Bone strength in children with growing pains: long-term follow-up.

OBJECTIVES: To examine the changes in bone strength in a cohort of children with 'growing pains' (GP) after 5 years follow-up and the correlation with pain outcome. METHODS: Bone strength was measured by quantitative ultrasound. Subjects were 39 children with GP previously studied. Controls were normograms based on the measurement of bone speed of sound in 1085 healthy children. Current GP status was assessed by parental questionnaires. Bone strength was compared with pain outcome. RESULTS: We examined 30/39 (77%) patients after 5 years. Bone strength was significantly increased when compared to the first study (Z score 0.65±1.77 vs. -0.62±0.90, p<0.001). While overall there was no significant difference in the bone strength between the 16 (53%) patients whose GP resolved and the 14 (47%) who continued to have GP episodes (p=0.71), all 6 (20%) patients with a speed of sound Z-score <-1 continued to have GP (p=0.003). CONCLUSIONS: Our findings that pain improves in most patients parallel to the increase in bone strength may support the hypothesis of GP representing in some patients a local overuse syndrome.

Protracted febrile myalgia in children and young adults with familial Mediterranean fever: analysis of 15 patients and suggested criteria for working diagnosis.

OBJECTIVES: To present an analysis of patients with protracted febrile myalgia (PFM), a rarely reported manifestation of familial Mediterranean fever (FMF), and propose clinical criteria for working diagnosis. METHODS: A multicenter retrospective cohort study of children with PFM was performed. Clinical and laboratory data were obtained by medical record review. RESULTS: The study group included 15 patients with PFM. PFM occurred as the presenting sign of FMF in 33%. FMF was diagnosed clinically in all and by genetic analysis in 93%. M694V allelic involvement was noted in 93% of the patients. PFM occurred at a mean age of 9 +/- 3.4 years and was characterized by severe generalized muscle pain in all patients and fever in 71%. Mean duration up to diagnosis was 15.5 +/- 6 days. Mean erythrocyte sedimentation rate was 104 +/- 26 mm/h; mean C-reactive protein was 15.4 +/- 6.3 mg%. Creatine kinase was normal. Treatment included corticosteroids (4 patients) and nonsteroidal anti-inflammatory drugs (NSAIDs) (9 patients) with a symptomatic relief achieved at a mean of 7.7 +/- 4.3 days and 5 +/- 3.8 days, respectively (p = 0.14) (mean severity score 3 and 2.2, respectively, p = 0.075). Symptomatic relief in 2 untreated patients was achieved at a mean of 45.5 days. CONCLUSION: Based on our data, we propose criteria for working diagnosis including: severe disabling myalgia of at least 5 days in a young patient with FMF, associated with fever, elevated levels of inflammatory markers and presence of at least one M694V mutation.

Outcome of a national Israeli cohort of pediatric systemic lupus erythematosus.

The aim of this study was to describe the clinical manifestations and outcomes of a national cohort of childhood systemic lupus erythematosus (cSLE). All cases of cSLE registered in the Israeli national registry of children with rheumatic diseases between 1987-2003 were examined for disease activity and damage by the SLE disease activity index (SLEDAI) and SLE collaborating clinics/American College of Rheumatology (SLICC/ACR) damage index. Demographic, clinical, laboratory and treatment factors were analysed for their effect on the outcome. One-hundred and two patients were identified, 81% females, with a mean age at diagnosis of 13.3 +/- 2.6 years. The mean SLEDAI score was 17.2 +/- 9.0 (range 2-60). Fifty four patients were followed for at least five years. The mean SLEDAI decreased to 7.6 +/- 6.3 (0-29) and the mean SLICC/ACR damage index was 0.7 +/- 1.6 (0-8). Five patients developed chronic renal failure. No patients died. No factors were found to be significantly associated with the outcome except the initial SLEDAI score. The five-year outcome of our national cSLE cohort was good; with relatively low activity and minimal damage in most patients. The initial SLEDAI predicted the development of late damage.

Antiphospholipid syndrome and recurrent thrombosis in children.

OBJECTIVE: Few studies have addressed antiphospholipid syndrome (APS) among children. Our aims were to analyze the clinical and laboratory manifestations in a pediatric APS cohort and to assess the influence of inherited thrombophilia factors on the outcome of children with APS. METHODS: This was a multicenter study of children with APS who had no previous systemic autoimmune disease. We retrospectively reviewed their clinical and laboratory data, including hereditary thrombophilic deficits and outcomes. RESULTS: The cohort comprised 28 patients (17 females, mean +/- SD age at onset 10.6 +/- 6.1 years). The most common initial manifestations of APS were venous thrombosis, stroke, and thrombocytopenia. Lupus anticoagulant was detected in 96% of those tested. After a mean +/- SD followup of 5.7 +/- 4.8 years, 16 children (57.1%) had central nervous system disease, 9 exhibited hematologic involvement, and 5 (all females) had systemic lupus erythematosus (SLE). None had renal, heart, or new skin disease. Seven of 24 patients exhibiting vascular thrombotic events had recurrences. Infants with perinatal stroke had monophasic disease, and other manifestations of APS did not develop later. Hereditary thrombophilia was more common in children who experienced a single episode of APS (8 [53.3%] of 15 patients) than in those who experienced recurrences (2 [28.6%] of 7 patients). However, only 2 patients in the latter group (28.6%) received anticoagulants after the first manifestation, compared with 12 (70.6%) of the 17 patients without recurrences. CONCLUSION: APS in children has unique features. SLE may develop in a significant percentage of girls presenting with APS. Hereditary thrombophilia did not predict recurrent thrombosis, whereas the preventive impact of anticoagulant treatment following the first thrombotic event was noteworthy.

Juvenile localized scleroderma: clinical and epidemiological features in 750 children. An international study.

OBJECTIVE: Juvenile localized scleroderma (JLS) includes a number of conditions often grouped together. With the long-term goal of developing uniform classification criteria, we studied the epidemiological, clinical and immunological features of children with JLS followed by paediatric rheumatology and dermatology centres. METHODS: A large, multicentre, multinational study was conducted by collecting information on the demographics, family history, triggering environmental factors, clinical and laboratory features, and treatment of patients with JLS. RESULTS: Seven hundred and fifty patients with JLS from 70 centres were enrolled into the study. The disease duration at diagnosis was 18 months. Linear scleroderma (LS) was the most frequent subtype (65%), followed by plaque morphea (PM) (26%), generalized morphea (GM) (7%) and deep morphea (DM) (2%). As many as 15% of patients had a mixed subtype. Ninety-one patients (12%) had a positive family history for rheumatic or autoimmune diseases; 100 (13.3%) reported environmental events as possible trigger. ANA was positive in 42.3% of the patients, with a higher prevalence in the LS-DM subtype than in the PM-GM subtype. Scl70 was detected in the sera of 3% of the patients, anticentromere antibody in 2%, anti-double-stranded DNA in 4%, anti-cardiolipin antibody in 13% and rheumatoid factor in 16%. Methotrexate was the drug most frequently used, especially during the last 5 yr. CONCLUSION: This study represents the largest collection of patients with JLS ever reported. The insidious onset of the disease, the delay in diagnosis, the recognition of mixed subtype and the better definition of the other subtypes should influence our efforts in educating trainees and practitioners and help in developing a comprehensive classification system for this syndrome.

Unintentional childhood poisoning in the Sharon area in Israel: a prospective 5-year study.

OBJECTIVES: To study the epidemiology and risk factors for unintentional exposure to poisoning among the Jewish and the Arab population in the Sharon area in Israel. METHODS: We prospectively evaluated visits to the pediatric emergency department because of unintentional poisoning exposure, at the Meir General Hospital. We collected demographic data, substance exposure data, and the clinical outcome of the poisoning. RESULTS: During the 5 years of the study, 502 children were evaluated for unintentional poisoning, 84% Jewish and 16% Arabs; 88.5% occurred in children younger than 5 years, with a peak incidence at the age of 2 years (39.5%). Medications including hormones, vitamins, and antibiotics were the most common cause of exposure. Most children (95%) had no symptoms or abnormal findings on physical examination (84%), and most (85%) were discharged after several hours of observation. However, children of Arab origin presented with severe clinical manifestations because of a high rate of pesticide poisoning. There was 1 death from organic phosphate poisoning. CONCLUSION: Exposure to poisoning is commonly encountered in children. Pesticides exposure is more common in the Arab community and is usually associated with more severe clinical manifestations. Educational preventive programs are mandatory.

PRINTO/PRES international website for families of children with rheumatic diseases: www.pediatric-rheumatology.printo.it.

OBJECTIVE: To prepare a website for families and health professionals containing up to date information about paediatric rheumatic diseases (PRD). METHODS: Firstly, paediatric rheumatology centres and family self help associations were surveyed to characterise current clinical practice of physicians providing care for children with PRD, research activities, and training facilities of each centre. Secondly, international consensus was reached on the content of the website. Finally, the website was developed and the texts translated. RESULTS: The web page contains three main sections: (a) description for families of the characteristics of 15 PRD; (b) list of paediatric rheumatology centres; (c) contact information for family self help associations. A version for 45 countries in 52 languages (with another three in progress) is now available on the web. 291 surveys from 171 centres and 102 family associations were received from 42 countries. The median proportion of time spent in paediatric practice in the centres examined was 100%, with 70% of this time dedicated to paediatric rheumatology. 90% of the centres were willing to perform clinical trials in the future. CONCLUSIONS: The PRINTO/PRES website provides a well defined and competent set of information about PRD, with appropriate multiple translated versions and easy web navigational direction.

Intravenous immunoglobulins in peripheral neuropathy associated with vasculitis.

BACKGROUND: Peripheral neuropathy is a prominent feature of the systemic and secondary vasculitides. Usually, it is responsive to corticosteroids, but in certain cases it may be resistant to corticosteroid or immunosuppressive treatment, or both. OBJECTIVE: To present patients who exhibited various inflammatory diseases accompanied with vasculitic peripheral neuropathies for which intravenous immunoglobulin (IVIg) was used for treatment. METHODS: Six patients with Sjögren's syndrome, systemic lupus erythematosus (SLE), vaccination induced vasculitis, Churg-Strauss vasculitis, mixed cryoglobulinaemia associated with hepatitis C infection, or sarcoidosis were included. All developed vasculitic peripheral neuropathy, and were treated with high dose IVIg (2 g/kg body weight). The patients were followed up for 1-5 years after this treatment. RESULTS: In four patients (Sjögren's syndrome, Churg-Strauss vasculitis, SLE, and vaccination induced vasculitis) the neuropathy resolved after IVIg treatment. CONCLUSION: IVIg may be beneficial in cases of resistant vasculitic peripheral neuropathy. IVIg should probably be considered as a sole or adjuvant treatment for patients with contraindications to conventional treatment, or alternatively, for patients in whom conventional treatment has failed.

"Unresolving pneumonia" as the main manifestation of atypical Kawasaki disease.

Two cases of atypical Kawasaki disease (KD) manifested as persistent lobar lung consolidation, prolonged fever, and active inflammatory laboratory markers unresponsive to antibiotic treatment are reported. One of the children developed a giant coronary aneurysm. Atypical KD should be considered in the differential diagnosis of young children with prolonged fever and lobar consolidation unresponsive to antibiotics.

Assessment of quality of life of parents of children with juvenile chronic arthritis.

The aim of the study was to assess the quality of life (QOL) and the psychological status of parents of children with juvenile chronic arthritis (JCA). The QOL, anxiety and depression of the parents of 28 children with JCA were evaluated and compared to those of the parents of 28 healthy children. Mothers of JCA children and mothers of healthy children reported similar QOL. The reported anxiety and depression levels were similar for mothers and fathers in both groups. The parents of children with pauciarticular-type JCA reported lower QOL and higher levels of anxiety and depression than the parents of children with other types, namely polyarticular and systemic JCA. These findings may be explained by the fact that the pauciarticular patients had shorter disease duration and were less frequently seen in the outpatient clinic. The QOL of mothers of children with JCA was found to be slightly impaired in the group of children with pauciarticular JCA. Future larger studies are needed to confirm these results, as the number of subjects in the three groups was rather low.

Convulsions and retinal haemorrhage: should we look further?

BACKGROUND AND AIMS: The prevalence of retinal haemorrhages after convulsions is not well established. As these haemorrhages are considered characteristic of child abuse, we investigated their occurrence after convulsive episodes to see whether the finding of haemorrhage should prompt further investigation. METHODS: Prospective study of 153 children (aged 2 months to 2 years), seen in the emergency department after a convulsive episode. After a thorough history and physical examination, a retinal examination was performed by an ophthalmologist. If findings were positive, further investigation was undertaken to rule out systemic disorder or child abuse. RESULTS: One child was found with unilateral retinal haemorrhages following an episode of a simple febrile convulsion. A thorough investigation uncovered no other reason for this finding. CONCLUSION: Retinal haemorrhages following a convulsive episode are rare. Such a finding should trigger an extensive search for other reasons, including child abuse.

Eosinophilic cystitis in a 4-year-old boy: successful long-term treatment with cyclosporin A.

A 4-year-old Jewish boy presented with dysuria, urinary dribbling, increased urinary frequency, and new onset of diurnal enuresis. An infiltrating solid mass involving the entire bladder wall was found. Biopsy revealed "tumor-forming" eosinophilic cystitis, a rare bladder lesion of unclear cause. Antitoxocariasis treatment was unsuccessful. High-dose corticosteroids failed. The child's clinical condition and bladder sonographic findings continued to deteriorate. Treatment with cyclosporin A was given for 8 months, with a complete clinical, radiologic, and histopathologic cure and no side effects. Two years of follow-up showed a complete recovery.

The Hebrew version of the Childhood Health Assessment Questionnaire (CHAQ) and the Child Health Questionnaire (CHQ).

We report herein the results of the cross-cultural adaptation and validation into the Hebrew language of the parent's version of two health related quality of life instruments. The Childhood Health Assessment Questionnaire (CHAQ) is a disease specific health instrument that measures functional ability in daily living activities in children with juvenile idiopathic arthritis (JIA). The Child Health Questionnaire (CHQ) is a generic health instrument designed to capture the physical and psychosocial well-being of children independently from the underlying disease. The Hebrew CHAQ-CHQ were fully developed with 3 forward and 3 backward translations. A total of 144 subjects were enrolled: 80 patients with JIA (12% systemic onset, 34% polyarticular onset, 23% extended oligoarticular subtype, and 31% persistent oligoarticular subtype) and 64 healthy children. The CHAQ clinically discriminated between healthy subjects and JIA patients, with the systemic, polyarticular and extended oligoarticular subtypes having a higher degree of disability, pain, and a lower overall well-being when compared to their healthy peers. Also the CHQ clinically discriminated between healthy subjects and JIA patients, with the JIA patients having a lower physical and psychosocial well-being when compared to their healthy peers. In conclusion the Hebrew version of the CHAQ-CHQ is a reliable, and valid tool for the functional, physical and psychosocial assessment of children with JIA.

Diffuse muscular haemorrhage as presenting sign of juvenile systemic lupus erythematosus and lupus anticoagulant hypoprothrombinaemia syndrome.

Lupus anticoagulants are closely related to systemic lupus erythemathosus (SLE) and to thrombotic events. We describe a 12 year-old girl with a bilateral intramuscular haemorrhage of the gastrocnemius muscles as her main initial presentation of juvenile SLE. Laboratory work-up revealed lupus anticoagulant-hypoprothrombinaemia syndrome (LAHS) with very low levels of factor II due to autoantibodies. She showed a good initial clinical and laboratory response to prednisone therapy, however steroid dependency developed. To the best of our knowledge, this is the first case reported of juvenile SLE presenting with LAHS.

Behçet's disease in Israel: the influence of ethnic origin on disease expression and severity.

OBJECTIVE: To evaluate the relationship between ethnic origin and manifestations of Behçet's disease (BD) in Israel. METHODS: We studied 100 Israeli patients with BD, 66 Jews and 34 Arabs. The 3 largest ethnic groups of Jewish patients originated from Iran/Iraq (n = 21), Turkey (n = 12), and North African countries (n = 21). Patients were evaluated with respect to the entire spectrum of disease manifestations, and a systemic severity score for BD was calculated for each patient. Disease expression was compared between Jewish and Arab patients and among Jewish ethnic groups. RESULTS: There were no statistically significant differences between Jewish and Arab patients with respect to male:female ratio, prevalence of HLA-B5, age of disease onset, or disease duration. Disease expression and severity score were also similar in the 2 groups, but Arab patients had a higher rate of posterior uveitis (20.6 vs 4.6%; p < 0.03). Among the 3 largest Jewish ethnic groups, patients of North African origin had a significantly higher rate of ocular disease (p < 0.01), mainly in the form of anterior uveitis (p < 0.01). These patients also had higher rates of arthritis, overall vascular disease, deep vein thrombosis, and neuro-Behçet without reaching statistical significance. The disease severity score in this group was significantly higher compared to the other Jewish ethnic groups (p < 0.02). CONCLUSION: The expression of BD is similar in Israeli Jewish and Arab patients but the latter have more severe eye disease. The disease in Israeli Jewish patients is most severe in those originating from North African countries.

False-high blood salicylate levels in neonates with hyperbilirubinemia.

Drug assays may yield false-positive results caused by cross-reacting compounds. After finding a serum salicylate concentration of 81 microg/mL by using Trinder's colorimetric method, in a comatose child admitted to the authors' pediatric intensive care unit, in the absence of reported salicylate intake, the authors aimed to compare this situation with the phenomenon involving endogenous digoxin-like substances, which cross-react with the routine assay of digoxin. None of the participants in the study had been exposed to salicylate. Salicylate concentration was measured in all patients using Trinder's colorimetric method and in the second stage of the study also by AxSYM salicylate assay. Salicylate concentration using Trinder's method was 18 +/- 25 (4-81) microg/mL among nine seriously ill children in the pediatric intensive care unit, of whom two children with extensive burns had salicylate levels of 30 and 81 microg/mL, respectively. Salicylate concentrations were 107 +/- 24 (45-143) microg/mL and 60 +/- 25 (28-92) microg/mL, among 18 premature newborns and 18 term newborns, with hyperbilirubinemia, respectively. In the second stage, which involved 22 jaundiced term newborns and cord blood from 21 pregnant women, Trinder's method yielded elevated salicylate blood levels among the hyperbilirubinemic infants: 82 +/- 5 (73-89) microg/mL; however, the AxSYM assay yielded significantly lower blood levels: 2.5 +/- 3.4 (0-10.9) microg/mL (P < 0.0001). Among the pregnant women, salicylate cord blood levels were found to be low-within the limit error of the assay with both assay methods. In conclusion, when salicylate intoxication is suspected, particularly during the neonatal period, it is advisable to measure salicylate levels by immunoassay technology.

Children with morphea have normal self-perception.

We evaluated the self-esteem and quality of life of 47 children with morphea with the use of the Harter self-perception profile for children and Visual Analog Scale. Most children with morphea have normal self-worth and a high quality of life. Morphea, like some other childhood chronic illnesses, does not impair self-esteem.

The use of naproxen in the treatment of children with rheumatic fever.

We evaluated the efficacy and safety of naproxen (10-20 mg/kg/d) for the treatment of arthritis and fever related to rheumatic fever in 19 children. Fever and arthritis resolved within a median of 1 day of beginning treatment (range, 1-2 and 1-30 days, respectively). The sole patient with prolonged arthritis had small joint involvement. No gastrointestinal, dermatologic, liver, or renal side effects were observed. None of the patients developed carditis over the following 6 months. Naproxen appears to be effective for the treatment of arthritis and fever related to rheumatic fever and is well tolerated.