Kimura’s Disease of the Clinical Characteristics, Treatment, and Prognosis of 34 Cases: A Retrospective Cross-Sectional Study

  

    
factor
    
Total
    
recurrence
    
P-value
  
  

    
Gender
    

    

    
0.482
  
  

    
Male
    
19
    
6
    

  
  

    
Female
    
4
    
2
    

  
  

    
Age
    

    

    
0.879
  
  

    
<40
    
11
    
4
    

  
  

    
>=40
    
12
    
4
    

  
  

    
Duration
    

    

    
0.006
  
  

    
<1
    
10
    
1
    

  
  

    
1~5
    
9
    
3
    

  
  

    
>5
    
4
    
4
    

  
  

    
Smoking history
    

    

    
0.955
  
  

    
none
    
20
    
7
    

  
  

    
have
    
3
    
1
    

  
  

    
Alcohol history
    

    

    
0.651
  
  

    
none
    
19
    
7
    

  
  

    
have
    
4
    
1
    

  
  

    
Site
    

    

    
0.214
  
  

    
Head and neck
    
20
    
6
    

  
  

    
Head, neck and other    parts
    
3
    
2
    

  
  

    
Multiplicity
    

    

    
0.363
  
  

    
Single
    
17
    
5
    

  
  

    
Multiple
    
6
    
3
    

  
  

    
Laterality
    

    

    
0.181
  
  

    
Unilateral
    
18
    
5
    

  
  

    
Bilateral
    
5
    
3
    

  
  

    
Maximum size, cm
    

    

    
0.113
  
  

    
<3cm
    
12
    
4
    

  
  

    
=3cm
    
9
    
4
    

  
  

    
swelling
    
2
    
0
    

  
  

    
Pruritus
    

    

    
0.591
  
  

    
None
    
16
    
5
    

  
  

    
Have
    
7
    
3
    

  
  

    
Hyperpigmentation
    

    

    
0.363
  
  

    
None
    
17
    
5
    

  
  

    
Have
    
6
    
3
    

  
  

    
Boundary
    

    

    
0.433
  
  

    
Clear
    
5
    
1
    

  
  

    
Unclear
    
18
    
7
    

  
  

    
Eosinophils (%)
    

    

    
0.175
  
  

    
Normal
    
3
    
0
    

  
  

    
Elevated
    
20
    
8
    

  
  

    
Eosinophil count (109/L)
    

    

    
0.175
  
  

    
Normal
    
3
    
0
    

  
  

    
Elevated
    
20
    
8
    

  
  

    
Neutrophils (%)
    

    

    
0.591
  
  

    
Decreased
    
7
    
3
    

  
  

    
Normal
    
16
    
5
    

  
  

    
Elevated
    

    

    

  
  

    
Lymphocytes (109/L)
    

    

    
0.021
  
  

    
Decreased
    
3
    
2
    

  
  

    
Normal
    
20
    
6
    

  
  

    
Elevated
    
0
    
0
    

  
  

    
Lymphocyte count (109/L)
    

    

    
0.175
  
  

    
Decreased
    
3
    
0
    

  
  

    
Normal
    
20
    
8
    

  
  

    
Elevated
    
0
    
0
    

  
  

    
Cardiovascular history
    

    

    
0.455
  
  

    
None
    
22
    
8
    

  
  

    
Have
    
1
    
0
    

  
  

    
Allergic reaction    history
    

    

    
0.591
  
  

    
None
    
16
    
5
    

  
  

    
Have
    
7
    
3
    
  
  

Table 4: Recurrence predictors.

Discussion

Kimura's disease is a chronic inflammatory disease and presents as a painless mass or subcutaneous nodule with pruritus occasionally. The lesions are single or multiple, and may appear in different locations over several years [7-11]. KD often involves the salivary glands, and cervical lymph nodes, and also involves other areas such as the armpits and groin. When salivary glands and cervical lymph nodes are involved, they need to be differentiated from malignant lymphoma, and parotid tumors such as Warthin's tumor.

In the study, the average duration of KD was 3.8 years, and the longest case was up to 30 years. 58.82% occurred unilaterally and 55.88% showed multiple. 30 cases developed in the head and neck region, of these, 53% involved the parotid gland, and 13.3% showed the eyelids. It may be considered that there are more lymph nodes in the head and face, so the parotid glands, eyelids, and other upper cervical lymph nodes were involved earlier. Gao et al [12] reported that increased eosinophils in the subcutaneous tissue induced the release of relevant cytokines and neurotransmitters, when delivered to the sensory nerve fibers in the subcutis, resulting in pruritus. In our study, all cases with pruritus were accompanied by elevated eosinophils, similar to our results. We found that the lesion skin was accompanied by hyperpigmentation, which has not been reported previously.

MRI helps identify the location and size of the mass and the diagnosis. Previously reported that KD was considered when MRI demonstrated an ill-defined lesion and increased lymph nodes, which is similar to this study [13,14]. In our study, it can be classified into two types according to the MRI, one is a well-defined nodular lesion and the other is an ill-defined patchy or lobulated lesion. Boundaries may be related to the duration of inflammatory infiltration around the lesion. In addition, increased lymph nodes and diffuse atrophy of subcutaneous fat at the lesion are characteristic imaging findings of KD.

The pathogenesis of KD is not clear. According to Munemura et al [15], when the body's immunity is disordered, a large number of T helper (Th) cells differentiate into type 2 helper T (Th2) cells and release cytokines, collectively activating eosinophils and causing serum eosinophilia. In our study, bone marrow puncture and blood routine showed eosinophils, which may be related to pathogenesis. Pathology is the gold standard for diagnosis, characteristics of KD include dense lymphoid follicular hyperplasia, massive eosinophilic infiltration, accumulation of micro-abscesses, venular hyperplasia, and differing extents of fibrosis [16-18]. Bi et al [19] reported of KD involving the eyelids, a lot of CD3-positive and partial CD20 positivity were present in the lymphoid follicles, and CD20-positive were observed in all areas. Gurram et al [20] showed CD3 and CD20 positivity in the submandibular region. BCL-6 is specific for B lymphocytes, and is often identified with reactive follicular hyperplasia, lymphomas, and malignant tumors [21]. In the study, it was found that a few IgG positives were because of the synthesis of B cells induced by cytokines released by Th cells [15,22,23].

Definite diagnosis is for better treatment, many treatment modalities have been proposed, including surgery, steroid, chemotherapy, radiotherapy, and combined treatment modalities, but there has been no consensus up to now. Some [24,25] reported recommending surgical resection with negative margins is preferred. Although it is considered to be a benign disease, KD is sensitive to radiotherapy and is the first choice for recurrent cases or patients with incomplete resections [26]. Multiple cases should be treated with steroids, but it is easy to relapse during the clinical course [27- 30], therefore, it is a second-line regimen in the treatment of KD. In the study, the recurrence rate for those who were treated by surgery alone was 17.39%, the recurrence rate for those who were treated by surgery and steroid was 8.69%, the recurrence rate for those who underwent combined surgery, steroid and, chemotherapy was 4.35%, the recurrence rate for those who was 4.35%, and 1 case were treated by surgery and radiotherapy who died 4 months after radiotherapy.

Recurrence rates are high even after treatment, which is related to ill-defined lesions and increased lymph nodes. In previous reports, we found that eosinophilia, maximum size of the mass, and pruritus are associated with recurrence [31]. Yang et al [14] followed up on 29 patients and found that symptom duration, bilateral, size, eosinophilia, and ill-defined mass were the main predictors of recurrence. Our study shows that duration longer than or equal to 5 years and lymphocyte decrease are associated with recurrence, which helps us to better reduce the recurrence rate.

Conclusions

In the study of 34 patients, our study confirmed that KD is considered with painless masses or lymph node involvement, accompanied by pruritus and hyperpigmentation, and eosinophilia. MRI showed well-defined nodular lesions or ill-defined patchy or lobulated lesions, increased lymph nodes and diffuse atrophy of subcutaneous fat at the lesion are characteristic imaging findings of KD. Pathology is the best way of diagnosis, immunohistochemistry showed diffuse expression of CD3, CD20, and CD21, as well as partial expression of Bcl-6 positivity and weak IgG4 positivity. After surgery, we can choose appropriate adjuvant treatment according to duration and lymphocytes to control recurrence.

Abbreviations

KD: Kimura's disease; TIVA: Total intravenous anesthesia; Ig E: Immunoglobulin E; MRI: Magnetic resonance imaging.

Authors’ Contributions

JX wrote the paper. PFX carried out data collection. CYH, CMH and KS were involved in statistical analysis. WQL and XQ modified the paper and designed this study concepts. All authors read and approved the final manuscript.

Funding

The authors received financial supports from Hubei Provincial Natural Science Foundation of China (2022CFB706, 2023AFB765), Fund of Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration (2022kqhm003) and Huazhong University of Science and Technology Teaching Research Project (2021158).

Availability of Data and Materials

The raw data are confidential and cannot be readily shared. Researchers need to obtain permission from the institutional Review Board and apply for data access to The Ethics Committee of The study was approved by the ethics committee of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology.

Declarations

Ethics Approval and Consent to Participate

The study was approved by the ethics committee of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology (TJ-JRB20231293). All participants volunteered for the study, were informed about the scope of the study and provided written consent.

Author Details

1Department of Stomatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. 2School of Stomatology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. 3Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, 030032, China.

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