Serum Sickness Research Articles

Rituximab Is an Alternative to Splenectomy in Adults with Chronic Immune Thrombocytopenic Purpura: Results of a Multicenter Prospective Phase 2 Study.

Background : Rituximab, a monoclonal anti-CD20 antibody, is a promising therapeutic agent for adults with immune thrombocytopenic purpura (ITP). Pooling results of the published literature suggest that rituximab achieves an initial response in about 50 % of adults with chronic ITP, with a 25–40% rate of sustained response. However, heterogeneity of patient pre-treatment status, short follow up and bias due to retrospective studies limit the interpretation of the data.Objective : To assess the safety and efficacy of rituximab in adults with chronic ITP (duration ≥ 6 months) and platelet count ≤ 30x109/L candidate to splenectomy.Methods : a multicenter prospective open-label single arm phase 2 trial designed according to Fleming's single stage procedure was conducted. After informed consent, non splenectomized adults received 4 weekly intravenous infusions of rituximab at a dose of 375 mg/m2. All other ITP treatments were stopped. Treatment success was defined as a platelet count ≥ 50 x109/L with at least a 2 fold increase of the initial value at one year after the first rituximab infusion. Patients who received another treatment during follow up were considered as non responders. A sample size of at least 56 patients was calculated by Fleming's single-stage design to ensure 90 % power for proving lack of efficacy if the true complete response rate was below 25%.Results : Sixty consecutive patients (40F/20M) were included over a 21 months period. Mean age was 48 years (range 18–84). Mean ITP duration was 4.8 years. Mean platelet count at inclusion was 16±10x109/L. All but one patient, in whom reversible serum sickness disease was diagnosed after 2 infusions, received 4 infusions of rituximab. Fifteen other patients experienced transient side effects that did not lead to treatment discontinuation. No patient was lost to follow up. Success was achieved in 40 % (24/60 patients) (95 % confidence interval 28% to 52%) and was found significantly different from 25% (p=0.007). Among the 24 long term responders, platelet count at one year was ≥ 150x109/L in 18 and between 50 and 150 x109/L in 6. Two other patients (3%) had and incomplete response defined as a platelet count at one year between 30 and 50 x109/L but at least 2 fold the initial value. Thirty four (57%) patients failed to respond and amongst them, 18 have already undergone splenectomy.Conclusion: rituximab appears to be a safe and good splenectomy-sparing strategy in adults with chronic ITP leading to a significant and durable response in 40% of the cases.

Infliximab Treatment in Pediatric IBD Patients: A Single‐centre Experience

Aim: Evaluation of the treatment effectiveness and side effects of episodic infliximab treatment in paediatric IBD patients. Methods: Retrospective study collecting data on clinical evolution, nutritional status and growth of 12 IBD patients <18y treated with infliximab infusions (2002-2006) (on a total of 37). Results: 11 Crohn's disease (10M) and 1 ulcerative colitis (1F) were started on infliximab because of partial or total steroid dependence. All had maintenance treatment with mesalazine and azathioprine. Modulen was used as adjuvant therapy. Median age at diagnosis: 11.9 y (10.5-14.1). Median age at start of infliximab treatment: 14.3y (12.8-17.8). Repeated infliximab infusions were administered on clinical demand. Median follow-up since infliximab: 21m (3m-4y). Complete remission (CR= total regression of symptoms 30d after infliximab infusion) was observed in 58% (7/12), partial remission (PR= regression of symptoms) in 33% (4/12) and no response in 1/12. Steroid withdrawal was possible in all infliximab treated patients. Side effects in 3/12: 2 immediate allergic reactions (future infusions were continued with concomitant use of oral antihistaminics and IV steroids), 1 patient with serum sickness & arthritis (stopped). 9/11 remaining patients continue to receive infliximab every 2-3m with concomitant azathioprine treatment. Growth improved significantly within 3m after start in the CR group but not in the PR group. Conclusions: These results confirm a good short term response to infliximab in paediatric patients with steroid dependent IBD. Side effects were comparable to what is known in adult patients. Many patients remain infliximab dependent. Hence, long term effects, now unknown, are relevant, necessitating careful follow-up of these patients.

In Vitro Monitoring of in Vivo Development of Human Anti-Thymoglobulin Antibodies by ELISA

Thymoglobulin (rATG), polyclonal immunoglobulin, is prepared from rabbits immunized with human thymocytes. It is effective in prevention and treatment of renal allograft rejection. Human antibodies against antilymphocyte preparations can reduce efficacy by accelerating drug clearance or by inducing serum sickness. We developed an enzyme-linked immunosorbent assay (ELISA) to study posttreatment development of anti-rATG. In an Institutional Review Board–approved trial, we tested 101 allograft recipients for anti-rATG antibodies. Patients received rATG intravenously at 1.25 to 2.0 mg/kg/d for 2 to 14 days. Serum samples were obtained pretreatment and at weeks 1, 2, 4, 6, and months 3 and 6 post-rATG. ELISA plates were coated with rATG (10 μg/mL). Samples were diluted 1:100 and tested in quadruplicate. Positive samples were titrated. Horseradish peroxidase-conjugated (HRPO) affinity-purified goat anti-human immunoglobulin G (H&L) antibody reacted with bound human antibody. A chromagenic substrate for HRPO was added and optical density (OD, 490 nm) was read. An OD of twice the negative control was considered positive. Mean ODs of negative and positive controls were 0.113 ± 0.030 and 1.042 ± 0.196, respectively. Ten patients had detectable anti-rATG before rATG administration (1:100). Thirty-five of 101 patients (35%) developed anti-rATG antibody. Patients showed an initial positive anti-rATG antibody from days 8 to 59 after infusion and titers from 1:100 to 1:4000. In spite of rATG’s postulated anti-B-cell activity, this study confirms that rATG induces sensitization at a frequency and titer seen with other xenogeneic antilymphocyte antibodies. Formation of such antixenoantibodies can have a negative impact on treatment response and hence warrant monitoring.

Rituximab‐induced serum sickness

A 46-year-old woman, who had suffered from Sjogren syndrome for over 25 years, developed an extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue of her right parotic gland. She was treated with monotherapy rituximab, 375 mg/m weekly with premedication consisting of 1000 mg paracetamol, 1 mg clemastin and 25 mg prednisolone. Two days after the second course of rituximab, she developed severe arthralgia of multiple joints. After a further 2 d, she had progressive skin lesions of her legs that were clinically suggestive of vasculitis (top, bottom). Her temperature was 38 C. Laboratory investigations showed normal values for blood count and creatinine. A diagnosis of serum sickness was made. A short course of prednisone 20 mg/d was given and the symptoms resolved over the next 5 d. Serum sickness is a type III hypersensitivity reaction resulting from the injection of foreign protein and subsequent formation of antibodies, occurring 4–10 after exposure. Clinical symptoms can include fever, arthralgia, lymphadenopathy and skin eruptions. Serum sickness caused by rituximab has been reported, but is uncommon.

Adalimumab Rapidly Induces Clinical Remission and Response in Patients with Moderate to Severe Crohnʼs Disease Who Had Secondary Failure to Infliximab Therapy

Purpose: To assess the safety and efficacy of adalimumab (ADA), a self-injectable, fully human anti-TNF monoclonal antibody, in the induction of clinical remission (CDAI < 150) and response in patients with active Crohn's disease (CD) who had secondary failure to infliximab (IFX) therapy. Methods: Patients with moderate to severe CD (CDAI 220–450) and secondary failure to IFX therapy were enrolled in GAIN, a Phase III, double-blind, placebo-controlled study, and were randomized to receive ADA, 160 mg sc at Wk 0 (BL) and 80 mg sc at Wk 2, or placebo (PBO) at both time points. Primary endpoint was remission at Wk 4. Secondary endpoints were clinical response (CR) defined as a decrease from BL CDAI of ≥70 or 100 (CR70/100) at Wk 4. Safety was assessed throughout the study. Results: Patients were randomized to receive ADA (N = 159) or PBO (N = 166). Baseline characteristics were similar between the two arms: mean age, 38 yrs; female, 65%; mean CDAI, 313 (± 62 SD); median CRP, 0.8 mg/dL; immunosuppressant use, 48%. Clinical remission and response rates observed in the ADA arm were significant vs. PBO. Serious adverse events (SAE) were observed in 4.8% of PBO patients (abscess, 3; sepsis, 1; CD flare, 1; dehydration, 1; abdominal pain, 1) and in 1.3% of ADA patients (CD flare, 1; dehydration, 1). No delayed-hypersensitivity (serum sickness) reactions or deaths occurred. The overall safety profile of ADA was consistent with prior CD trials and the existing RA database. Conclusions: Adalimumab rapidly and significantly induced clinical remission and response in patients with moderate to severe CD who had secondary failure to IFX. Adalimumab was well-tolerated.Table: Clinical Remission and Response in GAIN.

Bilateral Hand Transplantation: Six Years After the First Case

In this study we present our experience concerning bilateral hand transplantation. Two cases were performed: the first in January 2000 and the second in April 2003. Both recipients received the same immunosuppressive treatment, which was similar to those used in solid organ transplantation, including tacrolimus, prednisone and mycophenolate mofetil while antithymocyte globulins were added for induction. Both recipients presented two episodes of acute rejection (maculopapular lesions) in the first 3 months after transplantation; however, these were easily reversed after a few days increasing oral steroid doses and using topical immunosuppressants. The first recipient presented hyperglycemia and serum sickness while the second recipient suffered a thrombosis of the right ulnar artery and an osteomyelitis of left ulna. All the complications were successfully treated. Functional Magnetic Resonance Imaging (fMRI) showed that cortical hand representation progressively shifted from the lateral to the medial region in the motor cortex. After 6 and 2 years respectively, they showed a relevant sensorimotor recovery particularly of sensibility and activity of intrinsic muscles. They were able to perform the majority of daily activities and to lead a normal social life. The first recipient has been working since 2003. They are both satisfied with their grafted hands.

Apparent hemolysis following intravenous antithymocyte globulin treatment in a patient with marrow failure and a paroxysmal nocturnal hemoglobinuria clone

Antithymocyte globulin (ATG) is a commonly used medication in the treatment of aplastic anemia. Although serum sickness has been described with the use of ATG, few cases of acute intravascular hemolysis have been reported. We report a case of apparent ATG-related hemolysis in a patient with aplastic anemia and a paroxysmal nocturnal hemoglobinuria (PNH) clone. A 62-year-old, group A, RhoD+ man with aplastic anemia and an 11.6 percent glycosylphosphatidylinositol (GPI)-anchored protein-negative population of red cells (RBCs), representing approximately 190 mL of his RBC volume, and 90 percent GPI-negative neutrophils were scheduled to receive equine ATG at 40 mg per kg per day for 4 days. After the first infusion, he developed a 1.6 g per dL decline in hemoglobin concentration and an increase in serum lactate dehydrogenase (normal, 113-226 U/L) from 284 to 1127 U per L. The hemolytic process was complicated by acute renal failure characterized by an increase in serum creatinine from 0.9 to 4.2 mg per dL and the appearance of dark-colored urine. Pre- and post-ATG direct antiglobulin tests were negative. The temporal association of intravenous ATG to lysis of complement-sensitive RBCs suggests a causal relationship. Although intravascular hemolysis after ATG administration appears to be uncommon, the clinical consequences may be severe, and determining the pathophysiology may yield clues to the mechanism of intravascular hemolysis.

Bioinformatics and Multiepitope DNA Immunization to Design Rational Snake Antivenom

BackgroundSnake venom is a potentially lethal and complex mixture of hundreds of functionally diverse proteins that are difficult to purify and hence difficult to characterize. These difficulties have inhibited the development of toxin-targeted therapy, and conventional antivenom is still generated from the sera of horses or sheep immunized with whole venom. Although life-saving, antivenoms contain an immunoglobulin pool of unknown antigen specificity and known redundancy, which necessitates the delivery of large volumes of heterologous immunoglobulin to the envenomed victim, thus increasing the risk of anaphylactoid and serum sickness adverse effects. Here we exploit recent molecular sequence analysis and DNA immunization tools to design more rational toxin-targeted antivenom.Methods and FindingsWe developed a novel bioinformatic strategy that identified sequences encoding immunogenic and structurally significant epitopes from an expressed sequence tag database of a venom gland cDNA library of Echis ocellatus, the most medically important viper in Africa. Focusing upon snake venom metalloproteinases (SVMPs) that are responsible for the severe and frequently lethal hemorrhage in envenomed victims, we identified seven epitopes that we predicted would be represented in all isomers of this multimeric toxin and that we engineered into a single synthetic multiepitope DNA immunogen (epitope string). We compared the specificity and toxin-neutralizing efficacy of antiserum raised against the string to antisera raised against a single SVMP toxin (or domains) or antiserum raised by conventional (whole venom) immunization protocols. The SVMP string antiserum, as predicted in silico, contained antibody specificities to numerous SVMPs in E. ocellatus venom and venoms of several other African vipers. More significantly, the antiserum cross-specifically neutralized hemorrhage induced by E. ocellatus and Cerastes cerastes cerastes venoms. ConclusionsThese data provide valuable sequence and structure/function information of viper venom hemorrhagins but, more importantly, a new opportunity to design toxin-specific antivenoms—the first major conceptual change in antivenom design after more than a century of production. Furthermore, this approach may be adapted to immunotherapy design in other cases where targets are numerous, diverse, and poorly characterized such as those generated by hypermutation or antigenic variation.

Severe Serum Sickness Reaction to Oral and Intramuscular Penicillin

Serum sickness is a type III hypersensitivity reaction mediated by immune complex deposition with subsequent complement activation, small-vessel vasculitis, and tissue inflammation. Although the overall incidence of serum sickness is declining because of decreased use of heterologous sera and improved vaccinations, rare sporadic cases of serum sickness from nonprotein drugs such as penicillins continue to occur. Drug-induced serum sickness is usually self-limited, with symptoms lasting only 1-2 weeks before resolving. We report an unusual case of a severe and prolonged serum sickness reaction that occurred after exposure to an intramuscular penicillin depot injection (probable relationship by Naranjo score) and discuss how pharmacokinetics may have played a role. Clinicians should be familiar with serum sickness reactions particularly as they relate to long-acting penicillin preparations. Accurate diagnosis in conjunction with cessation of drug exposure and prompt initiation of antiinflammatory treatment with corticosteroids can produce complete recovery

The Third Age of Antimicrobial Therapy

was difficult to administer, and the use of animal serum was associated with significant adverse effects, including allergic reactions and serum sickness. The active ingredient in serum therapy was specific antibody, and the use of serum therapy required a specific diagnosis. Thus, to treat pneumococcal pneumonia, a physician would both have to accurately determine that the problem was caused by Streptococcus pneumoniae and to establish the serotype. Consequently, the development of serum therapy was a major catalyst for immunological research, as investigators tried to understand the nature of effective antibodies and develop rapid diagnostic methods. By the 1930s, the art of diagnosis was so advanced that it was possible to diagnose pneumococcal pneumonia within several hours by injecting sputum into mice, recovering the organism, and typing with serological reagents. The first age of antimicrobial therapy came to a relatively abrupt end in the late 1930s with the introduction of effective chemotherapy in the form of sulfonamide.

Prospective phase 1/2 study of rituximab in childhood and adolescent chronic immune thrombocytopenic purpura

AbstractWe assessed safety and efficacy of rituximab in a prospective study of 36 patients, age 2.6 to 18.3 years, with severe chronic immune thrombocytopenic purpura (ITP). The primary outcome of sustained platelets above 50 × 109/L (50 000/mm3) during 4 consecutive weeks, starting in weeks 9 to 12, was achieved by 11 of 36 patients (31%, confidence interval [CI], 16% to 48%). Median response time was 1 week (range, 1 to 7 weeks). Attainment of the primary outcome was not associated with age, prior pharmacologic responses, prior splenectomy, ITP duration, screening platelet count, refractoriness, or IgM reduction. First-dose, infusion-related toxicity was common (47%) despite premedication. Significant drug-related toxicities included third-dose hypotension (n = 1) and serum sickness (n = 2). Peripheral B cells were depleted in all subjects. IgM decreased 3.4% per week, but IgG did not significantly decrease. Rituximab was well tolerated, with manageable infusion-related side effects, but 6% of subjects developed serum sickness. Rituximab is beneficial for some pediatric patients with severe, chronic ITP.

Severe serum sickness following pneumococcal vaccination in an AIDS patient

Severe serum sickness following pneumococcal vaccination in an AIDS patient

8. Drug allergy

Drug reactions can be considered as being either predictable or unpredictable. A predictable reaction would be the result of the pharmacologic action of the medication. An unpredictable reaction might be idiosyncratic, might be drug intolerance, or might have or imply an immunologic basis, such as being IgE mediated. Immediate reactions that are not IgE mediated can be considered as pseudoallergic (non-IgE-mediated mast cell activation). This review will discuss allergic and immunologic reactions to immunomodulators, penicillins and cephalosporins, sulfonamides, aspirin, and nonselective nonsteroidal anti-inflammatory drugs and consider the serious drug-related conditions of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). The field of drug "allergy" has expanded to include adverse reactions associated with immunosuppressive medications, anticytokine therapies, and mAbs. The cytokine release reaction that occurs with anti-CD20 antibody infusions in patients with leukemia and white blood cell counts of greater than 50 x 10(9)/L is associated with high concentrations of TNF, IL-6, and IL-8. Because of the findings of fever, dyspnea, rigors, and hypotension, this reaction resembles the Jarisch-Herxheimer reaction that occurs 60 to 90 minutes after penicillin administration in patients with secondary syphilis. Furthermore, the care of the patient with penicillin allergy has been made more difficult in the absence of the major determinant, penicilloyl-polylysine, in that from 34% to 84% of patients who have positive skin test reactions to penicillin have exclusively positive reactions to the major determinant. SJS and TEN typically are caused by medications within 1 to 8 weeks of initiation of therapy. Evidence for death of the keratinocytes through (1) drug-specific cytotoxicity with the perforin-granzyme B-mediated killing and (2) activation of Fas on keratinocytes have provided explanations for the sloughing of skin. Unfortunately, intravenous immunoglobulin therapy for SJS and TEN has been disappointing.

Plasmapheresis and RATG-induced Serum Sickness

Recently, Bekir Tanriover et al. reported a beneficial effect of plasmapheresis in renal transplant patient with serum sickness (1). To their knowledge, this was the first report using plasma exchange to treat serum sickness after renal transplantion. However, in 1988 we published our experience with plasmapheresis in renal transplant patients with serum sickness (2). Patients with serum sickness after RATG were randomly allocated in two groups. Group 1 (n=8) was treated with analgesics and group II (n=7) with plasmapheresis. In group I, serum sickness lasted for ± 10–14 days with only a slight beneficial effect of analgesics. Six patients developed decreased renal function, which improved thereafter. The maximal rise in serum creatinine was 226.1±115.6 μ/mol. During plasmapheresis, an immediate relief of fever and arthralgia occurred and after 2 days serum sickness had completely disappeared. Before plasmapheresis, five of the seven patients showed an increased serum creatinine (maximal increase: 137.4±108 μmol/L). After plasmapheresis, serum creatinin decreased in 2–3 days to base values. There were no adverse effects of plasmapheresis. Since that time, plasmapheresis is the standard therapy for RATG-induced serum sickness in our unit. Maarten H.L. Christiaans Johannes P. van Hooff Department of Internal Medicine University Hospital Maastricht Maastricht, the Netherlands

Pegylated interferon plus rituximab in advanced stage, indolent lymphoma: is there CD20 antigen upregulation?

The anti-CD20 monoclonal antibody, rituximab, and interferon alpha (IFN) are active agents in advanced stage, indolent lymphoma. Some data obtained in vitro suggest upregulation of CD20 by IFN, and clinical trials have reported additive or synergistic activity of IFN with rituximab. A prospective phase II study in advanced stage, follicular and non-follicular indolent lymphoma was performed. Peginterferon alpha 2b (pegIFN) 0.5 μg/kg s.c. weekly × 6 and rituximab 375 mg/m2 i.v. weekly × 4 (beginning on week 3 of pegIFN) was administered. Quantitative CD20 antigen was measured pre-treatment and pre-rituximab in lymph node aspirates. Nine patients were treated: one complete response and three partial responses; however, all relapsed within 12 months and two were withdrawn for grade 3 toxicity (both with serum sickness). No up-regulation of CD20 was documented in seven patients studied (median change in CD20: decrease by 11.9%). PegIFN plus rituximab as delivered in this study is not recommended. PegIFN does not appear to upregulate CD20 expression in peripheral lymph node tumor cells.

Rituximab treatment for symptomatic chronic ITP

About 20% of the children diagnosed with acute idiopathic thrombocytopenic purpura (ITP) will run a chronic course. Only in a minority of these, platelet-count-enhancing treatments are indicated. Most treatment options are directed at decreasing platelet destruction including corticosteroids, intravenous immunoglobulins, splenectomy, and other immunosuppressive or immune modulating drugs. In children, rituximab seems to have similar efficacy as in adults with a lasting continuous remission rate of 30-35%. Toxicity includes fever, pruritus, throat tightness, and serum sickness that may be reason to discontinue rituximab treatment. No increased frequency of infections is noted. We conclude that rituximab should be given to those symptomatic ITP patients who would otherwise be referred for splenectomy; only those who fail rituximab treatment should proceed to surgery.

Antibody and cytokine serum levels in patients subjected to anti-rabies prophylaxis with serum-vaccination

Rabies is considered a fatal disease once clinical symptoms have developed. The aim of this study was to evaluate epidemiological aspects and immune response in patients attacked by domestic and wild animals and subjected to post-exposure rabies treatment with equine serum and associated vaccine. Thirty-three patients were evaluated; they were between 13 and 65 years old, 75.8% were male and 24.2% female, and from the Botucatu neighborhood. Twenty healthy control individuals with the same age range were also studied. Specific antibodies to equine immunoglobulins and IFN-gamma, IL-2, IL-4, and IL-10 production were evaluated by ELISA. IgM, IgE, IgG and subclasses, and rabies virus antibodies serum levels were determined by nephelometry and seroneutralization methods, respectively. No anaphylactic or serum sickness allergic reactions were observed in patients after treatment. Anti-equine IgG levels were significantly higher than those of IgM after 14 and 28 days of treatment. Protective antibodies to rabies virus > 0.5 UI/ml were detected in 84.6% and 75% of patients at days 14 and 28, respectively. IFN-gamma, IL-2 and IL-10 levels in patients before and 48h after treatment were significantly higher than in controls suggesting that both Th1 and Th2 cells were activated in the patients. Serum IgM levels were higher at day 14, and IgG2 and IgE levels were higher at day 28 of treatment. These results suggest that post-exposure rabies treatment in humans induces significant alterations in patient immune response characterized by increased levels of cytokines, serum levels of specific rabies virus antibodies, and the equine serum components employed in the treatment.

Evaluation of Angiogenesis and Vascular Endothelial Growth Factor Expression in the Bone Marrow of Patients with Aplastic Anemia

It is generally appreciated that bone marrow function and growth of myelopoietic cells depends on an intact microvasculature. A pivotal regulator of angiogenesis is vascular endothelial growth factor (VEGF). Here, we describe analysis of VEGF expression and microvessel density in the bone marrow of patients with aplastic anemia by immunohistochemistry. Bone marrow was examined at diagnosis and at the time of hematological remission after immunosuppressive therapy using anti-thymocyte globulin, cyclosporin A, and glucocorticoids or allogeneic stem cell transplantation. At diagnosis, both VEGF expression and microvessel density were found to be significantly lower in aplastic anemia compared to normal bone marrow (aplastic anemia, 1.1 +/- 0.7 events per field, versus controls, 5.9 +/- 3.0 events per field; P < 0.05). In response to successful therapy, VEGF and microvessel density in the bone marrow increased substantially. Serum VEGF levels were also found to be significantly lower at diagnosis in aplastic anemia compared to healthy controls (aplastic anemia, 51 +/- 35 pg/ml versus controls, 444 +/- 220 pg/ml; P < 0.05). VEGF in the serum increased substantially after successful immunosuppressive therapy or stem cell transplantation (P < 0.05). Taken together, these data show that aplastic anemia is associated with reduced angiogenesis and reduced VEGF expression.

Complications of plasma exchange in patients treated for clinically suspected thrombotic thrombocytopenic purpura‐hemolytic uremic syndrome

BACKGROUND: With the increased frequency of diagnosis and improved survival of thrombotic thrombocytopenic purpura-hemolytic-uremic syndrome (TTP-HUS), the morbidity of plasma exchange (PE) treatment has become more important. STUDY DESIGN AND METHODS: Data were prospectively collected on 71 consecutive patients referred to the Oklahoma Blood Institute (OBI) for PE treatment for clinically suspected TTP-HUS from mid-1996 to mid-1999. Complications were defined as major or minor, and distinguished between those related to central venous catheter access or to the plasma. RESULTS: Twenty-one patients (30%) had 27 major complications, which caused two deaths. The major complications included 2 episodes of hemorrhage after subclavian line insertion (1 death), 1 pneumothorax requiring a chest tube, 12 systemic infections (1 death), 7 episodes of catheter thrombosis requiring removal of the central venous catheter, 2 episodes of venous thrombosis requiring anticoagulant treatment, 2 episodes of hypoxemia and hypotension, and 1 episode of serum sickness. Minor complications occurred in 22 additional patients (31%). Twenty-eight patients (39%) had no complications. CONCLUSIONS: The morbidity and mortality of catheter placement and PE are important considerations when PE treatment for clinically suspected TTP-HUS is anticipated.

Toxoplasmosis-associated hemophagocytic syndrome in renal transplantation

Toxoplasmosis is an infrequent, often difficult to diagnose and potentially lethal disease in kidney transplant recipients. Among reported cases, a few were associated with hemophagocytic syndrome (HPS), a rare condition characterized by widespread proliferation of macrophages phagocytizing blood elements, accompanied by fever and pancytopenia. We report here the case of a patient who received a Toxoplasma gondii positive kidney allograft and developed invasive toxoplasmosis 10 days after surgery, with high fever, skin rash, arthralgias, and renal failure, followed by pneumonia, anemia, thrombocytopenia, liver dysfunction, and encephalitis. Mislead by the absence of Toxoplasma on blood smears, alveolar fluid, renal graft biopsy, and negative brain computed tomography, confusion with serum sickness, and simultaneous herpetic infection, we failed to make the right diagnosis and the patient died with septic shock 11 days later. An HPS was revealed by a late bone marrow analysis. This may well be the fourth case ever reported of toxoplasmosis-associated HPS in renal transplant recipients.