New for 99 from the ACR Conference:

ELEVATED SERUM LEVELS OF BOTH TH1 AND TH2 CYTOKINES IN PATIENTS WITH ADULT STILL'S DISEASE

                                                                ADOLESCENT-ONSET STILL'S DISEASE: CHARACTERISTICS AND EVOLUTION OF 9 CASES IN COMPARISON WITH ADULT AND JUVENILE-ONSET STILL DISEASE PATIENTS

 NEW CLASSIFICATION TREE AND CRITERIA SET, INCLUDING FERRITIN AND GLYCOSYLATED FERRITIN, FOR ADULT STILL'S DISEASE

• Abstract 1     HIGHLY ELEVATED LEVELS OF SERUM INTERLEUKIN-18 IN ADULT ONSET STILL'S DISEASE

• Abstract 2   HIGH DOSE CHEMOTHERAPY AND SYNGENEIC PROGENITOR CELL TRANSPLANTATION FOR SEVERE ADULT-ONSET STILL'S DISEASE

• Abstract 3   DOES SULFASALAZINE HAVE FREQUENT SIDE EFFECTS IN ADULT-ONSET STILL'S DISEASE?

• Abstract 4  A controlled study of the long-term prognosis of adult Still's disease                  

• Abstract 5    Two cases of adult Still's disease with atypical rash

• Abstract 6   Comparison of clinical features of childhood and  adult onset Still's disease

• Abstract 7    Evaluation of serum ferritin as a marker for adult Still's disease activity

• Abstract 8   Serum ferritin and isoferritins are tools for diagnosis of  active adult Still's disease

• Abstract 9    Treatment of Still disease in adults with intravenous  immunoglobulins

• Abstract 10    Adult Still's disease:  Manifestations and complications  in sixty-five cases in France.  Parts 1 & 2

• Abstract 11  Effect of novel polymorphisms in the interleukin-6 (IL-6) gene on IL-6  transcription and plasma IL-6 levels, and an association with systemic-onset juvenile chronic arthritis

• Abstract 12  Elevated circulating interleukin-7 levels in patients with systemic  juvenile rheumatoid arthritis

• Abstract 13    AOSD triggered by Hepatitis A and B vaccination

• Abstract 14     Adult-onset Still's disease; clinical and laboratory features, treatment and progress of 45 cases.
  

• Abstract 15   Adult Still's disease: manifestations, disease course, and outcome in 62 patients.

• Abstract 16    Adult Still's disease. Evolution of a clinical syndrome and diagnosis, treatment, and follow-up of 17 patients.
  

• Abstract 17     Severe sore throat as a presenting symptom of adult onset Still's disease: a case series and review of the literature.

• Abstract 18   Comparison of long term evolution of adult onset and  juvenile onset Still's disease, both followed up for more than 10 years.

• Abstract 19   Still disease in adults revealed by a digestive manifestation

• Abstract 20     Systemic amyloidosis in a patient with adult onset Still's disease.

• Abstract 21     Amyloidosis: prognosis and treatment.

• Abstract 22     Adult-onset Still's disease.
  
  

• More Research Abstracts Coming Soon

Abstract: 98
November 9, 1998
Poster Session A: Juvenile Rheumatoid Arthritis: Pathogenesis and Therapy
8:00-9:30 am, Hall B1/C

EVALUATION OF ACTIVATION INDUCED CELL DEATH IN PATIENTS WITH SYSTEMIC JUVENILE RHEUMATOID ARTHRITIS

P. Pignatti, F. De Benedetti, M. Massa¹, C. Meazza, F. Mazzoli, A. Martini

Clinica Pediatrica; ¹Lab. di Biotecnologie e Tecnologie Biomediche, IRCCS S. Matteo, Pavia, Italy


Lymphocytes, continually stimulated, die for activation induced cell death (AICD) which represents a pivotal mechanism for controlling the immune response. One of the pathway leading to apoptosis in lymphocytes is represented by the Fas/FasL system. Recently non funtional mutations of the death domain of Fas was demonstrated in patients with autoimmune lymphoproliferative disease suggesting that defects in inducing apoptosis could be responsible for autoimmune and/or inflammatory diseases. We evaluated the induction of apoptosis after activation of peripheral blood mononuclear cells (PBMC) with a moAb anti-CD3 and interleukin-2 (IL-2) for 5 days in 10 patients with systemic juvenile rheumatoid arthritis (s-JRA) and in 16 healthy controls. The percentage of apoptotic cells after the culture was evaluated by acridine orange staining in fluorescence microscopy and by propidium iodide in flow cytometry. After the activation the percentage of apoptotic PBMC was significantly higher (p = 0.011) in s-JRA patients (28.4 ± 14.3) than controls (16.8 ± 14.9). To verify which mechanism was responsible for the increased AICD, we activated PBMC as above in the presence or absence of a moAb neutralizing Fas or a moAb neutralizing TNF-a, and evaluated the percentage of apoptotic cells. In s-JRA patients (n = 4) the AICD was highly inhibited by the moAb neutralizing TNF-a (-56.4%). These data suggest that in s-JRA patients a preactivation of the apoptosis mechanism is present and that this AICD is caused by TNF-a. Then we evaluated the Fas/FasL system.; the percentage of Fas positive lymphocytes was comparable between patients and controls, both before (s-JRA 34 ± 16.5%; controls 27.1 ± 7.8%) and after activation with anti-CD3 and IL-2 (s-JRA > 90%, controls > 90%). In order to evaluate the function of Fas, after the activation of PBMC with anti-CD3 and IL-2 for 4 days, cells have been incubated for 16 hours with a moAb activating Fas; the percentage of apoptotic cells evaluated was lower in s-JRA patients (13.4 ± 10.7) than controls (16.1 ± 7.0), although not statistically significant (p = 0.09). These data suggest that a preactivation of apoptotic mechanisms, as shown by the increased AICD following ex-vivo activation, is present in s-JRA patients. The decreased induction of apoptosis obtained with the moAb anti-Fas might be secondary to the activation of alternative mechanisms of apoptosis as suggested by the data obtained with the neutralization of TNF-a.

Disclosure: work reported in this abstract was supported by:
Institutional support: IRCCS Pol. San Matteo.

Apoptosis and cell cycle regulation
Juvenile rheumatoid arthritis
Juvenile rheumatoid arthritis: pathophysiology

Abstract: 1196
November 10, 1998
Poster Session D: Miscellaneous Rheumatic Diseases
12:30-2:00 pm, Hall B1/C

CLINICAL CHARACTERISTICS, TREATMENT AND OUTCOME OF ADULT-ONSET STILL'S DISEASE IN SOUTHERN CHINESE

C.C. Mok, C.S. Lau, R.W.S. Wong

Department of Medicine, Queen Mary Hospital, Hong Kong


Objectives and Methods: To study the clinical characteristics, treatment outcome and complications of patients with adult-onset Still's disease (AOSD) in our local Chinese population. Patients with AOSD who attended our rheumatology clinics from 1967 to 1997 were followed up prospectively. Their clinical and laboratory features at presentation, treatment and outcome were recorded and compared with other reported series in the literature.
Results: Sixteen patients with AOSD were identified. They were diagnosed based on the criteria proposed by Cush and Medsger¹. Eleven (69%) were female. Nine (56%) had onset of the disease between 16 and 35 years of age. The commonest presenting features were fever (100%), arthritis (94%), rash (85%), weight loss (69%) and sore throat (63%). Fifteen patients presented with pyrexia of unknown origin and the median duration of fever before the establishment of the diagnosis was 6 weeks (range 4­75). The acute phase response was marked in all patients with gross elevation of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and complement levels. Hyperferritinemia (>5 times normal) was present in 90% of cases. Most patients (81%) required corticosteroid therapy and 85% of those steroid treated patients received additional disease modifying agents. The mean duration of follow up of our patients was 93.3 months (range 8­362). Five (33%) had monocyclic systemic disease, 6 (40%) had polycyclic systemic disease and 4 (27%) had frequent relapses which progressed into a chronic arthropathy.
Conclusions: AOSD in southern Chinese tends to run a benign course with few patients evolving into chronic inflammatory arthropathy. A significantly lower incidence of serositis, lung involvement and enlargement of the reticuloendothelial organs was observed at presentation when compared with patients of different ethnic origins.

References:
Cush JJ, Medsger TA, Christy WC, Herbert DC, Cooperstein LA. Adult-onset Still's disease. Clinical course and outcome. Arthritis Rheum 1987; 30: 186­94


Disclosure: work reported in this abstract was supported by:
Department of Medicine, Queen Mary Hospital, Hong Kong.

Fever
Rheumatoid arthritis: other
Rheumatologic disorders: other
Steroids
Outcomes research

Abstract: 583
November 9, 1998
ACR Concurrent Session: Inflammation and Pediatric Rheumatic Diseases
2:15-3:45 pm, Room 6D

DECREASED LEVELS OF INSULIN-LIKE GROWTH FACTOR BINDING PROTEIN-3 (IGFBP-3) AND INCREASED IGFBP-3 PROTEOLYSIS IN SYSTEMIC JUVENILE RHEUMATOID ARTHRITIS

F. De Benedetti, C. Meazza, M. Oliveri, P. Pignatti, M. Massa, F. Mazzoli, A. Martini

Clinica Pediatrica, Lab. di Biotecnologie e Tecnologie Biomediche, IRCCS Pol. S. Matteo, Pavia, Italy


Stunted growth is a common complication of childhood chronic inflammatory diseases. Inflammation affects insulin-like growth factor-I (IGF-I) levels, rather than decreasing growth hormone (GH) production. IGF-I is produced essentially by the liver in response to GH and mediates GH effects on most peripheral tissues. The great part of IGF-I circulates bound to IGF binding protein-3 and this binding affects the biological activity of IGF-I by markedly increasing IGF-I half-life. Since in patients with systemic juvenil rheumatoid arthritis (s-JRA) levels of IGF-I are markedly reduced, we measured IGFBP-3 levels in these patients. Immunoblotting (IB) analysis showed that serum levels of the intact IGFBP-3 38-42 Kd doublet were significantly lower than those of controls (p < 0.0001 by comparison of Z scores). By western ligand blotting no significant changes were found in the serum levels of the other IGFBPs. Serum levels of intact IGFBP-3 were inversely correlated with the number of active joints (Rs = -0.554, p = 0.03), CRP (Rs = -0.497, p = 0.02), and ESR (Rs = -0.624, p = 0.002). When total IGFBP-3 (sum of the intensities of the intact 38­42 Kd doublet and of the proteolytic fragments) was evaluated by densitometry, the difference among patients and controls did not reach statistical significance. This suggests normal IGFBP-3 production in s-JRA. To explain the decrease in intact IGFBP-3 levels we evaluated whether IGFBP-3 proteolytic degradation has occurred in vivo prior to IB analysis: the relative intensities of the proteolytic fragments and that of the intact 38­42 Kd doublet were determined by densitometry and in vivo proteolysis calculated (ratio of IGFBP-3 30 Kd proteolytic fragment/IGFBP-3 30 Kd proteolytic fragment + intact IGFBP-3 doublet) and expressed as a percentage of a control serum. In s-JRA patients in vivo proteolysis of IGFBP-3 (146.1 ± 31.5%) was significantly higher (p > 0.005) than that of controls (120.6 ± 32.4%). Incubation of sera from s-JRA patients, but not from controls, with a target exogenous IGFBP-3 resulted in a marked IGFBP-3 proteolytic degradation that was inhibited by the addition of EDTA, or aprotinin. Our results show that patients with s-JRA have markedly reduced levels of intact IGFBP-3, that IGFBP-3 production is substantially normal and that the low levels of intact IGFBP-3 are caused by proteolytic degradation of IGFBP-3 by a serum protease.

Disclosure: work reported in this abstract was supported by:
Institutional support: IRCCS Pol. San Matteo.

Insulin-like growth factors and IGF binding proteins
Juvenile rheumatoid arthritis
Juvenile rheumatoid arthritis: pathophysiology

Abstract: 96
November 9, 1998
Poster Session A: Juvenile Rheumatoid Arthritis: Pathogenesis and Therapy
8:00-9:30 am, Hall B1/C

EARLY PREDICTORS OF POOR OUTCOME IN SYSTEMIC ONSET JUVENILE RHEUMATOID ARTHRITIS ¯ A MULTICENTER COHORT STUDY

L.R. Spiegel, R. Schneider, B.A. Lang, N. Birdi, E.D. Silverman, R.M. Laxer, B.M. Feldman

University of Toronto, Dalhousie University, and University of Ottawa, Canada


Background: A set of criteria that predicts destructive arthritis in children with SoJRA has been described (J Pediatr 1992; 120: 200­5). Our objective was to examine the ability of these criteria to predict poor functional outcome in a large, multicentre cohort of children with SoJRA.
Methods: All children with SoJRA, seen at onset since 1980 in Toronto, 1988 in Halifax, and 1991 in Ottawa were screened. To be eligible, patients had to have been seen 6 months following presentation, and followed for at least 2 years. Patients were divided into 4 cohorts - those followed for 2 to 4 years, 4 to 7 years, 7 to 10 years and >10 years. Children were classified as high or low risk based on data from their 6 month visit. High risk patients had active systemic disease (persistent fever or corticosteroid requirement for control of systemic disease) and a platelet count > 600 × 109/L. Poor outcome was defined as moderate or severe disability (defined as a >0.75 score on the Childhood Health Assessment Questionnaire), or death due to disease.
Results: Of 122 eligible patients with SoJRA, we were able to contact 111 (91%) for outcome data. Mean followup was 7.7 years (SD 3.7). The mean age at outcome assessment was 13.5 years (SD 5.3). There were 51 males and 60 females. Twenty-four patients (22%) had moderate to severe disability. Two patients died. These 26 patients were considered to have a bad outcome. We could determine risk classification data for 104 patients. Twenty-four (23%) met high risk criteria at 6 months. Overall, the risk of a poor outcome was significantly higher in the high risk group (relative risk = 3.3, p = 0.0004). The relative risk was similar in all 4 followup cohorts.
Conclusions: Active systemic disease at 6 months - as characterized by fever or the need for corticosteroids, and thrombocytosis - strongly predicts the development of a poor functional outcome. Our study validates the previously developed SoJRA prognostic criteria.

Disclosure: work reported in this abstract was supported by:
Dr. Feldman is supported by a Ministry of Health Career Scientist Award.

Juvenile rheumatoid arthritis
Prognostic factors and predictors of therapeutic response
Outcomes research

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