Late complications of biliary atresia: hepatopulmonary syndrome and portopulmonary hypertension

Children with biliary atresia (BA) following Kasai portoenterostomy have a high risk for portal hypertension, however, while variceal and hemorrhagic complications have been more commonly studied, less frequent but no less possibly devastating complications of hepatopulmonary syndrome (HPS) and portopulmonary hypertension (PPH) remain less well understood. HPS and PPH both occur in a setting of portal hypertension, however, paradoxically patients with HPS develop pulmonic vasculature dilation leading to shunting and hypoxia, while those with PPH develop an opposite progression of pulmonary vasoconstriction eventually leading to cor pulmonale and decompensation. Given the near diametric evolution of diseases, HPS and PPH differ widely in therapy, though liver transplantation can have a role for treatment in either disease state. We reviewed our series of 320 pediatric patients with biliary atresia treated at our institution over 44 years, highlighting two cases that developed HPS and PPH, respectively, using these cases in further discussion of hepatopulmonary syndrome and portopulmonary hypertension regarding disease etiology, diagnosis, management, and prognosis. The complicated nature of these processes demand a careful multidisciplinary approach to optimize patient outcomes, including mindful evaluation for when transplantation may offer benefit.     

Cardiogenic shock: do not forget the possibility of Kawasaki disease

We report the case of a six-year-old boy who presented with cardiogenic shock due to Kawasaki disease (KD). He was misdiagnosed at first as septic shock. After careful examination, he was diagnosed as KD complicated with acute coronary syndrome, which leads to cardiogenic shock. Cardiogenic shock is often neglected as a complication of KD, and it tends to be misdiagnosed. We hereby call attention to KD, in some cases of which, it can lead to acute coronary syndrome in the acute phase.     

Decreased hepatic uptake of gallium-67 citrate in haemophagocytic syndrome occurring concomitantly with capillary leak syndrome

We describe a 4-year-old girl with haemophagocytic syndrome (HPS) in whom hepatic gallium-67 citrate (Ga-67) uptake was suppressed when the disease was in its acute phase and returned to normal when the disease was in remission. The prominent clinical feature of this case was the occurrence of systemic capillary leak syndrome (CLS). Because extravasation of plasma proteins may be the result of vascular endothelial injury in CLS, loss of hepatic Ga-67 uptake may reflect insult to the hepatic sinusoidal endothelium. This case suggests a possible role of sinusoidal endothelial cells in the mechanism of hepatic Ga-67 uptake and indicates the need for further study of Ga-67 uptake in patients with HPS.     

The role of UGT1A1*28 mutation in jaundiced infants with hypertrophic pyloric stenosis

Hypertrophic pyloric stenosis (HPS) may be accompanied by jaundice, a condition referred to as the icteropyloric syndrome (IPS). It has long been suspected that the etiology of IPS is an early manifestation of Gilbert's syndrome (GS). Clinical features common to both GS and IPS include jaundice precipitated by fasting and improved with feeding. Prevalence of jaundice in HPS is similar to that of clinically apparent GS in the general population. Discovery of a mutation in the promoter region of the bilirubin uridine diphosphate glucuronosyl transferase gene (UGT1A1*28) as the most common cause of GS has provided a tool to determine the role of GS in IPS. The aims of this study were to determine 1) the prevalence of IPS in a large group of infants with HPS, 2) whether disease severity contributed to the manifestation of IPS, and 3) whether GS played a role in IPS. Radioactive PCR and sequencing were used to determine the presence of UGT1A1*28 mutations. We determined a prevalence of IPS of 14.3% in HPS. Infants with IPS had significantly higher levels of alkalosis than infants with HPS alone. GS mutations were 4-fold higher in IPS (43.8%) than HPS (10.7%). In conclusion, the frequency of jaundice in HPS is similar to that of clinically apparent GS in the general population. Manifestation of IPS results from a more severe degree of metabolic disturbance and the presence of GS mutations.     

Acute vulvar ulceration as the main presenting manifestation of hemophagocytic syndrome

A 14-year-old female exhibited an acute vulvar ulcer during the course of hemophagocytic syndrome (HPS). The patient presented persistent high fever and a deep painful vulvar ulcer lasting for more than 2 weeks. Neither infection with sexually transmitted agents nor autoimmune disorder were found to be positive. The presence of hemophagocytosis in the bone marrow and elevation of urinary β-2-microglobulin ( β-2M) prompted the diagnosis of HPS. Acute vulvar ulcer is rare, but it should be recognized as a mucous manifestation of HPS. During the clinical course, urinary β-2M was the most sensitive marker for the evaluation of the disease activity of HPS.     

Childhood cirrhosis, hepatopulmonary syndrome and liver transplantation

Abstract: Objectives: The hepatopulmonary syndrome (HPS) is characterized as a triad: liver disease, intrapulmonary vascular dilatatiton, and arterial hypoxemia. The aim of this study is to analyze outcome of children with HPS in liver transplant era. Methods: Between September 1996 and November 2006, 172 cirrhotic patients (median age 5 years; range 0.2–22 years, M/F; 97/75) were followed at Ege University Pediatric Gastroenterology, Hepatology and Nutrition Unit. All patients were evaluated by chest radiography, arterial blood gas analysis, and alveolar‐arterial oxygen tension difference, contrast echocardiography (CEE) after and before the liver transplantation. Results: HPS was diagnosed in 33 patients (19%) by CEE. None of them had pulmonary hypertension. HPS was not found related to etiology of the liver disease. Portal hypertension was found related to the development of HPS (75.7% in patients with HPS and 54.6% in others, p = 0.02). 17 of 33 patients with HPS underwent liver transplantation. Preoperative and postoperative period of these patients was uneventful. Patients were extubated in the operating room except for two. Median follow up of transplanted children was 1.9 year (range; 0.75–10 years). Arterial blood gas analysis and CEE positivity regressed in all of them by postoperative 6th month. Conclusions: HPS is a serious and important complication of cirrhotic children that leads to tissue hypoxia and central cyanosis. HPS seems reversible after liver transplantation in all patients.     

Clinical features of acute kidney injury in patients with Kawasaki disease

Although acute kidney injury (AKI) is a common complication in hospitalized children, AKI has rarely been reported in patients with Kawasaki disease (KD). Herein, we review the clinical trajectories of AKI in patients with KD. A total of 39 patients with KD who developed AKI have been reported in 28 publications as case reports. The causes of AKI include prerenal AKI associated with acute heart failure (AHF), intrinsic AKI caused by tubulointerstitial nephritis (TIN), acute nephritic syndrome (ANS), hemolytic uremic syndrome (HUS), immune complex-mediated nephropathy, rhabdomyolysis, and KD shock syndrome (KDSS). Six of the 39 patients (15.4%) underwent renal replacement therapy. While AHF and multiple organ dysfunction syndrome developed in 41% and 68% of KD patients with AKI, respectively, all patients recovered without any renal sequelae. Although the precise pathogenic mechanism underlying the development of AKI in patients with KD is unknown, several possible mechanisms have been proposed, including T-cell-mediated immunologic abnormalities for TIN, renal and glomerular endothelial injury resulting from vasculitis for HUS, immune complex-mediated kidney injury for immune complex-mediated nephropathy and ASN, and capillary leak and an increased release of cytokines with myocardial dysfunction for KDSS.     

A case of Kawasaki disease associated with syndrome of inappropriate secretion of antidiuretic hormone

Kawasaki disease (KD) is an acute vasculitis of unknown aetiology with varied clinical manifestations. Although coronary arteritis is common in the course of KD, central nervous system involvement is rare. We report a case of KD in an infant who developed convulsions and apnoea during his illness associated with syndrome of inappropriate secretion of antidiuretic hormone (SIADH). CONCLUSION: The possibility of severe hyponatraemia should be anticipated in children with KD. Infants with KD are at risk of SIADH and should be monitored closely for its development.     

Kawasaki disease fact check: Myths,misconceptions and mysteries

Kawasaki disease (KD) is an important cause of childhood vasculitis and a common cause of acquired heart disease in children world‐wide. The emergence of Paediatric Multisystem Inflammatory Syndrome‐Temporally Associated with SARS‐CoV‐2, a KD‐like hyperinflammatory syndrome and the recent death of Dr Tomisaku Kawasaki make this a timely review. Although KD was described by Dr Kawasaki over 50 years ago, there is still no specific diagnostic test and the aetiology remains elusive. This article summarises the latest evidence, highlights important myths and misconceptions and discusses some of the mysteries that surround this disease.     

儿童噬血细胞综合征与人微小病毒B19感染的相关性及临床特征分析

目的探讨儿童噬血细胞综合征(HPS)与人微小病毒B19(HPVB19)感染可能存在的相关性,并对其临床特征进行分析。方法采用酶联免疫吸附试验(ELISA)和荧光定量PCR法对65例HPS患儿(HPS组)及65例健康体检儿童(对照组)进行HPVB19 Ig M、Ig G及HPVB19 DNA检测,并根据HPVB19DNA检测结果将HPS患儿分为HPVB19感染组(n=14)和非感染组(n=51),比较两组患儿临床资料。结果 HPS组HPVB19-Ig M阳性率(26%,17/65)显著高于对照组(9%,6/65)(P=0.011);而HPVB19-Ig G阳性率(38%,25/65)与对照组(29%,19/65)比较差异无统计学意义(P=0.266)。HPS组HPVB19感染率(22%,14/65)明显高于对照组(3%,2/65)(P=0.001)。与HPVB19非感染组HPS患儿比较,感染组患儿入院时血小板计数与血红蛋白水平显著降低,肝功能损伤更严重,发病时间更早,病程迁延时间更长(均P0.05)。结论 HPVB19感染与HPS发病可能具有相关性。HPVB19感染的HPS患儿起病更急,临床表现更为严重,病程迁延时间更长。     

Development of hepatopulmonary syndrome and portopulmonary hypertension in a paediatric liver transplant patient

BACKGROUND: Hepatopulmonary syndrome (HPS) and portopulmonary hypertension (PPH) are pulmonary vascular disorders which occur in patients with severe liver disease and/or portal hypertension. Although these syndromes are frequently diagnosed in patients undergoing assessment for liver transplantation, they seldom occur in the same patient. METHOD: This report describes a female paediatric patient, born with extra-hepatic biliary atresia, who required liver transplantation, at the age of 15, for secondary biliary cirrhosis. She had severe HPS prior to her first liver transplant, which resolved rapidly following surgery, as well as indirect evidence for PPH. She required a second liver transplant 1 yr later for chronic rejection. Whilst evaluating the patient for a third liver transplant, 4 yr later, severe PPH was discovered. The patient died 3 months later from right heart failure. CONCLUSION: HPS and PPH may coexist however they may show differing responses to liver transplantation with progression of PPH despite the resolution of HPS.     

Kawasaki disease: an update on diagnosis and treatment

Kawasaki disease (KD) is an acute multi-system vasculitis syndrome of unknown etiology occurring mostly in infants and children younger than 5 years of age. In developed countries, it is the leading cause of acquired heart disease in children. However, KD remains a mysterious disease. Some viruses potentially causing the condition have been isolated, but the results have not been able to be reproduced. This article reviews and summarizes different aspects of KD and provides updated information on diagnosis and treatment. The supplementary criteria for incomplete presentation of KD patients suggested by the American Heart Association, treatment (including tumor necrosis factor-alpha antagonist, methylprednisolone pulse therapy, statins, plasma exchange, and cytotoxic agents) for those with intravenous immunoglobulin treatment failure, and other experiences are also included in this review.     

An Old Autopsy Report Sheds Light on a “New” Disease: Infantile Polyarteritis Nodosa and Kawasaki Disease

Although Kawasaki disease (KD) was first discovered and identified in Japan by Kawasaki in the 1960s, fatal KD cases resulting from coronary artery aneurysms had been identified retrospectively in the West as early as 1871. Kawasaki initially postulated that this disease was a new, as yet unidentified, self-limiting illness with no fatal coronary sequelae. The connection between fatal cases, then diagnosed as infantile polyarteritis nodosa, was not made until the late 1970s. Kawasaki’s thoughts were reinforced by an apparent absence of nonfatal cases in the West before 1967. Close examination of a 1948 autopsy report suggests that nonfatal cases of KD did indeed exist, at least in the United States, before its emergence in Japan in the early 1950s. These nonfatal cases of KD were misdiagnosed as Stevens-Johnson syndrome. The autopsy report reviewed in this article reinforces the likelihood that KD did occur in the United States before it was identified as Kawasaki disease in Japan.     

Pediatric living donor liver transplantation for biliary atresia with hepatopulmonary syndrome: the gift of a second wind

Purpose

Hepatopulmonary syndrome (HPS) is a progressive, deteriorating complication of end-stage liver disease (ESLD) that occurs in 13?C47% of liver transplant candidates. Although LT is the only therapeutic option for HPS, it has a high morbidity and mortality, especially in patients with severe hypoxemia before transplantation, but the course of HPS after living donor liver transplantation (LDLT), especially for biliary atresia (BA) patients is not well established.

Patients and methods

The present study evaluated 122 patients who received an LDLT for BA and of these, 3 patients had HPS at the time of LDLT in a single-center series.

Results

Two patients of the HPS patients them had biliary and/or vascular complications, but they recovered uneventfully with interventional treatment. None of the patients required supplemental oxygen and had no residual cardiopulmonary abnormalities at a follow-up of more than 24?months.

Conclusion

Although a series of three patients is too small for definitive conclusion and further investigations must be conducted, pediatric LDLT can be a favorable therapeutic option for HPS.     

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??The ketogenic diet??KD?? has been used in the treatment of epilepsy in China mainland since 2004. Indications include glucose transporter protein 1??GLUT-1?? deficiency??pyruvate dehydrogenase deficiency??PDHD???? myoclonus astatic epilepsy ??Doose syndrome???? tuberous sclerosis complicated with epilepsy??Rett syndrome??Dravet syndrome??infant spasms??Landau Kleffner syndrome??Lafora disease??and super-refractory status epilepticus. The contraindications include fat metabolic pathway inborn errors??porphyrins diseases??and patients who are not able to cooperate with. The KD therapy complications are less??and by conservative treatment most are reversible. Transition from ordinary diet to KD often lasts 1—2 weeks?? 2??1—4??1 diet can produce ketosis of clinical therapeutic effect. It is recommended that KD might be tried at least for three months. Good responders should maintain the therapy for 2 years or so. It often takes 2 to 3 months for KD to turn back to normal diet. KD therapy should be combined with close follow-up and essessment??and it is considered safe in clinical practice.     

川崎病休克综合征早期识别与诊治研究进展

川崎病(KD)是儿童常见的急性血管炎,而川崎病休克综合征(KDSS)是KD少见而又严重的表现形式,近年来逐渐引起临床医师的关注,因其可出现在疾病早期,病情进展迅速,并伴有多系统器官受累,早期诊断困难,极易漏诊和误诊.本文综述了近年来KDSS诊断、早期识别、发病机制及治疗和预后等的研究进展.     

Secondary hemophagocytic syndrome after autologous hematopoietic cell transplant and immune therapy for neuroblastoma

Secondary hemophagocytic syndrome (HPS) has been described after autologous hematopoietic cell transplant (AutoHCT). We report two cases of secondary HPS after novel consolidation therapy for high‐risk neuroblastoma as part of an institutional phase 2 trial incorporating immunotherapy into a “standard” AutoHCT regimen. Both patients developed liver dysfunction beyond expected course of hepatic veno‐occlusive disease, coagulopathy, hyperferritinemia, and when evaluated, elevated soluble interleukin‐2 receptor and hemophagocytosis. These cases highlight the need for clinicians to have a high index of suspicion for immune‐related complications in patients receiving immune therapies.     

Safety from thromboembolism using intravenous immunoglobulin therapy in Kawasaki disease: Study of whole-blood viscosity

BACKGROUND: High-dose intravenous infusions of immunoglobulin (IVIG) are well established as a standard therapy for Kawasaki disease (KD) for reducing the risk of coronary artery aneurysms. IVIG therapy might increase the blood viscosity both in vitro and in vivo, which has been reported as a risk factor for cardiovascular or cerebrovascular thromboembolism in adults. METHODS: We measured the whole-blood viscosity in vitro, serum IgG and albumin, and blood hematocrit in 10 patients with KD and 10 with non-KD (five with acute encephalitis, one with sepsis, one with idiopathic thrombocytopenic purpura, one with Guillain-Barré syndrome, one with insulin-dependent diabetes mellitus, and one with Evans syndrome) before and after IVIG therapy. RESULTS: The blood viscosity increased significantly after IVIG therapy in the patients with non-KD, but did not increase in those with KD. CONCLUSION: The results of the present study suggest that the use of IVIG therapy for KD might be relatively safe, with no risk of thromboembolism due to hyperviscosity.     

Cardiopulmonary manifestations of portovenous shunts from congenital absence of the portal vein: Pulmonary hypertension and pulmonary vascular dilatation

Law YM, Mack CL, Sokol RJ, Rice M, Parsley L, Ivy D. Cardiopulmonary manifestations of portovenous shunts from congenital absence of the portal vein: Pulmonary hypertension and pulmonary vascular dilatation.
Pediatr Transplantation 2011: 15: E162–E168. © 2010 John Wiley & Sons A/S. Abstract: HPS and PPHTN are unusual and challenging pulmonary manifestations of liver disease. We report two pediatric cases in association with heterotaxy polysplenia syndrome and congenital absence of the portal vein. Both patients were symptomatic and hemodynamically compromised and required aggressive medical therapy. One patient with PPHTN alone achieved a successful liver transplant. The second child presented with combined HPS and PPHTN and exhibited a different evolution of pulmonary vascular disease. These cases illustrate associations that must be entertained in the setting of heterotaxy syndrome, cyanosis, or pulmonary hypertension and how strategic medical combined with surgical management can provide a good outcome.