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Otten M.H.,Sp 1546 | Prince F.H.M.,Erasmus MC Sophia Childrens Hospital | Twilt M.,Erasmus MC Sophia Childrens Hospital | Twilt M.,Leiden University | And 15 more authors.
Journal of Rheumatology | Year: 2011

Objective. To evaluate the effectiveness and safety of biological agents in children with enthe - sitis-related arthritis (ERA). Methods. All patients with ERA in whom a biological agent was initiated between 1999 and 2010 were selected from the Dutch Arthritis and Biologicals in Children (ABC) register. In this ongoing multicenter observational register, data on the course of the disease and medication use are retrieved prospectively at the start of the biological agent, after 3 months, and yearly thereafter. Inactive disease was assessed in accordance with the Wallace criteria. Results. Twenty-two patients with ERA started taking 1 or more biological agents: 20 took etanercept, 2 took adalimumab (1 switched from etanercept to adalimumab), and 2 took infliximab (1 switched from etanercept to infliximab). Characteristics: 77% were male, 77% had enthesitis, 68% were HLA-B27-positive. The median age of onset was 10.4 (IQR 9.4-12.0) years; median follow-up from the start of the biological agent was 1.2 (IQR 0.5-2.4) years. Intention-to-treat analysis shows that inactive disease was achieved in 7 of 22 patients (32%) after 3 months, 5 of 13 patients (38%) after 15 months, and 5 of 8 patients (63%) after 27 months of treatment. Two patients discontinued etanercept because of ineffectiveness, and switched to adalimumab (inactive disease achieved) or infliximab (decline in joints with arthritis after 3 months of treatment). One patient discontinued etanercept because of remission, but had flare and restarted treatment, with good clinical response. No serious adverse events occurred. Conclusion. Tumor necrosis factor (TNF)-blocking agents seem effective and safe for patients with ERA that was previously unresponsive to 1 or more DMARD. However, a sustained disease-free state could not be achieved, and none discontinued TNF-blocking agents successfully. The Journal of Rheumatology Copyright © 2011. All rights reserved. Source

Otten M.H.,Sophia Office | Prince F.H.M.,Sophia Office | Ten Cate R.,Leiden University | Van Rossum M.A.J.,Jan Medical | And 11 more authors.
Annals of the Rheumatic Diseases | Year: 2011

Objectives: To evaluate the effectiveness of tumour necrosis factor (TNF) blockers in juvenile psoriatic arthritis (JPsA). Methods: The study was a prospective ongoing multicentre, observational study of all Dutch juvenile idiopathic arthritis (JIA) patients using biologicals. The response of arthritis was assessed by American College of Rheumatology (ACR) paediatric response and Wallace inactive disease criteria. The response of psoriatic skin lesions was scored by a 5-point scale. Results: Eighteen JPsA patients (72% female, median age onset 11.1 (range 3.3-14.6) years, 50% psoriatic skin lesions, 39% nail pitting, 22% dactylitis) were studied. The median follow-up time since starting anti-TNFα was 26 (range 3-62) months. Seventeen patients started on etanercept and one started on adalimumab. After 3 months of treatment 83% of the patients achieved ACR30 response, increasing to 100% after 15 months. Inactive disease reached in 67% after 39 months. There was no discontinuation because of inefficacy. Six patients discontinued treatment after a good clinical response. However, five patients flared and restarted treatment, all with a good response. During treatment four patients (two JPsA and two JIA patients with other subtypes) developed de novo psoriasis. In four of the nine patients the pre-existing psoriatic skin lesions improved. Conclusion: Anti-TNFα therapy in JPsA seems effective in treating arthritis. However, in most patients the arthritis flared up after treatment discontinuation, emphasising the need to investigate optimal therapy duration. The psoriatic skin lesions did not respond well and four patients developed de novo psoriasis. Source

Otten M.H.,Erasmus MC Sophia Childrens Hospital | Prince F.H.M.,Erasmus MC Sophia Childrens Hospital | Anink J.,Erasmus MC Sophia Childrens Hospital | Ten Cate R.,Leiden University | And 12 more authors.
Annals of the Rheumatic Diseases | Year: 2013

Objective: To evaluate the effectiveness and safety of switching to a second or third biological agent in juvenile idiopathic arthritis ( JIA) after etanercept failure. Methods: The Arthritis and Biologicals in Children Register aims to include all Dutch JIA patients who have used biological agents. Data on the disease course were used to estimate drug survival with Kaplan-Meier and calculate adverse event (AE) rates. Results: Of 307 biologically naive JIA patients who started etanercept, 80 (26%) switched to a second and 22 (7%) to a third biological agent. During 1030 patientyears of follow-up after the introduction of etanercept, 49 switches to adalimumab, 28 infliximab, 17 anakinra, four abatacept and four trial drugs were evaluated. 84% (95% CI 80% to 88%) of patients who started etanercept as a first biological agent were, after 12 months, still on the drug, compared with 47% (95% CI 35% to 60%) who started a second and 51% (95% CI 26% to 76%) who started a third biological agent. Patients who switched because of primary ineffectiveness continued the second agent less often (32%, 95% CI 12% to 53%). After etanercept failure, drug continuation of adalimumab was similar to infliximab for patients with non-systemic JIA; anakinra was superior to a second TNF-blocker for systemic JIA. AE rates within first 12 months after initiation were comparable for each course and each biological agent. Conclusions: Switching to another biological agent is common, especially for systemic JIA patients. A second (and third) agent was less effective than the first. The choice of second biological agent by the physician mainly depends on availability and JIA category. Source

Van Munster M.P.,Hagaziekenhuis Juliana Childrens Hospital
BMJ case reports | Year: 2013

Acute otitis media is a very common disease in children. Most children recover with symptomatic therapy like potent analgesics, but occasionally serious complications occur. We present a 3-year-old girl who suffered from acute otitis media for already 2 weeks and presented with fever, abducens nerve palsy of her left eye and vomiting. She was finally diagnosed with an acute otitis media complicated by a mastoiditis, sinus thrombosis, meningitis and cerebellar empyema. Fusobacterium necrophorum was cultured from cerebrospinal fluid. The girl recovered following appropriate antibiotic and anticoagulation treatment. Source

Keukens L.,Hagaziekenhuis Juliana Childrens Hospital
BMJ case reports | Year: 2012

Persistent Mullerian duct syndrome (PMDS) is a rare syndrome and sometimes the cause of a common problem in paediatric and surgical practice, namely undescended testes. PMDS is a recessive disease in which there is a defect in anti-Mullerian hormone secretion or receptor activity resulting in persistence of Mullerian structures such as a uterus or fallopian tubes with otherwise normal virilisation. Here the authors present a case of a 1½-year-old boy who was referred to their hospital because of unilateral cryptorchidism. During laparoscopic surgery, two gonads were present joined together by a uterus-like structure. Additional investigations showed a normal male karyotype and biopsies of the gonads revealed infantile testis parenchyma making the diagnosis PMDS likely. Source

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