Michael J. Dillon

Management of high blood pressure in children and adolescents: recommendations of the European Society of Hypertension

Hypertension in children and adolescents has gained ground in cardiovascular medicine, thanks to the progress made in several areas of pathophysiological and clinical research. These guidelines represent a consensus among specialists involved in the detection and control of high blood pressure in children and adolescents. The guidelines synthesize a considerable amount of scientific data and clinical experience and represent best clinical wisdom upon which physicians, nurses and families should base their decisions. They call attention to the burden of hypertension in children and adolescents, and its contribution to the current epidemic of cardiovascular disease, these guidelines should encourage public policy makers, to develop a global effort to improve identification and treatment of high blood pressure among children and adolescents.

EULAR/PReS endorsed consensus criteria for the classification of childhood vasculitides

Background: There has been a lack of appropriate classification criteria for vasculitis in children. Objective: To develop a widely accepted general classification for the vasculitides observed in children and specific and realistic classification criteria for common childhood vasculitides (Henoch-Schönlein purpura (HSP), Kawasaki disease (KD), childhood polyarteritis nodosa (PAN), Wegener’s granulomatosis (WG), and Takayasu arteritis (TA)). Methods: The project was divided into two phases: (1) the Delphi technique was used to gather opinions from a wide spectrum of paediatric rheumatologists and nephrologists; (2) a consensus conference using nominal group technique was held. Ten international experts, all paediatricians, met for the consensus conference. Agreement of at least 80% of the participants was defined as consensus. Results: Consensus was reached to base the general working classification for childhood vasculitides on vessel size. The small vessel disease was further subcategorised into “granulomatous” and “non-granulomatous.” Final criteria were developed to classify a child as HSP, KD, childhood PAN, WG, or TA, with changes introduced based on paediatric experience. Mandatory criteria were suggested for all diseases except WG. Conclusions: It is hoped that the suggested criteria will be widely accepted around the world because of the reliable techniques used and the international and multispecialist composition of the expert group involved.

Epilepsy, Ataxia, Sensorineural Deafness, Tubulopathy, and KCNJ10 Mutations

BACKGROUND Five children from two consanguineous families presented with epilepsy beginning in infancy and severe ataxia, moderate sensorineural deafness, and a renal salt-losing tubulopathy with normotensive hypokalemic metabolic alkalosis. We investigated the genetic basis of this autosomal recessive disease, which we call the EAST syndrome (the presence of epilepsy, ataxia, sensorineural deafness, and tubulopathy). METHODS Whole-genome linkage analysis was performed in the four affected children in one of the families. Newly identified mutations in a potassium-channel gene were evaluated with the use of a heterologous expression system. Protein expression and function were further investigated in genetically modified mice. RESULTS Linkage analysis identified a single significant locus on chromosome 1q23.2 with a lod score of 4.98. This region contained the KCNJ10 gene, which encodes a potassium channel expressed in the brain, inner ear, and kidney. Sequencing of this candidate gene revealed homozygous missense mutations in affected persons in both families. These mutations, when expressed heterologously in xenopus oocytes, caused significant and specific decreases in potassium currents. Mice with Kcnj10 deletions became dehydrated, with definitive evidence of renal salt wasting. CONCLUSIONS Mutations in KCNJ10 cause a specific disorder, consisting of epilepsy, ataxia, sensorineural deafness, and tubulopathy. Our findings indicate that KCNJ10 plays a major role in renal salt handling and, hence, possibly also in blood-pressure maintenance and its regulation.

Autosomal recessive polycystic kidney disease

The clinical features of 55 cases of autosomal recessive polycystic kidney disease (ARPCKD) have been reviewed. Each had evidence of ARPCKD. The outcomes of 87% were known; 24 had died. Twenty-four of 31 were seen between 1980 and 1986; 7 could not be traced. Forty-five percent presented under 1 month; 38% between 1 month and 1 year; and 9 cases over 1 year. Hyponatraemia occurred in 15 out of 19 aged less than 3 months; hypertension occurred in 65%; splenomegaly in 47% of those surviving more than 3 months. Portocaval shunts were done in 5 aged 2–12 years. Thirteen died of renal failure, 6 under 1 year, and 7 between 1 year and 13 years. Life-table survival rates calculated from birth revealed that 86% were alive at 3 months, 79% at 1 year, 51% at 10 years, and 46% at 15 years. Calculations based on patients who survived to 1 year of age showed that 82% were alive at 10 years and 79% at 15 years. These results reveal an improved prognosis for a condition once assumed to be fatal.

Endothelial Dysfunction Late After Kawasaki Disease

BACKGROUND Kawasaki disease (KD) is a systemic vasculitis of childhood with widespread vascular endothelial damage in the acute stage. Long-term complications, such as myocardial infarction and death, are recognized, but the extent and nature of late vascular abnormalities that might predispose to these events have not been studied. METHODS AND RESULTS We used high-resolution ultrasound to study endothelial function in the brachial artery of 20 patients 5 to 17 years after acute KD (median, 11 years) and compared findings with those in 20 age- and sex-matched control subjects. Vascular responses to reactive hyperemia (with flow increase leading to endothelium-dependent dilation) and to sublingual glyceryl trinitrate (GTN; endothelium-independent dilation) were recorded. The relationship between endothelium-dependent vascular responses and features of the endothelium acute illness was examined. There was no difference in baseline vessel diameter, degree of reactive hyperemia, or response to GTN between patients and control subjects. In contrast, flow-mediated dilation was markedly reduced in KD patients compared with control subjects (3.1% versus 9.4%; P < .001). Late endothelium-dependent responses were not related to features of the acute illness. CONCLUSIONS Abnormalities of systemic endothelial function are present many years after resolution of acute KD, even in patients without detectable early coronary artery involvement. Because this may be an important factor in the genesis of late vascular complications, long-term follow-up of all patients with KD is indicated.

Kawasaki disease: an evidence based approach to diagnosis, treatment, and proposals for future research.

This article proposes a clinical guideline for the diagnosis and treatment of Kawasaki disease in the UK based on the best available evidence to date, and highlights areas of practice where evidence is anecdotal or based on retrospective data. Future research as proposed by the London Kawasaki Disease Research Group is outlined, and clinicians are invited to prospectively enrol their suspected cases into this collaborative research project.

Autosomal recessive polycystic kidney disease: long-term outcome of neonatal survivors

Abstract. Autosomal recessive polycystic kidney disease causes renal and hepatic dysfunction in childhood. We describe the clinical outcome of 52 children with this diagnosis born between 1950 and 1993. Currently 23 are alive, 24 dead and 5 have been lost to follow-up; 1 has been dialysed and 7 transplanted. Life-table analysis of the patients surviving the 1st month of life revealed an actuarial renal survival of 86% at 1 year and 67% at 15 years. The probability of requiring anti-hypertensive treatment was 39% at 1 year and 60% at 15 years of age. Bleeding from gastro-oesophageal varices occurred in 8 patients at a mean age of 12.5 years, and was preceded by haematological evidence of hypersplenism in 6 of them. The study indicates a relatively good prognosis for patients with this condition who survive the neonatal period and emphasises the importance of early detection and appropriate management of systemic and portal hypertension.

The polymorphonuclear leucocyte count in childhood haemolytic uraemic syndrome

Review of data from 79 children with the haemolytic uraemic syndrome (HUS) showed that the polymorphonuclear leucocyte (PMN) count at presentation in childhood HUS predicts outcome. Logistic regression analysis of several features at presentation identified only the PMN count and the presence of a diarrhoeal prodrome as having a significant effect on the outcome (P<0.01 andP<0.001 respectively). The geometric mean PMN count was significantly raised in 70 children who had typical HUS following a diarrhoeal prodrome (D+cases) compared with that of 9 children who had atypical disease without diarrhoea (D-cases) (t-test on log-transformed data,P<0.005). Fifty-seven children with D+HUS who recovered completely had a significantly lower geometric mean PMN count than D+cases with a bad outcome (P<0.001). Four of these patients, who died in the acute stage of the disease, had a significantly higher mean count than the rest of the D+patients (P<0.001). Multiple regression analysis demonstrated that the PMN count in D+cases was not significantly influenced by haemoglobin concentration, platelet count, length of the prodrome, or the administration of antibiotics in the prodromal period. A high PMN count at presentation in D+HUS indicates a poor prognosis. The data emphasise the heterogeneity of HUS and suggest that PMN participate in the pathogenesis of the disorder in typical D + cases but not in atypical D- cases.

Haemolytic-uraemic syndrome: an analysis of prognostic features.

Seventy-two children with the haemolytic-uraemic syndrome were seen between 1969 and 1980 at The Hospital for Sick Children and Guys Hospital, London. They probably constitute the majority of such cases in south-east England during that period. Boys and girls were affected equally, the mean age at presentation was 3.5 years, and a peak incidence of the disorder in summer months was observed. In 52 (72%) there was a history of diarrhoea at onset. Fifty-seven (78%) were managed by dialysis. Fifty (70%) of the 72 children had a favourable outcome with complete recovery, 3 (4%) died in the acute phase of the illness, 8 (11%) had residual hypertension or chronic renal failure, and 11 (16%) never recovered renal function. The probability of complete recovery of renal function was analysed by logistic regression which indicated that younger age, presentation in the summer months, diarrhoea at onset and, in those patients who were dialysed, a short prodromal illness were associated with a good outcome. Further analysis of the interaction among these variables in the patient group as a whole indicated that diarrhoea favoured a good outcome among boys but not girls.

Clinicopathologic review of twelve children with nephropathy, Wilms tumor, and genital abnormalities (Drash syndrome)

The clinicopathologic and radiologic features of 12 children with complete and incomplete forms of Drash syndrome are reported. Their common denominator was a nephropathy. Four had the full triad, consisting of nephropathy, Wilms tumor, and genital abnormalities; five had nephropathy and genital abnormalities, and three had nephropathy and Wilms tumor. Of the 11 children who had proteinuria, eight had the nephrotic syndrome. Of the 10 whose condition progressed to end-stage renal failure, seven were less than 3 years of age. The histologic features of Wilms tumor were favorable in all seven children, and the tumor was bilateral in three. Of the nine patients who had genital abnormalities, eight had 46,XY karyotype and either ambiguous genitalia (six patients) or normal female phenotype (two). One other patient had a normal 46,XX female karyotype and phenotype but had both müllerian and wolffian structures and a streak ovary. Nine patients had a distinct pelvicaliceal abnormality not previously reported as a feature of this syndrome. Other congenital abnormalities were aniridia, mental retardation, deafness, nystagmus, and cleft palate. This syndrome must be considered in any infant with unexplained nephropathy, particularly in young phenotypic female infants and in those children with ambiguous genitalia or Wilms tumor with an early presentation.