Kikuchi Disease

A 33-year-old Jamaican woman presented to the emergency department with subjective recurrent fever, right-sided cervical lymphadenopathy, diaphoresis, decreased appetite, 2.3-kg weight loss, and abdominal pain for the past 2 weeks. She also complained of constant, moderate, bilateral elbow and knee arthralgia.

The patient stated that she had had 3 similar episodes in the past, with each episode resolving within several months. The patient had a strong family history of autoimmune disorders, with Sjögren syndrome in her sister and systemic lupus erythematosus (SLE) in her aunt. The patient denied cough, sore throat, congestion, or rashes. The patient also denied any recent travel outside the United States.

Physical examination. Physical examination findings included a heart rate of 105 beats/min and a temperature of 38.5°C. Physical examination also revealed right-sided neck swelling, tender to palpation, along the posterior cervical lymph node chain from the mastoid process to the clavicle, without supraclavicular lymphadenopathy. There was no lymphadenopathy noted in the axillae or groin.

Diagnostic testing. Given the patient’s strong family history of autoimmune disorders, SLE lymphadenopathy was strongly suspected. Antinuclear antibody (ANA) titers were requested, the results of which were negative for Sjögren syndrome. Results of Epstein-Barr virus serology, rapid HIV RNA testing, and a tuberculosis test were negative. The patient denied recent contact with cats, reducing the potential for Bartonella henselae infection. Radiographs of the neck and chest also were normal.

Laboratory test results showed a white blood cell (WBC) count of 1700/μL (reference range, 3500-10,500 cells/μL), a hemoglobin (Hgb) of 11.1 g/dL (reference range, 12-15 g/dL), a hematocrit (Hct) of 32.8% (reference range, 34.9%-44.5%), and a platelet count of 13.5 x 10³/μL (reference range, 150-450 x 10³/μL), findings consistent with pancytopenia. The woman’s erythrocyte sedimentation rate (ESR) also was elevated at 47 mm/h (reference range, 0-20 mm/h). Repeated ANA titers were negative.

Figure. Lymph node biopsy showing diffuse large B-cell lymphoma and histiocytic necrotizing lymphadenitis.

A decision was made to obtain an excisional lymph node biopsy for pathologic evaluation of lymphadenopathy. The results indicated small patchy areas of necrosis with nuclear debris and apoptotic bodies associated with numerous histiocytes, small lymphocytes, and larger lymphocytes/immunoblasts (Figure). Overall findings were consistent with histiocytic necrotizing lymphadenitis. Flow cytometry did not identify a monotypic B cell, atypical T cell population, or aberrant antigen expression.

On the fourth day of admission, the patient’s WBC count dropped to 1400 cells/μL; Hgb fell to 9.6 g/dL, and Hct fell to 29.3%. The platelet count remained at 13.5 x 10³/μL.

Six days after admission, test results showed a WBC count of 2400 cells/μL, Hgb of 9.6 g/dL, Hct of 28.8%, and a platelet count of 17.4 x 10³/μL. The fever had subsided, and the patient was discharged with a recommendation to follow-up with a hematologist. Filgrastim was given to boost the patient’s bone marrow function, and her symptoms resolved spontaneously within a few days.

Discussion. Kikuchi disease, also known as Kikuchi-Fujimoto disease, classically is seen in young (< 40 years old) women among multiple ethnic groups. The etiology of the disease is unknown, but clinical presentation typically consists of fever, localized rashes, leukopenia, and cervical lymphadenopathy that is self-limited.^1,2 The pathology report description of a histiocytic necrotizing lymphadenitis points toward Kikuchi disease and differentiates it from a more severe alternative diagnosis.

Because of the epidemiologic overlap of patient populations with SLE, clinicians should always consider a diagnosis of SLE and use ANA antibody testing to rule out the presence of SLE lymphadenopathy. Kikuchi disease presents with acute systemic symptoms of fever and painful cervical lymphadenopathy.^3,4  Fever typically is low-grade and 1 week to 1 month in duration. Lymphadenopathy is localized to the cervical chain, and generalized lymphadenopathy is a very rare finding.⁵  Occasional extranodal manifestation of the skin is seen in 30% to 40% of cases, usually showing plaques, erythematous macules, patches, or nodules extending to the entire body.^6,7  Other symptoms may include fatigue, joint pain, night sweats, leukopenia, and rarely, elevated ESR or anemia.⁸ Relapse of Kikuchi disease has been reported, and a rare complication includes development of SLE; therefore, close monitoring of patients is warranted.⁹

 Excisional lymph node biopsy should always be performed to rule out the possibility of more-aggressive diseases such as lymphoma. In pathology, biopsy of affected lymph nodes typically reveals the presence of coagulative necrosis with abundant apoptotic karyorrhectic debris.^3,4  Early lymph node biopsies of Kikuchi disease may reveal numerous blast cells, which would raise suspicion for Hodgkin lymphoma. In fact, previous cases of Kikuchi disease misdiagnosed as Hodgkin lymphoma have been reported.¹⁰  However, the presence of polyclonal infiltrates and effective viral immunohistochemistry studies should rule down this diagnosis; most notably, CD15-, CD30-, and CD45-positive Reed-Sternberg cell variants would be present in Hodgkin lymphoma but not in Kikuchi disease. Progression of the disease would show histiocytic necrotizing infiltrates without neutrophils in a late lymph node biopsy. Definitive diagnosis of Kikuchi disease requires the presence of crescent-shaped histiocytes and plasmacytoid monocytes with scattered karyorrhexis.¹¹

Kikuchi disease is a rare, uncommon medical condition that health care providers may not considere in patients who present with cervical lymphadenopathy. Histopathology of the lymph nodes provides definitive diagnosis of Kikuchi disease and should be utilized to differentiate it from the far more aggressive Hodgkin lymphoma.

References:

1. Ferrer R. Lymphadenopathy: differential diagnosis and evaluation. Am Fam Physician. 1998;58(6):1313-1320.
2. Libman H. Generalized lymphadenopathy. J Gen Intern Med. 1987;2(1):48-58.
3. Kikuchi M. Lymphadenitis showing focal reticulum cell hyperplasia with nuclear debris and phagocytosis: a clinico-pathological study [in Japanese]. Nippon Ketsueki Gakkai Zasshi. 1972;35:379-380.
4. Fujimoto Y, Kojima Y, Yamaguchi K. Cervical subacute necrotizing lymphadenitis. A new clinicopathological entity [in Japanese]. Naika. 1972;20:920-927.
5. Dorfman RF, Berry GJ. Kikuchi’s histiocytic necrotizing lymphadenitis: an analysis of 108 cases with emphasis on differential diagnosis. Semin Diagn Pathol. 1988;5(4):329-345.
6. Yen A, Fearneyhough P, Raimer SS, Hudnall SD. EBV-associated Kikuchi’s histiocytic necrotizing lymphadenitis with cutaneous manifestations. J Am Acad Dermatol. 1997;36(2 pt 2):342-346.
7. Atwater AR, Longley BJ, Aughenbaugh WD. Kikuchi’s disease: case report and systematic review of cutaneous and histopathologic presentations. J Am Acad Dermatol. 2008;59(1):130-136.
8. Song JY, Cheong HJ, Kee SY, et al. Disease spectrum of cervical lymphadenitis: analysis based on ultrasound-guided core-needle gun biopsy. J Infect. 2007;55(4):310-316.
9. Rezayat T, Carroll MB, Ramsey BC, Smith A. A case of relapsing Kikuchi-Fujimoto disease. Case Rep Otolaryngol. 2013;2013:364795.
10. Dane F, Ozturk MA, Tecimer T, et al. A case of Kikuchi-Fujimoto disease misdiagnosed as Hodgkin’s lymphoma: the importance of a second opinion. J BUON. 2009;14(2):309-311.
11. Tsang WY, Chan JK, Ng CS. Kikuchi’s lymphadenitis: a morphologic analysis of 75 cases with special reference to unusual features. Am J Surg Pathol. 1994;18(3):219-231.