Frequency and characteristics of severe relapse in giant cell arteritis.

OBJECTIVES: To assess the frequency and characteristics of severe relapse in patients with giant cell arteritis (GCA) in a real-life setting. METHODS: In a monocentric database of 530 patients, we retrospectively analysed patients who experienced at least one relapse and distinguished severe from nonsevere relapses. Severe relapse was defined by the occurrence of an ischaemic event (ophthalmologic, neurologic, digestive, limb ischaemia), the occurrence of an aortic complication (i.e. new or worsening of aortic dilation, aortic dissection), or new or worsening of vascular stenosis. RESULTS: From the cohort of 530 patients, 242 (45.7%) patients experienced relapse at least once, including 13 (2.5% of the cohort) who experienced severe relapse. Among the 464 recorded relapses, 14 (3% of all relapses) were severe. Severe relapse corresponded to the following vascular events: a peripheral limb ischaemia in 6 patients, a visual event in 3 patients (including 2 acute anterior ischaemic anterior neuropathies), an aortic complication in 3 patients, a mesenteric ischaemia in one patient and an ischaemic stroke in one patient.When compared with the 229 patients who experienced nonsevere relapses, severe relapse patients were younger at diagnosis (p= 0.02), more frequently showed limb claudication at baseline (p< 0.0001) and fewer GCA-related cranial signs (p< 0.0001). At diagnosis, more large-vessel vasculitis on imaging (82% vs 36%, p= 0.002) were observed in patients with severe relapse. The death rate did not differ between patients with severe and nonsevere relapses. CONCLUSION: In a real-life setting, relapse affects nearly half of GCA patients, but severe relapse is rare.

The diagnostic challenge of patients with anti-U1-RNP antibodies.

Anti-U1-RNP antibodies are necessary for the diagnosis of mixed connective tissue disease (MCTD), but they are also prevalent in other connective tissue diseases, especially systemic lupus erythematosus (SLE), from which distinction remains challenging. We aimed to describe the presentation and outcome of patients with anti-U1-RNP antibodies and to identify factors to distinguish MCTD from SLE. We retrospectively applied the criteria sets for MCTD, SLE, systemic sclerosis (SSc) and rheumatoid arthritis (RA) to all patients displaying anti-U1-RNP antibodies in the hospital of Caen from 2000 to 2020. Thirty-six patients were included in the analysis. Eighteen patients (50%) satisfied at least one of the MCTD classifications, 11 of whom (61%) also met 2019 ACR/EULAR criteria for SLE. Twelve other patients only met SLE without MCTD criteria, and a total of 23 patients (64%) met SLE criteria. The most frequent manifestations included Raynaud's phenomenon (RP, 91%) and arthralgia (67%). We compared the characteristics of patients meeting only the MCTD (n = 7), SLE (n = 12), or both (n = 11) criteria. Patients meeting the MCTD criteria were more likely to display SSc features, including sclerodactyly (p < 0.01), swollen hands (p < 0.01), RP (p = 0.04) and esophageal reflux (p < 0.01). The presence of scleroderma features (swollen hands, sclerodactyly, gastro-oesophageal reflux), was significantly associated with the diagnosis of MCTD. Conversely, the absence of those manifestations suggested the diagnosis of another definite connective tissue disease, especially SLE.

Tolerance of glucocorticoids in giant cell arteritis: a study of patient-reported adverse events.

OBJECTIVE: To assess patients' self-reported glucocorticoid (GC)-related adverse events (AEs) in a GCA population. METHODS: A questionnaire was sent to the 100 patients most recently diagnosed with GCA in a tertiary centre. This questionnaire included open- and close-ended questions on the disease and GC effects. Eight primary AE areas were analysed: cardiovascular, metabolic, muscle, cognitive and psychologic, bone, cutaneous and hairiness, infective and visual complications. Including derivative subitems from preceding areas, a total of 18 GC-related AEs were analysed separately and according to GC duration. RESULTS: Ninety patients were analysed and 89 (99%) reported at least one GC-related AE [median 6 (range 1-11)]. Cognitive and psychological changes, primarily insomnia (72%), affected 90% of patients. Cutaneous changes and muscle loss affected 70% of patients, with frequent impairment of physical autonomy (P = 0.007) associated with this event. Metabolic issues, especially weight gain (40%) and diabetes mellitus (20%), affected 49% of patients. Conversely, vision troubles and bone fractures were mentioned by 42% and 9% of patients, respectively, and more frequently in patients who received GCs for >18 months (P = 0.01 and P = 0.007, respectively). Cardiovascular changes and infections affected 30% and 26% of patients, respectively. CONCLUSION: This real-life study of GC tolerance assessed using a self-evaluation provides pragmatic and updated data reminding us that GC tolerance remains more noteworthy than ever. This study suggests carefully monitoring GC-related AEs during follow-up and encourages GC-sparing strategies in some patients.

Steroid-sparing effect of anakinra in giant-cell arteritis: a case series with clinical, biological and iconographic long-term assessments.

OBJECTIVES: The treatment of GCA relies on corticosteroids but is burdened by a high rate of relapses and adverse effects. Anti-IL-6 treatments show a clear benefit with a significant steroid-sparing effect, but late relapses occur after treatment discontinuation. In addition to IL-6, IL-1 also appears to play a significant role in GCA pathophysiology. We report herein the efficacy of anakinra, an IL-1 receptor antagonist, in six GCA patients exhibiting corticosteroid dependence or resistance, specifically analysing the outcome of aortitis in four of them. METHODS: This retrospective study analysed the cases of all GCA patients treated with anakinra from the French Study Group for Large Vessel Vasculitis. RESULTS: After a median duration of anakinra therapy of 19 (18-32) months, all six patients exhibited complete clinical and biological remission. Among the four patients with large-vessel involvement, one had a disappearance of aortitis under anakinra and three showed a decrease in vascular uptake. After a median follow-up of 56 (48-63) months, corticosteroids were discontinued in four patients, and corticosteroid dosage could be decreased to 5 mg/day in two patients. One patient relapsed 13 months after anakinra introduction in the context of increasing the daily anakinra injection interval to every 48 h. Three patients experienced transient injection-site reactions, and one patient had pneumonia. CONCLUSION: In this short series, anakinra appears to be an efficient and safe steroid-sparing agent in refractory GCA, with a possible beneficial effect on large-vessel involvement.

Interest of immunodeficiency screening in adult after admission in medical intensive care unit for severe infection, a retrospective and a prospective study: the Intensive Care Unit and Primary and Secondary Immunodeficiency (ICUSPID) study.

BACKGROUND: Primary immunodeficiency (PID) in adults is rare and mostly revealed by infections. MATERIAL AND METHODS: Adults without predisposing factors who were admitted to an intensive care unit (ICU) for infection were screened for PID. RESULTS: Six PID cases were diagnosed, mostly revealed by encapsulated bacterial infections. CONCLUSION: Investigation of PID after ICU discharge should be considered to improve early detection.

Giant-cell arteritis: concordance study between aortic CT angiography and FDG-PET/CT in detection of large-vessel involvement.

PURPOSE: The purpose of our study was to assess the concordance of aortic CT angiography (CTA) and FDG-PET/CT in the detection of large-vessel involvement at diagnosis in patients with giant-cell arteritis (GCA). METHODS: We created a multicenter cohort of patients with GCA diagnosed between 2010 and 2015, and who underwent both FDG-PET/CT and aortic CTA before or in the first ten days following treatment introduction. Eight vascular segments were studied on each procedure. We calculated concordance between both imaging techniques in a per-patient and a per-segment analysis, using Cohen's kappa concordance index. RESULTS: We included 28 patients (21/7 women/men, median age 67 [56-82]). Nineteen patients had large-vessel involvement on PET/CT and 18 of these patients also presented positive findings on CTA. In a per-segment analysis, a median of 5 [1-7] and 3 [1-6] vascular territories were involved on positive PET/CT and CTA, respectively (p = 0.03). In qualitative analysis, i.e., positivity of the procedure suggesting a large-vessel involvement, the concordance rate between both procedures was 0.85 [0.64-1]. In quantitative analysis, i.e., per-segment analysis in both procedures, the global concordance rate was 0.64 [0.54-0.75]. Using FDG-PET/CT as a reference, CTA showed excellent sensitivity (95%) and specificity (100%) in a per-patient analysis. In a per-segment analysis, sensitivity and specificity were 61% and 97.9%, respectively. CONCLUSIONS: CTA and FDG-PET/CT were both able to detect large-vessel involvement in GCA with comparable results in a per-patient analysis. However, PET/CT showed higher performance in a per-segment analysis, especially in the detection of inflammation of the aorta's branches.

Evolution and outcomes of aortic dilations in giant cell arteritis.

OBJECTIVES: To identify factors associated with the progression of giant cell arteritis (GCA)-related or associated aortic dilations. METHODS: In this retrospective study, 47 GCA patients with aortic dilation were longitudinally analyzed. Each patient underwent ≥2 imaging scans of the aorta during the follow-up. Three progression statuses of aortic dilations were distinguished: fast-progressive (FP) defined by a progression of the aortic diameter ≥5 mm/year or ≥1 cm/2 years, slow progressive (SP) by a progression of the aortic diameter >1 mm during the follow-up, and not progressive (NP) when aortic diameter remained stable. RESULTS: Among the 47 patients with aortic dilation, the thoracic section was involved in 87 % of patients. Within a total follow-up of 89 [6-272] months, we identified 13 (28 %) patients with FP dilations, and 16 (34 %) and 18 (38 %) patients with SP and NP dilations, respectively. No differences regarding baseline characteristics, cardiovascular risk factors or treatments were observed among the 3 groups. However, FP patients more frequently showed atheromatous disease (p = 0.04), with a more frequent use of statins (p = 0.04) and antiplatelet agents (p = 0.02). Among the 27 (57 %) patients with aortitis, aortic dilation developed on an inflammatory segment in 23 (85 %). Among the FP patients who underwent aortic surgery with available histology (n = 3), all presented active vasculitis. CONCLUSION: This study suggests that aortic inflammation, as well as atheromatous disease, might participate in the fast progression of aortic dilation in GCA.

Efficacy and tolerance of methotrexate in a real-life monocentric cohort of patients with giant cell arteritis.

OBJECTIVES: To assess the indications, efficiency and tolerance profiles of methotrexate (MTX) in patients with giant cell arteritis (GCA) in a real-life setting. METHODS: From a monocentric database of >500 GCA patients, we retrospectively selected 49 patients who received MTX between 2010 and 2020. Cumulative glucocorticoid (GC) doses, the number of relapses and GC-related adverse events were recorded before, during and after MTX. We separately analyzed the 3 main indications of MTX, i.e., disease relapse, GC-sparing strategy, and GCA presentation. RESULTS: With a median follow-up of 84 [10-255] months, 25 (51%) and 18/41 (44%) patients relapsed during MTX treatment and after its discontinuation, respectively. Among the 40 patients who relapsed before MTX, 26 (65%) experienced a new relapse after MTX introduction. Once MTX was introduced, 24 (49%) patients were able to discontinue GC after 20.5 [7-64] months. No significant difference in cumulative GC doses were noted before and after MTX introduction with a total GC dose of 14.7 [1.05-69.4] grams. At the last follow-up, MTX was discontinued in 41 patients, including 13 (32%) due to clinicobiological remission, 12 (30%) due to treatment failure and 15 (36%) due to side effects. CONCLUSION: Our real-life study showed a modest beneficial effect of MTX on relapse in patients with GCA. However, we did not observe any GC-sparing effect in this study. Other studies are needed to assess the GC-sparing effect in patients in whom GC management is adapted from recent recommendations.

Evolution of the Therapeutic Management of Giant Cell Arteritis: Analysis of Real-Life Practices over Two Timeframes (2014-2017 and 2018-2020).

Objectives: To determine how therapeutic strategies for giant cell arteritis (GCA), especially glucocorticoid (GC) management, evolved between 2014 and 2020. Patients and Methods: Consecutive GCA patients followed for at least 24 months in a single tertiary center were enrolled and separated into two groups: those diagnosed from 2014 to 2017 and those diagnosed from 2018 to 2020. GC doses (mg/kg/day) were analyzed at onset, at Month 3 (M3) and, if continued, at M6, M12, M18 and M24. Physicians' practices were also individually analyzed. Results: Among the 180 patients included, 96 (53%) were diagnosed in 2014-2017 and 84 (47%) in 2018-2020. All patients received GC at diagnosis without a difference in the initial dose between the two groups (p = 0.07). At M3, the daily dose was lower in patients treated after 2017 (p = 0.002). In patients who still received GC at M6 (p = 0.0008), M12 (p = 0.01) and M24 (p = 0.02), the daily GC dose was still lower in patients treated after 2017. The proportion of patients who definitively discontinued GC use before M18 (42% versus 21%, p = 0.003) was higher in those treated after 2017. The rates of immunosuppressant use were not different between the two time periods (31% versus 38%, p = 0.34), but tocilizumab replaced methotrexate. Significant differences were observed among practitioners regarding the GC doses at M6 (p = 0.04) and M12 (p = 0.04), the total GC duration (p = 0.02) and the ability to stop GC before M18 (p = 0.007). Conclusions: This real-life study showed a global change in GC management over time for GCA patients, with important variability among physicians' practices.

Characteristics of ANCA-associated vasculitis with aneurysms: Case series and review of the literature.

INTRODUCTION: ANCA-associated vasculitis (AAV) is an exceptional cause of small and large vascular aneurysms. Here, we present the phenotypic characteristics of patients with AAV associated with the presence of aneurysms. METHODS: We conducted a retrospective multicenter study and a systematic review of the literature. Only AAV patients with positive ANCA results and > 1 aneurysm(s) were enrolled. Patients were recruited through a call of observations among the French Vasculitis Study Group (FVSG) and the French Internal Medicine Network. Patients with aneurysm rupture were compared to those without. RESULTS: We enrolled 51 patients in the cohort, including 31 (67%) with granulomatosis with polyangiitis. The median Birmingham Vasculitis Activity Score was 18 [6-41]. A total of 92 aneurysms were noted, 74% of which involved medium-sized arteries, particularly the renal artery. During a follow-up of 24 [6-56] months, 22 (43%) patients experienced aneurysmal rupture, 91% of which involved medium-sized vessels. Patients with aneurysmal rupture showed significantly more pulmonary infiltrates and higher creatinine levels at baseline than patients without rupture. Initial treatments did not differ between the two groups. Ten (20%) patients died during the follow-up, including three from an aneurysmal rupture. CONCLUSION: Aneurysms were more frequently observed in GPA patients and predominantly affected medium-sized vessels, especially the renal arteries. The risk of rupture was high and occurred in >40% of patients. Because of their increased mortality, further studies are required to better manage this subset of patients.

Preventive effect of beta-blockers in the development of aortic dilation in giant cell arteritis-related aortitis.

OBJECTIVES: To analyze whether beta-blockers (BBs), in addition to conventional care, can decrease the risk of aortic dilation in giant-cell arteritis (GCA)-related aortitis. METHODS: We conducted in a single medical center retrospective study including 65 consecutive patients with GCA-related aortitis who all underwent aortic morphology control during follow-up. The impact of previous cardiovascular (CV) risk factors and/or events on BB prescription and on the risk for new aortic dilation was analyzed using a weighted (8-point maximum) score between 0 (i.e., 0/8 CV risk factors and events) and 1 (i.e., 8/8). RESULTS: Among the 65 patients with GCA-related aortitis, 15 (23%) were taking BBs before GCA diagnosis and continued them thereafter. The vascular score was significantly higher in patients who received BBs (0.25 [0.125-0.625] vs. 0.125 [0-0.625] in patients without BBs, p < 0.0001). The median follow-up was 91 [25-163] months in GCA patients taking BBs and 61 [14-248] months in patients not taking BBs (p = 0.13). None of the patients taking BBs developed a new aortic dilation, whereas 15 (15/50; 30%) patients not taking BBs did (p = 0.01), as detected at a median time of 38 [6-120] months after the first imaging. Rates of other CV events during follow-up did not differ between the groups (p = 1). CONCLUSIONS: This study is the first to suggest that BBs in addition to conventional care in patients with GCA-related aortitis may help to prevent the risk of aortic dilation during follow-up. Larger-sized studies are required to confirm these results.

Impact of Glucocorticoid Cumulative Doses in a Real-Life Cohort of Patients Affected by Giant Cell Arteritis.

OBJECTIVES: To describe the impact of cumulative glucocorticoid (GC) doses on related adverse events (AEs) in giant cell arteritis (GCA) in a real-life setting. METHODS: The medical charts of the last 139 consecutive GCA patients followed in a tertiary centre were retrospectively analysed. The cumulative GC doses were calculated, and the main GC-related AEs were collected during the follow-up. RESULTS: After a median follow-up duration of 35.6 (2-111) months, the median cumulative GC dose in the 139 patients was 9184 (1770-24,640) mg, and 131 patients (94%) presented at least one GC-related AE. Infections (63%) were the most frequently reported GC-related AE, followed by metabolic events (63%), including weight gain in 51% of them. Cardiovascular and neuropsychiatric events occurred in 51% and 47% of patients, respectively. Osteoporotic fractures, muscular involvement, digestive events, geriatric deterioration, skin fragility, ophthalmologic complications and hypokalaemia were reported in <35% of patients. Cardiovascular events (p = 0.01), osteoporotic fractures (p = 0.004), cataract occurrence (p = 0.03), weight gain (p = 0.04) and infections (p = 0.01) were significantly associated with GC cumulative doses > 9 g. Longer GC durations were associated with cataract occurrence (p = 0.01), weight gain (p = 0.03) and all-grade infections (p = 0.048), especially herpes zoster occurrence (p = 0.003). Neuropsychiatric and metabolic events appeared within the first months after GC introduction, whereas herpes zoster recurred, and most cardiovascular AEs emerged after 1 year. Geriatric events, especially osteoporotic fractures, occurred 2 years after GC introduction. CONCLUSION: This study highlights how frequent GC-related AEs are and the impact of prolonged GC and cumulative doses.

Impact of Giant Cell Arteritis and Its Treatment on the Patient's Quality of Life: A Single-Center Self-Assessment Study.

Little is known about the impact of giant cell arteritis (GCA) and its treatment on patient-reported physical, mental, and psychic quality of life (QoL). In this monocentric study, a questionnaire was sent to the 100 last patients diagnosed with GCA and followed-up in a single tertiary center. Their physical, mental and psychic status were self-assessed via close-ended questions, the 12-item short form survey (SF-12) and the 15-item geriatric depression scale (GDS). We aimed to identify parameters that were significantly associated with moderate-to-severe disability in both physical and mental domains. Ninety patients were analyzable. Moderate to severe physical disability was found in 41 (46%) patients. In multivariate analysis, walking difficulties (OR, 95% CI 8.42 [2.98-26.82], p <0.0001), muscle mass and strength reduction (OR, 95% CI 4.38 [1.37-16.31], p = 0.01) and age >80 (OR, 95% CI 4.21 [1.44-13.61], p = 0.008) were independent findings associated with moderate to severe physical disability. Moderate to severe mental disability was found in 30 (33%) patients. In multivariate analysis, depressive mood (OR, 95% CI 11.05 [3.78-37.11], p < 0.0001), felt adverse events attributable to glucocorticoids (OR, 95% CI 10.54 [1.65-213.1], p = 0.01) and use of immune-suppressants (OR, 95% CI 3.50 [1.14-11.87], p = 0.03) were independent findings associated with moderate to severe mental disability. There was a statistically significant negative correlation between GDS and the physical and/or mental disability scores (GDS and PCS-12: r = -0.33, p = 0.0013; GDS and MCS-12: r = -0.36, p = 0.0005). In conclusion, this study identified via a self-assessment of patients with GCA some medical and modifiable findings that significantly affect their physical and mental quality of life. A better knowledge of these factors may help improve the care of GCA patients.

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.

New insights on IgA vasculitis with underlying solid tumor: a nationwide French study of 30 patients.

OBJECTIVE: IgA vasculitis (IgAV) frequently occurs during or after a mucosal infection; it also rarely occurs in patients with cancer. We hypothesized that cancer could impact the baseline characteristics and/or outcome of vasculitis. We aimed to describe the presentation of IgAV in patients with cancer (IgAV ca+) compared to patients without cancer. METHODS: We conducted a nationwide retrospective study of adult patients in France who presented with both IgAV and cancer. Baseline characteristics were described and compared with those of the 260 patients included in a nationwide French IgAV study. RESULTS: Thirty patients were included. The mean age was 69 ± 12 years; 80% were men. Compared to patients without underlying cancer, IgAV ca+ patients were older (69 ± 12 vs. 50 ± 18 years; p < 0.0001) and they presented more frequently with necrotic purpura (53 vs. 26%; p < 0.002) and intra-alveolar hemorrhage (10 vs. 0.5%; p < 0.0001). IgAV ca+ patients frequently had elevated serum IgA levels (79 vs. 53%; p < 0.034); most (n = 22, 73%) had adenocarcinoma or urothelial carcinoma involving the large intestines (n = 6), bladder (n = 5), and lung (n = 5). Most IgAV ca+ patients had progressive cancer (n = 21); a minority had metastatic disease (n = 2) at IgAV diagnosis. After a median follow-up of 3 months, 8 deaths were observed but none was related to IgAV. CONCLUSION: Compared to their noncancer counterpart, patients with IgAV related to cancer were older and more frequently presented with necrotizing purpura, intra-alveolar hemorrhage, and elevated serum IgA levels. Adult patients with IgAV and these latter characteristics should be carefully screened for cancer. Key Points • Clinical and biological characteristics of patients presenting with IgAV are distinct depending on the underlying cause of vasculitis related to cancer. • Patients with IgAV related to cancer are older, and compared to their counterparts without IgAV, they present more frequently with necrotic purpura, alveolar hemorrhage, and elevated serum IgA levels. • All adult patients with IgAV should be screened for cancer, and there should be a focus on elderly male patients presenting with necrotic purpura and/or alveolar hemorrhage.

Factors Associated with Relapse and Dependence on Glucocorticoids in Giant Cell Arteritis.

OBJECTIVE: To identify characteristics and factors associated with relapse and glucocorticoid (GC) dependence in patients with giant cell arteritis (GCA). METHODS: We retrospectively analyzed 326 consecutive patients with GCA followed for at least 12 months. Factors associated with relapse and GC dependence were identified in multivariable analyses. RESULTS: The 326 patients (73% women) were followed up for 62 (12-262) months. During followup, 171 (52%) patients relapsed, including 113 (35%) who developed GC dependence. Relapsing patients had less history of stroke (p = 0.01) and presented large-vessel vasculitis (LVV) more frequently on imaging (p = 0.01) than patients without relapse. During the first months, therapeutic strategy did not differ among relapsing and nonrelapsing patients. GC-dependent patients were less likely to have a history of stroke (p = 0.004) and presented LVV on imaging more frequently (p = 0.005) than patients without GC-dependent disease. In multivariable analyses, LVV was an independent predictive factor of relapse (HR 1.49, 95% CI 1.002-2.12; p = 0.04) and GC dependence (OR 2.19, 95% CI 1.19-4.05; p = 0.01). Conversely, stroke was a protective factor against relapse (HR 0.21, 95% CI 0.03-0.68; p = 0.005) and GC-dependent disease (OR 0.10, 95% CI 0.001-0.31; p = 0.0005). Patients with a GC-dependent disease who received a GC-sparing agent had a shorter GC treatment duration than those without (p = 0.008). CONCLUSION: In this study, LVV was an independent predictor of relapse and GC dependence. Further prospective studies are needed to confirm these findings and to determine whether patients with LVV require a different treatment approach.

Characteristics and outcomes of patients with ophthalmologic involvement in giant-cell arteritis: A case-control study.

PURPOSE: To describe the characteristics and outcome of patients with giant-cell arteritis (GCA)-related ophthalmologic involvement at diagnosis. METHODS: In a retrospective single-center cohort of 409 consecutive patients with GCA, we retrieved 104 patients with visual symptoms at GCA diagnosis and we compared them to 104 age- and sex-matched controls without ophthalmologic involvement. Each visual symptom was associated to an ophthalmologic diagnosis that was centrally re-assessed by an ophthalmologist. RESULTS: Compared to controls, patients with visual symptoms showed less fever (p = 0.0006), less polymyalgia rheumatica (p = 0.02) and lower acute phase reactants (p = 0.004). Blurred vision (in 60% of patients), amaurosis fugax (in 18%), diplopia (in 13%) and permanent visual loss (in 9%) were the four visual symptoms described by patients before GCA diagnosis. Anterior ischemic optic neuropathy (AION) was found in 47 (45%) patients, followed by central retinal artery occlusion (CRAO) in 15 (15%). Two patients had both involvements. The delay of glucocorticoids initiation was not different between patients with and without visual symptoms (p = 0.06). Among the 60 patients with initial AION and/or CRAO, 39 (65%) kept definite blindness or important visual damage, although 45 (75%) had received intravenous (IV) pulses of methylprednisolone. A new ischemic event (AION in all cases) occurred in 4% of patients with visual symptoms despite the initiation of treatment. CONCLUSION: Ophthalmologic involvement was observed in one-quarter of our GCA patients. AION is still associated with the worst visual prognosis, and IV methylprednisolone pulses did not reduce the risk of blindness in our study.

Intra-Alveolar Haemorrhage Complicating IgA Vasculitis: A Case Report, Literature Review and Discussion of Treatment.

INTRODUCTION: Immunoglobulin A vasculitis (IgAV) is a small-vessel vasculitis with IgA-dominant immune deposits. IgAV frequently involves the skin, gastrointestinal tract, joints and kidneys. In contrast to other types of small-vessel vasculitis, IgAV is rarely complicated by intra-alveolar haemorrhage (IAH). METHODS/RESULTS: We describe a patient with relapsing bladder cancer who presented with IAH during the course of IgAV successfully treated with corticosteroids alone. CONCLUSION: This case report reminds us that IgAV can manifest with IAH. There are no robust data to support the systematic use of cyclophosphamide or plasma exchange as first-line therapy for IgAV with IAH. LEARNING POINTS: Intra-alveolar haemorrhage in IgA vasculitis is an uncommon but important condition.The treatment strategies for IgA vasculitis and intra-alveolar haemorrhage and their rare association are discussed with reference to the literature.

Clinical Effect of Alpha-1 Antitrypsin Deficiency in Antineutrophil Cytoplasmic Antibody-associated Vasculitis: Results from a French Retrospective Monocentric Cohort.

OBJECTIVE: Deficiency in alpha-1 antitrypsin (AAT) is a possible pathogenic cofactor in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). However, the clinical effect of AAT deficiency remains poorly established in this setting. This study aimed to describe the clinical phenotypes and outcomes of AAV according to AAT phenotypes. METHODS: This study was conducted retrospectively at Caen University Hospital and included all consecutive granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) patients with positive proteinase 3-ANCA or myeloperoxidase-ANCA, from January 2000 or September 2011, respectively, to June 2016. AAT dosage (nephelometry) and phenotyping (isoelectric focusing in agarose gel) were performed. RESULTS: Among the 142 patients with AAV, including 88 GPA and 54 MPA, 102 (72%) had the MM phenotype, 5 (4%) had a nonpolymerogenic M-variant phenotype, 18 (13%) had the deficient allele MZ, 12 (8%) had MS, 2 (1%) had ZZ, 2 (1%) had SZ, and 1 (1%) had SS. M, Z, and S allele frequencies were 84%, 8%, and 6%, respectively. No association was observed between AAT deficiency and ANCA subtype or AAV phenotype, except for intraalveolar hemorrhage (IAH), which was more frequent in patients harboring at least 1 of the deficient Z or S alleles than in those without any deficient alleles (p < 0.01). Global, renal, or relapse-free survival rates were similar for all subgroups. CONCLUSION: This study shows that AAT deficiency confers, independently of ANCA subtype, a higher risk of IAH. Prospective studies are required to refine these data and to assess the need for replacement therapy in AAT-deficient patients with AAV.