Kikuchi’s disease presenting with aseptic meningitis Basem F. Khishfe MD PII: DOI: Reference:

S0735-6757(14)00217-4 doi: 10.1016/j.ajem.2014.03.029 YAJEM 54207

To appear in:

American Journal of Emergency Medicine

Received date: Accepted date:

11 March 2014 20 March 2014

Please cite this article as: Khishfe Basem F., Kikuchi’s disease presenting with aseptic meningitis, American Journal of Emergency Medicine (2014), doi: 10.1016/j.ajem.2014.03.029

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ACCEPTED MANUSCRIPT Title Page

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Abstract

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Title: Kikuchi’s disease presenting with aseptic meningitis Authors: Basem F. Khishfe M.D. Department of Emergency Medicine Cook County (Stroger) Hospital Laurie M. Krass Rush University Medical Center Erik K. Nordquist M.D. Department of Emergency Medicine Cook County (Stroger) Hospital Correspondent author and address for reprints: Basem F. Khishfe M.D. Cook County (Stroger) Hospital 1900 W Polk St Admin bldg, 10th floor Chicago, Il 60612 [email protected] Short running title: Kikuchi’s disease Sources of support and disclaimers: None Keywords: Kikuchi’s Disease; Aseptic Meningitis, Necrotizing Lymphadenitis

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Kikuchi’s disease is a self-limited disease characterized primarily by regional lymphadenopathy. Kikuchi’s disease was first described in 1972 as a lymphadenitis with specific histopathological findings. Extranodal manifestations have been reported, including rare neurological complications such as aseptic meningitis. This case report discusses a patient who presented to the emergency department with signs and symptoms suggestive of aseptic meningitis and was ultimately diagnosed with Kikuchi’s disease. We also review the epidemiology, clinical presentation, and laboratory findings typically found in patients with Kikuchi’s disease. Inclusion of Kikuchi’s disease in the differential

ACCEPTED MANUSCRIPT diagnosis for meningitis may help to establish a diagnosis in patients also presenting with

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regional lymphadenopathy.

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Introduction:

Kikuchi’s disease, also known as histiocytic necrotizing lymphadenitis, is a self-

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limited disease characterized primarily by regional lymphadenopathy. Kikuchi’s disease

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was first described in 1972 as a lymphadenitis with specific histopathological findings. Extranodal manifestations have been reported. Neurological complications, including

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aseptic meningitis, are rare [1]. Kikuchi’s disease is benign, usually resolving spontaneously within several months of presentation and is therefore often misdiagnosed.

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Here, we discuss the case of a patient who was found to have aseptic meningitis

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and was ultimately diagnosed with Kikuchi’s disease. We will briefly review the features of Kikuchi’s disease when accompanied by aseptic meningitis, with an emphasis on the

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initial presentation to the Emergency Department.

Case Report:

The patient was a 32-year-old African American male with no significant past medical history who presented to the emergency department complaining of severe headaches for approximately one month that had worsened over the preceding two 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 puncture with CSF cultures

ACCEPTED MANUSCRIPT that were negative for bacteria, cryptococcal antigen, acid-fast bacilli, and fungus. HIV test was also negative.

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During the first hospital stay, the patient was incidentally found to have cervical

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lymphadenopathy and underwent excisional biopsy. The patient reported having a previous episode of submandibular lymphadenopathy in 2008 without a specific

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diagnosis. Symptoms at that time resolved on their own without further treatment.

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At 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 five days of

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antibiotics at the outside hospital and was discharged without improvement in symptoms. On physical examination in the emergency department at the time of his second

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presentation, the patient was noted to have right supraclavicular lymphadenopathy with

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evidence of recent biopsy. Significant laboratory results included: white blood cell count 3.7 k/uL [4.4-10.6 k/uL], hemoglobin 9.4 g/dL [11.0-14.0 g/dL], AST 50 U/L [0-40 U/L],

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ALT 120 U/L [5-35 U/L], GGT 287 U/L [3-60 U/L], and direct bilirubin of 0.3 mg/dL

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[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-gamma release assay [QuantiFERON®–TB Gold In-Tube test] were both negative. Urine and blood cultures were also negative. The patient underwent repeat computed tomography of the head in the emergency department that noted meningeal enhancement and extra-axial bihemispheric hypodense fluid collections, concerning for leptomeningeal carcinomatosis versus 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],

ACCEPTED MANUSCRIPT white blood cell 14/uL [0-5/uL], lymphocytes 82% [40-80%], and monocytes 13% [1545%]. CSF cultures were negative for bacteria, fungi, and acid-fast bacilli. While

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admitted, the patient’s lymph node biopsy results were obtained from the outside

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hospital. They showed immunoblasts with lymphohistiocytic infiltration and nonspecific necrotic material, consistent with Kikuchi’s disease. The patient was started on

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methylprednisolone 500 mg IV every 12 hours with significant improvement in headache

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symptoms over 24 hours. The patient was subsequently discharged with a tapering dose

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of prednisone.

Discussion

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Kikuchi’s disease represents a clinical and histopathologic entity with unknown

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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

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often found in the posterior cervical triangle [2, 3]. Other clinical features associated with

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Kikuchi’s 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’s disease has been described in a variety of ethnic backgrounds. It is commonly seen in patients younger than 40 years of age [2]. Overall, there is a female predominance [5]. However, a presentation of aseptic meningitis in patients with Kikuchi’s disease has been described almost exclusively in Japanese patients [3]. The clinical findings in patients with Kikuchi’s disease presenting with aseptic meningitis are consistent with those of benign acute aseptic meningitis, including

ACCEPTED MANUSCRIPT pleocytosis with lymphocyte predominance [6]. However, it has been reported that 45% of Kikuchi’s disease patients with aseptic meningitis did not have meningismus,

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suggesting that a lack of specific signs typically associated with benign acute aseptic

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meningitis may be a distinguishing feature of Kikuchi’s disease [6]. The report also noted an increased number of cases of meningitis in male patients with Kikuchi’s disease.

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Neutropenia, anemia, and elevated ESR are also often present in patients with

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Kikuchi’s disease, as was seen in this patient [6]. Mild leukopenia has been reported in 20-58% of patients [7, 8]. Other laboratory derangements that may be present include

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elevated lactate dehydrogenase and aminotransferases. Extranodal manifestations of Kikuchi’s disease are rare but possible.

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Dermatologic manifestations are well documented and usually present as cutaneous

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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’s disease

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developing hepatomegaly or splenomegaly. Neurologic manifestations include aseptic

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meningitis, mononeuritis multiplex, and acute cerebellar ataxia [1, 10]. The most common neurological complication is aseptic meningitis, which is observed in 2.8-9.8% of Kikuchi’s disease cases [6]. Given the nonspecific clinical symptoms, lymph node biopsy is required to establish a diagnosis of Kikuchi’s disease [8, 11]. The disease course of Kikuchi’s 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

ACCEPTED MANUSCRIPT and relapsing cases [12, 13]. Steroids proved effective for treatment of debilitating headache in a patient with Kikuchi’s disease and aseptic meningitis [3].

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The differential diagnosis of Kikuchi’s disease includes SLE lymphadenitis,

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lymphoid malignancy, and various infectious etiologies. Given the differences in management of these diseases, it is important they be excluded before assigning a

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diagnosis of Kikuchi’s disease. Regarding Kikuchi’s disease presenting with symptoms

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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

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as well as lymphadenopathy [3]. Given the toxic effects of antitubercular agents, it is important to distinguish between these two diagnoses to avoid unnecessary harmful

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treatment [3].

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Conclusion

Aseptic meningitis with Kikuchi’s disease is a rare clinical presentation.

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Regardless, inclusion of Kikuchi’s disease in the differential diagnosis for meningitis

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may help to 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.

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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 lympha...
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