Skip to main content
Download PDF
  • Research article
  • Open access
  • Published:

Elevated serum IFN-γand IFN-γ/IL-6 ratio in Kikuchi-Fujimoto disease

Pediatric Rheumatology volume 21, Article number: 88 (2023) Cite this article

Abstract

Background

Kikuchi-Fujimoto disease (KFD) is typically a benign, self-limiting inflammatory disease. The diagnosis of KFD can be challenging for nonspecific symptoms, laboratory or imaging findings. In this study, we aimed to describe the clinical manifestations of patients with KFD and to access the potential role of serum cytokines in the diagnosis of this disease.

Methods

Patients with KFD were retrospectively enrolled from January 2015 to November 2021 at Shenzhen Children’s Hospital. Clinical data were collected from inpatient or outpatient medical records. Serum cytokines were detected by the Flowcytomix technique. Serum levels of cytokines were compared between patients with KFD and SJIA, or patients with KFD and KD. The data of patients without MAS were further analyzed. A receiver operating characteristic (ROC) curve analysis was further performed to access the potential role of serum cytokines in the diagnosis of KFD.

Results

Serum cytokines were detected in 25 (43.8%, 25/57) patients with a histological diagnosis of KFD. Compared to SJIA or KD patients, the KFD group had a significantly higher IFN-γ/IL-6 ratio and much lower levels of serum IL-6. The median level of serum IFN-γ in KFD was 41.65 pg/ml (range, 21.04–70.74 pg/ml), which was much higher than that in SJIA (median: 3.33 pg/ml, p = 0.16) or KD (median: 2.6 pg/ml, p = 0.01). After excluding patients with MAS, there was statistical significance in all comparisons of serum IFN-γ, IFN-γ/IL-6 ratio, and serum IL-6. The cutoff values of serum IFN-γ, IL-6, and IFN-γ/IL-6 ratio for differentiating KFD from SJIA were > 8.48 pg/ml, < 47.42 pg/ml, and > 0.45, respectively. The cutoff values of serum IFN-γ, IL-6, and IFN-γ/IL-6 ratio for differentiating KFD from KD were > 8.56 pg/ml, < 50.45 pg/ml, and > 0.45, respectively. The specificity of all those cutoff values for differentiating KFD from SJIA or KD was ≥ 94.7%.

Conclusions

For patients with fever of unknown etiology and lymphadenopathy, after excluding HLH or MAS, serum IFN-γ > 8.56 pg/mL and IFN-γ/IL-6 ratio > 0.45 may highly suggest the diagnosis of KFD; serum IL-6 > 50.45 pg/mL indicates that the probability of KFD may be small, and sJIA, KD, and acute infection should be excluded first.

Introduction

Kikuchi-Fujimoto disease (KFD) is a benign, self-limiting inflammatory disease characterized by fever and cervical lymphadenopathy. The diagnosis of KFD can be challenging since symptoms, laboratory and imaging findings in this disease are non-specific. KFD can frequently be mistaken for other diseases [1, 2]. Differential diagnoses include infectious lymphadenitis, malignancies such as lymphoma, and autoimmune/autoinflammatory diseases such as systemic lupus erythematosus (SLE), Systemic juvenile idiopathic arthritis (SJIA), and Kawasaki disease.

Although KFD is typically self-limited, some patients may have a prolonged or recurrent disease course, or even present with life-threatening complications such as hemophagocytic Lymphohistiocytosis(HLH) [3, 4]. Thus the accurate and timely diagnosis of this disease will be quite important in proper treatments and improving the prognosis of patients. Although histopathological diagnosis by a lymph node biopsy is crucial to differentiate KFD from other etiologies, it is invasive and may share overlapping histopathological features with other diseases [5, 6]. Therefore, biomarkers by rapid and non-invasive detection will be required in the early diagnosis of KFD.

IFN-γ are rarely encountered in non-specific lymphadenitis tissues, but are frequently detected in the surrounding dead tissue in KFD [7]. Serum levels of IFN-γ and IL-6 are reported to be elevated during the acute phase in KFD [8]. However, the potential role of serum cytokines in the diagnosis and differential diagnosis of this disease remains unknown. Differences from other inflammatory diseases are required to be explored.

Here, we performed a single, retrospective study to describe the clinical manifestations of patients with KFD and to access the potential role of serum cytokines in the diagnosis of this disease.

Patients and methods

Study population and design

Patients with KFD were retrospectively enrolled from January 2015 to November 2021 at Shenzhen Children’s Hospital. The study was approved by the ethics committee of the hospital. Written informed consent was obtained from all patients’ legal guardians. All patients with KFD were confirmed based on a typical histological diagnosis. Exclusion criteria included patients with a possible alternative diagnosis such as autoimmune diseases (SLE, Sjogren's disease, etc.), autoinflammation diseases (Kawasaki disease, SJIA, etc.), leukemia, lymphoma, lymphoproliferative diseases, or active infection.

The age-matched control groups included all the patients with SJIA or Kawasaki disease (KD) who met the inclusion criteria within the same study period. KD patients less than five years old were excluded to minimize the influence of age factors. Serum cytokines in three groups were all detected before treatment and after fever (≥ 38.5℃) caused by disease activity for at least 72 h by the Flowcytomix technique in the control groups. SJIA was diagnosed following the 2001 International League Against Rheumatism criteria [9, 10]. KD was diagnosed based on the diagnosis criteria provided by the American Heart Association in 2017 [11]. Macrophage activation syndrome (MAS) was diagnosed according to the 2016 EULAR/ACR/PRINTO classification criteria [12]. There were 31 SJIA patients and 27 KD patients fulfilling the inclusion criteria as the control groups, including six with SJIA-MAS.

Data collection

Clinical data were collected from inpatient or outpatient medical records. Data collected included clinical manifestations, laboratory findings, and levels of serum cytokines. Clinical symptoms and laboratory data were collected at the onset of KFD. Clinical manifestations were listed in Table 1. Laboratory variables included total leukocyte, neutrophils, lymphocyte and platelet counts, erythrocyte sedimentation rate (ESR), levels of hemoglobulin, C-reactive protein (CRP), aminotransferases, albumin, ferritin, fibrinogen, lactate dehydrogenase (LDH), and auto-antibodies such as anti-nuclear antibodies (ANA). Serum cytokines included IFN-γ, IL-10, IL-6, TNF-a, IL-4, and IL-2.

Table 1 Clinical and labortatory features of patients with KFD
Full size table

Statistical analysis

Continuous variables were presented as medians with interquartile ranges (IQR), and categorical variables were presented as frequencies and percentages. Unpaired Welch’s t-test for continuous data and Man-Whitney U test for categorical variables were performed. Differences in clinical features and laboratory findings were analyzed between patients with serum cytokines data and others. Serum levels of cytokines were compared between patients with KFD and SJIA, or patients with KFD and KD. The data of patients without MAS were further analyzed. We subsequently performed a receiver operating characteristic (ROC) curve analysis for the data with statistical differences between the two groups. Analysis was completed with GraphPad Prism 8.0 statistical software (GraphPad Software Inc., La Jolla, CA, USA). A p-value of < 0.05 was considered statistically significant.

Results

The clinical characteristics of KFD patients

We identified 57 patients with a histological diagnosis of KFD in Shenzhen Children’s Hospital, who were from the same cohort reported previously [13]. Of those, 15 patients had MAS. 25 diagnosed KFD since 2019 had serum cytokines measured, including six with KFD-MAS. The cytokine levels were not measured in the other patients. Clinical characteristics were summarized and compared in Table 1. The median age at diagnosis was 9.08 years (range, 6.92–12.17 yr). Male to female ratio in this study was 2:1. General clinical characteristics included lymphadenopathy (n = 54), fever (n = 53), hepatomegaly (n = 20), skin rash (n = 15), splenomegaly (n = 9), central nervous (n = 9) and respiratory symptoms (n = 7). Gastrointestinal symptoms and arthralgia/arthritis were present in five and one patient, respectively. There was no statistical difference in the clinical characteristics of KFD between patients with serum cytokine detection and patients without serum cytokine detection (Supplementary Table 1).

Abnormal laboratory findings included elevated erythrocyte sedimentation rate (median:40 mm/h, range: 20–59 mm/h), mild cytopenia (median:3530/μL, range: 2540–4620/μL), mild lymphopenia (median: 1415/μL, range: 1060–1820/μL), elevated levels of LDH (median: 431 IU/mL, range: 335-647 IU/mL) and ferritin (median: 312.5 ng/mL, range: 147–710.8 ng/mL). Ten patients had presented with positive auto-antibodies, including antinuclear antibody (ANA, n = 5), anti-SSA antibody (n = 2), anti-RNP antibody (n = 3), and anti-DNA antibody (n = 1).

Comparison of serum cytokine levels in patients with KFD, SJIA, or KD

Compared to SJIA patients in active disease, the KFD group had a significantly higher IFN-γ/IL-6 ratio (p = 0.0001), and much lower levels of serum IL-6 (p = 0.004) and IL-2 (p = 0.008). Although there was no statistical difference, the median serum IFN-γ level in KFD was 41.65 pg/ml (range: 21.04–70.74 pg/ml), which was much higher than that in SJIA (Table 2 and Fig. 1A-C). There were no significant differences in other serum cytokines, including IL-10, TNF-a, and IL-4 (Table 2).

Table 2 Serum cytokine levels in KFD, SJIA, and KD
Full size table
Fig. 1
figure 1

Serum cytokines levels of patients in KFD, SJIA, and KD. Serum IL-6, serum IFN-γ, and IFN-γ/IL-6 ratio in all patients (A, B, and C) and those without MAS (D, E, and F). Differences were analyzed between patients with KFD and SJIA, KFD and KD. Compared to patients with SJIA or KD, patients with KFD showed an elevation of serum IFN-γ and IFN-γ/IL-6 ratio, and a much lower level of serum IL-6. P-value was 0.16 for the comparison of serum IFN-γ between all KFD and SJIA patients (B). P-values for other comparisons were < 0.05

Full size image

Compared to KD patients, the KFD group had a significantly higher serum IFN-γlevel (p = 0.01) and IFN-γ/IL-6 ratio (p < 0.0001), and much lower levels of serum IL-6 (p = 0.019) and IL-4 (p = 0.01) (Table 2 and Fig. 1A-C). There were no significant differences in other serum cytokines, including IL-10, TNF-a, and IL-2 (Table 2).

Comparison of serum cytokine levels in patients without MAS

To exclude the influence of MAS, serum cytokine levels in patients without MAS were further analyzed. Compared to SJIA patients without MAS, the KFD group had a significantly higher serum IFN-γ level (p = 0.006) and IFN-γ/IL-6 ratio (p = 0.0003), and much lower levels of serum IL-6 (p = 0.007) and IL-2 (p = 0.016). There were no significant differences in other serum cytokines, including IL-10, TNF-a, and IL-4 (Table 3 and Fig. 1D-F). For the patients with MAS, there were no statistical differences in levels of those serum cytokines between the two groups (Table 3).

Table 3 Serum cytokine levels of patients in KFD, SJIA, and KD
Full size table

Compared to KD patients, the KFD group without MAS had a significantly higher serum IFN-γ level (p = 0.007) and IFN-γ/IL-6 ratio (p = 0.0003), and much lower levels of serum IL-6 (p = 0.018), TNF-a (p = 0.032), and IL-4 (p = 0.028) (Table 3 and Fig. 1D-F). There were no significant differences in serum levels of IL-10 and IL-2 (Table 3).

The potential role of serum cytokines in the diagnosis of KFD

A ROC curve analysis was performed to access the potential role of serum cytokines in the diagnosis of KFD. The cutoff values of serum IFN-γ, IL-6, IFN-γ/IL-6 ratio, and IL-2 for differentiating KFD from SJIA were > 8.48 pg/ml (AUC:0.99, 95%CI: 0.98–1.0, p < 0.0001), < 47.72 pg/ml(AUC:0.92, 95%CI: 0.84–0.99, p < 0.0001), > 0.45 (AUC:1, 95%CI: 1.0–1.0, p < 0.0001), and < 5.25 pg/ml pg/ml (AUC:0.64, 95%CI: 0.48–0.80, p = 0.1), respectively. Except for serum IL-2, both sensitivity and specificity of those cutoff values for identifying these two diseases were ≥ 80% (Table 4 and Fig. 2).

Table 4 Receiver operating characteristic curve analysis of serum cytokines in KFD, SJIA, and KD
Full size table
Fig. 2
figure 2

Receiver operating characteristic curves of serum cytokines. The role of serum IL-6, serum IFN-γ, and IFN-γ/IL-6 ratio in the differential diagnosis of KFD from SJIA without MAS (A, B, and C) and KD (D, E, and F)

Full size image

The cutoff values of serum IFN-γ, IL-6, IFN-γ/IL-6 ratio, and IL-2 were > 8.56 pg/ml (AUC:0.97, 95%CI: 0.94–1.0, p < 0.0001), < 50.45 pg/ml (AUC:0.8, 95%CI:0.67–0.93, p = 0.0006), > 0.45 (AUC:0.998, 95%CI: 0.99–1.0, p < 0.0001), and < 5.25 pg/ml (AUC:0.63, 95%CI: 0.47–0.79, p = 0.13), respectively. Except for the sensitivity of serum IL-6 and IL-2, both sensitivity and specificity of other cutoff values for differentiating KFD from KD were ≥ 85.2% (Table 4 and Fig. 2).

Discussion

As reported previously, clinical features and laboratory findings in this cohort were non-specific [14]. The most common manifestations were fever, cervical lymph node enlargement, skin rash, hepatosplenomegaly, headache, dizziness, mild cough, abdominal pain, and vomiting. Arthralgia/arthritis and oral ulcer were occasionally seen. Abnormal laboratory findings with variable occurrence could be found in KFD, including elevated erythrocyte sedimentation rate, mild cytopenia, mild lymphopenia, hyperferritinemia, elevated levels of LDH, and positive auto-antibodies.

IL-6 is synthesized by myeloid cells, such as macrophages and dendritic cells. Rapid production of IL-6 contributes to host defense during infection and tissue injury, but excessive IL-6 synthesis is involved in the pathogenesis of various diseases, such as SJIA, KD, Castleman disease, COVID-19 infection, etc. [15]. Four patients with KFD had increased serum IL-6 level during the acute phase [8]. More than half of the patients with KFD in this study also showed an increased level of serum IL-6 (60%, 15/25). Although serum IL-6 level in KFD was elevated, the increase was not as obvious as that in SJIA or KD. Serum IL-6 level in most patients with KFD (96%, 24/25) was less than 47.72 pg/ml, which was lower than that in SJIA or KD group. Thus the extremely higher level of serum IL-6 (> 47.72 pg/ml) may largely help to exclude the diagnosis of KFD. The role of IL-6 in the pathogenesis of KFD remains unclear. Further studies are required to explore its association with the pathogenesis of KFD.

Most patients with KFD in our cohort showed an increased serum IFN-γ level (96%, 24/25) and IFN-γ/IL-6 ratio. Serum IFN-γ level in most KFD patients (96%, 24/25) was > 8.56 pg/ml. And the IFN-γ/IL-6 ratio in all of them was > 0.45. Both were extremely higher than that in the other groups without MAS. However, for patients with MAS, our data showed no statistical differences in levels of serum cytokines or in IFN-γ/IL-6 ratio between patients KFD and SJIA. Therefore, for patients without MAS, serum IFN-γ level > 8.56 pg/ml combined with the IFN-γ/IL-6 ratio > 0.45 may help to exclude SJIA or KD, supporting the diagnosis of KFD.

IFN-γ predominantly produced by NK and T cells is a pleiotropic cytokine with multiple effects on the inflammatory response and on innate and adaptive immunity. Aberrant production of IFN-γ underlies a number of hyperinflammatory or immune-mediated diseases, such as primary hemophagocytic lymphohistiocytosis (HLH), various forms of secondary HLH, including MAS, and cytokine release syndrome [16, 17].  The statistical differences especially in serum IFN-γ level were lost in MAS-KFD versus SJIA-MAS. Compared to other serum cytokine levels, serum IFN-γ level is extremely over-secreted in patients with SJIA-MAS, which might eliminate some differences especially in serum IFN-γ level and IFN-γ/IL-6 ratio between two groups. Although IFN-γ was over-produced in most KFD patients, secondary HLH was relatively rare in this disease. Thus the role of IFN-γ in the pathogenesis of KFD and HLH/MAS might be quite different. Further studies including enough patients is required to clarify this phenomenon and reveal the underlying mechanism.

The limitations of this study are the small sample size in a single center and the that it is retrospective. Serum cytokines were not detected in more than half of KFD patients. Except for SJIA and KD, serum cytokines were not checked in most patients with other differential diseases, such as infectious lymphadenitis, lymphoma, etc. Future prospective studies with large sample sizes and more control groups may further explore the exact role of serum IFN-γ, IL-6, and IFN-γ/IL-6 ratio in the KFD diagnosis.

Conclusions

For patients with fever of unknown etiology and lymphadenopathy, after excluding HLH or MAS, serum IFN-γ > 8.56 pg/mL and IFN-γ/IL-6 ratio > 0.45 may highly suggest the diagnosis of KFD. Serum IL-6 > 50.45 pg/mL indicates that the probability of KFD may be small, and sJIA, KD, and infection should be excluded first.

Availability of data and materials

The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request.

Abbreviations

KFD:

Kikuchi-Fujimoto disease

SLE:

Systemic lupus erythematosus

SJIA:

Systemic juvenile idiopathic arthritis

KD:

Kawasaki disease

MAS:

Macrophage activation syndrome

AST:

Aspartate aminotransferase

ESR:

Erythrocyte sedimentation rate

CRP:

C-reactive protein

LDH:

Lactate dehydrogenase

IVIG:

Intravenous immunoglobulin

IQR:

Interquartile ranges

ROC:

Receiver operating characteristic curve

References

  1. Mathew LM, Kapila R, Schwartz RA. Kikuchi-Fujimoto disease: a diagnostic dilemma. Int J Dermatol. 2016;55(10):1069–75.

    Article  PubMed  Google Scholar 

  2. Perry AM, Choi SM. Kikuchi-Fujimoto disease: a review. Arch Pathol Lab Med. 2018;142(11):1341–6.

    Article  CAS  PubMed  Google Scholar 

  3. Yang Y, Lian H, Ma H, Zhao Y, Zhang Q, Zhang L, et al. Hemophagocytic lymphohistiocytosis associated with histiocytic necrotizing lymphadenitis: a clinical study of 13 children and literature review. J Pediatr. 2021;229:267-274.e3.

    Article  CAS  PubMed  Google Scholar 

  4. Lim GY, Cho B, Chung NG. Hemophagocytic lymphohistiocytosis preceded by Kikuchi disease in children. Pediatr Radiol. 2008;38(7):756–61.

    Article  PubMed  Google Scholar 

  5. Rai B, Pillinger MH, Panush RS. Coincident Kikuchi-Fujimoto’s disease and adult-onset Still’s disease: report of a patient from an uncommonly affected population and case-directed systematic review. Clin Rheumatol. 2021;40(12):4791–805.

    Article  PubMed  Google Scholar 

  6. Jeon YK, Paik JH, Park SS, Park SO, Kim YA, Kim JE, et al. Spectrum of lymph node pathology in adult onset Still’s disease; analysis of 12 patients with one follow up biopsy. J Clin Pathol. 2004;57(10):1052–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Ohshima K, Haraoka S, Takahata Y, Takada H, Tsutiya K, Suzuk K, et al. Interferon-gamma, interleukin-18, monokine induced by interferon-gamma and interferon-gamma-inducible protein-10 in histiocytic necrotizing lymphadenitis. Leuk Lymphoma. 2002;43(5):1115–20.

    Article  CAS  PubMed  Google Scholar 

  8. Kubota M, Tsukamoto R, Kurokawa K, Imai T, Furusho K. Elevated serum interferon gamma and interleukin-6 in patients with necrotizing lymphadenitis (Kikuchi’s disease). Br J Haematol. 1996;95(4):613–5.

    Article  CAS  PubMed  Google Scholar 

  9. Koker O, Demirkan FG, Cakmak F, Aktay AN. Performance of recent PRINTO criteria versus current ILAR criteria for systemic juvenile idiopathic arthritis: a single-centre experience. Mod Rheumatol. 2023;33(1):187–93.

    Article  PubMed  Google Scholar 

  10. Krumrey-Langkammerer M, Hafner R. Evaluation of the ILAR criteria for juvenile idiopathic arthritis. J Rheumatol. 2001;28(11):2544–7.

    CAS  PubMed  Google Scholar 

  11. McCrindle BW, Rowley AH, Newburger JW, Burns JC, Bolger AF, Gewitz M, et al. Diagnosis, treatment, and long-term management of kawasaki disease: a scientific statement for health professionals from the American Heart Association. Circulation. 2017;135(17):e927–99.

    Article  PubMed  Google Scholar 

  12. Ravelli A, Minoia F, Davi S, Horne A, Bovis F, Pistorio A, et al. 2016 classification criteria for macrophage activation syndrome complicating systemic Juvenile idiopathic arthritis: a European League Against Rheumatism/American College of Rheumatology/Paediatric Rheumatology International Trials Organisation Collaborative Initiative. Ann Rheum Dis. 2016;75(3):481–9.

    Article  CAS  PubMed  Google Scholar 

  13. Shen Z, Ling J, Zhu X, Yang J, He T. Macrophage activation syndrome in children with Kikuchi-Fujimoto disease. Pediatr Rheumatol Online J. 2023;21(1):10.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Kang HM, Kim JY, Choi EH, Lee HJ, Yun KW, Lee H. Clinical Characteristics of Severe Histiocytic Necrotizing Lymphadenitis (Kikuchi-Fujimoto Disease) in Children. J Pediatr. 2016;171:208-12.e1.

    Article  PubMed  Google Scholar 

  15. Aliyu M, Zohora FT, Anka AU, Ali K, Maleknia S, Saffarioun M, et al. Interleukin-6 cytokine: An overview of the immune regulation, immune dysregulation, and therapeutic approach. Int Immunopharmacol. 2022;111:109130.

    Article  CAS  PubMed  Google Scholar 

  16. De Benedetti F, Prencipe G, Bracaglia C, Marasco E, Grom AA. Targeting interferon-gamma in hyperinflammation: opportunities and challenges. Nat Rev Rheumatol. 2021;17(11):678–91.

    Article  PubMed  Google Scholar 

  17. Schoenborn JR, Wilson CB. Regulation of interferon-gamma during innate and adaptive immune responses. Adv Immunol. 2007;96:41–101.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank all the patients and their families for their participation.

Funding

This work was supported by the Sanming Project of Medicine in Shenzhen (SZSM201812002) and the Shenzhen Key Medical Discipline Construction Fund (SZGSP012).

Author information

Authors and Affiliations

  1. Department of Rheumatology and Immunology, Shenzhen Children’s Hospital, 7019 Yitian Road, Shenzhen, 518038, China

    Tingyan He, Zixuan Shen, Jiayun Ling, Xiaona Zhu & Jun Yang

Authors
  1. Tingyan He
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zixuan Shen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jiayun Ling
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xiaona Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jun Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Tingyan He designed the work, supervised the work, drafted and reviewed the manuscript. Zixuan Shen collected and analyzed the data. Jiayun Ling and Xiaona Zhu helped to collect the data. Jun Yang supervised the work and reviewed the manuscript. All authors reviewed and approved the final manuscript.

Corresponding author

Correspondence to Tingyan He.

Ethics declarations

Ethics approval and consent to participate

All participating members were enrolled with the approval of the ethics committee of Shenzhen Children’s Hospital and provided written consent from legal guardians.

Consent for publication

Written consent for publication of this anonymous information was obtained from patients’ legal guardians.

Competing interests

All authors declare no conflict of interest.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Additional file 1: Supplementary Table 1.

Clinical features of KFD patients with or without cytokine detection.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

He, T., Shen, Z., Ling, J. et al. Elevated serum IFN-γand IFN-γ/IL-6 ratio in Kikuchi-Fujimoto disease. Pediatr Rheumatol 21, 88 (2023). https://doi.org/10.1186/s12969-023-00877-w

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s12969-023-00877-w

Keywords

Pediatric Rheumatology

ISSN: 1546-0096