Bilateral pleural effusion and interstitial lung disease as unusual manifestations of kikuchi-fujimoto disease: case report and literature review
© Garcia-Zamalloa et al; licensee BioMed Central Ltd. 2010
Received: 27 May 2010
Accepted: 5 November 2010
Published: 5 November 2010
Kikuchi-Fujimoto's disease (KFD), also called histiocytic necrotizing lymphadenitis, is a rare, idiopathic and self-limited condition usually characterized by cervical lymphadenopathy and fever, most often affecting young patients. Aetiology is unknown. Differential diagnosis includes mainly malignant lymphoma, tuberculous lymphadenitis and systemic lupus erythematosus (SLE), so early diagnosis is crucial. Pleuropulmonary involvement due to isolated KFD has been seldom reported.
a 32-year-old man, on treatment for iatrogenic hypothyroidism, was admitted due to high grade fever and painful cervical lymphadenopathies. KFD was diagnosed by lymph node biopsy. Some days after admission the patient got worse, he developed generalized lymphadenopathy, bilateral pleural effusion and interstitial lung disease. All of them resolved with prednisone and after two years of following up he remains asymptomatic and without evidence of any other associated disease.
Pleural effusion and interstitial lung disease are very uncommon manifestations of KFD. In our experience, treatment with oral prednisone was effective.
Kikuchi-Fujimoto's disease (KFD), or histiocytic necrotizing lymphadenitis, was first described in Japan in 1972 as a self-limiting disease mostly affecting the cervical lymph nodes of young individuals, mainly females . In 1982 the first cases of KFD were reported in North America and Europe  and the disease is now reported worldwide. Although the aetiology is unknown, it has been suggested to be an apoptotic process mediated mainly by CD8-positive T lymphocytes, and viral or autoimmune factors are believed to be involved [1, 3]. Occasionally it may be associated with autoimmune disease, mostly systemic lupus erythematosus (SLE) [3, 4]. Enlargement of cervical lymph nodes, fever and leukopenia are the most prominent symptoms, although several other clinical manifestations have been reported [1, 3]. The authors report the first case of isolated KFD with interstitial lung disease and bilateral pleural effusion, which also improved quickly with oral prednisone.
KFD is a benign disease that usually resolves spontaneously within one to four months, affects all ethnic groups and is more common in young women (4:1 female:male ratio), manifests as localized lymphadenopathy, usually in the cervical region, and is commonly associated with fever and leukopenia [1, 5]. The aetiology of KFD remains obscure: a viral pathogenesis is thought to be the most likely candidate due to its self-limiting clinical course and the lack of neutrophilic response [4, 6]. It has been reported in association with Epstein-Barr virus, human herpesvirus, human herpesvirus 8, HIV, HTLV1, dengue virus, parvovirus B19, Yersinia enterocolítica, Bartonella, Brucella, Entamoeba histolytica and Toxoplasma [7, 8]. On the other hand, an autoimmune origin has also been suggested due to electron microscopic studies that have identified tubular reticular structures in the cytoplasm of stimulated lymphocytes and histiocytes in patients with KFD, which have also been noted within lymphocytes and endothelial cells of patients with systemic lupus erythematosus and other autoimmune disorders, so it is possible that KFD may represent an exuberant T-cell-mediated, self-limited immune response to a variety of non-specific stimuli in genetically susceptible individuals .
The differential diagnosis of lymph node enlargement in patients with the clinical signs of KFD includes mainly tuberculous and other infectious types of lymphadenitis, and malignant lymphoma . The diagnosis is confirmed by lymph node biopsy, when histopathology reveals necrotizing lymphadenitis restricted to the cortical and paracortical areas, with partial or complete loss of follicular architecture, marked karyorrhexis and absence of neutrophils, granulomatous reaction or lymphoma cells . Most KFD cases improve within a six-month period , and a wide range of recurrence rates have been reported, from 4% to 27% [10–12].
Kikuchi-Fujimoto disease has occasionally been described in association with simultaneous SLE [4, 5], Sjögren syndrome , antiphospholipid syndrome [4, 14], relapsing polychondritis  or even autoimmune hepatitis . On the other hand, unusual manifestations of isolated KFD include axillary and mesenteric lymphadenopathy, splenomegaly, parotid gland enlargement, skin rashes, arthralgias, myalgias, aseptic meningitis, bone marrow haemophagocytosis and liver dysfunction . Patients with arthritis [17, 18] or bilateral panuveitis  have been reported on occasion. KFD has seldom been reported in association with pulmonary involvement  and most such cases have been in patients who developed SLE . Wilkinson et al. described a 41-yr-old lady diagnosed with KFD who subsequently developed polymyositis with pulmonary involvement . Meanwhile, Kucukardali et al. reported one case of fatal pulmonary haemorrhage due to KFD upon post-mortem examination and three cases who developed KFD after transplantation and died of respiratory failure . Finally, one case of KFD associated with cryptogenic organizing pneumonia has been reported recently . In the present case, the patient developed isolated KFD with pleuropulmonary involvement due to interstitial lung infiltrate and pleural effusion, both bilateral and with rapid improvement and resolution with oral prednisone. The simultaneous hypothyroidism of the patient should not be ignored, nor its possible clinical co-expression. However, its presence several months before the development of KFD and even after the clinical and analytical resolution of the latter, combined with the absence of any other clinical symptoms related to thyroxine defficiency and the rapid development and improvement of the pleuropulmonary manifestations with prednisone, suggest an inflammatory rather than an endocrine aetiology.
In conclusion, pleuropulmonary involvement in patients with KFD has seldom been reported. We describe a patient with isolated KFD in whom bilateral pleural effusion and an interstitial lung pattern developed. Clinical and radiological responses to prednisone were excellent.
Disclosures: Conflicts of interests
The authors declare that they have no competing interests.
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-in-Chief of this journal.
The authors are grateful to Dr. J. Mar for his helpful advice during the preparation of this manuscript.
- Koybasi S, Saydam L, Gungen Y: Histiocytic Necrotizing Lymphadenitis of the neck. Am J Otolaryngol. 2003, 24: 344-347. 10.1016/S0196-0709(03)00061-9.View ArticlePubMedGoogle Scholar
- Pileri S, Kikuchi M, Helbron D, Lennert K: Histiocytic necrotizing lymphadenitis without granulocytic infiltration. Virchows Arch A Pathol Anat Histol. 1982, 395: 257-271. 10.1007/BF00429352.View ArticlePubMedGoogle Scholar
- Kucukardali Y, Solmazgul E, Kunter E, Oncul O, Yildirim S, Kaplan M: Kikuchi-Fujimoto disease: analysis of 244 cases. Clin Rheumatol. 2007, 26: 50-54. 10.1007/s10067-006-0230-5.View ArticlePubMedGoogle Scholar
- Chen HC, Lai JH, Huang GS, Gao HW, Chen CH, Kuo SY, Chang DM: Systemic lupus erythematosus with simultaneous onset of Kikuchi-Fujimoto's disease complicated with antiphospholipid antibody syndrome: a case report and review of the literature. Rheumatol Int. 2005, 25: 303-306. 10.1007/s00296-004-0507-4.View ArticlePubMedGoogle Scholar
- Santana A, Lessa B, Galrao L, Lima I, Mittermayer S: Kikuchi-Fujimoto's disease associated with systemic lupus erythematosus: case report and review of the literature. Clin Rheumatol. 2005, 24: 60-63. 10.1007/s10067-004-0923-6.View ArticlePubMedGoogle Scholar
- Hudnall SD, Chen T, Amr S, Young KH, Henry K: Detection of Human Herpesvirus DNA in Kikuchi-Fujimoto Disease and Reactive Lymphoid Hyperplasia. Int J Clin Exp Pathol. 2008, 1: 362-368.PubMedPubMed CentralGoogle Scholar
- Atwater AR, Longley J, Aughenbaugh WD: Kikuchi's disease: case report and systematic review of cutaneous and histopathologic presentations. J Am Acad Dermatol. 2008, 59: 130-136. 10.1016/j.jaad.2008.03.012.View ArticlePubMedGoogle Scholar
- Aydogan T, Kanbay M, Uraldi C, Kaya A, Uz B, Isik A, Akcay A, Erekul S: Kikuchi-Fujimoto disease secondary to Entamoeba histolytica: case report. J Infect. 2006, 53: 171-173. 10.1016/j.jinf.2005.12.007.View ArticleGoogle Scholar
- Bosch X, Guilabert A, Miquel R, Campo E: Enigmatic Kikuchi-Fujimoto disease: a comprehensive review. Am J Clin Pathol. 2004, 122: 141-152. 10.1309/YF081L4TKYWVYVPQ.View ArticlePubMedGoogle Scholar
- Phupong V, Poomtavorn Y: Kikuchi disease during pregnancy. Arch Gynecol Obstet. 2006, 274: 393-396. 10.1007/s00404-006-0197-0.View ArticlePubMedGoogle Scholar
- Song JY, Lee J, Park DW, Sohn JW, Suh SI, Kim IS, Kim WJ, Kim MJ, Cheong HJ: Clinical outcome and predictive factors of recurrence among patients with Kikuchi's disease. Int J Infect Dis. 2009, 13: 322-326. 10.1016/j.ijid.2008.06.022.View ArticlePubMedGoogle Scholar
- Han HJ, Lim GY, Yeo DM, Chung NG: Kikuchi's disease in children: clinical manifestations and imaging features. J Korean Med Sci. 2009, 24: 1105-1109. 10.3346/jkms.2009.24.6.1105.View ArticlePubMedPubMed CentralGoogle Scholar
- Soy M, Peynirci H, Bilgi S, Adali MK, Güresci S: Kikuchi-Fujimoto disease coexisted with Sjögren syndrome. Clin Rheumatol. 2007, 26: 607-608. 10.1007/s10067-005-0184-z.View ArticlePubMedGoogle Scholar
- Pappaioannou G, Speletas M, Kaloutsi V, Pavlitou-Tsiontsi A: Histiocytic necrotizing lymphadenitis (Kikuchi-Fujimoto disease) associated with antiphospholipid syndrome: case report and literature review. Ann Hematol. 2002, 81: 732-735. 10.1007/s00277-002-0562-4.View ArticleGoogle Scholar
- Mahajan T, Merriman RC, Stone MJ: Kikuchi-Fujimoto disease (histiocytic necrotizing lymphadenitis): report of a case with other autoimmune manifestations. Proc (Bayl Univ Med Cent). 2007, 20: 149-151.Google Scholar
- Shusang V, Marelli L, Beynon H, Davies N, Patch D, Dhillon AP, Burroughs AK: Autoimmune hepatitis associated with Kikuchi-Fujimoto disease. Eur J Gastroenterol Hepatol. 2008, 20: 79-82. 10.1097/MEG.0b013e32825a6a9e.View ArticlePubMedGoogle Scholar
- Douglas M, Bradbury R, Kannangara S, Mitchell D: Arthritis as an unusual manifestation of Kikuchi_Fujimoto disease. Rheumatology. 2003, 42: 1010-1012. 10.1093/rheumatology/keg247.View ArticlePubMedGoogle Scholar
- Graham LE: Kikuchi-Fujimoto disease and peripheral arthritis: a first!. Ann Rheum Dis. 2002, 61: 475-10.1136/ard.61.5.475.View ArticlePubMedPubMed CentralGoogle Scholar
- Taguri AH, McIlwaine GG: Bilateral panuveitis: a possible association with Kikuchi-Fujimoto disease. Am J Ophthlmol. 2001, 132: 419-421. 10.1016/S0002-9394(01)00934-5.View ArticleGoogle Scholar
- Sharma OP: Unusual systemic disorders associated with interstitial lung disease. Curr Opin Pulm Med. 2001, 7: 291-294. 10.1097/00063198-200109000-00007.View ArticlePubMedGoogle Scholar
- Wilkinson CE, Nichol F: Kikuchi-Fujimoto disease associated with polymiositis. Rheumatology. 2000, 39: 1302-1304. 10.1093/rheumatology/39.11.1302.View ArticlePubMedGoogle Scholar
- Hua F, Zhu L: Kikuchi-Fujimoto disease associated with cryptogenic organizing pneumonia: case report and literature review. BMC Infect Dis. 2010, 10: 64-View ArticlePubMedPubMed CentralGoogle Scholar
- The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2466/10/54/prepub
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.