Immunologic markers, uveitis, and keratoconjunctivitis sicca associated with human T-cell lymphotropic virus type 1

PURPOSE: To verify the occurrence of keratoconjunctivitis sicca (KCS) and human T-cell lymphotropic virus type 1 (HTLV-1) associated uveitis (HAU) and to evaluate the immunologic status related to HTLV-1. DESIGN: Cross-sectional study. METHODS: Ophthalmic examination (both eyes) and immunophenotyping of peripheral blood lymphocytes were performed in 207 infected asymptomatic blood donors (AS), 55 controls (NI), and 55 patients with HTLV-1 associated myelopathy (HAM/TSP). Examiner was masked to patient's serologic status. RESULTS: KCS was more frequent in HAM/TSP (30/55, 54.5%) than in NI and AS (07/55, 12.7% and 42/207, 20.3%, respectively). Presence of lacrimal hyposecretion in KCS individuals was higher in the HAM/TSP group (P < .001) as compared with NI and AS. HAU was found in 1/55 (1.82%) of HAM/TSP patients and 4/207 (1.93%) of HTLV-1 seropositive donors. Higher levels of activated CD4(+) and CD8(+) T cells were observed in HAM/TSP. Patients with HAU displayed higher percentage of both CD4(+) HLA-DR(+) and CD8(+)HLA-DR(+) when compared with NI and AS without HAU. CONCLUSIONS: Patients with HAM/TSP manifested more ophthalmologic symptoms than asymptomatic HTLV-1-infected individuals, with significantly higher KCS and immunologic alterations. Levels of activated CD8+ T cells could be used as a prognosis marker of inflammatory disease manifestation to follow-up AS individuals.     

Intermediate uveitis due to human T-cell lymphotropic virus type 1

CASE REPORT: The case of a 66-year-old woman with intermediate uveitis in both eyes and progressive weakness of lower limbs is reported. A human T-lymphotropic virus type 1 (HTLV-1) infection was detected in the serological study, with the patient being diagnosed with tropical spastic paraparesis and HTLV-1 intermediate uveitis. The patient made good progress with oral steroid treatment. DISCUSSION: The clinical and epidemiological aspects of HTLV-1 infection are discussed. We recommend a serological determination of the virus in intermediate uveitis of unknown origin in people from endemic areas or with neurological symptoms.     

Ocular manifestations of human T-cell lymphotropic virus type 1 infection

PURPOSE OF REVIEW: Human T-cell lymphotropic virus type 1 (HTLV-1) infection is endemic in Japan, the Caribbean islands, and parts of Central Africa and South America. Known ophthalmic manifestations of HTLV-1 include malignant infiltrates in patients with adult T-cell leukemia/lymphoma, retinal degeneration, neuroophthalmic disorders, and keratoconjunctivitis sicca in patients with HTLV-1-associated myelopathy/tropical spastic paraparesis, and HTLV-1-associated uveitis. This report reviews the recent developments and ocular findings reported in patients with HTLV-1-related diseases. RECENT FINDINGS: Most of the knowledge of the ocular manifestations of HTLV-1 comes from southwestern Japan, which has the highest incidence of infection worldwide. During the past few years, however, ocular disease associated with HTLV-1 has been described in patients from other endemic areas genetically distinct and geographically distant from Japan. The most interesting of these was the recognition of corneal pathology in Brazilian and Caribbean patients with HTLV-1 that have not been described in Japanese patients. Other developments include the use of molecular techniques in the diagnostic evaluation of ocular tissues from HTLV-1 patients, and clinical studies demonstrating choroidal involvement by indocyanine green angiography in patients with HTLV-1-associated uveitis, and suggesting that retinal vasculitis unresponsive to corticosteroid therapy maybe a poor prognostic sign. SUMMARY: The spectrum of ocular disease related to HTLV-1 continues to expand. Routine evaluation of HTLV-1-infected patients is important because immune-mediated or neoplastic ocular involvement may occur during the disease course. Genetic and environmental factors may play a role in the ocular manifestations of HTLV-1 in different populations.     

HTLV-1感染者的眼部临床表现

人类T淋巴细胞白血病病毒Ⅰ型(HTLV-1)感染比较少见,主要流行于日本、加勒比海地区、中非和南美洲。已知感染者主要眼部表现包括成人T细胞白血病(ATL)患者的眼部恶性浸润、视网膜变性、眼部神经病变,HTLV-1相关性脊髓病/热带痉挛性瘫痪(HAM/TSP)患者的干燥性角结膜炎及HTLV-1葡萄膜炎(HU)等。HTLV-1相关性眼部病变的范围正在扩大,病程中可能出现免疫调节失常引起的眼部病变或眼部肿瘤,遗传和环境因素可能在不同人群中HTLV-1患者的眼部表现起一定作用。本文就HTLV-1相关眼部表现及最新进展作一综述。     

Human T-cell lymphotropic virus type 1-associated retinal vasculitis in children.

PURPOSE: To describe predominant retinal vasculitis in children carrying human T-cell lymphotropic virus type 1 (HTLV-1). METHODS: The authors examined clinical records of patients with HTLV-1-associated uveitis between 1987 and 2001 in Kagoshima University Hospital and reviewed cases of extensive, smoldering retinal vasculitis. RESULTS: Three previously healthy teenagers noted mild visual symptoms and presented with extensive sheathing of retinal vessels, complicated by mild anterior segment inflammation. The retinal vascular disease responded poorly to systemic corticosteroids, had a smoldering course with persistent sheathing of retinal vessels, and eventually resulted in diffuse chorioretinal degeneration. Results of laboratory studies were unremarkable except for the presence of serum antibodies to HTLV-1. One patient developed HTLV-1-associated myelopathy 11 years after the onset of ocular disease. CONCLUSIONS: The retinal vasculitis differed from the retinal vascular changes commonly seen in HTLV-1-associated uveitis. The authors suggest a clinical disease HTLV-1-associated retinal vasculitis that affects young HTLV-1 carriers, characterized by smoldering retinal vasculitis with ultimate retinal degeneration.     

Isolation of the human T-cell leukemia/lymphotropic virus type III from the cornea

Corneoscleral donor tissue from a donor with a positive serum antibody to HTLV-III but without the overt clinical signs of the acquired immune deficiency syndrome (AIDS) was cultured for the presence of the human T-cell leukemia/lymphotropic virus type III (HTLV-III). The virus was isolated from the two corneal specimens in this patient after the tissue had been stored for four days in McCarey-Kaufman medium. The presence of HTLV-III was confirmed by the detection of viral core proteins (approximately 24,000 protein, termed P24 gag), by immunofluorescence of a touch preparation of the corneal epithelium as well as in cells cultured in vitro. The percentage of immunofluorescent cells detected by HTLV-III anti-P24 antibody ranged between 2% and 3%. These findings emphasize the possibility of transmission of this virus via corneal transplantation surgery. Although no documented cases of AIDS have occurred in corneal transplant recipients, serologic screening of donors before the use of the tissue for transplantation is advisable.     

Analysis of HLA class I and class II gene polymorphisms in Japanese patients with human T-cell lymphotropic virus type 1-associated uveitis

PURPOSE: To investigate the immunogenetic background of human T-cell lymphotropic virus type 1 (HTLV-1)-associated uveitis (HAU) that presents immune-mediated reactive changes in the uvea. METHODS: HLA class I and class II genes were studied in 51 patients with HAU, 192 asymptomatic HTLV-1 carriers, and 266 HTLV-1-seronegative controls using a high-resolution method of HLA DNA typing. The HLA alleles of HAU were compared with those of HTLV-1 carriers and healthy controls. RESULTS: We identified 62 distinct alleles of HLA-A, HLA-Cw, and HLA-B and 49 distinct alleles of HLA-DRB1 and HLA-DQB1 in patients with HAU, asymptomatic HTLV-1 carriers, and healthy controls. The relative frequencies of these HLA alleles did not differ among the three groups. CONCLUSION: The results suggest that HLA class I and class II genes do not contribute to susceptibility to HAU.     

Uveitis associated with varicella virus vaccine

PURPOSE: To report a case of uveitis associated with the live attenuated varicella virus vaccine (Varivax; Merck & Co, Inc, West Point, Pennsylvania) in a young, otherwise healthy girl. METHODS: The time of onset of uveitis in relation to vaccination and the number and the pattern of distribution of vesicles were noted. The patient received oral acyclovir and topical steroids and cycloplegic drops. RESULTS: The uveitis and vesicular rash improved significantly after 7 days of treatment. A literature review and communications with the drug's manufacturer disclosed no identifiable previous cases of uveitis associated with Varivax. CONCLUSIONS: Uveitis should be recognized as a possible adverse side effect of the varicella vaccine.     

Retinal vasculitis in human T-lymphotropic virus type I associated myelopathy.

Human T-lymphotropic virus type I (HTLV-I) has been recently found to be associated with slowly progressive myelopathy. We have seen 12 patients with HTLV-I associated myelopathy (HAM), three of whom showed retinal vasculitis. In addition two patients had ocular symptoms of vitreous opacity. Retinal vasculitis in these patients appears to be phlebitis and sheathing of retinal veins in the periphery of the fundus.     

Human T lymphotropic virus type 1 uveitis.

The human retroviruses, HTLV-I and HIV, are playing clinically important roles in a variety of ocular disorders, particularly in uveitis. Both viruses are integrated in the genome of infected T cells. HIV-I infection causes the death of the infected T cells, thereby affecting the host defence system and causing AIDS. Subsequent opportunistic infections of ocular tissues, such as CMV retinitis, are a serious problem in clinical ophthalmology all over the world. Another human retrovirus, HTLV-I, has been known as the causative agent of T cell malignancies (ATL and T cell lymphoma) and chronic myelopathy (HAM/TSP), and is now recognised as a causative agent for a specific type of intraocular inflammation characterised by vitreous opacities with mild iritis and mild retinal vasculitis (HTLV-I uveitis). The mechanism by which HTLV-I causes uveitis is still unknown, but our recent data suggest that it is most probably an immune mediated mechanism by activated CD4 T cells infected with the virus. HTLV-I uveitis, therefore, may implicate a significant role of retroviruses in autoimmune diseases and further the pathogenesis of diseases with infection/autoimmune overlap.     

Human T-cell leukemia/lymphotropic virus type III in the conjunctival epithelium of a patient with AIDS

The human T-cell leukemia/lymphotropic virus type III (HTLV-III), the causative agent of the acquired immunodeficiency syndrome (AIDS), has been isolated from the conjunctival epithelium of a 33-year-old woman with AIDS, suggesting that an important reservoir of the virus may be the ocular surface epithelial cells. The tears and conjunctival epithelium from normal controls were negative for HTLV-III. The finding of HTLV-III in the tears and conjunctival epithelium indicated that HTLV-III may be ubiquitous in bodily cells and fluids. Repeated contact with the tears and ocular surface epithelium of patients with AIDS may possibly facilitate transmission of HTLV-III, and precautions are advisable during routine ophthalmologic procedures such as glaucoma testing and contact-lens fitting.     

Isolation of the human T-cell leukemia/lymphotropic virus type III from aqueous humor in two patients with perivasculitis of the retinal vessels

Summary The human T-cell leukemia/lymphotropic virus type III (HTLV-III) has been isolated from aqueous humor in two patients with perivasculitis of the peripheral retinal vessels, an AIDS-related ocular manifestation. Both patients had antibodies to HTLV-III and although they presented with herpes zoster ophthalmicus, they did not present other symptoms known to be associated with HTLV-III infection. The isolation of HTLV-III from aqueous humor in these two patients with retinal perivasculitis suggests that the virus itself may play a role in the etiology of this ocular sign. The presence of infectious HTLV-III in the anterior chamber further emphasises the necessity to discard corneas from HTLV-III infected donors. Address for offprints: Mrs Suzy Sprecher-Goldberger, Institut Pasteur du Brabant, rue Engeland 642, Bruxelles/Uccle Belgium     

Ocular lesions in 200 patients infected by the human T-cell lymphotropic virus type 1 in martinique (French West Indies)

PURPOSE: To describe the ophthalmologic features observed in patients infected by the human T-cell lymphotropic virus, type 1 (HTLV-1) in Martinique (French West Indies). DESIGN: Prospective consecutive observational case series. METHODS: A complete ophthalmic examination was performed. PATIENTS: Of 200 patients infected by HTLV-1, 77 (38.5%) were seropositive and 123 (61.5%) had HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP). RESULTS: Uveitis was found in 29 cases (14.5%). Symptoms were mild and the uveitis had little effect on visual function. Ten cases of uveitis were discovered through a systematic examination and had no ocular symptoms. Most of the uveitis was anterior or intermediate. The lesions responded to corticosteroid therapy, but tended to recur. Keratoconjunctivitis sicca existed in 74 patients (37%), accompanied by lymphoplasmocytoid infiltration of the secondary salivary glands rated 3 or 4 on the Chisholm scale in nearly 50% of cases. Corneal alterations were observed in 20 cases (10%), and alterations in the retinal pigment epithelium in 3 cases. CONCLUSION: The three types of ocular affections seen most frequently were uveitis, keratoconjunctivitis sicca, and interstitial keratitis. In patients with HAM/TSP, uveitis was more frequent among younger patients, patients with earlier onset of HAM/TSP, and patients with severe motor disability. Because uveitis is related to a high intrathecal production of immunoglobulin, it could represent a marker for severity of HTLV-1 infection with respect to the course of HAM/TSP. The sicca syndrome related to HTLV-1 virus differs from primary or secondary Sj?gren syndrome, because it does not reveal any of the immunologic anomalies generally seen in this disease. Interstitial keratitis was more frequent among patients with HAM/TSP who had high proviral DNA levels.     

Human T-cell lymphotropic virus type-1 associated t-cell leukemia/lymphoma masquerading as necrotizing retinal vasculitis

OBJECTIVE: To report a case of adult T-cell leukemia/lymphoma (ATL) presenting as a bilateral retinal vasculitis and diagnosed by molecular detection of a rearrangement in the T-cell receptor (TCR) and the presence of the human T-cell lymphotropic virus type 1 (HTLV-1) pol gene in the malignant lymphoid cells. DESIGN: Case report. METHODS: Routine histologic and immunohistochemical analyses were performed on the retinal biopsy specimen before referral to the National Eye Institute. Lymphoid cells associated with granulomatous inflammation infiltrating the retina and surrounding retinal blood vessels were microdissected from the paraffin sections of the retinal biopsy specimen. The polymerase chain reaction (PCR) was performed using primers for the TCR gene and HTLV-1 pol and gag genes. RESULTS: Microscopic examination showed a necrotizing granulomatous retinal vasculitis with a predominant T-cell infiltrate detected by immunohistochemistry. Molecular analysis demonstrated a clonal rearrangement of the TCR and the presence of the HTLV-1 pol gene in the microdissected lymphoid cells diagnostic of ATL. CONCLUSIONS: Necrotizing retinitis and retinal vasculitis are rare manifestations of ATL. Human T-cell lymphotropic virus type 1 infection should be considered in the differential diagnosis of patients from endemic areas who have retinal vasculitis at presentation. This case further demonstrates the usefulness of microdissection and PCR for the diagnosis of ocular disease, including HTLV-1 infection.     

Human T lymphotropic virus type 1 uveitis after Graves' disease.

A distinct clinical entity of uveitis associated with human T lymphotropic virus type 1 (HTLV-I) has been reported previously. During the period between January 1989 and April 1992, 93 patients were observed with HTLV-I uveitis and a significant correlation was found between Graves' disease and HTLV-I uveitis. Sixteen of the 93 patients with HTLV-I uveitis (17.2%) had a previous history of Graves' disease. Fifteen patients were female (15/60, 25.0%) and one was male (1/33, 3.0%). Interestingly, uveitis occurred after the onset of Graves' disease in all cases. On the other hand, none of 222 patients with idiopathic uveitis who were seronegative to HTLV-I had a history of Graves' disease. Although the mechanisms by which HTLV-I causes the correlation between uveitis and Graves' disease are unknown, the present data suggest that immune mediated or autoimmune mechanisms are involved in HTLV-I uveitis.