Rheumatoid Arthritis: Lahdenne P

Honkanen V, Lahdenne P. · Helsingin yliopisto, lasten ja nuorten klinikka ja HYKS:n lasten ja nuorten sairaala PL 281, 00029 HYKS. · Duodecim. · Pubmed #11787127 No free full text.

This publication has no abstract.

Ruperto N, Lovell DJ, Cuttica R, Wilkinson N, Woo P, Espada G, Wouters C, Silverman ED, Balogh Z, Henrickson M, Apaz MT, Baildam E, Fasth A, Gerloni V, Lahdenne P, Prieur AM, Ravelli A, Saurenmann RK, Gamir ML, Wulffraat N, Marodi L, Petty RE, Joos R, Zulian F, McCurdy D, Myones BL, Nagy K, Reuman P, Szer I, Travers S, Beutler A, Keenan G, Clark J, Visvanathan S, Fasanmade A, Raychaudhuri A, Mendelsohn A, Martini A, Giannini EH, Anonymous00187, Anonymous00188. · IRCCS, Istituto G. Gaslini, Genoa, Italy. · Arthritis Rheum. · Pubmed #17763439 links to  free full text

Abstract: OBJECTIVE: To evaluate the safety and efficacy of infliximab in the treatment of juvenile rheumatoid arthritis (JRA). METHODS: This was an international, multicenter, randomized, placebo-controlled, double-blind study. One hundred twenty-two children with persistent polyarticular JRA despite prior methotrexate (MTX) therapy were randomized to receive infliximab or placebo for 14 weeks, after which all children received infliximab through week 44. Patients received MTX plus infliximab 3 mg/kg through week 44, or MTX plus placebo for 14 weeks followed by MTX plus infliximab 6 mg/kg through week 44. RESULTS: Although a higher proportion of patients in the 3 mg/kg infliximab group than in the placebo group had achieved responses according to the American College of Rheumatology (ACR) Pediatric 30 (Pedi 30) criteria for improvement at week 14 (63.8% and 49.2%, respectively), the between-group difference in this primary efficacy end point was not statistically significant (P = 0.12). By week 16, after the crossover from placebo to infliximab 6 mg/kg when all patients were receiving infliximab, an ACR Pedi 30 response was achieved in 73.2% of all patients. By week 52, ACR Pedi 50 and ACR Pedi 70 responses had been reached in 69.6% and 51.8%, respectively, of patients. Infliximab was generally well tolerated, but the safety profile of infliximab 3 mg/kg appeared less favorable than that of infliximab 6 mg/kg, with more frequent occurrences of serious adverse events, infusion reactions, antibodies to infliximab, and newly induced antinuclear antibodies and antibodies to double-stranded DNA observed with the 3 mg/kg dose. CONCLUSION: While infliximab at 3 mg/kg and 6 mg/kg showed durable efficacy at 1 year, achievement of the primary efficacy end point at 3 months did not differ significantly between infliximab-treated and placebo-treated patients. Safety data indicated that the 6-mg/kg dose may provide a more favorable risk/benefit profile. These results warrant further investigation in children with JRA.

Silverman E, Mouy R, Spiegel L, Jung LK, Saurenmann RK, Lahdenne P, Horneff G, Calvo I, Szer IS, Simpson K, Stewart JA, Strand V, Anonymous00113. · Department of Pediatrics, University of Toronto, Toronto. · N Engl J Med. · Pubmed #15843668 links to  free full text

Abstract: BACKGROUND: We compared the safety and efficacy of leflunomide with that of methotrexate in the treatment of polyarticular juvenile rheumatoid arthritis in a multinational, randomized, controlled trial. METHODS: Patients 3 to 17 years of age received leflunomide or methotrexate for 16 weeks in a double-dummy, blinded fashion, followed by a 32-week blinded extension. The rates of American College of Rheumatology Pediatric 30 percent responses (ACR Pedi 30) and the Percent Improvement Index were assessed at baseline and every 4 weeks for 16 weeks and every 8 weeks during the 32-week extension study. RESULTS: Of 94 patients randomized, 86 completed 16 weeks of treatment, 70 of whom entered the extension study. At week 16, more patients in the methotrexate group than in the leflunomide group had an ACR Pedi 30 response (89 percent vs. 68 percent, P=0.02), whereas the values for the Percent Improvement Index did not differ significantly (-52.87 percent vs. -44.41 percent, P=0.18). In both groups, the improvements achieved at week 16 were maintained at week 48. The most common adverse events in both groups included gastrointestinal symptoms, headache, and nasopharyngeal symptoms. Aminotransferase elevations were more frequent with methotrexate than with leflunomide during the initial study and the extension study. CONCLUSIONS: In patients with polyarticular juvenile rheumatoid arthritis, methotrexate and leflunomide both resulted in high rates of clinical improvement, but the rate was slightly greater for methotrexate. At the doses used in this study, methotrexate was more effective than leflunomide.

Saarinen J, Lehtonen K, Mälkiä E, Lahdenne P. · Department of Physiotherapy, Hospital for Children and Adolescents, HUCH, Helsinki, Finland. · Clin Exp Rheumatol. · Pubmed #19032836 No free full text.

Abstract: OBJECTIVE: The aim of this study was to measure lower extremity isometric strength in patients with juvenile idiopathic arthritis (JIA) and to evaluate the usefulness of an adjustable dynamometer chair in the clinical work. METHODS: Twenty-five children with JIA and 25 healthy, age-matched controls, aged 7-12 (mean age 10.1) were studied. The isometric maximal strength of knee and ankle muscles was measured on both sides using the dynamometer chair. Before and after the measurements the Children's Effort Rating Table (CERT) was used to assess physical effort and feelings of exertion during the measurements. RESULTS: In all the tested muscle groups, there was a trend towards lower muscle strength values in the patients with JIA but significant differences were found only in knee extension (at 80 degrees knee angle) on both sides and in ankle plantarflexion if both ankles had had arthritis. No difference was observed in perceived exertion between patients and controls, but both groups significantly sensed the exertion after the muscle strength measurement (mean exertion before, JIA/control 2.2/2.0, and after 5.9/5.8). CONCLUSION: Isometric muscle strength in children with JIA can be close to normal when the disease is not active. However, especially in knee extensors and ankle plantarflexors, muscle weakness may occur. From technical standpoint, an adjustable dynamometer chair can be used for assessment of isometric maximal strength in children with JIA.

Tynjälä P, Vähäsalo P, Honkanen V, Lahdenne P. · Department of Pediatric Rheumatology, Hospital for Children and Adolescents, Helsinki University Central Hospital, Helsinki, Finland. · Ann Rheum Dis. · Pubmed #18467515 No free full text.

Abstract: OBJECTIVES: To evaluate drug survival (continuation rates on drug) of anti-tumour necrosis factor (TNF) agents in juvenile idiopathic arthritis (JIA) and predictors for treatment discontinuation. METHODS: A retrospective observational study on JIA patients taking etanercept (n = 105) or infliximab (n = 104) with at least one year follow-up. Kaplan-Meier curves and log-rank statistics were used to compare treatments and a proportional hazards model to assess risk factors for discontinuation. RESULTS: Etanercept versus infliximab treatment survival at 12 months was 83% versus 80%, at 24 months 68% versus 68%, at 36 months 64% versus 53%, at 48 months 61% versus 48% (p = 0.194), respectively. Reasons for discontinuing the first biological treatment were inefficacy (etanercept 28% vs infliximab 20%, p = 0.445), adverse events (7% vs 22%, p = 0.002) or inactive disease (10% vs 16%, p = 0.068). Women (hazard ratio (HR) 2.8, 95% CI 1.3 to 5.8), patients with systemic JIA (HR 7.8, 95% CI 1.7 to 34.9) or those taking infliximab (HR 2.0, 95% CI 1.2 to 3.3) were at higher risk of treatment discontinuation. One-third of the patients were switched to the second anti-TNF therapy, which was discontinued less frequently than the first. At 12 months treatment survival of etanercept was 60%, infliximab 58% and adalimumab 66% as the second-line anti-TNF therapy. CONCLUSIONS: Although infliximab was discontinued more often than etanercept because of adverse events, during a 48-month follow-up the overall treatment survival of etanercept and infliximab as the first biological agent in JIA was comparable. A switch from one anti-TNF agent to another appears a reasonable therapeutic option.

Tynjälä P, Kotaniemi K, Lindahl P, Latva K, Aalto K, Honkanen V, Lahdenne P. · Department of Pediatric Rheumatology, Hospital for Children and Adolescents, Helsinki, Finland. · Rheumatology (Oxford). · Pubmed #18238789 No free full text.

Abstract: OBJECTIVE: To evaluate the efficacy of adalimumab in juvenile idiopathic arthritis (JIA)-associated uveitis. METHODS: Retrospective observational study of 20 patients with JIA and chronic uveitis on adalimumab treatment. The ocular inflammation and improvement was assessed according to the Standardization of Uveitis Nomenclature criteria. RESULTS: At the initiation of adalimumab, the mean age of patients was 13.4 yrs and the mean duration of uveitis 8.7 yrs. Seventeen (85%) patients had polyarticular JIA and 19 (95%) had previously been on anti-TNF treatment. The mean duration of adalimumab therapy was 18.7 months. Of the 20 patients, 7 (35%) showed improved activity, 1 (5%) worsening activity and in 12 (60%) no change was observed in the activity of uveitis. Those with improved activity were younger and had shorter disease duration. The mean number of flares/yr decreased from 1.9 to 1.4 during adalimumab treatment. Serious adverse events or side-effects were not observed. Seven patients discontinued adalimumab during the follow-up: six because of inefficacy and one because of inactive uveitis. CONCLUSION: Adalimumab is a potential treatment option in JIA-associated uveitis, even in patients non-responsive to previous other anti-TNF therapy.

Céspedes-Cruz A, Gutiérrez-Suárez R, Pistorio A, Ravelli A, Loy A, Murray KJ, Gerloni V, Wulffraat N, Oliveira S, Walsh J, Penades IC, Alpigiani MG, Lahdenne P, Saad-Magalhães C, Cortis E, Lepore L, Kimura Y, Wouters C, Martini A, Ruperto N, Anonymous00360. · IRCCS G Gaslini, Pediatria II, Reumatologia, PRINTO, Largo Gaslini, 5, 16147 Genova, Italy. · Ann Rheum Dis. · Pubmed #17875547 No free full text.

Abstract: OBJECTIVES: To examine the change in health-related quality of life (HRQOL) and its determinants in children with juvenile idiopathic arthritis (JIA) treated with methotrexate (MTX). METHODS: Patients were extracted from the PRINTO clinical trial which aimed to evaluate the efficacy and safety profile of MTX administered in standard, intermediate or higher doses (10, 15 and 30 mg/m(2)/week respectively). Children with polyarticular-course JIA, who were less than 18 years and had a complete HRQOL assessment were included. RESULTS: A total of 521 children were included. At baseline, patients with JIA showed poorer HRQOL (p<0.01) than healthy children. In 207/412 (50%) and 63 (15%) children, HRQOL values were 2 standard deviations below the mean of healthy controls in the physical and psychosocial summary scale, respectively. After 6 months of treatment with standard dose MTX, there was a statistically significant improvement in all HRQOL health concepts, particularly the physical ones. Similar improvements were observed in those who did not respond to a standard dose of MTX and were subsequently randomised to a higher dose. The presence of marked disability at baseline was associated with a fivefold increased risk of retaining poor physical health after 6 months of active treatment with standard dose MTX. Other less important determinants of retaining poor physical well-being were the baseline level of systemic inflammation, pain intensity and an antinuclear-antibody-negative status. CONCLUSIONS: MTX treatment produces a significant improvement across a wide range of HRQOL components, particularly in the physical domains, in patients with JIA.

Levälampi T, Honkanen V, Lahdenne P, Nieminen R, Hakala M, Moilanen E. · The Immunopharmacology Research Group, Medical School, University of Tampere and Research Unit, Tampere University Hospital, Tampere, Finland. · Scand J Rheumatol. · Pubmed #17657672 No free full text.

Abstract: OBJECTIVE: Infliximab is effective and well tolerated in the treatment of juvenile idiopathic arthritis (JIA). The aim of the present study was to measure circulating levels of inflammatory mediators in patients with JIA during treatment with infliximab. METHODS: Eight patients with active JIA refractory to standard treatments were treated with infliximab (3-4 mg/kg) at weeks 0, 2 and 6 and thereafter at approximately 6-week intervals up to 24 weeks. RESULTS: All patients (n = 8) responded to the treatment. By 6 weeks of treatment the number of active joints had reduced from 16+/-4 (mean+/-SEM) to 4+/-1 (p<0.01) and C-reactive protein (CRP) levels had fallen from 31+/-8 to 8+/-3 (p<0.001). Infliximab treatment also reduced the serum concentrations of interleukin-6 (IL-6), myeloperoxidase (MPO), and soluble adhesion molecules ICAM-1 (intercellular adhesion molecule-1), and E-selectin. Tumour necrosis factor-alpha (TNFalpha) levels tended to increase while the concentrations of endogenous TNF antagonists (sTNF-RI and sTNF-RII) reduced in most patients during treatment. CONCLUSIONS: Infliximab reduced serum levels of IL-6, MPO and soluble adhesion molecules in JIA patients, producing a good clinical response to the treatment.

Valta H, Lahdenne P, Jalanko H, Aalto K, Mäkitie O. · Hospital for Children and Adolescents, Metabolic Bone Clinic, University of Helsinki, Helsinki, Finland. · J Rheumatol. · Pubmed #17309121 No free full text.

Abstract: OBJECTIVE: To evaluate bone health and growth and their correlates in glucocorticoid (GC)-treated pediatric patients with juvenile idiopathic arthritis (JIA). METHODS: Consecutive patients with a history of JIA for >or= 2 years and systemic GC treatment for >or= 3 months were assessed for bone health and its determinants. Areal bone mineral density (aBMD) and vertebral body morphology were assessed with DEXA; Z scores were adjusted for calendar and bone age. Values were correlated with biochemistry, disease activity, and medications. RESULTS: Sixty-two patients (43 female; median age 11.8 yrs, median disease duration 5.6 yrs) were included. The median duration of GC treatment was 24 months and the median cumulative dose (as prednisolone) was 2.2 g. Four patients had had fractures. The median bone age-corrected aBMD Z score was -0.4 (range -2.9 to +1.8) for lumbar spine and -0.1 (range -2.1 to +2.4) for femoral neck. Abnormal vertebral morphology was observed in 6 patients (10%). No correlation was found between aBMD and disease characteristics or cumulative GC dose. The median Z score for height was +0.1 (range -2.9 to +1.5) and the median height-adjusted weight +4% (range -17% to +40%). CONCLUSION: Our study showed low prevalence of osteoporosis and normal growth in children with JIA. However, asymptomatic vertebral fractures were observed in 10% of the patients, indicating that DEXA alone may not be sufficient when evaluating bone health in these children. Osteoporosis still remains a concern in children with GC-treated JIA.

Oliveira S, Ravelli A, Pistorio A, Castell E, Malattia C, Prieur AM, Saad-Magalhães C, Murray KJ, Bae SC, Joos R, Foeldvari I, Duarte-Salazar C, Wulffraat N, Lahdenne P, Dolezalova P, de Inocencio J, Kanakoudi-Tsakalidou F, Hofer M, Nikishina I, Ozdogan H, Hashkes PJ, Landgraf JM, Martini A, Ruperto N, Anonymous00868. · IRCCS G. Gaslini, Pediatria II, Reumatologia, Pediatric Rheumatology International Trials Organization, Genoa, Italy. · Arthritis Rheum. · Pubmed #17266064 links to  free full text

Abstract: OBJECTIVE: To investigate the proxy-reported health-related quality of life (HRQOL) and its determinants in patients with juvenile idiopathic arthritis (JIA). METHODS: In this multinational, multicenter, cross-sectional study, HRQOL of patients with JIA was assessed through the Child Health Questionnaire (CHQ) and was compared with that of healthy children of similar age from the same geographic area. Potential determinants of HRQOL included demographic data, physician's and parent's global assessments, measures of joint inflammation, Childhood Health Assessment Questionnaire (CHAQ), and erythrocyte sedimentation rate. RESULTS: A total of 6,639 participants (3,324 with JIA and 3,315 healthy) were enrolled from 32 countries. The mean +/- SD physical and psychosocial summary scores of the CHQ were significantly lower in patients with JIA than in healthy children (physical: 44.5 +/- 10.6 versus 54.6 +/- 4.0, P < 0.0001; psychosocial: 47.6 +/- 8.7 versus 51.9 +/- 7.5, P < 0.0001), with the physical well-being domain being most impaired. Patients with persistent oligoarthritis had better HRQOL compared with other subtypes, whereas HRQOL was similar across patients with systemic arthritis, polyarthritis, and extended oligoarthritis. A CHAQ score >1 and a pain intensity rating >3.4 cm on a 10-cm visual analog scale were the strongest determinants of poorer HRQOL in the physical and psychosocial domains, respectively. CONCLUSION: We found that patients with JIA have a significant impairment of their HRQOL compared with healthy peers, particularly in the physical domain. Physical well-being was mostly affected by the level of functional impairment, whereas the intensity of pain had the greatest influence on psychosocial health.

Tynjälä P, Lindahl P, Honkanen V, Lahdenne P, Kotaniemi K. · Department of Pediatric Rheumatology, Research Unit, Hospital for Children and Adolescents, Helinski University Central Hospital, 00029 HUS, Finland. · Ann Rheum Dis. · Pubmed #17068061 No free full text.

Abstract: OBJECTIVE: To evaluate the efficacy of anti-tumour necrosis factor (anti-TNF) treatment in juvenile idiopathic arthritis (JIA)-associated uveitis. METHODS: 24 patients with uveitis taking etanercept and 21 taking infliximab were studied. The endpoint ophthalmological evaluation was at 24 months or at the termination of the first biological agent. The ocular inflammatory activity was graded on the basis of the number of anterior chamber cells. RESULTS: Of the 45 patients, uveitis improved in 14 (31%), no change was observed in 14 (31%) and the activity of uveitis increased in 17 (38%). Inflammatory activity improved more frequently (p=0.047) in the patients taking infliximab than in those taking etanercept. The number of uveitis flares/year was higher (p=0.015) in the patients taking etanercept (mean 1.4, range 0-3.2) than in those taking infliximab (mean 0.7, range 0-2). Uveitis developed for the first time while taking anti-TNF treatment in five patients-4 taking etanercept (2.2/100 patient-years) and 1 taking infliximab (1.1/100 patient-years). CONCLUSIONS: During anti-TNF treatment, the ophthalmological condition improved in one-third of the patients with uveitis. In chronic anterior uveitis, associated with refractory JIA, infliximab may be more effective than etanercept.

Tynjälä P, Lahdenne P, Vähäsalo P, Kautiainen H, Honkanen V. · Hospital for Children and Adolescents, Helsinki University Central Hospital, Research Unit, Lastenlinnantie 11 C 29, PL 280, 00029 HUS, Finland. · Ann Rheum Dis. · Pubmed #16449314 links to  free full text

Abstract: OBJECTIVES: To evaluate the impact of anti-tumour necrosis factor (TNF) treatment on growth and to identify the predictors for the change in growth in severe juvenile idiopathic arthritis (JIA). METHODS: Data from 71 JIA patients (43 on etanercept, 28 on infliximab) were reviewed two years before and two years on the anti-TNF treatment. The patients had polyarticular disease course (48 polyarthritis, 19 extended oligoarthritis, two systemic arthritis, and two enthesitis related arthritis). At the initiation of the anti-TNF treatment, their mean age was 9.6 years and the mean duration of JIA, 5.7 years. RESULTS: In the patients with delayed growth before anti-TNF treatment (n = 53), the growth velocity, measured as the change in height standard deviation score, accelerated +0.45 (95% confidence interval, 0.33 to 0.56) (p<0.001) during the anti-TNF treatment. In the patients with normal or accelerated growth before anti-TNF treatment (n = 18), the change in growth velocity was +0.05 (0.07 to 0.16) (p = 0.39). At two years on anti-TNF treatment, the growth velocity between these two groups was similar. No difference was found between the patients treated with etanercept or infliximab. A decelerating growth rate before the anti-TNF treatment was the strongest predictor for the observed increase in the growth velocity. The change in the inflammatory activity remained a significant predictor of the growth velocity even after the decrease in glucocorticoid dose was taken into account. CONCLUSIONS: In the treatment of polyarticular JIA, the anti-TNF treatment not only suppresses inflammation but also restores growth velocity.

Berntson L, Andersson Gäre B, Fasth A, Herlin T, Kristinsson J, Lahdenne P, Marhaug G, Nielsen S, Pelkonen P, Rygg M, Anonymous00387. · Department of Pediatrics, Falun Hospital, SE-791 82 Falun, Sweden. · J Rheumatol. · Pubmed #14528529 No free full text.

Abstract: OBJECTIVE: 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. METHOD: 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. RESULTS: 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. CONCLUSION: 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.

Lahdenne P, Vähäsalo P, Honkanen V. · Department of Paediatric Rheumatology, Hospital for Children and Adolescents, University of Helsinki, 00290 Helsinki, Finland. · Ann Rheum Dis. · Pubmed #12594111 links to  free full text

Abstract: OBJECTIVE: To study infliximab and etanercept in the treatment of refractory juvenile idiopathic arthritis (JIA). METHODS: In a non-randomised, prospective, open label study, 24 patients (mean age 10.2 years, range 3.3-16.3) with polyarticular JIA were treated with either infliximab (n=14) or etanercept (n=10). The patients had had active polyarthritis for at least one year and standard treatment had failed. Anti-tumour necrosis factor (TNF) treatment was added to the current drug treatment. Infliximab (3-4 mg/kg) was given intravenously at weeks 0, 2, and 6, and thereafter at 4 to 8 week intervals. Etanercept (0.4 mg/kg) was given subcutaneously twice a week. Improvement of the patients was assessed at 3, 6, and 12 months according to established JIA response criteria. RESULTS: In intention to treat analyses, patients in both treatment groups improved significantly. ACR Paediatric 50 was achieved at 3, 6, and 12 months by 9/10 (90%), 8/9 (89%), and 8/9 (89%) patients with etanercept and by 8/12 (67%), 10/12 (83%), and 7/9 (78%) with infliximab, respectively. At 12 months, ACR Paediatric 75 was achieved by 67% of patients in both treatment groups. Five withdrawals due to adverse effects or lack of efficacy occurred in the infliximab group and one due to lack of compliance in the etanercept group. CONCLUSION: In this open label clinical study of active JIA, both infliximab and etanercept provided a significant rapid and sustained reduction in disease activity. Adequately powered randomised controlled trials are needed to elucidate the long term safety and efficacy of TNF modulators in the treatment of JIA.

Pelkonen P, Lahdenne P, Lantto R, Honkanen V. · Hospital for Children and Adolescents, Helsinki University Central Hospital, Finland. · J Rheumatol. · Pubmed #12465167 No free full text.

This publication has no abstract.

Berntson L, Fasth A, Andersson-Gäre B, Herlin T, Kristinsson J, Lahdenne P, Marhaug G, Nielsen S, Pelkonen P, Rygg M. · Department of Pediatrics, Falun Hospital and Göteborg University, Göteborgm, Sweden. · J Rheumatol. · Pubmed #12415608 No free full text.

Abstract: OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: We suggest that second degree heredity for psoriasis be withdrawn as an exclusion criterion from the ILAR criteria.

Lahdenne P, Rapola J, Ylijoki H, Haapasaari J. · Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland. · J Rheumatol. · Pubmed #12415606 No free full text.

Abstract: OBJECTIVE: To evaluate hepatotoxicity in patients with juvenile idiopathic arthritis (JIA) receiving methotrexate (MTX) therapy with doses of 20-30 mg/m2 of body surface area. METHODS: We graded the histology of percutaneous liver biopsies from 34 patients with JIA receiving longterm (> 2.4 years) MTX therapy at the Rheumatism Foundation Hospital, Heinola, Finland, using the Roenigk classification scale. Medical records of the patients with JIA were retrospectively analyzed. RESULTS: Of 10 patients with MTX doses >/= 20 mg/m2, 4 had grade II, 5 had grade I histology, and one specimen with extensive steatosis as the only pathologic finding could not be classified. All 24 patients treated with low dose MTX had grade I histology. No specimen showed fibrosis or cirrhosis. In 2 patients with grade II histology, extensive portal tract inflammation resolved when MTX was discontinued for 6 months. CONCLUSION: Aggressive medical treatment of JIA with MTX at 20-30 mg/m2 with concomitant disease modifying antirheumatic drugs and corticosteroids may contribute to minor liver abnormalities that seem to be reversible.

Panelius J, Lahdenne P, Heikkilä T, Peltomaa M, Oksi J, Seppälä I. · Haartman Institute, Department of Bacteriology and Immunology, Turku University Central Hospital, Finland. · J Med Microbiol. · Pubmed #12358063 links to  free full text

Abstract: Genes for the outer-surface protein C (OspC) from three north European human isolates of Borrelia burgdorferi sensu stricto, B. afzelii and B. garinii were cloned and sequenced. Polyhistidine-tagged recombinant OspC (rOspC) proteins were produced in Escherichia coli and used, after biotinylation, as antigens on streptavidin-coated plates in enzyme-linked immunosorbent assays (ELISA). In IgM ELISA, 30% (5/17) and 35% (6/17) of patients with erythema migrans (EM) in the acute or convalescent phase, respectively, reacted with one to three rOspCs. Of the patients, 53% (8/15) with neuroborreliosis (NB) and 53% (8/15) with Lyme arthritis (LA) had IgM antibodies to OspC. The immunoreactivity was stronger against rOspC from B. afzelii and B. garinii than against rOspC from B. burgdorferi sensu stricto. In early Lyme borreliosis (LB), rOspC and flagella performed equally well in detecting IgM antibodies. Cross-reactive antibodies to rOspC were observed in serum samples from patients with rheumatoid factor positivity and with syphilis or Epstein-Barr virus (EBV) infection. In IgM ELISA, thiocyanate in the serum dilution buffer reduced EBV-associated non-specific positive reactions. Of the patient sera examined in IgG ELISA, 30% (5/17) with EM in the acute phase, 35% (6/17) with EM in the convalescent phase, 33% (5/15) with NB and 60% (9/15) with LA were positive. Because of the heterogeneity of OspC, a polyvalent antigen with several OspC variants from at least B. afzelii and B. garinii is needed to improve the sensitivity of OspC ELISA in the serodiagnosis of LB in Europe.

Berntson L, Fasth A, Andersson-Gäre B, Kristinsson J, Lahdenne P, Marhaug G, Nielsen S, Pelkonen P, Svensson E, Anonymous00091. · Department of Pediatrics, Hospital of Falun, Sweden. · J Rheumatol. · Pubmed #11764226 No free full text.

Abstract: OBJECTIVE: New classification criteria (ILAR) have been proposed for juvenile idiopathic arthritis (JIA). They are more descriptive than those formerly used [American College of Rheumatology (ACR), European League Against Rheumatism (EULAR)], but require validation against classifications already in use. We validated the ILAR criteria in relation to the EULAR criteria in a prospective, incidence, and population based setting, and analyzed their feasibility. METHODS: Construct validity of ILAR and EULAR classification criteria refers to how closely the 2 instruments are related and how each of them operates in classifying subgroups/categories. Twenty doctors in 5 Nordic countries collected data from the incidence cases within their catchment areas during an 18 month period beginning July 1, 1997. Clinical and serological data from the first year of disease were collected. RESULTS: A total of 322 patients were included. Classification according to the ILAR criteria was possible in 321 patients; 290 patients had a disease duration > or = 3 months and were classified according to the EULAR criteria. One child could only be classified according to the EULAR criteria. Thus, 31/322 (9.6%) children were classified according to the ILAR criteria only. Forty-eight of 321 (15%) patients did not fit into any category and 6% (20/321) fulfilled criteria for2 categories. In the ILAR classification 5 out of 7 categories/subgroups have 2 to 5 specified exclusion criteria that highly discriminate the definition of each patient. In our study the exclusion criteria were fulfilled to only a small extent. CONCLUSION: The EULAR and ILAR criteria differ concerning the operational definitions of the subvariables involved, which complicates their comparison. By using ILAR rather than EULAR criteria the number of cases with juvenile arthritis increased by 10%, considering the first half-year after onset. The validity of the ILAR criteria is low since they often exclude patients from subgroup classification and the possibility of having more than one diagnosis is not negligible. The specified exclusion criteria for some of the subgroups are difficult to fulfill in clinical work and variables involved could be questioned with regard to their consistency.

Panelius J, Lahdenne P, Saxen H, Heikkilä T, Seppälä I. · Haartman Institute, Department of Bacteriology and Immunology, Helsinki, Finland. · J Clin Microbiol. · Pubmed #11682523 links to  free full text

Abstract: Genes for flagellin A (FlaA) proteins from European borrelial strains of Borrelia burgdorferi sensu stricto, B. afzelii, and B. garinii were cloned and sequenced. An identity of 92 to 93% was observed in the flaA sequences of the different species. Polyhistidine-tagged recombinant FlaA (rFlaA) proteins were produced in Escherichia coli and used as antigens in Western blotting (WB) and enzyme-linked immunosorbent assay (ELISA). In immunoglobulin G (IgG) WB, 71% (10 of 14) of the sera from neuroborreliosis and 86% (12 of 14) of those from Lyme arthritis patients reacted with one to three rFlaAs. In IgG ELISA, 74% (14 of 19) and 79% (15 of 19) of patients with neuroborreliosis and arthritis, respectively, were positive. The immunoreactivity in local European patient sera was stronger against rFlaA from B. garinii and B. afzelii than against rFlaA from B. burgdorferi sensu stricto. Neither IgG nor IgM ELISA was sensitive in the serodiagnosis of erythema migrans. Serum samples from patients with syphilis and systemic lupus erythematosus showed mild cross-reactivity in IgG tests. Sera from Yersinia enterocolitica or beta-hemolytic Streptococcus infections showed only occasional responses. With IgM ELISA, 58% (11 of 19) and 37% (7 of 19) of patients with neuroborreliosis and arthritis, respectively, were positive. Cross-reactive antibodies to FlaA, especially in serum samples from patients with rheumatoid factor positivity and Epstein-Barr virus infection, reduced the specificity of IgM serodiagnosis. Therefore, rFlaA seems to have a limited role for IgM serodiagnosis, yet rFlaA might be useful in the IgG serodiagnosis of disseminated Lyme borreliosis.

Pelkonen P, Ruperto N, Honkanen V, Hannula S, Savolainen A, Lahdenne P, Anonymous00065. · Hospital for Children and Adolescents, University of Helsinki, 00029 Helsinki, Finland. · Clin Exp Rheumatol. · Pubmed #11510332 No free full text.

Abstract: We report herein the results of the cross-cultural adaptation and validation into the Finnish 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 Finnish CHAQ-CHQ were validated with 3 forward and 1 backward translations. A total of 161 subjects were enrolled: 89 patients with JIA (9% systemic onset, 44% polyarticular onset, 26% extended oligoarticular subtype, and 21% persistent oligoarticular subtype) and 72 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 systemic, polyarticular and extended oligoarticular subtypes having a lower physical and psychosocial well-being when compared to their healthy peers. In conclusion the Finnish version of the CHAQ-CHQ is a reliable and valid tool for the functional, physical and psychosocial assessment of children with JIA.