Knee joint synovitis in Behçet's disease: a sonographic study.

OBJECTIVE: The aim of this study was to investigate, using ultrasound (US), knee involvement in patients with Behçet's disease (BD). METHODS: Knee US was performed in 30 unselected Italian BD patients. Signs of arthritis (joint effusion, synovial proliferation) and presence of bone erosions and Baker's cysts were recorded. Power Doppler evaluation was performed. A semi-quantitative score was used for each structure examined, whereby 0 was to indicate the absence of any change and score from 1 to 3 the presence of mild to severe changes. A sum of the single scores was obtained. Disease activity was evaluated to identify the correlation with the US modifications. RESULTS: Twenty (66.6%) patients had symptomatic articular involvement and US showed knee involvement in 18 of them (60%). Synovial proliferation was detected in 14 (46%, positive power Doppler in 4), joint effusion in 14 (46%), bone surface erosions in 3 (10%). Four patients, asymptomatic for joint involvement, showed US alterations. Eleven patients showed a total score between 1 and 3, while the other 7 had a score between 4 and 6. Subjects with a higher US score presented an increased prevalence of acneiform skin lesions with respect to the group with US score 1-3. Statistical analysis showed a positive correlation between disease activity and US score in group 2 (p=0.04). CONCLUSION: This study confirms that peripheral joint involvement represents an important clinical aspect in italian BD patients and US evaluation is useful for the detection of this aspect.

Changing patterns of ocular manifestations in HIV seropositive patients treated with HAART.

PURPOSE: To report the changing patterns of ocular manifestations in human immunodeficiency virus (HIV) seropositive patients treated with highly active antiretroviral therapy (HAART). METHODS: The clinical charts of HIV seropositive patients, 735 examined from 1997 to 2003 and treated with HAART for at least 2 months (Group 1), and 838 untreated examined from 1988 to 1995 (Group 2), were reviewed to assess the frequency of ocular manifestations. RESULTS: HIV-related retinal microangiopathy and opportunistic retinal infections (cytomegalovirus retinitis and toxoplasmic retinochoroiditis) were significantly higher in Group 2 than 1 (p<0.0001), while in patients treated with HAART a statistically significant increase in the frequency of chalazion (p<0.0001), diabetic and hypertensive retinopathy (p<0.0001), lipid arc of the cornea (p<0.0001), cataract and glaucoma (p<0.0001), and uveitis (p=0.026) was observed. CONCLUSIONS: HAART therapy has induced a dramatic decrease in the incidence of HIV-related microangiopathy and opportunistic retinal infection and the occurrence of new lesions related both to the metabolic alterations induced by HAART and to immune reconstitution, such as uveitis.

Prognosis of juvenile rheumatoid arthritis-associated uveitis.

PURPOSE: To evaluate the clinical characteristics and the visual prognosis of uveitis in juvenile rheumatoid arthritis (JRA). METHODS: The authors examined 63 patients with uveitis and JRA observed from January 1985 to December 2000. The following characteristics of each patient were considered: age at first visit, age at onset of uveitis and arthritis, sex, laterality and localization of uveitis, ocular complications, antinuclear antibody (ANA) and human leukocyte antigen (HLA) DR11 positivity, and follow-up. A retrospective study on mid-time visual outcome and ocular complications was performed on 42 patients with more than 12 months of follow-up. RESULTS: A total of 76.2% of the patients were female, with a mean age of 8.1 years. Chronic anterior uveitis was bilateral in 77.8% of the cases and unilateral in 22.2%. Arthritis was oligoarticular at onset in 87.3% of cases, and polyarticular in 12.7%. Mean age at arthritis onset was 4.5 years and mean age at uveitis onset was 5.4 years. ANA were positive in 92% of cases and HLA DR11 was present in 36 of the 43 patients tested (83.7%). Among the 42 patients with more than 12 months of follow-up, ocular complications occurred in 90.5% of cases and the most frequent were cataract (64.4% of eyes) and band keratopathy (59.2% of eyes). Secondary glaucoma (25% of eyes) was associated with the worst visual prognosis. A total of 64.5% of eyes maintained a visual acuity between 20/33 and 20/20 at the end of the follow-up. CONCLUSIONS: Visual prognosis of uveitis associated with JRA is improving, owing to earlier diagnosis and intensive treatment. Ocular complications occurred frequently in patients with uveitis and JRA but they did not seem to seriously affect the final visual outcome. The authors did not observe any correlation between prognosis and sex, age at the onset of uveitis or arthritis, pattern of arthritis, or positivity for ANA or HLA DR11. In a percentage of cases, uveitis may develop before arthritis or years after the onset of arthritis; therefore, continuous ophthalmologic examinations are needed in young people with JRA.

Polymorphism of the Duffy erythrocyte chemokine receptor in Italian patients with Behçet's disease.

This study examined the hypothesis that the polymorphism of Duffy antigen receptor for chemokines (DARC) predisposes to and/or influences the clinical manifestations of Behçet's disease. The serum levels of IL-8 and monocyte chemotactic peptide (MCP)-1, two DARC-binding chemokines, were investigated and related to this polymorphism. Twenty-eight patients with Behçet's disease and 30 healthy blood donors were included in the study. No null phenotypes were found among the patients studied, and the frequencies of the other phenotypes (Fy((a+b-)), Fy((a+b+)), and Fy((a-b+))) did not significantly differ from those found in the blood donor group or reported in the general Caucasian population. No difference was found between the single phenotypes in terms of IL-8 and MCP-1 serum levels, and no relevant association between the clinical characteristics, Behçet's disease-associated human leukocyte antigen (HLA)-B51, and single phenotypes was observed. This investigation indicates that DARC is not a genetic trait significantly associated with or predisposing to Behçet's disease, at least in Caucasian Italians. However, the role of this polymorphism in the development and in the clinical course of the disease awaits further investigation.

Chorioretinopathy and discoid plaque-like lesions of the eyelids as useful indicators of systemic lupus erythematosus (SLE) progression.

Choroidal involvement in systemic lupus erythematosus (SLE) occurs infrequently. We report a 45-y-old woman with bilateral chorioretinopathy associated with SLE. Diagnosis was performed using indirect ophthalmoscopy, retinal fluorescein angiography (FA) and green indocianin angiography (ICG). In this patient chorioretinopathy and discoid-like plaque of the lids represented the only signs of SLE progression after 15 y of apparent remission of systemic disease.

Indocyanine green angiographic findings in Behçet disease.

BACKGROUND: The authors studied indocyanine green (ICG) angiographic features in proven cases of ocular Behçet disease. METHODS: Twenty-six patients (18 male, 8 female; mean age 39.9 +/- 8.9 years) with Behçet disease underwent simultaneous ICG and fluorescein angiography (FA) according to a uveitis angiographic standard protocol. Patients were divided into three groups based on their ocular disease duration: Group A (9 patients), less than 3-year duration; Group B (8 patients), 4- to 10-year duration; Group C (9 patients), more than 10-year duration. The relation between ICG angiographic findings and ocular disease duration and FA signs was delimited. RESULTS: Three findings were disclosed by ICG angiography: 1) poorly defined areas of intermediate and late hyperfluorescence (50% of eyes); 2) well-defined hypofluorescent areas becoming isofluorescent in the late phase (26.92% of eyes); and 3) large, poorly defined hypofluorescent areas visible up to the late phase (30.77% of eyes). The presence of ICG hypofluorescent areas up to the late phase was related to disease duration (P = 0.01), whereas ICG hypofluorescent areas becoming isofluorescent in the late phase were predominant in patients in early stages of ocular disease (P = 0.02). The presence or absence of FA signs did not indicate any significant correlation with the presence or absence of signs revealed by ICG angiography. CONCLUSION: Indocyanine green angiography enabled the identification of different choroidal abnormalities related to the ocular disease duration. The presence of some ICG findings undetectable with FA suggests that ICG and FA are complementary means to diagnose and monitor ocular vascular involvement in patients with Behçet disease.

Revised diagnostic criteria for Vogt-Koyanagi-Harada disease: report of an international committee on nomenclature.

PURPOSE: To present revised criteria for the diagnosis of Vogt-Koyanagi-Harada disease, a chronic, bilateral, granulomatous ocular and multisystem inflammatory condition of unknown cause. METHODS: Diagnostic criteria and nomenclature were subjects of discussion at the First International Workshop on Vogt-Koyanagi-Harada Disease on October 19-21, 1999, at the University of California, Los Angeles, Conference Center, Lake Arrowhead, California. A committee appointed by the workshop participants was charged with drafting revised criteria for Vogt-Koyanagi-Harada disease, based on discussions held during the conference. This article is the consensus committee report. RESULTS: New criteria, taking into account the multisystem nature of Vogt-Koyanagi-Harada disease, with allowance for the different ocular findings present in the early and late stages of the disease, were formulated and agreed upon by the committee. These criteria are based on additional knowledge and experience of experts in the field and are believed to reflect disease features more fully than previously published criteria. CONCLUSIONS: The revised definition of Vogt-Koyanagi-Harada disease, with expanded diagnostic criteria, will facilitate performance of studies involving homogeneous populations of patients, at various stages of disease, that address unanswered questions regarding treatment and disease mechanisms.

Treatment of severe ocular hypotony in AIDS patients with cytomegalovirus retinitis and cidofovir-associated uveitis.

OBJECTIVE: To describe the medical treatment of severe ocular hypotony in HIV-seropositive patients with cytomegalovirus retinitis and cidofovir-associated uveitis. PATIENTS AND METHODS: Two HIV-seropositive patients with cytomegalovirus retinitis and cidofovir-associated uveitis complicated by severe ocular hypotony were unresponsive to conventional therapy after treatment with cidofovir was stopped. They were subsequently treated successfully with ibopamine 2% eyedrops and dexamethasone 0.1% eyedrops. RESULTS: In both cases, an increase in intraocular pressure to normal values was observed on average 18.5 days after starting treatment. Intraocular pressure remained stable while on therapy for a mean follow-up of 9.5 months. During the follow-up period, any attempt to stop treatment was followed by an intraocular pressure decrease; conversely, restoration of therapy increased intraocular pressure to normal values. No reactivation of cidofovir-associated uveitis or cytomegalovirus retinitis was observed during the follow-up period. CONCLUSIONS: Ibopamine 2% eyedrops in combination with dexamethasone 0.1% eyedrops is a satisfactory therapy for severe ocular hypotony in patients with cytomegalovirus retinitis and cidofovir-associated uveitis.

Localization of the pathogenic gene of Behçet's disease by microsatellite analysis of three different populations.

PURPOSE: Behçet's disease (BD) is known to be associated with HLA-B51 in many ethnic groups. However, the pathogenic gene responsible for BD is as yet unknown. To localize the critical region of the pathogenic gene, microsatellite markers distributed around the HLA-B gene were investigated. The BD patients studied were of three ethnic origins: Japanese, Greek, or Italian. METHODS: The total group consisted of 172 BD patients, of whom were 95 Japanese, 55 Greek, and 22 Italian. Eight polymorphic microsatellite markers distributed within 1100 kb of the HLA-B gene were analyzed using PCR and subsequent automated fragment detection by fluorescent-based technology. RESULTS: Among the eight markers, allele 348 of the MIB microsatellite was remarkably common in all three BD populations (Japanese, PC: = 0.000014; Greek, PC: = 0. 00047; Italian, PC: = 0.11). However, HLA-B51 was found to be the marker most strongly associated with BD in each population (Japanese, PC: = 0.000000000017; Greek, PC: = 0.00000032; Italian, PC: = 0. 0074). In genotypic differentiation between the patients and controls, only HLA-B51 was found to be significantly associated with BD in all three populations. Stratification analysis suggested that significant associations of BD with MICA and other microsatellites resulted from a linkage disequilibrium with HLA-B51. CONCLUSIONS: These results suggest that the pathogenic gene of BD is HLA-B51 itself and not other genes located in the vicinity of HLA-B.

Ibopamine treatment in chronic hypotony secondary to long-lasting uveitis. A case report.

PURPOSE: To assess the clinical efficacy of ibopamine eye drops in severe hypotony secondary to chronic progressive uveitis. METHODS: Case report. A 47-year-old man with a 37-year history of diffuse uveitis and severe refractory hypotony was treated with topical 2% ibopamine (Trazyl) six times a day. Intraocular pressure, visual acuity, visual field and side effects were recorded during 15 months of follow-up. RESULTS: IOP, visual acuity and visual field increased after four days of therapy and lasted for two months when the drug was suspended because of the onset of filamentous keratopathy. A new course of treatment with 2% ibopamine eye drops in a different solvent (BSS) resulted in a stable increase in IOP, VA and visual field, with no side effects in a follow-up of 13 months. CONCLUSIONS: Ibopamine 2% eye drops in BSS solvent seem effective in the treatment of uveitis-related hypotony.

Long-term follow-up of anterior uveitis after cataract extraction and intraocular lens implantation.

PURPOSE: To assess whether cataract surgery and intraocular lens (IOL) implantation in patients with anterior uveitis interfere with the natural course of the ocular disease. SETTING: Tertiary care center at the University of Rome "La Sapienza", Rome, Italy. METHODS: Cataract extraction and IOL implantation were performed in 24 patients with uveitis-related cataract: 12 with Fuchs' heterochromic iridocyclitis (Group 1) and 12 with other types of anterior uveitis (Group 2). The mean follow-up in the 2 groups was 33.6 months and 24.8 months, respectively. The number and severity (inflammatory score) of uveitis relapses in all patients over the same period were recorded. RESULTS: After surgery, the mean number and severity of uveitis relapses decreased: Group 1, from 1.83 +/- 1.90 (SD) to 1.00 +/- 1.21 and from 1.08 +/- 0.90 to 0.92 +/- 0.67, respectively; Group 2, from 2.74 +/- 3.44 to 1.25 +/- 1.71 and from 1.83 +/- 1.10 to 1.25 +/- 0.75, respectively (P = .046). There were no statistically significant between-group differences. In Group 2, a trend toward worse visual rehabilitation was seen; this was significantly different from the result in Group 1 (P = .018) because of preoperative optic nerve damage, macula disease, or both. CONCLUSION: Cataract surgery and IOL implantation did not negatively influence the natural course of uveitis in patients with Fuchs' heterochromic iridocyclitis. Correct surgical timing, selection of cases, and adequate anti-inflammatory therapy may promote similar results in patients with other types of anterior uveitis.

Bilateral trochlear nerve palsy associated with cryptococcal meningitis in human immunodeficiency virus infection.

This is the report of a case of bilateral trochlear nerve palsy secondary to cryptococcal meningitis in a 34-year-old woman with acquired immune deficiency syndrome. Based on clinical and neuroradiologic findings, it is concluded that in the present case, a postinflammatory shrinking of the arachnoid has stretched the fourth cranial nerves at their point of emergence from the dorsal surface of the brainstem.

Herpes simplex virus vaccine in recurrent herpetic ocular infection.

PURPOSE: To evaluate the efficacy of an antiherpetic vaccine in recurrent herpetic ocular infections. METHODS: Twenty patients with herpes simplex virus 1-related recurrent keratitis/keratouveitis were prospectively enrolled and randomly assigned to receive either a specific vaccination with heat shock-inactivated herpes simplex virus type 1 (10 patients) or to be observed as controls (10 patients). The number, duration, and anatomic localization of relapses were recorded in all the patients for 12 months before inclusion in the study and for a similar period after the assignment of each subject to vaccine or control group. RESULTS: In the vaccine group, we observed a reduction both in the number (p = 0.016) and average duration (p = 0.050) of recurrences, whereas in the control group, no significant change was found comparing a 12-month period before and after inclusion in the study. The comparison between the two groups highlighted a significant reduction in the number (p = 0.013) and average duration (p = 0.051) of relapses in treated subjects, who did not show any significant vaccine-induced side effects. CONCLUSION: The use of a vaccination with heat shock-inactivated herpes simplex virus 1 seems to be able to reduce the number and duration of relapses in herpes simplex virus 1-related keratitis/keratouveitis.

Significant associations of HLA-B*5101 and B*5108, and lack of association of class II alleles with Behçet's disease in Italian patients.

Behçet's disease has been known to be strongly associated with human leukocyte antigen (HLA) B51, one of the split antigens of HLA-B5. An increased incidence of HLA-B51 in the patient group has also been reported in an Italian population. Since the B51 antigen has been recently identified to comprise nine alleles, B*5101-B*5109, we performed HLA-B51 allele genotyping by the polymerase chain reaction-sequencing based typing (PCR-SBT) method as well as serological HLA-A and -B typing among 21 Italian patients with Behçet's disease in order to investigate whether there is any correlation of one particular B51-associated allele with Behcet's disease. In addition, HLA class II genotyping was performed by the PCR-restriction fragment length polymorphism (RFLP) method. As a result, only the phenotype frequency of the B51 antigen was found to be significantly increased in the patient group as compared to the ethnically matched control group by the corrected P-value analysis (71.4% in patients vs. 17.9% in controls; chi2 = 14.26, Pc = 0.0042, R.R. = 11.5). In the B51 allele genotyping, 11 out of 15 B51-positive patients were B*5101 and the remaining four were B*5108, whereas all of 5 normal controls were B*5101, showing significant association of each allele with Behçet's disease. No significant difference was observed between the patient and control groups in the HLA class II allelic distribution. This study revealed a strong association of Behçet's disease in Italian with B*5108 as well as B*5101, providing important insight into the molecular mechanism underlying an HLA association with Behçet's disease.

Cardiac involvement in Behçet's disease.

To assess the prevalence and the extent of cardiac involvement in patients with Behçet's disease and to investigate the possible causes that may predispose to this involvement, 30 patients affected by Behçet's disease and 30 normal control subjects were submitted to M-mode, two-dimensional, and Doppler echocardiographic evaluation. Moreover, antinuclear and anticardiolipin autoantibodies were determined in the sera of both patients and control subjects. Finally, HLA-B51 positivity was assessed in the patients and in a historical control group. Mitral valve prolapse was observed in 50% and proximal aorta dilatation in 30% of the patients. There was a significant difference in the rate of these abnormalities in comparison with the control group. Left ventricular function parameters were similar between the two groups. The positivity rate of antinuclear and anticardiolipin autoantibodies was very low (7%), without differences between the groups. HLA-B51 was detected in 82.7% of the patients versus 21.7% in the control group (p < 0.00001). In conclusion, this study demonstrates a high rate of cardiac abnormalities in patients with Behçet's disease.

Trinucleotide repeat polymorphism within exon 5 of the MICA gene (MHC class I chain-related gene A): allele frequency data in the nine population groups Japanese, Northern Han, Hui, Uygur, Kazakhstan, Iranian, Saudi Arabian, Greek and Italian.

We recently identified a trinucleotide repeat polymorphism, (GCT)n, within the transmembrane (TM) segment of the human MHC class I MICA gene (MHC class I chain-related gene A). Five distinct alleles (A4, A5, A5.1, A6, A9) corresponding to 4, 5, 5 with one nucleotide insertion, 6 and 9 repetitions, respectively, have been detected in various HLA-homozygous B cell lines. Here we present allele frequencies for this trimeric short tandem repeat (STR) in 604 unrelated individuals collected from nine human populations (Japanese, Northern Han, Hui, Uygur, Kazakhstan, Iranian, Saudi Arabian, Greek and Italian) determined using the polymerase chain reaction (PCR) combined with fluorescent-based automated fragment detection technology. All alleles were present in each population, but allelic distributions varied from one population to another. No new alleles (such as A7 or A8) were identified. The evolutionary and structural significance of these data as well as the potential application to forensic medicine is discussed.

[Magnetic resonance of the encephalon in 17 patients with ocular Behçet's disease]. / Risonanza magnetica dell'encefalo in 17 pazienti affetti da malattia di Behçet oculare.

Behçet's disease is a chronic relapsing disorder of unknown etiology characterized by oral aphthous ulcerations, uveitis, genital ulcerations and bone lesions. A variety of other signs including polyarthritis, vascular conditions (blood vessel occlusions and aneurysms), epididymitis, gastrointestinal, pulmonary and heart lesions may also occur. Central nervous system (CNS) involvement is reported in 10-49% of cases and it is the first symptom of the disease in 5% of subjects. The neuro-Behçet's syndrome may appear as a brainstem syndrome, meningoencephalitis and an organic confusional syndrome or dementia. Cranial hypertension, mostly related to cerebral venous thrombosis, is also present in neuro-Behçet's disease and its incidence is reported in up to 10% of Behçet's patients. MRI is reportedly the most sensitive neuroradiologic approach to detect the focal lesions related to neuro-Behçet's disease and several single cases or series of Behçet's patients with neurologic signs have been examined with MRI. We used MRI to investigate CNS involvement in Behçet's disease patients with and without previous neurologic signs. MRI was carried out on 17 patients with ocular Behçet's disease without neurologic symptoms to assess the possible subclinical involvement of the CNS. Cerebrospinal fluid spaces were enlarged in 8 patients and 5 patients exhibited cortical atrophy. PD and T2-weighted hypersignal foci were demonstrated in parietal, frontal, subcortical and periventricular white matter in 6 subjects. Neuroradiologic abnormalities were found only in the patients with complete disease and with the disease diagnosed more than 10 years earlier. Even though the pathogenesis of these neuroradiologic abnormalities and their correlation with Behçet's disease remain to be clarified, our study suggests the possibility of subclinical CNS involvement in these patients, which may affect the therapeutic approach and their prognosis.