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.

Characterisation of community structure of bacteria in parallel mesophilic and thermophilic pilot scale anaerobe sludge digesters.

The aim of the present work was to compare the microbial communities of a mesophilic and a thermophilic pilot scale anaerobe sludge digester. For studying the communities cultivation independent chemotaxonomical methods (RQ and PLFA analyses) and T-RFLP were applied. Microbial communities of the mesophilic and thermophilic pilot digesters showed considerable differences, both concerning the species present, and their abundance. A Methanosarcina sp. dominated the thermophilic, while a Methanosaeta sp. the mesophilic digester among Archaea. Species diversity of Bacteria was reduced in the thermophilic digester. Based on the quinone patterns in both digesters the dominance of sulphate reducing respiratory bacteria could be detected. The PLFA profiles of the digester communities were similar though in minor components characteristic differences were shown. Level of branched chain fatty acids is slightly lower in the thermophilic digester that reports less Gram positive bacteria. The relative ratio of fatty acids characteristic to Enterobacteriaceae, Bacteroidetes and Clostridia shows differences between the two digesters: their importance generally decreased under thermophilic conditions. The sulphate reducer marker (15:1 and 17:1) fatty acids are present in low quantity in both digesters.

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.

The relation between adrenal function and the severity of bronchial hyperresponsiveness in children as measured by the methacholine provocation test.

BACKGROUND: There is no satisfactory explanation why some individuals experience severe attacks of asthma, yet others, exposed to similar stimuli, have a milder form of the disease. OBJECTIVE: We tested the hypothesis that children with more severe disease may have relative adrenal insufficiency compared to the children with milder disease. PATIENTS AND METHODS: Sixteen children with chronic asthma aged 8-16 years old were studied. Adrenal function was evaluated by the 24-h excretion of urinary free cortisol (UFC) before and after ACTH stimulation, and by plasma cortisol levels before and 60 min after ACTH administration. The severity of bronchial hyperresponsiveness was evaluated by the methacholine provocation test. RESULTS: Nine children had 20% fall in forced expiratory volume in 1 sec (FEV1) after a provocative concentration (PC20FEV1) of methacholine > or =2.5 mg/ml and were considered as having mild-moderate bronchial hyperresponsiveness (Group A). Seven children had a PC20FEV1 of < or =1.25 mg/ml and were considered as having severe bronchial hyperresponsiveness (Group B). No significant difference was found between the peak plasma cortisol response to ACTH between the two groups (634+/-182 and 586+/-137 nmol/l, respectively). However, there was a significant statistical difference (p <0.01) in the 24-h UFC response to ACTH between the children from Group A (345+/-107 nmol/m2 ) and the children from Group B (161+/-125 nmol/m2). CONCLUSIONS: Based on the low levels of 24-h UFC secretion in severely asthmatic children in our study, we propose the encouragement of provision of a short course of inhaled steroids to be kept at home for the emergency therapy of those children identified as having high-risk asthma.

Haemophilus influenza type b vaccine in Israel: experience in a paediatric ambulatory clinic.

In Israel, vaccination are the overall responsibility of the government. We were the first in Israel to give the Hib (Haemophilus influenza type b) vaccine to the population, through independent means, without government control. The aim of the study was to follow longitudinally the specific group of children vaccinated in our ambulatory clinic. In this study, 1,497 children between 2 and 52 [mean (SD) 13 (9)] months of age at the time of first vaccination were vaccinated with Hib vaccine. Over the next 7 years, they were followed up by repeated phone calls when parents were asked about hospitalisation and any serious infectious diseases. Of the 1,497, 1,444 were followed during the years 1992 to 1999 and 36 were hospitalised during this time. All blood and cerebrospinal fluid cultures were negative. No proven case of Hib infection could be demonstrated. Despite the small sample size, this study justifies the continued use of the vaccine along with maintaining surveillance for Hib infection.

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.

Neutropenia as a complication of intravenous immunoglobulin (IVIG) therapy in children with immune thrombocytopenic purpura: common and non-alarming.

UNLABELLED: Following reports on adult patients with neutropenia as a result of administration of intravenous immunoglobulin (IVIG) we have investigated the incidence and consequences of neutropenia following IVIG treatment in children with immune thrombocytopenic purpura (ITP). The medical records of 14 children with ITP who received IVIG as inpatients were reviewed. Past and present history, age, previous medications, complete blood count and differential before and after treatment with IVIG were recorded for each patient. The patients, aged 5.5 +/- 3.5 (0.5-11.5) years [mean +/- SD; range] received one or more courses of IVIG. Neutropenia (total neutrophils < 2000/mm3) was observed within 24 h after the first course of IVIG in five children (36%). The pretreatment neutrophil count in this group was not significantly different from that observed in the patients without IVIG-induced neutropenia (p = 0.98). The condition resolved spontaneously and without complications in all patients within 48 h. In a preliminary experiment in which bone marrow derived mononuclear cells were assayed for the clonogenicity in methylcellulose, there was no suppressive effect of IVIG on the number of CFU-GM colonies. CONCLUSIONS: Since IVIG is currently administered in a vast number of medical indications, neutropenia following IVIG administration may not be an uncommon finding. It seems to be transient and self limited.

Seasonal variation in systemic onset juvenile rheumatoid arthritis in Israel.

OBJECTIVE: To determine whether there is a seasonal peak onset of systemic juvenile rheumatoid arthritis (SOJRA) suggestive of an infectious etiology. We examined the seasonal variability of SOJRA in Israel. METHODS: A multicenter retrospective chart review of 59 patients with SOJRA, enrolled from 10 rheumatology units or pediatric departments in Israel. All patients met defined criteria of SOJRA. RESULTS: Fifty-nine patients (31 female, 28 male) were followed from 1982 to 1997. Their mean age was 7.1 +/- 4.3 years (range 0.9-16). Forty-six were Jewish and 13 were Arabs or of Bedouin origin. Eighteen patients (31%) had disease onset in the winter, 16 (27%) in the spring, 12 (20%) in the summer, and 13 (22%) in the fall. Twenty-eight patients had a monophasic disease subtype, while 31 had a chronic or cyclic subtype. The seasonal onset in the patients with the monophasic type versus the chronic or the cyclic type shows 7 versus 11 in the winter, 7 versus 9 in spring, 8 versus 4 in summer, and 6 versus 7 in fall, respectively. CONCLUSION: There is no seasonal pattern to SOJRA disease onset in Israel. However, the disease onset of patients having the chronic or the polycyclic subtype tends to be more common in winter and spring. Since patients with this type have more severe disease, it is possible that another specific infectious agent is one of the factors involved in the pathogenesis of the disease. Larger sampling and multicenter studies are required to clarify this point.

Hereditary insensitivity to pain with anhidrosis.

Hereditary sensory neuropathy type IV is an autosomal-recessive disorder characterized by congenital insensitivity to pain and anhidrosis and resulting in recurrent hyperpyrexia, self-mutilation, recurrent infections, chronic osteomyelitis, bone and joint deformities, and limb amputations. Described is a child with signs as well as skin and nerve biopsy results compatible with this disease, emphasizing the importance of early diagnosis and appropriate medical and educational care to prevent complications.

Juvenile Behçet's disease in Israel. The Pediatric Rheumatology Study Group of Israel.

OBJECTIVE: Behçet's disease (BD) is a vasculitis mainly observed in young adult males. Juvenile BD is rare and only small series of pediatric cases have been reported. The objective of this study was to define the epidemiology and clinical features of BD among Israeli children. METHODS: A questionnaire was sent to 8 pediatric rheumatology units in Israel and 30 cases of BD diagnosed before the age of 16 years were identified. RESULTS: Fifteen patients fulfilled the International Study Group Criteria for BD, while 15 had an incomplete form of BD. Among the patients with complete BD, stomatitis and skin involvement were the most common manifestations. Other symptoms included genital ulcers, uveitis, CNS involvement, arthritis, and gastrointestinal involvement. A positive family history was elicited in 3 patients. HLA B5 was found in 7 of 12 patients (58%). The 15 patients with incomplete BD all had recurrent stomatitis; other manifestations included uveitis, arthritis, and genital ulcers. HLA B5 was found in 94% of this group. CONCLUSION: Juvenile BD in Israel is not uncommon, and is frequently associated with HLA B5 positivity. This could indicate a genetic susceptibility in our region. Half of the patients in our series had an incomplete form of BD, which may represent a less severe variant of the disease. In any case, careful follow-up is required, since their condition could eventually evolve into complete BD.

Acute iron intoxication: significant differences between sexes.

Iron, one of the common medications in use among children and adults, is the leading cause of pediatric unintentional ingestion fatalities and is not an uncommon poisoning among adults. Accidental ingestion is common because iron-containing compounds are readily available, brightly colored, often sugar coated, and frequently considered harmless vitamins. There are no data on differences between sexes with regard to iron intoxication, and the management of iron overdose is the same for females and males. After oral administration by gavage of the LD50 of iron to Wistar rats, the pharmacokinetics of iron, baseline and peak serum iron levels, and mortality rates were compared between sexes. Prepubertal females died significantly more than males (p < 0.01), pubertal females died significantly earlier than males (p < 0.04), and the same was true among adult rats (p = 0.02). Baseline serum iron levels were not significantly different between prepubertal female and male rats, but female pubertal rats had significantly higher baseline iron levels than males (p = 0.006). After iron administration, females had significantly higher peak serum iron concentrations (p < 0.03). Mechanisms of iron absorption are still not completely known and, probably, there are differences in iron absorption between sexes, which may account for the differences in serum iron levels and mortality rates. While the therapeutic approach in cases of intoxication is individual, iron intoxication, as may be true for other poisonings also, treatments administered to females may need to be different from that given to males.

Intussusception: a 9-year survey (1986-1995).

BACKGROUND: Acute intussusception has different clinical features in various parts of the world. The goal of this study was to determine the clinical presentation in different ethnic groups in Israel. METHODS: A retrospective chart review of a 9-year period (1985-1995) was carried out at a university medical center. Data extracted included age, sex, ethnic origin, presenting symptoms and signs, the type of enema (barium or air), and the success rate of non-surgical reduction of the intussusception. RESULTS: Ninety patients suffering from intestinal obstruction due to acute intussusception were admitted. The triad of intermittent screaming attacks, lethargy, and vomiting was observed in 37.5% of study subjects. The majority of patients were admitted during the warmer months of the year. The average age of the patients was 7.8 +/- 3.7 months; 70% of them were between the ages of 4 and 9 months and 92.5% under 1 year of age. The female-to-male ratio was 1:2.1. Air enema was superior to the barium enema in achieving reduction (p < 0.01). The incidence in the Jewish population was similar to that observed in other surveys, and twice that found in the Arab population in our region (p < 0.05). CONCLUSIONS: The overall clinical presentation of acute intussusception found in our study does not differ from other studies. The lower incidence of acute intussusception found in the Arab population can be explained by ethnic, genetic, or nutritional factors.

[Recurrent pericarditis in familial Mediterranean fever].

The diagnosis of familial Mediterranean fever (FMF) is based on clinical evidence, since there is no specific diagnostic test. Manifestations are recurrent attacks of fever accompanied by serositis, mainly involving the peritoneum, pleura and joints. Although pericardial inflammation has been considered rare, when echocardiography is used to detect it, an incidence of 27% has been reported. We describe a boy of 11 and a girl of 15 years who developed recurrent pericarditis despite treatment with steroids, nonsteroidal anti-inflammatory drugs and pericardiocentesis. A few months after the first episode, both patients were admitted with typical bouts of FMF. Continuous prophylaxis with colchicine was initiated, and there were no further attacks during 18 and 10 month follow-ups, respectively. We conclude that acute or recurrent pericarditis in children or young adults of Mediterranean origin may be due to FMF.

Gaucher disease--the orthopaedic aspect. Report of seven cases.

Seven patients with Gaucher type 1 disease are presented: five female and two male. The orthopaedic problems encountered were: avascular necrosis of both femoral heads in two girls, bilateral bone infarctions of the femurs in all three girls, complicated by staphylococcal osteomyelitis of the right femur in one girl and by pathological fractures of both femurs in another girl, osteonecrosis of both humeral heads in one male adult patient, osteonecrosis of the femoral heads in two further adults (male and female), and a pathological fracture of the fourth lumbar vertebra in another adult woman with concomitant humeral head involvement. The patient with osteonecrosis of the humeral head was treated with a total shoulder arthroplasty, and the two patients with osteonecrosis of the femoral heads were treated with total hip arthroplasties, with satisfactory intermediate and long-term results.

Familial Mediterranean fever presenting with massive cardiac tamponade.

A 16-year-old girl, presenting initially with pericarditis and life threatening pericardial tamponade, developed clinical episodes characteristic of FMF few months later. This case report and several others reported previously, suggest that FMF should be considered in patients from certain ethnic groups presenting with pericardial effusion.

Chronic diffuse varioliform gastritis in a child. Total gastrectomy for acute massive bleeding.

Chronic diffuse varioliform gastritis is an uncommon, subacute, inflammatory gastric mucosal disease characterized by swollen congested rugae and disseminated mucosal erosions. The entity is exceptionally rare in children. The spectrum of reported symptoms is broad; frank hematemesis has never been reported in childhood. We present a child in whom the disease had a remarkably unusual clinical course. Because many caretakers were unaware of the existence of the disease in children, the patient had numerous hospitalizations and surgical procedures, until massive gastric bleeding resulted in unavoidable emergency total gastrectomy. Microscopical examination and immunofluorescent staining of the gastric mucosa confirmed the diagnosis of chronic diffuse varioliform gastritis.

Infantile idiopathic thrombocytopenic purpura.

Idiopathic thrombocytopenic purpura (ITP) in childhood is a benign disease, as only 10% to 20% of the patients have a chronic course. A retrospective study of 57 ITP patients ranging in age from four months to two years revealed that 30% of them proceeded to chronicity. Unlike ITP in the general pediatric population, chronic infantile ITP was characterized by male predominance, a high frequency of preceding viral infections, and lack of responsiveness to any of the known modalities of treatment.

Ultrasonographic and computed tomographic diagnosis of benign masseteric hypertrophy.

Benign masseteric hypertrophy in a young child is presented. Diagnosis was confirmed by sonography and computed tomography. Recognition of this disorder obviates the need for further invasive investigations.