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Introduction: Mucocutaneous eruptions are associated with many viral processes and present as erythema multiforme (EM), reactive infectious mucocutaneous eruption (RIME), Stevens Johnson syndrome (SJS) or toxic epidermal necrosis (TEN). Limited reports have described the association of COVID-19 and mucocutaneous eruptions in children and adults to date. Method(s): This was a multicenter descriptive case series performed at six tertiary medical centers. Inclusion required a clinical diagnosis of EM, RIME, SJS or TEN and a positive COVID-19 test (rapid antigen or PCR) less than 4 weeks prior to onset of dermatologic manifestation. Data was collected at time of each patient encounter. Result(s): A total of 7 patients met criteria and had a median age of 15 years for pediatric patients (<18 years of age) and 36 years for adult patients (>18 years of age). Patients were found to have a diagnosis of RIME in 85.7% of cases. Oral mucosal involvement was the most common clinical finding (100%), followed by ocular (57.1%), urogenital (57.1%) and skin (42.9%) involvement. 71.4% of cases required hospitalization for their cutaneous eruption. No patients died from their inflammatory condition. Discussion(s): This case series highlights the development of mucocutaneous eruptions in association with COVID-19 infection. Within our cohort, RIME was the most commonly identified COVID-associated eruption. These findings provide additional evidence that abnormalities in host immune response to viral pathogens play a role in severe mucocutaneous blistering conditions. Further investigation will aid our understanding of this disease to improve diagnostics and advance targeted treatments for patients in the future.
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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).
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The fast development of vaccines against the novel coronavirus disease is among the most critical steps taken to control this potentially fatal viral disease. Like other vaccines, the coronavirus disease 2019 (COVID-19) vaccines can also cause unwanted reactions. Erythema multiforme (EM) is among the oral mucocutaneous side effects of COVID-19 vaccines. This study aimed to comprehensively review the reported cases of EM since the global onset of COVID-19 vaccination. Data from 31 relevant studies regarding the type and dose of COVID-19 vaccines administered, time of initiation of symptoms, age, and gender of patients, site of involvement, patients' medical history, and treatment options were extracted. In total, 90 patients were identified with EM as a side effect of COVID-19 vaccination across studies. EM had the highest frequency after receiving the first dose of mRNA vaccines in older individuals. The first symptoms of EM appeared in less than 3 days in 45% and after 3 days in 55% of patients. EM is not a common side effect of COVID-19 vaccination, and fear of its occurrence should not impede vaccination.
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Since its emergence in December 2019, coronavirus disease 2019 (COVID-19) has been detrimental worldwide. Although COVID-19 infection is primarily known for its respiratory manifestations, extrapulmonary features are increasingly being reported. Among these, cutaneous manifestations are apparent but have a high likelihood of not being attributed to COVID-19. We present the case of a 63-year-old female unvaccinated against COVID-19. She presented with fever, cough, shortness of breath, and rash. The symptoms were present for four days and appeared after contact with a confirmed symptomatic COVID-19-positive family member. The rash started first on the chest and then spread to the face and whole body including the palms and soles. It was erythematous and maculopapular and is associated with ulceration and swelling of the lips. In places, it was confluent and had a target-like appearance. On admission, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction (PCR) was negative. As she was septic with initial suspicion of tick-borne infections, she was started on doxycycline. Given her symptoms on presentation, the suspicion of COVID-19 was very high, and the SARS-CoV-2 nasal swab PCR was repeated, which was negative yet again. With the index of suspicion being very high, her presentation was speculated to be atypical, especially in the setting of a target-like rash involving the palms and soles. The antibody was checked. IgG antibodies for SARS-CoV-2 were positive. All other antibodies for mycoplasma, Lyme disease, Ehrlichia, and Rocky Mountain spotted fever (RMSF) were negative. Parvovirus DNA and chikungunya IgG, antinuclear antibody (ANA), and antineutrophil cytoplasmic antibody (ANCA) screens were negative. IgG for mycoplasma, dengue, and herpes simplex virus 1 (HSV1) were positive. During all this time, the patient did not show clinical improvement in spite of being on antibiotics. In fact, her oxygen saturation dropped, and she required oxygen through the nasal cannula. A lung tissue biopsy taken on bronchoscopy showed chronic inflammation and organizing pneumonia. To note, mycoplasma DNA PCR and HSV culture from bronchoalveolar lavage (BAL) were negative. The patient was started on intravenous steroids. A confirmatory skin biopsy was done, and it showed perivascular, interstitial, and spongiotic dermatitis related to a viral infection. While on steroids, the patient improved dramatically. Her skin rash also improved, and she was discharged. On outpatient follow-up, she was doing exceptionally well with ambulatory oxygen saturation of 100%. This patient who was COVID-19 PCR-negative twice could have been easily deemed as not having COVID-19. However, the fact that she was unvaccinated, had positive sick contact with imaging concern for COVID-19 pneumonia, and COVID-19 antibody being positive and no other test being positive clearly attributes her manifestations to the virus. The presence of a rash could easily be misleading. Awareness of the fact that a rash like erythema multiforme (EM) could be a sign of underlying COVID-19 is extremely prudent and is an addition to the ever-expanding knowledge of this virus.
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Introduction: COVID-19 infection is a disease caused by the type 2 coronavirus that causes severe acute respiratory syndrome (SARS-CoV-2) that affects the respiratory mucosa and all those organs that present the type 2 angiotensin receptor (ACE2), within them the skin. Several authors have mentioned the importance of reporting and carrying out databases on skin lesions caused by this virus, since it is related to the detection, severity and prognosis of the systemic condition. Material(s) and Method(s): A retrospective cross-sectional observational study was carried out on the cases of patients who presented dermatological manifestations due to COVID-19, registered in the physical database of the National Specialized Hospital of Villa Nueva, Guatemala, from January 1st to December 31, 2021. Result(s): A total of 144 patients presented dermatological manifestations due to COVID-19, which were: acral lesions (42%), rash (21%), subcutaneous emphysema (12%), oral mucosal lesions (7%), necrosis (6%), erythema multiforme (5%), telogen effluvium (2%), vesicular lesions (2%), urticaria (1%), pityriasis rosea Gibert (1%) and livedo-type lesion (1%). A statistically significant association (p = 0,00) was found in patients who presented dermatological manifestations with vasculonecrotic damage as they were more likely to suffer from severe to critical disease (OR 2,91;95% CI 1063-3083). Conclusion(s): Early identification of cutaneous semiology is essential for timely management of complications associated with COVID-19 disease.Copyright © 2022 Elsevier Espana, S.L.U.
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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.
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Introduction: Varicella zoster virus is a highly infectious alpha-herpesvirus, pathogenic only to humans. The primary infection of varicella zoster virus causes chickenpox, which is contagious and primarily infects children and adolescents in India. Following the primary infection, the virus remains dormant in sensory root ganglia. Activation of the dormant virus in later stages of life causes herpes zoster infection which may vary from subclinical infection to typical zoster, scattered vesicles, zoster sine herpete or disseminated zoster, which depends on the individual's immune status. Case report: In this case series, we present two patients with herpes zoster involving the mandibular branch of the trigeminal nerve. Cytology revealed characteristic features of the infection including nuclear moulding, multinucleated giant cells and ballooning degeneration. Conclusion(s): More recently, patients presenting with herpes zoster have been reported to have sub-clinical Covid-19 infection, suggesting a possibility that herpes zoster might be an indicator for latent Covid-19. Timely detection and treatment of this infection can reduce the risk of post herpetic neuralgia.Copyright © 2022 Sciendo. All rights reserved.
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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
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The presence and reactivation of oral lesions such as herpetic gingivostomatitis, erythema multiforme, and candidiasis in a COVID-19 recovered patient could be related to COVID-19s profound role in immune dysregulation or related therapies.
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Reactive infectious mucocutaneous eruption (RIME) is a recently described entity in which there is prominent mucositis, most commonly involving the oral and urogenital mucosa, secondary to a variety of pathogens. There is typically minimal cutaneous involvement in RIME. This contrasts with erythema multiforme (EM) in which characteristic targetoid lesions predominate, usually in isolation (EM minor), but in a subset of cases, with severe mucositis (EM major). While the histopathologic features of RIME have not been as well defined, those of EM are characterized by epidermal apoptosis and interface dermatitis with lymphocytes making up the predominant cell type. We report a unique case of RIME in a 16-year-old male with COVID-19 characterized by significant mucositis involving the oral and genital mucosa, as well as numerous targetoid lesions on the trunk and extremities. Histopathologically, there was an inflammatory infiltrate obscuring and disrupting the epidermal interface, associated with epidermal necrosis, and blister formation. The infiltrate was composed of cells with irregular, non-segmented and elongate nuclei, with myeloid and histiocytoid cytomorphology. The cells were positive for myeloperoxidase, CD68, and CD163 (subset) suggesting myeloid lineage. RIME is a rarely reported COVID-19-related eruption, and targetoid lesions and myeloid interface reactions have not been described with RIME.
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There are several differences in illness presentation in clinical practice. Because diseases are ever-evolving, a single negative test cannot totally exclude the presence of a disease. The most frequent etiologies of erythema multiforme (EM), a prevalent mucocutaneous condition, are herpes infection and the use of numerous medicines. As a novel virus, SARS-CoV-2 is not often the primary differential for EM eruptions. This case represents a young female patient who presented solely with EM symptoms involving the distal parts of her upper and lower extremities after a positive swab for SARS-CoV-2. The condition improved with symptomatic treatment, and there were no major complications.
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The recently extended use of mRNA vaccines due to the COVID-19 pandemic has allowed the description of mul-tiple cutaneous adverse events including local injection site reactions, urticaria, and morbilliform eruptions. COVID-19 vaccine-related cutaneous reaction patterns can be divided into type Ⅰ hypersensitivity reactions, type Ⅳ hypersensitivity reactions, autoimmune-related, and functional angiopathies based on pathogenesis. Erythema multiforme (EM), a type IV hypersensitivity reaction, has also been reported from several centers. We experienced the remarkable im-provement of COVID-19 vaccine-related EM with systemic administration of prednisolone and summarized six cases experienced in our department. © 2022 Keiko Watanabe, et al. EnPress Publisher LLC. This work is li-.
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Erythema multiforme (EM) is a rare cell-mediated immune response characterized by target or iris patches or plaques that present symmetrically on the extremities. This condition may be associated with pruritus but is usually self-limited and spontaneously resolves within 5 weeks of onset;prodromal symptoms are rare. Several known cases have been linked to vaccination, but many vaccines used in pediatric care have been reported as causative agents of EM. This case study offers an association of EM following administration of the hepatitis A and pneumococcal vaccines.
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Introduction: Pfizer/BioNTech (BNT162b2) and Oxford/AstraZeneca (chAdOx1-S) COVID-19 vaccines were approved for emergency use. Clinical trials of both vaccines reported no safety concerns other than a few local and systemic reactions that resolved in few days for both vaccines. Cutaneous reactions to COVID-19 vaccination are generally minor and self-limited. The most common cutaneous reaction reported was a local injection-site reaction. Objective: Here we present 3 cases of erythema multiform following COVID-19 vaccination with positive rechallenge in 2 cases. Methods: Not applicable. Results: Case 1: A 51 year old woman with no past medical history presented with a macular, erythematous, round-shaped itchy rash on the hands, knees and soles. She denied having a neither recent illness nor sick contact. However, she received the first dose of the mRNA Pfizer/BioNTech (BNT162b2), 3 days earlier. Lesions disappeared in 7 days with local corticosteroid treatment. One month later and two days after receiving the second shot of the same vaccine, lesions reappeared and extended to upper members. Skin biopsy was compatible with erythema polymorph. Case 2: A 55 year old man with a past medical history of hypertension, presented 6 days following the 2nd shot of the mRNA Pfizer/ BioNTech (BNT162b2), vesicular eruptions on the upper and lower members. The outcome was favorable within 2 weeks under local corticosteroid. The patient reported that he had the same skin lesions in ankles and soles few days following the 1st shot of the same vaccine. Histological findings revealed an erythema polymorph. Case 3: A 57 year old woman with a medical history of hypertension and anxiety disorder presented with a worsening rash and fever for 6 days. The patient reported that she experienced fever, polyarthralgia and that she had received the second shot of Oxford/AstraZeneca (chAdOx1-S), the day before these symptoms appeared. On the physical examination, she had targetoid skin lesions over the trunk, on the ear, upper and lower members. Otherwise she had oral and genital mucosal ulcerations. A thoracic CT scan was performed because of the persistent fever and showed multiple enlarged lymph nodes, a layer of pericardial and plural effusion. A favorable outcome was observed in 3 weeks. Conclusion: Erythema multiform remains an exceptional COVID 19 vaccine adverse effect. Health care workers must be aware of this potential adverse effect or its recurrence and advise patients accordingly. Benefits of receiving a COVID 19 vaccine remains more important.
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Introduction: COVID-19 infection is a disease caused by the type 2 coronavirus that causes severe acute respiratory syndrome (SARS-CoV-2) that affects the respiratory mucosa and all those organs that present the type 2 angiotensin receptor (ACE2), within them the skin. Several authors have mentioned the importance of reporting and carrying out databases on skin lesions caused by this virus, since it is related to the detection, severity and prognosis of the systemic condition. Material and methods: A retrospective cross-sectional observational study was carried out on the cases of patients who presented dermatological manifestations due to COVID-19, registered in the physical database of the National Specialized Hospital of Villa Nueva, Guatemala, from January 1st to December 31, 2021. Results: A total of 144 patients presented dermatological manifestations due to COVID-19, which were: acral lesions (42%), rash (21%), subcutaneous emphysema (12%), oral mucosal lesions (7%), necrosis (6%), erythema multiforme (5%), telogen effluvium (2%), vesicular lesions (2%), urticaria (1%), pityriasis rosea Gibert (1%) and livedo-type lesion (1%). A statistically significant association (p = 0,00) was found in patients who presented dermatological manifestations with vasculonecrotic damage as they were more likely to suffer from severe to critical disease (OR 2,91;95% CI 1063-3083). Conclusions: Early identification of cutaneous semiology is essential for timely management of complications associated with COVID-19 disease.
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CASE: A 22-year-old woman with h/o asthma initially presented to the hospital with lip swelling and sore throat. She tested positive for COVID-19 and received a casirivimab-imdevimab (monoclonal antibody) infusion. She returned a week later with worsening lip swelling, dysphagia and conjunctivitis. Physical exam revealed edematous lips with vesicular lesions, no tongue swelling, tonsillar exudate, 4+ conjunctival injection bilaterally with purulent discharge, and shallow clean based clitoral ulceration. She reports no history of allergic reactions, angioedema or exposure to new medications. Nasopharyngolaryngoscopy showed no laryngeal edema but visualized exudates throughout the supraglottis and glottis. C4, ANA, CMV, EBV, throat and blood cultures were negative. STI testing was trichomonas positive and gonorrhea/chlamydia negative. Respiratory virus panel remained positive for COVID-19. HSV swab of lip lesion, HSV 1/2 IgG and IgM were negative. Mycoplasma pneumoniae IgG was elevated (0.60, negative is ≤0.09), IgM equivocal (0.85, negative is ≤0.76), and nasopharyngeal PCR negative. Conjunctival culture showed rare bacteria (S. Aureus) and no leukocytes. She initially received methylprednisolone IV due to concern for angioedema, acyclovir for empiric HSV treatment and empiric antibacterial moxifloxacin eye drops. Given lack of infectious trigger, her presentation was concerning for reactive infectious mucocutaneous eruption (RIME) associated with SARSCoV-2 or Mycoplasma. Prednisone 1mg/kg daily was initiated followed by improvement in oral mucositis and conjunctivitis within days. IMPACT/DISCUSSION: A broad differential is important when evaluating oral swelling and mucositis. Her lack of cutaneous involvement, medication exposure or family history and negative infectious, autoimmune and inflammatory workup make other causes including Stevens-Johnson syndrome, erythema multiforme, angioedema, and HSV less likely. Our final diagnosis of RIME describes mucocutaneous eruptions likely due to an immune response triggered by bacterial or viral infection. Our patient's RIME may be due to COVID-19 or Mycoplasma given her equivocal Mycoplasma IgM. Eruptions generally involve two or more mucosal sites and occur mostly in children and adolescents. Common presentations include oral erosions and ulcers, purulent bilateral conjunctivitis, or urogenital lesions, which were all seen in our patient. As this is a relatively rare and new condition, no standard of care treatment exists for RIME but systemic steroids have been effective in case reports for initial treatment and subsequent flares. CONCLUSION: RIME is a rare, newly described condition in young patients who develop postinfectious mucocutaneous eruptions of two or more mucosal sites. It has been recently reported in association with COVID-19 and its association with Mycoplasma infection is important to evaluate. This condition is important to recognize and treat given the requirement for higher dose steroids than that used for angioedema.
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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.