414 Original article
Pulmonary embolism as the initial clinical presentation of Kimura disease: case report and literature review Xu Yea, Ying Fenga and Suxia Linb Pulmonary embolism is clinically critical in that if misdiagnosed or delayed, the mortality is very high. The recognition of its risk factor or underlying disease is important for prevention of recurrence. Kimura disease is a rare, chronic inflammatory disease, which is seldom associated with thrombosis. We reported a 47-year-old male case presenting with pleural pain and dyspnoea and was found to have pulmonary embolism. After successful management of pulmonary embolism, he was noticed to have eosinophilia and lymphadenopathy. Pathologic examination of a resected lymph node has confirmed the diagnosis of Kimura disease. The patient was treated with corticosteroid and cyclosporine A, with a significant improvement of the symptoms and signs of Kimura disease and no recurrence of any thromboembolism. Associated literatures were reviewed to explore the pathogenesis underlying the thrombotic event in Kimura disease cases. It is suggested that hypereosinophilia may play a key role in
Introduction Acute pulmonary embolism is a critical condition requiring emergent treatment. It is defined by obstructive thrombosis of the pulmonary artery. The clinical presentation of acute pulmonary embolism ranges from mild dyspnoea to cardiac arrest, the wide variations in its clinical presentations rendering it easily misdiagnosed. Misdiagnosis of pulmonary embolism and the resulting delay in pertinent management can lead to fatal outcome. The annual incidence of pulmonary embolism is approximately three to six cases per 10 000 persons in the general population. The short-term mortality of pulmonary embolism ranges from less than 1% in haemodynamically stable patients with nonmassive pulmonary embolism and no signs of right heart overload to over 90% in patients who present with cardiorespiratory arrest [1]. Risk factors for thrombus formation include perioperative state, prolonged bed rest, antiphospholipid syndrome, malignancy, hereditary thrombophilia and some chronic inflammatory diseases [2]. Recognizing and successful management of the risk factor for diagnosed pulmonary embolism is of clinical significance to prevent it from recurring. Kimura disease is a chronic inflammatory disorder with angiolymphatic proliferation of unknown cause, usually affecting young men of Asian race. Patients with Kimura disease typically present with nontender subcutaneous swelling in head and neck region predominantly in preauricular and submandibular area. It may be associated with local or systemic lymphadenopathy, marked 0957-5235 Copyright ß 2015 Wolters Kluwer Health, Inc. All rights reserved.
thrombosis formation. The control of hypereosinophilia may contribute to the prevention of thrombosis and its recurrence in patients with Kimura disease. Blood Coagul Fibrinolysis 26:414–418 Copyright ß 2015 Wolters Kluwer Health, Inc. All rights reserved.
Blood Coagulation and Fibrinolysis 2015, 26:414–418 Keywords: hypereosinophilia, Kimura disease, pulmonary embolism a
Department of Hematology, Second Affiliated Hospital of Guangzhou Medical University and bDepartment of Pathology, Cancer Center, Sun-Yat-Sen University, Guangzhou, China Correspondence to Xu Ye, MD, Second Affiliated Hospital of Guangzhou Medical University, No. 250 Changgangdonglu, Guangzhou, 510260, China E-mail: [email protected] Received 15 January 2014 Revised 19 December 2014 Accepted 5 January 2015
peripheral eosinophilia and an elevated IgE level [3]. Kimura disease is usually seen in young adults, with most patients being aged between 20 and 40 years; men are affected more commonly than women, with a 3 : 1 ratio. Main systemic manifestation of the Kimura disease is renal involvement including notably proteinuria and nephrotic syndrome [4]. Thrombosis complications were rarely reported in patients with Kimura disease. We herein report a case presented as pulmonary embolism and was later on found to have the rare underlying cause of Kimura disease. As we know, this is the first report of pulmonary embolism developed in patients with Kimura disease.
Case presentation A 47-year-old man was admitted complaining of dizziness for 5 days and a feeling of tingling pain in his right hypochondria area and dyspnoea on exertion for 3 days. His pain could be relieved by oral paracetamol and exacerbated when lying down on the back. The patient used to be fairly healthy, but had complained of overall pruritus for 2 years. He used to see dermatologists constantly and was prescribed oral antihistamines to relieve his itching. When he began to feel pain and dyspnoea, he came to the outpatient department and had a blood routine test that showed increased white blood cell count of 18.98 109/l and decreased platelet count of about 33 109/l. The leukocyte differential showed prominent eosinophilia with an absolute eosinophil count of 9.52 109/l and eosinophil percentile of 50.21%. His haemoglobin level was normal. More than normal (50/ml) red blood cells were DOI:10.1097/MBC.0000000000000278
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Pulmonary embolism as the presentation of Kimura disease Ye et al. 415
present in his urine. But no proteinuria was present. His chest radiograph and abdominal ultrasonography were normal. With prominent eosinophilia and suspected diagnosis of haematologic disorders, he was referred to the Department of Hematology and was admitted for further examination and treatment. On admission, he was detected to have a fever with temperature of 38.58C, but his other vital signs were all within normal range. He also presented with multiple, prominent, nontender bilateral cervical, subaxillary and inguinal lymphadenopathy. Auscultation revealed decreased breathing sound on his right lower lung field. Sporadic dark red rashes were also noted on his lower extremities. Repeat blood routine test showed that his white blood cell count was 14.04 109/l with an absolute eosinophil count of 3.66 109/l and eosinophil percentile of 26.11% and normal platelet count. As his oxygen saturation dropped to 95%, a chest computed tomographic (CT) angiogram (CTA) was performed and confirmed pulmonary thrombosis with thrombus formation in the right main pulmonary artery and its branches. Patchy consolidation shadow was seen in the posterior basal segment of the right lower lobe of the lungs. A small amount of right pleural effusion was also noted. Anticoagulation therapy with 0.6 ml (6150AxaIU) subcutaneous injection of FraxiParine (GSK, China) per 12 h and successive oral warfarin together with intravenous antibiotics was administered. One week later, all the above symptoms and signs were relieved. Repeat chest CTA showed contracted consolidation shadow in the right lower lobe without signs of pleural effusion. On the 11th day, the patient was discharged without any complaint. He was on oral warfarin maintenance for 6 months with an international normalized ratio (INR) within 2.0–3.0. Although the patient did not complain of further respiratory symptoms, repeat chest CTA 3 months later showed smaller thrombus remaining in the right main and inferior pulmonary arteries but more in their distal branches and new thrombus formation was noted in the left main pulmonary and inferior pulmonary arteries together with a small amount of flaky fuzzy shadow in the left lingular lobe.
To screen for thrombophilia, the patient’s plasma protein C (PC), antithrombin (AT), free protein S (FPS) and vWF:Ag levels were measured using immunoturbidimetry method, and his factor VIII and factor XII activities were measured by coagulation method and the results were all within normal range except that his vWF:Ag level was 188%, which was relatively higher than normal (reference: 50160%). The lupus anticoagulant was detected with the dilute Russell viper venom time (DRVVT) method and the antiphospholipid antibodies were detected using the ELISA method. Both of them were negative. Detection for factor V Leiden mutation and thrombin G20210A mutation were performed with PCR restriction fragment length polymorphism method and rendered negative results. On follow-up, the patient gradually complained of itching feeling all over the body without rash. The feeling of itching could not be fully alleviated with antihistamines and his blood routine test result still showed significantly increased eosinophil count. On physical examination, he was noticed to have progressive multiple lymphadenopathies in cervical, subaxillary and inguinal regions. The biggest lymph node in his subaxillary region had a diameter of more than 5 cm. Lymph node biopsy was suggested and was at first refused by the patient. After repeat persuasion and afflicted by the enlarged lymph nodes and pruritus, the patient consented to receive right subaxillary lymph node biopsy 1 month later. The pathologic changes (Fig. 1) of the resected lymph node demonstrated hyperplastic lymphoid follicles with a patchy expansion of germinal centre and marked eosinophil infiltration within the inter-follicular area. Eosinophilic abscess formation and remarkable small blood vessel hyperplasia could be seen in some areas. Immunohistochemistry showed that the tissue was positive for CD20 in the follicles, Bcl-6 in the germinal centre, CD3 in the inter-follicular region, CD68 for the tissue, S100 sporadically and CD34 in blood vessels. Taking all the clinical features together, Kimura disease was diagnosed. At that time, the patient refused further treatment for the
Fig. 1
(a)
(b)
(c)
Pathologic histology of the patient’s resected lymph node. The pathologic changes of the resected lymph node demonstrated hyperplastic lymphoid follicles with patchy expansion of germinal centres and marked eosinophil infiltration within inter-follicular area (a). Eosinophil abscess formation (b) and remarkable small blood vessel hyperplasia (c) could be seen in some areas.
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
416 Blood Coagulation and Fibrinolysis 2015, Vol 26 No 4
Kimura disease. On further follow-up, his symptom of pruritus became worse and the lymphadenopathy progressed. Seven months after the onset, we referred his lymph node biopsy slides to another medical centre for pathologic diagnosis and the diagnosis of Kimura disease was suggested once again. Then, the patient was administered 0.5 mg/kg body weight oral prednisone daily. With corticosteroid treatment, his pruritus was gradually relieved, enlarged lymph nodes shrank partially together with improved eosinophilia. One week later, his white blood cell differential came back to normal. Prednisone was tapered. Repeat chest CTA performed 1 year after the onset showed normal pulmonary artery filling. But when prednisone was tapered to 10 mg per day, his pruritus recurred and eosinophilia developed again. We gave him 50 mg/day of thalidomide and his eosinophil count gradually came back to normal again. Two months later, he could not stand the constipation side effect of thalidomide and the dosage of thalidomide was tapered to 25 mg/day. But his eosinophilia and pruritus was gradually aggravated. He refused any treatment at that time. Two years after the onset, he came back with worsened pruritus and lymphadenopathy. Eosinophilia also exacerbated. His serum total IgE level was measured to be as high as 1081.34 IU/ml (reference: 050 IU/ml). He was then administered 50100 mg/day of cyclosporine A, which was tapered off 6 months later together with 5 mg/day of prednisone. With this treatment, his pruritus disappeared and lymphadenopathy was alleviated significantly. It is more than 3 years after the onset of the disease that the patient is still taking 5 mg/day of prednisone for maintenance and his eosinophil count remains normal without any symptoms of pruritus and any signs of thrombus formation.
Discussion Kimura disease was first described by Kim as a kind of eosinophilic hyperplastic lymphogranuloma in the Chinese Journal of Surgery in 1937 and was later systemically characterized by Kimura and Ishikawa in 1948 and thus got its name. It is a rare chronic inflammatory disease involving subcutaneous tissues presenting with painless, slowly enlarging soft tissue mass frequently involving the major salivary gland and lymph nodes of head and neck. Systemic symptoms such as fever, night sweats and weight loss are uncommon. Patients’ blood tests typically show peripheral blood eosinophilia and elevated serum IgE level. It mainly affects patients of Asian descent in their second, third and fourth decades of life with a male predilection (87%) [4]. Clinically, patients with Kimura disease usually present with firm, painless, single or multiple subcutaneous lesions in the head and neck, especially in the parotid and submandibular regions. Associated lymphadenopathy can be seen in 42100% of the cases. Other less common sites of involvement reported include the
preauricular area, epicranium, paranasal sinuses, orbits (including eyelids, conjunctiva and lacrimal glands), epiglottis, tympanic membrane and parapharyngeal space [5]. Rarely, the disease can involve nonhead and neck sites such as the axilla, groin, popliteal region, back of the trunk and forearm. A single case of Kimura disease with bone involvement has also been reported [6]. Two Chinese authors reported two cases of Kimura disease, respectively, involving the skull and right clavicle causing osteolytic lesions mimicking bone tumour [7,8]. Because of its variable, nonspecific clinical presentations, slow progression course and rarity, the first diagnosis of a Kimura disease in a patient may usually be neglected or misdiagnosed or sometimes be covered by its complications. The patient described here is atypical in that he did not present with any subcutaneous nodules or mass but only pruritus that may also be seen in a variety of other allergic diseases or parasitic diseases, although pruritus can be seen in 16.7 25% of cases with Kimura disease [9,10]. Even though he was noticed to have eosinophilia, the existence of a rare disease such as Kimura disease had not been included in the differential diagnosis by the haematologist he was first referred to. He might have had lymphadenopathy for some time, but neither the dermatologists nor the patient himself noticed it. In the present case, it was the complication of pulmonary embolism made the doctor notice his eosinophilia and then the multiple lymphadenopathies. The pathologic analysis of the lymph node biopsy finally confirmed the diagnosis of Kimura disease. For Kimura disease, the most reported complication has been nephrotic syndrome, whereas thrombotic complication was rarely reported. In 1986, Naito et al. [11] had reported a 45year-old Japanese man with marked eosinophilia, congestive heart failure and murmurs of aortic and mitral regurgitation. The histologic examination of his subcutaneous cervical mass biopsy revealed features of Kimura disease. Left ventriculography was suggestive of an extensive ventricular mural thrombus superimposed on a thickened endocardium. The ventricular thrombus was supposed to be the result of endomyocardial fibrosis and eosinophilia. Danis et al. [4] reported a 42-year-old Turkish man with Kimura disease and membranous nephrotic syndrome had bilaterally temporal artery and renal vein thrombosis. Liu et al. [12] reported a 40-year-old Chinese man who developed extensive thrombosis in the superior mesenteric vein, portal vein and splenic vein causing infarction of small bowel and spleen together with right upper extremity and left lower extremity deep venous thrombosis several days following transoceanic air flight travel. Five months later, Kimura disease was confirmed through lymph node biopsy after he developed a pruritic papular skin rash and right epitrochlear lymphadenopathy. Further blood analysis excluded other causes of hypercoagulability. Eguia et al. [13] reported a 34-year-old Chinese man with necrosis of several fingertips, the lateral side of his left
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Pulmonary embolism as the presentation of Kimura disease Ye et al. 417
foot and paresthesia of both legs, which they thought may be due to dermal vessel thrombosis and endothelial damage, although they did not show it in histologic analysis of the cutaneous biopsy. The patient also presented with significant eosinophilia and was later diagnosed Kimura disease by lymph node biopsy. Recently, Lee et al. [14] reported a case of Kimura disease complicated with bowel infarction and multiple arterial thrombi in the upper and lower extremities. Reports on cases with thrombotic events in a rare disease such as Kimura disease suggested that Kimura disease might be a disease with thrombophilic pathogenesis. Up to now, the cause and pathogenesis of Kimura disease is still unknown. Impairment or interference with immune regulation, atopic reaction to a persistent antigenic stimulus by arthropod bites, virus, trauma, neoplasm and even Candida antigenemia have been postulated to be causative [15]. Studies have demonstrated that elevated mRNA levels of interleukin (IL)4, IL-5 and IL-13 were found in patients with Kimura disease. Changes in the expression levels of these cytokines correlated with the disease activity [16]. Ohta et al. [17] found that the concentration of cytotoxic eosinophilic cationic protein in sera from patients with Kimura disease was significantly higher than normal controls and was associated with the disease activity suggesting that eosinophils play an important role in the pathogenesis of Kimura disease. They further found that the population of Th2 cells in Kimura disease was significantly increased and the number of Th2 cells was correlated with the titres of IgE [18]. Yamazaki et al. [19] found that Th2 cytokines such as IL-3, IL-4, IL-5, IL-13 or granulocyte-macrophage colony-stimulating factor (GM-CSF) produced by peripheral mononuclear cells in most of the Kimura disease cases were higher than those of controls and the ratio of Th2 subpopulation T cells was also increased. Among the cytokines, IL-13 and IL-4 are central T helper 2 (Th2) cytokines in the immune system and are potent activators of inflammatory responses and fibrosis during Th2 inflammation. IL-4 is the major factor regulating IgE production by B cells and is required for optimal Th2 differentiation and IL-13 is required for IL-4 function. IL-5 is essential for the maturation of eosinophils in bone marrow and for their release into the blood. It is also a major cytokine for mature eosinophil activation and accelerating differentiation, proliferation and chemotaxis of eosinophils. Taken together, the results from the above studies have demonstrated that increased Th2 cells may play important roles in the pathogenesis of Kimura disease through the increased syntheses of key Th2-type cytokines IL-4 and IL-5, which consequently upregulate eosinophil production, eosinophilic infiltration and IgE synthesis. Increase in eosinophil amount, that is, hypereosinophilia has been associated with thrombosis. An early study including 50 cases with idiopathic hypereosinophilia
syndrome (HES) suggested that eosinophil infiltration of endothelial cells in the endocardium and of the microvasculature had initiated cardiac thrombosis in severe cases [20]. Ames et al. [21] had reported three patients with Churg–Strauss syndrome (CSS) who had experienced thrombosis formation in the left subclavian vein, the left leg and the left middle cerebral artery, respectively. In a series summarizing 15 cases with HES, thrombotic and embolic complications developed in 10 patients, despite treatment with anticoagulants and inhibitors of platelet function, and were the cause of death in three [22]. Case reports of hypereosinophilia associated with thrombosis of the pulmonary artery, femoral vein, hepatic vein (Buddi–Chiari syndrome), coronary artery, renal vein and splenic vein have been published [23,24]. The mechanism behind the increased risk of thrombosis in patients with hypereosinophilia is still not clear. Studies exploring the effects of eosinophils and eosinophil-derived products on endothelial cells and on coagulation pathways have pointed towards a combination of eosinophil-mediated cytotoxicity towards endothelial cells, and a pro-coagulant state favoured by hypereosinophilia. By damaging endothelial cells, eosinophils expose the underlying tissue, naturally triggering the extrinsic coagulation pathway. Moreover, it has been shown that two of the eosinophil cationic proteins, the major basic protein (MBP) and eosinophil peroxidase, are able to activate platelets by evoking platelet secretion of 5-hydroxytryptamine, platelet alpha granule and lysosome components in vitro. Sera from hypereosinophilic patients containing elevated levels of MBP inhibited function of thrombomodulin as a cofactor for the thrombin-catalysed activation of PC anticoagulant system [25]. Eosinophil peroxidase has been shown to generate oxidants, which were potent inducers of tissue factor (TF). Moreover, researchers have found that patients with hypereosinophilic disorders expressed a higher level of TF. Eosinophils and their precursor cells stored TF within their granules, which, under activation, resulted in rapid TF exposure on the eosinophil cell membrane and increased TF transcript levels and the triggering of external coagulation pathway [26,27]. All these contribute to the prothrombotic manifestations seen in patients with hypereosinophilic conditions. In the present case, the pulmonary embolism occurred when the patient’s eosinophil count reached its peak and did not recur after eosinophilia was controlled. Without other detectable prothrombotic factors, we presume that hypereosinophilia as a result of Kimura disease was the main prothrombotic factor in this patient. Treatment for Kimura disease includes surgical resection, local irradiation, laser fulguration, cytotoxic therapy and regional or systemic steroid therapy. Complete surgical resection has been considered first-line treatment for Kimura disease with a recurrence rate up to 25%. In patients complicated with nephrotic syndrome,
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
418 Blood Coagulation and Fibrinolysis 2015, Vol 26 No 4
systemic corticosteroids are recommended. But tapering of steroids always resulted in disease recur. Case reported on successful treatment of Kimura disease with cyclosporine, pentoxifylline, vincristine, mycophenolate mofetil and intravenous immunoglobulin have been published [28–31]. Our patient received local lymph node resection only for the purpose of pathological diagnosis. Owing to the multiple lymph node involvement in this case, complete surgical resection is impossible. We prescribed oral corticosteroid with initial good response, but recurrence occurred after steroid tapering. Then, cyclosporine was administered resulting in good response and was later on tapered off. With maintenance low dosage of prednisone, he has been in good condition for more than 2 years now. In conclusion, we have reported a case with pulmonary embolism with underlying Kimura disease, which was successfully treated with anticoagulant therapy. His Kimura disease was later on diagnosed by pathologic examination of his resected lymph node and was successfully controlled with corticosteroid combined with cyclosporine A. We also reviewed associated literature to try to explore the pathogenesis mechanism leading to the severe thrombotic event in a Kimura disease patient without any other thrombophilia factors. It is implicated that prominent hypereosinophilia in cases with Kimura disease may lead to a tendency towards thrombosis formation so that the control of hypereosinophilia may contribute to the prevention of thrombosis and its recurrence in patients with Kimura disease.
5 6 7 8 9 10
11
12 13
14
15
16
17
18
19
20
Acknowledgements The authors would like to thank Dr Wu Bingyi (Department of Hematology, Zhujiang Hospital, Guangzhou, China) for his help in performing lymph node biopsy on the patient and Dr Ye Suzhen (Department of Medical Imaging, Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China) for the preparation of the patient’s imaging materials. Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.
21
22
23 24
25
26
Conflicts of interest
There are no conflicts of interest.
27
References 1
2
3
4
Rohacek M, Szucs-Farkas Z, Pfortmu¨ller CA, Zimmermann H, Exadaktylos A. Acute cardiac disorder or pneumonia and concomitant presence of pulmonary embolism. PLoS One 2012; 7:e47418. Ben Salah R, Frikha F, Kaddour N, Saidi N, Snoussi M, Marzouk S, et al. Risk factor for deep venous thrombosis in internal medicine: a retrospective study of 318 cases. Ann Cardiol Angeiol (Paris) 2014; 63:11–16. Armstrong WB, Allison G, Pena F, Kim JK. Kimura’s disease: two case reports and a literature review. Ann Otol Rhinol Laryngol 1998; 107:1066–1071. Danis R, Ozmen S, Akin D, Ozekinci S, Altintas A, Cil T, et al. Thrombosis of temporal artery and renal vein in Kimura-disease-related nephrotic syndrome. J Thromb Thrombolysis 2009; 27:115–118.
28
29 30
31
Park SW, Kim HJ, Sung KJ, Lee JH, Park IS. Kimura disease: CT and MR imaging findings. AJNR Am J Neuroradiol 2012; 33:784–788. Varshney MK, Kumar A, Khan SA, Yadav CS. Kimura disease of extremity: unusual manifestation in a long bone. Joint Bone Spine 2008; 75:492–494. Wang J, Wang Y. A case of skull Kimura’s disease. Chinese J Cardiol 2009; 43:1333–1334. Qiu Q, Xiang Y, Jiang J. A case of Kimura’s disease misdiagnosed with malignant bone tumor. Chin J Bone Tumor Bone Dis 2010; 9:373–374. Yu F, Teng H, Wang Z. The clinical features and management of eosinophilic lymphoid granuloma. J Clin Stomatol 2002; 18:54–55. Wang DY, Mao JH, Zhang Y, Gu WZ, Zhao SA, Chen YF, Liu AM. Kimura disease: a case report and review of the Chinese literature. Nephron Clin Pract 2009; 111:c55–c61. Naito H, Nakatsuka M, Yuki K, Yamada H. Giant left ventricular thrombi in the hypereosinophilic syndrome: report of two cases. J Cardiogr 1986; 16:475–488. Liu H, Al-Quran SZ, Lottenberg R. Thrombotic storm in Kimura disease. J Thromb Thrombolysis 2010; 29:354–357. Eguia B, Bachmeyer C, Charlotte F, Cabannes-Hamy A, Loustau V, Senet P, et al. Kimura disease with necrosis of the limbs and mononeuritis multiplex. Clin Exp Dermatol 2011; 36:329–331. Lee J, Hong YS. Kimura disease complicated with bowel infarction and multiple arterial thromboses in the extremities. J Clin Rheumatol 2014; 20:38–41. Fouda MA, Gheith O, Refaie A, El-Saeed M, Bakr A, Wafa E, et al. Kimura disease: a case report and review of the literature with a new management protocol. Int J Nephrol 2011; 2010:673908. Katagiri K, Itami S, Hatano Y, Yamaguchi T, Takayasu S. In vivo expression of IL-4, IL-5, IL-13 and IFN-gamma mRNAs in peripheral blood mononuclear cells and effect of cyclosporin A in a patient with Kimura’s disease. Br J Dermatol 1997; 137:972–977. Ohta N, Okazaki S, Fukase S, Akatsuka N, Aoyagi M, Yamakawa M. Serum concentrations of eosinophil cationic protein and eosinophils of patients with Kimura’s disease. Allergol Int 2007; 56:45–49. Ohta N, Fukase S, Suzuki Y, Ito T, Yoshitake H, Aoyagi M. Increase of Th2 and Tc1 cells in patients with Kimura’s disease. Auris Nasus Larynx 2011; 38:77–82. Yamazaki K, Kawashima H, Sato S, Tsunoda H, Yoshimura Y, Higuchi M, et al. Increased CD45RO(þ) CD62L(þ) CD4(þ) T-cell subpopulation responsible for Th2 response in Kimura’s disease. Hum Immunol 2013; 74:1097–1102. Fauci AS, Harley JB, Roberts WC, Ferrans VJ, Gralnick HR, Bjornson BH. NIH conference. The idiopathic hypereosinophilic syndrome. Clinical, pathophysiologic, and therapeutic considerations. Ann Intern Med 1982; 97:78–92. Ames PR, Roes L, Lupoli S, Pickering M, Brancaccio V, Khamashta MA, Hughes GR. Thrombosis in Churg-Strauss syndrome. Beyond vasculitis Br J Rheumatol 1996; 35:1181–1183. Spry CJ, Davies J, Tai PC, Olsen EG, Oakley CM, Goodwin JF. Clinical features of fifteen patients with the hypereosinophilic syndrome. Q J Med 1983; 52:1–22. Ko JH, Lin JW, Hui RC. Acute pulmonary embolism in a patient with hypereosinophilia and psoriasis. Chang Gung Med J 2011; 34 (Suppl 6):17–23. Jones PD, Moll S, Dellon ES. Pulmonary embolism in a patient with eosinophilic esophagitis: causal or coincidental? Case Rep Gastroenterol 2013; 7:82–88. Mukai HY, Ninomiya H, Ohtani K, Nagasawa T, Abe T. Major basic protein binding to thrombomodulin potentially contributes to the thrombosis in patients with eosinophilia. Br J Haematol 1995; 90:892–899. Moosbauer C, Morgenstern E, Cuvelier SL, Manukyan D, Bidzhekov K, Albrecht S, et al. Eosinophils are a major intravascular location for tissue factor storage and exposure. Blood 2007; 109:995–1002. Cugno M1, Marzano AV2, Lorini M3, Carbonelli V3, Tedeschi A4. Enhanced tissue factor expression by blood eosinophils from patients with hypereosinophilia: a possible link with thrombosis. PLoS One 2014; 9:e111862. Maleki D, Sayyah A, Rahimi-Rad MH, Gholami N. Kimura’s disease with eosinophilic panniculitis – treated with cyclosporine: a case report. Allergy Asthma Clin Immunol 2010; 6:5. Hongcharu W, Baldassano M, Taylor CR. Kimura’s disease with oral ulcers: response to pentoxifylline. J Am Acad Dermatol 2000; 43 (5 pt 2):905–907. Connelly A, Powell HR, Chan YF, Fuller D, Taylor RG. Vincristine treatment of nephritic syndrome complicated by Kimura disease. Pediatr Nephrol 2005; 20:516–518. Hernandez-Bautista V, Yamazaki-Nakashimada MA, Vazquez-Garcı´a R, Stamatelos-Albarra´n D, Carrasco-Daza D, Rodrı´guez-Lozano AL. Treatment of Kimura disease with intravenous immunoglobulin. Pediatrics 2011; 128:e1633–e1635.
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Pulmonary embolism as the initial clinical presentation of Kimura disease: case report and literature review Xu Yea, Ying Fenga and Suxia Linb Pulmonary embolism is clinically critical in that if misdiagnosed or delayed, the mortality is very high. The recognition of its risk factor or underlying disease is important for prevention of recurrence. Kimura disease is a rare, chronic inflammatory disease, which is seldom associated with thrombosis. We reported a 47-year-old male case presenting with pleural pain and dyspnoea and was found to have pulmonary embolism. After successful management of pulmonary embolism, he was noticed to have eosinophilia and lymphadenopathy. Pathologic examination of a resected lymph node has confirmed the diagnosis of Kimura disease. The patient was treated with corticosteroid and cyclosporine A, with a significant improvement of the symptoms and signs of Kimura disease and no recurrence of any thromboembolism. Associated literatures were reviewed to explore the pathogenesis underlying the thrombotic event in Kimura disease cases. It is suggested that hypereosinophilia may play a key role in
Introduction Acute pulmonary embolism is a critical condition requiring emergent treatment. It is defined by obstructive thrombosis of the pulmonary artery. The clinical presentation of acute pulmonary embolism ranges from mild dyspnoea to cardiac arrest, the wide variations in its clinical presentations rendering it easily misdiagnosed. Misdiagnosis of pulmonary embolism and the resulting delay in pertinent management can lead to fatal outcome. The annual incidence of pulmonary embolism is approximately three to six cases per 10 000 persons in the general population. The short-term mortality of pulmonary embolism ranges from less than 1% in haemodynamically stable patients with nonmassive pulmonary embolism and no signs of right heart overload to over 90% in patients who present with cardiorespiratory arrest [1]. Risk factors for thrombus formation include perioperative state, prolonged bed rest, antiphospholipid syndrome, malignancy, hereditary thrombophilia and some chronic inflammatory diseases [2]. Recognizing and successful management of the risk factor for diagnosed pulmonary embolism is of clinical significance to prevent it from recurring. Kimura disease is a chronic inflammatory disorder with angiolymphatic proliferation of unknown cause, usually affecting young men of Asian race. Patients with Kimura disease typically present with nontender subcutaneous swelling in head and neck region predominantly in preauricular and submandibular area. It may be associated with local or systemic lymphadenopathy, marked 0957-5235 Copyright ß 2015 Wolters Kluwer Health, Inc. All rights reserved.
thrombosis formation. The control of hypereosinophilia may contribute to the prevention of thrombosis and its recurrence in patients with Kimura disease. Blood Coagul Fibrinolysis 26:414–418 Copyright ß 2015 Wolters Kluwer Health, Inc. All rights reserved.
Blood Coagulation and Fibrinolysis 2015, 26:414–418 Keywords: hypereosinophilia, Kimura disease, pulmonary embolism a
Department of Hematology, Second Affiliated Hospital of Guangzhou Medical University and bDepartment of Pathology, Cancer Center, Sun-Yat-Sen University, Guangzhou, China Correspondence to Xu Ye, MD, Second Affiliated Hospital of Guangzhou Medical University, No. 250 Changgangdonglu, Guangzhou, 510260, China E-mail: [email protected] Received 15 January 2014 Revised 19 December 2014 Accepted 5 January 2015
peripheral eosinophilia and an elevated IgE level [3]. Kimura disease is usually seen in young adults, with most patients being aged between 20 and 40 years; men are affected more commonly than women, with a 3 : 1 ratio. Main systemic manifestation of the Kimura disease is renal involvement including notably proteinuria and nephrotic syndrome [4]. Thrombosis complications were rarely reported in patients with Kimura disease. We herein report a case presented as pulmonary embolism and was later on found to have the rare underlying cause of Kimura disease. As we know, this is the first report of pulmonary embolism developed in patients with Kimura disease.
Case presentation A 47-year-old man was admitted complaining of dizziness for 5 days and a feeling of tingling pain in his right hypochondria area and dyspnoea on exertion for 3 days. His pain could be relieved by oral paracetamol and exacerbated when lying down on the back. The patient used to be fairly healthy, but had complained of overall pruritus for 2 years. He used to see dermatologists constantly and was prescribed oral antihistamines to relieve his itching. When he began to feel pain and dyspnoea, he came to the outpatient department and had a blood routine test that showed increased white blood cell count of 18.98 109/l and decreased platelet count of about 33 109/l. The leukocyte differential showed prominent eosinophilia with an absolute eosinophil count of 9.52 109/l and eosinophil percentile of 50.21%. His haemoglobin level was normal. More than normal (50/ml) red blood cells were DOI:10.1097/MBC.0000000000000278
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Pulmonary embolism as the presentation of Kimura disease Ye et al. 415
present in his urine. But no proteinuria was present. His chest radiograph and abdominal ultrasonography were normal. With prominent eosinophilia and suspected diagnosis of haematologic disorders, he was referred to the Department of Hematology and was admitted for further examination and treatment. On admission, he was detected to have a fever with temperature of 38.58C, but his other vital signs were all within normal range. He also presented with multiple, prominent, nontender bilateral cervical, subaxillary and inguinal lymphadenopathy. Auscultation revealed decreased breathing sound on his right lower lung field. Sporadic dark red rashes were also noted on his lower extremities. Repeat blood routine test showed that his white blood cell count was 14.04 109/l with an absolute eosinophil count of 3.66 109/l and eosinophil percentile of 26.11% and normal platelet count. As his oxygen saturation dropped to 95%, a chest computed tomographic (CT) angiogram (CTA) was performed and confirmed pulmonary thrombosis with thrombus formation in the right main pulmonary artery and its branches. Patchy consolidation shadow was seen in the posterior basal segment of the right lower lobe of the lungs. A small amount of right pleural effusion was also noted. Anticoagulation therapy with 0.6 ml (6150AxaIU) subcutaneous injection of FraxiParine (GSK, China) per 12 h and successive oral warfarin together with intravenous antibiotics was administered. One week later, all the above symptoms and signs were relieved. Repeat chest CTA showed contracted consolidation shadow in the right lower lobe without signs of pleural effusion. On the 11th day, the patient was discharged without any complaint. He was on oral warfarin maintenance for 6 months with an international normalized ratio (INR) within 2.0–3.0. Although the patient did not complain of further respiratory symptoms, repeat chest CTA 3 months later showed smaller thrombus remaining in the right main and inferior pulmonary arteries but more in their distal branches and new thrombus formation was noted in the left main pulmonary and inferior pulmonary arteries together with a small amount of flaky fuzzy shadow in the left lingular lobe.
To screen for thrombophilia, the patient’s plasma protein C (PC), antithrombin (AT), free protein S (FPS) and vWF:Ag levels were measured using immunoturbidimetry method, and his factor VIII and factor XII activities were measured by coagulation method and the results were all within normal range except that his vWF:Ag level was 188%, which was relatively higher than normal (reference: 50160%). The lupus anticoagulant was detected with the dilute Russell viper venom time (DRVVT) method and the antiphospholipid antibodies were detected using the ELISA method. Both of them were negative. Detection for factor V Leiden mutation and thrombin G20210A mutation were performed with PCR restriction fragment length polymorphism method and rendered negative results. On follow-up, the patient gradually complained of itching feeling all over the body without rash. The feeling of itching could not be fully alleviated with antihistamines and his blood routine test result still showed significantly increased eosinophil count. On physical examination, he was noticed to have progressive multiple lymphadenopathies in cervical, subaxillary and inguinal regions. The biggest lymph node in his subaxillary region had a diameter of more than 5 cm. Lymph node biopsy was suggested and was at first refused by the patient. After repeat persuasion and afflicted by the enlarged lymph nodes and pruritus, the patient consented to receive right subaxillary lymph node biopsy 1 month later. The pathologic changes (Fig. 1) of the resected lymph node demonstrated hyperplastic lymphoid follicles with a patchy expansion of germinal centre and marked eosinophil infiltration within the inter-follicular area. Eosinophilic abscess formation and remarkable small blood vessel hyperplasia could be seen in some areas. Immunohistochemistry showed that the tissue was positive for CD20 in the follicles, Bcl-6 in the germinal centre, CD3 in the inter-follicular region, CD68 for the tissue, S100 sporadically and CD34 in blood vessels. Taking all the clinical features together, Kimura disease was diagnosed. At that time, the patient refused further treatment for the
Fig. 1
(a)
(b)
(c)
Pathologic histology of the patient’s resected lymph node. The pathologic changes of the resected lymph node demonstrated hyperplastic lymphoid follicles with patchy expansion of germinal centres and marked eosinophil infiltration within inter-follicular area (a). Eosinophil abscess formation (b) and remarkable small blood vessel hyperplasia (c) could be seen in some areas.
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
416 Blood Coagulation and Fibrinolysis 2015, Vol 26 No 4
Kimura disease. On further follow-up, his symptom of pruritus became worse and the lymphadenopathy progressed. Seven months after the onset, we referred his lymph node biopsy slides to another medical centre for pathologic diagnosis and the diagnosis of Kimura disease was suggested once again. Then, the patient was administered 0.5 mg/kg body weight oral prednisone daily. With corticosteroid treatment, his pruritus was gradually relieved, enlarged lymph nodes shrank partially together with improved eosinophilia. One week later, his white blood cell differential came back to normal. Prednisone was tapered. Repeat chest CTA performed 1 year after the onset showed normal pulmonary artery filling. But when prednisone was tapered to 10 mg per day, his pruritus recurred and eosinophilia developed again. We gave him 50 mg/day of thalidomide and his eosinophil count gradually came back to normal again. Two months later, he could not stand the constipation side effect of thalidomide and the dosage of thalidomide was tapered to 25 mg/day. But his eosinophilia and pruritus was gradually aggravated. He refused any treatment at that time. Two years after the onset, he came back with worsened pruritus and lymphadenopathy. Eosinophilia also exacerbated. His serum total IgE level was measured to be as high as 1081.34 IU/ml (reference: 050 IU/ml). He was then administered 50100 mg/day of cyclosporine A, which was tapered off 6 months later together with 5 mg/day of prednisone. With this treatment, his pruritus disappeared and lymphadenopathy was alleviated significantly. It is more than 3 years after the onset of the disease that the patient is still taking 5 mg/day of prednisone for maintenance and his eosinophil count remains normal without any symptoms of pruritus and any signs of thrombus formation.
Discussion Kimura disease was first described by Kim as a kind of eosinophilic hyperplastic lymphogranuloma in the Chinese Journal of Surgery in 1937 and was later systemically characterized by Kimura and Ishikawa in 1948 and thus got its name. It is a rare chronic inflammatory disease involving subcutaneous tissues presenting with painless, slowly enlarging soft tissue mass frequently involving the major salivary gland and lymph nodes of head and neck. Systemic symptoms such as fever, night sweats and weight loss are uncommon. Patients’ blood tests typically show peripheral blood eosinophilia and elevated serum IgE level. It mainly affects patients of Asian descent in their second, third and fourth decades of life with a male predilection (87%) [4]. Clinically, patients with Kimura disease usually present with firm, painless, single or multiple subcutaneous lesions in the head and neck, especially in the parotid and submandibular regions. Associated lymphadenopathy can be seen in 42100% of the cases. Other less common sites of involvement reported include the
preauricular area, epicranium, paranasal sinuses, orbits (including eyelids, conjunctiva and lacrimal glands), epiglottis, tympanic membrane and parapharyngeal space [5]. Rarely, the disease can involve nonhead and neck sites such as the axilla, groin, popliteal region, back of the trunk and forearm. A single case of Kimura disease with bone involvement has also been reported [6]. Two Chinese authors reported two cases of Kimura disease, respectively, involving the skull and right clavicle causing osteolytic lesions mimicking bone tumour [7,8]. Because of its variable, nonspecific clinical presentations, slow progression course and rarity, the first diagnosis of a Kimura disease in a patient may usually be neglected or misdiagnosed or sometimes be covered by its complications. The patient described here is atypical in that he did not present with any subcutaneous nodules or mass but only pruritus that may also be seen in a variety of other allergic diseases or parasitic diseases, although pruritus can be seen in 16.7 25% of cases with Kimura disease [9,10]. Even though he was noticed to have eosinophilia, the existence of a rare disease such as Kimura disease had not been included in the differential diagnosis by the haematologist he was first referred to. He might have had lymphadenopathy for some time, but neither the dermatologists nor the patient himself noticed it. In the present case, it was the complication of pulmonary embolism made the doctor notice his eosinophilia and then the multiple lymphadenopathies. The pathologic analysis of the lymph node biopsy finally confirmed the diagnosis of Kimura disease. For Kimura disease, the most reported complication has been nephrotic syndrome, whereas thrombotic complication was rarely reported. In 1986, Naito et al. [11] had reported a 45year-old Japanese man with marked eosinophilia, congestive heart failure and murmurs of aortic and mitral regurgitation. The histologic examination of his subcutaneous cervical mass biopsy revealed features of Kimura disease. Left ventriculography was suggestive of an extensive ventricular mural thrombus superimposed on a thickened endocardium. The ventricular thrombus was supposed to be the result of endomyocardial fibrosis and eosinophilia. Danis et al. [4] reported a 42-year-old Turkish man with Kimura disease and membranous nephrotic syndrome had bilaterally temporal artery and renal vein thrombosis. Liu et al. [12] reported a 40-year-old Chinese man who developed extensive thrombosis in the superior mesenteric vein, portal vein and splenic vein causing infarction of small bowel and spleen together with right upper extremity and left lower extremity deep venous thrombosis several days following transoceanic air flight travel. Five months later, Kimura disease was confirmed through lymph node biopsy after he developed a pruritic papular skin rash and right epitrochlear lymphadenopathy. Further blood analysis excluded other causes of hypercoagulability. Eguia et al. [13] reported a 34-year-old Chinese man with necrosis of several fingertips, the lateral side of his left
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Pulmonary embolism as the presentation of Kimura disease Ye et al. 417
foot and paresthesia of both legs, which they thought may be due to dermal vessel thrombosis and endothelial damage, although they did not show it in histologic analysis of the cutaneous biopsy. The patient also presented with significant eosinophilia and was later diagnosed Kimura disease by lymph node biopsy. Recently, Lee et al. [14] reported a case of Kimura disease complicated with bowel infarction and multiple arterial thrombi in the upper and lower extremities. Reports on cases with thrombotic events in a rare disease such as Kimura disease suggested that Kimura disease might be a disease with thrombophilic pathogenesis. Up to now, the cause and pathogenesis of Kimura disease is still unknown. Impairment or interference with immune regulation, atopic reaction to a persistent antigenic stimulus by arthropod bites, virus, trauma, neoplasm and even Candida antigenemia have been postulated to be causative [15]. Studies have demonstrated that elevated mRNA levels of interleukin (IL)4, IL-5 and IL-13 were found in patients with Kimura disease. Changes in the expression levels of these cytokines correlated with the disease activity [16]. Ohta et al. [17] found that the concentration of cytotoxic eosinophilic cationic protein in sera from patients with Kimura disease was significantly higher than normal controls and was associated with the disease activity suggesting that eosinophils play an important role in the pathogenesis of Kimura disease. They further found that the population of Th2 cells in Kimura disease was significantly increased and the number of Th2 cells was correlated with the titres of IgE [18]. Yamazaki et al. [19] found that Th2 cytokines such as IL-3, IL-4, IL-5, IL-13 or granulocyte-macrophage colony-stimulating factor (GM-CSF) produced by peripheral mononuclear cells in most of the Kimura disease cases were higher than those of controls and the ratio of Th2 subpopulation T cells was also increased. Among the cytokines, IL-13 and IL-4 are central T helper 2 (Th2) cytokines in the immune system and are potent activators of inflammatory responses and fibrosis during Th2 inflammation. IL-4 is the major factor regulating IgE production by B cells and is required for optimal Th2 differentiation and IL-13 is required for IL-4 function. IL-5 is essential for the maturation of eosinophils in bone marrow and for their release into the blood. It is also a major cytokine for mature eosinophil activation and accelerating differentiation, proliferation and chemotaxis of eosinophils. Taken together, the results from the above studies have demonstrated that increased Th2 cells may play important roles in the pathogenesis of Kimura disease through the increased syntheses of key Th2-type cytokines IL-4 and IL-5, which consequently upregulate eosinophil production, eosinophilic infiltration and IgE synthesis. Increase in eosinophil amount, that is, hypereosinophilia has been associated with thrombosis. An early study including 50 cases with idiopathic hypereosinophilia
syndrome (HES) suggested that eosinophil infiltration of endothelial cells in the endocardium and of the microvasculature had initiated cardiac thrombosis in severe cases [20]. Ames et al. [21] had reported three patients with Churg–Strauss syndrome (CSS) who had experienced thrombosis formation in the left subclavian vein, the left leg and the left middle cerebral artery, respectively. In a series summarizing 15 cases with HES, thrombotic and embolic complications developed in 10 patients, despite treatment with anticoagulants and inhibitors of platelet function, and were the cause of death in three [22]. Case reports of hypereosinophilia associated with thrombosis of the pulmonary artery, femoral vein, hepatic vein (Buddi–Chiari syndrome), coronary artery, renal vein and splenic vein have been published [23,24]. The mechanism behind the increased risk of thrombosis in patients with hypereosinophilia is still not clear. Studies exploring the effects of eosinophils and eosinophil-derived products on endothelial cells and on coagulation pathways have pointed towards a combination of eosinophil-mediated cytotoxicity towards endothelial cells, and a pro-coagulant state favoured by hypereosinophilia. By damaging endothelial cells, eosinophils expose the underlying tissue, naturally triggering the extrinsic coagulation pathway. Moreover, it has been shown that two of the eosinophil cationic proteins, the major basic protein (MBP) and eosinophil peroxidase, are able to activate platelets by evoking platelet secretion of 5-hydroxytryptamine, platelet alpha granule and lysosome components in vitro. Sera from hypereosinophilic patients containing elevated levels of MBP inhibited function of thrombomodulin as a cofactor for the thrombin-catalysed activation of PC anticoagulant system [25]. Eosinophil peroxidase has been shown to generate oxidants, which were potent inducers of tissue factor (TF). Moreover, researchers have found that patients with hypereosinophilic disorders expressed a higher level of TF. Eosinophils and their precursor cells stored TF within their granules, which, under activation, resulted in rapid TF exposure on the eosinophil cell membrane and increased TF transcript levels and the triggering of external coagulation pathway [26,27]. All these contribute to the prothrombotic manifestations seen in patients with hypereosinophilic conditions. In the present case, the pulmonary embolism occurred when the patient’s eosinophil count reached its peak and did not recur after eosinophilia was controlled. Without other detectable prothrombotic factors, we presume that hypereosinophilia as a result of Kimura disease was the main prothrombotic factor in this patient. Treatment for Kimura disease includes surgical resection, local irradiation, laser fulguration, cytotoxic therapy and regional or systemic steroid therapy. Complete surgical resection has been considered first-line treatment for Kimura disease with a recurrence rate up to 25%. In patients complicated with nephrotic syndrome,
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
418 Blood Coagulation and Fibrinolysis 2015, Vol 26 No 4
systemic corticosteroids are recommended. But tapering of steroids always resulted in disease recur. Case reported on successful treatment of Kimura disease with cyclosporine, pentoxifylline, vincristine, mycophenolate mofetil and intravenous immunoglobulin have been published [28–31]. Our patient received local lymph node resection only for the purpose of pathological diagnosis. Owing to the multiple lymph node involvement in this case, complete surgical resection is impossible. We prescribed oral corticosteroid with initial good response, but recurrence occurred after steroid tapering. Then, cyclosporine was administered resulting in good response and was later on tapered off. With maintenance low dosage of prednisone, he has been in good condition for more than 2 years now. In conclusion, we have reported a case with pulmonary embolism with underlying Kimura disease, which was successfully treated with anticoagulant therapy. His Kimura disease was later on diagnosed by pathologic examination of his resected lymph node and was successfully controlled with corticosteroid combined with cyclosporine A. We also reviewed associated literature to try to explore the pathogenesis mechanism leading to the severe thrombotic event in a Kimura disease patient without any other thrombophilia factors. It is implicated that prominent hypereosinophilia in cases with Kimura disease may lead to a tendency towards thrombosis formation so that the control of hypereosinophilia may contribute to the prevention of thrombosis and its recurrence in patients with Kimura disease.
5 6 7 8 9 10
11
12 13
14
15
16
17
18
19
20
Acknowledgements The authors would like to thank Dr Wu Bingyi (Department of Hematology, Zhujiang Hospital, Guangzhou, China) for his help in performing lymph node biopsy on the patient and Dr Ye Suzhen (Department of Medical Imaging, Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China) for the preparation of the patient’s imaging materials. Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.
21
22
23 24
25
26
Conflicts of interest
There are no conflicts of interest.
27
References 1
2
3
4
Rohacek M, Szucs-Farkas Z, Pfortmu¨ller CA, Zimmermann H, Exadaktylos A. Acute cardiac disorder or pneumonia and concomitant presence of pulmonary embolism. PLoS One 2012; 7:e47418. Ben Salah R, Frikha F, Kaddour N, Saidi N, Snoussi M, Marzouk S, et al. Risk factor for deep venous thrombosis in internal medicine: a retrospective study of 318 cases. Ann Cardiol Angeiol (Paris) 2014; 63:11–16. Armstrong WB, Allison G, Pena F, Kim JK. Kimura’s disease: two case reports and a literature review. Ann Otol Rhinol Laryngol 1998; 107:1066–1071. Danis R, Ozmen S, Akin D, Ozekinci S, Altintas A, Cil T, et al. Thrombosis of temporal artery and renal vein in Kimura-disease-related nephrotic syndrome. J Thromb Thrombolysis 2009; 27:115–118.
28
29 30
31
Park SW, Kim HJ, Sung KJ, Lee JH, Park IS. Kimura disease: CT and MR imaging findings. AJNR Am J Neuroradiol 2012; 33:784–788. Varshney MK, Kumar A, Khan SA, Yadav CS. Kimura disease of extremity: unusual manifestation in a long bone. Joint Bone Spine 2008; 75:492–494. Wang J, Wang Y. A case of skull Kimura’s disease. Chinese J Cardiol 2009; 43:1333–1334. Qiu Q, Xiang Y, Jiang J. A case of Kimura’s disease misdiagnosed with malignant bone tumor. Chin J Bone Tumor Bone Dis 2010; 9:373–374. Yu F, Teng H, Wang Z. The clinical features and management of eosinophilic lymphoid granuloma. J Clin Stomatol 2002; 18:54–55. Wang DY, Mao JH, Zhang Y, Gu WZ, Zhao SA, Chen YF, Liu AM. Kimura disease: a case report and review of the Chinese literature. Nephron Clin Pract 2009; 111:c55–c61. Naito H, Nakatsuka M, Yuki K, Yamada H. Giant left ventricular thrombi in the hypereosinophilic syndrome: report of two cases. J Cardiogr 1986; 16:475–488. Liu H, Al-Quran SZ, Lottenberg R. Thrombotic storm in Kimura disease. J Thromb Thrombolysis 2010; 29:354–357. Eguia B, Bachmeyer C, Charlotte F, Cabannes-Hamy A, Loustau V, Senet P, et al. Kimura disease with necrosis of the limbs and mononeuritis multiplex. Clin Exp Dermatol 2011; 36:329–331. Lee J, Hong YS. Kimura disease complicated with bowel infarction and multiple arterial thromboses in the extremities. J Clin Rheumatol 2014; 20:38–41. Fouda MA, Gheith O, Refaie A, El-Saeed M, Bakr A, Wafa E, et al. Kimura disease: a case report and review of the literature with a new management protocol. Int J Nephrol 2011; 2010:673908. Katagiri K, Itami S, Hatano Y, Yamaguchi T, Takayasu S. In vivo expression of IL-4, IL-5, IL-13 and IFN-gamma mRNAs in peripheral blood mononuclear cells and effect of cyclosporin A in a patient with Kimura’s disease. Br J Dermatol 1997; 137:972–977. Ohta N, Okazaki S, Fukase S, Akatsuka N, Aoyagi M, Yamakawa M. Serum concentrations of eosinophil cationic protein and eosinophils of patients with Kimura’s disease. Allergol Int 2007; 56:45–49. Ohta N, Fukase S, Suzuki Y, Ito T, Yoshitake H, Aoyagi M. Increase of Th2 and Tc1 cells in patients with Kimura’s disease. Auris Nasus Larynx 2011; 38:77–82. Yamazaki K, Kawashima H, Sato S, Tsunoda H, Yoshimura Y, Higuchi M, et al. Increased CD45RO(þ) CD62L(þ) CD4(þ) T-cell subpopulation responsible for Th2 response in Kimura’s disease. Hum Immunol 2013; 74:1097–1102. Fauci AS, Harley JB, Roberts WC, Ferrans VJ, Gralnick HR, Bjornson BH. NIH conference. The idiopathic hypereosinophilic syndrome. Clinical, pathophysiologic, and therapeutic considerations. Ann Intern Med 1982; 97:78–92. Ames PR, Roes L, Lupoli S, Pickering M, Brancaccio V, Khamashta MA, Hughes GR. Thrombosis in Churg-Strauss syndrome. Beyond vasculitis Br J Rheumatol 1996; 35:1181–1183. Spry CJ, Davies J, Tai PC, Olsen EG, Oakley CM, Goodwin JF. Clinical features of fifteen patients with the hypereosinophilic syndrome. Q J Med 1983; 52:1–22. Ko JH, Lin JW, Hui RC. Acute pulmonary embolism in a patient with hypereosinophilia and psoriasis. Chang Gung Med J 2011; 34 (Suppl 6):17–23. Jones PD, Moll S, Dellon ES. Pulmonary embolism in a patient with eosinophilic esophagitis: causal or coincidental? Case Rep Gastroenterol 2013; 7:82–88. Mukai HY, Ninomiya H, Ohtani K, Nagasawa T, Abe T. Major basic protein binding to thrombomodulin potentially contributes to the thrombosis in patients with eosinophilia. Br J Haematol 1995; 90:892–899. Moosbauer C, Morgenstern E, Cuvelier SL, Manukyan D, Bidzhekov K, Albrecht S, et al. Eosinophils are a major intravascular location for tissue factor storage and exposure. Blood 2007; 109:995–1002. Cugno M1, Marzano AV2, Lorini M3, Carbonelli V3, Tedeschi A4. Enhanced tissue factor expression by blood eosinophils from patients with hypereosinophilia: a possible link with thrombosis. PLoS One 2014; 9:e111862. Maleki D, Sayyah A, Rahimi-Rad MH, Gholami N. Kimura’s disease with eosinophilic panniculitis – treated with cyclosporine: a case report. Allergy Asthma Clin Immunol 2010; 6:5. Hongcharu W, Baldassano M, Taylor CR. Kimura’s disease with oral ulcers: response to pentoxifylline. J Am Acad Dermatol 2000; 43 (5 pt 2):905–907. Connelly A, Powell HR, Chan YF, Fuller D, Taylor RG. Vincristine treatment of nephritic syndrome complicated by Kimura disease. Pediatr Nephrol 2005; 20:516–518. Hernandez-Bautista V, Yamazaki-Nakashimada MA, Vazquez-Garcı´a R, Stamatelos-Albarra´n D, Carrasco-Daza D, Rodrı´guez-Lozano AL. Treatment of Kimura disease with intravenous immunoglobulin. Pediatrics 2011; 128:e1633–e1635.
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
