Kikuchi disease presenting with aseptic meningitis

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American Journal of Emergency Medicine

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Kikuchi disease presenting with Aseptic meningitis?


Kikuchi disease is a self-limited disease characterized primarily by regional lymphadenopathy. Kikuchi disease was first described in 1972 as a lymphadenitis with specific histoPathologic findings. Extranodal manifestations have been reported, including rare neuro- logic complications such as aseptic meningitis. This case report discusses a patient who presented to the ED with signs and symptoms suggestive of aseptic meningitis and was ultimately diagnosed with Kikuchi disease. We also review the epidemiology, clinical presenta- tion, and laboratory findings typically found in patients with Kikuchi disease. Inclusion of Kikuchi disease in the differential diagnosis for meningitis may help establish a diagnosis in patients also presenting with regional lymphadenopathy.

Kikuchi disease, also known as histiocytic necrotizing lymphade- nitis, is a self-limited disease characterized primarily by regional lymphadenopathy. Kikuchi disease was first described in 1972 as a lymphadenitis with specific histopathologic findings. Extranodal manifestations have been reported. neurologic complications, includ- ing aseptic meningitis, are rare [1]. Kikuchi disease is benign, usually resolving spontaneously within several months of presentation and is therefore often misdiagnosed.

Here, we discuss the case of a patient who was found to have aseptic meningitis and was ultimately diagnosed with Kikuchi disease. We will briefly review the features of Kikuchi disease when accompanied by aseptic meningitis, with an emphasis on the initial presentation to the emergency department (ED).

The patient was a 32-year-old African American man with no significant medical history who presented to the ED complaining of Severe headaches for approximately 1 month that had worsened over the preceding 2 weeks. The patient had been seen and admitted at an outside hospital for the same complaint and was suspected of having meningitis after computed tomography and magnetic resonance imaging showed meningeal thickening, cerebral edema, and diffuse leptomeningeal enhancement. The patient underwent lumbar punc- ture with cerebrospinal fluid cultures that were negative for bacteria, cryptococcal antigen, acid-fast bacilli, and fungus. Human immunodeficiency virus test was also negative.

During the first hospital stay, the patient was incidentally found to have cervical lymphadenopathy and underwent excisional biopsy. The patient reported having a previous episode of submandibular lymphadenopathy in 2008 without a specific diagnosis. Symptoms at that time resolved on their own without further treatment.

? Sources of support and disclaimers: None.

At the time of presentation, the patient also reported a 25-lb weight loss and night sweats but denied any other focal symptoms. The patient received a total of 5 days of antibiotics at the outside hospital and was discharged without improvement in symptoms.

On physical examination in the ED at the time of his second presentation, the patient was noted to have right supraclavicular lymphadenopathy with evidence of recent biopsy. Significant labora- tory results included white blood cell count, 3.7 k/uL (4.4-10.6 k/uL); hemoglobin level, 9.4 g/dL (11.0-14.0 g/dL); aspartate aminotrans- ferase, 50 U/L (0-40 U/L); alanine aminotransferase, 120 U/L (5-35 U/L); ?-Glutamyltransferase, 287 U/L (3-60 U/L); and direct bilirubin of

0.3 mg/dL (0.0-0.2 mg/dL). Sedimentation rate was 65 mm/hr (0-16 mm/hr), and lactate dehydrogenase was 148 U/L (85-210 U/L). Tuberculin skin test and interferon-? release assay (QuantiFERON-TB Gold In-Tube test, Valencia, CA) were both negative. Urine and blood cultures were also negative.

The patient underwent repeat computed tomography of the head in the ED that noted meningeal enhancement and extraaxial bihemi- spheric hypodense fluid collections, concerning for leptomeningeal carcinomatosis vs aseptic meningitis. The patient was admitted and underwent lumbar puncture with the following significant results: glucose, 82 mg/dL (50-70 mg/dL); protein, 63 mg/dL (20-50 mg/dL); white blood cell, 14/uL (0-5/uL); lymphocytes, 82% (40%-80%); and monocytes, 13% (15%-45%). Cerebrospinal fluid cultures were nega- tive for bacteria, fungi, and acid-fast bacilli. While admitted, the patient’s lymph node biopsy results were obtained from the outside hospital. They showed immunoblasts with lymphohistiocytic infiltra- tion and nonspecific necrotic material, consistent with Kikuchi disease. The patient was started on methylprednisolone 500 mg intravenously every 12 hours with significant improvement in headache symptoms over 24 hours. The patient was subsequently discharged with a tapering dose of prednisone.

Kikuchi disease represents a clinical and histopathologic entity with unknown etiology characterized by the presence of regional lymphadenopathy. Cervical lymphadenopathy is seen in 56% to 98% of cases. It may be unilateral or tender and is often found in the posterior cervical triangle [2,3]. Other clinical features associated with Kikuchi disease are low-grade fever and upper respiratory symptoms. Night sweats and weight loss have also been reported [4].

Although first described in young Japanese patients, Kikuchi disease has been described in a variety of ethnic backgrounds. It is commonly seen in patients younger than the age of 40 years [2]. Overall, there is a female predominance [5]. However, a presentation of aseptic meningitis in patients with Kikuchi disease has been described almost exclusively in Japanese patients [3].

The clinical findings in patients with Kikuchi disease presenting with aseptic meningitis are consistent with those of benign acute aseptic meningitis, including pleocytosis with lymphocyte

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predominance [6]. However, it has been reported that 45% of Kikuchi disease patients with aseptic meningitis did not have meningismus, suggesting that a lack of specific signs typically associated with benign acute aseptic meningitis may be a distinguishing feature of Kikuchi disease [6]. The report also noted an increased number of cases of meningitis in male patients with Kikuchi disease.

Neutropenia, anemia, and elevated erythrocyte sedimentation rate are also often present in patients with Kikuchi disease, as was seen in this patient [6]. Mild leukopenia has been reported in 20% to 58% of patients [7,8]. Other laboratory derangements that may be present include elevated lactate dehydrogenase and aminotransferases.

Extranodal manifestations of Kikuchi disease are rare but possible. dermatologic manifestations are well documented and usually present as cutaneous plaque-like lesions, although facial erythema and erythematous papules or ulcers have also been reported [4,9]. There are also rare cases of patients with Kikuchi disease developing hepatomegaly or splenomegaly. Neurologic manifestations include aseptic meningitis, mononeuritis multiplex, and acute cerebellar ataxia [1,10]. The most common neurologic complication is aseptic meningitis, which is observed in 2.8% to 9.8% of Kikuchi disease cases [6].

Given the nonspecific clinical symptoms, lymph node biopsy is required to establish a diagnosis of Kikuchi disease [8,11].

The disease course of Kikuchi disease is benign and self-limited, with symptoms usually resolving within 4 months [12]. There is a recurrence rate of 3% to 4%. Treatment is targeted at symptomatic relief, including antipyretics for persistent fever and analgesics for tender lymphadenopathy [1]. Corticosteroids have been used for recurrent and relapsing cases [12,13]. Steroids proved effective for treatment of debilitating headache in a patient with Kikuchi disease and aseptic meningitis [3].

The differential diagnosis of Kikuchi disease includes systemic lupus erythematosus lymphadenitis, lymphoid malignancy, and various infectious etiologies. Given the differences in management of these diseases, it is important that they be excluded before assigning a diagnosis of Kikuchi disease. Regarding Kikuchi disease presenting with symptoms of meningitis, it is essential to exclude other viral causes as well as bacterial with appropriate cultures. For example, tuberculous meningitis can cause similar CSF results as well as lymphadenopathy [3]. Given the toxic effects of antitubercular agents, it is important to distinguish between these 2 diagnoses to avoid unnecessary harmful treatment [3].

Aseptic meningitis with Kikuchi disease is a rare clinical presentation. Regardless, inclusion of Kikuchi disease in the differen- tial diagnosis for meningitis may help establish the diagnosis in patients also presenting with regional lymphadenopathy. Lymph

node biopsy should be considered early on to confirm a diagnosis and avoid unnecessary and potentially harmful treatments. For patients with aseptic meningitis presenting with severe headache, short-term corticosteroids may prove beneficial for symptomatic relief.

Basem F. Khishfe, MD

Department of Emergency Medicine Cook County (Stroger) Hospital, Chicago, IL

E-mail address: [email protected]

Laurie M. Krass, BS

Rush University Medical Center, Chicago, IL

Erik K. Nordquist, MD

Department of Emergency Medicine Cook County (Stroger) Hospital, Chicago, IL


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