{
  "abstract": "Objective To describe the clinical, biological and genetic characteristics of paediatric-onset A20 haploinsufficiency (HA20) and to identify key clinical features that may guide early diagnosis and management.Methods Multicentre, retrospective observational cohort study through the French national paediatric rheumatology network and national reference laboratories for genetic autoinflammatory diseases. 17 patients from 11 unrelated families, with disease onset before 18 years of age and carrying a tumour necrosis factor alpha-induced protein 3 ( TNFAIP3) mutation, were included.Results Median age at symptom onset was 3 years (range: 1 month–17 years) with a median diagnostic delay of 9.7 years (range: 1–43 years). Boys had a significantly earlier onset and diagnosis than girls. The most common initial manifestations were oral ulcers (64.7%), fever (64.7%), abdominal pain (47.1%), arthralgia (35.3%) and skin eruption (17.6%). Genital ulcers occurred in 17.6% at onset but in 52.9% during follow-up. Gastrointestinal involvement was frequent (abdominal pain in 76.5% of patients and colitis in 35.3%). Other features included arthralgia (52.9%), arthritis (29.4%), skin eruption (41.2%), lymphadenopathy (35.3%), hepatomegaly (11.8%), headache (17.6%) and uveitis (5.9%). C reactive protein (CRP) levels were significantly higher during flares. Three novel TNFAIP3 variants were identified. Colchicine was effective as monotherapy in 40%. TNF-inhibitors showed the highest efficacy (adalimumab 60%, infliximab 100%).Conclusions HA20 should be suspected in children with fever and gastrointestinal inflammation, even in the absence of oral/genital ulcers. Early onset colitis, the distinctive morphology of mucosal ulcers and a positive family history for HA20 are particularly suggestive. Early genetic testing may enable prompt diagnosis and targeted therapy.",
  "authors": [
    {
      "affiliations": [
        "Service de rhumatologie pédiatrique, Centre de référence des maladies auto-inflammatoires de l’enfant, Hôpital Bicêtre, AP-HP, Université Paris-Saclay, Bicêtre, France"
      ],
      "name": "Federica Anselmi"
    },
    {
      "affiliations": [
        "Hôpital Necker-Enfants Malades, Paris, France"
      ],
      "name": "Marie-Louise Frémond"
    },
    {
      "affiliations": [
        "Department of Pediatric Rheumatology, Lille University Hospital, Lille, Hauts-de-France, France"
      ],
      "name": "Heloise Remaux"
    },
    {
      "affiliations": [
        "Pediatric Nephrology, Rheumatology and Dermatology Unit, Hospices Civils de Lyon, Lyon, Auvergne-Rhône-Alpes, France"
      ],
      "name": "Audrey Laurent"
    },
    {
      "affiliations": [
        "Department of Clinical Immunology, Saint-Louis Hospital, Paris, Île-de-France, France"
      ],
      "name": "Claire Fieschi"
    },
    {
      "affiliations": [
        "Laboratory of Inflammatory Responses and Transcriptomic Networks in Diseases, Imagine Institute, Paris, Île-de-France, France"
      ],
      "name": "Adrien Schvartz"
    },
    {
      "affiliations": [
        "CHU Caen, Caen, Basse-Normandie, France"
      ],
      "name": "Alexandra Desdoits"
    },
    {
      "affiliations": [
        "Department of Internal Medicine and Clinical Immunology, Regional University Hospital Centre Tours Bretonneau Hospital, Tours, Centre-Val de Loire, France"
      ],
      "name": "Marie Charlotte Besse"
    },
    {
      "affiliations": [
        "Paediatric Infectious and Immunology Unit, University Hospital of Montpellier, Montpellier, Occitanie, France"
      ],
      "name": "Eric Jesiorski"
    },
    {
      "affiliations": [
        "Laboratory of Genetics for Rare and Autoinflammatory Diseases, University Hospital of Montpellier, Montpellier, Occitanie, France"
      ],
      "name": "Guilaine Boursier"
    },
    {
      "affiliations": [
        "Department of Genetics and Molecular Biology, Hôpitaux Universitaires Paris Centre, Paris, Île-de-France, France"
      ],
      "name": "Laurence Cuisset"
    },
    {
      "affiliations": [
        "Service de rhumatologie pédiatrique, Centre de référence des maladies auto-inflammatoires de l’enfant, Hôpital Bicêtre, AP-HP, Université Paris-Saclay, Bicêtre, France"
      ],
      "name": "Perrine Dusser"
    },
    {
      "affiliations": [
        "Service de rhumatologie pédiatrique, Centre de référence des maladies auto-inflammatoires de l’enfant, Hôpital Bicêtre, AP-HP, Université Paris-Saclay, Bicêtre, France"
      ],
      "name": "Isabelle Koné-Paut"
    }
  ],
  "title": "Tackling the diagnosis of HA20 in children: challenges of a highly variable clinical and genetic spectrum",
  "uid": "1d96488c-4f58-5a01-a6ee-52673701d313"
}