Various Clinical Presentation of Post-Transplant Lymphoproliferative Disorder in Head and Neck: A Case Series of 3 Patients / 대한이비인후과학회지

The outcome of solid organ and bone marrow transplantation has been dramatically improved with the development of immunosuppressive agent. However, the use of immunosuppressive agents could increase the risk of malignancies such as post-transplant lymphoproliferative disorder (PTLD). PTLD is regarded as the lymphoid malignancy of patients using immunosuppressive agents, and it could present diverse and non-specific symptoms. It involves various organs including the tonsil, adenoid, lymph node, and the brain. Because of its poor prognosis, an early suspicion of pathologic diagnosis is crucial for the treatment of PTLD. In this report, we demonstrate the case of three pediatric patients who had been treated for PTLD of various clinical presentations by early suspicion and pathologic diagnosis.

Brucellosis after renal transplantation: a report of one case and literature review / 器官移植

Objective To analyze and summarize the clinical features and diagnosis and treatment experience of brucellosis after renal transplantation. Methods Clinical data of one case with brucellosis after renal transplantation admitted to the 309thHospital of Chinese People's Liberation Army in October 2016 was collected. The clinical features, diagnosis and treatment were retrospectively analyzed. Clinical experience was summarized and literature review was conducted. Results At 3 months after renal transplantation, the patient suffered from temperature rise without known causes and presented with fever in the morning with a duration of 3 d. The route of infection was unknown, and the symptoms of alternative types of infection were not obvious. Empirical anti-infectious therapy was delivered for 1 week and yielded no efficacy. Blood culture test confirmed the diagnosis of brucella melitensis infection. The treatment included anti-infecting by the rifampicin, doxycycline, sulfamethoxazole, preventing the incidence of complications actively and protecting the liver and renal function. High clinical efficacy was achieved. During the 1-year follow up after discharge, the renal graft was stable and no other infectious symptoms, such as fever was found. Conclusions Brucellosis with unknown route of infection after renal transplantation is extremely rare and the common symptom is Malta fever. When the empirical anti-infectious treatment is not effective, blood culture and other related tests should be performed to confirm the diagnosis. The combination of rifampicin and doxycycline is recommended.

Clinical Observation of Enhanced Immunosuppressive Therapy in the Treatment of Refractory Nephrotic Syndrome / 中国药房

OBJECTIVE:To observe the clinical efficacy and safety of enhanced immunosuppressive therapy in the treatment of refractory nephrotic syndrome (RNS). METHODS:Totally 76 RNS patients were selected from 2 hospitals during Jan. 2012-Mar. 2015,and then divided into control group and observation group according to random number table,with 38 cases in each group. Two groups were given Prednisone acetate tablet 50 mg,qd;decreasing to 15 mg,qd,after urine protein returned to normal. Based on it,control group was given Leflunomide tablets 50 mg,qd;decreasing to 20 mg,qd,3 days later. Based on con-trol group,observation group was additionally given Mycophenolate mofetil dispersible tablet 750 mg,bid;decreasing to 500 mg, qd,3 months later. Both groups were treated for 6 months. Clinical efficacies,follow-up recurrence rate as well as renal function in-dexes and inflammatory cell factors before and after treatment,and the occurrence of ADR were compared between 2 groups. RE-SULTS:The total response rate of observation group(92.11%)was significantly higher than control group(73.68%),and fol-low-up recurrence rate(5.26%)was significantly lower than control group(23.68%),with statistical significance(P0.05). After treatment,24 h urinary protein quantification,urinary IL-6 and IL-8 levels of 2 groups decreased significantly,while the content of serum protein increased significantly;the observation group was significantly better than the control group,with sta-tistical significance(P0.05). The incidence of ADR in the control group and the observation group was 34.21% and 44.74% respec-tively,without statistical significance between 2 groups(P>0.05). CONCLUSIONS:Enhanced immunosuppressive therapy in the treatment of RNS can improve renal function,reduce inflammatory reaction and long-term recurrence risk,and have good therapeu-tic efficacy and safety.

The inhibition of common immunosuppressive drugs on the development of de novo donor specific antibodies / 中华器官移植杂志

Objective To explore the inhibition of different immunosuppressive drugs or immunosuppressive combination regiments on the development of de novo donor specific antibodies (dnDSA).Methods We used BABL/c mice and C57BL/6 mice alloimmunized using donor splenocytes for establishing model of producing dnDSA.After that,mice were divided into 10 groups,and were administrated with mycophenolate mofetil (MMF,300 mg· kg-1 · d-1);sirolimus (0.3 mg·kg-1 ·d-1);tacrolimus(0.9 mg· kg-1 · d-1);cyclosporine A (45 mg· kg-1 · d-1);MMF (150 mg· kg-1· d-1) + tacrolimus(0.45 mg · kg-1 · d-1);MMF (150 mg · kg-1 · d-1) + cyclosporine A (22.5 mg·kg-1 ·d-1);MMF (150 mg·kg-1 ·d-1) + sirolimus (0.15 mg·kg-1 ·d-1);sirolimus (0.15 mg· kg-1 · d-1) + tacrolimus (0.45 mg· kg-1 · d-1);sirolimus (0.15 mg· kg-1 · d-1) + cyclosporine A (22.5 mg· kg-1 · d-1);and placebo;respectively.Anti-serum was harvested and tested using flow cytometry.Results (1) Four weeks after sensitization,the dnDSA level in BALB/c and C57BL/6 group was 88.86％ and 25.58％.Comparing with control group(25.33％),there was a significant increase in BALB/c group(89.23％ versus 25.33％;P＜0.001),whereas no change was found in C57BL/6 group (25.58％ versus 25.33％;P =0.259),that we chose BABL/c mice as the model for sensitization.(2)After 4 weeks of sensitization and immunosupression,dnDSA level was 29.31％,46.33％,57.10％ and 66.35％ in MMF,sirolimus,cyclosporine A and tacrolimus monotherapy group respectively.In comparison to sensitization group,dnDSA level in all monotherapy arm reduced significantly.Intra-group analysis found MMF monotherapy had the most effective inhibition of dnDSA production,sirolimus came the second,and tacrolimus and cyelosporine A had equivalent effectiveness.dnDSA level was 31.00％,33.12％,45.18％,44.62％ and 61.60％ in MMF+ sirolimus,MMF+ tacrolimus,MMF+ cyclosporine A,sirolimus + cyclosporine A and sirolimus + tacrolimus combination treatment arm,respectively,which was much lower than that of sensitization group (P＜0.001,P＜0.001,P＜0.001,P＜0.001,P =0.015).MMF + tacrolimus and MMF+ sirolimus combination treatment had comparable effectiveness in dnDSA inhibition,which is greater than that of the rest of three combination.Conclusion Our data show that the effects of single immunosuppressive drugs on the level of dnDSA is MMF＞sirolimus＞cyclosporine A =tacrolimus,and that in combination regimens is MMF + tacrolimus =MMF + sirolimus＞MMF + cyclosporine A =sirolimus + cyclosporine A =sirolimus + tacrolimus.In conclusion,this study demonstrates that MMF+ tacrolimus combination treatment arm can minimize the development of dnDSA.But,this conclusion remains to be confirmed by future clinical studies.

Advances in treatment of Vogt-Koyanagi-Harada syndrome / 国际眼科杂志(Guoji Yanke Zazhi)

Vogt-Koyanagi-Harada (VKH)syndrome is an autoimmune disease attacking against pigmented cells, resulting in blindness and usually affecting multiple organs including ears, meninges, hair and skin.Correct diagnosis and immediate treatment in the early stage is vital to visual prognosis.Currently, corticosteroids is first-line drug.In addition, VKH patients refractory to corticosteroids can choose other treatment such as immunosuppressive agents and biological agents.

Experience of clinical treatment on patients on cirrhosis or liver cancer complicated with psoriasis after liver transplantation / 器官移植

Objective To summarize the clinical experience of immunosuppressive therapy for recipients suffering from psoriasis after liver transplantation. Methods Five patients diagnosed with cirrhosis or hepatocellular carcinoma (HCC)complicated with psoriasis after liver transplantation were recruited in this clinical trial. All participants were positive for serum biomarkers of hepatitis B virus (HBV). Induction therapy was adopted before surgery. Immunosuppressive regime of tacrolimus (FK506),mycophenolate mofetil (MMF)and adrenal cortical hormone (hormone) was implemented early after surgery. The hormone use was terminated within 1 week. Three cases of cirrhosis complicated with HCC due to chronic HBV infection were gradually switched to sirolimus substitution treatment within 1 month after liver transplantation. Two patients with cirrhosis were administered with FK506 with or without MMF following liver transplantation. All patients received anti-HBV therapy. Baseline data,changes in psoriasis area and severity index (PASI)score and adjustment of postoperative immunosuppressive agents were analyzed. Results Five patients undergoing transplantation were followed up until the submission date with a mean duration of (8. 3 ±1 . 5 )years and survived. Compared with preoperative values,PASI score was significantly reduced at postoperative 6 months (P<0. 05 ). Two patients with cirrhosis had recurrent psoriasis at 2 years after liver transplantation. PASI score was significantly increased and steadily declined after sirolimus substitution therapy. These patients remained physically stable and did not progress at postoperative 3 years. Three patients suffering from cirrhosis complicated with HCC presented with no recurrence of psoriasis postoperatively. Conclusions Sirolimus-based immunosuppressive therapy can effectively control the progression of psoriasis in liver transplantation recipients. Anti-HBV treatment should be simultaneously implemented for HBV positive patients.

Progress and prospect of treatment for ocular Beh(c)et disease / 中华实验眼科杂志

Ocular Beh(c)et disease,which usually presents as panuveitis,with characteristic of vision impairment and relapse,is one of the most refractory uveitis entities.Usually,one or more conventional immunosuppressive agents,such as glucocorticoid,ciclosporin,chlorambucil,cyclophosphamide,etc,are needed in disease management.However,long-term use of immunosuppressive agents would result in severe adverse effects.New biologics,such as interferon,antitumor necrosis factor agents,interleukin or its receptor antagonists,provide new therapeutic approaches to the treatment for this disease.This paper reviewed the conventional therapies and biologics applied in ocular Beh(c)et disease.

Prevention and therapy progress in allograft rejection of high - risk corneal transplantation / 国际眼科杂志(Guoji Yanke Zazhi)

High - risk corneal transplantation immunological rejection is a primary factor affecting the success or failure of the corneal transplantation. As a result, application of immunosuppressive agent in high - risk corneal transplantation rejection reaction occupies an irreplaceable position. However, many local and systemic adverse reactions appeared in the process of application. In order to improve the achievement ratio of the corneal transplantation, experts and scholars at home and abroad have obtained remarkable achievements in dosage form, route of administration and drug combination;meanwhile, a considerable progress was also made in genetic engineering. This paper is a review of prevention and treatment on high - risk corneal graft rejection reaction.

Clinical treatment of idiopathic orbital inflammatory pseudotumor / 中华实验眼科杂志

Idiopathic orbital inflammatory pseudotumor (IOIP) is a common ophthalmic disease with uncertain etiology and pathogenesis.It charactarized by chronic inflammatory cell infiltration and connective tissue proliferation.At present,its clinical treatments mainly include pharmacotherapy,radiation therapy and surgery,and the primary treating drugs include glucocorticosteroids and immunosuppressive agents.The mainstay of therapy is systemic glucocorticosteroids,although there is an increasing trend toward the use of alkylating agents,antimetabolites,monoclonal antibodies and other immunosuppressive agents.The progress in clinical treatment of IOIP was reviewed.

Clinical Outcomes of Cyclosporine Treatment for Noninfectious Uveitis

PURPOSE: To assess the clinical outcomes of cyclosporine treatment for noninfectious uveitis. METHODS: A retrospective review of medical records was completed for 182 noninfectious uveitis patients who were treated with cyclosporine between January 2001 and August 2010. Data was obtained relevant to demographic characteristics, anatomic classification, and laterality of uveitis, associated systemic disorder, dosage of cyclosporine and prednisolone, usage of other immunosuppressive drugs, visual acuity (VA), control of uveitic activity, and adverse effects during the cyclosporine use. RESULTS: Uveitic activity was controlled to a level of minimal inflammation in 89.0% and completely in 78.6% of patients by the median duration of 49 and 98 days, respectively. Prednisolone-sparing (dose < or =10 mg) control of inflammation equal to or less than the minimal activity was achieved in 75.3% of patients. VA was aggravated more than 0.2 logarithm of the minimum angle of resolution in 17.3% of eyes in spite of cyclosporine treatment for the mean follow-up of 698.4 days. Dose reduction and cessation of cyclosporine was required only in 3.3% and 9.3%, respectively, due to the intolerable toxicity, although 44.0% of patients experienced mild to moderate adverse effects. CONCLUSIONS: Cyclosporine combined with corticosteroids or other immunosuppressive drugs as needed is an effective treatment for noninfectious uveitis, thus minimizing the adverse effects of corticosteroids and other toxic drugs. However, careful monitoring for the toxicity of cyclosporine is needed, because a small group of patients cannot tolerate its toxicity.

Serial Interferon-gamma Release Assays for the Diagnosis of Latent Tuberculosis Infection in Patients Treated with Immunosuppressive Agents / 대한진단검사의학회지

BACKGROUND: We assessed the efficacy of serial interferon-gamma release assays (IGRAs) for the diagnosis of latent tuberculosis infection (LTBI) in patients receiving immunosuppressive agents for treatment of rheumatic diseases in Korea. METHODS: Of 276 patients who underwent consecutive screening with one of two IGRAs [QuantiFERON-TB Gold or QuantiFERON-TB Gold In-Tube], 66 patients were evaluated by the serial IGRA for detection of LTBI during therapy with immunosuppressive agents. Information on clinical diagnosis, medication, previous TB, blood cell count, tuberculin skin test, and interferon-gamma (IFN-gamma) level measured by IGRA was collected. RESULTS: Of the 66 patients, the initial IGRA was positive in 24.2%, negative in 65.2%, and indeterminate in 10.6%. Forty-six patients (69.7%) showed consistent IGRA results during follow-up, and 13 patients (19.7%) had consistently positive results. IGRA conversion rate was 12.1% (8/66) and reversion rate was 4.5% (3/66). Conversion of IGRA results was only observed in ankylosing spondylitis patients, and the median interval between the two tests in patients with conversion was 8.5 months. The mean IFN-gamma level in the group of patients with consistently positive IGRA results was higher than that in the group with inconsistently positive results, although this trend was not statistically significant (P=0.293). Indeterminate results were observed most frequently in patients with systemic lupus erythematosus. CONCLUSIONS: In patients receiving immunosuppressive agents, both IGRA conversions and reversions were observed. Serial IGRA testing may not be needed in patients with a positive initial IGRA result showing high IFN-gamma levels, because of high consistency in the test results.

Acute Zonal Occult Outer Retinopathy, Responsive to an Immunosuppressive Agent: A Case Report

PURPOSE: To report a case of acute zonal occult outer retinopathy (AZOOR), initially misdiagnosed as retrobulbar optic neuritis, which was responsive to an immunosuppressive agent. CASE SUMMARY: A 28-year-old female with photopsia and a visual field defect in the left eye was referred to a hospital. There were no fundus abnormalities to explain her left visual field defect. Neurologic examination and brain MRI were normal. The patient was diagnosed with retrobulbar optic neuritis and treated with high-dose steroids. Four months after the onset of symptoms, she visited our hospital. Visual acuity was hand motion in the left eye. No relative afferent pupillary defect in the left eye and no anterior segment or fundus abnormalities were observed. A visual field examination of the right eye was normal and revealed field defect in the left eye. No abnormality was noted in the visual evoked potential test or fluorescein angiography. All examinations of the right eye were normal. In the left eye, fundus autofluorescence showed a hyperautofluorescent spot at the posterior pole, there was a decreased response in electroretinography and spectral domain optic coherence tomography showed that the junction between the photoreceptor inner and outer segments (IS/OS) was faintly visible only in the fovea. With the presumptive diagnosis of AZOOR, the patient was treated with an immunosuppressive agent. Visual acuity improved to 20/80 in the left eye at 10 months after the onset of symptoms. CONCLUSIONS: Electroretinogaphy is essential to diagnose AZOOR in patients with photopsia, visual field defect and minimal or no fundus changes, especially in a young women. There is currently no proven standard treatment, however immunosuppressive agents may be helpful.

Adult Onset Still's Disease Developed in a Patient with Membranous Nephropathy Treated with Immunosuppressive Agent / 대한신장학회지

Adult onset Still's disease (AOSD) is a rare systemic inflammatory disease characterized by high spiking fever, leukocytosis, high serum ferritin, salmon-colored rash, arthritis, lymphadenopathy, and hepatosplenomegaly. The etiology of AOSD is obscure. AOSD is diagnosed after exclusion of infection, malignancy and other connective tissue diseases. A 53-year-old female patient with membranous nephropathy was admitted with high fever and leukocytosis. She was taking immunosuppressive agents with low dose steroid and cyclosporine to control of proteinuria caused by membranous nephropathy. She was initially treated with antibiotics, antiviral agent and antifungal agent to control of hidden infection. High spiking fever was sustained for 2 weeks and controlled after hydrocortisone treatment. AOSD was diagnosed according to the criteria of Yamaguchi. It should be considered that AOSD is a cause of high fever in patients treated with immunosuppressive agents.

Management of systemic lupus erythematosus / 대한내과학회지

Systemic lupus erythematosus (SLE) is an autoimmune disorder which affects the musculoskelectal system, skin, kidney, central nervous system, gastrointestinal tract, and vascular system. The therapeutic level depends on the severity of SLE activity and affected organ damage. The prognosis of SLE has greatly improved since treatment regimens combining corticosteroids and immunosuppressive agents have been widely adopted in therapeutic strategies. Immune suppression is evidently effective, however, sometimes leads to higher susceptibility to infectious and malignant diseases. Toxic effects and unexpectedly fatal complications of current therapies have been progressively reported. Currently, identifying novel molecular targets such as hyperactive B cells could be an important issue in the treatment of SLE. The aim of this review is the introduction of previous adopted therapies as well as emerging pharmacological options.

Mycophenolic Acid Induced Apoptosis in Human Jurkat Cells viathe Generation of Reactive Oxygen Species

PURPOSE: Mycophenolic acid (MPA) is the active agent of mycophenolate mofetil (MMF), which is an immunosuppressive drug. MPA is a selective inhibitor of inosine monophosphate dehydrogenase. The aim of this study was for demonstrate that mycophenolic acid induces apoptosis in human Jurkat cells via the generation of reactive oxygen species (ROS). METHODS: The cells were cultured in the presence or absence of MPA. Flow cytometric analysis was performed after propidium iodide staining. Western blotting for caspase 3, Bcl-2 and Bax proteins was also performed. RESULTS: MPA decreased the viability of Jurkat cells in a dose- and time-dependent manner. The MPA induced apoptotic cell death displayed nuclear fragmentation and sub G0/G1 phase arrest in the Jurkat cells. The expression of caspase-3 proteases in the MPA treated-Jurkat cells increased in a time-dependent manner. Treatment with MPA resulted in increased ROS generation in the Jurkat cells. There was a decreased expression of Bcl-2 and an increased expression of Bax protein in the MPA treated Jurkat cells. CONCLUSION: This result suggests that MPA-induced cytotoxicity is associated with a direct increase of both ROS generation and the expression of Bax protein.

Effects of individual antibiotic and immunosuppressive regime on postoperative infection in liver transplant recipients / 中国医师进修杂志

Objective To determine the effects of individual antibiotic and immunosuppressive regime on postoperative infection in liver transplant recipients. Method There were 31 cases of liver transplantation from March 2001 to May 2005. The recipients received individual antibiotic and immunosuppressive regime based on the drug susceptibility testing and monitoring of blood drug concentration. The incidence and pattern of infection and the mortality in these recipients were analyzed retrospectively. Results There were 15 episodes of infection during recipients' staying in hospital. The common etiologies were Enterobacter cloacae, pseudomonas aeruginosa, Klebsiella pneumoniae, Acinetobacter baumannii, and Staph. epidermidis. According to the drug sensitive test, targocid/tienam and tazocin were mostly used in antibiotic regime for treatment of postoperative infection. With monitoring of blood concentration, appropriate application of immunosuppressive agents decreased the incidence of infection from 86.7% before 2003 to 48.4% after 2003 (P0.05). Conclusion Individual application of antibiotic and immunosuppressive regime leads to the suppression of infections and other complications in liver transplant recipients.

Immunology research on human fetal liver cells transplantation in treatment of metabolic diseases / 上海第二医科大学学报

Objective To investigate the immunological reaction,serum and liver ?-L-iduronidase(IDUA) activity after human fetal liver cells(FLCs) transplantation therapy on mucopolysaccharidosis(MPS) which attribute to IDUA defect.Methods FLCs were transplanted into IDUA deficiency mice.T cell subsets(CD3,CD4 and CD8) was detected by flow cytometry,while IL-2,TNF-? and IFN-? by ELISA,and serum and liver IDUA activity by fluorospectrophotometer at different stage(before transplantation and 5,10,15 days after transplantation).Results Human FLCs survived in IDUA deficiency mice,bringing elevated serum and liver enzyme activity to receptor.T cell subsets,IL-2,TNF-? and IFN-? was significantly higher 5,10 and 15 days after transplantation than those before transplantation(P

Current treatment of Henoch-Schonlein purpura nephritis / 医学研究生学报

Henoch-Schonlein purpura nephritis(HSPN) is the common secondary glomerulonephritis.Patients with HSPN have various therapeutic reaction and prognosis owing to their varied clinical manifestations or histological changes,and accordingly different therapeutic regimens should be supplied.Patients with severe HSPN should be given active treatment.This article reviews the current treatment of HSPN.

Bilateral Breast Carcinoma after Treatment with Immunosuppressant

Bilateral breast cancer developed in a 45-year-old woman who received a renal transplant followed by immunosuppression with Cyclosporine. She underwent a left modified radical mastectomy, and right breast conserving surgery, with both axillary lymph nodes being dissect. Few cases have been reported on breast cancer associated with renal transplantation. Although a causal relationship with immunosuppression therapy and breast carcinoma was not implied, a heightened awareness of the possible coexistence of immunosuppression therapy and breast carcinomas are necessary.

Current and challenge in treatment of lupus nephritis / 中国实用内科杂志

Lupus nephritis (LN) is a major cause of morbidity and mortality in patients with systemic lupus erythematosus.Although the use of aggressive immunosuppression has improved both patient and renal survival over the past several decades,the optimal treatment of LN remains challenging.The therapeutic strategy and progress for patients with lupus nephritis are based on the accumulative evidences of the medicine,and must be personalized according to the patient condition.This paper discusses established and newer treatment options for LN.We also emphasize the challenges in the day-to-day management of lupus nephritis in the clinical practice.