Methylprednisolone-Induced Hypersensitivity Reaction in a Liver Transplant Recipient.

Corticosteroids have an essential role as an immunosuppressive agent in transplant; because of their anti-inflammatory properties, they rarely cause an allergic reaction. Here, we report a liver transplant recipient who developed an allergic reaction to intravenous methylprednisolone sodium succinate. The deceased-donor orthotopic liver transplant recipient received intravenous methylprednisolone sodium succinate for induction during transplant, which was followed by another intravenous dose and oral prednisone taper. She was later treated with intravenous methylprednisolone sodium succinate taper for acute cellular rejection, which had been confirmed with a second biopsy. After admission for further treatment, she received another 1 g of intravenous methylprednisolone sodium succinate dose. About 15 to 20 minutes after receiving this dose, she presented with a new-onset urticarial rash that started on the trunk and progressed with facial edema. She continued a course of intravenous and oral dexamethasone for treatment of rejection and later was restarted on and tolerated oral prednisone. This case highlights the importance and the possibility of using dexamethasone as an alternative treatment approach for those with similar reactions to intravenous methylprednisolone sodium succinate.

Antioxidant and anti-inflammatory effects of intravenously injected adipose derived mesenchymal stem cells in dogs with acute spinal cord injury.

INTRODUCTION: Mesenchymal stem cells can potentially be used in therapy for spinal cord injury (SCI). Methylprednisolone sodium succinate (MPSS) has been used as a scavenging agent in acute SCI treatment, but its use no longer recommended. This study aimed to identify ways to reduce the usage and risk of high doses of glucocorticoid steroids, and determine whether AD-MSCs could be used as an early alternative treatment modality for acute SCI. METHODS: Sixteen adult beagle dogs with SCI were assigned to four treatment groups: control, MPSS, AD-MSCs, and AD-MSCs + MPSS. Additionally, one dog was used to evaluate the distribution of AD-MSCs in the body after injection. AD-MSCs (1 × 10(7) cells) were injected intravenously once a day for 3 days beginning at 6 hours post-SCI. MPSS was also injected intravenously according to the standard protocol for acute SCI. A revised Tarlov scale was used to evaluate hindlimb functional recovery. The levels of markers for oxidative metabolism (3-nitrotyrosine, 4-hydroxynonenal, and protein carbonyl) and inflammation (cyclooxygenase-2, interleukin-6, and tumor necrosis factor-α) were also measured. RESULTS: At 7 days post-treatment, hindlimb movement had improved in the AD-MSCs and AD-MSCs + MPSS groups; however, subjects in the groups treated with MPSS exhibited gastrointestinal hemorrhages. Hematoxylin and eosin staining revealed fewer hemorrhages and lesser microglial infiltration in the AD-MSCs group. The green fluorescent protein-expressing AD-MSCs were clearly detected in the lung, spleen, and injured spinal cord; however, these cells were not detected in the liver and un-injured spinal cord. Levels of 3-nitrotyrosine were decreased in the MPSS and AD-MSCs + MPSS groups; 4-hydroxynenonal and cyclooxygenase-2 levels were decreased in all treatment groups; and interleukin-6, tumor necrosis factor-α, and phosphorylated-signal transducer and activator transcription 3 levels were decreased in the AD-MSCs and AD-MSCs + MPSS groups. CONCLUSION: Our results suggest that early intravenous injection of AD-MSCs after acute SCI may prevent further damage through enhancement of antioxidative and anti-inflammatory mechanisms, without inducing adverse effects. Additionally, this treatment could also be used as an alternative intravenous treatment modality for acute SCI.

[To treat or not to treat asymptomatic bacteriuria before methylprednisolone perfusion]. / Traiter ou ne pas traiter les bactériuries asymptomatiques avant bolus de méthylprednisolone?

The prescription of methylprednisolone for multiple sclerosis acute relapse involves sterilization of urine. An observational study was conducted to clarify the benefit of antibiotic prophylaxis in case of asymptomatic bacteriuria found before methylprednisolone. Ninety-seven patients were included; 32 patients had asymptomatic bacteriuria. Seventeen patients were treated and 15 were not. The number of urinary tract infections in the month following the methylprednisolone was the same in the two groups. The results seem in favor of a therapeutic abstention. A larger study will be performed to confirm these results and determine appropriate recommendations.

Local application of corticosteroids combined with surgery for the treatment of chronic subdural hematoma.

AIM: Combination treatment consisting of surgery and pre-or post-operative corticosteroids for chronic subdural hematoma (CSH) tend to have better outcomes than surgery only. However, there are many complications after long-term use of corticosteroids. In this study, we evaluated the clinical outcomes of local application of corticosteroids combined with surgery for CSH. MATERIAL AND METHODS: We retrospectively analysed the data of the patients undergoing surgery and local application of Methylprednisolone Sodium Succinate for Injection (MPSS) into the hematoma cavity. Neurological status was assessed by Markwalder's Grading Scale (MGS). Recurrence was defined as deteriorating neurological status with radiological evidence of reaccumulation. RESULTS: A total of 26 patients were enrolled in this study. During the follow-up period, all patients made excellent neurological recovery. 24 (92.3%) patients' MGS was grade 0 at 12 months after the surgery. There was no mortality or recurrence. 5 patients (19.2%) suffered postoperative complications, of which 2 developed some subdural air collection, 2 had a partial seizure attack and 1 developed an acute epidural hemorrhage. CONCLUSION: The results suggest that local application of MPSS combined with surgery is a safe and effective method in the management of CSH. It may reduce hematoma recurrence.

[Pneumatosis cystoides intestinalis in a patient with lung cancer].

We report a case of pneumatosis cystoides intestinalis (PCI) in a patient with lung cancer. A 60-year-old woman was admitted with multiple lung tumors and multiple brain tumors. She was given steroid hormones to reduce her brain edema. Total resection of a brain tumor yielded a pathological diagnosis of metastatic squamous cell carcinoma. During treatment, X-ray and CT images revealed intestinal pneumatosis and free air in the abdominal cavity, but a physical examination revealed no abnormal findings. She was given a diagnosis of PCI, and received conservative treatment. Her intestinal gas cysts and intra-abdominal free air disappeared spontaneously. PCI is an uncommon but important condition in which gas is found in a linear or cystic form in the submucosa or subserosa of the bowel wall. It is important to consider PCI as a possible complication in lung cancer patients who are given steroid hormones and systemic chemotherapy in the long-term.

[A case of Churg-Strauss syndrome with methylprednisolone sodium succinate allergy].

A 63-year-old man with a history of therapy for asthma was admitted to a neighborhood hospital for treatment of a lower limb blister, accompanied by edema, pain and systemic fever. Churg-Strauss syndrome was diagnosed based on an increase in peripheral blood eosinophils, positive MPO-ANCA and other findings. He was given an injection of methylprednisolone sodium succinate; however his lower limb pain, fever and peripheral blood eosinophilia worsened. Therefore, steroid-resistant Churg-Strauss syndrome was diagnosed, for which he was referred to our hospital for more intensive treatment. His lower limb pain, fever, peripheral blood eosinophilia and inflammatory reactions improved immediately after switching treatment to oral prednisolone. Since a challenge test using an intravenous infusion of methylprednisolone sodium succinate worsened the lower limb pain, fever and peripheral blood eosinophilia, a drug allergy was diagnosed together with Churg-Strauss syndrome.

Preoperative high-dose steroid administration attenuates the surgical stress response following liver resection: results of a prospective randomized study.

BACKGROUND/PURPOSE: Major abdominal surgery such as liver resection is associated with an excessive hyperinflammatory response and transient immunosuppression. We investigated the immunomodulating effect of preoperative pulse administration of high-dose methylprednisolone in patients undergoing hepatic resection without pedicle clamping. METHODS: Twenty patients who underwent hepatic resection were randomized into two groups: a steroid group (n = 10), in which patients were given 30 mg/kg per body weight (BW) methylprednisolone intravenously, and a control group (n = 10), in which patients received a placebo (sodium chloride) infusion. The main outcome parameter to assess systemic stress was the serum plasma level of interleukin-6 (IL-6). To evaluate cell-mediated immune function, human leukocyte antigen-DR (HLA-DR) expression on peripheral blood monocytes and lipopolysaccharide (LPS)-induced tumor necrosis factor-alpha (TNF-alpha) release by peripheral monocytes was measured. Other investigated serum parameters included C-reactive protein (CRP), total bilirubin, alanine aminotransferase (ALT), prothrombin time (PT)-INR, and cytokines such as IL-8 and IL-10 and TNF-alpha. Postoperative convalescence, complication rate, and length of hospital stay were compared between the groups. RESULTS: Postoperative plasma concentrations of IL-6 (days 1 and 2), IL-8 (days 2 and 3), and CRP (days 1-4) were significantly lower in the steroid than in the control group. The total bilirubin concentration was significantly lower on day 6 in the steroid than in the control group. Four hours after surgery, LPS-induced TNF-alpha secretion was significantly reduced in the steroid group, but it increased rapidly during the following days. HLA-DR, ALT, and PT-INR levels were not different between the two groups. The postoperative hospital stay in the steroid group was significantly lower compared to that in the control group (mean, 10.5 days versus 14.8 days; P < 0.05). No differences were found in the convalescence score or postoperative complication rate. CONCLUSIONS: Intravenous methylprednisolone administration before hepatic resection significantly reduced systemic inflammatory cytokine release. No adverse effect on immunity was noted due to the methylprednisolone. We found no significant difference in the convalescence score, but a significantly shorter hospital stay in the steroid group. Further studies with more patients are needed to elucidate the clinical impact of preoperative steroid bolus therapy in liver surgery.

Rituximab plus ASHAP for the treatment of patients with relapsed or refractory aggressive non-Hodgkin's lymphoma: a single-centre study of 20 patients.

The anti-CD20 antibody rituximab improves the results of first-line therapy in aggressive non-Hodgkin's lymphoma (NHL) of B cell lineage. The purpose of this retrospective study was to evaluate its efficacy and toxicity in combination with the doxorubicine, methylprednisolone, high-dose cytarabine, cisplatin (ASHAP) protocol, an established treatment regimen for relapsed or refractory aggressive NHL. After a median of four cycles, 9 of 20 patients treated achieved a complete remission and 6 a partial remission, resulting in a total response rate of 75%. Remissions were not only seen in patients with relapsed lymphomas but also in patients with primary refractory or transformed indolent lymphomas. The outcome in cases with an international prognostic index score > or =2 was poor. Five of 15 responders received consolidating high-dose therapy with autologous stem cell transplantation. All of them are in ongoing remission. The main toxicity was myelosuppression, with neutropenias or thrombocytopenias of World Health Organization (WHO) grades III or IV developing in more than 90% of the cycles. There was one therapy-related death due to neutropenic sepsis. Non-hematologic toxicity was generally mild. At the time of analysis, six patients have died. After a median observation time of 17.5 months, the 2-year overall survival rate is 62%. ASHAP plus rituximab is an active and well-tolerated salvage protocol for patients with relapsed or refractory aggressive NHL, which compares favourably with other immuno-chemotherapy regimens, especially in patients with primary refractory or transformed indolent lymphomas.

Worsening of asthma with systemic corticosteroids. A case report and review of literature.

Despite widespread use for treatment of asthma and allergies, glucocorticoids may cause allergic reactions, even anaphylaxis. The incidence of adverse reactions to systemic glucocorticoids is 0.3%. The most commonly reported corticosteroids causing anaphylaxis like reactions are hydrocortisone, prednisone, and methylprednisolone. Most authors agree that allergic reactions to systemic corticosteroids are possibly immunoglobulin E mediated. We report a patient with asthma, aspirin allergy, and nasal polyps who developed bronchospasm following the administration of intravenous methylprednisolone sodium succinate during an acute asthmatic attack. We discuss the differential diagnosis of worsening asthma despite adequate treatment, and suggest corticosteroid-induced bronchospasm in our patient. Corticosteroid-induced bronchospasm should be considered when asthmatics fail to improve, or frankly deteriorate with systemic corticosteroid therapy, particularly when a history of aspirin allergy is present. TEACHING POINT: Know the differential diagnosis for worsening of asthma despite adequate treatment. Consider corticosteroid-induced bronchospasm when asthmatics fail to improve, or frankly deteriorate with systemic corticosteroid therapy. Corticosteroid-induced bronchospasm is more commonly seen in asthmatics with a history of aspirin allergy.

Intratympanic steroid perfusion for refractory sudden sensorineural hearing loss.

OBJECTIVE: Patients with sudden sensorineural hearing loss (SSHL) can benefit from systemic steroid therapy. Unfortunately, some patients are not candidates for steroid therapy due to concern over possible complications. Furthermore, not all patients will benefit from steroid administration. This study evaluates the potential benefits and safety of treating patients with SSHL refractory to oral steroids with intratympanic steroid therapy. METHODS: A retrospective case review was performed on all patients who presented with sudden sensorineural hearing loss refractory to oral steroid therapy during the past year. Seventeen patients were identified. All patients underwent intratympanic steroid administration, via MicroWick placement and/or round window catheter placement. RESULTS: Nine patients with sudden sensorineural hearing loss showed an improvement with intratympanic steroid therapy, consisting of MicroWick placement with dexamethasone drop (Decadron) administration for 1-2 weeks and/or round window catheter placement with steroid perfusion. Only one of the patients presenting with hearing loss present for greater than 8 weeks benefited from intratympanic therapy. Complications were few and included tympanic membrane perforation, chronic otitis media, dysequilibrium, and dysguesia. CONCLUSIONS: Intratympanic steroid therapy can be beneficial in treating patients with sudden sensorineural hearing loss refractory to oral steroid use. EBM RATING: C.

Salvage chemotherapy according to the ASHAP protocol: a single-center study of 24 patients with relapsed or refractory aggressive non-Hodgkin's lymphomas.

Numerous salvage protocols for relapsed or refractory aggressive non-Hodgkin's lymphomas have been described. The purpose of this retrospective study was to evaluate the efficacy and the toxicity of the ASHAP protocol, which combines a continuous infusion of doxorubicin and cisplatin with high-dose cytarabine and methylprednisolone. Twenty-four patients with relapsed or refractory aggressive non-Hodgkin's lymphomas were treated with a median of 3 cycles (range: 1-5) of ASHAP. Twelve patients achieved a complete and four a partial remission for an overall response rate of 67%. The 3-year overall and progression-free survival rates were 60% and 40%, respectively. Ten of the responding patients were consolidated by high-dose chemotherapy. After a median follow-up of 15.5 months, four patients are in continuous complete remission, while six patients suffered relapses (two fatal). For reasons of low risk profile [international prognostic index (IPI) score of 0, n=2] or age >60 years ( n=4), consolidation was limited to involved-field radiotherapy in six patients. All of these patients are alive after a median follow-up of 37 months, with two relapses. Factors predicting a poor response to salvage therapy were primary refractory disease, elevated lactate dehydrogenase activity, and an IPI score of >/=2. The principal toxicity was myelosuppression with grade III or IV neutropenia or thrombocytopenia occurring in 88% or 75%, respectively, of the patients. Nonhematological toxicity was generally mild. There were no treatment-related deaths. The ASHAP regimen is a highly active and well-tolerated salvage protocol for patients with relapsed aggressive non-Hodgkin's lymphomas which compares favorably with other established protocols.

Stevens-Johnson syndrome developing in a girl with systemic lupus erythematosus on high-dose corticosteroid therapy.

Stevens-Johnson syndrome (SJS) is a vesiculobullous disease of the skin and mucosa. This generalized hypersensitivity reaction is well known to occur in association with certain drugs, particularly sulfonamides, nonsteroidal anti-inflammatory agents (NSAIDs), and anticonvulsants. The disease is usually seen in children and young adults and is often treated with corticosteroids. We present a 9-year-old girl with lupus nephritis who developed cutaneous bullae and mucositis while being treated with intravenous methylprednisolone. The initial differential diagnosis included bullous lupus, but skin biopsy specimen findings supported a diagnosis of SJS. She was treated with intravenous immunoglobulin (IVIg).

Effects of preoperative steroid administration on surgical stress in hepatic resection: prospective randomized trial.

HYPOTHESIS: Preoperative administration of methylprednisolone sodium succinate can control surgical stress in patients undergoing hepatic resection. DESIGN: A prospective randomized trial. SETTING: A university hospital department of surgery. PATIENTS: Thirty-three patients who underwent hepatic resection were classified into 2 groups: a control group (n = 16) and a steroid group (n = 17) in which patients were intravenously administered 500 mg of methylprednisolone 2 hours before surgery. MAIN OUTCOME MEASURES: Perioperative levels of interleukin (IL)-6 and IL-10 (serum and peritoneal), immunosuppressive acidic protein, Candida antigen, and other laboratory and clinical variables were measured. RESULTS: Postoperative levels of serum and peritoneal IL-6 and levels of C-reactive protein were significantly lower in the steroid group than in controls. Furthermore, serum and peritoneal IL-10 levels were significantly higher in the steroid group. The total bilirubin value on postoperative day 1 was significantly lower in the steroid group than in controls. Postoperative immunosuppressive acidic protein levels were also significantly lower in the steroid group, as was the positive rate of serum Candida antigen. No differences were found in the incidence of postoperative complications. CONCLUSIONS: Preoperative steroid administration significantly elevated anti-inflammatory cytokine IL-10 levels, suppressed the levels of inflammatory cytokines IL-6 and C-reactive protein, and prevented postoperative elevation of total bilirubin values. Furthermore, postoperative elevation of immunosuppressive acidic protein levels and the positive rate of Candida antigen were suppressed, indicating that the immune response was maintained by preoperative steroid administration.

[Central serous chorioretinopathy and systemic steroid therapy]. / Choriorétinite séreuse centrale et corticothérapie systémique. A propos de 14 cas.

BACKGROUND: The manifestations of the ocular toxicity of systemic corticosteroids include posterior subcapsular cataracts and glaucoma. We describe 14 cases of serous detachment of the macula due to central serous chorioretinopathy in patients given long-term steroid therapy, which may be another potential ocular side effect of corticosteroid. CASES REPORT: The 14 (9 men and 5 women) patients were aged from 39 to 55 year old. Their systemic diseases were allergic thrombopenic purpura, optic neuritis, kidney or heart transplant, Churg and Strauss vasculitis, facial palsy, rheumatoid arthritis, systemic lupus and a kidney tumor. None of the patients had hypertension. RESULTS: Serous detachment occurred between 6 days and 10 years after the start of steroid treatment. The higher the doses, the earlier the onset of ocular disease. All patients were symptomatic, with rapid onset of blurred vision. Serous detachment was bilateral in two cases. The fluorescein angiographic finding was in most cases a single small focal hyperfluorescent leak from the retinal pigment epithelium which appeared early in the angiogram and increased in size and intensity. No diffuse degradation of the retinal pigment epithelium was seen on the fluorescein angiogram. Five patients underwent laser photocoagulation of the leaking area followed by resorption of subretinal fluid. In other patients, the symptoms disappeared as the doses of steroid were reduced. CONCLUSION: The pathogenesis of central serous chorioretinopathy remains unclear and is controversial. Corticosteroids are known to worsen the prognosis of idiopathic central serous chorioretinopathy, and serous detachment has been reported after renal transplantation. In most of these cases, chorioretinopathy was combined with diffuse leakage from the choriocapillaris. We discuss the relationship between steroid therapy and focal leakage as seen in idiopathic central serous chorioretinopathy. In conclusion, we describe 14 cases of central serous retinopathy whose clinical and fluorescein angiography were fairly typical, without obvious diffuse degradation of the retinal pigment epithelium. All these patients had been given long-term steroid therapy for various diseases.

Risks and benefits of preoperative high dose methylprednisolone in surgical patients: a systematic review.

BACKGROUND: A single preoperative high dose of methylprednisolone (15 to 30 mg/kg) has been advocated in surgery, because it may inhibit the surgical stress response and thereby improve postoperative outcome and convalescence. However, these potential clinical benefits must be weighed against possible adverse effects. OBJECTIVE: To conduct a risk-benefit analysis using a meta-analysis, to compare complication rates and clinical advantages associated with the use of high dose methylprednisolone in surgical patients. METHODS: Randomised controlled trials of high dose methylprednisolone in elective and trauma surgery were systematically searched for in various literature databases. Outcome data on adverse effects, postoperative pain and hospital stay were extracted and statistically pooled in fixed-effects meta-analyses. RESULTS: We located 51 studies in elective cardiac and noncardiac surgery, as well as traumatology. Pooled data failed to show any significant increase in complication rates. In patients treated with corticosteroids, nonsignificantly more gastrointestinal bleeding and wound complications were observed; the 95% confidence interval boundaries of the numbers-needed-to-harm were 59 and 38, respectively. The only significant finding was a reduction of pulmonary complications (risk difference -3.5%; 95% confidence interval -1.0 to -6.1), mainly in trauma patients. CONCLUSION: For patients undergoing surgical procedures, a perioperative single-shot administration of high dose methylprednisolone is not associated with a significant increase in the incidence of adverse effects. In patients with multiple fractures, limited evidence suggests promising benefits of glucocorticoids on pulmonary complications.

Gastric hemorrhage in dogs given high doses of methylprednisolone sodium succinate.

OBJECTIVE: To determine whether healthy dogs given high doses of methylprednisolone sodium succinate (MPSS) develop gastrointestinal tract ulcers and hemorrhage. ANIMALS: 19 healthy male hound-type dogs. PROCEDURE: Dogs were assigned randomly to intravenously receive high doses of MPSS (30 mg/kg of body weight, initially, then 15 mg/kg 2 and 6 hours later, and, subsequently, every 6 hours for a total of 48 hours; n = 10) or an equal volume of saline (0.9% NaCl) solution (9). Gastroduodenoscopy was performed before and after treatment. Endoscopic evidence of gross hemorrhage in the cardia, fundus, antrum, and duodenum of each dog was graded from none (0) to severe (3), and a total stomach score was calculated as the sum of the regional gastric scores. Number of ulcers were recorded. The pH of gastric fluid and evidence of occult gastric and fecal blood were measured. Food retention was recorded. RESULTS: Gastric hemorrhage was evident in all dogs after MPSS administration and was severe in 9 of 10 dogs but not visible in any dog after saline treatment. Occult gastric blood was detected more commonly (9/10 vs 2/9), median gastric acidity was greater (pH 1 vs pH 3), and food was retained more commonly (7/10 vs 1/9) in the stomach of MPSS-treated dogs. CONCLUSIONS AND CLINICAL RELEVANCE: High doses of MPSS cause gastric hemorrhage in dogs. All dogs treated with high doses of MPSS should be treated with mucosal protectants or antacids to prevent gastric hemorrhage.

Efficacy of misoprostol in prevention of gastric hemorrhage in dogs treated with high doses of methylprednisolone sodium succinate.

OBJECTIVE: To determine whether administration of misoprostol prevents gastric hemorrhage in healthy dogs treated with high doses of methylprednisolone sodium succinate (MPSS). ANIMALS: 18 healthy hound-type dogs of both sexes. PROCEDURE: All dogs were given high doses of MPSS (30 mg/kg of body weight, initially, then 15 mg/kg 2 and 6 hours later, and, subsequently, q 6 h for a total of 48 hours) IV. Dogs were assigned randomly to receive concurrent treatment with misoprostol (4 to 6 microg/kg, PO, q 8 h; n = 9) or an empty gelatin capsule (9). Gastroduodenoscopy was performed before and after treatment. Hemorrhage was graded from none (0) to severe (3) for each cardia, fundus, antrum, and duodenum. A total stomach score was calculated as the sum of the regional stomach scores. Food retention was recorded, and pH of gastric fluid was determined. Gastric and fecal occult blood was measured. RESULTS: Gastric hemorrhage was evident in all dogs after MPSS administration, and its severity was similar in both groups. Median total stomach score was 6 for misoprostol-treated dogs and 5.5 for dogs given the gelatin capsule. Difference in gastric acidity, frequency of food retention, and incidence of occult blood in gastric fluid and feces was not apparent between the 2 groups. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of misoprostol (4 to 6 microg/kg, PO, q 8 h) does not prevent gastric hemorrhage caused by high doses of MPSS. Alternative prophylactic treatment should be considered.