A Child With Epstein-Barr Virus-associated Hemophagocytic Lymphohistiocytosis Complicated by Coronary Artery Lesion Mimicking Kawasaki Disease

Kato, Shogo; Yoshimura, Ken; Tanabe, Yuko; Kimata, Takahisa; Noda, Yukihiro; Kawasaki, Hirohide; Kaneko, Kazunari

doi:10.1097/mph.0b013e31828e5281

Cited by 14 publications

(10 citation statements)

References 18 publications

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“…As stated previously, both KD and EBV-HLH are autoinflammatory diseases complicated by immunologic dysfunction. There is considerable overlap between these conditions in terms of pathophysiology, such as increased serum levels of IL-6, IL-8, TNF-α and soluble IL-2 receptor [12]. Some studies indicated that EBV-infected CD8 + T cells and high levels of the cytokines in EBV-HLH may play some role in development of coronary artery lesions [12,13].…”

Section: Cardiovascular Complicationsmentioning

confidence: 99%

Epstein–Barr virus-related hemophagocytic lymphohistiocytosis complicated with coronary artery dilation and acute renal injury in a boy with a novel X-linked inhibitor of apoptosis protein (XIAP) variant: a case report

Chen

Lin

et al. 2020

BMC Pediatr

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Background X-linked lymphoproliferative disease (XLP) is a rare inherited X-linked primary immunodeficiency diseases (PID). One such disease, X-linked inhibitor of apoptosis protein (XIAP) deficiency, is characterized by Epstein–Barr virus-related hemophagocytic lymphohistiocytosis (EBV-HLH). However, EBV-HLH with coronary artery dilation and acute renal injury (AKI) in children is unusual. Case presentation We report the case of a young boy aged 17 months with a novel XIAP variant. He was initially diagnosed with EBV-HLH based on the HLH-2004 diagnostic criteria and the condition was accompanied by coronary artery dilation and acute renal injury. The comprehensive genetic analysis of peripheral blood-derived DNA revealed a hemizygous variant of the XIAP gene [c.116G > C(p.G39A)], which was inherited from his mother (heterozygous condition). After combined treatment with rituximab, intravenous immunoglobulin, corticosteroids, antiviral drugs, and mycophenolate mofetil (MMF) in addition to supportive therapy, his clinical manifestations and laboratory indexes were improved. The patient achieved complete remission with MMF treatment in the 8-month follow-up. Conclusions We report the [c.116G > C(p.G39A)] variant in the XIAP gene for the first time in a case of XLP-2 associated with EBV-HLH. For male patients with severe EBV-HLH, the possibility of XLP should be considered and molecular genetic testing should be used early in auxiliary diagnosis. Reports of EBV-HLH with coronary artery dilation and AKI in children are rare. In the patients with EBV-HLH, color Doppler echocardiography and urine tests should be monitored regularly. If necessary, renal biopsy can be performed to clarify the pathology. Treatment with rituximab, immunosuppressors and supportive therapy achieved a good effect, but long-term follow-up is required.

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Section: Cardiovascular Complicationsmentioning

confidence: 99%

Epstein–Barr virus-related hemophagocytic lymphohistiocytosis complicated with coronary artery dilation and acute renal injury in a boy with a novel X-linked inhibitor of apoptosis protein (XIAP) variant: a case report

Chen

Lin

et al. 2020

BMC Pediatr

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“…Because the symptoms and signs of these diseases are nonspecific, certain clinical parameters should be investigated carefully. The presence of CAE is a strong indication for KD, but it is also found in HLH that fulfills the criteria for KD (22) or SoJIA (23)(24)(25)(26)(27). Age-based anemia, low serum albumin, elevated ALT, and elevated leukocytes are supplemental laboratory criteria for diagnosing IKD in patients with elevated CRP and ESR, with a normal echocardiogram (28,29).…”

Section: Discussionmentioning

confidence: 99%

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

Jiang

Yang

2020

Front. Pediatr.

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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.

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“…Although several etiologies have been suggested to be involved in HLH, to date only one EBV-HLH case with a coronary artery aneurysm has been reported [5]. The previously reported EBV-HLH case fulfilled the diagnostic criteria of Kawasaki disease and was initially treated with high-dose intravenous immunoglobulins and oral aspirin.…”

Section: Discussionmentioning

confidence: 99%

“…It is well known that KD can cause arteritis resulting in coronary aneurism. Coronary artery aneurism was observed in the patients with HLH, who fulfilled the diagnostic criteria of KD [5]. …”

Section: Introductionmentioning

confidence: 99%

A case of Epstein-Barr virus–associated hemophagocytic lymphohistiocytosis with severe cardiac complications

et al. 2016

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BackgroundHemophagocytic lymphohistiocytosis (HLH) is a life threatening hematological disorder associated with severe systemic inflammation caused by an uncontrolled and ineffective immune response resulting in cytokine storm. Epstein-Barr virus (EBV) is the most common infectious agent in patients with the viral-associated HLH. Limited numbers of cases with cardiac complication have been demonstrated in other viral-associated HLH patients. Herein, we report a pediatric case of severe EBV-associated HLH with cardiac complications.Case presentationA previously healthy 4-year-old Japanese female was admitted to a local hospital with a four day history of fever. Despite antibiotic treatment, her fever persisted to day 7 of the illness. Finally, the diagnosis of HLH was confirmed by fulfilling diagnostic criteria for HLH and pathological analysis of bone marrow aspiration. Real-time PCR detected a high copy number of EBV DNA in the peripheral blood mononuclear cells (PBMCs) at the time of hospital admission. During treatment according to HLH-2004 protocol, sudden cardiopulmonary arrest (CPA) occurred on day 30 of the illness and immediate resuscitation was successful. Acute myocarditis was considered the cause of the CPA. Although the treatment regimen was completed on day 88 of the illness, a remarkably high copy number of EBV DNA was still detected in her PBMCs. Based on our flow cytometric in situ hybridization analysis that revealed EBV infection of only B lymphocytes, we decided to administer rituximab to control the abnormal EBV infection. Afterwards the amount of EBV DNA decreased gradually to undetectable level on day 130 of the illness. Unfortunately, a coronary artery aneurysm was discovered at the left main coronary artery on day 180 of the illness. Finally, the patient was discharged from the hospital on day 203 of the illness without sequelae except for a coronary aneurysm.ConclusionsIn this case report, EBV-HLH was complicated with cardiac symptoms such as myocarditis and coronary artery aneurysm. Although remarkably high copy number of EBV DNA was detected in PBMCs after completion of the HLH-2004 protocol, rituximab treatment resulted in a dramatic decrease of EBV DNA to undetectable levels. Rituximab treatment might have been beneficial for the patient’s survival.

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A Child With Epstein-Barr Virus-associated Hemophagocytic Lymphohistiocytosis Complicated by Coronary Artery Lesion Mimicking Kawasaki Disease

Cited by 14 publications

References 18 publications

Epstein–Barr virus-related hemophagocytic lymphohistiocytosis complicated with coronary artery dilation and acute renal injury in a boy with a novel X-linked inhibitor of apoptosis protein (XIAP) variant: a case report

Epstein–Barr virus-related hemophagocytic lymphohistiocytosis complicated with coronary artery dilation and acute renal injury in a boy with a novel X-linked inhibitor of apoptosis protein (XIAP) variant: a case report

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

A case of Epstein-Barr virus–associated hemophagocytic lymphohistiocytosis with severe cardiac complications

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