Pruritic Plaque on the Right Lower Limb: A Rare Case of Kimura Disease and Literature Review

ABSTRACT

Kimura disease, though rare in adolescents, should be considered in cases of persistent itchy nodules. Histopathology confirms diagnosis. Surgical excision is effective for localized lesions, with favorable outcomes. Early recognition prevents misdiagnosis and unnecessary treatments.

1. Introduction

Kimura disease (KD) is an uncommon benign lymphoproliferative disorder with an elusive etiology. It is most commonly observed in young adult males between the ages of 20 and 40 years, with a predilection for the head, neck, and extremities, often accompanied by regional lymph node enlargement and occasional involvement of the parotid and mandibular glands. The characteristics of lesions are typically non‐tender masses, which may also lead to the appearance of prurigo‐like nodules. While most patients exhibit no symptoms, a few may experience episodes of intense itching. Here, we present a case of a 16‐year‐old girl who sought medical attention at our hospital because of an itchy plaque on her right lower limb. Owing to the patient's non‐specific clinical signs, a series of routine blood tests and local histopathological examinations were conducted, culminating in a definitive diagnosis of KD. This case report underscores the exceptional presentation of KD solely as pruritic plaques and the importance of considering KD in the differential diagnosis alongside conditions such as pigmentary urticaria, dermatofibroma, and angiolymphoid hyperplasia with eosinophilia.

2. Case History/Examination

A 16‐year‐old girl presented with a 3‐month history of two brown, bean‐sized itchy plaques on her right lower limb (Figure 1). Initially, the rashes appeared as red patches on the inner aspect of the right thigh without an identifiable cause. The patient's persistent itching led to frequent scratching, which caused the lesions to expand and their color to deepen. Notably, the patient did not exhibit fever, joint swelling, pain, fatigue, or other related symptoms, and no history of hospitalization or familial predisposition was reported. Physical examination revealed two bean‐sized brown nodules on the inner side of the right thigh.

FIGURE 1.

Photograph of the patient's right lower limb.

3. Differential Diagnosis, Investigations and Treatment

The complement blood count and serum biochemical examination results were normal; chest CT did not show any abnormalities.

Given the non‐specific clinical presentation and atypical lesion location, several differential diagnoses were initially considered. These included pigmentary urticaria, which can present as pruritic hyperpigmented plaques; dermatofibroma, a benign dermal nodule common in adolescents; and angiolymphoid hyperplasia with eosinophilia (ALHE), which may share clinical and histologic features with Kimura disease, but is distinguished by prominent vascular proliferation with epithelioid endothelial cells.

To establish a definitive diagnosis, an incisional biopsy of the leg nodules was performed. Histological findings revealed a dense infiltration of lymphocytes and scattered eosinophils throughout the dermis, along with lymphoid follicle‐like structures and mild small‐vessel hyperplasia in the deeper dermis (Figure 2). Based on these findings, the patient's clinical presentation, histological findings, and final diagnosis of Kimura disease (KD) were established.

FIGURE 2.

The pathological characteristics of lower extremity lesions. (A–C) The epidermis shows no significant abnormalities, while notable infiltration of lymphocytes and eosinophils is observed in the dermis. (D, E) Lymphoid follicular‐like structures and dilated small blood vessels are also present. (A: SP × 40; B: SP × 200; C: SP × 400; D: SP × 200; E: SP × 400; hematoxylin and eosin staining)

Given the localized nature of the patient's condition, surgical excision of the lesions was selected as the treatment approach.

4. Outcome and Follow‐Up

After 3 months of follow‐up, no recurrence was observed.

5. Discussion

KD, also known as eosinophilic lymphogranuloma, is a rare chronic inflammatory condition. Its pathogenesis remains unclear, although it may be related to the proliferative responses induced by atopic hypersensitivity and chronic infection. Recently, Wu et al. [1]. explored the immunopathogenesis of KD through multi‐omics studies and identified excessive activation of the MAPK signaling pathway in eosinophils derived from KD, suggesting that the ERK/MAPK pathway is a potential pathogenic factor in KD.

Regarding clinical characteristics, we reviewed 43 case reports involving 77 patients [2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44] as detailed in Table 1. Our findings indicate that most KD cases occurred in Asia, particularly in China, Japan, and Southeast Asian countries, with a higher prevalence among young to middle‐aged males. The male‐to‐female ratios ranged from 3.5:1 to 9:1 [45]. In another study of 29 Chinese pediatric patients, the gender ratio was 28:1, with a median age of 12 years (range, 2.7–18 years) [46] at diagnosis; whereas in our case series, it was 30 years (range, 4–81 years). However, the sex ratio was 3.3:1, which may be attributed to the small sample size.

TABLE 1.

Features of 77 patients with Kimura disease.

Characteristics		No. of patients (%)
Sex	Male	59 (76.6%)
	Female	18 (23.4%)
Age (Years)	< 35	42 (54.5%)
	≥ 35	35 (45.5%)
Race	Asian	67 (87.0%)
	Black	5 (6.5%)
	White	3 (3.9%)
	Not reported	2 (2.6%)
Body site affected	Head and neck	61 (79.2%)
	Non‐head and neck	9 (11.7%)
	Extremities	5 (6.5%)
	Trunk	2 (2.6%)
Peripheral blood eosinophil percentages	Elevated	60 (77.9%)
	Normal	17 (22.1%)
IgE level in peripheral blood	Elevated	39 (50.6%)
	Normal	38 (49.4%)
Histopathology findings	Significant lymphoid follicle formation	54 (70.1%)
	Active germinal centers and deposits of eosinophilic substances	36 (46.8%)
	Eosinophilic infiltration	77 (100%)
	Eosinophilic microabscess	26 (33.8%)
	Small vessel hyperplasia and fibrous tissue hyperplasia	38 (49.4%)
Clinical management	SE	31 (40.3%)
	SE + OC	12 (15.6%)
	SE + R	2 (2.6%)
	OC + ISD	7 (9.1%)
	Biotherapy	2 (2.6%)
Comorbidities	Anaphylactic disease	5 (6.5%)
	Systemic mastocytosis and polycythemia vera	1 (1.3%)
	IgG4‐RD	2 (2.6%)
	Rheumatoid arthritis	1 (1.3%)
	Vascular lymphoid hyperplasia with eosinophilia	1 (1.3%)
	Nephrotic syndrome	4 (5.2%)
	Budd–Chiari syndrome	1 (1.3%)
	Rubinstein–Taybi syndrome	1 (1.3%)

Abbreviations: OC + ISD, oral corticosteroids and immunosuppressive drug; SE, surgical resection alone, surgical resection followed by oral corticosteroids; SE + R, surgical resection combined with radiotherapy.

KD is insidious at its onset and has a long clinical course. In our case review, KD lesions were predominantly located in the head and neck region (79.2%), particularly in the parotid gland, salivary glands, and lymph nodes [24, 30, 32]. Other affected regions included non‐head‐and‐neck areas (11.7%), such as the inguinal region, retroperitoneum, and mediastinum, as well as the extremities (6.5%) and trunk (2.6%). The primary manifestation is a painless subcutaneous mass in the head and neck region. Most patients were asymptomatic; although intense pruritus can occur and worsen with age [47]. Some patients present with early renal or bone invasion. Previous studies have also reported clinical presentations such as earlobe keloids [25], destructive bone lesions associated with soft tissue masses [29], or involvement of multiple lymph nodes across various regions [18]. Additionally, some patients exhibited comorbidities such as asthma, allergic rhinitis, urticaria (6.5%), nephrotic syndrome (5.2%), vasculitis, cutaneous amyloidosis, and juvenile temporal arteritis [48].

Peripheral blood eosinophilia (77.9%) and elevated IgE levels (50.6%) are commonly observed in KD, aiding in its diagnosis. Computed tomography (CT) and magnetic resonance imaging (MRI) are essential tools for evaluating specific cases [44, 49, 50], allowing the determination of the location, size, margins, and blood supply of the masses, as well as systemic lymph node involvement [50, 51]. The characteristic CT and MRI findings in head and neck KD include multiple ill‐defined enhancing masses within and around the parotid gland [50], accompanied by regional lymphadenopathy. Therefore, radiography plays a supplementary role in the diagnosis of KD.

KD progresses slowly and is often misdiagnosed because of the lack of overt clinical symptoms. Unlike in previous reports, our patient did not present with common painless masses or lymph node involvement. Instead, the patient exhibited two pea‐sized, dark brown, infiltrated plaques on the inner side of the right thigh, a rare dermatologic manifestation. Laboratory tests failed to provide specific positive results, initially leading to a presumptive diagnosis of urticaria pigmentosa based on the patient's history and related laboratory findings. However, histopathological examination confirmed the diagnosis of KD. This case highlights the importance of recognizing uncommon clinical presentations to improve diagnostic accuracy.

Histopathological examination remains the gold standard for diagnosing KD. Our review of 77 cases revealed the following typical pathological features: significant lymphoid follicle formation (70.1%), active germinal centers with eosinophilic material deposits (46.8%), eosinophilic infiltration (100%), eosinophilic microabscess formation (33.8%), and small vessel proliferation with fibrosis (49.4%). Consistent with previous studies, our patient's pathology showed dense lymphocytic infiltration throughout the dermis, scattered eosinophilic infiltration, lymphoid follicle‐like structures in deeper tissues, mild small vessel proliferation, and no epidermal abnormalities, all of which were consistent with the pathology of KD.

The patient's skin lesion, which was a pruritic brownish plaque on the lower extremity, closely resembled the typical presentation of urticaria pigmentosa. Clinically, differentiating these two conditions solely based on skin lesions is challenging. However, histopathological changes in urticaria pigmentosa include mast cell infiltration in the dermal papillae with metachromatic granules observable via Giemsa staining, which were absent in our case, ruling out urticaria pigmentosa. The primary differential diagnosis is angiolymphoid hyperplasia with eosinophilia (ALHE). ALHE is commonly observed in middle‐aged Western females and presents as pale‐red to reddish‐brown papules without lymph node or parotid gland involvement. In contrast, KD is more common in young Asian males and presents as subcutaneous nodules or masses with overlying skin of normal color, often involving the regional lymph nodes and salivary glands. Histopathologically, ALHE is characterized by vascular proliferation with varying degrees of eosinophilic and lymphocytic infiltration around the vessels, lack of eosinophilic microabscesses, germinal centers, and significant fibrosis, which are prominent features of KD [52, 53, 54]. Eosinophilic granuloma is a granulomatous condition characterized by the presence of eosinophils, plasma cells, lymphocytes, and fibrotic tissue. It commonly affects the skin, bones, and other organs. Clinically, it typically presents as localized erythematous patches, nodules, or masses, often accompanied by local discomfort or pain. Although eosinophilic granuloma may resemble the brownish plaques observed in the current case, histopathological features allow for clear differentiation. In our case, skin biopsy revealed dense dermal infiltration of lymphocytes and scattered eosinophils, but no well‐formed granulomatous structures were observed. In contrast, eosinophilic granuloma typically exhibits characteristic granulomas with central necrosis and a more prominent eosinophilic infiltrate. Therefore, despite some clinical overlap, the histopathological findings in this case do not support a diagnosis of eosinophilic granuloma.

Castleman disease is a rare lymphoproliferative disorder that is classified into unicentric and multicentric forms based on clinical presentation. Unicentric Castleman disease usually manifests as isolated lymphadenopathy and is often asymptomatic systemically, although localized skin nodules or masses may occasionally be present. Histologically, it is characterized by prominent lymphoid follicular hyperplasia, vascular proliferation, and varying degrees of plasma cell infiltration. In the present case, the patient exhibited no lymphadenopathy or systemic symptoms, and the skin lesions were confined to the inner aspect of the right thigh. Histopathological examination revealed dense lymphocytic infiltration with scattered eosinophils, follicle‐like lymphoid structures, and mild small‐vessel proliferation, without the typical architectural features of Castleman disease. These findings are more consistent with Kimura disease.

There are currently no standardized guidelines for the treatment of KD. A review of previous case reports revealed various treatment modalities, including surgery alone (40.3%), surgery combined with oral corticosteroids (15.6%), surgery combined with local radiotherapy (2.6%), oral corticosteroids combined with immunosuppressants (9.1%), and biologics (2.6%). Oral corticosteroids are the mainstay of pharmacotherapy for this disease, although some patients experience relapse after discontinuation. Owing to its notable side effects, radiotherapy is not recommended for lesions in critical areas such as the orbit and extraocular muscles. Therefore, treatment plans should be individualized, and novel therapeutic approaches should be explored. Yang et al. successfully treated a patient with KD and painless masses around the auricular regions using dupilumab. Kinoshita et al. reported that monotherapy with 300 mg of mepolizumab led to the resolution of clinical symptoms in a patient with KD, with early intervention potentially preventing secondary fibrosis. Given the limited number of KD cases and predominance of case reports in clinical studies, the optimal treatment strategy for KD remains unclear. Given the localized nature of the lesion in our patient and absence of pruritus or other discomfort, surgery was selected. The patient was followed up for 3 months postoperatively without signs of recurrence.

Author Contributions

Xiaoxiao Liu: visualization, writing – original draft. Xiaolan Zhang: resources, supervision, writing – review and editing.

Consent

Written informed consent was obtained from the patient's legal guardian to publish this case report and any accompanying images in accordance with the journal's patient consent policy.

Conflicts of Interest

The authors declare no conflicts of interest.

Liu X. and Zhang X., “Pruritic Plaque on the Right Lower Limb: A Rare Case of Kimura Disease and Literature Review,” Clinical Case Reports 13, no. 9 (2025): e70775, 10.1002/ccr3.70775.

Data Availability Statement

Data sharing is not applicable to this article as no new data were created or analyzed in this study.