High-dose Oral Glucocorticoids Research Articles

The efficacy and safety of half-dose glucocorticoids combined with rituximab versus high-dose glucocorticoids for initial treatment of minimal change disease: a single-center experience

BackgroundMinimal change disease (MCD) is a podocytopathy more commonly seen in children, but it also accounts for 10%–25% of adult nephrotic syndrome. High-dose oral glucocorticoids were recommended for initial treatment of MCD. However, long-term use of systemic corticosteroids is associated with significant adverse events, such as steroid-induced diabetes and infections. The aim of this study was to investigate the clinical efficacy and safety of half-dose glucocorticoids combined with rituximab (RTX) for the initial treatment of MCD.MethodsWe recruited 74 patients with MCD confirmed by renal biopsy. Twenty patients were treated with RTX alone with 1000 mg at d1 and d15, 28 patients received half-dose prednisolone (0.5 mg/kg) per day combined with RTX with 1000 mg at d1, and 26 patients received high-dose prednisolone (1 mg/kg) per day. Treatment responses, including complete remission (CR) and partial remission (PR), and outcome adverse events such as steroid-induced diabetes and infections were compared among the three groups after 12 months of follow-up.ResultsAt the 12-month follow-up, the CR rates were 50%, 96.4%, and 96.2% for the RTX group, half-dose prednisolone combined with RTX group, and high-dose prednisolone group, respectively. There was no statistical difference between the half-dose prednisolone combined with RTX group and high-dose prednisolone group on CR and PR and kidney function (P > 0.05). Compared with the high-dose prednisolone group, the half-dose prednisolone combined with RTX group had a reduced incidence of adverse events of steroid diabetes (P = 0.041), especially in patients older than 55 years of age.ConclusionThe efficiency of half-dose prednisolone combined with RTX is not inferior to the recommended treatment regimen, and this regimen can effectively reduce the incidence of steroid-induced diabetes in patients with MCD. Moreover, we recommend a half-dose prednisolone combined with RTX treatment for elderly patients with MCD.

Characteristics of COVID-19 and Impact of Disease Activity in Patients with Adult-Onset Still's Disease.

This study aimed to characterize the morbidity, hospitalization, and mortality rates among patients with adult-onset Still's disease (AOSD) affected by coronavirus disease 2019 (COVID-19) and explore the impact of COVID-19 on the disease activity of AOSD. Data on the clinical and demographic characteristics, COVID-19-related symptoms, and outcomes were retrospectively collected. Patients were stratified according to COVID-19 severity and associations between risk factors and outcomes were analyzed using multivariate logistic regression. The disease activity of patients with AOSD flares after COVID-19 was described. A total of 188 patients with AOSD were followed up, of whom 75.5% (n = 142) had a confirmed or highly suspected COVID-19. Patients on medium or high-dose oral glucocorticoids or Janus kinase (JAK) inhibitors were at increased risk of developing moderate to severe COVID-19. Six patients suffered flares of AOSD following COVID-19 in a short period; however, the relapse rate was not statistically increased compared with patients without COVID-19. Patients with AOSD receiving medium or high-dose glucocorticoid therapy or JAK inhibitors had worse COVID-19 outcomes. Further work is needed to explore risk factors affecting COVID-19 outcomes and the impact of COVID-19 on disease activity in AOSD.

Childhood-onset systemic lupus erythematosus: characteristics and the prospect of glucocorticoid pulse therapy.

Childhood-onset systemic lupus erythematosus (cSLE) is an autoimmune disease that results in significant damage and often needs more aggressive treatment. Compared to adult-onset SLE, cSLE has a stronger genetic background and more prevalent elevated type I Interferon expression. The management of cSLE is more challenging because the disease itself and treatment can affect physical, psychological and emotional growth and development. High dose oral glucocorticoid (GC) has become the rule for treating moderate to severe cSLE activity. However, GC-related side effects and potential toxicities are problems that cannot be ignored. Recent studies have suggested that GC pulse therapy can achieve disease remission rapidly and reduce GC-related side effects with a reduction in oral prednisone doses. This article reviews characteristics, including pathogenesis and manifestations of cSLE, and summarized the existing evidence on GC therapy, especially on GC pulse therapy in cSLE, followed by our proposal for GC therapy according to the clinical effects and pathogenesis.

Common mental health disorders in adults with inflammatory skin conditions: nationwide population-based matched cohort studies in the UK

BackgroundPsoriasis and atopic eczema are common inflammatory skin diseases. Existing research has identified increased risks of common mental disorders (anxiety, depression) in people with eczema and psoriasis; however, explanations for the associations remain unclear. We aimed to establish the risk factors for mental illness in those with eczema or psoriasis and identify the population groups most at risk.MethodsWe used routinely collected data from the UK Clinical Practice Research Datalink (CPRD) GOLD. Adults registered with a general practice in CPRD (1997–2019) were eligible for inclusion. Individuals with eczema/psoriasis were matched (age, sex, practice) to up to five adults without eczema/psoriasis. We used Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for hazards of anxiety or depression in people with eczema/psoriasis compared to people without. We adjusted for known confounders (deprivation, asthma [eczema], psoriatic arthritis [psoriasis], Charlson comorbidity index, calendar period) and potential mediators (harmful alcohol use, body mass index [BMI], smoking status, and, in eczema only, sleep quality [insomnia diagnoses, specific sleep problem medications] and high-dose oral glucocorticoids).ResultsWe identified two cohorts with and without eczema (1,032,782, matched to 4,990,125 without), and with and without psoriasis (366,884, matched to 1,834,330 without). Sleep quality was imbalanced in the eczema cohorts, twice as many people with eczema had evidence of poor sleep at baseline than those without eczema, including over 20% of those with severe eczema. After adjusting for potential confounders and mediators, eczema and psoriasis were associated with anxiety (adjusted HR [95% CI]: eczema 1.14 [1.13–1.16], psoriasis 1.17 [1.15–1.19]) and depression (adjusted HR [95% CI]: eczema 1.11 [1.1–1.12], psoriasis 1.21 [1.19–1.22]). However, we found evidence that these increased hazards are unlikely to be constant over time and were especially high 1-year after study entry.ConclusionsAtopic eczema and psoriasis are associated with increased incidence of anxiety and depression in adults. These associations may be mediated through known modifiable risk factors, especially sleep quality in people with eczema. Our findings highlight potential opportunities for the prevention of anxiety and depression in people with eczema/psoriasis through treatment of modifiable risk factors and enhanced eczema/psoriasis management.

Successful treatment of nephrotic syndrome due to pregnancy-related crescentic IgA nephropathy: a case report

BackgroundCrescentic immunoglobulin A (IgA) nephropathy, defined as > 50% of the glomeruli with crescents, often has a poor renal prognosis. Because of the high prevalence of pre-eclampsia in the second trimester of pregnancy, we often fail to investigate the new onset of glomerulonephritis and the aggravation of subclinical nephropathies. We report a case of nephrotic syndrome suggestive of crescentic IgA nephropathy possibly triggered by pregnancy.Case presentationA 33-year-old multipara was referred for persistent proteinuria, hematuria, and hypoalbuminemia two months postpartum. The patient was diagnosed with proteinuria for the first time at 36 weeks of gestation. The patient was normotensive during pregnancy. Renal biopsy revealed crescentic IgA nephropathy, with cellular crescents in 80% of the glomeruli and no global sclerosis. After treatment with pulse steroids followed by high-dose oral glucocorticoids and tonsillectomy, a gradual improvement was seen in proteinuria, hematuria, and hypoalbuminemia.ConclusionAlthough the precise mechanism remains unclear, pregnancy possibly triggered the new onset of crescentic IgA nephropathy or the aggravation of subclinical IgA nephropathy.

Impact of previous glucocorticoid therapy on diagnostic accuracy of [18F] FDG PET-CT in giant cell arteritis

To evaluate the impact of prior glucocorticoid (GC) treatment on the diagnostic accuracy of 18F-FDG PET-CT in giant cell arteritis (GCA). Retrospective study of a consecutive cohort of 85 patients with proven GCA who received high-dose GC before PET-CT. Thirty-nine patients previously treated with methylprednisolone (MP) boluses, of whom 37% were PET-CT (uptakes grade 3 or 2) positive. The positivity rate was 80% with MP doses of 125mg, 33% with 250 or 500mg, and 0% with doses of 1g. If we also classify as positive those cases with a grade 1 uptake (with a circumferencial uptake and smooth linear or long segmental pattern, possibly indicative of "apparently inactive" vasculitis), the positivity rate increases to 62% (100%, 50-60%, and 33% for the different MP doses, respectively). In patients with new-onset GCA treated with high-dose oral GC, PET-CT positivity was 54.5% in patients treated for less than two weeks, 38.5% in those treated for 2 to 4 weeks, and 25% in those treated for 4 to 6 weeks (increasing to 91%, 77%, and 50%, respectively, if we include cases with grade 1 uptake and these characteristics). In patients with relapsing/refractory GCA, or who developed GCA having a prior history of PMR, PET-CT positivity reached 54% despite long-term treatment with low-to-moderate doses of GC (68% including cases with a grade 1 uptake). A late 18F-FDG PET-CT (beyond the first 10 days of treatment) can also be informative in a considerable percentage of cases.

362 COMPLETE HEART BLOCK AS A RARE MANIFESTATION OF GRANULOMATOSIS WITH POLYANGIITIS: A CASE REPORT

Abstract A 42-year-old male with prior smoking habit presented at our emergency department after atraumatic syncope preceded by severe pain in the left lower limb. He had no past relevant medical history until one month prior to presentation, when the onset and persistence of nonproductive cough deemed the performance of a chest computed tomography (CT), which showed a 28 mm pulmonary nodule. A positron emission tomography-CT scan performed thereafter showed hypercaptation of the apical pulmonary nodule (SUV 6.87), and hypercaptation of the left nasal cavities. He was not on daily medications. On presentation the patient complained of dyspnoea at rest with no chest pain. On physical examination the left foot was cold and numb with no pedidial pulses. Laboratory assessment showed leukocytosis, thrombocytosis, anemia and elevated C-reactive protein, troponin I, NTproBNP and creatinine levels. The 12-lead electrocardiogram showed sinus rhythm with complete atrioventricular block and ventricular escape rhythm at 40 bpm; the transthoracic echocardiography revealed a mildly impaired left ventricular systolic function with basal septal hypokinesis; a chest-CT scan confirmed the stability of the aforementioned pulmonary lesions. The patient was transported to the catheterization laboratory for temporary pacemaker insertion and coronary angiography, which depicted distal occlusion of the first septal branch, the first diagonal branch and the obtuse marginal branch; no percutaneous coronary intervention was performed. The patient was then transferred to our Coronary Intensive Care Unit: due to persistent ischemia of the left lower limb, and several unsuccessful procedures to restore limb vascularization, a leg amputation above the knee was performed on day 2 of hospitalization. Meanwhile, the patient also developed fever, epididymitis, digital infarcts with bilateral hand purpura, upper and lower extremities paresthesia, worsening renal failure, persistent anemia and leukocytosis with eosinophilia. Neoplastic markers, blood cultures and urine cultures resulted negative; urine sediment examination showed cylinders, leucocytes and severe dysmorphic microhematuria suggestive of glomerulonephritis; bronchoalveolar lavage showed inflammatory cells. A rheumatologic screening was also performed, showing high titer of cANCA (125 UI/ml) hinting at a systemic vasculitis. The histopathological results of the amputated limb depicting marked necrotizing vasculitis with extensive involvement of small-medium caliber and larger caliber arterial vessels. Based on these clinical and laboratory findings, a diagnosis of granulomatosis with polyangiitis (GPA) with myocardial infarction due to coronary involvement and subsequent atrioventricular block was made on day 4 of hospitalization. Daily 500 mg boluses of intravenous methylprednisolone were administered for three days since day 4 of hospitalization, followed by high dose oral glucocorticoids (prednisone 1 mg/kg/day) and subsequent remission induction therapy with rituximab 375 mg/m2 weekly. Renal function progressively improved; heart conduction abnormalities gradually recovered and there was a marked reduction of the size of the pulmonary nodule. GPA presents remains one of the most challenging diagnostic dilemmas in clinical medicine. Despite we performed a prompt diagnosis, a leg amputation had to be done due to the common rapid progression of the disease. Clinicians should be aware of the various manifestations of GPA and bear in mind the possibility of coronary vasculitis.

609 LUPUS IN SHEEP'S CLOTHING: A CARDIAC TAMPONADE DUE TO ACUTE POLYSIEROSITIS IN A SLE PATIENT.

Abstract This case describes a cardiac tamponade in systemic lupus erythematosus (SLE), an uncommon but life-threatening condition that needs prompt recognition. A 33-year-old woman with therapy-resistant SLE presented to the Emergency Department with chest pain and fever for 3 days. She was hemodynamically stable, the ECG showed signs of pericarditis and echocardiography showed a minimal pericardial effusion. Pericarditis was diagnosed and the patient was admitted to the Cardiology Ward. Seven hours later her symptoms deteriorated, presenting hemodynamic instability with hypotension and tachycardia. The ECG showed low QRS voltage and electrical alternans, echocardiography confirmed cardiac tamponade. The patient underwent an emergency pericardiocentesis with 220 mL of serous citrine liquid removed and immediate regression of symptoms. The cytology exam revealed inflammatory cells with no evidence of malignancy, blood culture and effusion fluid's tests came back negative. A Thoraco-abdominal CT revealed also bilateral pleural effusion (not present at the admission) and ascites. Signs, symptoms and medical history suggested SLE flare-up and high-dose oral glucocorticoid therapy was started. Our report highlights a rare presentation of life-threatening polyserositis in SLE flare-up. Although pericarditis and pericardial effusion are frequently-reported SLE's cardiovascular complications, rapid development of cardiac tamponade is far from common. Acute cardiac tamponade, like in our case, is an indication for emergency pericardial drainage to restore an adequate cardiac output. We describe an out of ordinary case of a patient in whom an accurate and timely diagnosis of SLE–related cardiac tamponade has been live–saving.

Postdischarge Glucocorticoid Use and Clinical Outcomes of Multisystem Inflammatory Syndrome in Children

Minimal data are available regarding the postdischarge treatment of multisystem inflammatory syndrome in children (MIS-C). To evaluate clinical characteristics associated with duration of postdischarge glucocorticoid use and assess postdischarge clinical course, laboratory test result trajectories, and adverse events in a multicenter cohort with MIS-C. This retrospective cohort study included patients with MIS-C hospitalized with severe illness and followed up for 3 months in an ambulatory setting. Patients younger than 21 years who were admitted between May 15, 2020, and May 31, 2021, at 13 US hospitals were included. Inclusion criteria were inpatient treatment comprising intravenous immunoglobulin, diagnosis of cardiovascular dysfunction (vasopressor requirement or left ventricular ejection fraction ≤55%), and availability of complete outpatient data for 3 months. Glucocorticoid treatment. Main outcomes were patient characteristics associated with postdischarge glucocorticoid treatment, laboratory test result trajectories, and adverse events. Multivariable regression was used to evaluate factors associated with postdischarge weight gain (≥2 kg in 3 months) and hyperglycemia during illness. Among 186 patients, the median age was 10.4 years (IQR, 6.7-14.2 years); most were male (107 [57.5%]), Black non-Hispanic (60 [32.3%]), and Hispanic or Latino (59 [31.7%]). Most children were critically ill (intensive care unit admission, 163 [87.6%]; vasopressor receipt, 134 [72.0%]) and received inpatient glucocorticoid treatment (178 [95.7%]). Most were discharged with continued glucocorticoid treatment (173 [93.0%]); median discharge dose was 42 mg/d (IQR, 30-60 mg/d) or 1.1 mg/kg/d (IQR, 0.7-1.7 mg/kg/d). Inpatient severity of illness was not associated with duration of postdischarge glucocorticoid treatment. Outpatient treatment duration varied (median, 23 days; IQR, 15-32 days). Time to normalization of C-reactive protein and ferritin levels was similar for glucocorticoid duration of less than 3 weeks vs 3 or more weeks. Readmission occurred in 7 patients (3.8%); none was for cardiovascular dysfunction. Hyperglycemia developed in 14 patients (8.1%). Seventy-five patients (43%) gained 2 kg or more after discharge (median 4.1 kg; IQR, 3.0-6.0 kg). Inpatient high-dose intravenous and oral glucocorticoid therapy was associated with postdischarge weight gain (adjusted odds ratio, 6.91; 95% CI, 1.92-24.91). In this multicenter cohort of patients with MIS-C and cardiovascular dysfunction, postdischarge glucocorticoid treatment was often prolonged, but clinical outcomes were similar in patients prescribed shorter courses. Outpatient weight gain was common. Readmission was infrequent, with none for cardiovascular dysfunction. These findings suggest that strategies are needed to optimize postdischarge glucocorticoid courses for patients with MIS-C.

Association of Race and Ethnicity With Medication Use for Pediatric Lupus in the Childhood Arthritis and Rheumatology Research Alliance Registry.

Black and Hispanic children with pediatric lupus (pSLE) have higher morbidity and mortality than non-Hispanic White children. The extent to which differences in outcomes are due to treatment disparities, including medication use, is unknown. We aimed to determine whether medication use in pSLE is associated with race and ethnicity in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry. Patients with pSLE enrolled in the CARRA Registry from 2017 to 2020 were included. Multivariable mixed-effect logistic regression, adjusted for site of care, was used to compare use of antimalarials, high-dose oral glucocorticoids, and rituximab in Black and Hispanic children. We identified 639 children with pSLE, of whom 480 had at least 1 year of follow-up. At enrollment, 89% of patients were prescribed an antimalarial and 50% were on high-dose glucocorticoids. Of those with 1 year of follow-up, 12% received rituximab. Nephritis, shorter disease duration, and higher Systemic Lupus Erythematosus Disease Activity Index 2000 scores were associated with high-dose glucocorticoid use. Antimalarial use was higher among those with nephritis and lower in children with no insurance. Rituximab use was associated with Black race in the fixed-effects model but not when adjusted for site of care. We identified differences in medication use by race and insurance status. Site of care was associated with the racial differences observed in rituximab use. Further research is needed to optimize pSLE treatments particularly where use is highly variable, including glucocorticoid dosing and use of rituximab, and understand the impact of practice variation on disparities in pSLE outcomes.

Bullous systemic lupus erythematosus with nephrotic syndrome in an adolescent girl: a case report

Bullous systemic lupus erythematosus is an uncommon autoimmune subepidermal vesiculobullous disease occurring in less than 5% of patients with systemic lupus erythematosus. The diagnosis of bullous systemic lupus erythematosus is based on clinical picture, histopathological findings, direct immunofluorescence and other immunologic tests. Importantly, establishing the diagnosis of bullous systemic lupus erythematosus requires the occurrence of systemic lupus erythematosus according to the American College of Rheumatology criteria. We report a case of bullous systemic lupus erythematosus in a 16-year-old Vietnamese girl, who demonstrated an acquired vesiculobullous eruption associated with nephrotic syndrome and fulfilled the European League Against Rheumatism/ American College of Rheumatology 2019 classification criteria of systemic lupus erythematosus. Clinical examination showed numerous tense, clear fluid-filled vesicles and bullae affecting the whole body with the predilection for the face, neck, chest, abdomen and bilateral inner thigh areas. Erosions were observed on the tongue and the buccal mucosa. Histopathologic examination showed subepidermal vesicle containing abundant neutrophils and perivascular mixed inflammatory cell infiltration. Microabscesses at tips of dermal papillae and the features of a leukocytoclastic vasculitis were not seen. Direct immunofluorescence of perilesional skin biopsies demonstrated linear deposition of IgG, IgA, IgM and C3 in the basement membrane zone. Linear immunoglobulin deposition displayed a u-serrated pattern with the predominant staining intensity of IgG. Serologic tests showed positive antinuclear antibody. Complement components assay revealed low levels of C3 (66.5 mg/dL) and C4 (3,9mg/dL). Proteinuria level was increased to 3.5g/24 hours. The final diagnosis of bullous systemic lupus erythematosus with nephrotic syndrome was made. The patient was treated with a high-dose oral glucocorticoid scheme and showed significant clinical improvement.

LISTERIA BACTEREMIA PRESENTING WITH CEREBRAL ABSCESS AND ENDOCARDITIS IN AN ELDERLY PATIENT WITH CHRONIC IMMUNE THROMBOCYTOPENIA

TOPIC: Cardiovascular Disease TYPE: Medical Student/Resident Case Reports INTRODUCTION: Listeria monocytogenes, an intracellular gram-positive bacillus, is a ubiquitous foodborne pathogen that causes Listeriosis. Its clinical spectrum ranges from mild, self-limiting gastroenteritis in immunocompetent individuals to severe, life-threatening, invasive disease affecting persons at the extremes of age, pregnant women, and individuals with cell-mediated immunodeficiencies. Central nervous system involvement by is common – presenting as meningitis, meningoencephalitis or, less frequently, rhombencephalitis. Listerial brain abscesses are rare. Moreover, only 5-8% of these infections are complicated by infective endocarditis (IE). CASE PRESENTATION: A 70-year-old Caucasian man with chronic immune thrombocytopenia (ITP) presented to the ED with acute onset of altered mental status and right-sided weakness. He was afebrile, with no heart murmurs or peripheral stigmata of IE. Neurologic exam findings included disorientation, expressive aphasia, and right-sided hemiparesis. Laboratory findings were unremarkable except for leukocytosis and hyponatremia. Brain MRI showed an irregular rim-enhancing lesion in the left frontal lobe with surrounding edema and midline shift. The lesion was excised with adjacent necrotic tissue and frozen sections were highly suspicious for a high-grade glial neoplasm. He was started empirically on vancomycin, ceftriaxone and metronidazole. Eventually, the organism was identified as Listeria monocytogenes from two sets of blood cultures; hence, antibiotics were de-escalated to ampicillin and gentamicin. Transesophageal echocardiography (TEE) showed mitral valve vegetation. The patient developed fever on day 4; by day 6, he began to defervesce and showed improvement in mental status. On day 9, he was discharged to the inpatient rehabilitation center to complete a total of 6 weeks on IV ampicillin and IV gentamicin. Pathology of the brain mass was subsequently reported as listerial brain abscess with no evidence of malignancy. DISCUSSION: Chronic treatment with high-dose oral glucocorticoids and pre-existing ITP have been independently implicated as predisposing factors in listerial brain abscess. There is a propensity to misdiagnose listerial brain abscess as an intracranial neoplasm due to similar clinical/imaging findings, especially when fever is absent at presentation. In addition, Listeria monocytogenes is an atypical cause of IE. Our patient had no pre-existing structural or valvular heart disease, but he satisfied two major diagnostic criteria for IE – two separate positive blood cultures of Listeria monocytogenes and a TEE demonstrating mitral valve vegetation. CONCLUSIONS: A high index of suspicion is necessary for early recognition and successful treatment of listerial brain abscess and listerial endocarditis in high-risk patients. REFERENCE #1: Tiri B, Priante G, Saraca LM, Martella LA, Cappanera S, Francisci D. Listeria monocytogenes brain abscess: controversial issues for the treatment—two cases and literature review. Case Rep Infect Dis. 2018;2018(6549496):1-9. REFERENCE #2: Hohmann EL, Portnoy DA. Listeria monocytogenes infections. In: Jameson JL, Kasper DL, Longo DL, Fauci AS, Hauser SL, Loscalzo J, eds. Harrison's Principles of Internal Medicine. 20th ed. New York, NY: McGraw-Hill Education; 2018:1100-1102. REFERENCE #3: Garcia-Granja PE, Lopez J, Vilacosta I, Olmos C, Sarria C, Roman JAS. Infective endocarditis due to Listeria monocytogenes: a report of 4 patients. Cardiol. 2016;69(7):699–709. DISCLOSURES: No relevant relationships by Nili Gujadhur, source=Web Response no disclosure on file for Vanessa Karimi; No relevant relationships by Olushola Ogunleye, source=Web Response

Giant Cell Arteritis: A Systematic Review and Meta-Analysis of Test Accuracy and Benefits and Harms of Common Treatments.

This systematic review compares treatment options for patients with giant cell arteritis (GCA) and evaluates the test accuracy of studies used in diagnosing and monitoring GCA. These studies were used to inform evidence‐based recommendations for the American College of Rheumatology (ACR)/Vasculitis Foundation (VF) vasculitis management guidelines. A systematic review and search of articles in English in Ovid Medline, PubMed, Embase, and the Cochrane Library was conducted. Articles were screened for suitability, and studies presenting the highest level of evidence were given preference. Three hundred ninety‐nine full‐text articles addressing GCA questions were reviewed to inform 27 Population, Intervention, Comparison, and Outcome questions. No benefit was found with intravenous glucocorticoids (GCs) compared with high‐dose oral GCs in patients with cranial ischemic symptoms (27.4% vs 12.3%; odds ratio [OR] 2.39 [95% confidence interval (CI) 0.75‐7.62], [very low certainty of evidence]). Weekly tocilizumab with a 26‐week GC taper was superior to a 52‐week GC taper in patients achieving remission (risk ratio 4.00 [95% CI 1.97‐8.12], [low certainty of evidence]). Non‐GC immunosuppressive therapies with GCs compared with GCs alone showed no statistically significant in relapse at 1 year (OR 0.87 [95% CI 0.73‐1.04], [moderate certainty of evidence]) or serious adverse events (OR 0.81 [95% CI 0.54‐1.20]; [moderate certainty of evidence]). Temporal artery biopsy has a sensitivity of 61% (95% CI 38%‐79%) and a specificity of 98% (95% CI 95%‐99%) in patients with a clinical diagnosis of suspected GCA. This comprehensive systematic review synthesizes and evaluates the benefits and harms of different treatment options and the accuracy of commonly used tests for the diagnosis and monitoring of GCA.

Intravenous methylprednisolone induces rapid improvement in non-infectious uveitis: a multicentre study of 112 patients.

Rapid control of intraocular inflammation in non-infectious uveitis (NIU) is mandatory to avoid irreversible structural and functional damage. In this study, we assessed the efficacy and safety of intravenous methylprednisolone (IVMP) pulses in the treatment of NIU. A retrospective case series of 112 patients who received IVMP for the treatment of NIU, either isolated or associated with different underlying diseases, was studied. Intraocular inflammation (anterior chamber cells and vitritis) was the primary outcome measure. Secondary outcome measures were macular thickness and best corrected visual acuity (BCVA). Patients were assessed at baseline visit, and at days 2-5, 7, 15 and 30 after initiation of IVMP pulse therapy. A total of 112 patients (mean age 42±14.5 yrs) were assessed. An underlying immune-mediated disease was diagnosed in 73 patients. Inflammatory ocular patterns were panuveitis (n=68), posterior uveitis (n=30), anterior uveitis (AU) (n=12), and intermediate uveitis (n=2). Additionally, patients presented cystoid macular oedema (CME) (n=50), retinal vasculitis (n=37), and exudative retinal detachment (n=31). Therapies used before IVMP included intraocular glucocorticoids (n=4), high-dose oral systemic glucocorticoids (n=77), and conventional (n=107) or biologic (n=40) immunosuppressive drugs. IVMP dose ranged from 80 to 1,000 mg/day for 3-5 consecutive days. Improvement was observed in AU, vitritis, BCVA, CME, and retinal vasculitis. At first month evaluation, total remission was achieved in 19 patients. Side effects of IVMP were respiratory infections (n=3), uncontrolled hyperglycaemia (n=1), herpes zoster (n=1), and oral candidiasis (n=1). IVMP pulse therapy was effective and safe, and achieved rapid control of NIU.

Oral Glucocorticoids and Incident Treatment of Diabetes Mellitus, Hypertension, and Venous Thromboembolism in Children.

Rates of incident treatment were quantified in this study for diabetes mellitus, hypertension, and venous thromboembolism (VTE) associated with oral glucocorticoid exposure in children aged 1-18 years. The retrospective cohort included more than 930,000 children diagnosed with autoimmune diseases (namely, inflammatory bowel disease, juvenile idiopathic arthritis, or psoriasis) or a nonimmune comparator condition (attention-deficit/hyperactivity disorder) identified using US Medicaid claims (2000-2010). Associations of glucocorticoid dose per age- and sex-imputed weight with incident treated diabetes, hypertension, and VTE were estimated using Cox regression models. Crude rates were lowest for VTE (unexposed: 0.5/million person-days (95% confidence interval (CI): 0.4, 0.6); currently exposed: 15.6/million person-days (95% CI: 11.8, 20.1)) and highest for hypertension (unexposed: 6.7/million person-days (95% CI: 6.5, 7.0); currently exposed: 74.4/million person-days (95% CI: 65.7, 83.9)). Absolute rates for all outcomes were higher in unexposed and exposed children with autoimmune diseases compared with those with attention-deficit/hyperactivity disorder. Strong dose-dependent relationships were found between current glucocorticoid exposure and all outcomes (adjusted hazard ratios for high-dose glucocorticoids: for diabetes mellitus, 5.93 (95% CI: 3.94, 8.91); for hypertension, 19.13 (95% CI: 15.43, 23.73); for VTE, 16.16 (95% CI: 8.94, 29.22)). These results suggest strong relative risks, but low absolute risks, of newly treated VTE, diabetes, and especially hypertension in children taking high-dose oral glucocorticoids.

Seventy years after Hench's Nobel prize: revisiting the use of glucocorticoids in systemic lupus erythematosus.

In 1950, Hench, Kendall and Reichstein were awarded with the Nobel Prize in Physiology and Medicine for the isolation and first therapeutic use of glucocorticoids. Since then, they have become one of the main agents in the treatment of systemic lupus erythematosus (SLE). The use of high-dose oral glucocorticoids (usually 1 mg/kg/day of prednisone equivalent) have become the rule for treating moderate to severe lupus activity. In addition, tapering schemes have not been well defined, all this leading to prolonged exposures to potentially damaging amounts of glucocorticoids. Several studies have shown that glucocorticoids are a major cause of toxicity in SLE in a dose-dependent manner, with prolonged doses greater than 7.5 mg/day being associated with damage accrual. Thus, there is an urgent need for different therapeutic schedules that can achieve a rapid and durable control of lupus activity while reducing the many unwanted effects of glucocorticoids. Recent data show that pulses of methyl-prednisolone are an effective first-line therapy to treat lupus flares (not only severe ones) without major short or long-term toxicity and allowing a reduction in oral prednisone doses. Universal use of hydroxychloroquine - always recommended, infrequently accomplished - and early therapy with immunosuppressive drugs also help control SLE and reduce prednisone load. Results from observational studies confirm the more rapid achievement of remission and the reduction of long-term damage using these combination schedules with reduced prednisone doses. Seventy years after their first therapeutic use, we are learning to use glucocorticoids in a more efficient and safe manner.

47. Claudication, Cerebral infarct and Cyclophosphamide

IntroductionWe present a severe and rare case of GCA involving the right middle cerebral artery (MCA) resulting in an ischaemic stroke. Our patient presented in 2017, before tocilizumab was approved as a treatment option in refractory GCA. Intravenous cyclophosphamide was used as a glucocorticoid-sparing agent in this patient with good response. This case contributes to our current limited evidence base in the treatment and prognosis of intracranial GCA.Case descriptionThe patient was 75 years old when referred by his GP with a four-month history of left temporal headache, jaw claudication and weight loss in August 2017. He had type 2 diabetes and hypertension. He also had a stroke in 2015 and was subsequently found to have paroxysmal atrial fibrillation so was commenced on rivaroxaban. His bloods showed ESR of 66 and CRP 18. ESR had been persistently raised for two months. Ophthalmology assessment revealed bilateral cataracts only. A clinical diagnosis of GCA was made and he was commenced on prednisolone 60mg daily. A biopsy of his left temporal artery was performed six days later and the histology showed transmural inflammation with multinucleated giant cells. His headache and jaw claudication improved with prednisolone but he was still experiencing localised temporal artery tenderness. In the last week of September 2017, he presented to the Emergency Department with a two-day history of incoordination and left arm weakness. MRI of his head showed small foci of infarcts in the right MCA territory. He had suffered an ischaemic stroke likely secondary to GCA despite being treated with high dose oral glucocorticoid. He was given three pulses of intravenous methylprednisolone followed by intravenous cyclophosphamide.Subsequent CT angiogram (CTA) confirmed the involvement of intracranial arteries – circumferential thickening of the right internal carotid artery with near complete occlusion of right cavernous and intracranial segments. There was also mural thickening involving the left vertebral artery. He went on to have five more cycles of cyclophosphamide and responded well to treatment. Oral methotrexate 15mg weekly was added in two weeks after the last course of cyclophosphamide. During his last clinic visit, he was taking prednisolone 2mg daily and the plan was to taper the dose down to zero over eight weeks.DiscussionThough uncommon, GCA can affect vertebrobasilar arteries causing strokes. The involvement of intracranial arteries, on the other hand, is thought to be extremely uncommon in GCA due to their increased wall thickness. There is only a limited number of intracranial GCA cases reported in the medical literature. A review of nearly 500 patients with a diagnosis of central nervous system vasculitis at the Mayo Clinic identified only two patients with convincing evidence of intracranial GCA.Our patient’s MRI and CTA were reviewed in the neuroradiology multidisciplinary meeting and the consensus was that there was a near complete occlusion of the right MCA due to a vasculitic process. Importantly, his GCA went into remission and he has not had any relapses thus far (21 months since his initial presentation). He has also improved from the stroke point of view. We have been able to reduce his prednisolone dose to a minimal level.The use of oral or intravenous cyclophosphamide in the treatment of refractory GCA have been reported. It was found to be effective in inducing a sustained remission in a majority of patients in a series of 35 patients in Germany. However, significant adverse events were reported in one third of the patients.Our patient tolerated intravenous cyclophosphamide therapy well. He was given fluconazole and co-trimoxazole as prophylactics. He did not report any major infections or adverse events during the four-month period when he was on cyclophosphamide.Key learning pointsThis case represents a severe variant of GCA. Our patient was only referred to secondary care after being unwell for several months. It illustrates the importance of promptly initiating investigations and treatment when GCA is suspected. This case demonstrates the importance of following up with patients closely as well as working closely with the multispecialty team in managing patients with GCA. Conflicts of interestThe authors have declared no conflicts of interest.

Experiencia con rituximab en el tratamiento de las enfermedades ampollares autoinmunes

BackgroundPemphigus vulgaris and foliaceus are bullous autoimmune diseases caused by antibodies directed against desmoglein 1 and/or 3. The standard treatment is high-dose oral glucocorticoids and other immunosuppressants such as azathioprine or mycophenolate. Rituximab (RTX), an anti-CD20 monoclonal antibody, has been shown effective in the treatment of these entities. ObjectiveTo assess the degree of response to RTX (partial response/complete response) and the time to reach it; the time to relapse, the evolution of anti-desmoglein antibodies 1/3 and the possible adverse effects. Patients and methodsThis is a retrospective descriptive and single institution study including all patients diagnosed with pemphigus vulgaris or pemphigus foliaceus treated with RTX and with a minimum post-treatment follow-up of 6 months. ResultsSix patients were included (4 pemphigus vulgaris and 2 pemphigus foliaceus) with a mean follow-up of 84 months. The total number of RTX cycles administered was 15, reaching a complete response in 7 cycles, a partial response in 6 and no response in 1. An improvement in the Autoimmune Bullous Skin Disorder Intensity Score was observed both in the cutaneous involvement (range 0-150; mean pre/pos-RTX 3,19/1) as in the oral extension (range 0-11; mean pre/pos-RTX 9,21/1,33). The mean time to relapse was 20.75 months. Only two patients had mild immediate adverse effects during drug perfusion (headache and high blood pressure). DiscusionRTX is an effective and safe drug in the management of pemphigus. It could achieve long remission periods without therapy or with minimal concomitant one, permitting to avoid AE of chronic treatment with corticosteroids.

Reduction in stiffness of proximal leg muscles during the first 6 months of glucocorticoid therapy for giant cell arteritis: A pilot study using shear wave elastography.

To investigate muscle stiffness changes in patients treated for giant cell arteritis (GCA) with high-dose oral glucocorticoids. Using ultrasound elastography, shear wave velocity (SWV) was measured in the quadriceps, hamstrings and biceps brachii muscles of 14 patients with GCA (4 male, mean age±SD, 68.2±4.3years) within the first 2weeks of initiating glucocorticoid treatment (baseline) and repeated after 3 and 6months treatment. Muscle strength and performance tests were performed at each visit. Baseline measures were compared with those from 14 healthy controls. Linear mixed models were used to test for change in patient measures over time. At baseline, muscle SWV in patients was not significantly different from controls. With glucocorticoid treatment, there was a reduction in SWV in the leg but not the arm muscles. SWV decreased by a mean of 14% (range 8.3%-17.3%; P=.001) after 3months and 18% (range 10.2%-25.3%; P<.001) after 6-months in the quadriceps and hamstrings during the resting position. The baseline, 3 and 6months mean SWV (±SD) for the vastus lateralis were 1.62±0.16m/s, 1.40±0.10m/s and 1.31±0.06m/s, respectively (P<.001). In the patient group as a whole, there was no significant change in muscle strength. However, there were moderate correlations (r=.54-.69) between exhibiting weaker muscle strength at follow-up visits and a greater reduction in SWV. Glucocorticoid therapy in patients with GCA was associated with a significant reduction in proximal leg muscle stiffness during the first 6months. Future research should study a larger sample of patients for a longer duration to investigate if diminished muscle stiffness precedes signs of glucocorticoid-induced myopathy.

Current management of juvenile dermatomyositis in Germany and Austria: an online survey of pediatric rheumatologists and pediatric neurologists

BackgroundJuvenile Dermatomyositis (JDM) is a rare pediatric autoimmune disease with broad variations of the individual course. Data on the optimal management are mostly lacking. Currently treatment decisions are often based on experts’ opinions. In order to develop consensus-based treatment strategies for JDM in Germany a survey was pursued to analyze the current clinical practice.MethodsAn online survey addressing all members of the Society for Pediatric Rheumatology (GKJR) in Germany and Austria and pediatric neurologists with expertise in JDM was performed in February/March of 2016. The questionnaire consisted of 5 case scenarios including diagnostic criteria, treatment of moderate, severe and refractory JDM, using either multiple choice or a 5-point Likert scale. Basic descriptive statistics were used to analyze the findings.ResultsThe survey was completed by 60 pediatric rheumatologists and 7 pediatric neurologists experienced in the management of JDM. Typical findings allowing a diagnosis were considered to be: typical skin changes, proximal muscle weakness, MRI findings, elevated muscle enzymes, nailfold capillary changes, presence of calcinosis and muscle biopsy. Regarding induction treatment of moderate/severe JDM: 59%/74% opted for intermittent intravenous methylprednisolone (IVMP) pulse therapy, and 21%/40% for conventional high-dose oral glucocorticoids. Methotrexate (MTX) was the preferred disease-modifying conventional anti-rheumatic drug (cDMARD) for moderate and severe JDM. Regarding the management of refractory moderate or severe JDM, intravenous immune globulins, mycophenolate mofetil and rituximab were preferred treatment options.ConclusionThere is consensus about the diagnosis of JDM strongly supported by classic clinical and MRI findings. There is great variety in the treatment of JDM in Germany regarding both induction and maintenance therapy. The development of consensus-based treatment strategies for JDM based on harmonization of current clinical practice is essential in order to allow comparative effectiveness research in the future.