Abstract Objectives This study aimed to estimate the prevalence of ANCA-associated vasculitis (AAV). That is, granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic ...granulomatosis with polyangiitis (EGPA), in Southern France in 2018, and evaluate differences among Europeans and non-Europeans. Methods This population-based, cross-sectional study used four sources (hospitals, community-based physicians, laboratories, National Health Insurance) to identify adults ≥15 years diagnosed with GPA, MPA or EGPA, living in Hérault and Gard in 2018. Cases were defined using the ACR/EULAR classification criteria, and if necessary, the European Medicines Agency algorithm. Prevalence estimates were standardised to the world population and capture-recapture analysis was used to assess the comprehensiveness of the estimation. The influence of geographical origin was evaluated. Results A total of 202 patients were selected, with 86 cases of GPA (42.6%), 85 cases of MPA (42.1%) and 31 cases of EGPA (15.3%). The standardised prevalence estimates per million inhabitants for 2018 were: 103 (95%CI 84–125) for AAV, 48 (95%CI 35–64) for GPA, 39 (95%CI 28–53) for MPA and 16 (95%CI 9–26) for EGPA, 36 (95%CI 25–50) for anti-PR3 positive AAV, 46 (95%CI 34–61) for anti-MPO positive AAV, and 16 (95%CI 9–26) for ANCA-negative AAV. The global estimation of comprehensiveness by capture-recapture analysis was 80.5%. The number of AAV cases was higher for non-European residents (P = 0.001), particularly for MPA (P < 0.0001). Conclusion We provide a new estimate of AAV prevalence in France and show a higher prevalence of MPA in non-European patients.
The aim of this study was to determine the characteristics, treatment, and outcome according to each etiology of pachymeningitis.We conducted a retrospective multicenter French nationwide study ...between 2000 and 2016 to describe the characteristics, outcome, and treatment of pachymeningitis.We included 60 patients (median age 55.5 years; interquartile range IQR 30-80, female/male ratio 0.43). Neurologic signs were present in 59 patients (98%) and consisted of headache in 43 (72%), cranial nerve palsy in 33 (55%), confusion in 10 (17%), seizures in 7 (12%), and focal neurologic signs in 9 (15%). Fever and weight loss were present in 8 (13%) and 13 cases (22%), respectively. Cerebral venous thrombosis was present in 8 cases (13%). Analysis of cerebrospinal fluid showed moderate hyperproteinorachia (median 0.68 g/L; IQR 0.46-3.2) with or without pleiocytosis. Diagnosis included idiopathic pachymeningitis (n = 18; 30%); granulomatosis with polyangiitis (n = 13; 17%); Erdheim-Chester disease (n = 10; 17%); IgG4-related disease and tuberculosis (n = 3; 5% each); Rosai-Dofman disease, microscopic polyangiitis, and sarcoidosis (n = 2, 3% each); cryptococcal meningitis, Lyme disease, ear-nose-throat infection, postlumbar puncture, low spinal-fluid pressure syndrome, and lymphoma (n = 1 each). We found no difference in demographics and neurologic presentation among idiopathic pachymeningitis, Erdheim-Chester disease, and granulomatosis with polyangiitis. In contrast, frequencies were lower with idiopathic pachymeningitis than Erdheim-Chester disease for general signs (6% and 40%, respectively, P = .041) and complete neurologic response (0% vs 39%, P = .045).The detection of extraneurologic signs and routine screening are needed to classify the pachymeningitis origin. Prospective studies are warranted to determine the best treatment in each case.
Objective
We report cases of myelodysplastic syndrome/myeloproliferative neoplasms (MDS/MPN) with trisomy 8 associated with inflammatory and autoimmune diseases (IADs).
Method
Data for 21 patients ...with trisomy 8‐MDS/MPN and IADs were analyzed and compared to 103 patients with trisomy 8‐MDS/MPN without IADs.
Results
The median age of MDS/MPN patients with IADs was 67 59‐80. The IADs were Behçet's‐like disease in 11 (52%) patients, inflammatory arthritis in 4 (19%) and Sjögren's syndrome, autoimmune hemolytic anemia, aseptic abscess, periarteritis nodosa, Sweet's syndrome and unclassified vasculitis in one patient each. Overall, 17/21 (81%) patients with IADs received treatment (88% with steroids), with complete and partial response in 7/17 (35%) and 8/17 (47%), respectively. The effect of MDS treatment on IADs could be assessed in seven patients receiving azacytidine: five achieved remission and two partial response. As compared with the 103 trisomy 8‐MDS/MPN cases without IADs, those with IADs were more often non‐European (P = 0.005) and had poor karyotype (P < 0.001). We found no difference in overall survival or acute myeloid leukemia progression between trisomy 8‐associated MDS/MPN with and without IADs.
Conclusion
The spectrum of IADs associated with trisomy 8‐positive MDS/MPN is dominated by Behçet's‐like disease. Steroid therapy is effective, but mostly sparing therapies are necessary. Azacytidine could be an effective alternative.
Systemic inflammatory and autoimmune diseases (SIADs) associated with myelodysplastic syndromes are often difficult to treat. Corticosteroids are efficient but only usually at high doses. The use of ...biologics needs to be specified.
In a French multicenter retrospective study, we analyzed the efficacy and safety of biologics (tumor necrosis factor-α TNF-α antagonists, tocilizumab, rituximab and anakinra) for SIADs associated with myelodysplastic syndromes (MDSs). Clinical, biological and overall treatment responses were evaluated. When several lines of treatment were used, data were analyzed before and at the end of each treatment line and were pooled to compare overall response among steroids, disease-modifying anti-rheumatic drugs (DMARDs) and biologics.
We included 29 patients (median age 67years interquartile range 62–76, 83% males) with MDS-related SIADs treated with at least one biologic. The MDSs were predominantly refractory anemia with excess blasts 1 (38%) and refractory cytopenia with multilineage dysplasia (21%). The SIADs were mainly arthritis (n=6; 20%), relapsing polychondritis (n=8; 30%) and vasculitis (n=10; 34%). During a 3-year median follow-up (IQR 1.3–4.5), a total of 114 lines of treatments were used for all patients: steroids alone (22%), DMARDs (23%), TNF-α antagonists (14%), anakinra (10%), rituximab (10%), tocilizumab (7%) and azacytidine (9%). Considering all 114 lines, overall response (complete and partial) was shown in 54% cases. Overall response was more frequent with steroids (78%) and rituximab (66%) than DMARDs (45%) and other biologics (33%) (p<0.05). Rituximab had better response in vasculitis and TNF-α antagonists in arthritis. During follow-up, 20 patients (71%) presented at least one severe infection.
This nationwide study demonstrates the efficacy of steroids for SIAD-associated MDSs but a high frequency of steroid dependence. The response to biologics seems low, but rituximab and azacytidine seem promising.
The aim of this study was to determine the characteristics, treatment, and outcome according to each etiology of pachymeningitis.We conducted a retrospective multicenter French nationwide study ...between 2000 and 2016 to describe the characteristics, outcome, and treatment of pachymeningitis.We included 60 patients (median age 55.5 years; interquartile range IQR 30-80, female/male ratio 0.43). Neurologic signs were present in 59 patients (98%) and consisted of headache in 43 (72%), cranial nerve palsy in 33 (55%), confusion in 10 (17%), seizures in 7 (12%), and focal neurologic signs in 9 (15%). Fever and weight loss were present in 8 (13%) and 13 cases (22%), respectively. Cerebral venous thrombosis was present in 8 cases (13%). Analysis of cerebrospinal fluid showed moderate hyperproteinorachia (median 0.68 g/L; IQR 0.46-3.2) with or without pleiocytosis. Diagnosis included idiopathic pachymeningitis (n = 18; 30%); granulomatosis with polyangiitis (n = 13; 17%); Erdheim-Chester disease (n = 10; 17%); IgG4-related disease and tuberculosis (n = 3; 5% each); Rosai-Dofman disease, microscopic polyangiitis, and sarcoidosis (n = 2, 3% each); cryptococcal meningitis, Lyme disease, ear-nose-throat infection, postlumbar puncture, low spinal-fluid pressure syndrome, and lymphoma (n = 1 each). We found no difference in demographics and neurologic presentation among idiopathic pachymeningitis, Erdheim-Chester disease, and granulomatosis with polyangiitis. In contrast, frequencies were lower with idiopathic pachymeningitis than Erdheim-Chester disease for general signs (6% and 40%, respectively, P = .041) and complete neurologic response (0% vs 39%, P = .045).The detection of extraneurologic signs and routine screening are needed to classify the pachymeningitis origin. Prospective studies are warranted to determine the best treatment in each case.
Background: AID are seen in 10-30% of MDS and CMML. After initial response to steroids, AID are often poorly controlled and steroid-sparing drugs are difficult to use due to the underlying MDS/CMML. ...Some case reports suggest a beneficial role of AZA treatment in AID associated to MDS/CMML.
Methods: We retrospectively analyzed 22 MDS/CMML patients (pts) with AID who received AZA in French centers between January 2007 and May 2014.
Results: Median age of the 22 pts was 70y (range 41-84), including 6F/16M. Diagnosis of MDS/CMML preceded AID (n=8) by a median of 17 months (mo), was concomitant with (n=7) or followed AID (n=7) by a median of 20 mo. 14 pts had lower risk IPSS and 8 higher risk IPSS. AID diagnosis included: Behçet's disease (n=4), polymyalgia rheumatica (n=4), relapsing polychondritis (RP) (n=4), giant cell arteritis (n=2), Sweet's syndrome (n=2), SLE (n=2), Sjögren's (n=1), adult onset Still's disease (n=1), unclassified small vessel vasculitis (n=1) and seronegative polyarthritis (n=1). One pt presented with both RP and Sweet's syndrome. 12 (55%) AID were considered atypical and 10 (45%) fulfilled complete diagnostic criteria. Before AZA, 21 pts (96%) had received steroids and 16 (73%) a median of 2 immunomodulatory drugs (IMD) (range 1-6) in addition to steroids.
At AZA onset, AID was still active (n=14), in PR (n=6) and in CR (n=2). 19 pts still reported asthenia (n=17), weight loss (n=8), fever >38°5 (n=8), rheumatologic signs (n=15), skin involvement (n=10), oral aphtosis (n=4). 9 pts were steroid dependent or resistant. 20 pts were treated with steroids (91%, median dose of 23 mg/d). 13 pts were non-responders to IMD and 11 received concomitant IMD, without efficacy in 7 pts.
AZA was the first-line treatment of MDS/CMML in 13 pts (59%) and was in 9 pts preceded by: intensive chemotherapy (n=3), LEN (n=2), HY (n=2), allo SCT (n=2) and LDaraC (n=2). Median interval between MDS/CMML diagnosis and AZA onset was 9 mo (range 1-93). At AZA onset, IPSS was low (n=4), int-1 (n=7), int-2 (n=8) and high (n=3). Pts received a median of 6 cycles of AZA (range 3-14); 1 pt received 3 cycles, 5 received 5 cycles; 9 pts received more than 6 cycles. Complete remission (CR) of AID was observed in 16 pts (73%), partial remission (PR) in 3 pts (14%) and no effect or worsening of AID in 3 pts (14%). All responses were observed within 3 cycles, but 8 PR of AID after 3 cycles became CR after 6 mo. Discontinuation of steroids was possible in 3 pts (14%) and dose reduction in 14 pts (64%), to a median of 9 mg/d, (range 0-30), (p=0.001). Discontinuation of IMD was possible in 7 pts (32%). Altogether, dose reduction or discontinuation of steroids and/or IMD after AZA was possible in 16 cases (73%). Good response of AID symptoms (including PR and CR) or discontinuation of IST was noted in 19 patients (86%). Median CRP decreased from 40 mg/L to 15 mg/L (p=0.28). Response of MDS/CMML to AZA (IWG2006 criteria) was seen in 12 pts (55%), including CR in 9 pts (41%), PR in 1, SD+HI-E in 1, mCR in 1, SD in 8 and PD in 2. No uncommon side effects to AZA were seen.
MDS/CMML and AID evolution was concordant in 13 pts (59%): both improved (n=11) or worsened (n=2). AID improved while MDS worsened (n=8) and vice versa (n=1). With a median FU from response to AZA of 8 mo, only 3 relapses of AID were seen after 3 (n=1) and after 19 mo (n=2), and 5 pts had a response > 12 mo. Seven pts (32%) progressed to AML and 10 pts (45%) had died, with 8 deaths occurring in IPSS high or int 2 pts. Median survival from AZA onset was 16 months in IPSS high or int-2 MDS and was not reached in IPSS low and int-1 MDS.
Conclusions: AZA frequently seems effective in controlling steroid-dependent AID associated with MDS/CMML, but prospective studies are necessary to confirm those findings.
Fenaux:JANSSEN: Honoraria, Research Funding; CELGENE: Honoraria, Research Funding; AMGEN: Honoraria, Research Funding; NOVARTIS: Honoraria, Research Funding.
Abstract only Introduction: Kawasaki disease (KD) is a vasculitis that occurs mostly among children and exceptionally in adults. We report data from a French observatory of adult KD. Patients and ...methods: Adult patients diagnosed with KD in 16 French centers were included. Patients were classified as complete KD or incomplete KD according to IKDC or probable KD. Results: We included 24 patients with a median age of 29 years (22-39) and a sex ratio (M / F) 2.42, 12 complete KD, 9 incomplete KD and 3 probable KD without any other cause. Time to diagnosis was 13 days (10-20.5). Main events were: fever (100%), extremities changes (21/24, 87.5%), rash (22/24, 92%), conjunctivitis (16/24, 16, 66%), cheilitis (15/24, 63%), strawberry tongue (11/24, 46%), adenopathy (10/24, 42%), cardiac abnormalities (11/24, 46%), cardiogenic shock (n = 1), myo-pericarditis (n = 3) and left heart failure (n = 1). Median CRP was 228mg/L (166-311), SGOT: 68 IU/L (51-139), SGPT: 125 IU/L (69-190), platelets 372 G/L (209-630) and leukocytes 16 G/L (8.3-20). Cardiac involvement was researched in 23 patients (96%) by achieving: echocardiography (20/24), coronary scanners (6/24), coronary angiography (5/24), cardiac MRI (2/24) and stress tests (2/24). An arteritic vascular disease was found in 11 patients (46%): coronary aneurysms (8/24, 33%), coronary arteritis (10/24; 42%) and peripheral arteritis (2/24, 8.3%) with acute lower limb ischemia (1/24, 4.2%) and splenic infarction (1/24, 4.2%). Patients received: intravenous immunoglobulin (17/24; 71%): aspirin (21/24, 88%). After 6 months, it persisted 5 aneurysm (20.8%). Complications noticed during the last follow-up were: heart failure (1/24, 4.3%), aneurysm (3/24, 12.5%). Conclusion: The adult KD is a rare disease that can have bad prognosis in short or long term and leave irreversible damage. The high rate of cardiac complication could be due to the long diagnosis delay, the absence of the gold standard treatment in 30% of cases or a selectional bias due to the difficulty to diagnose this disease in adulthood.
Objective Kawasaki disease (KD) is a vasculitis that mostly occurs in young children and rarely in adults. We analyzed the characteristics of adult-onset KD (AKD) in France. Methods We collected ...retrospective and prospective data for patients with a diagnosis of KD occurring after the age of 18 years. Cases were obtained via various French medical networks and identified from the international literature. Results We included 43 patients of AKD at 26 institution from 1992 to 2015, with mean (SD) age 30 (11) years (range 18–68) and sex ratio (M/F) 1.2; 34 patients met the American Heart Association criteria and 9 were incomplete AKD. The median time to diagnosis was 13 days (interquartile range 8–21). The main symptoms were fever (100%), exanthema (98%), changes in the extremities (91%), conjunctivitis (77%), oral cavity changes (89%), cervical adenitis (55%) and cardiac abnormalities (45%). Overall, 35% of patients showed large-vessel vasculitis: coronary vasculitis (26%) and coronary aneurysm (19%). Treatment was mostly intravenous immunoglobulins (79%) and aspirin (81%). Four patients showed myocardial infarction due to coronary vasculitis, but none were treated with IVIg because of late diagnosis. After a median follow-up of 5 months (range 1–117), persistent aneurysm was noted in 9% of cases. Damage was significantly lower with early treatment than late or no treatment (p = 0.01). Conclusion Given the high frequency of cardiac involvement and complications in this series of AKD, diagnosis and treatment should not be delayed, and early IVIg treatment seems to improve the outcome
PDF
