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1.
Adv Exp Med Biol ; 1447: 191-207, 2024.
Article in English | MEDLINE | ID: mdl-38724794

ABSTRACT

Atopic dermatitis has a substantial impact on sleep, appearance, psychological well-being, and other qualities of life. The visual appearance of lichenification, cheilitis, hyperpigmentation, ichthyosis, and erythema can be socially stigmatizing, and treatment of these symptoms is challenging. In managing pruritus in patients, practitioners should assess and document pruritus through questionnaires at each routine visit. Initially, practitioners should advise patients to employ nonpharmaceutical treatments such as emollients with wet wraps, elimination of triggers, changing scratching habits, and psychological interventions. If these methods of treatment are not successful or if the disease presentation is severe, pharmacological therapies should be employed. This chapter describes the therapeutic ladder for pruritus in atopic dermatitis and discusses each treatment modality in further detail for practitioners to advise their patients.First-line topical pharmaceutical agents include topical glucocorticoids and topical calcineurin inhibitors. Second-line topical agents include coal tar, menthol, capsaicin, or doxepin. After the use of topical agents has been exhausted, primary systemic agents can be applied. These include sedating antihistamines, nonsedating antihistamines, oral glucocorticoids, or cyclosporine A. Finally, neuromodulating or immunomodulating agents can be attempted, including SSRI/SNRIs, TCAs, immunosuppressants, neural modulators, and opioid receptor modulators. Outside of pharmacological treatments, phototherapy has been shown to provide a dramatic improvement of pruritus in atopic dermatitis and can be used at any stage of treatment including as a first-line agent.


Subject(s)
Dermatitis, Atopic , Pruritus , Humans , Antipruritics/therapeutic use , Calcineurin Inhibitors/therapeutic use , Dermatitis, Atopic/therapy , Dermatitis, Atopic/complications , Glucocorticoids/therapeutic use , Histamine Antagonists/therapeutic use , Phototherapy/methods , Pruritus/therapy , Pruritus/etiology , Pruritus/physiopathology , Pruritus/drug therapy
2.
BMJ Case Rep ; 17(5)2024 May 02.
Article in English | MEDLINE | ID: mdl-38697679

ABSTRACT

Ornithine transcarbamylase deficiency (OTCD) is a rare, X linked disorder that can manifest in late adulthood in heterozygous females as severe hyperammonaemia following environmental stressors. We present a case of hyperammonaemic encephalopathy that was triggered by glucocorticoid administration in an adult woman with heterozygous OTCD with clinical response to haemodialysis, ammonia scavengers and a high-calorie, low-protein diet.


Subject(s)
Hyperammonemia , Ornithine Carbamoyltransferase Deficiency Disease , Humans , Female , Ornithine Carbamoyltransferase Deficiency Disease/complications , Ornithine Carbamoyltransferase Deficiency Disease/diagnosis , Hyperammonemia/chemically induced , Glucocorticoids/therapeutic use , Glucocorticoids/adverse effects , Renal Dialysis , Brain Diseases/chemically induced , Brain Diseases/etiology , Middle Aged , Diet, Protein-Restricted/adverse effects
3.
J Orthop Surg Res ; 19(1): 294, 2024 May 14.
Article in English | MEDLINE | ID: mdl-38745231

ABSTRACT

BACKGROUND: Osteonecrosis of the femoral head caused by glucocorticoids (GIONFH) is a significant issue resulting from prolonged or excessive clinical glucocorticoid use. Astaxanthin, an orange-red carotenoid present in marine organisms, has been the focus of this study to explore its impact and mechanism on osteoblast apoptosis induced by dexamethasone (Dex) and GIONFH. METHODS: In this experiment, bioinformatic prediction, molecular docking and dynamics simulation, cytotoxicity assay, osteogenic differentiation, qRT-PCR analysis, terminal uridine nickend labeling (TUNEL) assay, determination of intracellular ROS, mitochondrial function assay, immunofluorescence, GIONFH rat model construction, micro-computed tomography (micro-CT) scans were performed. RESULTS: Our research demonstrated that a low dose of astaxanthin was non-toxic to healthy osteoblasts and restored the osteogenic function of Dex-treated osteoblasts by reducing oxidative stress, mitochondrial dysfunction, and apoptosis. Furthermore, astaxanthin rescued the dysfunction in poor bone quality, bone metabolism and angiogenesis of GIONFH rats. The mechanism behind this involves astaxanthin counteracting Dex-induced osteogenic damage by activating the Nrf2 pathway. CONCLUSION: Astaxanthin shields osteoblasts from glucocorticoid-induced oxidative stress and mitochondrial dysfunction via Nrf2 pathway activation, making it a potential therapeutic agent for GIONFH treatment.


Subject(s)
Femur Head Necrosis , Glucocorticoids , Mitochondria , NF-E2-Related Factor 2 , Osteoblasts , Osteogenesis , Oxidative Stress , Xanthophylls , Animals , Xanthophylls/pharmacology , Oxidative Stress/drug effects , NF-E2-Related Factor 2/metabolism , Glucocorticoids/adverse effects , Glucocorticoids/toxicity , Femur Head Necrosis/chemically induced , Femur Head Necrosis/metabolism , Osteogenesis/drug effects , Mitochondria/drug effects , Mitochondria/metabolism , Rats , Osteoblasts/drug effects , Osteoblasts/metabolism , Male , Dexamethasone/pharmacology , Dexamethasone/adverse effects , Rats, Sprague-Dawley , Apoptosis/drug effects , Disease Models, Animal
4.
Proc Biol Sci ; 291(2022): 20240371, 2024 May.
Article in English | MEDLINE | ID: mdl-38714210

ABSTRACT

Naked mole-rats (Heterocephalus glaber) live in large colonies with one breeding female (queen), one to three breeding males (BMs) and the remainder are non-reproductive subordinates. The animals have a linear dominance rank with the breeders at the top of the hierarchy. We investigated how dominance rank in naked mole-rats differs with exploration (the propensity to explore a novel environment) and related endocrine markers. Exploration behaviour, faecal progestagen metabolite (fPM), faecal glucocorticoid metabolite (fGCM), faecal androgen metabolite (fAM) and plasma prolactin concentrations were quantified in breeding, high-, middle- and low-ranked females and males from five naked mole-rat colonies. There were no significant differences between the dominance rank and exploration behaviour. Interestingly, the queens and high-ranking females had higher fGCM and fAM concentrations compared with middle- and low-ranked females. The queens had significantly higher fPM concentrations than all other ranked females, since they are responsible for procreation. In the males, the BMs had higher fGCM concentrations compared with high- and low-ranked males. In addition, BMs and middle-ranking males had overall higher prolactin levels than all other ranked males, which could be linked to cooperative care. Overall, the results suggest that physiological reproductive suppression is linked to high dominance rank.


Subject(s)
Androgens , Feces , Mole Rats , Prolactin , Social Dominance , Animals , Male , Female , Prolactin/metabolism , Prolactin/blood , Feces/chemistry , Mole Rats/physiology , Androgens/metabolism , Androgens/blood , Glucocorticoids/metabolism , Exploratory Behavior , Progestins/metabolism
5.
Eur J Endocrinol ; 190(5): G25-G51, 2024 May 02.
Article in English | MEDLINE | ID: mdl-38714321

ABSTRACT

Glucocorticoids are widely prescribed as anti-inflammatory and immunosuppressive agents. This results in at least 1% of the population using chronic glucocorticoid therapy, being at risk for glucocorticoid-induced adrenal insufficiency. This risk is dependent on the dose, duration and potency of the glucocorticoid, route of administration, and individual susceptibility. Once glucocorticoid-induced adrenal insufficiency develops or is suspected, it necessitates careful education and management of affected patients. Tapering glucocorticoids can be challenging when symptoms of glucocorticoid withdrawal develop, which overlap with those of adrenal insufficiency. In general, tapering of glucocorticoids can be more rapidly within a supraphysiological range, followed by a slower taper when on physiological glucocorticoid dosing. The degree and persistence of HPA axis suppression after cessation of glucocorticoid therapy are dependent on overall exposure and recovery of adrenal function varies greatly amongst individuals. This first European Society of Endocrinology/Endocrine Society joint clinical practice guideline provides guidance on this clinically relevant condition to aid clinicians involved in the care of patients on chronic glucocorticoid therapy.


Subject(s)
Adrenal Insufficiency , Endocrinology , Glucocorticoids , Humans , Glucocorticoids/adverse effects , Glucocorticoids/therapeutic use , Glucocorticoids/administration & dosage , Adrenal Insufficiency/diagnosis , Adrenal Insufficiency/chemically induced , Adrenal Insufficiency/therapy , Adrenal Insufficiency/drug therapy , Endocrinology/standards , Endocrinology/methods , Europe , Societies, Medical/standards
6.
BMJ Open Gastroenterol ; 11(1)2024 May 07.
Article in English | MEDLINE | ID: mdl-38719549

ABSTRACT

BACKGROUND AND OBJECTIVE: The influence of concomitant prednisolone on clinical outcomes and safety in infliximab-treated ulcerative colitis (UC) patients is unknown. DESIGN, SETTING, PARTICIPANTS AND OUTCOME MEASURES: A retrospective cohort study was performed, including 147 UC patients treated with infliximab at a tertiary inflammatory bowel disease (IBD) centre. Primary outcome was corticosteroid-free clinical remission (CFCR) at week 14 and week 52. Patients were grouped according to prednisolone tapering regimens: standard (≤5 mg/week), fast (>5 mg/week), direct discontinuation or no prednisolone. Patients intolerant to corticosteroids and patients stopping corticosteroids in preparation for surgery including colectomy during their initial admission were excluded. RESULTS: There was no overall association between prednisolone exposure or no exposure and CFCR at weeks 14 or 52 of infliximab. The proportion of patients with C reactive protein ≤5 mg/L was higher in the standard tapering at week 14 as compared with faster regimens or no prednisolone. In subgroup analyses, the standard tapering was associated with a higher rate of CFCR at week 14 compared with the fast-tapering regimen in patients receiving ≥40 mg prednisolone at initiation of infliximab (64.3% vs 26.3%, p=0.04) and among patients admitted with acute severe UC (66.6% vs 23.5%, p<0.05). Similar data were seen at week 52. Prednisolone did not affect infliximab trough levels but increased infection rates (10/77 vs 2/70, p=0.03), in particular C. difficile infection. CONCLUSION: In UC patients with limited disease burden, prednisolone did not affect effectiveness of infliximab. However, patients with increased disease burden seem to benefit from corticosteroid combination therapy.


Subject(s)
Colitis, Ulcerative , Gastrointestinal Agents , Infliximab , Prednisolone , Remission Induction , Humans , Colitis, Ulcerative/drug therapy , Infliximab/administration & dosage , Infliximab/therapeutic use , Retrospective Studies , Prednisolone/administration & dosage , Prednisolone/therapeutic use , Male , Female , Adult , Middle Aged , Treatment Outcome , Remission Induction/methods , Gastrointestinal Agents/administration & dosage , Gastrointestinal Agents/therapeutic use , Drug Tapering/methods , Anti-Inflammatory Agents/administration & dosage , Anti-Inflammatory Agents/therapeutic use , Anti-Inflammatory Agents/adverse effects , C-Reactive Protein/analysis , C-Reactive Protein/metabolism , Glucocorticoids/administration & dosage , Glucocorticoids/therapeutic use , Glucocorticoids/adverse effects , Drug Therapy, Combination
9.
Clin Lab ; 70(5)2024 May 01.
Article in English | MEDLINE | ID: mdl-38747922

ABSTRACT

BACKGROUND: The goal was to explore the cognition of diagnosis and treatment level of IgG4-related diseases mainly involving lymph nodes. METHODS: The clinical manifestations, laboratory indicators, histopathology, and therapeutic effects of a patient with IgG4-RD suspected of lymphoma were analyzed and the relevant literature was reviewed. RESULTS: Lymph node biopsy showed reactive hyperplasia of lymph node tissue. The liver biochemical indexes were abnormal and the bone marrow smear showed atypical lymphocytes. Lymph node section: IgG4+ cells > 100/HPF (IgG4/IgG > 40%). The serum IgG4 level was 17,200 mg/L, and the diagnosis was IgG4-RD. Oral glucocorticoids took effect after 2 weeks, and no significant enlargement of lymph nodes was observed. CONCLUSIONS: For the diagnosis of IgG4-RD, at present, histopathology is still the gold standard, but a single result cannot diagnose the disease. Comprehensive judgment should be made by combining clinical symptoms, serum IgG4 level and imaging results to prevent misdiagnosis and missed diagnosis, and to avoid over-diagnosis. Short-term hormonal diagnostic therapy may be used in highly suspected patients who cannot be diagnosed. Once diagnosed, standardized medication, adhere to follow-up, regular review, to prevent recurrence and adverse drug reactions.


Subject(s)
Immunoglobulin G4-Related Disease , Immunoglobulin G , Liver Diseases , Humans , Immunoglobulin G/blood , Immunoglobulin G4-Related Disease/diagnosis , Immunoglobulin G4-Related Disease/drug therapy , Immunoglobulin G4-Related Disease/blood , Liver Diseases/diagnosis , Liver Diseases/immunology , Liver Diseases/blood , Glucocorticoids/therapeutic use , Lymph Nodes/pathology , Male , Middle Aged
10.
Clin Exp Rheumatol ; 42(5): 947-960, 2024 May.
Article in English | MEDLINE | ID: mdl-38743447

ABSTRACT

New evidence from 2023 has slightly shifted some perspectives on rheumatoid arthritis (RA) management. Glucocorticoids have reaffirmed their role as bridging therapy, while novel studies on JAK inhibitors have examined efficacy, mechanism of action, and their potential in high-risk populations, bolstering our understanding with real-world data.Additionally, among treatment strategies, achieving low disease activity has emerged as comparable to achieving remission in the long term, and new insights have been gained regarding tapering both biological and conventional synthetic DMARDs. Furthermore, novel approaches have been proposed for managing difficult-to-treat RA and pre-RA. In this paper, the reviewers aim to present the most relevant studies published during the last year in the field of RA management.


Subject(s)
Antirheumatic Agents , Arthritis, Rheumatoid , Glucocorticoids , Janus Kinase Inhibitors , Humans , Arthritis, Rheumatoid/drug therapy , Antirheumatic Agents/therapeutic use , Glucocorticoids/therapeutic use , Janus Kinase Inhibitors/therapeutic use , Remission Induction , Treatment Outcome
12.
Cancer Cell ; 42(5): 833-849.e12, 2024 May 13.
Article in English | MEDLINE | ID: mdl-38701792

ABSTRACT

Glucocorticoids have been used for decades to treat lymphomas without an established mechanism of action. Using functional genomic, proteomic, and chemical screens, we discover that glucocorticoids inhibit oncogenic signaling by the B cell receptor (BCR), a recurrent feature of aggressive B cell malignancies, including diffuse large B cell lymphoma and Burkitt lymphoma. Glucocorticoids induce the glucocorticoid receptor (GR) to directly transactivate genes encoding negative regulators of BCR stability (LAPTM5; KLHL14) and the PI3 kinase pathway (INPP5D; DDIT4). GR directly represses transcription of CSK, a kinase that limits the activity of BCR-proximal Src-family kinases. CSK inhibition attenuates the constitutive BCR signaling of lymphomas by hyperactivating Src-family kinases, triggering their ubiquitination and degradation. With the knowledge that glucocorticoids disable oncogenic BCR signaling, they can now be deployed rationally to treat BCR-dependent aggressive lymphomas and used to construct mechanistically sound combination regimens with inhibitors of BTK, PI3 kinase, BCL2, and CSK.


Subject(s)
Glucocorticoids , Receptors, Antigen, B-Cell , Humans , Glucocorticoids/pharmacology , Receptors, Antigen, B-Cell/metabolism , Animals , Signal Transduction/drug effects , Receptors, Glucocorticoid/metabolism , Mice , Cell Line, Tumor , Lymphoma, Large B-Cell, Diffuse/drug therapy , Lymphoma, Large B-Cell, Diffuse/genetics , Lymphoma, Large B-Cell, Diffuse/metabolism , Burkitt Lymphoma/drug therapy , Burkitt Lymphoma/genetics , Burkitt Lymphoma/metabolism , Burkitt Lymphoma/pathology , Molecular Targeted Therapy/methods , Phosphatidylinositol 3-Kinases/metabolism , src-Family Kinases/metabolism , Gene Expression Regulation, Neoplastic/drug effects
14.
J Orthop Surg Res ; 19(1): 292, 2024 May 12.
Article in English | MEDLINE | ID: mdl-38735955

ABSTRACT

BACKGROUND: In this retrospective case investigation, we analysed the data of patients with osteonecrosis of the femoral head (ONFH) to reveal demographic and clinical diagnostic features of ONFH in three northeastern provinces of China and provide a reference for its prevention, diagnosis, and treatment. METHODS: We collected data from patients in Beijing Orthopaedic Hospital of Liaoning, focusing on the aetiology and diagnosis of ONFH. Medical records and self-designed questionnaires were used to collect information for statistical analysis, including age, aetiology, reason for glucocorticoid use, hospital level at first visit, and diagnosis. RESULTS: In total, 906 patients with complete medical records were included in the analysis. The mean patient age was 47.65 ± 12.12 years. The peak age distribution was in the 40s for men and the 50s for women. Among the total cohort, 72 patients (7.95%; 40 men and 32 women) had traumatic ONFH, 198 (21.85%; 131 men and 67 women) had steroid-induced ONFH, 230 (25.39%; 121 men and 109 women) had idiopathic ONFH, and 406 (44.81%; 397 men and 9 women) had alcohol-induced ONFH. Six hundred and twenty patients were diagnosed with ONFH at the first visit, while 286 patients were misdiagnosed, with a diagnosis rate of 68.43%. The diagnosis rate at the first visit in tertiary hospitals was 76.14%. The diagnosis rate at the first visit in second-class hospitals was 52.07%.ONFH was most likely to be misdiagnosed as lumbar disc herniation. CONCLUSIONS: Most patients with ONFH in three northeastern provinces of China were middle-aged, male, and had alcohol-induced ONFH. The misdiagnosis rate of ONFH at the first visit was very high, especially for misdiagnosis of lumbar disc herniation, indicating that the diagnosis of ONFH requires further improvement.


Subject(s)
Femur Head Necrosis , Humans , Male , Female , Femur Head Necrosis/epidemiology , Femur Head Necrosis/diagnosis , Femur Head Necrosis/etiology , Middle Aged , Adult , China/epidemiology , Retrospective Studies , Aged , Young Adult , Adolescent , Glucocorticoids/therapeutic use
15.
Sci Rep ; 14(1): 10867, 2024 05 13.
Article in English | MEDLINE | ID: mdl-38740863

ABSTRACT

Chronic psychosocial stress induced by the chronic subordinate colony housing (CSC, 19 Days) paradigm promotes functional splenic in vitro glucocorticoid (GC) resistance, but only if associated with significant bite wounding or prior abdominal transmitter implantation. Moreover, sensory contact to social defeat of conspecifics represents a social stressor for the observer individual. As the occurence and severity of bite wounding is not adequately controllable, the present study aimed to develop an animal model, allowing a bite wound-independent, more reliable generation of chronically-stressed mice characterized by functional splenic in vitro GC resistance. Therefore, male C57BL/6N mice received a standardized sterile intraperitoneal (i.p.) incision surgery or SHAM treatment one week prior to 19-days of (i) CSC, (ii) witnessing social defeat during CSC exposure in sensory contact (SENS) or (iii) single-housing for control (SHC), before assessing basal and LPS-induced splenic in vitro cell viability and GC resistance. Our results indicate that individually-housed SENS but not CSC mice develop mild signs of splenic in vitro GC resistance, when undergoing prior i.p.-wounding. Taken together and considering that future studies are warranted, our findings support the hypothesis that the combination of repeated standardized i.p.-wounding with chronic sensory stress exposure represents an adequate tool to induce functional splenic in vitro GC resistance independent of the occurrence of uncontrollable bite wounds required in social stress paradigms to induce a comparable phenotype.


Subject(s)
Glucocorticoids , Mice, Inbred C57BL , Spleen , Stress, Psychological , Animals , Male , Spleen/metabolism , Mice , Disease Models, Animal , Social Defeat
16.
Front Endocrinol (Lausanne) ; 15: 1384365, 2024.
Article in English | MEDLINE | ID: mdl-38715797

ABSTRACT

Importance: Subacute thyroiditis (SAT) is a self-limiting and inflammatory thyroid disease. Although SAT usually improves on its own within weeks, it needs treatment when patients have pain, fever, and symptoms of thyrotoxicosis. Therapeutic drugs mainly include non-steroidal anti-inflammatory drugs (NSAIDs) and glucocorticoids. Currently, there is no systematic review or meta-analysis of the comparison of outcomes between NSAIDs and glucocorticoids for the treatment of SAT. Objectives: To conduct a systematic review and meta-analysis on the outcomes in subacute thyroiditis patients treated with glucocorticoids or NSAIDs. Data sources: Using the four electronic databases, including PubMed, Embase, Cochrane Library, Wanfang database and Web of Science. All publications until 21 June 2023 were searched. The reference lists of all selected articles were independently screened to identify additional studies left out in the initial search. Study selection: The literature comparing outcomes between glucocorticoids and non-steroidal anti-inflammatory drugs for patients with subacute thyroiditis will be included. Data extraction and synthesis: Two independent investigators (Anqi Yuan and Jialu Wu) extracted the data following Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines (PRISMA) and then evaluated the quality of the eligible studies with the Newcastle-Ottawa Scale. Fixed-effects models for the meta-analyses were applied. Heterogeneity was assessed with the chi-squared (x²) test (Cochran's Q) and inconsistency index (I²). The robustness of the results was tested with the sensitivity analyses. The bias of publication was assessed with the Harbord test. Main outcomes and measures: The incidence of permanent hypothyroidism in SAT patients treated with corticosteroids or NSAIDs. Results: Our study included a total of ten comparative cohort studies with 1337 participants. We found that the incidence of developing permanent hypothyroidism in the SAT patients who received glucocorticoids treatment was significantly lower than those who received NSAIDs treatment. (OR, 0.56; 95% CI, 0.36-0.88; P = 0.01). The risk of permanent hypothyroidism in patients who received prednisone at an average initial dose < 40 mg/d was significantly lower than that in patients who received NSAIDs (OR, 0.37; 95% CI, 0.14-0.94; P = 0.04). There was no significant difference in the occurrence of permanent hypothyroidism between SAT patients who received an average initial dose ≥ 40 mg/d of prednisone and those who received only NSAIDs (OR, 0.7; 95% CI, 0.14-3.53; P = 0.67). In addition, the recurrence rate was observably higher in those receiving glucocorticoids than in those receiving NSAIDs (OR, 1.98; 95% CI, 1.12-3.5; p = 0.02). The recurrence rate was significantly higher in patients with an average initial prednisone dose of < 40 mg/d than in the NSAIDs group. There was no significant difference in the recurrence rate between patients in the mean initial prednisone dose ≥ 40 mg/d group and those in the NSAIDs group. Conclusions and relevance: In this meta-analysis, we compared the treatment outcomes of SAT patients between glucocorticoids and NSAIDs. Our results indicated that glucocorticoid treatment was associated with a lower incidence of permanent hypothyroidism than NSAID treatment. Patients treated with NSAIDs might have a lower recurrence rate. This finding might help to understand the outcome of the disease when choosing different drugs and help physicians to make appropriate decisions. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023427332.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal , Glucocorticoids , Thyroiditis, Subacute , Humans , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Thyroiditis, Subacute/drug therapy , Glucocorticoids/therapeutic use , Glucocorticoids/adverse effects , Glucocorticoids/administration & dosage , Treatment Outcome
17.
Adv Rheumatol ; 64(1): 38, 2024 May 08.
Article in English | MEDLINE | ID: mdl-38720354

ABSTRACT

BACKGROUND: This study examines the association of standard-of-care systemic lupus erythematosus (SLE) medications with key outcomes such as low disease activity attainment, flares, damage accrual, and steroid-sparing, for which there is current paucity of data. METHODS: The Asia Pacific Lupus Collaboration (APLC) prospectively collects data across numerous sites regarding demographic and disease characteristics, medication use, and lupus outcomes. Using propensity score methods and panel logistic regression models, we determined the association between lupus medications and outcomes. RESULTS: Among 1707 patients followed over 12,689 visits for a median of 2.19 years, 1332 (78.03%) patients achieved the Lupus Low Disease Activity State (LLDAS), 976 (57.18%) experienced flares, and on most visits patients were taking an anti-malarial (69.86%) or immunosuppressive drug (76.37%). Prednisolone, hydroxychloroquine and azathioprine were utilised with similar frequency across all organ domains; methotrexate for musculoskeletal activity. There were differences in medication utilisation between countries, with hydroxychloroquine less frequently, and calcineurin inhibitors more frequently, used in Japan. More patients taking leflunomide, methotrexate, chloroquine/hydroxychloroquine, azathioprine, and mycophenolate mofetil/mycophenolic acid were taking ≤ 7.5 mg/day of prednisolone (compared to > 7.5 mg/day) suggesting a steroid-sparing effect. Patients taking tacrolimus were more likely (Odds Ratio [95% Confidence Interval] 13.58 [2.23-82.78], p = 0.005) to attain LLDAS. Patients taking azathioprine (OR 0.67 [0.53-0.86], p = 0.001) and methotrexate (OR 0.68 [0.47-0.98], p = 0.038) were less likely to attain LLDAS. Patients taking mycophenolate mofetil were less likely to experience a flare (OR 0.79 [0.64-0.97], p = 0.025). None of the drugs was associated with a reduction in damage accrual. CONCLUSIONS: This study suggests a steroid-sparing benefit for most commonly used standard of care immunosuppressants used in SLE treatment, some of which were associated with an increased likelihood of attaining LLDAS, or reduced incidence of flares. It also highlights the unmet need for effective treatments in lupus.


Subject(s)
Antimalarials , Azathioprine , Glucocorticoids , Hydroxychloroquine , Immunosuppressive Agents , Lupus Erythematosus, Systemic , Methotrexate , Prednisolone , Standard of Care , Humans , Lupus Erythematosus, Systemic/drug therapy , Female , Immunosuppressive Agents/therapeutic use , Hydroxychloroquine/therapeutic use , Male , Glucocorticoids/therapeutic use , Adult , Azathioprine/therapeutic use , Prednisolone/therapeutic use , Methotrexate/therapeutic use , Antimalarials/therapeutic use , Cohort Studies , Middle Aged , Mycophenolic Acid/therapeutic use , Leflunomide/therapeutic use , Calcineurin Inhibitors/therapeutic use , Logistic Models , Propensity Score , Severity of Illness Index , Tacrolimus/therapeutic use , Symptom Flare Up , Treatment Outcome , Antirheumatic Agents/therapeutic use
18.
Front Immunol ; 15: 1366101, 2024.
Article in English | MEDLINE | ID: mdl-38707905

ABSTRACT

We report here the case of a 50-year-old man who was first diagnosed with myelodysplastic syndrome with excess blasts-2 (MDS-EB-2) and underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) in 2019, resulting in complete remission. However, he was diagnosed in 2021 with several autoimmune disorders, including autoimmune hepatitis (AIH), Hashimoto's thyroiditis (HT), and autoimmune hemolytic anemia (AIHA). This is referred as multiple autoimmune syndrome (MAS), which is a rare occurrence after allo-HSCT, as previously noted in the literature. Despite being treated with glucocorticoids, cyclosporine A, and other medications, the patient did not fully recover. To address the glucocorticoid-refractory MAS, a four-week course of rituximab (RTX) at a weekly dose of 100mg was administered, which significantly improved the patient's condition. Thus, this case report underscores the importance of implementing alternative treatments in patients with post-transplant autoimmune diseases, who are glucocorticoid-refractory or glucocorticoid-dependent, and highlights the effectiveness of RTX as second-line therapy.


Subject(s)
Autoimmune Diseases , Glucocorticoids , Hematopoietic Stem Cell Transplantation , Transplantation, Homologous , Humans , Hematopoietic Stem Cell Transplantation/adverse effects , Male , Middle Aged , Glucocorticoids/therapeutic use , Autoimmune Diseases/etiology , Autoimmune Diseases/therapy , Rituximab/therapeutic use , Anemia, Hemolytic, Autoimmune/etiology , Anemia, Hemolytic, Autoimmune/therapy , Anemia, Hemolytic, Autoimmune/drug therapy , Drug Resistance
19.
Neurology ; 102(10): e209206, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38710006

ABSTRACT

BACKGROUND AND OBJECTIVES: Clinical trials in Duchenne muscular dystrophy (DMD) require 3-6 months of stable glucocorticoids, and the primary outcome is explored at 48-52 weeks. The factors that influence the clinical outcome assessment (COA) trajectories soon after glucocorticoid initiation are relevant for the design and analysis of clinical trials of novel drugs. We describe early COA trajectories, associated factors, and the time from glucocorticoid initiation to COA peak. METHODS: This was a prospective 18-month analysis of the Finding the Optimum Corticosteroid Regimen for Duchenne Muscular Dystrophy study. Four COAs were investigated: rise from supine velocity (RFV), 10-meter walk/run velocity (10MWRV), North Star Ambulatory Assessment (NSAA) total score, and 6-minute walk test distance (6MWT). The relationships of baseline age (4-5 vs 6-7 years), COA baseline performance, genotype, and glucocorticoid regimen (daily vs intermittent) with the COA trajectories were evaluated using linear mixed-effects models. RESULTS: One hundred ninety-six glucocorticoid-naïve boys with DMD aged 4-7 years were enrolled. The mean age at baseline was 5.9 ± 1.0 years, 66% (n = 130) were on daily regimens, 55% (n = 107) showed a 6MWT distance >330 metres; 41% (n = 78) showed RFV >0.2 rise/s; 76% (n = 149) showed 10MWRV >0.142 10m/s, and 41.0% (n = 79) showed NSAA total score >22 points. Mean COA trajectories differed by age at glucocorticoid initiation (p < 0.01 for RFV, 10MWRV, and NSAA; p < 0.05 for 6MWT) and regimen (p < 0.01 for RFV, 10MWRV, and NSAA). Boys younger than 6 years reached their peak performance 12-18 months after glucocorticoid initiation. Boys aged 6 years or older on a daily regimen peaked between months 9 and 12 and those on an intermittent regimen by 9 months. The baseline COA performance was associated with the NSAA (p < 0.01) and the 6MWT trajectory in boys younger than 6 years on a daily regimen (p < 0.01). Differences in the mean trajectories by genotype were not significant. DISCUSSION: Glucocorticoid regimen, age, duration of glucocorticoid exposure, and baseline COA performance need to be considered in the design and analysis of clinical trials in young boys with DMD.


Subject(s)
Glucocorticoids , Muscular Dystrophy, Duchenne , Humans , Muscular Dystrophy, Duchenne/drug therapy , Muscular Dystrophy, Duchenne/physiopathology , Male , Glucocorticoids/administration & dosage , Glucocorticoids/therapeutic use , Child, Preschool , Child , Prospective Studies , Treatment Outcome , Outcome Assessment, Health Care , Age Factors
20.
Respir Res ; 25(1): 196, 2024 May 07.
Article in English | MEDLINE | ID: mdl-38715030

ABSTRACT

BACKGROUND: The treatment response to corticosteroids in patients with sarcoidosis is highly variable. CD4+ T cells are central in sarcoid pathogenesis and their phenotype in peripheral blood (PB) associates with disease course. We hypothesized that the phenotype of circulating T cells in patients with sarcoidosis may correlate with the response to prednisone treatment. Therefore, we aimed to correlate frequencies and phenotypes of circulating T cells at baseline with the pulmonary function response at 3 and 12 months during prednisone treatment in patients with pulmonary sarcoidosis. METHODS: We used multi-color flow cytometry to quantify activation marker expression on PB T cell populations in 22 treatment-naïve patients and 21 healthy controls (HCs). Pulmonary function tests at baseline, 3 and 12 months were used to measure treatment effect. RESULTS: Patients with sarcoidosis showed an absolute forced vital capacity (FVC) increase of 14.2% predicted (± 10.6, p < 0.0001) between baseline and 3 months. Good response to prednisone (defined as absolute FVC increase of ≥ 10% predicted) was observed in 12 patients. CD4+ memory T cells and regulatory T cells from patients with sarcoidosis displayed an aberrant phenotype at baseline, compared to HCs. Good responders at 3 months had significantly increased baseline proportions of PD-1+CD4+ memory T cells and PD-1+ regulatory T cells, compared to poor responders and HCs. Moreover, decreased fractions of CD25+ cells and increased fractions of PD-1+ cells within the CD4+ memory T cell population correlated with ≥ 10% FVC increase at 12 months. During treatment, the aberrantly activated phenotype of memory and regulatory T cells reversed. CONCLUSIONS: Increased proportions of circulating PD-1+CD4+ memory T cells and PD-1+ regulatory T cells and decreased proportions of CD25+CD4+ memory T cells associate with good FVC response to prednisone in pulmonary sarcoidosis, representing promising new blood biomarkers for prednisone efficacy. TRIAL REGISTRATION: NL44805.078.13.


Subject(s)
Prednisone , Programmed Cell Death 1 Receptor , Sarcoidosis, Pulmonary , T-Lymphocytes, Regulatory , Humans , Male , Sarcoidosis, Pulmonary/drug therapy , Sarcoidosis, Pulmonary/blood , Sarcoidosis, Pulmonary/immunology , Sarcoidosis, Pulmonary/diagnosis , Female , Middle Aged , Prednisone/therapeutic use , T-Lymphocytes, Regulatory/drug effects , T-Lymphocytes, Regulatory/immunology , Adult , Treatment Outcome , Memory T Cells/drug effects , Memory T Cells/immunology , Memory T Cells/metabolism , CD4-Positive T-Lymphocytes/drug effects , CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/metabolism , Glucocorticoids/therapeutic use , Vital Capacity/drug effects , Aged
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