High-dose Methylprednisolone Therapy Research Articles

Reversible posterior leukoencephalopathy in a patient with minimal-change nephrotic syndrome

A 9-year-old boy with nephrotic syndrome was transferred to our hospital because of acute renal failure and disturbance of consciousness after high-dose methylprednisolone therapy. He developed severe headache, visual disturbance, and generalized seizures. Brain computed tomography (CT) scan revealed multiple, bilateral, low-density areas in the parieto-occipital lobes. Magnetic resonance imaging (MRI) disclosed a high signal intensity area on T2-weighted images and a low signal intensity area on T1-weighted images in the same lesion. Follow-up brain CT scan and MRI, 2 weeks after the first studies, showed complete resolution of the abnormal lesions, which suggested the diagnosis of reversible posterior leukoencephalopathy syndrome (RPLS). Hypertension and high-dose methylprednisolone administration to the patient in the nephrotic state may be causes of this uncommon syndrome in this case. This is the first report of RPLS in nephrotic syndrome with hypertension not associated with cyclosporine administration.

High-Dose Methylprednisolone Therapy in Multiple Sclerosis Induces Apoptosis in Peripheral Blood Leukocytes

Apoptosis is supposed to contribute to the elimination of T cells from the inflamed central nervous system in the natural disease course of multiple sclerosis (MS). In the animal model experimental autoimmune encephalomyelitis, T-cell apoptosis can be induced by high-dose glucocorticoid (GC) administration. To study the effects of intravenous high-dose GC therapy in MS on T-cell apoptosis ex vivo. Sixty-six patients with MS (28 with relapsing-remitting MS, 22 with secondary chronic progressive MS, and 16 with primary chronic progressive MS) and 16 control patients receiving corticosteroids for other disorders were included in the study. Blood samples were collected before and immediately after the first infusion of 500 to 1000 mg of methylprednisolone given during 2 hours in the early morning. Gradient-isolated peripheral blood leukocytes (PBLs) were cultured, unstimulated, with corticosteroids (positive control), the mitogen phytohemagglutinin, or anti-T-cell receptor monoclonal antibody. For investigation of apoptosis, PBLs were cultured overnight and analyzed by immunoflow cytometry using TUNEL (terminal transferase-mediated dUTP biotin nick end labeling) or annexin labeling in combination with CD4, CD8, CD22, CD56, or bcl-2 staining. Proliferation was measured by (3)H-thymidine incorporation. For cytokine determination, supernatants were collected after 48 hours of culture. After in vivo corticosteroid treatment, apoptosis of unstimulated PBLs was markedly and significantly augmented in all 3 MS subgroups. Fluorescence-activated cell sorter analysis showed that apoptosis affected predominantly CD4 T cells. Natural killer cells showed a relative increase after GC therapy without a change in the rate of apoptotic cells. Expression of bcl-2 in T-cell subpopulations was not significantly modified by high-dose GC therapy. Culture supernatants of T-cell receptor-stimulated PBLs after GC therapy contained lower concentrations of interleukin 2, interferon gamma, and tumor necrosis factor alpha than those from PBLs taken before pulse therapy. Similar changes in the rate of apoptosis and cytokine production were seen in controls. Corticosteroid pulse therapy is a strong inducer of leukocyte apoptosis. Induction of apoptosis might contribute to the down-regulation of T-cell activity and thereby terminate inflammation in the central nervous system.

HIGH-DOSE ORAL METHYLPREDNISOLONE THERAPY IN CHILDHOOD HEMANGIOMAS

The authors report their experience with high-dose oral methylprednisolone therapy (HDMP)in 15 infants with complicated hemangiomas. The starting dose for methylprednisolone was 30 mg/kg/day for 5 days, then the dose was tapered gradually every 5 days to 20, 10, 5, 2.5, and finally to 1 mg/kg/day. Therapy was then stopped and the patients were followed. An initial response was evident in 12 patients. Nine out of 12 responders showed regrowth signs. After regrowth, 4 cases received prednisolone at doses between 1 to 5 mg/kg/day and 3 patients received a second course with HDMP as additional corticosteroid therapy. Overall, 9 out of 15 cases were responders; very good and good responses were obtained in 5, partial response in 4, and therapy failure in 5 cases. One child was not available for evaluation of response. A very rapid initial response was observed in subglottic and periocular hemangiomas. Side effects were not serious and resolved after discontinuation of treatment. Although the number of patients is small in this study, overall response rate with HDMP regimen seems not to be superior to the regimens that use lower doses (5 mg/kg/day), but it provides a high initial response rate and the duration of therapy is short. Therefore, it may be useful for treating hemangiomas that fail to respond with low doses, especially in centers with limited resources where other treatment modalities cannot be used at the moment.

EFFECT OF SHORT-COURSE, HIGH-DOSE STEROID THERAPY IN A CHILD WITH MYELODYSPLASTIC SYNDROME

High-dose methylprednisolone (HDMP) has been shown to induce differentiation of myeloid leukemic cells with a remarkable antileukemic effect in children with various subtypes of acute myeloblastic leukemia (AML). Here the beneficial effect of short-course HDMP therapy in a child with myelodysplastic syndrome (MDS) is reported. Oral methylprednisolone sodium succinate (Prednol-L) was administered at a single daily dose of 30 mg/kg for 5 days to a 4-year-old girl with refractory anemia with excess of blasts and hypocellular bone marrow before the initiation of chemotherapy. In addition to dramatic clinical improvement, the patient's white blood cell count increased from 2.3 2 10 9 /L to 5.0 2 10 9 /L, and peripheral blood blast cells disappeared 4 days after HDMP treatment. Repeated bone marrow aspirate 1 week after the initiation of HDMP disclosed increased cellularity with no blasts. Furthermore, short-course HDMP treatment stimulated the increase in the number of peripheral blood lymphocytes and CD3 + , CD4 + , CD8 + , CD19 + , CD34 + , and NK cells. Results obtained with HDMP from the previous studies and the present case suggest that high-dose methylprednisoloneis a promising agent in the treatment of MDS and it is recommended as an initial treatment especially for MDS children with hypocellular bone marrow at presentation.

IMMUNE THROMBOCYTOPENIA AND HEMOLYTIC ANEMIA AS A PRESENTING MANIFESTATION OF HODGKIN DISEASE

A very unusual clinical presentation of Hodgkin disease with immune thrombocytopenia and autoimmune hemolytic anemia is reported. A 6.5-year-old boy presented with thrombocytopenia, Coombs' positive hemolytic anemia, and multiple small posterior cervical lymph nodes. After a course of high-dose methylprednisolone therapy with a diagnosis of Evans syndrome, complete response for thrombocytopenia and partial response for anemia was achieved. Six weeks later there was a sudden increase in the size of left posterior cervical lymph nodes and a biopsy was compatible with Hodgkin disease, mixed cellularity type. The child was successfully treated with chemotherapy and radiation therapy. He has been off therapy for 28 months and has no clinical or laboratory evidence of autoimmune cytopenia. A combination of immune thrombocytopenia and autoimmune hemolytic anemia may be associated with Hodgkin disease. The recognition of this clinical picture as a complication of Hodgkin disease has important implications. This complication appeares to be managed best by the definitive treatment of Hodgkin disease.

Severe Systemic Inflammatory Response Syndrome With Shock and ARDS Resulting From Still's Disease: Clinical Response With High-Dose Pulse Methylprednisolone Therapy

Adult-onset Still's disease, the adult variant of the systemic form of juvenile arthritis, is an uncommon systemic inflammatory disorder of unknown etiology characterized by high spiking fevers, neutrophilic leukocytosis, arthritis, and an evanescent rash. There is often a delay in reaching a firm diagnosis. Differential diagnoses include infection, malignancy, and various immunologic disorders. Increased ferritin levels are of particular value in establishing the diagnosis. Clinical response to high-dose corticosteroids may be dramatic. We report a case of a 29-year-old woman who had recently been investigated for fever of unknown origin, and who presented to our hospital with high fever and hypotension. Her condition rapidly deteriorated with the development of ARDS, disseminated intravascular coagulation, and shock. The patient had a markedly elevated serum ferritin concentration of 26,000 ng/mL. High-dose pulse methylprednisolone therapy resulted in a remarkable clinical improvement. Such a severe case of systemic inflammatory response syndrome, masquerading as septic shock, has not been reported previously.

Changes of Hemostatic Factors in Children with Acute Lymphoblastic Leukemia Receiving Combined Chemotherapy Including High Dose Methylprednisolone and L-Asparaginase

In this study, protein C (PC), protein S (PS), heparin cofactor II (HCFII), prothrombin fragment 1+2 (PF 1,2), thrombin-antithrombin III complex (TAT), von Willebrand factor (vWF) and thrombomodulin (TM) were investigated in 19 patients with acute lymphoblastic leukemia, (ALL) receiving combined chemotherapy including L-asparaginase (L-ASP) and high dose methylprednisolone (HDMP). HDMP was administered in doses of 30 mg/kg/day for 7 days, and 20 mg/kg/day for another 7 days. In order to evaluate the effect of HDMP on the hemostatic system, the 8 patients studied here received HDMP (30 mg/kg/day) therapy for 4 days before the combined chemotherapy. These parameters were also studied in 12 healthy children as a control group. PC levels were normal in the patients while PS levels were decreased both before and after combined chemotherapies. Patients with ALL have laboratory signs of coagulation activation such as PF 1,2, TAT prior to initiation of chemotherapy. With combined chemotherapy, TAT levels were found to be normal while PF1,2 were not. TM levels were found to be increased both before and after therapies whereas HCFII and vWF levels were not different from those of the control group. The short course of HDMP therapy did not prominently influence these hemostatic parameters.These results indicate that both the malignant process and the drugs used in combined chemotherapy cause a decrease in natural inhibitors and an increase in procoagulant activity and endothelial injury. These hemostatic changes may contribute to a thrombotic tendency in the patients with ALL.

Subcutaneous Panniculitic T-Cell Lymphoma Developing in a Child With Idiopathic Myelofibrosis

Subcutaneous panniculitic T-cell lymphoma is reported in a child with idiopathic myelofibrosis. Both disease entities are rarely seen in children. A girl aged 5 years and 9 months had pancytopenia and severe constitutional symptoms. Idiopathic myelofibrosis was subsequently diagnosed. A transient response was achieved after treatment with a course of high-dose methylprednisolone therapy. However, proptosis and skin nodules developed during tapering of steroid therapy. A computed tomography scan of the orbit also revealed a mass lesion in the right lacrimal gland region. A skin biopsy specimen showed a subcutaneous panniculitic T-cell lymphoma. The clinical course was marked by high fever, profound pancytopenia, massive gastrointestinal bleeding, and severe, recurrent infections. Her condition rapidly deteriorated, and she died from polymicrobial sepsis 4 months after her initial examination. Subcutaneous panniculitic T-cell lymphoma is a distinctive clinicopathologic entity that is rarely seen in children. The association of myelofibrosis and peripheral T-cell lymphoma as seen in this has been rarely reported.

Corticosteroid therapy augments gastroduodenal permeability to sucrose.

The aim of the present study was to investigate whether corticosteroid therapy alters gastroduodenal mucosal permeability and whether permeability alteration is associated with macroscopic mucosal damage. Eight patients taking oral corticosteroid therapy (total prednisone-equivalent dose, 1.5+/-0.1 g; duration, approximately 30 days), nine patients with multiple sclerosis taking high-dose intravenous methyl-prednisolone therapy (total dose, 11.7+/-0.5 g; duration, approximately 9 days), and 20 age- and gender-matched controls were studied. Gastroduodenal permeability was determined using sucrose as a site-specific permeability probe. Five-hour urine was collected after ingesting 100 g of sucrose and its urinary excretion rate was measured using high-pressure liquid chromatography. Gastroduodenal endoscopy was performed before steroid therapy to exclude subjects with evidence of macroscopic mucosal lesions. The sucrose test and endoscopy were repeated after completion of corticosteroid therapy. The urinary sucrose excretion rates were similar in the control group and in patient groups before corticosteroid therapy. The median excretion rate of sucrose increased four (one to 28)- and eight (two to 35)-fold, respectively, as compared with pretreatment values in patients taking oral steroid and high-dose intravenous methyl-prednisolone therapy (p < 0.01). Considering all patients together, subjects who received a mean prednisone-equivalent dose of 8.4+/-1.5 g exhibited mucosal lesions, whereas patients who received 3.3+/-1.8 g did not (p = 0.06). The post-therapy increments in sucrose excretion rates were associated with neither the presence of macroscopic lesions nor with the total steroid dose received. Corticosteroid therapy augments gastroduodenal permeability and high doses are associated with macroscopic mucosal lesions. Steroid-induced permeability increase does not appear to be associated with the presence of macroscopic mucosal lesions.

Corticosteroid therapy augments gastroduodenal permeability to sucrose

Objective: The aim of the present study was to investigate whether corticosteroid therapy alters gastroduodenal mucosal permeability and whether permeability alteration is associated with macroscopic mucosal damage. Methods: Eight patients taking oral corticosteroid therapy (total prednisone-equivalent dose, 1.5 ± 0.1 g; duration, ∼30 days), nine patients with multiple sclerosis taking high-dose intravenous methyl-prednisolone therapy (total dose, 11.7 ± 0.5 g; duration, ∼9 days), and 20 age- and gender-matched controls were studied. Gastroduodenal permeability was determined using sucrose as a site-specific permeability probe. Five-hour urine was collected after ingesting 100 g of sucrose and its urinary excretion rate was measured using high-pressure liquid chromatography. Gastroduodenal endoscopy was performed before steroid therapy to exclude subjects with evidence of macroscopic mucosal lesions. The sucrose test and endoscopy were repeated after completion of corticosteroid therapy. Results: The urinary sucrose excretion rates were similar in the control group and in patient groups before corticosteroid therapy. The median excretion rate of sucrose increased four (one to 28)- and eight (two to 35)-fold, respectively, as compared with pretreatment values in patients taking oral steroid and high-dose intravenous methyl-prednisolone therapy ( p < 0.01). Considering all patients together, subjects who received a mean prednisone-equivalent dose of 8.4 ± 1.5 g exhibited mucosal lesions, whereas patients who received 3.3 ± 1.8 g did not ( p = 0.06). The posttherapy increments in sucrose excretion rates were associated with neither the presence of macroscopic lesions nor with the total steroid dose received. Conclusions: Corticosteroid therapy augments gastroduodenal permeability and high doses are associated with macroscopic mucosal lesions. Steroid-induced permeability increase does not appear to be associated with the presence of macroscopic mucosal lesions.

Double-blind, randomized, placebo-controlled study of oral, high-dose methylprednisolone in attacks of MS

There is only limited evidence from adequately controlled clinical trials to support high-dose methylprednisolone therapy for attacks of multiple sclerosis (MS) and none supporting oral administration. We assessed the effect of oral high-dose methylprednisolone therapy in attacks of MS. Twenty-five patients with an attack of MS lasting less than 4 weeks were randomized to placebo treatment. Twenty-six patients received oral methylprednisolone (500 mg once a day for 5 days with a 10-day tapering period). The patients received scores on the Scripps Neurological Rating Scale (NRS) and Kurtzke Expanded Disability Status Scale. The symptoms were scored on a visual analog scale (VAS) before treatment and after 1, 3, and 8 weeks of treatment. Primary efficacy measures were NRS and VAS scores in the first 3 weeks and changes in NRS score and answers to an efficacy questionnaire administered after 8 weeks of treatment. Changes in NRS scores among methylprednisolone- and placebo-treated patients differed significantly in the first 3 weeks and after 8 weeks (p = 0.005 and p = 0.0007). VAS scores the first 3 weeks and treatment efficacy after 8 weeks also favored a beneficial effect of methylprednisolone treatment (p = 0.02 and p = 0.05). After 1, 3, and 8 weeks, 4%, 24%, and 32% in the placebo group and 31%, 54%, and 65% in the methylprednisolone group had improved one point on the Expanded Disability Status Scale score (all p < 0.05). No serious adverse events were seen. Oral high-dose methylprednisolone is recommended for managing attacks of MS.

Plasma soluble interleukin-2 receptor levels in patients with idiopathic thrombocytopenic purpura.

Soluble interleukin-2 receptor (slL-2R) was measured in the plasma of 31 patients with idiopathic thrombocytopenic purpura (ITP) and 22 normal controls. When thrombocytopenia persisted longer than 6 months, the diagnosis of chronic ITP was made. Twenty patients had acute ITP, 11 patients had chronic ITP, and all patients received high-dose methylprednisolone (HDMP) (30 mg/kg/d for 3 days, 20 mg/kg/d for 4 days). The sIL-2R levels of the patients were determined before being giving HDMP and 14 days after the end of HDMP therapy. Platelet counts were determined before administration of HDMP, one day after the end of HDMP therapy, and once every 28 days for 7 months thereafter. There was not a significant difference between the mean pre-treatment plasma sIL-2R levels of both acute and chronic ITP groups (P > 0.05), and these were higher than that of the control group (P < 0.001). The mean post-treatment sIL-2R level of the chronic ITP group was significantly higher than those of both the control and post-treatment acute ITP groups (P < 0.001). There were negative correlations between the plasma sIL-2R levels and platelet counts of both group patients in the pre-treatment period and between post-treatment sIL-2R levels and platelet counts in chronic ITP group (P < 0.05). We think that there was a good correlation between prognosis of ITP and sIL-2R levels after HDMP therapy, and platelet counts in patients with ITP are linked to sIL-2R levels.

High Dose Methylprednisolone Therapy in Patients with Acute Respiratory Distress Syndrome Caused by Severe Pneumonia

High Dose Methylprednisolone Therapy in Patients with Acute Respiratory Distress Syndrome Caused by Severe Pneumonia

Severe malabsorption in autoimmune polyendocrinopathy-candidosis-ectodermal dystrophy syndrome successfully treated with immunosuppression

A 15 year old boy with autoimmune polyendocrinopathy-candidosis-ectodermal dystrophy syndrome suffered recurrent episodes of severe intractable diarrhoea, steatorrhoea, and hypocalcaemia. The only treatment modality, which controlled the malabsorption syndrome, was...

Pulse Methylprednisolone Therapy in Landau-Kleffner Syndrome

Landau-Kleffner syndrome (LKS) is a subtype of acquired childhood aphasia associated with characteristic paroxysmal EEG recording of spikes and spike and wave complexes. The seizures, which start independently of the onset of aphasia, usually respond to antiepileptic drugs and have a good prognosis, but recovery of aphasia is variable. Steroid therapy has been recommended in recent years. We report an 8-year old girl with LKS who received intravenous high-dose methylprednisolone therapy without any side effect.

Failure of pulse intravenous methylprednisolone treatment in juvenile dermatomyositis

OBJECTIVE. To review the experience with high-dose intravenous pulse methylprednisolone (IVMP) therapy in patients with juvenile dermatomyositis (JDM) in our institution. STUDY DESIGN. We reviewed the charts of seven consecutive patients (four female subjects; three male subjects; age 3 to 18 years [mean age 8 years]) treated for JDM between 1989 and 1992. RESULTS. All patients met the criteria of Bohan and Peter for JDM and were treated within 3 months of onset of weakness. All received initial treatment with IVMP, 30 mg/kg per day for 3 days, administered weekly for between 1 and 4 weeks. Treatment with orally administered prednisone was required because of deteriorating muscle strength and persistent elevation of creatine kinase activity despite IVMP in five patients, increased skin vasculitis in one patient, and elevated creatine kinase activity with no improvement in strength in one patient. CONCLUSION. We conclude that muscle strength in patients with JDM may deteriorate during pulse IVMP therapy when this is used alone as initial treatment, even early in the course of the illness. We recommend either conventional high doses of orally administered corticosteroids or IVMP with oral corticosteroid therapy as initial treatment of JDM. (J P EDIATR 1996;128:429-32)

Increased serum human granulocyte colony-stimulating factor (G-CSF) levels following intravenous infusion of high-dose methylprednisolone.

Serum granulocyte colony-stimulating factor (G-CSF) level were measured for 24 h in 6 patients with hematological disorders and two patients with Graves' disease associated with malignant exophthalmos after iv infusion of high-dose methylprednisolone (HDMP) (20 mg/kg BW) for 2 h starting at 0900 h. Saline solution (500 ml) was infused iv for 2 h as a control on two days before starting the HDMP therapy. Serum G-CSF levels increased with the mean peak values at 4 h after the HDMP therapy (mean +/- SD: 488.1 +/- 125.8 pg/ml vs. saline control 74.4 +/- 21.9 pg/ml, P < 0.01). Circulating absolute neutrophil counts (ANC) also increased with the mean peak values at 24 h after the HDMP (6,057 +/- 1,460 / microliters vs. saline control 2,007 +/- 390 / microliters, P < 0.025). These findings indicate that glucocorticoid has a stimulating effect on G-CSF release and that the increased G-CSF release could be involved, at least partly, in neutrophilia induced by glucocorticoid.

Decline of muscle fiber conduction velocity during short-term high-dose methylprednisolone therapy

Decline of muscle fiber conduction velocity during short-term high-dose methylprednisolone therapy

High-dose intravenous methylprednisolone therapy for patients with Diamond-Blackfan anemia refractory to conventional doses of prednisone

Objectives: To assess the efficacy and toxicity of very high doses of glucocorticoids in patients with congenital pure red cell aplasia (Diamond-Blackfan anemia) who did not respond to standard doses of prednisone. Study designs: We prospectively treated eight patients with transfusion-dependent Diamond-Blackfan anemia with high intravenous doses of methylprednisolone. All patients had previously not responded to one or more oral courses of prednisone in standard doses and were dependent on erythrocyte transfusions. Every patient initially received methylprednisolone at a dose of 30 mg/kg per day, followed by slow tapering for 4 weeks, but none responded. All patients then received a second treatment course starting at 100 mg of methylprednisolone per kilogram per day, again followed by slow tapering of the dosage. Results: Three patients had a complete response that has been sustained for 21+, 31+, and 41+ months, respectively. One patient had a partial response. Toxic effects included a rise in serum alanine aminotransferase activity in all patients, transient diabetes mellitus in one child, and three episodes of bacteremia in two patients with intravenous access devices. Conclusions: We conclude that very high doses of methylprednisolone may induce sustained remission in some patients with transfusion-dependent Diamond-Blackfan anemia refractory to standard-dose prednisone therapy. (J P EDIATR 1995;127:654-9)

High-dose methylprednisolone is an alternative treatment for adults with autoimmune thrombocytopenic purpura refractory to intravenous immunoglobulins and oral corticosteroids.

Eight patients with severe chronic autoimmune thrombocytopenic purpura (AITP) refractory to high-dose intravenous immunoglobulin (IVIgG) and/or oral prednisone were treated with one to three infusions of high-dose methylprednisolone (HDMP) (15 mg/kg/day). The mean platelet count before treatment was 12 +/- 10 x 10(9)/L. HDMP therapy led to a safe platelet count (> 50 x 10(9)/L) after 2-5 days in five patients, and a minimal platelet increase (34 x 10(9)/L) able to stop bleeding in a sixth patient. The effect of HDMP was, however, transient in four of five responders. No side effects were observed, even in the four patients older than 70 years. HDMP thus appears to be a good alternative in emergency situations or prior to surgery for patients with AITP refractory to conventional therapy.