Typical Bone Scintigraphy Presentation of Erdheim-Chester Disease in a Patient Diagnosed With IgG4-Related Disease.

ABSTRACT: A 50-year-old woman presented a dry syndrome, joint pain, inflammatory syndrome, polyclonal hypergammaglobulinemia, and tubulointerstitial nephritis. Imaging studies (including FDG PET/CT) revealed infrarenal retroperitoneal fibrosis with periaortitis and hypermetabolic osteosclerotic lesions. Bone scintigraphy demonstrated intense uptake in the femoral, tibial, and radial regions, suggestive of non-Langerhans histiocytosis, specifically Erdheim-Chester disease. A bone biopsy confirmed the presence of IgG4-positive plasma cells but no histiocytes. The patient received corticosteroid therapy followed by rituximab, resulting in a complete response. This case suggests an atypical manifestation of bone lesions in IgG4-related disease, emphasizing the diagnostic challenge between IgG4-related disease and Erdheim-Chester disease.

Prognostic value of complement serum C3 level and glomerular C3 deposits in anti-glomerular basement membrane disease.

Background and objectives: Activation of the complement system is involved in the pathogenesis of anti-glomerular basement membrane (anti-GBM) disease. Glomerular deposits of complement 3 (C3) are often detected on kidney biopsies. The primary objective of this study was to analyze the prognostic value of the serum C3 level and the presence of C3 glomerular deposits in patients with anti-GBM disease. Methods: We conducted a retrospective cohort study of 150 single-positive patients with anti-GBM disease diagnosed between 1997 and 2017. Patients were categorized according to the serum C3 level (forming a low C3 (C3<1.23 g/L) and a high C3 (C3≥1.23 g/L) groups) and positivity for C3 glomerular staining (forming the C3+ and C3- groups). The main outcomes were kidney survival and patient survival. Results: Of the 150 patients included, 89 (65%) were men. The median [interquartile range (IQR)] age was 45 [26-64]. At diagnosis, kidney involvement was characterized by a median [IQR] peak serum creatinine (SCr) level of 578 [298-977] µmol/L, and 106 (71%) patients required dialysis. Patients in the low C3 group (72 patients) had more severe kidney disease at presentation, as characterized by higher prevalences of oligoanuria, peak SCr ≥500 µmol/L (69%, vs. 53% in the high C3 group; p=0.03), nephrotic syndrome (42%, vs. 24%, respectively; p=0.02) and fibrous forms on the kidney biopsy (21%, vs. 8%, respectively; p=0.04). Similarly, we observed a negative association between the presence of C3 glomerular deposits (in 52 (41%) patients) and the prevalence of cellular forms (83%, vs. 58% in the C3- group; p=0.003) and acute tubulo-interstitial lesions (60%, vs. 36% in the C3- group; p=0.007). When considering patients not on dialysis at diagnosis, the kidney survival rate at 12 months was poorer in the C3+ group (50% [25-76], vs. 91% [78-100] in the C3- group; p=0.01), with a hazard ratio [95% confidence interval] of 5.71 [1.13-28.85] (p=0.04, after adjusting for SCr). Conclusion: In patients with anti-GBM disease, a low serum C3 level and the presence of C3 glomerular deposits were associated with more severe disease and histological kidney involvement at diagnosis. In patients not on dialysis at diagnosis, the presence of C3 deposits was associated with worse kidney survival.

Rituximab resistance at 3months of induction therapy in newly diagnosed or relapsing ANCA-associated vasculitis: A French multicentre retrospective study in 116 patients.

OBJECTIVE: To evaluate rituximab (RTX) resistance at 3months (M3) of induction therapy in antineutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV). METHODS: Multicentre French retrospective study conducted between 2010 and 2020 including patients with newly diagnosed or relapsing AAV (granulomatosis with polyangiitis or microscopic polyangiitis) having received induction therapy with RTX. Primary endpoint was the presence of RTX resistance at 3months (M3) defined as uncontrolled disease (worsening feature on the BVAS/WG 1month after RTX induction) or disease flare (increase in BVAS/WG of≥1 point before M3). RESULTS: Out of 121 patients included, we analysed 116 patients. Fourteen patients (12%) had RTX resistance at M3 with no difference in baseline demographics, vasculitis type, ANCA type, disease status or organ involvement. Patients with RTX resistance at M3 had a greater proportion of localized disease (43% vs. 18%, P<0.05) and were less often treated by initial methylprednisolone (MP) pulse (21% vs. 58%, P<0.01). Out of the 14 patients with RTX resistance, seven received additional immunosuppressive therapy. All patients were in remission at 6months. Compared to responders, patients with RTX resistance at M3 were less often treated with prophylactic trimethoprim-sulfamethoxazole (57% vs. 85%, P<0.05). Twenty-four patients died during follow-up, one-third of them from infections and half of them from SARS-CoV-2. CONCLUSION: Twelve percent of patients had RTX resistance at M3. These patients more often had localized form of the disease and were less treated by initial MP pulse and by prophylactic trimethoprim-sulfamethoxazole.

Abnormal T-cell phenotype in episodic angioedema with hypereosinophilia (Gleich syndrome): Frequency, clinical implication, and prognosis.

BACKGROUND: Episodic angioedema with eosinophilia (EAE) (Gleich syndrome) is a rare disorder consisting of recurrent episodes of angioedema, hypereosinophilia, and frequent elevated serum IgM level. METHODS: We conducted a retrospective multicenter nationwide study regarding the clinical spectrum and therapeutic management of patients with EAE in France. RESULTS: A total of 30 patients with a median age at diagnosis of 41 years (range, 5-84) were included. The median duration of each crisis was 5.5 days (range, 1-90), with swelling affecting mainly the face and the upper limbs. Total serum IgM levels were increased in 20 patients (67%). Abnormal T-cell immunophenotypes were detected in 12 patients (40%), of whom 5 (17%) showed evidence of clonal T-cell receptor gamma locus gene (TRG) rearrangement. The median duration of follow-up was 53 months (range, 31-99). The presence of an abnormal T-cell population was the sole factor associated with a shorter time to flare (hazard ratio, 4.15; 95% confidence interval, 1.18-14.66; P = .02). At last follow-up, 3 patients (10%) were able to have all treatments withdrawn and 11 (37%) were in clinical and biologic remission with less than 10 mg of prednisone daily. CONCLUSION: EAE is a heterogeneous condition that encompasses several disease forms. Although patients usually respond well to glucocorticoids, those with evidence of abnormal T-cell phenotype have a shorter time to flare.

A "Leopard Man" Aspect on 18 F-FDG PET/CT Revealing a VEXAS Syndrome.

ABSTRACT: VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is an adult-onset autoinflammatory disease caused by somatic UBA1 mutations first described in 2020. Most of these patients met clinical criteria for an inflammatory syndrome (relapsing polychondritis, Sweet syndrome, polyarteritis nodosa, or giant-cell arteritis) or a hematologic condition (myelodysplastic syndrome or multiple myeloma) or both. We described here an FDG PET/CT "leopard man" appearance, with abnormal marrow recruitment the findings, in a 70-year-old man diagnosed with a VEXAS syndrome.

Rituximab vs Cyclophosphamide Induction Therapy for Patients With Granulomatosis With Polyangiitis.

Importance: Results of randomized clinical trials have demonstrated rituximab's noninferiority to cyclophosphamide as induction therapy for antineutrophil cytoplasm antibody (ANCA)-associated vasculitides (AAV), with neither treatment having a specific advantage for granulomatosis with polyangiitis (GPA). However, post hoc analysis results have suggested that rituximab might be more effective than cyclophosphamide in inducing remission in patients with proteinase 3-positive AAV. Objective: To compare the effectiveness of rituximab and cyclophosphamide in inducing GPA remission in a large population of unselected patients. Design, Setting, and Participants: This comparative effectiveness study used multicenter target trial emulation observational data from 32 French hospitals in the French Vasculitis Study Group Registry. Groups were determined according to treatments received, without any intervention from the investigators. Inverse probability of treatment weighting was used to correct for baseline imbalance between groups. Participants included patients with newly diagnosed or relapsing GPA who satisfied American College of Rheumatology classification criteria and/or Chapel Hill Consensus Conference nomenclature. Data were analyzed from October 1, 2021, to May 31, 2022. Exposures: At least 1 infusion of rituximab or cyclophosphamide for induction therapy between April 1, 2008, and April 1, 2018. Main Outcomes and Measures: The primary outcome was remission rate at month 6 (±2 months), with remission defined as a Birmingham Vasculitis Activity Score (BVAS) of 0 and prednisone dose of 10 mg/d or less. The BVAS is a validated tool for small-vessel vasculitis and used to assess the level of disease activity, with a numerical weight attached to each involved organ system. The BVAS has a range of 0 to 63 points; a score of 0 indicates no disease activity. Subgroup analyses included the primary outcome for patients with a new diagnosis, for most recently treated patients, and for patients with myeloperoxidase-ANCA positivity. Results: Among 194 patients with GPA included in the analysis (mean [SD] age, 54 [15] years; 110 men [56.7%]), 165 (85.1%) had a new diagnosis, and 147 of 182 with data available (80.8%) had proteinase 3-ANCA positivity. Sixty-one patients received rituximab and 133 received cyclophosphamide for induction therapy. In the weighted analysis, the primary outcome was reached for 73.1% of patients receiving rituximab vs 40.1% receiving cyclophosphamide (relative risk [RR], 1.82 [95% CI, 1.22-2.73]; risk difference, 33.0% [95% CI, 12.2%-53.8%]; E value for RR, 3.05). Similar results were observed in the subgroup of patients with newly diagnosed GPA and those with a more recent treatment. In the subset of 27 patients with myeloperoxidase-ANCA-positive GPA, 8 of 10 rituximab recipients and 8 of 17 cyclophosphamide recipients met the primary end point (unweighted RR, 1.73 [95% CI, 0.96-3.11]). Conclusions and Relevance: In this comparativeness effectiveness study using clinical data, rituximab induction therapy for GPA was more frequently associated with remission than cyclophosphamide. These results inform clinical decision-making concerning the choice of remission induction therapy for this subset of patients with AAV.

Comparative study of granulomatosis with polyangiitis subsets according to ANCA status: data from the French Vasculitis Study Group Registry.

OBJECTIVE: To investigate whether antineutrophil cytoplasm antibody (ANCA)-negative and myeloperoxidase (MPO)-ANCA-positive granulomatosis with polyangiitis (GPA) differ from proteinase-3 (PR3)-ANCA-positive GPA. METHODS: Diagnostic characteristics and outcomes of newly diagnosed French Vasculitis Study Group Registry patients with ANCA-negative, MPO-ANCA-positive or PR3-ANCA-positive GPA satisfying American College of Rheumatology criteria and/or Chapel Hill Conference Consensus Nomenclature were compared. RESULTS: Among 727 GPA, 62 (8.5%) were ANCA-negative, 119 (16.4%) MPO-ANCA-positive and 546 (75.1%) PR3-ANCA-positive. ANCA-negative patients had significantly (p<0.05) more limited disease (17.7% vs 5.8%) and less kidney involvement (35.5% vs 58.9%) than those PR3-ANCA-positive or MPO-ANCA-positive, with comparable relapse-free (RFS) and overall survival (OS). MPO-ANCA-positive versus PR3-ANCA-positive and ANCA-negative patients were significantly more often female (52.9% vs 42.1%), older (59.8 vs 51.9 years), with more frequent kidney involvement (65.5% vs 55.2%) and less arthralgias (34.5% vs 55.1%), purpura (8.4% vs 17.1%) or eye involvement (18.5% vs 28.4%); RFS was similar but OS was lower before age adjustment. PR3-positive patients' RFS was significantly lower than for ANCA-negative and MPO-positive groups combined, with OS higher before age adjustment. PR3-ANCA-positivity independently predicted relapse for all GPA forms combined but not when comparing only PR3-ANCA-positive versus MPO-ANCA-positive patients. CONCLUSIONS: Based on this large cohort, ANCA-negative versus ANCA-positive patients more frequently had limited disease but similar RFS and OS. MPO-ANCA-positive patients had similar RFS but lower OS due to their older age. PR3-ANCA-positive GPA patients' RFS was lower than those of the two other subsets combined but that difference did not persist when comparing only PR3 versus MPO-ANCA-positive patients.

Management of nonviral mixed cryoglobulinemia vasculitis refractory to rituximab: Data from a European collaborative study and review of the literature.

BACKGROUND: Glucocorticoids (GCs) plus rituximab (RTX) represent the first-line treatment of nonviral mixed cryoglobulinemia vasculitis (CryoVas). However, data on therapeutic management and outcome of patients refractory to RTX are lacking. METHODS: We conducted a European collaborative retrospective multicenter study of patients with nonviral mixed CryoVas refractory to RTX and performed a literature review. RESULTS: Twenty-six original cases and 7 additional patients from the literature were included. All patients but one had type 2 cryoglobulinemia, and causes were autoimmune disease (51%), malignant hemopathy (12%) or essential CryoVas (42%). CryoVas was primary refractory to RTX in 42%, while 58% had an initial response to RTX before immune escape. After RTX failure, patients received a median of 1 (IQR, 1-3) line of treatment, representing 65 treatment periods during follow-up. Main treatments used were GCs in 92%, alkylating agents in 43%, RTX in combination with other treatments in 46%, and belimumab in 17%. Combination of anti-CD20 plus belimumab, alkylating agents alone and anti-CD20 plus alkylating agents provided the highest rates of clinical response in 100% 82% and 73%, respectively, but showed poor immunological response, in 50%, 30% and 38%, respectively. Rates of severe infection were 57%, 9% and 0% in patients receiving anti-CD20 plus belimumab, alkylating agents alone and anti-CD20 plus alkylating agents, respectively. CONCLUSION: In patients with nonviral mixed CryoVas refractory to RTX, anti-CD20 plus belimumab, and alkylating agents associated or not with anti-CD20, provide the highest rates of clinical response. However, anti-CD20 plus belimumab was frequently associated with severe infections.

Localized versus systemic granulomatosis with polyangiitis: data from the French Vasculitis Study Group Registry.

OBJECTIVE: To describe the main features at diagnosis and evolution over time of patients with localized granulomatosis with polyangiitis (L-GPA) compared with those of systemic GPA (S-GPA). METHODS: EULAR definitions of L-GPA, i.e. upper and/or lower respiratory tract involvement, and S-GPA were applied to patients from the French Vasculitis Study Group Registry. L-GPA and S-GPA patients' characteristics at diagnosis and long-term outcomes were analysed and compared. RESULTS: Among the 795 Registry patients, 79 (10%) had L-GPA. Their main clinical manifestations were rhinitis, lung nodules, sinusitis and otitis. L-GPA vs S-GPA patients at diagnosis, respectively, were younger, more frequently had saddle nose deformity or subglottic stenosis and were less often PR3-ANCA-positive. L-GPA vs S-GPA induction therapy less frequently included CYC but more often a combination of MTX and glucocorticoids; 64% of MTX-treated patients experienced disease progression within 18 months post-diagnosis. L- and S-GPA patients' estimated relapse-free-survival probabilities, relapse rates and refractory disease rates at each time point were comparable, but L-GPA patients had more frequent ENT and lung relapses, and higher overall survival rates (P<0.02). Over a median follow-up of 3.5 years, 18 (22.8%) L-GPA progressed to S-GPA, either as a relapse after a period in remission or more frequently in the context of refractory disease. L-GPA patients experienced more ENT-related damage. CONCLUSIONS: The relapse risks of L-GPA and S-GPA were similar, but relapse patterns differed and L-GPA overall survival rate was higher. About one-quarter of L-GPA patients developed S-GPA over time, but without end-stage organ involvement.

Significance of eosinophilia in granulomatosis with polyangiitis: data from the French Vasculitis Study Group Registry.

OBJECTIVE: To describe disease presentation and long-term outcome of granulomatosis with polyangiitis (GPA) patients according to blood eosinophils count (Eos) at vasculitis diagnosis. METHODS: Data from newly diagnosed GPA patients registered in the French Vasculitis Study Group database with available eosinophil count at diagnosis were reviewed. Disease characteristics, rate and type of relapses, and overall survival were analysed according to Eos, categorized as normal (<500/mm3), mild-to-moderate hypereosinophilia (HE) (between 500 and 1500/mm3) and severe HE (>1500/mm3). RESULTS: Three hundred and fifty-four patients were included. At diagnosis, 90 (25.4%) patients had HE ≥500/mm3; they were more likely male (73% vs 56%, P = 0.006) and had more frequent cutaneous manifestations (49% vs 33%, P = 0.01), peripheral neuropathy (32% vs 17%, P = 0.004) and higher BVAS (21 vs 18, P = 0.01), compared with those with Eos <500/mm3. Patients with severe HE (n = 28; median Eos 2355, range 1500-9114) had more frequent renal function worsening at presentation (P = 0.008). After a median follow-up of 3.95 (interquartile range 1.95-6.76) years, no difference was found in overall relapse rates according to baseline Eos, but those with HE experienced more neurological (P = 0.013) and skin (P = 0.024) relapses and had more frequently peripheral neuropathy as damage at last follow-up (P = 0.02). Overall survival was not significantly different in patients with normal Eos or HE at diagnosis. (P = 0.08). CONCLUSIONS: Blood HE at diagnosis, observed in about one-quarter of GPA patients, identifies a subgroup of patients with a more severe disease and higher rate of skin and neurological involvement both at presentation and during follow-up.

ANCA-Negative Pauci-immune Necrotizing Glomerulonephritis: A Case Series and a New Clinical Classification.

RATIONALE & OBJECTIVE: Pauci-immune necrotizing glomerulonephritis (PING) is usually associated with the presence of antineutrophil cytoplasmic antibodies (ANCA). However, a minority (2%-3%) of patients with PING do not have detectable ANCA. We assessed the clinical spectrum and outcome of patients with ANCA-negative PING. STUDY DESIGN: Case series. SETTING & PARTICIPANTS: 74 patients with ANCA-negative PING diagnosed in 19 French nephrology centers between August 2006 and December 2018 were included in the series. Patients' medical files were reviewed, and kidney biopsies were centrally reexamined by pathologists who were masked to the diagnosis. FINDINGS: Median age at diagnosis was 69 (IQR, 61-76) years. The clinical and pathological features were remarkable for a high frequency of extrarenal manifestations (54%), nephrotic syndrome (32%), and endocapillary hypercellularity (31%). Three main subtypes of ANCA-negative PING were observed: infection-associated (n=9[12%]), malignancy-associated (n=6[8%]), and primary (n=57[77%]). For patients with primary PING, induction treatment included mainly corticosteroids (n=56[98%]), cyclophosphamide (n=37[65%]), and rituximab (n=5[9%]). Maintenance treatment consisted mainly of corticosteroids (n=42[74%]), azathioprine (n=18[32%]), and mycophenolate mofetil (n=11[19%]). After a median follow-up period of 28 months, 28 (38%) patients had died and 20 (27%) developed kidney failure (estimated glomerular filtration rate<15mL/min/1.73m2). Eleven (21%) patients (9 with primary and 2 with malignancy-associated PING) relapsed. LIMITATIONS: Retrospective study and limited number of patients; electron microscopy was not performed to confirm the absence of glomerular immune deposits. CONCLUSIONS: Within the spectrum of ANCA-negative PING, infection and malignancy-associated forms represent a distinct clinical subset. This new clinical classification may inform the management of ANCA-negative PING, which remains a severe form of vasculitis with high morbidity and mortality rates despite immunosuppressive treatments.

USAID Associated with Myeloid Neoplasm and VEXAS Syndrome: Two Differential Diagnoses of Suspected Adult Onset Still's Disease in Elderly Patients.

BACKGROUND: Patients with solid cancers and hematopoietic malignancy can experience systemic symptoms compatible with adult-onset Still's disease (AOSD). The newly described VEXAS, associated with somatic UBA1 mutations, exhibits an overlap of clinical and/or biological pictures with auto inflammatory signs and myelodysplastic syndrome (MDS). OBJECTIVES: To describe a cohort of patients with signs of undifferentiated systemic autoinflammatory disorder (USAID) concordant with AOSD and MDS/chronic myelomonocytic leukemia (CMML) and the prevalence of VEXAS proposed management and outcome. METHODS: A French multicenter retrospective study from the MINHEMON study group also used for other published works with the support of multidisciplinary and complementary networks of physicians and a control group of 104 MDS/CMML. RESULTS: Twenty-six patients were included with a median age at first signs of USAID of 70.5 years with male predominance (4:1). Five patients met the criteria for confirmed AOSD. The most frequent subtypes were MDS with a blast excess (31%) and MDS with multilineage dysplasia (18%). Seven patients presented with acute myeloid leukemia and twelve died during a median follow-up of 2.5 years. Six out of 18 tested patients displayed a somatic UBA1 mutation concordant with VEXAS, including one woman. High-dose corticosteroids led to a response in 13/16 cases and targeted biological therapy alone or in association in 10/12 patients (anakinra, tocilizumab, and infliximab). Azacytidine resulted in complete or partial response in systemic symptoms for 10/12 (83%) patients including 3 VEXAS. CONCLUSIONS: Systemic form of VEXAS syndrome can mimic AOSD. The suspicion of USAID or AOSD in older males with atypia should prompt an evaluation of underlying MDS and assessment of somatic UBA1 mutation.

Disease Activity and Adverse Events in Patients with ANCA-Associated Vasculitides Undergoing Long-Term Dialysis.

BACKGROUND AND OBJECTIVES: Kidney impairment of ANCA-associated vasculitides can lead to kidney failure. Patients with kidney failure may suffer from vasculitis relapses but are also at high risk of infections and cardiovascular events, which questions the maintenance of immunosuppressive therapy. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Patients with ANCA-associated vasculitides initiating long-term dialysis between 2008 and 2012 in France registered in the national Renal Epidemiology and Information Network registry and paired with the National Health System database were included. We analyzed the proportion of patients in remission off immunosuppression over time and overall and event-free survival on dialysis (considering transplantation as a competing risk). We compared the incidence of vasculitis relapses, serious infections, cardiovascular events, and cancers before and after dialysis initiation. RESULTS: In total, 229 patients were included: 142 with granulomatous polyangiitis and 87 with microscopic polyangiitis. Mean follow-up after dialysis initiation was 4.6±2.7 years; 82 patients received a kidney transplant. The proportion of patients in remission off immunosuppression increased from 23% at dialysis initiation to 62% after 5 years. Overall survival rates on dialysis were 86%, 69%, and 62% at 1, 3, and 5 years, respectively. Main causes of death were infections (35%) and cardiovascular events (26%) but not vasculitis flares (6%). The incidence of vasculitis relapses decreased from 57 to seven episodes per 100 person-years before and after dialysis initiation (P=0.05). Overall, during follow-up, 45% of patients experienced a serious infection and 45% had a cardiovascular event, whereas 13% experienced a vasculitis relapse. CONCLUSIONS: The proportion of patients with ANCA-associated vasculitis in remission off immunosuppression increases with time spent on dialysis. In this cohort, patients were far less likely to relapse from their vasculitis than to display serious infectious or cardiovascular events. PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2021_11_08_CJN03190321.mp3.

Reappraisal of Renal Arteritis in ANCA-associated Vasculitis: Clinical Characteristics, Pathology, and Outcome.

BACKGROUND: Renal involvement in ANCA-associated vasculitis (AAV) is associated with poor outcomes. The clinical significance of arteritis of the small kidney arteries has not been evaluated in detail. METHODS: In a multicenter cohort of patients with AAV and renal involvement, we sought to describe the clinicopathologic characteristics of patients with AAV who had renal arteritis at diagnosis, and to retrospectively analyze their prognostic value. RESULTS: We included 251 patients diagnosed with AAV and renal involvement between 2000 and 2019, including 34 patients (13.5%) with arteritis. Patients with AAV-associated arteritis were older, and had a more pronounced inflammatory syndrome compared with patients without arteritis; they also had significantly lower renal survival (P=0.01). In multivariable analysis, the ANCA renal risk score, age at diagnosis, history of diabetes mellitus, and arteritis on index kidney biopsy were independently associated with ESKD. The addition of the arteritis status significantly improved the discrimination of the ANCA renal risk score, with a concordance index (C-index) of 0.77 for the ANCA renal risk score alone, versus a C-index of 0.80 for the ANCA renal risk score plus arteritis status (P=0.008); ESKD-free survival was significantly worse for patients with an arteritis involving small arteries who were classified as having low or moderate risk, according to the ANCA renal risk score. In two external validation cohorts, we confirmed the incidence and phenotype of this AAV subtype. CONCLUSIONS: Our findings suggest AAV with renal arteritis represents a different subtype of AAV with specific clinical and histologic characteristics. The prognostic contribution of the arteritis status remains to be prospectively confirmed.

Granulomatosis with polyangiitis: Study of 795 patients from the French Vasculitis Study Group registry.

OBJECTIVE: To describe the characteristics and long-term outcomes of patients with granulomatosis with polyangiitis (GPA) from the French Vasculitis Study Group database. METHODS: Patients' clinical and laboratory characteristics, Birmingham Vasculitis Activity Score (BVAS)-assessed disease activity, malignancies, opportunistic infections, and vital status were collected at diagnosis and each visit. Estimated probabilities and predictors of overall (OS) and relapse-free survival (RFS) were analyzed by Cox regression. RESULTS: We enrolled 795 newly diagnosed patients, followed for a median of 3.5 years. Initial clinical manifestations involved ear, nose & throat (ENT; 80%), lungs (68%) and kidneys (56%). Among the 728 available ELISA results, 75.0% were PR3-ANCA-positive, 16.5% MPO-ANCA-positive and 62 (8.5%) ANCA-negative. Relapses occurred in 394 (50%) patients, involving ≥1 organ(s) affected at onset in 179 (46%), mainly ENT, lungs and kidneys, with mean BVAS 10.2 points below that at diagnosis (p<0.001). Five- and 10-year RFS rates were 37% and 17%, respectively. PR3-ANCA-positivity independently predicted relapse (p = 0.05) and prolonged survival (p = 0.038). OS-but not RFS-improved significantly over time (p<0.001); 10-year OS reached 88.2% (95% CI 83.9 to 92.7) for the 660 patients diagnosed after 2000. Infections were the main causes of death. Malignancy or opportunistic infection each occurred in ≤5% of the patients. CONCLUSION: Survival has improved dramatically over the last decades but the high relapse rate remains a major concern for GPA patients, once again stressing the need for therapeutic strategy optimization to lower it. PR3-ANCA-positivity was associated with increased probability of relapse and survival.

Sustained Remission of Granulomatosis With Polyangiitis After Discontinuation of Glucocorticoids and Immunosuppressant Therapy: Data From the French Vasculitis Study Group Registry.

OBJECTIVE: Data on sustained remission of granulomatosis with polyangiitis (GPA) after discontinuation of therapy (referred to as GPA with sustained remission off-therapy [SROT]) are scarce. In the present study, SROT among GPA patients from the French Vasculitis Study Group Registry was evaluated to identify factors associated with its occurrence and durability. METHODS: For inclusion of patients in the study, the diagnosis of GPA had to meet the GPA classification criteria defined by the American College of Rheumatology and/or the revised Chapel Hill Consensus Conference nomenclature for vasculitis. SROT was defined as achievement of remission (a Birmingham Vasculitis Activity Score of 0) that was sustained for ≥6 consecutive months after having discontinued glucocorticoid (GC) and immunosuppressant treatments. The characteristics of the patients at baseline and treatments received were compared at 3, 5, and 10 years postdiagnosis according to whether or not SROT had been reached and maintained. RESULTS: Among 795 patients with GPA, 92 GPA patients with SROT at 3 years postdiagnosis were compared to 342 control subjects who had experienced disease relapse and/or were still receiving GCs or immunosuppressants. No baseline differences were found, but patients with SROT at 3 years postdiagnosis had more frequently received intravenous cyclophosphamide as induction therapy compared to control subjects (P = 0.01), with a higher median number of infusions (P = 0.05). At 5 years postdiagnosis, no baseline differences were observed between groups, but patients with SROT at 5 years postdiagnosis had received more cyclophosphamide infusions compared to control subjects (P = 0.03). More patients with SROT had received rituximab as maintenance therapy than control subjects at 3 years and 5 years postdiagnosis (P = 0.09 and P < 0.001, respectively). Of the 74 patients enrolled in the GPA Registry with 10-year follow-up data after having received conventional maintenance therapy, 15 (20%) had reached SROT at 3 years, and 5 (7%) maintained SROT at 10 years postdiagnosis. CONCLUSION: After conventional therapies, 7% of GPA patients had reached SROT at 10 years postdiagnosis. No baseline vasculitis characteristics distinguished patients who achieved/maintained SROT from those who experienced disease relapse and/or those who continued to receive GCs or immunosuppressant therapy, but patients with SROT had received more intensive induction therapy and rituximab as maintenance therapy more frequently.

French recommendations for the management of systemic necrotizing vasculitides (polyarteritis nodosa and ANCA-associated vasculitides).

Systemic necrotizing vasculitis comprises a group of diseases resembling polyarteritis nodosa and anti-neutrophil cytoplasmic antibody-associated vasculitis (ANCA): granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis, and microscopic polyangiitis. The definitive diagnosis is made in cooperation with a reference center for autoimmune diseases and rare systemic diseases or a competency center. The management goals are: to obtain remission and, in the long term, healing; to reduce the risk of relapses; to limit and reduce the sequelae linked to the disease; to limit the side effects and the sequelae linked to the treatments; to improve or at least maintain the best possible quality of life; and to maintain socio-professional integration and/or allow a rapid return to school and/or professional activity. Information and therapeutic education of the patients and those around them are an integral part of the care. All health professionals and patients should be informed of the existence of patient associations. The treatment of vasculitis is based on variable combinations of glucocorticoids and immunosuppressants, chosen and adapted according to the disease concerned, the severity and/or extent of the disease, and the underlying factors (age, kidney function, etc.). Follow-up clinical and paraclinical examinations must be carried out regularly to clarify the progression of the disease, detect and manage treatment failures and possible relapses early on, and limit sequelae and complications (early then late) related to the disease or treatment. A distinction is made between the induction therapy, lasting approximately 3-6 months and aimed at putting the disease into remission, and the maintenance treatment, lasting 12-48 months, or even longer. The role of the increase or testing positive again for ANCA as a predictor of a relapse, which has long been controversial, now seems to have greater consensus: Anti-myeloperoxidase ANCAs are less often associated with a relapse of vasculitis than anti-PR3 ANCA.

[Intravascular large B cell lymphoma pathological findings led by positron emission tomography findings: About one case]. / Diagnostic histologique de lymphome intravasculaire guidé par une hyperfixation corticale rénale à la tomographie par émission de positons : à propos d'un cas.

Intravascular large B cell lymphoma is a rare non-Hodgkin large B cell lymphoma disease, with heterogeneous clinical manifestation and difficult pathological diagnosis. Positron emission tomography may be helpfull in this context and has already been reported. A 45-year-old woman was admitted for persistent high fever, inflammatory syndrome and unexplained haemophagocytic syndrome. Bilateral cortical renal hypermetabolism at positron emission tomography initially misled to pyelonephritis diagnosis and secondarily led to kidney biopsy, which showed intravascular large B cell lymphoma. Renal involvement in intravascular large B cell lymphoma is rare and is usually characterized by acute renal failure and proteinuria. Global hypermetabolism at positron emission tomography has already been described in this context, but cortical hypermetabolism has never been associated with pathological findings. In front of persistent high fever without etiology, this positron emission tomography feature must lead to intravascular large B cell lymphoma suspicion and to kidney biopsy to obtain pathological proof.

ANCA-associated vasculitides: Recommendations of the French Vasculitis Study Group on the use of immunosuppressants and biotherapies for remission induction and maintenance.

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.