Delayed Kawasaki disease in an adult previously infected with SARS-CoV-2.

Introduction

Kawasaki disease (KD) is an acute febrile multisystem inflammatory disease that usually affects young children. Although rare in adults, a few adult KD cases have been reported1, 2, 3, 4; however, owing to its paucity, diagnosis and treatment of KD is often delayed. Recently, multisystem inflammatory syndrome (MIS) with significant overlap with KD has been described in adults after infection with SARS-CoV-2. Such diseases are important to keep on the differential diagnosis, especially during the current pandemic. Here we describe a case of delayed onset of KD in a 40-year–old man with a history of SARS-CoV-2 infection.

Case report

In July 2021, a 40-year–old Caucasian man presented to the dermatology clinic for assessment of a rash. Six months prior to this presentation, in January 2021, the patient had been infected with SARS-CoV-2 (confirmed by polymerase chain reaction [PCR] testing). During this episode, the patient experienced acute fatigue, dyspnea, myalgias, and headaches for a duration of approximately 7 days, followed by prolonged symptoms of mild dyspnea, fatigue, and anosmia for a period of approximately 3 months. This was followed by a period of approximately 3 months during which the patient was asymptomatic and well. At presentation to the dermatology clinic, the patient reported a 10-day history of high fever (maximum oral temperature of 39.0 °C), chills, fatigue, abdominal pain, nausea, persistent headaches, myalgias, and arthralgias that failed to respond to high doses (up to 7.5 g/day) of acetaminophen. On presentation, the patient appeared generally unwell, was febrile, and he had bilateral nonpurulent conjunctivitis; cervical lymphadenopathy; strawberry-red tongue with prominent papillae; bilateral feet erythema, edema, and desquamation; and an erythematous rash in the perineal and genital area, extending to the inner thighs (Fig 1). Based on these clinical findings, a diagnosis of complete KD was made, and the patient was sent to the emergency room for further workup and initiation of treatment.

Fig 1

Initial dermatologic manifestations consistent with Kawasaki disease. A, Strawberry tongue (erythema and prominent papillae), with associated lip fissuring in the right oral commissure and lip chapping on the upper vermilion lip. B, erythema and edema on both feet. C, Polymorphous exanthem in the inguinal regions. D, Polymorphous exanthem in the anterior chest regions.

The patient’s past medical history was significant for IgG4-related disease, diagnosed 4 years previously when he presented with enlarged lacrimal glands and cervical lymphadenopathy. However, his disease was quiescent for the past 2 years. He also had a history of diabetes, chronic sinusitis, and an episode of herpes simplex virus-associated meningoencephalitis in the 4 years prior.

In the emergency room, the patient was febrile at 38.5 °C. Blood work for liver function revealed elevated levels of the following: total bilirubin, 116 μmol/L (normal range, 3-17 μmol/L); conjugated bilirubin, 63 μmol/L (normal range, 0-5 μmol/L); alanine transaminase, 434 U/L (normal range, 5-40 U/L); and alkaline phosphatase, 492 U/L (normal range, 40-125 U/L). Given that the infectious and autoimmune hepatitis workup was negative, his liver dysfunction was considered secondary to his excessive acetaminophen intake in the days preceding his hospital visit; drug-induced liver injury was subsequently confirmed via liver biopsy. He also had leukocytosis (12.7 × 109/L; normal range, 4-11 × 109/L), mainly neutrophilic; severe anemia (hemoglobin, 46 g/L; normal range, 140-175 g/L), requiring blood transfusion; hypoalbuminemia (29 g/L; normal range, 35-51 g/L); mild thrombocytosis (443 × 109/L; normal range, 150-400 × 109/L); and elevated C-reactive protein (108 mg/L; normal range, 0-10 mg/L).

Cardiac troponins were negative. Echocardiogram revealed diffuse, uniformly enlarged arteries, but no coronary aneurysms. The patient’s extensive infectious workup all returned negative, including blood cultures and serologies for HIV, syphilis, streptococcal pharyngitis, mononucleosis, and respiratory viruses. Additionally, SARS-CoV-2 nasopharyngeal PCR was performed on admission and repeated a second time; results for both were negative.

Given his clinical presentation, the patient was started on intravenous immunoglobulin (IVIg) treatment at a dose of 2 g/kg per day for 3 days. Although he was also empirically given 1 dose of ceftriaxone (2 g) intravenously, this was discontinued after throat cultures returned negative. Because of his significant 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 his arthralgias and nausea, with down-trending of his liver enzymes and inflammatory markers. The patient’s erythematous rash and acral edema almost fully resolved, leaving behind only marked desquamation on his hands and feet (Fig 2). However, 2 days after completing his IVIg course, the patient’s fever returned (maximum temperature, 38.6 °C), prompting the decision to start a second course of IVIg (same as initial dose) for another 3 days. By day 3, the patient’s fever resolved, and he remained afebrile thereafter.

Fig 2

Dermatologic manifestations after intravenous immunoglobulin. A, Bilateral desquamation, with prominence in the periungual regions of the hands. B, Desquamation, with prominence in the periungual regions of the feet.

The day after completing his second IVIg course, the patient was still experiencing headaches and myalgias. Given the patient’s liver function tests and concern for potential effects of the inflammatory cascade on his coronary artery system, a course of prednisone at 60 mg daily was initiated. Within 24 hours of starting the steroid treatment, the patient’s symptoms fully resolved. Coronary computed tomography was performed, which did not reveal any coronary artery aneurysms. The patient was discharged with a prednisone taper over 3 weeks.

Discussion

The well-established diagnostic criteria for KD have not been fully validated in adults. However, existing case reports suggest that adenopathy, arthralgias, and transaminitis occur more frequently in adults, whereas cheilitis, meningitis/encephalitis, and thrombocytosis are less common. In addition, HIV infection, especially AIDS, has been found to be associated with one-fifth of KD cases in adults.

During the COVID-19 pandemic, reports have emerged of adult patients presenting with a KD-like MIS. The Center for Disease Control defines MIS in adults as a patient ≥21 years with severe extrapulmonary organ system dysfunction and laboratory evidence of acute inflammation, but without severe respiratory illness. The Center for Disease Control criteria also requires the detection of SARS-CoV-2 during admission or in the preceding 12 weeks. Although standardized treatments for MIS in adults have not yet been established, given the significant clinical overlap, regimens used to date are similar to those administered in KD, such as the use of IVIg, systemic glucocorticoids, and aspirin. Our patient met the criteria for complete KD. Given that infectious agents have been hypothesized to cause KD, SARS-CoV-2 should be added to the list of potential triggers. Although MIS in adults was on the differential, ultimately, a positive SARS-CoV-2 PCR at the time of admission and in the preceding weeks was not demonstrated.

The patient’s delayed presentation of KD was unusual. We hypothesize that his history of immune dysregulation, evidenced by previous IgG4-related disease and herpes simplex virus-associated encephalitis, predisposed him to prolonged SARS-CoV-2 symptoms and subsequently an abnormal immune response, resulting in KD. Studies involving children who develop MIS after COVID have shown maintenance of elevated levels of monocyte-activating IgG antibodies. Given the significant overlap of KD and MIS and the important role of monocyte activation in KD, we propose that SARS-CoV-2–specific antibodies may also play a role in the immunopathogenesis of delayed KD in adults, especially adults who present with prolonged or chronic COVID symptoms well beyond acute COVID infection. This, in turn, could explain why our patient had delayed presentation of KD with a negative SARS-CoV-2 PCR during his admission.

It is important to keep this classically pediatric diagnosis in the differential when assessing adults during the current COVID-19 pandemic and beyond, especially in patients with known immune dysregulation. KD has previously been diagnosed retrospectively because of the presence of myocardial infarction caused by coronary aneurysms, and such missed or delayed diagnoses can result in avoidable morbidity and mortality. Further reporting and education on the presentation, management, and outcomes of KD, especially following SARS-CoV-2 infection in adults, may lead to earlier diagnosis and management. Future directions could include measuring patients’ immunologic profiles and including quantitative antibody titers, especially in patients presenting with prolonged COVID symptoms to help distinguish between MIS in adults and KD as well as to elucidate the underlying immunopathogenesis of inflammatory processes resulting from SARS-CoV-2 infection.

Conflicts of interest

None disclosed.