Blueberry Muffin Rash as the Presenting Sign of Aicardi–Goutières Syndrome

Abstract:  A 36-week gestation singleton male infant was born with hypoglycemia, thrombocytopenia, transaminitis, microcephaly, and a generalized eruption of bluish-red nonblanching macules and papules. Head computed tomography showed intracranial calcifications and enlarged ventricles. Skin biopsy was consistent with extramedullary hematopoiesis, with no evidence of neoplastic infiltrate. Family history was notable for parental consanguinity and twin sisters with the diagnosis of Aicardi–Goutières syndrome, a rare autosomal recessive progressive encephalopathy. Although the infant’s clinical presentation at birth suggested an infectious etiology, extensive testing for infection, including TORCH titers, was negative. Cerebrospinal fluid analysis revealed persistent lymphocytosis and an elevated interferon alpha level, consistent with the diagnosis of Aicardi–Goutières syndrome. Although there have been no reported cases of a blueberry muffin rash in Aicardi–Goutières syndrome, it is biologically plausible for this cutaneous manifestation to occur in the setting of a genetic condition that mimics the clinical phenotype of a congenital viral infection. As the capacity to test for different infectious etiologies and genetic syndromes increases, so must the differential diagnosis of a neonatal blueberry muffin rash. It is important to identify these rare syndromes because of their prognostic implications, risk of recurrence with future pregnancies and need for prompt genetic counseling.