Childhood-onset hypocomplementaemic urticarial vasculitis in France: phenotypic and genotypic diversity in 10 children

Hypocomplementaemic urticarial vasculitis (HUV) is a rare small-vessel vasculitis characterized by the combination of urticarial vasculitis and hypocomplementaemia. HUV may occur in isolation or be associated with systemic diseases such as systemic lupus erythematosus (SLE). Recently, loss-of-function variants in DNASE1L3 have been reported to cause familial forms of HUV. We aimed to describe the clinical and genetic features of childhood-onset HUV cases in France. We conducted a nationwide retrospective study in France that included 10 patients with childhood-onset HUV. Ten children, all girls, were included. Their median age at onset was 9.5 years (range: 2–14 years), and the median delay between onset and diagnosis was 13 months (range: 6–55 months). Phenotypes were heterogeneous: 3 had systemic HUV syndrome (S-HUVS), all associated with DNASE1L3 deficiency, including 2 siblings; 4 had non-systemic HUVS (NS-HUVS), one of whom had a C2 deficiency; and 3 had SLE-associated HUV. Musculoskeletal features were the most common extracutaneous manifestation (9/10). The most severe manifestations were observed in children with S-HUVS, including pulmonary haemorrhage (2/3) and glomerulonephritis (2/3). Anti-nuclear antibodies were positive in 9/10 patients, anti-C1q antibodies in 6/10, and anti-neutrophil cytoplasmic antibodies in 5/10. Antihistamines were widely used in NS-HUVS, while S-HUVS and SLE-associated HUV required immunosuppressive treatments. Hydroxychloroquine was used in 8/10 patients. These 10 cases highlight the heterogeneity and potential severity of childhood-onset HUV. We report the third familial form of HUVS associated with DNASE1L3 deficiency and an extremely rare case of HUVS associated with C2 deficiency. Childhood-onset HUV is a rare disease with phenotypic and genotypic heterogeneity. Systemic HUVS, associated with DNASE1L3 deficiency but not with positive anti-C1q, is the most severe form. A genetic testing should be systematically performed in childhood-onset HUV.