Monoarticular juvenile idiopathic arthritis as a distinct clinical entity A proof-of-concept study.

BACKGROUND: Currently, monoarticular Juvenile Idiopathic Arthritis (monoJIA) is included in the ILAR classification as oligoarticular subtype although various aspects, from clinical practice, suggest it as a separate entity. OBJECTIVES: To describe the clinical characteristics of persistent monoJIA. METHODS: Patients with oligoJIA and with at least two years follow-up entered the study. Those with monoarticular onset and persistent monoarticular course were compared with those with oligoJIA. Variables considered were: sex, age at onset, presence of benign joint hypermobility (BJH), ANA, uveitis, therapy and outcome. Patients who had not undergone clinical follow-up for more than 12 months were contacted by structured telephone interview. RESULTS: Of 347 patients with oligoJIA, 196 with monoarticular onset entered the study and 118 (60.2%), identified as persistent monoJIA, were compared with 229 oligoJIA. The mean follow-up was 11.4 years. The switch from monoarticular onset to oligoarticular course of 78 patients (38.8%) occurred by the first three years from onset. In comparison with oligoJIA, the most significant features of monoJIA were later age at onset (6.1 vs. 4.7 years), lower female prevalence (70.3 vs. 83.4%), higher frequency of BJH (61.9 vs. 46.3%), lower frequency of uveitis (14.4 vs. 34.1%) and ANA+ (68.6 vs. 89.5%) and better long-term outcome. CONCLUSIONS: MonoJIA, defined as persistent arthritis of unknown origin of a single joint for at least three years, seems to be a separate clinical entity from oligoJIA. This evidence may be taken into consideration for its possible inclusion into the new classification criteria for JIA and open new therapeutic perspectives.

Methotrexate Monotherapy in Juvenile Idiopathic Arthritis Associated Uveitis: Myth or Reality?

OBJECTIVE: To evaluate the long-term efficacy of methotrexate (MTX) monotherapy in patients with juvenile idiopathic arthritis-associated uveitis (JIA-U). METHODS: We analyzed a cohort of patients with JIA-U treated with MTX monotherapy, divided into two groups depending on whether MTX was started before (on-MTX group) or after uveitis diagnosis (MTX-naïve group). The primary endpoint was the time between uveitis inactivity and first relapse. RESULTS: 84 patients entered the study. The median duration of remission on MTX monotherapy resulted 8.2 months. The on-MTX group showed a significant longer time interval between arthritis and uveitis onset and higher need for biologic agents (bDMARD). During follow-up, 40 patients (47.6%) needed bDMARD due to poor control of uveitis. Clinical remission off medication was achieved in 11.9% of patients, all belonging to the MTX-naïve group. CONCLUSIONS: MTX monotherapy, although effective in early stages of JIA-U, showed poor disease control in the long term.

The eye involvement in monogenic autoinflammatory diseases: literature review and update.

Monogenic autoinflammatory diseases (AIDs) are rare entities characterised by improper activation of the innate immune system. This in turn determines recurrent episodes of systemic inflammation characterised by fever, which is variously combined with a wide range of inflammatory manifestations involving the skin, joints, serous membranes, gastrointestinal tract, and central nervous system. As shown by research efforts conducted during the last decade, the eye is not exempt from the systemic inflammatory process and may be involved in almost all of the most frequent AIDs, with several distinct peculiarities. Ocular affections may severely impact patients' quality of life due to orbital pain, impairment of visual acuity, and/ or long-term, sight-threatening complications. Consequently, in the context of a multidisciplinary team, ophthalmologists should be aware of ocular manifestations related to these disorders as they may have a dominant diagnostic weight in patients with a challenging presentation as well as a salient role in therapeutic choice in sight-threatening situations. This review describes a variety of aspects of ophthalmologic involvement in AIDs, looking at both well-recognised eye manifestations as well as rarely reported ocular presentations, with a particular focus on the recent literature.

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.

Ocular nonsuicidal self-injury in a teenager.

A 14-year-old male teen presented with unilateral episcleritis, unresponsive to topical and systemic corticosteroid therapy, without a history of ocular trauma or evidence for systemic diseases. The presence of foreign bodies in the conjunctival mucus of the hyperemic fornix has been noticed during one of the follow-up examinations. The toxicological analysis of conjunctival mucus revealed the presence of ethylene glycolmonomethyl ether and triethilene glicolebuthyl ether, used as solvents in nail polish removers and all-purpose cleaners. An unexpected etiology of chemical self-inflicted episcleritis was determined. The teen was admitted to a psychological assessment, after which a psychotherapeutic treatment was recommended. Episcleritis is characterized by the acute onset of ocular pain and redness, with a frequent recurrent and stressful course. Since it can be associated with life-threatening systemic vasculitides, a prompt, aggressive immunosuppressive therapy may be considered, both for the ocular inflammation and for the underlying systemic condition. Rarely episcleritis does not improve despite topical and systemic therapy, administered in a stepladder way. The reported teenager case needed a complex multidisciplinary approach to achieve the correct diagnosis and to avoid unnecessary treatments. In the case of recognized "nonsuicidal self-injury," a psychological evaluation is strongly recommended, to identify and address underlying neuropsychiatric problems.

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.

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.

Torpedo maculopathy: a morphofunctional evaluation.

To describe the optical coherence tomography (OCT), the standard short-wavelength fundus autofluorescence (SW-FAF) and near-infrared fundus autofluorescence (NIR-FAF), and the microperimetric findings in a child with a unique unilateral lesion of the temporal macula previously called torpedo maculopathy. A 4-year-old female with torpedo maculopathy was evaluated with spectral-domain OCT (SD-OCT), standard SW-FAF (excitation 488 nm, emission >500 nm) and NIR-FAF (excitation 787 nm, emission >800 nm). Microperimetry was performed to assess retinal sensitivity changes correlated to the macular lesion. SD-OCT showed an abnormally thin retinal pigment epithelium signal and an increased signal transmission in the choroid corresponding to the torpedo lesion with no neuroretinal changes. SW-FAF resulted in normal fluorescence of the lesion except for a small hyperfluorescent area at the tail level. NIR-FAF showed hypofluorescence corresponding to the lesion. Macular microperimetry showed reduced retinal sensitivity along the pigmented margins of the lesion with normal values over the lesion. The patient was re-evaluated 12 months later and no change was documented with all diagnostic techniques. This case supports a congenital defect of retinal pigment epithelium. The absence of both functional changes at lesion level and neuroretinal changes at OCT may depend on the very early detection of this lesion.

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.

Abatacept for severe anti-tumor necrosis factor alpha refractory juvenile idiopathic arthritis-related uveitis.

OBJECTIVE: 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 alpha (anti-TNFalpha) agents. METHODS: Patients with JIA-related uveitis refractory to immunosuppressive and anti-TNFalpha agents were treated with intravenous abatacept (10 mg/kg monthly). Side effects, frequency of uveitis flares, and ocular complications before and after treatment were reported. RESULTS: Seven patients (6 females and 1 male) with a mean uveitis duration of 11.6 years entered the study. All patients had failed previous immunosuppressive therapy and >or=2 anti-TNFalpha treatments. All patients responded to abatacept and 6 maintained a clinical remission after a mean of 9.2 months of treatment. One patient withdrew from the study with oral mycosis and arthritis flare; no other patients had side effects. The mean frequency of uveitis flares during the 6 months before and after treatment decreased from 3.7 to 0.7 episodes. No new ocular complications or worsening of preexisting ones were reported. CONCLUSION: Abatacept treatment led to sustained improvement in severe anti-TNFalpha-resistant JIA-related uveitis and was well tolerated in all but 1 patient. These results provide new insights into a possible indication of abatacept for the treatment of uveitis.

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.

Early predictors of severe course of uveitis in oligoarticular juvenile idiopathic arthritis.

OBJECTIVE: To determine whether demographic, clinical, and laboratory variables at onset of arthritis can predict the development and the severity of anterior uveitis (AU) in oligoarticular juvenile idiopathic arthritis (JIA). METHODS: In a retrospective study, a cohort of 366 patients with oligoarticular onset JIA from 3 pediatric rheumatology centers were evaluated. Patients were classified in 3 groups: severe uveitis (SU) with a mean >/= 2 uveitis relapses/year with complications or need for immunosuppressive therapy; mild uveitis (MU) with a mean