Macrophage activation syndrome: a potentially fatal complication of rheumatic disorders.

AIMS: To review the precipitating events, clinical features, treatment, and outcome of macrophage activation syndrome (MAS). METHODS: Retrospective review of cases of MAS from a prospectively collected database of children with rheumatic diseases from 1980 to 2000. RESULTS: Nine patients (eight girls) were considered to have evidence of MAS. The primary diagnosis was systemic onset juvenile idiopathic arthritis in seven, enthesitis related arthritis in one, and chronic infantile neurological cutaneous articular syndrome in one. Mean age of onset was 5.7 years, and duration prior to MAS, 4.2 years. No medication was identified as a trigger. Eight had infections prior to MAS; specific infectious agents were identified in four. High grade fever, new onset hepatosplenomegaly, and lymphadenopathy were common clinical features. Platelet counts fell dramatically, from an average of 346 to 99 x 10(9)/l. Mean erythrocyte sedimentation rate (in three patients) fell from 115 to 28 mm/h. Eight had abnormal liver function during the disease course, and six had coagulopathy. Bone marrow examination supported the diagnosis with definite haemophagocytosis in four of seven. All received high dose steroids (eight intravenous, one oral), five cyclosporin, two cyclophosphamide, and one antithymocyte globulin. Two of three patients with significant renal impairment died. CONCLUSION: MAS is a rare and potentially fatal complication of childhood rheumatic disorders. Most of our patients were female, and most cases were preceded by infection. Bone marrow studies support the diagnosis. Deranged renal function may be a poor prognostic sign. Aggressive early therapy is essential.     

Unsuspected Pneumocystis carinii pneumonia at presentation of severe primary immunodeficiency

BACKGROUND—Pneumocystis carinii is an important pathogen in immunodeficiency but may be an unrecognised cause of respiratory compromise.
OBJECTIVES—To ascertain the incidence of P carinii pneumonia (PCP) at presentation of severe combined immunodeficiency (SCID), whether it had been diagnosed, and the effect of treatment on outcome.
SETTING—The supraregional paediatric bone marrow transplant unit for primary immunodeficiencies at Newcastle General Hospital.
METHODS—Retrospective case note review of infants referred with a diagnosis of SCID from 1992 to 1998.
RESULTS—Ten of 50 infants had PCP at presentation; only one was diagnosed before transfer. Eight were diagnosed by bronchoalveolar lavage and two by lung biopsy. In only one was P carinii identified in nasopharyngeal secretions. Five required ventilation for respiratory failure but all were successfully treated with co-trimoxazole and methylprednisolone with or without nebulised budesonide. Nine survived to bone marrow transplantation and four are long term survivors after bone marrow transplantation; no deaths were related to PCP.
CONCLUSIONS—PCP is a common presenting feature of SCID but is rarely recognised. Bronchoalveolar lavage or lung biopsy are needed for diagnosis. Treatment with co-trimoxazole is highly successful.

     

Validation of an asthma symptom diary for interventional studies

OBJECTIVE—The Pediatric Asthma Diary was developed and validated to assess efficacy of interventions in children with asthma.
DESIGN, PATIENTS, AND SETTING—Diary validation was performed in a three week, prospective study of 106 children aged 6-14 years with asthma. Children were classified at baseline as either stable (requiring no additional asthma treatment) or new onset/worse (requiring either addition of or increase in anti-inflammatory treatment).
RESULTS—A daytime symptom scale and "day without asthma" were defined from diary questions. Both measures demonstrated significant validity and responsiveness to anti-inflammatory treatment. The stable group experienced a higher percentage of days without asthma during week 1 compared with the new onset/worse group (39.6% v 11.6%, respectively). The new onset/worse patients experienced significant improvement in days without asthma (24.5%) compared with stable patients (6.4%).
CONCLUSIONS—The Pediatric Asthma Diary daytime symptom scale and day without asthma are acceptable measures for use in asthma intervention studies of children aged 6-14 years.

     

Academic career after treatment for acute lymphoblastic leukaemia

AIM—To evaluate academic career in long term survivors of childhood acute lymphoblastic leukaemia (ALL), in comparison to their healthy siblings.
PATIENTS—Ninety four children treated for ALL with cranial irradiation 18 or 25 Gy and intrathecal methotrexate as CNS prophylaxis. Median age at evaluation was 20 years; median follow up since diagnosis was 15 years at the time of the study.
METHODS—Patients and their 134 siblings completed a questionnaire on school career. The percentage of referrals to special primary schools for learning disabled, and the final level of secondary education in patients and siblings were compared, using a six point classification. Within the patient group, the effect of possible risk factors (age at diagnosis, irradiation dose, and gender) was investigated.
RESULTS—Significantly more patients than siblings were placed in special educational programmes. A significant difference was found for level of secondary education. No effect of gender or irradiation dose was found, but younger age at diagnosis was significantly related to both referrals and school levels.
CONCLUSION—Treatment for childhood ALL with cranial irradiation and chemotherapy at a young age is clearly associated with poorer academic career.

     

The abnormal nucleus as a cause of congenital facial palsy

BACKGROUND—Congenital facial palsy (CFP) is clinically defined as facial palsy present at birth. It is associated with considerable disfigurement and causes functional and emotional problems for the affected child. The aetiology of the majority of cases however, remains elusive.
AIMS—To investigate the role of a neuroanatomical abnormality as a cause of unilateral CFP.
METHODS—Magnetic resonance imaging (MRI) scans were performed on 21 patients with unilateral CFP. Fifteen patients had unilateral CFP only; six suffered from syndromes which can include unilateral CFP.
RESULTS—Of the 15 patients with unilateral CFP only, four (27%) had an abnormal nucleus or an abnormal weighting of this area on the MRI scan, compared to one (17%) of the remaining six patients.
CONCLUSION—Developmental abnormalities of the facial nucleus itself constitute an important, and previously ignored, cause of monosymptomatic unilateral CFP.

     

Diagnosis, classification, and management of erythema multiforme and Stevens-Johnson syndrome

BACKGROUND—In adults, erythema multiforme (EM) is thought to be mainly related to herpes infection and Stevens-Johnson syndrome (SJS) to drug reactions.
AIMS—To investigate this hypothesis in children, and to review our experience in the management of these patients.
METHODS—A retrospective analysis of 77 paediatric cases of EM or SJS admitted to the Children''s Hospital in Bordeaux between 1974and 1998.
RESULTS—Thirty five cases, inadequately documented or misdiagnosed mostly as urticarias or non-EM drug reactions were excluded. Among the remaining 42 patients (14 girls and 28 boys), 22 had EM (11EM minor and 11 EM major), 17 had SJS, and three had isolated mucous membrane involvement and were classified separately. Childhood EM was mostly related to herpes infection and SJS to infectious agents, especially Mycoplasma pneumoniae. Only two cases were firmly attributed to drugs (antibiotics). No patient died. EM and SJS sequelae were minor and steroids were of no overall benefit.
CONCLUSION—In paediatric practice EM is frequently misdiagnosed. The proposal that SJS is drug related in adults does not apply to children, and in our recruitment EM and SJS are mostly triggered by infectious agents. The course of both diseases, even though dramatic at onset, leads to low morbidity and mortality when appropriate symptomatic treatment is given.

     

ARC syndrome: an expanding range of phenotypes

AIM—To describe the clinical phenotype in infants with ARC syndrome, the association of arthrogryposis, renal tubular acidosis, and cholestasis.
METHODS—The medical records for six patients with ARC syndrome were reviewed, presenting over 10 years to three paediatric referral centres.
RESULTS—All patients had the typical pattern of arthrogryposis. Renal Fanconi syndrome was present in all but one patient, who presented with nephrogenic diabetes insipidus. Although all patients had severe cholestasis, serum γ glutamyltransferase values were normal. Many of our patients showed dysmorphic features or ichthyosis. All had recurrent febrile illnesses, diarrhoea, and failed to thrive. Blood films revealed abnormally large platelets.
CONCLUSIONS—ARC syndrome exhibits notable clinical variability and may not be as rare as previously thought. The association of Fanconi syndrome, ichthyosis, dysmorphism, jaundice, and diarrhoea has previously been reported as a separate syndrome: our observations indicate that it is part of the ARC spectrum.

     

Ovarian function after bone marrow transplantation performed before menarche

AIM—To examine the long term effect of bone marrow transplantation (BMT) on ovarian function in girls.
METHODS—Eighteen girls who underwent BMT before menarche, had been disease free for more than six years, and were over 14 years of age at the time of study were investigated. The preparative regimen consisted of irradiation and chemotherapy. The occurrence of menarche and changes in basal serum follicle stimulating hormone (FSH) concentrations were studied.
RESULTS—Twelve patients achieved menarche at a median age of 12.8 years. Age at transplant was significantly younger in patients who achieved menarche than in those who did not (mean (SD), 7.2 (0.5) v 11.1 (1.7) years). Basal FSH began to rise to menopausal concentrations after 10 years of age, and the girls who did not experience menarche had a sustained rise in FSH concentrations. Among those with raised FSH concentrations, five girls experienced menarche while serum FSH values were decreasing and four achieved menarche while FSH remained raised.
CONCLUSIONS—The high incidence of menarche suggests a favourable outcome of ovarian function in girls who undergo BMT at a young age.

     

Fine needle aspiration biopsy of thyroid nodules

BACKGROUND—Fine needle aspiration biopsy (FNA) is a routine diagnostic technique for evaluating thyroid nodules. Many reports in adults consider that FNA is superior to thyroid ultrasonography (USG) and radionuclide scanning (RS). Only five studies have been published on FNA of childhood thyroid nodules.
AIMS—To investigate the reliability of FNA in the evaluation and management of thyroid nodules, and compare the results of FNA, USG, and RS with regard to final histopathological diagnosis.
METHODS—FNA was performed in 46 children with thyroid nodules after USG and RS examination. We investigated the sensitivity, specificity, accuracy, and positive and negative predictive values of USG, RS, and FNA in their management.
RESULTS—Six patients who had malignant or suspicious cells on FNA examination underwent immediate surgery. The other 40 patients received medical treatment according to their hormonal status. Fifteen of these nodules either disappeared or decreased in number and/or size. Surgery was performed in 25 patients who did not respond to therapy. Statistical analysis revealed sensitivity, specificity, accuracy, and positive and negative predictive values respectively as follows: 60%, 59%, 59%, 15%, and 92% for USG; 30%, 42%, 39%, 12%, and 68% for SC; 100%, 95%, 95%, 67%, and 100% for FNAB.
CONCLUSION—FNAB is as reliable in children as in adults for definitive diagnosis of thyroid nodules. Using this technique avoids unnecessary thyroid surgery in children.

     

Long term complications of inferior vena cava thrombosis

AIM—To evaluate the long term outcome after paediatric inferior vena cava (IVC) thrombosis.
METHODS—A combined retrospective and prospective study on infants and children with IVC thrombosis treated at Aachen and Maastricht University Hospitals between 1980 and 1999.
RESULTS—Forty patients were enrolled, including four with preceding cardiac catheterisation, 18 with central venous saphenous lines, and an additional eight with umbilical venous catheters. Six patients died within three months of diagnosis; one patient was lost to follow up. Twelve of the remaining 33 patients had suffered from limited IVC thrombosis; during follow up (for up to nine years) none showed persisting caval obstruction (successful thrombolysis, n = 2; spontaneous recanalisation, n = 10). The remaining 21 patients presented with extensive IVC thrombosis. During follow up (for up to 18 years) complete restitution was found in only four cases (one thrombolysis, two surgery, one spontaneous recanalisation). Persisting iliac and/or caval venous obstruction occurred in 17patients, including six with thrombolysis. Varicose veins were found in 12, and post-thrombotic syndrome in seven of these cases. According to Kaplan-Meier analysis, 30% of patients with persisting venous disease will develop post-thrombotic syndrome within 10years of the thrombotic event.
CONCLUSIONS—Infants and children with extensive IVC thrombosis are at high risk for persisting venous disease and serious long term complications. Prospective trials are urgently needed to establish effective treatment strategies and to improve long term prognosis. Central venous catheters, contributing to IVC thrombosis in the majority of cases reported here, should be inserted only if essential.

     

Concentrations of antimony in infants dying from SIDS and infants dying from other causes

BACKGROUND—A patient with cystic fibrosis (CF) and repeated calcium oxalate renal stones prompted us to investigate other children for risk factors for this recognised complication of CF.
METHODS—Twenty four hour urinary excretion of calcium, oxalate, and glycolate was measured in children with CF and no symptoms of renal tract stones. Normal diet and treatments were continued.
RESULTS—In 26 children (aged 5-15.9 years) oxalate excretion was correlated with age; 14 of 26 children had oxalate excretion above an age appropriate normal range. There was a positive correlation between oxalate excretion and glycolate excretion. Mean calcium excretion was 0.06 mmol/kg/24 h with 21 of 24 children having calcium excretion below the normal range.
CONCLUSIONS—Hyperoxaluria may reflect malabsorption although correlation between excretion of oxalate and glycolate suggests a portion of the excess oxalate is derived from metabolic processes. The hypocalciuria observed here may protect children with CF from renal stones.

     

Interleukin 8 in middle ear fluid during acute otitis media: correlation with aetiology and bacterial eradication

OBJECTIVES—To study the concentration of interleukin 8 (IL-8) in the middle ear fluid of children with acute otitis media and the association between IL-8 concentrations, aetiology of acute otitis media, and bacteriological sterilisation.
STUDY DESIGN—Middle ear fluid was obtained by tympanocentesis at enrolment (day 1) and on day 4-5 in 81 children aged 3-36 months with acute otitis media who received antibiotic treatment. IL-8 concentrations were measured by enzyme linked immunosorbent assay.
RESULTS—101 samples were obtained on day 1 and 47 samples on day 4-5. 94 pathogens were isolated in 79 of 101 samples obtained on day 1: 56 Haemophilus influenzae, 35 Streptococcus pneumoniae, 2 Moraxella catarrhalis, and 1 Streptococcus pyogenes. Among 40paired, initially culture positive samples, sterilisation was achieved on day 4-5 in 22 but not in 18 (13 H influenzae, 2 S pneumoniae, and 3 H influenzae and S pneumoniae concomitantly). IL-8 was detected in 96 of 101 and 46 of 47 samples obtained on days 1 and 4-5, respectively. Mean (SD) IL-8 concentration on day 1 was significantly higher in culture positive than in negative samples (12 636 (23 317) v 5920 (7080) pg/ml). In paired samples, IL-8 concentration fell in 12 of 22 ears in which sterilisation was achieved and in 9 of 21 ears with persistent or new infection. Mean (SD) IL-8 concentrations on day 4-5 were significantly higher in culture positive than in negative samples (15 420 (15 418) v 6695 (5092) pg/ml).
CONCLUSIONS—Higher IL-8 concentrations are found in culture positive middle ear fluid in acute otitis media. Bacterial eradication is associated with a fall in these concentrations.

     

Accidents and resulting injuries in premobile infants: data from the ALSPAC study

BACKGROUND AND AIMS—Little is known about injuries resulting from accidents in premobile infants. We aimed to describe the pattern of minor accidents in infants and their resulting injuries.
METHODS—The ALSPAC study collected data in successive postal questionnaires. At 6 months of age, parents were asked to describe any accident since birth. The type of fall, distance fallen, resulting injury, and help sought were independently coded. Burns were similarly coded.
RESULTS—A total of 11 466 responses were available. In 2554 children, 3357 falls were reported; 53% fell from beds or settees and 12% fell from arms or while being carried. Only 14% reported visible injury, of which 56% were bruises; 97% of injuries specified involved the head. Only 21 falls (<1%) resulted in concussion or fracture. A burn or scald occurred in 172 cases (1.5%). The main causes of scalds were hot drinks and water, with contact burns caused by radiators, cookers, and hot food.
CONCLUSIONS—Falls in young infants are common while burns are rare. Injuries from falls are infrequent, predominantly trivial, and almost entirely confined to the head. Falls from beds and settees did not result in skull fractures. Serious injury was the result of complex accidents.

     

A randomised controlled trial of short term growth and collagen turnover in asthmatics treated with inhaled formoterol and budesonide

AIMS—To determine effects on short term growth and collagen turnover of adding formoterol (Eformoterol) to half the glucocorticoid dose in children with asthma, treated with inhaled budesonide (Pulmicort Turbuhaler).
DESIGN—A randomised double blind, placebo controlled crossover study with two six-week periods.
SETTING—Outpatient clinic in secondary referral centre.
SUBJECTS—A total of 27 prepubertal children aged 6-13 years.
INTERVENTIONS—Formoterol 12 µg and dry powder budesonide 100 µg twice daily in one period; placebo and dry powder budesonide 200 µg twice daily in the other.
OUTCOME MEASURES—Primary outcome measures were lower leg growth rate, and serum and urine markers of type I and type III collagen turnover. Secondary outcome measures were inflammation markers in serum, and parameters of asthma control.
RESULTS—During budesonide 200 µg twice daily treatment, mean lower leg growth rate was 0.14 mm/week (p = 0.02) lower than during the formoterol and budesonide period. Similar statistically significant effects on markers of collagen turnover were found, whereas inflammation markers and asthma control did not vary statistically significantly between the two periods.
CONCLUSIONS—In children treated with inhaled glucocorticoids, halving the dose and adding formoterol is associated with faster short term growth and an increase in markers of collagen turnover, with no loss of asthma control.

     

Growth hormone treatment in young children with Down's syndrome: effects on growth and psychomotor development

BACKGROUND—Learning disability and short stature are cardinal signs of Down''s syndrome. Insulin-like growth factor I (IGF-I), regulated by growth hormone (GH) from about 6 months of age, may be involved in brain development.
AIMS—To study long term effects of GH on linear growth and psychomotor development in young children with Down''s syndrome.
Study design—Fifteen children with Down''s syndrome were treated with GH for three years from the age of 6 to 9 months (mean, 7.4). Linear growth, psychomotor development, skeletal maturation, serum concentrations of IGF-I and its binding proteins (BPs), and cerebrospinal fluid (CSF) concentrations of IGF-II were studied.
RESULTS—The mean height of the study group increased from −1.8 to −0.8 SDS (Swedish standard) during treatment, whereas that of a Down''s syndrome control group fell from −1.7 to −2.2 SDS. Growth velocity declined after treatment stopped. Head growth did not accelerate during treatment. No significant difference in mental or gross motor development was found. The low concentrations of serum IGF-I and IGFBP-3 became normal during GH treatment.
CONCLUSIONS—GH treatment results in normal growth velocity in Down''s syndrome but does not affect head circumference or mental or gross motor development. Growth velocity declines after treatment stops.

     

Central nervous system imaging and congenital melanocytic naevi

AIM—To establish the prevalence of central nervous system (CNS) abnormalities on magnetic resonance imaging (MRI) in a population of children with congenital melanocytic naevi (CMN) over the head and/or spine, and to compare this with clinical findings.
METHODS—Forty three patients identified from outpatient clinics underwent MRI of the brain and/or spine. These were reported by a paediatric radiologist and findings compared with the clinical picture.
RESULTS—Nine patients had abnormal clinical neurology, seven had abnormal findings on MRI, and six had both abnormal clinical and radiological findings. Only three of the abnormal MRIs showed features of intracranial melanosis. Three others showed structural brain abnormalities: one choroid plexus papilloma, one cerebellar astrocytoma, and one posterior fossa arachnoid cyst; the first two of these have not previously been described in association with CMN. The last abnormal MRI showed equivocal changes requiring reimaging.
CONCLUSIONS—The prevalence of radiological CNS abnormality in this group of children was 7/43. Six of these developed abnormal clinical neurological signs within the first 18 months of life, but two did not do so until after the MRI. Two of the CNS lesions were operable; for this reason we support the routine use of early MRI in this group.

     

Prevention of cerebral palsy in glutaric aciduria type 1 by dietary management

AIMS—To study retrospectively the effects of treatment and the clinical outcome in 12 patients with glutaric aciduria type 1; and to compare the outcome in 6 patients diagnosed as a result of family screening with 6 patients who were diagnosed late after symptomatic presentation.
SETTING—The National Centre for Inherited Metabolic Disorders, The Children''s Hospital, Dublin, Ireland.
RESULT—Four of the 6 children detected on screening are developmentally normal, 1 died, and the remaining 1 has mild mental handicap. All 6 of the late diagnosed symptomatic group suffered dyskinetic cerebral palsy and 5 have died.
CONCLUSION—Experience of 50 patient treatment years has shown that early intensive management can alter the natural history of this rare disorder.
     

Maimonides (1135-1204) and his philosophy of medicine

AIM—To quantify the exposure of very low birthweight neonates to ionising radiation from diagnostic x-rays.
METHODS—Retrospective analysis was made of all radiographs performed over 18 months in an integrated special care baby unit and regional neonatal surgical unit in a large teaching hospital of surviving inborn babies of very low birthweight (<1500 g) admitted to the unit.
RESULTS—Fifty five VLBW neonates were treated for a total of 3296 days and received 498 radiographs (median 5 per infant). The mean effective radiation dose was 0.04 mSv and the maximum for one infant was 0.54mSv.
CONCLUSIONS—The radiation burden in this group of neonates is low and the benefits of diagnostic radiographs far outweigh any potential radiation risks.