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ABSTRACT: In patients with juvenile idiopathic arthritis (JIA) temporomandibular joint (TMJ) involvement is a common cause of severe growth disturbances. Extent of growth deviation depends on age of onset and duration of arthritis in the TMJ. TMJ arthritis is difficult to diagnose at an early stage since relatively few symptoms and clinical findings are related to this joint. The pathologic process can affect growth long before radiographic changes are seen. We investigated the relationship between TMJ arthritis and symptoms and clinical findings to suggest a clinical routine for diagnosing TMJ arthritis. We also describe the course of TMJ arthritis in relation to a commonly used radiographic method versus MRI.
Fifteen children with JIA were examined 4 times at 6 month intervals for TMJ involvement by clinical examination, MRI-scanning, and orthopantomograms (OPG). At baseline, 10 healthy children served as a control group.
Patients reported more inability to chew and open their mouth than the control group. Translation of the condyle and range of mandibular movements were diminished in the arthritis group. Decreased translation was correlated to condylar changes seen on both OPG and MRI. MRI was superior to OPG in following changes of the condyle over time, and inflammation was detected in nearly all joints.
OPG cannot be recommended for diagnosis or to follow the course of changes in the TMJ. We advocate recording condylar translation and mandibular range of motion as a current clinical routine to find early TMJ arthritis in contrast to the often used OPG performed in our study, which was an uncertain method.
The Journal of Rheumatology 08/2008; 35(8):1668-75. · 3.69 Impact Factor
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Troels Herlin
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ABSTRACT: In recent years the treatment of juvenile idiopathic arthritis (JIA) has undergone marked changes. There is substantial evidence that inhibitors of tumor necrosis factor alpha (TNFalpha) like etanercept, infliximab and adalimumab show significant efficacy when standard therapy fails, and long-term tolerability is fairly good. Patients with systemic JIA do not respond well to treatment with TNF inhibitors, but they may benefit from treatment with IL-1 and IL-6 receptor antagonists. Our knowledge is still limited regarding which patients respond to a specific biological therapy.
Ugeskrift for laeger 07/2008; 170(24):2105-8.
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ABSTRACT: The aim of this investigation was to study the effect of intra-articular (i.a.) corticosteroid injections (IACIs) in the temporomandibular joint (TMJ) on mandibular development in antigen-induced TMJ arthritis. Ten-week-old female New Zealand white rabbits (n = 42) were randomly divided into four groups: group A, control (no injections); group B, placebo (repeated i.a. TMJ saline injections); group C, untreated arthritis (repeated induction of TMJ arthritis); and group D, steroid (repeated induction of TMJ arthritis + IACI). All animals had two tantalum implants inserted in the right side of the mandible serving as stable landmarks for later growth analysis. One implant was inserted close to the symphysis and one in the molar region. Computerized tomographic (CT) full-head scans were carried out at 14 (T1) and 26 (T2) weeks of age. (Dropout of animals at T2; group C, n = 7, and group D, n = 3.) Absolute and relative intra- and inter-group growth variations were evaluated during the growth period by comparison of CT scans. One-way analysis of variance was used for T1 statistical analysis, and absolute intra-group and relative inter-group growth differences between T1 and T2 were evaluated by Student's t-tests. At T2, the animals in the group A had greater sagittal and vertical mandibular growth compared with the other three groups. TMJ arthritis caused diminished mandibular growth. However, relative mandibular growth was significantly less in group D. The findings of this study do not indicate a positive long-term effect in the use of IACI in the TMJ as an early treatment intervention against TMJ inflammation in growing individuals.
The European Journal of Orthodontics 05/2008; 30(2):111-9. · 0.89 Impact Factor
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ABSTRACT: Pain is one of the primary symptoms of juvenile idiopathic arthritis (JIA). JIA patients have reduced pain tolerance and pain threshold compared to healthy controls. In children with JIA the greater use of coping strategies such as problem-solving, positive self-statements and distraction consistently have predicted less arthritis-related pain, even after controlling for relevant medical and demographic variables. Interventions specifically designed to modify maladaptive pain coping strategies and pain-related health beliefs may be effective in reducing pain in children with JIA.
Ugeskrift for laeger 03/2008; 170(8):636-8.
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ABSTRACT: To compare the inflammatory changes of antigen-induced temporomandibular joint (TMJ) arthritis in rabbits by different histological methods and to evaluate the immunomodulatory effect of intra-articular corticosteroid injections histologically.
35 rabbits (10 weeks old) pre-sensibilized with ovalbumin were divided into three groups: a placebo group of five (saline), an arthritis group of 15 (ovalbumin) and a steroid-treated group of 15 (ovalbumin + corticosteroid). Additionally, a group of seven rabbits receiving no sensibilization with ovalbumin and no intra-articular injections served as controls. Histomorphometry of the inflammatory changes in the subsynovial connective tissue (SSCT) of the TMJ included: (i) semi-quantitative (S-Q) scoring of inflammation and synovial proliferation, (ii) thickness measurements and fractional surface and (iii) stereological quantitative assessment of volume and plasma cells in thick sections of the SSCT by an optical fractionator.
The histomorphometry showed synovial proliferation in both the arthritis and the steroid groups. The plasma cell count obtained by the optical fractionator was significantly reduced when treating the TMJ with corticosteroids. However, the thickness of the synovial lining and volume of the SSCT as well as S-Q scoring of inflammation showed no difference between the arthritis and the steroid-treated groups. The optical fractionator proved a superior tool compared to S-Q assessments.
Counting of plasma cells in the SSCT showed that corticosteroids reduced the inflammation, but did not eliminate it. Semiquantitative scoring of synovial proliferation and inflammation demonstrated low sensitivity regarding changes in immunomodulation in antigen-induced arthritis compared to stereological quantitative estimations using an optical fractionator.
Journal of Oral Pathology and Medicine 03/2008; 37(7):437-44. · 1.63 Impact Factor
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ABSTRACT: Variables for assessment of disease activity of juvenile idiopathic arthritis (JIA) were studied, in order to develop a disease activity score for children with JIA.
One randomly chosen hospital visit was studied for each of 312 patients with JIA, with regard to disease activity variables. The physician global assessment score visual analog scale (physician GA) was used as a dependent variable in comparisons between potential disease activity variables. Previous studies have shown this variable to be the most sensitive to changes in JIA disease activity and to be comparable between patients.
Based on Spearman's rank order correlation the number of active joints had a strong association with the physician GA. The median physician GA score rose markedly for each active large joint, but less for small joints, although small joints were also statistically important in assessing disease activity. Among the laboratory data, the erythrocyte sedimentation rate, C-reactive protein level, and platelet count showed weak correlations to the physician GA.
In preparation of a disease activity score for children with JIA the importance of both the number and size of joints involved needs further evaluation.
The Journal of Rheumatology 11/2007; 34(10):2106-11. · 3.69 Impact Factor
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ABSTRACT: Loss of joint cartilage is a feature of destructive disease in JIA. The cartilage of most joints can be visualized with ultrasonography (US). Our present study focuses on discriminant validity of US in children. We studied reproducibility between and within a skilled and a non-skilled investigator of US assessment of cartilage thickness in small and large joints in healthy children.
In 11 healthy children (5 girls/6 boys), aged 9.6 years (9.3-10 years), 110 joints were examined. Cartilage thickness of the right and left hip, knee, ankle, 2nd metacarpophalangeal (MCP), and 2nd proximal interphalangeal (PIP) joint independently. The joints were examined twice, two days apart by a skilled and a non-skilled investigator. Mean cartilage thickness in the five joints was: hip 2.59 +/- 0.41, knee 3.67 +/- 0.64, ankle 1.08 +/- 0.31, MCP 1.52 +/- 0.27 and PIP 0.73 +/- 0.15 mm. We found the same mean differences in CTh of 0.6 mm in the inter-observer part with regard of the PIP joint. Within investigators (intra-observer), the smallest mean difference of CTh was found in the MCP joint with -0.004 (skilled) and 0.013 mm (non-skilled).
We found the level of agreement between observers within a 95% Confidence Interval in assessment of cartilage thickness in hip-, knee-, ankle-, MCP-, and PIP joints in healthy children. Observer variability seems not to relate to joint size but to the positioning of the joints and the transducer. These factors seem to be of major importance for reproducible US measurements. The smallest difference in measurement of cartilage thickness between observers was found in the PIP joint, and within observers in the MCP joint and it seems that using EULAR standard US guidelines is feasible for a pediatric setting. The use of US in children is promising. Studies on larger groups of children are needed to confirm the validation and variability of US in children as well as determining the smallest detectable difference of US measures.
Pediatric Rheumatology 02/2007; 5:3. · 1.44 Impact Factor
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ABSTRACT: Abstract
Background
Loss of joint cartilage is a feature of destructive disease in JIA. The cartilage of most joints can be visualized with ultrasonography (US). Our present study focuses on discriminant validity of US in children. We studied reproducibility between and within a skilled and a non-skilled investigator of US assessment of cartilage thickness in small and large joints in healthy children.
Methods and results
In 11 healthy children (5 girls/6 boys), aged 9.6 years (9.3–10 years), 110 joints were examined. Cartilage thickness of the right and left hip, knee, ankle, 2<sup>nd </sup>metacarpophalangeal (MCP), and 2<sup>nd </sup>proximal interphalangeal (PIP) joint independently. The joints were examined twice, two days apart by a skilled and a non-skilled investigator. Mean cartilage thickness in the five joints was: hip 2.59 ± 0.41, knee 3.67 ± 0.64, ankle 1.08 ± 0.31, MCP 1.52 ± 0.27 and PIP 0.73 ± 0.15 mm. We found the same mean differences in CTh of 0.6 mm in the inter-observer part with regard of the PIP joint. Within investigators (intra-observer), the smallest mean difference of CTh was found in the MCP joint with -0.004 (skilled) and 0.013 mm (non-skilled).
Conclusion
We found the level of agreement between observers within a 95% Confidence Interval in assessment of cartilage thickness in hip-, knee-, ankle-, MCP-, and PIP joints in healthy children. Observer variability seems not to relate to joint size but to the positioning of the joints and the transducer. These factors seem to be of major importance for reproducible US measurements. The smallest difference in measurement of cartilage thickness between observers was found in the PIP joint, and within observers in the MCP joint and it seems that using EULAR standard US guidelines is feasible for a pediatric setting. The use of US in children is promising. Studies on larger groups of children are needed to confirm the validation and variability of US in children as well as determining the smallest detectable difference of US measures.
Pediatric Rheumatology. 01/2007;
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ABSTRACT: To examine whether pain-specific beliefs and coping strategies of patients with juvenile idiopathic arthritis (JIA) independently predict their reported pain, while controlling for relevant demographic variables, disease activity, and parent-rated disability. To compare use of pain-coping strategies and pain-related beliefs of a selected subgroup of patients with high pain and low disease activity (high pain group) with the remaining patients.
Children with JIA (n = 56) completed the Pain Coping Questionnaire, a revised version of the Survey of Pain Attitudes, and a 3-week pain diary. The parents completed the Childhood Health Assessment Questionnaire (CHAQ). Second order principal component analyses were conducted in order to reduce the number of independent variables. Regression analyses of the dependent measure were performed. The use of coping strategies and health beliefs were compared using t-tests for independent samples. Pearson's correlation coefficients were calculated to examine the direct associations between each individual coping and belief scale, and the pain measure.
Only the CHAQ and the cognitive belief composite factor score made statistically significant contribution to the prediction of pain after controlling for other variables. Significant differences were found between the scores of high pain patients and the rest of the group for the health belief subscale of disability (mean +/- SD 2.0 +/- 0.6 and 1.2 +/- 0.7, respectively), and for the health belief subscale of harm (mean +/- SD 2.7 +/- 0.6 and 1.8 +/- 0.7, respectively). Significant correlations were obtained between the pain measure and the pain-coping subscale of catastrophizing, the pain belief subscales of disability, harm, solicitude (inverse), control, and medical cure.
These results support a model of pain experience in patients with JIA where psychological factors are strongly influential. It may be efficient to focus behavioral interventions on a subgroup of children where the pain experience seems to be in discordance with the disease activity.
Arthritis & Rheumatism 05/2005; 53(2):178-84. · 7.87 Impact Factor
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ABSTRACT: Involvement of the temporomandibular joint (TMJ) in patients with juvenile idiopathic arthritis (JIA) can cause severe craniofacial growth disturbances if not treated in the initial stage. Magnetic resonance imaging (MRI) is an efficient method for detecting early inflammatory changes of the TMJ. We investigated correlation between findings from the clinical examination with MRI of the TMJ, and describe development of the MR image over time.
Fifteen children with newly diagnosed JIA (mean age 12.0 yrs) were examined clinically and with MRI enhanced with Gd-DTPA 4 times at 6-8 month intervals. Clinical and MRI findings were scored. MRI variables included T1 weighted images before and after administration of Gd-DTPA with and without fat suppression.
A total of 115 joints were examined during the 2 year period: 93% showed enhancement, 71% condylar erosions, 26% pannus, and 23% joint fluid accumulation of the TMJ. In all except one child, one or both TMJ showed enhancement of the synovial membrane during the examination period. Symptoms were rare. All patients showing mild to severe findings by clinical examination also had pathological signs on the enhanced MRI, but not all patients without clinical findings had a normal MRI.
TMJ involvement in patients with JIA is very common, and MRI findings such as synovial enhancement, pannus, and joint fluid fluctuate over time. The clinical examination may be used as a filter, where children showing no clinical signs could be selected for enhanced MRI.
The Journal of Rheumatology 02/2005; 32(1):162-9. · 3.69 Impact Factor
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ABSTRACT: To find the incidence of juvenile arthritis according to the ILAR and EULAR criteria within defined areas in the Nordic countries, and to study the validity of the ILAR and EULAR criteria from this perspective.
A longitudinal, prospective, population based study with patients enrolled according to the ILAR and EULAR criteria. Twenty doctors in Iceland, Norway, Sweden, Denmark, and Finland collected data from the incidence cases within their catchment areas over a period of 1.5 years, beginning July 1, 1997. Clinical and serological data from the first year of the disease were collected.
In the whole group of 315 patients, the incidence rate was 15 per 100,000 children/year (95% CI 13-17) according to the ILAR criteria, varying from 7 (1-13) in Iceland, 19 (7-31) and 23 (10-36) from 2 different regions in Norway, and 9 (5-12) and 16 (9-23) from 2 different areas in Denmark, to 15 (12-18) in Sweden and 21/100,000/year (15-26) in the Helsinki region in Finland. An early peak in distribution for age of onset was found in girls but not in boys. The number of antinuclear antibody (ANA) positive children in the whole group, made up of children who had undergone at least one analyzed ANA test, was 123/315 (39%). Girls were ANA positive in 83/197 (42%) and boys in 40/118 (34%). Uveitis developed in 27/315 (8.6%) children during the first 6 months of the disease.
Incidence rates of juvenile arthritis for areas within the Nordic countries were in accord with previous data. The ILAR criteria present slightly higher incidence rates, with a shorter disease duration for inclusion, compared to the EULAR criteria. Patients in one subgroup in either of the criteria sets do not necessarily belong to the expected subgroup in the other set of criteria; e.g., for juvenile ankylosing spondylitis (EULAR) and enthesitis related arthritis (ILAR). Our epidemiological findings are a reminder to be aware of possible new subgroups in children with juvenile arthritis.
The Journal of Rheumatology 11/2003; 30(10):2275-82. · 3.69 Impact Factor
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ABSTRACT: To evaluate how heredity for psoriasis influences classification according to the International League of Associations for Rheumatology (ILAR). Heredity for psoriasis is currently both an exclusion and an inclusion criterion for different types of childhood arthritis according to ILAR classification criteria.
Twenty physicians in 5 Nordic countries prospectively collected data from the incident cases in their catchment areas over an 18 month period beginning July 1, 1997. Clinical and serological data from the first year of disease were collected.
Of the 321 patients included who could be classified according to ILAR criteria for childhood arthritis, 50 (15.6%) patients were excluded from 55 classification events and fulfilled criteria for "other arthritis 1" i.e., did not fulfill criteria for any of the other classification categories, primarily because of heredity for psoriasis. If psoriasis in second degree relatives was disregarded as an exclusion criterion, only 8.7% of the patients remained in the "other arthritis 1" subgroup. For 20.6% of the whole group, heredity for psoriasis in a first or second degree relative (or both) and its distribution among arthritis subgroups did not differ except for juvenile psoriatic arthritis.
We suggest that second degree heredity for psoriasis be withdrawn as an exclusion criterion from the ILAR criteria.
The Journal of Rheumatology 12/2002; 29(11):2454-8. · 3.69 Impact Factor
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Troels Herlin
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ABSTRACT: The new classification of juvenile idiopathic arthritis (JIA) is described in this review. Clinical characteristics divide JIA in to subtypes: systemic, oligoarticular (persistent and extended type), RF-positive and--negative polyarticular, enthesitis-related arthritis and psoriatic arthritis. In addition to the clinical characteristics, genetic and biochemical differences suggest that JIA could be regarded as a general term covering various diseases. Complications described are uveitis, temporomandibular joint affection and growth disturbances. The therapeutic strategy should be planned individually according to age, subtype and disease activity and carried out as teamwork with several specialties. Drugs showing significant effectiveness in controlled studies are primarily methotrexate and sulphasalazine. An immunomodulating agent, etanercept, a soluble TNF alpha-receptor fusion protein, has shown a promising effect in severe polyarticular JIA refractory to methotrexate treatment.
Ugeskrift for laeger 09/2002; 164(34):3941-6.
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ABSTRACT: We describe the ANCA profile of two monozygotic triplets (A and B) treated with propylthiouracil (PTU) for hyperthyroidism who developed LE-like manifestations. Triplet C also developed hyperthyroidism but was not treated with PTU and never experienced LE-like symptoms. Triplet A and B showed a marked rise in P-ANCA titer to 1:1280 after PTU was introduced whereas triplet C never had a titer higher than 1:80. Consecutive sera were investigated for ANCA to six different neutrophil granule proteins. Triplet A and B, but not C, both developed a strongly positive elastase-ANCA. Our results confirm the importance of a genetic factor influencing the susceptibility to drug-induced LE.
Scandinavian Journal of Rheumatology 02/2002; 31(1):46-9. · 2.47 Impact Factor
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ABSTRACT: To assess disease characteristics and outcome in Danish juvenile dermatomyositis (JDM) patients (1977-2007).
Medical record review of hospital records identified from the National Patient Register.
Fifty-seven JDM patients were identified. Follow-up time was 7 years (range 0.06-30). Female:male ratio was 2.5:1. Mean age at disease onset was 7 years (SD±3.7), range 1.5-16.0 years. Diagnostic delay was 0.7 years (SD±1.6), range 0.04-9 years. Mean disease duration was 3.7 years (SD±3.5), range 0.7-9 years. Thirty-nine patients (70%) were in full remission. Three patients (5%) were deceased. Disease/treatment-induced damage was present in 35 (61%) patients. Decreased pulmonary function occurred early in the disease course (median 10 months), osteoporosis and calcinosis occurred later (median 18 and 22 months). Four patients developed persistent damage within the first 6 months, four developed calcinosis within the first year. Shorter disease duration was associated with less damage (p=0.004). In a multivariate assessment analysis age >10 years at disease onset was associated with more damage (p<0.01), OR 10.96 (CI 1.6-73.6), and disease duration >4 years was associated with calcinosis (p=0.01) OR 23.2 (CI 2.6-206.2).
We present a nationwide retrospective study of Danish JDM patients from 1977-2007. Although 70% were in remission, 61% of the patients had clinical signs of damage. Only a few patients developed damage within the first year of the disease. Longer disease duration and higher age at disease onset was correlated with more disease damage.
Clinical and experimental rheumatology 28(5):782-9. · 2.15 Impact Factor
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ABSTRACT: Despite multiple treatment modalities, protein-losing enteropathy remains a serious complication to Fontan-type operations. Observations suggest inflammation to be involved in the pathogenesis of this condition, and immunomodulating treatment with high-dose intravenous immunoglobulin may modify the condition positively.
Four patients with protein-losing enteropathy occurring after the total cavopulmonary connection, presenting with edema, hypoalbuminemia, and hypogammaglobulinemia, received intravenous immunoglobulin replacement therapy.
Standard replacement dose (1 g/kg) was used with intervals between infusions adjusted according to albumin and gamma globulin levels. Treatment periods ranged from 1 year to 5.3 years.
Intravenous immunoglobulin treatment was associated with significant increase in plasma albumin and to some extent in immunoglobulin G levels, as well as resolution of edema and the children started to thrive normally. During treatment, no serious infections or serious side effects were seen. Additional follow-up intervals ranged from 2 years to 2.8 years, during which only one episode of clinical relapse was registered and treated.
We find the increase in albumin level and the resolution of protein-losing enteropathy symptoms after treatment with intravenous immunoglobulin of particular interest considering this serious complication to Fontan-type operations.
Congenital Heart Disease 6(6):624-9. · 0.90 Impact Factor
