HTLV-1 infected persons ocular clinical manifestations of_2232

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HTLV-1 infected persons ocular clinical manifestations of_2232

HTLV-1 infected persons ocular clinical manifestations of

     Author: Jiang Feng, CAI Ping, Jin-chang, LIU Xiu-


     Abstract Human T cell leukemia virus type ? (HTLV-1)

    infection is relatively rare, mainly popular in Japan, the

    Caribbean, Central and South America. Known to infect primarily by ocular manifestations, including adult T-cell

    leukemia (ATL) in patients with malignant infiltration of the eye, retinal degeneration, eye neuropathy, HTLV-1 associated

    myelopathy / tropical spastic paraparesis (HAM / TSP) in patients with keratoconjunctivitis sicca, and HTLV-1 uveitis

    (HU) and so on. HTLV-1 related eye diseases are growing in scope, duration of abnormal immune regulation may occur in the eye caused by disease or eye cancer, genetic and environmental factors may be different populations of patients with HTLV-1

    play a role in ocular manifestations . In this paper, HTLV-1-

    related ocular manifestations and the latest developments are reviewed.

     Key words human T cell leukemia virus type ?

     0 Introduction

     Human T-cell leukemia virus type ? (HTLV-1) was first

    discovered in 1980 belongs to reverse tumor virus RNA virus family subfamily mammalian C-type virus, was the first one was found with human disease-related retrovirus. HTLV-1 mainly via

    sexual contact, blood transfusion, mother to child vertical transmission and breast-feeding, etc. [1]. Diagnosis is

    primarily dependent on serological detection methods are

commonly used enzyme-linked immunosorbent assay, particle

    agglutination, immunofluorescence, Western blot and radioimmunoassay precipitation detection. HTLV-1 occurs mainly

    in Japan, the Caribbean, Central and South America. It is reported that the positive rate of serum in southwestern Japan was as high as 37%, far more than other areas, such as the Caribbean (2% ~ 6%), Brazil (0.08% ~ 1.8%) and the United States (0.02%) and other non-endemic areas [2 -4].

     With the human immunodeficiency virus HIV (previously considered to be HTLV-3) similar to, HTLV-1 is also the main

    target cells of CD4 T cells. HTLV-1 with the following exact

    relationship between the disease: adult T-cell leukemia (ATL),

    is a kind of malignant CD4 lymphocytes; HTLV-1 associated

    myelopathy / tropical spastic paraparesis (HAM / TSP), is a

    kind of spinal cord removal sheath lesions; HTLV-1 uveitis

    (HU), is a form of HTLV-1 as the carrier of the uveitis of

    unknown etiology [1]. Among them, the most prevalent HU. In addition, HTLV-1 was seen with a number of inflammatory diseases, including early childhood dermatitis, alveolitis, polymyositis, arthritis, and Sjogren syndrome, [2].

     1 HTLV-1 uveitis

     To date, the vast majority of HTLV-1-related eye

    diseases reported are from Japan, it is reported the estimated prevalence rate of HU in Japan 112/100 000 [5]. In 1992 the first Japanese scholar from the serum epidemiology, ophthalmology, and virology to describe the HU, they found that uveitis of unknown etiology in patients with serum positive rate of HTLV-1 is higher than a clear cause of

    uveitis patients and in the serum of these patients to detect HTLV-1 virus-like particles [6]. HTLV-1 uveitis, mostly

    recurrent clinical manifestations of acute moderate to severe vitreous inflammation accompanied by mild iritis and retinal

    vasculitis. Application of corticosteroids after the treatment most patients the prognosis is still good, and the complication rate is not high [6]. Previously reported ophthalmic manifestations of HTLV-1 In addition to HU, is also

    including adult T-cell leukemia (ATL) in patients with

    malignant infiltration of the eye, retinal degeneration, eye neuropathy, HTLV-1 associated myelopathy / tropical spastic paralysis (HAM / TSP) in patients with keratoconjunctivitis sicca and outer scleritis [7,8].

     Two studies of 182 cases of Japanese patients with long-

    term follow-up HU [5,6], found that HU patients were women, more common, male and female prevalence ratio of 1.7:2.0, but the initial age of onset is earlier in men, women, men 34.8 years , women 48.1 years. About 60% of patients with uveitis for the monocular and multi-floating shadow associated with

    blurred vision and immediate. Nearly 20% of patients with mild anterior segment checkup shows granulomatous inflammation and lesions, vitreous granular, flocculent, and groups such as

    massive vitreous opacity inflammatory changes are the most characteristic performance. Retinal vasculitis, exudative retinopathy and optic nerve degeneration rates were 60%, 25% and 20%. About 75% of the HU in the anatomical part of

    intermediate uveitis. The majority of cases on the course of 4 ~ 8wk of local or systemic hormone therapy response is good, 40% ~ 50% of the victims are susceptible to relapse. HU can cause a series of complications, including cataracts, glaucoma, permanent vitreous opacity, epiretinal membranes, retinal choroidal degeneration and retinal vascular occlusion; and about 33% of patients with optic atrophy, visual acuity decreased to 0.3,4% ~ 10% even decreased to 0.3 below; only 3% of patients with cystoid macular edema. 8 patients were

    diagnosed at the HU before the HAM / TSP, 4 patients were diagnosed after at the HU out of HAM / TSP. 15% ~ 20% of patients due to Graves disease in HU treatment before the verdict, Methimazole. HU did not occur in patients with ATL.

    And different from previous studies, this research suggests that two HU may lead to other ocular complications, and affect vision. In another study, 43 cases of HU in patients with hyperthyroidism before the onset HU accept Methimazole treatment, of which only 2 cases occurred in patients with Graves eye disease, 1 patient also suffered from HU, HAM, and hyperthyroidism [9], Graves disease and HU suggesting that there may be some relationship, Deguchi et al [10] deduced the reason for the excessive levels of thyroid hormones may change the immune environment, stimulating HTLV-1 viral replication,

    leading to a large number of HTLV-1 infection of lymphocytes

    In addition Methimazole in vivo effects of thyroid hormones may also be related to the occurrence HU. Early studies

    suggest that HU is subject to HTLV-1 infected T cells to

    secrete inflammatory cytokines such as IL-2, IL-6, IL-8, TNF-

    α and INF-γ and other eye tissues caused by infiltration [11].

     2 HLTV-1-related retinal vasculitis

     Retinal vascular sheath and fundus fluorescein angiography of vascular leakage in the retina of the characteristic features of vascular inflammation [12,13], but also a major performance HU, which require the hormone treatment. A total of three studies described the HLTV-1-

    related retinal vasculitis [14-16]. One study reported 1 cases

    of Jamaican women in ATL patients with necrotizing retinal vasculitis, vitreous inflammation with bilateral lesions showed significantly around the sheath of the retinal blood

    vessels, multifocal punctate retinitis, macular edema and optic disc and fundus fluorescein angiography Contrast vascular leakage. Systemic vasculitis was no significant correlation with retinal disease, systemic hormone therapy after the initial symptoms improved, but as the hormone

    reduction, lesion to integration of necrotizing retinal vasculitis with retinal detachment. To further rule out infectious retinitis, retinal detachment surgery in the line of retinal biopsy prompted necrotizing granulomatous retinal

    vasculitis. Did not find any clinical HTLV-1 positive

    performance, until the blood and brain tissue tests proved that the patient was ATL patients. The case prompted to ATL in the clinical manifestations can be similar with the HU, the diagnosis of retinal vasculitis in patients with HTLV-1

    infection should also be considered, especially in the HTLV-1

    endemic areas. Another study reported three cases of Japanese young people to HTLV-1-positive patients, showing a wide range of pairs of hormone therapy ineffective retinal vasculitis, and eventually developed into retinal degeneration. Including two cases of rapid disease progression in patients, showing mild anterior segment inflammation, retinal vein significantly around the sheath, vein dilation, extensive retinal exudation,

    and macular edema, optic disc, fundus fluorescein angiography can be seen around the optic disc and retinal vein coloring leakage . There are two cases of young women one cases of patients with retinal vasculitis 11a after being diagnosed

    with disease HAM / TSP. In addition 1 patient had a history of 22a of retinal vasculitis, manifested as retinal vein sheath, retinal artery narrowing, diffuse chorioretinal degeneration, extensive loss of retinal pigment epithelium induced by fundus

    fluorescein angiography of vascular filling delay and diffuse high - fluorescence, and the corresponding vision and ERG

    abnormalities. In the first three studies, researchers found 83 cases of ATL in patients with lymphoma, 1 case of bilateral retinal vasculitis with infiltration of patients and the patients, including fundus fluorescein angiography, including all the clinical eye examination. Study found that as the ATL onset, eye damage initially manifested as peripheral retinal infiltration, and to form retinal vein inflammation spread to other regions of the retina, vitreous inflammation only in end-stage disease only appeared. And with the progress of eye damage, despite drug treatment, the patient's general situation is still deteriorating rapidly, suggesting that ATL

    occurs in patients with retinal vasculitis may be prompted to poor prognosis. Some studies that the chronic inflammatory process of the retinal blood vessels leading to the pathogenic mechanism of retinal degeneration by the HTLV-1 infected T

    cells, eventually causing the spinal cord degeneration (HAM / TSP) of the pathogenic mechanism similar to [17].

     3 HTLV-1 associated chorioretinopathy

     Although fundus fluorescein angiography is considered the diagnosis of retinal vasculitis of the gold standard, but the indocyanine green angiography (ICGA) can provide better images of choroidal circulation. Sakurai et al [18] on 27 cases of HU in patients with 54 rows ICGA examination, 83% of the affected eye can be seen very early ICG choroidal vascular

    leakage, 20% of the affected eye can be found in small low-

    fluorescent early point, and continue until late . We surmise that the performance of high fluorescent spots may lead to leakage of choroidal inflammatory choroidal circulatory

    disturbance, and thus the performance of low fluorescent spots. ICG choroidal vascular leakage and a high point and the availability of fluorescent membrane vitreous opacity no significant correlation, ICG seen and retinal vasculitis has not determined the relationship between activity. Currently on the HU reports of patients with choroidal damage is limited, yet more research is needed to reveal the situation of HU in patients with choroidal involvement.

     Four non-Japanese region of the eye in patients with

    HTLV-1 expression

     Yamamoto et al [3] in 1999 first reported outside of Japan endemic areas the prevalence of HTLV-1 in serum and

    ocular manifestations. Sao Paulo, Brazil were studied in 190 cases of uveitis patients (65.1% white, 12% black, 21.1%

    mixed, 3.7% Asian) of the HTLV-1 prevalence and asymptomatic

    HTLV-1 carriers of the ocular manifestations. The results showed that 190 cases of uveitis in patients with HTLV-1

    seroprevalence rate was 0.5%, a clear cause of uveitis in patients with HTLV-1 were negative, 53 cases of uveitis of unknown etiology in patients with HTLV-1 seroprevalence rate

    was 1.9%. Epidemiological studies have shown that Japan's HU uveitis of unknown etiology in patients with HTLV-1

    seropositive rate than the known causes of uveitis in patients

    with high 4 to 8 times, with similar, this research suggests that uveitis of unknown etiology HTLV-1 in patients with serum

    positive rate than the known causes of uveitis in patients with high 10 times. Although the 105 cases of HTLV-1 carriers

    in the three cases have the same HU ocular manifestations, HTLV-1 seronegative patients and asymptomatic HTLV-1 carriers

    in the only meaningful difference between, HTLV-1 carriers in

    in the tear film break-up time were more extended. Merle et al

    [19] in 2002 on the French West Indies, 200 HTLV-1

    seropositive patients (77 patients with asymptomatic carriers and 123 cases of HAM / TSP patients) study found that keratoconjunctivitis sicca, uveal inflammation and corneal stromal keratitis is the HTLV-1 infection of the most common

    ocular manifestations. 29 patients (14.5%) of anterior uveitis and intermediate uveitis of the precise effects of hormone therapy. And Japanese scholars of different pairs of HU reports, the study found no uveitis associated with retinal

    vasculitis and hyperthyroidism. Asymptomatic carriers and HAM / TSP patients with similar incidence of uveitis. However, when compared with the asymptomatic carriers, HAM / TSP patients with early age at onset of uveitis; with no uveitis

    in HAM / TSP compared with patients suffering from uveitis of the HAM / TSP patients will lead to more severe muscle movement dysfunction. In addition, HAM / TSP patients more likely to induce keratoconjunctivitis sicca, the sick rate was 37%, 50% of HAM / TSP patients two plasma cell infiltration of lymphocytes in the salivary glands. HTLV-1 associated

    keratoconjunctivitis sicca is considered in patients with HIV and HCV is described in greater relevance of Sjogren's syndrome, Sjogren syndrome associated with less. Reposted

    elsewhere in the paper for free download http://

     5 HTLV-1-related keratopathy

     Three independent research groups described in 2001 in patients with asymptomatic HTLV-1 and HTLV-1-related disease

    in patients with corneal disease correlation, while in Japan there were no similar reports [4,20,21]. Merle et al [4,19] reviewed 119 cases of HAM / TSP patients and 75 cases of asymptomatic HTLV-1 carriers and found that 20 patients

    (10.3%) of the existence of bilateral peripheral corneal

    stroma-like white round cluster of shallow turbid , slightly higher than the surface, a diameter of 0.5 ~ 2.0mm, no obvious irritation, ulcers and do not form new blood vessels, and the poor response of local hormone therapy. The corneal abnormalities in HAM / TSP patients, more common, accompanied by corneal stroma proliferation of lymphocytes plasma cells infiltration, which is HTLV-1 induced inflammatory

    infiltration similar to other organs. The researchers called these corneal lesions associated with chronic HTLV-1 stromal

    keratitis. Buggage, etc. [20] reported 3 cases of Jamaica ATL patients with elevated levels of serum immunoglobulin and asymptomatic corneal damage, of which 1 patient the existence and matrix related to central corneal thinning in shallow

    areas is poor, the other one cases of patients there is an extension of the cornea scattered to the corneal stroma edge of the gray murky, muddy area between the substrate and transparent; the first three cases of patients had peripheral corneal scar formation, substrate thinning,

    neovascularization, as well as the conjunctiva and skin nodules similar to ATL. The former two cases of corneal opacity in patients with acquired immune protein may consider keratopathy, 3 patients were considered likely to ATL caused

    by peripheral ulcerative keratitis. Castelo Branco et al [21] subsequently reported the southwest of the Brazilian Amazon 20 cases of asymptomatic corneal opacity associated with the HTLV-1 patients. Yamamoto et al [3] in 1999, Sao Paulo, Brazil

    described in asymptomatic carriers of HTLV-1 spot and circular

    infiltration of the cornea, which may be the first sign that HLTV-1-related damage to the cornea. In all these studies, researchers have not found any other disease could explain the

    damage the cornea. The existence of patients with corneal damage are from HTLV-1 endemic areas (temperate and tropical climate), no precise contact with the Japanese descent, suggesting that genetic and environmental factors may play a role in corneal disease. One on the elevated levels of serum immunoglobulin and HTLV-1-related disease in patients with

    corneal opacity link between research indicates that a simple high-agammaglobulinemia and can not lead to HTLV-1 in patients

    with corneal damage [22]. Merle et al [4] that the HTLV-1

    associated peripheral keratopathy more like a symptom of corneal proliferation of plasma cells infiltrating lymphocytes left after inactive scar.

     6 HTLV-1 related to the molecular biology of eye disease

     Two recent studies have reported the use of molecular biological analysis techniques can effectively diagnose HTLV-

    1-related eye diseases [14,23]. In a study, the researchers mentioned earlier, the presence of peripheral corneal scar formation, damage to substrate thinning and conjunctival

    conjunctival biopsy Jamaican male patient was diagnosed as T-

    cell lymphoma [23]. Molecular analysis of the tumor cells using microdissection and the polymerase chain reaction, resulting cloned T-cell receptor, and in tumor cells found in

    HTLV-1 gag gene, supporting the formation of the virus in tumor play a role in perspective. Another study, researchers associated with vasculitis of the Jamaican women in ATL patient was perivascular granulomatous infiltration biopsy, using microdissection and the polymerase chain reaction analysis of T cells, results showed that T-cell malignancy

    there is T cell receptor gene rearrangement, and found that the HTLV-1 pol gene, confirmed the HTLV-1 can cause ATL [14].

     In summary, HTLV-1 continues to expand the scope of

    ocular manifestations. Since HTLV-1-related eye disease in the

    onset of multiple symptoms, the latter part of the development of diversification, it is recommended for HTLV-1 seropositive

    patients with follow-up should be routine eye. The majority of

    HTLV-1-related eye disease and immune regulation related to the corticosteroid hormone treatment response is good, but there will still be difficult to detect clinically tumor lesions, the need for more aggressive treatment. Must be clear

    of genetic and environmental factors on the different races in different parts of the eye in patients with HTLV-1 on the

    performance of needed further study.


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