Intravenous Gammaglobulin Therapy Research Articles

A Case of Kawasaki Disease with Re-dilatation of the Coronary Artery Five Years after the Onset

We experienced a case of Kawasaki disease with re-dilatation of coronary artery aneurysm five years after the onset. [Patient profile] The patient is a 12-year-old boy. He suffered from Kawasaki disease at the age of four years. Intravenous gamma-globulin (IVGG) therapy with 300 mg/kg/day was administered for 5 days, and additional IVGG with 1g/kg/day was administered furthermore. However, in spite of IVGG therapy, the aneurysms were developed on the both coronary arteries, which were confirmed by the cardiac catheterization one year later. (AHA Committee Report: Segment 2: two aneurysms; 4.8mm, 5.0mm in diameter, Segment 6: 4,3mm, Segment 11: 4.1mm). Thereafter, the coronary aneurysm on LAD regressed gradually. We depicted this regression of LAD aneurysm by the echocardiography at 4 years after the onset. (Segment 6: 2.4mm in diameter). However, further follow-up echocardiography revealed re-dilatation of the aneurysm on the same region of LAD one year later. (Segment 6: 7.4mm in diameter). We also confirmed this re-dilatation of the aneurysm without stenotic lesions by cardiac catheterization. [Discussion] There have been reported that the regressed aneurysms sometimes develop to the stenotic lesions late after the onset. However, there are a few reports in which a newly developed aneurysm emerged late after the onset of Kawasaki disease. [Conclusions] Re-dilatation of the regressed aneurysm is a very unique clinical course as a long-term Kawasaki disease. While the mechanism of the re-dilatation of this patient is still un-known, we must be careful to follow him up.

Inflammatory Pulmonary Nodules in Kawasaki Disease

Significant pulmonary manifestations of Kawasaki disease (KD) are uncommon. However, epidemiologic data from KD epidemics reveal an association between KD and a recent respiratory illness, and peribronchial cuffing or interstitial infiltrates have been reported on chest X-rays in 15% of acute KD patients. Moreover, pneumonia has been documented in 86% of autopsied acute stage cases. We report two children with KD in whom pulmonary nodules developed. The first was a 4-month-old boy with fatal acute KD. This patient had symptoms of cough and nasal congestion, and autopsy revealed inflammatory nodules in the lung as well as large coronary artery aneurysms. The second patient was a 6-month-old boy with atypical KD complicated by a coronary aneurysm in whom three peripheral pulmonary nodules were noted on chest Xray and confirmed by chest CT scan. One nodule was biopsied, revealing a non-encapsulated fibrovascular nodule infiltrated by numerous mononuclear cells. The patient was treated for KD with intravenous gammaglobulin and aspirin therapy, and did well. To characterize further the histologic features and inflammatory component of these nodules, immunohistochemistry was performed on tissue sections using antibodies to common leukocyte antigen (LCA) and Factor VIII-related antigen. In both cases, there was marked LCA positivity within the lesions indicating the presence of inflammatory mononuclear cells, and marked Factor VIII-related antigen positivity within and around the nodules, indicating extensive angiogenesis. We propose that there is a spectrum of severity of pulmonary involvement in KD, ranging from subclinical or symptomatic interstitial micronodular infiltrates to larger inflammatory pulmonary nodules. These infiltrates and nodules are likely a host response to the etiologic agent and may resolve with the disease process. Recognition of this pulmonary complication of KD may enable cautious observation of such lesions for spontaneous resolution; biopsy may be unnecessary unless the lesions persist after acute KD has resolved.

Effect of Plasma Exchange in Kawasaki Disease Refractory to High Dose Intravenous Gammaglobulin Therapy

Background: In Kawasaki disease (KD), administration of intravenous gammma-globulin (IVGG) reduced frequency of coronary artery lesion (CAL) from 25% to 8%. However, approximately 500 children still develop CAL every year in Japan. We evaluated the efficacy and safety of plasma exchange (PE) for children with KD intractable to IVGG therapy. Patients and Methods: Among 255 children with KD treated with initial IVGG, 119 children were identified at high risk for CAL according to the increases in fractional changes (FC) of white blood cell count, neutrophils, and CRP between baseline and 1 to 2 days after IVGG treatment. Seventy-five were administered additional IVGG, and finally 50 of them were underwent the PE therapy in 3 consecutive days. All the children were serially monitored for the development of CAL by echocardiography during the course of the disease until days 28-30. The incidence of CAL was compared among the children treated and those untreated with PE. Results: The demographic differences between the treated and untreated children were not significant on admission. The PE therapy was safely performed without any adverse reactions, and has completed in each child. Out of 50 children treated PE, only 10 (20.0%) had CAL, including temporary dilatation in 7, persistent CAL in 1, and giant aneurysms in 2 children. In contrast, 24 children (40.7%) among 69 without PE were affected with CAL, including giant aneurysm in 5 (P < 0.0004). Conclusions: We suggested that PE therapy performed within 10 days after the onset of the disease should be effective and safe for the children with KD intractable to the IVGG therapy. The PE therapy may be applied as soon as possible when the fractional increases in inflammatory markers after the initial IVGG are determined.

Adult Patients of Kawasaki Disease with Acute Myocardial Infarction Who had not been Pointed Out Coronary Artery Lesions Previously

We experienced two adult patients of Kawasaki disease with acute myocardial infarction who had not been pointed out coronary artery lesions previously. [Case 1: 27years old. Male] He suffered from Kawasaki disease at the age of one year. He did not receive any treatment of intravenous gamma-globulin therapy or aspirin. The cardiac catheterization at the age of 7 years revealed no coronary artery lesion. Thereafter, he had received follow-up examination once a year until 17 years old. He came to our outpatient clinic again because of recent recurrent chest pain at 22 years old. Further examinations including the cardiac catheterization, the treadmill test and the myocardial scintigraphy did not show any abnormalities and we concluded that his chest pain did not result from the coronary artery lesions of Kawasaki disease. After 5 years from these examinations, he suffered from an acute myocardial infarction with total occlusion of the right coronary artery (AHA Committee Report: Segment 2). He recovered well after the emergent percutaneus transluminal coronary anigioplasty (PTCA). [Case 2: 33 years old. Male] He suffered from Kawasaki disease at the age of two years. Any coronary artery lesion was not detected at that time. He had not received follow-up examinations since a few years after the onset. He had a chest pain at 30 years after the onset and had an acute myocardial infarction next year. The cardiac catheterization revealed 99% stenosis at segment 11, and total occlusion with well developed collaterals at segment 2. He recovered well after the directional coronary atherectomy (DCA) for the lesion at segment 11. [Conclusions] The patients with Kawasaki disease at the early era have grown to the young adult. They did not receive an accurate evaluation for the coronary artery lesions by echocardiography at the acute phase of Kawasaki disease. They did not receive effective therapy of gamma-globulin either. Those patients may have concealed coronary artery lesions. These two cases demonstrate well the high risk of those patients for the sudden onset of ischemic heart disease.

Oxygen Radicals Activity as a Predictor of Coronary Artery Lesions in Kawasaki Disease

Background Neutrophil-derived Oxygen radicals (OR) play a role in a wide variety of diseases including vasculitis syndrome, however, little is known about causal relation between coronary artery lesions (CAL) in Kawasaki disease (KD) and OR activity.Objective To investigate a role of OR in CAL. Methods 27 patients with KD were enrolled within 7 days from the onset of illness. All patients were treated orally with aspirin (ASA), and 21 patients, selected by Harada scoring system, also received intravenous gammaglobulin therapy (IVGG). IVGG was administered as daily infusions of 200mg/Kg for five consecutive days. Patients were retrospectively divided into the following three groups according to IVGG and CAL: Severe group, patients with CAL treated with IVGG (n=3); Moderate group, patients without CAL treated with IVGG (n=18); and Mild group, patients without CAL not needed IVGG (n=6). 15 healthy children were studied as controls. Neutrophil-derived OR were measured as intracellular chemilluminescense (ICCL) of whole blood by luminol-dependent chemilluminescense method using luminol-binding microsheres. Serial changes in ICCL values were monitored from acute to convalescent phases in every patient.Results Significant differences were observed in pretreatment ICCL values among the three groups with KD (p<0.05). The mean ICCL values in mild, moderate and severe groups of KD were 13.7±5.5x105cpm, 34.8±9.3x105cpm, and 71.2±10.1x105cpm, respectively, while that in control was 3.1±1.2x105cpm (p<0.01). In IVGG groups, the ICCL values were significantly decreased at 1 and 4 weeks after treatment: 19.2±8.4x105cpm and 8.1±3.3x105cpm in moderate group (p<0.05), and 39.8±7.7x105cpm and 20.3±9.2x105cpm in severe group (p<0.05). Thus, patients with CAL (severe group) had persistently much higher ICCL values than patients without CAL (mild and moderate groups)(p<0.05).Conclusions OR activity was well correlated with severity of KD in acute phase and decreased in parallel with IVGG. OR activety appears to be useful for predicting the risk of CAL despite IVGG, and possibly helping earlier decision on an alternative treatment.

A Case of Kawasaki Disease in NICU

[Background] Kawasaki disease (KD) in children younger than 3 months of age is rarely observed. The rarity of disease in early infants may be due to protective effects of transplacental immunity and/or low level of exposure to infectious agent. We report a case of an infant who developed KD in a neonatal intensive care unit (NICU). [Case report] A male infant was born at 31 weeks of gestation; weighed 1772g, and admitted to our NICU. At 84 days of age, he presented with high fever, exanthema and dyspnea. He was diagnosed with pneumonia and treated with intravenous antibiotics and gammaglobulin (150 mg/kg/day, 3 consecutive days). The high fever lasted even after improvement of respiratory lesions, which were followed by bilateral conjectival injection, bright red lips and edematous changes in palms and soles. He was diagnosed with KD at 93 days of age (9 days of illness). Right and left coronary arteries were dilated up to 2 mm. He was treated with high-dose gammaglobulin (1500 mg/kg/dose), however, fever and other symptoms persisted. He developed pericardial effusion and bilateral coronary arterial aneurysms (4.5 mm), despite 4 additional gammaglobulin injections (1000 mg/kg/dose, respectively). Beginning at 24 days of illness, he was treated with intravenous ulinastatin (15000 U/kg/day) for 5 days, and fever and all other symptoms disappeared. He was discharged at 63 days of illness. Follow-up cardiac catheterization and angiography at 2 months after discharge confirmed bilateral coronary arterial aneurysms. [Discussion] The present case developed KD even in extremely isolated environment as NICU. One possible explanation is that premature infants receive insufficent passive immunity from their mothers. In this infant, ulinastatin therapy was effective. Thus this treatment should be considered for young infants who are resistant to intravenous gammaglobulin therapy

Pyogenic Arthritis, Pyoderma Gangrenosum, and Acne Syndrome (PAPA Syndrome) Associated With Hypogammaglobulinemia and Elevated Serum Tumor Necrosis Factor-α Levels

Pyogenic aseptic arthritis, pyoderma gangrenosum, and cystic acne (PAPA) syndrome is an unusual triad that was recently mapped to a chromosome 15q mutation. We describe a patient from this kindred in whom hypogammaglobulinemia and elevated tumor necrosis factor-alpha serum levels were detected. The patient responded well to intravenous gammaglobulin and intra-articular corticosteroid therapy. Immune abnormalities can be found in PAPA syndrome and could be the consequence of the chromosomal abnormalities affecting candidate genes on this chromosome with subsequent abnormalities in cytokine or chemokine secretion. Rheumatologists should be alert for this syndrome. Correction of the immune abnormalities may be effective in controlling the disease manifestations.

Giant coronary aneurysms due to Kawasaki disease: A case−control study

Epidemiologic features of giant coronary aneurysm due to Kawasaki disease and its risk factors are still not clear. Sixty-six patients with giant coronary aneurysms were reported to a 15th nationwide survey of Kawasaki disease in Japan. With all other patients treated in the same hospital as a control group, odds ratios were calculated for certain potential risk factors. Infant males aged less than 1 year,neutrophil concentration among leukocyte, late administration of intravenous gammaglobulin (IVGG) therapy and additional administration of IVGGwere considered as risk factors of giant coronary aneurysms due to Kawasaki disease. In univariate analysis, use of IVGG therapy and a large amount of IVGG (2500+ mg/kg)elevated the risk, whereas the relationship disappeared after the adjustment. The observation of 66 cases with giant coronary aneurysms due to Kawasaki disease reported to the nationwide survey provides some risk factors and consideration about the aneurysms.

Evaluation and review: Symposium covers indications for the use of intravenous immunoglobulin

Immunoglobulins are a heterogeneous group of humoral antibodies produced in response to antigen stimulation. For the most part, therapeutic immunoglobulins represent polyvalent immunoglobulins derived from thousands of donors, hyperimmune immunoglobulins directed toward single antigens or infectious agents, or the more recent engineered immunoglobulins with monoclonal specificity that are used for targeted immunotherapy. The intent of the meeting was to evaluate and review the current indications for the use of intravenous immunoglobulin (IVIG). Discussions included IVIG’s pathogenesis and mechanisms of action in various disease states, safety issues, and problems related to availability. One goal of the meeting was to develop a current consensus on IVIG use and safety. Although many articles have been written about immunomodulant high-dose, IVIG therapy, its action mechanisms are more complex than simple “reticuloendothelial blockade.” Speakers at this symposium considered state-of-the-art immunoglobulin therapy but also focused on action mechanisms and, in particular, an appreciation of the role of inflammatory cytokines, adhesion molecules, and cellular receptors in replacement and immunomodulatory therapy. Advances in IVIG purification and specificity refinement have been achieved recently by implementing purification strategies, in particular solvent and detergent treatment. The safety issues were addressed in terms of reducing side effects, processing advancements, and pathogen safety in both IVIG and other human plasmaderived therapeutic proteins. A presentation by Miller et al addressed this issue. They emphasized that even though pathogen safety records for IVIG and other plasma proteins are excellent, the industry remains active in improving the safety margin. Their paper focused on strategies designed to eliminate the potential for transmitting known and unknown infectious agents. Considering action mechanisms and broader applications of intravenous gamma globulin therapy, Ott et al addressed the FcγRIIB receptor as a potential molecular target. Their article addressed the role of cell surface inhibitory receptors in attenuating immune responses and their role in activating any inhibitory signals. Further discussion also focused on IVIG’s immunomodulatory and anti-inflammatory effects with a shift in focus towards organ-specific applications in special circumstances. Issues addressed included the regulation of innate immunity, IVIG’s role in apoptosis, and Fc receptor function and its influence on cytokine cascades. Modlin presented the role of toll-like receptors in human innate immune responses to microbial pathogens. Toll-like receptors seem to integrate after their activation with other aspects of host defense mechanisms such as the activation of cytokines, including IL-12 and other host defense mechanisms. His article addressed the intricate dynamics of the cytokine receptor cascade’s enhancement of innate immunity. The role of humoral immune responses in microbial defense mechanisms is well appreciated. New applications in other infectious diseases also have been addressed. To this end, the potential use of intravenous Evaluation and review: Symposium covers indications for the use of intravenous immunoglobulin

FcγRIIB as a potential molecular target for intravenous gamma globulin therapy

The ability of the immune system to respond appropriately to foreign antigen is dependent on a delicate balance of activating and inhibitory signals. Recently, the role of cell surface inhibitory receptors in attenuating immune responses, thereby preventing pathologic conditions including autoimmunity and atopy, has been recognized. It is postulated that the beneficial effects of intravenous gamma globulin in the treatment of immune disorders may be attributable, at least in part, to engagement of FcγRIIB, a member of the recently described family of immune inhibitory receptors. Recent genetic and biochemical studies have identified the SH2 domain-containing inositol 5-phosphatase (SHIP) as a critical effector in FcγRIIB inhibitory signaling. This review summarizes recent work from our laboratory and others aimed to define the mechanism(s) by which FcγRIIB and its effector, SHIP, inhibit immune responses. Elucidation of these mechanisms may lead to the development of therapeutic strategies for the treatment of autoimmune and inflammatory pathologies that specifically target FcγRIIB or its effector(s). (J Allergy Clin Immunol 2001;108:S95-8.)

Initial fetal platelet counts predict the response to intravenous gammaglobulin therapy in fetuses that are affected by PLA1 incompatibility

Objective: Fetal alloimmune thrombocytopenia is the result of maternal fetal platelet antigen incompatibility; intracranial hemorrhage is its most serious complication. Our previous studies have demonstrated an inability to accurately predict fetal platelet counts in this disorder. The goal of the present investigation was to identify factors that would predict the response of the fetal platelet count to therapy so that use of fetal blood sampling could be minimized. Study Design: Patients who were eligible for the study were all those who (1) had alloimmune thrombocytopenia secondary to PlA1 (HPA-1a, ZwA) platelet antigen incompatibility, (2) were treated with maternally administered intravenous immunoglobulin at 1 g/kg of body weight per week, with or without low dose steroids, and (3) had percutaneous fetal blood sampling before the initiation of therapy (first fetal blood sampling) and again 3 to 7 weeks afterwards (second fetal blood sampling). Results: In this retrospective review, 74 patients who were affected by alloimmune thrombocytopenia had a median platelet count of 21,000 per microliter at the first fetal blood sampling and 47,000 per microliter at the second fetal blood sampling, with a median increase in platelet count of 24,000 per microliter. Response to treatment was defined as either (1) an improvement in platelet count (the second fetal blood sampling greater than the first fetal blood sampling, and second fetal blood sampling >20,000 per microliter) or (2) a minimal decline in platelet count (the first fetal blood sampling ≥40,000 per microliter and the difference between the first and second fetal blood sampling ≤ 10,000 per microliter). The first fetal blood sampling had prognostic value for the second fetal blood sampling (P =.0001), although the previous sibling birth platelet count and history of sibling intracranial hemorrhage did not predict the platelet count at the first or second fetal blood sampling or the change in platelet count between the samplings. When the patients were segregated to first fetal blood sampling of >20,000 per microliter versus ≤20,000 per microliter, the response rates for the 2 groups were 89% (33/37 patients) versus 51% (19/37 patients; P =.001). Conclusion: In fetal alloimmune thrombocytopenia secondary to PlA1 platelet antigen incompatibility, fetuses with platelet counts >20,000 per microliter at the initiation of therapy were predicted to maintain their platelet count at the second fetal blood sampling at >20,000 per microliter. The characteristics of the previous sibling, as previously reported, did not predict the initial fetal blood sampling, the second fetal blood sampling, or the response to treatment. (Am J Obstet Gynecol 2001;185: 976-80.)

Severe Evans's syndrome secondary to interleukin-2 therapy: treatment with chimeric monoclonal anti-CD20 antibody.

Interleukin-2 (IL-2) acts by increasing the efficiency of the immune system to exert a tumoricidal effect. Although it is well known that immune stimulation with IL-2 plays a role in unmasking autoimmune phenomena such as autoimmune thyroiditis, hematological effects such as anemia and thrombocytopenia are more frequently due to toxic non-immune mechanisms. We describe a patient who developed severe Evans's syndrome [autoimmune hemolytic anemia (AHA) and immune thrombocytopenic purpura (ITP)] secondary to IL-2 therapy. ITP was refractory to multiple treatment modalities including steroids and splenectomy. ITP and AHA were initially managed with intravenous gamma globulin therapy and frequent blood transfusions, respectively. Ultimately, immunosuppressive therapy with cyclophosphamide and chimeric monoclonal anti-CD20 antibody (rituximab) were successful in inducing complete remission of Evans's syndrome.

Asymmetric antibodies and pregnancy.

Asymmetric IgG antibodies (AAb) possess a mannose-rich oligosaccharide residue bound to one of the Fab regions, making them unable to activate immunoeffector mechanisms. The proportion of asymmetric antibodies is increased after prolonged immunization with particulate antigens like cellular spleen cells. During pregnancy, AAb were found in serum and bound to placenta with specific activity to paternal antigens. No previous reports about the status of AAb in recurrent spontaneous abortion (RSA) patients have been published to date. Therefore, the aim of the present study was to analyze the percentage of asymmetric IgG molecules in serum samples of (a) healthy pregnant and non-pregnant women, (b) pregnant women with a history of RSA, and (c) non-pregnant RSA patients receiving paternal lymphocyte immunotherapy (LIT) or intravenous gammaglobulin therapy (IVIgs). A previously-described differential ELISA technique was used to determine the percentage of IgG that was of the asymmetric type. During normal pregnancy, there was an increase in the percentage of high ConA affinity IgG serum molecules with a major increase at the second trimester. Pregnant RSA patients at the second trimester had lower values. When evaluating non-pregnant RSA patients who received LIT, it was observed that the immunized patients expressed a higher percentage of asymmetric IgG antibodies. The pregnant patients who received IVIgs had a percentage of AAbs comparable to normal pregnant patients. Additionally, the presence of IgG asymmetric molecules was confirmed in commercial gammaglobulin preparations. Results suggest a protective role of AAb during pregnancy.

Management and outcome of persistent or recurrent fever after initial intravenous gamma globulin therapy in acute Kawasaki disease.

To determine differences in clinical characteristics, laboratory findings, and cardiac complications between patients with acute Kawasaki disease who received additional treatment for persistent or recurrent fever vs those who did not. Nonconcurrent case series; medical record review. Tertiary care pediatric hospital. One hundred eighty-five consecutive patients diagnosed as having acute Kawasaki disease at The Hospital for Sick Children, Toronto, Ontario, from 1995 to 1997. Prevalence of cardiac complications. Twenty-one patients (11%) received additional treatment with intravenous gamma globulin (IVGG) with or without intravenous methylprednisolone for persistent fever lasting for more than 48 hours or recurrent fever after initial treatment with IVGG. Patients who received additional treatment did not differ significantly from other patients regarding age, sex, race, or diagnostic criteria. Compared with the patients who did not receive additional therapy, the patients who received additional treatment had shorter median interval from fever onset to initial dose of IVGG (5 vs 6 days; P=.006) and longer total days of fever (9 vs 6 days; P<.001). Initial laboratory investigations did not differ significantly. On initial echocardiography, patients who received additional therapy were significantly more likely to have pericardial effusion (33% vs 15%; P=.04), ventricular dysfunction (14% vs 2%; P= .002), and coronary artery ectasia (76% vs 43%; P=.004) but not aneurysms (10% vs 5%; P= .47). At 12 months after diagnosis, there were no significant differences between the 2 groups regarding the prevalence of coronary artery ectasia or aneurysms. Patients receiving additional treatment for persistent or recurrent fever have similar demographic and clinical characteristics, greater initial cardiac involvement, and similar overall outcomes.

Management of fetal alloimmune thrombocytopenia-a less invasive option?

Fetal alloimmune thrombocytopenia (FAITP) is a condition associated with significant infant morbidity and mortality. We report on the West of Scotland experience of 30 pregnancies complicated by FAITP over a 17-year period (1982-98). Management options included serial cordocentesis together with platelet transfusion, and maternal intravenous gammaglobulin (IVIgG) therapy. Of those pregnancies managed by serial cordocentesis all had poor outcomes. Weekly IVIgG was administered to the remaining pregnancies, all of which had a good outcome although four infants were thrombocytopenic at birth. None of these cases had previously been complicated by intracranial haemorrhage. In the milder end of the spectrum of FAITP we would suggest that IVIgG is an alternative treatment option.

Coronary risk factors in acute Kawasaki disease: correlation of serum immunoglobulin levels with coronary complications.

To determine the usefulness of the IgG z-score (age and sex-standardized serum IgG level) before intravenous gamma globulin therapy (IVGG) in predicting the occurrence or severity of coronary complications in Kawasaki disease (KD). A case-control study of clinical and laboratory findings with 88 children in the early stage of acute KD who received IVGG (100 or 200 mg/kg for 2-5 days) therapy. Of these, 20 cases had persistent coronary arterial lesions (small aneurysm, moderate aneurysm or large aneurysm persisting more than 1 month). The controls comprised 68 children with no coronary aneurysms or transient small aneurysm only observed within 1 month after the onset of KD. The association between serum levels of immunoglobulin G (IgG). IgM, IgA as well as other coronary risk factors previously reported and the occurrence of the coronary arterial lesions was evaluated using logistic regression analysis. After adjustment for age, gender, total IVGG dose before the 9th illness day and other traditional coronary risk factors, the odds ratio for the persistent coronary aneurysm associated with lower serum IgG z-score (< -0.7485 vs > or = -0.7485), was 30.3 (95% confidence interval, 3.8-243.2). Furthermore, the serum IgG z-score was inversely correlated with the severity of the coronary arterial lesion. The IgG z-score before IVGG therapy in the early stage of KD provides useful information on the risk factors for persistent coronary aneurysm and is a novel, additional indicator for therapy to prevent the coronary complications in acute KD.

Intravenous gammaglobulin therapy for acquired von Willebrand disease

Intravenous gammaglobulin therapy for acquired von Willebrand disease

Lower level of serum potassium and higher level of C‐reactive protein as an independent risk factor for giant aneurysms in Kawasaki disease*

Giant aneurysms are the most serious issue of patients with Kawasaki disease (KD). To clarify risk factors for these giant aneurysms, we conducted a matched case‐control study. Among the patients reported in nationwide surveys, 117 patients with giant aneurysms had an unequivocal new diagnosis and presented at the treatment center within 9 d of illness. We obtained clinical information on admission of about 69 patients (case) from the treatment centers. One control was selected for each case, an age‐ and sex‐matched patient without coronary involvement, reported from the same treatment center at about the same time as the case, and we obtained the same clinical information about controls. Fourteen variables were analysed with a conditional logistic regression model: body temperature, hematocrit, hemoglobin, numbers of leukocyte and platelets, concentrations of serum albumin, globulin, total cholesterol, sodium, potassium and chloride, erythrocyte sedimentation rate, C‐reactive protein and alanine aminotransferase activity. After adjustment for age, duration of illness before admission and use of intravenous gamma globulin therapy, C‐reactive protein [odds ratio (OR)= 1.142, 95% confidence interval (CI) 1.054‐1.237], alanine aminotransferase activity (OR= 1.008, 95% CI 1.002‐1.014), serum sodium concentration (OR = 0.877, 95% CI 0.770‐0.999) and serum potassium concentration (OR = 0.319, 95% CI 0.124‐0.822) were significantly related to the risk for giant aneurysms. Further analyses with these four explanatory variables revealed that C‐reactive protein (OR = 1.159,95% CI 1.022‐1.315) and serum potassium concentration (OR = 0.222,95% CI 0.052–0.948) met the significant level. Thus, the values for serum C‐reactive protein and potassium are independent risk factors for the development of the giant aneurysms of Kawasaki disease.

Lower level of serum potassium and higher level of C-reactive protein as an independent risk factor for giant aneurysms in Kawasaki disease.

Giant aneurysms are the most serious issue of patients with Kawasaki disease (KD). To clarify risk factors for these giant aneurysms, we conducted a matched case-control study. Among the patients reported in nationwide surveys, 117 patients with giant aneurysms had an unequivocal new diagnosis and presented at the treatment center within 9 d of illness. We obtained clinical information on admission of about 69 patients (case) from the treatment centers. One control was selected for each case, an age- and sex-matched patient without coronary involvement, reported from the same treatment center at about the same time as the case, and we obtained the same clinical information about controls. Fourteen variables were analysed with a conditional logistic regression model: body temperature, hematocrit, hemoglobin, numbers of leukocyte and platelets, concentrations of serum albumin, globulin, total cholesterol, sodium, potassium and chloride, erythrocyte sedimentation rate, C-reactive protein and alanine aminotransferase activity. After adjustment for age, duration of illness before admission and use of intravenous gamma globulin therapy, C-reactive protein [odds ratio (OR)=1.142, 95% confidence interval (CI) 1.054-1.237], alanine aminotransferase activity (OR=1.008, 95% CI 1.002-1.014), serum sodium concentration (OR=0.877, 95% CI 0.770-0.999) and serum potassium concentration (OR=0.319, 95% CI 0.124-0.822) were significantly related to the risk for giant aneurysms. Further analyses with these four explanatory variables revealed that C-reactive protein (OR=1.159, 95% CI 1.022-1.315) and serum potassium concentration (OR=0.222, 95% CI 0.052-0.948) met the significant level. Thus, the values for serum C-reactive protein and potassium are independent risk factors for the development of the giant aneurysms of Kawasaki disease.

Kawasaki disease.

Incidence of Kawasaki disease in Japan is 10 times higher than in the United States. Approximately 10% of patients have atypical clinical presentations. Because echocardiographic or angiographic evidence of coronary artery complications is needed for diagnosis, such atypical cases often result in either delay or omission of intravenous gamma globulin therapy and higher incidence of coronary artery aneurysms than those patients with classical presentations. Despite ongoing research, no universally accepted etiologic theory exists today. Intravenous gamma globulin remains the mainstay of the acute phase treatment of Kawasaki disease. However, reported transmission of hepatitis C virus via a brand of intravenous gamm globulin leaves us with a lingering concern about the safety of this treatment. In terms of long-term follow-up, emergencence of a number of newer diagnostic modalities is promising and warrants careful evaluation. Surgical therapy for coronary artery disease needs to be approached cautiously.