key: cord-0828674-pbn8ef6h authors: Wang, Sheila; Lu, Jessica; Merati, Nickoo; Lefrançois, Philippe title: Delayed Kawasaki disease in an adult previously infected with SARS-CoV-2 date: 2022-03-03 journal: JAAD Case Rep DOI: 10.1016/j.jdcr.2022.02.015 sha: 07a9ce819cadbfaf91a9f3ba535df8a0c5bf8075 doc_id: 828674 cord_uid: pbn8ef6h nan Word count: 1,236 12 Reference count: 9 13 Figure/ In July 2021, a 40 year-old Caucasian man presented to the dermatology clinic for assessment of a rash. 44 6 months prior to this presentation, the patient had previously been infected with SARS-CoV-2 in 45 January 2021 (confirmed by PCR testing). During this episode, the patient acutely experienced fatigue, 46 dyspnea, myalgias and headaches for a duration of approximately 7 days, followed by a period of 47 approximately 3 months of the prolonged symptoms of mild dyspnea, fatigue, and anosmia. This was 48 followed by a period of approximately 3 months when the patient was asymptomatic and well. At 49 presentation to the dermatology clinic, the patient reported a 10-day history of high fever (maximum 50 oral temperature of 39.0°C), chills, fatigue, abdominal pain and nausea, persistent headaches, myalgias, 51 and arthralgias that were not responsive to high doses (up to 7.5 grams per day) of acetaminophen. On 52 presentation, the patient appeared generally unwell, was febrile, and had bilateral non-purulent 53 conjunctivitis, cervical lymphadenopathy, strawberry-red tongue with prominent papillae; bilateral feet 54 erythema, edema and desquamation, and an erythematous rash of the perineal and genital area 55 extending to the inner thighs ( Figure 1 ). Based on these clinical findings, a diagnosis of complete KD was 56 made and the patient was sent to the emergency room for further work-up and treatment initiation. 57 58 The patient's past medical history was significant for IgG4-related disease diagnosed 4 years prior, when 59 he presented with enlarged lacrimal glands and cervical lymphadenopathy. However, his disease was 60 quiescent in the past 2 years. He also had a history of diabetes, chronic sinusitis, and an episode of HSV 61 meningoencephalitis in the 4 years prior. In the emergency room, the patient was febrile at 38.5°C. Blood work revealed elevated liver function 64 tests: total bilirubin 116 µmol/L (normal 3-17), conjugated bilirubin 63 µmol/L (normal 0-5), ALT 434 U/L 65 (normal 5-40) and ALP 492 U/L (normal 40-125). Given that infectious and autoimmune hepatitis work-66 up was negative, his liver dysfunction was considered secondary to his excessive acetaminophen intake 67 in the days preceding his hospital visit: drug-induced liver injury was subsequently confirmed via liver 68 biopsy. He also had leukocytosis (12.7 x 10 9 /L, normal 4-11), mainly neutrophilic, severe anemia Given his clinical presentation, the patient was started on intravenous immunoglobulin (IVIg) treatment 79 at a dose of 2g/kg per day for 3 days. Although he was also empirically given one dose of Ceftriaxone 80 (2g) intravenously, this was discontinued after throat cultures returned negative. Due to his significant 81 liver dysfunction, the decision was made to not start aspirin. With IVIg, the patient's fever subsided within 24 hours, and he experienced significant improvement of 84 his arthralgias and nausea, with down-trending of his liver enzymes and inflammatory markers. The 85 patient's erythematous rash and acral edema almost fully resolved, leaving behind only marked 86 desquamation on his hands and feet ( Figure 2 ). However, 2 days after completing his IVIg course, the 87 patient's fever returned (maximum temperature 38.6°C), prompting the decision to start a second 88 course of IVIg (same as initial dose) for another 3 days: by day 3, the patient's fever resolved and he 89 remained afebrile thereafter. The day after completing his second IVIg course, the patient was still experiencing headaches and 92 myalgias. Given the patient's liver function tests and concern for potential effects of the inflammatory 93 cascade on his coronary artery system, a course of prednisone at 60mg daily was initiated. Within 24 94 hours of starting steroid treatment, the patient's symptoms fully resolved. A coronary CT was performed 95 that did not reveal any coronary artery aneurysms. The patient was discharged with a prednisone taper 96 over 3 weeks. Discussion 99 100 The well-established diagnostic criteria for KD have not been fully validated in adults. However, existing 101 case reports suggest that adenopathy, arthralgias, and transaminitis occur more frequently in adults, 102 whilst cheilitis, meningitis/encephalitis, and thrombocytosis are less common. In addition, HIV infection, 103 especially AIDS, has been found to be associated with one fifth of adult KD cases (Sève, 2011) . During the SARS-CoV-2 pandemic, reports have emerged of adult patients presenting with a KD-like 106 multisystem inflammatory syndrome (MIS-A). The CDC defines MIS-A as a patient ≥21 years with severe 107 extrapulmonary organ system dysfunction, and laboratory evidence of acute inflammation, but without 108 severe respiratory illness: it also requires positive detection of SARS-CoV-2 during admission or in the 109 preceding 12 weeks (Kerkerian, 2021 The patient's delayed presentation of KD was unusual: we hypothesize that his history of immune 118 dysregulation, evidenced by prior IgG4-related disease and HSV encephalitis, predisposed him to 119 prolonged SARS-CoV-2 symptoms and subsequently an abnormal immune response resulting in KD. 120 Studies on children who develop MIS after COVID have shown maintenance of elevated levels of 121 monocyte-activating IgG antibodies (Bartsch, 2021) . Given the significant overlap of KD and MIS, and the 122 important role of monocyte activation in KD, we propose that SARS-CoV-2-specific antibodies may also 123 play a role in the immunopathogenesis of delayed KD in adults, especially adults who present with 124 prolonged or chronic COVID symptoms well beyond acute COVID infection. This, in turn, could explain 125 why our patient had delayed presentation of KD with a negative SARS-CoV-2 PCR during his admission. 126 127 It is important to keep this classically-pediatric diagnosis in the differential when assessing adults during 128 the current SARS-COV-2 pandemic and beyond, especially in patients with known immune 129 dysregulation. KD has previously been diagnosed retrospectively due to the presence of myocardial 130 infarction caused by coronary aneurysms (Gomard-Mennesson, 2010), and such missed or delayed 131 diagnoses can result in avoidable morbidity and mortality. Further reporting and education on the 132 presentation, management, and outcomes of KD, especially following SARS-COV-2 infection in adults, 133 may lead to earlier diagnosis and management. Future directions could include measuring patients' 134 immunologic profiles, including quantitative antibody titers, especially in patients presenting with 135 prolonged COVID symptoms to help distinguish between MIS-A versus KD, as well as elucidate the 136 underlying immunopathogenesis of inflammatory processes resulting from SARS-COV-2 infection. 137 138 Humoral signatures of protective and pathological SARS-CoV-2 141 infection in children Adult-onset Kawasaki disease: A great masquerader An Adult Kawasaki Disease with Coronary 147 Artery Involvement: A Unique Case Report and Literature Review Kawasaki disease in adults: report of 10 cases Multisystem inflammatory syndrome in an adult after SARS-CoV-2 infection. 153 Adult Kawasaki disease in a European patient: a case 156 report and review of the literature Case Series of Multisystem Inflammatory Syndrome in Adults 159 Associated with SARS-CoV-2 Infection -United Kingdom and United States Kawasaki disease in adult patients. La Revue de Médecine Interne A Case of Adult-Onset Kawasaki Disease Shock 166 Syndrome Complicated by Coronary Aneurysms Fig 1. Initial dermatologic manifestations consistent with Kawasaki disease Strawberry tongue (erythema, prominent papillae) with associated lip fissuring in right oral 176 commissure and lip chapping on upper vermilion lip. B, Bilateral feet erythema and edema. C Polymorphous exanthem in the inguinal regions. D, anterior chest regions