Novel structural elements within the nonproteolytic clostridium botulinum type F toxin gene cluster.

We sequenced for the first time the complete neurotoxin gene cluster of a nonproteolytic Clostridium botulinum type F. The neurotoxin gene cluster contained a novel gene arrangement that, compared to other C. botulinum neurotoxin gene clusters, lacked the regulatory botR gene and contained an intergenic is element between its orfX2 and orfX3 genes.

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.

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.

Susceptibilities of Yersinia pestis strains to 12 antimicrobial agents.

Ninety-two strains of Yersinia pestis recovered over a 21-year period were evaluated for susceptibility to traditional and newer antimicrobial agents. In vitro resistance was noted only against rifampin and imipenem (approximately 20% of strains). The most active compounds (MIC at which 90% of the isolates tested are inhibited) against Y. pestis were cefixime, ceftriaxone, trimethoprim-sulfamethoxazole, and trovafloxacin.

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.

Poststreptococcal uveitis.

PURPOSE: To report that uveitis may be a manifestation of poststreptococcal syndrome. METHODS: Case report. Documented attacks of bilateral uveitis were clearly associated with streptococcal infection. RESULTS: Group A streptococcal infection was evident in all bilateral uveitis attacks, which were treated with local or systemic corticosteroids and penicillin. The frequency and severity of the attacks were reduced by penicillin prophylaxis and tonsillectomy. CONCLUSIONS: Uveitis should be included as a possible manifestation of poststreptococcal syndrome. If coexisting streptococcal infection is demonstrated, penicillin prophylaxis should be considered.

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.

Sulphasalazine in the treatment of pauciarticular-onset juvenile chronic arthritis.

Sulphasalazine in a dose of 50 mg/kg/day was administered to ten patients with pauciarticular-onset juvenile chronic arthritis (JCA), with active disease not adequately controlled by nonsteroidal anti-inflammatory drugs (NSAID). The treatment was initiated with 1/4 of this dose and increased by weekly increments of 250-500 mg until the total dose was reached. In all patients sulphasalazine was the first disease-modifying agent tried. Among nine of the ten patients there was significant improvement in all clinical scores, including the number of active joints and the severity grading (tenderness and limitation of motion). Within 3 months of sulphasalazine therapy the laboratory measurements revealed marked improvement in the erythrocyte sedimentation rate (ESR) and haemoglobin values. One patient, in whom the ESR and haemoglobin were normal at onset, had no change in clinical scores. Transient skin rash and elevated liver enzyme levels developed in one patient. These preliminary data suggest that sulphasalazine is an effective and safe second-line agent in the management of pauciarticular-onset JCA. More trials with this drug are needed, including double blind, to study efficacy and safety of sulphasalazine in JCA.

[Poststreptococcal reactive arthritis].

Reactive arthritis is defined as arthritis of 1 or more joints, in association with infection at a distant site, but without the infective agent being found in the synovial fluid. Patients with Group A beta-hemolytic streptococcal infection and articular disease, who do not fulfill the modified Jones criteria for diagnosis of acute rheumatic fever, have been classified as having poststreptococcal reactive arthritis. We describe 6 patients seen during the winter of 1991 who had various clinical presentations of poststreptococcal reactive arthritis. This condition is considered by some as a distinct disease, but by others as part of the spectrum of acute rheumatic fever.

Hepatic, cutaneous and hematologic manifestations in juvenile chronic arthritis.

Two patients suffering from systemic onset juvenile chronic arthritis (JCA) with a polyarticular course developed an acute illness shortly after commencing a new second line drug (gold and penicillamine). The clinical picture consisted of fever, rash, lymphadenopathy and hepatomegaly with elevated liver enzymes and hematological changes. The possible relationship of the disease to second line drugs is discussed.

HLA and complement C4 antigens in polyarticular onset seronegative juvenile chronic arthritis: association of early onset with HLA-DRw8.

HLA-A,B,C,DR and DQ antigens were tested in 53 British Caucasian patients with polyarticular onset seronegative juvenile chronic arthritis (JCA); C4 allotypes were also tested in 46. A strong association with HLA-DRw8 was found (RR = 6.1, Fp = 7.6 x 10(-5)), with increased -B5(51) and C4A QO, and decreased -DR7 frequencies. DRw8 incidence correlated with an onset under 5 years, 9 of 12 DRw8+ cases being in this subgroup (Fp = less than 0.06), whereas B5 and C4A QO were prevalent in late onset (greater than or equal to 5 years). Erosions after 5 years associated with HLA-DRw6, and their absence with -Cw1 and -DR5. Genetic susceptibility factors and a further subdivision by onset age are thus demonstrated in this disease. Comparative data suggest that the genetic basis of susceptibility to early onset disease is similar to that of pauciarticular JCA.