Upper respiratory tract and orofacial manifestations of new-onset giant cell arteritis: results from a large, prospective inception cohort study.

OBJECTIVES: Giant cell arteritis (GCA) often features upper respiratory tract (URT) and orofacial manifestations, which signal the involvement of external carotid artery branches. In this study, we aimed to describe the frequency of various URT/orofacial symptoms at GCA onset, as well as the main characteristics of patients presenting these symptoms. METHODS: We included all patients who were newly diagnosed with GCA between 1976 and April 2022 at the Internal Medicine Department of a tertiary-care hospital. Ten URT or orofacial symptoms were prospectively examined systematically in each patient. We used multivariate analyses to identify the GCA characteristics, including URT/orofacial symptoms, associated with temporal artery biopsy (TAB) positivity. RESULTS: At least 1 URT/orofacial symptom was present in 68.6% of the 599 patients (3 or more symptoms in 30% of cases). Jaw claudication, maxillary pain, and pain during mouth opening were the most prevalent symptoms. Dry cough was recorded in 17% of cases. GCA patients with URT/orofacial symptoms had more clinical abnormalities of the temporal artery bed and ischaemic ophthalmological complications, but less large-vessel vasculitis according to imaging. The likelihood of a positive TAB was increased in patients with an abnormal temporal artery upon clinical examination (OR 4.16; CI 2.75-6.37, p < 0.001) or jaw claudication (OR 2.18; CI 1.35-3.65, p = 0.002), and decreased in those with hoarseness (OR 0.47; CI 0.26-0.87, p = 0.02) or earache (OR 0.54; CI 0.31-0.95, p = 0.03). Isolated URT/orofacial presentation (i.e., without headache or visual signs) accounted for 5.2% of the entire cohort. CONCLUSIONS: Oral-facial symptoms were present in two-thirds of GCS cases. Thus, they could serve as leading clinical clues for a GCA diagnosis, and are a risk factor for permanent visual loss. Several URT/orofacial symptoms such as jaw claudication, hoarseness, and earache influenced the likelihood of a positive TAB. Isolated URT/orofacial presentation of GCA is a rare but potentially challenging occurrence.

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.

Precipitating factors of catastrophic antiphospholipid syndrome: the role of anticoagulant treatment in a series of 112 patients.

BACKGROUND: The prevention of catastrophic antiphospholipid syndrome (CAPS), a rare complication of antiphospholipid syndrome (APS), is a major goal. OBJECTIVES: We analyzed its precipitating factors, focusing on anticoagulation immediately before CAPS episodes. METHODS: We retrospectively analyzed patients in the French multicenter APS/systemic lupus erythematosus database with at least 1 CAPS episode. Then we compared each patient with known APS before CAPS with 2 patients with non-CAPS APS matched for age, sex, center, and APS phenotype. RESULTS: We included 112 patients with CAPS (70% women; mean age, 43 ± 15 years). At least 1 standard precipitating factor of CAPS was observed for 67 patients (64%), which were mainly infections (n = 28, 27%), pregnancy (n = 23, 22%), and surgery (n = 16, 15%). Before the CAPS episode, 67 (60%) patients already had a diagnosis of APS. Of the 61 treated with anticoagulants, 32 (48%) received vitamin K antagonists (VKAs), 23 (34%) heparin, and 2 (3%) a direct oral anticoagulant. They were less likely than their matched patients with APS without CAPS to receive VKA (48% vs 66%, p = .001). Among those treated with VKA, 72% had a subtherapeutic international normalized ratio (ie, <2) versus 28% in patients with APS without CAPS (p < .001). Finally, excluding pregnant patients (n = 14) for whom we could not differentiate the effect of treatment from that of pregnancy, we were left with 47 cases, 32 (68%) of whom had recently begun a direct oral anticoagulant, planned bridging therapy, or had VKA treatment with international normalized ratio <2. CONCLUSION: These results strongly suggest that suboptimal anticoagulation management can trigger CAPS in patients with thrombotic APS.

Characterisation of a high-risk profile for maternal thrombotic and severe haemorrhagic complications in pregnant women with antiphospholipid syndrome in France (GR2): a multicentre, prospective, observational study.

BACKGROUND: Prospective data about the risks of thrombotic and severe haemorrhagic complications during pregnancy and post partum are unavailable for women with antiphospholipid syndrome. We aimed to assess thrombotic and haemorrhagic events in a prospective cohort of pregnant women with antiphospholipid syndrome. METHODS: This multicentre, prospective, observational study was done at 76 centres in France. To be eligible for this study, women had to have diagnosis of antiphospholipid syndrome; have conceived before April 17, 2020; have an ongoing pregnancy that had reached 12 weeks of gestation; and be included in the study before 18 weeks of gestation. Exclusion criteria were active systemic lupus erythematosus nephropathy, or a multifetal pregnancy. Severe haemorrhage was defined as the need for red blood cell transfusion or maternal intensive care unit admission because of bleeding or invasive procedures, defined as interventional radiology or surgery, to control bleeding. The GR2 study is registered with ClinicalTrials.gov, NCT02450396. FINDINGS: Between May 26, 2014, and April 17, 2020, 168 pregnancies in 27 centres met the inclusion criteria for the study. 89 (53%) of 168 women had a history of thrombosis. The median term at inclusion was 8 weeks gestation. 16 (10%) of 168 women (95%CI 5-15) had a thrombotic (six [4%] women; 95% CI 1-8) or severe haemorrhagic event (12 [7%] women; 95% CI 4-12). There were no deaths during the study. The main risk factors for thrombotic events were lupus anticoagulant positivity at inclusion (six [100%] of six women with thrombosis vs 78 [51%] of 152 of those with no thrombosis; p=0·030) and placental insufficiency (four [67%] of six women vs 28 [17%] of 162 women; p=0·013). The main risk factors for severe haemorrhagic events were pre-existing maternal hypertension (four [33%] of 12 women vs 11 [7%] of 156 women; p=0·014), lupus anticoagulant positivity at inclusion (12 [100%] of 12 women vs 72 [49%] of 146 women; p<0·0001) and during antiphospholipid history (12 [100%] of 12 women vs 104 [67%] of 156 women; p=0·019), triple antiphospholipid antibody positivity (eight [67%] of 12 women vs 36 [24%] of 147 women; p=0·0040), placental insufficiency (five [42%] of 12 women vs 27 [17%] of 156 women; p=0·038), and preterm delivery at 34 weeks or earlier (five [45%] of 11 women vs 12 [8%] of 145 women; p=0·0030). INTERPRETATION: Despite treatment adhering to international recommendations, a proportion of women with antiphospholipid syndrome developed a thrombotic or severe haemorrhagic complication related to pregnancy, most frequently in the post-partum period. Lupus anticoagulant and placental insufficiency were risk factors for these life-threatening complications. These complications are difficult to prevent, but knowledge of the antenatal characteristics associated with them should increase awareness and help physicians manage these high-risk pregnancies. FUNDING: Lupus France, association des Sclérodermiques de France, association Gougerot Sjögren, Association Francophone contre la Polychondrite chronique atrophiante, AFM-Telethon, the French Society of Internal Medicine and Rheumatology, Cochin Hospital, the French Health Ministry, FOREUM, the Association Prix Veronique Roualet, and UCB.

Systematic review of observational studies of the impact of cardiovascular risk factors on preeclampsia in sub-saharan Africa.

BACKGROUND: Maternal mortality is a public health issue, particularly in low- and middle-income countries (LMIC). Sub-Saharan Africa (SSA) is the region most affected worldwide by maternal mortality, and preeclampsia is one of the main causes. We performed a systematic review of observational studies to identify the impact of cardiovascular risk factors on preeclampsia in SSA with a more representative sample. METHODS: Databases: PubMed and Google Scholar were searched to identify published studies. Studies were included if they reported results on the link between at least one cardiovascular risk factor and preeclampsia. Relevant studies quality was assessed with the Newcastle-Ottawa Scale (NOS). Odds ratios and relative risk (RR) were reported with their confidence intervals. RESULTS: Twelve articles (8 case-controls, 3 cohorts, 1 cross-sectional) were included in this review, with a total of 24,369 pregnant women. Cardiovascular risk factors such as chronic hypertension, overweight, obesity, diabetes and alcohol were significantly associated with a high risk of preeclampsia. Very few data were available concerning some risk factors. None of the articles reported tobacco consumption as a preeclampsia risk factor. There is a lack of data from French-speaking SSA countries. CONCLUSION: Cardiovascular risk factors increase the risk of preeclampsia. Our results suggest the need for prospective cohort studies to ascertain this association in order to reduce maternal mortality due to preeclampsia.

Abdominal symptoms during Sjogren's syndrome: a pilot study

Abstract Background: Abdominal symptoms in patients with primary Sjögren syndrome (pSS) are poorly documented. The objective of the study was to describe the abdominal symptoms of patients with pSS and to assess their association with characteristics of the disease. Methods: One hundred and fifty patients with pSS were evaluated using a composite global symptom score for abdominal symptoms and their severity. Data concerning the clinical and biological characteristics of pSS and abdominal disorders were also collected. Results: Of the patients with pSS, 95% suffered from abdominal symptoms (median global symptom score 7.5 ±5.5 points out of 30). More than half of the patients experienced abdominal tension (68%), upper abdominal pain (54%), abdominal discomfort (58%) and/or constipation (54%). Regarding the pSS activity, in relation to European League Against Rheumatism (EULAR) Sjogren syndrome disease activity index score items, general and central nervous system involvement wereassociated with a high global symptom score. The EULAR Sjogren Syndrome Patient Reported Index (ESSPRI) symptom score was positively correlated with the global symptom score (p < 0.01). Multivariate analysis showed a significant association between a high global symptom score and SSA seronegativity, gastroparesis, and ESSPRI score (p < 0.01 for each). Conclusions: The majority of patients with pSS suffered abdominal symptoms. There is currently no therapeutic recommendation because of the lack of information on the underlying pathophysiological mechanisms. Trial registration: NCT03157011. Date of registration: July 17, 2017.(AU)

Steroid-sparing effect and toxicity of dapsone treatment in giant cell arteritis: A single-center, retrospective study of 70 patients.

Although a glucocorticoid (GC)-sparing strategy is needed for patients with giant cell arteritis (GCA) suffering from refractory disease or serious treatment-related complications, evidence of efficacy in this setting of immunosuppressive drugs and biotherapies is lacking. Herein, we evaluated the GC-sparing effects and tolerability of addition of dapsone (DDS) to prednisone therapy in patients with GCA. We retrospectively assessed data on 18 GCA patients who received DDS as a first-line treatment (DDS-1 group) and 52 patients who received it as a second- or third-line treatment for refractory GCA, with or without excessive GC-related toxicity (DDS-2 group). Of these 70 patients, 63 belonged to an inception cohort of 478 patients, whereas the remaining 7 were referred to our department for resistant GCA. In all, 52 patients were assessable for DDS efficacy. The baseline characteristics of the DDS-1 patients were similar to those of 395 GCA patients (control group) who received prednisone alone. DDS-1 patients had a more sustained decrease in GC dose with a lower mean prednisone dose at 12 months, and they comprised higher proportions who achieved GC withdrawal within the first year, who stopped prednisone treatment, and who recovered from GCA (P < 0.001 for each variable). Patients in the DDS-2 group achieved a mean rate of prednisone reduction of 65% and a prednisone dose reduction of 16.9 ±â€Š13.3 mg/d. The monthly decreases in the prednisone dose were 2.4 and 1.25 mg in DDS-1 and DDS-2 patients, respectively. DDS-induced side effects were recorded in 44 (64%) assessable patients. These side effects led to lowering of the DDS dose by 25 mg/d in 11 (16%) patients and permanent cessation of DDS in 14 patients (20%), due to allergic skin rash in 7, agranulocytosis in 2, icteric hepatitis in 2, and excessive hemolysis in 2 patients. DDS is a potent GC-sparing agent in GCA that should be evaluated in prospective studies. However, DDS use should be restricted to refractory GCA patients due to its toxicity, and close clinical and laboratory monitoring for 3 months is necessary.

Risk Factors for Permanent Visual Loss in Biopsy-proven Giant Cell Arteritis: A Study of 339 Patients.

OBJECTIVE: To determine the risk factors for permanent visual loss (PVL) in patients with biopsy-proven giant cell arteritis (GCA) and the usefulness of the factors in clinical practice. METHODS: From 1976 through 2015, the clinical charts and laboratory results of 339 patients with biopsy-proven GCA were recorded prospectively at the time of diagnosis. We used multivariable logistic regression analysis to determine which of 24 pretreatment characteristics were associated with PVL. RESULTS: Visual ischemic manifestations occurred in 108 patients, including PVL in 53 (16%), bilaterally in 15 patients (28%). The independent predictors associated with an increased risk of PVL were age (OR 1.06, 95% CI 1.01-1.12, p = 0.01), a history of transient visual ischemic symptoms (OR 2.62, 95% CI 1.29-5.29, p < 0.01), and jaw claudication (OR 2.11, 95% CI 1.09-4.10, p = 0.03). The presence of fever (OR 0.30, 95% CI 0.14-0.64, p < 0.01) and rheumatic symptoms (OR 0.23, 95% CI 0.10-0.57, p = 0.001) were associated with a markedly reduced risk of developing visual loss (3.7% if features were both present). No laboratory variables were independently associated with PVL. CONCLUSION: The visual ischemic risk of untreated GCA can be readily estimated upon simple clinical findings, but not laboratory variables. However, we did not identify a subgroup of patients carrying no risk of developing visual loss. Glucocorticoid treatment remains, therefore, urgent for any patient with a high clinical suspicion index.

Serum neurotrophin profile in systemic sclerosis.

BACKGROUND: Neurotrophins (NTs) are able to activate lymphocytes and fibroblasts; they can modulate angiogenesis and sympathic vascular function. Thus, they can be implicated in the three pathogenic processes of systemic sclerosis (SSc). The aims of this study are to determine blood levels of Nerve Growth Factor (NGF), Brain-Derived Neurotrophic Factor (BDNF) and Neurotrophin-3 (NT-3) in SSc and to correlate them with clinical and biological data. METHODS: Serum samples were obtained from 55 SSc patients and 32 control subjects to measure NTs levels by ELISA and to determine their relationships with SSc profiles. FINDINGS: Serum NGF levels were higher in SSc patients (288.26 ± 170.34 pg/mL) than in control subjects (170.34 ± 50.8 pg/mL, p<0.001) and correlated with gammaglobulins levels and the presence of both anti-cardiolipin and anti-Scl-70 antibodies (p<0.05). In contrast, BDNF levels were lower in SSc patients than in controls (1121.9 ± 158.1 vs 1372.9 ± 190.9 pg/mL, p<0.0001), especially in pulmonary arterial hypertension and diffuse SSc as compared to limited forms (all p<0.05). NT-3 levels were similar in SSc and in the control group (2657.2 ± 2296 vs 2959.3 ± 2555 pg/mL, NS). BDNF levels correlated negatively with increased NGF levels in the SSc group (and not in controls). CONCLUSION: Low BDNF serum levels were not previously documented in SSc, particularly in the diffuse SSc subset and in patients with pulmonary hypertension or anti-Scl-70 antibodies. The negative correlation between NGF and BDNF levels observed in SSc and not in healthy controls could be implicated in sympathic vascular dysfunction in SSc.