Steroid Withdrawal
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Steven Toh ◽  
Chean Chung Shen

Chronic relapsing inflammatory optic neuropathy (CRION) is a recently described form of recurrent isolated subacute optic neuropathy, with accumulating evidence that it is a nosological distinct entity. The condition is highly responsive to systemic steroid treatment and prone to relapse on steroid withdrawal. Diagnosis and management of this condition is often challenging. This 33-year-old lady with family history of multiple sclerosis (MS), with uniocular visual loss of her right eye since 2 years old without apparent cause, presented with reduction of vision and loss of colour vision in the left eye, associated with painful eye movement. There was internuclear ophthalmoplegia but slit lamp examination were unremarkable. She had no other related sensory or motor symptoms. Magnetic resonance imaging (MRI) did not reveal any features of MS. Aquaporin-4 antibody, anti-MOG and gene testing for Leber’s hereditary optic neuropathy were all negative. Metabolic, infective, and other autoimmune causes were also excluded. Visual evoked potential studies of left eye showed a mild reduction in amplitude with no prolongation of latency. Her multiple optic neuritis recurrences were treated with intravenous steroids followed by tapering regime of oral prednisolone with good effect. Knowledge of this rare condition as part of the differential diagnoses of possible aetiologies of optic neuropathy is important among Ophthalmologists, as prompt diagnosis and steroid treatment helped reduce the associated risk of blindness. Multiple relapses after initial successful treatment of inflammatory optic neuropathy should raise the suspicion of CRION.International Journal of Human and Health Sciences Supplementary Issue-2: 2021 Page: S19

2021 ◽  
Vol 53 (7) ◽  
pp. 2216-2226
Valentine Gierczak ◽  
Johan Noble ◽  
Paolo Malvezzi ◽  
Bénédicte Janbon ◽  
Florian Terrec ◽  

2021 ◽  
Macarena Gajardo ◽  
Angela Delucchi ◽  
Diego Pérez ◽  
José M. Cancino ◽  
Carla Gálvez ◽  

2021 ◽  
Vol 17 (1) ◽  
Serife Uzun ◽  
Zixi Wang ◽  
Tory A. McKnight ◽  
Paul Ehrlich ◽  
Erin Thanik ◽  

Abstract Rationale We recently showed that multicomponent traditional Chinese medicine (TCM) therapy had steroid-sparing effects in moderate-to-severe eczema. We sought to evaluate TCM effects in severe eczema in a 7-year-old male with refractory disease and corticosteroid withdrawal syndrome. Methods Prior to referral, the patient had been treated since infancy with increasingly intensive standard of care, including high-dose topical and systemic corticosteroid and antibiotic therapy and was unable to tolerate further steroid treatment. The patient was administered a combination of oral and topical TCM for 17 months following discontinuation of his steroid regimen. His overall medical condition was assessed by SCORAD criteria and laboratory evaluations of serum IgE, absolute eosinophil count, and liver and kidney function tests. Results The patient showed rapid improvement of clinical measures of disease after starting TCM therapy, with marked improvement of sleep quality within the first week, complete resolution of itching, oozing, and erythema at 2 weeks, and a 79% and 99% decrease in his SCORAD values after one month and 3–6 months of TCM, respectively. Serum total IgE decreased by 75% (from 19,000 to 4630 (kIU/L), and absolute eosinophil counts decreased by 60% (from 1000 to 427 cells/μL) after 12 months of treatment. The patient did not require oral or topical steroids during the 17-month trial of TCM. TCM was tapered without complications. His dermatologic manifestations continued to be well-controlled 3 months after discontinuation. Conclusion This case study suggests TCM should be further evaluated in controlled clinical studies of patients with severe, refractory eczema and steroid withdrawal syndrome.

Dixon Kaufman ◽  
E. Steve Woodle ◽  
Adele Shields ◽  
John Leone ◽  
Arthur Matas ◽  

Immunosuppressive therapy in kidney transplantation is associated with numerous toxicities. CD28-mediated T cell costimulation blockade using belatacept may reduce long-term nephrotoxicity, compared with calcineurin inhibitor-based immunosuppression. The efficacy and safety of simultaneous calcineurin inhibitor avoidance and rapid steroid withdrawal were tested in a randomized, prospective, multi-center study. MethodsAll kidney transplants were performed using rapid steroid withdrawal immunosuppression. Recipients were randomized to 1:1:1 to receive belatacept with alemtuzumab induction, belatacept with rabbit antithymocyte globulin (rATG) induction, or tacrolimus with rATG induction. The composite endpoint consisted of death, kidney allograft loss, or an MDRD calculated eGFR of <45 ml/min/1.73m2 at 2 years. ResultsThe composite endpoint was observed for 11/107 (10%) participants assigned to belatacept/alemtuzumab, 13/104 (13%) assigned to belatacept /rATG, and 21/105 (21%) assigned to tacrolimus/rATG (belatacept/alemtuzumab vs tacrolimus/rATG p = 0.99: belatacept/rATG vs tacrolimus/rATG p = 0.66). Patient and graft survival rates were similar between all groups. eGFR <45 ml/min/1.73m2 was observed for 9/107 (8%) participants assigned to belatacept/alemtuzuab, 8/104 (8%) participants assigned to belatacept/rATG, and 20/105 (19%) participants assigned to tacrolimus/rATG (p<0.05 for each belatacept group vs tacrolimus/rATG). Biopsy-proven acute rejection was observed for 20/107 (19%) participants assigned to belatacept/alemtuzuab, 26/104 (25%) participants assigned to belatacept/rATG, and 7/105 (7%) participants assigned to tacrolimus/rATG (belatacept/alemtuzumab vs tacrolimus/rATG p = 0.006: belatacept/rATG vs tacrolimus/rATG p < 0.001). Gastrointestinal and neurologic adverse events were less frequent with belatacept versus calcineurin based immunosuppression. ConclusionsOverall two-year outcomes were similar comparing maintenance immunosuppression based on belatacept versus tacrolimus, each protocol with rapid steroid withdrawal. The incidence of eGFR <45 ml/min/1.73m2 was significantly lower but the incidence of biopsy proven acute rejection significantly higher with belatacept compared with tacrolimus.

2021 ◽  
Vol 7 (7) ◽  
pp. e706
Itunu Owoyemi ◽  
Srijan Tandukar ◽  
Dana R. Jorgensen ◽  
Christine M. Wu ◽  
Puneet Sood ◽  

2021 ◽  
Vol 12 ◽  
Paola Krall ◽  
Dominique Yañez ◽  
Angélica Rojo ◽  
Ángela Delucchi ◽  
Miguel Córdova ◽  

Background: Tacrolimus (TAC) and mycophenolic acid (MPA) are the main immunosuppressive drugs used in pediatric kidney transplantation. Single nucleotide polymorphisms (SNPs) in metabolizing enzymes and transporters might influence plasma levels of these drugs. Herein, we sought to determine the influence of SNPs on CYP3A5, MRP2 and UGT1A9 genes in Chilean pediatric kidney recipients using TAC and MPA.Patients and Methods: A prospective study was performed on 104 pediatric kidney recipients that used TAC and MPA for immunosuppression. The median age at the time of transplantation was 8.1 years [Q1–Q3 4.5–11.6 years] and the main clinical diagnosis was a structural anomaly. In a subgroup of patients, a complete steroid withdrawal was made at day 7. The CYP3A5 polymorphism (ancestral allele *1; variant allele *3) was determined in the entire cohort, while MRP2 -24G &gt; A, UGT1A9 -275T &gt; A, and UGT1A9 -2152C &gt; T polymorphisms were determined in 53 patients. Genotypes were associated with trough drug concentrations (C0), dose requirements normalized by weight (TAC-D mg/kg) or body surface (MPA-D mg/m2), trough levels normalized by dose requirements (C0/D), and area under the curve in 12 h normalized by dose requirements (AUC0–12h/D).Results: The frequencies of the variant alleles CYP3A5*3, MRP2-24A, UGT1A9-275A, and UGT1A9-2152T were 76.9, 22.1, 6.6, and 2.9%, respectively. AUC0–12h/TAC-D were 1.6-fold higher in CYP3A5*3/*3 patients than in CYP3A5*1 carriers (CYP3A5*1/*3 and CYP3A5*1/*1). When analyzing patients with steroid withdrawal, CYP3A5*3/*3 patients had 1.7-fold higher AUC0–12h/TAC-D than the other genotypes. Patients carrying the CYP3A5*3/*3 genotype had higher TAC-C0, lower TAC-D and higher TAC-C0/D, consistently in a 6-months follow-up. Creatinine clearance was stable during the follow-up, regardless of the genotype. No significant differences between MRP2 and UGT1A9 genotypes were observed in MPA-C0, MPA-D or MPA-C0/D. However, patients carrying the UGT1A9-275A allele had lower AUC0–12h/MPA-D than those carrying the UGT1A9-275T ancestral allele.Conclusions: These results support that CYP3A5 and UGT1A9 genotyping in pediatric recipients might be useful and advisable to guide TAC and MPA dosing and monitoring in children that undergo kidney transplantation.

2021 ◽  
Vol 10 (8) ◽  
pp. 1670
Masaaki Okihara ◽  
Hironori Takeuchi ◽  
Yukiko Kikuchi ◽  
Isao Akashi ◽  
Yu Kihara ◽  

Recently, steroid reduction/withdrawal regimens have been attempted to minimize the side effects of steroids in renal transplantation. However, some recipients have experienced an increase/resumption of steroid administrations and acute graft rejection (AR). Therefore, we investigated the relationship between the individual lymphocyte sensitivity to steroids and the clinical outcome after steroid reduction/withdrawal. We cultured peripheral blood mononuclear cells (PBMCs) isolated from 24 recipients with concanavalin A (Con A) in the presence of methylprednisolone (MPSL) or cortisol (COR) for four days, and the 50% of PBMC proliferation (IC50) values and the PBMC sensitivity to steroids were calculated. Regarding the experience of steroid increase/resumption and incidence of AR within one year of steroid reduction/withdrawal, the IC50 values of these drugs before transplantation in the clinical event group were significantly higher than those in the event-free group. The cumulative incidence of steroid increase/resumption and AR in the PBMC high-sensitivity groups to these drugs before transplantation were significantly lower than those in the low-sensitivity groups. These observations suggested that an individual’s lymphocyte sensitivity to steroids could be a reliable biomarker to predict the clinical outcome after steroid reduction/withdrawal and to select the patients whose dose of steroids can be decreased and/or withdrawn after transplantation.

2021 ◽  
Vol Publish Ahead of Print ◽  
Sunjae Bae ◽  
Mara A. McAdams-DeMarco ◽  
Allan B. Massie ◽  
Jacqueline M. Garonzik-Wang ◽  
Josef Coresh ◽  

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