New definition of RIME: Mucocutaneous eruptions, bullous lesions and multi-mucosal involvement

Objectives: A 14-year-old female patient presents with marked haemorrhagic, adherent crusting of the upper and lower lip and enoral vesicles and erosions. Two weeks before, she had suffered from a respiratory tract infection. She did not take antibiotics but ibuprofen. One week later, she described a swelling and crusting of the upper and lower lips. Urogenital mucosa was also erosive. There was no ocular involvement. Another week later, cocard-like single lesions with partly central blister formation developed. A flaccid blister of 15 mm in diameter was detected in the left ear helix. In total, there was a limited cutaneous involvement of <10% BSA. The girl was admitted to the paediatric clinic. Method(s): Due to mucocutaneous eruptions, bullous lesions and multimucosal involvement, we assumed a Steven-Johnson syndrome or reactive infectious mucocutaneous eruption (RIME). Intravenous rehydration and prophylactic administration of cefotaxime and aciclovir were given. She was balanced and given analgesia with novalgin. The recent increased intake of ibuprofen was discontinued. Local therapy included mometasone cream and serasept dressings. During the inpatient stay, the general condition stabilised and the skin efflorescence's showed a clear regression. Result(s): The microbiological smears for COVID-19, HSV, VZV, mycoplasma, and chlamydia were negative. Discussion(s): As adult classifications for blistering severe cutaneous adverse reactions are limited applicable in children, Ramien et al. proposed revised paediatric-focused clinical criteria 2021. They leave traditional definitions of EEM, SJS and TEN. But they distinguish erythema multiforme (EM) for classic targets with/without mucosal involvement, RIME for cases with mucosal predominance and a respiratory infection trigger, and drug-induced epidermal necrolysis (DEN) for cases caused by medications. (Ramien BJD 2021) There are no current guidelines for RIME therapy. A reasonable management approach includes symptomatic therapy, treatment of identifiable infectious triggers (if possible), consulting urologists, ophthalmologists and gynaecologists (if necessary), immunosuppression, and psychological support. (Ramien ClinExpDermatol 2021).

Toxic epidermal necrolysis as a result of chlorthalidone and cyclophosphamide combination

Case report Introduction: Toxic epidermal necrolysis (TEN), is an immune-mediated disease characterized by severe mucocutaneous symptoms and is the result of an inflammatory response that leads to keratinocyte necrosis and perivascular lymphocyte infiltration, mostly drug-related. Case report: A 35-year- old male, with a history of recently diagnosed systemic lupus under treatment with prednisone, hydroxychloroquine, mycophenolate and cotrimoxazole forte evolves with persistent proteinuria, it is decided to add losartan, chlorthalidone and atorvastatin. Nevertheless despite immunosuppression, proteinuria and skin involvement persisted, so mycophenolate was suspended and a bolus of cyclophosphamide 1 g was administered. Eight weeks after adjusting treatment, the patient went to the emergency department due to a confluent, pruritic, maculopapular rash with blistering lesions on the trunk, upper limbs, face, and oral mucosa, associated with fever over 38degreeC, that evolved during one week. On admission, the following was confirmed: confluent erythematous macular exanthem associated with multiple flaccid blisters on the chest, upper limbs and neck, Nikolsky's sign (+), keratoconjunctivitis and dryness on the lips. Admission tests included complete blood count with no leukocytosis or eosinophilia, ESR 29 mm/hr, C-RP 19.8 mg/L, no liver profile abnormalities, creatinine 0.8 mg/dl, and urine test with proteinuria 300 mg/dl. Negative infectious study for mycoplasma, herpes 6 virus, cytomegalovirus, Epstein barr virus, hepatitis A, B, C, E and SARS-COV2 virus. Due to severe mucosal skin involvement, TEN/SJS was suspected v/s (TEN)-like Lupus presentation, drugs used prior to admission (chlorthalidone, losartan, atorvastatin) were discontinued, and treatment was started with Hydrocortisone 100 mg every 8 hours IV, Immunoglobulin 2 g/kg daily IV for 4 days, plus skin and mucous membrane care. Patient had a favorable evolution, with resolution of skin and mucosal lesions and no signs of infection. Skin biopsy showed necrotic epidermis, necrotic basal keratinocytes, and sparse lymphocytic inflammatory infiltrate in the papillary dermis, consistent with erythema multiforme/toxic epidermal necrolysis. Conclusion(s): Extensive mucosal involvement is one of the cardinal signs of the presentation of SJS/ETN and given its severity, a high index of suspicion is important with the consequent suspension of suspected drugs and support management for a favorable evolution. In this case the suspected culprit drug was the combination of cyclophosphamide and chlorthalidone, due to reports of increased toxicity of cyclophosphamide in combination with diuretic drugs.

Anesthetic management of toxic epidermal necrolysis: a report of two cases

Toxic epidermal necrolysis (TEN), is an acute, life-threatening emergent disease involving the skin and mucous membranes with serious systemic complications. It is characterized by widespread epidermal sloughing. Drugs are the most common triggers of TEN, but infection, vaccination, radiation therapy and malignant neoplasms can all induce it in susceptible patients. We report two cases in whom a hair dye and a COVID-19 vaccine (BioNTech, Pfizer) were believed to be the causative agents. These patients have to undergo repeated debridements of the necrotic tissue. In this manuscript the anesthetic management of TEN patients is discussed. Detailed preoperative evaluation, aggressive fluid and electrolyte replacement, avoidance of hypothermia during debridement, minimizing anesthetic agents and limiting traumatic procedures are key points in the management.Copyright © 2023 Faculty of Anaesthesia, Pain and Intensive Care, AFMS. All rights reserved.

Clinico-Epidemiological Profile of Cutaneous Adverse Drug Reactions at Rural Tertiary Care Centre

Background: Cutaneous adverse drug reactions (CADRs), also known as toxidermia, are skin manifestations resulting from systemic drug administration and it constituted 10%-30% among all reported adverse drug reactions (ADRs). These reactions range from mild morbilliform drug rash to much more severe reactions. Material(s) and Method(s): A retrospective observational study was conducted at dermatology outpatient department of rural based tertiary care center for a duration of 03 years from August 2019 to July 2022, a total of 211 patients who had been clinically diagnosed or were suspected to have drug reactions were studied. Result(s): In this observation there was male preponderance (59.72%) and majority of patients were in their 3rd and 4th decade (40.28%) with maculopapular drug rash (33.17%) being most common clinical profile of CADRs, followed by urticaria (23.70%). Less frequently seen CADRs were acneiform eruptions (21), hair Loss (9), photodermatitis (9), generalised pruritus (7), erythroderma (2), pityriasis rosea (2), Stevens Johnson Syndrome-Toxic Epidermal Necrolysis (SJS-TEN) (4), lichenoid drug eruptions (3), Vasculitis (1) and pustular drug eruption (1). The most common group of drugs causing CADRs were antibiotics (40.28%), followed by NSAIDs (28.43%). Conclusion(s): Cutaneous Adverse Drug Reactions (CADRs) are price we pay for the benefits of modern drug therapy;knowledge of these reactions is important for treating physician as prompt recognition and treatment can prove lifesaving.Copyright © 2022 Academic Medicine and Pharmacy

Toxic epidermal necrolysis and Stevens-Johnson syndrome after COVID-19 infection and vaccination.

Stevens-Johnson Syndrome (SJS) is a rare but severe skin reaction characterized by blistering and peeling of the skin and ulcerations of mucous membranes; toxic epidermal necrolysis (TEN) is a subset of SJS characterized by the involvement of >30% of the skin. Though previously associated with drugs and infections, discussions on the association between TEN/SJS and COVID-19 have been limited. We present a review of TEN/SJS after COVID-19 infection and vaccination. Literature searches were conducted on PubMed and Google Scholar from 2019 to 8/2022. Thirty-eight articles were selected based on subject relevance, and references within selected articles were also screened for relevance. As of 8/2022, there have been 34 published cases of TEN, SJS, and SJS-TEN overlap after COVID-19 infection and vaccination, including 12 cases after vaccination and 22 cases after infection. Multiple authors hypothesize that virotopes or excipients in COVID-19 vaccines can activate T-cells or cytokines to induce TEN/SJS. Meanwhile, some hypothesize that COVID-19 infection induces immune activation that can trigger TEN/SJS or increase susceptibility to drug-induced TEN/SJS. Treatments for post-infection and post-vaccination TEN/SJS vary significantly. We recommend remaining vigilant for this rare and severe potential complication.

Multidisciplinary Treatment in Toxic Epidermal Necrolysis.

Toxic epidermal necrolysis, Leyll's syndrome (TEN), is a rare mucocutaneous blistering disease burdened with high mortality rates. The diagnosis of TEN is based on clinical symptoms and histopathological findings. In approximately 90% of cases, it is a severe adverse reaction to drugs. In TEN, not only is the skin affected, but also mucosa and organs' epithelium. There are no unequivocal recommendations in regard to systemic and topical treatment of the patients. The aim of this paper is to review available literature and propose unified protocols to be discussed. Early management and multidisciplinary treatment are necessary to improve patients' outcome. Treatment of patients with TEN suspicions should be initiated with early drug withdrawal. TEN patients, like patients with burns, require intensive care and multidisciplinary management. Each patient with TEN should be provided with adequate fluid resuscitation, respiratory support, nutritional treatment, pain control, infection prophylaxis, anticoagulant therapy, and gastric ulcer prophylaxis. The key to local treatment of patients with TEN is the use of nonadherent dressings that do not damage the epidermis during the change. The aim of the systemic treatment is purification of the blood stream from the causative agent. The most efficient way to clarify serum of TEN patients' is the combination of plasmapheresis and IVIG. Immunomodulatory therapy can reduce the mortality five times in comparison with the patients with immunosuppression or lack of full protocol.

Managing the ADR of Stevens-Johnson syndrome/toxic epidermal necrolysis.

INTRODUCTION: Stevens-Johnson syndrome and toxic epidermal necrolysis are severe, life-threatening adverse drug reactions that are collectively known as epidermal necrolysis. The abrupt detachment of the skin and mucositis results in systemic complications such as fluid and electrolyte disturbances, hypothermia, sepsis, organ failure, and death. Management is multidisciplinary and complex. AREAS COVERED: This present article reviews the principles and best practices in the care of patients with epidermal necrolysis. These include having prompt admissions to optimal care facilities, coordinated specialized care during the acute phase, as well as long-term follow-up to manage chronic sequelae. EXPERT OPINION: Patients with epidermal necrolysis should be managed in specialized/reference centers that are experienced with the management of the disease. Multi-disciplinary supportive care remains the cornerstone. Current evidence precludes definitive recommendation on any immunomodulatory agent as treatment. Long-term follow-up is required in order to diagnose and treat any chronic sequelae.

Toxic epidermal necrolysis and Stevens-Johnson syndrome after COVID-19 infection and vaccination

Stevens-Johnson Syndrome (SJS) is a rare but severe skin reaction characterized by blistering and peeling of the skin and ulcerations of mucous membranes;toxic epidermal necrolysis (TEN) is a subset of SJS characterized by the involvement of >30% of the skin. Though previously associated with drugs and infections, discussions on the association between TEN/SJS and COVID-19 have been limited. We present a review of TEN/SJS after COVID-19 infection and vaccination. Literature searches were conducted on PubMed and Google Scholar from 2019 to 8/2022. Thirty-eight articles were selected based on subject relevance, and references within selected articles were also screened for relevance. As of 8/2022, there have been 34 published cases of TEN, SJS, and SJS-TEN overlap after COVID-19 infection and vaccination, including 12 cases after vaccination and 22 cases after infection. Multiple authors hypothesize that virotopes or excipients in COVID-19 vaccines can activate T-cells or cytokines to induce TEN/SJS. Meanwhile, some hypothesize that COVID-19 infection induces immune activation that can trigger TEN/SJS or increase susceptibility to drug-induced TEN/SJS. Treatments for post-infection and post-vaccination TEN/SJS vary significantly. We recommend remaining vigilant for this rare and severe potential complication.

COVID-19 vaccine provocation test outcome in high-risk allergic patients: A retrospective study from a tertiary hospital in Indonesia.

Background: High COVID-19 vaccine coverage is essential. Patients who are considered high risk for hypersensitivity reactions and have had an allergic reaction to the COVID-19 vaccine are usually referred to an allergist for assessment of vaccination. Administration of a vaccine graded challenge (also known as a provocation test) is an option that can be considered in this population. This primary objective of this study is to describe the outcome of the COVID-19 vaccine provocation test and to understand the predicting factors associated with hypersensitivity reaction after the provocation test as the secondary objective. Methods: Adult patients with a history of hypersensitivity reaction to the first COVID-19 vaccine and high-allergic patients who underwent COVID-19 vaccine provocation test up until May 2022 were included. A protocol using skin prick test (SPT), intradermal test (IDT), followed by graded challenge was developed for the determined vaccine used. Results: A total of 232 patients were included in the analysis. Twenty-eight had hypersensitivity to their first COVID-19 vaccine dose and 204 were high risk for allergic reaction. Hypersensitivity reactions occurred in 20 patients (8.6%, 95% CI: 5-12.2%), consisting of 4 reactions after SPT, 9 after IDT, 7 during or after titrated challenge. Half of the reactions were mild; however, 3 patients developed severe reactions. Patients with history of anaphylaxis were more likely to experience hypersensitivity reaction after provocation test (aRR = 2.79, 95% CI: 1.05-7.42). Conclusion: Provocation test in COVID-19 vaccination has a high success rate in patients with a history of hypersensitivity to the first COVID-19 vaccine and in high allergic patients. History of anaphylaxis is associated with hypersensitivity reaction after a COVID-19 vaccine provocation test.

MULTISYSTEM INFLAMMATORY SYNDROME IN ADULTS (MIS-A) FOLLOWING SARS-COV-2 INFECTION PRESENTING AS TOXIC EPIDERMAL NECROLYSIS

SESSION TITLE: COVID-Related Critical Care Cases SESSION TYPE: Case Reports PRESENTED ON: 10/19/2022 11:15 am - 12:15 pm INTRODUCTION: Multisystem Inflammatory Syndrome in Adult (MIS-A) is a rare hyperinflammatory response occurring 2 to 6 weeks after COVID-19 resembling Kawasaki disease. CASE PRESENTATION: A 23-year-old male presented to the emergency room with fevers, cough, shortness of breath, fatigue and painful rashes all over his body. 3 weeks prior, he was diagnosed with COVID-19 which was managed conservatively at home. He recovered within 3 days. He had received 2 doses of Moderna COVID-19 vaccine 6 months prior. He denied recent drug intake. Vitals were BP 116/78 mmHg, heart rate 164/min, temperature 97.3℉, SpO2 96% on room air. Physical exam revealed macular erythematous rash in his trunk and extremities. Leukocyte count was 4 k/uL, hemoglobin 15.5 g/dL, platelets 99 k/uL, sodium 126 mmol/L, bicarbonate 20 mmol/L, BUN 30 mg/dL, creatinine 2.2 mg/dL, lactate 5.1 mmol/L, ferritin >7500 ng/mL, total bilirubin 7.6 mg/dL, AST 298 U/L, ALT 291 U/L, ALP 106 U/L, procalcitonin 14.71 ng/mL, D-dimer 11.98 FEUug/mL. Troponin-I peaked at 1359 pg/mL. CT angiography of the chest showed clear lung fields without pulmonary embolism. Venous doppler was negative. Echocardiogram showed normal biventricular function and valves. An extensive infectious disease workup was negative. He was suspected to have MIS-A from recent COVID-19. He was started on methylprednisolone 1g/day, intravenous immunoglobulin (IVIG), anakinra and empiric antibiotics. Over the next 2 days, there was progression of rash with sloughing of skin in his trunk, back and extremities with bullae on his legs, and thigh sparing the face (figures). Skin biopsy revealed epidermal necrobiosis with apoptosis consistent with Toxic Epidermal Necrolysis (TEN). On day 3, he had a cardiac arrest from ventricular fibrillation but was successfully resuscitated. Subsequently, he was intubated, and required escalating vasopressor support for shock. On day 5, he also developed non-purulent conjunctivitis. On day 6, he was transferred to a higher center with a burns unit. However, despite aggressive supportive measures he succumbed to refractory shock the following day. DISCUSSION: Our patient fit the criteria for MIS-A outlined by CDC (1) with age ≥21 years, fevers, rash with non-purulent conjunctivitis for primary clinical criteria, hypotension and thrombocytopenia for secondary clinical criteria, several laboratory criteria, negative infectious work-up with a history of recent COVID-19. It is unclear if the COVID-19 vaccine increased his risk of MIS-A. There have been case reports of MIS-A presenting as TEN following COVID-19 and COVID-19 vaccines in the absence of typical triggering drugs. (2,3) MIS-A is treated with high dose steroids, IVIG, tocilizumab and supportive measures. Anakinra was used for our patient because of liver dysfunction. CONCLUSIONS: MIS-A following COVID-19 can also present as life-threatening skin reactions like TEN in the absence of triggering drugs. Reference #1: Retrieved from https://www.cdc.gov/mis/index.html Reference #2: Narang I, Panthagani AP, Lewis M, Chohan B, Ferguson A, Nambi R. COVID-19-induced toxic epidermal necrolysis. Clin Exp Dermatol. 2021;46(5):927-929. Reference #3: Kherlopian A, Zhao C, Ge L, Forward E, Fischer G. A case of toxic epidermal necrolysis after ChAdOx1 nCov-19 (AZD1222) vaccination. Australas J Dermatol. 2022;63(1):e93-e95. DISCLOSURES: No relevant relationships by Fady Jamous No relevant relationships by Swaminathan Perinkulam Sathyanarayanan

GRESIF: A Project for the Management of Severe Adverse Drug Reactions (SCARs). The Experience of Lombardy and Piedmont: An International Journal of Medical Toxicology and Drug Experience

Introduction: In Lombardy and Piedmont (Northern Italy, about 14 million people) the GRESIF pharmacovigilance network project, aimed to collect, assess, treat and prevent severe systemic drug reactions was activated in 2021, supported by the Italian Medicines Agency (AIFA). GRESIF involves regional and hospital pharmacovigilance centers, and several hospital wards: burn, dermatology, allergology, internal medicine, infectivology and intensive care departments. The registry collects in the National Pharmacovigilance Network all reports of suspected adverse drug reactions (ADRs) concerning Toxic Epidermal Necrolysis (TEN), Stevens-Johnson Syndrome (SJS), Drug reaction with eosinophilia and systemic symptoms (DRESS) and Acute Generalized Exanthematous Pustulosis (AGEP). Objective: The specific objectives of the study are to early detect severe systemic ADRs, evaluate their incidence, morbidity and mortality rates, focus on new generation drugs such as RNA antivirals and oncological drugs, implement and optimize guidelines, manage long-term sequelae by follow-up and create a consultable web-based database. Methods: We have drawn up the guidelines [1,2], through a multidisciplinary approach in order to improve the management of very complex patients even in facilities that are not habitually involved in the treatment of these pathologies. This document aims to support professionals in standardizing diagnostic criteria and methods of therapeutic approach. Its useful to inform the general practitioner about responsible drugs and give some information about risk /benefit on the riexposure. Results: In 2021, 27 cases of SJS/TEN, 18 cases of DRESS and no cases of AGEP were collected. There is a female prevalence (25 cases out 44);the age range is from 20 to 93 years. The median age of patients in Lombardy and in Piedmont is respectively 55 and 66 for females, 47 and 63 for males. The total mortality for cases of SJS/ TEN is about 19% and for DRESS we have no deaths. More frequent suspected drugs are antibiotics, followed by allopurinol and anticonvulsants. Noteworthy is the presence of 4 cases of severe ADR related to anti Covid19 RNA vaccines. In all cases, according to the guidelines, the timely discontinuation of the responsible drug was fundamental as the general management. Furthermore we started a study for the HLA typing of these patients. We enrolled 18 cases and the results showed that 6 patients who received allopurinol were all positive to HLA B 58:01. Conclusion: Despite being extremely rare but serious reactions, the absolute need to implement shared diagnostic and therapeutic protocols to be applied promptly is highlighted, in order to reduce both patient mortality and long-term sequelae.

Severe Toxic Epidermal Necrolysis and Drug Reaction with Eosinophilia and Systemic Symptoms Overlap Syndrome Treated with Benralizumab: A Case Report

TEN/DRESS overlap syndrome can be difficult to diagnose, especially if it is masked by comorbidities in critically ill patients in intensive care units. The existing therapy for the two conditions is also a major challenge for the treating team. A possible alternative, especially for refractory cases, is benralizumab as an IL-5-receptor alpha-chain-specific humanized monoclonal antibody (IgG1k). We are able to show a successful treatment in this case report.

Toxic Epidermal Necrolysis(TEN) Associated with covid-19 Infection, a Case Report

Introduction: Covid-19 infection has been spreading worldwide since December 2019. Skin manifestations are common as 60% of patients had skin involvement such as rashes, chilblains, urticaria, purpura and vasculitis (1). Toxic Epidermal Necrolysis (TEN) is a life-threatening dermatological disease with > 30% of body surface area involved. TEN pathophysiology is linked to immune system activation triggered by drugs or infections or unknown causes (2). We are reporting a case of biopsy confirmed TEN in pediatrics patient with history of recent Covid19 infection. Case Description: A 6-year-old boy with history of mild Covid 19 infection two weeks ago presented with fever, oral ulcers and maculopapular rash on the trunk and extremities for 2 days. He was admitted for supportive care. His skin rash was progressing to violaceous targetoid lesions on the trunk and extremities with genital erosion, Nickolsky sign was positive. He had purulent conjunctivitis and crusted lips lesions with deepithelization of the oral mucosa. SCROTEN score was 2 for detachment more than 30%, low bicarbonate of 19. All virology tests came out negative including respiratory and blood PCR testing. A 4-mm punch skin biopsy histopathology was consistent with TEN. He was treated with supportive care, IVIG 1 g/Kg daily for 5 days, IV dexamethasone shifted later to oral Prednisolone, Cyclosporin 3 mg/kg/day. His rash and oral mucositis improved within 1 week and he was discharged in stable condition. He was seen in the clinic after 1 month of discharge and recovery of the skin, oral and eye mucosa was observed. Discussion: This report presented a case of a child with TEN and history of recent Covid-19 infection. Most cases of TEN are triggered by drugs and some by infections (3)(4). There were case reports of TEN associated with Covid 19 infection in adults with probable association with drugs such as hydroxychloroquine (3), Allopurinol (5), Lamotrigine (6), one case with no history of drug exposure (7). In a report of more than 5000 pediatrics patients with Covid-19 infection only one patient had SJS (8). Another case of 8-year-old boy with Covid-19 infection who developed SJS rash was reported (9). Both pediatrics cases had history of Amoxicillin- Clavulanate use. In our case the relationship between Covid-19 infection and TEN is not clear as the child had a history of Ibuprofen use that could be the culprit trigger. However, Covid-19 could still be the trigger in this case. It is worth reporting this case to keep in mind the wide spectrum of dermatological presentation in Covid-19 patients. Conclusion: Whether Covid 19 infection can trigger TEN in pediatrics patient is an important question that needs larger studies, yet it is worth reporting this case of possible correlation between Covid 19 and TEN in pediatrics.

Toxic epidermal necrolysis after first dose of Pfizer-BioNTech (BNT162b2) vaccination with pharmacogenomic testing.

Toxic epidermal necrolysis (TEN) is a rare and acute life-threatening condition and one of the severe cutaneous adverse drug reactions. There are limited data on TEN from the COVID-19 vaccine regarding its pathogenesis, treatment, and prognosis, particularly in children. We report a case of COVID-19 vaccine-induced TEN and the patient's human leukocyte antigen pharmacogenomic profile.

ERYTHEMA MULTIFORME MAJOR (EMM) POST SECOND COVID-19 VACCINATION: A CASE REPORT

CASE: Our patient is a 52-year-old female with a history of gastroesophageal reflux and hypertension. 36 hours after receiving the second Pfizer COVID-19 vaccine, she developed lip and tongue swelling, mucosal ulcerations, and respiratory distress. There was no conjunctivitis or genital involvement. She denied taking any new medications, supplements, or food that might have led to the reactions. She initially presented to an outside hospital and required intubation prior to transfer to our facility. A bedside esophagogastroduodenoscopy (EGD) was performed noting extensive Grade D erosive esophagitis and gastric ulcerations with friability. When the endoscope was removed a 34cm section of necrotic esophageal tissue was removed from the airway. Despite intravenous steroid treatment, she continued to have esophageal scarring and was unable to tolerate food by mouth. Therefore, a gastrostomy tube was placed. Since that time, she has required several recurrent EGDs for esophageal dilation due to scarring. It has now been six months from her initial injury, and unfortunately, the patient is still unable to take PO and is dependent on tube feedings. IMPACT/DISCUSSION: The coronavirus pandemic began in December 2019. At the time of this report, SARS-CoV-2 infection has been the cause of 5.48 million deaths worldwide and 836,000 deaths in the United States alone. In addition, this global pandemic has had severe economic and social implications. There are currently three vaccines authorized by the United States Food and Drug Administration for emergency use. I report an extremely uncommon complication of the Pfizer COVID-19 vaccine: a case of Eryethema Multiforme Major that occurred after the second dose vaccine without exposure to any other drug. Eryethema Multiforme is divided into major and minor forms and is regarded as distinct from Stevens- Johnson syndrome and toxic epidermal necrolysis. It is related to infections, usually Herpes Simplex Virus, or less commonly, to medications. In Erythema Multiforme, mucous membrane involvement is absent or mild. Erythema Multiforme Major is an immune mediated skin reaction involving the oral cavity and mucosa that is serious and occasionally life threatening. There have been several reported cases of Erythema Multiforme following COVID-19 vaccination but only one other cases of Erythema Multiforme Major associated with the mRnA-1273 SARS-CoV-2 vaccine (Moderna.) CONCLUSION: This case highlights an extremely rare vaccine consequence. The benefits still greatly outweigh the risks of vaccination, and this case does not diminish the importance of COVID-19 vaccination to effectively control this pandemic.

Challenges in the management of toxic epidermal necrolysis and COVID-19: a case report

With the outbreak of the emergent coronavirus, there have been sparse reports of severe cutaneous adverse reactions in some severely ill patients (Chen XY, Yan BX, Man XY. TNFα inhibitor may be effective for severe COVID-19: learning from toxic epidermal necrolysis. Ther Adv Respir Dis 2020;14: 1753466620926800). It is thought that this is due to clonal expansion of CD8+ cytotoxic T lymphocytes and natural killer cells that occurs during the cytokine storm elicited by the virus or the use of unconventional drugs to treat patients (Rossi CM, Beretta FN, Traverso G et al. A case report of toxic epidermal necrolysis (TEN) in a patient with COVID-19 treated with hydroxychloroquine: are these two partners in crime? Clin Mol Allergy 2020;18: 19;Saha M, D'Cruz A, Paul N et al. Toxic epidermal necrolysis and co-existent SARS-CoV-2 (COVID-19) treated with intravenous immunoglobulin:'Killing 2 birds with one stone'. J Eur Acad Dermatol Venereol 2020;35: e97-8). In a minority of cases, viral or autoimmune forms of toxic epidermal necrolysis (TEN) may be implicated (Chen et al.;Rossi et al.). However, very little research, has been done to decipher the association or pathogenesis with TEN and the novel virus. We report an interesting case of a 51-year-old woman who developed a rash on her face, flanks and periumbilical area immediately after an intensive care admission with respiratory failure secondary to confirmed COVID-19 pneumonitis. The patient had a background of gout on allopurinol and type 2 diabetes. There were no changes in medications. While admitted, she was started on broad spectrum antibiotics. On examination, there were large, confluent patches of erythema with a targetoid appearance on the face, upper limbs and trunk, and tense blistering over the forearms. Biopsy showed full thickness epidermal necrosis and subepidermal bullous formation. An autoimmune and bullous screen was negative. Prognosis was poor with the critical care team considering end-of-life management. However, with the diagnosis of a reversible condition, supportive therapy was continued. With continued intensive care intervention, steroids and barrier protection, her TEN gradually resolved as she recovered from COVID-19, and she had a favourable outcome with only residual milia and signs of re-epithelialization.

SYSTEMIC IMMUNOMODULATING THERAPIES FOR STEVENS-JOHNSON SYNDROME AND TOXIC EPIDERMAL NECROLYSIS IN A COVID-19 PATIENT. A CASE REPORT

Stevens-Johnson syndrome and toxic epidermal necrolysis are rare serious disorders that affect the skin and mucous membranes. These reactions are most commonly caused by drugs and, rarely, infections. While discontinuing the offending drug and supportive care are primordial, there are no consensus treatment guidelines on the optimal use of systemic immunomodulatory agents. Here, we report a case of a 57-year-old woman, who had recently recovered from COVID-19 infection, with Stevens-Johnson syndrome/toxic epidermal necrolysis overlap most likely triggered by dorzolamide eye drops. The patient was successfully treated with a single subcutaneous dose of etanercept combined with oral cyclosporine, corticosteroids and intravenous immunoglobulins. The progression of skin lesions ceased after administration of etanercept. In addition, a significant clinical improvement was observed a few days after treatment with immunoglobulins, without complications or important side effects.