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Kikuchi's disease: A case report and review of the literature. (Original Article).


Kikuchi's disease is a necrotizing lymphadenitis that is prevalent in Asia and is being increasingly recognized in other areas of the world. It usually occurs in women in their late 20s or early 30s and manifests as a posterior cervical adenopathy. It resolves spontaneously, usually over a period of several weeks to 6 months. Its initial clinical appearance is commonly similar to that of a lymphoma, and it can be pathologically misdiagnosed as such. Kikuchi's disease might be associated with systemic lupus erythematosus. We report a case of Kikuchi's disease that occurred in a 36-year-old Asian woman. We discuss the clinical features, differential diagnosis, radiographic evaluation, and pathology of this case, and we review the literature in an effort to assist otolaryngologists in diagnosing this benign and uncommon entity.


Kikuchi's disease, also called Kikuchi-Fujimoto disease, was once known as subacute necrotizing lymphadenitis. It is increasingly recognized as a benign cause of cervical adenopathy in young adults, predominantly women. In 1972, both Kikuchi (1) and Fujimoto et al (2) described this disease in the Japanese literature. Five years later, Kikuchi suggested that the cause of necrotizing lymphadenitis was acute toxoplasmic infection. (3) The first case that was identified outside of Japan was published in 1982. (4) In 1985, the first case report appeared in the otolaryngology literature, when Gleeson et al described the histologic features and differential diagnosis of Kikuchi's disease. (5) Most reports of Kikuchi's disease have been published in the pathology literature, and there appears to be a paucity of familiarity with this condition among otolaryngologists.

Kikuchi's disease usually manifests as a localized cervical adenopathy, primarily in the posterior neck of young women. Its course is benign, and it normally resolves spontaneously in a matter of weeks to 6 months. It can be easily confused with lymphoma, both clinically and pathologically. The cause of Kikuchi's disease is unknown. It might be associated with systemic lupus erythematosus (SLE). The diagnosis is primarily made by tissue biopsy, but there is a report of fine-needle aspiration diagnosis. (6) In this article, we describe a case of Kikuchi's disease, and we review the clinical features of this benign entity, which might be seen in an otolaryngology service.

Case report

We evaluated a 36-year-old woman of Asian descent who had migrated from her native Philippines to Germany. She had been referred to our otolaryngology service for assessment of a 6-week history of a gradually progressive fullness in the posterior triangle. She denied any associated fever, chills, night sweats, fatigue, and cough, and she had experienced no recent trauma or dental work. Her history included travel to the Philippines, China, Hong Kong, the United States, and--most recently--Italy, France, Belgium, the Netherlands, and the Czech Republic.

At the age of 15 years, she had moved from Manila to Chicago; 2 months later, she developed fever, chills, and tender cervical lymphadenopathy. When her lymphadenopathy failed to improve with antibiotic treatment, she underwent an excisional lymph node biopsy. The biopsy results were consistent with necrotizing lymphadenitis. Since then, she had not experienced any symptoms until the current episode. Her medical history also included a positive skin test for purified protein derivative, for which she had been treated with a 6-month course of isoniazid. Because the woman worked in a medical laboratory, she was routinely screened with chest x-rays, and she had no clinical symptoms or evidence of tuberculosis. She had had chronic urticaria for several years, but she had not experienced any episode during the preceding 6 months. She had recently undergone [I.sup.131] treatment for Graves' disease. Her family history was noncontributory.

On head and neck examination, we detected a deep, 2.5 x 2.5-cm right posterior triangle adenopathy that was located just posterior to the sternocleidomastoid muscle in the area corresponding to Erb's point. The enlarged node was firm, nontender, and somewhat mobile. She had several smaller lymphadenopathies in the same area. No other cervical masses were detected, and findings on the remainder of the head and neck examination were unremarkable. Both of her lungs were clear on auscultation, and her cardiac and abdominal findings were normal.

We prescribed a trial of amoxicillin, but subsequent examinations revealed no change in her lymphadenopathy. Laboratory studies were ordered, and they showed a leukocyte count of 4.2 x [10.sup.9]/L with 39.5% neutrophils. Her hematocrit and hemoglobin levels were 42.4% and 14.1 g/dl, respectively. Her thyroid-stimulating hormone level was 3.6 [micro]U/ml, and her thyroxine ([T.sub.4]) level was 1.28 [micro]g/dl, both within normal limits. Tests for human immunodeficiency virus and borreliosis were negative, and her rapid plasma reagin test was nonreactive. Her angiotensin-converting enzyme level was normal at 40 nmol/ml/min. Her antinuclear antibody (ANA) screen was positive (1:320 titer), and the pattern was homogeneous.

Findings on chest x-ray were interpreted as normal. Fine-needle aspiration biopsy detected polymorphic lymphocytes and macrophages consistent with reactive lymphadenopathy and a single group of epithelioid cells of uncertain origin. Tests performed for acid-fast bacilli and other bacteria were negative. Computed tomography (CT) of the neck demonstrated bilateral posterior triangle lymphadenopathy that was more prominent on the right (figure 1). The largest node was 1.2 cm in diameter.

Analysis of an excisional lymph node biopsy detected stellate necrosis with surrounding histiocytic inflammation. Neutrophilic inflammation was absent. Stains for acid-fast bacilli, fungi, bacteria, spirochetes, and cat-scratch bacilli were negative. These findings were consistent with Kikuchi's disease, and the diagnosis was confirmed by the Armed Forces Institute of Pathology. The patient required no treatment, and she was provided with reassurance and education. At her 6-month follow-up visit, her cervical lymphadenopathy had resolved and she was doing well.

For her positive ANA test, the patient was referred to a rheumatologist, and a further laboratory work-up was positive for Scl-70 and antineutrophil cytoplasmic auto-antibodies. The rheumatologist noted that a positive ANA titer is sometimes found in patients who have an autoimmune thyroid disease, such as Graves' disease. This is one possible explanation for our patient's elevated titer. Our patient had no clinical evidence of an associated connective tissue disease, and she was advised to return to the office in 6 months for a repeat screening for SLE.


Demographics. The female-to-male ratio in Kikuchi's disease is approximately 4:1, although one study of 79 patients found a ratio of only 1.1:1. (7) The age range of affected individuals is wide, but most patients are in their late 20s or early 30s (mean age: 30 yr). (8) Although the large majority of Kikuchi's disease cases have been seen in Japan, where it was initially described, many other countries have since added cases to the literature. Dorfman and Berry reported 108 cases, 88 of which (81.5%) occurred in the United States. (8) It has been suggested that most patients with this disease are Asian, but 68 of Dorfman and Berry's 108 patients (63.0%) were white. It could be that this disease is under-recognized and under-reported outside of eastern Asia, thereby skewing its reported demographics.

Etiology. The etiology of Kikuchi's disease is controversial. No genetic predisposition or environmental factor has been identified. Yet a role for heredity or environment is plausible in light of the large number of cases that have been reported in Japan and the fact that many of the cases reported in Europe and the United States involved patients of Asian descent.

Several other possible etiologies have been postulated. For example, some authors believe an infectious process is at work, based on the transient and self-limited nature of Kikuchi's disease and the associated constitutional and upper respiratory tract infection-like symptoms. Among the infectious organisms that have been proposed are Yersinia enterocolitica, cytomegalovirus (CMV), human herpesvirus (HHV), varicella-zoster virus, parainfluenza virus, and Epstein-Barr virus (EBV). However, studies thus far have failed to demonstrate a relationship between Kikuchi's disease and either HHV or EBV. (8,9) Likewise, Martinez-Vazquez et al evaluated seven lymph node specimens by polymerase chain reaction for viral DNA (specifically, herpes simplex virus types 1 and 2, varicella-zoster virus, CMV, HHV6, HHV8, and EBV) and found no evidence implicating these pathogens. (10) Moreover, an early study (3) suggested that toxoplasmosis might be a cause of Kikuchi's disease, but this theory has since been discounted; Dorf man and Berry wrote that "there should be no difficulty in distinguishing toxoplasmic lymphadenitis from Kikuchi's disease" based on pathology. (8) For now, the most popular theory is simply that some type of virus is the culprit.

Signs and symptoms. Patients with Kikuchi's disease usually have painless cervical lymphadenopathy; generalized lymphadenopathy has been reported in some cases. When pain is reported, it is usually described as mild tenderness. The cervical lymph nodes are affected in approximately 80% of patients." Of these patients, the posterior triangle lymph nodes are affected in 65 to 70% of cases. (12,13) Other affected sites include the axillary (14%) and supraclavicular (12%) nodal chains. (11) Additional signs and symptoms can include fever, hepatosplenomegaly, headache, anorexia, nausea, vomiting, skin lesions, and constitutional disturbances (e.g., night sweats, weight loss, and malaise).

Cutaneous involvement is not usually noted, although Seno et al reported cutaneous lesions in approximately 30% of the cases they reviewed. (14) Skin lesions have been described as maculopapular, morbilliform or rubella-like, urticarial, and drug eruption-like; disseminated erythema has also been reported. These dermatologic findings are not pathognomonic, and no particularly characteristic skin lesion has been identified. Sumiyoshi et al reported that in seven patients with cutaneous involvement, most had facial lesions; six of the seven were men. (15,16) Although these men had a more severe clinical course than most patients, they all recovered without complication. Dorfman and Berry reported the presence of a facial butterfly pattern in two of four patients who had a rash, and both were women; one of these women was ultimately diagnosed with SLE. (8)

The possible association between Kikuchi's disease and SLE is important because Kikuchi' s disease might be the initial diagnosis in patients who go on to develop SLE. It has been suggested that Kikuchi's disease might represent a self-limited SLE-like autoimmune disorder. (17) A lag time of 10 months to 3 years has been reported between the diagnosis of Kikuchi's disease and the subsequent onset of SLE. (7,18) Therefore, it is recommended that patients with Kikuchi's disease be monitored long term for the development of SLE. (8,19) The specific frequency and duration of follow-up is not known, but perhaps as more data are collected and awareness of the association between the two diseases increases, patients will be monitored more often and the ideal frequency and length of a prudent follow-up can be defined.

Differential diagnosis. The list of differential diagnoses of a neck mass is extensive. Important entities that merit consideration include, but are not limited to:

* autoimmune processes, such as SLE

* neoplasms, such as malignant lymphoma and metastatic carcinoma

* infections, including infectious mononucleosis, toxoplasmosis, Y enterocolitica, tularemia, cat-scratch disease, tuberculosis, and acquired immunodeficiency syndrome

* noninfectious inflammatory conditions, including Kawasaki's disease and Still's disease (especially in children)

* a variety of other conditions, such as lymph node infarction associated with vasculitis, trauma, or lymphadenitis of an infectious nature

Because the scope of the differential diagnosis is broad and awareness of Kikuchi's disease is low, it is not surprising that Kikuchi's disease is initially presumed to be another entity. For example, it has often been initially misdiagnosed as a malignant lymphoma. In such cases, it is important that the examining physician relay the patient's history to the pathologist and share any clinical suspicions that might help avoid a misdiagnosis. Turner et al reported a series in which 10 of a subset of 25 patients (40.0%) with Kikuchi's disease were given an initial pathologic diagnosis of either a large-cell lymphoma or Hodgkin's disease; several other patients were also suspected of possibly having cancer. (13) As a result, 11 of these patients underwent invasive procedures, including bone marrow, skin, and repeat lymph node biopsies. Four of these 11 patients also underwent extensive staging examinations and additional biopsies (one patient underwent a staging laparotomy). In another case of misdiagnosis, Jay araj et al reported that a patient with Kikuchi' s disease was initially treated with antituberculous medications for presumed cervical tuberculosis. (20)

Imaging studies. There is no radiographic finding particular to Kikuchi's disease that will establish a concrete diagnosis by itself. Nonetheless, a chest x-ray should be obtained during the work-up of cervical lymphadenopathy to look for evidence of tuberculosis or malignancy. Ultrasonography and/or CT of the neck can be helpful prior to obtaining a biopsy specimen. On CT, cervical lymph nodes are uniformly enlarged and might exhibit enhancement on postcontrast images. (21) On ultrasonography, nodes can be either heterogeneous or homogeneous, and they are surrounded by rims that are hyperechoic relative to the lymph node itself. (21,22) Lupus lymphadenitis and malignant lymphoma can be radiologically similar to Kikuchi's disease, and they should be ruled out.

Laboratory studies. Laboratory tests cannot confirm a diagnosis of Kikuchi' s disease, but they are helpful in ruling out other causes of cervical lymphadenopathy, such as lupus lymphadenitis. In a subset of 26 patients with Kikuchi's disease, Turner et al reported that white blood cell counts were normal in 21 patients (80.8%); the other five patients had leukopenia (range: 1.9 to 3.3 x [10.sup.3]/ml). (13) Later, Garcia et al published a case report and literature review in which they noted that 50% of patients with Kikuchi' s disease had mild granulocytopenia. (11) Most patients with Kikuchi's disease also have elevated erythrocyte sedimentation rates and C-reactive protein levels. (4,8) Our patient had mild neutropenia (39.5%) on her initial evaluation, and her lymphocyte percentage was 49.1%, near the upper limit of normal.

Fine-needle aspiration. In our patient, we performed a fine-needle aspiration biopsy prior to an excisional biopsy. The aspirate contained polymorphic lymphocytes, macrophages, and a group of epithelial cells of uncertain origin. Although these findings were consistent with reactive lymphadenopathy, they were nonspecific and nondiagnostic. Hsueh et al have advocated that fine-needle aspiration of the lymph node alone should be sufficient for a diagnosis in patients who have typical cytologic features in lymph node aspirates and typical clinical features. (6) However, most other authors rely on a formal biopsy for tissue diagnosis. Typical findings in fine-needle aspiration specimens include lymphocytes (small and atypical), some reactive phagocytic histiocytes, and "intense extracellular debris." (6) In patients who have the typical clinical features of Kikuchi's disease but whose fine-needle aspiration analysis is not diagnostic, a diagnosis can be confirmed by either repeat fine-needle aspiration or, prefe rably, by an excisional lymph node biopsy.

Excisional biopsy. Gross examination of an excisional biopsy specimen generally reveals tan or brown lymph nodes, 1 to 3 cm in diameter, without obvious necrosis. Histologic analysis of affected lymph nodes generally reveals patchy necrosis, primarily in the paracortical area, and numerous adjacent crescentic histiocytes, lymphocytes, macrophages, and immunoblasts (predominantly T cell) (figure 2). The histiocytes and macrophages contain phagocytized nuclear debris from degenerated lymphocytes. Granulomas are absent. Residual normal architecture or reactive findings are often present adjacent to the lesions. These histologic features, in conjunction with an absence or paucity of neutrophils, are consistent findings in Kikuchi's disease.

Histopathologic types. In 1995, Kuo studied histopathologic changes in 79 patients with Kikuchi's disease and proposed three histopathologic types: proliferative, necrotizing, and xanthomatous. (7) Perhaps this classification system will lead to a better understanding of the pathogenesis and clinical evolution of Kikuchi's disease. The absence of hematoxylin bodies and neutrophils, the near-absence of plasma cells, and a tendency toward more widespread necrosis are important factors in distinguishing Kikuchi's disease from SLE.

Drug treatment. As mentioned, Kikuchi's disease itself usually does not require treatment, although Jang et al recently suggested that patients with advanced disease might benefit from systemic prednisone to speed resolution. (23) Treatment is indicated, of course, for patients whose disease is complicated by other factors. For example, a corticosteroid or an immunosuppressant is indicated in cases that are complicated by an increase in lactate dehydrogenase and serum ANA titers. (24) Likewise, acetaminophen or a nonsteroidal anti-inflammatory drug might be necessary to treat pyrexia and/or lymphadenopathic pain.

Outcomes. Symptoms of Kikuchi's disease tend to spontaneously disappear in a matter of weeks to 6 months; in some rare cases, symptoms have persisted for a longer period. A recurrence rate of 3.3% has been reported. (7) Two deaths associated with Kikuchi's disease have been reported. One patient died of a lupus-like syndrome, (24) and the other (who had multifocal Kikuchi's disease) died of sudden heart failure 72 hours after a cervical lymph node biopsy was performed under local anesthesia. (19)


(1.) Kikuchi M. Lymphadenitis showing focal reticulum cell hyperplasia with nuclear debris and phagocytosis. Nippon Ketsueki Gakkai Zasshi 1972;35:379-80.

(2.) Fujimoto Y, Kozima Y, Yamaguchi K. Cervical subacute necrotizing lymphadenitis. A new clinicopatholgical entity. Naika 1972;20:920-7.

(3.) Kikuchi M, Yoshizumi T, Nakamura H. Necrotizing lymphadenitis: Possible acute toxoplasmic infection. Virchows Arch A Pathol Anat Histol 1977;376:247-53.

(4.) Pileri S, Kikuchi M, Helbron D, Lennert K. Histiocytic necrotizing lymphadenitis without granulocytic infiltration. Virchows Arch A Pathol Anat Histol 1982;395:257-71.

(5.) Gleeson MJ, Siodlak MZ, Barbatis C, Salama NY. Kikuchi's--a new cause of cervical lymphadenopathy. J Laryngol Otol 1985;99:935-9.

(6.) Hsueh EJ, Ko WS, Hwang WS, Yam LT. Fine-needle aspiration of histiocytic necrotizing lymphadenitis (Kikuchi's disease). Diagn Cytopathol 1993;9:448-52.

(7.) Kuo TT. Kikuchi's disease (histiocytic necrotizing lymphadenitis). A clinicopathologic study of 79 cases with an analysis of histologic subtypes, immunohistology, and DNA ploidy. Am J Surg Pathol 1995;19:798-809.

(8.) Dorfman RF, Berry GJ. Kikuchi's histiocytic necrotizing lymphadenitis: An analysis of 108 cases with emphasis on differential diagnosis. Semin Diagn Pathol 1988;5:329-45.

(9.) Ho]lingsworth HC, Peiper SC, Weiss LM, et al. An investigation of the viral pathogenesis of Kikuchi-Fujimoto disease. Lack of evidence for Epstein-Barr virus or human herpesvirus type 6 as the causative agents. Arch Pathol Lab Med 1994;118:134-40.

(10.) Martinez-Vazquez C, Potel C, Angulo M, et al. Nosocomial Kikuchi's disease--a search for herpesvirus sequences in lymph node tissues using PCR. Infection 2001;29:143-7.

(11.) Garcia CE, Girdhar-Gopal HV, Dorfman DM. Kikuchi-Fujimoto disease of the neck update. Update. Ann Otol Rhinol Laryngol 1993;102:11-5.

(12.) Chamulak GA, Brynes RK, Nathwani BN. Kikuchi-Fujimoto disease mimicking malignant lymphoma. Am J Surg Pathol 1990;14:514-23.

(13.) Turner RR, Martin J, Dorfman RF. Necrotizing lymphadenitis. A study of 30 cases. Am J Surg Pathol 1983;7:115-23.

(14.) Seno A, Torigoe R, Shimoe K, et al. Kikuchi's disease (histiocytic necrotizing lymphadenitis) with cutaneous involvement. J Am Acad Dermatol 1994;30:504-6.

(15.) Sumiyoshi Y, Kikuchi M, Ohshima K, et al. A case of histiocytic necrotizing lymphadenitis with bone marrow and skin involvement. Virchows Arch A Pathol Anat Histopathol 1992;420:275-9.

(16.) Sumiyoshi Y, Kikuchi M, Takeshita M, et al. Immunohistological study of skin involvement in Kikuchi's disease. Virchows Arch B Cell Pathol Incl Mol Pathol 1992;62:263-9.

(17.) Imamura M, Ueno H, Matsuura A, et al. An ultrastructural study of subacute necrotizing lymphadenitis. Am J Pathol 1982;107:292-9.

(18.) Vila LM, Mayor AM, Silvestrini IE. Therapeutic response and long-term follow-up in a systemic lupus erythematosus patient presenting with Kikuchi's disease. Lupus 2001;10:126-8.

(19.) Lin SH, Ko WS, Lee HS, Hwang WS. Kikuchi's disease associated with lupus-like syndrome--a fatal case [letter]. J Rheumatol 1992;19:1995-6.

(20.) Jayaraj SM, Lloyd J, Frosh AC, Patel KS. Kikuchi-Fujimoto's syndrome masquerading as tuberculosis. J Laryngol Otol 1999:113:82-4.

(21.) Fulcher AS. Cervical lymphadenopathy due to Kikuchi disease: US and CT appearance. J Comput Assist Tomogr 1993;17:131-3.

(22.) Ogawa M, Ueda S, Ohto M, et al. Ultrasonography of cervical lymphadenopathy in a patient with Kikuchi's disease [letter]. Acta Radiol 1991;32:260-1.

(23.) Jang YJ, Park KH, Seok HJ. Management of Kikuchi's disease using glucocorticoid. J Laryagol Otol 2000;114:709-11.

(24.) Chan JK, Wong KC, Ng CS. A fatal case of multicentric Kikuchi's histiocytic necrotizing lymphadenitis. Cancer 1989;63:1856-62.

From the Department of Otolaryngology-Head and Neck Surgery, Landstuhl Regional Medical Center, Landstuhl, Germany (Dr. Baumgartner), and the Department of Otolaryngology-Head and Neck Surgery, Brooke Army Medical Center, San Antonio, Tex. (Dr. Helling).

Reprint requests: Eric Helling, MD, Asst. Chief, Otolaryngology-Head and Neck Surgery, Brooke Army Medical Center, San Antonio, TX 09054. Phone: (210) 916-2107; fax: (210) 916-1247; e-mail:

The views expressed in this article are those of the authors and do not reflect the official policy or position of the United States Army, the Department of Defense, or the United States government. No financial support or funding was received for this work.
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Comment:Kikuchi's disease: A case report and review of the literature. (Original Article).
Author:Helling, Eric R.
Publication:Ear, Nose and Throat Journal
Geographic Code:90ASI
Date:May 1, 2002
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