Hemophagocytic lymphohistiocytosis triggered by relapsing polychondritis:A case report

BACKGROUND Hemophagocytic lymphohistiocytosis(HLH)is a rare,life-threatening disorder caused by abnormal histiocytes and T cell activation.In adults,it is predominantly associated with infections,cancers,and autoimmune diseases.Relapsing polychondritis(RP),another rare disease,is diagnosed based on symptoms without specific tests,featuring cartilage inflammation characterized by swelling,redness,and pain,rarely inducing HLH.CASE SUMMARY A 74-year-old woman visited the emergency room with a fever of 38.6℃.Blood tests,cultures,and imaging were performed to evaluate fever.Results showed increased fluorescent antinuclear antibody levels and mild cytopenia,with no other specific findings.Imaging revealed lymph node enlargement was observed;however,biopsy results were inconclusive.Upon re-evaluation of the physical exam,inflammatory signs suggestive of RP were observed in the ears and nose,prompting a tissue biopsy for confirmation.Simultaneously,persistent fever accompanied by cytopenia prompted a bone marrow examination,revealing hemophagocytic cells.After finding no significant results in blood culture,viral markers,and tissue examination of enlarged lymph nodes,HLH was diagnosed by RP.Treatment involved methylprednisolone followed by azathioprine.After two months,bone marrow examination confirmed resolution of hemophagocytosis,with normalization of hyperferritinemia and pancytopenia.CONCLUSION Thorough physical examination enabled diagnosis and treatment of HLH trig gered by RP in patients presenting with fever of unknown origin.

Uncharted Territory: Frequent Relapsing, Steroid Sensitive Secondary Minimal Change Nephrotic Syndrome Cause by Solid Tumor of the Gastro-Esophageal Junction —(Case Presentation and Review of the Literature)

We reported a biopsy proved case of minimal change nephrotic syndrome in a 72-year-old patient. The minimal change nephrotic syndrome has been steroid sensitive, but the patient had 7 relapses over a span of 5 years. Each time the dose of steroid is tapered, a relapse of the nephrotic syndrome occurred. Eventually, the patient was complaining of dysphagia and difficulty swallowing. Hospital work-up with barium swallow, endoscopy, and CT of the chest, abdomen and pelvis, revealed a focal stenotic lesion with mild to moderate esophageal dysmotility 7/15/2022. A diagnosis of an ulcerating lesion with biopsy confirmed a neuro-endocrine carcinoma of the gastro-esophageal junction was entertained. The CT of the chest/abdomen/pelvis, 7/19/2022, has shown, an esophageal mass of 5.1 × 5.6 × 7 cm of the gastro-esophageal junction with ulceration. No evidence of spread beyond the esophagus and stomach. The histology revealed a poorly differentiated neuroendocrine tumor of the gastro-esophageal junction. The patient underwent several rounds of chemotherapy, radiation, and surgery culminating in tumor control. His nephrotic syndrome was resolved after the tumor has been controlled by surgery and chemotherapy.

Diagnosis and management of relapsing pancreatitis associated with cystic neoplasms of the pancreas

One of the most important causes of relapsing pancreatitis is a cystic neoplasm of the pancreas. These low grade malignancies may cause pancreatitis by obstructing or communicating with a pancreatic duct. Patients with relapsing pancreatitis and a focal fluid fluid collection should be investigated for the possibility of a mucinous cystic neoplasm. Cross sectional imaging can provide a diagnosis with the imaging findings of a low attenuation cystic lesion containing mural calcification (CT scanning) or a lobular T2 enhancing lesion (MRCP). Endoscopic ultrasound can provide more detailed imaging with the ability to guide fine needle aspiration of the cyst fluid. Cyst fluid analysis can provide a diagnosis of a mucinous cystic lesion with the combination of cytology (mucinous epithelium), elevated carcinoembryonic antigen (CEA), and the presence of DNA mutations. Management of these patients consists of surgical resection and monitoring in patients not able to withstand surgery.

Relapsing polychondritis with p-ANCA associated vasculitis: Which triggers the other?

Relapsing polychondritis(RP) is a rare autoimmune disease with chronic inflammatory/destructive lesions of the cartilaginous tissues. In one third of the cases it is associated with other autoimmune disorders, mostly with anti-neutrophil cytoplasmic antibody(ANCA) associated vasculitis(AAV). We report three cases of RP with p-ANCA positive AAV. In the first patient RP developed 1.5 years after the onset of AAV. In the others the signs of RP were present before the onset of severe crescent glomerulonephritis. Patients responded well on steroid and cyclophosphamide. In dialysis dependent cases plasmapheresis was also used successfully. During the 2 and 1.5 years of follow up, they were symptom-free, and had stable glomerular filtration rate. The first patient died after four years of follow-up due to the complications of sudden unset pancytopenia,which raises the possibility of associated hemophagocytic syndrome. In the setting of RP or AAV physicians should always be aware of the possibility of sudden or insidious appearance of the other disease.

Immunomodulatory activity of berberine in alleviating experimental chronic relapsing colitis via inhibition of the JAK/STAT signalling

Aim Ulcerative colitis （UC） is an increasingly common condition particularly in developed countries. The lack of satisfactory treatment fuels the search for alternative therapeutic strategies. In the present study, we as- sessed the preclinical activity of berberine for the treatment of dextran sodium sulphate （DSS）-induced chronic re- lapsing colitis in C57BL/6 mice. Methods Colitis of mice was induced by three cycles of 2.0% DSS. From day13 onward, colitis mice were orally administered with 20 mg/kg berberine for 30 days. The disease severity was de- termined by daily monitoring the body weight, stool consistency, and stool bleeding of mice. At the end of treat- ment, colons were collected and subjected to histological, RT-qPCR, Western blot, and LC-MS analyses. Lympho- eytes were isolated from spleens and cultured for assessment of eytokine secretion. Results Berberine significantly ameliorated disease severity, colon shortening, histological injuries of colitis mice. Further, berberine treatment consistently and notably regulated DSS-assoeiated increase in mRNAs levels of Thl7-related eytokines （inhibition of IL-17 and ROR-γt） in the colon out of all tested eytokines. Moreover, the increases of TNF-α, IL-6 and IL-23 mRNA, and the phosphorylated STAT3 in colons of DSS - treated mice were significantly reversed by berberine. In addition, berberine directly inhibited TNF-α and IL-17 secretion from cultured lymphoeytes upon PMA/ionomyein -1 re-stimulation. In the meanwhile, a six-time amount of berberine in colon tissue （4.26 ± 2.62 ng · g^-1 colon） was measured when compared that in serum （0.76 ± 0.23 ng · m1^-1） and no detected histological changes was found in major organs of colitis mice. Conclusion We demonstrate for the first time that berberine exerts immuno- modulatory effect in alleviating DSS-indueed chronic relapsing colitis via inhibition of the JAK/STAT signalling acti- vation in the inflamed colon. The demonstration of activity in this model supports the possibility of clinical efficacy of berberine in treating chronic UC.

Eustachian tube involvement in a patient with relapsing polychondritis detected by magnetic resonance imaging:A case report

BACKGROUND Relapsing polychondritis(RP)is a rare inflammatory disease involving the systemic cartilage,such as the auricle,trachea,and bronchiole,among others.A patient with RP shows variable symptoms based on the involved cartilage.CASE SUMMARY A 72-year-old Japanese woman with a history of redness of the bilateral auricles for 3 d was referred to a clinician.The clinician prescribed antibiotics to the patient;however,the symptoms worsened;thus,she was referred to our hospital.Head and neck magnetic resonance imaging(MRI)showed edematous auricle with remarkable contrast,fluid collection in the bilateral mastoid cells,suggesting otitis media.The eustachian tube(ET)on the right side was also edematous with contrast enhancement.The patient was suspected of RP according to the diagnostic criteria.A biopsy of the auricular cartilage was performed by an otorhinolaryngologist,confirming pathological proof of RP.Treatments with steroids were immediately administered thereafter.CONCLUSION We highlight a rare case of RP with radiologically confirmed involvement of ET in the MRI.

Relapsing polychondritis causing breathlessness: Two case reports

BACKGROUND Relapsing polychondritis is a rare multisystem autoimmune disease that mainly involves systemic cartilage and proteoglycan-rich tissues.If the larynx and trachea are involved,the patient’s condition deteriorates rapidly.When relapsing polychondritis becomes more advanced,the airways collapse and treatment is difficult,rendering a poor prognosis.Therefore,the diagnosis method,treatment strategy and prognosis of relapsing polychondritis with larynx and trachea involvement need to be elucidated to improve clinicians’awareness of the disease.CASE SUMMARY A man and a woman were admitted because of breathlessness.Relapsing polychondritis was diagnosed after a series of accessory examinations.They were both treated with glucocorticoids and immunosuppressants,and underwent tracheotomy as their breathing difficulties could not be relieved by the medication.CONCLUSION The two cases highlight the importance of the timely diagnosis,full evaluation and initiating individualized treatment of relapsing polychondritis with larynx and trachea involvement.Laryngoscopy,bronchoscopy and pathological examination are helpful in diagnosis of this disease.

Relapsing polychondritis with isolated tracheobronchial involvement complicated with Sjogren's syndrome:A case report

BACKGROUNDRelapsing polychondritis (RP) is a rare, long-term, and potentially life-threateningdisease characterised by recurrent paroxysmal inflammation that can involve anddestroy the cartilage of the external ear, nose, larynx, and trachea.CASE SUMMARYWe here report a case of RP involving solely the tracheobronchial cartilage ring(and not the auricular. nasal or articular cartilage) complicated by Sjögren's syndrome in a 47-year-old female whose delayed diagnosis caused a sharpdecline in pulmonary function. After corticosteroid treatment, her pulmonaryfunction improved.CONCLUSIONIn such cases, our experience suggested that 18F-fluorodeoxyglucose positronemission tomography/computed tomography (18F-FDG PET/CT) and fiberopticbronchoscopy should be used to diagnose airway chondritis as relapsing polychondritisin the early phase of disease.

Relapsing Polychondritis Associated with Myelodysplastic Syndrome

A 62-year-old man had arthritis and an infiltrated purpuric eruption of the legs. He presented then a cyanosis and aches of the left ear’s pinna with a voice disturbance and an inflammatory aspect of the nose. He had an anemia and a thrombopenia. The infectious and auto-immune research was negative. The laryngo-tracheal scan revealed calcifications of the larynx, the trachea and the initial portion of bronchi. Moreover, the biopsy from ear’s pinna cartilage confirmed the diagnosis of chondritis and peri-chondritis. He was thus considered to have the association with relapsing polychondritis and a myelodysplastic syndrome. The patient was treated with corticosteroids and iterative transfusions. The articular and skinny patient’s symptoms completely resolved. The anemia and the thrombopenia were partially improved. The relapsing polychondritis can be considered as paraneoplastic complication in the context of a myelodysplastic syndrome or as a fortuitous association. The mechanism of such an association remains unknown.

Impact of an Exercise Training Program in a Patient with Relapsing Polychondritis: A Case Report

Background: Exercise training has demonstrating to be safe and promote benefits for several rheumatologic autoimmune diseases. However, no study has evaluated the safety and benefits of exercise in relapsing polychondritis. Aim: To evaluate the effectiveness of an exercise training program in a patient with relapsing polychondritis. Case presentation: A 67-year-old female patient with relapsing polychondritis in remission was submitted to a 12-week, twice weekly, aerobic and resistance training program. Aerobic capacity, muscle strength and function capacity, as well as body composition, were evaluated at baseline and after 12-weeks. Conclusions: Exercise training program demonstrated to be effective for increasing aerobic capacity, muscle strength and function, and for improving body composition in the patient. Further studies are necessary to confirm these findings.

Stenosis of the Subglottic Trachea Revealing Relapsing Polychondritis of a Young Adult

Relapsing polychondritis is a rare inflammatory disease involving essentially cartilaginous structures. Other systemic manifestations can be encountered as the eye and ear disturbance. Aortic aneurysms affect few cases. If affection of airway cartilages occurs, prognosis may be worsened by eventual stenotic lesions. We report a 22-year-old woman with Relapsing polychondritis. When she was referred to our hospital 4 weeks after the onset of respiratory symptoms, she was having severe breathing difficulty. Immediate tracheostomy followed by steroid therapy improved her respiratory condition, although the treatment was complicated because of her diabetes. While airway involvement of Relapsing polychondritis can be life threatening, it is curable with steroid therapy. Clinicians should keep in mind that airway obstruction could be caused by this disease.

Larngeal Manifestations of Relapsing Polychondritis

The incidence of Relapsing Polychondritis is estimated to be 3.5 cases per million with only 600 cases being reported in the world. It can affect any age ranging from 5 to 84 years with predominance in the fourth and fifth decade. Male to female ratio varies from 1:1 to 1:3. It is believed to be an immunologic reaction to collagen Type II which is predominantly presented in the cartilaginous structures of the body and in the eye. The diagnosis is based on the presence of three or more clinical signs, one clinical sign in addition to histological confirmation, or involvement of two or more sites with a favorable response to treatment based on Mc Adam diagnostic criteria. The otolaryngologic manifestations of RP span the ears, nose, larynx and tracheobronchial tree. The symptoms include change in voice quality, respiratory discomfort, stridor, dyspnea, cough, chocking, anterior neck tenderness mainly over the thyroid cartilage and cricoid cartilages, aspiration and difficulty in swallowing. The laryngeal manifestations should be evaluated using high resolution computerized tomography, Magnetic resonance imaging, pulmonary function testing, plain radiography and pulmonary function testing.

A Case of Relapsing Polychondritis Successfully Treated with Combination of a Glucocorticoid and Cyclosporine

Relapsing polychondritis is a rare cartilaginous inflammatory disease affecting the external ear, nose, peripheral joints and tracheobronchial tree. It is characterized by recurrent inflammation and degeneration of cartilage and connective tissue. A 72-year-old man complained of dyspnea, cough and wheezing for 2 months. Diffuse wall thickening and narrowing from the trachea to segmental bronchus were seen on chest CT. Tracheostomy was performed in order to avoid as-phyxia, and he was diagnosed as relapsing polychondritis on the basis of pathology evaluation of a tracheal biopsy specimen. He was treated with high doses of a glucocorticoid, with which his symptoms improved. However, the cough and wheezing recurred after tapering of the glucocorticoid. His symptoms thereafter were improved by combination of the glucocorticoid with cyclosporine. The immunosuppressive agent provided effective treatment for glucocorticoid-resistant relapsing polychondritis.

Evaluation of oxidative and nitrosative stress in relapsing remitting multiple sclerosis

Multiple sclerosis (MS) is a chronic autoimmune disorder affecting the central nervous system (CNS) through demyelination and neurodegeneration. Several lines of evidence support a role for oxidative and nitrative stress (OS and NS) in pathogenesis of multiple sclerosis. The mechanism of influence of OS and NS on blood-brainbarrier (BBB) has critical importance for evaluating antioxidant therapies. As far as we know, markers of oxidative and nitrative stress in MS patients have been investigated independently for their relationship with the state of the blood-brain-barrier. Blood plasma samples of 58 patients with relapse-remitting MS (RRMS) with normal (Group A, n = 48, 36.2 ± 10.5 years) and damaged BBB (Group B, n = 10, 38.2 ± 11.2 years) and of 44 healthy controls (39.2 ± 14.9 years) were analyzed. TAS (total antioxidant plasma status), lipoperoxides, protein carbonyls, 3-nitrotyrosine and uric acid were evaluated in each group. Our results confirmed decreased TAS (Group A: 1.35 ± 0.55 mmol/l, P e level of lipoperoxidation positively correlated with the state of BBB (P of protein’s carbonyls (A: 0.48 ± 0.11 nmol/mg protein, P nmol/l, P ed damage to plasma proteins, what was confirmed by their positive mutual correlation (P The level of uric acid was physiological and correlated negatively with protein’s carbonyls (P 0.05) while there was no significant relationship with 3-nitotyrosine. The results suggest the role of this antioxidant in the protection of the proteins against OS what was confirmed by its positive correlation with TAS

The treatment of relapsing primary nephrotic syndrome in children

Objective: To explore better therapy and reduce the rate of re-relapse of primary nephritic syndrome in children who had been treated with corticosteroids but relapsed. Methods: Eighty relapsers were enrolled from Jan. 1994 to Apr. 2000, who were randomly divided into two groups. The treatment group (n=39) had been treated with tripterysium glucosides for three months,with the control group (n=41) members were treated with cyclophosphmide (CTX) by intermission intravenous pulse, with total dose of CTX not being more than 150 mg/kg. Prednisone, meanwhile, was given to both groups. The total treatment period of prednisone was prolonged by 12-18 months. Results: After following up for 3-7 years, the re-relapse rates of both groups were observed. The re-relapse rate of the treatment group was 28.2% to 29.3% in the CTX-controlled group. The re-relapse rates between two groups were almost similar, and with no observed significant difference (P>0.05). The side effect of tripterysium glucosides was less than that of CTX. Conclusion: For the treatment of relapsing nephritic syndrome in children, the combination of tripterysium glucosides and prolonged corticosteroid therapy is as effective as the regimen of CTX plus prolonged use of prednisone.

Efficacy and Safety of Antibiotics for the Treatment of Relapsing Fever:A Systematic Review and Network Meta-analysis

Relapsing fever is an acute infectious disease caused by a variety of relapsing fever-associated spirochetes,for which no optimal treatment has been developed.The purposes of this study were to compare the efficacy and safety of commonly used antibiotics for the treatment of relapsing fever using a network meta-analysis approach and to explore the advantages of each drug based on the current evidence.This study examined nine published studies involving 1416 patients with relapsing fever treated with penicillin,erythromycin,tetracycline,doxycycline,minocycline or chloramphenicol.The odds ratio(OR)and 95% confidence interval(CI)were used as influence indices for discontinuous data,and the efficacy and safety of drugs were ranked by the surface under the cumulative ranking(SUCRA)curve.The primary outcomes of this study were mortality and cure rates,and the secondary outcomes were the rates of Jarisch-Herxheimer reaction and relapse.Erythromycin(SUCRA,84.5%)was the most effective antibiotic for reducing mortality,whereas tetracycline was the most effective antibiotic for improving the cure rate(SUCRA,69.3%)and reducing the relapse rate(SUCRA,79.7%),and minocycline(SUCRA,66.4%)was the most effective antibiotic for reducing Jarisch-Herxheimer reactions.In addition,our network meta-analysis showed that tetracycline is superior to penicillin for improving the cure rate(OR,5.91;95%CI,2.21-15.81)and reducing the relapse rate(OR,0.16;95%CI,0.04-0.67).

Long-term prognosis and its associated predictive factors in patients with eosinophilic gastroenteritis

BACKGROUND Eosinophilic gastroenteritis(EGE)is a chronic recurrent disease with abnormal eosinophilic infiltration in the gastrointestinal tract.Glucocorticoids remain the most common treatment method.However,disease relapse and glucocorticoid dependence remain notable problems.To date,few studies have illuminated the prognosis of EGE and risk factors for disease relapse.AIM To describe the clinical characteristics of EGE and possible predictive factors for disease relapse based on long-term follow-up.METHODS This was a retrospective cohort study of 55 patients diagnosed with EGE admitted to one medical center between 2013 and 2022.Clinical records were collected and analyzed.Kaplan-Meier curves and log-rank tests were conducted to reveal the risk factors for long-term relapse-free survival(RFS).RESULTS EGE showed a median onset age of 38 years and a slight female predominance(56.4%).The main clinical symptoms were abdominal pain(89.1%),diarrhea(61.8%),nausea(52.7%),distension(49.1%)and vomiting(47.3%).Forty-three(78.2%)patients received glucocorticoid treatment,and compared with patients without glucocorticoid treatments,they were more likely to have elevated serum immunoglobin E(IgE)(86.8%vs 50.0%,P=0.022)and descending duodenal involvement(62.8%vs 27.3%,P=0.046)at diagnosis.With a median follow-up of 67 mo,all patients survived,and 56.4%had at least one relapse.Six variables at baseline might have been associated with the overall RFS rate,including age at diagnosis<40 years[hazard ratio(HR)2.0408,95%confidence interval(CI):1.0082–4.1312,P=0.044],body mass index(BMI)>24 kg/m^(2)(HR 0.3922,95%CI:0.1916-0.8027,P=0.014),disease duration from symptom onset to diagnosis>3.5 mo(HR 2.4725,95%CI:1.220-5.0110,P=0.011),vomiting(HR 3.1259,95%CI:1.5246-6.4093,P=0.001),total serum IgE>300 KU/L at diagnosis(HR 0.2773,95%CI:0.1204-0.6384,P=0.022)and glucocorticoid treatment(HR 6.1434,95%CI:2.8446-13.2676,P=0.003).CONCLUSION In patients with EGE,younger onset age,longer disease course,vomiting and glucocorticoid treatment were risk factors for disease relapse,whereas higher BMI and total IgE level at baseline were protective.

Autoimmune pancreatitis:Cornerstones and future perspectives

Autoimmune pancreatitis(AIP)is an autoimmune subtype of chronic pancreatitis resulting from the aberrant immune response against the pancreas,leading to inflammation and fibrosis.Although AIP is rare,its incidence is increasing and is often misdiagnosed as other pancreatic diseases.AIP is commonly classified into two types.Type 1 AIP(AIP-1)is typically associated with elevated serum immunoglobulin G4(IgG4)levels and systemic manifestations,while type 2 AIP is typically a more localized form of the disease,and may coexist with other autoimmune disorders,especially inflammatory bowel diseases.Additionally,there is emerging recognition of a third type(type 3 AIP),which refers to immunotherapy-triggered AIP,although this classification is still gaining acceptance in medical literature.The clinical manifestations of AIP mainly include painless jaundice and weight loss.Elevated serum IgG4 levels are particularly characteristic of AIP-1.Diagnosis relies on a combination of clinical,laboratory,radiological,and histological findings,given the similarity of AIP symptoms to other pancreatic disorders.The mainstay of treatment for AIP is steroid therapy,which is effective in most cases.Severe cases might require additional imm-unosuppressive agents.This review aims to summarize the current knowledge of AIP,encompassing its epidemiology,etiology,clinical presentation,diagnosis,and treatment options.We also address the challenges and controversies in diagnosing and treating AIP,such as distinguishing it from pancreatic cancer and managing long-term treatment,highlighting the need for increased awareness and knowledge of this complex disease.

Efficacy and Safety of Teriflunomide in Chinese Patients with Relapsing Forms of Multiple Sclerosis: A Subgroup Analysis of the Phase 3 TOWER Study

Background:Disease-modifying therapy is the standard treatment for patients with multiple sclerosis (MS)in remission.The primary objective of the current analysis was to assess the efficacy and safety of two teriflunomide doses (7mg and 14mg)in the subgroup of Chinese patients with relapsing MS included in the TOWER study. Methods:TOWER was a multicenter,multinational,randomized, double-blind,parallel-group (three groups),placebo-controlled study.This subgroup analysis includes 148 Chinese patients randomized to receive either teriflunomide 7mg (n =51), teriflunomide 14mg (n=43),or placebo (n=54). Results:Of the 148patients in the intent-to-treat population, adjusted annualized-relapse rates were 0.63(95% confidence interval [CI]:0.44,0.92)in the placebo group,0.48(95%CI:0.33, 0.70)in the teriflunomide 7mg group,and 0.18(95%CI:0.09,0.36)in the terifltmomide 14mg group;this corresponded to a significant relative risk reduction in the teriflunomide 14mg group versus placebo (-71.2%,P =0.0012).Terifiunomide 14mg also tended to reduce 12-week confirmed disability worsening by 68.1% compared with placebo (hazard ratio:0.319,P =0.1194).There were no differences across all treatment groups in the proportion of patients with treatment-emergent adverse events (TEAEs;72.2% in the placebo group,74.5%in the teriflunomide 7mg group,and 69.8% in the teriflunomide 14mg group);corresponding proportions for serious adverse events were 11.1%,3.9%,and 11.6%,respectively.The most frequently reported TEAEs with teriflunomide versus placebo were neutropenia,increased alanine aminotransferase,and hair thinning. Conclusions:Teriflunomide was as effective and safe in the Chinese subpopulation as it was in the overall population of patients in the TOWER trial.Teriflunomide has the potential to meet unmet medical needs for MS patients in China.

Usefulness of mizoribine administration in children with frequently relapsing nephrotic syndrome, and the relationship between pharmacokinetic parameters and efficacy: a multicenter prospective cohort study in China

Background Mizoribine (MZR) is an immunosuppressant used to treat adult nephropathy.There is little experience with the drug in treating Chinese children with frequently relapsing nephrotic syndrome (FRNS).We investigated the efficacy and safety for treating MZR with FRNS.Furthermore,the relationship between efficacy and serum concentration was investigated.Methods A prospective multicenter observational 12-month study was performed for evaluating the usefulness of MZR with FRNS.Serum MZR concentration was measured,and the relationships between pharmacokinetic parameters (Cmax,AUC),number of relapses,and urinary protein were evaluated.Results Eighty-two pediatric patients from four hospitals were treated with MZR and prednisone.MZR treatment significantly reduced the number of relapses and steroid doses.A correlation between pharmacokinetic parameters and relapses was observed,which fits well with the sigmoidal Emax model.Even in the relationship between pharmacokinetic parameters and urinary proteins,it was recognized that there was a threshold in the pharmacokinetic parameters for the therapeutic effect similar to the results obtained with the sigmoidal Emax model.Eleven patients (13.4%) experienced mild adverse events.Conclusions MZR therapy was effective in reducing the number of relapses and steroid doses.No severe adverse reactions were observed.Therapeutically effective serum concentrations were estimated to be Cmax > about 2 μg/mL or AUC > about 10 lag h/mL.MZR and steroid treatment were effective and safe for pediatric FRNS.