Case Report: Periorbital Edema as an Overlooked Presentation of Epstein-Barr Virus

Infectious mononucleosis (IM), most commonly caused by Epstein-Barr virus (EBV), classically presents with fever, pharyngitis, and cervical lymphadenopathy. However, less common manifestations such as bilateral periorbital edema, known as Hoagland sign, may precede or obscure more typical features, complicating diagnosis. Although described in the literature for decades, Hoagland sign remains underrecognized in clinical practice, especially in pediatric and young adult patients. This oversight can lead to misdiagnosis, delayed testing, unnecessary antibiotic use, and patient distress.

We present 2 cases of female patients, one pediatric and one young adult, who initially presented with bilateral periorbital edema and nonspecific systemic symptoms. In both cases, infectious mononucleosis was not initially suspected. One patient was treated for streptococcal pharyngitis and later developed a rash typical of antibiotic-associated IM. The second patient was denied EBV testing at an urgent care clinic despite a direct request, due to provider unfamiliarity with the association between periorbital edema and IM. Both were eventually diagnosed with EBV via serologic testing and recovered with supportive care.

These cases highlight a critical gap in provider awareness that, if addressed, could reduce diagnostic delays and improve patient care. Recognizing Hoagland sign as a valid early clue for IM, particularly in female patients,can help differentiate benign viral illness from more concerning differentials such as orbital cellulitis, nephrotic syndrome, or allergic reactions. This report serves as a clinical reminder to include EBV in the differential diagnosis of atraumatic, bilateral eyelid swelling and to educate frontline providers on this underappreciated presentation.