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Frontiers in Immunology 2023Childhood-onset systemic lupus erythematosus (cSLE) is an autoimmune disease that results in significant damage and often needs more aggressive treatment. Compared to... (Review)
Review
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.
Topics: Child; Adult; Humans; Glucocorticoids; Autoimmune Diseases; Prednisone; Drug-Related Side Effects and Adverse Reactions; Lupus Erythematosus, Systemic
PubMed: 37638017
DOI: 10.3389/fimmu.2023.1128754 -
BMC Musculoskeletal Disorders Dec 2023Current research on autophagy is mainly focused on intervertebral disc tissues and cells, while there is few on human peripheral blood sample. therefore, this study...
BACKGROUND
Current research on autophagy is mainly focused on intervertebral disc tissues and cells, while there is few on human peripheral blood sample. therefore, this study constructed a diagnostic model to identify autophagy-related markers of intervertebral disc degeneration (IVDD).
METHODS
GSE150408 and GSE124272 datasets were acquired from the Gene Expression Omnibus database, and differential expression analysis was performed. The IVDD-autophagy genes were obtained using Weighted Gene Coexpression Network Analysis, and a diagnostic model was constructed and validated, followed by Gene Set Variation Analysis (GSVA) and Gene Set Enrichment Analysis (GSEA). Meanwhile, miRNA-gene and transcription factor-gene interaction networks were constructed. In addition, drug-gene interactions and target genes of methylprednisolone and glucosamine were analyzed.
RESULTS
A total of 1,776 differentially expressed genes were identified between IVDD and control samples, and the composition of the four immune cell types was significantly different between the IVDD and control samples. The Meturquoise and Mebrown modules were significantly related to immune cells, with significant differences between the control and IVDD samples. A diagnostic model was constructed using five key IVDD-autophagy genes. The area under the curve values of the model in the training and validation datasets were 0.907 and 0.984, respectively. The enrichment scores of the two pathways were significantly different between the IVDD and healthy groups. Eight pathways in the IVDD and healthy groups had significant differences. A total of 16 miRNAs and 3 transcription factors were predicted to be of great value. In total, 84 significantly related drugs were screened for five key IVDD-autophagy genes in the diagnostic model, and three common autophagy-related target genes of methylprednisolone and glucosamine were predicted.
CONCLUSION
This study constructs a reliable autophagy-related diagnostic model that is strongly related to the immune microenvironment of IVD. Autophagy-related genes, including PHF23, RAB24, STAT3, TOMM5, and DNAJB9, may participate in IVDD pathogenesis. In addition, methylprednisolone and glucosamine may exert therapeutic effects on IVDD by targeting CTSD, VEGFA, and BAX genes through apoptosis, as well as the sphingolipid and AGE-RAGE signaling pathways in diabetic complications.
Topics: Humans; Intervertebral Disc Degeneration; Intervertebral Disc; Transcription Factors; Autophagy; Methylprednisolone; Glucosamine; Membrane Proteins; Molecular Chaperones; HSP40 Heat-Shock Proteins; Homeodomain Proteins
PubMed: 38041088
DOI: 10.1186/s12891-023-06886-w -
Kidney360 Sep 2023The contribution of IV methylprednisolone to glucocorticoid toxicity is often overlooked with limited evidence supporting its use. Markedly reduced cumulative...
KEY POINTS
The contribution of IV methylprednisolone to glucocorticoid toxicity is often overlooked with limited evidence supporting its use. Markedly reduced cumulative glucocorticoid dosing for remission induction therapy in AAV is safe and effective. Reduced IV methylprednisolone and radical steroid avoidance strategies have not been shown to have any significant adverse effect on outcomes.
BACKGROUND
Glucocorticoids (GCs) remain integral to the management of ANCA-associated vasculitis (AAV), but are associated with significant adverse effects. Recent studies have shown reduced oral GC dosing to be safe and effective; however, data guiding the use of intravenous (IV) methylprednisolone (MTP) are limited.
METHOD
A single-center retrospective cohort of patients with AAV were divided into two groups: low-dose GC (patients receiving 250 mg of IV MTP, followed by a tapering course of 30 mg of prednisolone daily) versus high-dose GC (1.5 g of IV MTP, followed by a tapering course of 40–60 mg of prednisolone daily). Primary outcomes included ESKD and mortality, and secondary outcomes included GC-related toxicity, remission, and relapse rates. This study was applied to patients with newly diagnosed AAV, including those with severe or life-threatening disease.
RESULTS
Sixty-five patients were included in the final analysis—34 in the high-dose treatment group and 31 in the low-dose treatment group. At diagnosis, more advanced renal impairment and histological disease were present in the low-dose cohort. The rate of ESKD was similar between the groups at 6 and 12 months ( = 0.22, = 0.60, respectively). More deaths occurred in the high-dose group (26.5% versus 6.5%, = 0.05), although this was not significant on multivariable analysis ( = 0.06). Remission rates were comparable, and there was no significant difference in relapses. Adverse events were seen in both groups, but patients in the high-dose group experienced a higher incidence of severe infections, weight gain, and steroid-induced diabetes.
CONCLUSION
We demonstrate that a markedly reduced dose of IV MTP with a lower overall cumulative dose of GCs is safe and effective in the management of severe AAV disease, with no significant difference in primary outcomes.
Topics: Humans; Methylprednisolone; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Immunosuppressive Agents; Remission Induction
PubMed: 37668468
DOI: 10.34067/KID.0000000000000222 -
International Immunopharmacology Dec 2023Bullous pemphigoid (BP) is a common subepidermal bullous disease. Dupilumab is a novel treatment for BP. However, its long-term efficacy and safety have not been...
BACKGROUND
Bullous pemphigoid (BP) is a common subepidermal bullous disease. Dupilumab is a novel treatment for BP. However, its long-term efficacy and safety have not been demonstrated in prospective studies.
OBJECTIVE
Evaluate the long-term efficacy and safety of dupilumab in treating severe BP.
METHODS
Patients were divided into two groups: the methylprednisolone monotherapy group (M), and the methylprednisolone and dupilumab combination therapy group (D + M). This study consisted of two stages. The first stage focused on the initial treatment phase, where the early efficacy and safety was evaluated. The study then entered the 12-month maintenance treatment stage, where we assessed recurrence in both groups. Additionally, we evaluated the rate of healing of skin lesions, glucocorticoids burden and length of hospital stay and various laboratory test indicators.
RESULTS
After four weeks of treatment, the Bullous Pemphigoid Disease Area Index (BPDAI) and pruritus Numerical Rating Scale scores of the D + M group decreased significantly more than those of the M group. The median BPDAI at week 4 was 0 (range: 0.0-3.0) in the D + M group and 10.0 (5.0-12.0) in the M group (P < 0.001). Patients treated with dupilumab experienced a faster cessation of new blisters, quicker glucocorticoid reduction, shorter healing times, and shorter hospital stays (P < 0.001). Additionally, after two weeks of treatment, the levels of eosinophils and immunoglobulin E also decreased (P < 0.001). Follow-up studies further demonstrated that dupilumab monotherapy was associated with a lower recurrence rate. Notably, no serious adverse effects were observed in the study.
CONCLUSIONS
Our study provides evidence for the efficacy of dupilumab in the treatment of BP based on prospective studies. Additionally, our findings suggest that dupilumab can be considered a reliable single-agent maintenance treatment due to its good safety profile and lower relapse.
Topics: Humans; Pemphigoid, Bullous; Prospective Studies; Antibodies, Monoclonal, Humanized; Methylprednisolone
PubMed: 37925949
DOI: 10.1016/j.intimp.2023.111157 -
Yonsei Medical Journal Nov 2023Acute ascending hemorrhagic longitudinally extensive transverse myelitis is a rare inflammatory demyelinating disorder, which invades several vertebral segments and...
Acute ascending hemorrhagic longitudinally extensive transverse myelitis is a rare inflammatory demyelinating disorder, which invades several vertebral segments and progresses rapidly and manifests severe symptoms. We present a case of acute necrotizing myelitis associated with COVID-19 infection. A 10-year-old female, with no previous medical history and no prior administration of COVID-19 vaccination, contracted COVID-19 in early April 2022. Two weeks later, she suffered from severe posterior neck pain and also presented with motor weakness and numbness in both lower extremities, making it difficult to walk independently and spontaneously void urine. Initial spinal cord MR showed longitudinally segmental extensive T2 hyperintensities. Cerebrospinal fluid (CSF) analysis revealed elevated red blood cell, normal white blood cell, and elevated protein levels and absence of oligoclonal bands. CSF culture and viral polymerase chain reaction were negative. Autoimmune work-up was negative. She was started on intravenous methylprednisolone 1g/day for 5 days and immunoglobulin (Ig) 2 g/kg for 5 days. She was also treated with six courses of therapeutic plasma exchange. Nevertheless, her pain and motor weakness persisted. She eventually developed respiratory failure. Follow-up MR presented a newly noted small hemorrhagic component. She was consequently treated with two additional courses of methylprednisolone and Ig. At 6-months follow-up, neurological examination showed improvement with normal sensory function and motor grade IV function in both upper extremities. We present the case of acute necrotizing myelitis associated with COVID-19 infection. Multiple courses of methylprednisolone and Ig showed mild improvement in motor and sensory function. However, poor prognosis was unavoidable due to rapid progression of the disease.
Topics: Humans; Female; Child; Myelitis, Transverse; COVID-19 Vaccines; COVID-19; Methylprednisolone
PubMed: 37880851
DOI: 10.3349/ymj.2023.0202 -
Dermatology Practical & Conceptual Oct 2023Alopecia areata (AA) is a common, non-scarring, autoimmune hair loss disorder, varying in severity from small round hairless patches to the total loss of scalp or body... (Review)
Review
INTRODUCTION
Alopecia areata (AA) is a common, non-scarring, autoimmune hair loss disorder, varying in severity from small round hairless patches to the total loss of scalp or body hair. As steroid pulse therapy outcomes for AA vary, this study aimed to review the related literature regarding the efficacy, relapse rates, side effects, and prognostic factors associated with the response to different pulse corticosteroid treatments.
METHODS
We performed a literature search on August 29, 2022, to provide an overview of the efficacy of pulse steroid therapy in patients with AA. The terms "pulse steroid therapy AND alopecia areata" and "pulse corticosteroid therapy AND alopecia areata" were searched on PubMed and Google Scholar.
RESULTS
A total of 24 articles were assessed. There was no difference in outcomes and side effects between intravenous and oral pulse corticosteroid therapy. The relapse rate and efficacy depended on the time of AA onset, age, and AA type: improved outcomes and decreased relapse were linked with recent onset (<6 months), a younger age (<10 years), and the multifocal type of AA. Patients with a past medical history of atopy, nail pitting, or thyroid disease and those with severe forms of AA like alopecia totalis and alopecia universalis had the least improvement.
CONCLUSIONS
All kinds of mentioned systemic pulse corticosteroids effectively induce hair regrowth in AA. Betamethasone pulse seems to be the most effective agent (followed by intramuscular triamcinolone), especially in severe cases, but more side effects may accompany it. Combining this agent with other medications can reduce the dosage and side effects. Pulses of prednisolone and methylprednisolone are less effective but safer, as they have low relapse rates and adverse effects. A combination of them with other drugs can increase their efficacy.
PubMed: 37992355
DOI: 10.5826/dpc.1304a255 -
Cureus Oct 2023Tolosa-Hunt syndrome (THS) is an idiopathic inflammatory condition involving the cavernous sinus and orbital apex with an incidence of 1 case per million per year. We...
Tolosa-Hunt syndrome (THS) is an idiopathic inflammatory condition involving the cavernous sinus and orbital apex with an incidence of 1 case per million per year. We report on a case of a 70-year-old male with atypical MRI findings, vision loss, and painless ophthalmoplegia. Ophthalmic evaluation revealed his best-corrected visual acuity was 20/40 in the right eye and counting fingers at a 0.5-foot distance in the left eye. External examination of the left eye revealed limited ocular movement, proptosis, and a positive relative afferent pupillary defect. Complete blood count, inflammatory markers, and full biochemistry tests, including thyroid and liver function tests, were within the normal range. A magnetic resonance imaging of the orbits with and without contrast demonstrated a homogenously enhancing lesion at the posterior intraconal compartment of the left orbit, extending to the orbital apex with the involvement of the adjacent extraocular muscles. The patient was started on intravenous methylprednisolone 60 mg daily and later discharged on prednisone 5 mg daily with partial symptom improvement on follow-up. Resection and biopsy revealed a soft tissue lesion with mixed inflammatory infiltrate. The clinical, pathological, and imaging findings favored the diagnosis of THS.
PubMed: 37936989
DOI: 10.7759/cureus.46635 -
Advanced Science (Weinheim,... Jun 2024Neural stem cells (NSCs) transplantation is an attractive and promising treatment strategy for spinal cord injury (SCI). Various pathological processes including the...
Neural stem cells (NSCs) transplantation is an attractive and promising treatment strategy for spinal cord injury (SCI). Various pathological processes including the severe inflammatory cascade and difficulty in stable proliferation and differentiation of NSCs limit its application and translation. Here, a novel physico-chemical bifunctional neural stem cells delivery system containing magnetic nanoparticles (MNPs and methylprednisolone (MP) is designed to repair SCI, the former regulates NSCs differentiation through magnetic mechanical stimulation in the chronic phase, while the latter alleviates inflammatory response in the acute phase. The delivery system releases MP to promote microglial M2 polarization, inhibit M1 polarization, and reduce neuronal apoptosis. Meanwhile, NSCs tend to differentiate into functional neurons with magnetic mechanical stimulation generated by MNPs in the static magnetic field, which is related to the activation of the PI3K/AKT/mTOR pathway. SCI mice achieve better functional recovery after receiving NSCs transplantation via physico-chemical bifunctional delivery system, which has milder inflammation, higher number of M2 microglia, more functional neurons, and axonal regeneration. Together, this bifunctional NSCs delivery system combined physical mechanical stimulation and chemical drug therapy is demonstrated to be effective, which provides new treatment insights into clinical transformation of SCI repair.
Topics: Animals; Spinal Cord Injuries; Methylprednisolone; Mice; Neural Stem Cells; Magnetite Nanoparticles; Disease Models, Animal; Cell Differentiation; Stem Cell Transplantation
PubMed: 38516757
DOI: 10.1002/advs.202308993 -
Neurology(R) Neuroimmunology &... Jul 2023Erythropoietin (EPO) is a candidate neuroprotective drug. We assessed its long-term safety and efficacy as an adjunct to methylprednisolone in patients with optic...
BACKGROUND AND OBJECTIVE
Erythropoietin (EPO) is a candidate neuroprotective drug. We assessed its long-term safety and efficacy as an adjunct to methylprednisolone in patients with optic neuritis and focused on conversions to multiple sclerosis (MS).
METHODS
The TONE trial randomized 108 patients with acute optic neuritis but without previously known MS to either 33,000 IU EPO or placebo in conjunction with 1,000 mg methylprednisolone daily for 3 days. After reaching the primary end point at 6 months, we conducted an open-label follow-up 2 years after randomization.
RESULTS
The follow-up was attended by 83 of 103 initially analyzed patients (81%). There were no previously unreported adverse events. The adjusted treatment difference of peripapillary retinal nerve fiber layer atrophy in relation to the fellow eye at baseline was 1.27 µm (95% CI -6.45 to 8.98, = 0.74). The adjusted treatment difference in low-contrast letter acuity was 2.87 on the 2.5% Sloan chart score (95% CI -7.92 to 13.65). Vision-related quality of life was similar in both treatment arms (National Eye Institute Visual Functioning Questionnaire median score [IQR]: 94.0 [88.0 to 96.9] in the EPO and 93.4 [89.5 to 97.4] in the placebo group). The rate of multiple sclerosis-free survival was 38% in the placebo and 53% in the EPO group (hazard ratio: 1.67, 95% CI 0.96 to 2.88, = 0.068).
DISCUSSION
In line with the results at 6 months, we found neither structural nor functional benefits in the visual system of patients with optic neuritis as a clinically isolated syndrome, 2 years after EPO administration. Although there were fewer early conversions to MS in the EPO group, the difference across the 2-year window was not statistically significant.
CLASSIFICATION OF EVIDENCE
This study provides Class II evidence that for patients with acute optic neuritis, EPO as an adjunct to methylprednisolone is well tolerated and does not improve long-term visual outcomes.
TRIAL REGISTRATION INFORMATION
The trial was preregistered before commencement at clinicaltrials.gov (NCT01962571).
Topics: Humans; Follow-Up Studies; Quality of Life; Visual Acuity; Erythropoietin; Methylprednisolone; Optic Neuritis; Multiple Sclerosis
PubMed: 37094997
DOI: 10.1212/NXI.0000000000200067 -
Clinical Nephrology. Case Studies 2023We present two atypical cases of calciphylaxis presenting with ocular ischemic pathology - both without the hallmark cutaneous manifestations - to raise awareness of...
PURPOSE
We present two atypical cases of calciphylaxis presenting with ocular ischemic pathology - both without the hallmark cutaneous manifestations - to raise awareness of this rare yet highly disabling condition.
OBSERVATIONS
We report two cases of ophthalmic calciphylaxis presenting as (1) anterior ischemic optic neuropathy (AION) and cilioretinal artery occlusion in a 76-year-old woman with pre-dialysis kidney failure, and (2) AION with contralateral central retinal artery occlusion (CRAO) in a 44-year-old man on hemodialysis.
CONCLUSION AND IMPORTANCE
These cases highlight the need for judicious clinical suspicion of calciphylaxis in patients with kidney failure, presenting with microvascular ischemic ophthalmic pathology such as AION or CRAO. Confirmation with temporal artery biopsy is essential to direct targeted individualized multi-disciplinary treatment of calciphylaxis and avoid unnecessary steroid exposure in cases masquerading as giant cell arteritis (GCA).
PubMed: 38169875
DOI: 10.5414/CNCS111088