A Aneja

A Garcia-Zamalloa

A Kumar

D González-Ballester

F Hua

G Dumas

I Nakamura

JE Kim

K Yoshioka

T Kuo

VN Maturu

Y Yoshida

YJ Jang

Z Boujaoude

SpringerPlus

Nobuhito Naito

Tsutomu Shinohara

Hisanori Machida

Hiroyuki Hino

Keishi Naruse

Fumitaka Ogushi

Crossref

Naito et al. SpringerPlus  (2015) 4:693 DOI 10.1186/s40064-015-1500-yCASE STUDYKikuchi-Fujimoto disease associated with community acquired pneumonia showing intrathoratic lymphadenopathy without cervical lesionsNobuhito Naito1, Tsutomu Shinohara2*, Hisanori Machida1, Hiroyuki Hino3, Keishi Naruse4  and Fumitaka Ogushi1Abstract Introduction: Kikuchi-Fujimoto disease (KFD), or histiocytic necrotizing lymphadenitis, is a rare entity of unknown etiology in young adults that is typically characterized by cervical lymphadenopathy and persistent fever. The patho-genesis of KFD has been suggested to be an abnormal immune response, and infections or autoimmune diseases are considered to be involved in KFD. However, KFD associated with community acquired pneumonia (CAP) has not been reported.Case description: A 35-year-old male was admitted due to high fever, diffuse air-space consolidation in the right lung with ipsilateral pleural effusion and massive mediastinal and hilar lymphadenopathy without cervical lesions. On clinical suspicion of malignant lymphoma complicated with pneumonia, we performed a video-assisted thoraco-scopic lymph node biopsy, and the diagnosis of KFD was established. Complete cure of the intrathoratic lesions was observed by administration of β-lactam antibiotics alone without steroid therapy.Discussion and evaluation: Previous large case series have identified no pathogenic relationship between KFD and pneumonia. The hilar adenopathy could have caused airway compression leading to pneumonia.Conclusions: KFD should be considered in the differential diagnosis of massive mediastinal and hilar lymphad-enopathy, even when there are no superficial lesions. In addition, we need to bear in mind that unexpected disorders occasionally coexist with common diseases.Keywords: Kikuchi-Fujimoto disease, Community acquired pneumonia, Intrathoratic lymphadenopathy© 2015 Naito et al. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.BackgroundKikuchi-Fujimoto disease (KFD) is a clinicopathologi-cal entity typically characterized by cervical lymphad-enopathy, persistent fever, and histiocytic necrotizing lymphadenitis of unknown etiology in young adults. The histopathologic changes can be classified into three histo-logic types; proliferative, necrotizing, and xanthomatous types (Kuo 1995). The clinical course of KFD is relatively benign and typically self-limiting, although corticosteroid therapy has been used for some patients with compli-cated KFD (Jang et al. 2000; Yoshioka et al. 2010). Gen-erally, KFD localizes in the cervical region, and systemic lymph nodes involvement is unusual (Dumas et al. 2014; Nakamura et  al. 2009). Especially, deep lesions without cervical lymphadenopathy are extremely rare (Yoshida et al. 2011). The pathogenesis of KFD has been suggested to be an abnormal immune response, and infections (e.g., Epstein-Barr virus, parainfluenza virus, human her-pes virus, human immunodeficiency virus, Toxoplasma and Yersinia enterocolitica) or autoimmune diseases (e.g., systemic lupus erythematosus) are considered to Open Access*Correspondence:  shinoharat@kochi2.hosp.go.jp 2 Department of Clinical Investigation, National Hospital Organization National Kochi Hospital, 1-2-25 Asakuranishimachi, Kochi 780-8077, JapanFull list of author information is available at the end of the articlePage 2 of 4Naito et al. SpringerPlus  (2015) 4:693 be involved in KFD (Dumas et al. 2014). However, KFD associated with community acquired pneumonia (CAP) has not been reported.Case descriptionA 35-year-old male with complaints of high fever and malaise for 3  days visited a nearby clinic, where antibi-otic therapy (ceftriaxone 1  g/day) was started based on leukocytosis (10,000/µl) and elevated serum C-reactive protein (CRP) level (7.39 mg/dl). Two days later, he was referred to our hospital for further examination. Physical examination indicated reduced respiratory sounds in the left lung. Hepatosplenomegaly and superficial lymphad-enopathy were not observed. Chest X-ray and enhanced computed tomography (CT) showed diffuse air-space consolidation in the right lung with ipsilateral pleural effusion and massive mediastinal and hilar lymphad-enopathy (Fig. 1a–c). Elevated serum levels of AST (206 U/L), ALT (286 U/L), LDH (446 U/l) and soluble interleu-kin-2 receptor (sIL-2R) (2550 U/ml), but not angiotensin converting enzyme (7 IU/l), were observed. A thoracente-sis revealed neutrophilic effusion with negative cytology. Sputum, blood, and pleural effusion cultures of bacteria using conventional methods were negative, probably due to antibiotic therapy started before collection of the specimens. On clinical suspicion of malignant lymphoma (ML) complicated with pneumonia, we performed a video-assisted thoracoscopic lymph node biopsy while continuing administration of β-lactam antibiotics (tazo-bactam/piperacillin: TAZ/PIPC 13.5 g/day). Histological examinations of the biopsy specimens revealed irregu-lar necrotic areas that consisted of debris and intense karyorrhexis. Prominent histiocytic cells admixed with plasma cells, large lymphocytes and immunoblasts were observed around these areas without neutrophils. Lym-phoma cells were not detected. Immunohistochemical studies showed histiocytic cells were strongly positive for CD68 (Fig.  2a–c). These histological findings were compatible with the necrotizing type of KFD. When the final pathological diagnosis was established, the clini-cal course had already turned favorable. Therefore, we continued administration of TAZ/PIPC alone for a total period of 10  days without steroid therapy. Two weeks after the admission, leukocytosis and serum levels of CRP and LDH were reduced to a normal range. Elevated liver enzymes, observed in 24  % of patients with KFD (Dumas et al. 2014), disappeared. sIL-2R, which was very high for KFD (Nakamura et  al. 2009), also normalized after 1 month. Follow-up chest CT showed no consolida-tion, pleural effusion and lymphadenopathy (Fig.  1d–f). Antibody titers for Epstein-Barr virus using a fluorescent antibody method and the particle agglutination titer for Fig. 1 Chest enhanced CT images (a, d lung parenchyma window; b, c, e, f mediastinal window). a–c Diffuse air-space consolidation in the right lung with ipsilateral pleural effusion and massive mediastinal and hilar lymphadenopathy (arrows) at admission. d–f Disappearance of consolida-tion, pleural effusion and lymphadenopathy after the treatmentPage 3 of 4Naito et al. SpringerPlus  (2015) 4:693 Mycoplasma pneumoniae did not rise during the treat-ment. At 2  years’ follow-up, no evidence of recurrence was detected.DiscussionIn the present case, physical examination and enhanced CT showed no lymphadenopathies except for intratho-ratic lesions. Although several cases of KFD with lym-phadenopathy in atypical location(s) have been reported (González-Ballester et  al. 2010; Aneja et  al. 2014), the presence of cervical lymphadenopathy was a common and distinctive feature of KFD excluding a few cases (Dumas et  al. 2014; Nakamura et  al. 2009). Previously, Yoshida et  al. reported mediastinal lymphadenopathy without cervical adenopathy in middle-aged men diag-nosed with KFD by mediastinal lymph node biopsy (Yoshida et  al. 2011). However, the patient had no res-piratory symptoms and concomitant diseases. On the other side, a few cases of KFD, diagnosed by cervical lymph node biopsy, presented with interstitial pneu-monia (Garcia-Zamalloa et  al. 2010) or cryptogenic organizing pneumonia (COP) (Hua and Zhu 2010), and were successfully treated with oral prednisone (1  mg/kg/day). However, to the best of our knowledge, this manuscript is the first case report of KFD associated with CAP, which is also extremely rare in the location of lymphadenopathy.The complete disappearance of diffuse consolidations by β-lactam antibiotic and parapneumonic effusion with neutrophilic predominance suggested that the etiology of CAP in this case was bacterial infection. In addition, acute illness, high fever, pleural effusion and the unilat-erality of consolidation observed in this case are atypi-cal findings for COP (Hua and Zhu 2010). Although the localization of histiocytic necrotizing lymphadenitis in the regional lymph nodes of the lung was observed, previous large case series have identified no pathogenic relationship between KFD and pneumonia (Dumas et al. 2014; Nakamura et al. 2009). The hilar adenopathy could have caused airway compression leading to pneumonia, but we did not confirm the airway stenosis by broncho-scopic examination.The diagnostic difficulty was differentiating this case from ML. Although 18-fluorodeoxyglucose positron emission/computed tomography (FDG PET/CT) tends to be done to distinguish benign from malignant lesions, conventional or dual phase FDG PET/CT does not nec-essarily distinguish sarcoidosis and tuberculosis from ML in the mediastinal region (Kumar et al. 2011; Maturu et  al. 2014). Therefore, we performed a video-assisted thoracoscopic lymph node biopsy without FDG PET/CT examination. In addition, it was recently reported that FDG PET/CT findings of KFD are indistinguishable from those of ML which has no extranodal involvement (Kim et al. 2014). Endobronchial ultrasound with trans-bronchial needle aspiration is a promising alternative method for diagnosis of mediastinal and hilar lymphad-enopathy due to ML, nonlymphoma malignancy and sarcoidosis (Boujaoude et al. 2012). However, the tissue samples obtained by this method are too small to diag-nose KFD.ConclusionKFD should be considered in the differential diagno-sis of massive mediastinal and hilar lymphadenopa-thy, even when there are no superficial lesions. More molecular biological research is needed to obtain insight into the essential pathogenic factors involved in KFD in order to develop a simple diagnostic method as a definitive diagnosis of KFD in the mediastinal and hilar regions is currently only possible by examining surgical biopsy tissue. In addition, we need to bear in mind that unexpected disorders occasionally coexist with common diseases.Fig. 2 Pathological findings of mediastinal lymph nodes (a, b hematoxylin and eosin staining: c immunohistochemical staining). a Irregular necrotic areas consisted of debris and intense karyorrhexis. b Prominent histiocytic cells admixed with plasma cells, large lymphocytes and immu-noblasts around necrotic areas without neutrophils. c Positive stain for CD68 on histiocytic cellsPage 4 of 4Naito et al. SpringerPlus  (2015) 4:693 ConsentWritten informed consent was obtained from the patient for publication of this case report and any accompany-ing images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.AbbreviationsKFD: Kikuchi-Fujimoto disease; CAP: community acquired pneumonia; CRP: C-reactive protein; CT: computed tomography; sIL-2R: soluble interleukin-2 receptor; ML: malignant lymphoma; TAZ/PIPC: tazobactam/piperacillin; COP: cryptogenic organizing pneumonia; FDG PET/CT: 18-fluorodeoxyglucose positron emission/computed tomography.Authors’ contributionsNN drafted the initial manuscript. TS edited and submitted the manuscript. HM and HH were involved in diagnosing and treating the patient. KN per-formed pathological studies. FO was the attending physician throughout the disease course. All authors read and approved the final manuscript.Author details1 Division of Pulmonary Medicine, National Hospital Organization National Kochi Hospital, 1-2-25 Asakuranishimachi, Kochi 780-8077, Japan. 2 Depart-ment of Clinical Investigation, National Hospital Organization National Kochi Hospital, 1-2-25 Asakuranishimachi, Kochi 780-8077, Japan. 3 Division of Tho-racic Surgery, National Hospital Organization National Kochi Hospital, 1-2-25 Asakuranishimachi, Kochi 780-8077, Japan. 4 Division of Pathology, National Hospital Organization National Kochi Hospital, 1-2-25 Asakuranishimachi, Kochi 780-8077, Japan. AcknowledgmentsWe thank Yukihisa Komatsu (Division of Radiology, National Hospital Organiza-tion National Kochi Hospital) for his contribution to this article.Competing interestsThe authors declare that they have no competing interests.Sources of supportWe disclose there are no sources of funding or financial support.Received: 20 September 2015   Accepted: 2 November 2015ReferencesAneja A, Maheswari KU, Gayathri Devi HJ et al (2014) A rare case of multifocal lymphadenopathy in a young male. Oxf Med Case Reports 2014:141–144Boujaoude Z, Dahdel M, Pratter M et al (2012) Endobronchial ultrasound with transbronchial needle aspiration in the diagnosis of bilateral hilar and mediastinal lymphadenopathy. J Bronchol Interv Pulmonol 19:19–23Dumas G, Prendki V, Haroche J et al (2014) Kikuchi-Fujimoto disease: retrospec-tive study of 91 cases and review of the literature. Medicine (Baltimore) 93:372–382Garcia-Zamalloa A, Taboada-Gomez J, Bernardo-Galán P et al (2010) Bilateral pleural effusion and interstitial lung disease as unusual manifestations of Kikuchi-Fujimoto disease: case report and literature review. BMC Pulm Med 10:54González-Ballester D, Blanco-Fernández G, Tejero-García M et al (2010) Kikuchi-Fujimoto, abdominal tumor as atypical location. Rev Esp Enferm Dig 102:455–457Hua F, Zhu L (2010) Kikuchi Fujimoto disease associated with cryptogenic organizing pneumonia: case report and literature review. BMC Infect Dis 10:64Jang YJ, Park KH, Seok HJ (2000) Management of Kikuchi’s disease using gluco-corticoid. J Laryngol Otol 114:709–711Kim JE, Lee EK, Lee JM et al (2014) Kikuchi-Fujimoto disease mimicking malignant lymphoma with 2-[(18)F]fluoro-2-deoxy-d-glucose PET/CT in children. Korean J Pediatr 57:226–231Kumar A, Dutta R, Kannan U et al (2011) Evaluation of mediastinal lymph nodes using F-FDG PET-CT scan and its histopathologic correlation. Ann Thorac Med. 6:11–616Kuo T (1995) Kikuchi’s disease (histiocytic necrotizing lymphadenitis): a clin-icopathologic study of 79 cases with an analysis of histologic subtypes, immunohistology, and DNA ploidy. Am J Surg Pathol 19:798–809Maturu VN, Agarwal R, Aggarwal AN et al (2014) Dual-time point whole-body 18F-fluorodeoxyglucose PET/CT imaging in undiagnosed mediastinal lymphadenopathy: a prospective study of 117 patients with sarcoidosis and TB. Chest 146:e216–e220Nakamura I, Imamura A, Yanagisawa N et al (2009) Medical study of 69 cases diagnosed as Kikuchi’s disease. Kansenshogaku Zasshi 83:363–368 (in Japanese)Yoshida Y, Matsuzawa Y, Rikitake H et al (2011) Mediastinal lymphadenopathy without cervical lymphadenopathy in a case of Kikuchi-Fujimoto disease. Intern Med 50:649–652Yoshioka K, Miyashita T, Nakamura T et al (2010) Treatment of histiocytic necrotizing lymphadenitis (Kikuchi’s disease) with prolonged fever by a single course of methylprednisolone pulse therapy without maintenance therapy: experience with 13 cases. Inter Med 49:2267–2270

Kikuchi-Fujimoto disease associated with community acquired pneumonia showing intrathoratic lymphadenopathy without cervical lesions

https://springerplus.springeropen.com/track/pdf/10.1186/s40064-015-1500-y?site=springerplus.springeropen.com

Kikuchi-Fujimoto disease associated with community acquired pneumonia showing intrathoratic lymphadenopathy without cervical lesions

Abstract

Similar works

Full text

Available Versions

Crossref