Chronic granulomatous disease identified in the evaluation of atypical Kawasaki disease in an infant

Abstract

An 8-week-old full-term male was admitted after 5 days of fever and cough. He was previously admitted at 3 weeks of age for a Klebsiella pneumoniae urinary tract infection (UTI) and treated with 10 days of antibiotics. Blood and cerebrospinal fluid cultures, serum inflammatory markers, and respiratory viral testing obtained at that time were negative. During the current admission, urine cultures grew Klebsiella oxytoca and he was again treated for a UTI.His fevers persisted and on day 8 of illness he met criteria for atypical Kawasaki disease with elevated inflammatory markers, elevated liver enzymes, thrombocytosis, leukocytosis, and anemia. Prior to initiating IVIG, the patient underwent abdominal ultrasound to rule out occult infection, revealing multiple liver and spleen abscesses. Aspirated fluid grew Serratia marcescens and he was started on cefepime. Additional imaging of the chest, abdomen, and pelvis revealed pulmonary nodules. Evaluation of these nodules demonstrated no additional mycobacterial, fungal, or bacterial infections.Chronic granulomatous disease (CGD) was suspected based on the patient’s age, multi-organ abscesses with Serratia marcescens, and parental consanguinity (first cousins). Neutrophil oxidative burst testing showed absent ROS production. Genetic testing demonstrated a homozygous pathogenic variant in NCF2 (exon 3 deletion), confirming the diagnosis of autosomal-recessive CGD. He received high-dose methylprednisolone with a prolonged taper to promote antibiotic penetration of his CGD-associated liver abscesses. Repeat imaging showed interval improvement and the patient began prophylactic itraconazole and trimethoprim-sulfamethoxazole.Familial testing revealed heterozygous carrier status of the same NCF2 variant in both parents and the patient’s two sisters. At 10 months of age, the patient underwent a 10/10 matched sibling bone marrow transplant. Chimerism studies showed rapid neutrophil engraftment with delayed T cell engraftment. As of follow up at 12 months of age, he has appropriate post-transplant weight gain, no infectious complications, and no evidence of GVHD.Initial presentation in patients with CGD and liver/spleen abscesses can be insidious with isolated fever and elevated inflammatory markers. Such patients can readily meet criteria for atypical Kawasaki disease, highlighting the importance of maintaining a broad differential diagnosis for fever of unknown origin with a high index of suspicion for primary immunodeficiency.