High-dose Prednisolone Therapy Research Articles

DRESS as a rare differential diagnosis in eosinophilia, skin rash and acute hepatitis

A 21-year-old female patient presented with fever, pharyngitis, lymphadenopathy and generalized exanthema that had started 2 weeks prior. Allergies were not known, the family and travel history were negative. Due to depression, Duloxetine had been taken for 1.5 years, and due to bipolar disorder, a treatment with Lamotrigine was started four weeks prior but was stopped because of increased transaminase levels. Laboratory findings on admission showed eosinophilia (1.327 /nl), lymphocytosis and acute hepatitis (GOT 428 U/l, GPT 438 U/l) with deranged coagulation. Inflammatory parameters were increased. Ultrasound revealed hepatosplenomegaly with ascites. Acute viral or parasitic infection was excluded serologically. A skin biopsy showed a perivascular inflammatory infiltrate, compatible with a drug reaction. An inflammatory infiltrate was found in the liver biopsy, consistent with drug-induced hepatitis. Cough, dyspnea and pleural effusion occurred. In summary of the findings and with the help of the RegiSCAR-Score, the diagnosis of drug reaction with eosinophilia and systemic symptoms (DRESS) could be made. Under high-dose prednisolone therapy, a gradual decrease of transaminases and reconstitution of liver synthesis could be observed.In patients with eosinophilia, lymphadenopathy, acute hepatitis and generalized exanthema, DRESS is a rare but-due to its potentially life-threatening consequences-important differential diagnosis. The most important measure is to stop the suspected inducing medication immediately. Severe cases should be treated with high-dose systemic corticosteroids.

Severe and Prolonged Liver Damage in Pityriasis Rubra Pilaris Treated with acitretin: a Case Report

Acitretin is a systemic retinoid that is used in dermatology for treatment of various inflammatory and especially hyperkeratotic diseases. Elevation of liver enzymes may occur occasionally but normally resolves spontaneously, at the latest after termination of acitretin. However, it can very rarely develop into a life-threatening adverse event including drug-induced liver injury (DILI). A 45-year-old man with classical pityriasis rubra pilaris, a frequently severe, inflammatory skin disease, was started on acitretin. After a seemingly harmless elevation of transaminases, a few weeks after initiation of acitretin, the patient experienced a dramatic course of liver injury with hepatic jaundice though acitretin was stopped immediately. Eventually, laboratory values recovered upon high-dose oral prednisolone therapy. Prescribing physicians should keep in mind that acitretin might induce severe liver injury. Even after termination of acitretin laboratory values should be monitored for a while in order to recognize symptomless but harmful drug-induced liver injury in time.

Hyperkinesia after High-Dose Prednisolone Therapy in a Patient with West Syndrome

Hyperkinesia after High-Dose Prednisolone Therapy in a Patient with West Syndrome

EP11 A case of COVID-19 induced myocarditis in a healthcare-worker

EP11 A case of COVID-19 induced myocarditis in a healthcare-worker

Prednisolone-induced diabetes mellitus in the cat: a historical cohort.

Prednisolone is a commonly used drug in cats and potential adverse effects include hyperglycaemia and diabetes mellitus. The aims of this study were to evaluate the frequency and investigate potential predisposing risk factors for the development of prednisolone-induced diabetes mellitus (PIDM) in cats. The electronic records of a tertiary referral centre were searched for cats receiving prednisolone at a starting dose of ⩾1.9 mg/kg/day, for >3 weeks and with follow-up data available for >3 months between January 2007 and July 2019. One hundred and forty-three cats were included in the study. Of the 143 cats, 14 cats (9.7%) were diagnosed with PIDM. Twelve out of 14 cats (85.7%) developed diabetes within 3 months of the initiation of therapy. Cats requiring high-dose prednisolone therapy should be closely monitored over the first 3 months of therapy for the development of PIDM.

Glucocorticoid induces human beta cell dysfunction by involving riborepressor GAS5 LincRNA

ObjectiveA widely recognized metabolic side effect of glucocorticoid (GC) therapy is steroid-induced diabetes mellitus (DM). However, studies on the molecular basis of GC-induced pancreatic beta cell dysfunction in human beta cells are lacking. The significance of non-coding RNAs in various cellular processes is emerging. In this study, we aimed to show the direct negative impact of GC on beta cell function and elucidate the role of riborepressor GAS5 lincRNA in the GC signaling pathway in human pancreatic beta cells. MethodsPatients undergoing two weeks of high-dose prednisolone therapy were monitored for C-peptide levels. Human pancreatic islets and the human beta cell line EndoC-βH1 were incubated in pharmacological concentrations of dexamethasone. The GAS5 level was modulated using anti-sense LNA gapmeR or short oligonucleotides with GAS5 HREM (hormone response element motif). Immunoblotting and/or real-time PCR were used to assess changes in protein and RNA expression, respectively. Functional characterization included glucose-stimulated insulin secretion and apoptosis assays. Correlation analysis was performed on RNAseq data of human pancreatic islets. ResultsWe found reduced C-peptide levels in patients undergoing high-dose GC therapy. Human islets and the human beta cell line EndoC-βH1 exposed to GC exhibited reduced insulin secretion and increased apoptosis. Concomitantly, reduced expression of important beta cell transcription factors, PDX1 and NKX6-1, as well as exocytotic protein SYT13 were observed. The expression of the glucocorticoid receptor was decreased, while that of serum and glucocorticoid-regulated kinase 1 (SGK1) was elevated. The expression of these genes was found to significantly correlate with GAS5 in human islet transcriptomics data. Increasing GAS5 levels using GAS5 HREM alleviated the inhibitory effects of dexamethasone on insulin secretion. ConclusionsThe direct adverse effect of glucocorticoid in human beta cell function is mediated via important beta cell proteins and components of the GC signaling pathway in an intricate interplay with GAS5 lincRNA, a potentially novel therapeutic target to counter GC-mediated beta cell dysfunction.

Acute tubulointerstitial nephritis and IgM deposits on glomerular capillary walls after immunotherapy with nivolumab for metastatic renal cell carcinoma

Nivolumab is an anti-programmed cell death-1 antibody that is utilized as an immune checkpoint inhibitor for several malignancies. However, this agent is associated with immune-related adverse events (irAEs), mainly in the spectrum of autoimmune disease including interstitial pneumonia, colitis, type 1 diabetes, and renal impairment. We herein present the case of a 59-year-old man with renal cell carcinoma who developed worsening renal function approximately 4 months after initiation of nivolumab. Urinalysis showed proteinuria and microscopic hematuria along with increase levels of N-acetyl-β-d-glucosaminidase. Renal biopsy revealed acute tubulointerstitial nephritis and thickening of the glomerular basement membranes. Immunofluorescence showed granular IgM deposits in capillary loops. We initiated high-dose prednisolone therapy with nivolumab, which improved renal function and achieved complete remission of proteinuria. Although renal irAEs are considered to be rare and glomerulonephropathy is not typical presentation, physicians need the close monitoring of renal function and urinalysis in patients under immunotherapy with this agents. In addition, our case provides a possible link between nivolumab and immune-mediated glomerulonephropathy.

Successful Tocilizumab Therapy for Macrophage Activation Syndrome Associated with Adult-Onset Still's Disease: A Case-Based Review.

We report the case of a 71-year-old Japanese woman with adult-onset Still's disease (AOSD) in whom macrophage activation syndrome (MAS) developed despite therapy with oral high-dose prednisolone and intravenous methylprednisolone pulse therapy twice. She was successfully treated with tocilizumab (TCZ). Soon afterward, her fever ceased and high levels of both ferritin and C-reactive protein levels decreased. Her course was complicated by disseminated intravascular coagulation, cytomegalovirus infection, and Pneumocystis jirovecii pneumonia. After these were resolved, AOSD-associated MAS was well controlled. She was discharged on hospital day 87. Although biologics such as TCZ are becoming established for the treatment of AOSD, there is no recommended therapy for AOSD-associated MAS. Several biologics have been tried for this complication, but their efficacy and safety remain controversial. We reviewed reported cases of AOSD-associated MAS successfully treated with various biologics. TCZ initiation after adequate nonselective immunosuppressive therapy, such as methylprednisolone pulse therapy or a prednisolone-based combination of immunosuppressants, can be an effective treatment for AOSD-associated MAS. On the other hand, biologics given after insufficient immunosuppressive therapy may cause MAS. A strategy combining adequate immunosuppression and a biologic could be safe if special attention is given to adverse events such as opportunistic infections or biologic-associated MAS.

Unsuspected Cardiovascular Involvement in Relapsing Polychondritis

A 51-year-old man presented with a prodrome of arthralgia, intermittent oral ulceration, and raised inflammatory markers. He was extensively investigated; however, no firm diagnosis could be established, and he remained under regular surveillance by rheumatology and infectious disease services. After 12 months, he presented with painful ear swelling. Clinical examination revealed a swollen tender ear (Figure 1) and a soft diastolic heart murmur. Serum inflammatory markers were raised, with a c-reactive protein (CRP) of 28 mg/L and an erythrocyte sedimentation rate (ESR) of 25 mm/h. Figure 1. Tender, erythematous left ear. Biopsy of affected cartilage showed characteristic features of auricular chondritis (Figure 2). Echocardiogram (Movie I in the Data Supplement) revealed mild aortic incompetence, a left ventricular ejection fraction of 60%, aortic root dilatation, and an incidental patent foramen ovale (Movie II in the Data Supplement). Computed tomography (CT) of the thorax demonstrated no tracheal abnormality; however, aortic root dilatation of 4.6 cm was noted (Figure 3). A fasting positron emission tomography-CT (PET-CT) showed increased F-18 fluorodeoxyglucose accumulation in the ascending aorta (Figure 4), and a diagnosis of relapsing polychondritis with secondary aortitis with structural aortic dilatation was made. Figure 2. Left ear biopsy identified cartilage with perichondrial inflammatory granulation tissue. Figure 3. Coronal computed tomography of thorax with contrast demonstrating aortic root dilatation of 4.6 cm at the level of the sinuses with mural …

Efficacy of perioperative high-dose prednisolone therapy during thymectomy in myasthenia gravis patients

BackgroundThis study aimed to investigate the benefits of administering perioperative high-dose prednisolone in conjunction with thymectomy in patients with myasthenia gravis.MethodsWe retrospectively reviewed data from patients with Myasthenia Gravis Foundation of America Clinical Class I to IIIB who had undergone an extended thymectomy between 1992 and 2009. Perioperative high-dose prednisolone was administered at starting doses of 10 to 20 mg and escalated up to 100 mg on alternate days. The treatment group comprised 70 patients receiving perioperative high-dose prednisolone, whereas the control group included 61 patients not treated with preoperative steroids. The two groups were compared with respect to baseline clinical characteristics, incidence of postoperative complications, and follow-up disease status.ResultsPrednisolone-treated patients presented with more advanced disease compared to controls (Class IIB or greater, 42 [60.0%] versus 7 [11.3%], respectively; P < 0.001). Mean preoperative%FVC was lower and FEV1.0% was higher in treated patients than in controls (%FVC: 92.4 ± 2.3% versus 99.5 ± 2.4%, respectively; P = 0.037, FEV1.0%: 85.2 ± 1.3% versus 81.4 ± 0.9%, respectively; P = 0.017). The groups were similar in other variables including presence of thymoma, and operative procedure. In the treatment group, disease status was significantly improved only by the induction of high-dose prednisolone before the surgery (P < 0.001), and these patients discontinued anti-cholinesterase therapy more frequently than controls (P < 0.001). Moreover, the treatment group demonstrated markedly lower rates of postoperative crisis (12.2% versus 2.9%, respectively; P = 0.045). The incidence of infection, wound dehiscence, and diabetes mellitus were comparable between groups. Survival analysis demonstrated higher rates of treated patients with improved disease status at three and five years (92% and 96%, respectively) compared to controls (57% and 76%, respectively; P < 0.001). Likewise, significantly greater proportions of treated patients achieved complete stable remission or pharmacologic remission at three, five, and ten years (23%, 42%, and 72%, respectively) compared to controls (10%, 20%, and 44%, respectively; P = 0.002).ConclusionsPerioperative high-dose prednisolone therapy is a safe, promising strategy for managing patients with myasthenia gravis and may reduce the incidence of postoperative crisis while improving disease status.

Effects of Short-Course Oral Corticosteroid Therapy in Early Dengue Infection in Vietnamese Patients: A Randomized, Placebo-Controlled Trial

Patients with dengue can experience a variety of serious complications including hypovolemic shock, thrombocytopenia, and bleeding. These problems occur as plasma viremia is resolving and are thought to be immunologically mediated. Early corticosteroid therapy may prevent the development of such complications but could also prolong viral clearance. We performed a randomized, placebo-controlled, blinded trial of low-dose (0.5 mg/kg) or high-dose (2 mg/kg) oral prednisolone therapy for 3 days in Vietnamese patients aged 5-20 years admitted with dengue and fever for ≤72 hours, aiming to assess potential harms from steroid use during the viremic phase. Intention-to-treat analysis was performed using linear trend tests with a range of clinical and virological endpoints specified in advance. In addition to recognized complications of dengue, we focused on the are under the curve for serial plasma viremia measurements and the number of days after enrollment to negative viremia and dengue nonstructural protein 1 status. Between August 2009 and January 2011, 225 participants were randomized to 1 of the 3 treatment arms. Baseline characteristics were similar across the groups. All patients recovered fully and adverse events were infrequent. Aside from a trend toward hyperglycemia in the steroid recipients, we found no association between treatment allocation and any of the predefined clinical, hematological, or virological endpoints. Use of oral prednisolone during the early acute phase of dengue infection was not associated with prolongation of viremia or other adverse effects. Although not powered to assess efficacy, we found no reduction in the development of shock or other recognized complications of dengue virus infection in this study.

Early Aggressive Treatment Strategy against Myasthenia Gravis

Background/Aims: In treating myasthenia gravis (MG), our aims were to achieve early minimal manifestations (MM) by performing early aggressive therapy (EAT) using plasmapheresis and high-dose intravenous methylprednisolone, and then to maintain the status with low-dose oral corticosteroids (EAT strategy). We examined the merits of the EAT strategy. Methods: We retrospectively analyzed long-term effects of the EAT strategy (duration of therapy: 4.1 years) for 49 de novo MG patients and compared the effects to those of high-dose oral prednisolone therapy for 22 patients. Results: The EAT group achieved marked early improve- ment with much lower doses of oral prednisolone compared to the high-dose prednisolone group. The patients who achieved MM with prednisolone ≤5 mg/day were more frequent in the EAT group at both 1 year (57.1 vs. 4.5%) and final observation (77.6 vs. 27.3%). Both new-onset diabetes and patients who had complained of moon face were less frequent in the EAT group. However, in the EAT group, due to a temporary inability to maintain MM, additional short-term hospitalizations to return to MM by EAT were required. Conclusions: The EAT strategy has advantages of early improvement with less frequent steroid-related complications. The labor and cost required are evident disadvantages.

Benefit and a possible risk of tocilizumab therapy for adult-onset Still’s disease accompanied by macrophage-activation syndrome

We report a 57-year-old female case of intractable adult-onset Still's disease (AOSD). Initial high-dose prednisolone therapy was ineffective, and macrophage-activation syndrome (MAS) manifested after one session of additional tocilizumab therapy. After successful treatment for MAS with lipo-dexamethasone and cyclosporin, tocilizumab therapy aided in the rapid reduction of the therapeutic steroid dose. Tocilizumab may be useful for maintenance therapy for AOSD, although its efficacy is unclear for the highly active phase of the disease.

Non-myeloablative Cord blood stem cell treatment for hormone resistent ulcerative colitis

Objective To study the therapeutic effects of non-myeloablative cord blood stem cell for hormone resistent ulcerative colitis （UC）and endoscopic changes. Methods Eleven UC patients（6 males, 5 females） , aged 18 to 61 years old, and unresponsive to high-dose prednisolone therapy more than 3-28 years, were included. Four cases were left-sided colitis, 7 were pancolitis. Ten were severe cases and 1 was moderate, others were active. Stem cells of CD34~ , CDll7＋ , CD133＋ , C-kit＋ and Sca-1 ＋ were extracted from a total of 60-120 ml cord blood with the isolation kit. The total account was more than 1.0 ~ l0s , and the cell activity was more than 96%. The stems ceils were prepared with normal saline （ 10 ml） to suspen- sion, which was injected into inferior mensenteric artery via femoral catheterization. Those who received pre- treatment corticosteroid resumed their previous therapy . Hormone administration gradually decreased and then ceased at the relief of symptoms. Results After 12 weeks of treatment with stem cell, the total clinical effects were completely remission in 7 cases, improvement in 3 patients, and inefficiency in one case. The clinical symptomatic remissions were complete remission in 7 cases, partial in 3, and inefficiency in 1. The colonoscopic remissions included complete remission in 6 cases, partial in 4, and inefficiency in 1. And the histologic remissions included complete remission in 6 cases, partial in 4, and inefficiency in 1. Bowel movements decreased from 11.5 times to 1.6 per day, erythrocyte sendimentation rate decreased from 44. 5 mm/h to 11.5 mm/h and C reaction protein decreased from 22. 3 mg/L to 6. 1 mg/L. The Sourtherland dis- ease active index （DAI） decreased from 11.1 to 2. 32. Hormone administration ceased in 10 cases and de- creased in 1. There were no complications. The patients were followed up for 12 months, and complete remis- sion in 5 patients, improvement in 3 others and relapse in 2 were observed. Conclusion Non-myeloablative Cord blood stem cell treatment for hormone resistent ulcerative colitis , safe and effective, is of help to relieve symptoms, heal lesions, improve histology, decrease DAI. Therefore, corticosteroid can be withdrawn. Key words: Colitis, ulcerative; Cord blood stem cell

Sauropus androgynus-associated bronchiolitis obliterans of mother and daughter – autopsy report

Sauropus androgynus (SA) is a vegetable that causes constrictive bronchiolitis obliterans (BO) with consequent findings classified into injury, inflammation and fibrosis, according to clinical factors including amount of SA exposure, period of SA exposure, and individual predisposition. We reported mother and daughter SABO autopsy cases with similar clinical course, including 11 month SA exposure and Aspergillosis infection after high dose prednisolone therapy. Their major differences were in the amount of SA exposure (mother: 1440 g, daughter: 2190 g) and the survival period post exposure (mother: 21 months, daughter: 32 months). The histopathological comparison between them showed a statistical difference in the density of foamy macrophage accumulation of moderately obstructed airways, but not in the extent of fibrosis, elastic lamina destruction, or smooth muscle hyperplasia. Foamy macrophages tend to accumulate relatively early in the course of SABO at the site with severe damage, accelerating BO formation for as long as the patient survives.

Tocilizumab dramatically ameliorated life-threatening diarrhea due to secondary amyloidosis associated with rheumatoid arthritis

Severe diarrhea improved dramatically with administration of the humanized anti-interleukin-6 receptor antibody tocilizumab (TCZ) in a patient with secondary reactive amyloidosis, which was associated with rheumatoid arthritis (RA). A 53-year-old woman with RA went into hypovolemic shock because of severe watery diarrhea associated with gastrointestinal amyloidosis. The high-dose prednisolone therapy and glucocorticoid pulse therapy did not improve her intractable diarrhea. After TCZ administration, the life-threatening diarrhea lessened in about 6 h, and her vital signs became stable the next day. Perforation of the small intestine, however, occurred 2 days after TCZ administration. Whether TCZ could have been involved in the perforation in such a short time is unknown. Surgery was successful, and the patient recovered. TCZ may work immediately in diarrhea associated with secondary amyloidosis.

Early aggressive intra-venous pulse cyclophosphamide therapy for interstitial lung disease in a patient with systemic sclerosis. A case report

Interstitial lung disease is an important cause of mortality and morbidity in patients with systemic sclerosis (SSc). There are currently no recommended guidelines for management of these patients. This is probably due to the rarity of this condition, as well as clinical trials with only a small number of cases. There are published case report and case series along with the two main trials, viz. Scleroderma Lung Study and the Fibrosing Alveolitis Study, but again, there is no consensus on treatment protocols. In this report, we present a case of aggressive interstitial lung disease in a patient with SSc, which improved dramatically on treatment with intra-venous cyclophosphamide and high dose prednisolone therapy.

Recovery of the hypothalamic-pituitary-adrenal axis from suppression by short-term, high-dose intravenous prednisolone therapy in patients with MS.

We have studied the recovery of the hypothalamic-pituitary-adrenal (HPA) axis from inhibition by short-term, intravenous high-dose, corticosteroid therapy (IVHDCT) without subsequent oral replacement therapy in 10 patients with relapsing-remitting or progressive multiple sclerosis (MS) using the human corticotrophin-releasing hormone (hCRH) test. There was significant HPA suppression with profoundly decreased basal and peak plasma ACTH and cortisol levels 24 h after cessation of therapy. However, at 48 h the pituitary response was greatly enhanced with peak ACTH concentrations rising by more than 100% over baseline values in 7 of 10 patients. Basal and stimulated ACTH concentrations returned to pre-treatment levels at 120 h. Basal and stimulated plasma cortisol levels remained subnormal in 6 patients 120 h after IVHDCT. We conclude that IVHDCT without oral replacement therapy in MS patients is endocrinologically safe.

Experience of Epidural Steroids in Transverse Myelitis -A case report-

Transverse myelitis is a focal inflammatory disorder of the spinal cord characterized by motor, sensory, and autonomic dysfunction. A 41-year-old man with transverse myelitis and no pre-existing neurologic disease presented with hypesthesia, numbness, weakness in the both lower extremities, back pain, decreased libido, constipation, and dysuria. A MRI test showed intramedullary high signal intensity between T4 and T8 on a T2-weighted image. After high-dose intravenous methylprednisolone and oral prednisolone therapy, he showed facial swelling and acneiform eruption. Therefore, we injected 40 mg methylprednisolone via an epidural route. A 7-dose serial treatment improved most symptoms. A follow up MRI showed radiological improvement. We report a case of transverse myelitis treated by epidural steroids.

Steroid-refractory severe hepatic failure in adult onset Still’s disease responding to cyclosporine

We report two Japanese women with severe hepatic dysfunction and adult onset Still's disease. A 51-year-old woman had been diagnosed with adult onset Still's disease 3 years earlier. She relapsed while on maintenance therapy with prednisolone and methotrexate. After induction of remission with methylprednisolone pulse therapy, indomethacin, and methotrexate, severe hepatic failure occurred. This patient lacked the typical symptoms of adult onset Still's disease. The second patient was a 32-year-old woman with typical adult onset Still's disease. Remission was induced by high-dose prednisolone and methylprednisolone pulse therapy plus cyclosporine. After she stopped cyclosporine, severe liver dysfunction occurred. In both patients, liver dysfunction occurred during high-dose steroid therapy, and oral cyclosporine (3 mg/kg per day) dramatically improved their liver function. When steroid-resistant severe hepatic failure occurs in patients with adult onset Still's disease, cyclosporine may be the immunosuppressant of choice.