Mizoribine pulse therapy for a pediatric patient with steroid-resistant nephrotic syndrome

A 12-year-old Japanese boy was referred to our hospital with a 2-month history of persistent proteinuria. Despite urinary protein excretion in the nephrotic range, associated with hypoproteinemia, the patient did not complain of any disability. A percutaneous renal biopsy revealed minor glomerular abnormalities, without any evidence of immune complex deposition. Therapy with prednisolone (60 mg/day) was initiated, and while the proteinuria decreased after 4-week therapy, elevated urinary protein excretion persisted thereafter, at 1-2 g/day. Because of the steroid-resistant proteinuria, mizoribine (MZR), was started at 150 mg/day (3 mg/kg), administered as a single daily dose an immunosuppressive agent, in combination with prednisolone. Although there was some fluctuation in the urinary protein excretion, heavy proteinuria persisted for the next 4 weeks. The peak blood level of MZR was 0.9 microg/ml. Since we have previously reported the efficacy and safety of oral MZR pulse therapy, which is associated with higher peak serum MZR levels than conventional MZR therapy in selected patients with lupus nephritis, we adopted MZR pulse therapy for this patient, after obtaining informed consent. MZR was started at the daily dose of 300 mg (6 mg/kg), administered as a single dose before breakfast, twice a week (on Monday and Thursday). The peak blood level of MZR then increased to 1.29 microg/ml. Thereafter, despite a gradual reduction of the concomitantly administered prednisolone dose, the urinary protein excretion decreased rapidly to around 0.3 g/day and remained at this level thereafter. No adverse effects of MZR were observed. Based on these clinical observations, we suggest that oral MZR pulse therapy may be the treatment of choice in selected patients of steroid-resistant nephrotic syndrome, in addition to those of lupus nephritis.     

氮芥联合低分子肝素治疗难治性肾病综合征的临床观察

【目的】观察氮芥联合低分子肝素（LMWH）治疗难治性肾病综合征的疗效。【方法】28例难治性肾病综合征患者予盐酸氮芥静脉注射，由1mg开始，隔日注射1次，每次加量1mg，至5mg后每周注射2次，累积量达1．5～2．0mg／kg体重（约80～100mg）后停药；联合低分子肝素5000u皮下注射，1日两次。【结果】总有效率85．7％，治疗期间无严重不良反应，治疗前后尿量、尿蛋白、血浆白蛋白、总胆固醇、甘油三酯均有显著变化（P＜0．05）。伴肾功能不全者肾功能均恢复正常。【结论】氮芥联合低分子肝素治疗难治性肾病综合征安全有效。     

Cyclosporine versus azathioprine therapy in high-risk idiopathic membranous nephropathy patients: A 3-year prospective study

There is no consensus regarding the modality of therapy for idiopathic membranous nephropathy (IMN), especially for patients who did not react to treatment with cytotoxic drugs. This study followed prospectively for 3-year IMN patients who did not react to Ponticelli protocol comparing effects of 2-year course of cyclosporine (CsA) with azathioprine (Aza) treatment both with small doses of prednisolone. Twenty-three patients were randomly assigned to receive either cyclosporine at 3 mg/kg per day (10 patients) or azathioprine at 1.5 to 2 mg/kg (13 patients). Both groups were comparable regarding age, sex and renal function, except for proteinuria, which was significantly greater in CsA group (P = 0.003). Similar rate of remission of nephrotic syndrome (NS) have been noted at the end of treatment (80% CsA versus 93% Aza). During last year, follow-up relapses of NS were more frequent in Aza group (5 versus 1). A fall in proteinuria was recorded in both groups during treatment, but it rose significantly in Aza group (1.5 g/day versus 3.1 g/day, P = 0.04) and remained unchanged in CsA group (3.9 g/day versus 4.1 g/day) after treatment cessation. Renal function deteriorated in Aza group (sCr 120.5 versus 269.8 μmol/L; P < 0.01) and was stable in CsA group. In conclusion, CsA and steroids may be a very important option in the management of high-risk IMN patients. Long-term treatment is necessary for achievement of full therapeutic effect. Treatment with Aza did not have long-term benefits particularly regarding renal function preservation.     

小剂量环孢素A联合小剂量激素治疗原发性肾病综合征疗效观察

目的 观察小剂量环孢素A（CsA）联合小剂量强的松在原发性肾病综合征治疗中的疗效、不良反应及其与足量强的松的比较.方法 67例原发性肾病综合征均经肾活检病理检查证实,前瞻性非随机观察18个月以上.治疗组（n=41）：小剂量CsA联合小剂量强的松,其中难治性肾病综合征8例,强的松0.5 mg· kg-1·d-1 ＋CsA 2.5 mg·kg-1·d-1,强的松最大剂量30 mg/d,连服2～3个月后每隔2～4周强的松、CsA在原剂量基础上交替递减10％或持续应用原剂量.对照组（n=26）：足量强的松组,强的松1.0 mg·kg-1·d-1,强的松最大剂量60 mg/d,连服2～3个月后每隔2～4周在原剂量基础上递减10％.其中10例联合环磷酰胺（CTX）治疗,CTX0.8 g·次-1·月-1,加入生理盐水500 ml静脉滴注,或口服0.1 g/d,CTX总量6.0～8.0g.观察两组治疗前、治疗3、6、9、12、18个月24h尿蛋白定量（MTP）、肝功能（TP、ALB、ALT）、肾功能（Cr、UA）、血糖、血脂（TC、LDL）及不良反应.结果 两组患者治疗后MTP及ALB水平较治疗前均明显好转（P＜0.01）,治疗18个月后治疗组和对照组总有效率（显效＋有效）分别为80.5％和84.6％,两组间无统计学差异（P＞0.05）.治疗组12个月时完全缓解率有升高趋势（P＜0.01）,但18个月后又降至正常,28例显效患者18个月后停CsA随访3年中有5例（17.9％）复发,复发后再次治疗仍然有效.治疗组不良反应：齿龈增生1例,血压升高4例,血尿酸升高6例,停药后或用药均可控制.结论 与足量强的松治疗原发性肾病综合征比较,小剂量CsA联合小剂量强的松具有等同疗效,又可减少CsA及激素毒副作用,为治疗原发性肾病综合征提供了一个比较经济有效安全的方法.     

他克莫司替代环孢素A为基础方案治疗不同病理类型慢性移植肾肾病:有效性和安全性

背景:研究证实以他可莫司代替环孢索A的免疫抑制方案能够改善移植肾的功能,提高移植肾的牛存率,但国内外尚未报道这种以他可莫司联合霉酚酸酯为主的免疫抑制方案是否对所有病理类型的慢性移植肾肾病(chronic allograft nephropathy,CAN)都有相同或相似临床有效性.目的:观察以他可莫司联合霉酚酸酯为基础的免疫抑制方案对不同病理类型CAN的有效性和安全性.方法:59例接受尸体供肾移植患者,移植后均接受以环孢素A为主的免疫抑制方案;经病理证实和分型后分为2组:CAN伴慢性排斥组(n=31)和CAN不伴慢性排斥组(n=28).所有患者在被病理证实为CAN时,立即停止环孢素A,转换为他可莫司联合霉酚酸酯为主的免疫抑制方案,他可莫司的起始剂量为0.08 mg/(kg·d),其目标血药质量浓度为5～8 μg/L.,霉酚酸酯按固定剂量1.0 g/d,2次/d.根据患者的自身情况和药物的副作用调整药物剂量.随访期间,所有患者血肌酐、总胆固醇、三酰甘油和低密度脂蛋白、24 h蛋白尿和肾小球滤过率及并发症发生情况.结果与结论:59例患者均进入结果分析.随访6个月后,CAN伴慢性排斥组和CAN不伴慢性排斥组患者血肌酐、总胆同醇、三酰甘油和低密度脂蛋白和24 h蛋白尿均较转换前明显降低(P<0.05),CAN伴慢性排斥组更明显(P<0.05),两组肾小球滤过率均明显升高(P<0.05).CAN伴慢性排斥组中20例患者好转,7例患者稳定,4例患者无效;CAN不伴慢性排斥组中9例患者好转,15例患者稳定,4例患者无效.两组有效率分别为64.5%,32.1%,差异有显著性意义(P<0.05).与转换前相比较,患者高血压的发病率和高脂血症的发病率有显著性下降(P<0.05),而糖尿病、机会性感染和恶性肿瘤的发病率无统计学意义.提示以他可莫司联合霉酚酸酯为基础的免疫抑制方案可以显著性的改善CAN患者移植肾肾功能,尤其是对CAN伴慢性排斥反应患者.     

Efficacy of a loading dose of oral chloroquine in a 36-hour treatment schedule for uncomplicated plasmodium falciparum malaria.

The efficacy of a loading dose of 20 mg of chloroquine per kg of body weight per os given at intervals during the first day was evaluated in 27 patients in Madagascar with Plasmodium falciparum malaria. The conventional regimen of 25 mg/kg over 3 days (schedule 1) was thus compared with a regimen of 30 mg/kg over 2 days (schedule 2; one dose of 10 mg/kg followed by two doses of 5 mg/kg at 6-h intervals on the first day and two doses of 5 mg/kg at 12-h intervals on the second day) in terms of their clinical and parasitological efficacies, tolerance, and drug concentration-time curves. At 24 h schedule 2 gave higher chloroquine levels in blood, which induced a more rapid decrease in parasitemia. The time required for a 50% decrease in the initial parasitemia was shorter in patients on schedule 2 (14.3 +/- 1.6 h) than it was in patients on schedule 1 (35.5 +/- 5.4 h; P less than 0.01). Moreover, negative blood smears were obtained more rapidly with schedule 2 (50.8 +/- 3.7 h) than with schedule 1 (72 +/- 8.7 h). As predicted by the drug concentration-time curve, no high, potentially toxic peak drug concentration appeared and no adverse effects were observed with the loading dose regimen (schedule 2). These findings support the idea that a loading dose of 20 mg/kg given at intervals during the first 12 h is well tolerated and can be used to obtain a more rapid decrease in parasitemia and to shorten the treatment time of uncomplicated chloroquine-susceptible falciparum malaria in the field.     

Renal biopsy findings in children receiving long-term treatment with cyclosporine a given as a single daily dose

Long-term treatment of childhood nephrotic syndrome (NS) and rheumatic diseases with cyclosporine A (CsA) given as a single daily dose may yield better results and allow safer use of the drug than the conventional twice-daily dosing. However, the safety of such long-term treatment from the histological standpoint remains to be established. Posttreatment renal biopsy was conducted in a total of eight children (5 with minimal change NS, 2 with focal segmental glomerulosclerosis and 1 with X-linked immune dysregulation, polyendocrinopathy and enteropathy) receiving CsA as a single daily dose, after a mean treatment duration of 20 months (9-36 months). The initial daily dose of CsA (Neoral) was 2.0 mg/kg, given as a single daily dose before breakfast. The dose was subsequently adjusted to achieve a peak (between 1 and 2 hrs post-dosing, C1-C2) blood level of around 800 ng/ml. The mean daily CsA dose, mean C1-C2 blood level, and mean trough blood level in the subjects were 1.9 +/- 0.6 mg/kg, 803.8 +/- 117.2 ng/ml and 36.1 +/- 12.7 ng/ml, respectively. The result revealed no evidence of CsA-related nephrotoxicity, including arteriopathy, striped interstitial fibrosis or tubular atrophy, in any of the study participants. Also, no significant changes were observed in the mean estimated glomerular filtration rate as compared to the pretreatment values (127.6 +/- 14.9 ml/min/1.73 m(2) vs 115.6 +/- 22.8 ml/min/1.73 m(2), and except for mild hypertrichosis, no significant adverse effects of CsA were observed. These findings lend further support to the safety of long-term low-dose CsA treatment (median treatment duration in this study, 20 months), with the drug administered as a single daily dose while maintaining a peak (C1-C2) blood level of around 800 ng/ml.     

Nephrotic syndrome and acute interstitial nephritis associated with the use of diclofenac.

Commonly reported renal complications of non-steroidal anti-inflammatory drugs (NSAID) include acute renal failure and/or acute interstitial nephritis; in rare cases a nephrotic syndrome was also observed. In most cases this was due to the development of secondary membranous nephropathy. Following withdrawal of the drug the nephrotic syndrome usually resolved rapidly. We report a 65-year-old woman who developed a nephrotic syndrome and acute renal failure during 6 months of treatment with the NSAID diclofenac. Renal biopsy revealed both, membranous nephropathy and interstitial nephritis. After discontinuation of diclofenac and treatment with prednisone 1 mg/kg/day, furosemide 400 mg/day and simvastatin at a dose of 20 mg/day, creatinine clearance gradually increased and after 5 months of treatment complete remission of the nephrotic syndrome was observed.     

Long-term azathioprine therapy in two children with steroid-dependent minimal-change nephrotic syndrome.

Long-term azathioprine therapy as an alternative treatment to cyclophosphamide was done in 2 children with steroid-dependent minimal-change nephrotic syndrome (MCNS). They had already been treated with prednisolone, intravenous methyl-prednisolone pulse therapy, cyclophosphamide and mizoribine. Although cyclophosphamide had been proved to be effective in maintaining their remission, the cumulative dose of the agent limited another course of cyclophosphamide therapy. Since ciclosporine therapy is much expensive, a trial of azathioprine (2 mg/kg per day) was started, and the therapy resulted in inducing sustained remission and reducing prednisolone. The patients were well tolerated the long-term azathioprine therapy over a year. Although the efficacy of azathioprine in the management of childhood MCNS might be restricted, we therefore suggest that this agent should be reconsidered as an alternative treatment to cyclophosphamide.     

Cyclosporin therapy in minimal change nephritis

In 5 cases with minimal change nephritis Cyclosporine A has been added to the conventional steroid therapy, when relapse of nephrotic syndrome occurred while reducing the daily prednisolone dose. The intended cyclosporine trough level ranged from 250 ng/ml to 450 ng/ml whole blood, estimated by the RIA method. Proteinuria disappeared in 4 out of the 5 cases, in the other one urinary protein excretion was strikingly reduced. In the 4 cases with complete remission of proteinuria prednisolone was tapered. These patients have cyclosporine A as the sole immunosuppressive drug since 56 weeks and do not show proteinuria. Side effects of cyclosporine therapy have been slight deterioration of kidney function in 2 out of the 5 cases and the occurrence of hypertension in 4 patients.     

Transfer of Aminonucleoside Nephrosis by Renal Transplantation

The pathogenesis of aminonucleoside of puromycin (PA) nephrotic syndrome in rats was studied using renal transplantation to separate systemic from renal factors. The nephrotic syndrome was transferred by transplantation of kidneys from rats with established proteinuria. Bilaterally nephrectomized normal rats receiving kidneys removed as early as 15 min after intravenous PA injection (100 mg/kg) of donors also developed proteinuria (602+/-125 mg/24 hr) and a nephrotic syndrome after the usual induction period of 4-7 days observed in this disease. Arterial perfusion of isolated kidneys with PA (50 mg/kg) followed by perfusion with isotonic saline 3 min later and then transplantation to normal bilaterally nephrectomized rats led to a nephrotic syndrome. Urine protein excretion was 494+/-42 mg on the 7th day after transplantation. In contrast, urine protein excretion after transplantation of normal kidneys to normal bilaterally nephrectomized rats was 40+/-20 mg on the 7th day. Exposure of a normal kidney to a nephrotic host environment by transplantation of a normal kidney to a unilaterally nephrectomized PA-injected rat did not transfer the disease to the normal kidney. After removal of the nephrotic kidney 11-13 days after transplantation, proteinuria of the donor kidney was normal (21+/-13 mg on day 15). These studies indicate that pathogenesis of aminonucleoside nephrosis involves programming of the kidney directly by PA within minutes after exposure although increased urinary protein excretion does not occur until several days later.     

肾移植受者CYP3A5基因多态性对他克莫司血药浓度及疗效的影响

背景:关于欧美人群中CYP3A5基因与他克莫司血药浓度之间关系已有报道,然而这些研究的数据多来自于移植后1个月~1年,缺乏移植后早期的资料.目的:探讨CYP3A 基因多态性与肾移植受者他克莫司血药浓度的关系,分析CYP3A5基因型对肾移植后排斥反应和毒性及不良反应的影响.方法:按CYP3A5基因多态性将45例采用他克莫司+霉酚酸酯+泼尼松三联免疫抑制方案的肾移植患者分为*1/*1型组(11例)、*1/*3型组(15例)和*3/*3型组(19例),他克莫司初始剂量均为0.15 mg/(kg·d),1周后根据目标浓度调整他克莫司剂量.结果与结论:术后7 d,1个月,3个月* 3/* 3型组他克莫司血药浓度/剂量比显著高于* 1/*3型组和*1/*1型组(P < 0.05) ;3个月内*1/*1型组急性排斥反应的比例显著高于*1/*3型组和*3/*3型组(P < 0.05).3个月内*3/*3型组高血糖、神经及肾毒性等不良反应显著高于*1/*1型组.结果可见*1/*1基因型患者在肾移植早期难以达到有效目标血药浓度,使该组3个月内的急性排斥反应发生率明显升高,不合适采用目前他克莫司的初始剂量方案作为早期的抗排斥反应方案;*3/*3基因型患者他克莫司血药浓度明显升高,使3个月内毒性及不良反应发生率也明显升高.因此,根据CYP3A5 基因多态性作为他克莫司个体化用药的依据,既能使* 1 /* 1型患者早期急性排斥反应的发生率下降,又能使* 3 /*3型患者的药物不良反应减少,提高肾移植的临床效果.     

Chromosomal aberrations in lymphocytes of patients with systemic lupus erythematosus during cytostatic therapy

AIM: To study cytogenetics of peripheral blood lymphocytes in patients with systemic lupus erythematosus (SLE) in the course of therapy with a selective immunodepressant sandimmun and universal cytostatic cyclophosphamide. MATERIAL AND METHODS: 30 women with lupus-nephritis and nephrotic syndrome received sandimmun in a dose 2.5-7 mg/kg plus 10-20 mg prednisolone for a month with gradual lowering of sandimmun dose to 2.5-5 mg/kg and prednisolone to 0-10 mg/day. 10 patients with lupus-nephritis were given cyclophosphamide in a dose 1000 mg as a single intravenous drip once a month for 6 months in combination with 30-40 mg prednisolone for a month with the dose reduction to 20 mg/day. Sandimmun and cyclophosphamide effects on mutagenesis were studied in 72-120-h PHA-stimulated lymphocyte cultures. Chromosomal aberrations (CA) were assessed according to A.F. Zakharov's classification and proposals of International workshop in Melburn (1993). RESULTS: Sandimmun therapy on day 14 did not increase CA frequency but led to appearance of "premature chromosome condensation phenomenon" (PCC). PCC diminished after one month of sandimmun therapy and disappeared after 3-6 months. Cyclophosphamide provoked a rise in the incidence of both chromatide aberrations and CA. CONCLUSION: Sandimmun does not increase CA incidence in lymphocytes. On the contrary, it promoted the fall in this incidence while syclophosphamide stimulated CA and chromatide aberrations. This trend was observed till the end of cyclophosphamide administration.     

High-dose ibuprofen for patent ductus arteriosus in extremely preterm infants: a randomized controlled study

Our aim was to assess the hypothesis that a high-dose regimen of ibuprofen is more effective than the standard-dose regimen in closing patent ductus arteriosus (PDA) without increasing adverse effects. Infants of gestational age <29 weeks, with respiratory distress syndrome (RDS) and echocardiographic evidence of significant PDA at 12-24 h of life, were randomized to receive a standard (10-5-5 mg/kg/day) or high-dose (20-10-10 mg/kg/day) course of ibuprofen. We studied 70 infants, 35 of whom received the standard dose of ibuprofen and the other 35 the high dose. Of the infants treated with the standard-dose regimen, 37% had persistent PDA as compared with 14% of those treated with the high-dose regimen (P = 0.03). No differences in the occurrence of adverse effects were observed between the two groups. The high-dose ibuprofen regimen is more effective than the standard-dose regimen in closing PDA in preterm infants <29 weeks of gestation without increasing the adverse effect rate.     

Treatment of Idiopathic Membranous Nephropathy. Is the Anti-CD20 Antibody Rituximab a Reasonable Option?

BACKGROUND: Membranous nephropathy (MN) is characterized by proteinuria and other symptoms of the nephrotic syndrome. In many cases, the etiology is unknown. Whether and how to treat MN is still a controversial question. Despite the use of corticosteroids and alkylating agents, up to 40% of patients still progress to end-stage renal failure. CASE REPORT: A 40-year-old male patient with biopsy-proven idiopathic MN was initially treated with prednisolone and chlorambucil because of a proteinuria of 22 g/d. Treatment with cyclosporine was started because the nephrotic syndrome failed to improve. Proteinuria was reduced to a minimum of 4 g/d. Cyclosporine was stopped after 17 months leading to a fast relapse. Therapy with an ACE inhibitor and AT(1) receptor antagonist and retreatment with cyclosporine improved proteinuria. Cyclosporine was terminated after a total of 24 months. 5 months later, relapse occurred with a high proteinuria of 34 g/d. The monoclonal anti-CD20 antibody rituximab (375 mg/m(2)) was given four times every 4 weeks. 4 weeks and 4 months after the end of treatment, proteinuria decreased to 780 mg/d and < 150 mg/d, but renal function remained impaired (creatinine clearance 65 ml/min, stage 2 according to K/DOQI). Now, remission of proteinuria (< 150 mg/d) has been stable for almost 2 years. However, renal insufficiency progressed further (creatinine clearance 45 ml/min, stage 3 according to K/DOQI). CONCLUSION: Rituximab offers the possibility for a targeted treatment of idiopathic MN. Based on the existing evidence and experience from this case, rituximab can be recommended as a new treatment option for MN, possibly before starting any treatment with cytotoxic agents and high-dose prednisolone carrying the risk of severe side effects. However, long-term results of this treatment are still lacking.     

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.     

PFAPA syndrome mimicking familial Mediterranean fever: report of a Turkish child

The PFAPA (Periodic Fever, Aphthous stomatitis, Pharyngitis, Adenitidis) syndrome is characterized by periodic fever, adenitis, pharyngitis, and aphthous stomatitis. Herein, we present a Turkish child with PFAPA syndrome mimicking familial Mediterranean fever because of a rare presentation. A 9-year-old boy was admitted with recurrent fever, aphthous stomatitis, sore throat, headache, and general body pains, lasting 2 to 3 days since 3.5 years of age. He was completely symptom-free between the attacks. He was diagnosed as having familial Mediterranean fever according to the clinical findings when he was 6 years of age and Colchicum tablet was administrated. Despite colchicines therapy for 8 months, his attacks did not subside; therefore, the drug was discontinued. He had high fever, a painful cervical lymphadenopathy, aphthous stomatitis, and tonsillo-pharyngitis. The patient was then diagnosed as having PFAPA syndrome. He was given a single dose of prednisolone (0.35 mg/kg/dose). His complaints dramatically and completely disappeared 3 h after administration of the drug. During the 8^th month of follow-up, a similar febrile attack lasting only 1 day was noted and it was controlled with a single dose of prednisolone (0.5 mg/kg/day). At this writing the patient is in the 12^th month of follow-up, and there have been no symptoms after the second attack. In conclusion, our patient shows that PFAPA syndrome can be confused with familial Mediterranean fever. We also would like to emphasize that the typical PFAPA syndrome can be easily diagnosed by detailed history-taking and physical findings.     

Thrombopoietin receptor agonists in refractory immune thrombocytopenia: differential responses to eltrombopag and romiplostim: a case report and possible explanations

What is known and Objective: Although new thrombopoietin (TPO) receptor agonist drugs, such as romiplostim and eltrombopag, are highly effective and well tolerated for patients with immune thrombocytopenia (ITP) refractory to first‐line treatments such as prednisolone, the cross‐resistance of these two TPO receptor agonists is still unknown. Case summary: An 84‐year‐old Japanese female patient with steroid‐refractory ITP received eltrombopag with a gradually increasing dose schedule from 12·5 to 25 mg/day, 37·5 mg/day and finally 50 mg/day. As no increase in platelet count was observed even at the maximum dose of 50 mg/day, and eltrombopag‐related grade 3 elevation of aspartate aminotransferase was observed, another TPO receptor agonist, romiplostim, was administered at 1 μg/kg/week subcutaneously. A rapid increase in platelet count was observed 1 week after the first injection. The dose of romiplostim was escalated to 4 μg/kg according to the platelet count and a complete response was achieved 7 weeks after the first injection without any adverse events. What is new and Conclusion: The successful treatment of ITP refractory to eltrombopag with romiplostim strongly suggests that the absence of cross‐resistance between these two approved TPO receptor agonists and possible differences in mechanism of action. Further study of the mechanisms of action of TPO receptor agonists is called for along with further exploration of the potential of romiplostim in refractory ITP.     

A comparison of a standard-dose prednisone regimen and mycophenolate mofetil combined with a lower prednisone dose in chinese adults with idiopathic nephrotic syndrome who were carriers of hepatitis B surface antigen: A prospective cohort study

Background: When receiving immunosuppressive therapy, patients with idiopathic nephrotic syndrome who are also carriers of hepatitis B virus (HBV) surface antigen (HBsAg) are at risk for reactivation of HBV.Objective: This study compared the effectiveness and tolerability of a standard-dose prednisone regimen with those of the combination of mycophenolate mofetil (MMF) and a lower prednisone dose for the treatment of idiopathic nephrotic syndrome characterized by minimal-change nephropathy or slight mesangial proliferative glomerulonephritis in Chinese adults who were also carriers of HBsAg, a combination here termed MSNS-HBV.Methods: This was a prospective, open-label cohort study in Chinese adults with MSNS-HBV. Patients were self-assigned to 1 of 2 treatment groups: the standard prednisone regimen of 1 mg/kg daily or oral MMF 0.5 to 1.0 g BID combined with the lower pred-nisone dose of 0.5 mg/kg daily. The planned duration of treatment was 36 weeks, with an additional 60 weeks of follow-up. The primary outcome measures were rates of complete remission of idiopathic nephrotic syndrome (a decrease in daily proteinuria to within the normal range [<0.3 g]) and rates of HBV reactivation (detectable serum HBV DNA). Secondary outcome measures included relapse rates (>1+ albuminuria on dipstick urinalysis on 3 consecutive days), alanine ami-notransferase (ALT) elevations (>50 U/L), use of la-mivudine 100 mg/d (added if HBV DNA titers reached ≥10⁵ copies/mL), and adverse effects.Results: The intent-to-treat population included 41 patients (22 prednisone, 19 MMF). In patients who completed the study, rates of complete remission after 24 weeks of treatment were 78.9% (15/19) in the prednisone group and 76.5% (13/17) in the MMF group; 2 and 3 patients in the respective groups had a partial remission, and 2 and 1 patient had no response. HBV reactivation occurred in 63.6% (14/22) and 36.8% (7/19) of patients (P = 0.047). The only significant difference in the study was in the probability of HBV reactivation between groups (P = 0.043, log-rank test). During follow-up, at least 1 relapse occurred in 46.7% (7/15) and 30.8% (4/13) of patients. Elevations in ALT were observed in 36.4% (8/22) and 26.3% (5/19) of patients, and the addition of lamivu-dine was required in 40.9% (9/22) and 21.1% (4/19) of patients. The most frequent adverse effects in both groups were infections (27.3% and 26.3%), followed by gastrointestinal symptoms (13.6% and 21.1%). Two MMF patients developed leukopenia. One patient in the prednisone group discontinued treatment because of severe hepatitis, and 1 patient in the MMF group discontinued because of severe pulmonary infection.Conclusions: Among the adult Chinese patients with MSNS-HBV who completed this study, there were no significant differences in remission rates of idiopathic nephrotic syndrome between the standard prednisone regimen and the combination of MMF and a reduced prednisone dose. Rates of HBV reactivation, however, were significantly lower in the combination-therapy group.