Unusual Hemodynamic Presentation of Pediatric Kikuchi‐Fujimoto Disease: Persistent Sinus Bradycardia and Vasopressor‐Dependent Hypotension

ABSTRACT

Kikuchi‐Fujimoto disease rarely presents with vasopressor‐dependent hypotension requiring pediatric intensive care despite preserved cardiac function. This case highlights the importance of early excisional lymph node biopsy for timely diagnosis and appropriate management of children with unexplained hemodynamic instability and necrotizing cervical lymphadenopathy.

Key Clinical Message

Persistent bradycardia and vasopressor‐dependent hypotension represent rare hemodynamic manifestations of pediatric Kikuchi‐Fujimoto disease despite normal cardiac biomarkers and preserved ventricular function. Early lymph node biopsy is essential when necrotizing cervical lymphadenopathy remains unexplained.

Abbreviations

ALP

alkaline phosphatase

CBC

complete blood count

CRP

C‐reactive protein

ECG

electrocardiography

ESR

erythrocyte sedimentation rate

HLH

hemophagocytic lymphohistiocytosis

INR

international normalized ratio

IV

intravenous

KFD

Kikuchi‐Fujimoto disease

MRI

magnetic resonance imaging

PICU

pediatric intensive care unit

SLE

systemic lupus erythematosus

1. Introduction

Kikuchi‐Fujimoto disease (KFD), also known as histiocytic necrotizing lymphadenitis, is an uncommon benign inflammatory disorder characterized by self‐limited necrotizing lymphadenitis of uncertain etiology [1]. Although initially described in East Asian populations, KFD has now been reported worldwide across all age groups [2]. The true incidence of KFD remains unknown, largely because definitive diagnosis relies on excisional lymph node histopathology, whereas its nonspecific clinical manifestations frequently mimic infectious lymphadenitis, lymphoma, and systemic autoimmune diseases, resulting in delayed or missed diagnosis [2, 3]. Current evidence supports an immune‐mediated pathogenesis characterized by an exaggerated T‐cell–mediated response in genetically susceptible individuals, potentially triggered by infectious or other unidentified stimuli; however, no single causative pathogen has been consistently demonstrated [1, 4]. Children typically present with unilateral cervical lymphadenopathy and prolonged fever. A contemporary review of the pediatric literature, including 34 published studies comprising 670 children with KFD, reported cervical lymphadenopathy in 96.3% of patients, fever in 77.1%, leukopenia in 56%, and elevated erythrocyte sedimentation rate (ESR) in 56%, whereas C‐reactive protein (CRP) elevation was observed in only approximately one‐third of cases [5]. The absence of specific clinical, laboratory, or radiological findings frequently delays diagnosis and results in extensive investigations for bacterial lymphadenitis, tuberculosis, lymphoma, and systemic autoimmune diseases. Consequently, excisional lymph node biopsy remains the diagnostic gold standard [3, 4].

Although KFD generally follows a benign and self‐limited clinical course, severe systemic manifestations have been increasingly recognized. Reported complications include hemophagocytic lymphohistiocytosis (HLH), aseptic meningitis, encephalitis, peripheral neuropathy, hepatic involvement, myocarditis, pericarditis, and other rare multisystem manifestations requiring hospitalization or intensive care [2, 6]. Recurrence has been reported in approximately 3%–12% of pediatric patients, whereas subsequent development of systemic lupus erythematosus (SLE) has been described in a small proportion, supporting long‐term clinical surveillance following recovery [7]. Cardiovascular involvement in KFD is rare and has been described predominantly in isolated case reports, most commonly as myocarditis, pericarditis, or nonspecific electrocardiographic abnormalities [1, 8].

Persistent sinus bradycardia associated with vasopressor‐dependent hypotension in the absence of biochemical or echocardiographic evidence of myocardial injury represents an unusual clinical phenotype that may closely mimic late presentation of culture‐negative septic shock and delay recognition of the underlying diagnosis. We report a child with biopsy‐confirmed KFD presenting with sinus bradycardia and vasopressor‐dependent hypotension requiring pediatric intensive care support, followed by rapid and sustained hemodynamic recovery after corticosteroid therapy. This case expands the recognized cardiovascular spectrum of pediatric KFD and highlights the importance of considering this disease in children with unexplained necrotizing cervical lymphadenopathy despite negative infectious investigations.

2. Case History/Examination

A previously healthy, fully vaccinated 11‐year‐old boy presented with a 6‐day history of intermittent high‐grade fever (maximum temperature, 39.5°C), progressive left‐sided cervical swelling, dizziness, and generalized fatigue. He denied respiratory, gastrointestinal, urinary, musculoskeletal, or dermatologic symptoms. There was no history of seizures, recent medication exposure, trauma, toxic ingestion, or significant past medical history. On admission, the patient appeared persistently pale and looked unwell, although he remained fully alert with preserved peripheral perfusion. Physical examination demonstrated unilateral left‐side tender cervical lymphadenopathy without overlying skin erythema or fluctuation. Cardiovascular assessment revealed sinus bradycardia (heart rate ranging from 55 to 65 beats per minute while awake) associated with hypotension for age (blood pressure ranging from 81–88/50–54 mmHg), despite preserved peripheral perfusion and blood lactate levels. No cardiac murmur, hepatosplenomegaly, generalized lymphadenopathy, rash, arthritis, or focal neurological deficits were identified. Urine output remained adequate throughout admission. Because of persistent hypotension requiring close hemodynamic monitoring and support, the patient was admitted to the pediatric intensive care unit (PICU). He remained fully alert and well perfused despite persistent sinus bradycardia and hypotension.

3. Differential Diagnosis, Investigations and Treatment

Initial laboratory investigations demonstrated normal complete blood count (CBC), renal and liver function, serum electrolytes, international normalized ratio (INR), lactate, creatine kinase, troponin‐I, ferritin, and blood gas analysis. Serum alkaline phosphatase (ALP) was 88 U/L, below the age‐adjusted pediatric reference range [9]. Inflammatory markers showed negative CRP and procalcitonin levels with mildly elevated ESR (25 mm/h). Laboratory findings are summarized in Table 1. Peripheral blood film was unremarkable, demonstrating no abnormal cells and only a few reactive lymphocytes. Blood and urine cultures remained sterile, respiratory multiplex polymerase chain reaction (BioFire) was negative, and targeted investigations for atypical pathogens, including Brucella species and Mycobacterium tuberculosis , were negative. Epstein–Barr virus serology demonstrated previous exposure without serological evidence of acute infection (Table 2).

TABLE 1.

Initial blood work results for the patient.

Test [unit]	Result
White blood count (WBC)	4.8 × 109/L
Hemoglobin	11.1 g/dL
Platelet Count	291 × 109/L
C‐reactive protein (CRP), quantitative	3.3 mg/L
Procalcitonin (PCT)	0.08 ng/mL
Erythrocyte sedimentation rate (ESR)	25 mm/h
Ferritin	169 μg/L
Sodium	134 mmol/L
Serum potassium	4.1 mmol/L
Chloride	101 mmol/L
Corrected calcium	2.24 mmol/L
Blood urea nitrogen	3.7 mmol/L
Creatinine	67 μmol/L
Glucose	4.9 mmol/L
Lactate	1.7 mmol/L
International normalized ratio (INR)	1.1
Albumin	38 g/L
Alanine aminotransferase (ALT)	6 U/L
Aspartate aminotransferase (AST)	15 U/L
Alkaline phosphatase (ALP)	88 U/L
Creatine kinase (CK)	60 U/L
Thyroid‐stimulating hormone	1.4 uIU/mL
Free T4	16.02 pmol/L
pH	7.33
Partial pressure of carbon dioxide (pCO2)	48.1 mmHg
Bicarbonate (HCO3)	22.7 mmol/L
Base excess	−0.4

TABLE 2.

Comprehensive microbiological and serological investigations excluding alternative infectious etiologies.

Test	Result
Blood cultures (2 consecutive days)	Negative
Urine culture	No growth
Brucella Ab Rose Bengal	Negative
Brucella serology (IgM, IgG)	Negative
Group A Streptococcus (PCR)	Negative
Respiratory multiplex PCR (BioFire)	Negative
Epstein–Barr virus IgG	Positive
Epstein–Barr virus IgM	Negative
Cervical lymph node bacterial culture	No growth
Cervical lymph node Ziehl–Neelsen stain	No acid‐fast bacilli detected
Cervical lymph node Mycobacterium tuberculosis culture	Negative
Cervical lymph node periodic acid–Schiff stain	Negative
Cervical lymph node CD3 immunohistochemistry	Positive (T lymphocytes)

Electrocardiography (ECG) demonstrated sinus bradycardia without conduction abnormalities or ischemic changes. Transthoracic echocardiography showed preserved biventricular systolic function with mild aortic regurgitation and trivial tricuspid regurgitation, without evidence of myocarditis, pericardial effusion, or structural heart disease. Neck ultrasonography for the lesion revealed cervical lymphadenopathy without abscess formation. Given the unexplained persistent sinus bradycardia and hypotension, contrast‐enhanced magnetic resonance imaging (MRI) of the brain and neck was performed to evaluate potential central or cervical structural causes. The examination excluded intracranial pathology and deep neck abscess, whereas demonstrating a necrotic cervical lymph node adjacent to the carotid sheath (Figure 1).

FIGURE 1.

Neck magnetic resonance imaging. Short tau inversion recovery (STIR) sequence image (A) and contrast‐enhanced T1‐weighted image (B) demonstrate multiple enlarged left‐sided posterior cervical lymph nodes representing necrotic lymphadenitis adjacent to the carotid sheath with mild regional soft tissue post‐contrast enhancement/edema (arrow).

Empirical intravenous (IV) ceftriaxone and clindamycin were initiated on admission together with fluid resuscitation (cumulative 40 mL/kg of isotonic crystalloid) as septic shock and toxic shock syndrome were initially considered. Despite these interventions, persistent pallor, hypotension, and bradycardia remained unchanged, although the patient maintained adequate perfusion and oxygenation on room air and required no respiratory support. Because of persistent hemodynamic instability, a low‐dose peripheral epinephrine infusion (0.05 μg/kg/min) was started, resulting in transient improvement in blood pressure and heart rate; atropine was not administered. Subsequent clinical assessment, persistently negative microbiological investigations, necrotizing cervical lymphadenopathy on imaging, normal cardiac evaluation, and the absence of diagnostic criteria for sepsis or toxic shock syndrome prompted reconsideration of the differential diagnosis, including atypical bacterial and granulomatous infections, lymphoma, KFD, and other inflammatory disorders. Antimicrobial therapy was discontinued on Day 4 after sepsis and toxic shock syndrome were considered unlikely.

Repeated attempts to discontinue epinephrine over the subsequent 7 days were unsuccessful because of recurrent hypotension and bradycardia, prompting multidisciplinary discussion regarding the underlying diagnosis and further management. Although corticosteroid therapy was considered because of persistent vasopressor dependence, it was deferred until a definitive diagnosis was established as tuberculosis/malignancy remained part of the differential diagnoses. Consequently, an excisional biopsy of the affected cervical lymph node was performed before initiating steroid therapy. Histopathological examination demonstrated necrotizing histiocytic lymphadenitis with abundant karyorrhectic debris, crescentic histiocytes, plasmacytoid dendritic cells, and an absence of neutrophilic infiltration, confirming KFD (Figure 2). Ziehl–Neelsen staining demonstrated no acid‐fast bacilli, periodic acid–Schiff staining with and without diastase revealed no fungal organisms, and immunohistochemistry showed abundant CD3‐positive T lymphocytes (Table 2). The principal findings and their clinical significance are summarized in Table 3. Following histopathological confirmation, IV hydrocortisone was initiated with a single dose of 50 mg/m², followed the next day by 12.5 mg/m² every 6 h. IV hydrocortisone was transitioned to oral hydrocortisone on treatment Day 3. At 3 weeks, therapy was converted to an equivalent dose of oral prednisolone under pediatric rheumatology supervision, followed by gradual tapering over 4 weeks.

FIGURE 2.

Histopathological findings from the excised cervical lymph node. (A) Necrotic foci bordered by histiocytes, plasma cells, and reactive lymphocytes. (B) Sheets of histiocytes, including cells with crescent‐shaped nuclei, with characteristic absence of neutrophils. These findings are consistent with Kikuchi‐Fujimoto disease.

TABLE 3.

Summary of the main diagnostic findings and their clinical interpretations.

Finding	Result	Interpretation
Histopathology	Confirmed Kikuchi‐Fujimoto disease	Diagnostic
Antinuclear antibodies (ANA)	Negative	Strongly argues against active SLE (though not absolute)
Anti‐double‐stranded DNA antibodies	68.2 IU/mL a	Mild isolated positivity; needs interpretation in context
Complement (C3)	Normal	Against active immune complex‐mediated lupus
Urinalysis	Normal, no RBCs	No evidence of lupus nephritis
Creatinine	Normal	Normal renal function
Complete blood count	Normal	No lupus‐associated cytopenias; against active infectious disease
C‐reactive protein/procalcitonin (PCT)	Normal	Against active infectious disease

^a Anti‐dsDNA titer (normal RR 0–35 IU/mL).

4. Outcome and Follow‐Up

Clinical improvement was observed shortly after initiation of IV hydrocortisone. Epinephrine infusion was successfully discontinued within 3 h without recurrence of hypotension. Heart rate progressively increased from 45–55 to 70–80 beats/min over the subsequent 5 days. Blood pressure increased from approximately 85/50 mmHg off vasoactive support (or approximately 100/50 mmHg while receiving epinephrine) to approximately 119/70 mmHg within 3 h of corticosteroid administration and remained stable without further vasopressor requirement. The patient remained under close observation in the PICU for an additional 2 days before transfer to the pediatric ward.

At the 4‐ and 8‐week outpatient follow‐up visits, the patient remained clinically well, with complete resolution of cervical lymphadenopathy, no recurrence, and sustained normal heart rate and blood pressure. Antinuclear antibody was negative, whereas anti‐double‐stranded DNA antibody was mildly elevated. In the absence of clinical features of SLE, together with normal complement levels, renal function, urinalysis, and hematologic parameters, these findings were considered insufficient to establish a diagnosis of SLE. Given the recognized association between KFD and subsequent SLE, long‐term rheumatology follow‐up with serial clinical and serologic assessment was arranged.

5. Discussion

The principal finding of this report is the occurrence of persistent sinus bradycardia and vasopressor‐dependent hypotension in a child with biopsy‐confirmed KFD in the absence of biochemical or echocardiographic evidence of myocardial injury. Although cardiovascular involvement has occasionally been described in KFD, published reports have predominantly involved myocarditis, pericarditis, or acute heart failure [8]. The combination of profound sinus bradycardia, preserved ventricular function, normal cardiac biomarkers, and rapid hemodynamic recovery following corticosteroid therapy represents an unusual clinical phenotype that may closely mimic culture‐negative septic shock. This case also highlights the diagnostic challenge encountered in children presenting with fever and hemodynamic instability despite minimal laboratory evidence of systemic inflammation. Notably, serum ALP was low (88 U/L), consistent with pediatric reports identifying low ALP activity as a potential supportive laboratory feature during the acute phase of KFD [10, 11]. Throughout admission, inflammatory and cardiac biomarkers, as well as routine microbiological investigations, remained unrevealing, whereas repeated cardiovascular assessment demonstrated preserved myocardial function. These findings reduced the likelihood of bacterial septic shock and clinically significant myocarditis, emphasizing that KFD should remain a diagnostic consideration when unexplained necrotizing cervical lymphadenopathy coexists with discordant laboratory findings.

The identification of a necrotic cervical lymph node on MRI fundamentally altered the diagnostic approach and prompted excisional biopsy, which established the diagnosis. This emphasizes the importance of early tissue diagnosis when persistent cervical lymphadenopathy remains unexplained despite comprehensive infectious evaluation. In similar clinical scenarios, delaying biopsy in favor of repeated empirical investigations may prolong diagnostic uncertainty and postpone disease‐specific therapy [2]. The mechanism underlying the profound bradycardia and hypotension observed in our patient remains uncertain. Their rapid improvement following corticosteroid therapy favors an inflammation‐mediated process rather than primary myocardial dysfunction, potentially involving transient autonomic dysregulation.

A more localized autonomic mechanism is also plausible given the anatomical findings. The proximity of the necrotic lymph node to the carotid sheath raises the possibility of secondary carotid sinus–baroreflex activation from local inflammatory involvement. Carotid sinus syndrome is uncommon in children, with rare pediatric reports associated with cervical lesions adjacent to the carotid sheath [12]. In adults, cervical masses and lymphadenopathy have similarly been associated with recurrent syncope, bradycardia, and hypotension, predominantly through mechanical compression of the carotid sinus [13, 14, 15]. Similar mechanisms have been described with other cervical pathological processes; however, direct evidence supporting this mechanism in KFD is currently lacking [16]. In our patient, however, hemodynamic improvement occurred within hours of hydrocortisone administration, making rapid reduction in lymph node size unlikely. Attenuation of local inflammation affecting the carotid sinus–baroreflex pathway may therefore provide a plausible explanation for the rapid response. Nevertheless, carotid sinus syndrome was not formally demonstrated, and this proposed mechanism remains hypothesis‐generating.

The prompt clinical response to corticosteroid therapy was particularly noteworthy. Although corticosteroids are generally reserved for severe or complicated KFD, this case further supports their potential role in selected patients presenting with significant systemic involvement after exclusion of infectious, malignant, and other alternative diagnoses [17]. From a pediatric critical care perspective, this case broadens the recognized clinical spectrum of KFD and reinforces several practical lessons. Persistent hemodynamic instability should not be considered synonymous with bacterial sepsis, particularly when inflammatory markers, cardiac biomarkers, and serial echocardiography remain discordant with the severity of illness. In children with persistent fever and necrotizing cervical lymphadenopathy, early excisional lymph node biopsy should be considered when the initial diagnostic evaluation is inconclusive, as timely histopathological diagnosis may substantially alter management and avoid unnecessary investigations or prolonged empirical therapy.

This report has several limitations. As a single case, causal relationships between KFD and the observed cardiovascular manifestations cannot be definitively established. Although the temporal association between corticosteroid therapy and rapid hemodynamic recovery strongly suggests an inflammation‐mediated mechanism, spontaneous clinical improvement cannot be completely excluded. In addition, autonomic function testing and cardiac MRI were not performed; therefore, transient autonomic dysfunction, carotid sinus involvement, and subclinical myocardial inflammation remain speculative explanations rather than confirmed mechanisms.

6. Conclusion

Kikuchi‐Fujimoto disease should be considered in children with fever, necrotizing cervical lymphadenopathy, and unexplained hemodynamic instability despite negative infectious investigations. This case highlights an uncommon presentation with persistent sinus bradycardia and vasopressor‐dependent hypotension without evidence of myocardial injury. Early excisional lymph node biopsy and timely corticosteroid therapy were pivotal to establishing the diagnosis and achieving rapid clinical recovery.

Author Contributions

Abdulla Alfraij: conceptualization, methodology, data curation, writing – original draft, supervision, project administration. Fatma Mothafar: writing – review and editing, investigation. Wasmi Alfadhli: investigation, writing – review and editing. Ali Ashkanani: investigation, writing – review and editing. Lujain A. Kamal: writing – review and editing, investigation. Esmail Redha: investigation, writing – review and editing. Abdulrahman Aldaithan: conceptualization, methodology, writing – review and editing.

Funding

The authors have nothing to report.

Consent

We confirm that written consent for the publication was obtained from the child's parents.

Conflicts of Interest

The authors declare no conflicts of interest.

Data Availability Statement

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.