Infection-Related Death among Persons with Refractory Juvenile Idiopathic Arthritis.

Severe infections are emerging as major risk factors for death among children with juvenile idiopathic arthritis (JIA). In particular, children with refractory JIA treated with long-term, multiple, and often combined immunosuppressive and antiinflammatory agents, including the new biological disease-modifying antirheumatic drugs (DMARDs), are at increased risk for severe infections and death. We investigated 4 persons with JIA who died during 1994-2013, three of overwhelming central venous catheter-related bacterial sepsis caused by coagulase-negative Staphylococus or α-hemolytic Streptococcus infection and 1 of disseminated adenovirus and Epstein-Barr virus infection). All 4 had active JIA refractory to long-term therapy with multiple and combined conventional and biological DMARDs. Two died while receiving high-dose systemic corticosteroids, methotrexate, and after recent exposure to anti-tumor necrosis factor-α biological DMARDs, and 2 during hematopoietic stem cell transplantation procedure. Reporting all cases of severe infections and especially deaths in these children is of paramount importance for accurate surveillance.

Delineating the role of multiple intraarticular corticosteroid injections in the management of juvenile idiopathic arthritis in the biologic era.

OBJECTIVE: To investigate the outcome and predicting factors of multiple intraarticular corticosteroid (IAC) injections in children with juvenile idiopathic arthritis (JIA). METHODS: The clinical charts of patients who received their first IAC injection in ≥3 joints between January 2002 and December 2011 were reviewed. The corticosteroid used was triamcinolone hexacetonide for large joints and methylprednisolone acetate for small or difficult to access joints. In each patient, the followup period after IAC injection was censored in case of synovitis flare or at the last visit with continued remission. Predictors included sex, age at disease onset, JIA category, antinuclear antibody (ANA) status, age and disease duration, disease course, general anesthesia, number and type of injected joints, acute-phase reactants, and concomitant systemic medications. RESULTS: A total of 220 patients who had 1,096 joints injected were included. Following IAC therapy, 66.4% of patients had synovitis flare after a median of 0.5 years, whereas 33.6% of patients had sustained remission after a median of 0.9 years. The cumulative probability of survival without synovitis flare was 50.0%, 31.5%, and 19.5% at 1, 2, and 3 years, respectively. On Cox regression analysis, positive C-reactive protein value, negative ANA, lack of concomitant methotrexate administration, and a polyarticular (versus an oligoarticular) disease course were the strongest predictors for synovitis flare. CONCLUSION: Multiple IAC injection therapy induced sustained remission of joint synovitis in a substantial proportion of patients. A controlled trial comparing multiple IAC injection therapy and methotrexate versus methotrexate and a tumor necrosis factor antagonist is worthy of consideration.

Adalimumab: long-term safety in 23 458 patients from global clinical trials in rheumatoid arthritis, juvenile idiopathic arthritis, ankylosing spondylitis, psoriatic arthritis, psoriasis and Crohn's disease.

BACKGROUND: As long-term treatment with antitumour necrosis factor (TNF) drugs becomes accepted practice, the risk assessment requires an understanding of anti-TNF long-term safety. Registry safety data in rheumatoid arthritis (RA) are available, but these patients may not be monitored as closely as patients in a clinical trial. Cross-indication safety reviews of available anti-TNF agents are limited. OBJECTIVE: To analyse the long-term safety of adalimumab treatment. METHODS: This analysis included 23 458 patients exposed to adalimumab in 71 global clinical trials in RA, juvenile idiopathic arthritis, ankylosing spondylitis (AS), psoriatic arthritis, psoriasis (Ps) and Crohn's disease (CD). Events per 100 patient-years were calculated using events reported after the first dose through 70 days after the last dose. Standardised incidence rates for malignancies were calculated using a National Cancer Institute database. Standardised death rates were calculated using WHO data. RESULTS: The most frequently reported serious adverse events across indications were infections with greatest incidence in RA and CD trials. Overall malignancy rates for adalimumab-treated patients were as expected for the general population; the incidence of lymphoma was increased in patients with RA, but within the range expected in RA without anti-TNF therapy; non-melanoma skin cancer incidence was raised in RA, Ps and CD. In all indications, death rates were lower than, or equivalent to, those expected in the general population. CONCLUSIONS: Analysis of adverse events of interest through nearly 12 years of adalimumab exposure in clinical trials across indications demonstrated individual differences in rates by disease populations, no new safety signals and a safety profile consistent with known information about the anti-TNF class.

[Stem cell treatment of autoimmune disease]. / Stammzelltherapie bei Autoimmunerkrankungen.

Over 1,500 patients world wide have received a hematopoietic stem cell transplant (HSCT) as treatment for a severe autoimmune disease. Most of these have been autologous and mostly have occurred in the past 15 years. Over 1,000 of these have been registered in the European Group for Bone Marrow Transplantation (EBMT) and European League Against Rheumatism (EULAR) combined data base. A recent retrospective analysis of 900 patients (1) showed that the majority had multiple sclerosis (n = 345) followed by systemic sclerosis (n = 175), systemic lupus erythematosus (n = 85), rheumatoid arthritis (n = 89), juvenile idiopathic arthritis (n = 65) and idiopathic cytopenic purpura (n = 37). An overall 85 % 5-year-survival and 43 % progression-free survival was seen, with 100-day-transplant-related-mortality (TRM) ranging between 1 % (rheumatoid arthritis) and 11 % (systemic lupus erythematosus and juvenile idiopathic arthritis). Around 30 % of patients in all disease subgroups had a complete response, often durable despite full immune reconstitution. In many, e. g. systemic sclerosis, morphological improvement such as reduction of skin collagen and normalisation of microvasculature was documented, beyond any predicted known effects of intense immunosuppression alone. The high TRM was in part related to conditioning intensity, comorbidity and age, and the final risk/benefit assessment will be made after the results of the three randomised propective clinical trials are known. [nl]Recently, multipotent mesenchymal stromal cells have been tested in various autoimmune diseases, exploiting their immune modulating properties and apparent low acute toxicity. Despite encouraging small phase I/II studies, no positive data from randomised, prospective studies are as yet available in the peer reviewed literature.

Survival rates of children with acute lymphoblastic leukemia presenting to a pediatric rheumatologist in the United States.

BACKGROUND: Approximately 30% of pediatric acute lymphoblastic leukemia patients present with musculoskeletal symptoms and are often referred first to a pediatric rheumatologist. We examined the survival and causes of death of these patients presenting to a pediatric rheumatologist and compared the rates with that reported in the hematology-oncology literature. PROCEDURE: We used the Pediatric Rheumatology Disease Registry, including 49,023 patients from 62 centers, newly diagnosed between 1992 and 2001. Identifiers were matched with the Social Security Death Index censored for March 2005. Deaths were confirmed by death certificates, referring physicians, and medical records. Causes of death were derived by chart review or from the death certificate. RESULTS: There were 7 deaths of 89 patients (7.9%, 95% confidence interval: 3.9%-15.4%) with acute lymphoblastic leukemia with a 5-year survival rate of 95.5% (88.3 to 98.3) and 10-year survival rate of 89.8% (79.0% to 95.2%). The causes of death were sepsis (bacterial and/or fungal) in 4 (57%) patients, the disease in 2 (29%) and post bone-marrow transplantation in 1 (14%). CONCLUSION: The overall survival of patients with acute lymphoblastic leukemia seen first by pediatric rheumatologists is higher than the range reported in the pediatric oncology literature for the same period of diagnosis.

Mortality outcomes in pediatric rheumatology in the US.

OBJECTIVE: To describe mortality rates, causes of death, and potential mortality risk factors in pediatric rheumatic diseases in the US. METHODS: We used the Indianapolis Pediatric Rheumatology Disease Registry, which includes 49,023 patients from 62 centers who were newly diagnosed between 1992 and 2001. Identifiers were matched with the Social Security Death Index censored for March 2005. Deaths were confirmed by death certificates, referring physicians, and medical records. Causes of death were derived by chart review or from the death certificate. Standardized mortality ratios (SMRs) and 95% confidence intervals (95% CIs) were determined. RESULTS: After excluding patients with malignancy, 110 deaths among 48,885 patients (0.23%) were confirmed. Patients had been followed up for a mean +/- SD of 7.9 +/- 2.7 years. The SMR of the entire cohort was significantly decreased (0.65 [95% CI 0.53-0.78]), with differences in patients followed up for > or =9 years. The SMR was significantly greater for systemic lupus erythematosus (3.06 [95% CI 1.78-4.90]) and dermatomyositis (2.64 [95% CI 0.86-6.17]) but not for systemic juvenile rheumatoid arthritis (1.8 [95% CI 0.66-3.92]). The SMR was significantly decreased in pain syndromes (0.41 [95% CI 0.21-0.72]). Causes of death were related to the rheumatic diagnosis (including complications) in 39 patients (35%), treatment complications in 11 (10%), non-natural causes in 25 (23%), background disease in 23 (21%), and were unknown in 12 patients (11%). Rheumatic diagnoses, age at diagnosis, sex, and early use of systemic steroids and methotrexate were significantly associated with the risk of death. CONCLUSION: Our findings indicate that the overall mortality rate for pediatric rheumatic diseases was not increased. Even for the diseases and conditions associated with increased mortality, mortality rates were significantly lower than those reported in previous studies.

Childhood acute lymphoblastic leukemia presenting with osteoarticular syndrome--characteristics and prognosis.

UNLABELLED: Children with leukemia often present with osteoarticular syndrome as a first complaint thus mimicking juvenile idiopathic arthritis. The objective of the present study was to determine the frequency of osteoarticular syndrome at the onset of acute lymphoblastic leukemia in childhood, the clinical and laboratory specificity of such patients and the prognostic value of osteoarticular syndrome as an initial symptom. PATIENTS AND METHODS: We studied 60 children with acute lymphoblastic leukemia at a mean age of 5 +/- 0.5 years between February 2002 and October 2007. RESULTS: Osteoarticular syndrome was present as an initial symptom of leukemia in 18 (30.5%) patients. The oligoarticular involvement was prevalent--in 8 children (44%). Middle-sized joints were affected more commonly--in 10 patients (55.6%), followed by large joints and spine. Laboratory results in patients with osteoarticular syndrome show more often normal or slightly decreased platelet count, higher values of lactate dehydrogenase and rarely--leukocytosis (> 20 x 10(9)/l). Parablasts in the blood film were detected in 13 children (72.2%) with osteoarticular syndrome. Event-free survival in patients with osteoarticular syndrome is comparable to that of the remaining group of acute lymphoblastic leukemia patients. In conclusion we point out that there should be frequent blood tests in children with osteoarticular syndrome and timely bone marrow biopsy in cases with atypical signs of juvenile arthritis.

Autologous T cell depleted haematopoietic stem cell transplantation in children with severe juvenile idiopathic arthritis in the UK (2000-2007).

UNLABELLED: As part of collaborative multi-centre study started in 2000, 7 children in the UK fulfilled the inclusion criteria for treatment with autologous T cell depleted (TCD) haematopoietic stem cell transplantation (HSCT) for severe juvenile idiopathic arthritis (JIA). Here we report on the outcome and transplant-related complications. OUTCOME: The initial, often dramatic clinical response in all patients was followed in 4 with sustained benefit, including the withdrawal of immunosuppressive and anti-inflammatory treatment, significant catch-up growth and immense improvement of the quality of life during 5-8 years long follow-up. Two patients relapsed within 1-12 months, and one died 4 months post transplant. COMPLICATIONS: Adenovirus reactivation with dissemination was lethal in one patient, whilst Epstein-Barr (EBV) and cytomegalovirus (CMV) reactivation-driven haemophagocytic syndrome responded to antiviral and immunomodulatory treatment in 2 patients. Both the conditioning and the T cell depletion of the graft, leading to severe immunosuppression and prolonged immune system function reconstitution, are the main predisposing factors for potentially life-threatening transplant-related complications. CONCLUSIONS: Autologous TCD HSCT for children with severe JIA results in two-phase response. The initial remission seen in all patients is due to immunosuppressive conditioning. This is followed by sustained drug-free remission in over 50% of patients, which is due to 'immunomodulatory' effects of TCD HSCT. The procedure carries a significant morbidity and mortality risk. However, this risk should be balanced against the risks of life-threatening infections occurring in this very selective group of patients on long-term and combined immunosuppressive and anti-inflammatory therapies. How to correctly identify and appropriately assess the patients in need for autologous TCD HSCT, particularly in relation to optimizing the timing for the procedure in regards to the newly available therapies with different biologic response modifiers, are some of the most important questions awaiting answers from this on-going study.

[Current value of stem-cell transplantation in autoimmune diseases]. / Aktueller Stellenwert der Stammzelltransplantation bei Autoimmunerkrankungen.

Transplantations of autologous or allogeneic stem cells from bone marrow or peripheral blood are preformed for the treatment of resistant autoimmune diseases. Data have been systematically collected since 1996. We describe the historical development of this procedure for autoimmune diseases, the possible mechanisms of action, the options for stem cell collection, purging and conditioning (high-dose chemotherapy, combination with monoclonal anti-T- or B-cell antibodies, total body irradiation), as well as the reported outcomes in the literature.

Autologous stem cell transplantation in autoimmune diseases.

Since 1996, approximately 1,000 patients have received an autologous hematopoietic stem cell transplant (HSCT) as treatment for a severe autoimmune disease (AD). The European Group for Blood and Marrow Transplantation (EBMT)/European League Against Rheumatism (EULAR) Autoimmune Disease Working Party have registered more than 800 patients and works in close collaboration with networks in the United States where several hundred more AD patients have been similarly transplanted. The majority of ADs were multiple sclerosis (MS), systemic sclerosis (SSc), systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), juvenile idiopathic arthritis, and immune cytopenias. Many patients have experienced long-term disease-free remissions and immune reconstitution studies have shown in some cases that a "resetting" of autoimmunity is possible. The initially high treatment-related mortality (TRM) is reduced significantly in the later years, and the phase I/II experience is now being verified in several international prospective randomized clinical trials. In addition, the past several years have seen a growing interest in the role and potential therapeutic application of mesenchymal stem cells (MSC) in the immunomodulation of AD, as in the early experience with acute-graft-versus host disease (GvHD).

Remission status follow-up in children with juvenile idiopathic arthritis

OBJETIVO: Caracterizar a atividade inflamatória articular e sistêmica na artrite idiopática juvenil (AIJ), determinando o estado de remissão com e sem uso de medicação. MÉTODOS: Um total de 165 casos de AIJ, acompanhados em média por 3,6 anos, foram revisados para caracterização de episódios de inatividade, remissão clínica com e sem medicação. Os dados obtidos foram analisados por meio de estatística descritiva, análise de sobrevida, comparação das curvas de Kaplan-Meier, teste de log rank e análise de regressão logística binária para determinação de fatores preditivos para a remissão ou atividade persistente. RESULTADOS: Dos casos revisados, 108 preencheram os critérios de inclusão: 57 pacientes (52,7 por cento) apresentaram um total de 71 episódios de inatividade, com 2,9 anos em média para cada episódio; 36 episódios (50,7 por cento) de inatividade resultaram em remissão clínica sem medicação, sendo 35 por cento do subtipo oligoarticular persistente. A probabilidade de remissão clínica com medicação em 2 anos foi de 81, 82, 97 e 83 por cento para casos de AIJ oligoarticular persistente, oligoarticular estendida, poliarticular e sistêmica, respectivamente. A probabilidade de remissão clínica sem medicação em 5 anos após o início da remissão foi de 40 e 67 por cento para pacientes com AIJ oligoarticular persistente e sistêmica, respectivamente. Houve associação significante da atividade persistente com o uso combinado de medicações para artrite. A idade de início da AIJ foi o único fator preditivo para remissão clínica (p = 0,002). CONCLUSÃO: Nesta coorte, a probabilidade da AIJ evoluir para remissão clínica foi maior nos subtipos oligoarticular persistente e sistêmico, comparados ao curso poliarticular.

OBJECTIVE: To characterize articular and systemic inflammatory activity in juvenile idiopathic arthritis (JIA), identifying remission status with and without medication. METHODS: A total of 165 JIA cases, followed for a mean period of 3.6 years, were reviewed in order to characterize episodes of inactivity and clinical remission on and off medication. The resulting data were analyzed by means of descriptive statistics, survival analysis, by comparison of Kaplan-Meier curves, log rank testing and binary logistic regression analysis in order to identify predictive factors for remission or persistent activity. RESULTS: One hundred and eight of the cases reviewed fulfilled the inclusion criteria: 57 patients (52.7 percent) exhibited a total of 71 episodes of inactivity, with a mean of 2.9 years per episode; 36 inactivity episodes (50.7 percent) resulted in clinical remission off medication, 35 percent of which were of the persistent oligoarticular subtype. The probability of clinical remission on medication over 2 years was 81, 82, 97 and 83 percent for cases of persistent oligoarticular, extended oligoarticular, polyarticular and systemic JIA, respectively. The probability of clinical remission off medication 5 years after onset of remission was 40 and 67 percent for patients with persistent oligoarticular and systemic JIA, respectively. Persistent disease activity was significantly associated with the use of an anti-rheumatic drug combination. Age at JIA onset was the only factor that predicted clinical remission (p = 0.002). CONCLUSIONS: In this cohort, the probability of JIA progressing to clinical remission was greater for the persistent oligoarticular and systemic subtypes, when compared with polyarticular cases.

Treatment of refractory autoimmune diseases with autologous stem cell transplantation: focus on juvenile idiopathic arthritis.

Autologous stem cell transplantation (ASCT) can be performed in a variety of refractory autoimmune diseases. A retrospective multicenter analysis is presented to evaluate safety and efficacy of ASCT for refractory juvenile idiopathic arthritis. In all, 18 of the 34 patients (53%) with a follow-up of 12 to 60 months achieved a drug-free complete remission. There were three cases (9%) of transplant-related mortality and two cases of disease-related mortality (6%). Infectious complications were seen frequently. We propose adjustments in future protocols to reduce this mortality in this high-risk patient group.

National study of cause-specific mortality in rheumatoid arthritis, juvenile chronic arthritis, and other rheumatic conditions: a 20 year followup study.

OBJECTIVE: To quantify risks for cause-specific mortality among hospitalized patients with rheumatoid arthritis (RA), juvenile chronic arthritis (JCA), and 4 other rheumatic conditions in a nationwide, population based cohort over a 20 year period. METHODS: All subjects were identified from Scottish hospital inpatient records from 1981 to 2000 and were followed up by computer linkage to the national registry of deaths. Expected mortality was calculated from national mortality rates and was related to the observed incidence by the standardized mortality ratio (SMR) and the corresponding 95% confidence interval (95% CI). RESULTS: Overall mortality was elevated in each of the 6 rheumatic conditions examined, most notably in JCA (males: SMR 3.4, 95% CI 2.0,5.5; females: SMR 5.1, 95% CI 3.2,7.8). Among patients with RA, there was an increased risk for death in all International Classification of Disease chapters other than those relating to mental disorders. Specific causes of death with an increased risk for subjects with RA included lung cancer [males: 1.4 (1.2,1.5); females: 1.6 (1.5,1.8)], hematopoietic malignancies [M: 1.8 (1.4,2.3); F: 2.0 (1.7,2.3)], coronary artery disease (CAD) [M: 1.6 (1.5,1.7); F: 1.95 (1.9,2.0)], respiratory infections [M: 1.9 (1.7,2.2); F: 2.4 (2.3,2.6)], chronic obstructive pulmonary disease [M: 1.8 (1.6,2.0); F: 2.1 (1.9,2.3)], and renal failure [M: 3.1 (2.5,3.9); F: 3.5 (3.0,4.0)]. Conversely, RA subjects were less likely to die from gastrointestinal tract malignancies [M: 0.82 (0.7,1.0); F: 0.8 (0.7,0.9)]. CONCLUSION: Population studies for primary data collection are required to extend our knowledge about the underlying mechanisms of early mortality in patients with rheumatic conditions.

Reactive haemophagocytic syndrome in children with inflammatory disorders. A retrospective study of 24 patients.

BACKGROUND: The reactive haemophagocytic syndrome (RHS) is a little-known life-threatening complication of rheumatic diseases in children. It reflects the extreme vulnerability of these patients, especially those with systemic-onset juvenile chronic arthritis (JCA). This immunohaematological process may be triggered by events such as herpes virus infection and non-steroidal anti-inflammatory drug therapy. Treatment has not been standardized. METHODS: We characterized this unusual disorder and determined its incidence by carrying out a retrospective study of patients identified over a 10-yr period in French paediatric units. RESULTS: Twenty-four cases (nine males, 15 females) were studied. Eighteen had typical systemic-onset JCA, two had polyarthritis, two had lupus and two had unclassifiable disorders. Clinical features at diagnosis included high spiking fever (24 patients), enlargement of the liver and spleen (14), haemorrhagic diathesis (six), pulmonary involvement (12) and neurological abnormalities (coma or seizures) (12). RHS was the first manifestation of systemic disease in three cases. Admission to intensive care was required in ten cases. Hypofibrinogenaemia, elevated liver enzymes and hypertriglyceridaemia were found consistently. Phagocytic histiocytes were found in 14 of 17 bone marrow smears. RHS was presumed to have been precipitated by infection in 11 cases (four Epstein-Barr virus, three varicella-zoster virus, one parvovirus B19, one Coxsackie virus, one Salmonella, one Pneumocystis carinii) and by the introduction of medication in three cases (Salazopyrin plus methotrexate; morniflumate; aspirin). Macrophage activation was indicated by high levels of monokines in the serum of two patients. Twenty patients had only one episode, three had an early relapse and one patient had two relapses. The treatment regimen was tailored to each child as the clinical course was variable. There was no response to intravenous immunoglobulins, which were used in four cases. Intravenous steroids at doses ranging from conventional to pulse methylprednisolone induced remission in 15 of 21 episodes when used alone as the first-line treatment. Cyclosporin A was consistently and rapidly effective, both when used as second-line therapy in all seven of the episodes in which steroids failed and in all five patients who received it as their first-line treatment. This supports a central role of T lymphocytes in the haemophagocytic syndrome. Two patients died. One patient with lupus died of congestive fulminant heart failure after 4 days, despite treatment with intravenous steroids and immunoglobulins, and one patient with systemic-onset JCA died from multiorgan failure despite aggressive therapy with pulsed steroids and etoposide. CONCLUSIONS: RHS may be a more common complication of systemic disease in childhood than previously thought. This life-threatening complication should be diagnosed promptly, as it calls for the immediate withdrawal of potentially triggering medications, anti-infective therapy when relevant, and urgent immunosuppressive treatment, measures that are very often effective. Cyclosporin A may be the drug of choice.

Chlorambucil in severe juvenile chronic arthritis: longterm followup with special reference to amyloidosis.

OBJECTIVE: To assess the effectiveness and side effects of chlorambucil therapy and patient outcome in juvenile chronic arthritis (JCA) treated with chlorambucil. METHODS: Followup of 79 consecutive patients with JCA refractory to previous therapy, in whom chlorambucil treatment was initiated from 1982 to 1995. Mean treatment duration was 7 months in 72 patients and more than 20 months in 6 patients with amyloidosis and 1 with severe iridocyclitis. RESULTS: Within 6 months, remission was attained in 41 patients (52%): 29 of these relapsed after a mean period of 2.5 years (range 0.3-8.3). Twenty-one (27%) patients did not respond. Seven out of 11 patients with secondary amyloidosis had proteinuria, which cleared completely in 4 and almost completely in 1. In 16 patients (20%) chlorambucil was stopped because of side effects, and in 1 because of infection. After a mean followup of 8.5 years, 14 patients (18%) were in complete remission without drugs, 34 (43%) had minor symptoms only, but 26 (33%) had limitations in daily activities. Five (6%) had died (2 of leukemia; 2 of infection, 0.5 and 3.3 years after withdrawal of chlorambucil; 1 of amyloidosis). CONCLUSION: Chlorambucil was found to be a very potent drug for JCA with acceptable short term, but serious longterm side effects. It may still be useful in JCA complicated by amyloidosis.

Dialysis treatment in patients with rheumatoid arthritis.

The results of dialysis treatment in 24 rheumatoid arthritis patients, 20 chronic rheumatoid arthritis (RA) and 4 juvenile rheumatoid arthritis (JRA), were analysed. Presence of secondary amyloidosis, renal function, morbidity and survival were examined. Amyloidosis was present in 13 patients. Especially among amyloidosis patients, renal function declined rapidly in the last year before dialysis started. On average, 63 days per patient-year were spent in the hospital, 58% was dialysis-related, mainly due to vascular access problems. Hospitalization was even more widespread in amyloidosis patients (79 days, 72% dialysis-related). Median survival in RA patients with amyloidosis was 11 months; in RA patients without amyloidosis this was 29 months. Two-year survival was only 1 out of 10 for the RA amyloidosis patients; for the RA non-amyloidosis patients this was 5 out of 6 (p < 0.01). Cardiovascular causes of death were most frequent. In conclusion, high morbidity and low survival make RA patients with amyloidosis a high-risk group on renal replacement therapy.

Adult onset Still's disease in northern India: comparison with juvenile onset Still's disease.

The present study compared the clinical and laboratory picture, the disease course and outcome in 31 patients having adult onset Still's disease (AOSD) with 23 patients having juvenile onset Still's disease (JOSD). The median age at disease onset was 20 and 7 yr for AOSD and JOSD patients, respectively. On analysing and comparing our data on these two groups, no significant differences emerged except that adults had a significantly lower time interval from disease onset to remission as compared to juveniles. Upon comparison of data on our AOSD patients with that published from abroad, rash, adenopathy and sore throat were less frequent. No clinical or laboratory variables were found to predict the subsequent disease course and outcome in either group. The functional outcome was good in about 70% of both groups and mortality was low. It is concluded that the clinical picture and outcome in AOSD is similar to that of JOSD.

Amyloidosis in juvenile chronic arthritis: a morbidity and mortality study.

A retrospective study of 79 juvenile arthritic patients with reactive amyloidosis for a mean of 10 years (3 months-24.25 years) from the onset of amyloidosis was performed. Eighty percent of those treated with chlorambucil (n = 57) were alive compared with 23.5% of patients not treated with chlorambucil (n = 19) 10 years after diagnosis. Renal failure was the cause of death in 82.3% and infection in 11.7%. Side effects included one chlorambucil-treated patient who developed acute leukaemia, and seven patients who developed severe leucopenia and four thrombocytopenia. Fifteen patients are no longer on cytotoxic therapy and are in remission. Analysis of their fertility status showed that there were 5 normal births in 3 women and 2 terminations of pregnancy in 23 chlorambucil-treated women of child bearing age. Six women had ovarian failure. None of the male patients fathered a child.

A nutritional screening test for use in children and adolescents with juvenile rheumatoid arthritis.

Protein-energy malnutrition (PEM) has been demonstrated in about 35% of patients with juvenile rheumatoid arthritis (JRA), but fewer than 8% of children with rheumatic diseases were reported in a national survey to have been seen by a pediatric dietitian. We demonstrate the development of a nutritional screening test for PEM in patients with JRA for use by all health care professionals. Nutritional assessment of 74 patients with JRA was conducted using a standardized 11 variable profile comprised of upper body anthropometric and biochemical measurements. The sensitivity, specificity, predictive values and index of validity were calculated for individual and selected clusters of nutritional variables to predict the need for referral for PEM compared to the independent review by 2 pediatric dietitians to refer or not refer to a dietitian for further evaluation or care. Arm circumference less than or equal to 10th percentile for age and sex matched norms was selected as the screening test for PEM in patients with JRA due to a combination of excellent measurement characteristics (sensitivity 0.80, specificity 0.86, positive predictive value 0.90, negative predictive value 0.73, index of validity 0.88) and ease of measurement.