Rheumatoid Arthritis: Harjacek M

Harjacek M. · Klinika za djecje bolesti Zagreb, Klaićeva 16, 10000 Zagreb. · Reumatizam. · Pubmed #18351134 No free full text.

Abstract: Progress in the field of pediatric rheumatolgy has been extraordinary; subspecialty is accepted as essential, vital, indispensible and distinct from adult rheumatology. It is clear that arthritis in children is more heterogeneous than RA. Although there are similarities between the inflammatory arthritides occuring in adults and children, RA and JIA appear to be distinct phenotypically with exception for the older child with RF-positive polyarticular arthritis. Progress in molecular biology has enabled us to diagnose those children earlier, and treat them more efficaciously with variety of drugs and biologic agents. In recent years a new group of hereditary autoinflammatory disorders has emerged. These rare syndromes are charaterized by recurrent episodes of seemingly unprovoked, intermittent inflammation. In the near future we will be able to distinguish various subtypes of autoimune/autoinflammatory diseases earlier in the course, have a better understanding of the biomarkers and other prognostic factors, and most importantly treat them earlier with extended set of various new exciting drugs and biological therapy.

Gutiérrez-Suárez R, Pistorio A, Cespedes Cruz A, Norambuena X, Flato B, Rumba I, Harjacek M, Nielsen S, Susic G, Mihaylova D, Huemer C, Melo-Gomes J, Andersson-Gare B, Balogh Z, De Cunto C, Vesely R, Pagava K, Romicka AM, Burgos-Vargas R, Martini A, Ruperto N, Anonymous00034. · IRCCS G. Gaslini, Università di Genova, Pediatria II - Reumatologia, Largo Gaslini, 5 16147 Genova, Italy. · Rheumatology (Oxford). · Pubmed #16877459 links to  free full text

Abstract: OBJECTIVES: To compare health-related quality of life (HRQL) and to identify clinical determinants for poor HRQL of patients with juvenile idiopathic arthritis (JIA) coming from three geographic areas. METHODS: The HRQL was assessed through the Child Health Questionnaire (CHQ). A total of 30 countries were included grouped in three geographic areas: 16 countries in Western Europe; 10 in Eastern Europe; and four in Latin America. Potential determinants of poor HRQL included demographic data, physician's and parent's global assessments, measures of joint inflammation, disability as measured by Childhood Health Assessment Questionnaire (CHAQ) and erythrocyte sedimentation rate. Poor HRQL was defined as a CHQ physical summary score (PhS) or psychosocial summary score (PsS) <2 S.D. from that of healthy children. RESULTS: A total of 3167 patients with JIA, younger than 18 yrs, were included in this study. The most affected health concepts (<2 S.D. from healthy children) that differentiate the three geographic areas include physical functioning, bodily pain/discomfort, global health, general health perception, change in health with respect to the previous year, self-esteem and family cohesion. Determinants for poor HRQL were similar across geographic areas with physical well-being mostly affected by the level of disability while the psychosocial well-being by the intensity of pain. CONCLUSION: We found that patients with JIA have a significant impairment of their HRQL compared with healthy peers, particularly in the physical domain. Disability and pain are the most important determinants of physical and psychosocial well-being irrespective of the geographic area of origin.

Harjacek M, Ruperto N, Ostojic J, Bukovac LT, Anonymous00062. · Children's Hospital Zagreb, Department of Pediatrics, Klaiceva 16, 10 000 Zagreb, Croatia. · Clin Exp Rheumatol. · Pubmed #11510329 No free full text.

Abstract: We report herein the results of the cross-cultural adaptation and validation into the Croatian 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 Croatian CHAQ-CHQ were fully validated with 3 forward and 3 backward translations. A total of 139 subjects were enrolled: 75 patients with JIA (19% systemic onset, 20% polyarticular onset, 17% extended oligoarticular subtype, and 44% persistent oligoarticular subtype) and 64 healthy children. CHAQ clinically discriminated between healthy subjects and JIA patients, with the 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 polyarticular onset and extended oligoarticular subtypes having a lower physical and psychosocial well-being when compared to their healthy peers. In conclusion the Croatian version of the CHAQ-CHQ is a reliable, and valid tool for the functional, physical and psychosocial assessment of children with JIA.

Harjacek M, Diaz-Cano S, De Miguel M, Wolfe H, Maldonado CA, Rabinovich GA. · Department of Pathology, New England Medical Center, Boston, Massachusetts, USA. · J Rheumatol. · Pubmed #11508600 No free full text.

Abstract: OBJECTIVE: Juvenile idiopathic arthritis (JIA) is characterized by hyperplasia of synovial cells and accumulation of mononuclear inflammatory infiltrates, which are locally maintained through a balance between cell proliferation and apoptosis. Although defective clearance of activated T cells in RA joints has been explained by alterations of the Fas-Fas ligand system, this has not been confirmed in synovial tissue of patients with JIA. We evaluated the relation between expression of galectin-1 (Gal-1) and galectin-3 (Gal-3) (beta-galactoside-binding proteins with pro- and anti-apoptotic properties, respectively) and the apoptosis and proliferation rates of infiltrative lymphocytes in synovial tissue of patients with JIA. METHODS: Using slide cytometry and in situ end labeling we observed dysregulated apoptosis of infiltrating mononuclear cells within the synovial tissue of patients with JIA. RESULTS: Patients with pauciarticular JIA showed minimal apoptosis, high Bcl-2 expression, and high or normal proliferation rates, while patients with polyarticular disease showed the lowest apoptotic indexes, accompanied by low Bcl-2 expression and low proliferation rates. We found that Gal-1 expression is downregulated and Gal-3 expression is upregulated in synovial tissue from patients with JIA. CONCLUSION: In patients with polyarticular JIA, accumulation of inflammatory cells is mainly due to downregulated apoptosis, whereas in patients with pauciarticular disease the process results from increased proliferation. Defective mononuclear apoptosis in synovial inflammatory infiltrates from patients with JIA could be explained in part by decreased Gal-1 and increased Gal-3 expression.

Harjacek M, Diaz-Cano S, Alman BA, Coburn J, Ruthazer R, Wolfe H, Steere AC. · Department of Medicine, New England Medical Center, Tufts University School of Medicine, Boston, MA 02111, USA. · J Rheumatol. · Pubmed #10685820 No free full text.

Abstract: OBJECTIVE: To examine the cytokine profiles in synovium of patients with juvenile rheumatoid arthritis (JRA) or Lyme arthritis, 2 chronic inflammatory arthritides that affect children. METHODS: We used in situ hybridization with specific riboprobes to determine the expression of mRNA for proinflammatory or antiinflammatory cytokines in synovial samples from 5 patients with early, untreated JRA, 15 patients with late, treated JRA, and 9 patients with chronic Lyme arthritis. For comparison, synovia were examined from 6 patients with rheumatoid or psoriatic arthritis, and from 9 patients with various orthopedic conditions. RESULTS: Among the children with early, untreated JRA, a median of 3 to 8% of inflammatory cells in synovial samples expressed mRNA for the proinflammatory cytokines interleukin 1beta (IL-1beta), tumor necrosis factor-alpha(TNF-alpha), or interferon-gamma (IFN-gamma). Although a median of 3.9% of the cells expressed mRNA for the antiinflammatory cytokine IL-10, none had IL-4 mRNA. Most of the patients with late, treated JRA, chronic Lyme arthritis, rheumatoid, or psoriatic arthritis had mRNA for each of these proinflammatory cytokines in about 1% of the cells, whereas mRNA for the antiinflammatory cytokines was less frequent. The inflammatory cell density was much less in the synovium of patients with various orthopedic conditions, but about 1% of the infiltrating cells expressed mRNA for at least one of the proinflammatory cytokines. CONCLUSION: Patients with early or late JRA or chronic Lyme arthritis have expression of mRNA in synovial tissue primarily for proinflammatory cytokines, with less expression of antiinflammatory cytokines.