Maria Elisabetta Zannin

Abatacept for severe anti–tumor necrosis factor α refractory juvenile idiopathic arthritis–related uveitis

To evaluate the safety and efficacy of abatacept in patients with severe juvenile idiopathic arthritis (JIA)–related uveitis refractory or intolerant to immunosuppressive and anti–tumor necrosis factor α (anti‐TNFα) agents.

Safety and efficacy of infliximab and adalimumab for refractory uveitis in juvenile idiopathic arthritis: 1-year followup data from the Italian Registry.

Objective. To evaluate safety and efficacy of adalimumab (ADA) and infliximab (IFX) for the treatment of juvenile idiopathic arthritis-related anterior uveitis (JIA-AU). Methods. Starting January 2007, patients with JIA-AU treated with IFX and ADA were managed by a standard protocol and data were entered into the National Italian Registry (NIR). At baseline, all patients were refractory to standard immunosuppressive treatment and/or were corticosteroid-dependent. Data recorded every 3 months included uveitis course, number/type of ocular complications, drug-related adverse events (AE), treatment change or withdrawal, and laboratory measures. Data of patients treated for at least 1 year were retrieved from the NIR and analyzed using descriptive statistics. Treatment efficacy was based on change in uveitis course and in number of ocular complications. Results. Up to December 2009, data for 108 patients with JIA-AU treated with anti-tumor necrosis factor-α agents were recorded in the NIR and data from 91, with at least 12 months’ followup, were included in the study. Forty-eight patients were treated with IFX, 43 with ADA. Forty-seven patients (55.3%) achieved remission of AU, 28 (32.9%) had recurrent AU, and 10 (11.8%) maintained a chronic course. A higher remission rate was observed with ADA (67.4% vs 42.8% with IFX; p = 0.025). Ocular complications decreased from 0.47 to 0.32 per subject. Five patients experienced resolution of structural complications. No patient reported serious AE; 8 (8.8%) experienced 11 minor AE (9 with IFX, 2 with ADA). Conclusion. IFX and ADA appear to be effective and safe for treatment of refractory JIA-related uveitis, with a better performance of ADA in the medium-term period.

Ocular involvement in children with localised scleroderma: A multi-centre study

Background: Most of the available documentation in the literature on ocular involvement in localised scleroderma (LS) are descriptions of single cases in adult patients. This article reports the frequency and specific features of ocular involvement in a large cohort of children with juvenile LS (JLS). Methods: Data from a large, multi-centre, multinational study of children with LS were used to collect and analyse specific information on ocular involvement. Results: 24 out of 750 patients (3.2%) revealed a significant ocular involvement. 16 were female and 8 male. 16 patients (66.7%) had scleroderma “en coup de sabre” (ECDS) of the face, 5 (20.8%) had the linear subtype, 2 (8.3%) had generalised morphea (GM) and one (4.2%) had plaque morphea (PM). Of the 24 patients with eye involvement, 10 patients (41.7%) reported adnexa (eyelids and eyelashes) abnormalities, 7 (29.2%) anterior segment inflammation (5 anterior uveitis, 2 episcleritis) and 3 central nervous system-related abnormalities. 4 patients presented single findings such as paralytic strabismus (1), pseudopapilloedema (1) and refractive errors (2). Other extracutaneous manifestations were detected in a significantly higher number of patients with ocular involvement and were mostly neurological. Conclusion: Ocular abnormalities are not unusual in patients with JLS, especially in the ECDS subtype. They are frequently associated with other internal organ involvement, particularly the central nervous system (CNS). Careful ophthalmic monitoring is recommended for every patient with JLS, but is mandatory in those with skin lesions on the face and/or concomitant CNS involvement.

Clinical Features and Outcome of Cogan Syndrome

OBJECTIVE To review the clinical features of Cogan syndrome, a rare vasculitis characterized by systemic, ocular, and audiovestibular symptoms. STUDY DESIGN Clinical records of patients with Cogan syndrome followed at 2 pediatric rheumatology institutions and those from a database search were reviewed. Data included clinical features at onset and during the disease course, treatments, and outcomes. RESULTS Twenty-three children with Cogan syndrome (15 males; mean age, 11.4 years [range, 4-18 years]) were included in the analysis. Eleven patients (47.8%) exhibited systemic features at disease onset, including fever, arthralgias-arthritis or myalgias, headache, and weight loss. Twenty-one patients (91.3%) had ocular symptoms, due mainly to interstitial keratitis, uveitis, or conjunctivitis/episcleritis. Vestibular symptoms (39.1%) included vertigo, vomiting, and dizziness. Auditory involvement (65.2%) consisted of sensorineural hearing loss, tinnitus, and deafness. Four patients had cardiac valve involvement, and 3 had skin manifestations. After a median 2 years of follow-up, 30.4% of the patients were in clinical remission, but all others had irreversible complications (deafness, 21.7%; sensorineural hearing loss, 13.0%; vestibular dysfunction, 4.3%; ocular complications, 13.0%; cardiac valve damage, 17.4%). CONCLUSION Audiovestibular and ocular involvement have a major impact on prognosis in children with Cogan syndrome.

Timing of uveitis onset in oligoarticular juvenile idiopathic arthritis (JIA) is the main predictor of severe course uveitis

Purpose:  Aim of the present study was to validate a statistical model to predict a severe course of anterior uveitis (AU) in patients with juvenile idiopathic arthritis (JIA).

Comparable Efficacy of Abatacept Used as First-line or Second-line Biological Agent for Severe Juvenile Idiopathic Arthritis-related Uveitis.

Objective. Abatacept (ABA) has recently been proposed as second-line treatment in patients with juvenile idiopathic arthritis (JIA)–associated uveitis refractory to anti–tumor necrosis factor-α (anti-TNF) agents, but little is known about its efficacy as a first-line approach. The aim of the present study was to compare the safety and efficacy of ABA as a first-line biological agent (ABA-1) with that of ABA as a second-line treatment after 1 or more anti-TNF agents (ABA-2), in patients with severe JIA-related uveitis. Methods. In this multicenter study, we collected data on patients with severe JIA-related uveitis treated with ABA as a first-line or second-line biological agent. Changes in frequency of uveitis flares/year and ocular complications before and after ABA treatment, clinical remission, and side effects were recorded. Results. Thirty-five patients with a mean age of 10.8 years were treated with ABA for a mean period of 19.6 months. In 4 patients, ABA administration was discontinued, owing to inefficacy on arthritis in 3 cases and allergic reaction in 1. Thirty-one patients, 14 in the ABA-1 group and 17 in the ABA-2 group, completed the 12-month followup period; of these, 17 (54.8%) had clinical remission. The mean frequency of uveitis flares decreased from 4.1 to 1.2 in the ABA-1 group (p = 0.002) and from 3.7 to 1.2 in the ABA-2 group (p = 0.004). Preexisting ocular complications improved or remained stable in all but 5 patients, all in the ABA-2 group. No significant difference was found between the efficacy of the 2 treatment modalities. ABA confirmed its good safety profile. Conclusion. ABA, used as first-line biological treatment or after 1 or more anti-TNF agents, induces a comparable improvement in severe refractory JIA-related uveitis.

Grade III lipaemia retinalis in a newborn.

Editor, L ipaemia retinalis, first described in 1880 and recently recognized as a paediatric disease, occurs rarely in patients with hyperlipidaemia. In typical cases, ophthalmoscopy evidences creamy-white retinal vessels. Although the picture is graded clinically (Table 1), grade III cases are extremely rare. The first daughter of non-consanguineous parents; spontaneous birth (weight 3430 g) following a full-term uneventful pregnancy. The family history revealed hypercholesterolaemia and hypertrigliceridaemia in the paternal grandfather, grandmother and father, which was moderate, mild and very mild, respectively. The patient underwent phototherapy for jaundice from blood group incompatibility and, a few days after birth, was discharged from hospital in a good clinical condition. However, at 28 days of life, she was admitted to hospital with fever and feeding problems. Breastfed, and weighing 4045 g, on the first evening of hospitalization the patient had biliary vomiting. Laboratory investigations were performed, but the presence of lypaemic serum precluded blood sample analysis. On transferral to the paediatric intensive care unit for diagnosis and treatment, the clinical examination revealed multiple facial little tip-head xanthomas, and the laboratory investigation a slight increase in leukocytes (17 000 wc ⁄ml), platelets (600 000 ⁄ml) and C-reactive protein (114 mg ⁄ l). The creamy aspect of the lipaemic serum precluded the determination of coagulation (prothrombin and thromboplastin time) and albuminaemia and creatininaemia levels. Triglycerides were 12 380 mg ⁄dl (normal value < 200 mg ⁄dl) and total cholesterol 820 mg ⁄dl (n.v. < 200 mg ⁄dl). Serum chylomicron levels were also elevated markedly. At pancreatic amylase measurement plasma level was normal, as were other bio-humoral values including haemogas. On the suspending of enteral feeding, lipid-free parenteral nutrition, heparin (10 U ⁄kg ⁄hr), ampicillin and gentamycin administration were started; abdominal echography showed a normal liver and pancreas, whereas ophthalmoscopy evidenced pale optic discs and creamy-white arteries and veins, and a salmon-pink retina. The clinical picture was typical of lipaemia retinalis (Figs 1 and 2). Three days after suspending breast-feeding, parenteral nutrition was started; laboratory examinations showed reduced triglycerides (3750 mg ⁄dl) and total cholesterol (440 mg ⁄dl) levels. All other biohumoral parameters were normal. Low lipid formula (Basic-F Nutricia) feeding was started and heparin infusion suspended. After another 3 days on the new diet, blood lipids appeared normal, as did the fundus, except for a minimal retinal haemorrhage in the right eye. At follow-up 5 months later, the visual function (Teller Acuity Cards) and ophthalmological findings were normal. Laboratory examinations in the parents confirmed mild hypercholesterolaemia in the father. At DNA analysis, the infant had a familial type 1 lipoprotein–lipases deficit. To our knowledge, the only cases of lipaemia retinalis in newborns reported in the literature are in two infants aged 29 days (Hayasaka et al. 1985) and 35 days (Cypel et al. 2008), and in a 77-day-old pre-term infant (Rotchford et al. 1997) in whom lipaemia retinalis was associated with retinopathy of prematurity. Treatments proposed include the administration of a fat-restricted diet, increased protein and carbohydrate, and ⁄or the addition of medium-chain triglycerides and soluble-fat vitamins. Our patient received parenteral nutrition and heparin infusion to lower the risk of small-vessels thrombosis before returning to a diet of artificial skimmed milk. Broad-spectrum antibiotic therapy, started on admission because of the clinical suspicion of sepsis without a laboratory confirmation, was withdrawn on obtaining blood culture results and an improvement in the clinical condition. Prompt interruption of enteral nutrition, intravenous hydratation with no-lipid-balanced solutions, strict monitoring of vital signs and pancreatic enzymes plasma levels are crucial therapeutic strategies. While waiting for normal plasma fat levels to be restored, low-dose heparin infusion may help to prevent small-vessel obstruction. Fig. 1. Pale optic disc: all vessels (arteries and veins) with creamy aspect; salmoncoloured retina, typical of lipaemia retinalis.

Longterm Safety and Efficacy of Adalimumab and Infliximab for Uveitis Associated with Juvenile Idiopathic Arthritis

Objective. Anti-TNF-α agents have significantly changed the management of juvenile idiopathic arthritis (JIA). We evaluated the safety and efficacy of adalimumab (ADA) and infliximab (IFX) for the treatment of JIA-associated uveitis in patients treated for ≥ 2 years. Methods. Patients with JIA-associated uveitis treated with IFX and ADA were managed by a standardized protocol and data were entered in the ORCHIDEA registry. At baseline, all patients were refractory to standard immunosuppressive treatment or were corticosteroid-dependent. Data recorded every 3 months were uveitis course, number/type of ocular flares and complications, drug-related adverse events (AE), and treatment switch or withdrawal. Data of patients treated for ≥ 2 years were analyzed by descriptive statistics. Results. Up to December 2014, 154 patients with ≥ 24 months followup were included in the study. Fifty-nine patients were treated with IFX and 95 with ADA. Clinical remission, defined as the absence of flares for > 6 months on treatment, was achieved in 69 patients (44.8%), with a better remission rate for ADA (60.0%) as compared to IFX (20.3%; p < 0.001). A significant reduction of flares was observed in all patients without difference between the 2 treatment modalities. The number of new ocular complications decreased in both groups but was lower for ADA (p = 0.015). No serious AE were recorded; 16.4% of patients experienced 35 minor AE and the incidence rate was lower with ADA than with IFX. Conclusion. At the 2-year followup, ADA showed a better efficacy and safety profile than IFX for the treatment of refractory JIA-associated uveitis.

Cogan’s Syndrome

Patient: A 28 year old man, Caucasian. Chief complain 3/2000: Redness and light sensitivity in both eyes. Past ocular history: Two year history of bilateral keratitis treated with topical steroids with initial improvement and subsequently become unresponsive. Past medical history: Idiopathic hearing loss since 1996, unresponsive to systemic cyclophosphamide and high doses of prednisone. Review of systems:-Headache: constant and in the frontal region, poorly responsive to conventional pain medications.-Back pain and arthralgia.-Subcutaneous nodules, rash on the volar part of the left arm. Figure 1: skin nodules and rash Previous work-up:-Chest X-ray: possible left hilar adenopathy.-Chest CT scan: normal.-FTA-Abs, Lyme test, ACE, ESR: all normals. Examination: Visual acuity: OD=20/30 PH OS=20/20 PH Slit-lamp: corneal neovascularization and abundant lipid deposition in the stroma in the superior half of both corneas. Figure 2: corneal neovascularization in OD(left) and in OS(right) Corneal sensation: normal.

Ocular involvement in an HIV-infected patient: not always an infectious disease. An interesting case without apparent cause

We describe the case of a young girl with vertically-transmitted HIV infection who presented with chronic ocular inflammation characterized by several relapses and remissions. Good viral and immunological status made infective or neoplastic causes unlikely; the diagnosis was challenging and finally spontaneous remission was observed after several months. Clinical and histopathological findings made idiopathic orbital inflammatory syndrome the most probable diagnosis for our patient.