Abstract Text: Trauma-induced sterile necrotising fasciitis (NF) is an under-reported presentation of NFKB1 haploinsufficiency, compared to CVID-related manifestations. We report a case with intramuscular injections-induced ulcers, abscesses and scarring from age four years. At 26 years age, she underwent caesarean section, complicated by presumptive wound infection requiring ICU admission, debridement surgeries and skin graft. Wound healing was delayed with significant hernia and scar. At 26 years she was found to have sever pan-hypogammaglobinaemia, diagnosed as CVID , and started on immunoglobulin replacement, which continued subcutaneously. At age 32 years, she underwent hernia repair with abdominoplasty, which was complicated by NF, and neutrophilia (30), leading to significant loss of the anterior abdominal wall. Her CVID-phenotype was of sinopulmonary infections, psoriasis, and recently liver derangement. Her variant was paternally inherited heterozygous copy-number-loss leading to pathogenic deletion of all NFKB1 coding exons2-24, which might explain the severe early onset. NF was reported only in NFKB1 truncating variants. Her father is well, illustrating reported incomplete penetrance of NFKB1-NF that will inform genetic-counselling. She had normal neutrophil-oxidative-burst (DHR) on PMA stimulation, which could be NFKB1-indepednet. Further neutrophil function assessment is being arranged. Delayed wound healing with peripheral neutrophilia mimics leukocyte-adhesion-defects not corrected by immunoglobulins-replacement. Nevertheless, deep-tissue trauma triggers NF in NFKB1-haploinsufficiency without infection. Steroids and anti-IL1 blocking are reported to accelerate wound healing, in keeping with reported high IL1B/IL8. Further studies are required to elucidate the mechanism of necrotising-fasciitis in NFKB1 haploinsufficiency and inform management.
