Tissue-infiltrating immune cells contribute to understanding the pathogenesis of Kimura disease: A case report.

RATIONALE: Kimura disease (KD) is a rare, chronic inflammatory disorder characterized by subcutaneous granuloma in the head and neck region, as well as increased eosinophil counts and high serum immunoglobulin E (IgE) levels. Kimura disease is suspected to be an IgE-mediated disease, associated with an allergic response, in which antigen-specific B cells are stimulated to undergo specific IgE class switching with disease-specific CD4+ T (Th) cells help. Thus, exploration of the Th cells in affected tissues with KD is a highly promising field of the investigation. However, there have been no reports with direct evidence to implicate Th cells in affected lesions with KD. Here we quantitatively demonstrate that CD4+ GATA3+ T cells and interleukin (IL)-4+ IgE+ c-kit+ mast cells prominently infiltrate in affected lesion with KD. PATIENT CONCERNS: A 56-year-old Japanese man who exhibited painless swelling in the left parotid region. DIAGNOSES: Diagnosis of KD was made based on characteristic histopathologic findings, in conjunction with peripheral eosinophilia and elevated serum IgE levels. INTERVENTIONS: The patient underwent corticosteroid therapy and had been followed for 2 years. OUTCOMES: We report a rare case of KD of the parotid region in a 56-year-old man, followed by corticosteroid therapy for 2 years. The mass decreased in size and skin itchiness decreased after therapy. He was discharged without any complications. Furthermore, we quantitatively demonstrate the dominance of CD4+ GATA3+ T cells in affected tissues of KD and detect IL-4+ IgE+ c-kit+ mast cells in lesions by multicolor staining approaches. LESSONS: The findings from this case suggest that peripheral blood eosinophilia might serve as a marker of recurrent disease, long-term follow-up is necessary due to the possibility of recurrent. Interactions among expanded IgE+ B cells, CD4+ GATA3+ T cells, eosinophils, and activated mast cells might play a critical role in the pathogenesis of KD.

The clinicopathological characteristics of Kimura disease in Chinese patients.

INTRODUCTION: Kimura disease (KD) is a rare idiopathic inflammatory disorder of unknown etiology. Unusual presentations of KD might cause diagnostic difficulty or be misdiagnosed as malignancy if clinical suspicion is insufficiently high. Here, we aimed to determine the clinicopathological features of Chinese KD patients to reveal further insights into the natural history and treatment of this disease. METHOD: The clinical data of 46 cases of KD diagnosed at Peking Union Medical College Hospital from January 1980 to December 2018 were analyzed retrospectively through case record review. RESULTS: Of 46 cases, 40 were male and six were female. The age at onset ranged from 2 to 56 years (median 27 years). All patients presented with either single (26.1%) or multi-focal (73.9%) subcutaneous masses. Twenty-nine (63.0%) cases presented with head and neck subcutaneous masses, and 9 cases (19.6%) involved different parts of the body. Parotid, submandibular, and lacrimal gland involvement occurred in 17 (37.0%), 3 (6.5%), and 2 cases (4.3%), respectively. Nephrotic syndrome was present in three cases (6.5%), and thromboembolism was present in five cases (10.9%). During follow-up, thirteen patients (13/28, 46.4%) relapsed over 1-13 years (median 8.5 years). The recurrence rate in patients receiving corticosteroids, surgery, and combined surgery and radiotherapy was 30.8%, 66.7%, and 50.0%, respectively. One patient was diagnosed with T cell lymphoma 1 year after diagnosis of KD. CONCLUSIONS: KD is characterized by subcutaneous masses but it is also a systemic disease. Given the high rate of recurrence and reported association with lymphoma, patients require careful long-term follow-up.Key Points• Kimura disease (KD) is a rare inflammatory disorder of unknown etiology that is endemic in Asia.• Clinicians must regard and manage KD as a systemic disease.• There is no consensus on optimal treatments and further studies are necessary to improve outcomes.• Given the high rate of recurrence and reported association with lymphoma, patients require careful long-term follow-up.

Nephrotic syndrome associated with Kimura's disease: a case report and literature review.

BACKGROUND: Kimura's disease (KD) is a rare chronic inflammatory disorder with a high incidence of renal involvement. In this report, we present a case study of KD-associated nephrotic syndrome combined with minimal change disease (MCD) and acute renal tubular injury. Meanwhile, the clinical and histopathological characteristics of 26 patients with KD presenting with renal involvement were retrospectively evaluated. CASE PRESENTATION: Here, we report a case study of a 59-year-old male patient with KD confirmed by a lymph node biopsy. He developed widespread edema and decreased urine output. A palpable swollen mobile and non-tender lymph node behind the left ear was observed upon admission. A renal biopsy revealed minimal-change lesions and acute renal tubular injury. The patient received hemodialysis because of the oliguria and renal insufficiency, and an initial dose of 40 mg/d methylprednisolone and then continued treatment with 40 mg/d prednisolone. He exhibited a good clinical response to the steroid after 6 weeks of treatment. Of the other 26 patients included in the review, 13 patients presented with mesangial proliferative glomerulonephritis, 4 with membranous nephropathy, 3 with MCD, 3 with focal segmental glomerulosclerosis, 2 with IgA nephropathy and 1 with acute tubular injury. With the exception of 2 patients who progressed to end-stage renal disease and received hemodialysis, the majority of patients responded well to treatment with corticosteroids alone. CONCLUSIONS: MCD combined with acute renal tubular injury is rare in patients with KD presenting with renal involvement. Corticosteroids may be a beneficial treatment for renal injury in patients with KD.

Nephrotic syndrome during the tapering of oral steroids after pathological diagnosis of Kimura disease from a lacrimal gland mass: case report and review of 10 Japanese patients.

A 42-year-old man with eosinophilia and high serum immunoglobulin E (IgE) developed a lacrimal gland mass on the left side. Excisional biopsy revealed hyperplasia of lymphoid follicles, and infiltration with lymphocytes and eosinophils around lacrimal gland acini, leading to the pathological diagnosis of Kimura disease. IgE-positive cells were mainly found along follicular dendritic cells, and a small number of IgG4-positive cells was present. One month after oral prednisolone was started at 40 mg daily and tapered to 10 mg daily, he developed lower leg edema on both sides and marked proteinuria (10.8 g/day). Renal biopsy showed no glomerular abnormalities, no immunoglobulin deposition, and no tubulointerstitial infiltration with eosinophils, leading to the diagnosis of minimal change nephrotic syndrome. Proteinuria subsided in response to an increased dose of prednisolone to 30 mg daily. Proteinuria relapsed three times in the following 5 years when oral prednisolone was tapered. In conclusion, Kimura disease manifested as an orbital mass and did not relapse. However, nephrotic syndrome relapsed frequently with background eosinophilia and high serum IgE. This study reviewed the clinical features of 10 Japanese patients with Kimura disease associated with proteinuria.

Kimura's disease: A case presentation of postauricular swelling.

Kimura's disease (KD) is a rare chronic inflammatory disease of subcutaneous tissues and occurs predominantly in head and neck region. It is seen primarily in young Asian males. Typical clinical presentations are painless subcutaneous masses, regional lymph node enlargement, blood and tissue hypereosinophilia, and increased serum IgE levels. Here, we present a case of a 27-year-old female who presented with unilateral single nodular swelling in the right postauricular region. The diagnosis of KD was done based on characteristic histopathologic finding in conjunction with peripheral eosinophilia and increase in serum IgE levels.

Intraparotid Kimura disease.

INTRODUCTION: Intraparotid locations are extremely rare in Kimura disease, especially in Europe. CASE REPORT: A 31-year-old man presented with intraparotid Kimura disease, managed by parotidectomy. DISCUSSION/CONCLUSION: The case was analyzed in the light of a review of the literature, focusing on the diagnostic and anatomopathologic problems encountered, and the physiopathology and treatment of this pathology. Any parotid mass found in a patient of Far-Eastern origin showing hypereosinophilia should suggest a diagnosis of intraparotid Kimura disease.

Angiolymphoid hyperplasia with eosinophilia and Kimura's disease coexisting in the same patient: evidence for a spectrum of disease.

The relationship between angiolymphoid hyperplasia with eosinophilia (ALHE) and Kimura's disease has always been contentious. Initially, ALHE and Kimura's disease were thought to be conditions within the same disease spectrum, but it is now widely accepted that they are two separate disease entities. The two lesions may coexist in one patient. Thus, ALHE and Kimura's disease may be different manifestations of the one disease.

Epitrochlear mass in a patient on maintenance hemodialysis--Kimura disease.

Kimura disease is a rare benign inflammatory disorder presenting as subcutaneous masses or lymphnodal mass in the cervical region. Kimura disease is reported sparsely in patients on maintenance hemodialysis. We report an unusual location of Kimura disease in a patient on maintenance hemodialysis, who had a prolonged, persistent asymptomatic eosinophilia.

Effective treatment of Kimura's disease with leflunomide in combination with glucocorticoids.

Kimura's disease (KD) is a rare, benign, chronic inflammatory disease which typically presents as persisting or recurring tumor-like lesions in the head and neck area that can be easily misdiagnosed. We report one patient with KD treated with leflunomide in combination with glucocorticoids and analyzed the literature on treatment of KD. The patient had a recurrent mass in the left upper arm with eosinophilia and elevated serum IgE but no renal involvement. The clinical manifestations improved markedly within 1 month, and blood eosinophil count and serum IgE normalized. Corticosteroids were then tapered gradually without recurrence or severe side effects in the 2-year follow-up period. Literature analysis identified four different non-drug interventions and 18 different drugs for treating KD, most of which were obtained from case reports. Our use of combination therapy of leflunomide and glucocorticoids suggests the need for a controlled trial for the treatment of this rare disorder.

Increase of Th2 and Tc1 cells in patients with Kimura's disease.

OBJECTIVE: A Th1/Th2 cytokine imbalance with a predominance of Th2 cytokines has been suggested to be of pathogenic importance in Kimura's disease. METHODS: To evaluate the role of Th1/Th2 cytokines in Kimura's disease, the subsets of Th1, Th2, Tc1 and Tc2 cells from patients with Kimura's disease were examined by intracellular cytokine flow cytometry. The expressions of IL-5, eotaxin and RANTES in the lesions were investigated by RT-PCR. RESULTS: The population of Th2 and Tc1 cells in Kimura's disease was significantly increased compared with these cells in control (p<0.05). Th1 and Tc2 cells in Kimura's disease were not significantly increased compared with control subjects. The titers of IgE and the number of Th2 cells were correlated. The expression of IL-5 and RANES was observed in the lesions of patients with Kimura's disease. CONCLUSION: These results indicate that the predominance of Th2 and Tc1 cells might contribute to the mechanism in pathogenesis of Kimura's disease.

Angiolymphoid hyperplasia with eosinophilia successfully treated with oral steroids.

Angiolymphoid hyperplasia with eosinophilia is a rare benign vascular lesion most commonly affecting the head and neck region. This article reports a case of a 26-year-old white woman with rapidly enlarging nodules of the upper lip and cheek treated successfully with oral corticosteroids and cetirizine. Morbidity and cosmetic deformity associated with radical surgery to the face and possible consequences of radiation treatment were avoided. There were no long-term complications.

Thrombosis of temporal artery and renal vein in Kimura-disease-related nephrotic syndrome.

Kimura disease (KD) is an angiolymphoid proliferative disorder of unknown etiology, occurs mainly in Asian patients, presenting with subcutaneous slowly growing masses, with a predilection for preauricular and submandibular regions. The clinical course of the disease is thought to be benign. Concomitant peripheral blood eosinophilia and elevated serum immunoglobulin E levels are often observed. Main systemic manifestation of the KD is renal involvement. Renal abnormalities, notably proteinuria and nephrotic syndrome have been found to be associated with KD. We report a 42-year-old man with KD and a steroid-sensitive membraneous nephrotic syndrome with bilaterally temporal artery and renal vein thrombosis. This is the first reported case of KD associated nephrotic syndrome complicated with wide arterial and venous thrombosis from Anatolia.

Serum concentrations of eosinophil cationic protein and eosinophils of patients with Kimura's disease.

BACKGROUND: To clarify the role of eosinophils in the pathogenesis of Kimura's disease and the values of measuring serum levels of eosinophil cationic protein (ECP) for monitoring disease activity might be very important, but there are few reports about this matter. METHODS: A total 14 serum and 7 tissue samples from patients with Kimura's disease were studied. The concentrations of ECP and cytokines (interleukin-4 (IL-4), granulocyte-macrophage colony-stimulating factor (GM-CSF), and interleukin 5 (IL-5)) in sera from patients with Kimura's disease were measured by enzyme-linked immunosorbent assay (ELISA). The density of eosinophils and the degree of activation of eosinophils in the tissue were also studied immunohistochemically. RESULTS: The concentration of ECP in sera from patients with Kimura's disease was significantly higher than that in the control group (p<0.05). At the time of the remission, a significant decrease of ECP was observed. In interfollicular areas, most infiltrated eosinophils were positive for EG2 antibody (64.0-94.0%) and the mean percentage of EG2-positive eosinophils was 75.7%. The concentrations of IL-4, GM-CSF, and IL-5 in sera from patients with Kimura's disease were within normal ranges or below the detectable level in all sera examined. CONCLUSIONS: Our findings suggest that eosinophils play an important role in the pathogenesis of Kimura's disease and ECP may be used as an additional parameter of disease activity.

Angiolymphoid hyperplasia with eosinophilia (epithelioid haemangioma) occurring within multiple deep lymph nodes and presenting with weight loss and raised CA-125 levels.

We report a case of angiolymphoid hyperplasia with eosinophilia (epithelioid haemangioma) involving multiple deep mediastinal, abdominal and intramammary lymph nodes in a 52-year-old woman with weight loss and raised CA-125 levels. The unusual clinical presentation with raised CA-125 levels and its occurrence within multiple deep visceral lymph nodes has never been reported in literature.

Kimura's disease: a diagnostic and therapeutic challenge.

INTRODUCTION: Kimura's disease (KD) is a rare, benign, chronic inflammatory disease with unknown aetiology. Its manifestation is protean. KD has a predilection for the head and neck area, and typically presents as tumour-like lesions that could be easily misdiagnosed. We review our experience with four recent cases. METHODS: Over a four-year period, all patients admitted to Singapore General Hospital with KD of the head and neck region were retrospectively reviewed. Biodata, presenting symptoms and clinical parameters, especially serum eosinophil levels, preoperative investigations, type of surgical procedures and outcome were documented. RESULTS: Four patients presented with KD of the head and neck and displayed varied manifestations of the disease. All the patients had raised serum eosinophil levels. None of them had renal involvement. Preoperative computed tomography were performed in two of the patients and showed features suggestive of KD. Fine-needle aspiration cytology that was performed in two patients was not useful in the diagnosis. All the patients underwent surgical excision of the lesions. Only one patient had multiple recurrence, both at the original and remote sites in the head and neck. CONCLUSION: The clinical presentation and behaviour of KD is very variable. Preoperative imaging is useful in the diagnosis of the disease but the final diagnosis is histological. Surgical excision is the current treatment of choice but recurrence is common. A high index of suspicion and awareness is vital in the early diagnosis and management of KD.

[Kimura's disease on the hard palate in a patient from Martinique]. / Maladie de Kimura à localisation palatine chez un Antillais.

INTRODUCTION: We report an observation of Kimura's disease (angiolymphoid hyperplasia with eosinophilia) in a Black patient from West Indies, in a rare localisation on hard palate. EXEGESIS: A 46-year-old male patient from French West Indies (Martinique) presented with a tumor of hard palate evolving from 2 years with locoregional lymph nodes. He had a history of chronic urticaria, prurigo, rhinitis and alopecia areata. Pathological examination of the tumor was consistent with the diagnosis of Kimura's disease. Blood tests showed hypereosinophilia, elevation of IgG and IgE. The serology of Toxocara canis with Western blott was positive. Corticosteroid therapy (0.7 mg/kg/d) and albendazole (800 mg/d) allowed regression of the tumor, lymph nodes, and urticaria. The remaining tumor was surgically excised. CONCLUSION: Kimura's disease was first described in Japanese young men, between 20 and 40 years old, with subcutaneous nodules on head and neck area. Involvement of oral mucosa is rare, and the occurence in West Indian patients has been rarely reported.