|Year : 2014 | Volume
| Issue : 1 | Page : 52-56
Unusual presentation of kimura's disease
Amol W Diwan, Gauri P Godbole, Himanshu S Pophale, Suhas R Kulkarni
Department of Pulmonary Medicine, Smt. Kashibai Navale Medical College and General Hospital, Narhe, Pune, Maharashtra, India
|Date of Web Publication||7-Mar-2014|
Amol W Diwan
Department of Pulmonary Medicine, Smt. Kashibai Navale Medical College and General Hospital, Off Pune-Banglore Highway, Narhe, Pune - 411 041, Maharashtra
Kimura's disease is a rare form of chronic eosinophilic inflammatory disorder with associated lymphadenopathy in head and neck region and serous cavity effusions and marked predilection for the head and neck with a tendency to present as a discrete, enlarging mass. Although many cases of Kimura's disease with head and neck lymphadenopathy and nephrotic syndrome have been described in the literature, only two cases of Kimura's disease presenting with pleural effusion have been reported recently. There are no reports of Kimura's disease with ascites. We report the case of a 38-year-old nondiabetic, normotensive man who had undergone inguinal node biopsy consistent with Kimura's disease, 8 months before he presented to us. On admission, he had right moderate pleural effusion, but no ascites or any lymph nodal involvement. He developed recurrent pleural effusion and ascites in the ward. Initially he showed good remission with systemic steroids, but later on was refractory to further necessary treatment. He also rapidly developed signs of nephrotic syndrome. In spite of vigorous treatment, patient died of severe hypovolemia, hypoproteinemia, and nephropathy.
ملخص البحث :
تشرح هذه الحالة عرضاً غير عادي لمريض يعاني من مرض كيمورا والذي ادخل المستشفى بعد تشخيصه وكان يعاني من تجمع سوائل في الرئة واستسقاء في البطن والمتلازمة الكلوية. ولم تؤدي جميع وسائل العلاج إلى نتيجة ايجابية. يعتبر مرضى كيمورا نوعية نادرة من التهابات اليوزيني المزمن مصحوبا بتضخم في الغدد الليمفاوية في منطقة الرأس والرقبة وتجمع سائل في الرئة. وقد يظهر بشكل خاص كورم في منطقة العنق والرأس وربما يؤدي هذا المرض إلى مضاعفات كثيرة في عدة أعضاء من الجسم.
Keywords: Ascites, angiolymphoid hyperplasia with eosinophilia, Kimura′s disease, pleural effusion, nephrotic syndrome
|How to cite this article:|
Diwan AW, Godbole GP, Pophale HS, Kulkarni SR. Unusual presentation of kimura's disease. Saudi J Med Med Sci 2014;2:52-6
| Introduction|| |
Kimura's disease, also known as epithelioid hemangioma, atypical pyogenic granuloma, and cutaneous eosinophilic lymphofolliculosis, was first reported by Chinese authors Kimm and Szeto in 1937.  The definitive description was published by Kimura et al.  in Japan in 1948. It is usually seen in young adults, with most patients aged between 20 and 40 years; men are affected more commonly than women. ,
Kimura's disease is a chronic eosinophilic inflammatory disorder which presents with a slowly enlarging soft tissue mass and regional lymphadenopathy most commonly seen in the head and neck region. Salivary gland involvement has also been reported.  Although Kimura's disease mainly affects the head and neck, involvement of the extremities and inguinal lymph nodes has been reported. , Peripheral eosinophilia is common , and serum IgE levels are often elevated. , Histologically, it is manifested by an abnormal proliferation of lymphoid follicles and vascular endothelium, and eosinophilic infiltrates involving the interfollicular areas and sinusoidal areas.  An allergic reaction (parasite, virus, fungi, or toxin), trauma, and abnormal autoimmune reactions have all been postulated in the pathogenesis with unclear role. ,,, Various systemic manifestations are reported, which include nephrotic syndrome, bronchial asthma,  and gastrointestinal involvement. ,, Renal involvement with proteinuria and nephrotic syndrome ,,,,, is the only systemic manifestation which has significant impact on progression of disease and its further prognosis.  Renal impairment is probably due to immune complex-mediated damage or to Th2-dominant immune response disorders. 
For diagnosis of Kimura's disease, fine needle aspiration cytology (FNAC) is a safe procedure, but has only limited value. , Pathologic diagnosis is frequently based on the excision biopsy of the involved node.  Tuberculosis, lymphoma, angiolymphoid hyperplasia with eosinophilia (ALHE), angioimmunoblastic lymphadenopathy, Castelman's disease, Mikulicz's disease, and pyogenic granuloma ,,,, have been reported in the differential diagnosis.
The optimal treatment for Kimura's disease is controversial till today. It seldom resolves spontaneously and malignant transformation has not been reported to date. , Treatment of choice for Kimura's disease includes surgical excision of cutaneous lesions and steroid therapy. In cases refractory to surgical and medical therapy, radiation may be considered. ,,, Recently, combined treatments with steroids and cyclosporine have been reported. ,,,,
Only two cases of Kimura's disease presenting with pleural effusion have been reported recently, , but there are no reports of Kimura's disease with ascites. We report this case to increase awareness that Kimura's disease can present as massive exudative serous effusions and nephrotic syndrome, both unresponsive to steroids and cyclosporine, which can result in severe hypoproteinemia and hypovolemia leading to death of the patient.
| Case Report|| |
A 38-year-old nondiabetic, normotensive male presented with complaints of dry, irritating cough, right-sided chest pain, weight loss of more than 10 kg, and low-grade fever since 6 months, right moderate effusion on chest radiography [Figure 1], and normal abdominal ultrasound at the time of admission. He neither had lymph node involvement in the neck or thorax nor had any cutaneous manifestations any time during the course of the illness [Figure 2]. Detailed history revealed that he had a slowly enlarging mass in the right inguinal region 8 months ago, which was treated with antibiotics following which it subsided but re-appeared within 10 days of stopping the antibiotics. FNAC of inguinal lymph node revealed inflammatory cells, and differential count revealed marked eosinophilia. As patient was not having any local infection or any other obvious etiology, a diagnosis was not reached. Hence, excision biopsy was performed which was consistent with Kimura's disease [Figure 3]. He was not put on any treatment for the same after this diagnosis.
|Figure 2: Chest X-ray 2. No lymph node involvement in the neck or thorax on chest radiography|
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|Figure 3: Histology slide 1. Initial histological photomicrograph based on which diagnosis of Kimura's disease was made|
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Eight months after this diagnosis, he came to us with negative history of allergy, parasitic infestation, or any significant drug history. Literature review showed many cases reported with cervical lymphadenopathy and salivary gland involvement, but our patient did not have any evidence of cutaneous lesions and there were no accessible lymph nodes or salivary gland involvement. A complete blood count showed an increased absolute eosinophil count (630/mm 3 ). Serum IgE was raised (11,700 IU/ml; with a reference range <250 IU/ml). Tuberculin skin test (Mantoux skin test) showed 24-mm induration. Pleural fluid was exudative with predominance of eosinophils. Pleural fluid Adenosine Deaminaseestimation showed values repeatedly less than 10 IU. Initial pleural fluid analysis reports were negative for tuberculous or malignant effusion. Thoracocentesis was done many times, but he had recurrent pleural collection. Bronchoscopy showed collapsed right lower lobe with plenty of secretions which did not yield any significant finding on microbiological and pathological examination. Computed tomography of the chest did not reveal any significant clues except effusion and underlying collapsed right lung [Figure 4] and [Figure 5].
|Figure 4: CT image 1. No lymph node involvement in the neck or thorax on computerized tomography|
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|Figure 5: CT image 2. Right moderate effusion and underlying collapsed right lung on computerized tomography|
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To rule out pleural malignancy, thoracoscopy was done and it showed few nodular deposits on parietal pleura which were taken for histopathologic examination. Biopsy of the pleural nodules showed sheets and clusters of mesothelial cells and dispersed spindle cells and was negative for granulomatous inflammation or malignancy [Figure 6].
|Figure 6: Histology slide 2. Biopsy of pleural nodule showing sheet and clusters of mesothelial cells and dispersed spindle cells. No evidence of granulomatous inflammation or malignancy|
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Right intercostal drain insertion was done after thoracoscopy, which drained more than a liter of pleural fluid on daily basis. Considering the possibility of tuberculous pleural effusion (strongly positive tuberculin skin test) with Kimura's disease, patient was started empirically on four-drug anti-tuberculous treatment (isoniazide 300 mg, rifampicin 450 mg, pyrazinamide 1500 mg, and ethambutol 1200 mg), along with high-dose prednisolone therapy (1 mg/kg body weight, i.e. 60 mg/day). Initially he showed good remission of the pleural collection and systemic symptoms. But after a week, he started having an increasingly larger pleural collection for which cyclosporine was added at 100 mg/day. Two days after starting cyclosporine, he developed severe hyperkalemia and hypotension. Electrocardiogram showed tall T waves with non-specific ST-T changes. Immediately patient was shifted to intensive care unit, and anti-TB drugs and cyclosporine were withdrawn but prednisolone was continued. Intercostal drainage with underwater seal was continued with significant drainage. Antihyperkalemic treatment did not bring down serum potassium to normal level for several days and he had persistent hyperkalemia.
Subsequently, 3 weeks after admission, a repeat abdominal sonography was done which revealed massive ascites with multiple mesenteric lymphadenopathy. Tuberculosis Polymerase Chain Reaction of ascitic fluid and Antinuclear Antibody test were negative. The massive ascites caused decreased oral intake. As he had persistently high daily pleural fluid output along with ascites and no other cause for recurrent pleural collection, we suspected that the cause for high pleural fluid output was secondary to massive ascites with transdiaphragmatic diffusion of fluid into the pleural cavity. To confirm this, we performed abdominal scintigraphy with 99Technitium which showed evidence of tracer excretion through the intercostal drain, suggestive of transdiaphargmatic flow of the tracer molecule [Figure 7]. His urine analysis and renal parameters were within normal limits (urea 50 mg/dl, serum creatinine 1.44 mg/dl), but he had significant proteinuria (11.46 g/24 h), profound hypoproteinemia (total protein 5 g/dl and albumin 2.6 g/dl), and generalized edema in spite of albumin supplementation, which is suggestive of nephrotic syndrome. But both ascitic and pleural fluids were still persistently exudative. Considering ascites as the cause of recurrent pleural collection, we had planned mesenteric lymph node biopsy and peritoneo-saphenous shunt to relieve the ascites and the secondary pleural collection. Bone scan showed no evidence of skeletal involvement.
Significant proteinuria and third-space fluid loss resulted in generalized edema. Hence, parenteral nutrition (kabiven) was started. He received fresh frozen plasma and Packed Cell Volume for deranged coagulation parameters. Inotropic support was continued for persistent hypotension. Our patient did not respond to steroids or any kind of treatment. General condition of the patient went on deteriorating rapidly and we could not get any time to investigate the abdominal and renal pathology in detail. Inspite of aggressive resuscitative measures and within a short time, patient succumbed to death due to hypoproteinemia, hypotension, and nephropathy.
| Discussion|| |
A comparison of our case with most of the reported cases of Kimura's disease in the literature was made. [Table 1] Most of the cases of Kimura's disease have shown excellent response to steroids ,, and cyclosporine, ,,, but the course of Kimura's disease can be progressive even after treatment, with lesions frequently persisting or recurring despite treatment. ,, In our patient, rapid deterioration of general condition could have been due to advanced abdominal and renal pathology in spite of the steroid treatment. Profound proteinuria can lead to transudative pleural effusion due to low plasma oncotic pressure and high hydrostatic pressure. However, contrary to this explanation, our patient had exudative effusion right from the beginning. The cause for proteinuria and recurrent effusion could be due to rapid progression of disease and renal decompensation. In spite of high protein supplementation and steroid treatment, patient continued to have profound proteinuria which caused generalized edema.
|Table 1: Comparison of our case with other reported cases of Kimura's disease|
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Even if Kimura's disease is considered as a local benign disease, missing the differential can be fatal to the patient due to rapid progression and may even become refractory to steroid and immunosuppressive regimens as in our case.
To summarize, we conclude from our study that Kimura's disease should be one of the differentials in patients with refractory effusions, ascites, and deranged renal parameters. In fact, a high index of suspicion will help diagnose patients before they land up with more advanced or morbid clinical presentations and before they become resistant to steroid treatment. In the scenario of high incidence of tuberculosis in the Indian population and the tremendous increase in HIV infection, sporadic appearance of Kimura's disease may be missed in the differential diagnosis unless the index of suspicion is high.
| Acknowledgments|| |
We acknowledge Dr. Sujit Nilegaonkar, Department of Nuclear Medicine, Smt. Kashibai Navale Hospital, Narhe, Pune for helping us with abdomino-thoracic scintigraphy.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]