Sex: F
Vaccine: COVID19
Symptoms: Metabolic function test, SARS-CoV-2 test, Skin test, Thyroid function test
Clinical narrative: Generalized granuloma annulare after COVID-19 vaccination; This is a literature report.  A 58-year-old woman with a history of hyperlipidemia and bipolar disorder presented at the dermatology clinic because of a 3-month rash, which began 2 weeks after her second dose of the Pfizer COVID-19 vaccine. The rash began on her trunk and spread to her upper and lower extremities. She endorsed mild pruritus. Examination revealed multiple papules coalescing into plaques with central clearing on the back, flank, inguinal folds, and extremities. Based on morphology, a diagnosis of generalized GA was favored, and a punch biopsy provided confirmation. Punch biopsy showed an interstitial histiocytic infiltrate in the papillary dermis in a palisading array with central necrobiosis consistent with granuloma annulare.Laboratory tests revealed a normal complete blood cell count, comprehensive metabolic panel, thyroid function, and hemoglobin A1c; HIV and hepatitis panels were negative. A real-time polymerase chain reaction test result for SARS-CoV-2 was negative. The patient had elevated levels of total cholesterol (299 mg/dL; reference range, <200 mg/dL) and low-density lipoprotein-cholesterol (196 mg/dL; reference range, <100 mg/dL). Treatment was initiated with an intramuscular injection of triamcinolone 40 mg and clobetasol 0.05% topical cream with improvement 1 month later, at which point she was started on hydroxychloroquine 200 mg twice a day following clearance from an ophthalmologist. At follow-up 2 months later, there was a reduction and flattening of the skin lesions. She was continued on hydroxychloroquine 200 mg twice a day and topical clobetasol. The patient was advised to receive the COVID-19 booster dose through a shared decision-making process, as the benefits of vaccination were deemed to be greater than the possible risk of a GA flare. The patient followed up 2 weeks after receiving the Pfizer COVID-19 booster dose, complaining of new lesions, increased itching, and redness of her rash, which started less than a week after the third dose. The patient was instructed to continue her current treatment, and hydroxyzine 25 mg every night at bedtime was prescribed. Although GA is considered a benign disease, it can cause significant distress, especially in generalized cases. The patient has a history of hyperlipidemia, which, along with diabetes, has been cited as a likely risk factor for GA; however, more studies are needed to better substantiate this relationship. To author's knowledge, no studies have evaluated the time sequence between dyslipidemia and the onset of generalized GA. Dyslipidemia was considered as a possible etiology; however, given her 10-year history of hyperlipidemia and treatment with a statin, we concluded that the presentation of generalized GA 2 weeks after COVID-19 vaccination was more likely attributed to the vaccination rather than the hyperlipidemia. It is important to acknowledge that since the majority of cases of GA are idiopathic, the onset of generalized disease in this patient following administration of the COVID-19 vaccine could simply be a temporal coincidence. That being said, the patient's flare developing after the booster dose does provide more evidence to support the vaccine as a contributor. The nebulous nature of the etiology of GA is likely the culprit reason for this patient not experiencing generalized GA after her first dose of the vaccine. It is also possible that threshold titers of a stimulatory antigen were not present until after the second vaccine dose or that immunologic memory was naive until the second dose; initial testing of the Pfizer and Moderna vaccines showed that a relatively weak immune response was elicited after the first dose; a more robust response followed, when the second dose was given. This may be the reason why the patient experienced a flare only after her second dose and is the reason why current guidelines recommend a 2-dosage schedule for the aforementioned COVID-19 vaccines. Additionally, the patient experienced the flare less than 1 week after receiving the COVID-19 booster dose, which fact further supported the correlation between the vaccine and her disease. Upon exposure to the booster dose, the faster onset of disease flares is consistent with delayed-type hypersensitivity reactions that result from subsequent exposure to the stimulus. To author's knowledge, this case is the first reported in the literature of generalized GA occurring after COVID-19 vaccination.  No follow-up attempts are possible; information about lot/batch number cannot be obtained. No further information is expected.; Sender's Comments: Based on the current available information and the plausible drug-event temporal association, a possible contributory role of the suspect product BNT162B2 to the development of the event granuloma annulare  cannot be totally excluded.   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.