Months Of Glucocorticoid Therapy Research Articles

Use of immunosuppressants and biologics in giant cell arteritis: Recommendations of the French Study Group for Large Vessel Vasculitis (GEFA)

PurposeAn updated revision of the 2016 recommendations from the French Study Group for Large Vessel Vasculitis (GEFA) was needed to better delineate the place and management of immunosuppressants or biologics in giant cell arteritis (GCA). MethodsA panel of 18 physicians, including internists and rheumatologists, constituted the task force of this project and drafted the recommendations. Twelve additional readers were asked to analyse and comment on the recommendations. Two face-to-face virtual meetings were held to discuss and validate the recommendations. Each member voted individually, and a>85% consensus was required to validate each recommendation. ResultsFrom the initial 6 questions, 26 recommendations were validated. The following main recommendations were validated. (1) Subcutaneous 162mg tocilizumab (TCZ) for at least 12months should be used first when glucocorticoid (GC)-sparing treatment is needed with the objective of discontinuing GCs within the subsequent 6months. (2) GCA patients who have experienced any of the following conditions must receive TCZ at GCA diagnosis with 6months of GC therapy: major cardiovascular event, osteoporosis with fracture, psychiatric event with GC use, complicated diabetes mellitus, or any previous>6months of GC treatment. (3) In patients in whom GC discontinuation is not possible after 12months of treatment because of persistent disease activity or in patients in whom GC-related adverse events are unacceptable, TCZ (or alternatively methotrexate) may be proposed. ConclusionsThese recommendations were constructed based on the results of the published literature and the experts’ experiences to standardise therapeutic practices in France. Further updates will likely be necessary following new publications.

Persistent enlargement of the pancreatic gland after glucocorticoid therapy increases the risk of relapse in IgG4-related autoimmune pancreatitis.

This study aims to clarify the relationship between the changes of pancreatic size after glucocorticoid (GC) therapy and relapse in IgG4-related autoimmune pancreatitis (AIP). We prospectively enrolled 205 newly diagnosed IgG4-related AIP patients. 145 patients were followed up for more than 3years. These patients were divided into three groups according to the changes of pancreatic size after treatment of 6months: pancreatic swelling, normal size, and pancreatic atrophy. Baseline clinical and laboratory parameters were compared among three groups. Kaplan-Meier survival analysis was performed in the 134 patients based on GC therapy. Besides, Cox regression analysis and logistic regression analysis were performed to identify risk factors associated with relapse and the potential variables affecting changes of pancreatic size after treatment. Age at diagnosis, white blood cell count, and serum IgG1 level at baseline were significantly different among the three groups. After treatment of 6months, the pancreas of most patients (n = 81, 55.9%) could return to normal size, while persistent pancreatic swelling was found in 24.1% patients (n = 35), and atrophy was observed in 20.0% of the patients (n = 29). Kaplan-Meier survival analysis presented patients with pancreatic swelling after 6months of GC therapy were more likely to relapse in the follow-up of 3years. Persistent pancreatic swelling after treatment and salivary gland involvement at baseline were independent risk variables associated with relapse in IgG4-related AIP patients, while GC-based therapy was a protective factor of relapse. Logistic regression analysis revealed that older age at diagnosis was associated with pancreatic atrophy and higher baseline serum IgG1 level was associated with pancreatic swelling after treatment of 6months. Patients with persistent pancreatic swelling after GC-based therapy of 6months were more likely to relapse in the follow-up of 3years. Older age at diagnosis and higher baseline serum IgG1 level were potential variables associated with pancreatic atrophy or swelling after treatment of 6months. Key Points • Patients with persistent pancreatic swelling after glucocorticoid-based therapy were more likely to relapse in IgG4-related autoimmune pancreatitis. • Older age at diagnosis was associated with pancreatic atrophy after glucocorticoid-based therapy. • Higher baseline serum IgG1 level was associated pancreatic swelling after glucocorticoid-based therapy.

The protean manifestations of central nervous system IgG4-related hypertrophic pachymeningitis: a report of two cases

BackgroundIgG4-related hypertrophic pachymeningitis is a relative newly recognized and rare manifestation of IgG4-related disease, an immune-mediated fibroinflammatory tumefactive disorder. Fewer than 80 patients have been reported in the literature, and it can mimic common neurosurgical conditions. We describe the clinical presentation of two patients that were initially considered to have a subdural collection, tuberculous meningitis, and a cervical spinal meningioma, but were eventually diagnosed with this disease.Case presentationTwo ethnic Chinese men, 86 and 62 years old, experienced a 4-week history of headache. Both patients had a history of autoimmune disease, namely glomerulonephritis and Grave’s disease, respectively. Magnetic resonance brain imaging revealed diffuse dural thickening with the latter patient exhibiting homogeneous and intense gadolinium-contrast enhancement. Since the 86-year-old patient also had progressive bilateral visual loss, giant cell arteritis was suspected and a 2-week course of glucocorticoid therapy was prescribed, but his symptoms failed to improve. The 62-year-old patient also had accompanying low-grade fever and was treated empirically as having tuberculous meningitis although there were no confirmatory microbiological findings. This patient further developed right hemiparesis, and additional imaging revealed a C4/5 intradural-extramedullary contrast-enhancing lesion resembling a meningioma causing cord compression. Both patients underwent neurosurgical intervention with the former undergoing a dural biopsy and the latter having the cervical lesion resected. The final diagnosis was IgG4-related hypertrophic pachymeningitis with the hallmark histological features of lymphoplasmacytic infiltration of IgG4+ plasma cells, storiform fibrosis, and obliterative phlebitis. In addition, their serum IgG4 levels were elevated (i.e., > 135 mg/dL). Both patients received at least 6 months of glucocorticoid therapy while the latter also had azathioprine. Their symptoms improved significantly and recurrent lesions were not detected on follow-up imaging.ConclusionsA high index of suspicion for this condition is suggested when a male patient with a history of autoimmune disease and compatible radiological findings, experiences subacute headache that is disproportionate to the degree of dural involvement. Neurosurgeons should consider early meningeal biopsy to establish a definitive histological diagnosis in order for early effective immunosuppressive treatment to be initiated and to avoid unnecessary morbidity.

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.

65-Year-Old Woman With Intermittent Fevers, Lower Extremity Paresthesia, Weight Loss, and Malaise

65-Year-Old Woman With Intermittent Fevers, Lower Extremity Paresthesia, Weight Loss, and Malaise

Osteoporosis in children with chronic illness: lessons from natural history studies that guide clinical practice

Children with serious chronic illnesses have the potential for significant bone morbidity, particularly in the context of disorders with impaired muscle function and the need for glucocorticoid (GC) treatment. Recently, studies have shown that vertebral fractures are often the first sign of osteoporosis in this context. Longitudinal studies have taught us that vertebral fractures are most frequent in the first year of GC therapy among children with GC-treated diseases, that vertebral fractures are often asymptomatic and thereby go undetected in the absence of routine monitoring, and that even asymptomatic vertebral fractures predict an increased risk of future fractures. Other discrete clinical predictors of incident vertebral fractures are evident early in the course of GC therapy, including decreases in spine BMD Z-scores and increases in body mass index Z-scores in the first 6 months of GC therapy. Taken together, these observations highlight that the first year of GC therapy is a critical period for monitoring in order to identify bone morbidity in a timely fashion. Children with risk factors for bone morbidity other than GC therapy (such as neuromuscular disorders and immobilization) are also at increased risk for vertebral and non-vertebral fractures fractures. As such, routine surveillance for vertebral fractures (for example, with a lateral spine radiograph) is now considered a key facet of the bone health evaluation in children with chronic immobilization or GC-treated diseases. While some risk factors for osteoporosis will be permanent (such as immobilization arising from disorders such as cerebral palsy), other children will experience transient threats to bone health. This is an important distinction, since children with transient threats have the potential for vertebral body reshaping, either spontaneously or with bone-targeted treatment such as bisphosphonate therapy. Recovery from fracture-induced deformity is growth-dependent, underscoring the importance of timely diagnosis and intervention during childhood in those with limited potential for spontaneous vertebral body reshaping. Prevention begins with optimization of conservative measures, including physical activity, nutrition, treatment of co-morbid endocrinopathies and aggressive treatment of the underlying disease using the lowest effective GC dose. These measures may be insufficient to prevent first-time fractures in some, raising the need for bone-specific therapy in line with a secondary prevention approach. Secondary prevention is predicated upon identification of early signs of osteoporosis and intervention to prevent disease progression. Since bone-targeted treatment is typically reserved for children with overt fragility, careful monitoring to avoid advanced osteoporosis presentations is paramount. Bisphosphonates are the most commonly prescribed agents in children; however, interest in the use of novel osteo-anabolic therapy is mounting given bone histomorphometric observations that osteoporosis in children with serious chronic illnesses is typically characterized by significant reductions in bone turnover.

Incident Vertebral Fractures and Risk Factors in the First Three Years Following Glucocorticoid Initiation Among Pediatric Patients With Rheumatic Disorders.

Vertebral fractures are an important yet underrecognized manifestation of osteoporosis in children with chronic, glucocorticoid-treated illnesses. Our goal was to determine the incidence and clinical predictors of vertebral fractures in the 3 years following glucocorticoid initiation among pediatric patients with rheumatic disorders. Incident vertebral fractures were evaluated according to the Genant semiquantitative method on lateral radiographs at baseline and then annually in the 3 years following glucocorticoid initiation. Extended Cox models were used to assess the association between vertebral fractures and clinical risk predictors. A total of 134 children with rheumatic disorders were enrolled in the study (mean ± standard deviation (SD) age 9.9 ± 4.4 years; 65% girls). The unadjusted vertebral fracture incidence rate was 4.4 per 100 person-years, with a 3-year incidence proportion of 12.4%. The highest annual incidence occurred in the first year (6.0%; 95% confidence interval (CI) 2.9% to 11.7%). Almost one-half of the patients with fractures were asymptomatic. Every 0.5 mg/kg increase in average daily glucocorticoid (prednisone equivalents) dose was associated with a twofold increased fracture risk (hazard ratio (HR) 2.0; 95% CI 1.1 to 3.5). Other predictors of increased vertebral fracture risk included: (1) increases in disease severity scores between baseline and 12 months; (2) increases in body mass index Z-scores in the first 6 months of each 12-month period preceding the annual fracture assessment; and (3) decreases in lumbar spine bone mineral density Z-scores in the first 6 months of glucocorticoid therapy. As such, we observed that a clinically significant number of children with rheumatic disorders developed incident vertebral fractures in the 3 years following glucocorticoid initiation. Almost one-half of the children were asymptomatic and thereby would have been undiagnosed in the absence of radiographic monitoring. In addition, discrete clinical predictors of incident vertebral fractures were evident early in the course of glucocorticoid therapy.

Secondary Retroperitoneal Fibrosis Due to Polyarteritis Nodosa Evaluated by F-18 FDG PET/CT

A 38-year-old man presented with fever, low back pain, orchialgia, and weight loss for two months. He had recently begun dialysis. Laboratory studies revealed CRP 16.0 mg/dl and sCr 13.08 mg/dl. FDG PET/CT demonstrated uptake in a periaortic mass, medium sized visceral arteries, hydronephrosis. Histological examination of the mass revealed retroperitoneal fibrosis (RPF). 3D-CT angiography showed multiple aneurysms, consistent with polyarteritis nodosa (PAN). RPF secondary to PAN was clinically diagnosed. All the symptoms and abnormal laboratory and FDG PET/CT findings have disappeared after three months of glucocorticoid therapy.

Soluble intercellular adhesion molecule-1 (sICAM-1) in sera of patients with Graves' ophthalmopathy and thyroid diseases.

Intercellular adhesion molecule, a ligand for the leucocyte integrins CD11a/CD18 (LFA-1) and CD11b/CD18 (Mac-1), that plays an important role in a variety of inflammatory and immune-mediated mechanisms, is strongly expressed in retroocular connective tissue from patients with Graves' ophthalmopathy (GO) and involved in lymphocyte attachment to cultured retroocular fibroblasts via the ICAM-1/LFA-1-mediated pathway. Here, we report the detection and functional activity of a soluble form of the ICAM-1 molecule (sICAM-1) in sera from patients with GO and other thyroid diseases. Serum concentrations for sICAM-1 were determined using a highly sensitive ELISA. Compared with normal controls, patients with hyperthyroid or euthyroid GO and patients with Riedel's invasive fibrous thyroiditis revealed markedly elevated sICAM-1 serum concentrations (all P < 0.0001). In patients with Graves' disease (GD) without clinical GO and in patients with Hashimoto's thyroiditis (HT), sICAM-1 levels were elevated to a lesser degree (both P < 0.001). sICAM-1 serum levels in patients with non-autoimmune hyperthyroidism due to a toxic adenoma were not significantly different from normal controls. In a separate group of 12 patients with severe inflammatory GO, sICAM-1 serum levels markedly declined (P < 0.0001) within 3 months of glucocorticoid therapy in nine patients who responded to this form of treatment with a decrease in periorbital inflammation. In contrast, sICAM-1 serum levels remained unchanged in three patients with poor response to steroids and persistent inflammatory periorbital disease. When tested in a cell adhesion assay, GO sera containing elevated concentrations of sICAM-1 were found to enhance the attachment of peripheral blood mononuclear cells (PBMC) to interferon-gamma (IFN-gamma)-treated retroocular fibroblasts in a dose-dependent manner, up to a maximal stimulation of approximately 5.5-fold (P < 0.001). This effect was abolished by preabsorption of sera with a MoAb against ICAM-1 and inhibited, in a dose-dependent manner, by coincubation with increasing concentrations of purified sICAM-1. In conclusion, sICAM-1 concentrations are markedly elevated in sera from patients with GO, and changes in sICAM-1 serum levels during glucocorticoid therapy closely parallel changes in the degree of inflammation. Given the capacity of sICAM-1 to modulate the adhesion of lymphocytes to retroocular fibroblasts in vitro, sICAM-1 may play a role in the ongoing immune process within the connective tissue in GO.

Glucocorticoid-Induced Osteoporosis

Glucocorticoids are the most common cause of drug-induced osteoporosis. Given the widespread use of oral glucocorticoids in the treatment of autoimmune, pulmonary, gastrointestinal disorders and organ transplantation, attention to glucocorticoid-induced osteoporosis has substantially increased. Bone loss occurs rapidly in the first few months of glucocorticoid therapy. Trabecular bone is affected more than cortical bone. Glucocorticoid treatment is associated with a substantially increased risk of fractures, particularly hip and vertebral fractures. The skeletal effects of glucocorticoids are both dose- and duration-dependent. The patophysiology of glucocorticoid-induced osteoporosis is a complex process, several mechanisms are proposed but not yet fully highlighted. Despite several evidence-based guidelines for the prevention and treatment of glucocorticoid-induced osteoporosis and the availability of effective therapeutic options, the proportion of individuals with appropriate evaluation and treatment remains relatively low.

Cortisol, Dehydroepiandrosterone Sulfate, and Androstenedione Levels in Patients with Polymyalgia Rheumatica during Twelve Months of Glucocorticoid Therapy

This paper aims to evaluate adrenal gland hormone levels in patients with polymyalgia rheumatica (PMR) during glucocorticoid (GC) therapy. A lower than expected basal production of cortisol was found in active and glucocorticoid-untreated PMR patients, particularly females. The abrupt onset of PMR with clinical features similar to those of the steroid-withdrawal syndrome or adrenal insufficiency, as well as the clinical response to GC therapy in elderly people already age-disposed to an inadequate adrenal and anti-inflammatory response, might represent the most significant pathophysiological basis of the disease.

Cyclical etidronate plus ergocalciferol prevents glucocorticoid-induced bone loss in postmenopausal women

To assess the benefit of cyclical etidronate plus ergocalciferol for the prevention of glucocorticoid-induced bone loss in a 2-year, prospective, open study based in an osteoporosis clinic. Group 1 consisted of 15 postmenopausal women (mean age 62.6 +/- 3.3 years) who commenced glucocorticoid therapy and were treated with cyclical etidronate (400 mg/d for the first month; thereafter, 400 mg/d for 2 weeks of every 3-month period), elemental calcium (1 g/d), and ergocalciferol (0.5 mg/wk). Group 2 consisted of 11 postmenopausal women (mean age 60.2 +/- 4.7 years) with glucocorticoid-induced osteoporosis, who were attending the clinic at the same time and were treated with calcium supplements only (1 g/d). Lumbar spine and femoral neck bone mineral densities (BMD) were measured at baseline and after 12 and 24 months of glucocorticoid therapy using a dual energy x-ray absorptiometer. The two groups did not differ with respect to age, years since the menopause, mean daily glucocorticoid dose, and baseline BMD values. During the first year of therapy, mean lumbar spine BMD increased from an initial value of 0.88 g/cm2 to 0.94 g/cm2, an increase of 7% per year (95% confidence interval [CI] 3.7% to 10.2%; P < 0.001 compared with controls). Significant increases in BMD of 2.5% per year were also observed in the femoral neck (95% CI -1% to 6%; P < 0.01 compared with controls). After the second year of cyclical etidronate therapy, femoral neck BMD continued to increase (P < 0.05 compared with value at 12 months), while lumbar spine BMD remained stable. Chronic glucocorticoid therapy may result in bone loss at most skeletal sites. Therapy with cyclical etidronate plus ergocalciferol not only prevented glucocorticoid-induced bone loss, but even increased lumbar spine and femoral neck BMD in postmenopausal women commencing glucocorticoid therapy.