Emmanuel Héron

The Clinical Spectrum and Therapeutic Management of Hypocomplementemic Urticarial Vasculitis: Data From a French Nationwide Study of Fifty‐Seven Patients

Hypocomplementemic urticarial vasculitis (HUV) is an uncommon vasculitis of unknown etiology that is rarely described in the literature. We undertook this study to analyze the clinical spectrum and the therapeutic management of patients with HUV.

Hypoglycemia-Induced Blood Pressure Elevation in Patients With Diabetes

B lood pressure elevation secondary to hypoglycemia has been demonstrated in human experimentation through the activation of the sympathoadrenal system. Though hypoglycemia is a fact of life for patients with both type 1 and type 2 diabetes mellitus, blood pressure (BP) variations after hypoglycemic events has not been clarified. Our aim was to determine the relationship between glucose level and BP swings in patients with diabetes under everyday conditions.

Successful use of infliximab therapy in sight-threatening corticosteroid-resistant Vogt-Koyanagi-Harada disease.

Purpose: To report an experience with infliximab in severe corticosteroid-resistant Vogt-Koyanagi-Harada (VKH) disease. Design: Interventional case series. Methods: The medical records of 2 adult patients were reviewed. Results: Both patients had a visual acuity reduced to hand motion perception bilaterally after 1 month of high-dose corticosteroid therapy, due to multiple exudative retinal detachment involving the fovea. Visual acuity and OCT findings improved immediately after the first infliximab infusion, retinal detachments fully resolved after 1 month and visual acuity returned to normal within 6 months. Despite a negative pretreatment screening, one patient developed multivisceral tuberculosis, which led to infliximab discontinuation after the 7th infusion and was cured by a 9-month ambulatory antibiotic regimen. The other patient received 11 well-tolerated infliximab infusions. Respectively, 9 and 4 months after infliximab discontinuation both patients had normal vision and OCT findings. Conclusion: Infliximab showed tremendous therapeutic efficacy in sight-threatening corticosteroid-resistant VKH disease.

Multiple Sclerosis-related Uveitis: Does MS Treatment Affect Uveitis Course?

ABSTRACT Purpose: Few data are available regarding the optimal treatment of multiple sclerosis (MS)-related uveitis. The aim of this study was to describe clinical features of MS-associated uveitis and determine how MS treatment affects the course of uveitis. Methods: Retrospective, multicenter study. Patients were divided into two groups according to the use (group 2) or not (group 1) of immunomodulatory drugs. Characteristics of uveitis and treatment were reviewed. Results: A total of 68 eyes from 36 patients (17 in group 1 and 19 in group 2) were included. All patients were treated with topical and/or systemic steroids for uveitis. Uveitis occurred 1–17 years prior to neurologic symptoms in 78% of patients. Uveitis was more severe in group 2 (p<0.05), with a tendency toward a higher rate of chronic uveitis (p = 0.06). Conclusions: MS-related uveitis has often a favorable evolution. Patients on interferon-beta have more severe and chronic uveitis. As far as we are concerned, interferon-beta given on the sole indication of uveitis is not recommended. If steroid-sparing agent is required for intraocular inflammation, immunosuppressive drugs should be considered.

Clinicopathologic characteristics, treatment, and outcomes of tubulointerstitial nephritis and uveitis syndrome in adults: A national retrospective strobe-compliant study.

AbstractTubulointerstitial nephritis and uveitis (TINU) syndrome is a rare disease, defined by the association of idiopathic acute TINU. The aim of our work was to determine the characteristics of adult TINU syndrome in France, and to assess factors (including treatment) influencing medium-term prognosis.We conducted a nationwide study including 20 French hospitals. Clinical, laboratory, and renal histopathologic data of 41 biopsy-proven TINU syndromes were retrospectively collected. The patients were diagnosed between January 1, 1999 and December 1, 2015.Twenty-five females and 16 males were included (F/M ratio: 1.6:1). The median age at disease onset was 46.8 years (range 16.8–77.4) with a median serum creatinine level at 207 &mgr;mol/L (range 100–1687) and a median estimated glomerular filtration rate (eGFR) at 27 mL/min per 1.73 m2 (range 2–73). Twenty-nine patients (71%) had a bilateral anterior uveitis and 24 (59%) had deterioration in general health at presentation. Moderate proteinuria was found in 32 patients (78%) (median proteinuria 0.52 g/24 h; range 0.10–2.10), aseptic leukocyturia in 25/36 patients (70%). The evaluation of renal biopsies revealed 41 patients (100%) with an acute tubulointerstitial nephritis, 19/39 patients (49%) with light to moderate fibrosis and 5 patients (12%) with an acute tubular necrosis. Thirty-six patients (88%) were treated with oral corticosteroids. After 1 year of follow-up, the median eGFR was 76 mL/min per 1.73 m2 (range 17–119) and 32% of the patients suffered from moderate to severe chronic kidney disease. Serum creatinine (P < 0.001, r = −0.54), serum bicarbonate and phosphate levels (respectively, P = 0.01, r = 0.53; and P = 0.04, r = 0.46), and age (P = 0.03, r = −0.37) at the 1st symptoms were associated with eGFR after 1 year. During the 1st year 40% of patients had uveitis relapses. The use of oral corticosteroids was not associated with a better kidney function but was associated with fewer uveitis relapses (P = 0.44 and 0.02, respectively).In our study, 32% of patients were suffering from moderate to severe chronic kidney disease after 1 year of follow-up, and 40% had uveitis relapses during this follow-up. This work also suggests that oral corticosteroids are effective for the treatment of TINU syndromes uveitis.

Familial central retinal vein occlusion

AimTo report four cases of central retinal vein occlusion (CRVO) in a French family.Patients and methodsOphthalmological examination and medical work-up of seven members of the family.ResultsThere were four cases of CRVO in two consecutive generations. Three of them had CRVO in both eyes. Arterial hypertension was present in two, associated to glaucoma in one. Medical work-up did not reveal additional risk factors.ConclusionsWe report a case of familial clustering of CRVO. Our cases combined to other cases reported in the literature provide arguments for the existence in some subjects of a genetic predisposition of CRVO. Additional case series are however needed to confirm this hypothesis.

Late posterior segment relapses in a series of Vogt-Koyanagi-Harada disease

e recently reported that 73.8%of subjects diagnosed withVogt–Koyanaga–Harada (VKH) dis-ease experienced recurrences (Erreraet al. 2011). Based on our experience,we believed that finding an exudativeretinal detachment (ERD) thatresponded to corticosteroids or othermedical treatment more than 1 yearafter onset is low. To better evaluatelate posterior recurrences, we reviewedthe records of a large series of 45patients with VKH disease from fourtertiary centres. The median follow-upduration was 34 months since initialpresentation.Late posterior segment relapses weredefined as posterior segment manifes-tations of inflammation occurring laterthan 52 weeks after first presentationof VKH (Garcia-Valenzuela et al.2000; Sachdev et al. 2008; Dolz-Marcoet al. 2011). The study adhered to thetenets of the Declaration of Helsinki.Relapsing ERDs were noted within10 months after presentation in 16(84%) of 19 subjects who experiencedsuch reactivation, with only four expe-riencing late ERDs, one of whom alsohad early relapses. Report of foursubjects with late ERDs relapses at amedian of 19 months (16–25 months).By examination and optical coher-ence tomography (OCT), subretinalfluid was limited localized areas ofsubmacular ERDs in all late posteriorsegment relapses (Fig. 1).Intravenous pulse therapy was usedwithin the first month for three of thefour subjects who experienced a lateposterior reactivation. In the fourthsubject, the diagnosis of VKH diseasewas made 3 months after the firstinflammatory signs, which caused adelay in the initiation of the correcttreatment. This latter subject had treat-ment with corticosteroids for only1 month, while the other three subjectsreceived an initial duration of systemiccorticosteroids for at least 6 months.In all four subjects, immunosuppres-sive therapy (infliximab, cyclosporin orinterferon) was initiated after the firstrelapse because response to therapywith corticosteroid at acceptable long-term doses was insufficient.All four subjects had been on immu-nomodulatory agents (cyclophospha-mide, infliximab and azathioprine),but these agents had been stopped 5to 13 months prior to the relapse.In one subject, the relapse occurredwhile he was taking 25 mg/day ofprednisone. He had responded to rein-troduction of high-dose corticotherapyfor an episode 6 months previously,and he was on tapering of therapy. Thesecond subject was receiving bothprednisone and cyclophosphamide.The third was on infliximab and low-dose oral corticosteroids at the time ofrelapse.In the experience at our institutionsthere were 4 late relapses (ERDs) of 45subjects with an incidence rate of 12cases per 1000 VKH affected person-years. Late relapses as ERDs occurredin patients receiving early intravenouspulse corticosteroids, and all four hadbeen on other corticosteroid-sparingimmunomodulatory therapy at somepoint. One possible explanation is thatthe need for more aggressive treatmentin our patients with late relapses ofVKH may be a marker of more severedisease. Early corticosteroid-sparingimmunomodulatory therapy might beuseful as first-line therapy to reduce thedevelopment of complications (AbuEl-Asrar et al. 2013). Although it is

Findings in Detection of Herpesviridae by Polymerase Chain Reaction and Intraocular Antibody Production in a Case Series of Anterior Uveitis

Purpose: To target the use of two biologic tests in the diagnostic of viral Herpesviridae anterior uveitis (AC) by the consideration of clinical behavior and delay of intraocular sampling. Methods: Aqueous humor samples were collected from 42 patients suspected of having AU of infectious origin at presentation. The diagnosis of infectious uveitis was confirmed by quantification of antibodies with the Goldmann-Witmer coefficient (GWC) and/or detection of Herpesviridae genomes with PCR. The data were compared with data of 16 uveitis control samples used to calculate the specificity of the tests. Results: Sixteen out of 42 eyes (38%) had a final diagnosis of anterior segment infectious uveitis of viral origin (Herpesviridae) confirmed by PCR positive result (5/14 eyes; 14 of the 16 eyes were tested by PCR) and/or specific intraocular antibody synthesis (14/16 eyes). Conclusions: While the GWC is progressively less often performed, these findings suggest that it still has a role in AU suspected of herpesvirus etiology.

Tolérance glycémique des bolus intraveineux de méthylprednisolone en milieu ophtalmologique

INTRODUCTION: Short-term, high-dose intravenous methylprednisolone therapy, also called pulse methylprednisolone, is widely used in a variety of inflammatory eye diseases. Monitoring blood glucose during this therapy is recommended. We evaluated the clinical implications of glycemia monitoring during repeated pulse methylprednisolone for eye disease. PATIENTS AND METHODS: During the year 2000, 224 patients received 120-1 000 mg daily intravenous methylprednisolone for 3 consecutive days for acute optic neuritis (n=91), severe uveitis (n=35), ocular infectious diseases (n=22), corneal graft rejection (n=17) and miscellaneous disorders (n=59). Serial morning fasting blood glucose, i.e., before the first pulse and the day after each pulse, and specific hypoglycemic drug interventions were recorded. RESULTS: All patients showed a median 50% increase in fasting glucose after the first pulse with no significant difference between diabetic and nondiabetic patients. Thereafter, the 196 nondiabetic patients showed a spontaneous decrease in their fasting glucose towards baseline values despite the following infusions. However, none of them required hypoglycemic intervention. In contrast, the 28 diabetic patients demonstrated further increases in blood glucose levels and seven received rapid-release treatment. CONCLUSION: Glucose tolerance of pulse methylprednisolone was excellent in nondiabetic patients; close glycemia monitoring seems necessary only for patients with diabetes.

Contribution of diagnostic tests for the etiological assessment of uveitis, data from the ULISSE study (Uveitis: Clinical and medicoeconomic evaluation of a standardized strategy of the etiological diagnosis)

PURPOSE ULISSE is the only study that prospectively assessed the efficiency of a standardized strategy, compared to an open strategy for the etiologic diagnosis of uveitis. Our aim was to evaluate the diagnostic yield of the tests prescribed in the ULISSE study to clarify their relevance. METHODS ULISSE is a non-inferiority, prospective, multicenter and cluster randomized study. The standardized strategy is a two-steps strategy: in the first step, common standard tests were performed, and in the second step, tests were guided by the clinical and anatomic type of uveitis. We reported the relevance of the diagnostic tests used in the standardized strategy, as well as the profitability of the tests that were prescribed to more than twenty patients in each group. Based on diagnostic criteria, either an ophthalmologist, or an internist, established the profitability of a test by considering whether the test lead to a diagnosis or not. RESULTS Among the 676 patients included (standardized 303; open 373), a diagnosis was made for 152 (50.4%) in the standardized group and 203 (54.4%) in the open group. The most common entities were HLA-B27 associated uveitis (22%), spondyloarthritis (11%), sarcoidosis (18%), tuberculosis (10.7%) and herpes virus infections (8.5%). Among the first steps systematic tests, tuberculin skin test was the most contributive investigation (17.1%), followed by chest X-ray (8.4%), C reactive protein and ESR (6.6% and 5.1%), complete blood count (2.2%) and VDRL (2.0%). The second steps most often contributive tests were: HLA B27 (56.3%), chest-CT (30.3%) and angiotensin converting enzyme (ACE) (16.5%). HLA B27 and ACE were significantly more contributive in the standardized group than in the open group. Immunological tests were never contributive. Among the free investigations, or among the investigations guided by clinical or paraclinical findings, the most often contributive tests were: Quantiferon® (24%), electrophoresis of serum protein (7.8%) and sacroiliac imagery (46.4%). Intracellular serologies (1.7%), serum calcium (2.1%) and hepatic tests (3.3%) were exceptionally contributive. Among the third intention tests, labial salivary gland biopsies were contributive in 17.9% of cases, but the profitability of other invasive investigations (anterior chamber tap, vitrectomy, bronchoscopy and lumbar puncture) or specialized imagery (18F-FDG PET, Brain MRI) could not be determined since these test were rarely performed. CONCLUSION Only a few diagnostic tests are useful for the etiological assessment of uveitis. They are often cheap, simple, more often guided by the clinical findings, and lead to an etiological diagnosis in most patients. On the other hand, some tests are never or exceptionally contributive, such as immunological tests or intracellular serologies. Further studies are required to evaluate the profitability of third intention imagery and invasive investigations.