Glucocorticoid Cessation Research Articles

Glucocorticoid use in psoriatic arthritis and treatment outcomes: does the gender have a role?

BackgroundSystemic glucocorticoids are commonly used in practice in the treatment of psoriatic arthritis. However, authorities advise against prescribing it, primarily because of the risk of psoriasis flare-ups. The authors aimed to assess the glucocorticoid use in psoriatic arthritis (PsA), factors associated with the use of glucocorticoids and to uncover whether gender has an impact on glucocorticoid use and treatment responses. Disease-modifying antirheumatic drug (DMARD)-naive PsA patients were included in this cross-sectional study. Baseline clinical and demographic characteristics were recorded. After starting DMARD treatment, patients were followed for 2 years. The number of patients who started glucocorticoids, the clinical demographics of these patients, the duration of glucocorticoid administration, and the dose for administration were recorded. Patient outcomes and gender differences were analyzed. Disease activity was measured using the Disease Activity Scale 28 (DAS28-CRP) and the Disease Activity Index for Psoriatic Arthritis (DAPSA).ResultsFifty-five of the 141 patients (39%) received glucocorticoids at the 2-year follow-up. There was no difference between the sexes who are in remission-low disease activity (LDA) on cDMARD monotherapy (p = 0.300). Glucocorticoid usage (p = 0.660), dose (p = 0.054), and duration (p = 0.159) did not differ between male and female patients. Higher glucocorticoid doses were associated with dactylitis, higher CRP levels, higher DAS-28 and DAPSA scores, and longer (> 3 months) glucocorticoid administration. Glucocorticoid duration was longer in patients with higher TJS, SJS, serum CRP, higher DAS-28 and DAPSA scores, and higher glucocorticoid doses. Sustained remission-LDA was achieved in 16 of 55 patients after cessation of glucocorticoids and no sex difference was observed.ConclusionSystemic glucocorticoids are commonly prescribed in PsA, and when added to treatment even for short periods and in low doses, they help achieve significant disease control. Except for axial involvement, there is no difference in treatment responses between male and female patients, making it unnecessary to make a gender distinction in the treatment algorithm. Given these findings, prospective studies are needed to evaluate glucocorticoids as a bridging treatment in PsA, such as rheumatoid arthritis.

Clinical Features of Paediatric Inflammatory Epidermolysis Bullosa Acquisita: A Case Series Study.

Epidermolysis bullosa acquisita (EBA) rarely develops in childhood. This study retrospectively recruited paediatric patients with EBA (age ≤ 16 years), diagnosed by clinical and histopathological features and results of immunofluorescence, immunoblotting and enzyme-linked immunosorbent assay (ELISA), and reviews their clinical manifestations, histopathology, immunological features, and responses to various treatments. All 7 included patients presented with inflammatory EBA. Among them, 3 had a bullous pemphigoid-like phenotype. Pathologically, in addition to dermal-epidermal blistering, in all patients, the distribution of neutrophils was superficial perivascular or interstitial, or in the dermal papilla. Mixed neutrophils and eosinophils were detected in 2 of the 3 patients with bullous pemphigoid-like phenotypes. In addition to treatment with glucocorticoids, dapsone was administered in 4 patients, while thalidomide and sulfasalazine were administered in 1 patient. All patients responded to the these therapies. Relapse was mainly due to reduction and cessation of glucocorticoids. In conclusion, EBA in childhood may be unique, and thus distinct from its adult counterpart. Specific treatment and follow-up protocols are required for therapy of this rare autoimmune skin disease in children.

Post–COVID-19 autoimmune hypoglycemia: A case report

ABSTRACT Insulin autoimmune hypoglycemia is characterized by insulin autoantibodies causing initially hyperglycemia followed by hypoglycemia. The authors describe a case of a patient who presented with recurrent episodes of severe hypoglycemia 1 month after COVID-19 infection. Blood glucose monitoring during admission revealed postprandial hyperglycemia ranging from 15 to 18 mmol/L followed by severe hypoglycemic episodes. His insulin at the time of hypoglycemia (blood glucose level 1.5 mmol/L) was 255 mU/L (3–25 mU/L). C-peptide was 3.3 nmol/L (0.3–1.4 nmol/L), and β-hydroxybutyric acid was 0.06 mmol/L (<0.27 mmol/L). The anti-insulin antibodies level elevated at 403 U/mL (<0.5 U/mL). A diagnosis of post–COVID-19 autoimmune hypoglycemia was performed, and the patient was started on high-dose prednisolone 60 mg/day with gradual tapering over 3 months. Metformin and acarbose were also started to treat hyperglycemia. On follow-up after glucocorticoid cessation, blood glucose profile stabilized with no hypoglycemia or hyperglycemia. This is the fourth case report written in the literature.

Relapse rate and predictors of relapse after cessation of glucocorticoid maintenance therapy in type 1 autoimmune pancreatitis: a multicenter retrospective study

BackgroundType 1 autoimmune pancreatitis responds well to glucocorticoid therapy with a high remission rate. Moreover, glucocorticoid maintenance therapy can help prevent relapse. However, the relapse rate following cessation of long-term glucocorticoid therapy is unknown. The aim of this study was to clarify the relapse rate and predictors of relapse following long-term glucocorticoid therapy cessation.MethodsWe analyzed 94 patients who achieved remission after undergoing glucocorticoid therapy, discontinued treatment after at least 6 months of maintenance therapy, and were subsequently followed up for at least 6 months. The patients were divided into three groups based on treatment duration (< 18, 18–36, and ≥ 36 months), and their relapse rates were compared. Univariate and multivariate analyses of clinical factors were conducted to identify relapse predictors.ResultsAfter discontinuing glucocorticoid therapy, relapse was observed in 43 (45.7%) patients, with cumulative relapse rates of 28.2% at 1 year, 42.1% at 3 years, 47.0% at 5 years, and a plateau of 77.6% at 9 years. Of the 43 patients who relapsed, 25 (58.1%) relapsed within 1 year after after cessation of glucocorticoid therapy. Relapse and cumulative relapse rates did not differ significantly according to treatment duration. In the multivariate analysis, an elevated serum IgG4 level at the time of glucocorticoid cessation was found to be an independent predictor of relapse (hazard ratio, 4.511; p < 0.001).ConclusionsA high relapse rate occurred after cessation of glucocorticoid maintenance therapy, regardless of the duration of maintenance therapy, especially within the first year after cessation. However, the normalization of long-term serum IgG4 levels may be a factor in considering cessation.

Recovery of steroid induced adrenal insufficiency.

Secondary adrenal insufficiency can result from insufficient stimulation of the adrenal glands due to inadequate secretion or synthesis of adrenocorticotropic hormone (ACTH). This can be caused by hypopituitarism, central nervous system injury (tumors, radiation, and surgery) or long-term glucocorticoid therapy. Glucocorticoids were introduced in the 1950s, and have been used for their anti-inflammatory and other pharmacological effects, and also as replacement therapy for adrenal insufficiency. However, chronic glucocorticoid use may lead to suppression of the hypothalamic pituitary adrenal axis through negative feedback. This may lead to secondary adrenal insufficiency. Typically, the hypothalamic pituitary adrenal axis recovers after cessation of glucocorticoids, but the timing of recovery can be variable and can take anywhere from 6-12 months. Understanding the effect of exogenous glucocorticoids on the hypothalamic pituitary adrenal axis, recovery of the axis, and tests used to assess the recovery, are crucial to avoid prescribing unnecessary steroid replacement or missing a critical diagnosis with detrimental consequences.

Clinical characteristics of adrenal crisis in adult population with and without predisposing chronic adrenal insufficiency: a retrospective cohort study

BackgroundAdrenal crisis (AC) occurs in various clinical conditions but previous epidemiological studies in AC are limited to chronic adrenal insufficiency (AI) and sepsis. The aim of this study was to investigate characteristics of AC patients, including predisposing diseases and to describe candidate risk factors for AC such as comorbidities and glucocorticoid (GC) therapy.MethodsWe conducted a retrospective cohort study using a claims database on 7.4 million patients from 145 acute care hospitals between January 1, 2003 and April 30, 2014. We identified AC patients who met the following criteria: 1) disease name with ICD-10 corresponded with AI; 2) therapeutic GC administration (hydrocortisone equivalent dose ≥100 mg/day); 3) admission; and 4) age ≥18 years.ResultsWe identified 504 patients with AC (median age, 71 years; interquartile range, 59 to 80; 50.6% male). As predisposing conditions, primary AI and central AI accounted for 23 (4.6%) and 136 patients (27.0%), respectively. In the remaining AC patients (68.5%), comorbidities such as cancer, autoimmune diseases, and renal failure were frequent. The most frequent indication for hospitalization was AC (16.3%), followed by pituitary disease (14.7%), cancer (14.7%), AI-related clinical symptoms (11.5%), and infection (11.1%). Admission under oral GC treatment was reported in 104 patients (20.6%). Twenty-six patients were admitted within 14 days after GC cessation (5.2%).ConclusionsThese findings present an overview of patients with AC in general practice settings, clarifying that predisposing factors for AC were complicated and that patients other than those with chronic AI were older and had more comorbid conditions than those with primary and central AI.

Clinical analysis of 123 cases of primary immune thrombocytopenia in adults

Objective To investigate the clinical characteristics of primary immune thrombocytopenia (ITP) in adults and to summarize the experience in order to improve the clinical diagnosis and treatment of ITP. Methods from February 2008 to June 2014, a total of 123 cases of adult patients with ITP in Taizhou People's Hospital affiliated to Yangzhou University were collected into this study, as the research object. The clinical data, clinical manifestation, laboratory examination, treatment and therapeutic effect of 123 cases of adult ITP were retrospectively analyzed. The study protocol was approved by the Ethical Review Board of Investigation in Human at Taizhou People's Hospital affiliated to Yangzhou University. Informed consent was obtained from all participants. All adult ITP patients peripheral blood and bone marrow like, immunological indexes were detected; and the adult ITP patients in different age patients with male and female incidence ratio were statistically analyzed. Results ①The ratio of male to female was 1∶9.5 in patients with ITP from 21to 40 years old, and the ratio of male to female was 1∶2.3 in patients with ITP from 41 to 60 years old There was significant difference between incidence rates of male and female in two age periods(χ2=4.474, P=0.034). ②19 out of 123 cases of adult ITP patients had a clear incentive, and incentives were all upper respiratory tract infection. Adult ITP patients's bleeding parts from high frequency to low were as follows: the skin and mucosa, menorrhagia, urinary tract and digestive tract and intracranial hemorrhage .The complications of adult ITP patients with pulmonary infection were 4 cases, and femoral head necrosis were 2 cases. The occurrence of steroid diabetes were 12 cases. Low potassium were 8 cases. Before treatment, the adult ITP platelet count in patients was (14.6±12.2)×109/L. The number of bone marrow megakaryocytes were increased in 75 cases (61%), and the rest 48 cases (39%) were normal. All the patients had megakaryocyte maturation disorder. ③The follow-up time was 3 months to 32 years, and the median time was 42 months. After first-line treatment of glucocorticoid treatment scheme, 69 cases of patients (56.1%) obtained complete response (CR), partial response (PR) were 29 cases (23.6%) and non-response (NR) were 25 cases (20.3%). After cessation of glucocorticoids, platelet count of 69 cases obtained CR maintained at a normal level, and platelet count of 29 cases obtained PR were more than 30×109/L, without obvious bleeding manifestations. 25 cases of NR patients were treated with second-line therapy. second-line therapy respectively were vincristine, cyclosporine A (CSA) and rituximab and splenectomy, and treatment efficiency were 44.4%. 50.0%, 80.0% and 85.7%, respectively. Conclusion Adult ITP treatment should pay attention to the principle of individual treatment, so that the blood platelet count increased to a safe level, and over treatment should be avoided as far as possible. Key words: Thrombocytopenia; Adult; Glucocorticoids

Glucocorticoid-induced osteoporosis: who to treat with what agent?

Among the adverse events of glucocorticoid treatment are bone loss and fractures. Despite available, effective preventive measures, many patients receiving or initiating glucocorticoid therapy are not appropriately evaluated and treated for bone health and fracture risk. Populations with, or at risk of, glucocorticoid-induced osteoporosis (GIOP) to target for these measures are defined on the basis of dose and duration of glucocorticoid therapy and bone mineral density. That patients with GIOP should be treated as early as possible is generally agreed upon; however, diversity remains in intervention thresholds and management guidelines. The FRAX(®) algorithm provides a 10-year probability of fracture that can be adjusted according to glucocorticoid dose. There is no evidence that GIOP and postmenopausal osteoporosis respond differently to treatments. Available anti-osteoporotic therapies such as anti-resorptives including bisphosphonates and the bone anabolic agent teriparatide are effective for the management of GIOP. Prevention with calcium and vitamin D supplementation is less effective than specific anti-osteoporotic treatment. Anti-osteoporotic treatment should be stopped at the time of glucocorticoid cessation, unless the patient remains at increased risk of fracture.

Management of Glucocorticoid-Induced Osteoporosis

This review summarizes the available evidence-based data that form the basis for therapeutic intervention and covers the current status of glucocorticoid-induced osteoporosis (GIOP) management, regulatory requirements, and risk-assessment options. Glucocorticoids are known to cause bone loss and fractures, yet many patients receiving or initiating glucocorticoid therapy are not appropriately evaluated and treated. An European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis workshop was convened to discuss GIOP management and to provide a report by a panel of experts. An expert panel reviewed the available studies that discussed approved therapeutic agents, focusing on randomized and controlled clinical trials reporting on bone mineral density and/or fracture risk of at least 48weeks' duration. There is no evidence that GIOP and postmenopausal osteoporosis respond differently to treatments. The FRAX algorithm can be adjusted according to glucocorticoid dose. Available antiosteoporotic therapies such as bisphosphonates and teriparatide are efficacious in GIOP management. Several other agents approved for the treatment of postmenopausal osteoporosis may become available for GIOP. It is advised to stop antiosteoporotic treatment after glucocorticoid cessation, unless the patient remains at increased risk of fracture. Calcium and vitamin D supplementation as an osteoporosis-prevention measure is less effective than specific antiosteoporotic treatment. Fracture end-point studies and additional studies investigating specific subpopulations (pediatric, premenopausal, or elderly patients) would strengthen the evidence base and facilitate the development of intervention thresholds and treatment guidelines.

The effects of glucocorticoid on microarchitecture, collagen, mineral and mechanical properties of sheep femur cortical bone

In this study, 18 female skeletally mature sheep were randomly allocated into three groups of six each. Group 1 (glucocorticoid-1) received prednisolone treatment (0.60 mg/kg/day, five times weekly) for 7 months. Group 2 (glucocorticoid-2) received the same treatment regime followed by observation of 3 months without treatment. Group 3 was left untreated and served as controls. All sheep received a restricted diet with low calcium and phosphorus. At sacrifice, cortical bone samples from the femur midshaft of each sheep were harvested, micro-CT scanned and subjected to three-point bending and tensile strength testing. Bone collagen and mineral were determined. Cortical porosity was significantly increased in the glucocorticoid-2 compared with the glucocorticoid-1 and control groups. Apparent density was significantly decreased in the glucocorticoid-2 compared with the glucocorticoid-1 group. Collagen content was significantly increased in the glucocorticoid-2 compared with the glucocorticoid-1 and control groups. Bone mineral content did not differ between the groups. Neither the three-point bending mechanical properties nor the tensile mechanical properties differed significantly between the groups, while there was a trend towards decreasing bending mechanical properties in the glucocorticoid-2 group. In conclusion, 7 months of glucocorticoid treatment with malnutrition had a significant impact on the cortical microarchitecture of the sheep femur midshaft. These observed changes occurred 3 months after glucocorticoid cessation, suggesting a delayed effect of glucocorticoid on cortical bone. Thus, changes in cortical bone beyond cancellous bone might further increase fracture risk in patients treated with glucocorticoids. This model might be used as a glucocorticoid-induced osteoporotic model for orthopaedic biomaterial, joint prosthesis and medical device researches.

Lentivectors for Regulated and Reversible Cutaneous Gene Delivery

Systemic administration of therapeutic proteins has value in treating a wide variety of disorders, including erythropoietin (Epo)-responsive anemias. Recombinant proteins, however, are costly and require repeated injections, while gene delivery approaches have suffered from inefficiency and difficulties with regulation. The skin effectively delivers polypeptides to the circulation, and improved approaches would support sustainable, topically regulated protein expression after a single vector injection. Toward this goal, we generated lentivectors in which both gene delivery and persistence in skin are regulated by administration of distinct steroid ligands. Following a single injection of regulated lentivector into human skin regenerated on immunodeficient mice, topical glucocorticoid ligands regulated Epo levels and hematocrit over time. Abrogation of gene delivery was achieved by both glucocorticoid cessation and proviral excision via a 4-hydroxytamoxifen-inducible Cre recombinase. These findings establish an approach to durable, topically controlled systemic delivery of therapeutic proteins from human skin tissue.