Juvenile idiopathic arthritis (JIA) is a complex rheumatic disease with both autoimmune and autoinflammatory components. Recently, familial cases of systemic-onset JIA have been attributed to mutations in LACC1/FAMIN. We describe three affected siblings from a Moroccan consanguineous family with an early-onset chronic, symmetric and erosive arthritis previously diagnosed as rheumatoid factor (RF)-negative polyarticular JIA. Autozygosity mapping identified four homozygous regions shared by all patients, located in chromosomes 3, 6 (n:2) and 13, containing over 330 genes. Subsequent whole exome sequencing identified two potential candidate variants within these regions (in FARS2 and LACC1/FAMIN). Genotyping of a cohort of healthy Moroccan individuals (n: 352) and bioinformatics analyses finally supported the frameshift c.128_129delGT mutation in the LACC1/FAMIN gene, leading to a truncated protein (p.Cys43Tyrfs*6), as the most probable causative gene defect. Additional targeted sequencing studies performed in patients with systemic-onset JIA (n:23) and RF-negative polyarticular JIA (n: 44) revealed no pathogenic LACC1/FAMIN mutations. Our findings support the homozygous genotype in the LACC1/FAMIN gene as the defect underlying the family here described with a recessively inherited severe inflammatory joint disease. Our evidences provide further support to the involvement of LACC1/FAMIN deficiency in different types of JIA in addition to the initially described systemic-onset JIA.

Background: Osteoarticular infections (OAIs) are typically treated initially with intravenous antibiotics. The objective of this study was to evaluate whether an exclusive oral treatment in selected children may be appropriate. Methods: The Spanish Network of Osteoarticular Infections is a nationwide multicenter registry comprising 37 hospitals in Spain. The registry prospectively includes clinical characteristics and outcome of children with OAI. One of the hospitals from RioPed offers oral treatment to children meeting certain criteria. Patients were classified into 2 groups. Group 1: management with initial intravenous antibiotic therapy. Group 2: patients exclusively treated with oral antibiotics. A comparison between the 2 groups was performed. Results: We compared 893 children who initially received intravenous antibiotics (group 1) with 64 children who received exclusively oral therapy (group 2). Patients from group 2 were younger (33.9 vs. 20.3 months; P = 0.001), had a lower percentage of Staphylococcus aureus (23.3% vs. 3.1%; P < 0.001), a higher proportion of Kingella kingae (12.1% vs. 28.1%; P = 0.001), higher erythrocyte sedimentation rate/C-reactive protein (CRP) ratio (1.4 interquartile range 0.6–3.6 vs. 3.3 interquartile range 1.7–5.7; P < 0.001) and showed lower rate of fever (63% vs. 48.8%; P = 0.024) than in group 1. Complications were not found in group 2. Conclusions: An exclusively oral administration could be a safe option in selected patients with OAI. Low-risk criteria are proposed: good general condition, no underlying disease, 6 months to 3 years old, appropriate oral tolerance, C-reactive protein <80 mg/L, erythrocyte sedimentation rate/C-reactive protein ratio ≥0.67, no skin injury, no recent surgery, no cervical spondylodiscitis and no local complications at onset.

Objective: To evaluate the efficacy of colchicine therapy in pediatric patients with PFAPA syndrome who present with an incomplete response to the standard treatment or with frequent episodes (an interval of less than 14 days between two disease flares). Methods: A multicenter cohort study of children diagnosed with PFAPA syndrome and treated with colchicine was performed in three separate hospitals located in Spain. The patients clinical and laboratory data were reviewed by accessing their medical records. Response to colchicine was evaluated after 12 months of treatment for frequency, duration, and intensity of PFAPA episodes. Results: A total of 13 children were included in our study, 43% of whom were boys. Median age of the colchicine therapy initiation was 6 years (interquartile range (IQR)=3-9.5). Following a 12-month period of colchicine therapy (median dosage of 0.02 mg/kg/day; IQR=0.02-0.03), a significant decrease in the median number of flares (median 8; IQR=7-14 vs 3; IQR=2-4; p=0.005) and the duration of disease episodes (median 4 days; IQR=3.25-5.125 vs 1 day; IQR=1-2; p=0.003) was observed. Furthermore, the highest degree of fever during disease flares was reduced from median 40ºC (IQR=39.5-40) to 38.5ºC (IQR=37.7-38.9) (p=0.002). Conclusion: Colchicine therapy decreased the frequency and intensity of PFAPA. The use of colchicine could be an effective treatment in pediatric patients with PFAPA syndrome who present with frequent or severe relapses. Cite this article as: Quintana-Ortega C, Seoane-Reula E, Fernández L, Camacho M, Olbrich P, Neth O, et al. Colchicine treatment in children with periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome: A multicenter study in Spain. Eur J Rheumatol 2021; 8(2): 73-8.

Minimally invasive management of pediatric osteoarticular infections

In children under 4, septic arthritis of the hip (SAH) caused by Kingella kingae (SAH-KK) can be misdiagnosed, as it does not meet classic septic joint criteria (fever > 38.5°, pain, limited range of motion, and inability to bear weight). The objective of this study was to report clinical and paraclinical characteristics in a large cohort of children with confirmed SAH-KK and to evaluate the reliability of the Kocher (KC) and Caird criteria (CC) in predicting SAH-KK. Medical records of 140 children with confirmed SAH-KK were collected. Data on sex, age, temperature on admission, weight-bearing status, white blood cell (WBC) count, platelet count, C-reactive protein (CRP) value, and erythrocyte sedimentation rate (ESR) were extracted. The study focused on the sensitivity of KC (body temperature, refusal to bear weight, leukocytosis, and ESR) and CC (KC criteria plus CRP level). All patients had bacteriologically confirmed SAH-KK; most had mild symptoms and near-normal inflammatory markers. CRP (76.2%) had the highest sensitivity, followed by weight-bearing status (73.8%) and WBC count (69.6%). Body temperature and ESR exceeded cutoff values in less than 50% of cases. Among 77 patients fulfilling all KC, 49 (63.5%) had less than a 40% probability of SAH. Of 50 children with complete CC, 20 (40%) had a 62.4% or lower probability of SAH. KC and CC are not sufficiently accurate to confidently exclude SAH-KK in preschool-aged children due to heterogeneous clinical presentations. Further studies are needed to redefine diagnostic criteria based on patient age and causative pathogens.