (aciclovir) prophylaxes in addition to stomach medicine (lansoprazole), we judged the skin event to be due to drug eruption caused by one of these concomitant drugs. Therefore, we stopped all five, but continued with mogamulizumab. Despite their discontinuation and treatment with topical steroids, the skin rashes continued to worsen. We started the patient on 30 mg oral prednisolone, which improved the skin symptoms. The patient was then able to complete the eight planned infusions, and oral prednisolone was tapered off. She was discharged from hospital 8 days after her eighth infusion (day 65), and thereafter seen as an outpatient. However, she had to be readmitted as an emergency patient at day 75 because of fulminant skin rashes. These included erythemas, scale-like plaques, vesicles, blisters and erosions over many areas of the body. Her lips were swollen and oral mucosa was erosive (Fig. 2a). Skin biopsy revealed marked liquefaction, degeneration and perivascular inflammation with dominant CD8-positive cells but almost complete lack of FOXP3-positive cells (Fig. 2b). We diagnosed her as a SJS, and immediately started steroid pulse therapy (methylprednisolone 500 mg/day ×3 days), followed by oral prednisolone. Her skin and mucosal lesions improved gradually, and became inactive. At the same time, her general condition improved. Thus, we again tapered the steroid dose, and she was discharged at day 144. However, she had to come back yet again as an emergency patient on day 151 for the same reason as before, with fulminant skin rashes. We prescribed her mini-steroid pulse therapy (methylprednisolone 125 mg/day ×1 day), followed by oral prednisolone. Once more, her skin lesions improved gradually. Over this whole period, complete ATL remission was maintained by mogamulizumab. The HTLV-1 provirus load in PBMC pre-treatment, and at days 121 and 162 was 750.1, 0.0 (under the limit of detection) and 0.8 copies/1000 cells, respectively. These post-treatment values are strikingly low, considering that median HTLV-1 load in asymptomatic carriers reported by other investigators is 18.0 copies/1000 cells.
We also analyzed CD4, CD25 and FOXP3 expression by PBMC during and after antibody treatment (Fig. 1, middle panels). Before treatment, the majority of the patient's PBMC consisted of CD4-positive and CD25-positive ATL cells. Just before the 5th antibody infusion (day 29), around the time when her skin rash first appeared, the proportion of CD25highFOXP3+/CD4+ cells was markedly reduced, to 2.2%. This is low even compared to healthy individuals (CD25highFOXP3+/CD4+ cells, mean 3.3%, median 3.3%, range 2.6–4.4%) (Fig. 3). Around the time of SJS onset, the proportion of cells in the Treg subset was further reduced. The proportion of CD25highFOXP3+/CD4+ cells at days 64, 85 and 114 was 1.8%, 1.6% and 0.7%, respectively. The striking reduction of the Treg subset persisted until 4 months after the last of the eight antibody infusions (day 171).