pernio, temporally associated with the second dose of Pfizer mRNA SARS-CoV-2 vaccine.; This is a literature report from the The journal of dermatology, 2021, doi: 10.1111/bjd.20404 entitled Pernio after COVID-19 Vaccination.  A 64-year-old male presented to the emergency department in January 2021 with violaceous skin discoloration for 10 days that started on the left hallux and gradually spread to all toes on the bilateral feet. The patient received the second dose of the Pfizer COVID-19 vaccine 3 days prior to onset of the left toe discoloration. He denied hot or cold exposure, numbness, tingling, or pain. He denied history of pernio or other similar lesions, Raynaud's phenomenon, oral ulcers, photosensitivity, vascular disease, cardiac disease, hypercoaguable state, cardiac procedure, or autoimmune diseases. He denied previous or current symptoms of COVID-19 or exposure to those with COVID symptoms or a positive test. The estimated local prevalence of the virus was 7.6%. The patient had three negative COVID-19 PCR tests in the two months prior to presentation, and negative testing at presentation. The patient denied any adverse reactions after the first dose of the vaccine. The patient had painless, dark erythematous to violaceous discoloration of the bilateral toes, with an intact bulla on the left hallux. Abnormalities on initial laboratory studies included elevated C-reactive protein (CRP). The differential diagnosis included idiopathic pernio, connective tissue disease, hypercoagulable state, vasculitis/vasculopathy, COVID-19 infection, or reaction to the vaccine. Laboratory workup including Hepatitis B, Hepatitis C, HIV, ANA, ANCA, antiphospholipid antibodies, complements C3/C4/CH50, rheumatoid factor, and serum and urine protein electrophoresis was initiated to rule out other etiologies in the differential diagnosis. The key differentiating feature between COVID-19-associated pernio and idiopathic pernio is the lack of association with cold exposure. Idiopathic pernio was unlikely as the local weather was relatively mild; daily temperatures averaged 9 degree-20 degree C in the weeks before and after the lesions appeared. The patient was in stable condition and was discharged with clobetasol 0.05% ointment for the affected toes with plan to follow up in the outpatient dermatology clinic in two weeks. At follow up 15 days after initial presentation (28 days after vaccination), the clinical appearance of the toe discoloration was unchanged. The patient's symptoms were now exacerbated by cold temperatures and improved with rewarming and leg elevation. Laboratory workup was unrevealing. A punch biopsy of the left great toe was obtained, which revealed pathology consistent with pernio and immunohistochemistry (IHC) staining for SARS-CoV-2 of the tissue was negative. COVID infection remained a possibility. However, negative testing and lack of symptoms or contact with infected individuals argued against this. Thus, the final diagnosis was pernio, temporally associated with the second dose of Pfizer mRNA SARS-CoV-2 vaccine. The patient was counseled to use clobetasol as needed and avoiding cold exposure. This presentation suggests possible attribution of the pernio-like lesions to an immune response triggered by the COVID-19 mRNA vaccine, potentially similar to the immune response after Sars-CoV-2 itself, which also triggers pernio.; Sender's Comments: Based on the available public information and temporal association, the causal association cannot be excluded for the event Pernio, temporally associated with the second dose of Pfizer mRNA SARS-CoV-2 vaccine. The impact of this report on the benefit/risk profile of the Pfizer product is evaluated as part of Pfizer procedures for safety evaluation, including the review and analysis of aggregate data for adverse events. Any safety concern identified as part of this review, as well as any appropriate action in response, will be promptly notified to Regulatory Authorities, Ethics Committees, and Investigators, as appropriate.