Infliximab efficacy and safety against refractory systemic necrotising vasculitides: long-term follow-up of 15 patients.

BACKGROUND: Results of uncontrolled studies have suggested that infliximab is efficacious against systemic necrotising vasculitides (SNV) refractory to conventional treatment. However, its safety and ability to induce and maintain remission over the long term remain unknown. OBJECTIVES: To report the use of infliximab to treat refractory SNV, focusing on patients' longer-term outcomes. METHODS: The medical charts of patients given adjunctive infliximab for refractory SNV >/=2 years before this evaluation were reviewed retrospectively. RESULTS: The 15 patients (median age 46 (range 20-69) years, median follow-up 35 (24-41) months) included 10 with Wegener's granulomatosis, 1 microscopic polyangiitis, 3 rheumatoid arthritis-associated and 1 cryoglobulinaemia-related vasculitides. Infliximab was taken for a median time of 8 (2-31) months; 2 patients are still being treated. By day 45, 11 patients had entered remission (Birmingham Vasculitis Activity Score (BVAS) = 0) and 4 others had responded (BVAS decrease >/=50%). Five patients achieved sustained remissions (>/=6 months, corticosteroids

Interleukin-1 receptor antagonist (anakinra) treatment in patients with systemic-onset juvenile idiopathic arthritis or adult onset Still disease: preliminary experience in France.

BACKGROUND: Anakinra treatment has been reported to be effective in some patients with systemic-onset juvenile idiopathic arthritis (SoJIA) or adult-onset Still disease (AoSD). OBJECTIVES: To assess the efficacy and the safety of anakinra treatment in SoJIA and AoSD. METHODS: SoJIA and AoSD patients were treated with anakinra (1-2 mg/kg/day in children, 100 mg/day in adults); we analysed its effect on fever, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels, numbers of swollen and tender joints, the assessment of disease activity (by physician and parent/patient) and pain (by parent/patient), and American College of Rheumatology (ACR) pediatric core set criteria for JIA activity. RESULTS: A total of 35 patients were included, 20 with SoJIA and 15 with AoSD. Their mean age (range) at the onset of treatment was 12.4 (3-23) and 38.1 (22-62) years, respectively; disease duration was 7.0 (1-16) and 7.8 (2-27) years, respectively. Active arthritis was present in all cases but one. Of the 20 SoJIA patients, 5 achieved ACR 50% improvement in symptoms (ACR50) response criteria at 6 months. Steroid dose had been decreased by 15% to 78% in 10 cases. A total of 11 of the 15 AoSD patients achieved at least a 50% improvement for all disease markers (mean follow-up: 17.5 (11-27) months). Steroids had been stopped in two cases and the dose was decreased by 45% to 95% in 12 patients. Two patients stopped anakinra due to severe skin reaction, and two patients due to infection: one visceral leishmaniasis and one varicella. CONCLUSION: Anakinra was effective in most AoSD patients, but less than half SoJIA patients achieved a marked and sustained improvement.

Clinical outcome in children with chronic recurrent multifocal osteomyelitis.

OBJECTIVE: To determine the clinical outcome of children with chronic recurrent multifocal osteomyelitis (CRMO). METHODS: We retrospectively reviewed clinical, biological and radiological data of children with CRMO at five French paediatric centres. Outcome data were obtained through review of hospital charts and questionnaires sent to all patients to assess disease activity and educational and vocational achievement. RESULTS: Forty patients were assessed (34 females and 6 males) with a median age at diagnosis of 11.5 yrs (range 2-17). Median number of initial bony lesions was 2 at onset, and 3.5 over disease course. Median time since diagnosis was 3.5 yrs (range 0.5-15) and median duration of active disease 2.7 yrs (range 0.5-13.5). Nine (22.5%) patients had psychological or physical sequelae. Twenty-nine children (72.5%) responded to the questionnaire. Twenty-six had no physical disability as judged by the HAQ 0-1, two had moderate disability (HAQ: 1-2) and one had severe disability (HAQ: 2-3). Seventeen patients (58.6%) had active disease at follow-up (after 6 months to 15 yrs since diagnosis) and continued to have pain (median value of visual analogue scale: 10/100). CRMO had interfered with patient's education in two cases. CONCLUSIONS: Clinical outcome of children with CRMO is generally good, but a sizeable proportion of patients have active disease at follow-up, and a minority of patients can have a severe and prolonged disease course despite intensive treatments. Further studies are required to determine predictive factors for severe disease.

[Laboratory studies in pediatric bone and joint infections]. / Marqueurs de l'inflammation et infection ostéoarticulaire.

The diagnosis of acute osteomyelitis and septic arthritis is a clinical one. Acute-phase reactants, such as white blood cell (WBC) count, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) are useful to help the clinicians at the time of initial diagnosis. The WBC count may be normal in up to 80 % of cases and it is not a reliable indicator. The ESR is elevated in 80 % of cases. CRP is elevated more than 80 % of cases. CRP rises rapidly within 48 hours of admission and returns to normal within a week after appropriate therapy. Its rapid kinetics is useful for follow-up of the response treatment. Patients who require surgical drainage procedures have prolonged time to normalization of CRP. PCT is a useful specific marker for predicting severe infection but its sensibility to detect bone and joint infections seems to be low.

A large national cohort of French patients with chronic recurrent multifocal osteitis.

OBJECTIVE: To document more fully the characteristics of chronic recurrent multifocal osteomyelitis (CRMO) in pediatric patients, to collect data on the outcomes and management of the disease, and to define prognostic factors. METHODS: One hundred seventy-eight patients were included (123 female patients and 55 male patients), with a mean ± SD age at diagnosis of 10.9 ± 2.9 years. Inclusion criteria were a diagnosis of CRMO, evidence of at least one lesion of osteitis confirmed by imaging, and development of the syndrome before age 18 years. RESULTS: Longitudinal clinical and imaging studies revealed that only 12 of 178 CRMO patients (7%) had unifocal lesions at the last medical visit. We were able to apply the clinical chronic nonbacterial osteomyelitis score to 110 of 178 patients (62%), which indicated that bone biopsy could have been avoided in 27 cases (25%). At the last medical visit, disease was in remission in only 73 of 171 patients (43%) (41% receiving therapy) after a mean ± SD of 47.9 ± 38.9 months; 44 of 171 patients (26%) experienced sequelae. Using cluster analysis, the CRMO cohort was separated into 3 homogeneous phenotypes (severe, mild, and intermediate). Patients with the severe phenotype had the worst prognosis. This group was entirely composed of male patients, most of whom had the multifocal form of CRMO and inflammatory syndrome. Patients with the mild phenotype had the best prognosis. This group was primarily composed of female patients with a unifocal form of CRMO and infrequent clavicle involvement and inflammatory syndrome. Patients with the intermediate phenotype had a good prognosis but greater reliance on treatment. This group primarily included female patients with multifocal lesions and inflammatory syndrome. CONCLUSION: This is the largest CRMO cohort described in the literature to date. Clinical evolution and imaging investigations confirmed the multifocal pattern of the disease. Three distinct subgroups of CRMO patients were distinguished, with very different prognoses.

Administration of methylprednisolone pulse in chronic arthritis in children.

The authors retrospectively evaluated the results of methylprednisolone pulse in 15 children with chronic arthritis (JRA - 13 cases, spondyloarthropathy - 2 cases). Methylprednisolone succinate was administered at a dosage of 700 mg/m2 by an I.V. infusion pump on 3 consecutive days. A dramatic clinical improvement was obtained in 12/15 cases at day 4. In 7 cases, multiple pulses (between 2 and 8 courses) were administered to obtain better control of the disease and a decrease in the daily dosage of corticosteroids. Only mild and transient side effects were observed; moreover, previous corticosteroid side effects (especially growth retardation) decreased. The duration of clinical benefit was between 2 weeks and 10 months. Disease modifying agents should always be associated with MP pulse therapy to obtain a prolonged response.

Complications of intra-articular injections of triamcinolone hexacetonide in chronic arthritis in children.

Intra-articular injections of triamcinolone hexacetonide (THA) are a useful therapy in JRA and HLA B 27 related arthritis (B 27 RA). Published data have indicated good results and few side effects. We evaluate here the frequency of occurrence of local side effects in 35 children with JRA (115 joints treated) and 13 children with B 27 RA (29 joints treated). With a mean follow up of 25 months in JRA and 18 months in B 27 RA, we observed 12 cases (8.3%) of subcutaneous tissue atrophy with local depigmentation (knees 5 cases, wrists 2 cases, ankles 3 cases, metatarsophalangeal joints 2 cases) and 7 cases (4.9%) of intra-articular calcifications all in the JRA group (wrists 3 cases, knees 2 cases, ankles 2 cases). Youth and joint size are possible predisposing factors for subcutaneous tissue atrophy and intra-articular calcification. Spontaneous improvement previously reported for these local side effects was not observed in our study. These results underline the necessity of discussing on a case by case basis whether intra-articular, non long-acting corticosteroid or THA are indicated. THA must be injected with a rigorous technique and with a dosage adapted to the articular volume.

Chronic hepatitis during rheumatoid arthritis.

Chronic hepatitis is infrequently reported in the course of RA (1.9%). We report 6 cases with such an association. The six patients were all female (mean age: 59.5 years) with typical RA (ACR criteria), and sicca syndrome in 5 cases. Chronic hepatitis always developed after the onset of RA (delay: 1 to 47 years). Laboratory findings revealed a mild increase of transaminases. Alkaline phosphatase were increased in 3 cases. Liver insufficiency was present in 4 cases and polyclonal hypergammaglobulinemia in 6 cases. Rheumatoid factors were detected in 5 cases; antinuclear antibodies and anti-smooth muscle antibodies were also detected in 5 cases. Histological examination of liver biopsy disclosed active chronic hepatitis in 5 cases (with cirrhosis in 3 cases) and persistent chronic hepatitis in 1 case. Steroid therapy was administered in 4 cases of active chronic hepatitis with clinical and biological improvement (18 months to 6 years follow-up). One patient died of gastric bleeding.

Induction of autoantibodies in refractory rheumatoid arthritis treated by infliximab.

OBJECTIVES: To investigate autoantibody induction in rheumatoid arthritis (RA) patients treated with infliximab. METHODS: We included 59 refractory RA patients treated with infliximab in combination with low-dose prednisone and methotrexate or leflunomide. We tested the sera of the patients for antinuclear antibodies (ANA), rheumatoid factor (RF), anti double-stranded DNA antibodies (anti dsDNA), anti-histone and anti-extractable nuclear antigen antibodies (aENA) at baseline and before infusion at weeks 6 and 30. Infliximab, initiated at a dose of 3 mg/kg, was increased to 5 mg/kg if insufficient improvement was observed after three infusions. RESULTS: At week 6, only the frequency of anti-histone IgM antibody-positive patients had significantly increased (19 vs 42%, p = 0.009). At week 30, the frequency of patients with ANA had increased from 29% to 69% (p < 0.001), that of patients with anti-dsDNA antibodies had increased from 0% to 3% for IgG (NS) and from 0% to 32% for IgM (p < 0.001); the frequency of antihistone IgG detection had increased from 22% to 32% (p = 0.04) and that of IgM detection, from 18% to 79% (p < 0.001). No lupus-like syndrome was observed. RF decreased significantly (87 IU to 52.5 IU, from baseline to week 30; p < 0.001). No significant difference was observed between the 16 non-responders and the responders, in terms of autoantibody status at baseline and changes with infliximab therapy. CONCLUSION: Infliximab therapy lead to the selective and delayed induction of autoantibodies. This induction was not associated with clinical symptoms until week 30 and did not differ between responders and non-responders.

The French version of the Childhood Health Assessment Questionnaire (CHAQ) and the Child Health Questionnaire (CHQ).

We report the results of the cross-cultural adaptation and validation into the French language of two health status instruments. The Childhood Health Assessment Questionnaire (CHAQ) is a disease specific instrument that measures functional ability in daily living activities in children with juvenile idiopathic arthritis (JIA). The Child Health Questionnaire (CHQ) is a generic health related quality of life instrument designed to capture the physical and psychosocial well-being of children independently from the underlying disease. Five hundred children were enrolled including 306 patients with JIA classified into systemic (23%), polyarticular (22%), extended oligoarticular (25%), and persistent oligoarticular (30%) subtypes, and 194 healthy children. Both instruments were reliable with intra-class correlation (ICC) coefficients for the test-retest procedure of 0.91 for the CHAQ, and 0.87 and 0.89 for the physical and psychosocial summary scores of CHQ, respectively. Agreement between parents and children evaluated for the CHAQ was high with an ICC of 0.89 for the disability index; weighted kappa coefficients for the 8 domains ranged from 0.61 to 0.72. Convergent validity was demonstrated by significant correlations with the JIA core set of variables (physician and parent global assessment, scores for active joints and joints with limited range of motion, erythrocyte sedimentation rate) for both instruments. Both CHAQ and CHQ discriminated between healthy and JIA children, but only the disease specific CHAQ questionnaire discriminated clearly between the 4 JIA subtypes. In conclusion, the French versions of the CHAQ and the CHQ are reliable, and valid health assessment questionnaires to be used in children suffering from JIA.

Overview of the radiology of juvenile idiopathic arthritis (JIA).

Plain films remain the basic tool for diagnosis and follow-up evaluation of juvenile idiopathic arthritis (JIA). In this paper, we review the new classification of JIA: systemic arthritis. oligoarthritis (persistent), oligoarthritis (extended), polyarticular arthritis (rheumatoid factor negative), polyarticular arthritis (rheumatoid factor positive), enthesitis-related arthritis, psoriatic arthritis and unclassified arthritis. We will also review regional abnormalities of three stages: an early stage, an intermediate stage, a late stage, as well as the differential diagnosis.

Postpartal sacral fracture without osteoporosis.

Stress fractures of the sacrum during pregnancy or the postpartum seem uncommon. We report a new case of nontrauma-related postpartal sacral fracture. Only four similar cases have been reported to date. The patient was 36 years of age and her fracture was diagnosed four weeks after her first delivery. Vitamin D levels were low, but there was no osteomalacia. Other standard laboratory tests were normal, as were absorptiometry measurements at the lumbar spine and femur. Rheumatologists should consider sacral fracture in pregnant or nursing patients with buttock pain. Magnetic resonance imaging is the diagnostic investigation of choice.

Chronic recurrent multifocal osteomyelitis: five-year outcomes in 14 pediatric cases.

OBJECTIVE: To determine the clinical presentation and outcomes of chronic recurrent multifocal osteomyelitis (CRMO) in pediatric patients. PATIENTS AND METHODS: Ten girls and four boys were followed up between 1993 and 1999 for CRMO diagnosed on the basis of radiographic bone lesions with, at the same sites, increased radionuclide uptake, negative microbiological specimens, and histological evidence of nonspecific osteomyelitis. RESULTS: Mean age at CRMO was 9.6+/-3.4 years, mean disease duration was 5.3+/-2.5 years, and mean number of flares per patient was 5.9+/-3.7. Thirty-four percent of lesions were in the metaphyses of the lower limb bones, 14% in the pelvis, and 13% in the chest wall (with clavicular lesions in four patients). Three patients had skin lesions (psoriasis in two and palmoplantar pustulosis in one). Eight patients received antibiotic therapy, for 2 months at the most, to no advantage in the short term. Nonsteroidal anti-inflammatory drugs were used in all 14 patients and glucocorticoid therapy in four. Sulfasalazine was used in five patients, to good effect in four. Mean follow-up was 5.3+/-2.5 years. At last follow-up, eight patients had active disease, including one with synovitis and one with Takayashu's disease. CONCLUSION: As compared to SAPHO syndrome, skin lesions and chest wall involvement are less common in CRMO. The long-term prognosis is guarded: in our study only six of 14 patients were in remission at last follow-up.

[Fibroblastic rheumatism: a case report]. / Rhumatisme fibroblastique: à propos d'un cas.

UNLABELLED: Fibroblastic rheumatism is a rare entity. Nineteen cases were reported in the literature, and among them, only one in a child. CASE REPORT: Cam. (born August 19, 1988) had an onset of disease in October 1996 with nodules on the MCP and PIP, elbows and tibia, with partial improvement after three months. In April 1997, she suffered from arthralgia and stiffness of both wrists, and then of the big toes. X-rays showed destructive and erosive lesions on both wrists and on the PIP of the second and third fingers and the big toes. Laboratory investigations disclosed normal values for ESR and CRP and negative results for ANA and RF. The diagnosis of fibroblastic rheumatism was based on the typical histologic pattern of a nodule. The treatment associated colchicin and rehabilitation. In August 1998, the wrists' stiffness began to improve, though the big toes remained totally stiff. The radiologic erosive lesions did not show progress. COMMENTS: The diagnosis of fibroblastic rheumatism is based on the histologic pattern of the nodules. The erosive evolution of the arthropathies is infrequent (8/15 cases in adults). Juvenile onset is very rare; only one case has been reported, in a 10-year-old boy. The mechanism of the disease remains unknown. As it is very rare, the therapeutic strategies are not well established. CONCLUSION: This disease should be considered among the causes of juvenile arthritis with erosion.

[Idiopathic juvenile osteoporosis: a new observation]. / Ostéoporose juvénile idiopathique: une nouvelle observation.

UNLABELLED: Idiopathic juvenile osteoporosis is a rare form of bone demineralization which occurs during childhood. The mechanism of disease remains unknown. We report a new case which illustrates the main difficulties of diagnosis and treatment. CASE REPORT: A 7 year old girl was admitted because of painful disability of her lower limbs. Diagnosis was based on radiological signs, total bone density and bone histologic pattern. Plasma levels of calcium, phosphorus, alkaline phosphatases, 25-OH D3 and parathormone were within the normal range value. Other diseases associated with bone demineralization, such as enteric malabsorption, endocrine or tumoral diseases, were excluded. Recovery occurred after some months of treatment with calcium, vitamin D and rehabilitation, but we could not establish a clear causal relationship. CONCLUSION: The relative role of increased bone resorption or defective osteoblast function remain to be discussed. Recovery often occurs with or without treatment, but sequelae can lead to disability.

[Chronic recurrent multifocal osteomyelitis in children]. / Ostéite chronique multifocale récurrente de l'enfant.

We have studied retrospectively a series of 10 children presenting with chronic multifocal osteomyelitis (8 girls, 2 boys, 7 to 16 years). All patients had plain films, bone scintigraphies and histological studies. Three had CT scan and/or MRI. compared with literature data, we observed only one case of palmoplantar pustulosis and only 2 cases of lysis of the medial extremity of the clavicle; in addition, we report one case of lateral extremity of the clavicle and 2 vertebral locations. The radiological pattern was typical: at the beginning of the disease, plain films showed lytic areas which became progressively osteosclerotic with enlargement of the bone. In all the cases, bone scintigraphy revealed high uptake areas which were often infraclinical. The diagnosis was delayed from 3 months to 3 years. This emphasizes the difficulty of the diagnosis which relies on the association of clinical, biological and radiological elements. Biopsies are required to rule out an infectious bacterial osteomyelitis or a tumoral process. The pathogenesis of OCMR remains unknown, but the relation with the SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis) syndrome is general accepted because of the similar features of the osteitis. The long term follow up appears to be uncertain 6 of our patients are still symptomatic after five years despite anti inflammatory treatment.

[Juvenile spondylarthropathy]. / Spondylarthropathie juvénile.

EPIDEMIOLOGY: Juvenile spondylarthropathy accounts for about 20% of all cases of chronic juvenile idiopathic arthritis. The spondyloarthropathy concept includes chronic inflammatory rheumatic conditions involving the spine, peripheral joints, and tendon insertions. There is an HLA B27 linkage and the condition predominates in boys, mean age 11 years. CLINICAL PRESENTATION: The usual clinical signs are asymmetrical involvement of the joints of the lower limbs associated in 30 to 50% of the cases with enthesiopathy. The diagnosis is based on the B Amor criteria and ESSG. The clinical course follows an episodic pattern in 80% of the cases. TREATMENT: Nonsteroidal antiinflammatory drugs and local care are used. Sulfasalazine can be useful but its efficacy has not been proven. The functional prognosis is relatively good; spinal ankylosis is uncommon and hip involvement (destructive coxitis) occur in 30% of patients. About 80% of the patients have minor or no disability after a 10-year course.

[Treatment of Felty's syndrome accompanied by agranulocytosis using high-dose corticoids. 3 cases]. / Traitement du syndrome de Felty avec agranulocytose par assauts cortisoniques. Trois cas.

Three cases of severe Felty's syndrome (neutrophils 80/mm3 in 2 cases and 800/mm3 in one) with enlarged spleen (1 case) and leg ulcer (2 cases) were treated with high doses of corticosteroids (methylprednisolone 1 g by intravenous infusion over 3 hours, on 3 consecutive days). In all 3 patients a dramatic result was obtained, the granulocytes returning to normal values in 24 to 48 hours. In 2 cases, an early relapse (1 month) required a second course in high dosage; after a follow-up of 36 and 8 months respectively, the number of granulocytes remains stable under prednisone 5 to 10 mg/day. The third patient was improved by one single course of infusions and remains stable after 18 months. It must be noted that one patient had previously been treated with plasma exchange and another with corticosteroids without any significant result.

[Spondylarthropathies in children]. / Spondylarthropathies de l'enfant.

The term juvenile spondylarthropathy is used for all the inflammatory articular diseases beginning before the age of 16 years and associating peripheral arthritis, enthesiopathy and sometimes spinal involvement, cutaneous or enteric manifestations. The disease occurs more often in boys (85% of cases) between the age of 10 and 12 years. A family history is found in a third of the cases and there is a close linkage to HLA B27 (85% of cases). Asymmetrical arthritis is mainly located on the lower limbs; spinal involvement (lumbar, dorsal spine or sacro-iliac joint) is rare at onset and may occur later. Enthesiopathies involve the calcaneus and the anterior tibial tuberosity. The diagnosis is easy with the usual set of criteria. Functional prognosis is usually good, except in severe cases with destructive hip involvement. Treatment is based on non steroidal anti-inflammatory drugs and/or local injections; long-term treatments (such as salazosulfapy-ridine) are sometimes useful in uncontrolled cases.

[Treatment of juvenile spondyloarthropathies with sulfasalazine]. / Traitement des spondyloarthropathies juvéniles par la sulfasalazine.

The efficacy and safety of sulfasalazine for the treatment of juvenile spondyloarthropathy were evaluated in an open study. Twenty-three patients (17 boys and 6 girls) with juvenile spondyloarthropathy inadequately controlled by nonsteroidal antiinflammatory therapy were given sulfasalazine in an average dosage of 39 mg/kg/d. After 3 months, 20 patients exhibited marked clinical improvement; of these 20, 14 discontinued or reduced their nonsteroidal antiinflammatory drug. Mean erythrocyte sedimentation rate fell significantly from 36.8 to 13.7 mm/h. After 12 months. 78% of the patients were in remission. Sulfasalazine was stopped in five patients of which none had evidence of disease relapse 6 to 12 months later. Side effects were infrequent: 2 patients had a skin rash requiring drug withdrawal and two developed mild neutropenia. These data suggest that sulfasalazine is an effective and safe second-line drug for the management of severe juvenile spondyloarthropathies.