Gwenola Maigne

Glomerular lesions in patients with sickle cell disease.

Sickle cell disease (SCD) is an increasing cause of chronic kidney disease, but the spectrum of glomerular lesions and their underlying mechanisms remain poorly described. We reviewed 18 renal biopsies from patients with SCD and glomerular involvement and studied the expression of hypoxic markers in the biopsy specimens. Four histopathologic variants were distinguished: focal segmental glomerulosclerosis (FSGS) (39%), membranoproliferative glomerulonephritis (28%), thrombotic microangiopathy glomerulopathy (17%), and specific sickle cell disease glomerulopathy (17%). Chronic organ damage and history of acute chest syndrome were associated with the occurrence of SCD glomerulopathy. All patients exhibited macroalbuminuria but only 6 patients displayed impaired renal function. SCD was not associated with a specific FSGS histologic variant. Long-term follow-up analysis revealed that 50% of patients exhibited chronic kidney disease. Regardless of the histologic variants, immunohistochemistry did not reveal a specific induction of hypoxic markers (inducible nitric oxide synthase [iNOS], nitrotyrosine, hypoxia-inducible factor [HIF]-1&agr;) at the time of renal biopsy. This large study shows that a wide spectrum of glomerular lesions is associated with SCD. Whatever lesions are observed, the renal prognosis is poor, and early renoprotective treatment is necessary. Hypoxic state does not seem to play a key role in the progression of glomerular lesions, but its potential role at an early stage of glomerular injury requires further investigation. Abbreviations: FSGS = focal segmental glomerulosclerosis, GFR = glomerular filtration rate, HIF = hypoxia-inducible factor, iNOS = inducible nitric oxide synthase, MPGN = membranoproliferative glomerulonephritis, NOS = not otherwise specified, SCD = sickle cell disease, SCDG = specific sickle cell disease glomerulopathy, TMA = thrombotic microangiopathy.

18F-fluorodeoxyglucose positron emission tomography and the risk of subsequent aortic complications in giant-cell arteritis: A multicenter cohort of 130 patients.

AbstractPrevious studies reported a 2- to 17-fold higher risk of aortic complications (dilation or dissection) in patients with giant-cell arteritis (GCA). We aimed to determine whether or not GCA patients with large-vessel involvement demonstrated by positron emission tomography with 18F-fluorodeoxyglucose combined with computed tomography (FDG-PET/CT) have a higher risk of aortic complications. We conducted a retrospective multicenter study between 1995 and 2014. Patients were included if they fulfilled at least 3 American College of Rheumatology criteria for GCA, or 2 criteria associated with extratemporal biopsy-proven giant-cell vasculitis; they underwent at least 1 FDG-PET/CT scan at diagnosis or during follow-up; and the morphology of the aorta was assessed by medical imaging at diagnosis. Patients with an aortic complication at the time of diagnosis were excluded. Of the 130 patients included [85 women (65%), median age 70 (50–86)], GCA was biopsy proven in 77 (59%). FDG-PET/CT was performed at diagnosis in 63 (48%) patients and during the follow-up period in the 67 (52%) remaining patients. FDG-PET/CT was positive in 38/63 (60%) patients at diagnosis and in 31/67 (46%) patients when performed during follow-up (P = NS). One hundred four patients (80%) underwent at least 1 morphological assessment of the aorta during follow-up. Nine (9%) patients developed aortic complications (dilation in all and dissection in 1) at a median time of 33 (6–129) months after diagnosis. All of them displayed large-vessel inflammation on previous FDG-PET/CT. A positive FDG-PET/CT was significantly associated with a higher risk of aortic complications (P = 0.004).In our study, a positive FDG-PET/CT was associated with an increased risk of aortic complications at 5 years.

Efficacy of Azacitidine in autoimmune and inflammatory disorders associated with myelodysplastic syndromes and chronic myelomonocytic leukemia

This retrospective study describes efficacy of Azacitidine on autoimmune disorders (AID) associated with MDS/CMML in 22 patients. Response of AID to Azacitidine was observed in 19 patients (86%). Reduction or discontinuation of steroids and/or immunosuppressive therapy (IST) was possible in 16 cases (73%). Hematologic response was seen in 55% of the patients. MDS/CMML and AID evolution was concordant in 13 cases (59%): both favorable (n=11), both unfavorable (n=2), but AID improved while MDS/CMML worsened (n=8) and vice versa (n=1). Azacitidine frequently seems effective in controlling steroid-dependent AID associated with MDS/CMML, but prospective studies are necessary to confirm those findings.

Giant-cell arteritis without cranial manifestations: Working diagnosis of a distinct disease pattern.

AbstractDiagnosis of giant-cell arteritis (GCA) is challenging in the absence of cardinal cranial symptoms/signs. We aimed to describe the clinical presentation, diagnostic process, and disease course of GCA patients without cranial symptoms, and to compare them to those of patients with typical cranial presentation. In this retrospective multicenter study, we enrolled patients with GCA who satisfied at least 3 of the 5 American College of Rheumatology criteria for GCA, or 2 criteria associated with contributory vascular biopsy other than temporal artery biopsy or with demonstration of large-vessel involvement; underwent iconographic evaluation of large arterial vessels (aortic CT scan or a positron emission tomography with 18F-fluorodeoxyglucose combined with computed tomography (FDG-PET/CT) scan or cardiac echography combined with a large-vessel Doppler) at diagnosis. We divided the cohort into 2 groups, distinguishing between patients without cranial symptoms/signs (i.e., headaches, clinical temporal artery anomaly, jaw claudication, ophthalmologic symptoms) and those with cranial symptoms/signs. In the entire cohort of 143 patients, all of whom underwent vascular biopsy and vascular imaging, we detected 31 (22%) patients with no cranial symptoms/signs. In the latter, diagnosis was biopsy proven in an arterial sample in 23 cases (74% of patients, on a temporal site in 20 cases and on an extratemporal site in 3). One-third of these 31 patients displayed extracranial symptoms/signs whereas the remaining two-thirds presented only with constitutional symptoms and/or inflammatory laboratory test results. Compared to the 112 patients with cardinal cranial clinical symptoms/signs, patients without cranial manifestations displayed lower levels of inflammatory laboratory parameters (C-reactive level: 68 [9–250] mg/L vs 120 [3–120] mg/L; P < 0.01), highest rate of aorta and aortic branch involvement identified (19/31 (61%) vs 42/112 (38%); P = 0.02) and also a lower rate of disease relapse (12/31 (39%) vs 67/112 (60%); P = 0.04). Our results suggest that patients without cranial symptoms/signs are prone to lower inflammatory laboratory parameters, fewer relapses, and more large-vessel involvement than those displaying cardinal cranial manifestations. Further studies are therefore required in order to determine whether these 2 subgroups of patients have a different prognosis, and therefore warrant different therapeutic and monitoring regimens.

Giant Cell Arteritis-related Stroke: A Retrospective Multicenter Case-control Study.

Objective. Our aim was to describe patients with giant cell arteritis (GCA)–related stroke and to compare them with a control group of GCA patients without stroke. Methods. We created a retrospective multicenter cohort of patients with (1) GCA diagnosed according to the American College of Rheumatology criteria between 1995 and 2015, and (2) stroke occurring at the time of GCA diagnosis or occurring within 4 weeks of starting GCA therapy. The control group consisted of GCA patients without stroke. Results. Forty patients [21 women (53%), median age 78 (60–91) yrs] with GCA-related stroke were included and were compared with 200 control patients. Stroke occurred at GCA diagnosis in 29 patients (73%), whereas it occurred after diagnosis in 11 patients. Vertebrobasilar territory was involved in 29 patients (73%). Seven patients died within a few hours or days following stroke. Compared with the control group, stroke patients had more ophthalmic ischemic symptoms [25 (63%) vs 50 (25%), p < 0.001]. Conversely, they demonstrated lower biological inflammatory variables [C-reactive protein: 61 (28–185) mg/l vs 99 (6–400) mg/l, p = 0.04] and less anemia [22/37 (59%) vs 137/167 (79%), p = 0.03] than patients without stroke. Multivariate logistic regression revealed that the best predictors for the occurrence of stroke were the presence of ophthalmic ischemic symptoms at diagnosis (OR 5, 95% CI 2.14–12.33, p = 0.0002) and the absence of anemia (OR 0.39, 95% CI 0.16–0.99, p = 0.04). Conclusion. Stroke, especially in the vertebrobasilar territory, is more likely to occur in patients with GCA who experience recent ophthalmic ischemic symptoms and who exhibit low inflammatory variables.

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

BackgroundPrimary immunodeficiency (PID) in adults is rare and mostly revealed by infections.Material and MethodsAdults without predisposing factors who were admitted to an intensive care unit (ICU) for infection were screened for PID.ResultsSix PID cases were diagnosed, mostly revealed by encapsulated bacterial infections.ConclusionInvestigation of PID after ICU discharge should be considered to improve early detection.