Performance of the preliminary definition of improvement in juvenile chronic arthritis patients treated with methotrexate

OBJECTIVE—To investigate the performance of the core set of outcome measures and the preliminary definition of improvement (PDI) in the assessment of response to methotrexate (MTX) treatment in children with juvenile chronic arthritis (JCA).
METHODS—Data were obtained from an open label, non-controlled trial designed to investigate the efficacy of MTX in children with JCA. All patients had the core set of variables assessed at baseline and after six months of treatment. Variables in the core set are: (1) physician global assessment of disease activity; (2) parent or patient (if appropriate in age) global assessment of overall well being; (3) functional ability; (4) number of joints with active arthritis; (5) number of joints with limited range of motion; (6) erythrocyte sedimentation rate. The PDI specifies that to be classified as improved, a patient must show at least 30% improvement from baseline in three of any six variables in the core set, with no more than one of the remaining variables worsening by more than 30%.
RESULTS—A total of 111 JCA patients were included in the study. According to the PDI, after six months of MTX treatment 73 patients (66%) were classified as improved and 38 (34%) as not improved. Among the core set variables, parent assessment detected the highest percentage of patients improved (72%) and functional assessment the lowest (37%).
CONCLUSION—The PDI identifies about two thirds of patients with JCA treated with low dose MTX as improved. This proportion is similar to that expected to improve based upon a previous controlled study of low dose, oral MTX and provides preliminary evidence of the definition''s validity.

     

Pulmonary function in children with juvenile idiopathic arthritis and effects of methotrexate therapy

Summary Objective To evaluate impairment of lung function as an adverse effect associated with methotrexate therapy in patients with juvenile idiopathic arthritis (JIA). Methods We performed pulmonary function testing including diffusion capacity for carbon monoxide as measured by the single breath method (DLCO-SB) in 89 children with juvenile idiopathic arthritis. Forty (45%) were treated with methotrexate for a median of 24 months (range 3 to 120 months). Except for the presence of asthma in two children, there was no clinical or radiological evidence of pulmonary disease. Results Pulmonary function testing demonstrated moderate airway obstruction in two children with known bronchial asthma. Neither obstructive nor restrictive alteration of ventilation was found in any other patient. Two juvenile idiopathic arthritis patients showed a reduced CO diffusion capacity of 64 and 67%. One of them was treated with methotrexate. Conclusions With regard to lung function impairment treatment with low dose methotrexate appears to be safe even when performed for several years reaching a total amount of up to 3.5 g. In contrast to studies performed in adult rheumatoid arthritis patients, in children with juvenile idiopathic arthritis impairment of lung function is a rare event. Received: 23 February 2001 Accepted: 16 May 2001     

Mucolipidosis: A mimicker of juvenile idiopathic arthritis

Juvenile idiopathic arthritis is the most common form of chronic arthritis in children and at times misdiagnosed in those presenting with arthropathy secondary to non-inflammatory causes. The overlap of symptoms often pose a diagnostic challenge for clinicians. This mostly results in a delayed diagnosis subjecting children to unnecessary use of long-term immunosuppressants and disease-modifying drugs. We present the case of a 9-year-old boy who was previously misdiagnosed as a case of juvenile idiopathic arthritis. Detailed evaluation later led to the diagnosis of mucolipidosis (type III) which was confirmed on genetic testing. Emphasis on detailed history and clinical examination including the subtle hints like lack of signs of inflammation, family history, no morning stiffness and normal inflammatory markers should be picked up to make a timely diagnosis. In today's era of genetic testing and diagnosis, it is prudent to offer these tests for such patients to make an accurate diagnosis and prognosticate them for the long-term outcome.     

Unilateral pachydermodactyly misdiagnosed as juvenile idiopathic arthritis: A case report

Rationale:Pachydermodactyly is a rare, benign disease that can manifest in healthy adolescent boys as painless, spindle-shaped, soft-tissue swelling of the proximal interphalangeal joints in the hand. It is usually bilateral, with symmetrical joint enlargement. There are relatively few documented cases of pachydermodactyly worldwide, signifying either a low incidence or lack of recognition by physicians; therefore, its diagnosis is challenging.Patient concerns:A 16-year-old boy with a 3-year history of painless unilateral swelling of the proximal interphalangeal joints of his left hand was misdiagnosed with juvenile idiopathic arthritis and was treated with oral methotrexate for 1 year. He had a history of frequent finger cracking.Diagnosis:He had normal levels of inflammatory markers, including erythrocyte sedimentation rate and C-reactive protein. His autoantibody profile results were normal, and radiography of his hands showed soft tissue swelling with no bone abnormalities. Therefore, the patient was diagnosed with Parkinson disease.Interventions:Methotrexate was discontinued, and a skin biopsy was performed, which revealed hyperkeratosis in the epidermis with thick collagenous fibers in the dermis. Therefore, the patient was informed of the benign nature of the disease and was advised to stop cracking his fingers.Outcomes:After regular follow-up, there was no progression of the patient''s symptoms, and repeated blood tests revealed normal results.Lessons:Pachydermodactyly should be considered in the differential diagnosis of painless swelling in adolescent men with normal blood testing. Early recognition of this rare benign condition helps physicians appropriately reassure the patient and his parents without exposing them to unnecessary therapy.     

Clinical characteristics of influenza virus infection in juvenile idiopathic arthritis patients treated with tocilizumab

Background

Inhibition of interleukin-6 (IL-6) signaling by tocilizumab is highly effective for treatment of refractory juvenile idiopathic arthritis (JIA). It appears that IL-6 plays an important role in the immune response to the influenza virus, but it is not clear whether treatment with tocilizumab affects the severity of influenza.

Methods

We retrospectively collected clinical and laboratory data from JIA patients (n = 33) treated with tocilizumab. Ten patients who developed influenza (tocilizumab group; 10.1 %, 10/99 patient-years) were analyzed. Eleven JIA patients who experienced influenza during conventional treatments, without tocilizumab (control group), were compared with the tocilizumab group.

Results

Of the 10 patients in the tocilizumab group, 6 patients did not have high fever (>38 °C), and the other 4 febrile patients recovered from fever in 1 day. White blood cell counts and lymphocyte counts were significantly lower at the acute phase of infection compared with data from before influenza infection. The degree of fever and level of C-reactive protein in the tocilizumab group were significantly reduced compared with the control group.

Conclusions

IL-6 inhibition by tocilizumab reduced inflammation associated with infection and resulted in mild symptoms during influenza. Leukopenia might be a useful indicator of viral infection, including influenza, during tocilizumab treatment.     

Leukocytapheresis for the treatment of refractory systemic-onset juvenile idiopathic arthritis

Although leukocytapheresis (LCAP) has been reported to be effective for the treatment of various autoimmune disorders, little information has been published yet on the efficacy and safety of LCAP for the treatment of systemic-onset juvenile idiopathic arthritis (SOJIA). A pilot trial of LCAP was therefore conducted on two children with refractory SOJIA using a granulocyte apheresis filter packed with cellulose acetate beads in an attempt to control the disease flares. Following three to eight sessions of LCAP, the joint symptoms gradually resolved without any increase in the dose of corticosteroids. The procedure was associated with a decrease in the serum interleukin-6. No severe adverse effects were observed except for mild nausea. However, efficacy of LCAP sustained in a short time since both patients subsequently developed flares after 3 months of the treatment.     

A survey of foot problems in juvenile idiopathic arthritis

Background: Evidence suggests that foot problems are common in juvenile idiopathic arthritis (JIA), with prevalence estimates over 90%. The aim of this survey was to describe foot‐related impairment and disability associated with JIA and foot‐care provision in patients managed under modern treatment paradigms, including disease‐modifying anti‐rheumatic drugs (DMARDs) and biologic therapies. Methods: The Juvenile Arthritis Foot Disability Index (JAFI), Child Health Assessment Questionnaire (CHAQ), and pain visual analogue scale (VAS) were recorded in 30 consecutive established JIA patients attending routine outpatient clinics. Foot deformity score, active/limited joint counts, walking speed, double‐support time (s) (DS) and step length symmetry index % (SI) were also measured. Foot‐care provision in the preceding 12 months was determined from medical records. Results: Sixty‐three per cent of children reported some foot impairment, with a median (range) JAFI subscale score of 1 (0–3); 53% reported foot‐related activity limitation, with a JAFI subscale score of 1 (0–4); and 60% reported participation restriction, with a JAFI subscale score of 1 (0–3). Other reported variables were CHAQ 0.38 (0–2), VAS pain 22 (0–79), foot deformity 6 (0–20), active joints 0 (0–7), limited joints 0 (0–31), walking speed 1.09 m/s (0.84–1.38 m/s), DS 0.22 s (0.08–0.26 s) and SI ±4.0% (±0.2–±31.0%). A total of 23/30 medical records were reviewed and 15/23 children had received DMARDS, 8/23 biologic agents and 20/23 multiple intra‐articular corticosteroid injections. Ten children received specialist podiatry care comprising footwear advice, orthotic therapy and silicone digital splints together with intrinsic muscle strengthening exercises. Conclusion: Despite frequent use of DMARD/biologic therapy and specialist podiatry‐led foot care, foot‐related impairment and disability persists in some children with JIA. Copyright © 2008 John Wiley & Sons, Ltd.     

Safety and effectiveness of etanercept for treatment of juvenile idiopathic arthritis: Results from a postmarketing surveillance

Objectives: The objectives of this surveillance were to determine safety and effectiveness of etanercept in patients with juvenile idiopathic arthritis (JIA).

Methods: In this postmarketing surveillance, patients aged 5–16 years with active polyarthritis JIA were treated with etanercept at the doses approved in the Japanese package insert. The occurrence and seriousness of adverse events (AEs) were assessed using the Japanese Medical Dictionary for Regulatory Activities version 15.1. Effectiveness was determined as the improvement from baseline in disease activity score in 28 joints (DAS28)–erythrocyte sedimentation rate (ESR), remission, and physician’s assessment of overall improvement. The number of responders was expressed as a percentage. The last observation carried forward method was used to impute missing data.

Results: Safety analysis included 102 patients; 22 patients experienced 36 treatment-related AEs, three of which were unexpected. None of the AEs were deemed to need special safety warnings. Effectiveness analysis included 87 patients. At 24 weeks, 29/46 (63.0%) patients demonstrated either good or moderate response in DAS28-4/ESR and treatment was assessed to be markedly effective or effective by physicians in 79/83 (95.2%) patients.

Conclusions: These data are consistent with earlier reports showing that etanercept was effective and demonstrated no safety signals in patients with JIA.     

Interleukin-6 in juvenile idiopathic arthritis

Abstract

Juvenile idiopathic arthritis (JIA) is a chronic childhood arthritis. Its pathogenesis is very complicated, with the involvement of not only immune cells but various types of parenchymal cells, and is affected by both genetic and environmental predispositions. The clinical spectrum from inflammation to related conditions is largely mediated by cytokines including interleukin (IL)-6. Fluctuations in IL-6 and its related molecules can modulate the pathogenesis and the clinical presentation positively or negatively. The recent clinical impact of IL-6 blockade on JIA has begun a therapeutic paradigm shift. This review describes the characteristics of JIA, mainly focused on IL-6 with the current therapeutic perspective.     

Characteristics of FDG-PET findings in the diagnosis of systemic juvenile idiopathic arthritis

Objective: To examine and delineate inflammatory focus in patients with juvenile idiopathic arthritis (JIA), ¹⁸F-Fluoro-deoxy-glucose (FDG)-positron emission tomography (PET) (¹⁸F-FDG-PET) was applied to patients with JIA, and the images of these patients were compared.

Methods: Sixty-eight children (59 with systemic JIA (s-JIA) and 9 with polyarticular JIA) were included. The diagnosis of JIA was done to meet the International League of Associations for Rheumatology (ILAR) criteria. After 6-h fasting, whole-body positron emission tomography (PET) scans were acquired 60 min after intravenous injection of 3–5 MBq/kg ¹⁸F-FDG. The interpretation of ¹⁸F-FDG uptake was based on visual characteristics.

Results: Two types of PET images were outstanding in s-JIA; one was ¹⁸F-FDG uptake in red bone marrow, such as the spine, pelvis, and long bones as well as spleen (12 cases), and other type was the uptake in the major joints, such as hips, elbows, wrists, knees, and ankles (8 cases). The former findings were correlated with elevated levels of inflammatory markers, while the latter were with significantly increased levels of MMP-3 (p?<?0.05).

Conclusion: There was a noticeable accumulation of ¹⁸F-FDG uptake in bone marrow of s-JIA patients which may indicate the inflammatory focus of this disease and play an important role in the pathogenic basis of arthritis and systemic inflammation of s-JIA.