Meta-analysis of the results of intravenous gamma globulin treatment of coronary artery lesions in Kawasaki disease

The objective of this study was to evaluate the efficacy of intravenous gamma globulin (IVGG) therapy on the prevention of coronary artery lesions (CALs) in patients with Kawasaki disease (KD), with reference to the literature on meta-analyses in randomized controlled studies. Studies from 1984 to the end of 2000 obtained from the National Library of Medicine or from the bibliographies of these articles were used in the analysis. The total number of patients with KD covered in 17 articles was 4020. All the articles were examined for the number of doses per day, the duration of administration, and the total number of IVGG doses. The number of patients in each group was counted, and the incidence of CALs was evaluated at 30 or 60 days after onset. The results of these searches were further analyzed by meta-analytical methods. The administration of IVGG significantly decreased the incidence of CALs in a dose-dependent manner: At 30 days after onset the incidence of CALs was 29.4% without IVGG but 21.6% with a total dosage of IVGG < 1000mg/kg, 10.8% with a total dosage of 1000–2000mg/kg, and 10.2% with a total dosage of 2000mg/kg. Compared with the incidence of CALs without IVGG, the odds ratio (OR) was 0.662 [95% confidence interval (CI) 0.519–0.815)] at <1000mg/kg, 0.292 (95% CI 0.222–0.371) with 1000–2000mg/kg, and 0.274 (95% CI 0.207–0.349) with 2000mg/kg. At 60 days, the values had decreased to 17.3%, 13.8% [OR 0.767 (95% CI 0.585–1.005)], 5.8% [OR 0.296 (95% CI 0.200–0.436)], and 4.9% [OR 0.244 (95% CI 0.170–0.349)], respectively. The meta-analyses also indicated that high doses of IVGG (2000mg/kg per day) given in a single dose prevented CALs more effectively than the same dosages divided into five daily doses in the patients with KD: The incidence of CALs at 30 days after disease onset was 2.4% with a single dose versus 12.9% with divided doses. Compared with divided doses, the OR with a single dose was 0.164 (95% CI 0.064–0.393) and 2.8% versus 6.1% at 60 days [OR 0.450 (95% CI 0.206–0.956)]. We clearly confirmed that higher doses of IVGG (2000mg/kg per day) administered in a single infusion were more effective for preventing CALs, as evaluated during both the subacute and convalescent phases of KD.     

Meta-analysis of the results of intravenous gamma globulin treatment of coronary artery lesions in Kawasaki disease

Abstract

The objective of this study was to evaluate the efficacy of intravenous gamma globulin (IVGG) therapy on the prevention of coronary artery lesions (CALs) in patients with Kawasaki disease (KD), with reference to the literature on meta-analyses in randomized controlled studies. Studies from 1984 to the end of 2000 obtained from the National Library of Medicine or from the bibliographies of these articles were used in the analysis. The total number of patients with KD covered in 17 articles was 4020. All the articles were examined for the number of doses per day, the duration of administration, and the total number of IVGG doses. The number of patients in each group was counted, and the incidence of CALs was evaluated at 30 or 60 days after onset. The results of these searches were further analyzed by meta-analytical methods. The administration of IVGG significantly decreased the incidence of CALs in a dose-dependent manner: At 30 days after onset the incidence of CALs was 29.4% without IVGG but 21.6% with a total dosage of IVGG < 1000?mg/kg, 10.8% with a total dosage of 1000–2000?mg/kg, and 10.2% with a total dosage of ≥2000?mg/kg. Compared with the incidence of CALs without IVGG, the odds ratio (OR) was 0.662 [95% confidence interval (CI) 0.519–0.815)] at <1000?mg/kg, 0.292 (95% CI 0.222–0.371) with 1000–2000?mg/kg, and 0.274 (95% CI 0.207–0.349) with ≥2000?mg/kg. At 60 days, the values had decreased to 17.3%, 13.8% [OR 0.767 (95% CI 0.585–1.005)], 5.8% [OR 0.296 (95% CI 0.200–0.436)], and 4.9% [OR 0.244 (95% CI 0.170–0.349)], respectively. The meta-analyses also indicated that high doses of IVGG (≥2000?mg/kg per day) given in a single dose prevented CALs more effectively than the same dosages divided into five daily doses in the patients with KD: The incidence of CALs at 30 days after disease onset was 2.4% with a single dose versus 12.9% with divided doses. Compared with divided doses, the OR with a single dose was 0.164 (95% CI 0.064–0.393) and 2.8% versus 6.1% at 60 days [OR 0.450 (95% CI 0.206–0.956)]. We clearly confirmed that higher doses of IVGG (≥2000?mg/kg per day) administered in a single infusion were more effective for preventing CALs, as evaluated during both the subacute and convalescent phases of KD.     

Intravenous gamma-globulin therapy improves hypercytokinemia in the acute phase of Kawasaki disease

Abstract

Proinflammatory cytokinemia and subsequent endothelial cell activation are the major pathological features of Kawasaki disease (KD), which progresses to systemic vasculitis and results in coronary artery lesions (CALs). We studied the serum levels of proinflammatory cytokines and of the soluble receptors before and after intravenous gamma-globulin (IVGG) treatment to investigate whether the anti-inflammatory effect of IVGG was due to the reduction of increased serum levels of their cytokines and soluble receptors. In the acute phase of KD, the serum levels of interleukin (IL)-2 and IL-5, as well as those of IL-6, IL-10, and interferon-γ, were markedly higher than those in controls. The level of tumor necrosis factor-α was higher than that in the control, but the difference was slight and not significant. The soluble IL-6 receptor levels were lower than those of the controls. After IVGG administration, the increased levels of these cytokines and soluble receptors were abruptly down-regulated to within their normal ranges. The patients enrolled in the present study were all effectively treated with IVGG, without a steroid, and improved without any residual CALs. Overall, IVGG administration to patients with KD was found to be effective in reducing inflammatory processes and in preventing CALs, and was followed by reduction of the serum levels of the proinflammatory cytokines and their receptors.     

Intravenous gamma-globulin therapy improves hypercytokinemia in the acute phase of Kawasaki disease

Proinflammatory cytokinemia and subsequent endothelial cell activation are the major pathological features of Kawasaki disease (KD), which progresses to systemic vasculitis and results in coronary artery lesions (CALs). We studied the serum levels of proinflammatory cytokines and of the soluble receptors before and after intravenous gamma-globulin (IVGG) treatment to investigate whether the anti-inflammatory effect of IVGG was due to the reduction of increased serum levels of their cytokines and soluble receptors. In the acute phase of KD, the serum levels of interleukin (IL)-2 and IL-5, as well as those of IL-6, IL-10, and interferon-γ, were markedly higher than those in controls. The level of tumor necrosis factor-α was higher than that in the control, but the difference was slight and not significant. The soluble IL-6 receptor levels were lower than those of the controls. After IVGG administration, the increased levels of these cytokines and soluble receptors were abruptly down-regulated to within their normal ranges. The patients enrolled in the present study were all effectively treated with IVGG, without a steroid, and improved without any residual CALs. Overall, IVGG administration to patients with KD was found to be effective in reducing inflammatory processes and in preventing CALs, and was followed by reduction of the serum levels of the proinflammatory cytokines and their receptors.     

Clinical relevance of the risk factors for coronary artery lesions in Kawasaki disease

We aimed to investigate which factors are associated with coronary artery lesions (CALs) during the acute and chronic stages in Taiwanese children with Kawasaki disease (KD). A total of 216 children with KD were enrolled. Clinical and laboratory data were obtained for each child within 7 days of illness. The patients were classified into KD children without acute CALs (n=135) and those with acute CALs (n=81) according to echocardiography data at Week 2 after treatment. Then, KD children with acute CALs were further divided into those without chronic CALs (n=55) and with chronic CALs (n=26) according to annual echocardiography data. During acute stage of KD, neutrophil count (<54%) [odds ratio (OR)=0.44, p=0.041]; second dose of intravenous immunoglobulin (IVIG) treatment (OR=5.01, p=0.009); and platelet count (≤400,000) (OR=0.42, p=0.006) were correlated with the risk of acute CALs. During chronic stage of KD, age (12-60 months) (OR=0.25, p=0.042); first dose of IVIG treatment (OR=0.12, p=0.005); and band count (≥3%) (OR=3.51, p=0.032) were correlated with the risk of chronic CALs. Our results suggest that the effects of neutrophil count, doses of IVIG treatment, and platelet count on CALs in acute KD are important. Age, doses of IVIG treatment, and band count are related to the persistence of CALs in chronic stage of KD.     

Evaluation of intravenous immunoglobulin resistance and coronary artery lesions in relation to Th1/Th2 cytokine profiles in patients with Kawasaki disease

Objective

To investigate the roles of serum Th1 and Th2 cytokines in Kawasaki disease (KD) and determine whether the Th1/Th2 cytokine profiles in children with KD may be involved in intravenous immunoglobulin (IVIG) resistance and development of coronary artery lesions (CALs).

Methods

Serum Th1 and Th2 cytokines, including interferon‐γ (IFNγ), tumor necrosis factor α (TNFα), interleukin‐10 (IL‐10), IL‐6, IL‐4, and IL‐2, were measured using a cytometric bead array in the serum of 143 patients with KD before and after treatment with IVIG (pre‐IVIG, at 3 days after temperature normalization following IVIG treatment [post‐IVIG], and 1 month posttreatment).

Results

Levels of IL‐6, IL‐10, TNFα, and IFNγ were significantly increased in KD patients pre‐IVIG. Post‐IVIG, the levels of IL‐6, IL‐10, and IFNγ quickly decreased. The levels of TNFα decreased significantly after IVIG treatment in KD patients without CALs post‐IVIG and in KD patients who were IVIG responders, but increased slightly in KD patients with CALs post‐IVIG and in KD patients who were IVIG nonresponders. Before IVIG treatment, the levels of IL‐4, IL‐6, IL‐10, and IFNγ were significantly higher in KD patients with CALs than in those without CALs. The post‐IVIG levels of IL‐6 and IL‐10 were significantly higher in IVIG nonresponders than in IVIG responders. Pre‐IVIG, an IL‐10 level >8 pg/ml had a sensitivity of 75.0% and a specificity of 64.4% for predicting CALs, while a TNFα level <2 pg/ml had a sensitivity of 66.7% and a specificity of 74.2% for predicting IVIG resistance. Post‐IVIG, an IL‐6 level >10 pg/ml had a sensitivity of 67.9% and a specificity of 81.7% for predicting CALs, while an IL‐10 level >6 pg/ml had a sensitivity of 53.6% and a specificity of 86% for predicting CALs.

Conclusion

Determination of the serum Th1/Th2 cytokine profile may be helpful for predicting the disease prognosis and targeting treatment strategies in patients with KD.

     

Association Between Dose of Glucocorticoids and Coronary Artery Lesions in Kawasaki Disease

Objective

Several studies revealed the efficacy of glucocorticoids on prevention of coronary artery lesions (CALs) in Kawasaki disease (KD) patients. However, impacts of different doses of glucocorticoids on clinical outcomes of KD remain unknown.

Methods

Using the Japanese Diagnosis Procedure Combination inpatient database, we evaluated KD patients who were treated with normal‐dose (prednisolone 0.5–4.0 mg/kg/day) or high‐dose (methylprednisolone 10–40 mg/kg/day) glucocorticoids. We investigated risks of CALs and readmission, total hospitalization cost, and length of hospital stay in the acute phase of KD using propensity score matching, stabilized propensity‐score inverse probability of treatment weighting, and instrumental variable methods.

Results

We identified a total of 3,220 patients with KD who were treated with normal‐dose (n = 2,453) or high‐dose (n = 767) glucocorticoids in addition to intravenous immunoglobulin. One‐to‐one propensity‐matched analyses with 744 pairs demonstrated no significant differences between the normal‐dose and the high‐dose groups in risk of CALs (risk ratio [RR] 0.83, 95% confidence interval [95% CI] 0.49, 1.40) and risk of readmissions (RR 0.85, 95% CI 0.65, 1.11). Stabilized propensity‐score inverse probability weighting and instrumental variable analyses showed similar results to the propensity score matching analyses.

Conclusion

Risks of CALs and readmissions and total hospitalization costs were similar between the normal‐dose and the high‐dose glucocorticoids groups for patients with KD, whereas total length of hospital stay was shorter in the high‐dose group than that in the normal‐dose group.

     

Multisystem Inflammatory Syndrome Following SARS-CoV-2 Infection in Children: One Year after the Onset of the Pandemic in a High-Incidence Area

SARS-CoV-2 infection in children can trigger cardiovascular manifestations potentially requiring an intensive treatment and defining a new entity named Multisystem Inflammatory Syndrome in Children (MIS-C), whose features partially overlap with Kawasaki Disease (KD). A cross-sectional study including all diagnoses of MIS-C and KD from April 2020 to May 2021 in our metropolitan area was conducted evaluating clinical, laboratory (including immunological response, cytokines, and markers of myocardial damage), and cardiac (coronary and non-coronary) features at onset of the diseases. Evolution of ventricular dysfunction, valve regurgitations, and coronary lesions was documented. The severity of the disease was also considered based on the need for inotropic support and ICU admission. Twenty-four MIS-C were diagnosed (14 boys, median age 82 months): 13/24 cases (54.17%) presented left ventricular dysfunction, 12/24 (50%) required inotropic support, and 10/24 (41.67%) developed coronary anomalies (CALs). All patients received steroids and IVIG at a median time of 5 days (IQR1:4, IQR3:6.5) from onset of fever and heart function normalized 6 days (IQR1: 5, IQR3: 7) after therapy, while CALs persisted in one. One patient (12.5%) required infliximab because of refractory disease and still presented CALs 18 days after therapy. During the same study period, 15 KD were diagnosed: none had ventricular dysfunction, while 7/15 (46.67%) developed CALs. Three out of 15 patients (20%) still presented CALs 46 days from onset. Compared to KD, MIS-C pts have significantly higher IL8 and similar lymphocytes subpopulations. Despite a more severe presentation and initial cardiac findings compared to KD, the myocardial injury in MIS-C has a rapid response to immunomodulatory treatment (median time 6 days), in terms of ventricular function, valve regurgitations, and troponin. Incidence of CALs is similar at onset, but it tends to regress in most of the cases of MIS-C differently than in KD where CALs persist in up to 40% in the subacute stage after treatment.     

Study on the relationship between mean platelet volume and platelet distribution width with coronary artery lesion in children with Kawasaki disease

Mean platelet volume (MPV) and platelet distribution width (PDW) are correlated with platelet function and may be a more sensitive index than platelet number as a marker of clinical interest in various disorders. Therefore, this study was designed to answer the following questions: do MPV and PDW levels change in Kawasaki disease (KD), is there any relation between CAL in children with MPV and PDW and whether MPV and PDW might support a diagnosis of incomplete KD. A total of 309 KD patients and 160 sex-age matched healthy subjects were enrolled into the study. For all subjects following tests were performed: MPV, PDW, platelet count, white blood cells counts (WBC), C reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Patients with CALs were assigned to three groups depending on the extent of CALs which were visualized by echocardiography: dilatation and/or ectasia, aneurysm and giant aneurysms. We compared patients with fever and four or five of the principal criteria (complete KD, cKD) to the other patients (iKD). Compared with healthy controls a significant decrease in MPV and PDW (p??0.05). However, MPV and PDW were significantly lower in patients with iKD than in group with cKD (p?=?0.003, p?=?0.014, respectively). It was first shown that patients with KD have lower MPV and PDW than control subjects. The diagnosis of iKD is challenging but can be supported by the presence of lower MPV and PDW.     

Kikuchi's disease with hemophagocytic lymphohistiocytosis: A case report and literature review

Introduction:Kikuchi''s disease (KD) is a rare form of necrotizing lymphadenitis that rarely occurs in association with hemophagocytic lymphohistiocytosis (HLH) in children.Patient concerns:We report the case of a 4-year-5-month-old boy who suffered from fever, cervical lymphadenopathy, pancytopenia, hypertriglyceridemia, splenomegaly, low NK cell activity.Diagnoses:A diagnosis of KD with HLH was made based on the results of biopsy of cervical lymph node and HLH-2004 trial guidelines.Interventions:The patient was treated with corticosteroids, cyclosporine, etoposide, continuous hemodiafiltration (HDF), and plasma exchange (PE).Outcomes:He showed a complete response to therapy, and his condition gradually improved. He was discharged on day 45 after admission due to his good recovery status.Conclusion:HLH can be associated with KD, especially in childhood, and may have an aggressive clinical course. Continuous HDF and PE and chemotherapy should be reserved for those patients who fail to respond to IVIG and corticosteroids.     

Maintenance treatment of adults with chronic refractory immune thrombocytopenic purpura using repeated intravenous infusions of gammaglobulin [see comments]

Intravenous infusion of gammaglobulin (IVGG) has been extensively used in the treatment of immune thrombocytopenic purpura (ITP) in adults to acutely raise the platelet count but not as a maintenance therapy. This report describes the maintenance treatment of adults with chronic ITP using repeated infusions of 800 to 1,000 mg/kg of IVGG. Sixteen of 40 patients were able to discontinue all therapy after receiving between one and 15 infusions. Five patients achieved remission and 11 other patients became stable without therapy (SWT) maintaining a platelet count greater than 20,000/microL without bleeding. The average quantity of gammaglobulin received for all patients was 606 g per patient. Of the 30 patients who underwent but did not respond to splenectomy, 11 (37%) were able to discontinue all therapy by either achieving remission (5) or becoming SWT (6). None of the five patients who achieved remission did so after only the initial therapy; all first received between one and 12 maintenance infusions. The ten splenectomized patients who were unresponsive to IVGG also failed to subsequently respond to conventional therapy including immunosuppressive agents and androgens. No toxicity of IVGG was seen except for postinfusion headaches. IVGG is an effective although expensive maintenance therapy for adults with ITP and is useful in patients who have not responded to splenectomy.     

Isolated thrombocytopenia in patients infected with HIV: treatment with intravenous gammaglobulin

Isolated thrombocytopenia occurs frequently in patients infected with HIV. Studies of mechanisms of thrombocytopenia and clinical response to therapy suggest that the thrombocytopenia is often antibody mediated (ITP). The best approach to treatment of these patients is uncertain in that the routine modalities (steroids, splenectomy, vinca alkaloids) that are used to increase the platelet count in patients with classic ITP are known to be immunosuppressive. We report here the results of intravenous gammaglobulin (IVGG) treatment of 22 patients with HIV-related acute and chronic ITP who had severe thrombocytopenia and bleeding symptoms. Only one patient had an opportunistic infection at the time of treatment. Eight patients were homosexual, eight had hemophilia, three were i.v. drug abusers, two children had congenital acquisition of HIV, and one was the wife of an HIV + i.v. drug abuser. The average pretreatment platelet count was 22,000/microliter (hemophiliacs were treated at higher platelet counts than were the other patients), and the mean peak platelet count measured on days 5 to 8 was 182,000/microliter. Nineteen of 22 patients had peak platelet counts greater than 50,000/microliter following IVGG and 17/22 had peak counts greater than 100,000/microliter. After the initial infusions, all but three refractory patients could maintain adequate platelet counts with IVGG alone infused no more often than once every 2 weeks. The outcomes for the 22 patients after multiple maintenance IVGG infusions were remission, 5; stable without therapy, 1; maintenance, 13; and refractory, 3. The eight hemophiliacs with ITP responded better than did the eight homosexual ITP patients; their mean peak platelet count was 227,000/microliter versus 142,000/microliter in the homosexuals. In summary, patients with HIV-related ITP without opportunistic infections responded well to IVGG, with peak platelet counts comparable to those of ITP patients not infected with HIV. IVGG may be a useful therapy of ITP in HIV+ patients, since it appears to be less immunosuppressive than are conventional therapies, and none of the 22 HIV+ patients developed an opportunistic infection while receiving IVGG alone.     

Intravenous treatment with gammaglobulin in adults with immune thrombocytopenic purpura: review of the literature

The results of high-dose intravenous gammaglobulin therapy (IVGG) of adults with immune thrombocytopenic purpura (ITP) were reviewed in 28 published reports which included 282 patients. Overall, 64% of the patients responded to IVGG with a peak platelet count greater than 100,000/mm3; 83% had peak platelet counts greater than 50,000/mm3. Unmodified immunoglobulin was superior to modified immunoglobulin; 70% of the patients treated with the former having platelet increases to greater than 100,000/mm3 compared to only 49% of those treated with the latter. More patients were refractory among those who had had ITP for at least 3 years. A higher peak platelet count immediately after IVGG administration was correlated with a longer duration of the platelet response. Patients above the age of 60 tended to have a weaker response to IVGG than did younger patients, and females tended to respond better than males. A pre-IVGG platelet count of less than 10,000/mm3 was not associated with a poor response to IVGG. While there is still no way to reliably predict response prior to therapy in an individual patient, the above information may help in the decision of whether or not treatment with IVGG is likely to be successful. It also suggests that inhibition of antiplatelet antibody production is an important mechanism of IVGG effect at least in some patients.     

Elevated d‐Dimer Level is a Risk Factor for Coronary Artery Lesions Accompanying Intravenous Immunoglobulin‐Unresponsive Kawasaki Disease

Although there are many reports on the resistance of Kawasaki disease (KD) to initial intravenous immunoglobulin (IVIg) therapy, risk factors for coronary artery lesions in such cases remain to be established. The objective of this study was to explore when additional therapies should be administered and to identify factors helpful for selecting a therapeutic option. Based on their written clinical records, we performed a retrospective review of KD patients who did not respond to initial IVIg therapy and who therefore then underwent plasma exchange (PE) therapy. This was a case‐control study to compare the presence or absence of acute coronary lesions in patients treated by PE for IVIg‐unresponsive KD at Yokohama City University Hospital or at Yokohama City University Medical Center. Fifteen of 44 patients had acute coronary artery lesions (CAL) correlating with high levels of white blood cells (WBC) (P = 0.045), d ‐dimer (P = 0.008), and fibrin/fibrinogen degradation products (P = 0.009) and lower levels of fibrinogen (P = 0.013) prior to PE therapy. There was a strong correlation between pre‐PE levels of albumin and d ‐dimer (Pearson's correlation coefficient of 0.610). Multivariate analyses revealed that the odds ratio for CAL when d ‐dimer was ≥ 4.5 μg/mL was 25.06 (95% CI, 2.56–244.91, P = 0.006). d ‐dimer elevation and albumin decline in IVIg‐unresponsive KD patients could be risk factors for acute CAL, suggesting the possibility that angitis has spread throughout the arterial system, as far as the coronary artery.     

Corticosteroid-resistant multiple colonic ulcers in a patient with systemic lupus erythematosus/systemic sclerosis overlap syndrome effectively treated with intravenous cyclophosphamide pulse therapy

We report a rare case of a 17-year-old female with overlap syndrome (systemic lupus erythematosus and systemic sclerosis) who developed severe abdominal pain and bloody diarrhea accompanied by central nervous system lupus. Colonoscopy revealed multiple irregular and linear ulcers throughout the colon, which were resistant to corticosteroid pulse therapy and plasma exchange. The patient finally recovered after treatment with a relatively low dose of monthly intravenous cyclophosphamide (250mg/m²) pulse therapy.     

Serum ferritin levels as a useful diagnostic marker for the distinction of systemic juvenile idiopathic arthritis and Kawasaki disease

Objectives: The clinical features and laboratory parameters of patients with Kawasaki disease (KD) and systemic juvenile idiopathic arthritis (s-JIA) tend to overlap. Furthermore, there have been no definitive biomarkers for these diseases, making clinical diagnosis difficult. The purpose of this study was to investigate the diagnostic value of serum ferritin levels for differentiating KD from s-JIA and predicting the disease severity of KD.

Methods: We analyzed 228 patients with KD and 81 patients with s-JIA. Serum ferritin levels were compared between patients with s-JIA and KD. Furthermore, serum ferritin levels in patients with KD were compared with respect to clinical features such as responsiveness to intravenous immunoglobulin (IVIG) therapy.

Results: Serum ferritin levels in KD patients with no response to IVIG therapy were significantly higher than those in KD patients with a good response to IVIG therapy. Serum ferritin levels in patients with KD needing plasma exchange (PE) were significantly higher than those in patients not needing PE. However, serum ferritin levels overlapped between severe KD patients with nonresponsiveness to IVIG therapy or needing PE and other patients with mild KD. Furthermore, patients with s-JIA showed a distinct elevation of serum ferritin levels compared with KD patients. The cutoff value of serum ferritin levels for differentiating KD from s-JIA was 369.6?ng/ml.

Conclusions: Serum ferritin levels were significantly elevated in s-JIA patients compared with KD patients. Measurement of serum ferritin levels can be useful for differentiating s-JIA from KD.     

Long-term treatment of refractory HIV-related immune thrombocytopenia in a patient with haemophilia A.

Haemophilia A patient developed symptomatic immune thrombocytopenia 5 years after HIV seroconversion without any progression of the viral disease. He displayed major bleeding with less than 30 x 10(9) platelets/l. No increase in platelet count was obtained using steroids, azidothymidine and alpha-interferon, while the patient was responsive only to high-dose intravenous immunoglobulins (IVGG). The patient remained responsive to IVGG for 1 year, and the repeated infusions of immunoglobulins were effective in safely maintaining the platelet count, with peak counts above 100 x 10(9)/l. On the contrary, after a single course of six plasma exchanges the patient became symptomatic and completely refractory to IVGG during the next month. In conclusion, IVGG could be effectively used in a long-term regimen in haemophiliacs with refractory HIV-ITP to avoid the risk of haemorrhages and to delay splenectomy.     

Rituximab in the treatment of relapsed thrombotic thrombocytopenic purpura

Several reports have defined nonfamilial thrombotic thrombocytopenic purpura (TTP) as an autoimmune disorder caused by antibodies to von Willebrands factor-cleaving protease (vWF-CP). This raises the possibility that rituximab, a monoclonal antibody against CD20 present in B-lymphoid cells, may have utility in the treatment of TTP. We report five consecutively treated patients with relapsed TTP who responded rapidly to immune suppression by rituximab at our institution. These two male and three female patients had a median age of 37 years (27–70). The median time from diagnosis to therapy was 24 months (8–60). Prior therapies included plasma exchange and corticosteroids in all cases, splenectomy (4), vincristine and aspirin (3), and azathioprine (2). The median number of plasma exchanges received prior to therapy was 59 (21–158). The cohort had a median platelet count of 48×10⁹/l (23–110), median hemoglobin of 9 g/dl (8–11), and median lactate dehydrogenase of 632 IU/l (311–945) prior to administration of rituximab. Analysis of vWF-CP activity demonstrated absent or decreased activity with detectable inhibitors in four patients. All patients attained a complete response. The median time to response after the first dose of rituximab was 5 weeks. Responses are maintained in all patients from 10 to 21 months after treatment. This report adds to the evidence that rituximab has efficacy in nonfamilial TTP and warrants further study.     

The effect of plasma exchange on entecavir-treated chronic hepatitis B patients with hepatic de-compensation and acute-on-chronic liver failure

Background and aims

Various studies showed that entecavir (ETV) failed to improve the short-term survival in chronic hepatitis B (CHB) patients with severe acute exacerbation (SAE) and hepatic de-compensation or acute-on-chronic liver failure (ACLF). One study concluded that plasma exchange (PE) significantly decreased the short-term mortality of CHB patients with ACLF who were treated with lamivudine (LAM). Our study was designed to examine the effect of PE on CHB patients with ACLF who were treated with ETV.

Methods

From August 2010 to January 2015, 38 (PE group) and 120 (control group) consecutive CHB-naïve patients with hepatic de-compensation and ACLF treated with PE plus ETV and ETV, respectively, were recruited. The primary endpoint was liver-related mortality at week 12. Biochemical and virological responses were also studied.

Results

At baseline, the PE group had higher serum alanine aminotransferase (ALT) levels and model for end-stage liver disease (MELD) scores, and had lower albumin levels than the control group. The cumulative survival rate at week 4 and week 12 in the PE group and control group were, respectively, 37 and 18 %, and 29 and 14 % (p < 0.001, by log rank test). While the bilirubin levels in the PE group were more quickly lowered by PE therapy (p < 0.001), the decrease of ALT levels and virological response were similar in the two groups (p > 0.05). Univariate analysis showed that the control group had a higher liver-related mortality (p = 0.038) at week 12 than the PE group. Multivariate analysis showed that hepatic encephalopathy, ascites, PE treatment, and MELD scores were independent factors for liver-related mortality at week 12.

Conclusions

PE significantly improved the short-term survival of CHB patients with hepatic de-compensation and ACLF who were treated with ETV. Hepatic encephalopathy, ascites, PE treatment, and MELD scores were independent factors for liver-related mortality at week 12.

     

Findings in the pulmonary vascular bed in the remote phase after Kawasaki disease

Kawasaki disease (KD) is a form of systemic vasculitis that causes chronic changes in arterial walls, including pulmonary arteries. The aim of this study was to test the hypothesis that pulmonary arterial wall properties and hemodynamics are abnormal after the resolution of KD. Pulmonary arterial input impedance was measured during cardiac catheterization (4.8 ± 4.5 years after disease onset) in 47 consecutive patients (mean age 7.8 ± 5.7 years) with KD and coronary artery lesions (CALs) in the acute phase and 42 control patients (mean age 6.7 ± 4.6 years). Patients with KD were subdivided into 2 groups: 28 with persistent CALs and 19 with regressed CALs. There were no significant differences in characteristic impedance and peripheral vascular resistance between patients with KD and controls. Compared with controls, patients with persistent CALs had significantly lower pulmonary arterial compliance, suggesting increased wall stiffness of the peripheral pulmonary vascular bed (p <0.05, analysis of variance). Patients with persistent CALs also exhibited increased wave reflection compared with other groups (p <0.05, analysis of variance). In conclusion, unlike patients with regressed CALs, patients with persistent CALs have abnormal mechanical properties and hemodynamics of the pulmonary artery after KD. Together with previous reports of abnormal properties of coronary and systemic arteries, these data suggest that KD vasculitis causes chronic changes in arterial wall properties in the entire arterial system to varying degrees and extent. The fate of these abnormalities in the pulmonary bed and other arterial systems and their potential adverse effects must be monitored in long-term follow-up.