LAUSR

To the Editor The NOD-like receptor family CARD domain containing 4 (NLRC4) gene was initially described in 2001; however, it is only since 2014 that its mutations, mostly heterozygous gainof-function mutations with complete penetrance, have been associated with distinct syndromes and diseases, known as NLRC4 inflammasomopathies [1]. They are characterized from recurrent episodes of autoinflammation due to hyperactivation and spontaneous formation of the NLRC4 inflammasome, a large multimolecular cytosolic complex that mediates, through caspase-1, the proteolytic cleavage of immature pro-IL-1β and pro-IL-18 to their mature biologically active forms and a programmed inflammatory cell death process known as pyroptosis [1]. Until now, three NLRC4 inflammasomopathy phenotypes have been described in a total of 37 cases: autoinflammation with infantile enterocolitis (AIFEC) in 10 cases, familial cold autoinflammatory syndrome 4 (FCAS4) in 26 cases belonging to only two families, and neonatal-onset multisystem inflammatory disease (NOMID) in 1 case [1–3]. Given the rarity of the disease and the diversity of clinical presentation, we report the case of a boy with NLRC4 inflammasomopathy presenting with AIFEC syndrome. This report focuses on some new appearing symptoms and differences from previously reported patients, namely AIFEC-associated perirectal abscesses and milk protein allergy. A male Caucasian full-term neonate, born to nonconsanguineous parents and with no allergies, presented at 20 days of age with bloody diarrhea, dehydration, weight loss (− 1 Kg from birthweight), respiratory distress, abdominal distension, hypothermia, and metabolic acidosis (pH 7.11, HCO3 4.1 mmol/L). The boy was fed since birth with breastmilk and formula. Routine laboratory investigations showed leukocytosis (WBC 24 × 10/L), increased serum C-reactive protein (CRP, 82 mg/L, normal < 10 mg/L) and procalcitonin levels (16 ng/mL, normal < 0.5 ng/mL), hypertransaminasaemia (AST 89 IU/L, normal < 45 IU/L), thrombocytopenia (platelets 18 × 10/L), coagulopathy (prothrombin time 21.6 s, fibrinogen 74 mg/dL, d-dimers 1.4 μg/mL), hyperferritinemia (1,680 μg/L, normal range 10–150 μg/L), and decreased glomerular filtration rate (14 mL/min/1.73 m). Blood, urine, CSF, and stool cultures did not reveal any microorganism. The baby was mechanically ventilated for 24 h, treated with intravenous fluids, inotropes, and antibiotics for suspected sepsis and transfused with fresh frozen plasma, packed red blood cells, and platelets. After recovery, he was fed with an elemental formula, due to food intolerance, in combination with total parenteral nutrition. Serum immunotrypsinogen, fecal trypsin, and a chloride sweat test for cystic fibrosis, were all normal. Abdominal ultrasonography was normal too, apart from mild hepatosplenomegaly. No abnormal findings were observed macroscopically on gastroscopy and colonoscopy; histology showed moderate chronic inflammation (Fig. 1a) and eosinophilic infiltration of the duodenum (Fig. 1b), mild eosinophilic infiltration of the esophagus, gastric mucosa and rectum, and mild-tomoderate chronic rectal inflammation. * Tania Siahanidou [email protected]