High-dose Methylprednisolone Pulse Therapy Research Articles

MRI Findings and Steroid Therapy for Neuralgic Amyotrophy in Children

Neuralgic amyotrophy is not uncommon in adults but is relatively rare in children. We recently encountered 2 cases of neuralgic amyotrophy in children. Patient 1 was a 7-year-old girl who developed a right leg paralysis after an epileptic seizure. Lumbar plexus T(2)-weighted magnetic resonance imaging (MRI) revealed a hyperintense and thickened portion extending from the root to the knee region of the right sciatic nerve, and T(1)-weighted conventional spin echo with gadolinium administration revealed enhancement. Patient 2 was a 4-year-old boy who experienced a sudden onset of severe right arm pain and paralysis. T(2)-weighted MRI with a short tau inversion recovery revealed a slightly thickened and high intensity region at the right C(6)-C(8) level. After high-dose methylprednisolone pulse therapy was performed in each case, patient 1 experienced complete recovery, whereas patient 2 experienced only amelioration of pain. A diagnosis of neuralgic amyotrophy in children was facilitated by an MRI study (T(2) weighed with short tau inversion recovery and T(1) weighted with gadolinium enhancement), and early steroid therapy might have improved the condition of these children.

Spontaneous pregnancy in a patient with a relapse of lymphocytic hypophysitis successfully treated with azathioprine and glucocorticoids

We report a rare case of recurrent lymphocytic hypophysitis (LyH) after transsphenoidal surgery and high dose methylprednisolone pulse therapy (HDMPT). The patient was treated with azathioprine, and achieved spontaneous pregnancy. A 22-year-old nulliparous female was seen in June 2004 due to headaches, diplopia and left eye ptosis, and bilateral milky nipple discharge. Six months prior she had undergone transsphenoidal pituitary tumor resection at another hospital, and the histopathological diagnosis was ‘‘pituitary tumor with inflammatory response.’’ The patient had no significant medical history, menarche at age 16, and regular cycles until March 2004. Physical examination was normal except for left eye ptosis and adduction limitation, and bilateral milky nipple discharge. Routine laboratory tests and T3, T4, TSH, LH, FSH, E2, prolactin, ACTH, cortisol, and 24 h urinary free cortisol were within normal limits. Thyroid autoantibodies (TGAb and TPOAb) and TSH receptor antibody were negative. Magnetic resonance imaging (MRI) showed abnormal, enhancing, irregular soft tissue signals with unclear boundaries in the sellar region and suprasellar cistern. Histopathological examination revealed lymphocyte, histiocyte, and neutrophil infiltration in the pituitary tissue, consistent with LyH. High dose methylprednisolone pulse therapy (HDMPT) was begun, and her symptoms rapidly improved. MRI showed the pituitary significantly reduced in size and the lesions had disappeared. The patient was asymptomatic until December 2005 when she experienced headaches, diplopia, and nausea and vomiting. MRI showed normal hypothalamic and pituitary morphology, and abnormal enhancement on the right side of the dorsum sellae and near the tentorium cerebelli. She was treated with azathioprine 100 mg/day for 16 weeks, and prednisone 30 mg/ day (decreased 5 mg/week until withdrawal). After treatment, she experienced regular menstrual cycles and conceived spontaneously in April 2009. Her pregnancy and delivery were uneventful with no LyH relapse during pregnancy or to date. The natural course of LyH can include sellar massoccupying effects, pituitary disorders, diabetes insipidus, and hyperprolactinemia [1]. MRI findings are not specific enough to distinguish LyH from pituitary adenomas; thus careful correlation with clinical and laboratory findings is critical [1]. Transsphenoidal resection of pituitary lesions, drugs (corticosteroids, azathioprine, and methotrexate), and radiotherapy have all been used to treat LyH; however, none are effective in all cases [1, 2]. Lecube et al. [3] first reported the successful treatment of LyH using azathioprine in a patient who failed corticosteroid treatment, and subsequently other authors have reported success with azathioprine [4]. Lymphocytic hypophysitis (LyH) is significantly correlated with pregnancy; of 210 reported cases in females, 120 (57%) occurred during pregnancy or the postpartum period, primarily in the final month of pregnancy or first 2 months postpartum [5]. If onset is during pregnancy, complications or adverse effects on the fetus are unlikely, and the condition may gradually resolve after delivery. A history of pregnancy-related LyH is not associated with relapse Z. Lu and G. Yang contributed equally.

Successful Multidrug Treatment of a Pediatric Patient with Severe Churg-Strauss Syndrome Refractory to Prednisolone

Churg-Strauss syndrome (CSS), which is characterized by systemic small-vessel vasculitis of unknown etiology, is associated with a history of asthma. Although reports of CSS occurring in children are limited, effective treatment of pediatric patients with severe CSS remains challenging. A 10-year-old Japanese boy with a 6-month history of asthma treated with a leukotriene modifier, pranlukast, developed high fever, pleural infiltration, and pericarditis that were associated with marked hypereosinophilia (10,350 eosinophils/µl). Owing to his persistent high fever, mononeuritis multiplex, and severe abdominal pain that was refractory to prednisolone, his general condition progressively deteriorated thereafter. Although intravenous high-dose immunoglobulin administration was transiently effective for mononeuritis multiplex, the recurrent high fever and severe abdominal pain remained refractory. An endoscopic study revealed ulcerative lesions of the total colon. In this context, we treated the patient with an aggressive multidrug immunosuppressive regimen consisting of a high-dose methylprednisolone pulse plus short-course intravenous cyclophosphamide pulse therapy, followed by oral tacrolimus combined with prednisolone. After the rescue multidrug treatment, his severe clinical signs dramatically subsided within a short time, and the concomitantly administered prednisolone was successfully tapered without flare. At present, 12 months after the presentation, he is free from CSS signs or therapy-related toxicity except for an occasional mild asthma attack. Although further close observation should be needed to draw a long-term outcome in this patient, we believe that aggressive multidrug immunosuppressive treatment should be considered as an alternative rescue treatment in selected patients with severe CSS, even with pediatric-onset disease, that is refractory to prednisolone.

Recurrent autoimmune hypophysitis successfully treated with glucocorticoids plus azathioprine: a report of three cases

Recurrent autoimmune hypophysitis is a rare autoimmune endocrine disease involving lymphocytic infiltration and chronic pituitary inflammation. It is even more rare than primary hypophysitis. The objective of the study was to evaluate the efficacy of glucocorticoid treatment combined with azathioprine for treating three cases of recurrent autoimmune lymphocytic hypophysitis encountered within a two-year period. The clinical features and follow-up data of these cases were analyzed, including results of treatment with glucocorticoids combined with azathioprine. All three patients were female and presented with the following clinical characteristics: case 1 was a 22-year-old with headache and diplopia; case 2 was a 70-year-old with dry mouth, polydipsia, and polyuria; case 3, a 32-year-old, with polydipsia, polyuria and menstrual disorders with headache and dizziness. Regarding recurrence, case 1 recurred 4 months after surgery and again 14 months after discontinuing prednisone; case 2 relapsed 16 months after receiving high-dose methylprednisolone pulse therapy; and case 3 recurred during the period of prednisone dose reduction. The patients were treated with glucocorticoids plus azathioprine, and positive responses were seen in all three cases. Symptoms were relieved, and MRI revealed significant reduction of lesions during follow-up. Pituitary function resumed in cases 1 and 3; permanent hypopituitarism was present in case 2. At last follow-up, MRI showed no further recurrence of disease in any patient. Treatment and responses of these patients with autoimmune hypophysitis suggest that glucocorticoid therapy combined with azothioprine is effective treatment for recurrent autoimmune hypophysitis. Endocrine and radiologic studies are an essential part of follow-up.

TLR recognition of self nucleic acids hampers glucocorticoid activity in lupus

Glucocorticoids are widely used to treat patients with autoimmune diseases such as systemic lupus erythematosus (SLE). However, regimens used to treat many such conditions cannot maintain disease control in the majority of SLE patients and more aggressive approaches such as high-dose methylprednisolone pulse therapy are used to provide transient reductions in disease activity. The primary anti-inflammatory mechanism of glucocorticoids is thought to be NF-kappaB inhibition. Recognition of self nucleic acids by toll-like receptors TLR7 and TLR9 on B cells and plasmacytoid dendritic cells (PDCs) is an important step in the pathogenesis of SLE, promoting anti-nuclear antibodies and the production of type I interferon (IFN), both correlated with the severity of disease. Following their activation by self-nucleic acid-associated immune complexes, PDCs migrate to the tissues. We demonstrate, in vitro and in vivo, that stimulation of PDCs through TLR7 and 9 can account for the reduced activity of glucocorticoids to inhibit the IFN pathway in SLE patients and in two lupus-prone mouse strains. The triggering of PDCs through TLR7 and 9 by nucleic acid-containing immune complexes or by synthetic ligands activates the NF-kappaB pathway essential for PDC survival. Glucocorticoids do not affect NF-kappaB activation in PDCs, preventing glucocorticoid induction of PDC death and the consequent reduction of systemic IFN-alpha levels. These findings unveil a new role for self nucleic acid recognition by TLRs and indicate that inhibitors of TLR7 and 9 signalling could prove to be effective corticosteroid-sparing drugs.

A Case of Giant Cell Granulomatous Hypophysitis with Recurrent Hypoosmolar Hyponatremia

A 39-year-old woman presented with a 20 day history of recurrent hypoosmolar hyponatremia. Because her volume status seemed to be normal, the most suspected causes of her hyponatremia were adrenal insufficiency and hypothyroidism. Endocrinologic examination, including a combined pituitary function test, showed TSH and ACTH deficiency without GH deficiency, and hyperprolactinemia was also present. Sella MRI showed a pituitary mass, stalk thickening and loss of the normal neurohypophysial hyperintense signal on the T1 weighted image. Pathologic exam demonstrated granulomatous lesions and Langhans' multinucleated giant cells with inflammatory cell infiltration. After high dose methylprednisolone pulse therapy (1 g/day for 3 days) with subsequent prednisolone and levothyoxine replacement, there was no more recurrence of the hyponatremia. The sella MRI on the 6th month showed decreased mass size, narrowed stalk thickening and the reappearance of the normal neurohyphophysial hyperintense signal. She is currently in a good general condition and is receiving hormone replacement therapy.

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.

Precordial T-wave inversion of “cardiac memory” pattern after high-dose methylprednisolone pulse therapy

‘‘Cardiac memory’’ (CM) refers to T-wave abnormalities that manifest on resumption of a normal ventricular activation pattern after a period of abnormal ventricular activation, such as ventricular pacing, transient left bundlebranch block, ventricular arrhythmias, or Wolf–Parkinson– White syndrome [1]. Pacing-induced T-wave inversion (TWI), the most common clinical example of CM, is usually localized to precordial and inferior leads [1, 2]. Postpacing CM often produces striking precordial TWI that may persist for long periods of time after the pacing is discontinued, thus obscuring their causal relationship. As a result, TWI due to CM represents an important confounder in the diagnosis of myocardial infarction [2, 3]. Diagnostic features to differentiate by vector direction analysis pacinginduced CM from TWI that results from ischemia and infarction have been described only recently: the combination of (a) positive TaVL, (b) positive or isoelectric TI, and (c) maximal precordial TWI [ TWIIII was 92% sensitive and 100% specific for CM, discriminating it from ischemic precordial TWI [4]. The use of corticosteroids with caution is recommended in patients with congestive heart failure because long-term use has been associated with fluid retention and hypertension. Potentially severe side effects of high-dose pulse corticosteroid therapy are noted. Problems included arrhythmias, myocardial infarctions, and sudden death [5]. In one early report, most of the patients had underlying renal disease and/or were undergoing renal transplantation; all of the patients having the cardiovascular reactions associated with the corticosteroid received individual doses of at least 250 mg of methylprednisolone or its equivalent. However, cause–effect relationship between high-dose corticosteroid therapy and severe cardiovascular reactions has not been scientifically proven by a controlled trial [6]. Severe complications of pulse methylprednisolone, mainly cardiovascular, are strongly related to underlying comorbidities. In one recent study of 146 consecutive patients treated by three pulses of 250, 500 or 1,000 mg/day methylprednisolone for various eye diseases, 88.4% had one ore more side effect(s), mainly transient and of mild intensity; myocardial ischemia was observed in 2.1% with known coronary insufficiency or high cardiovascular risk; blood pressure levels of at least 180/110 mmHg were recorded in 3.4%; bradycardia occurred in 14 patients (9.7%), with symptomatic in one patient [7]. We report a case of a young adult who developed atypical angina at rest associated with precordial ECG changes with TWI after a 4 days pulse methylprednisolone therapy. On May 20, 2007, the 26-year-old man was admitted because of the feeling of a lump of gradual onset in the throat and with pain radiating to the jaw. There was no chest discomfort. Symptoms were constantly present, aggravated by swallowing but otherwise independent of daily activities and neither worsened by respiration nor exacerbated when lying down. There were no associated complaints like belching, vomiting, diaphoresis, dyspnea, syncope or palpitation. Five days before, on May 15, a 4 days course of high dose methylprednisolone therapy of 1,000 mg per day intravenously had been initiated for the treatment of idiopathic orbital inflammatory syndrome (IOIS) also known as J. Rottensteiner A. Kaneppele I. Stockner G. Panizza C. J. Wiedermann (&) Division of Internal Medicine 2, Department of Internal Medicine, Central Hospital of Bolzano, Lorenz Bohler Street 5, 39100 Bolzano (BZ), Italy e-mail: christian.wiedermann@asbz.it

Effect of High Dose Methylprednisolone Pulse Therapy Followed by Oral Prednisolone Administration on the Production of Anti-TSH Receptor Antibodies and Clinical Outcome in Graves' Disease

Little is known about the immunosuppressive effect of glucocorticoids on TSH receptor antibodies. We observed the long-term prognosis and serum TSH binding inhibitor immunoglobulin (TBII) levels in patients with Graves' ophthalmopathy who had received intravenous methylprednisolone pulse therapy (pulse therapy) followed by oral prednisolone administration in order to ascertain how long the immunosuppressive effect of glucocorticoids continued. This is the first report on the effect of pulse therapy on Graves' disease outcome. We observed 67 patients who were treated by antithyroid drugs (ATD) alone for 2 years after pulse therapy. TBII was evaluated before and 3, 6, 12, 18, and 24 months after pulse therapy. The mean TBII decreased significantly 3 months after pulse therapy (p<0.001), and was maintained until 24 months. There were 24 patients whose TBII was positive (>15%) at 24 months, in whom the mean TBII decreased significantly 3 to 6 months after pulse therapy (p<0.001), but increased again at 12 to 24 months (p<0.05). Thus, the immunosuppressive effect of glucocorticoids may be lost at 12 months after pulse therapy in these patients. The remission rate in the pulse therapy group was 40.98%, and that of the control patient group was 48.57%. There was no significant difference between the two. These results suggest that the immunosuppressive effect of pulse therapy was temporary, and that pulse therapy did not increase remission rate of Graves' disease.

High-Dose Pulse Corticosteroid Therapy in the Treatment of Severe Alopecia areata

Objective: The present monocenter prospective study was designed to evaluate the efficacy of intravenous high-dose methylprednisolone pulse therapy in patients with severe alopecia areata (AA). Methods: 30 patients (aged 14–56 years) were treated with methylprednisolone (8 mg/kg body weight) intravenously on 3 consecutive days at 4-week intervals for at least 3 courses. Results: 67% of patients with AA plurifocalis showed >50% regrowth of hair. None of the patients with AA totalis or universalis and only 1 patient with ophiasic AA responded to therapy. In patients with AA plurifocalis, higher response rates could be observed in those suffering from long-term disease compared to patients treated during their first episodes of AA (73 vs. 57%). Conclusion: High-dose methylprednisolone pulse therapy is an effective and well-tolerated treatment for patients with severe AA plurifocalis but might be less beneficial for patients with ophiasic AA, AA totalis or universalis.

Methylprednisolone pulse療法およびrhG-CSF投与により改善したstreptomycinが原因と考えられた重症型再生不良性貧血

Methylprednisolone pulse療法およびrhG-CSF投与により改善したstreptomycinが原因と考えられた重症型再生不良性貧血

D-Penicillamine Induced Pemphigus Treated with Methylprednisolone Pulse Therapy

A patient with severe rheumatoid arthritis received d-penicillamine treatment for 16 months. She developed mild pruritus 6 months after d-penicillamine initiation, and severe pemphigus 10 months after d-penicillamine was changed to azathioprine. Subsequent methylprednisolone pulse therapy resulted in a transient clinical remission of pemphigus. A literature review of d-penicillamine induced pemphigus and high dose methylprednisolone pulse therapy is presented.

Glucocorticoid receptors in glioblastoma multiforme: a new approach to antineoplastic glucocorticoid therapy.

Glucocorticoid receptors were measured in tissue samples from 12 patients with glioblastoma multiforme. The receptor was found in all patients. The concentration of glucocorticoid receptor was found to be high in the periphery of the tumour, low in the surrounding brain tissue and low in the central part of the tumour in 6 of the patients. The possible role of the glucocorticoid receptor distribution in relation to growth regulation is discussed. A decreasing receptor concentration found at reoperation in two patients indicates a possible antineoplastic effect of high dose methylprednisolone pulse therapy on glucocorticoid receptor positive glioblastomas.