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ObjectiveTo identify characteristics of granulomatosis with polyangiitis (GPA) associated with induction failure, describe salvage therapies and their efficacy.MethodsWe conducted a nationwide retrospective case-control study of GPA with induction failure between 2006 and 2021. Each patient with induction failure was randomly paired to three controls matched for age, sex and induction treatment.ResultsWe included 51 patients with GPA and induction failure (29 men and 22 women). At induction therapy, median age was 49 years. Twenty-seven patients received intravenous cyclophosphamide (ivCYC) and 24 rituximab (RTX) as induction therapy. Patients with ivCYC induction failure more frequently had PR3-ANCA (93% vs 70%, P = 0.02), relapsing disease (41% vs 7%, P 100 µmol/l in 42% vs 8%, P = 0.02) compared with controls. After salvage therapy, remission was achieved at 6 months in 35 (69%) patients. The most frequent salvage therapy was switching from ivCYC to RTX (or vice versa), showing an efficacy in 21/29 (72%). Remission was achieved in nine (50%) patients with inappropriate response to ivCYC, while in patients with progression after RTX induction, remission was achieved in four (100%) who received ivCYC (with or without immunomodulatory therapy), but only in three (50%) after adding immunomodulatory therapy alone.ConclusionIn patients with induction failure, characteristics of GPA, salvage therapies and their efficacy vary according to induction therapy and failure modality.

Objective The association of IgA vasculitis (IgAV) and IBD is rarely described, mainly during anti-TNF-α therapy. We aimed to describe the association of IgAV and IBD. Methods We retrospectively analysed the association of IgAV and IBD through the implication of the GETAID and FVSG networks. Characteristics of IBD and IgAV were collected using a standardized case report form. Results Forty-three cases were included. IBD [mainly Crohn’s disease (CD) in 58%] preceded IgAV in 38 (88%), with median interval of 9.2 (IQR 5.4–15.4) years. In these 38 patients, at IgAV diagnosis, five (13%) had active IBD and 28 (74%) were treated with anti-TNF-α for a median duration of 31.5 (IQR 19–56) months. Main IgAV manifestations were purpura all patients (100%), joints in 20/35 (57%), renal in 15/35 (43%) and gastrointestinal in 11/35 (31%) involvement. IgAV was treated with glucocorticoids in 25 (66%), colchicine in six (16%), CYC in six (16%) and anti-TNF-α were discontinued in 15/28 (54%). No IgAV relapse occurred when TNF-α blockers were stopped, vs 23% in patients pursuing it. Conversely, five (33%) had IBD flare or complication after anti-TNF-α cessation vs one (8%) in those continuing biologics. Anti-TNF-α were resumed in six (40%), with subsequent IgAV relapse in four (67%). Conclusions This large cohort suggests that TNF-α blockers may promote the onset of IgAV in IBD. Discontinuation of anti-TNF-α was associated with vasculitis remission but increased risk of IBD relapses, whereas continuation of anti-TNF-α was associated with IBD remission but vasculitis relapse.

Granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) are rare systemic necrotizing vasculitis. The national incidence and prevalence of GPA/MPA and patient mortality remain unknown in France. A real-life study using retrospective data from the French National Health Data System was set up to describe the epidemiology and demographic characteristics of hospitalized GPA and MPA patients, overall and by disease.All adult patients (≥18 years of age) hospitalized for GPA (ICD-10 M31.3) or MPA (ICD-10 M31.7) between 01 and 01-2010 and 31-12-2017 and affiliated to the General health insurance Scheme (covering 76% of the French population) were included in this national retrospective observational study. Descriptive analyses, univariate and multivariable logistic models, Kaplan-Meier survival analysis, and Cox models were performed.The study involved 4445 prevalent GPA patients (including 1578 incident patients) and 1833 prevalent MPA patients (878 incident patients). Distinction between GPA and MPA diagnosis could not be made for 303 patients (149 incident patients). In people aged over 20 years, the age-standardized incidence rates of GPA and MPA were 0.5 and 0.3/100,000 person-years, respectively and the age-standardized prevalence rates were 10 and 4/100,000 person-years, respectively. The standardized mortality ratios in GPA and MPA patients aged over 20 years were 2.0 and 2.7, respectively, and remained constant. Renal failure, pulmonary and urinary tract infections, as well as coronary disease were more frequent among MPA than GPA patients. One-year survival rates among GPA and MPA patients were 96% (95%CI 94%-97%) and 94% (92%-95%), respectively. Five-year survival rates among GPA and MPA patients were 81% (95% CI 79%-83%) and 72% (68%-75%), respectively. After adjusting for comorbidities, the risk of death was still higher in MPA (hazard ratio 1.26 [95%CI 1.06-1.50]) than in GPA patients.Despite advances in the therapeutic management of patients, mortality rates are still high and stable over time, highlighting the need for improved management.

Background Gastrointestinal (GI) involvement was described to be a poor prognostic factor in systemic necrotizing vasculitis. Its prognostic significance may vary according to clinical presentation and vasculitis subtype. Aims This study investigated risk-factors associated to poor outcome in GI-involvement of vasculitis. Methods Patients with systemic vasculitis as defined by the 2012 Chapel Hill Consensus Conference and presenting with GI involvement were retrospectively included. Baseline characteristics, treatments and outcome were recorded. Primary endpoint was a composite of admission to intensive care unit (ICU), emergency surgical procedure, or death. Results Two hundred and thirteen patients were included. Vasculitis were distributed as follows: 41% IgA vasculitis, 27% ANCA-associated vasculitis, 17% polyarteritis nodosa (PAN), and 15% other vasculitis. Eighty-three (39%) patients fulfilled the composite primary endpoint within 6 months. Predictive factors associated with the primary endpoint included PAN subtype (OR 3.08, 95% CI 1.29–7.34), performance status (OR 1.40, 1.05–1.87), use of morphine (OR 2.51, 0.87–7.24), abdominal guarding (OR 3.08, 1.01–9.37), ileus (OR 2.29, 0.98–5.32), melena (OR 2.74, 1.17–6.42), increased leukocytes (per G/L, OR 1.05, 1.00–1.10), low hemoglobin (per g/dL, OR 0.80, 0.71–0.91) and increased CRP (log mg/L, OR 1.21, 0.94–1.56). A risk prediction model for the achievement of primary endpoint had a very good performance [C-statistics 0.853 (0.810 to 0.895], and for overall survival as well. Conclusions Vasculitis presenting with GI involvement have a poor outcome in more than one third of cases. An easy-to-use risk prediction model had a very good performance to predict the admission to ICU, emergency surgical procedure, or death.

Objective Eosinophilic granulomatosis with polyangiitis (EGPA) is a systemic small-vessel vasculitis characterized by asthma, hypereosinophilia and ANCA positivity in 40% of patients. Renal involvement is rare and poorly described, leading to this renal biopsy-proven based study in a large EGPA cohort. Methods We conducted a retrospective multicentre study including patients fulfilling the 1990 ACR criteria and/or the 2012 revised Chapel Hill Consensus Conference criteria for EGPA and/or the modified criteria of the MIRRA trial, with biopsy-proven nephropathy. Results Sixty-three patients [27 women, median age 60 years (18–83)] were included. Renal disease was present at vasculitis diagnosis in 54 patients (86%). ANCA were positive in 53 cases (84%) with anti-MPO specificity in 44 (83%). All patients had late-onset asthma. Peripheral neuropathy was present in 29 cases (46%), alveolar haemorrhage in 10 (16%). The most common renal presentation was acute renal failure (75%). Renal biopsy revealed pauci-immune necrotizing GN in 49 cases (78%). Membranous nephropathy (10%) and membranoproliferative GN (3%) were mostly observed in ANCA-negative patients. Pure acute interstitial nephritis was found in six cases (10%); important interstitial inflammation was observed in 28 (44%). All patients received steroids with adjunctive immunosuppression in 54 cases (86%). After a median follow-up of 51 months (1–296), 58 patients (92%) were alive, nine (14%) were on chronic dialysis and two (3%) had undergone kidney transplantation. Conclusion Necrotizing pauci-immune GN is the most common renal presentation in ANCA-positive EGPA. ANCA-negative patients had frequent atypical renal presentation with other glomerulopathies such as membranous nephropathy. An important eosinophilic interstitial infiltration was observed in almost 50% of cases.

Objectives To describe the effectiveness and safety of biologics for the treatment of relapsing and/or refractory polyarteritis nodosa (PAN). Methods A retrospective European collaborative study was conducted in patients with PAN who received biologics for relapsing and/or refractory disease. Results Forty-two patients with PAN received a total of 53 biologic courses, including TNF-α blockers in 15 cases, rituximab (RTX) in 18 cases, tocilizumab (TCZ) in 10 cases and other biologics in 10 cases. TNF-α blockers and TCZ were mainly used for refractory diseases whereas RTX was mainly initiated for relapsing disease. After a median follow-up of 29 (8–50) months, remission, partial response, treatment failure and treatment discontinuation due to severe adverse events occurred in, respectively, 40%, 13%, 40% and 7% of patients receiving TNF-α blockers, 50%, none, 30% and 20% of TCZ recipients, and 33%, 11%, 56% and none of the RTX recipients. No remission was noted in patients treated with other biologics. Severe adverse events were observed in 14 (28%) patients without significant differences between the three biologics, leading to early biologics discontinuation in only three cases. Conclusion These results suggest that TCZ may be effective in relapsing and/or refractory PAN. Our data warrant further study to confirm these findings.

Objective The aim of this study was to describe the efficacy and safety of rituximab and MTX (RTX/MTX) combination therapy in ANCA-associated vasculitides (AAV). Methods A retrospective French nationwide study was conducted in patients with AAV who received RTX/MTX combination therapy for persistently active disease. Results Seventeen patients were included. All patients had granulomatosis with polyangiitis (GPA), with positive ANCA in 76% of them, mainly with PR3-ANCA specificity. Sixteen patients (94%) had priorly failed to achieve remission with RTX and 11 (65%) with CYC. Patients had experienced a median of 3 (2–4) flares. Manifestations requiring RTX/MTX combination therapy were subglottic or bronchial stenosis in 6 patients (35%), orbital mass in 6 (35%), disabling ENT involvement in 2 (12%), and epiduritis and pachymeningitis in 1 case (6%) each. The median follow-up duration for the RTX/MTX combination therapy was 11 months (11–26 months). At 6 months, global response had been achieved in 15 patients (88%), including partial response in 11 (65%) and complete response in 4 (24%). At last evaluation, global response had been achieved in 16 patients (94%). Seven patients (41%) experienced severe adverse events (grade 3 or 4), including infections in 4 (24%) and hepatitis in 2 (12%). Combination therapy was withdrawn in 4 patients (24%), but never for safety concerns. In contrast, the MTX dose was decreased in 2 patients (12%) because of adverse events. One patient died of an unknown cause. Conclusion RTX/MTX combination therapy could be an effective salvage therapy to treat persistently active GPA with granulomatous manifestations, with an acceptable safety profile.

Background and ObjectivesSpinal cord sarcoidosis is a rare manifestation of sarcoidosis with a consequent risk of neurologic sequelae for the patient. We investigated prognostic factors and efficacy of immunosuppressive treatments in a longitudinal cohort.MethodsWe retrospectively studied patients with spinal cord sarcoidosis followed between 1995 and 2021 in 7 centers in France. Patients with definite, probable, or possible spinal cord sarcoidosis according to the Neurosarcoidosis Consortium Consensus Group criteria and with spinal cord involvement confirmed by MRI were included. We analyzed relapse or progression rate with a Poisson model, initial Rankin score with a linear model, and change in the Rankin score during follow-up with a logistic model.ResultsA total of 97 patients were followed for a median of 7.8 years. Overall mean relapse or progression rate was 0.17 per person-year and decreased over time. At last visit, 46 (47.4%) patients had a loss of autonomy (Rankin score ≥2). The main prognostic factors significantly associated with relapse or progression rate were gadolinium enhancement (relative rate [95% CI] 0.61 [0.4, 0.95]) or meningeal involvement (relative rate [95% CI] 2.05 [1.31, 3.19]) on spinal cord MRI and cell count (relative rate [95% CI] per 1 log increase 1.16 [1.01, 1.33]) on CSF analysis. Relapse or progression rate was not significantly associated with initial Rankin score or Expanded Disability Status Scale. Tumor necrosis factor–α (TNF-α) antagonists significantly decreased relapse or progression rate compared with corticosteroids alone (relative rate [95% CI] 0.33 [0.11, 0.98]). Azathioprine was significantly less effective than methotrexate on relapse or progression rate (relative rate [95% CI] 2.83 [1.04, 7.75]) and change in Rankin score (mean difference [95% CI] 0.65 [0.23, 1.08]).DiscussionRegarding the relapse or progression rate, meningeal localization of sarcoidosis was associated with a worse prognosis, TNF-α antagonists resulted in a significant decrease compared to corticosteroids alone, and methotrexate was more effective than azathioprine.Classification of EvidenceThis study provides Class IV evidence that in individuals with spinal cord neurosarcoidosis, TNF-α antagonists were associated with decreased relapse or progression rate compared to corticosteroids alone, but other therapies showed no significant benefit.

Objective To describe the efficacy and safety of off-label use of biologics for refractory and/or relapsing granulomatosis with polyangiitis (GPA). Methods We conducted a French retrospective study including GPA patients who received off-label biologics for refractory and/or relapsing disease after failure of conventional immunosuppressive regimens. Results Among 26 patients included, 18 received infliximab (IFX), 2 adalimumab (ADA) and 6 abatacept (ABA). Biologics were initiated in median as 4th-line therapy (IQR 3–6) for relapsing and/or refractory disease in 23 (88%) and/or significant glucocorticoid-dependency in 8 cases (31%). At biologics initiation, median (IQR) BVAS and prednisone dose in anti- TNF-α and ABA recipients were 7 (3–8) and 2 (1–6), and 20 (13–30) mg/day and 20 (15–25) mg/day, respectively. Clinical manifestations requiring biologics were mainly pulmonary and ENT manifestations in 58% each. Anti-TNF-α and ABA were continued for a median duration of 8 months (IQR 6–13) and 11 months (IQR 6–18) respectively. Anti-TNF-α recipients showed remission, partial response and treatment failure in 10%, 30% and 60% at 6 months, and 25%, 20% and 55% at 12 months, respectively. ABA recipients showed remission, partial response and treatment failure in 17%, 33% and 50% at 6 months and 17%, 33% and 50% at 12 months. One patient treated with IFX experienced life-threatening reaction while one patient treated with ABA experienced a severe infection. Conclusion This real-life study suggests that off-label use of anti-TNF-α and abatacept shows efficacy in less than 50% of refractory and/or relapsing GPA.

International audience; Recently, concerns have been raised about an increased risk of cardiac sarcoidosis in patients with sarcoid uveitis. While cardiac sarcoidosis has a high mortality burden, there is still a lack of precise data on this association. The objective of this study is to describe the frequency and type of cardiac complications associated with sarcoidosis of a large cohort of patients with sarcoid uveitis. We analyzed the cardiac outcomes of a monocentric retrospective cohort of consecutive adults with a diagnosis of sarcoid uveitis between January 2004 and March 2020 in a tertiary French university hospital. A total of 294 patients with a final diagnosis of sarcoid uveitis were included. At final follow-up, seven (2.4%) patients of the cohort had cardiac sarcoidosis. Cardiac sarcoidosis was more frequent among patients with previously reported systemic sarcoidosis (p = 0.008). The prevalence of cardiac sarcoidosis among patients with sarcoid uveitis is low, but patients with previously diagnosed sarcoidosis or those who develop systemic sarcoidosis during follow-up appear to be at increased risk.

Case series Patients: Male, 19-year-old • Female, 31-year-old Final Diagnosis: TAFRO syndrome Symptoms: Fever • splenomegaly • lymphadenopathies Medication: — Clinical Procedure: — Specialty: Hematology Objective: Unusual clinical course Background: Thrombocytopenia, anasarca, fever, reticulin fibrosis/renal failure, and organomegaly (TAFRO) syndrome is a variant of idiopathic multicentric Castleman disease. Adrenal hemorrhage has rarely been reported in TAFRO syndrome, and previous cases have mainly been Asian patients. This report is of two Caucasian patients with TAFRO syndrome presenting with acute adrenal insufficiency due to bilateral adrenal hemorrhage. Case Reports: Case 1 was a 19-year-old Caucasian man with no significant past medical history who was admitted with acute abdominal pain, vomiting, anorexia, and moderate weight loss. Case 2 was a 31-year-old Caucasian woman with no past medical history who was admitted to hospital with fever, dyspnea, thoracic and abdominal pain, polyarthralgia, and hypotension. Both patients had splenomegaly, mild lymphadenopathy, thrombocytopenia, acute kidney injury, and myelofibrosis. In both cases, lymph node biopsy histology showed mixed-type idiopathic multicentric Castleman disease. In both patients, a diagnosis of TAFRO was made, and they developed bilateral adrenal hemorrhage with adrenal insufficiency. Case 1 was treated with high-dose steroids, followed by tocilizumab infusion. Due to persistent thrombocytopenia, second-line treatment commenced with rituximab, but the patient relapsed two months later. Tocilizumab treatment was recommenced, which was followed by an immuno-allergic adverse event. He then had a good response to sirolimus. Case 2 died nine months after diagnosis due to acute respiratory distress. Conclusions: Two cases of TAFRO syndrome presented with acute adrenal insufficiency due to bilateral adrenal hemorrhage. The symptoms were only partially controlled with tocilizumab, rituximab, and tacrolimus. Adrenal hemorrhage may be a specific manifestation of TAFRO syndrome.

Additional file 5. Appendix 5—List of procedures and services needed for follow-up care and treatment of long-term conditions 21—Systemic necrotizing vasculitis.

Additional file 2. Appendix 2—Medications which may be associated with the occurrence of vasculitis.

Additional file 1. Appendix 1—List of referral centers and centers for specialized care of the organization FAI2R for systemic autoimmune and autoinflammatory diseases.

Additional file 3. Vasculitis activity score—Birmingham vasculitis activity score version 2003.

Additional file 4. Appendix 4—Sequelae score—Vasculitis damage index.

Objectives Only a third of patients with eosinophilic granulomatosis with polyangiitis (EGPA) are ANCA-positive, mainly directed against MPO. ANCA directed against PR3 are rarely found in EGPA. We aimed to examine the significance of PR3-ANCA in EGPA. Methods We set up a retrospective European multicentre cohort including 845 patients. Baseline characteristics and outcomes were analysed and compared according to ANCA status. Results ANCA status was available for 734 patients: 508 (69.2%) ANCA-negative, 210 (28.6%) MPO-ANCA and 16 (2.2%) PR3-ANCA. At baseline, PR3-ANCA patients, compared with those with MPO-ANCA and ANCA-negative, less frequently had active asthma (69% vs 91% and 93%, P = 0.003, respectively) and peripheral neuropathy (31% vs 71% and 47%, P Conclusion PR3-ANCA EGPA patients differ from those with MPO-ANCA and negative ANCA, and share clinical features with granulomatosis with polyangiitis. This suggests that PR3-ANCA EGPA could be a particular form of PR3-ANCA-associated vasculitis.

Objective.To report efficacy and tolerance of interleukin 1 blockade in adult patients with mevalonate kinase deficiency (MKD).Methods.We retrospectively collected data on 13 patients with MKD who had received anakinra (n = 10) and canakinumab (n = 7).Results.Anakinra resulted in complete or partial remission in 3/10 and 5/10 patients, respectively, and no efficacy in 2/10, but a switch to canakinumab led to partial remission. Canakinumab resulted in complete or partial remission in 3/7 and 4/7 patients, respectively.Conclusion.These data support frequent partial responses, showing a better response with canakinumab. The genotype and therapeutic outcomes correlation should help in the personalization of treatment.

OBJECTIVE: Temporal arteritis (TA) is a typical manifestation of giant cell arteritis (GCA). Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAVs) are rarely revealed by TA manifestations, leading to a risk of misdiagnosis of GCA and inappropriate treatments. This study was undertaken to describe the clinical, biologic, and histologic presentations and outcomes in cases of TA revealing AAV (TA-AAV) compared to controls with classic GCA. METHODS: In this retrospective case-control study, the characteristics of patients with TA-AAV were compared to those of control subjects with classic GCA. Log-rank test, with hazard ratios (HRs) and 95% confidence intervals (95% CIs), was used to assess the risk of treatment failure. RESULTS: Fifty patients with TA-AAV (median age 70 years) were included. Thirty-three patients (66%) presented with atypical symptoms of GCA (ear, nose, and throat involvement in 32% of patients, and renal, pulmonary, and neurologic involvement in 26%, 20%, and 16% of patients, respectively). Blood samples were screened for ANCAs at the time of disease onset in 33 patients, and results were positive in 88%, leading to a diagnosis of early TA-AAV in 20 patients. The diagnosis of AAV was delayed a median interval of 15 months in 30 patients. Compared to controls with GCA, patients with TA-AAV were younger (median age 70 years versus 74 years), were more frequently men (48% versus 30%), and had high frequencies of atypical manifestations and higher C-reactive protein levels (median 10.8 mg/dl versus 7.0 mg/dl). In patients with TA-AAV, temporal artery biopsy (TAB) showed fibrinoid necrosis and small branch vasculitis in 23% of patients each, whereas neither of these characteristics was evident in controls with GCA. Treatment failure-free survival was comparable between early TA-AAV cases and GCA controls, whereas those with delayed TA-AAV had a significantly higher risk of treatment failure compared to controls (HR 3.85, 95% CI 1.97-7.51; P < 0.0001). CONCLUSION: TA-AAV should be considered diagnostically in cases of atypical manifestations of GCA, refractoriness to glucocorticoid treatment, or early relapse. Analysis of TAB specimens for the detection of small branch vasculitis and/or fibrinoid necrosis could be useful. Detection of ANCAs should be performed in cases of suspected GCA with atypical clinical features and/or evidence of temporal artery abnormalities on TAB. ispartof: ARTHRITIS & RHEUMATOLOGY vol:73 issue:2 pages:286-294 ispartof: location:United States status: published

Background: Polyarteritis nodosa (PAN) is a rare systemic necrotizing vasculitis of medium- and small-sized arteries, not associated with antineutrophil cytoplasmic antibodies (ANCA). Conventional treatments include glucocorticoids (GCs) for non-severe disease and a combination of GCs and immunosuppressive agents for severe disease. Nevertheless, some patients have refractory and/or relapsing disease. Objectives: We examined the use of off-label biological therapy for relapsing/refractory PAN. Methods: This retrospective European collaborative study included patients with PAN meeting ACR criteria and/or Chapel Hill Consensus Conference 2012 definitions. Treatment efficacy and safety are recorded. Remission was defined as the absence of vasculitis manifestations (BVAS = 0) with a prednisone dose ≤5 mg/day. Partial response was defined as a BVAS = 0 with a prednisone dose between 6 and 10 mg/day. Results: Fifty-one patients (24 men, 27 women; median age 51 years) were included. Eighteen (35%) patients received TNF-alpha blockers, 16 (31%) received rituximab (RTX), 9 (18%) tocilizumab (TCZ), and 8 (16%) other biologics (including alemtuzumab in 3, anakinra in 2, interferon-alpha in 2 and abatacept in one). Previous treatments were: GCs in all cases, including methylprednisolone infusions (72%) and oral GCs (92%), cyclophosphamide (61%), azathioprine (53%), methotrexate (45%) and mycophenolate mofetil (47%). At inclusion, median BVAS was 5 (range 0-18), including 5 (2-12) in the TNF-alpha blockers group, 5 (2-12) in the RTX group and 4 (0-6) in the TCZ group. After median follow-up of 34.4 months (IQR 21.5-59.5), remissions, partial responses and treatment failure, respectively, were noted in 41%, 6% and 53% for TNF-alpha blockers recipients, 25%, 12% and 63% for RTX recipients, and 57%, 0% and 43% for TCZ recipients. No remission was noted in patients treated with anakinra, alemtuzumab and abatacept. Median BVAS dropped to 3 at 6 months, 0 at 12 months and 0 at last follow-up in the TNF-alpha blockers group, to 3.5, 0 and 2 in the RTX group, respectively, and 0, 0 and 0 in the TCZ group. A GC-sparing effect seemed more important with TNF-alpha blockers and TCZ. Median GCs dose decreased from the baseline 15 mg/day to 10 at 6 months, 5 at 12 months and 5 at last follow-up in the TNF-alpha blockers group, from 15 mg/day to 10 at 6 months, 5 at 12 months and 10 at last follow-up in the RTX group, and from 15 mg/day to 7 at 6 months, 5 at 12 months and 5 at last follow-up in the TCZ group. Four (22%) patients stopped TNF-alpha blockers because of allergic reaction in one and refractory disease in 3. Six (38%) stopped RTX because of refractory disease. Finally, 4 (44%) stopped TCZ because of adverse events in 2 (testicular abscess and worsening renal failure) and refractory disease in 2. Conclusion: The results of this study suggest that TNF-alpha blockers and TCZ may achieve higher rates of remission and GC-sparing in relapsing and/or refractory PAN than other biologics. Our data warrant further study to confirm or not these findings. Disclosure of Interests: Alice Canzian: None declared, Omer Karadag: None declared, Anne Contis: None declared, Francois Maurier: None declared, Silvia Sartorelli: None declared, Laure Denis: None declared, Sebastien Sanges: None declared, Claire De Moreuil: None declared, Cecile-Audrey Durel: None declared, Stephane Durupt: None declared, Marie Jachiet: None declared, Diane Rouzaud: None declared, Carlo Salvarani: None declared, Franco Schiavon: None declared, Lorenzo Dagna Consultant for: Prof Lorenzo Dagna received consultation honoraria from Abbvie, Amgen, Biogen, Bristol-Myers Squibb, Celltrion, Novartis, Pfizer, Sanofi-Genzyme, and SOBI., Fabrice Bonnet: None declared, David Jayne Grant/research support from: David Jayne has received research grants from Chemocentryx, GSK, Roche/Genentech and Sanofi-Genzyme. He has received consultancy fees from Astra-Zeneca, Boehringer-Ingelheim, Chemocentryx, Chugai, GSK, Infla-RX, Insmed and Takeda, Loic Guillevin: None declared, Benjamin Terrier: None declared

Background Eosinophilic granulomatosis with polyangiitis (EGPA) (Churg–Strauss) is a small-vessel necrotizing vasculitis characterized by blood and tissue eosinophilia and asthma. Glucocorticoids (GCs) control the disease, but GC-dependence is frequent. Evolving concepts distinguish vasculitis-related symptoms from asthma and/or ENT manifestations. That distinction has become even more important since the development of B-cell and eosinophil-targeted therapies. Objectives This study aimed to describe and identify characteristics predicting long-term EGPA outcomes. Methods We set up a multicenter European cohort that included 636 EGPA patients. Based on recent consensus, we distinguished 4 EGPA-evolutionary profiles: GC-dependent asthma and/or ENT manifestations (requiring prednisone >7.5 mg/d), ≥1 vasculitis relapse(s) (excluding asthma and/or ENT flares), both phenotypes, and complete remission (no GC-dependent asthma/ENT signs, no vasculitis relapse and prednisone Results After median follow-up of 63 (IQR 30-110) months, 35.8% had GC-dependent asthma and/or ENT manifestations, 12.9% had ≥1 vasculitis relapse(s), 14.3% had both phenotypes, 14.6% were in complete remission, 14.4% were in partial remission and 7.8% had not reach remission. Patients with GC-dependent asthma/ENT manifestations were younger at diagnosis (p Patients with vasculitis relapse(s) had more frequently neurological manifestations at diagnosis (p=0.002) and MPO-ANCA positivity (p Finally, patients in complete remission were older (p Conclusion EGPA seems to evolve toward distinct phenotypic profiles, which could be identified using baseline and follow-up characteristics. Early identification of those profiles could allow guided choices of the best therapeutic option. Disclosure of Interests Matthias Papo: None declared, Renato A. Sinico: None declared, Vitor Teixeira: None declared, Maria-Letizia Urban: None declared, Juliane Mahrhold: None declared, Sara Monti: None declared, Giulia Cassone: None declared, Franco Schiavon: None declared, Benjamin Seeliger: None declared, Thomas Neumann: None declared, Claus Kroegel: None declared, Matthieu Groh: None declared, Chiara Marvisi: None declared, Maxime Samson: None declared, Thomas Barba: None declared, David Jayne Grant/research support from: David Jayne has received research grants from Chemocentryx, GSK, Roche/Genentech and Sanofi-Genzyme. He has received consultancy fees from Astra-Zeneca, Boehringer-Ingelheim, Chemocentryx, Chugai, GSK, Infla-RX, Insmed and Takeda, Bernhard Hellmich Consultant for: Roche, Speakers bureau: Abbvie, MSD, Roche, Novartis, Pfizer, Carlomaurizio Montecucco Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Sanofi, Genzyme, Lilly, MSD, Pfizer, UCB, Carlo Salvarani Grant/research support from: Roche, Consultant for: Eli Lilly and Company, Roche, Abbvie, Jean-Emmanuel Kahn: None declared, Bernard Bonnotte: None declared, Cecile-Audrey Durel: None declared, Luc Mouthon: None declared, Xavier Puechal: None declared, Loic Guillevin: None declared, Giacomo Emmi: None declared, Augusto Vaglio: None declared, Benjamin Terrier: None declared

Age at onset of large-vessel vasculitis (LVV) is commonly used to distinguish giant cell arteritis (GCA) and Takayasu arteritis (TA). However, LVV between age 50 and 60 years may be difficult to classify.We conducted a retrospective study including LVV aged between 50 and 60 years at onset (LVVWe included 183 LVV

Background: Eosinophilic granulomatosis with polyangiitis (EGPA) (Churg–Strauss) is a small-vessel necrotizing vasculitis characterized by blood and tissue eosinophilia and asthma. Glucocorticoids (GCs) represent the treatment cornerstone. So far, EGPA management has been based on conventional immunosuppressants, but GC-dependence remains frequent. Recently, therapies targeting B cells and interleukin-5 have been prescribed, but data on large cohorts are lacking. Objectives: This study aimed to describe therapeutic management and efficacy of treatments in EGPA patients. Methods: We set up a multicenter European cohort that included 636 EGPA patients. Treatments used, complete remission rates and vasculitis relapse-free survival were recorded. Complete remission was defined as absence of vasculitis relapse and prednisone dose Results: For induction, cyclophosphamide (CYC) was the most frequently prescribed immunosuppressant (36.2%), more often in patients with FFS ≥1 (P Complete remission rates were similar between conventional immunosuppressants (CYC, AZA or MTX) and GCs alone. Vasculitis relapse-free survival was also similar between CYC, AZA or MTX and GCs alone. Similar results were observed for first vasculitis relapse treatments. During follow-up, GC-dependent asthma and/or ENT manifestations were treated with AZA (40%), MTX (25%), mycophenolate mofetil (16%), rituximab (RTX) (21%), CYC (19%), cyclosporine (6%), omalizumab (5.9%) and mepolizumab (5.5%), allowing GC-tapering ≤7.5mg/in 23%, 31%, 17%, 43%, 5%, 71%, 25% and 50%, respectively. Conventional immunosuppressants were mostly used in first and second line, while eosinophil-targeted biotherapies were used in 4th or 5th lines. Conclusion: In EGPA patients, the response to conventional immunosuppressants, in addition to GCs, is often disappointing compared to GCs alone, without clear benefit on complete remission rates and relapse-free survival. In contrast, notwithstanding a small number of treated patients, eosinophil-targeted therapies seemed promising to treat asthma and/or ENT manifestations. Disclosure of Interests: Matthias Papo: None declared, Renato A. Sinico: None declared, Vitor Teixeira: None declared, Maria-Letizia Urban: None declared, Juliane Mahrhold: None declared, Sara Monti: None declared, Giulia Cassone: None declared, Franco Schiavon: None declared, Benjamin Seeliger: None declared, Thomas Neumann: None declared, Claus Kroegel: None declared, Matthieu Groh: None declared, Chiara Marvisi: None declared, Maxime Samson: None declared, Thomas Barba: None declared, David Jayne Grant/research support from: David Jayne has received research grants from Chemocentryx, GSK, Roche/Genentech and Sanofi-Genzyme. He has received consultancy fees from Astra-Zeneca, Boehringer-Ingelheim, Chemocentryx, Chugai, GSK, Infla-RX, Insmed and Takeda, Bernhard Hellmich Consultant for: Roche, Speakers bureau: Abbvie, MSD, Roche, Novartis, Pfizer, Carlomaurizio Montecucco Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Sanofi, Genzyme, Lilly, MSD, Pfizer, UCB, Carlo Salvarani Grant/research support from: Roche, Consultant for: Eli Lilly and Company, Roche, Abbvie, Jean-Emmanuel Kahn: None declared, Bernard Bonnotte: None declared, Cecile-Audrey Durel: None declared, Xavier Puechal: None declared, Luc Mouthon: None declared, Loic Guillevin: None declared, Giacomo Emmi: None declared, Augusto Vaglio: None declared, Benjamin Terrier: None declared

Objective To assess the long-term outcome in eosinophilic granulomatosis with polyangiitis (Churg-Strauss) (EGPA). Methods A total of 101 patients fulfilling the American College of Rheumatology criteria for EGPA were included between 1990 and 2011. Clinical features, antineutrophil cytoplasm autoantibodies (ANCAs), and Five-Factors Score (FFS) were assessed at diagnosis. Overall and cumulative survival rates, relapse-free survival, and sequelae were studied based on ANCA status and FFS. Results The rate of cardiomyopathy did not differ according to ANCA status. A total of 79.6% of patients achieved first remission, but 81.1% relapsed. ANCA-positive patients did not relapse more frequently but exhibited more severe disease with mononeuritis (P = 0.0004) and renal involvement (P = 0.02). Being Italian was the only prognostic factor associated with a higher relapse-free survival (P = 0.01), thanks to a longer maintenance of immunosuppressive drugs, suggesting the need for prolonged low-dose corticosteroids. Overall, survival reached 93.1% after a median followup of 6 years. No factor was associated with mortality, but patients over age 65 years with cardiomyopathy or ANCA positivity had more serious outcomes. Sequelae affected 83.2% of patients. Ear, nose, and throat (ENT) involvement was a protective factor for renal (P = 0.04) and cardiac (P = 0.03) morbidity. ANCA positivity was correlated with chronic kidney disease (P = 0.03) and chronic neurologic disability (P = 0.02). Conclusion The actual challenges of EGPA management concern morbidity prevention and quality of life improvement. Long-term corticosteroid treatment appears to reduce relapse risk. ENT involvement is associated with less renal and cardiac morbidity. ANCA positivity predicts renal and neurologic damage.

Background: Sarcoidosis is one of the leading causes of uveitis. To date, no studies have assessed the factors specifically related with recovery in ocular sarcoidosis. In this study, we aimed to determine factors associated with ocular and extraocular recovery in patients with sarcoid uveitis. Methods: A retrospective study of sarcoid uveitis, with a three-year minimum follow-up in Lyon University Hospital between December 2003 and December 2019. Patients presented biopsy-proven sarcoidosis or presumed sarcoid. Recovery was defined by a disease-free status, spontaneously or despite being off all treatments for three years or more. Results: 143 patients were included: 110 with biopsy-proven and 33 with presumed sarcoid uveitis. Seventy-one percent were women, the median age at presentation was 53 years, and 71% were Caucasian. Chronic uveitis was the main clinical presentation (75%), mostly panuveitis (48%) with bilateral involvement (82%). After a median follow-up of 83.5 months, recovery was reported in 26% of patients. In multivariable analysis, Caucasian ethnicity (p = 0.007) and anterior uveitis (p = 0.008) were significantly associated with recovery, while increased intraocular pressure was negatively associated (p = 0.039). Conclusion: In this large European cohort, one quarter of patients recovered. Caucasian ethnicity and anterior uveitis are associated with ocular and extraocular recovery.

Treatment of vasculitides associated with anti-neutrophil cytoplasm antibodies (ANCA) (AAVs) has evolved dramatically in recent years, particularly since the demonstration of rituximab efficacy as remission induction and maintenance therapy for granulomatosis with polyangiitis and microscopic polyangiitis. In 2013, the French Vasculitis Study Group (FVSG) published recommendations for its use by clinicians. Since then, new data have made it possible to better specify and codify prescription of rituximab to treat AAVs. Herein, the FVSG Recommendations Committee, an expert panel comprised of physicians with extensive experience in the treatment and management of vasculitides, presents its consensus guidelines based on literature analysis, the results of prospective therapeutic trials and personal experience.

Objective Orbital mass is a rare and sight-threatening manifestation of ANCA-associated vasculitides, which remains a therapeutic challenge. We aimed to describe the presentation, therapeutic management and outcome of ANCA-associated vasculitides-related orbital mass. Methods We conducted a French nationwide retrospective study of patients with orbital mass in the setting of ANCA-associated vasculitides according to ACR criteria and/or Chapel Hill Consensus Conference definitions. Results Fifty-nine patients [33 women, median age 46 (range 7–90) years] were included. Fifty-six (95%) patients had granulomatosis with polyangiitis, two eosinophilic granulomatosis with polyangiitis and one microscopic polyangiitis. Orbital mass was unilateral in 47 (80%) cases, and seemed to develop from ENT involvement in most cases. Orbital mass biopsy was available in 32 (54%) patients, showing lymphoplasmacytic infiltration in 65%, fibrosis in 55%, granulomas in 48% and vasculitis in 36%. All patients but one received glucocorticoids as first-line therapy associated with immunosuppressive agents in 82%, mainly cyclophosphamide. Response to therapy was noted in 52% of patients treated with cyclophosphamide compared with 91% of those treated with rituximab. Twenty-seven (46%) patients required a second-line therapy because of relapse (59%) or refractory course (41%). Sequelae included visual impairment in 28%, with definitive blindness in 17%. Refractory course was associated with PR3-ANCA positivity, visual loss and contiguous pachymeningitis. Conclusion Orbital mass is associated with refractory course and high frequency of sequelae, especially blindness. Refractory course is associated with PR3-ANCA positivity, visual loss and contiguous pachymeningitis.

Introduction La periarterite noueuse (PAN) est une vascularite necrosante touchant les vaisseaux de moyen ou petit calibre, sans glomerulonephrite ou vascularite des arterioles, capillaires ou veinules, et non-associee aux ANCA. Le traitement standard repose sur les glucocorticoides (GCs) associees ou non a des immunosuppresseurs conventionnels selon la presence ou non de facteurs de mauvais pronostic. Cependant, certains patients ont une maladie refractaire ou des rechutes. Nous avons etudie l’utilisation hors-AMM des biotherapies pour le traitement de PAN refractaires ou en rechute. Patients et methodes Etude retrospective, multicentrique europeenne, ayant inclut les patients atteints de PAN repondant aux criteres ACR et/ou a la definition de la Conference de consensus de Chapel Hill. L’efficacite et la tolerance des medicaments ont ete analysees. La remission etait definie par l’absence des manifestations actives de vascularite (BVAS = 0) et une dose de prednisone ≤ 5 mg/jour. La reponse partielle est definie par un score BVAS = 0 et une dose de GCs > 5 et ≤ 10 mg/jour. Resultats Cinquante et un patients ont ete inclus (24 hommes, âge moyen 51 ans). Dix-huit (35 %) patients ont recu un anti-TNF-α, 16 (31 %) du rituximab (RTX), 9 (18 %) du tocilizumab (TCZ), et 8 (16 %) d’autres biotherapies (alemtuzumab chez 3, anakinra chez 2, interferon-achez 2 et abatacept chez un). Les traitements precedemment recus etaient : GCs chez tous les patients, dont bolus de methylprednisolone (72 %) et GCs oraux (92 %), cyclophosphamide (61 %), azathioprine (53 %), methotrexate (45 %) et mycophenolate mofetil (47 %). A la mise sous biotherapies, le BVAS median etait 5 (extremes 0-18), dont 5 (2-12) dans le groupe traite par anti-TNF-α, 5 (2-12) dans le groupe traite par RTX et 4 (0-6) dans le groupe traite par TCZ. Apres un suivi median de 34,4 mois (IQR 21,5-59,5), les remissions, les reponses partielles et les echecs etaient observes dans 41 %, 6 % et 53 % dans le groupe traite par anti-TNF-α, respectivement, 25 %, 12 % et 63 % dans le groupe traite par RTX, et 57 %, 0 % et 43 % dans le groupe traite par TCZ. Il n’etait pas observe de remission chez les patients traites paranakinra, alemtuzumab et abatacept. Le BVAS median baissait de 5 a 3 a 6 mois, 0 a 12 mois et 0 au dernier suivi dans le groupe anti-TNF-α, de 5 a 3.5, 0 et 2 dans le groupe RTX, respectivement, et de 4 a 0, 0 et 0 dans le groupe TCZ. L’effet d’epargne cortisonique semblait plus important dans les groupes traites par anti-TNF-α et TCZ. La dose mediane de GCs baissait de 15 mg/j a 10 a 6 mois, 5 a 12 mois et 5 au dernier suivi dans le groupe anti-TNF-α, de 15 mg/j a 10 a 6 mois, 5 a 12 mois et 10 au dernier suivi dans le groupe RTX, et de 15 mg/j a 7 a 6 mois, 5 a 12 mois et 5 au dernier suivi dans le groupe TCZ. Quatre (22 %) patients ont arrete les anti-TNF-α en raison d’une reaction allergique chez un patient et d’un echec chez 3 patients. Six (38 %) patients ont arrete le RTX en raison d’un echec. Enfin, quatre (44 %) patients ont arrete le TCZ en raison d’effets indesirables chez 2 patients et d’un echec chez 2. Conclusion Les resultats de cette etude montrent que les anti-TNF-α et le TCZ sont associes a des taux remissions plus importants et un meilleur effet d’epargne cortisonique en cas de maladie refractaire ou en rechute que les autres biotherapies. D’autres etudes seront necessaires afin de confirmer ou infirmer ces conclusions.

Introduction La granulomatose eosinophilique avec polyangeite (GEPA) est une vascularite necrosante des petits et moyens vaisseaux riche en eosinophiles associee dans environ 40 % des cas a la presence d’anticorps anti-cytoplasme des polynucleaires neutrophiles (ANCA). L’atteinte renale de la GEPA est moins severe et moins frequente que dans les autres vascularites a ANCA, estimee entre 15 et 25 %. Elle est peu decrite dans la litterature. Nous avons mene une etude observationnelle multicentrique de 63 patients presentant une atteinte renale prouvee histologiquement au cours de la GEPA. Patients et methodes Apres appel a observations, nous avons inclus les patients diagnostiques GEPA selon les criteres ACR 1990 et/ou les criteres modifies issus de l’etude MIRRA et ayant beneficies d’une ponction biopsie renale. Les caracteristiques cliniques, biologiques et histologiques ont ete recueillies au diagnostic et a la date des dernieres nouvelles. Resultats Soixante-trois patients (femmes 42,9 %, âge median au diagnostic de GEPA 60 ans) ont ete inclus. L’atteinte renale etait inaugurale chez 54 patients (86 %) et apparaissait au cours du suivi chez 9 patients (14 %) avec un âge median au diagnostic de l’atteinte renale de 63 ans (18–83). La duree mediane de suivi apres le diagnostic d’atteinte renale etait de 51 mois (1–296). Les ANCA etaient positifs chez 53 patients (84,1 %), dont 46 (86,6 %) etaient de type myeloperoxydase (MPO). Tous les patients avaient un asthme de revelation tardive. Quarante-huit patients (76,2 %) presentaient des signes generaux, 44 (69,8 %) une sinusite, 33 (52,4 %) des signes articulaires, 29 (46 %) une neuropathie peripherique, 25 (39,7 %) des signes cutanes, 23 (36,5 %) des polypes nasaux, 22 (34,9 %) une rhinite, 9 (14,3 %) une atteinte cardiaque specifique. Une hemorragie alveolaire etait rapportee chez 9 patients (18,4 %) sur 49 (donnee manquante chez 14 patients). Au diagnostic d’atteinte renale, il existait une insuffisance renale aigue chez 47 patients (74,6 %). La creatinine mediane etait a 180 μmol/L (75–1070). Il existait une proteinurie chez 60 patients (95,2 %) avec une mediane de 1 g/24 h (0,2–17,0) et une hematurie chez 53 patients (84,1 %). Cinq patients (7,9 %) ont necessite une dialyse d’emblee. Sur le plan histologique, on notait une glomerulonephrite extra-capillaire chez 50 patients (79,4 %), une nephrite interstitielle chez 39 patients (61,9 %), une glomerulonephrite extra-membraneuse chez 6 patients (9,5 %), la presence de granulomes chez 3 patients (4,8 %), une glomerulonephrite membrano-proliferative chez 2 patients (3,2 %), une angeite et une histologie compatible avec une maladie a IgG4 chez 1 patient (1,6 %) respectivement. Plusieurs patterns histologiques pouvaient etre associes. Sur le plan therapeutique, tous les patients ont recu une corticotherapie orale, precedee de bolus intraveineux chez 40 patients (63,5 %). Un traitement immunosuppresseur etait parfois associe en induction : cyclophosphamide chez 40 patients (63,5 %), rituximab chez 7 patients (11,1 %), echanges plasmatiques chez 6 patients (9,5 %). En traitement d’entretien, les donnees etaient disponibles chez 59 patients. Un traitement par azathioprine etait prescrit chez 28 patients (47,5 %), rituximab chez 9 patients (15,3 %), anti-calcineurine chez 5 patients (8,5 %), mycophenolate mofetil chez 4 patients (6,8 %), methotrexate et cyclophosphamide per os chez 2 patients (3,4 %) respectivement. A la date des dernieres nouvelles, 5 patients (8,1 %) etaient decedes : une hemorragie alveolaire, un cancer, un sepsis, et 2 de cause inconnue. Neuf patients (14,5 %) etaient en dialyse chronique, 2 (3,2 %) avaient beneficie d’une greffe renale. La maladie etait en remission chez 37 patients (60,7 %), refractaire chez 2 patients (3,3 %) et dependante au traitement chez 19 patients (31,1 %). La dose mediane de corticoides etait de 5 mg/j. Les donnees biologiques etaient disponibles pour 52 patients : la creatinine mediane etait a 115 μmol/L (53–222 μmol/L) avec une hematurie persistante chez 10/35 patients (28,6 %). Conclusion L’atteinte renale au cours de la GEPA est le plus souvent inaugurale chez des patients ayant des ANCA positifs de type MPO et un phenotype clinique vascularitique. Les anomalies du sediment urinaire sont associees a une insuffisance renale aigue en general moderee dans pres de trois quarts des cas. La glomerulonephrite aigue extra-capillaire est le pattern histologique le plus frequent, mais une nephrite interstitielle est presente dans plus de la moitie des cas et il existe des cas non exceptionnels de glomerulonephrite extra-membraneuse. L’evolution se fait souvent vers une insuffisance renale chronique moderee, mais le recours a une dialyse extracorporelle est parfois necessaire.

Introduction Le deficit en mevalonate kinase (MKD) est une maladie auto inflammatoire genetique rare de transmission autosomique recessive associee a des mutations du gene MVK, caracterisee par des episodes de fievre recurrente des les premiers mois de vie et pouvant s’associer a une constellation de symptomes. Les traitements anti-inflammatoires ou immunosuppresseurs sont d’efficacite limitee. L’interleukine(IL)-1β a un role central dans la physiopathologie du MKD. L’experience avec l’anakinra et le canakinumab a ete rapportee dans des cas cliniques ou des petites series de cas, le plus souvent pediatriques et avec une duree de suivi limitee. L’objectif etait de decrire l’efficacite et la tolerance des anti-IL1 en continu chez des patients adultes atteints de MKD. Materiels et methodes Etude retrospective multicentrique des patients ≥ 16 ans atteints de MVK traites par anti-IL1 recenses grâce au centre national de reference adulte des maladies auto-inflammatoires. Resultats Treize patients ont ete inclus, dont 8 ont ete diagnostiques a l’âge adulte. Le traitement continu par anti-IL1 a ete introduit ou poursuivi a l’âge adulte pour tous les patients. Trois patients avaient une mutation a l’etat homozygote : V377I (n = 2) et A148 T (n = 1). Les autres patients etaient heterozygotes composites pour la mutation V377I, associee a I268 T (n = 2), del 631–633 (n = 2), R176 K, G335D, G305A, A147 T, T342I, ou T243Yfs*34 (n = 1 chacun). L’anakinra a permis une remission complete ou partielle chez, respectivement 3/10 et 5/10 patients, et a ete sans efficacite chez 2/10 patients (suivi median de 16 mois). Une perte d’efficacite rapide a ete notee chez 2 patients, apres 3 et 5 mois. Six patients avaient des effets secondaires : reactions aux points d’injection, infections recidivantes (infections ORL (n = 1) et infections pulmonaires (n = 1), et/ou prise ponderale. Le canakinumab entraina une remission complete ou partielle chez respectivement 3/7 et 4/7 patients (suivi median de 18 mois). Une perte d’efficacite a ete notee chez 1 patient en 12 mois. Un patient avait des infections pulmonaires recidivantes. Les 2 patients en echec de l’anakinra en continu etaient en remission partielle prolongee sous canakinumab. Le patient homozygote A148 T est le seul a avoir une reponse complete prolongee sous anakinra. A l’inverse, seuls les 2 patients avec deletion 631–633 n’ont pas repondu a l’anakinra. Discussion Dans les series rapportees, l’anakinra permet une reponse complete chez 12,5–30 % des patients, une reponse partielle chez 50–87,5 % des patients et est inefficace chez 0–20 % des cas. Le canakinumab offre des reponses completes et partielles respectivement dans 50–80 et 20–50 % des cas. Le canakinumab a recemment ete approuve dans cette indication par l’agence europeenne du medicament. Les donnees sur les correlations genotype–efficacite des traitements sont tres limitees, mais permettraient un traitement personnalise. Certains patients peuvent necessiter des doses plus importantes de canakinumab. Des doses plus importantes d’anakinra pourraient aussi permettre une meilleure reponse, mais du fait de ses injections quotidiennes souvent douloureuses, un changement pour le canakinumab est souvent prefere. Cela pourrait expliquer en partie le fait que le canakinumab semble avoir une meilleure efficacite que l’anakinra. Conclusion Les anti–IL1 sont des traitements efficaces dans le MKD, mais avec neanmoins une efficacite souvent partielle ou une perte de reponse au long cours. Ces constatations sont en accord avec les donnees experimentales, qui suggerent que le MKD est une maladie multicytokinique.

International audience; Sarcoidosis of the spinal cord is a rare disease. The aims of this study are to describe the features of spinal cord sarcoidosis (SCS) and identify prognostic markers. We analyzed 20 patients over a 20-year period in 8 French hospitals. There were 12 men (60 %), mostly Caucasian (75 %). The median ages at diagnosis of sarcoidosis and myelitis were 34.5 and 37 years, respectively. SCS revealed sarcoidosis in 12 patients (60 %). Eleven patients presented with motor deficit (55 %) and 9 had sphincter dysfunction (45 %). The median initial Edmus Grading Scale (EGS) score was 2.5. The cerebrospinal fluid (CSF) showed elevated protein level (median: 1.00 g/L, interquartile range (IQR) 0.72-1.97), low glucose level (median 2.84 mmol/L, IQR 1.42-3.45), and elevated white cell count (median 22/mm3, IQR 6-45). The cervical and thoracic cords were most often affected (90 %). All patients received steroids and an immunosuppressive drug was added in 10 cases (50 %). After a mean follow-up of 52.1 months (range 8-43), 18 patients had partial response (90 %), 7 displayed functional impairment (35 %), and the median final EGS score was 1. Six patients experienced relapse (30 %). There was an association between the initial and the final EGS scores (p = 0.006). High CSF protein level showed a trend toward an association with relapse (p = 0.076). The spinal cord lesion was often the presenting feature of sarcoidosis. Most patients experienced clinical improvement with corticosteroids and/or immunosuppressive treatment. The long-term functional prognosis was correlated with the initial severity

Introduction Les atteintes oculaires au cours des vascularites associees aux ANCA (VAA) sont multiples et surviennent principalement chez les patients atteints de granulomatose avec polyangeite (GPA). Les pseudo-tumeurs inflammatoires orbitaires (PTIO) sont des manifestations rares pouvant engager le pronostic visuel, et sont reputees comme particulierement refractaires aux traitements. Nous decrivons dans cette etude les caracteristiques initiales et evolutives de patients atteints de PTIO dans le cadre d’une VAA. Patients et methodes Nous avons realise une etude retrospective multicentrique incluant les patients atteints de PTIO associee a une VAA. Le diagnostic de VAA devait repondre aux criteres de l’ACR et/ou a la nomenclature de Chapel-Hill. La presentation clinique, radiologique et anatomo-pathologique etait recueillie, ainsi que les differentes lignes therapeutiques recues avec leur efficacite et les sequelles eventuelles des patients atteints de PTIO dans le cadre d’une VAA. Resultats Cinquante-sept patients (femmes 54,4 %, âge median 48 ans, dont 2 patents pediatriques) ont ete inclus, dont 55 granulomatoses avec polyangeite (GPA, 96 %), une granulomatose eosinophilique avec polyangeite (2 %)et une polyangeite microscopique (2 %). Le diagnostic de VAA et d’atteinte orbitaire etait concomitant chez 26 patients (46 %), tandis que l’atteinte orbitaire survenait au cours du suivi chez 23 patients (40 %). Chez 8 patients, le diagnostic de PTIO precedait celui de VAA. Les ANCA etaient positifs chez 50 patients (88 %), avec une specificite anti-PR3 dans 72 % des cas, anti-MPO dans 24 % et sans specificite dans 4 %. Une confirmation histologique de la vascularite etait obtenue chez 49 patients (86 %), et 28 (49 %) patients disposaient d’une histologie orbitaire. L’histologie orbitaire retrouvait a differents degres des lesions de vascularite, des granulomes, des infiltrats inflammatoires lymphoplasmocytaires, et des lesions de fibrose. Cinquante-quatre (97 %) patients avaient une atteinte extra-oculaire, principalement ORL (88 %) et pulmonaire (37 %) avec un BVAS median a 9 au diagnostic de l’atteinte orbitaire. L’atteinte orbitaire etait unilaterale pure chez 45 patients (79 %). Les manifestations oculaires revelatrices etaient : exophtalmie (95 %), douleur orbitaire (51 %), œdeme palpebral (42 %), diplopie (37 %), baisse d’acuite visuelle (BAV) (33 %), paralysie oculomotrice (26 %). Six patients (11 %) avaient une cecite au diagnostic. Les patients ont recu en moyenne 1,7 lignes de traitement durant un suivi median de 6 ans. Tous sauf un (initialement etiquete lymphome de MALT orbitaire) ont recu une corticotherapie en premiere ligne, seule dans 10 (18 %) cas et associee a un immunosuppresseur dans les autres cas. Les traitements immunosuppresseurs utilises en 1re ligne etaient : cyclophosphamide (43 %), rituximab (18 %), methotrexate (9 %), mycophenolate mofetil (7 %), azathioprine (4 %), infliximab (2 %), et immunoglobulines intraveineuses (2 %). Deux patients ont eu une chirurgie premiere associee (enucleation et exerese), et un patienta eu une radiotherapie associee. Apres la premiere ligne de traitement, 16 patients (28 %) avaient une reponse clinique complete, 27 (47 %) une reponse clinique partielle, 10 (18 %) une maladie orbitaire inchangee, et 4 (7 %) une progression clinique. Quarante-huit pour cent des patients ont recu 2 lignes therapeutiques dont 37 % pour une maladie refractaire, 18 % 3 lignes, 5 % 4 lignes et 2 % 5 lignes. Le BVAS median a la fin du suivi est a 0. Les sequelles cliniques a la fin du suivi etaient : diplopie par extension aux muscles orbitaires (38 %), BAV (29 %) essentiellement par compression du nerf optique, lyse osseuse du cadre orbitaire (21 %), et cecite dans 9 cas (16 %). Deux patients sont decedes a la fin du suivi dont un d’une complication du traitement (toxicite hematologique). Conclusion L’atteinte orbitaire survient preferentiellement au diagnostic de VAA ou au cours du suivi, et est revelee par une exophtalmie quasi-constante. Le traitement permet seulement une regression partielle de la symptomatologie expliquant le mauvais pronostic visuel avec cecite non exceptionnelle. La reponse au traitement doit etre analysee en regard des donnees histologiques orbitaires, notamment pour distinguer les lesions plutot granulomateuse de celles qui pourraient s’integrer dans le cadre d’une maladie associee aux IgG4. Au total, l’histologie orbitaire semble un element clef pour decider de la meilleure conduite a tenir therapeutique et esperer limiter les sequelles visuelles.

A 53-year-old woman presenting with oral candidiasis was diagnosed with HIV-1 infection. The CD4 cell count nadir was 71 cells/mm (5%) and viral load was 445 000 copies/ml. Treatment was initiated with emtricitabine/tenofovir and boosted darunavir. One month later, she presented seizures with psychomotor slowdown, left upper-limb paresis, cerebellar syndrome, left homonymous hemianopsia, and cortical blindness. Her HIV viral

To assess the long-term outcome in eosinophilic granulomatosis with polyangiitis (Churg-Strauss) (EGPA).A total of 101 patients fulfilling the American College of Rheumatology criteria for EGPA were included between 1990 and 2011. Clinical features, antineutrophil cytoplasm autoantibodies (ANCAs), and Five-Factors Score (FFS) were assessed at diagnosis. Overall and cumulative survival rates, relapse-free survival, and sequelae were studied based on ANCA status and FFS.The rate of cardiomyopathy did not differ according to ANCA status. A total of 79.6% of patients achieved first remission, but 81.1% relapsed. ANCA-positive patients did not relapse more frequently but exhibited more severe disease with mononeuritis (P = 0.0004) and renal involvement (P = 0.02). Being Italian was the only prognostic factor associated with a higher relapse-free survival (P = 0.01), thanks to a longer maintenance of immunosuppressive drugs, suggesting the need for prolonged low-dose corticosteroids. Overall, survival reached 93.1% after a median followup of 6 years. No factor was associated with mortality, but patients over age 65 years with cardiomyopathy or ANCA positivity had more serious outcomes. Sequelae affected 83.2% of patients. Ear, nose, and throat (ENT) involvement was a protective factor for renal (P = 0.04) and cardiac (P = 0.03) morbidity. ANCA positivity was correlated with chronic kidney disease (P = 0.03) and chronic neurologic disability (P = 0.02).The actual challenges of EGPA management concern morbidity prevention and quality of life improvement. Long-term corticosteroid treatment appears to reduce relapse risk. ENT involvement is associated with less renal and cardiac morbidity. ANCA positivity predicts renal and neurologic damage.

Introduction Le syndrome hyper-IgD est une fievre hereditaire rare appartenant au spectre des deficits en mevalonate kinase avec des acces febriles recurrents debutant dans la premiere annee de vie [1] . Les cas a l’âge adulte sont exceptionnels. Nous avons mene une etude observationnelle multicentrique de 23 patients atteints d’un deficit en mevalonate kinase diagnostique a l’âge adulte. Materiels et methodes Nous avons identifie les cas de janvier 2000 a decembre 2014 a partir des bases de donnees des 2 laboratoires de genetiques competents et du laboratoire de biochimie specialise a Lyon. Ont ete inclus les patients âges de plus de 16 ans au moment du diagnostic, et prouves genetiquement, ou avec une activite mevalonate kinase effondree et/ou une elevation de l’acide mevalonique urinaire per-crise avec une histoire personnelle de fievre recurrente ou de deficit en mevalonate kinase familial genetiquement prouve. Les donnees demographiques, les signes cliniques, les parametres biologiques et les traitements recus ont ete recueillis. Resultats Sur les 27 patients depistes, 23 ont ete analyses et 4 exclus (âge au diagnostic avant 16 ans, donnees recueillies insuffisantes). Il s’agissait de 14 femmes (60,9 %) et 9 hommes (39,1 %). Une patiente etait asymptomatique. La duree moyenne de suivi etait de 7 ans (1–13). L’âge moyen au diagnostic etait de 40 ans (16–79), avec un âge moyen au debut des symptomes de 9 ans (0,5–77). Le retard diagnostique etait de 30,6 ans (mediane). Treize patients (59,1 %) developpaient les premiers signes cliniques avant l’âge de 5 ans, et 81,8 % avant l’âge de 10 ans. Au moment du diagnostic, 9 patients (40,9 %) avaient de 1 a 2 crises/mois, et 11 (50 %) ≤ 1/mois. On retrouvait des facteurs declenchant chez 16 patients (72,7 %). En considerant les patients symptomatiques en poussee, tous presentaient une fievre et un syndrome inflammatoire ([proteine c-reactive] mediane : 24,1 mg/dL). Des symptomes articulaires etaient notes chez 21 patients (95,5 %), des signes digestifs (douleurs abdominales, diarrhee, vomissement) chez 20 (90,9 %), des signes cutanes et des adenopathies chez 19 respectivement (86,4 %), une pharyngite chez 14 (63,6 %), une hepatomegalie et/ou splenomegalie chez 11 (50 %). Vingt patients sur 21 testes (95,2 %) avaient une elevation des IgD seriques (mediane 812 mg/L, 330–3750). L’activite mevalonate kinase etait diminuee a 0,1 μkat/kg protein (0–0,45) (17 patients testes). L’acide mevalonique urinaire per-crise etait eleve a 5,1 mmol/mol de creatinine (1,7–28,2) (13 patients testes). Le diagnostic etait genetique chez 21 patients : 5 homozygotes et 16 heterozygotes composites. Dix-neuf patients ont recu des corticoides, 16 des AINS, 9 des anti-IL1ra, et 5 des anti-TNFα. Plus de 65 % des patients avaient une diminution de la frequence et de la severite des crises spontanement avec l’âge. Sept patients (35 %) etaient en remission a la derniere visite. Une patiente a developpe une amylose AA avec insuffisance renale dialysee. Cinq patients (21,7 %) sont decedes (choc septique n = 2, neoplasie solide n = 2, suicide n = 1). Discussion Nous rapportons la premiere serie de patients atteints de deficit en mevalonate kinase diagnostique exclusivement a l’âge adulte. Les 2 series princeps font principalement etat de cas pediatriques [1] , [2] . Les phenotypes cliniques pediatriques et a l’âge adulte ne different pas significativement. Les premiers symptomes apparaissent habituellement dans la premiere annee de vie, mais il existe un probable biais de memorisation dans notre serie expliquant un âge moyen aux premiers symptomes de 9 ans. Nous confirmons le retard diagnostique important, de plus de 30 ans dans notre serie. Le dosage des IgD pourrait etre un element d’orientation pour le diagnostic de deficit en mevalonate kinase a l’âge adulte devant une fievre hereditaire (elevation chez 95 % des patients). Plus de 65 % des patients presentent une diminution de la frequence et de la severite des acces febriles avec l’âge mais seuls 35 % etaient en remission a la derniere visite. Nous rapportons le 6eme cas d’amylose AA dans un contexte de deficit en mevalonate kinase. Conclusion Le deficit en mevalonate kinase est une fievre hereditaire rare de revelation souvent pediatrique avec des symptomes debutant dans la premiere annee de vie, mais qui doit etre evoque a l’âge adulte devant une clinique compatible et une elevation franche des IgD seriques. L’amylose AA est une complication exceptionnelle mais a redouter.