P2.259: No Suspicion for NOCARH: A Cautionary Tale of Anchoring Bias

Introduction: Neonatal onset of cytopenia autoinflammation rash and hemophagocytic lymphohistiocytosis syndrome (NOCARH), a subset of hemophagocytic lymphohistiocytosis (HLH), is a rare and life-threatening condition characterized by uncontrolled immune response. It presents a diagnostic challenge in neonates due to the overlap of clinical features with other conditions, particularly congenital infections. We report a case of NOCARH in a late pre-term neonate, highlighting an atypical age group and the diagnostic difficulty of this syndrome.

Case Description: A 1 day old ex-35 week neonate presented to a level 4 NICU with pancytopenia; extensive maculopapular rash on her extremities, torso, and face; abdominal distention; hepatomegaly; abnormal findings on abdominal film; and a systolic murmur. Initial symptoms prompted concern for congenital infection and necrotizing enterocolitis. Comprehensive infectious disease testing yielded negative results. She was subsequently evaluated for immunodeficiency, liver, and thyroid related diseases. Persistent profound pancytopenia, elevated inflammatory markers, episodic rashes, growth failure, worsening cholestasis, and new onset lymphadenopathy at three weeks of age prompted expansion of differential and evaluation for NOCARH despite not fitting clearly into diagnostic criteria. Bone marrow biopsy confirmed the diagnosis with findings of hemophagocytosis without malignancy. Genetic evaluation identified a heterozygous pathogenic CDC42 mutation consistent with NOCARH syndrome.

Treatment included the administration of dexamethasone, intravenous immunoglobulin, and emapalumab, a monoclonal antibody targeting IFN-γ. Prophylactic antimicrobials were initiated in the setting of immunosuppression. Bone marrow transplantation is planned to achieve long-term disease control.

Discussion: This case underscores the challenges associated with diagnosing (NOCARH), particularly when initial clinical suspicion is anchored to more common conditions such as congenital infections or immunodeficiencies. The overlapping presentation of these conditions can lead to delays in considering HLH spectrum disorders, potentially postponing the initiation of life-saving interventions.

Anchoring bias played a significant role in the early diagnostic approach in this case. Given the patient's gestational age, initial signs, and laboratory findings, the clinical team focused on ruling out congenital infections, metabolic disorders, and immune deficiencies. Despite negative infectious disease workup, persistent pancytopenia, worsening cholestasis, and the emergence of lymphadenopathy prompted reconsideration of the differential diagnosis. The expansion of the diagnostic scope allowed for recognition of HLH and, ultimately, the identification of a pathogenic CDC42 mutation confirming NOCARH syndrome.

Conclusion: This case highlights the hazards of anchoring bias when evaluation for initial suspected medical condition is inconclusive. Early diagnosis and targeted therapy are critical to improving outcomes in this rare, high-mortality condition. Pediatricians and neonatologists should be aware of the potential for HLH to present in neonates, particularly in association with genetic syndromes like NOCARH.