Sweet syndrome induced by SARS-CoV-2 Pfizer-BioNTech mRNA vaccineAS Darrigade, MD1, H Théophile, MD2, P Sanchez-Pena, MD2, B Milpied, MD1, M Colbert4, MD, S Pedeboscq5, MD, T Pistone6, MD, ML Jullié, MD7, J Seneschal, MD, PhD1,31 : Department of Adult and Pediatric Dermatology, Bordeaux University Hospitals, France2 : Department of pharmacovigilancy, Bordeaux University Hospitals, France3 : Research Unit INSERM U10354 : Department of geriatry, Clinic Bordeaux Nord, Bordeaux, France5 : Department of pharmacology, Bordeaux University Hospitals, France6: Department of infectious disease, Bordeaux University Hospitals, France7: Department of anatomopathology, Bordeaux University Hospitals, FranceManuscript word count: 607Key words : sweet syndrome, SARS-CoV-2, Pfizer-BioNTech mRNA vaccine, delayed hypersensitivity, IDRCorresponding author: A.S. Darrigade, Dermatology Department, Saint-André Hospital, 1, rue Jean Burguet 33000 Bordeaux, FrancePhone: +33556794705Fax: +email@example.comFunding source: No financial disclosuresFinancial Disclosure: No external funding for this manuscriptTo the editor,A 45-year-old woman, without any past medical history or allergy presented in our clinic with a rapid onset of diffuse skin eruptions. Five days earlier, she received the first injection of the SARS-CoV-2 Pfizer-BioNTech mRNA. Concomitantly she took 1000mg paracetamol to prevent any post-vaccination syndrome. She well tolerated the preceding vaccines (influenza every year) before this one.The eruption started 24h after vaccine injection and was composed at time of the clinical exam of erythematous infiltrated papulosis located all over the body, without face involvement (Figure 1). No other extracutaneous symptoms were noted. Blood exams showed increased blood count levels with increased neutrophils count (8.77G/l), hepatic cytolysis (AST 67UI/L and ALT 116UI/l) with high level of PCR (115mg/l). SARS-CoV-2 PCR test and serology were negative. Viral tests for EBV, CMV, parvovirus B19, and Herpes simplex/Herpes zoster showed only a slight EBV reactivation. Histopathological examination of the skin biopsy showed a hyperplastic epidermis with an edematous papillary dermis. A superficial and deep dermal perivascular, periadnexal and interstitial dense infiltrate composed of neutrophils, eosinophils and lymphocytes was also a feature. Leukocytoclastic vasculitis was also seen (Figure 2A-2B). Clinical and pathological exams were compatible with the diagnosis of SS induced by SARS-CoV-2 Pfizer-BioNTech mRNA vaccine. Systemic steroid therapy (prednisone 0.5mg/kg/d) for five days was started and led to rapid improvement of the skin condition without any recurrence after treatment discontinuation. She did not receive the second vaccine injection.Patch-tests performed (14 days after steroid treatment stop, one month after SS) on both on healed and normal skin with pur SARS-CoV-2 Pfizer-BioNTech mRNA vaccine prepared less than 4 hours before were negative (Figure 1C 2-3). Then, intradermoreaction (IDR) with vaccine diluted at 1/10 on normal skin was positive in delayed reading (Figure 1C 1). Cutaneous biopsy was realized on the positive IDR reaction, showing an abundant inflammatory infiltrate predominantly with lymphocytes (Figure 2C).Cutaneous reactions after vaccine injection are rare, and heterogenous1. They could be related to the vaccine or the adjuvant. In addition, vaccine could trigger flares of chronic inflammatory conditions as it was previously reported1. At that time, minor local side effects are reported with SARS-CoV-2 vaccines such as pain, swelling or redness; hypersensitivity reactions were anaphylactic reaction but no severe delayed hypersensitivity are reported2-3. Three cases of acute febrile neutrophilic dermatosis are reported in the international bank of WHO, one in United Kingdom, one in United States of America and our case. Under SARS-CoV-2 Pfizer-BioNTech mRNA vaccine four cases of vasculitis had been reported after injection. In France one case of relapse of neutrophilic disorder was reported one day after SARS-CoV-2 Pfizer-BioNTech mRNA vaccine. The adjuvant associated with the SARS-CoV-2 Pfizer-BioNTech mRNA vaccine is polyethylene glycol (PEG) 20003. However our patient never received infusion containing PEG or polysorbate before. Patch-tests with PEG or polysorbate alone were not performed because of the negativity of the patch-test with the SARS-CoV-2 Pfizer-BioNTech mRNA vaccine. Only 10 cases of SS induced by vaccine are published so far including: 3 with seasonal influenza, 1 with influenza A, 2 with pneumococcal, 2 tuberculosis, 2 small pox4. SS is an acute inflammatory skin disease associated with important infiltration of neutrophils. Leukocytoclastic vasculitis could be present in SS5. One case of SS in a patient receiving pneumococcal vaccine showed the presence of dermal vasculitis associated with infiltration of neutrophils6. In case of anaphylactic reaction under SARS-CoV-2 Pfizer-BioNTech mRNA vaccine, the risk of relapse with the Moderna SARS-CoV-2 mRNA vaccine or SARS-CoV-2 vaccines with an adenovirus carrier and protein subunit remains unknown3, in case of SS even more.To conclude we report the first case of SS induce by SARS-CoV-2 Pfizer-BioNTech mRNA vaccine confirmed by positive IDR.
Due to COVID-19 global pandemic, treatment with HCQ, although controversial, has been widely prescribed. The aim of our study was to identify drug-drug interactions (DDI) between HCQ and long-term treatments of COVID-19 patients, focusing on drugs which can cause or promote QT prolongation. From March 13 to April 14 2020, 61 patients were treated with HCQ in our hospital. More than a half of patients (62%) had at least one DDI between HCQ and their long-term treatments. A large number of drug classes were involved, included contraindicated drugs The mean of co-medication contraindicated or not recommended with HCQ per patient was 1.9 CI95% [1.48 to 2.27]. All contraindicated drugs were discontinued at the beginning of HCQ treatment due to multidisciplinary meetings involving physicians and clinical pharmacists. To our knowledge this is the first study about DDI between HCQ and long-term treatments of COVID-19 patients.