Uveitis in juvenile Behçet's disease: clinical course and visual outcome compared with adult patients.

PURPOSE: To characterize the disease course and visual outcome of uveitis in juvenile Behçet's disease (BD) compared with adults. METHODS: The study population included 13 children (mean age 14+/-2.4 years; 22 eyes) and 16 adults (mean age 30+/-8.8 years; 27 eyes) with uveitis in BD diagnosed between 1997 and 2007. RESULTS: The male/female ratio was 1.6:1 in the paediatric group and 3:1 in the adult group. Five children (38%) and four adults (25%) had complete BD. Mean duration of follow-up for both groups was 4.7 years. The children had more acute exacerbations (4.1+/-2.7 vs2.3+/-1.5, P=0.054). Treatment in both groups included systemic steroids and immunosuppressive agents. In children, mean initial visual acuity in the affected eyes (n=22) was 0.6+/-0.7 logMAR (range, 0-2.2). It decreased during exacerbations in 15 eyes (68%; mean, 1.6+/-0.8 logMAR), severely reduced (worse than 1 logMAR) in 11 eyes (50%; mean, 2.0+/-0.45 logMAR), and improved significantly in 12 of 13 promptly treated eyes (92%; 6/12 or better in 11; mean 0.2+/-0.4 logMAR, P<0.001). The visual outcome pattern was similar in the adults. CONCLUSIONS: Uveitis in juvenile BD is characterized by frequent exacerbations of explosive nature with profoundly reduced visual acuity. Similar disease pattern was observed in children and adults, as well as in patients with complete or incomplete disease. Early diagnosis, even before all systemic criteria are fulfilled, is important because early aggressive therapy can achieve long-term useful visual acuity.

Iloprost treatment for refractory Raynaud's phenomenon in two infants.

Raynaud's phenomenon (RP) is rare in young children. We describe two infants with severe RP, manifesting as fingertip necrosis, who were resistant to conventional vasodilators and were treated successfully with iloprost, a prostacyclin analogue. The application of iloprost is safe and should be considered in children with threatening ischemic digits.

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.

Vitamin D deficiency and insufficiency in Orthodox and non-Orthodox Jewish mothers in Israel.

BACKGROUND: The modest clothing that Orthodox Jewish women wear exposes very little of their skin to sunlight. Under these conditions they may develop vitamin D deficiency, even in sunny Israel. OBJECTIVES: To determine and compare the vitamin D nutritional status in Jewish orthodox mothers to that of non-orthodox mothers who live in the same metropolitan area in Israel. METHODS: 25-Hydroxyvitamin D was measured by competitive protein-binding radioassay in the sera of 341 Jewish Israeli mothers (156 orthodox and 185 non-orthodox). The sera were obtained 48-72 hours after childbirth during the late summer of 1998 and the spring of 1999. RESULTS: The mean (SD) serum concentration of 25-OHD was significantly (P < 0.002) lower (13.5 +/- 7.5 ng/ml) in the orthodox than in the non-orthodox mothers (18.6 +/- 9.6 ng/ml). Vitamin D deficiency (< 5 ng/ml) and insufficiency (< 10 ng/ml) were more common in the orthodox mothers (5.1% and 32.7% respectively) than in the non-orthodox mothers (2.7% and 13%, respectively). In subgroups of mothers supplemented with 400 units of vitamin D daily during pregnancy, vitamin D deficiency and insufficiency were less common (2.2% and 13%, respectively) in orthodox and non-orthodox mothers (0% and 8.1%, respectively). Vitamin D insufficiency was more common in the winter than in the summer only among non-orthodox mothers. CONCLUSIONS: The high prevalence of vitamin D deficiency and insufficiency in Israeli mothers raises the question whether vitamin D supplements should be given to pregnant women in Israel, at least to orthodox mothers.

New insight into calcinosis of juvenile dermatomyositis: a study of composition and treatment.

Milk of calcium developed in 2 children with juvenile dermatomyositis. The fluid of the collection contained macrophages, interleukin-6, IL-1, and tumor necrosis factor. The patient who had dystrophic calcinosis had a dramatic improvement with the introduction of alendronate. These findings suggest that calcinosis of juvenile dermatomyositis may be mediated by activated macrophages and that alendronate can be an effective treatment for this condition.

Close association of HLA-B52 and HLA-B44 antigens in Israeli Arab adolescents with recurrent aphthous stomatitis.

OBJECTIVES: To investigate the incidence and clinical features of recurrent aphthous stomatitis (RAS) among Israeli Arab adolescents and to determine the HLA typing profile in affected subjects. STUDY DESIGN: Cross-sectional study. SETTING: Junior high school in the largest Arab town in Israel. PARTICIPANTS: Four hundred seventy-seven Israeli Arab junior high school students filled out a questionnaire. Students who reported more than 4 episodes of RAS during the previous year were interviewed by telephone. Those whose responses were confirmed were invited to the clinic. Of these, 22 were chosen at random for HLA typing. Findings were compared with those in 117 healthy Israeli Arabs who were candidate donors of bone marrow to patients at the Institute of Hematology-Oncology, Schneider Children's Medical Center of Israel, Petah Tiqva. RESULTS: Recurrent aphthous stomatitis was confirmed in 80 subjects (16.7%). Of the 22 patients who underwent HLA typing, 7 (31.4%) had HLA-B52 antigens and 8 (36.4%) had HLA-B44 antigens; corresponding figures for the control group were 10 subjects (8.5%) (P = .007) and 9 subjects (7.7%) (P = .001), respectively. CONCLUSIONS: There is a close association of HLA-B52 and HLA-B44 in Israeli Arab youths with RAS. Long-term follow-up is needed to determine the relationship between RAS and Behçet disease.

Amyopathic dermatomyositis in children: a diagnostic and therapeutic dilemma.

Juvenile dermatomyositis is an inflammatory disease of unknown etiology that primarily affects skin and muscles. The pathognomonic Gottron's sign consists of symmetric macules and papules on the dorsal aspect of the interphalangeal joints and exterior areas of the big joints. A periorbital violaceous (heliotrope) skin rash is also characteristic. There may be a discordance in time of presentation of the skin and muscle disease, and a small subset of patients apparently do not develop muscle disease at all. The absence of muscle involvement is termed 'amyopathic dermatomyositis.'We describe two children who presented with the characteristic rash of juvenile dermatomyositis but with no clinical evidence of muscle involvement. One developed muscle weakness 3 years later. Neither patient had a full muscle work-up at the onset of the disease, which left questions about diagnoses and whether or not there may have been subtle muscle involvement. On the basis of our literature review, the outcome of these patients is uncertain, although it appears that myositis develops in many, maybe most, affected children. We suggest that in the absence of muscle disease, application of sunscreen and administration of hydroxychloroquine sulfate may ameliorate the rash. More aggressive treatment will need to be given when muscle involvement can be demonstrated.

Scintigraphic evaluation of calcinosis in juvenile dermatomyositis with Tc-99m MDP.

Two children with juvenile dermatomyositis and extensive, debilitating soft tissue calcifications are described. Whole-body bone scans with Tc-99m MDP were performed in both cases before and during specific treatment for the calcinosis. Baseline studies showed marked tracer localization in the soft tissues and provided an objective baseline assessment of the extent of the soft tissue calcifications. Follow-up studies showed gradual clearance of the extraskeletal uptake and were useful in monitoring the therapeutic response. These cases show that skeletal scintigraphy can function as a useful auxiliary tool to evaluate calcinosis in children with juvenile dermatomyositis.

Renal outcome and vascular morbidity in systemic lupus erythematosus (SLE): lack of association with the angiotensin-converting enzyme gene polymorphism.

OBJECTIVES: The angiotensin-converting enzyme (ACE) gene polymorphism has been associated with worse outcome in various chronic glomerular disorders and in hypertension. Because nephritis and vascular morbidity are prominent determinants of outcome in systemic lupus erythematosus (SLE), we studied the distribution and prognostic effect the ACE genotype might have on the outcome of SLE. METHODS: Fifty-six consecutive Israeli SLE patients and 48 (sex and ethnic origin matched) healthy individuals were evaluated for the ACE genotype by a polymerase chain reaction-based assay. The clinical and laboratory parameters of the patients as well as the SLE disease activity index (SLEDAI) and the presence of hypertension, diabetes mellitus, ischemic heart disease, congestive heart failure, and stroke were correlated with the ACE genotype. RESULTS: The distribution of the ACE genotype D/D, D/I, and I/I in the lupus group was 59%, 36%, and 5%, respectively, similar to the distribution in the control group (54%, 31%, and 15%, respectively). We failed to find any significant association between the ACE genotype and disease manifestations, SLEDAI, renal function, or cardiovascular and cerebrovascular morbidity. The clinical and laboratory parameters associated with renal outcome and vascular morbidity in our cohort are described. CONCLUSIONS: No difference was found between the distribution of the ACE genotype in lupus patients and the general population in Israel. Renal function as well as cardiovascular and cerebrovascular morbidity among Israeli patients with SLE are disease-related and independent of the ACE gene polymorphism.

Childhood Behçet's disease: clinical features and comparison with adult-onset disease.

OBJECTIVE: To study the clinical spectrum of Behçet's disease (BD) in childhood, in comparison to adult-onset disease. METHODS: Nineteen children, who fulfilled disease criteria up to the age of 16 yr, were studied. The results were compared to those of 34 adult patients with BD. An activity index and severity score were calculated for both study groups. RESULTS: The mean age of disease onset was 6.9+/-3.9 yr, similar ages of onset were found in males and females. The clinical spectrum of childhood BD resembled that of adult disease; however, the prevalence of certain manifestations was different between children and adults. Children with BD had significantly less genital ulcers, less vascular thromboses and more non-specific gastrointestinal symptoms, as well as central nervous system involvement and arthralgia. A relatively high prevalence of uveitis was found in childhood BD. The activity index and severity score were significantly lower in children than in adults. CONCLUSION: Our results point to a similar systemic expression of BD in children and adults; however, the disease seems to run a less severe course in children.

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.

Conversion reaction: management by the paediatrician.

UNLABELLED: We describe the diagnosis and management of 47 children with conversion reaction seen during the past 9 years in our outpatient department. Some illustrative cases are reported in detail. The study shows that conversion reactions in children can often be accurately diagnosed by detailed history and physical examination. When the diagnosis was made early and presented with certainty, both parental acceptance and the child's recovery were easier, and the need for expensive and unnecessary diagnostic procedures was eliminated. Immediate intervention by the paediatrician prevented perpetuation of the problem, secondary gains and continuing family stress. Most of the patients recovered after a few days without recurrence. The major role of the paediatrician is emphasized. Co-operation between the patients, parents and the paediatrician is important, as is close follow up. CONCLUSION: Paediatricians cope successfully with children with conversion reaction with early diagnosis and immediate intervention.

Colchicine-induced myoneuropathy in childhood.

UNLABELLED: Colchicine is used in the treatment of gouty arthritis, familial Mediterranean fever, amyloidosis, Behcet disease and dermatoses. Myoneuropathy is a rare side-effect reported either with intoxication or in elderly patients with chronic renal insufficiency causing elevated plasma drug levels. We report the first two cases of myoneuropathy in children, both taking appropriate doses of colchicine, and having normal renal function. The myoneuropathic changes were reversible after stopping treatment. The cause of colchicine myoneuropathy is unclear. CONCLUSION: In children treated with colchicine, neuromuscular phenomena of unknown aetiology may be related to the drug, even with a lack of intoxication or renal insufficiency.

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.

Mode of presentation and multisystem involvement in Behçet's disease: the influence of sex and age of disease onset.

OBJECTIVE: To evaluate the correlation between the age at onset of Behcet's disease (BD) and sex distribution, mode of disease appearance, and number of organs involved during the disease. METHODS: BD was defined according to the International Study Group criteria. Data from medical files and from patient interviews were collected. Results were analyzed for children and adults, according to age at disease onset. A systemic involvement index was calculated as the sum of visceral organ systems involved. RESULTS: Fifty-nine patients with BD were studied, 26 male and 33 female. The mean age at disease onset was 8.4 +/- 4.5 years in children and 29.8 +/- 7.9 years in adults. The age of onset was significantly lower in male versus female patients. BD presented in children almost entirely as recurrent aphthous stomatitis, while in adults, less than one-third of patients presented first with oral ulcers. The mean age at disease onset of patients who presented first with oral ulcers was significantly lower than the age of patients presenting first with non-oral aphthosis. The mean systemic involvement index was higher in adult onset than in juvenile onset disease. A significant linear correlation was found between age of disease onset and total number of visceral organ systems involved. CONCLUSION: BD was observed to occur earlier in males than in females. The first manifestation of BD in children is almost exclusively in the form of oral ulcers, while older patients have a large proportion of non-oral aphthosis as their first disease manifestation. Disease onset at an older age is positively correlated with increased disease spectrum.