The mediating effect of fatigue in impaired quality of life in systemic lupus erythematosus: mediation analysis of the French EQUAL cohort.

OBJECTIVES: Mediation analyses were conducted to measure the extent to which musculoskeletal (MSK) flares and depression affected physical health through excessive fatigue. METHODS: Mediation analyses were performed in a large multicentre cohort of SLE patients. Domains of the LupusQoL and SLEQOL questionnaires were selected as outcomes, MSK flares according to the SELENA-SLEDAI flare index (SFI-R) score and depression defined by Center for Epidemiologic Studies-Depression scale (CES-D) scale as exposures and different fatigue domains from MFI-20 and LupusQoL questionnaires as mediators. For each model, total, direct, indirect effects and proportion of effect mediated by fatigue (i.e. proportion of change in health-related quality of life) were determined. RESULTS: Of the 336 patients, 94 (28%) had MSK flares at inclusion and 99 (29.5%) were considered with depression. The proportion of the total effect of MSK flares on physical health impairment explained by fatigue ranged from 59.6% to 78% using the LupusQOL 'Physical health' domain and from 51.1% to 73.7% using the SLEQOL 'Physical functioning' domain, depending on the fatigue domain selected. The proportion of the total effect of depression on physical health impairment explained by fatigue ranged from 68.8% to 87.6% using the LupusQOL 'Physical health' domain and from 79.3% to 103.2% using the SLEQOL 'Physical functioning' domain, depending on the fatigue domain selected. CONCLUSIONS: The effect of MSK flares and depression on physical health impairment is largely mediated by fatigue. Thus, the patient's perception of disease activity as measured by physical health is largely influenced by fatigue. In addition, fatigue has a significant negative impact on quality of lifeof SLE patients with depression. TRIAL REGISTRATION: ClinicalTrials.gov, http://clinicaltrials.gov, NCT01904812.

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.

Disease-specific quality of life following a flare in systemic lupus erythematosus: an item response theory analysis of the French EQUAL cohort.

OBJECTIVE: To explore, at an item-level, the effect of disease activity (DA) on specific health-related quality of life (HRQoL) in SLE patients using an item response theory longitudinal model. METHODS: This prospective longitudinal multicentre French cohort EQUAL followed SLE patients over 2 years. Specific HRQoL according to LupusQoL and SLEQOL was collected every 3 months. DA according to SELENA-SLEDAI flare index (SFI) and revised SELENA-SLEDAI flare index (SFI-R) was evaluated every 6 months. Regarding DA according to SFI and each SFI-R type of flare, specific HRQoL of remitting patients was compared with non-flaring patients fitting a linear logistic model with relaxed assumptions for each domain of the questionnaires. RESULTS: Between December 2011 and July 2015, 336 patients were included (89.9% female). LupusQoL and SLEQOL items related to physical HRQoL (physical health, physical functioning, pain) were most affected by musculoskeletal and cutaneous flares. Cutaneous flares had significant influence on self-image. Neurological or psychiatric flares had a more severe impact on specific HRQoL. Patient HRQoL was impacted up to 18 months after a flare. CONCLUSION: Item response theory analysis is able to pinpoint items that are influenced by a given patient group in terms of a latent trait change. Item-level analysis provides a new way of interpreting HRQoL variation in SLE patients, permitting a better understanding of DA impact on HRQoL. This kind of analysis could be easily implemented for the comparison of groups in a clinical trial. TRIAL REGISTRATION: ClinicalTrials.gov, http://clinicaltrials.gov, NCT01904812.

Efficacy of Biological-Targeted Treatments in Takayasu Arteritis: Multicenter, Retrospective Study of 49 Patients.

BACKGROUND: The goal of this work was to assess the safety and efficacy of biologics (ie, tumor necrosis factor-α antagonists and tocilizumab) in patients with Takayasu arteritis. METHODS AND RESULTS: This was a retrospective, multicenter study of the characteristics and outcomes of 49 patients with Takayasu arteritis (80% female; median age, 42 years [20-55 years] treated by tumor necrosis factor-α antagonists [80%] or tocilizumab [20%]) and fulfilling American College of Rheumatology or Ishikawa criteria. Factors associated with complete response were assessed. Eighty-eight percent of patients with Takayasu arteritis were inadequately controlled with or were intolerant to conventional immunosuppressive therapy (median number, 3 [1-5]). Overall response (ie, complete and partial) to biological-targeted treatments at 6 and 12 months was 75% and 83%, respectively. There were significantly lower C-reactive protein levels at the initiation of biological-targeted treatments (22 mg/L [10-46 mg/L] versus 58 mg/L [26-76 mg/L]; P=0.006) and a trend toward fewer immunosuppressants drugs used before biologics (P=0.054) in responders (ie, complete or partial responders) relative to nonresponders to biological-targeted treatments. C-reactive protein levels and daily prednisone dose significantly decreased after 12 months of biological-targeted treatments (30 versus 6 mg/L [P<0.05] and 15 versus 7.5 mg [P<0.05] at baseline and 12 months, respectively). The 3-year relapse-free survival was 90.9% (83.5%-99%) over the biological treatment period compared with 58.7% (43.3%-79.7%; P=0.0025) with disease-modifying antirheumatic drugs. No difference in efficacy was found between tumor necrosis factor-α antagonists and tocilizumab. After a median follow-up of 24 months (2-95 months), 21% of patients experienced adverse effects, with biological-targeted treatments discontinued in 6.6% of cases. CONCLUSION: This nationwide study shows a high efficacy of biological-targeted treatments in refractory patients with Takayasu arteritis with an acceptable safety profile.

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.

Assessment of Prescriptions in Elderly Patients Hospitalized in Medicine Departments.

Drug-related iatrogenesis is an important issue in the elderly population, and preventing iatrogenic accidents helps to reduce hospitalizations. Our study's objective was to evaluate prescriptions in the geriatric population of our establishment. The study conducted is a targeted clinical audit. Ten criteria were tested on the hospital prescriptions of people over 75 years old in 11 medical departments, before and after improvement actions. The non-compliance threshold was set at 10% of prescriptions for each criterion. In each phase, 165 patients were included. Four criteria were non-compliant (NC) in the first phase: the presence of Potentially Inappropriate Medications for the Elderly (PIMs) (NC = 57.6%), the adaptation of the medication to renal clearance (NC = 24.9%), the presence of illogical combination (NC = 9.7%), and the total anti-cholinergic score of the prescription (NC = 12.1%). After the implementation of improvement actions, the number of non-compliant criteria decreased between the two phases, from four to two. We obtained a significant improvement for three of the four criteria found to be non-compliant in the first phase. The criterion adaptation to renal function is close to compliance (NC = 10.1%) and the PIMs criterion remained non-compliant after reassessment (NC = 32.1%). Vigilance must be ongoing in order to limit drug iatrogeny, particularly in frail elderly patients.

Myocardial infarction during giant cell arteritis: A cohort study.

BACKGROUND: Cardiovascular risk is increased in giant cell arteritis (GCA). We aimed to characterize myocardial infarction (MI) in a GCA cohort, and to compare the GCA and non-GCA population affected by MI. METHODS: In patients with a biopsy-proven diagnosis of GCA between 1 January 2001 and 31 December 2016 in Côte D'Or (France), we identified patients with MI by crossing data from the territorial myocardial infarction registry (Observatoire des Infarctus de Côte d'Or) database. Five controls (non-GCA + MI) were paired with one case (GCA + MI) after matching for age, sex, cardiovascular risk factors and prior cardiovascular disease. MI were characterized as type 1 MI (T1MI), resulting from thrombus formation due to atherothrombotic disease, or type 2 MI (T2MI), due to a myocardial supply/demand mismatch. GCA-related MI was defined as MI occurring within 3 months of a GCA flare (before or after). RESULTS: Among 251 biopsy-proven GCA patients, 13 MI cases were identified and paired with 65 controls. MI was GCA-related in 6/13 cases, accounting for 2.4% (6/251) of our cohort. T2MI was more frequently GCA-related than GCA-unrelated (80% vs. 16.7%, p = 0.080), and GCA diagnosis was the only identified triggering factor in 75% of GCA-related T2MI. GCA-unrelated MI were more frequently T1MI and occurred in patients who had received a higher cumulative dose of prednisone (p = 0.032). GCA was not associated with poorer one-year survival. CONCLUSIONS: GCA-related MI are mainly T2MI probably caused by systemic inflammation rather than coronaritis. GCA-unrelated MI are predominantly T1MI associated with atherothrombotic coronary artery disease.

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; ●●: ●●-●●.

Tolerability of opioids in patients with acute pain due to nonmalignant musculoskeletal disease. A hospital-based observational study.

OBJECTIVE: To evaluate the prevalence of adverse effects of opioids used to treat acute nonmalignant musculoskeletal pain. METHODS: Prospective, single-center, observational study in patients admitted to a rheumatology department for a nonmalignant painful musculoskeletal condition with onset within the last 3 months and a need for WHO Class III analgesics. The following side effects were recorded daily: nausea and vomiting, constipation, pruritus, urinary retention, drowsiness, confusion, and hallucinations. RESULTS: The 75 study patients (46 women and 29 men with a mean age of 56.4 years) were admitted for nerve root pain, osteoporotic vertebral fracture, inflammatory joint disease, or other disorders. First-line treatment was sustained-release morphine sulfate in a mean starting dosage of 55.2 mg/day. The dosage was increased if needed (mean maximum dosage, 78.3 mg/day). Mean treatment duration was 8.9 days. Adverse effects were recorded in 73.3% of patients but were usually minor, requiring no change in the treatment regimen. Eight patients experienced serious adverse effects (confusion in five and urinary retention in three) that resolved with no change in treatment in two patients, after dosage reduction in two patients and after substitution of fentanyl or hydromorphone hydrochloride in four patients. Treatment discontinuation was not associated with adverse effects. CONCLUSIONS: Morphine is often responsible for adverse effects in patients with acute nonmalignant musculoskeletal pain. These effects are usually moderate and very rarely require discontinuation of the drug.

Diagnostic usefulness of routine Lyme serology in patients with early inflammatory arthritis in nonendemic areas.

OBJECTIVE: To evaluate the diagnostic usefulness of routine Lyme serology in patients who live in nonendemic areas and present with early inflammatory joint disease. METHODS: All patients admitted to a rheumatology department of a nonendemic area of France for evaluation of joint disease with onset within the last year. The evaluation included a medical history, a thorough physical examination, an electrocardiogram, and an ELISA for antibodies to Borrelia burgdorferi. RESULTS: We included 90 patients, 51 women and 39 men, with a mean age of 48.1 +/- 17.9 years. Mean duration of joint symptoms was 4.3 +/- 4.3 months, with a median of 3 months. A patient (1.1%) reported a tick bite and no patients had a history of erythema migrans. Lyme serology was negative in all 90 patients. CONCLUSION: These results do not support routine Lyme serology in patients living in nonendemic areas and presenting with early inflammatory joint disease. However, Lyme serology remains appropriate in patients with features suggestive of Lyme disease. Given that Lyme disease is amenable to curative treatment, a larger study is in order to confirm our findings.

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.

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.

Dorsal prevertebral lesions in Wegener granulomatosis: report on four cases.

Retroperitoneal fibrosis has been reported in several patients with Wegener granulomatosis (WG), but only three isolated cases of dorsal prevertebral lesions, closely resembling fibrosing mediastinitis, have been published so far. We describe four new WG patients (two men, two women), 49-59 years old at diagnosis, with dorsal prevertebral lesions, mainly right-sided, and with adjacent pleural thickening in two. These lesions were detected on computed-tomography scans at diagnosis in two patients, and occurred later in the two others. Only one of them had mild back pain. Two patients' lesions were biopsied, revealing granulomatous inflammation. In one patient, the lesion regressed under WG treatment. Lesion size did not change in the remainings. Intralesional calcifications appeared in two. None of the patients had local bone erosion, vascular or neurological complications. These prevertebral lesions might represent a dorsal form of retroperitoneal fibrosis in WG, but usually with a more benign presentation and course. WG should be included in the differential diagnosis of fibrosing mediastinitis (with tuberculosis, neoplastic diseases, sarcoidosis, histiocytosis and inflammatory pseudotumor), which may have a similar radiological appearance.

[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.

Amiodarone-related acute respiratory distress syndrome following sudden withdrawal of steroids.

Acute lung toxicity is a rare but classical complication of amiodarone therapy. We report the case of a patient who developed an optic neuropathy after 15 years of amiodarone administration, and who was treated for 2 weeks with steroids. Following withdrawal of steroids, the patient rapidly developed an acute respiratory distress syndrome. Postmortem lung histologic examination was consistent with amiodarone-induced pneumonitis. Since this complication is thought to be of immunological origin, we speculate that the sudden withdrawal of steroids was implicated in the development of the acute lung injury.