Mass cytometry reveals atypical immune profile notably impaired maturation of memory CD4 T with Gb3-related CD27 expression in CD4 T cells in Fabry disease.

Fabry disease (FD) is an X-linked disease characterized by an accumulation of glycosphingolipids, notably of globotriaosylceramide (Gb3) and globotriaosylsphingosine (lysoGb3) leading to renal failure, cardiomyopathy, and cerebral strokes. Inflammatory processes are involved in the pathophysiology. We investigated the immunological phenotype of peripheral blood mononuclear cells in Fabry patients depending on the clinical phenotype, treatment, Gb3, and lysoGb3 levels and the presence of anti-drug antibodies (ADA). Leucocytes from 41 male patients and 20 controls were analyzed with mass cytometry using both unsupervised and supervised algorithms. FD patients had an increased expression of CD27 and CD28 in memory CD45- and CD45 + CCR7-CD4 T cells (respectively p < 0.014 and p < 0.02). Percentage of CD45RA-CCR7-CD27 + CD28+ cells in CD4 T cells was correlated with plasma lysoGb3 (r = 0.60; p = 0.0036) and phenotype (p < 0.003). The correlation between Gb3 and CD27 in CD4 T cells almost reached significance (r = 0.33; p = 0.058). There was no immune profile associated with the presence of ADA. Treatment with agalsidase beta was associated with an increased proportion of Natural Killer cells. These findings provide valuable insights for understanding FD, linking Gb3 accumulation to inflammation, and proposing new prognostic biomarkers.

The functional disabilities of the dominant and opposite hands in patients with systemic sclerosis.

OBJECTIVES: Hand involvement in patients with systemic sclerosis (SSc) is responsible for 75% of the overall disability but varies greatly among individuals. No study has yet compared the functionalities between the two hands of SSc patients. We thus evaluated the joint limitations and extent of skin involvement in the dominant and contralateral hands. METHODS: This prospective, descriptive, comparative single-centre study enrolled SSc patients diagnosed using the ACR/EULAR criteria. We assessed limitations in the joint range of motion during active and passive mobilisation; the first commissure opening angles; the Kapandji scale and Rodnan hand scores; the digital pressures; the finger brachial pressure indices; and the number of telangiectasias, calcinosis, digital ulcerations, and painful joints on each hand. RESULTS: Thirty patients were included. Spontaneous flexion joint limitations were significantly greater in the dominant hand (p<0.0001). The Kapandji score was lower (p<0.001) and the Rodnan hand score significantly higher, for the dominant hand (p<0.001). The digital pressure was similar between the hands. CONCLUSIONS: The dominant hand exhibited significantly more skin sclerosis and mean flexion deterioration, a lower Kapandji score, and a tendency toward reduced mean extension, compared with the other hand. No vascular pathology was noted in either hand. Larger studies are needed to confirm these results and to draw therapeutic conclusions.

Use of complementary and alternative medicine by patients treated for systemic lupus erythematosus, primary Sjögren's syndrome or systemic sclerosis in a french rural region.

BACKGROUND: Complementary and alternative medicine (CAM) is composed of a wide range of interventions and frequently used in parallel with conventional medicine. The aim of this study was to assess the prevalence, modalities, and association factors of CAM utilization in patients treated for systemic lupus erythematosus, primary Sjögren's syndrome or systemic sclerosis. PATIENTS AND METHODS: This was a prospective single-center observational study conducted in a french university hospital center. Inclusion criteria were patients followed for systemic lupus erythematosus, primary Sjögren's syndrome or systemic sclerosis. Data were collected with a survey which assessed socio-demographic, disease characteristics, CAM use details, life quality and anxiety score. RESULTS: A total of 121 patients were included, mostly women (87%), with an average age of 56 years. Proportion of patients seeking CAM was 55%. A total of 186 CAM interventions were recorded: most common was osteopathy, homeopathy and acupuncture. Patients were looking for well-being (22%), reducing their fatigue (18%) and pain (33%). Concerning physical and mental feeling after CAM use, a subjective improvement was reported in 89% of cases. In multivariate analysis, CAM use by patient was associated with these 3 variables : coming from a Western culture, being professionally active, having a poor quality of life and anxiety scores. CONCLUSION AND OUTLOOK: This is the first study to focus on CAM use in patients followed for three AID in a french rural region. The current challenge is to enrich conventional medicine with CAM that are effective and safe through supervised programs to move towards an integrative medicine.

BOB-ACG study: Pulse methylprednisolone to prevent bilateral ophthalmologic damage in giant cell arteritis. A multicentre retrospective study with propensity score analysis.

INTRODUCTION: Giant cell arteritis (GCA) is complicated in 10 to 20% of cases by permanent visual ischemia (PVI). International guidelines advocate the use of intravenous pulse of methylprednisolone from 250 to 1000mg per day, for three days, followed by oral prednisone at 1mg/kg per day. The aim of this study is to assess whether this strategy significantly reduces the risk of early PVI of the second eye, compared with direct prednisone at 1mg/kg per day. METHODS: We conducted a multicentre retrospective observational study over the past 15 years in 13 French hospital centres. Inclusion criteria included: new case of GCA; strictly unilateral PVI, prednisone at dose greater than or equal to 0.9mg/kg per day; for the intravenous methylprednisolone (IV-MP) group, total dose between 900 and 5000mg, close follow-up and knowledge of visual status at 1 month of treatment, or earlier, in case of contralateral PVI. The groups were compared on demographic, clinical, biological, iconographic, and therapeutic parameters. Statistical analysis was optimised using propensity scores. RESULTS: One hundred and sixteen patients were included, 86 in the IV-MP group and 30 in the direct prednisone group. One patient in the direct prednisone group and 13 in the IV-MP group bilateralised, without significant difference between the two strategies (3.3% vs 15.1%). Investigation of the association between IV-MP patients and contralateral PVI through classical logistic regression, matching or stratification on propensity score did not show a significant association. Weighting on propensity score shows a significant association between IV-MP patients and contralateral PVI (OR=12.9 [3.4; 94.3]; P<0.001). Improvement in visual acuity of the initially affected eye was not significantly associated with IV-MP (visual acuity difference 0.02 vs -0.28 LogMar), even in the case of early management, i.e., within the first 48hours after the onset of PVI (n=61; visual acuity difference -0.11 vs 0.25 LogMar). Complications attributable to corticosteroid therapy in the first month were significantly more frequent in the IV-MP group (31.8 vs 10.7%; P<0.05). DISCUSSION: Our data do not support the routine use of pulse IV-MP for GCA complicated by unilateral PVI to avoid bilateral ophthalmologic damage. It might be safer to not give pulse IV-MP to selected patients with high risks of glucocorticoids pulse side effects. A prospective randomised multicentre study comparing pulse IV-MP and prednisone at 1mg/kg per day is desirable.

Efficacy and Safety of Rituximab-Based Treatments in Angioedema With Acquired C1-Inhibitor Deficiency.

BACKGROUND: Angioedema (AE) due to acquired C1-inhibitor (C1-INH) deficiency (AAE-C1-INH) is related to excessive consumption of C1-INH or to anti-C1-INH antibodies, and is frequently associated with lymphoproliferative syndromes or monoclonal gammopathies. Standard of care for prophylactic treatment in this condition is not established. Rituximab may be effective to prevent attacks, especially if the lymphoid hemopathy is controlled, but data are scarce. OBJECTIVE: To evaluate efficacy of rituximab in AAE-C1-INH. METHODS: A retrospective multicenter study was carried out in France, including patients with AAE-C1-INH treated with rituximab between April 2005 and July 2019. RESULTS: Fifty-five patients with AAE-C1-INH were included in the study, and 23 of them had an anti-C1-INH antibody. A lymphoid malignancy was identified in 39 patients, and a monoclonal gammopathy in 9. There was no associated condition in 7 cases. Thirty patients received rituximab alone or in association with chemotherapy (n = 25). Among 51 patients with available follow-up, 34 patients were in clinical remission and 17 patients had active AE after a median follow-up of 3.9 years (interquartile range, 1.5-7.7). Three patients died. The presence of anti-C1-INH antibodies was associated with a lower probability of AE remission (hazard ratio, 0.29 [95% CI, 0.12-0.67]; P = .004). Relapse was less frequent in patients with lymphoma (risk ratio, 0.27 [95% CI, 0.09-0.80]; P = .019) and in patients treated with rituximab and chemotherapy (risk ratio, 0.31 [95% CI, 0.12-0.79]; P = .014). CONCLUSIONS: Rituximab is an efficient and well-tolerated therapeutic option in AE, especially in lymphoid malignancies and in the absence of detectable anti-C1-INH antibodies.

Frequency and Significance of Hepatic Involvement in New-Onset Giant Cell Arteritis: A Study of 514 Patients.

Abnormalities of liver function in giant cell arteritis (GCA) have long been described1 and are present at the acute phase of the disease in 30% to 60% of cases.2-4 Hepatic involvement is mostly anicteric cholestasis (eg, elevated alkaline phosphatase [ALP] and gamma-glutamyl transferase [GGT]), and, more rarely, cytolytic hepatitis (eg, elevated aspartate aminotransferase [AST] and/or alanine aminotransferase [ALT]).

Use of high-plex data provides novel insights into the temporal artery processes of giant cell arteritis.

Objective: To identify the key coding genes underlying the biomarkers and pathways associated with giant cell arteritis (GCA), we performed an in situ spatial profiling of molecules involved in the temporal arteries of GCA patients and controls. Furthermore, we performed pharmacogenomic network analysis to identify potential treatment targets. Methods: Using human formalin-fixed paraffin-embedded temporal artery biopsy samples (GCA, n = 9; controls, n = 7), we performed a whole transcriptome analysis using the NanoString GeoMx Digital Spatial Profiler. In total, 59 regions of interest were selected in the intima, media, adventitia, and perivascular adipose tissue (PVAT). Differentially expressed genes (DEGs) (fold-change > 2 or < -2, p-adjusted < 0.01) were compared across each layer to build a spatial and pharmacogenomic network and to explore the pathophysiological mechanisms of GCA. Results: Most of the transcriptome (12,076 genes) was upregulated in GCA arteries, compared to control arteries. Among the screened genes, 282, 227, 40, and 5 DEGs were identified in the intima, media, adventitia, and PVAT, respectively. Genes involved in the immune process and vascular remodeling were upregulated within GCA temporal arteries but differed across the arterial layers. The immune-related functions and vascular remodeling were limited to the intima and media. Conclusion: This study is the first to perform an in situ spatial profiling characterization of the molecules involved in GCA. The pharmacogenomic network analysis identified potential target genes for approved and novel immunotherapies.

New-onset giant cell arteritis with lower ESR and CRP level carries a similar ischemic risk to other forms of the disease but has an excellent late prognosis: a case-control study.

INTRODUCTION: Biopsy-proven giant cell arteritis (GCA) occasionally presents without acute-phase reaction. In this setting, GCA may be initially overlooked and glucocorticoid treatment unduly delayed, potentially increasing ischemic risk. PATIENTS AND METHODS: From an inception cohort of patients with newly diagnosed, biopsy-verified GCA, we retrieved all cases without elevation of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) level before starting glucocorticoid treatment. We compared the baseline features and outcomes of these patients and two additional patients recruited after GCA diagnosis with those of 42 randomly selected patients with high baseline ESR and CRP. RESULTS: Of 396 patients, 14 (3.5%) had lower baseline values of both ESR and CRP. Lower baseline ESR and CRP were associated with fewer American College of Rheumatology criteria met (p < 0.001, 95% CI - 1.1; - 0.9), and less jaw claudication (p = 0.06, 95% CI 0.8; 44.9), but similar rates of permanent blindness (p = 1.0). Patients with lower ESR and CRP also showed obvious differences regarding mean blood cell counts and mean hemoglobin level, but also less anti-cardiolipin antibody positivity (p = 0.04, 95% CI 0.8; ∞) and hepatic cholestasis (p = 0.03, 95% CI 1.0; 422). Patients with lower ESR and CRP had fewer GCA relapses (p = 0.03, 95% CI - 1.1; - 0.1), fewer glucocorticoid-induced complications (p = 0.01, 95% CI - 2.0; - 0.1), and successfully stopped glucocorticoids sooner than the other patients (18.3 months vs 34 months in average, p = 0.02, 95% CI - 27;- 0.9). CONCLUSION: Biopsy-proven GCA presenting with lower ESR and CRP is not an exceptional occurrence. It is clinically less typical but carries similar ischemic risk to other forms of the disease. Conversely, the late GCA prognosis of these patients is excellent.

Relationship between histopathological features of non-infectious aortitis and the results of pre-operative 18F-FDG-PET/CT: a retrospective study of 16 patients.

OBJECTIVES: To describe the characteristics of 18F-fluorodeoxyglucose positron-emission tomography/computed-tomography (18FDG-PET/CT) findings before surgery in patients with active, histologically confirmed aortitis, and to correlate the degree of arterial wall inflammation with PETVAS score. METHODS: This was a multiple-centre retrospective study including cases with histologically proven active, non-infectious aortitis who had a 18FDG-PET/CT performed within one year before surgery for aneurysm repair. PETVAS score was determined by radiologists blinded to the pathology findings. Cardiovascular pathologists reviewed aortic tissue samples and graded the degree of inflammation in the vessel wall. RESULTS: Sixteen patients were included (8 giant cell arteritis, 4 clinically isolated aortitis, 2 Takayasu's arteritis, 1 relapsing polychondritis, and 1 rheumatoid arthritis). In 5/16 (31%) patients, 18FDG-PET/CT did not detect the presence of aortic inflammation; two of whom were being treated with glucocorticoids at the time of procedure. Ascending thoracic and abdominal aorta had the highest FDG uptake among the affected territories. Patients without active aortitis on 18FDG-PET/CT were significantly older (p=0.027), had a lower PETVAS score (p=0.007), and had a lower degree of adventitial inflammation (p=0.035). In contrast, there was no difference between 18FDG-PET/CT active and inactive aortitis patients as regards the timing between PET/CT and surgery, serum CRP level (during 18FDG-PET/CT) and, FDG uptake per study site. CONCLUSIONS: In histologically proved aortitis, 18FDG-PET/CT before surgery did not detect vascular inflammation in 31% patients, and PETVAS score correlated with the degree of adventitial histopathologic inflammation.

Clinical, biological, and ophthalmological characteristics differentiating arteritic from non-arteritic anterior ischaemic optic neuropathy.

BACKGROUND/AIMS: To identify characteristics that can distinguish AAION from NAAION in emergency practice. METHODS: This is a multicentre retrospective case-control study. Ninety-four patients with AAION were compared to ninety-four consecutive patients with NAAION. We compared the clinical, biological, and ophthalmological characteristics at baseline of patients with AAION and those with NAAION. RESULTS: Patients with AAION were older and more likely to have arterial hypertension. Cephalic symptoms and acute-phase reactants were more frequent in AAION. Profound vision loss and bilateral involvement were more frequent in AAION at baseline. Central retinal and cilioretinal artery occlusions was only observed in AAION, and delayed choroidal perfusion was more frequently observed in AAION than in NAAION. Using logistic regression, an age >70 years (OR = 3.4, IC95% = 0.8-16.1, p = 0.105), absence of splinter haemorrhage (OR = 4.9, IC95% = 1.4-20.5, p = 0.019), delayed choroidal perfusion (OR = 7.2, IC95% = 2.0-28.0, p = 0.003), CRP > 7 mg/L (OR = 43.6, IC95% = 11.6-229.1, p < 0.001) and platelets >400 × G/L (OR = 27.5, IC95% = 4.6-270.9, p = 0.001) were independently associated with a diagnosis of AAION. An easy-to-use score based on these variables accurately distinguished AAION from NAAION with a sensitivity of 93.3% and specificity of 92.4%. CONCLUSION: In patients presenting with AION, a set of ophthalmological and laboratory criteria can efficiently discriminate patients with AAION and NAAION and can identify which patients would benefit from high-dose glucocorticoids. External validation of our results is required.

Temporal artery biopsy: A technical guide and review of its importance and indications.

Temporal artery biopsy (TAB) is a surgical procedure that enables the histological diagnosis of giant cell arteritis (GCA). Performing a TAB requires expertise and a precise approach. Nevertheless, available data supports the value of tissue diagnosis in managing GCA. The current therapeutic recommendation for GCA is long-term glucocorticoid therapy, with an increasing emphasis on the addition of immunosuppressants/biotherapies. Though effective, immunosuppressants and other such biotherapies may put the patient at more risk. Optimizing the diagnosis through tissue evaluation is therefore important in weighing the risks and benefits of initiating therapeutic intervention. We evaluate the evidence supporting the importance of TAB and its indications. We also describe what technical approaches should be used to maximize sensitivity and to avoid possible complications during the procedure.

Immune-Mediated Diseases Following COVID-19 Vaccination: Report of a Teaching Hospital-Based Case-Series.

The occurrence and course of immune-mediated diseases (IMDs) following COVID-19 vaccination has been little explored so far. We retrieved, among adult patients hospitalized at the Internal Department of a French university hospital up to May 2022, all those who had developed, or relapsed to, an IMD less than 3 weeks following COVID-19 vaccination, without other triggers. Twenty-seven (24 new-onset) post-COVID-19 vaccine IMDs were recorded. They comprised giant cell arteritis or polymyalgia rheumatica (n = 16, HLA-DRB1*04 in 58% of 12 assessed GCA cases), immune-mediated necrotizing myositis or acute rhabdomyolysis, systemic vasculitis, immune thrombocytopenic purpura, rheumatoid arthritis, anti-synthetase syndrome, and adult-onset Still's disease. The causative vaccines were mRNA-based (20 cases) or viral vector-based (7 cases). The IMD typically occurred after the first vaccine dose, with an average delay of 8 (5 SD) days. The patients' mean age was 67 years, and 58% were women. The IMDs had protracted courses in all but three of the patients and typically required high-dose glucocorticoids, in combination with immunomodulators in 13 patients. One patient died of intractable rhabdomyolysis, whereas five suffered permanent damage from IMDs. Eleven patients with well-controlled IMDs completed their COVID-19 vaccination schedule, and two suffered mild IMD relapses. There is a risk of IMDs, notably GCA/PMR, and muscle disorders, following COVID-19 vaccination. Such adverse reactions typically occurred after the first dose, raising concern about subsequent COVID-19 vaccinations. However, early re-challenge in well-controlled IMDs appeared safe.

The Spectrum of Still's Disease: A Comparative Analysis of Phenotypic Forms in a Cohort of 238 Patients.

Still's disease (SD) is a heterogeneous autoinflammatory disorder for which several phenotypes have been described. We conducted a retrospective study to re-evaluate the dichotomous view of the disease, to compare the juvenile and adult forms, and to look for prognostic factors. We collected data from ten French centers, seeking patients with a diagnosis of adult-onset SD (AOSD) or systemic juvenile idiopathic arthritis (sJIA). We identified 238 patients, 152 (64%) of whom had AOSD while 86 (36%) had sJIA. The median age at SD onset was 26.6 years. In patients with identifiable patterns, the course of SD was systemic in 159 patients (74%), chronic in 55 (26%). Sore throat and myalgia were more frequent in patients with AOSD. Abnormal liver tests, serum ferritin and C-reactive protein levels were higher in AOSD group. Fever and skin rash were predictive of complete remission or recovery and high lactate dehydrogenase level was a poor prognosis factor. Symptoms such as splenomegaly, skin rash, high polymorphonuclear neutrophils count and macrophage activation syndrome were predictive of a systemic phenotype. Overall, there were no major differences between sJIA and AOSD. Our results are consistent with the "biphasic" model of an autoinflammatory disease that can progress to chronic arthritis if not treated early.

Giant cell arteritis-related stroke in a large inception cohort: A comparative study.

OBJECTIVE: Stroke caused by giant cell arteritis (GCA) is a rare but devastating condition and early recognition is of critical importance. The features of GCA-related stroke were compared with those of GCA without stroke and atherosclerosis-related or embolic stroke with the aim of more readily diagnosing GCA. METHODS: The study group consisted of 19 patients who experienced GCA-related strokes within an inception cohort (1982-2021) of GCA from the internal medicine department, and the control groups each consisted of 541 GCA patients without a stroke and 40 consecutive patients > 50 years of age with usual first ever stroke from the neurology department of a French university hospital. Clinical, laboratory, and imaging findings associated with GCA related-stroke were determined using logistic regression analyses. Early survival curves were estimated using the Kaplan-Meier method and compared using the log rank test. RESULTS: Amongst 560 patients included in the inception cohort, 19 (3.4%) developed GCA-related stroke. GCA-related stroke patients had more comorbid conditions (p = 0.03) and aortitis on imaging (p = 0.02), but less headache (p < 0.01) and scalp tenderness (p = 0.01). Multivariate logistic regression analysis showed that absence of involvement of the anterior circulation (OR = 0.1 - CI: 0.01-0.5), external carotid ultrasound (ECU) abnormalities (OR = 8.1 - CI: 1.3-73.9), and C-reactive protein (CRP) levels > 3 mg/dL (OR = 15.4 - CI: 1.9-197.1) were independently associated with GCA-related stroke. Early survival of GCA-related stroke patients was significantly decreased compared with control stroke patients (p = 0.02) and GCA patients without stroke (p < 0.001). CONCLUSIONS: The location of stroke and assessment of ECU results and CRP level could help improve the prognosis of GCA-related stroke by bringing this condition to the clinician's attention more quickly, thus shortening diagnostic delay.

Features and risk factors for new (secondary) permanent visual involvement in giant cell arteritis.

OBJECTIVES: New permanent visual loss (PVL) in treated patients with giant cell arteritis (GCA) is a rare but worrisome occurrence. In this study, we aimed to describe the frequency and main features of new PVL occurring after the beginning of glucocorticoid therapy in patients with newly diagnosed GCA. METHODS: We included in an inception cohort all consecutive patients newly diagnosed with GCA in the internal medicine department of a tertiary-care hospital between 1976 and May 2020. The study population comprised all the patients without bilateral PVL before treatment who were followed for at least one year. Only well-documented visual events that set after the initiation of glucocorticoid treatment were regarded as new PVL. RESULTS: Eleven out of 502 patients (2.2%) experienced a new PVL including 6 occurrences during the initial therapeutic phase and 5 during the tapering phase. Patients with new PVL during treatment had higher mean age, more often displayed temporal artery abnormalities on physical examination, and had higher mean platelet counts at GCA onset. There was a strong excess risk of contralateral recurrence during treatment in patients with unilateral loss at GCA onset compared with patients with uncomplicated GCA (10.5% vs 1.1%, OR=10.26, p<0.001). CONCLUSIONS: New PVL in treated GCA is a rare, but significant occurrence. Older patients and patients who already had unilateral PVL at diagnosis have higher risk of new ischaemic visual loss during treatment compared to the other patients. Close clinical, laboratory, and eye monitoring of these high-risk patients is of paramount importance.

Intraoperative findings during temporal artery biopsy: keys to optimise the diagnosis of giant cell arteritis.

The objective of this study was to describe the perioperative findings during temporal artery biopsy (TAB) and the characteristics associated with a diagnosis of giant cell arteritis (GCA). Perioperative findings were prospectively described by a single operator blinded to the clinical and laboratory characteristics of the patients on 40 consecutive TABs, of which 21 were positive (53%) for GCA. Patients with a TAB positive for GCA (TAB+) more frequently had abnormalities on palpation of the temporal artery than negative TAB (TAB-) patients (mainly pulse abolition (p=0.007), indurated artery (p=0.002), and painful artery (p=0.021)). The appearance of a big artery (p<0.001), a thickened artery (p<0.001), and an indurated artery at incision (p<0.001) was significantly associated with a positive TAB. A multivariate model identified a big artery, no local bleeding, and pain during artery traction as being associated with TAB positivity (sensitivity 71.4% and specificity 89.5%). The appearance of the temporal artery during TAB is important in predicting the positivity of the biopsy. Whether this should influence the optimal length of the TAB warrants a prospective study.

Diagnostic Value of 18F-FDG PET/CT vs. Chest-Abdomen-Pelvis CT Scan in Management of Patients with Fever of Unknown Origin, Inflammation of Unknown Origin or Episodic Fever of Unknown Origin: A Comparative Multicentre Prospective Study.

Fluorodesoxyglucose Positron Emission Tomography (PET/CT) has never been compared to Chest-Abdomen-Pelvis CT (CAPCT) in patients with a fever of unknown origin (FUO), inflammation of unknown origin (IUO) and episodic fever of unknown origin (EFUO) through a prospective and multicentre study. In this study, we investigated the diagnostic value of PET/CT compared to CAPCT in these patients. The trial was performed between 1 May 2008 through 28 February 2013 with 7 French University Hospital centres. Patients who fulfilled the FUO, IUO or EFUO criteria were included. Diagnostic orientation (DO), diagnostic contribution (DC) and time for diagnosis of both imaging resources were evaluated. One hundred and three patients were included with 35 FUO, 35 IUO and 33 EFUO patients. PET/CT showed both a higher DO (28.2% vs. 7.8%, p < 0.001) and DC (19.4% vs. 5.8%, p < 0.001) than CAPCT and reduced the time for diagnosis in patients (3.8 vs. 17.6 months, p = 0.02). Arthralgia (OR 4.90, p = 0.0012), DO of PET/CT (OR 4.09, p = 0.016), CRP > 30 mg/L (OR 3.70, p = 0.033), and chills (OR 3.06, p = 0.0248) were associated with the achievement of a diagnosis (Se: 89.1%, Sp: 56.8%). PET/CT both orients and contributes to diagnoses at a higher rate than CAPCT, especially in patients with FUO and IUO, and reduces the time for diagnosis.

Improvement of Treg immune response after treatment with tocilizumab in giant cell arteritis.

OBJECTIVES: To study the percentage, suppressive function and plasticity of Treg in giant cell arteritis (GCA), and the effects of glucocorticoids and tocilizumab. METHODS: Blood samples were obtained from 40 controls and 43 GCA patients at baseline and after treatment with glucocorticoids + IV tocilizumab (n = 20) or glucocorticoids (n = 23). Treg percentage and phenotype were assessed by flow cytometry. Suppressive function of Treg was assessed by measuring their ability to inhibit effector T-cell (Teff) proliferation and polarisation into Th1 and Th17 cells. RESULTS: Treg (CD4+CD25highFoxP3+) frequency in total CD4+ T cells was decreased in active GCA patients when compared to controls (2.5% vs. 4.7%, P < 0.001) and increased after treatment with tocilizumab but worsened after treatment with glucocorticoids alone. Treg lacking exon 2 of FoxP3 were increased in GCA patients when compared to controls (23% vs. 10% of total Treg, P = 0.0096) and normalised after treatment with tocilizumab + glucocorticoids but not glucocorticoids alone. In GCA patients, Treg were unable to control Teff proliferation and induced ˜50% increase in the amount of IL-17+ Teff, which was improved after in vitro blockade of the IL-6 pathway by tocilizumab. CONCLUSION: This study reports quantitative and functional disruptions in the regulatory immune response of GCA patients and demonstrates that, unlike glucocorticoids, tocilizumab improves Treg immune response.

Characteristics and Clinical Value of 18F-FDG PET/CT in the Management of Adult-Onset Still's Disease: 35 Cases.

While the diagnosis of adult-onset Still's disease (AOSD) involves the exclusion of differential diagnoses, the characteristics and value of 18F-Fluorodeoxyglucose (18F-FDG) Positron Emission Tomography coupled with CT (PET/CT) in the management of AOSD remain poorly known. Our retrospective study included patients from four centers, fulfilling Yamaguchi or Fautrel criteria, who underwent a PET/CT during an active AOSD. Thirty-five patients were included. At the time of PET/CT, the Yamaguchi criteria were met in 23 of 29 evaluable cases. PET/CT showed bone marrow (74.3%), lymph node (74.3%), and splenic (48.6%) FDG uptake. Despite arthralgia or arthritis in most patients, joints were rarely the sites of 18F-FDG accumulation. The spatial distribution of 18F-FDG uptake was nonspecific, and its intensity could be similar to malignant disease. Lymph node or bone marrow biopsy was performed after PET/CT in 20 patients (57.1%). The intensity of bone marrow; splenic and lymph node hypermetabolism appeared to be correlated with disease activity. Abnormal PET/CT in the cervical lymph nodes and age ≥ 60 years seemed to be predictive factors for monocyclic evolution. The clinical value of PET/CT is not in direct diagnosis; but as an aid in excluding differential diagnoses by searching for their scintigraphic features and guiding biopsy.

An immunohistochemical analysis of fibroblasts in giant cell arteritis.

BACKGROUND: Giant cell arteritis (GCA) is a systemic vasculitis of large and medium vessels characterized by an inflammatory arterial infiltrate. GCA begins in the adventitia and leads to vascular remodeling by promoting proliferation of myofibroblasts in the intima. The morphology of the fibroblasts in the adventitia in GCA is unclear. Access to temporal artery biopsies allows morphological studies and evaluation of the microenvironment of the arterial wall. We evaluated the distribution of vascular fibroblasts and of markers of their activation in GCA. METHODS: Formalin-fixed paraffin-embedded tissue sections from 29 patients with GCA and 36 controls were examined. Immunohistochemistry was performed for CD90, vimentin, desmin, alpha-smooth muscle actin (ASMA), prolyl-4-hydroxylase (P4H), and myosin to evaluate the distribution of fibroblasts within the intima, media, and adventitia. RESULTS: Temporal arteries from patients with GCA showed increased levels of CD90, vimentin, and ASMA in the adventitia and intima compared to the controls. Desmin was expressed only in the media in both groups. P4H was expressed similarly in the adventitia and intima in the two groups. Adventitial and intimal CD90+ cells co-expressed P4H, ASMA, and myosin at a high level in GCA. CONCLUSION: The results suggest a role for adventitial fibroblasts in GCA. Inhibiting the differentiation of adventitial fibroblasts to myofibroblasts has therapeutic potential for GCA.