G. Pugnet

Recovery of Adrenal Function after Long-Term Glucocorticoid Therapy for Giant Cell Arteritis: A Cohort Study

Objectives Giant cell arteritis (GCA) is a chronic systemic vasculitis of large and medium-sized arteries, for which long-term glucocorticoid (GC) treatment is needed. During GC withdrawal patients can suffer adrenal insufficiency. We sought to determine the time until recovery of adrenal function after long-term GC therapy, and to assess the prevalence and predictors for secondary adrenal insufficiency. Subjects and Design 150 patients meeting the ACR criteria for GCA between 1984 and 2012 were analyzed. All received the same GC treatment protocol. The low-dose ACTH stimulation test was repeated annually until adrenal recovery. Biographical, clinical and laboratory data were collected prospectively and compared. Results At the first ACTH test, 74 (49%) patients were non-responders: of these, the mean time until recovery of adrenal function was 14 months (max: 51 months). A normal test response occurred within 36 months in 85% of patients. However, adrenal function never recovered in 5% of patients. GC of >15 mg/day at 6 months, GC of >9.5 mg/day at 12 months, treatment duration of >19 months, a cumulative GC dose of >8.5 g, and a basal cortisol concentration of <386 nmol/L were all statistically associated with a negative response in the first ACTH test (p <0.05). Conclusion Adrenal insufficiency in patients with GCA, treated long-term with GC, was frequent but transitory. Thus, physicians’ vigilance should be increased and an ACTH test should be performed when GC causes the above associated statistical factors.

Is Statin Exposure Associated with Occurrence or Better Outcome in Giant Cell Arteritis? Results from a French Population-based Study

Objective. To investigate the potential association between statin use and giant cell arteritis (GCA) course. Methods. Using the French National Health Insurance system, we included patients with incident GCA from the Midi-Pyrenees region, southern France, from January 2005 to December 2008 and randomly selected 6 controls matched by age, sex, and date of diagnosis. Statin exposure was compared between patients with GCA and their controls before GCA occurrence with a logistic regression. Influence of statin exposure on prednisone requirements during GCA course was explored with a Cox model, considering statin exposure as a time-varying variable. Results. The cohort included 103 patients (80 women, mean age 74.8 ± 9 yrs, mean followup 48.9 ± 14.8 mos), compared to 606 controls. Statin exposure (27.2% of patients with GCA and 23.4% of controls) was not associated with GCA occurrence (adjusted OR 1.2, 95% CI 0.76–1.96; p = 0.41). Diabetes mellitus was significantly associated to GCA occurrence (adjusted OR 0.38, 95% CI 0.11–0.72; p = 0.008). After diagnosis, exposure to statins up to 20 months was associated with maintenance while taking low prednisone doses (p = 0.01). Conclusion. Statin exposure was not associated with GCA occurrence in the general population. However, exposure to statins up to 20 months may favor a quicker corticosteroid tapering. Based on those results, statin effect on GCA course should not be definitively ruled out.

Giant Cell Arteritis as a Cause of Acute Myocarditis in the Elderly

To the Editor: Giant cell arteritis (GCA) is the most common vasculitis in those over age 50 years. The main symptoms are headache, jaw claudication, polymyalgia rheumatica, visual loss, fatigue, and fever. Pericarditis and myocardial infarction due to coronary arteritis have been rarely reported1,2,3. Myopericarditis has been described in only 3 patients1,2. We describe a new case of acute myopericarditis occurring in a patient with previously undiagnosed GCA. An 82-year-old woman was admitted to the emergency department for an acute retrosternal chest pain radiating to both arms and lasting for 30 min. She had no cardiovascular risk factors. She had also had 3 months of fatigue, weight loss, polymyalgia, a bitemporal headache, and jaw claudication. Examination revealed tender temporal arteries. There were no symptoms of chronic or acute heart failure. … Address correspondence to Dr. G. Pugnet, Service de Medecine Interne, CHU Toulouse-Purpan, Place du Docteur Baylac, TSA 40031, 31059 Toulouse cedex, France. E-mail: gpugnet{at}cict.fr

Fréquence et déterminants de l'insuffisance surrénalienne biologique dépistée par le test au Synacthène® à 250 μg lors du sevrage d'une corticothérapie prolongée. Étude chez 100 patients

PURPOSE The frequency of adrenal insufficiency after a prolonged, continuous course of oral high-dose corticosteroids is poorly documented. We evaluated it retrospectively in our internal medicine department. METHODS The patients were included between February 2000 and June 2007 and were administered a Synacthene 250 microg test (ST250) before tapering prednisone dose below 5mg per day. A non-responsive test was defined by a cortisol increase below 18 microg/dL, 60 min after stimulation. We also studied the risk factors associated with biological adrenal insufficiency by a multivariate logistic regression analysis. RESULTS Hundred patients were included (mean age: 61.5+/-16.3 years). Mean initial dose of corticosteroids was 65.5+/-112 mg/d. Forty-five patients failed to respond to the ST250. A normal ST250 was negatively associated with a duration of corticosteroids therapy longer than 19.5 months (OR=0.38 [0.15-0.94]; p=0.04) and positively with an age over 63.5 years (OR=2.5 [1.1-6.4]; p=0.05). Two patients experienced a clinical adrenal insufficiency crisis. CONCLUSION Biological adrenal insufficiency is very common after a prolonged course of oral high-dose corticosteroids. The risk does not seem to increase with age. The clinical benefit of a systematic ST250 at the time of corticosteroids withdrawal followed by hydrocortisone substitution if the test is non responsive remains unknown, and this practice is still a matter of debate.Purpose The frequency of adrenal insufficiency after a prolonged, continuous course of oral high-dose corticosteroids is poorly documented. We evaluated it retrospectively in our internal medicine department.

Intravenous immunoglobulins in systemic sclerosis: Data from a French nationwide cohort of 46 patients and review of the literature

BACKGROUND As intravenous immunoglobulins (IVIG) exhibit immunomodulatory and antifibrotic properties, they may be a relevant treatment for systemic sclerosis (SSc). The objectives of this work were thus to report on the efficacy and safety of IVIG in a population of SSc patients and to review the available literature. METHODS 46 patients from 19 French centers were retrospectively recruited. They were included if they had a diagnosis of SSc and received at least 1 IVIG infusion at a dosage >1g/kg/cycle. Relevant data collected at IVIG discontinuation were compared to those collected at IVIG initiation. A comprehensive literature review was performed. RESULTS We observed a significant improvement of muscle pain (74% vs. 20%, p<0.0001), muscle weakness (45% vs. 21%, p=0.01), joint pain (44% vs. 19%, p=0.02), CK levels (1069±1552UI vs. 288±449UI, p<0.0001) and CRP levels (13.1±17.6mg/L vs. 9.2±16.6mg/L, p=0.001). We also noted a trend for an improvement of gastro-esophageal reflux disease (68% vs. 53%, p=0.06) and bowel symptoms (42% vs. 27%, p=0.06). Skin and cardiorespiratory involvements remained stable. Finally, corticosteroid daily dose was significantly lower by the end of treatment (13.0±11.6mg/day vs. 8.9±10.4mg/day, p=0.01). Only two severe adverse events were reported (one case of deep vein thrombosis and one case of diffuse edematous syndrome). CONCLUSION Our work suggests that IVIG are a safe therapeutic option that may be effective in improving musculoskeletal involvement, systemic inflammation, digestive tract symptoms and could be corticosteroid sparing.

Abatacept in relapsing polychondritis

Dear Editor, We read with great interest the open clinical trial of four relapsing polychondritis (RP) patients treated with abatacept by Peng and Rodriguez recently published in the Annals of the Rheumatic Diseases .1 Indeed, as the authors pointed out, there is rational to block T-cell pathway in this disease, though the biologic agents most used as second-line therapy after corticosteroids (CS) are proinflammatory cytokines blockers as tumor necrosis factor (TNF) inhibitors or tocilizumab.2 Of note, rituximab seems not efficient in this disease.3 Despite this rational, the study by Peng and Rodriguez is the first report of abatacept use in RP since we reported a first case in 2010.4 Results from this nice small clinical trial using abatacept subcutaneously at the dose of 125 mg weekly are mitigated: three patients experienced a considerable improvement on ear, nose and throat (ENT) …

Mycobacterial-immune reconstitution inflammatory syndrome: a cause of acute interstitial nephritis during HIV infection

Kidney injury during HIV infection encompasses a wide variety of disorders, including acute interstitial nephritis. We report a case of acute granulomatous interstitial nephritis related to a mycobacterial-triggered immune reconstitution inflammatory syndrome (IRIS) in an HIV-infected patient. IRIS is an emerging health concern during HIV infection and should be considered in the diagnostic frame of acute renal failure during immune restoration.

Article originalFréquence et déterminants de l’insuffisance surrénalienne biologique dépistée par le test au Synacthène® à 250 μg lors du sevrage d’une corticothérapie prolongée. Étude chez 100 patientsFrequency and factors associated with biological adrenal insufficiency screened by the 250 μg corticotropin stimulation test after a prolonged course of systemic glucocorticoid therapy. A study of 100 patients

PURPOSE The frequency of adrenal insufficiency after a prolonged, continuous course of oral high-dose corticosteroids is poorly documented. We evaluated it retrospectively in our internal medicine department. METHODS The patients were included between February 2000 and June 2007 and were administered a Synacthene 250 microg test (ST250) before tapering prednisone dose below 5mg per day. A non-responsive test was defined by a cortisol increase below 18 microg/dL, 60 min after stimulation. We also studied the risk factors associated with biological adrenal insufficiency by a multivariate logistic regression analysis. RESULTS Hundred patients were included (mean age: 61.5+/-16.3 years). Mean initial dose of corticosteroids was 65.5+/-112 mg/d. Forty-five patients failed to respond to the ST250. A normal ST250 was negatively associated with a duration of corticosteroids therapy longer than 19.5 months (OR=0.38 [0.15-0.94]; p=0.04) and positively with an age over 63.5 years (OR=2.5 [1.1-6.4]; p=0.05). Two patients experienced a clinical adrenal insufficiency crisis. CONCLUSION Biological adrenal insufficiency is very common after a prolonged course of oral high-dose corticosteroids. The risk does not seem to increase with age. The clinical benefit of a systematic ST250 at the time of corticosteroids withdrawal followed by hydrocortisone substitution if the test is non responsive remains unknown, and this practice is still a matter of debate.Purpose The frequency of adrenal insufficiency after a prolonged, continuous course of oral high-dose corticosteroids is poorly documented. We evaluated it retrospectively in our internal medicine department.

Predictors of Cardiovascular Hospitalization in Giant Cell Arteritis: Effect of Statin Exposure. A French Population-based Study.

Objective. To identify predictors and protectors for cardiovascular hospitalization in a giant cell arteritis (GCA) population-based cohort. Methods. Using the French National Health Insurance system, we included patients with incident GCA from the Midi-Pyrenees region, southern France, from January 2005 to December 2008 and randomly selected 6 controls matched by sex and age at calendar date. We used a Cox model to identify independent predictors for cardiovascular hospitalization [combining stroke, coronary artery disease (CAD), heart failure, peripheral arterial disease, or cardiac arrhythmias]. Results. Among 103 patients with GCA followed 48.9 ± 14.8 months, the incidence rates of hospitalization for cardiovascular disease, atherosclerotic disease (combining stroke, CAD, and peripheral arterial disease), heart failure, and cardiac arrhythmias were 48.6, 17.5, 14.8, and 9.8 events per 1000 person-years versus 14.9, 4.6, 6.2, and 2.5 events per 1000 person-years among controls, respectively. In patients with GCA, cardiovascular comorbidities at diagnosis (HR 6.2, 2.0–19.2), age over 77 years (HR 5.0, 1.40–17.54), as well as the cumulative defined daily dose of statins (HR 0.993, 0.986–0.999) were independent predictors for subsequent cardiovascular hospitalization. None of the 25 patients with GCA who were taking platelet aggregation inhibitors experienced a cardiovascular hospitalization during followup. Conclusion. Patients with GCA present a high risk of cardiovascular hospitalization after diagnosis. In patients with incident GCA from the Midi-Pyrenees region, southern France, statin therapy was associated with reduced cardiovascular hospitalizations.

Tumor necrosis factor inhibitors added to nonbiological immunosuppressants vs. nonbiological immunosuppressants alone: a different signal of cancer risk according to the condition. A disproportionality analysis in a nationwide pharmacovigilance database

We aimed at detecting a signal of an increased risk of cancer in patients treated with TNF inhibitor (TNFi) and nonbiological immunosuppressant (NBIS), compared with NBIS alone for autoimmune diseases. Secondly, we aimed at comparing this risk between the different TNFis. We conducted a disproportionality analysis (case/noncase study) from the French National PharmacoVigilance Database. We selected all the reports of serious adverse drug reactions from 2000 to 2010 in patients treated with NBIS for labeled indications of TNFi. Cases were all the reports of cancer that occurred after a minimal 3‐month exposure to NBIS. Noncases were all the other reports. We searched for exposure to TNFi and calculated reporting odds ratios (RORs), stratified by condition and type of cancer and adjusted by age, gender, history of cancer, type of NBIS and year of reporting. Of the 1918 reports included in the study population, 217 were cases (135 solid and 82 blood cancers). A safety signal was found in rheumatoid arthritis (RA) (ROR: 5.43, 95% CI[3.52–8.38]) particularly for nonmelanoma skin cancer (NMSC) (20.17[2.49–163.36]), and in psoriasis/psoriatic arthritis (3.45[1.09–10.92]). No signal was found in inflammatory bowel diseases (IBD) and ankylosing spondylitis, whatever the type of cancer. There was no difference between TNFis. This study puts the argument of an increased risk of cancer (particularly NMSC) in patients with rheumatoid arthritis exposed to TNFi and NBIS compared with NBIS alone, but not in IBD and ankylosing spondylitis patients. No signal was detected for melanoma potentially related to the lack of power. The signal seems similar whatever the TNFi.