Type 1 interferonopathy presenting as juvenile idiopathic arthritis with interstitial lung disease: report of a new phenotype.

BACKGROUND: STING-associated vasculopathy with onset in infancy (SAVI) is a type 1 interferonopathy manifesting as a pulmonary and vascular syndrome resulting from gain-of-function mutations in TMEM173, the gene encoding STING. Familial reports in the literature are sparse. CASE PRESENTATION: We report a case series of SAVI in a three generation kindred, with a phenotype of interstitial lung disease (ILD) and rheumatoid factor positive polyarticular juvenile idiopathic arthritis (JIA). Current and historical medical records were reviewed for clinical and laboratory information. Whole blood from cases 1 and 2, plus stored appendicectomy tissue from case 3, underwent DNA sequencing of the TMEM173 gene. Peripheral blood RNA was obtained from cases 1 and 2 for functional assessment of the TMEM173 mutation. DNA sequencing identified the same heterozygous TMEM173 mutation (c.463G > A; p.Val155Met) in all three cases, consistent with a diagnosis of the autosomal dominant condition SAVI. Functional assessment of this mutation identified a prominent interferon signature which was confirmed on repeat testing. CONCLUSIONS: SAVI presented in this family as ILD with early onset juvenile rheumatoid arthritis. This condition should be considered in all rheumatoid arthritis patients with early-onset ILD and in all JIA patients with ILD.

The child with joint pain in primary care.

Joint pains are a common reason for children to present to primary care. The differential diagnosis is large including some diseases that do not primarily affect the musculoskeletal system. Although the cause for many patients will be benign and self-resolving, in rare cases the diagnosis is associated with long-term morbidity and mortality if not detected early and appropriately treated. These include primary and secondary malignancies, septic arthritis, osteomyelitis, inflammatory arthritis, slipped upper femoral epiphysis (SUFE) and non-accidental injury. We highlight the importance of a thorough history and directed yet comprehensive examination. A diagnostic algorithm is provided to direct primary care physicians' clinical assessment and investigation with the evidence base where available. In many cases, tests are not required, but if there is suspicion of malignancy, infection or inflammatory conditions, laboratory tests including full blood count, blood film, erythrocyte sedimentation rate, C-reactive protein and lactate dehydrogenase help to support or exclude the diagnosis. Autoimmune tests, such as antinuclear antibodies and rheumatoid factor, have no diagnostic role in juvenile idiopathic arthritis; therefore, we advise against any form of 'rheumatological/autoimmune disease screen' in primary care. Imaging does have a place in the diagnosis of joint pains in children, with plain radiographs being most appropriate for suspected fractures and SUFE, whilst ultrasound is better for the detection of inflammatory or infective effusions. The appropriate referral of children to paediatric rheumatologists, oncologists, orthopaedic surgeons and the emergency department are discussed.