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.

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.

Behcet's disease associated with HLA-B51 and DRw52 antigens in Italians.

Thirty-eight Italian patients with Behcet's disease, all with ocular involvement, (28 complete type and ten incomplete) were typed for HLA A,B,DR, and DQ antigens. A significant increase of HLA-B51 (p less than 0.00001) and DRw52 (p = 0.045) with no significant difference between complete and incomplete syndrome was found. The involvement of B51 antigen as the main immunogenetic factor in the disease is suggested by the high value of relative risk (RR = 16.03). However, the association with the II class antigen DRw52 (RR = 2.77) cannot be easily explained as a secondary association due to linkage disequilibria with B51.

Failure to find a B51 IEF variant associated with Behçet's disease.

HLA B51 antigen from 8 Italian Behçet's disease (BD) patients and 8 healthy controls were analyzed by isoelectric focusing (IEF). No differences were found in the migration patterns.

Vogt-Koyanagi-Harada disease and HLA type in Italian patients.

PURPOSE: To study the frequencies of human leukocyte antigen (HLA) specificities in Italian patients with Vogt-Koyanagi-Harada disease and to correlate the presence of each specificity to the clinical features. METHODS: Human leukocyte antigen specificities were determined by standard microlymphocytotoxicity assay in 16 patients with Vogt-Koyanagi-Harada disease and compared with HLA specificities of 116 healthy controls. RESULTS: HLA-DR4 was statistically related to Vogt-Koyanagi-Harada disease (P = .0063), whereas only a trend toward a significant association between the disease and HLA-B41 was found (P = .06). HLA-DQ1 was detected in a disproportionate number of controls (68.9%) compared with patients (37.5%). CONCLUSIONS: HLA-DR4 was significantly related to Vogt-Koyanagi-Harada disease in Caucasian European patients, specifically in Italian patients, as it was described in other racial groups. No clear relation was found between the ophthalmologic and systemic manifestations of Vogt-Koyanagi-Harada disease and the presence of HLA specificities.

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.

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.

Clinical serological correlations in the evaluation of Sjögren's syndrome.

Fifty-six subjects (46 females and 10 males) with signs of Sjögren's Syndrome (SS) have been evaluated for clinical and serological parameters. In 12 subjects such clinical signs were associated with a definite connective tissue disease (secondary SS): Rheumatoid Arthritis (2 cases), Systemic Lupus Erythematosus (4 cases), Progressive Systemic Sclerosis (4 cases), Essential Mixed Cryoglobulinemia (2 cases). All patients underwent a lip biopsy which was evaluated according to the Chisholm-Mason scale. Six out of 56 subjects (10.7%) had a normal salivary gland with few lymphocytes (class I); 5 (10%) had a scattered lymphoid infiltrate containing less than 1 focus/4 mm2 (class II); 36 (64.3%) had one focus/4 mm2 (class III) and, finally, 9 (16%) had more than 1 focus/4 mm2 (class IV). The great majority (91%) of the patients had some abnormalities at the ophthalmological examination (Schirmer test, Break up times, van Bijsterveld score): even those with a class I lip biopsy. Xerostomia was present in 69% of the patients, xerophthalmia in 78%, arthralgias in 78%, parotid swelling in 19%, Raynaud's phenomenon in 16%, recurrent abortion in 9 patients. The prevalence of autoantibodies in the group of primary SS was high: ANA 43.2%, anti-Ha 40%, anti-Ro 12%, anti-phospholipids 52.2%, rheumatoid factor (RF) 45.7%. A decrease of lysozyme concentration in tears and saliva has been demonstrated and a correlation between level of lysozyme and lip-biopsy has been observed.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

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.

Uveitis in children.

Uveitis is diagnosed more often in adults than in children but in children the prevalence of chronic inflammation and the difficulty of an early diagnosis may worsen the visual prognosis. The different incidence of the presumed or defined etiologies in the various ages is probably responsible for the better classification of uveitis in childhood (71% versus 55% in adult patients). Juvenile rheumatoid arthritis is the most common identifiable etiology of pediatric anterior uveitis (28%). However, its long-term prognosis is not satisfactory and ophthalmic surveillance protocols are necessary especially for ANA and HLA DR11 positive girls with the pauci articular form of the disease. Intermediate uveitis is idiopathic in 98% of the cases and accounts for 20-26% of all pediatric uveitis; cystoid macular edema in these patients is the leading cause of visual impairment. Toxoplasmosis is the most frequent cause of posterior uveitis (43%) and of uveitis in childhood (12%); involvement is bilateral in 50-60% of cases. Diffuse uveitis forms are uncommon in children, but their course is particularly severe. They may either be the natural evolution of a posterior uveitis or the presenting sign of a systemic disease typical of the third decade of life, such as sarcoidosis, Behçet's disease, Vogt-Koyanagi-Harada's disease. Masquerade syndromes including retinoblastoma, leukemia and lymphoma, intraocular foreign body, retinitis pigmentosa may contribute to confusion in the differential diagnosis of inflammatory disease of the uveal tract in childhood.

Treatment of clinically resistant cytomegalovirus retinitis in AIDS patients: combination of intravenous ganciclovir and intravitreal foscarnet.

The treatment of clinically resistant cytomegalovirus retinitis in AIDS patients requires a combination of foscarnet and ganciclovir, but the poor clinical condition of some patients may weigh against this intravenous regimen. We treated three patients with high-dose intravitreal foscarnet (2400 micrograms/0.1 ml; 25 injections; mean follow-up 14.6 weeks) combined with intravenous ganciclovir (5 mg/kg twice daily), and obtained complete control of the retinitis in a mean time of 3.4 weeks with no ocular or systemic side effects and no other eye/organ cytomegalovirus dissemination. This combined therapy seems useful for clinically resistant cytomegalovirus retinitis in AIDS patients.

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.

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.

The lactoferrin tear test in the diagnosis of Sjögren's syndrome.

PURPOSE: To assess the sensitivity and specificity of the lactoferrin tear test (LTT) in the diagnosis of keratoconjunctivitis sicca due to Sjögren's syndrome (SS), comparing it with the other lacrimal tests and with immunological tests. METHODS: 25 patients suffering from SS (24 women and 1 man, median age 51.5 years, s.d. 16.3); control group: 20 patients with various kinds of conjunctivitis without dry eye. Tests in both groups: Schirmer I (ST), BUT, ferning test, lactoferrin immunoassay, fluorescein and Rose Bengal staining. Immunological tests: serum titers of anti-nuclear (ANA), anti-DNA, anti-ENA (SS-A, SS-B, RNP, FR) antibodies. In the patients with SS, labial salivary gland biopsy was also performed. RESULTS: LTT had a specificity of 95% and a sensitivity of 72%, compared to 85% and 64% for the Schirmer I test. The ferning test has the highest sensitivity (92%), and none of the cases positive to BUT was negative to the ferning test. The combination of LTT and ferning test gave a value of 78% compared to 70% with ST. The correlations between positive LTT and positive ANA, SS-A and labial biopsy were respectively 83%, 67% and 80%, as against 67%, 50% and 65% for the Schirmer I test. CONCLUSIONS: In our study, LTT showed very high specificity, good sensitivity particularly when combined with qualitative tear tests, and a good correlation with the immunological and bioptic tests for SS. Since it is easy to perform, in our opinion LTT can be included in the diagnostic routine for keratoconjunctivitis sicca in SS.

Immunological and viral markers of HIV infection and retinal microangiopathy.

The relationship between retinal microangiopathy and some features of human immunodeficiency virus (HIV) infection such as HIV antigenemia, antibodies to the viral proteins, T lymphocyte subsets, were studied in 71 patients with acquired immunodeficiency syndrome (AIDS). The absence of antibodies to the HIV p24 protein was significantly related to retinal microangiopathy (p = 0.0051) and more closely to retinal cotton-wool spots (p = 0.0007); the combination of positive antigenemia with the absence of antibodies to p24, which is typical of the later phases of HIV infection, was found in a larger percentage of patients with cotton-wool spots (p = 0.0013) than in subjects with every sign of microangiopathy (p = 0.0546). T-helper (CD4+) cells count below 200 cells/mm3 was also detected in a higher percentage of patients with HIV-related retinal microangiopathy (p = 0.009). These findings suggest that retinal microangiopathy and especially retinal cotton-wool spots are related to the progression of immunodeficiency.

Relapsing bilateral uveitis and papilledema in sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease).

Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease) is a non-hereditary histiocytic proliferative disorder affecting young people, with extranodal manifestations in 28-43% of cases. Eye involvement is infrequent. Lymphoproliferation in the soft tissues of the orbit and in the lids has been reported in 12% of cases but intraocular involvement is rare. We describe the case of a 12-year-old boy affected by Rosai-Dorfman disease with bilateral relapsing uveitis and papilledema that appeared four years before the onset of lymphadenopathy.

Behçets disease in children.

Ophthalmic and clinical analysis were carried out on 16 children and 122 adult patients affected by Behçet's disease (BD) to delineate the clinical features of BD in childhood and to investigate the differences between the expression of the disease in children and adults. The mean follow-up period was 7.8 and 7 years, respectively. Pediatric onset of BD was found in 7.6% of all the cases with a male:female ratio of 1.29:1. The complete type of the disease was observed in 50% of the children. No statistical significant differences were noted between children and adults in the incidence of oral aphthae, genital ulcers, skin lesions, arthritis, gastrointestinal involvement, neuropsychiatric symptoms and the presence of HLA-B51. Thrombophlebitis was associated with the onset of the disease in adult age (P=0.022). Uveitis alone or in combination with other major symptoms was the presenting sign in a higher percentage of children (P=0.077), As in adults, in children diffuse uveitis was the most common type of ocular inflammation, while ocular complications have been found mainly in children (P=0.021), who more frequently developed cataract, maculopathy and retinal detachment (P=0.024). Both adult and young male patients have shown a lower age at onset and higher rate of optic atrophy than females. In conclusion, no significant differences have been found between children and adults in the expression of the major and most of the minor symptoms of BD. Ocular involvement in childhood may be very severe, as was confirmed by the high frequency of diffuse uveitis and ocular complications. Young males, as adult males, showed an earlier onset of the disease and a worse ocular prognosis.

Retinal cotton-wool-like spots: a marker for AIDS?

The prognostic value of ocular manifestations and their correlation with immune changes in HIV-infected subjects (75 PGL, 23 ARC, and 17 AIDS) have been longitudinally studied with an average follow-up of one year (3 to 22 months). The most common ocular manifestations were retinal cotton-wool-like spots, observed in 58.8% of AIDS patients and in 76.9% of those with ocular involvement. Two of three ARC patients who showed cotton-wool-like spots developed PCP a few weeks after ophthalmoscopic examination. A close correlation between ocular changes and decrease of CD4+ lymphocytes was observed. In our opinion, these ocular manifestations are as useful an indicator as opportunistic infections or AIDS-related neoplasias in the prognosis of HIV infection.