Health related quality of life, remission and low lupus disease activity state in patients with systemic lupus erythematosus.

OBJECTIVES: To measure the association between systemic lupus erythematosus (SLE) remission and scores of patients reported outcome measures (PRO). METHODS: We performed a prospective cohort study of SLE patients with a 2-year follow-up, recording LupusPRO, LupusQol, SLEQOL, and SF-36 questionnaires. Remission was defined as remission-off-treatment (ROFT) and remission-on-treatment (RONT) according to the DORIS consensus. Mixed models accounting for repeated measures were used to compare groups as follow: ROFT and RONT versus no remission, and Lupus Low Disease activity state (LLDAS) versus no LLDAS. RESULTS: A total of 1478 medical visits and 2547 PRO questionnaires were collected during the follow-up from the 336 recruited patients. A between-group difference in PRO scores reaching at least 5 points on a 0-100 scale was obtained in the following domains: "lupus symptoms" (LLDAS: +5 points on the 0-100 scale, RONT: +9 and ROFT: +5), "lupus medication" (LLDAS: +5, RONT: +8 and ROFT: +9), "pain vitality" (LLDAS: +6, RONT: +9 and ROFT: +6) of LupusPRO, "role emotional" (LLDAS: +5, RONT: +8), "role physical" (RONT: +7 and ROFT: +7), "bodily pain" (RONT: +6), "mental health" (RONT: +5) and "social functioning" (RONT: +6) of SF-36. In contrast, a between-group difference reaching at least 5 points was not achieved for any of the LupusQol and SLEQOL domains. CONCLUSIONS: RONT, ROFT, and LLDAS were associated with significant and clinically relevant higher quality of life in most PRO domains of LupusPRO (disease-specific) and SF-36 (generic) questionnaires, but not with LupusQol and SLEQOL disease-specific questionnaires.

Haploinsufficiency of the Primary Familial Brain Calcification Gene SLC20A2 Mediated by Disruption of a Regulatory Element.

OBJECTIVE: Primary familial brain calcification (PFBC) is a rare cerebral microvascular calcifying disorder with diverse neuropsychiatric expression. Five genes were reported as PFBC causative when carrying pathogenic variants. Haploinsufficiency of SLC20A2, which encodes an inorganic phosphate importer, is a major cause of autosomal-dominant PFBC. However, PFBC remains genetically unexplained in a proportion of patients, suggesting the existence of additional genes or cryptic mutations. We analyzed exome sequencing data of 71 unrelated, genetically unexplained PFBC patients with the aim to detect copy number variations that may disrupt the expression of core PFBC-causing genes. METHODS: After the identification of a deletion upstream of SLC20A2, we assessed its consequences on gene function by reverse transcriptase droplet digital polymerase chain reaction (RT-ddPCR), an ex vivo inorganic phosphate uptake assay, and introduced the deletion of a putative SLC20A2 enhancer mapping to this region in human embryonic kidney 293 (HEK293) cells by clustered regularly interspaced short palindromic repeats (CRISPR) - CRISPR-associated protein 9 (Cas9). RESULTS: The 8p11.21 deletion, segregating with PFBC in a family, mapped 35 kb upstream of SLC20A2. The deletion carriers/normal controls ratio of relative SLC20A2 mRNA levels was 60.2% (P < 0.001). This was comparable with that of patients carrying an SLC20A2 premature stop codon (63.4%; P < 0.001). The proband exhibited a 39.3% decrease of inorganic phosphate uptake in blood (P = 0.015). In HEK293 cells, we observed a 39.8% decrease in relative SLC20A2 mRNA levels after normalization on DNA copy number (P < 0.001). DISCUSSION: We identified a deletion of an enhancer of SLC20A2 expression, with carriers showing haploinsufficiency in similar ranges to loss-of-function alleles, and we observed reduced mRNA levels after deleting this element in a cellular model. We propose a 3-step strategy to identify and easily assess the effect of such events. © 2020 International Parkinson and Movement Disorder Society.

Involvement and prognosis value of CD8(+) T cells in giant cell arteritis.

CD8(+) T cells participate in the pathogenesis of some vasculitides. However, little is known about their role in Giant Cell Arteritis (GCA). This study was conducted to investigate CD8(+) T cell involvement in the pathogenesis of GCA. Analyses were performed at diagnosis and after 3 months of glucocorticoid treatment in 34 GCA patients and 26 age-matched healthy volunteers. Percentages of CD8(+) T-cell subsets, spectratype analysis of the TCR Vß families of CD8(+) T cells, levels of cytokines and chemokines and immunohistochemistry of temporal artery biopsies (TAB) were assessed. Among total CD8(+) T cells, percentages of circulating cytotoxic CD8 T lymphocytes (CTL, CD3(+)CD8(+)perforin(+)granzymeB(+)), Tc17 (CD3(+)CD8(+)IL-17(+)), CD63(+)CD8(+) T cells and levels of soluble granzymes A and B were higher in patients than in controls, whereas the percentage of Tc1 cells (CD3(+)CD8(+)IFN-γ(+)) was similar. Moreover, CD8(+) T cells displayed a restricted TCR repertoire in GCA patients. Percentages of circulating CTL, Tc17 and soluble levels of granzymes A and B decreased after treatment. CXCR3 expression on CD8(+) T cells and its serum ligands (CXCL9, -10, -11) were higher in patients. Analyses of TAB revealed high expression of CXCL9 and -10 associated with infiltration by CXCR3(+)CD8(+) T cells expressing granzyme B and TiA1. The intensity of the CD8 T-cell infiltrate in TAB was predictive of the severity of the disease. This study demonstrates the implication and the prognostic value of CD8(+) T-cells in GCA and suggests that CD8(+) T-cells are recruited within the vascular wall through an interaction between CXCR3 and its ligands.

Responsiveness of the 36-item Short Form Health Survey and the Lupus Quality of Life questionnaire in SLE.

OBJECTIVES: This study aimed to estimate the responsiveness to change of a generic [the 36-item Short Form Health Survey (SF-36)] and a specific health-related quality of life questionnaire [the Lupus Quality if Life questionnaire (LupusQoL)] according to SLE patients' self-reported changes in health status. METHODS: In a cohort of 185 SLE patients, quality of life (QoL) was measured three times at 3 month intervals by the LupusQoL and SF-36 questionnaires. Anchors for responsiveness were defined by patients' global assessment of disease impact according to changes in a visual analogue scale (VAS), a 7-point Likert scale and a 0-3 scale of five patient-reported symptoms. Mean change and s.d. in worsening and improving patients according to anchors were estimated using mixed models for repeated measures. Standardized response means (SRMs) were calculated in each group. RESULTS: Patients [mean age 39.6 years (s.d. 10.5), mean Safety of Estrogen in Lupus Erythematosus National Assessment-SLEDAI score 2.6 (s.d. 3.5)] answered a total of 515 questionnaires. For the VAS and Likert global anchors, worsening patients showed a significant decrease in all LupusQoL domains except for burden to others, body image and fatigue and all SF-36 domains with low to moderate responsiveness. Improving patients had a significant increase in all LupusQoL domains except for intimate relationship and all SF-36 domains except for physical functioning and global health with low to moderate responsiveness. Regarding similar domains in the SF-36 and LupusQoL, SRMs were higher in LupusQoL domains in improving patients, while SF-36 domains had larger SRMs in worsening patients. CONCLUSION: Both the SF-36 and LupusQoL were responsive to changes in QoL in SLE patients over a 3 month interval. LupusQoL seems to be more appropriate to measure improvements in QoL.

Stroke associated with giant cell arteritis: a population-based study.

BACKGROUND: Giant cell arteritis (GCA) is the most common vasculitis in people ≥50 years and can be associated with stroke. We aimed to evaluate the epidemiology and characteristics of stroke in patients with GCA. METHODS: All patients with a biopsy-proven diagnosis of GCA were identified among residents of the city of Dijon, France (152 000 inhabitants), between 2001 and 2012 using a prospective database. Among these, patients who suffered from stroke were retrieved by crossing data from the population-based Dijon Stroke Registry. Demographics and clinical features were recorded. We considered that the stroke was GCA-related if the stroke revealed GCA or occurred between the onset of symptoms and 4 weeks after the start of treatment. RESULTS: Among the 57 biopsy-proven patients with GCA (incidence rate 10.9/100 000/year in individuals ≥50 years), 4 (7.0%) experienced a GCA-related stroke. Three were men and all had ≥2 vascular risk factors and were ≥80 years. The stroke was vertebrobasilar for 3/4 patients and undetermined for the remaining one. The incidence rate of GCA-related stroke in patients ≥50 years was 0.76/100 000/year (95% CI 0 to 2.47), 1.36/100 000/year in men (95% CI 0 to 3.63) and 0.33/100 000/year (95% CI 0 to 1.45) in women. CONCLUSIONS: This population-based study demonstrated that GCA-related stroke essentially affects the vertebrobasilar territory and mainly occurs in old men with associated vascular risk factors. Although rare, GCA symptoms must be searched for in elderly patients with stroke, and optimal vascular prevention must be conducted carefully in patients with GCA with a high vascular risk before initiating GCA treatment.

Th1 and Th17 lymphocytes expressing CD161 are implicated in giant cell arteritis and polymyalgia rheumatica pathogenesis.

OBJECTIVE: Giant cell arteritis (GCA) is the most frequently occurring vasculitis in elderly individuals, and its pathogenesis is not fully understood. The objective of this study was to decipher the role of the major CD4+ T cell subsets in GCA and its rheumatologic form, polymyalgia rheumatica (PMR). METHODS: A prospective study of the phenotype and the function of major CD4+ T cell subsets (Th1, Th17, and Treg cells) was performed in 34 untreated patients with GCA or PMR, in comparison with 31 healthy control subjects and with the 27 treated patients who remained after the 7 others withdrew. RESULTS: Compared with control subjects, patients with GCA and patients with PMR had a decreased frequency of Treg cells and Th1 cells, whereas the percentage of Th17 cells was significantly increased. Furthermore, an analysis of temporal artery biopsy specimens obtained from patients affected by GCA for whom biopsy results were positive demonstrated massive infiltration by Th17 and Th1 lymphocytes without any Treg cells. After glucocorticoid treatment, the percentages of circulating Th1 and Th17 cells decreased, whereas no change in the Treg cell frequency was observed. The frequency of CD161+CD4+ T cells, which are considered to be Th17 cell precursors, was similar in patients and control subjects. However, these cells highly infiltrated GCA temporal artery biopsy specimens, and their ability to produce interleukin-17 in vitro was significantly enhanced in patients with GCA and patients with PMR and was correlated with a decrease in the phosphorylated form of STAT-1. CONCLUSION: This study is the first to demonstrate that the frequency of Treg cells is decreased in patients with GCA and patients with PMR, and that CD161+CD4+ T lymphocytes, differentiated into Th1 cells and Th17 cells, are involved in the pathogenesis of GCA and PMR.

LupusQoL-FR is valid to assess quality of life in patients with systemic lupus erythematosus.

OBJECTIVE: To cross-culturally adapt the LupusQoL into French, to test its measurement properties and to further investigate its domain structure. METHODS: The cultural adaptation process according to guidelines and pre-testing resulted in the LupusQoL-FR. SLE patients completed the LupusQoL-FR at baseline, 15 days, 3 months and 6 months. Validity was studied through content and construct validity (factorial and Rasch analysis for structural validity, Spearman's correlation and Mann-Whitney tests for external validity). Cronbach's α and intra-class correlation coefficients were computed for reliability. The standardized response mean was computed to evaluate responsiveness. RESULTS: In all, 182 patients, age 39.6 (10.6) years, mostly outpatients [mean SELENA-SLEDAI 2.6 (3.5)] were recruited. Factor analysis with eight imposed factors was very close to the original LupusQoL. A screeplot with parallel analysis showed that LupusQoL domains could be aggregated in two physical and mental scales. Both eight- and two-factor structures showed a good Rasch fit, internal consistency (Cronbach's α: 0.85-0.95), and test-retest reliability (intra-class correlation coefficient 0.79-0.95). External convergent (correlation with SF-36, r=0.59-0.78) and divergent validity (according to SELENA-SLEDAI) were also satisfactory. CONCLUSION: The LupusQoL-FR is valid to assess quality of life in SLE patients. A two-factor structure of physical and mental aggregated scales is a valid alternative to the original eight-domain structure.

Churg-Strauss syndrome: retrospective study in Burgundian population in France in past 10 years.

Churg-Strauss Syndrome (SCS) is a systemic vasculitis associated with asthma and eosinophilia. The aim of our work is to describe this pathology in the Burgundian population in France. We counted from the hospitalisation data-processing summaries, the whole of the SCS hospitalised in Burgundy between 1998 and 2008. During the follow-up, the clinical and paraclinical characteristics of every patient were collected. The average prevalence is of 11.3 per million inhabitants and the incidence is of 1.2 new cases per million inhabitants per annum. There exists however, a great prevalence disparity and incidence amongst the various departments of the area. The patient's average follow-up is of 7.7 years. In 23% of the cases one finds a starting factor for vasculitis. The delay between the first signs and the diagnostic is an average of 61 months. The ANCA are positive in 26% of cases and of anti-myeloperoxidase specificity in 83% of cases (P < 0.001). The most profitable biopsies are essentially cutaneous and neuromuscular. At the diagnostic, two-third of the patients have had a treatment adapted according to the current recommendations based on the Five Factor Score. The remission rate within a 1-year period is of 77%. The remission is strongly correlated to the therapeutic protocol associating corticoids and cyclophosphamide (P < 0.05). In conclusion, the prevalence of SCS in our area is similar to that observed in other European regions. However, this vasculitis remains a difficult and often a tardive diagnostic pathology.

Tocilizumab as an add-on therapy to glucocorticoids during the first 3 months of treatment of Giant cell arteritis: A prospective study.

BACKGROUND: The aim of this study was to evaluate tocilizumab (TCZ) as an add-on therapy to glucocorticoids (GC) during the first 3 months of treatment of giant cell arteritis (GCA). METHODS: GCA patients, as defined by ≥3/5 ACR criteria and positive temporal artery biopsy (TAB) or angio-CT-scan or PET-scan-proven aortitis, were included in this prospective open-label study. Prednisone was started at 0.7 mg/kg/day and then tapered according to a standardized protocol. All patients received four infusions of TCZ (8 mg/kg/4 weeks) after inclusion. The primary endpoint was the percentage of patients in remission with ≤0.1 mg/kg/day of prednisone at week 26 (W26). Patients were followed for 52 weeks and data prospectively recorded. RESULTS: Twenty patients with a median (IQR) age of 72 (69-78) years were included. TAB were positive in 17/19 (90%) patients and 7/16 (44%) had aortitis. Remission was obtained in all cases. At W26, 15 (75%) patients met the primary endpoint. Ten patients experienced relapse during follow-up, mainly patients with aortitis (P = 0.048), or CRP >70 mg/L (P = 0.036) or hemoglobin ≤10 g/dL (P = 0.015) at diagnosis. Among 64 adverse events (AE) reported in 18 patients, three were severe and 30, mostly non-severe infections (n = 15) and hypercholesterolemia (n = 8), were imputable to the study. CONCLUSION: This study shows that an alternative strategy using a short-term treatment with TCZ can be proposed to spare GC for the treatment of GCA. However, 50% of patients experienced relapse during the 9 months following TCZ discontinuation, especially patients with aortitis, or CRP > 70 mg/L or Hb ≤ 10 g/dL at diagnosis. TRIAL REGISTRATION: ClinicalTrials.gov (NCT01910038).

Giant cell arteritis (Horton's disease) in very elderly patients aged 80 years and older: A study of 25 cases.

AIM: Analysis of the characteristics of very elderly patients with giant cell arteritis (GCA). METHODS: Patients aged 80 years and older diagnosed with GCA in our department between 1 January 2002 and 31 July 2008 were retrospectively included. For each patient, we recorded general characteristics, reason(s) for hospitalization, specialty of the physician or department that referred the patient to us, medical history, treatment at admission, GCA clinical features, time to diagnosis of GCA, biological screening and GCA treatment. RESULTS: We analyzed 25 clinical records, 18 women and seven men with a mean age of 83.9 years. General weakness, visual loss and inflammatory syndrome were the principal reasons for hospitalization. Patients were mainly referred by general practitioners or ophthalmological departments. At diagnosis, headache and musculoskeletal disorders were the most frequent signs (52% each), before general weakness and visual disorders. Time to diagnosis was 2.2 months. Inflammatory syndrome was very frequent (92%). Biopsy of the temporal artery confirmed GCA in 16 cases. Corticosteroid therapy (CST) mean dose was 0.9 mg/kg/day. Because of the positive evolution, CST was stopped in nine patients after 22.7 ± 15 months. A total of 22 patients received a preventive osteoporosis treatment. After 3 months of CST, clinical signs and IS vanished in 22 patients. CST complications, mainly infection, appeared in 17 patients. CONCLUSION: Clinical and biological features of GCA in the very elderly patients of the present study were comparable with those described in the literature in younger patients. However, it must be pointed out that our patients were not compared with a younger population in this study. Geriatr Gerontol Int 2015; ●●: ●●-●●.

A New Prognosis Score to Predict Mortality After Acute Pneumonia in Very Elderly Patients.

OBJECTIVES: Acute pneumonia (AP) induces an excess of mortality among the elderly. We evaluated the value of a new predictive biomarker index compared to usual prognosis scores for predicting in-hospital and 1-year mortalities in elderly inpatients with AP. DESIGN: Retrospective study in 6 clinical departments of a university hospital. SETTING: Burgundy university hospital (France). PARTICIPANTS: All patients aged 75 and over with AP and hospitalized between January 1 and June 30, 2013, in the departments of medicine (5) and intensive care (1) of our university hospital. MEASUREMENTS: A new index, which we named UBMo, was created by multiplying the uremia (U in the formula) by the N-terminal-pro-brain natriuretic peptide (NT-proBNP) plasmatic rate (B), divided by the monocyte count (Mo). RESULTS: Among the 217 patients included, there were 138 community-acquired pneumonia, 56 nursing home-acquired pneumonia, and 23 hospital-acquired pneumonia. In-hospital and 1-year mortality rates were respectively 19.8% and 43.8%. In multivariate analysis, Pneumonia Severity Index (PSI), unlike CURB-65 (confusion, urea >7 mmol/L, respiratory rate ≥30 breaths/min, blood pressure <90 mmHg systolic or ≤60 mmHg diastolic, age ≥65) score, was associated with in-hospital and 1-year mortalities. UBMo index performed better than PSI and CURB-65 scores in predicting both in-hospital and 1-year mortalities. For in-hospital mortality, the areas under the receiver operating characteristic curves (AUCs) were 0.89 (95% CI = 0.84-0.94), 0.72 (95% CI = 0.65-0.80), and 0.63 (95% CI = 0.54-0.72), respectively, for the 3 scores. For 1-year mortality, the AUCs were 0.93 (95% CI = 0.89-0.98), 0.66 (95% CI = 0.59-0.74), and 0.58 (95% CI = 0.50-0.66), respectively, for the 3 scores. The cut point for the UBMo index of 20,000 × 10-9 ng·mmol/L had a sensitivity of 93.1% and 80.9% and a specificity of 76.3% and 95.8%, respectively, for in-hospital and 1-year mortalities. CONCLUSION: If confirmed by prospective studies, the UBMo index appears very efficient in identifying patients at high risk of in-hospital and 1-year mortalities after an AP.

Etiologies and prognostic factors of leukocytoclastic vasculitis with skin involvement: A retrospective study in 112 patients.

In this study, outcomes of patients with leukocytoclastic vasculitis (LCV) were analyzed focusing on clinical, histopathology and laboratory findings, relapses, and survival.Data from patients with cutaneous vasculitis diagnosed between January 1, 2000, and December 31, 2010, at Dijon University Hospital (France) were retrospectively reviewed. LCV was defined as perivascular neutrophilic infiltrate, endothelial cell nuclear swelling, extravasation of red blood cells, and/or fibrin deposition in vessels. Patients were classified according to the 2012 Chapel Hill Consensus Conference. Relapses were defined as the recurrence of vasculitis symptoms after a period of remission >1 month. Time to relapse and/or death was calculated from the date of diagnosis. Univariate and multivariate (Cox model) analyses were performed.A total of 112 patients (57 males and 55 females), with a mean age of 60 ±â€Š19 (18-98) years, were analyzed. Overall follow-up was 61 ±â€Š38 months. At diagnosis, all patients had skin lesions, purpura being the most common (n = 83). Lesions were associated with systemic involvement in 55 (51%) patients. Only 41 (36.6%) patients received specific treatment: glucocorticoids in 29 of 41 (70.7%) and immunosuppressants in 9 of 41 (22%). Sixty-two patients (55%) had LCV due to underlying causes, 29 (25.9%) had single-organ cutaneous small vessel vasculitis (SoCSVV), and 21 (18.8%) had unclassifiable LCV. Twenty patients of the cohort (18%) experienced relapse, 14 ±â€Š13 (1-40) months after the diagnosis of LCV. None of the 29 patients with SoCSVV relapsed. Independent risk factors for relapse were vascular thrombosis in the biopsy [hazard ratio (HR) = 4.9; P = 0.017], peripheral neuropathy (HR = 9.8; P = 0.001), hepatitis (HR = 3.1; P = 0.004), and positive antineutrophil cytoplasm antibodies (ANCA, HR = 5.9 P = 0.005). In contrast, SoCSVV was a protective factor for relapse (HR = 0.12; P = 0.043).The 1-, 3-, and 6-year overall survival rates were 99%, 83%, and 71%, respectively, with no difference between relapsers and nonrelapsers (P = 0.960) or between SoCSVV and unclassifiable LCV (P = 0.588).This study demonstrates that global survival for LCV patients is good but relapses remain frequent, especially when the cutaneous biopsy shows vascular thrombosis, or in patients with peripheral neuropathy or hepatitis. Conversely, SoCSVV is a protective factor for relapse.

Clinicopathologic characteristics, treatment, and outcomes of tubulointerstitial nephritis and uveitis syndrome in adults: A national retrospective strobe-compliant study.

Tubulointerstitial nephritis and uveitis (TINU) syndrome is a rare disease, defined by the association of idiopathic acute TINU. The aim of our work was to determine the characteristics of adult TINU syndrome in France, and to assess factors (including treatment) influencing medium-term prognosis.We conducted a nationwide study including 20 French hospitals. Clinical, laboratory, and renal histopathologic data of 41 biopsy-proven TINU syndromes were retrospectively collected. The patients were diagnosed between January 1, 1999 and December 1, 2015.Twenty-five females and 16 males were included (F/M ratio: 1.6:1). The median age at disease onset was 46.8 years (range 16.8-77.4) with a median serum creatinine level at 207 µmol/L (range 100-1687) and a median estimated glomerular filtration rate (eGFR) at 27 mL/min per 1.73 m (range 2-73). Twenty-nine patients (71%) had a bilateral anterior uveitis and 24 (59%) had deterioration in general health at presentation. Moderate proteinuria was found in 32 patients (78%) (median proteinuria 0.52 g/24 h; range 0.10-2.10), aseptic leukocyturia in 25/36 patients (70%). The evaluation of renal biopsies revealed 41 patients (100%) with an acute tubulointerstitial nephritis, 19/39 patients (49%) with light to moderate fibrosis and 5 patients (12%) with an acute tubular necrosis. Thirty-six patients (88%) were treated with oral corticosteroids. After 1 year of follow-up, the median eGFR was 76 mL/min per 1.73 m (range 17-119) and 32% of the patients suffered from moderate to severe chronic kidney disease. Serum creatinine (P < 0.001, r = -0.54), serum bicarbonate and phosphate levels (respectively, P = 0.01, r = 0.53; and P = 0.04, r = 0.46), and age (P = 0.03, r = -0.37) at the 1st symptoms were associated with eGFR after 1 year. During the 1st year 40% of patients had uveitis relapses. The use of oral corticosteroids was not associated with a better kidney function but was associated with fewer uveitis relapses (P = 0.44 and 0.02, respectively).In our study, 32% of patients were suffering from moderate to severe chronic kidney disease after 1 year of follow-up, and 40% had uveitis relapses during this follow-up. This work also suggests that oral corticosteroids are effective for the treatment of TINU syndrome's uveitis.

Joint symptoms in patients on bupropion therapy.

OBJECTIVE: To describe joint symptoms related to bupropion therapy. METHODS: We retrospectively reviewed adverse events in bupropion-treated patients reported to the Bourgogne Drug Surveillance Center, France, between October 2001 and December 2002. Joint symptoms classified by the causality assessment as related to bupropion were identified and examined. RESULTS: Four cases were found. Three patients had semi-delayed hypersensitivity reactions resembling serum sickness, manifesting as urticaria and arthralgia with or without a fever. The remaining patient had an unusual presentation consisting in acute monoarthritis of the wrist that started a few days after bupropion initiation. CONCLUSION: Hypersensitivity reactions to bupropion are fairly common and include rare cases of serum sickness-like reaction. Urticaria and incapacitating arthralgia are at the forefront of the clinical picture and may require a brief period of inpatient care. Antihistamines are the treatment of choice. Other manifestations such as acute monoarthritis might occur, although this awaits confirmation as we identified a single case.

Should mild hypogammaglobulinemia be managed as severe hypogammaglobulinemia? A study of 389 patients with secondary hypogammaglobulinemia.

BACKGROUND: Although secondary hypogammaglobulinemia is more frequent than primary hypogammaglobulinemia, its etiology and management are poorly described, particularly for mild hypogammaglobulinemia. METHODS: This retrospective observational study included all adult patients with a gammaglobulin level <6.4g/L on serum electrophoresis identified at Dijon teaching hospital between April and September 2012. Clinico-biological features, etiologies and infectious complications were collected at inclusion and compared between group 1 (gammaglobulin <5g/L, severe hypogammaglobulinemia), and group 2 (gammaglobulin <6.4 and ≥5g/L, mild hypogammaglobulinemia). RESULTS: Among the 4011 serum electrophoreses, 570 samples from 389 patients had gammaglobulin levels below 6.4g/L: 156 (40%) in group 1 and 233 (60%) in group 2. Mean age±SD was 67 (15) years, and sex ratio was 1.04 (M/F) with no difference between the two groups. An etiology was identified in 79% and 58% of patients in groups 1 and 2, respectively (p<0.0001). The main etiologies were similar in both groups and included malignant hemopathy treated with cytostatic agents (n=129, 33%), smoldering or newly-diagnosed hemopathy without treatment (n=49, 13%) and immunosuppressive treatment (n=91, 23%). The incidence of hypogammaglobulinemia-related infections was 22/100/year, with no significant difference between the two groups (p=0.17). Vaccination coverage against pneumococcus was 33%, and higher in group 1 (46% vs. 24%; p<0.0001). When no cause was known at inclusion, an etiology was discovered in 22/130 patients (17%), 11 in each group. CONCLUSIONS: Though mild hypogammaglobulinemia does not meet the classical criteria for hypogammaglobulinemia (<5g/L), the etiology and infectious risk are similar. It therefore requires investigation and vaccination.

Efficacy of tocilizumab in refractory giant cell arteritis.

Giant cell arteritis is the most frequent form of vasculitis characterized by a high risk of vascular thrombosis. Major complications are blindness and other vascular ischemia but bowel ischemic involvement is rare. Treatment is based on long-term steroid therapy with numerous side effects. The efficacy of immunosuppressive drugs like azathioprine methotrexate or anti-tumor necrosis factor antibodies appears to be too low to reduce the use of steroids. Th17 lymphocytes and interleukin-6 play an important role in pathogenesis of giant cell arteritis. We report here a case of effective interleukin-6 blocker in the treatment of refractory giant cell arteritis with ileitis and high-dose steroid dependence despite 2 years of treatment with steroids and methotrexate. After infusions of tocilizumab, no relapse at 6 months was found despite the decrease in corticosteroids.

[Renal involvement in cancer and renal paraneoplastic syndromes]. / Syndromes paranéoplasiques à expression rénale et atteintes rénales des cancers.

BACKGROUND: Renal alterations in the context of neoplastic disease are relatively frequent manifestations but are overall poorly reported. MATERIAL AND METHODS: A search in the English and French literature was performed using the following key words: "cancer", "renal", "paraneoplastic syndrome", "glomerulopathy" and "kidney failure". RESULTS: The various renal manifestations can be divided into specific and paraneoplastic. They include paraneoplastic glomerulopathies (membranous glomerulonephristis being the most frequent), direct involvement of the renal parenchyma, hydroelectrolytic abnormalities (hypercalcemia, inappropriate antidiuretic hormone secretion…), retroperitoneal fibrosis, micro-angiothrombotic disease and tumor lysis syndrome. Anticancer and symptomatic treatments do not guaranty complete recovery in all cases. CONCLUSION: The frequency and the severity of some renal manifestations associated with malignant hemopathies and carcinomas indicates a need for initial renal-oriented work-up and follow-up.

Efficacy of tocilizumab in two patients with anti-TNF-alpha refractory uveitis.

PURPOSE: To report on two patients with refractory uveitis treated with tocilizumab; a new humanized monoclonal antibody against the interleukin-6 receptor (IL-6R). DESIGN: Retrospective interventional case series. METHODS: Both patients received a monthly infusion of tocilizumab 8 mg/kg; associated with corticosteroids. Outcome measures were visual acuity and central retinal thickness evaluated with optical coherence tomography. RESULTS: An improvement in visual acuity and a decrease in macular edema were observed in these two patients. CONCLUSIONS: Tocilizumab seems to be a promising treatment in refractory uveitis. A prospective study is needed to evaluate the role of this new agent in the management of refractory uveitis.

[Routine ankle brachial pressure index measurement for peripheral artery disease diagnosis in internal medicine department: Comparison with the recommendations of the Haute Autorité de Santé. Prospective descriptive study about 106 patients]. / Mesure systématique des index de pression systolique à la cheville pour le dépistage de l'artériopathie oblitérante des membres inférieurs dans les services de médecine interne : comparaison aux recommandations de la Haute Autorité de santé. Étude prospective descriptive chez 106 patients.

PURPOSE: The ankle brachial pressure index (ABPI) makes it possible to diagnose peripheral artery disease (PAD) and identify patients with a vascular risk. Recently, the Haute Autorité de santé (HAS) issued guidelines. We wanted to determine the interest and impact of these guidelines when applied to patients hospitalised in an internal medicine department. METHODS: We systematically measured the ABPI in two internal medicine departments. We compared the results obtained with the screening criteria and the good practices recommended by the HAS. RESULTS: The screening criteria recommended by the HAS were already applied in 91% of our 97 patients. PAD was found in 37.1% of patients. In 83% of cases, the diagnosis was unknown (p = 0.02). The PAD was symptomatic in 83% of the known PAD cases, and 3.3% in newly-diagnosed cases (p < 0.001)). The sensitivity of the HAS screening criteria applied to our population was 100% but almost patients justifies ABPI screening. The specificity was 11.5%, the positive predictive value 40% and the negative predictive value 100%. The optimal treatment recommended was implemented in only 50% of patients with known arteriopathy and in 10% of newly-diagnose PAD (p = 0.04). CONCLUSION: PAD prevalence is high in internal medicine department and systematic measurement of ABPI is effective. Determining patients to screen with the HAS criteria has a poor impact in our patients. The optimal treatment is still extremely under-prescribed even in patients with known PAD.

Clinical spectrum, treatment, and outcome of patients with type II mixed cryoglobulinemia without evidence of hepatitis C infection.

OBJECTIVE: The clinical spectrum, etiologies, and best therapeutic approaches of type II mixed cryoglobulinemia (MC) not associated with hepatitis C virus (HCV) infection have been poorly described to date. We studied the clinical presentation and outcome of patients with type II MC with no evidence of HCV. METHODS: This was a multicenter retrospective study on the clinical presentation and outcome of patients with type II MC without evidence of HCV infection. Only patients with symptomatic MC were included. RESULTS: Thirty-three patients were included (median followup 67.2 mo). Extensive investigations for associated diseases were performed at presentation. MC was related to an autoimmune disease in 14 patients, to a lymphoid malignancy in 4 patients, and to an infectious disease in 2 patients, while MC was classified as essential (primary) in 13. Essential MC tended to be more severe than secondary disease with, in particular, more frequent renal and peripheral nerve involvement. Most patients were treated with steroid with or without immunosuppressive agents, mainly cyclophosphamide. These treatments were unable to induce sustained remission. One patient was successfully treated with lenalidomide. Seven patients with nonmalignant MC were treated with rituximab; 2 had a sustained complete remission, 3 improved greatly but relapsed within 5 months, and 2 experienced a disease flare. CONCLUSION: An important proportion of non HCV-related type II MC remains essential. Efforts should be made to find other etiologies than HCV, because treatments with steroid and immunosuppressants are not satisfactory, especially in severe forms. In these situations anti-CD20 therapy may present the best option but should be used with caution. New agents such as lenalidomide remain to be evaluated.