Agustín Remesal

Discontinuation of Etanercept After Successful Treatment in Patients with Juvenile Idiopathic Arthritis

To the Editor: Etanercept (ETN) has been used to treat patients with juvenile idiopathic arthritis (JIA) with demonstrated efficacy and safety1,2. However, few studies have addressed the appropriate time and the way to discontinue the drug once the disease is inactive. We analyzed the progress of patients with JIA after discontinuation of ETN and the clinical response to reintroduction of the drug in those who relapsed. A retrospective chart review 2004 to 2009 revealed that therapy with ETN had been discontinued in 26 patients with JIA due to inactive disease (16 female, 10 male). The mean age at discontinuation of drug was 11 ± 2 (range 2.6–18.8) years. The clinical subtypes of JIA were 11 cases of enthesitis-related arthritis, 7 rheumatoid factor-negative polyarthritis, 2 systemic JIA with polyarticular involvement, 1 psoriatic arthritis, and 1 persistent oligoarticular arthritis. Inactive disease was defined according to the criteria of Wallace, et al 3, which required no joints with active arthritis, no … Address correspondence to Dr. Remesal; E-mail: agusremesal{at}hotmail.com

Anti-adalimumab antibodies in paediatric rheumatology patients: a pilot experience

zero. These cases illustrate the potential added value of belimumab after rituximab treatment in active LN. It should be noted that both patients continue to have low disease activity while on belimumab monotherapy. To our knowledge, this is the first report of LN patients treated with two consecutive B cell targeted treatments. In both patients, belimumab halted the full repopulation of circulating B cells after rituximab. From a pathophysiological point of view, it is well appreciated that autoantibody-positive disease is found specifically in LN and that B cell hyperactivity is a landmark in SLE [5]. It is tempting to speculate that the clinical improvement of these patients is due to a synergic effect of rituximab and belimumab. Previously, two randomized trials (BLISS-52 AND BLISS-76) showed beneficial effects of belimumab in reducing concomitant immunosuppression in autoantibody-positive SLE without major organ involvement and without previous rituximab treatment. Recently one patient with active LN was reported to have a beneficial response to belimumab, albeit in conjunction with pulse steroids [6]. Currently we await the results of a randomized trial assessing belimumab’s efficacy in LN (NCT01639339). This report describes belimumab as rescue treatment in refractory LN due to commonly seen gastrointestinal intolerance to MMF [7]. The present report encourages further research into the clinical yield of combining B cell targeted treatment in the difficult population of SLE patients with major organ involvement or refractory disease.

A family carrying a homozygous LACC1 truncated mutation expands the clinical phenotype of this disease beyond systemic-onset juvenile idiopathic arthritis

We identified a consanguineous Moroccan family with three affected siblings diagnosed with rheumatoid factor-negative polyarticular juvenile idiopathic arthritis. They all suffered from an early-onset (2-4 years-old) chronic and symmetric polyarthritis affecting both large and small joints. The joint involvement was markedly erosive in two siblings, with the older sister requiring hip prosthetic replacement at the age of 18 years. None of the patients had fever, skin rash, uveitis or other extra-articular manifestations. Laboratory analyses revealed leukocytosis, thrombocytosis, severe anaemia, marked increase of inflammatory markers and negative results for rheumatoid factor, anti-nuclear antibodies and HLA-B27.

Outpatients with acute osteoarticular infections had favourable outcomes when they received just oral antibiotics without intravenous antibiotics

The traditional approach for acute paediatric osteoarticular infections (OAI) has comprised initial intravenous antibiotics followed by prompt oral antibiotics. We assessed how providing just oral antibiotics compared to the traditional two‐step approach.

Unexpected Relevant Role of Gene Mosaicism in Primary Immunodeficiency Diseases

Background: Postzygotic de novo mutations lead to the phenomenon of gene mosaicism. The 3 main types are called somatic, gonadal, and gonosomal mosaicism, which differ in terms of the body distribution of postzygotic mutations. Mosaicism has been reported occasionally in patients with primary immunodeficiency diseases (PIDs) since the early 1990s, but its real involvement has not been systematically addressed. Objective: We sought to investigate the incidence of gene mosaicism in patients with PIDs. Methods: The amplicon‐based deep sequencing method was used in the 3 parts of the study that establish (1) the allele frequency of germline variants (n = 100), (2) the incidence of parental gonosomal mosaicism in families with PIDs with de novo mutations (n = 92), and (3) the incidence of mosaicism in families with PIDs with moderate‐to‐high suspicion of gene mosaicism (n = 36). Additional investigations evaluated body distribution of postzygotic mutations, their stability over time, and their characteristics. Results: The range of allele frequency (44.1% to 55.6%) was established for germline variants. Those with minor allele frequencies of less than 44.1% were assumed to be postzygotic. Mosaicism was detected in 30 (23.4%) of 128 families with PIDs, with a variable minor allele frequency (0.8% to 40.5%). Parental gonosomal mosaicism was detected in 6 (6.5%) of 92 families with de novo mutations, and a high incidence of mosaicism (63.9%) was detected among families with moderate‐to‐high suspicion of gene mosaicism. In most analyzed cases mosaicism was found to be both uniformly distributed and stable over time. Conclusion: This study represents the largest performed to date to investigate mosaicism in patients with PIDs, revealing that it affects approximately 25% of enrolled families. Our results might have serious consequences regarding treatment and genetic counseling and reinforce the use of next‐generation sequencing–based methods in the routine analyses of PIDs. GRAPHICAL ABSTRACT Figure. No caption available.

Oral treatment of osteoarticular infections caused by Kingella kingae in children

The therapeutic approach to musculoskeletal infections in pediatric patients has been substantially modified, particularly due to the increasing use of sequential therapy consisting of initial intravenous antibiotics quickly followed by a short course of oral antibiotics (1). To our knowledge, there is no series published on patients entirely treated with oral antibiotics. In the Pediatric Rheumatology Unit of our tertiary care hospital, oral treatment is offered to children diagnosed with osteoarticular infection (OAI), acute hematogenous osteomyelitis (OM), and septic arthritis (SA) and with suspected Kingella kingae (K. kingae) infection and who meet the following criteria: Age less than 4 years old, with good general condition and possibility of follow-up as outpatients.

Clinical manifestations of four patients diagnosed with early-onset sarcoidosis or sarcoid-like syndrome

Sarcoidosis is a rare multisystemic granulomatous disease. Pulmonary involvement is common in adults, but any organ can be affected.

Switching to an alternative biological agent in juvenile idiopathic arthritis (II)

Initial* End* ۵ p Initial* End* ۵ p Initial* End* ۵ p ETA 3.25 0.5 -6 0.00 28 12 -5 0.00 13.2 2.3 -5 0.00 ADA 2.42 0.4 -3 0.01 17 13 -1 0.26 5.58 1.2 -2 0.06 AK 5.36 0.00 -3 0.01 62 9 -2 0.02 69.5 2.9 -2 0.03 TCZ 6.45 0.86 -3 0.01 46 4 -3 0.01 95.6 0.6 -3 0.01 IFX 4.9 0.00 47 6