Current perspectives of autologous stem cell transplantation for severe juvenile idiopathic arthritis

The majority of children with Juvenile Idiopathic Arthritis can nowadays be treated adequately. However despite the use of combinations of antirheumatic drugs, corticosteroids and the newer so called biologicals (blocking the TNF, Interleukin 1 or Interleukin 6 pathways) a proportion of children with arthritis remain resistant also to these therapies and suffer from a very severe, debilitating and potentially fatal disease. For such children autologous stem cell transplantation (ASCT) is successfully performed since 1997. Here we describe the long term outcome of the initial cohort of children with resistant Juvenile Idiopathic arthritis, treated with ASCT. The initial cohort of children was treated with a conditioning regimen containing Cyclophosphamide, anti thymocyte globulins and low dose Total Body irradiation. Overall favourable responses were seen, with a drug free remission rate of 50–55 %. In the more recent years late relapses were noted with lower percentages for drug free long term outcome. Special emphasis is given on 2 cases showing very late relapses, occurring after 7 and 9 years. The observed relapses are often less severe compared to the situation before SCT and can be treated successfully with conventional drugs in the majority of cases. More recently, ASCT was performed in 4 JIA children with a fludarabin containing regimen in stead of low dose TBI. With a 4 to 5 year follow up, these 4 patients are all in drug free full remission. Allogeneic transplant with an HLA matched family donor was reported in 2 JIA cases. Follow up of 1 and 3 year is sofar show clinical disease remission and tapering of medition. In conclusion, given the favourable long term outcome, SCT remains a valuable treatment option for children with drug resistant JIA.     

Proxy‐reported health‐related quality of life of patients with juvenile idiopathic arthritis: The pediatric rheumatology international trials organization multinational quality of life cohort study

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.     

Immunology in the medical practice.XXXII. Transplantation of autologous hematopoietic stem cells for treatment of refractory auto-immune diseases; preliminary favorable results with 35 patients

The objective of this study was to document the experiences in the first Dutch pilot studies of the effect of transplantation of autologous haematopoietic stem cells in patients with therapy-resistant autoimmune disease. The first results in 21 adults and 14 children are promising: remission of the disease was achieved in 13 patients, while in the others a significant reduction of disease activity was seen with a corresponding improvement of the quality of life. Infectious complications were frequently observed. Two children with systemic juvenile idiopathic arthritis developed a fatal infection-associated macrophage activation syndrome. Multicentre randomised studies are necessary to study the effects of autologous stem cell transplantation and modifications such as T-cell depletion.     

Clostridium difficile-associated reactive arthritis in two children

In adults, reactive arthritis (ReA) following Clostridium difficile-enterocolitis has been documented. In children, only one case of C. difficile-associated ReA has been reported. We now describe two other cases of ReA associated with C. difficile in children. The characteristics of ReA due to C. difficile appear to be similar in adults and children. Both children show polyarthritis after an episode of diarrhoea with positive stool cultures for C. difficile. Arthritis is asymmetrical with a self-limiting course. Nonsteroidal antiinflammatory drug (NSAID) therapy is sufficient. One case is remarkable because of its prolonged course of ReA despite NSAID therapy, and its association with the presence of HLA-B27 antigen.     

Autologous hemopoietic stem-cell transplantation for children with refractory autoimmune disease

Autologous stem cell transplantation (ASCT) has been proposed as a possible treatment for severe autoimmune diseases such as rheumatoid arthritis (RA), multiple sclerosis (MS), systemic sclerosis, and systemic lupus erythematosus (SLE). To date, more than 250 patients with various autoimmune disorders have undergone an ASCT since 1996. Among them, there is a very limited number of children. This review summarizes the experience with ASCT for pediatric rheumatic diseases. Most reported cases concern juvenile idiopathic arthritis (JIA). Experience with ASCT for childhood SLE, Scleroderma, or Dermatomyositis is very limited. To date, 12 children with severe systemic or polyarticular JIA, all with progressive disease activity despite the use of corticosteroids, MTX, CsA, or Cyclophosphamide were treated in our center with ASCT. Rheumatologic follow-up at 3-month intervals up to 36 months showed a marked decrease in arthritis severity as expressed by the core-set criteria for juvenile chronic arthritis (JCA) activity. However, these children remain at risk for severe viral infections due to the prolonged lymfopenia. ASCT in this severely ill patient group induces a very significant and drug-free remission of the disease, but carries a significantly risk of developing fatal MAS.