Bilateral acute acquired toxoplasmic retinochoroiditis after steroid therapy for hantavirus pulmonary syndrome: case report.

Description of a case of acute acquired ocular toxoplasmosis following hantavirus pulmonary syndrome. A 41-year-old man presenting hantavirus pulmonary syndrome, confirmed in the laboratory by detection of IgM antibodies to the virus, was submitted to high doses of intravenous corticosteroids for two months. After clinical improvement of hantavirus pulmonary syndrome the patient presented visual loss in both eyes that was secondary to a toxoplasmosis retinitis. The retinitis resolved with anti-toxoplasma therapy. Acquired toxoplasmic retinochoroiditis can occur following steroid therapy for hantavirus pulmonary syndrome.

Bilateral acute acquired toxoplasmic retinochoroiditis after steroid therapy for hantavirus pulmonary syndrome: case report

Description of a case of acute acquired ocular toxoplasmosis following hantavirus pulmonary syndrome. A 41-year-old man presenting hantavirus pulmonary syndrome, confirmed in the laboratory by detection of IgM antibodies to the virus, was submitted to high doses of intravenous corticosteroids for two months. After clinical improvement of hantavirus pulmonary syndrome the patient presented visual loss in both eyes that was secondary to a toxoplasmosis retinitis. The retinitis resolved with anti-toxoplasma therapy. Acquired toxoplasmic retinochoroiditis can occur following steroid therapy for hantavirus pulmonary syndrome.

Descrição de um caso de toxoplasmose ocular adquirida pós-síndrome pulmonar por hantavírus. Paciente com 41 anos do sexo masculino apresentando síndrome pulmonar por hantavírus, confirmado no laboratório pela detecção de anticorpos IGM para o vírus, foi submetido a altas doses de corticosteróides intravenosos durante dois meses. Após melhora clínica da síndrome pulmonar por hantavírus, apresentou perda visual em ambos os olhos secundária a retinite por toxoplasmose confirmada com sorologia (IGG e IGM positivo) A retinite resolveu após terapia sistêmica específica. A retinite por toxoplasmose pode ocorrer após terapia sistêmica com esteróide para síndrome pulmonar por hantavírus.

Poststreptococcal syndrome uveitis: a descriptive case series and literature review.

PURPOSE: To describe the clinical features in a series of patients with poststreptococcal uveitis and to review literature on the pathophysiology and management. DESIGN: Retrospective and descriptive case series. PARTICIPANTS: Ten consecutive cases of poststreptococcal syndrome uveitis diagnosed between 1996 and 2003. METHODS: Review of patient case notes. MAIN OUTCOME MEASURES: Age, laterality, clinical features, and anti-streptococcal lysin O titers. RESULTS: Ten consecutive cases of poststreptococcal syndrome uveitis were identified. All our cases had bilateral nongranulomatous inflammation and raised anti-streptococcal lysin O titers. Collating data from previous reports and this series showed that 96% of the patients were below 40 years of age, and 87.5% had evidence of previous streptococcal infection. One third of the patients had posterior segment involvement. In our patients, this was in the form of vitritis, focal retinitis, optic disc swelling, and multifocal choroiditis. CONCLUSIONS: Poststreptococcal syndrome uveitis should be considered in the etiology of acute bilateral nongranulomatous uveitis in children and young patients.

Histoplasmosis-like choroiditis in a nonendemic area: the northwest United States.

PURPOSE: Histoplasmosis is not endemic in the U.S. northwest, but a type of multifocal choroiditis resembling ocular histoplasmosis occurs there. This study was designed to find a group of affected patients and study their clinical characteristics and immunologic responses to Histoplasma antigens. METHOD: Ten patients were found in the authors' files whose geographic histories made it unlikely that they had ever been exposed to Histoplasma capsulatum and yet they had features of ocular histoplasmosis. They were recalled for examination and testing by lymphocyte-stimulation assay for previous exposure to histoplasmosis. RESULTS: The clinical features of these patients resembled those of patients with ocular histoplasmosis, but their histories and the results of the assay did not support H. capsulatum as the cause of the ocular disease. CONCLUSION: This study confirmed that there is a type of choroiditis that resembles ocular histoplasmosis but is due to another agent or agents.

Induction of experimental autoimmune anterior uveitis by a self-antigen: melanin complex without adjuvant.

PURPOSE: Experimental autoimmune anterior uveitis (EAAU) is an organ-specific autoimmune disease induced by immunization with bovine melanin-associated antigen (MAA) and two adjuvants (complete Freund's adjuvant and purified pertussis toxin). This study was undertaken to explore whether an adjuvant is required in the induction of EAAU. METHODS: Insoluble MAA was extracted from the bovine iris and ciliary body. Soluble bovine MAA was derived by treatment of insoluble MAA with the proteolytic enzyme, V8 protease. Lewis rats were immunized with the insoluble or soluble antigen, with or without adjuvant (complete Freund's adjuvant and purified pertussis toxin). Adoptive transfer of CD4+ and CD8+ T cells was performed to investigate the pathogenesis of EAAU. RESULTS: Experimental autoimmune anterior uveitis can be induced in Lewis rats by immunization with 100 g insoluble bovine MAA alone without the use of adjuvants. The disease can be adoptively transferred to naive syngenic rats by primed CD4+ T cells. In contrast, soluble bovine MAA was not uveitogenic unless adjuvants were employed. CONCLUSIONS: The data suggest that EAAU can be induced in the Lewis rat without addition of an adjuvant. Future studies concerning the pathogenesis of EAAU can now be performed without the possible confounding effect of an adjuvant.

Cyclosporine therapy suppresses ocular and lacrimal gland disease in MRL/Mp-lpr/lpr mice.

PURPOSE: MRL/Mp-lpr/lpr (MRL/lpr) mice spontaneously develop an autoimmune disease characterized by lymphoproliferation, vasculitis, glomerulonephritis, autoantibody production, and ocular and lacrimal gland inflammation. Lacrimal gland lesions in MRL/lpr mice are a model for the human disorder Sjögren's syndrome. The target organ lesions in MRL/lpr mice, including those in the eye and lacrimal gland, are composed largely of CD4+ T cells, with lesser numbers of CD8+ T cells and B cells. Cyclosporine therapy was evaluated for its effect on the autoimmune disease, particularly in the eye and lacrimal gland. METHODS: MRL/lpr mice were administered cyclosporine intraperitoneally at a dosage of 2 mg daily from age 1 to 5 months. Animals were killed at 5 months and evaluated for the presence of autoimmune disease. Control groups consisted of animals given daily injections with either saline or the cyclosporine diluent. RESULTS: Cyclosporine therapy was effective in reducing the ocular and lacrimal gland disease. Intraocular inflammation was present in 73% of control animals but in only 15% of cyclosporine-treated animals (P < 0.003). Multifocal lacrimal gland inflammatory infiltrates were present in 100% of controls but in only 23% of cyclosporine-treated animals (P < 0.0001). Mean percent area involved by lacrimal gland inflammation was reduced from 19.7% to 4.7% by cyclosporine therapy (P = 0.0003). Systemic autoimmune disease manifestations, including lymphoproliferation, vasculitis, glomerulonephritis, and serologic abnormalities, also were improved. CONCLUSIONS: Chronic cyclosporine therapy, started at an early age, is effective in controlling the autoimmune disease in MRL/lpr mice, including the ocular and lacrimal gland lesions.

Immunopathology of reactivation of experimental ocular histoplasmosis.

We have established a non-human primate model of experimental ocular histoplasmosis. This model has been shown to result in chronic lesions that resemble typical 'histo spots' or choroidal scars but that contain infiltrates of lymphocytes for as long as 10 yr following intracarotid injection of live Histoplasma capsulatum. Using this model, we attempted to reactive these late choroidal lesions via intracarotid challenge with specific antigen (heat-killed H. capsulatum). No clinical changes suggestive of reactivation of these lesions were observed following this antigenic challenge. However, immunopathologic analysis of choroidal lesions at 1, 3 and 7 days after antigenic challenge revealed significant increases in both the numbers of inflammatory cells and the relative percentages of the helper/inducer lymphocyte and macrophage populations. Our results demonstrate that, following antigenic challenge, a cellular change, consistent with a type IV delayed hypersensitivity, can be observed in previously active, but clinically quiescent, histoplasmosis lesions. In light of the many parallels between our primate experimental model and human ocular histoplasmosis, our findings suggest that, in the human, significant immunopathologic activity may occur subclinically in the choroid of affected individuals. It is possible that repeated bouts of subclinical reactivation may induce or enhance chronic choroiditis and, over many years, ultimately produce slow progressive damage to the Bruch's membrane/retinal pigment epithelium complex, resulting in clinically 'active' macular disease and, in selected cases, subretinal neovascularization.

Experimental autoimmune posterior uveitis accompanied by epitheloid cell accumulations (EAPU). A new type of experimental ocular disease induced by immunization with PEP-65, a pigment epithelial polypeptide preparation.

Purified retinal pigment epithelial cells of bovine eyes have been fractionated by a series of buffer and detergent extractions. The electropherogram of the buffer-insoluble, Triton X-100-soluble fraction (RPE-TS) exhibits a major polypeptide band of M(r) 65 kDa and a variety of minor components. Electrophoretically purified 65 kDa-band protein (PEP-65) is immunologically unrelated to the known uveitogenic photoreceptor proteins, to other neural retina proteins, and to PEP-X, the RPE-melanin-bound uveitogenic antigen. An immunocytochemical study of eye tissues suggests that it is exclusively located in the RPE. Immunization of Lewis rats with PEP-65 or affinity-purified RPE-TS induces a new type of ocular disease: experimental autoimmune posterior uveitis accompanied by epitheloid cell accumulations (monocytes) adjacent to the RPE (EAPU). The disease starts 9 days after immunization, provided that pertussis toxin is used as co-adjuvant. The first clinical signs are transient flare and cells in the anterior chamber. Choroiditis develops, and epitheloid cells accumulate focally along one or both sides of the Bruch's membrane-RPE layer. Such foci resemble, in some respects, Dálen-Fuchs nodules which occur in human sympathetic ophthalmia. Areas of inflammation are frequently localized in the chorioretinal periphery adjacent to the pars plana. Vitreous cell infiltration is the most prominent clinical feature of EAPU. During at least 2 months, extending chorioretinal areas containing epitheloid cell collections remain while the adjacent photoreceptor cells sometimes disappear without being invaded by these cells. Retinal vasculitis is seldomly observed and pinealitis is absent. EAPU has the latter feature in common with PEP-X-induced experimental autoimmune anterior uveitis (EAAU). The two diseases differ from the various photoreceptor antigen-induced forms of EAU where pinealitis and inflammation of the neural retina are prominent features. However, just as in EAU and EAAU, EAPU can be adoptively transferred, and is inhibited by cyclosporin treatment suggesting T-cell dependency.

Pneumocystis carinii and Mycobacterium avium-intracellulare infection of the choroid.

It has been hypothesized that coinfection with mycobacteria occurs in patients with Pneumocystis carinii choroiditis, but cases demonstrating ocular infection by both organisms have not been reported. This study reports the case of a patient with P. carinii choroiditis who was treated with intravenous trimethoprim and sulfamethoxazole, followed by intravenous trimethoprim and dapsone. The choroidal lesions failed to resolve despite 6 weeks of treatment, and the patient died from massive pulmonary infection caused by P. carinii, Mycobacterium avium-intracellulare, and cytomegalovirus infections. Ocular histologic and electron microscopic examinations revealed choroidal infection by both P. carinii and M. avium-intracellulare. Serum levels of sulfamethoxazole were below the recommended therapeutic range for treating P. carinii infection during the first week of therapy, but adequate drug levels were subsequently obtained. Failure of choroidal lesions of P. carinii to resolve in some cases may suggest insufficient antimicrobial levels in the blood or raise the possibility of coexistent M. avium-intracellulare or other opportunistic infection.

Epstein-Barr virus antibodies in multifocal choroiditis and panuveitis.

Although it has been reported that patients with multifocal choroiditis and panuveitis have serologic evidence of a chronic or persistent Epstein-Barr virus infection, our patients did not seem to have other stigmata of Epstein-Barr virus infection. To reappraise the serologic evidence of chronic Epstein-Barr virus infection, the Epstein-Barr antibody levels in 11 patients with multifocal choroiditis and panuveitis and 11 sex- and age-matched control patients were measured. Neither the antiviral capsid antigen IgG (P = .15) nor the antinuclear antigen (P = .2) antibody titers of the patients with multifocal choroiditis and panuveitis were significantly different than those of the control patients. Neither the patients with multifocal choroiditis and panuveitis nor the control patients had increased antiviral capsid antigen IgM titers. One patient with multifocal choroiditis and panuveitis and three control patients had positive anti-early antigen antibody titers (P = .59). The results of this study do not support the hypothesis that patients with multifocal choroiditis and panuveitis have serologic evidence of chronic or persistent Epstein-Barr virus infection as a characteristic finding.

[Gonarthritis, lymphadenopathy and disseminated choroiditis as a primary manifestation of Lyme borreliosis. Case report and discussion of diagnostic possibilities in Lyme borreliosis]. / Gonarthritis, Lymphadenopathie und disseminierte Chorioiditis als primäre Manifestation einer Lyme-Borreliose. Kasuistik und Diskussion der diagnostischen Möglichkeiten bei der Lyme-Borreliose.

A 26-year-old female patient was admitted to the hospital because of bilateral gonarthritis, lymphadenopathy and disseminated chorioiditis as primary manifestation of Lyme borreliosis. Antibody titers against Borrelia burgdorferi did not reach diagnostic levels as determined by an indirect immunofluorescence assay. However, diagnosis was established by the detection of IgG and IgM antibodies in Western blot analysis, and by the demonstration of an enhanced T-cell proliferation to Borrelia burgdorferi in a lymphocyte proliferation assay. This case report indicates that arthritides may already occur in stage II (disseminated infection) of Lyme borreliosis. Therefore, Lyme borreliosis must be considered in patients with chorioiditis and pauciarticular arthritis. In the case of non-diagnostic antibody titers in indirect immunofluorescence tests (or ELISA), Western blot analysis and lymphocyte proliferation assays should be performed in addition.

Lack of the HLA-DR2 specificity in multifocal choroiditis and panuveitis.

The prevalence of the HLA-B7 and HLA-DR2 specificities in 17 unrelated patients with multifocal choroiditis and panuveitis, 11 with and six without subretinal neovascularisation, was evaluated and compared with those of two different groups. The first group was 17 patients with subretinal neovascularisation associated with presumed ocular histoplasmosis syndrome, and the second was a group of 105 eye patients with no retinal disease. HLA-DR2 was not found in any patient with multifocal choroiditis and panuveitis, but it was found in 13 patients with presumed ocular histoplasmosis syndrome (p = 6.72 x 10(-5), comparison of the groups with subretinal neovascularisation). The lack of HLA-DR2 was also significant in comparison with the control group of eye patients (p = 0.041). This study suggests that patients with multifocal choroiditis and panuveitis and presumed ocular histoplasmosis syndrome have differing genetic predispositions, though the fundus pictures in these entities have many similarities.

Immune responsiveness to retinal S-antigen and opsin in serpiginous choroiditis and other retinal diseases.

The immune responsiveness to bovine retinal S-antigen and opsin has been investigated in some retinal disorders by means of in vitro lymphocyte proliferation, leukocyte migration inhibition and enzyme linked immune sorbent assays (ELISA). Sensitisation to S-antigen was observed in serpiginous choroiditis, but not in acute posterior multifocal placoid pigment epitheliopathy (APMPPE) or retinitis pigmentosa. No significant immune responsiveness was detected to opsin in any of the three diseases. Elevated antibody titers to S-antigen were observed in some individual patients and healthy subjects. However, none of the patient groups exhibited an elevated antibody titer as compared to the control group. Although serpiginous choroiditis and APMPPE share some prominent clinical characteristics, the sensitisation in the former disease may perhaps be attributed to more severe and prolonged damage of the photoreceptor cells and blood-retina barrier. A combination of previous and present results suggests that in immunological investigations of retinitis pigmentosa patients it is more effective to use human than bovine S-antigen as test antigen because a species specific epitope seems to be involved.

Pharmacologic modulation of acute ocular inflammation. I. Adenosine.

Modulation of signal transduction at the surface of inflammatory cells appears to influence acute inflammation. Adenosine, a well-known chemical messenger, inhibits the production of superoxide by stimulated neutrophils. In experimental allergic uveitis induced by sensitization with retinal 's' antigen, treatment with adenosine produced a marked reduction in the expected inflammation.

Immunopathology of acute experimental histoplasmic choroiditis in the primate.

The immunopathologic features of experimental acute histoplasmic choroiditis were studied in the nonhuman primate. Using an indirect immunoperoxidase technique, a panel of hybridoma-derived anti-human monoclonal antibodies, recognizing distinct lymphoid cell and macrophage surface antigens, have been adapted for use in the primate system. Twenty-two individual foci of histoplasmic choroiditis from five eyes were studied at time periods from 20 to 60 days post intracarotid injection of yeast phase Histoplasma capsulatum. A mononuclear and granulocytic cell infiltration was seen in all lesions. The predominant cell type was the CAPPEL+ T lymphocyte (suppressor/cytotoxic subset). Other cell types found in smaller numbers were OKT4+ T cells (helper/inducer subset), OK7+ (peripheral B lymphocytes), IgD+ (mantle B cells) and OKM1+ cells (macrophages and polymorphonuclear leukocytes). Herein, we present immunopathologic data on the acute phase of experimental ocular histoplasmosis.

Epstein-Barr viral antibodies in multifocal choroiditis and panuveitis.

A syndrome of multifocal choroiditis, pigment epithelial disturbance, and inflammatory vitreous cells was found to be associated with Epstein-Barr virus specific antibodies. The ten patients in this series had positive viral capsid antigen IgM or Epstein-Barr early antigen antibody titers. Patients with this syndrome were generally healthy and had no history of a clinical episode of infectious mononucleosis. No patient from the control group with other ocular diseases had positive viral capsid antigen IgM or early antibody titers. All patients in the study group and most of the control patients had viral capsid antigen IgG and Epstein-Barr nuclear antigen antibodies, indicating a previous exposure to the virus as expected in an adult population.

Humoral and cellular immune response in ocular histoplasmosis.

We have compared several humoral and cellular immune responses in ocular and in acute histoplasmosis syndromes. T-lymphocyte subset analysis revealed elevated ratios of T-helper/T-suppressor lymphocytes in ten of 22 patients with ocular histoplasmosis, whereas ratios were depressed in 18 of 22 with acute histoplasmosis syndromes. Lymphocyte transformation responses to mitogens and to histoplasma antigens were similar in both acute and ocular histoplasmosis. However, histoplasma antibody levels as measured by immunodiffusion, complement fixation, and radioimmunoassay were elevated in only three of 22 patients with ocular histoplasmosis, compared with 18 of 22 with acute histoplasmosis. Natural killer cell cytotoxicity was depressed in ten of 20 patients with ocular histoplasmosis compared with none of 18 with acute histoplasmosis. These findings support the clinical observations that ocular histoplasmosis and acute histoplasmosis syndrome are seldom, if ever, seen in the same patient.