Cardio-pulmonary involvement in juvenile systemic lupus erythematosus.

Cardio-pulmonary manifestations of systemic lupus erythematosus (SLE) are well recognized in adults. We report the occurrence of clinically significant cardio-pulmonary disease in a cohort of predominantly Caucasian children with SLE. All children with SLE attending the Royal Liverpool Children's NHS Trust between 1995 and 2003 were reviewed. Of 29 children with SLE, 27 (93%) were Caucasian. Nine (31%) had cardio-respiratory complications: cardiac only (n = 1); respiratory only (n = 4); both cardiac and respiratory manifestations (n = 4). Median (range) duration of follow-up of affected children: four years (six months to 11 years). Six out of eight (75%) presented with respiratory complications before SLE was diagnosed. Three children had pericardial effusions, one requiring pericardiocentesis for tamponade. One had cardiac conduction defects and another significant pulmonary hypertension. Respiratory complications comprised: interstitial lung disease (n = 4), with two showing evidence of pulmonary fibrosis; pleural effusions (n = 2), pulmonary haemorrhage (n = 1) and lupus pneumonitis (n = 1). Disease course was complicated by CMV infection in one child. Lung biopsy was performed in five cases. Seven were treated with cyclophosphamide with significant improvement in symptoms/lung function. Of this predominantly Caucasian paediatric cohort with SLE, 31% had significant cardio-pulmonary involvement. All children with SLE should have regular monitoring of their cardio-respiratory status.

Deep venous thrombosis and pulmonary embolism following chickenpox.

An 11-year-old girl developed proximal deep venous thrombosis and bilateral pulmonary embolism associated with antiphospholipid syndrome following chickenpox. She responded to prolonged anticoagulation therapy.

Nutritional impairment in juvenile idiopathic arthritis.

OBJECTIVE: To investigate the relationship between nutritional impairment, measured by body mass index (BMI), expressed as an age- and sex-standardized standard deviation score (BMI SDS), and disease and patient characteristics in a UK cohort of children with juvenile idiopathic arthritis (JIA). A subgroup with available dietary information were analysed separately. METHODS: Important disease and patient characteristics (age, gender, disease subtype, swollen joint count, painful joint count, restricted joint count, treatment and dietary assessment) were assessed as potential explanatory measures of BMI SDS in a multiple linear regression. RESULTS: Data were collected on 123 consecutive patients. Twenty were nutritionally impaired. In multiple regression analysis excluding the dietary data, disease subtype [persistent oligoarthritis and polyarthritis (rheumatoid factor-negative)], five or more joints with reduced range of movement and being younger were associated with lower BMI SDS (P<0.001). When energy and protein intake were included in the analysis for a subgroup of children, the resulting model retained only disease subtype as a predictor of a low BMI SDS (P = 0.013). CONCLUSIONS: In this unselected population of children with JIA, 16% had evidence of undernutrition. The most commonly affected subtype was oligoarthritis, a previously unreported finding. There is no evidence from this study that this nutritional impairment results from inadequate food intake and it is likely that it is multifactorial in aetiology, disease subtype being the most important factor.

Immunoglobulin levels in methotrexate treated paediatric rheumatology patients.

Retrospective review of serum immunoglobulin levels in 78 methotrexate treated paediatric rheumatology patients showed that IgG, IgA, and IgM levels fell significantly by 26%, 21%, and 17% respectively while on methotrexate. Six patients with systemic disease showed a fall in IgG to below the normal range.

Nitrous oxide analgesia during intra-articular injection for juvenile idiopathic arthritis.

AIMS: To evaluate the efficacy and safety of nitrous oxide-oxygen for children with juvenile idiopathic arthritis (JIA) undergoing intra-articular corticosteroid injection. METHODS: A total of 55 consecutive patients with JIA undergoing intra-articular corticosteroid injection, using self administered nitrous oxide-oxygen for analgesia were studied. Patient, nurse, and parent pain scores were compared using a 0-10 cm visual analogue scale (VAS) immediately after the procedure. RESULTS: A total of 70 joints were injected in 55 patients (median age 13.54 years). The median pain score for patient, nurse, and parent was 1 (0-10 cm VAS). The mean rank patient score was 2.12, which was greater than the nurse score (1.97), which was greater than the parent score (1.91). These differences were significant. There were no serious adverse events in any patient. CONCLUSIONS: Nitrous oxide-oxygen provides safe and effective analgesia for intra-articular injection in children. In some cases, nurses and parents underestimated pain related to the procedure compared to the child.

Improved case confirmation in meningococcal disease with whole blood Taqman PCR.

BACKGROUND: The clinical diagnosis of meningococcal disease (MCD) can be difficult. Non-culture methods like the previous ELISA meningococcal PCR improved case confirmation rates, but were not ideal. A Taqman meningococcal PCR, using DNA extracted from serum (S-Taqman), which has an improved sensitivity compared to the ELISA method in vitro, was introduced into clinical practice in July 1997. A new whole blood DNA extraction method for Taqman (WB-Taqman) was introduced in September 1999. AIMS: To determine the degree of improvement in the confirmation rate in clinically diagnosed MCD, following the introduction of WB-Taqman. METHODS: A total of 192 patients (WB-Taqman) with possible or probable MCD, including those admitted to our paediatric intensive care unit, were studied. Admission EDTA samples obtained were sent for bacterial DNA detection at the Meningococcal Reference Unit (MRU), Manchester. These patients were compared to 319 patients with possible and probable MCD, seen at the same hospital prior to the introduction of WB-Taqman. RESULTS: Following the introduction of WB-Taqman, 82 of the 95 probable cases (88%) had a positive meningococcal PCR result. This gives a diagnostic sensitivity and specificity for WB-Taqman of 87% and 100% respectively. Following WB-Taqman all blood culture positive patients were also PCR positive. Confirmation of cases by PCR rose from 47% (S-Taqman, n = 166) to 88% (WB-Taqman). When all confirmatory tests were included, case confirmation increased from 72% (S-Taqman) to 94% (WB-Taqman). CONCLUSION: The sensitivity of PCR in confirming clinical MCD has improved significantly with this new method. The gold standard for confirming cases of MCD is now the WB-Taqman PCR.

Myositis in children with meningococcal disease: a role for tumour necrosis factor-alpha and interleukin-8?

OBJECTIVES: Myalgia is under-recognized in meningococcal disease (MCD). In septic shock, myositis is thought to be mediated by pro-inflammatory cytokines such as tumour necrosis factor-alpha (TNF-alpha), interleukin-8 (IL-8) and interleukin-6 (IL-6) but this has never previously been studied in MCD. We aimed to demonstrate whether muscle damage mediated via TNF-alpha and other pro-inflammatory cytokines occurs in MCD, as estimated by creatine kinase skeletal muscle isoenzyme (CK-MM) and cardiac isoenzyme (CK-MB) concentrations. METHODS: A total of 68 children, median age 2.7 years, with a diagnosis of MCD were prospectively studied. Severity of disease was measured using the Glasgow Meningococcal Septicaemia Prognostic Score (GMSPS). Severe disease was defined as a GMSPS of > or =8. TNF-alpha, IL-8, IL-6 and IL-1Ra concentrations were determined on samples taken on admission. RESULTS: CK-MM correlated significantly with TNF-alpha, IL-8 and GMSPS. There was no significant correlation between CK-MB and TNF-alpha or IL-6, but CK-MB correlated with GMSPS and IL-8. Fifty-six percent of children with MCD had evidence of muscle damage as manifested by elevated CK-MM. CONCLUSIONS: TNF-alpha and IL-8 may be potential mediators in the pathophysiology of skeletal muscle damage in MCD.

Meningococcal bacterial DNA load at presentation correlates with disease severity.

AIMS: To determine bacterial loads in meningococcal disease (MCD), their relation with disease severity, and the factors which determine bacterial load. METHODS: Meningococcal DNA quantification was performed by the Taqman PCR method on admission and sequential blood samples from patients with MCD. Disease severity was assessed using the Glasgow Septicaemia Prognostic Score (GMSPS, range 0-15, severe disease > or =8). RESULTS: Median admission bacterial load was 1.6 x 10(6) DNA copies/ml of blood (range 2.2 x 10(4) to 1.6 x 10(8)). Bacterial load was significantly higher in patients with severe (8.4 x 10(6)) compared to milder disease (1.1 x 10(6), p = 0.018). This difference was greater in septicaemic patients (median 1.6 x 10(7) versus 9.2 x 10(5), p < 0.001). Bacterial loads were significantly higher in patients that died (p = 0.017). Admission bacterial load was independent of the duration of clinical symptoms prior to admission, with no difference between the duration of symptoms in mild or severe cases (median, 10.5 and 11 hours respectively). Bacterial loads were independent of DNA elimination rates following treatment. CONCLUSION: Patients with MCD have higher bacterial loads than previously determined with quantitative culture methods. Admission bacterial load is significantly higher in patients with severe disease (GMSPS > or =8) and maximum load is highest in those who die. Bacterial load is independent of the duration of clinical symptoms or the decline in DNA load.

Neurodevelopmental outcome in meningococcal disease: a case-control study.

AIMS: To determine long term neurodevelopmental outcome following the spectrum of meningococcal infection. METHODS: Between 1988 and 1990, 152 cases of meningococcal disease were recruited; 139 survived. Between 1998 and 1999, 115 survivors (83%) were evaluated, together with 115 sex and age matched controls. Standard measures of neurological function, coordination, cognition, behaviour, and hearing were used to assess neurodevelopmental status. RESULTS: One case has spastic quadriplegia. Gross neurological examination was normal in all other cases and all controls. Five cases and no controls have significant hearing loss. Cases performed at a lower level than controls on measures of coordination, cognition, and behaviour. Four cases and no controls had major impairments. The adjusted odds ratios for moderate and minor impairments were 3.6 (95% CI 1.3 to 10.3) and 1.6 (95% CI 0.8 to 3.4) respectively. CONCLUSION: The majority of survivors from this cohort do not have gross neurological deficits. However, when objective measures of motor function, cognitive ability, and behaviour were applied significant detriments were found in meningococcal survivors.

Morbidity in reflex sympathetic dystrophy.

Reflex sympathetic dystrophy (RSD), an unusual diagnosis in general paediatrics, is well recognised by paediatric rheumatologists. This study reports the presentation and the clinical course of 46 patients (35 female, age range 8-15.2) with RSD. The patients saw professionals from an average of 2.3 specialties (range 1-5). Twenty five (54%) had a history of trauma. Median time to diagnosis was 12 weeks (range 1-130). Many children had multiple investigations and treatments. Once diagnosis was made, treatment followed with physiotherapy and analgesics. Median time to recovery was seven weeks (range 1-140), with 27.5% relapsing. Nine children required assessment by the child and adolescent psychiatry team. This disease, though rare, has significant morbidity and it is therefore important to raise clinicians' awareness of RSD in childhood. Children with the condition may then be recognised and referred for appropriate management earlier, and spared unnecessary investigations and treatments which may exacerbate the condition.

Increasing microbiological confirmation and changing epidemiology of meningococcal disease on Merseyside, England.

OBJECTIVES: To determine, for the last 5 years in children on Merseyside with clinical meningococcal disease (MCD), the impact on diagnostic yield of newer bacteriologic methods; bacterial antigen detection (AD) and polymerase chain reaction (PCR). METHODS: Prospective data collection at Royal Liverpool Children's Hospital over two epochs: 1 September 1992 to 30 April 1994 (epoch A, n = 126) and 17 November 1997 to 15 September 1998 (epoch B, n = 85). RESULTS: Epoch A was compared with epoch B. Diagnosis was confirmed by detection of meningococci in 78 of 126 (61.9%) versus 64 of 85 (75.3%, P = 0.04), but with a significantly lower rate of positive blood and cerebrospinal fluid culture in the later epoch. The proportion of cases receiving penicillin pretreatment was unchanged at 32%, but the proportion undergoing lumbar puncture decreased significantly. Median ages were higher in epoch B: 1.7 years versus 2.49 years (P = 0.013, Mann-Whitney). There was a significant increase in the proportion of cases due to serogroup C (14/78 (18%) versus 30/64 (46.9%), P = 0.001). CONCLUSIONS: Culture detection of meningococci from children with MCD has reduced, as less lumbar punctures are done. However, improved diagnosis by PCR and AD has increased microbiological confirmation overall. Serogroup C disease and the median age of cases continue to rise.

Admission cortisol and adrenocorticotrophic hormone levels in children with meningococcal disease: evidence of adrenal insufficiency?

OBJECTIVE: To measure admission cortisol and adrenocorticotrophic hormone (ACTH) levels in children with meningococcal disease to try and determine the prevalence of adrenal insufficiency. DESIGN: Prospective observational study. SETTING: Pediatric departments of four hospitals in Merseyside, United Kingdom. PATIENTS: Ninety-six children with meningococcal disease; 29 with hypotension, ten of whom died. MEASUREMENTS AND MAIN RESULTS: Admission cortisol, ACTH, and proinflammatory cytokine levels were measured. Serial cortisol levels also were measured during the first 48 hrs. Significantly lower cortisol levels were found in those who died compared with survivors. Significantly higher ACTH levels also were found in those who died. However, no child had a cortisol level <5 microg/dL (<138 nmol/L) implying definite adrenal insufficiency. Three of 29 children with hypotension had plasma cortisol levels implying possible adrenal insufficiency (<18 microg/dL [<497 nmol/L]), but high ACTH levels were only found in one of those three. Cortisol levels decreased significantly after antibiotic treatment, unless steroid therapy was administered. ACTH levels did not correlate with cortisol or proinflammatory cytokine levels. CONCLUSIONS: Children with meningococcal disease have a wide range of initial plasma cortisol levels, with lower levels found in those who die. Many factors may affect cortisol levels, but adrenal insufficiency is probably uncommon.