Immunosuppressive Treatment Protocols Research Articles

Electronic Alert System Significantly Increases HBV Screening Rates Before Immunosuppressive Treatments.

Hepatitis B Virus (HBV) screening rates before starting immunosuppressive treatments are suboptimal. The aim of the study was to evaluate the efficacy of a new electronic alert system in increasing HBV screening rates. The electronic alert system, HBVision2, identifies patients at risk of HBV reactivation when a pre-determined International Classification of Diseases (ICD)-10 code is entered into the hospital's database or immunosuppressive treatment is prescribed. The system evaluates the prior Hepatitis B Surfage Antigen (HBsAg) and anti-Hepatitis B Core Immunglobulin G (HBc IgG) results and sends an alert code to the clinician for screening if serology is not completely available or consult a specialist in case of positive serology. The HBV screening and consultation rates of patients before (control group) and after HBVision2 were retrospectively compared. The clinical course of unscreened and/or unconsulted patients was determined, and the clinical efficacy of HBVision2 in preventing HBVr was predicted. Control group included 815 patients (52.6% male, mean age: 60 ± 12, 82.5% with oncologic malignancy) and study group included 504 patients (56% male, mean age: 60 ± 13, 91.4% with oncologic malignancy). Groups were similar with respect to gender, mean age, and HBVr risk profile of the immunosuppressive treatment protocols. Overall, both HBsAg (from 55.1% to 93.1%) and anti- HBc IgG screening rates significantly increased (from 4.3% to 79.4%) after the electronic alert system (P < .001, for both). Consultation rates of anti-HBc IgG-positive patients significantly increased from 40% to 72.7% (P = .012). HBVr developed in 2 patients (2.6%) who were not screened and/or consulted after the alert system. Alert program prevented the development of HBVr in 10 patients (1.9%) of the study group and decreased the development of HBVr by 80%. Electronic alert system significantly improved HBsAg and anti-HBc IgG screening rates before starting immunosuppressive treatment and prevented the development of HBVr to a great extent. However, screening rates are still below optimal and need to be improved.

Clinical follow up of renal transplant recipients with COVID-19: a case series

COVID-19 has been recognized to become a worldwide health concern at an alarming rate over time and to be more progressive and fatal in specific risk populations. This study aims to determine the clinical features of COVID-19 in kidney transplant recipients (KTRxs) and contribute to the regulation of these patients’ immunosuppressive treatments and COVID-19 treatment protocols. The trial comprised eleven KTRxs with COVID-19. Immunosuppressive treatments such as antimetabolite cessation, calcineurin inhibitor dosage adjustments based on blood levels, and low-dose corticosteroids were all controlled. All patients received antiviral medication and low-molecular-weight-heparin (LMWH) as part of initial treatment. The steroid dose was then raised, and anti-cytokine therapies were provided in the setting of clinical worsening. The mean age of the patients was 50.3±11.2 years and 8 (73%) of them were male. The average time since transplantion was 6.82±3.34 years. Due to COVID-19 progression, the steroid dosage was raised in eight patients, anakinra and tocilizumab was added in five and one of the patients respectively. In five (%45) patients, the need for critical care arose and plasmapheresis was used in three of them. At the end of the follow-up, nine of our patients had made a complete recovery, whereas two (18.2%) had perished. Consistent with the literature, the data in presented study may also support the severe and fatal course of COVID-19 in KTRxs. It may be proposed that KTRxs with COVID-19 should be admitted to the hospital and constantly monitored, and certain effective management techniques should be initiated early depending on clinical circumstances.

Japanese Single-Center Experience of Kidney Transplant: Experience in a Japanese Private Hospital

We reviewed the results of cases of kidney transplant (KTx) that were conducted at the Toda Chuo General Hospital, a private hospital located in Saitama, Japan. A total of 312 patients with end-stage renal failure underwent KTx between January 1992 and December 2019 at Toda Chuo General Hospital. There were 191 men and 121 women. Their mean age was 45.7 years. Of the 312 cases, 310 were living-related KTx, while 2 were deceased donor KTx. The immunosuppressive treatment protocol mainly consisted of 4-drug therapy with methylprednisolone, tacrolimus, mycophenolate mofetil, and basiliximab. Patient survival was 99.7% at 1 year, 99.3% at 5 years, and 97.3% at 10 years. Renal allograft survival was 98.4% at 1 year, 91.7% at 5 years, and 86.5% at 10 years. However, death-censored renal allograft survival was 98.7% at 1 year, 92.4% at 5 years, and 89.0% at 10 years. Among the 312 patients, 33 grafts were lost during the observation period. The loss was because of chronic antibody-mediated rejection in 19 patients, death with function in 6 patients, and acute antibody-mediated rejection in 2 patients. The prognosis of patients and their grafts, which were managed following the immunosuppression protocol at our institute, was relatively good. KTx in a private hospital in Japan is at par with the global standard.

Acrodystrophic axonal polyneuropathy with celiac disease: a case report

BackgroundPatients with celiac disease present with not only gastrointestinal symptoms but also extraintestinal manifestations such as anemia, osteopathy, dermatitis herpetiformis, and celiac neuropathy. Despite a fairly wide range of celiac neuropathies, we report a case of the acrodystrophic variant of celiac polyneuropathy, which has not been previously described.Case presentationA 41-year-old Ukrainian male suffered from symmetric, sensorimotor axonal polyneuropathy and encephalopathy associated with celiac disease, which is characterized by severe trophic disorders in the lower extremities (trophic ulcers, hyperkeratosis, and anhidrosis). Acrodystrophic changes in the lower extremities were due to both neurogenic and direct immunoinflammatory damaging effects. Clinical–electrophysiological dissociation was also noted, which was represented by a gross axonal lesion with the preservation of muscle strength. The absence of enteropathic manifestations was accompanied by the pronounced histological changes in the duodenal mucosa by IIIb stage of Marsh. A gluten-free diet in combination with membrane plasma exchange and intravenous pulse methylprednisolone was prescribed to reduce the severity of sensory disorders and regression of encephalopathy within 7 months.ConclusionCeliac disease may be a potential cause of neuropathy and encephalopathy in adult patients. Further immunosuppressive treatment protocols for both intestinal and extraintestinal manifestations of celiac disease are required.

P1762THE EFFECT OF IMMUNOSUPPRESSIVE THERAPY ON THE CLINICAL FOLLOW-UP OF BK VIRUS IN KIDNEY TRANSPLANT RECIPIENTS

Abstract Background and Aims BK virus nephropathy occurs in up to 10% of kidney transplant recipients and can result in graft loss. The reactivation of BK virus is largely asymptomatic, and routine surveillance especially in the first 12-24 months after transplant is necessary for early recognition and intervention. Reduced immunosuppression and antiviral treatment in the early stages may be effective in stopping BK virus replication. This study is designed to investigate the effect of management in immunosuppressive therapy on BK virus titers and graft functions in our kidney transplant group. Method A total of 370 kidney transplant recipients between the ages of 18-69 years and receiving a triple immunosuppressive therapy (Tacrolimus+Mycophenoloic Acid+Prednisolone) were included in the study. Demographic characteristics, BK virus titers, serum creatinine and immunosuppressive drug (Tacrolimus, Everolimus) levels were measured at regular intervals in the first 24 months. Among these patients 43 of them were found to have BK virus positivity. At the time of the detection of BK virus positivity, patients were divided into three groups regarding the change in the immunosuppressive protocols: Group I: Tacrolimus + Everolimus + Prednisolone, Group II: Everolimus + Prednisolone, Group III: Tacrolimus + Prednisolone. BK virus titers and graft functions of all three groups were compared with each other. SPSS 15 for Windows was used for statistical analysis. Results The mean age of the patients was 45.3 years, and the mean duration of transplantation was 16.3 months at the time of the BK virus positivity. During the follow-up, mean Tacrolimus levels were found to be in their highest value (14.1 ng/mL) in the posttransplant three months while BK virus titer reached the highest value (1.1x106 copies/ml) in the posttransplant seven to nine months. Increased creatinine values two months after BK virus positivity were strongly correlated (p = 0.02, p = 0.008, p = 0.05, p = 0.002 at 6th, 9th, 12th and 24th months, respectively). A significant decrease in BK virus titers was observed in all three groups due to reductions in immunosuppressive treatment protocol (p = 0.005, p = 0.003, p = 0.028, in groups I, II, III respectively). Conclusion Our study favors the benefits of the prospective screening for BK virus to identify early viral replication, permit intervention, and prevent progression to nephropathy or allograft loss. The best studied treatment for BK viremia and nephropathy is careful reduction of immunosuppression

Immunosuppressive Drugs Alter α1-Antitrypsin Production in Hepatocytes: Implications for Epithelial Gap Repair.

Immunosuppressive drugs are an inherent component of hematopoietic stem cell transplantation (HSCT) for the prevention of acute graft-versus-host disease (GVHD). Circulating α1-antitrypsin (AAT), a serine-protease inhibitor produced predominantly by hepatocytes that rises during acute phase responses, is lost in patient's stool due to gastrointestinal GVHD, and its augmentation has been found to attenuate GVHD. Here we explored the effect of immunosuppressive drugs on hepatocyte production of AAT and intestinal epithelial gap repair. The effect of commonly used immunosuppressants on AAT production was examined in vitro using HepG2 cells and primary mouse hepatocytes, and their impact on human intestinal epithelial cell line gap repair was evaluated. Sera from 12 allogeneic HSCT recipients, obtained at 14 days post-transplantation, predating the diagnosis of GVHD (n=6), were examined for reepithelialization, with added clinical-grade AAT. Rapamycin compromised AAT production under inflammatory conditions. Mycophenolate mofetil and cyclosporine A (CSA) inhibited reepithelialization; AAT minimized the effect of CSA. Patient sera displayed superior gap repair with exogenous AAT. Functional insufficiency in circulating AAT may be the result of drug toxicities leading to ineffective gut reepithelization and compromised gut lining. Taken together, our data strengthen the rationale for incorporating AAT augmentation therapy into immunosuppressive treatment protocols.

Hemophagocytic Lymphohistiocytosis: Clinical Presentations and Diagnosis

Hemophagocytic lymphohistiocytosis (HLH) is an overwhelming clinical syndrome associated with extreme immune activation. Familial HLH is caused by autosomal-recessive inheritance of gene mutations that cripple lymphocyte cytotoxicity. X-linked lymphoproliferative diseases and mutations in Nod-like receptor caspase activation and recruitment domain containing protein 4 (NLRC4) also feature HLH as a predominant manifestation. In addition, "secondary" HLH may occur in immunocompromized patients or in individuals with previously intact immune responses in the context of strong immunologic triggers such as EBV infection, malignancy, rheumatologic disease, and drug hypersensitivity. Regardless of the etiology, HLH is often fatal unless recognized and treated aggressively. Research over the last 20 years has led to many advances in diagnosis and treatment. Rapid testing strategies designed to quickly screen for immune activation and cytotoxic lymphocyte dysfunction are now clinically available and genetic panels/testing algorithms may accelerate a genetic diagnosis. Immunosuppressive treatment protocols have been refined, and experience is gaining with alternative and salvage approaches. However, these advances improve the outcome of patients only when the diagnosis of HLH is made. Ongoing education is needed to ensure medical providers can appropriately recognize and diagnose HLH. This Grand Rounds Review will summarize the clinical and diagnostic features of HLH and highlight known genetic causes.

Effects of Two Immunosuppressive Treatment Protocols for IgA Nephropathy.

The role of immunosuppression in IgA nephropathy (IgAN) is controversial. In the Supportive Versus Immunosuppressive Therapy for the Treatment of Progressive IgA Nephropathy (STOP-IgAN) Trial, 162 patients with IgAN and proteinuria >0.75 g/d after 6 months of optimized supportive care were randomized into two groups: continued supportive care or additional immunosuppression (GFR≥60 ml/min per 1.73 m2: 6-month corticosteroid monotherapy; GFR=30-59 ml/min per 1.73 m2: cyclophosphamide for 3 months followed by azathioprine plus oral prednisolone). Coprimary end points were full clinical remission and GFR loss ≥15 ml/min per 1.73 m2 during the 3-year trial phase. In this secondary intention to treat analysis, we separately analyzed data from each immunosuppression subgroup and the corresponding patients on supportive care. Full clinical remission occurred in 11 (20%) patients receiving corticosteroid monotherapy and three (6%) patients on supportive care (odds ratio, 5.31; 95% confidence interval, 1.07 to 26.36; P=0.02), but the rate did not differ between patients receiving immunosuppressive combination and controls on supportive care (11% versus 4%, respectively; P=0.30). The end point of GFR loss ≥15 ml/min per 1.73 m2 did not differ between groups. Only corticosteroid monotherapy transiently reduced proteinuria at 12 months. Severe infections, impaired glucose tolerance, and/or weight gain in the first year were more frequent with either immunosuppressive regimen than with supportive care. In conclusion, only corticosteroid monotherapy induced disease remission in a minority of patients who had IgAN with relatively well preserved GFR and persistent proteinuria. Neither immunosuppressive regimen prevented GFR loss, and both associated with substantial adverse events.

Monotherapie met prednisolone bij honden met meningo-encefalitis van onbekende oorsprong

Meningo-encefalitis van onbekende oorsprong is een vaak gediagnosticeerde neurologische aandoening die meestal fataal afloopt. Het doel van deze retrospectieve studie was het evalueren van drie behandelingsschema’s enkel bestaande uit prednisolone, gedoseerd in een afbouwend schema van drie, acht of achttien weken. De diagnose werd gesteld aan de hand van in de literatuur beschreven klinische criteria. Zevenendertig honden werden in de studie opgenomen, waarvan er zeventien, vijftien en zes respectievelijk het gedurende drie-, acht- en achttien-weken afbouwend schema toegediend kregen. Er werd een significant verschil waargenomen in overlevingstijd tussen de drie schema’s. Zevenendertig % van de honden in de studie stierf of werd geëuthanaseerd wegens de aandoening. Verrassend genoeg werd de hoogste mortaliteit vastgesteld in de groep die behandeld werd met het acht weken afbouwend schema (56%), gevolgd door het drie weken (26%) en het achttien weken afbouwend schema (0%). Gebaseerd op deze resultaten kunnen er geen definitieve conclusies getrokken worden voor wat betreft het ideale cortisonebehandelingsschema voor honden met meningo-encefalitis van onbekende oorsprong, maar een meer agressief en immunosuppressief schema zou kunnen leiden tot een lagere mortaliteit.

Comparison of Clinical Outcomes in Hepatitis B Virus–Positive and –Negative Renal Transplant Recipients

Our aim was to compare the short- and long-term clinical outcomes of hepatitis B surface antigen–positive (HbsAg+) renal transplant recipients with HbsAg− recipients. A total of 204 patients who underwent renal transplantation in our center between 2001 and 2014 were included in the study. The patients were divided into 2 groups. Group 1 was the HbsAg− group (n = 136), and group 2 was the HbsAg+ group (n = 68). There was no significant difference between the groups in terms of lymphocyte crossmatches, numbers of mismatches, immunosuppressive treatment protocols, and induction treatments. In the HbsAg+ group, 51 patients were hepatitis B virus DNA+, 64 patients were HbeAg−, and 4 patients were HbeAg+. A total of 57 patients (83.8%) were treated with lamivudine, 4 patients (5.9%) with entecavir, and 7 patients (10.3%) with tenofovir for hepatitis B infection. Graft and patient survival rates, graft functions, acute hepatitis rates, acute rejection rates, and other clinical outcomes of the groups were compared. Demographic data and immunologic risk profiles of the groups were similar. Acute rejection rates, graft survival rates, and patient survival rates were similar. Acute hepatitis rates, glomerular filtration rates on the last controls, and delayed graft function rates were higher in group 2, whereas chronic allograft dysfunction and new-onset diabetes mellitus after transplantation rates were similar between the groups. Our study revealed that graft and patient survival, and acute rejection rates were similar between HbsAg+ and HbsAg− recipients, whereas acute hepatitis rate was higher in HbsAg+ recipients.

The role of midkine in the inflammatory process and its correlation with other inflammatory markers in renal transplant recipients.

Midkine (MK), which is expressed in the proximal tubular epithelial cells of the kidney, is thought to have a role in the pathophysiology of inflammation-related renal diseases. Both immunological and nonimmunological mechanisms may affect renal functions negatively during the early and late post-transplantation periods. We aimed in our study to evaluate the relationship of MK with clinical findings and inflammatory markers, including high sensitivity C-reactive protein (hs-CRP), interleukin (IL-6) and tumor necrosis factor (TNF-α) in the pretransplant and post-transplant period. Forty-one consecutive patients transplanted from living related donors were included in this prospective observational study. All patients received the same immunosuppressive treatment protocol. MK, hsCRP, IL-6 and TNF-α levels were measured before and 2 months after renal transplantation. Pretransplant MK levels correlated positively with hsCRP (r = 0.41, p = 0.004) and IL-6 (r = 0.58, p&lt;0.001). The mean post-transplant MK level was found to be higher than the pretransplant level (143 ± 350 pg/mL, 2792 ± 4235 pg/mL respectively, p = &lt;0.001), while the mean hsCRP, IL-6 and TNF-α levels did not change significantly. Post-transplant IL-6 correlated significantly with MK (r = 0.388, p = 0.012), hsCRP (r = 0.41, p = 0.007) and TNF-α (r = 0.348, p = 0.026). There was no significant correlation between clinical findings and inflammatory markers. MK may be a good inflammatory marker in renal transplant recipients as in other inflammatory diseases. Moreover, it seems that it is not affected by factors other than inflammation during the post-transplantation period.

Evaluation of the safety and tolerability of rivaroxaban in dogs with presumed primary immune-mediated hemolytic anemia.

To evaluate the safety and tolerability of rivaroxaban (RIV), an oral direct factor Xa inhibitory drug, in dogs with presumed primary immune-mediated hemolytic anemia (pIMHA). Prospective, multicenter, positive-controlled, unblinded clinical trial. Client-owned dogs were enrolled between October 2012 and March 2014. Private referral centers. Twenty-four client-owned dogs with pIMHA. Enrolled dogs were randomized in 2 treatment groups to receive by mouth RIV or clopidogrel (CL) and low-dose aspirin (LDA). All dogs were monitored for 90 days from the enrollment in the study. Enrolled dogs were given a standardized immunosuppressive protocol and RIV or CL and LDA. There was no identifiable adverse drug reaction, evidence of hemorrhage, significant prolongation of prothrombin time or activated partial thromboplastin time, or increase in transfusion requirements associated with RIV therapy compared to CL and LDA in dogs with pIMHA. There was no significant difference between treatment groups with respect to thrombotic events, survival rates to discharge, at 1 month and 3 months from diagnosis. This study suggests that RIV at a median dose of 0.89 mg/kg by mouth once daily was safe and well tolerated in a small group of dogs with presumed pIMHA able to tolerate oral medications and treated with a standardized immunosuppressive treatment protocol. Conclusions regarding the relative efficacy of RIV as compared to CL and LDA cannot be made due to the small size of the treatment groups and because pharmacodynamic effects were not assessed.

Quantification of the Immunosuppressant Tacrolimus on Dried Blood Spots Using LC-MS/MS

The calcineurin inhibitor tacrolimus is the cornerstone of most immunosuppressive treatment protocols after solid organ transplantation in the United States. Tacrolimus is a narrow therapeutic index drug and as such requires therapeutic drug monitoring and dose adjustment based on its whole blood trough concentrations. To facilitate home therapeutic drug and adherence monitoring, the collection of dried blood spots is an attractive concept. After a finger stick, the patient collects a blood drop on filter paper at home. After the blood is dried, it is mailed to the analytical laboratory where tacrolimus is quantified using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) in combination with a simple manual protein precipitation step and online column extraction. For tacrolimus analysis, a 6-mm disc is punched from the saturated center of the blood spot. The blood spot is homogenized using a bullet blender and then proteins are precipitated with methanol/0.2 M ZnSO4 containing the internal standard D2,(13)C-tacrolimus. After vortexing and centrifugation, 100 µl of supernatant is injected into an online extraction column and washed with 5 ml/min of 0.1 formic acid/acetonitrile (7:3, v:v) for 1 min. Hereafter, the switching valve is activated and the analytes are back-flushed onto the analytical column (and separated using a 0.1% formic acid/acetonitrile gradient). Tacrolimus is quantified in the positive multi reaction mode (MRM) using a tandem mass spectrometer. The assay is linear from 1 to 50 ng/ml. Inter-assay variability (3.6%-6.1%) and accuracy (91.7%-101.6%) as assessed over 20 days meet acceptance criteria. Average extraction recovery is 95.5%. There are no relevant carry-over, matrix interferences and matrix effects. Tacrolimus is stable in dried blood spots at RT and at +4 °C for 1 week. Extracted samples in the autosampler are stable at +4 °C for at least 72 hr.

Prognostic factors for remission of and survival in acquired hemophilia A (AHA): results from the GTH-AH 01/2010 study

AbstractAcquired hemophilia A (AHA) is caused by autoantibodies against factor VIII (FVIII). Immunosuppressive treatment (IST) results in remission of disease in 60% to 80% of patients over a period of days to months. IST is associated with frequent adverse events, including infections as a leading cause of death. Predictors of time to remission could help guide IST intensity but have not been established. We analyzed prognostic factors in 102 prospectively enrolled patients treated with a uniform IST protocol. Partial remission (PR; defined as no active bleeding, FVIII restored >50 IU/dL, hemostatic treatment stopped >24 hours) was achieved by 83% of patients after a median of 31 days (range 7-362). Patients with baseline FVIII <1 IU/dL achieved PR less often and later (77%, 43 days) than patients with ≥1 IU/dL (89%, 24 days). After adjustment for other baseline characteristics, low FVIII remained associated with a lower rate of PR (hazard ratio 0.52, 95% confidence interval 0.33-0.81, P < .01). In contrast, PR achieved on steroids alone within ≤21 days was more common in patients with FVIII ≥1 IU/dL and inhibitor concentration <20 BU/mL (odds ratio 11.2, P < .0001). Low FVIII was also associated with a lower rate of complete remission and decreased survival. In conclusion, presenting FVIII and inhibitor concentration are potentially useful to tailor IST in AHA.

Prognostic Parameters For Remission Of and Survival In Acquired Hemophilia A: Results Of The GTH-AH 01/2010 Multicenter Study

Acquired hemophilia A (AHA) is a rare autoimmune disorder caused by neutralizing autoantibodies against coagulation factor VIII (FVIII:C). Immunosuppressive treatment may result in remission of disease over a period of days to months. Until remission, patients are at high risk of bleeding and complications from immunosuppression. Prognostic parameters to predict remission and the time needed to achieve remission could be helpful to guide treatment intensity, but have not been established so far. GTH-AH01/2010 was a prospective multicenter cohort study using a standardized immunosuppressive treatment protocol. The primary study endpoint was time to achieve partial remission (PR, defined as FVIII:C activity >50 IU/dl after cessation of any hemotherapy for >24h, and no active bleeding). Secondary endpoints were time to achieve complete remission (CR, defined as PR plus negative FVIII:C inhibitor, steroid tapered to 15 mg/d, or equivalent, they received prednisolone (100 mg/d) and rituximab from day 1. If cyclophosphamide was contraindicated, patients received prednisolone (100 mg/d) and rituximab from day 21. One hundred twenty-four patients from 21 treatment centers in Germany and Austria were enrolled between April 2010 and April 2013 (36 months). The patients from two centers not compliant with the treatment protocol were excluded (N=18), as were patients in whom AHA was not confirmed (N=2) or follow-up was too short at the time of this analysis (N=7). The remaining 97 patients from 17 centers were followed for a median of 256 days (interquartile range [IQR] 84-561). Median age was 74 years (IQR 64-82). AHA was associated with other autoimmune disorders (19%), malignancy (12%), pregnancy or puerperium (5%), but was most often idiopathic (66%). The median FVIII:C activity at baseline was 1 IU/dl (IQR =1 IU/dl) had a strong impact on the time to achieve PR (HR 2.76 [95% confidence interval 1.73-4.42], p<0.001) and CR (HR 2.36 [1.34-4.14], p<0.01). Baseline FVIII:C activity was also a predictor of PR and CR when other cutoffs were used (2 or 3 IU/dl instead of 1 IU/dl), or when it was analyzed as a continuous variable in Cox regression analysis. In contrast, FVIII:C inhibitor titer assessed by the local laboratory did not affect time to PR or CR significantly. OS after 300 days, estimated by the Kaplan Meier method, was 69%. Age, WHO performance status, and FVIII:C activity at baseline were independent predictors of OS. In summary, GTH-AH 01/2010 is the largest prospective study of patients with AHA treated according to a standardized protocol. The study demonstrated a robust effect of baseline FVIII:C activity on the time needed to achieve PR and CR. Baseline FVIII:C activity, together with age and performance status, also affected OS. Therefore, baseline FVIII:C activity may be considered to guide individually tailored immunosuppression in future studies. Disclosures: Tiede: Baxter: Consultancy, Honoraria, Research Funding; Bayer: Consultancy, Honoraria, Research Funding; Biotest: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; Novo Nordisk: Consultancy, Honoraria, Research Funding; Biogen Idec: Consultancy; CSL Behring: Consultancy, Honoraria, Research Funding. Off Label Use: Prednisolone, cyclophosphamid, and rituximab for immunosuppression in acquired hemophilia. Klamroth: Bayer: Honoraria, Research Funding; Baxter: Honoraria, Research Funding; CSL Behring: Honoraria, Research Funding; Novo Nordisk: Honoraria, Research Funding. Gottstein: Novo Nordisk: Honoraria; Baxter: Honoraria. Holstein: Baxter: Honoraria, Speakers Bureau. Scharf: CSL Behring: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria; Biotest: Consultancy, Honoraria, Research Funding; Bayer: Consultancy, Honoraria; Baxter: Consultancy, Honoraria, Research Funding. Huth-Kuhne: SRH Kurpfalz Hospital and Hemophilia Center: Consultancy, Employment, Honoraria, Membership on an entity’s Board of Directors or advisory committees. Greil: Roche: Consultancy, Honoraria, Research Funding. Miesbach: Novo Nordisk: Consultancy, Honoraria, Research Funding; Baxter: Consultancy, Honoraria, Research Funding. Trappe: Roche: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau, Travel Other; AMGEN: Research Funding, Travel, Travel Other; CSL Behring: Honoraria, Research Funding, Speakers Bureau, Travel, Travel Other; Mundipharma: Research Funding, Travel, Travel Other; Takeda: Consultancy, Research Funding, Travel Other; Novartis: Consultancy, Research Funding, Travel, Travel Other; Novartis: Research Funding, Travel Other; Cellgen: Travel, Travel Other. Knoebl: Novo Nordisk: Consultancy, Honoraria; Baxter: Consultancy, Honoraria.

Mucocutaneous disorders in renal transplant recipients receiving sirolimus‐based immunosuppressive therapy: a prospective, case–control study

Sirolimus (SRL) has some dermatologic complications including acneiform eruptions, edema, aphthous ulceration, and onychopathy. However, controlled studies reporting the prevalence and clinical characteristics of mucocutaneous disorders are scarce. To investigate the prevalence and clinical spectrum of mucocutaneous disorders in renal transplant recipients (RTRs) receiving SRL and to compare the findings with those in RTRs not receiving SRL. Fifty RTRs (35 men, 15 women; mean age, 34.6 ± 11.6 yr) receiving SRL, 50 RTRs (36 men, 14 women; mean age, 34.4 ± 11.3 yr) not on SRL were screened for mucocutaneous disorders. In RTRs receiving SRL, skin infection (78%) was the most common dermatologic disorder followed by facial hyperpigmentation (50%) and acneiform eruption (46%). Herpes simplex virus infections (14%) and seborrheic dermatitis (38%) were significantly more common in RTRs on SRL (p < 0.05); the frequencies of edema, aphthous ulceration, acne, and longitudinal nail ridging were similar in both groups (p > 0.05). This study had a small sample size. The investigator was not blinded to immunosuppressive treatment protocols. Renal transplant recipients receiving SRL are more likely to develop seborrheic dermatitis and herpes simplex virus infections than those not taking SRL. Whereas, they are not more prone to edema, aphthous ulceration, acne, or longitudinal nail ridging.

The spectrum of CNS vasculitis in children and adults

Children and adults who present with severe, newly acquired neurological or psychiatric deficits should be evaluated for an underlying inflammatory brain disease-the inflammation could be reversible, if diagnosed and treated rapidly. In our experience, primary angiitis of the central nervous system (PACNS) is the most common inflammatory brain disease and is increasingly recognized across patients of all ages. Distinct disease subtypes have been reported with characteristic disease courses, neuroimaging features and histopathological findings. In this Review, we provide a comprehensive comparison of childhood and adult PACNS, revealing distinct gender distributions, characteristic presenting clinical phenotypes and tailored differential diagnosis evaluations in the different subtypes of PACNS. Novel and traditional laboratory markers can help to define disease subtype and activity, whilst MRI and angiography can aid diagnosis in both children and adults. Characteristic patterns of parenchymal lesions and vessel involvement have been identified in PACNS and differ markedly between subtypes. Brain histopathology has also revealed distinct inflammatory pathways at different ages. Immunosuppressive treatment protocols have been shown to be effective and safe across the age spectrum; overall, in the past few years, the mortality of PACNS has decreased dramatically.

Discontinuous drug combination therapy in autoimmune ocular disorders

This study aimed to assess the effectiveness of a steroid-sparing immunosuppressive treatment (IST) protocol in the control of severe or steroid-resistant autoimmune ocular inflammatory diseases. We carried out a prospective, non-randomized clinical study. Patients presenting with ocular inflammations that failed to respond adequately to steroids alone after monotherapy for a mean period of 9 +/- 2 months (internal control) were offered the option to switch to a combined IST. The protocol consisted of different immunosuppressive drugs added in a stepladder sequence, where each drug (including the steroids) was administered discontinuously. Main outcome measures were control of inflammation, visual acuity and safety of treatment. A total of 76 subjects (121 affected eyes) enrolled in the IST protocol. Mean length of follow-up was 43 +/- 15 months. Complete control of inflammation was achieved in 86% of patients. During the first year of IST, the rate of inflammatory recurrences/patient was 0.78 +/- 1.13. This ratio diminished further during succeeding follow-up. Mean best corrected visual acuity improved from 0.31 logMAR to 0.24 logMAR (p < 0.001). Blood pressure and uric acid blood levels significantly altered for the worse in the study group. Immunosuppressive treatment was effective in achieving inflammatory quiescence in a large majority of patients. The study also demonstrated the longterm safety of the protocol and its steroid-sparing effect.

Clinical Characteristics of Vogt–Koyanagi–Harada Syndrome in Chinese Patients

To characterize the clinical features of Vogt-Koyanagi-Harada syndrome (VKH) in Chinese patients. Retrospective noncomparative case series. A total of 410 consecutive VKH patients examined from August 1995 to April 2005. Charts of these patients were reviewed according to international VKH criteria. Patients who consulted us within 2 weeks after a uveitis attack were classified into group 1; between 2 weeks and 2 months into group 2; and after 2 months into group 3. The history and clinical findings of all of the patients were reviewed. Laser flare-cell photometry, fundus fluorescein angiography, indocyanine green angiography, optical coherence tomography, B-scan ultrasonography, and ultrasound biomicroscopy were performed in certain cases. Corticosteroids were mainly used to treat patients in groups 1 and 2, whereas cyclosporine or chlorambucil in combination with corticosteroids were prescribed for patients in group 3. Demographics, clinical presentation, and ancillary examinations of the patients in all 3 groups. The patients were diagnosed as having either complete (n = 273), incomplete (n = 76), or probable (n = 61) VKH syndrome. Exudative retinal detachment and either choroiditis or chorioretinitis were the main findings in group 1. Posterior uveitis with mild to moderate anterior uveitis simulating a nongranulomatous inflammation as evidenced by dust keratic precipitates, anterior chamber cells, and flare was noted in group 2. Recurrent granulomatous anterior uveitis with a "sunset glow" fundus was observed in group 3. Complicated cataract was the most common complication in the patients in group 3. At the final visit, the uveitis was completely controlled in all patients and a best-corrected visual acuity of <20/200 was 1.9%/eye-year, 1.2%/eye-year, and 6%/eye-year in groups 1, 2, and 3, respectively. Vogt-Koyanagi-Harada syndrome in Chinese patients is characterized by early posterior uveitis, and if the syndrome is not controlled, subsequent recurrent granulomatous anterior uveitis. Good visual prognosis is possible if the patients are managed according to a tailored immunosuppressive treatment protocol.

Sirolimus as Primary Immunosuppression Agent in Kidney Transplant Recipients: Akdeniz University Experience

Objectives Recently usage of sirolimus as the primary immunosuppressant is widening among kidney transplant recipients. We reviewed the clinical follow-up of patients transplanted at our center using sirolimus protocols. Methods Sirolimus including primary immunosuppressive treatment protocols were begun in February 2002. Among the 21 patients (15 men, six women) who received sirolimus, six patients were prescribed sirolimus + prednisolone; seven, sirolimus + mycophenolate mofetil + prednisolone; and eight, sirolimus + cyclosporine + prednisolone. The mean age of the patients was 32.9 ± 7.3 years and the mean posttransplantation follow-up, 13.2 ± 4.5 months. Results Three patients experienced acute rejection episodes, which were treated successfully with steroids. None of the patients had either hematologic or wound healing problems. Lymphoceles developed in eight patients. Serum creatinine level was 1.4 ± 0.5 mg/dL at 12 months. There was a serious increase in serum cholesterol and triglyceride levels starting from the first month posttransplant (total cholesterol levels pretransplant and at 1 month, respectively: 159.3 ± 29.5 and 255.7 ± 52.3 mg/dL, P = .0001; triglycerides pretransplant and at 1 month, respectively: 146.9 ± 89.5 and 215.1 ± 102.5 mg/dL, P = .001). Despite routine antihyperlipemic treatment those high levels were maintained for 12 months. Conclusions We achieved 100% graft and patient survival rates for 1 year among patients who were using sirolimus. But the most important role in defining the morbidity and mortality in this group of patients is cardiovascular events; for this reason the abnormalities in the lipid profile must be taken seriously.