Kikuchi–Fujimoto Disease Associated with Hashimoto’s Thyroiditis: A Case Report

Abstract

Background

Kikuchi–Fujimoto disease (KFD) is a rare, benign, and self-limiting disorder characterized primarily by cervical lymphadenopathy and fever. Although the disease has been reported worldwide, it is more frequently observed in young women of Asian descent. The etiology of this disease remains unclear. Kikuchi–Fujimoto disease has been reported in association with several autoimmune disorders. Its coexistence with Hashimoto’s thyroiditis is rarely described in the literature.

Objective

To present a case of KFD associated with Hashimoto’s thyroiditis and highlight the importance of considering this diagnosis in patients with autoimmune disorders.

Case Presentation

A 37-year-old woman with a known history of Hashimoto’s thyroiditis who presented with rapidly enlarging cervical lymphadenopathy. Laboratory investigations, Ultrasonography, and Excisional lymph node biopsy were performed.

Results

Laboratory tests revealed mild anemia, elevated ESR, and positive anti-TPO antibodies. Ultrasound showed multiple hypoechoic cervical lymph nodes. Biopsy confirmed KFD with characteristic histopathological features. The patient improved spontaneously without specific treatment.

Conclusions and Significance

This case underscores the importance of including KFD in the differential diagnosis of cervical lymphadenopathy, particularly in young women with autoimmune diseases. Clinicians should be aware of this rare association to avoid misdiagnosis and unnecessary interventions.

Introduction

Kikuchi-Fujimoto disease (KFD) is a rare, benign, self-limiting lymphadenopathy of unknown etiology, first described in Japan in 1972.^1,2 It predominantly affects young women of Asian descent and may be associated with autoimmune conditions (eg, SLE) or viral infections (eg, EBV, CMV).³ However, its coexistence with Hashimoto’s thyroiditis is rarely described in the literature, making this case particularly unique. This case highlights the importance of considering KFD in the differential diagnosis of cervical lymphadenopathy in patients with autoimmune thyroiditis, especially in settings where the disease is underrecognized, such as Syria, where misdiagnosis can lead to unnecessary treatments.

The disease typically presents with fever and cervical lymphadenopathy, and resolves spontaneously within 1–6 months. Herein, we report a case of KFD in a 37-year-old woman with pre-existing Hashimoto’s thyroiditis to describe this rare association.

Case Presentation

A 37-year-old woman presented to the Department of Otolaryngology–Head and Neck Surgery with rapidly enlarging left- sided cervical lymphadenopathy for one and a half months, accompanied by fever, chills, myalgia, arthralgia, and generalized malaise. She had a 5-year history of Hashimoto’s thyroiditis. She had been receiving levothyroxine replacement therapy at a dose of 100 μg once daily.

Examination revealed several enlarged lymph nodes (0.5–3 cm) in the left posterior cervical triangle. The nodes were mobile and non-adherent to skin. Some nodes were closely packed with ill-defined borders and mild tenderness. No lymphadenopathy was detected on the contralateral side of the neck or in other regions of the body. The remainder of the head and neck examination was unremarkable. Flexible fiberoptic endoscopic examination of the nasal cavity, nasopharynx, and larynx was normal.

Laboratory investigations showed mild anemia (Hb 11.6 g/dL), relative lymphocytosis (lymphocytes 44%), elevated ESR (29 mm/hr), low TSH (0.29 μIU/mL), normal free T4 (1.34 ng/dL), and markedly elevated anti-TPO antibodies (280 IU/mL) (Table 1).

Table 1.

Summary of Laboratory Findings

Test category	Test Name	Result	Reference Range	Units	Interpretation
Hematology	Leukocytes (WBC)	7300	4500-10500	/mm3	Normal
	Neutrophils	45%	40-65%	%	Normal
	Lymphocytes	44%	25-40%	%	Relative increasea
	Monocytes	8%	2-8%	%	Normal
	Eosinophils	3%	0-4%	%	Normal
	Basophils	0%	0-1%	%	Normal
	Red Blood cell (RBC)	3.95	F: 4–5.4	x 106/mm3	Mild Anemiab
	Hemoglobin (Hb)	11.60	F: 12–16	g/dl	Mild Anemiab
	Hematocrit	36.30	F: 35–47	%	Normal
	Mean corpuscular volume (MCV)	91.9	78-96	Fl	Normal
	Mean corpuscular Hemoglobin (MCH)	29.4	27-32	Pg	Normal
	Red Cell Distribution Width (RDW)	14.3	11-16	%	Normal
	Platelets	268	150-450	X103/mm3	Normal
	Erythrocyte sedimentation Rate (ESR)	(1hr): 29 (2hr):60	F: (18–50Y): 0–20	Mm/hr.	Elevatedc
Hormones	Thyroid stimulating Hormone (TSH)	0.29	0.3–5.0	µlu/mL	Lowd
	Free Thyroxine (Free T4)	1.34	0.80–1.8	Ng/dl	Normal
	Anti- Thyroid peroxidase Antibody (Anti-TPO)	280	0-35	IU/mL	Elevatedc
Immunochemistry & serology	C-Reactive Protein (CRP)	4.8	0-5.0		Normal
	EBV IgG	10.00	< 18.00	U/mL	Negative
	EBV IgM	15.00	< 20.00	U/mL
	CMV IgG	0.20	< 0.60	U/mL	Negative
	CMV IgM	10.00	< 30.00	AU/mL
	ANA	< 1:40	< 1:40		Negative
	Anti-dsDNA	2.0	0-7	IU/mL	Negative
	LDH	200	140-280	U/L

Notes: ^a shows a relative increase in lymphocytes ratio. ^b shows a mild anemia in the patient. ^c show high value of ESR and TPO which consistent with Hashimoto thyroiditis. ^d shows low value of TSH which consistent with Hashimoto thyroiditis.

Neck ultrasound revealed atrophic thyroid gland with heterogeneous echotexture (Figure 1A) and multiple hypoechoic cervical lymph nodes with minimal vascularity (Figure 1B). CT could not be performed because the patient could not afford the cost. Excisional biopsy of a superficial 0.5 cm lymph node was done under local anesthesia (selected for easy access and minimal risk).

Figure 1.

(A) Ultrasound imaging reveals an atrophic thyroid gland with a heterogeneous parenchyma. (B) Ultrasound imaging shows a hypoechoic, lobulated lymph node in the left posterior cervical triangle with minimal internal vascularity.

Histopathology showed partial effacement of nodal architecture with areas of pale necrosis surrounded by abundant karyorrhectic debris, commonly described as “nuclear dust” (Figure 2A). These areas were infiltrated by histiocytes and plasmacytoid dendritic cells. The histiocytic population included phagocytic cells with eosinophilic cytoplasm and crescent-shaped nuclei (crescentic histiocytes), as well as non-phagocytic histiocytes (Figure 2B and C). Notably, neutrophils were absent. Tuberculous lymphadenitis was excluded because no Langhans giant cells or caseating granulomas were identified, and Ziehl–Neelsen staining was negative. Furthermore, no atypical cells or evidence of malignancy was observed.

Figure 2.

(A) Histopathological examination showing histiocytes with nuclear dust and a pale necrotic area (H&E stain,10hpf). (B) Pale necrotic area with nuclear dust, histiocytes, and plasmacytoid dendritic cells (H&E stain, 40hpf). (C) Histopathological examination showing histiocytes with nuclear dust and a pale necrotic area (H&E stain, 40 hpf).

Immunohistochemical analysis showed positivity for CD3 and CD68. CD20 staining highlighted scattered cells but was negative in the karyorrhectic areas, while CD1a staining was negative. Based on these histopathological and immunohistochemical findings, a final diagnosis of Kikuchi disease (histiocytic necrotizing lymphadenitis) was established.

The patient was counselled about the self-limiting nature of KFD, and a conservative approach with observation only was adopted. Her levothyroxine dose (100 μg daily) was maintained unchanged throughout the follow-up period. No postoperative complications, such as bleeding, infection, or hematoma, were observed.

At 6 weeks follow-up, she reported improvement and regression of lymphadenopathy. Two months later, she developed new contralateral cervical lymphadenopathy (self-reported as large), which resolved spontaneously after another 2 months; no further investigations were done as she had traveled abroad.

Discussion

Kikuchi–Fujimoto disease (KFD) is a rare self-limiting lymphadenopathy of unknown etiology, predominantly affecting young Asian women.^4–6 In the Middle East, it accounts for ~0.6% of lymph node biopsies, with only three reported Syrian cases.^7–9Viral infections (eg, EBV, CMV, and HIV) and autoimmune mechanisms are leading hypotheses.¹⁰ KFD is frequently associated with SLE, Sjögren’s syndrome, and Graves’ disease.⁶ Therefore, ANA and anti-dsDNA screening is recommended in KFD patients, especially those with autoimmune background. The coexistence of KFD with Hashimoto’s thyroiditis is rarely reported.^8,11,12

A 16-year-old Vietnamese girl presented with prolonged fever, tender cervical lymphadenopathy, and hypothyroidism. Following an extensive evaluation that excluded the common causes of fever of unknown origin, a cervical lymph node biopsy was performed and demonstrated findings consistent with Kikuchi–Fujimoto disease (KFD). The patient was also found to have an elevated anti-thyroid peroxidase antibody titre, supporting a concurrent diagnosis of Hashimoto’s thyroiditis.¹³ In another reported case, a 19-year-old Greek woman with a known history of Hashimoto’s thyroiditis developed fever accompanied by tender right anterior cervical lymphadenopathy. Subsequent evaluation and lymph node biopsy established the diagnosis of Kikuchi–Fujimoto disease.¹⁴ Similarly, a 29-year-old Black African woman was diagnosed with Kikuchi–Fujimoto disease and subsequently developed Hashimoto’s thyroiditis, which was identified approximately three months after the initial diagnosis of KFD.¹⁵

Hashimoto’s involves T-cell-mediated thyroid destruction^11,16 and complement pathway impairment in both conditions suggests shared immunological pathways.¹⁷ Our patient had confirmed Hashimoto’s with elevated anti-TPO antibodies. Clinically, KFD presents with fever and tender cervical lymphadenopathy, often with elevated ESR and mild anemia.⁶ Differential diagnoses include lymphoma, SLE, tuberculosis, and viral infections.¹⁸ In our patient, tuberculosis was initially suspected due to the presence of night sweats and fever; however, it was excluded by negative Ziehl–Neelsen staining and the absence of caseating granulomas or Langhans giant cells. Lymphoma was considered; however, the absence of atypical cells, characteristic histopathological features (paracortical necrosis and karyorrhectic debris), absence of features suggestive of lymphoma (such as diffuse effacement of architecture or a monomorphic atypical lymphoid population), and a normal LDH level (200 U/L) made this diagnosis unlikely. SLE was excluded as ANA and anti-dsDNA were both negative (<1:40 and 2.0 IU/mL, respectively), and the patient had no clinical features suggestive of SLE. EBV and CMV infections were also excluded, as serological testing for EBV IgG, EBV IgM, CMV IgG, and CMV IgM were all negative.

Excisional biopsy remains the gold standard for diagnosis,¹⁹ it typically shows paracortical necrosis, karyorrhectic debris, and histiocytic infiltration, with T-cell predominance (CD8+ > CD4+) and markers like CD68.²⁰ Ultrasound findings in our patient were consistent with Hashimoto’s thyroiditis and showed hypoechoic lymph nodes with minimal vascularity. Based on the exclusion of other possible causes through detailed differential diagnosis, along with the characteristic histopathological and immunohistochemical findings, the diagnosis of Kikuchi–Fujimoto disease was confirmed.

In most cases, KFD is self-limiting and requires only supportive care, though corticosteroids may be used in severe cases.^6,20 The patient was informed about the self-limiting nature of KFD and expressed satisfaction with the conservative approach. Her symptoms and lymphadenopathy resolved spontaneously, consistent with the known clinical course of the disease.

To the best of our knowledge, only one case of KFD coexisting with Hashimoto’s thyroiditis has been previously reported in Syria, in a pregnant woman from Aleppo.⁹ Our case represents the second documented case of this rare association in the country, and the first in a non-pregnant patient, highlighting its rarity and the importance of considering this diagnosis in patients with autoimmune thyroiditis, especially in underrecognized settings. The main limitation of this report was the lack of long-term follow-up as the patient traveled abroad. Another limitation to acknowledge is that our study was conducted on a single patient. While this case provided valuable insights, the findings may not be fully generalizable to a broader population and larger studies are required.

Conclusion

Kikuchi–Fujimoto disease should be considered in the differential diagnosis of cervical lymphadenopathy, especially in young patients with autoimmune thyroiditis. Its coexistence with Hashimoto’s thyroiditis is rare but clinically significant. Early recognition and histopathological confirmation are essential to avoid misdiagnosis and unnecessary treatment.

Funding Statement

The authors did not receive funding for this paper.

Data Sharing Statement

The laboratory tests are available from the corresponding author on reasonable request.

Ethics Approval and Consent to Participate

Case reports are exempt from ethical approval in our university.

Consent for Publication

Written informed consent was obtained from the patient for publication of this case report and any accompanying images.

Disclosure

The authors declare that they have no competing interests.