Updates on HTLV-1 Uveitis

Abstract

HTLV-1 uveitis (HU) is the third clinical entity to be designated as an HTLV-1-associated disease. Although HU is considered to be the second-most frequent HTLV-1-associated disease in Japan, information on HU is limited compared to that on adult T-cell leukemia/lymphoma (ATL) and HTLV-1-associated myelopathy (HAM). Recent studies have addressed several long-standing uncertainties about HU. HTLV-1-related diseases are known to be caused mainly through vertical transmission (mother-to-child transmission), but emerging HTLV-1 infection by horizontal transmission (such as sexual transmission) has become a major problem in metropolitan areas, such as Tokyo, Japan. Investigation in Tokyo showed that horizontal transmission of HTLV-1 was responsible for HU with severe and persistent ocular inflammation. The development of ATL and HAM is known to be related to a high provirus load and hence involves a long latency period. On the other hand, factors contributing to the development of HU are poorly understood. Recent investigations revealed that severe HU occurs against a background of Graves' disease despite a low provirus load and short latency period. This review highlights the recent knowledge on HU and provides an update on the topic of HU in consideration of a recent nationwide survey.

Keywords: Graves’ disease; HTLV-1 uveitis; Human T-cell lymphotropic virus; biologics; horizontal transmission.

Figure 1

Horizontal transmission of HTLV-1 is responsible for HTLV-1 uveitis. (A) Vitreous opacity is seen in the right eye. (B) Severe and persistent ocular inflammation of horizontally transmitted HU resulted in retinal detachment (Reproduced with permission from Kamoi et al., Lancet Infect. Dis. 2021 [44]).

Figure 2

HU occurred after methimazole treatment following the onset of Graves’ disease. (A) Vitreous opacity is seen in the right eye. (B) Retinal vasculitis can be seen by fluorescein angiography (Reproduced with permission from Kamoi et al., Lancet 2022 [43]).

Figure 3

Ocular infiltration in ATL. Multiple knob-like ATL cell ocular infiltrates are seen (KAMOI sign). The KAMOI sign (A,B; white arrows) can be seen at the bulbar conjunctiva around the corneal limbus and at the palpebral conjunctiva around the lacrimal punctum (A) and in the retina (B). Multiple infiltrating ATL cells in the vitreous tend to form clusters (C) (Reproduced with permission from Kamoi et al., Cornea 2016 [62]; Kamoi. Front. Microbiol. 2020 [19]).

Figure 4

Frosted branch angiitis after allogenic hematopoietic stem-cell transplantation (Reproduced with permission from Kamoi et al., Lancet Haematol. 2020 [75]).