Pure Red Cell Aplasia in Systemic Onset Juvenile Idiopathic Arthritis

Common causes of anemia in juvenile idiopathic arthritis are anemia of chronic disease and iron deficiency. We report a 4 year old boy with biopsy proven systemic onset juvenile idiopathic arthritis and severe anemia. Bone marrow aspiration revealed pure red cell aplasia without evidence of hemophagocytosis. This rare, unexplained but well known entity responded to corticosteroids.     

Validation of Classification Criteria of Macrophage Activation Syndrome in Japanese Patients With Systemic Juvenile Idiopathic Arthritis

Objective

To validate whether the 2016 American College of Rheumatology/European League Against Rheumatism classification criteria of macrophage activation syndrome (MAS) complicating systemic juvenile idiopathic arthritis (JIA) is practical in the real world.

Methods

A combination of expert consensus and analysis of real patient data was conducted by a panel of 15 pediatric rheumatologists. A total of 65 profiles comprised 18 patients with systemic JIA–associated MAS and 47 patients with active systemic JIA without evidence of MAS. From these profiles, 10 patient data points for full‐blown MAS, 11 patient data points for MAS onset, and 47 patient data points for acute systemic JIA without MAS were evaluated.

Results

Evaluation of the classification criteria to discriminate full‐blown MAS from acute systemic JIA without MAS showed a sensitivity of 1.000 and specificity of 1.000 at the time of full‐blown MAS. Sensitivity was 0.636 and specificity was 1.000 at the time of MAS onset. The number of measurement items that fulfilled the criteria increased in full‐blown MAS compared to that at MAS onset. At MAS onset, the positive rates of patients who met the criteria for platelet counts and triglycerides were low, whereas those for aspartate aminotransferase were relatively high. At full‐blown MAS, the number of patients who met the criteria for each measurement item increased.

Conclusion

The classification criteria for MAS complicating systemic JIA had a very high diagnostic performance. However, the diagnostic sensitivity for MAS onset was relatively low. For the early diagnosis of MAS in systemic JIA, the dynamics of laboratory values during the course of MAS should be further investigated.

     

Pulmonary Hypertension and Other Potentially Fatal Pulmonary Complications in Systemic Juvenile Idiopathic Arthritis

Objective

Systemic juvenile idiopathic arthritis (JIA) is characterized by fevers, rash, and arthritis, for which interleukin‐1 (IL‐1) and IL‐6 inhibitors appear to be effective treatments. Pulmonary arterial hypertension (PAH), interstitial lung disease (ILD), and alveolar proteinosis (AP) have recently been reported with increased frequency in systemic JIA patients. Our aim was to characterize and compare systemic JIA patients with these complications to a larger cohort of systemic JIA patients.

Methods

Systemic JIA patients who developed PAH, ILD, and/or AP were identified through an electronic Listserv and their demographic, systemic JIA, and pulmonary disease characteristics as well as their medication exposure information were collected. Patients with these features were compared to a cohort of systemic JIA patients enrolled in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) registry.

Results

The patients (n = 25) were significantly (P < 0.05) more likely than the CARRA registry cohort (n = 389) to be female; have more systemic features; and have been exposed to an IL‐1 inhibitor, tocilizumab, corticosteroids, intravenous immunoglobulin, cyclosporine, and cyclophosphamide. Twenty patients (80%) were diagnosed with pulmonary disease after 2004. Twenty patients (80%) had macrophage activation syndrome (MAS) during their disease course and 15 patients (60%) had MAS at pulmonary diagnosis. Sixteen patients had PAH, 5 had AP, and 7 had ILD. Seventeen patients (68%) were taking or recently discontinued (<1 month) a biologic agent at pulmonary symptom onset; 12 patients (48%) were taking anti–IL‐1 therapy (primarily anakinra). Seventeen patients (68%) died at a mean of 10.2 months from the diagnosis of pulmonary complications.

Conclusion

PAH, AP, and ILD are underrecognized complications of systemic JIA that are frequently fatal. These complications may be the result of severe uncontrolled systemic disease activity and may be influenced by medication exposure.     

Association between Serum Inflammatory Cytokines and Disease Activity in Juvenile Idiopathic Arthritis

Circulating interleukin-1β (IL-1β), IL-6, tumour necrosis factor-α (TNF-α), osteocalcin, and conventional parameters of inflammation were examined serially in 14 children with juvenile idiopathic arthritis (JIA) to determine any correlation with the disease activity. Serum IL-1β was undetectable in all JIA patients. Serum IL-6, white blood cell counts, platelet counts, erythrocyte sedimentation rate and C-reactive protein levels were significantly elevated in the active phase of JIA, whereas hemoglobin levels were significantly lower. Osteocalcin levels were decreased and TNF-α increased in active JIA status, but these differences showed no statistical significance. We concluded that inflammatory cytokines play an important role in JIA. Monitoring IL-6 in children with JIA is useful in determining disease activity and response to therapy. These findings confirm earlier reports. Received: 21 June 2000 / Accepted: 10 September 2001     

Effect of Biologic Therapy on Clinical and Laboratory Features of Macrophage Activation Syndrome Associated With Systemic Juvenile Idiopathic Arthritis

Objective

To assess performance of the 2016 macrophage activation syndrome (MAS) classification criteria for patients with systemic juvenile idiopathic arthritis (JIA) who develop MAS while treated with biologic medications.

Methods

A systematic literature review was performed to identify patients with MAS while being treated with interleukin (IL)‐1 and IL‐6 blocking agents. Clinical and laboratory information was compared to a large previously compiled historical cohort.

Results

Eighteen publications were identified, and after removing duplicates, 35 patients treated with canakinumab and 49 patients with tocilizumab were available for analysis; 5 anakinra‐treated patients were excluded due to limited numbers. MAS classification criteria were less likely to classify tocilizumab‐treated patients as having MAS compared to the historical cohort or canakinumab‐treated patients (56.7%, 78.5%, and 84%, respectively; P < 0.01). Patients who developed MAS while treated with canakinumab trended towards lower ferritin at MAS onset than the historical cohort (4,050 versus 5,353 ng/ml; P = 0.18) but had no differences in other cardinal clinical or laboratory features. In comparison, patients who developed MAS while treated with tocilizumab were less likely febrile and had notably lower ferritin levels (1,152 versus 5,353 ng/ml; P < 0.001). Other features of MAS were more pronounced in patients treated with tocilizumab, including lower platelet counts, lower fibrinogen, and higher aspartate aminotransferase levels. Mortality rates for patients with MAS treated with tocilizumab or canakinumab were not significantly different from the historical cohort.

Conclusion

These findings show substantial alterations in MAS features that may limit utility of defined criteria for diagnosis of systemic JIA patients treated with biologic agents.

     

A Case Report of Successful Treatment With Plasma Exchange for Hemophagocytic Syndrome Associated With Severe Systemic Juvenile Idiopathic Arthritis in an Infant Girl

Abstract: An infantile case of hemophagocytic syndrome (HPS) with systemic juvenile idiopathic arthritis (s-JIA), refractory to methylprednisolone pulse therapy and cyclosporine A administration, was successfully treated by plasma exchange. The patient was a one-year-old Japanese girl who had developed recurrent steroid-dependent signs, including fever, skin eruption, and hepatopathy, while in France, where she had been diagnosed as having s-JIA at eight months of age. As a high fever and rheumatoid rash were evident on arrival at our hospital, she was admitted and given intravenous methylprednisolone pulse therapy and cyclosporine A. She developed pancytopenia with a generalized clonic seizure, high fever, and liver dysfunction after her cytomegalovirus (CMV) titer became positive during the course of treatment; therefore, she was treated with ganciclovir. She was subsequently diagnosed as having HPS complicating s-JIA from the findings of a bone marrow aspirate. At this time, her blood examination data including a high level of C-reactive protein and hyperferritinemia, suggested that her s-JIA was very active, and the pancytopenia continued after her CMV titer became negative. Therefore, CMV infection against a background of active s-JIA could have triggered the HPS in this case. Because the HPS was resistant to an immunosuppressive regime of methylprednisolone pulse therapy and cyclosporine A, plasma exchange therapy was started. After three sessions of this therapy, the patient's symptoms and laboratory data were markedly improved. Our experience suggests that plasma exchange should be considered as a therapeutic tool for HPS refractory to conventional therapy.     

Anakinra for Myocarditis in Juvenile Idiopathic Arthritis

A 20-year-old pregnant woman with a history of juvenile idiopathic arthritis presented with flu-like symptoms, systemic inflammation with myocarditis, and severe cardiomyopathy. Six weeks earlier, her chronic-arthritis therapy had been changed from anakinra, an interleukin-1β receptor antagonist, to etanercept. When she resumed taking anakinra, her condition improved dramatically, including a complete recovery of ventricular function.Myocarditis is a well-recognized complication of systemic vasculitides. This unusual case emphasizes the important pathophysiologic role of interleukin receptors in the successful treatment of myocarditis. We suggest that clinical cardiologists be aware of the therapeutic usefulness of biological agents such as anakinra in patients with rheumatic conditions.Key words: Anti-inflammatory agents/therapeutic use, antirheumatic agents/therapeutic use, arthritis, juvenile rheumatoid/complications/drug therapy, disease susceptibility, heart/drug effects, interferon-beta/therapeutic use, interleukin 1 receptor antagonist protein, myocarditis/diagnosis, treatment outcome, ventricular dysfunction, left/drug effectsCardiac involvement in chronic rheumatic conditions is well recognized and is possibly associated with higher cardiovascular morbidity and mortality rates. The cardiac manifestations include vasculitis, accelerated atherosclerosis, congestive heart failure, valvular abnormalities, pulmonary hypertension, conduction system abnormalities, pericarditis, and myocarditis. Immunologic mediators such as interleukin-1, tumor necrosis factor (TNF), and other cytokines play a key role in the pathophysiologic course of chronic rheumatic conditions and their cardiac manifestations. It is crucial to recognize cardiac abnormalities and to initiate anti-inflammatory therapies promptly. We describe the case of a young woman with a history of juvenile idiopathic arthritis who presented with myocarditis, and we discuss the outcome of her therapy with an interleukin-1β receptor antagonist.     

Pain Intensity Variability and Its Relationship With Quality of Life in Youths With Juvenile Idiopathic Arthritis

Objective

To describe variability of pain intensity experienced by youths with juvenile idiopathic arthritis (JIA) and examine factors related to within‐day patterns of pain and the relationship between magnitude of pain variability and quality of life.

Methods

Pain intensity was self‐reported on a visual analog scale (VAS; range 0–100) by 112 youths with JIA ages 8–18 years using electronic diaries 3 times per day for 7 days. Average absolute change in pain (AAC) was computed as a measure of the magnitude of pain variability for each participant. Logistic regression was used to examine the relationship between demographic and disease characteristics and the probability of having high pain variability (AAC ≥10 VAS units). Linear regression was used to examine the relationship between quality of life (assessed by the Pediatric Quality of Life Inventory) and AAC. The generalized estimating equations approach was used to examine the relationship between the time of day and pain intensity.

Results

The mean ± SD AAC was 15.6 ± 10.5. The majority of youths (65%) had high AAC (≥10 VAS units). Disease severity predicted high pain variability (β = 0.02, P = 0.044). Higher AAC predicted lower quality of life (adjusted R² = 0.194, β = ?0.59, P = 0.003). Within‐day patterns of pain intensity varied by JIA subtype and sex.

Conclusion

This study characterized the pain intensity variability experienced by youths with JIA. Pain variability throughout the day was common, varied by JIA subtype and sex, and was related to quality of life. These findings have implications for future pain research, patient education, and development of clinical interventions for this population.

     

Heading Toward a Modern Imaging Approach in Juvenile Idiopathic Arthritis

MR imaging and musculoskeletal ultrasound are expanding their utility in the assessment of patients with chronic inflammatory arthritis. These imaging techniques, by providing additional and more sensitive information over clinical examination and conventional radiographs, are promising tools for the diagnosis, prognosis and assessment of treatment efficacy in patients with juvenile idiopathic arthritis (JIA). Owing to the peculiarities of the growing skeleton, knowledge of imaging in healthy children is of high priority. A sound understanding of growth-related changes is of foremost value in establishing whether the apparent changes on joint surface reflect real damage or are actually part of normal development. This review explores current evidence and suggests a new workflow for imaging in JIA, in which conventional and modern imaging modalities can be integrated for optimal management.