Severe Recurrent Fever Episodes With Clinical Diagnosis of Hemophagocytic Lymphohistiocytosis, Incomplete Kawasaki Disease and Systemic-Onset Juvenile Idiopathic Arthritis: A Case Report and Literature Review

Abstract

The pathogeneses of recurrent fever are quite complicated when excluding repeated infections. Recurrent fever is a common symptom for autoinflammatory diseases, relapse of Systemic-onset juvenile idiopathic arthritis (SoJIA) and recurrent Kawasaki disease (KD). There are no specific diagnostic laboratory tests for the diseases. Some studies showed that KD was the precursor of hemophagocytic lymphohistiocytosis (HLH). Macrophage activation syndrome (MAS) is another form of HLH in SoJIA. Cytokine disturbances are considered to be involved in the pathogenesis of the diseases. We describe a Chinese female toddler that developed three separate fever episodes with eventual diagnose of SoJIA within about 10 months. The first episode was diagnosed as IKD, immunoglobulin nonresponsive KD, and HLH. The second and third episodes were diagnosed as IKD and SoJIA, respectively. The fever was hard to be relieved by antipyretics, and the peak axillary temperature was above 40 • C. For every fever episode, infections were excluded. For the first episode, trends over time of hemoglobin, platelets, fibrinogen, and triglycerides indicated HLH, which was finally diagnosed and treated according to the HLH-2004 protocol. For the second episode 6 months later, after excluding an HLH relapse and infections, IKD was finally diagnosed. Oral aspirin was administered, and the HLH treatment was ceased. The third episode occurred 3 months later, and SoJIA was finally diagnosed. For each episode, except for relative tests, we only tested for cytokines interleukin-1β, interleukin-6, and interferon-γ, due to limited laboratory test availability. These cytokines were elevated during remission and rose much higher in the fever phases. The case showed the difficulty to differentiating the recurrent fever in clinical practice. Surveillance of routine laboratory parameters over time might reveal a trend that indicates possible disease, even when parameter values Jiang and Yang Severe Recurrent Fever Episodes do not meet diagnostic criteria. Changes in cytokine profiles are promising markers for differentiating recurrent fever diseases in future. An unknown immunological defect for the case may contribute to the recurrent immunological insults, and we are following up the recurrence of fever episode.

Overlapping clinical features of systemic juvenile idiopathic arthritis and SARS-CoV-2-related multisystem inflammatory syndrome in children

“…Lower lymphocyte and thrombocyte levels and higher pro-BNP and ferritin levels were observed more often in MIS-C compared to KD. However, ferritin levels were the highest in MAS/sJIA [ 30 ].…”

Overlapping Features in Kawasaki Disease-Related Arthritis and Systemic-Onset Juvenile Idiopathic Arthritis: A Nationwide Study in Japan

“…Continued fever-onset/biologic patients showed high serum levels of ferritin and IL-18 and frequently became chronic, which were characteristics of SoJIA ( 28 , 29 ). There have been several case reports of SoJIA after receiving the diagnosis of KD ( 7 , 10 , 13 ). The early diagnosis of SoJIA is difficult because it starts with high fever, skin rash, and lymphadenopathy, which is not differentiated from KD, without apparent arthritis ( 8 , 30 ).…”

“…The diagnosis of SoJIA or KD at the disease onset is challenging because of common principal features and due to the absence of biomarkers for each disease (7,(9)(10)(11)(12)(13).…”

“…The diagnosis of SoJIA or KD at the disease onset is challenging because of common principal features and due to the absence of biomarkers for each disease ( 7 , 9 – 13 ). In the case of arthritis, a considerable observation period is needed to determine whether the main lesion is joint or vascular inflammation.…”

Impact of Kawasaki disease on juvenile idiopathic arthritis in real-world patients: A population-based cohort study

“…Arthritis is a self-limiting condition and has no association with cartilage destruction ( 6 ); several cases of JIA have been reported ( 7 ). Diagnosis of KD or JIA is challenging owing to their shared features and the lack of knowledge on relevant biomarkers ( 7 , 8 ). Kawasaki-disease-related arthritis is more frequently associated with coronary artery abnormalities than is non-Kawasaki-disease-related arthritis ( 9 , 10 ).…”