Kawasaki Disease Outcomes: It’s Not Just the Heart! Free

Kawasaki disease (KD), first described in 1967, is the most common pediatric acquired cardiac disease in the west.^1,2  It is characterized by a systemic inflammatory storm leading to a constellation of symptoms including conjunctivitis, skin rash, lymphadenopathy, mucosal membrane changes and supportive laboratory findings including increased inflammatory markers, elevated serum white blood cells, elevated platelet count, elevated liver enzymes, anemia, elevated white blood cells in the urine, and/or decreased albumin.³  In its severest form it may present in shock requiring critical care support.⁴  Despite more than 50 years of research, the cause remains unknown, and the diagnosis is made according to diagnostic criteria.^1,5  Thus, when multisystem inflammatory syndrome in children (MIS-C), a new illness which shares some features with KD, emerged during the 2019 novel coronavirus disease (COVID-19) pandemic, hope was raised that a cause of KD might be discovered.^6–10  The most dreaded sequalae of KD is development of coronary artery abnormalities (CAAs) including aneurysms, which typically occur either in the acute phase or shortly after.^1,11  Thankfully, with prompt immune therapy, the incidence of CAAs dropped to only 4%.¹  Despite the favorable prognosis, some children and their parents still suffer from anxiety and stress related to their KD diagnosis even after they have recovered from the acute phase of illness.¹² 

In this edition of Hospital Pediatrics, Naimi et al¹³  evaluated the long-term impact of KD hospitalization on health-related quality of life (HRQOL). Upon admission, the caregivers were asked to fill out two parent-proxy Pediatric Quality of Life Inventory (PedsQL) surveys, one reflecting the HRQOL at time of admission and one reflecting a baseline HRQOL (1 month prior to admission). The parents were also asked to fill out 2 more PedsQL surveys, one completed 2 to 12 weeks after hospital discharge (short term) and one completed at least one year following hospital discharge (long term). At hospital admission, the PedsQL total score (0–100 scale; the higher the score the better) was lower for KD patients compared with patients admitted with pneumonia (means 40.5 vs 49.5, P = .029). Although patients admitted with KD had significantly greater HRQOL decline from baseline to admission, at long-term follow-up, no difference was found in HRQOL between patients admitted with KD and those admitted with pneumonia. The comparison with pneumonia was chosen as the two conditions typically require only one acute care admission. The strength of this paper is the use of prospectively collected longitudinal data from individual parent surveys.¹³ 

The current publication confirmed what we know about HRQOL in the acute phase of KD. The same institution has previously assessed the immediate HRQOL in children admitted with KD and compared it to age, sex and race matched children who were admitted with either pneumonia (n = 65) or newly diagnosed cancer (n = 67). Shortly after admission, research staff asked caregivers to complete two PedsQL forms: one measuring HRQOL at admission and a second 1 month prior to admission. The authors noted a 45% decline in total PedsQL score from baseline to admission among children with KD, which was a greater drop in HRQOL than in the other two groups. Of note, nonintravenous immunoglobulin (IVIG) respondents suffered a greater drop in HRQOL than IVIG respondants.¹⁴  This suggests the need for psychosocial interventions for children diagnosed with KD and their parents in the acute phase of KD. Providers should not only concentrate on the cardiac involvement but the entire wellbeing of children with KD.

More reassuring in Naimi et al article was the finding that 89% of KD patients reached their preadmission baseline PedsQL scores by one year post discharge.¹³  This is in alignment with some previous publications. Muta H, et al performed a cross sectional observational study of patients who had KD, including 68 (27%) patients with CAAs and 19 (8%) with either giant aneurysms, ischemic changes, or both. Not only were the HRQOL scores not lower, but they were actually statistically higher than scores from the national norms at a mean interval of >18 years from KD onset.¹⁵  While surprising, the magnitude of the difference is small and is of uncertain clinical significance. In contrast, van Oers HA, et al, in a cross-sectional study that included 288 parents of KD patients, found higher parental perceptions of child vulnerability score, to a degree, similar to parents of a chronically ill child at an interval of ∼6 years from KD onset. Interestingly, most of the children whose parents were included in the study had recovered completely from the acute phase illness and none of the studied parental (gender, age, education, country of birth), child (gender) and disease characteristics (interval from KD onset to study participation, duration of hospital admission, persistent CAA at follow-up, or admission to critical care unit) were significantly associated with the vulnerability score.¹⁶  The differences in the medium to long term outcomes might be related to the tool used, the respondents (parents versus patients), interval since KD diagnosis, or specific characteristics of the KD cohorts unique to the individual centers.¹⁵  Case in point, in one cohort of KD patients, those assessed at a young age had an impaired HRQOL, but it resolved when assessing similar children at an older age.¹⁷ 

The cohort included in Naimi et al¹³  article included a larger than expected portion of children who developed CAAs (48%). This is similar to previous reports assessing HRQOL in children with KD. Patients with worse aneurysms tend to participate in research more frequently than patients with normal CAs.¹⁵  Regardless, we should be reassured that despite presence of CAAs, the perceived long term HRQOL is high.

In summary, the HRQOL in children with KD was shown to drop during the acute phase admission but recovered almost completely by the time of one year follow up. Pediatricians, pediatric hospitalists, and subspecialists, like cardiologists, ought to be aware of the impact of KD on the wellbeing of children and their families and intervene appropriately, empowered by the fact that, for most, a complete recovery is on the horizon. We ought to send the right message to families, especially those with normal coronary arteries, that their children are normal and are expected to have a full recovery without any exercise restrictions; a message endorsed by the American College of Cardiology Quality Network.¹⁸ 

Lastly, this single center manuscript was under powered to assess differences in HRQOL among KD subtypes, IVIG responsiveness, or CAAs presence.¹³  At any given center, the number of new patients admitted with KD remains low. Our community will benefit from multicenter, international KD collaboratives like the International KD registry.^19,20  That being said, the team at Seattle Children’s Hospital ought to be congratulated for establishing two institutional databases that helped accomplish their recent publications, namely the KD Research Program; a multidisciplinary prospectively collected database that included clinical, treatment and echocardiogram finding for children admitted with KD, and the Outcomes Assessment Program, which routinely assess child HRQOL of patients discharged from their institution.^13,14