Abstract
Familial hemophagocytic lymphohistiocytosis (HLH) is a rare genetic and life-threatening immunodeficiency disease. Here, we present a 38-year-old male who initially developed multiple annular to irregular erythema accompanied by a fever after COVID-19 vaccination. He was diagnosed with HLH with evidence of leukocytopenia in a full blood test, elevations of ferritin and sCD25, decreased NK cell function, and hemophagocytosis of a bone marrow biopsy specimen. A genetic examination revealed two probable disease-causing heterozygous mutations on UNC13D associated with type 3 familial HLH. A review of the case reports relevant to HLH following COVID-19 vaccination and the cutaneous manifestations of HLH with genetic defects suggests the necessity that individuals with preexisting immune dysregulation or diseases not classified should be cautious about COVID-19 vaccination and reminds clinicians that various recalcitrant skin lesions may be a sign of HLH.