In clinical practice, there are a lot of variations in disease manifestations. Diseases are constantly evolving, and one negative test cannot completely rule out a disease. Erythema multiforme (EM) is a common mucocutaneous disease that can be linked to a lot of etiologies, with the most common being herpes simplex virus (HSV) types 1 and 2, Mycoplasma pneumoniae, and the use of various drugs. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new virus, and traditionally it is not the first differential for EM eruptions. We report the case of a 52-year-old female patient with a history of multiple drug use, pneumonia-like symptoms, an initial negative viral panel for SARS-CoV-2, followed by a positive polymerase chain reaction (PCR) test, asymptomatic coronavirus disease 2019 (COVID-19) clinical course, and break-out of typical targetoid lesions of EM. Throughout her hospital stay, the patient maintained her oxygenation levels and improved clinically with steroids and symptomatic treatment. She regained her health and was counseled to quit smoking, alcohol, and opioid usage at the time of discharge from the hospital, and a regular follow-up with her primary care practitioner (PCP) was advised.
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