CNS Inflammation as the First Sign of Complement Factor I Deficiency: A Severe Myelitis Treated With Intense Immunotherapy and Eculizumab

OBJECTIVES: Complement factor I (CFI) deficiency is a rare autosomal recessive inborn error of immunity. In this report, we highlight that complete CFI deficiency may present with isolated and severe CNS inflammation without associated systemic features nor prior non-CNS episodes. This inflammation may respond to complement blockade therapy. METHODS: This is a case description of a young girl with severe longitudinal transverse myelitis treated with aggressive immunotherapy that included eculizumab. Published cases of CFI-associated CNS inflammation were reviewed and discussed. RESULTS: A primary immunodeficiency panel revealed 2 germline pathogenic variants in the CFI gene. Further complement testing of the index case and her family confirmed complete CFI deficiency. DISCUSSION: We describe a unique case of severe spinal inflammation secondary to complete CFI deficiency. Although rare, isolated CNS inflammation may be the primary manifestation of complete CFI deficiency. To halt the uncontrolled complement-mediated inflammation associated with CFI deficiency, prompt targeted blockade of the complement pathway using eculizumab may be life changing in the acute phase. Long-lasting blockade of the complement pathway is also essential to prevent relapse in this subgroup of patients.

Impact of Blood Sampling on Anemia in the PICU: A Prospective Cohort Study.

OBJECTIVES: Fifty percent of children are anemic after a critical illness. Iatrogenic blood testing may be a contributor to this problem. The objectives of this study were to describe blood sampling practice in a PICU, determine patient factors associated with increased sampling, and examine the association among blood sampling volume, anemia at PICU discharge, and change in hemoglobin from PICU entry to PICU discharge. DESIGN: Prospective observational cohort study. SETTING: PICU of Sainte-Justine University Hospital. PATIENTS: All children consecutively admitted during a 4-month period. MEASUREMENTS AND MAIN RESULTS: Four hundred twenty-three children were enrolled. Mean blood volume sampled was 3.9 (±19) mL/kg/stay, of which 26% was discarded volume. Children with central venous or arterial access were sampled more than those without access (p < 0.05). Children with sepsis, shock, or cardiac surgery were most sampled, those with a primary respiratory diagnosis; the least (p < 0.001). We detected a strong association between blood sample volume and mechanical ventilation (H, 81.35; p < 0.0001), but no association with severity of illness (Worst Pediatric Logistic Organ Dysfunction score) (R, -0.044; p = 0.43). Multivariate analysis (n = 314) showed a significant association between the volume of blood sampled (as continuous variable) and anemia at discharge (adjusted OR, 1.63; 95% CI, 1.18-2.45; p = 0.003). We lacked power to detect an association between blood sampling and change in hemoglobin from PICU admission to PICU discharge. CONCLUSIONS: Diagnostic blood sampling in PICU is associated with anemia at discharge. Twenty-five percent of blood losses from sampling is wasted. Volumes are highest for patients with sepsis, shock, or cardiac surgery, and in patients with vascular access or ventilatory support.

An Atypical Case of Atypical Hemolytic Uremic Syndrome.

We present the case of a 2-month-old infant presenting with pallor and laboratory results showing: hemoglobin 5.1 (10 to 1.5) g/dL, MCV 94.7 (75 to 105) fL, leukocytes 17.4 (7 to 15) ×10/µL, platelets 259 (150 to 450) ×10/µL, hyperbilirubinemia and renal dysfunction. A hemolytic anemia with tubular injury secondary to hemoglobinuria was suspected. Hyperhydration and packed cells were given but she deteriorated. Fluid overload with anuria further complicated the course necessating hemodialysis. Atypical hemolytic uremic syndrome was suspected and eculizumab was administered resulting in rapid improvement. Genetic analysis revealed a mutation in the gene encoding complement factor H and atypical hemolytic uremic syndrome was confirmed.