Refractory auto-inflammatory syndrome associated with digenic transmission of low-penetrance tumour necrosis factor receptor-associated periodic syndrome and cryopyrin-associated periodic syndrome mutations

Two dominant periodic fevers, tumour necrosis factor (TNF) receptor-associated periodic syndrome (TRAPS) and cryopyrin-associated periodic syndrome (CAPS), are prominent auto-inflammatory disorders. Mutations in the 55 kDa TNF receptor superfamily 1A gene ( TNFRSF1A ) and in the cold-induced auto-inflammatory syndrome 1 gene ( CIAS1 ) were recently associated with TRAPS1 and CAPS,2 respectively. Following publications describing the efficacy of etanercept (enbrel), a recombinant human TNF receptor 1B fusion protein in patients with TRAPS3 and anakinra (kineret), a recombinant human interleukin-1 (IL1)-receptor antagonist, in patients with CAPS,4 targeted biotherapies have been repeatedly and successfully given for these two conditions. Our proband (fig 1) is a 36-year-old French woman who presented with rashes of urticaria and oedema precipitated by exposure to heat and water. These rashes, lasting a …