Anaphylaxis After the Covid-19 Vaccine; This is a literature report.   Authors reported a case of the first patient at the (Hospital), who had immediate anaphylaxis after administration of the Pfizer-BioNTech Covid-19 vaccine. Authors highlighted that the patient never had an episode of anaphylaxis previously and had nonreactive skin testing for polyethylene glycol, polysorbatecontaining vaccines, as well as the Covid-19 vaccine itself. Importantly, she had an underlying condition that predisposed her to non-IgE-mediated anaphylaxis. The case is a 34-year-old female healthcare professional, who presented to the Allergy and Immunology clinic for evaluation of an anaphylaxis event that occurred after administration of the first dose of the Pfizer-BioNTech Covid-19 vaccine. The patient had negative SARS-CoV-2 nucleic acid tests 109 and 39 days before immunization. She noted in the interview to have been subjectively overheated while standing in line waiting to receive the first dose of the vaccine. Within 3 min of vaccine administration, she developed flushing, urticaria on her extremities and face, generalized pruritus, tongue swelling, nausea, light-headedness, racing pulse, and shortness of breath with absence of wheezing. Emergency medical personnel responded and administered intramuscular epinephrine and diphenhydramine. She noted substantial relief within minutes of administration of these medicines. The patient was transported to the emergency department for monitoring and had no further reaction. After discharge, she noted erythema and hives around the site of injection, which were nearly resolved by the time of our evaluation 2 days later. Two years earlier, she noted a large hive at the site of injection that took days to resolve after receiving preservative free quadrivalent influenza vaccine, Fluarix (GlaxoSmithKline) without associated systemic symptoms. Two months before the anaphylaxis event, she received Afluria (Seqirus), quadrivalent preservative-free influenza vaccine. Again, she noted a large local hive at the site of injection without a systemic reaction. She also described a history of childhood asthma and eczema but had never had an episode of anaphylaxis. She lastly described a greater than 10-year history of inducible episodes of pruritus, swelling, and hives that were most notable at times of sweating. She noted an inability to take warm showers as well as limitations with exercise due to pruritus and hives in what was suspicious for cholinergic urticaria. Authors performed an examination, laboratory studies, and several procedures for evaluating her anaphylaxis episode. Laboratory evaluation showed elevation in C-reactive protein (CRP) (1.27 mg/dL) 2 days following immunization, negative chronic urticaria (CU) index (4.3), and IgE levels (74.98 IU/mL) within the reference range. Dermatographism was not present. Skin examination revealed no skin findings of cutaneous mastocytosis. Serum tryptase was 4.7 ug/L and 5.4 ug/L checked 7 and 26 days, respectively, after the event and was within reference range; tryptase was not checked before or during the event. The tryptase alpha/beta 1 (TPSAB1) copy number variation test did not reveal tandem duplication(s) of TPSAB1 by allele-specific PCR. Prick puncture skin testing for polyethylene glycol, Prevnar 23 (Merck), and Pfizer-BioNTech Covid-19 (Pfizer) was negative. She scored 11 of 21 on the cholinergic urticaria disease severity standardized scale, suggesting moderate level of the disease. Authors further confirmed cholinergic urticaria via exercise provocation challenge guided by a standardized protocol. Based on the history and findings, her systemic reaction after receiving the Covid-19 vaccine was most consistent with anaphylaxis from a severe episode of cholinergic urticaria. Cholinergic urticaria has a known association with anaphylaxis although most people usually have only cutaneous symptoms. Because of her newly diagnosed cholinergic urticaria and recent anaphylaxis episode, authors recommended she carry an epinephrine auto-injector. Authors also recommended non-sedating antihistamine therapy for prevention of urticaria during bathing and exercise once she was done breastfeeding. Lastly, authors recommended all vaccines including the second dose of the Covid-19 vaccine be administered under supervision in a cool room without excessive clothing. The protection data after a single dose of the vaccine was unclear at the time so administering a single dose was not considered ideal. Based on the evaluation and the patient's increased risk for SARS-CoV-2 exposure, she, after informed decision making, accepted a second dose of the Pfizer-BioNTech Covid-19 vaccine. Authors recommended against pre-medications since they were able perform the challenge in a cool room and confirm that she was not sweating or overheating. Authors also did not want to mask an IgE-mediated reaction in the event of false-negative skin testing. In addition, the patient did not want to use any antihistamines as her infant was not weaned and still breastfeeding. She tolerated her second dose, without premedication, exhibiting only transient, mild nausea and a sense of warmth, but without any objective findings. Vaccines have an overall excellent safety profile; this includes data from Covid-19 vaccine clinical trials. Authors highlighted that the patient showed propensity for allergic reactions even before administration of the Covid-19 vaccine based on her localized reaction to the influenza vaccines and her history of cholinergic urticaria. It was important for them to evaluate whether IgE-mediated anaphylaxis might underlie her case. Authors showed that the patient had nonreactive skin testing with both 1:1 epicutaneous and 1:100 and 1:10 intradermal Covid-19 vaccine and drugs containing polysorbate 80. However, more data are needed to determine skin testing's role in predicting IgE-mediated Covid-19 vaccine allergy. Likewise, evaluation of mast cell activation in addition to IgE-mediated allergy needs to be considered after any episode of anaphylaxis or potentially severe cutaneous reaction to Covid-19 vaccinations. Evaluations should include the evaluation of inducible urticaria disorders, hereditary alpha tryptasemia, mastocytosis, and idiopathic mast cell activation disorders. Assuming that immediate Covid-19 vaccine reactions correlate to an IgE-mediated allergy ignores other non-contraindicating etiologies and potentially erroneously denies patients the benefit of immunization. Thus, the general public should be aware of immune conditions that may place a person at risk of anaphylaxis, but that these may not be specific to the Covid-19 vaccine. Distinctly, CDC guidance notes "If you had an immediate allergic reaction after getting a shot of a Covid-19 vaccine, you should not get a second shot of that vaccine, even if your allergic reaction was not severe enough to require emergency care." The fact that the patient with a common mast cell disorder was able to safely receive the second dose of the Covid-19 vaccine following anaphylaxis suggests that anaphylaxis may not represent an absolute contraindication but validates the recommendation that these cases should be evaluated by an allergist and an immunologist for directed care and not be categorically denied the Covid-19 vaccine.  Prior patient reactions and cholinergic urticaria exercise provocation test. Left Upper: Large local hive after influenza vaccine. Left Lower: Prior cholinergic urticaria around the cheeks triggered by heat. Middle: Baseline skin before cholinergic urticaria exercise provocation test. Right: Urticaria in face and arms after exercise provocation challenge. Skin test for Covid-19 vaccine and components. Left: Skin test results corresponding to components labels on right. Top Image is right arm. Bottom image is left arm. Right: Organized skin test panel with further component and administration details along with flare and wheal size. (Note: Actual test location varies to organized panel.).  No follow-up attempts are possible; information about lot/batch number cannot be obtained.; Sender's Comments: Based on the current available information and the consistency with the known safety profile of the suspect product BNT162B2, a possible contributory role of the suspect product BNT162B2 to the development of event Anaphylaxis cannot be totally excluded.