Juvenile Chronic Arthritis Patients Research Articles

Prevalence of periprosthetic osteolysis after total hip replacement in patients with rheumatic diseases.

Periprosthetic osteolysis (PO) is a frequent complication in patients with joint implants. There are no data regarding the prevalence of PO in patients with rheumatoid arthritis (RA), juvenile chronic arthritis (JCA), ankylosing spondylitis (AS), and osteoarthritis (OA).ObjectivesTo evaluate the prevalence of PO in patients with RA, JCA, AS, and OA, who have undergone total hip replacement (THR), and to identify factors associated with its development.MethodsThe study included patients diagnosed with RA (ACR 1987), AS (modified New York criteria), JCA (European 1977 criteria), and osteoarthritis (OA) (ACR 1990 criteria) with unilateral or bilateral THR. Demographic, clinical, and therapeutic data were collected. Panoramic pelvic plain radiographs were performed, to determine the presence of PO at acetabular and femoral levels. Images were read by two independent observers.ResultsOne hundred twenty-two hip prostheses were analyzed (74 cemented, 30 cementless, and 18 hybrids). The average time from prosthesis implantation to pelvic radiograph was comparable among groups. PO was observed in 72 hips (59%). In 55% of cases, PO was detected on the femoral component, with a lower prevalence in RA (53%) vs AS (64.7%) and JCA (76.5%). Acetabular PO was more frequent in JCA patients (58.8%), compared with RA (11.6%) and OA (28.5%) patients (P = 0.0001 and P = 0.06, respectively). There was no significant association between the presence of PO and clinical, functional, or therapeutic features.ConclusionThe prevalence of PO was 59%, being more frequent at the femoral level. Larger studies must be carried out to determine the clinical significance of radiologic PO.

Antinucleosome antibodies in juvenile chronic arthritis

A broad range of autoantibodies have been detected in juvenile chronic arthritis (JCA) patients, although, none of them can be considered specific for this entity. Antinuclear antibody (ANA) is routinely searched in these patients mainly because it is associated with uveitis, a comorbidity that is particularly frequent in the oligoarticular form. Nevertheless, the ANA specific antigen target in JCA is unknown. In this study, we aimed to search for antinucleosome antibodies in 30 adult JCA patients and to study possible associations with clinical profile. Ten individuals (33.3%) were positive for antinucleosome antibodies and seven (70%) were simultaneously ANA positive (p = 0.01). We did not find any significant association among antinucleosome and JCA form, uveitis, age of onset, gender, or functional index. We conclude that in JCA, there is a prevalence of 33.3% of antinucleosome antibodies. Further investigations are needed to understand the ANA positivity found in this disease as far as the clinical impact of this finding.

Detection of IL-2 at mRNA and protein levels in synovial infiltrates from inflammatory arthropathies using biotinylated oligonucleotide probes in situ

A non-radioactive in situ hybridization method for IL-2 mRNA detection based on the use of four biotinylated oligonucleotide probes, plus appropriate positive and negative control probes was developed and applied to synovial surgical and needle biopsies from rheumatoid arthritis (RA), spondyloarthropathy (SpA), psoriatic arthritis (PsA) and juvenile chronic arthritis (JCA) patients. In eight surgical biopsies (six RA, one SpA, one PsA) this non-radioactive system showed similar sensitivity to that of a previously described 32P-labelled probe system, and in addition detected IL-2 mRNA in five out of seven biopsies from SpA and PsA patients and in two out of two JCA needle biopsies. IL-2 mRNA was found in the absence of IL-2 protein in RA biopsies (six surgical, 12 needle), but variable amounts of IL-2 protein were detected in six out of seven needle biopsies from SpA, PsA and JCA patients, where CD3+ lymphoid infiltrates were present. These data suggest differences in IL-2 regulation and expression in RA and non-RA inflammatory arthropathies.

Plasma TNF binding capacity in patients with juvenile idiopathic arthritis

Introduction Tumour necrosis factor (TNF)-α and TNF-β, also called lymphotoxin (LT), are bound by soluble truncated TNF receptors (sTNFRI and II) that are released from cell surfaces and act as natural inhibitors of TNF-induced inflammation. We investigated the plasma levels of sTNFRI and II in parallel with LT binding capacity (LTBC) in 44 patients with juvenile chronic arthritis (JIA). Methods LTBC was determined by spiking diluted plasma samples with 1000 pg/ml of human recombinant LT. Detectable LT was measured by an in-house ELISA and LTBC was expressed in arbitrary units (AU) as the percentage value of bound LT to added LT. The levels of sTNFRI and-II were measured by ELISA (R&D). Results We found slightly reduced sTNFRI and II levels in JIA patients ( n=44) compared with healthy controls sTNFRI: 1118 pg/ml (656–2074) [mean (range)] vs. 1262 pg/ml (819–2280) p=0.015; sTNFRII: 1953 pg/ml (889–4476) vs. 2311 pg/ml (1309–4186) p=0.008. The sTNFRI levels correlated positively with morning stiffness ( r=0.30, p=0.044), physician's global assessment ( r=0.39; p=0.009) and CRP ( r=0.43; p=0.0048). sTNFRII did not correlate with measures of disease activity. In contrast, patient LTBC values were elevated compared to controls: 44 AU (36–52) vs. 31 AU (13–41) [mean (range)], p<0.0001, but did not correlate with disease activity. Conclusion Despite overall slightly reduced plasma levels of sTNFRI and II, the capacity to bind TNF appeared to be increased in plasma samples from JIA patients.

Intravenous regional administration of corticosteroids in juvenile chronic arthritis.

Treatment of juvenile chronic arthritis patients with longstanding multiple joint or tendon involvement that is resistant to medication remains a challenge. For 20 years, we have been treating these severely ill patients with intravenous regional glucocorticoids (a modified Bier's block). Since 1996, all juvenile chronic arthritis patients have been followed prospectively by an occupational therapist who has registered the grip strength and range of motion at an average of 6 months after treatment. In 22/40 wrists and hands, increased grip strength was recorded. The mean grip strength increased for the whole group from 47 to 59 N and the flexion lag decreased. The effect of intravenous regional steroid treatment may be limited from a long-term perspective, but in our series, half of the patients showed a considerable improvement after 6 months. Surgical synovectomy can be postponed and perhaps even be omitted.

Factors playing a role in the development of decreased bone mineral density in juvenile chronic arthritis

The aims of this study were to evaluate bone mineral density (BMD) in patients with juvenile chronic arthritis (JCA), compare them with healthy controls, and assess the effects of disease activity and corticosteroid treatment on BMD. Twenty-eight patients diagnosed with JCA and 45 healthy controls were included in this study. Disease activity was determined by clinical and laboratory evaluation, Articular Disease Severity Score (ADSS), and the Juvenile Arthritis Functional Assessment Report (JAFAR). Bone mineral density of the lumbar spine was measured by dual energy X-ray absorptiometry (DEXA). Patients with JCA showed significant decreases in BMD compared with healthy controls. The JCA patients treated with corticosteroids showed significantly lower BMDs than the healthy control group. Age of the patients and age of onset were found to correlate with BMD. Our study showed that glucocorticoids were involved in the development of osteoporosis in JCA, with many other factors affecting bone mineralization. We could not demonstrate any relationship between BMD and disease activity, but the study data suggest that early onset disease is also an important factor in the development of osteoporosis in JCA.

Stem cell transplantation for autoimmune disease: progress and problems

The current status of stem cell transplantation in rheumatoid arthritis, juvenile chronic arthritis, systemic lupus erythematosus, and systemic sclerosis are reviewed. From a large European bone marrow transplant registry, a birds' eye view of stem cell transplantation for autoimmune disease can be obtained. Among 43 rheumatoid arthritis patients, 35 juvenile chronic arthritis patients, 34 systemic lupus erythematosus patients, and 58 systemic sclerosis patients who underwent stem cell transplantation, initial responses in most patients were good to excellent. Although initial transplant related mortality was low for rheumatoid arthritis, somewhat higher rates for juvenile chronic arthritis, systemic lupus erythematosus, and systemic sclerosis may be falling with modifications in the stem cell transplantation regimens. In rheumatoid arthritis and systemic lupus erythematosus treatment, the criteria for patient selection are still not clear and the therapeutic regimens for stem cell transplantation (and whether follow-up treatment is necessary) are not fully defined. In juvenile chronic arthritis, responses are encouraging although little fully published data beyond that from the European Bone Marrow Transplant Registry exist. In systemic sclerosis, criteria for patient selection and a limited number of stem cell transplantation regimens have been agreed on and controlled trials are underway.

Circulating interleukin-6, soluble interleukin-2 receptors, tumor necrosis factor alpha, and interleukin-10 levels in juvenile chronic arthritis: correlations with soft tissue vascularity assessed by power Doppler sonography

Nineteen patients with juvenile chronic arthritis (JCA), ten with systemic (s)-JCA, and nine with polyarticular-onset (p)-JCA were examined for interleukin (IL)-6, tumor necrosis factor (TNF)-alpha, IL-2R, and IL-10 levels. Power Doppler sonography (PDS) for the more affected knee was used in all of them to evaluate soft tissue vascularity. Serum levels of IL-6 were significantly higher in JCA patients than in controls (P<0.007). Patients with p-JCA showed higher levels of IL-6 than patients with s-JCA, and the difference was statistically nonsignificant. Serum IL-6 levels in all patients correlated significantly with the degree of vascularity detected by PDS (P<0.01). This correlation was more pronounced in p-JCA patients (P<0.01 in p-JCA vs P<0.05 in s-JCA). Serum levels of TNF-alpha were higher in patients with JCA than in controls (P<0.0001). Serum levels of TNF-alpha were significantly greater in patients with s-JCA than in p-JCA (P=0.008). Soluble IL-2R levels were higher in patients with JCA than controls (P<0.0002). Serum levels of IL-2R correlated significantly with pannus thickness in p-JCA (P<0.01) and inversely with methoxetrate (MTX) duration in s-JCA (P<0.05). Serum levels of IL-10 were significantly higher in JCA patients than in controls ( P<0.0008). Serum IL-10 levels in all patients correlated significantly inversely with hemoglobin levels (r=-0.50, P<0.05), total leukocytic count (TLC) (r=-0.58, P<0.01), and intra-articular steroid injection (r=+0.56, P<0.01). In s-JCA, IL-10 levels correlated significantly with MTX weekly dose ( P<0.05). In conclusion, a significant correlation of serum IL-6 levels with the degree of knee joint vascularity was found, and this correlation was more pronounced in p-JCA, which may stress the role of IL-6 as an inducer of neoangiogenesis in JCA.

THE RUSSIAN VERSION OF THE CHILDHOOD HEALTH ASSESSMENT QUESTIONNAIRES(CHAQ) AND THE CHILD HEALTH QUESTIONNAIRES (CAQ)

We report herein the results of the cross-cultural adaptation and validation into the Russian 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 chronic arthritis (JCA). 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 Russian CHAQ-CHQ were fully validated with 3 forward and 3 backward translations. A total of 146 subjects were enrolled: 86 patients with JCA (23% systemic onset, 39% polyarticular onset, 15% extended oligoarlicular subtype, and 23% persistent oligoarticular subtype) and 60 healthy children. The CHAQ clinically discriminated between healthy subjects and JCA patients, with the systemic, polyarticular and extended oligoarticular subtypes having a higher degree of disability, pain, and a lower overall wellbeing when compared to their healthy peers. Also the CHQ clinically discriminated between healthy subjects and JCA patients, with the systemic onset, polyarticular onset and extended oligoarticular subtypes having a lower physical and psychosocial well-being when compared to their healthy peers. In conclusion the Russian version of the CHAQ-CHQ is a reliable, and valid tool for the functional, physical and psychosocial assessment of children with JCA.

The cervical spine in mutilant juvenile chronic arthritis

Objective. To describe inflammatory cervical spine disorders in juvenile chronic arthritis (JCA) patients with arthritis mutilans (AM) hand deformity. Methods. The series consisted of 18 patients affected by AM hand deformity who fulfilled the European League of Associations for Rheumatology criteria for JCA. The patient records and the most recent cervical spine radiographs were evaluated for subluxations, atlantoaxial impaction (AAI) and apophyseal joint ankylosis. Results. Seventeen (94%) patients had subluxation, AAI or apophyseal joint ankylosis in the cervical spine. Apophyseal joint ankylosis was noted in 12 (67%) patients and AAI in 10 (56%). Anterior atlantoaxial subluxation was detected in five (28%) patients. Conclusion. Almost all of the JCA patients with AM hand deformity evinced some inflammatory changes in the cervical spine. Apophyseal joint ankylosis, AAI and multiplicity of changes in cervical spine may be considered characteristic in this subset of JCA patients. Patients with JCA and AM hand deformity tend to have severe changes also in the cervical spine.

The mandibular condyle in juvenile chronic arthritis patients with mandibular hypoplasia

Abstract.In 12 JCA patients with severe mandibular hypoplasia, who all strongly demanded early treatment, 21 mandibular condyles were replaced by costochondral grafts. All of them had radiographic morphological changes in the mandibular condyles with varying degrees of destruction of the articular cartilages. Severe pathological changes in the lower joint compartments were consistently observed at surgery. Hence, the lower joint compartments were obstructed with granulomatous tissue, whereas the upper compartments were without macroscopic pathological changes. These findings indicated a polarized involvement of the temporomandibular joint (TMJ) in juvenile chronic arthritis (JCA). The extent of condylar articular surface destruction at histological examination varied from focal to total cartilage destruction. Inflammation of the subchondral bone marrow was a frequent finding. In spite of considerable arthritic destruction of the condyles, only one patient had TMJ pain, while a restricted mouth opening capacity was a more frequent finding. Thus, TMJ pain did not seem to constitute a reliable symptom of serious arthritic destruction of the mandibular condyle.

Refraction in juvenile chronic arthritis: a long-term follow-up study, with emphasis on myopia.

Assessment of refraction anomalies in juvenile chronic arthritis (JCA) on a long-term follow-up basis. Sixty-five adults, 52 females and 13 males, with a history of active JCA had a complete ophthalmic evaluation including subjective refractioning on average 26.4 years after JCA onset. The age range was 22-49 years. The refraction ranged from -8.12 D to +6.5 D with a mean (SD) of -0.64 (2.16) D. The mean refraction in the JCA group was significantly more towards myopia than that of a coeval adult hospital-based sample used as controls (p = 0.008). Twenty-eight out of the 65 (43%) had a negative refractive value of at least 0.37 D. Myopia onset age ranged from 8 to 31 years. In those able to specify their myopia onset by first purchase of spectacles (n = 25) the JCA onset had preceded the myopia, with a mean (SD) interval of 10.1 (5.4) years. The elevated myopia figure of 43% among JCA patients suggests an association between myopia and JCA. In lack of more precise indicators and in accordance with older literature, an explanation might be a weakening effect of chronic inflammation on scleral connective tissue.

Predictors of Sibling Relationship Characteristics in Youth With Juvenile Chronic Arthritis

Relationships between 20 children with juvenile chronic arthritis (JCA) and their siblings were compared with relationships among 20 comparison sibling pairs. Participants ranging in age from 7 to 21 years were interviewed using the Sibling Relationships Questionnaire-Revised. Parents completed ratings of their families' and children's behavior and an illness activity rating scale. Siblings in the JCA and comparison groups did not differ in perceptions of their relationships or in their family structure. Age, sex, birth order, and age difference between siblings were associated with sibling relationship variables, whereas adaptive behavior was not a significant factor. Among JCA patients, severity of illness was positively associated with perceived conflict with siblings.

Sugar printing rheumatic diseases: a potential method for disease differentiation using immunoglobulin G oligosaccharides.

To look for oligosaccharide structural variants of IgG that may be unique to specific rheumatic diseases. Using normal-phase high-performance liquid chromatography technology, a comparison was made of the oligosaccharide pools released from serum IgG from patients with systemic lupus erythematosus (SLE) (n = 10), ankylosing spondylitis (AS) (n = 10), primary Sjögren's syndrome (n = 6), juvenile chronic arthritis (JCA) (n = 13), psoriatic arthritis (n = 9), rheumatoid arthritis (RA) (n = 5), and healthy control individuals (n = 19). The oligosaccharide pools were resolved into 13 peaks and the relative proportions of the peaks in each disease group was significantly different from that in healthy controls (P < 0.0001-0.05). A characteristic serum IgG oligosaccharide profile, or sugar print, for each of the rheumatic diseases was found. The sugar prints exhibited a range of glycosylation patterns whereby all RA (P < 0.0001) and JCA (P < 0.006) patients had predominantly agalactosyl structures, while SLE (P < 0.03-0.0001) and AS (P < 0.025-0.0001) patients had predominantly digalactosyl structures. The data suggest that each disease is associated with a specific mechanism that gives rise to alterations in the normal glycosylation pattern of IgG. Sugar printing of IgG is therefore a potential means for the differentiation of rheumatic diseases and may provide insight into disease pathogenesis.

Autologous stem cell transplantation: an alternative for refractory juvenile chronic arthritis.

Juvenile chronic arthritis (JCA), the most frequent transplanted children with JCA is in line with this ‘theoretical concept’ [7]. autoimmune disease of childhood, is not a benign disease. Functional disability occurs in 20–30% of patients Of course, many questions have to be dealt with. Is ASCT the treatment of choice? After ASCT, the with JCA and 5–10% develop a serious handicap [1]. Children with a polyarticular and systemic-onset form immunogenetic genotype does not change. However, the alternative, allogeneic stem cell transplantation, is not are especially at risk. To improve the outcome of these patients is a challenge for paediatric rheumatologists. acceptable because of the higher mortality risk in a nonlethal disease. What is the best conditioning regimen? A To improve disease outcome, immunosuppressive drugs like methotrexate [2], cyclosporin [3] and azathiohot topic is the use of total body irradiation (TBI). In experimental animal models, TBI is necessary to sustain prine [4] have been introduced in the treatment of JCA. Although these drugs have been proven to be effective remission [8]. On the other hand, TBI is rather toxic with a risk for infertility, growth retardation and cancer in a substantial number of the JCA patients, the disease lingers on and results in more or less serious functional [9]. Another issue is the handling of the graft. Should we deplete for T cells and which method do we use for handicaps. Treatment strategies resembling those used as an depletion [10]? Last, but not least, is the question whether we should use bone marrow as a source of stem induction regimen for haematological malignancies are now being introduced. An example is the treatment cells or pure blood. The latter method certainly has advantages. Collection is much easier and in general regimen built up from methothrexate, pulses of methylprednisolone and cyclophosphamide [5]. The toxicity of more stem cells can be harvested. However, the patient should be pre-treated with G-CSF, which in theory this treatment regimen is high and effectiveness has not been proven. Case reports of adult patients with autocould worsen the disease and, especially in the systemiconset form, the risk of inducing macrophage-activating immune diseases treated with autologous or allogeneic stem cell transplantation for a secondary haematological syndrome. In this issue of Rheumatology, many experts are malignancy or bone marrow aplasia showed that patients may be cured of their original ‘autoimmune’ invited to give their opinion on the above-mentioned questions. Of course, we cannot solve all the answers at disease [6 ]. This success motivated rheumatologists and haematologists to use autologous stem cell transplantathis stage, but the experience in experimental models and of the use of bone marrow (stem cell ) transplanttion (ASCT ) for the treatment of autoimmune diseases and there is a rapid expanding experience with ASCT ation in haematological malignancies can direct our way. In this issue, the first results are presented after ASCT [6 ]. The advantage of ASCT is that the conditioning treatment leads to radical eradication of mature T cells, of four children with JCA [7], one child with systemic scleroderma [11] and patients with systemic lupus erythwhile the stem cells are rescued by collecting them in advance. Theoretically, another advantage is that naive ematosus [12]. Although the follow-up period is rather short, the first results are promising. Of course, longT cells should be re-educated after ASCT, resulting in peripheral tolerance. In this way, ASCT should not only term follow-up is necessary to determine the real place of ASCT in the treatment of these autoimmune diseases. be regarded as a heavy immunosuppressive (myeloablative) treatment, but should also induce protective In May, during the ‘First workshop on the use of autologous stem cell transplantation in rheumatic dis‘anti-inflammatory’ responses. The experience in the first eases of childhood’, we reached consensus about inclusion criteria for JCA, the conditioning regimen and graft Accepted 15 March 1999. handling, which is published in this issue [13]. It is Correspondence to: N. M. Wulffraat, Department of Paediatric important that we restrict ourselves to a very limited Immunology, University Hospital for Children, ‘HET Wilhelmina Kinderziekenhuis’, Utrecht, The Netherlands. number of protocols, so we can really compare and

Final Height, Armspan, Subischial Leg Length and Body Proportions in Juvenile Chronic Arthritis

Objective: Assessment of growth disturbances in adults with a history of juvenile chronic arthritis (JCA). Material and Methods: Sixty-five subjects, 52 premenopausal females and 13 males with a mean age (range) of 32.2 years (22.3–49.4) participated. Mean age at disease onset was 5.7 years (0.8–15.8) and mean disease duration was 12.4 years (0.4–32). The follow-up time ranged from 18.7 to 46.9 years with a mean of 26.4 years. For each participant standard deviation scores (z-scores) for final height, delta-height (the difference between observed and expected height), armspan, subischial leg length and sitting height ratio, were calculated. Results: The study group as a whole did not exhibit linear growth impairment. The categorical distribution of heights differed significantly from a expected distribution in a healthy population (p < 0.001). A height z-score < –2 SD was present in 10.7% of the study group, of whom all had polyarticular course of JCA. Polyarticular and systemic course of JCA (versus pauciarticular) (p = 0.022), systemic steroid treatment (p = 0.006) and Steinbrocker functional class II–IV (vs. I) in 1979 (p = 0.043) were variables associated with reduced delta-height. In linear regression analyses, disease severity defining variables were statistically significant predictors of reduced final height and armspan. 27% of the study subjects had significantly reduced arm span (p < 0.001). Subischial leg length and body proportions (sitting height ratio) were normal. Conclusion: Our findings suggest that functionally impaired polyarticular and systemic JCA patients treated with systemic steroids may be at an increased risk of developing reduced final height and armspan. Disease control achieved by an aggressive therapeutic approach, if possible with a minimal use of systemic steroids, may reduce growth impairment in JCA.

Rationale for high-dose cyclophosphamide and medium-dose total body irradiation in the conditioning of children with progressive systemic and polyarticular juvenile chronic arthritis before autologous stem cell transplantation.

Despite the fact that the aetiology of juvenile chronic arthritis (JCA) is unknown, there is ample indirect evidence of a pivotal role of T cells in the onset and probably also in the maintenance of this autoimmune disease. Notwithstanding adequate firstand second-line anti-rheumatic therapy, systemic-onset JCA and polyarticular JCA will lead to destructive arthritis, growth retardation and severe invalidity in 10–25% of the cases. In order to halt the disease progression in the latter group of JCA patients, a clinical trial was started in F. 1. Autologous T-cell-depleted BMT of JCA patients. order to study the effect of severe immune suppression followed by ‘unbiased’ immune recovery on the course of the disease. Based on animal studies, showing the immunity severely, but is supposed not to be myeloregression of adjuvant-induced arthritis by bone marrow ablative. The short-term effect may be the occurrence transplantation (BMT), both allogeneic and T-cellof viral infections or reactivations, especially with herpes depleted autologous BMT [1, 2], a study protocol for viruses. The possible long-term side-effects may be a autologous stem cell transplantation in children with slightly increased risk for premature cataract formation severe progressive systemic and polyarticular JCA was and some effect on spermatogenesis in boys. Our experidrafted. ence so far with this pre-treatment in eight children, There are two conditions which have to be fulfilled in who received an allogeneic BMT for severe aplastic order for autologous stem cell transplantation to posanaemia, four of whom were prepubertal at BMT and sibly be effective in the treatment of JCA, i.e. first, the reached final height at evaluation [3], is as follows: no conditioning has to wipe out the (dysfunctioning) adverse effect has been observed on physical growth, all immunological memory and, second, the re-infused graft recipients had a normal pubertal development, but haematopoietic stem cell suspension has to be purged the boys had a somewhat decreased testicular volume, of mature ‘memory’ T cells. In order to achieve these indicating germ cell damage. Both the boys and the girls goals, the following procedure has been proposed: a showed normal function of the gonads and thyroid pre-treatment regimen comparable to the one in use for gland by endocrinological testing on follow-up. It is still allogeneic BMT of transfusion-sensitized patients with too early to assess fathering/mothering possibilities in severe aplastic anaemia (frequently also an autoimmune this group of ex-BMT recipients. A slight increase in disease), followed by the re-infusion of a T-cell-depleted secondary malignancies has to be expected, as was also (TCD) autologous BMT, i.e. containing ∏104 T cells/kg seen after immunosuppression or allogeneic BMT for body weight of the recipient (see the scheme in Fig. 1). severe aplastic anaemia [4]. Although the use of radiSuch a conditioning suppresses host memory T-cell ation, mostly limited-field irradiation such as total lymphoid irradiation or thoracoabdominal irradiation, was found in that retrospective study to be a strong risk Accepted 15 March 1999.

Assessment of bone mineral density in adults with a history of juvenile chronic arthritis: A cross-sectional long-term followup study

Objective To assess bone mineral density (BMD) and bone turnover in adults with a history of juvenile chronic arthritis (JCA) or persistent JCA, and to identify predictors of reduced BMD. Methods Sixty-five white patients (mean age 32.2 years) with a history of JCA and 65 age-, sex-, height-, and weight-matched healthy control subjects participated in the study. Densitometry of the left hip and the lumbar spine was performed, and osteocalcin (bone formation marker) and crosslinks (bone resorption marker) were measured. In addition, bone-related clinical parameters were assessed in the JCA group. Results BMD in the hip and lumbar spine was significantly lower in the JCA group than in the controls. Levels of osteocalcin and crosslinks were significantly increased in the JCA group. According to WHO definitions, significantly more subjects in the JCA group had “osteopenia” and “osteoporosis” than would be expected in a normal population sample. Active disease at the time of the study (1996–1997), baseline erosions evaluated in 1979, Steinbrocker functional class in 1996–1997, polyarticular course of JCA, and history of systemic steroid treatment for more than 1 year were significantly associated with reduced BMD. In linear regression analysis including both the JCA and control groups, presence of JCA proved to be the factor most strongly associated with reduced BMD, explaining ∼20% of its variation. Conclusion Reduced BMD and evidence of increased bone turnover suggest that JCA patients may be at risk of developing premature osteoporosis and associated fractures later in life. The data are consistent with the concept that BMD in JCA is determined by many factors.

Assessment of bone mineral density in adults with a history of juvenile chronic arthritis: a cross-sectional long-term followup study.

To assess bone mineral density (BMD) and bone turnover in adults with a history of juvenile chronic arthritis (JCA) or persistent JCA, and to identify predictors of reduced BMD. Sixty-five white patients (mean age 32.2 years) with a history of JCA and 65 age-, sex-, height-, and weight-matched healthy control subjects participated in the study. Densitometry of the left hip and the lumbar spine was performed, and osteocalcin (bone formation marker) and crosslinks (bone resorption marker) were measured. In addition, bone-related clinical parameters were assessed in the JCA group. BMD in the hip and lumbar spine was significantly lower in the JCA group than in the controls. Levels of osteocalcin and crosslinks were significantly increased in the JCA group. According to WHO definitions, significantly more subjects in the JCA group had "osteopenia" and "osteoporosis" than would be expected in a normal population sample. Active disease at the time of the study (1996-1997), baseline erosions evaluated in 1979, Steinbrocker functional class in 1996-1997, polyarticular course of JCA, and history of systemic steroid treatment for more than 1 year were significantly associated with reduced BMD. In linear regression analysis including both the JCA and control groups, presence of JCA proved to be the factor most strongly associated with reduced BMD, explaining approximately 20% of its variation. Reduced BMD and evidence of increased bone turnover suggest that JCA patients may be at risk of developing premature osteoporosis and associated fractures later in life. The data are consistent with the concept that BMD in JCA is determined by many factors.

Soluble intercellular adhesion molecule‐1 in paediatric connective tissue diseases

The intercellular adhesion molecule‐1 (ICAM‐1) is a cytokine‐induced glycoprotein involved in the recruitment of cells into tissues undergoing inflammatory responses. The aim of this study was to compare the levels of soluble ICAM‐1 (s‐ICAM‐1) in children with juvenile chronic arthritis (JCA) and systemic lupus erythematosus (SLE) and to evaluate the usefulness of this molecule as marker of disease activity. Levels of s‐ICAM‐1 were measured in sera using a monoclonal antibody sandwich enzyme‐linked immunoassay. Serum levels (mean ± SD) of s‐ICAM‐1 in 37 children with JCA, 18 patients suffering from SLE and 25 healthy controls were 609 ± 184, 513 ± 139 and 210 ± 95 ng/ml, respectively. A significant difference could be demonstrated between the levels of s‐ICAM‐1 in sera from each disease, as a group, and those of healthy controls. Higher levels of s‐ICAM‐1 were recorded in JCA patients with systemic features and patients who had polyarthritis than in children who were pauciarticular. A positive correlation was observed between s‐ICAM‐1 levels and disease activity score in SLE patients. Moreover, s‐ICAM‐1 levels closely followed clinical conditions in five children with SLE during follow‐up. The data show that s‐ICAM‐1 levels are increased in children suffering from connective tissue diseases and reflect disease status or activity, suggesting the usefulness of this molecule in the follow‐up of these diseases.