Kikuchi disease

Kikuchi Disease

Syed A.A. Rizvi, PhD, MBA
Sultan S. Ahmed, MD
Ayman M. Saleh, PhD
Jasmin Ahmed, BS, MS, MD
Michael O'Laughlin, BS
Shazia Zafar, MD
Souhad B. Younes, MD
Volume 15 - Issue 2 - February 2016

A 17-year-old female with no medical history presented to our emergency department due to 2 weeks of intermittent fever and enlarged lymph nodes. She noted that fever was present on most days, with a maximum temperature of 101.5°F. The patient reported large, painful nodes that first began in her axilla and then in her neck. 

Review of systems was significant for a 5-lb weight loss, fatigue, night sweats, dry mouth, mouth sores, and decreased appetite. She denied headaches, joint pain, nausea, vomiting, diarrhea, and upper-respiratory infection symptoms. 

Head/neck CT with contrast showing several enlarged lymph nodes, with the largest on the right cervical region. The patient was diagnosed with possible mononucleosis; Epsein-Barr virus (EBV) titers were obtained. She was sent home to follow up with a hematologist. Lab work at the hematologist office showed leukopenia with elevated IgG and negative IgM EBV titers. Fevers persisted and lymphadenopathy did not improve, so the patient was admitted to the pediatric ward for further evaluation.  

On admission, vital signs were within normal range, with no fever. During her examination, the patient was nontoxic appearing, and in no distress. Significant exam findings included bilateral enlarged anterior and posterior cervical nodes that were tender to palpation. No obvious supraclavicular lymphadenopathy was palpated.  The rest of the exam was unremarkable. Complete blood count (CBC) showed mild leukopenia, with a normal differential. C-reactive protein was mildly elevated at 1.8 mg/L. Lactate dehydrogenase (LDH) was 869 U/L and uric acid 3.6 mg/dL. A complete metabolic panel was unremarkable. 

A neck computed tomography (CT) scan with contrast showed nonspecific, non-necrotic bilateral neck lymphadenopathy. The largest lymph nodes were along the right jugular chain, measuring 3 × 2 cm. A chest CT showed bilateral axillary lymphadenopathy, with the largest collection of lymph nodes in the left upper axillary region, measuring 3 × 2 cm. No mediastinal or hilar lymphadenopathy was noted. 

The patient was empirically started on clindamycin, ceftriaxone, and azithromycin. Workup was expanded, and the patient was tested for HIV, syphilis, systemic lupus erythematosus (SLE), tularemia, brucellosis, enterovirus, tuberculosis, cytomegalovirus, Mycoplasma bacteria, toxoplasmosis, and fungal infections. An immunodeficiency panel, thyroid panel and echocardiogram were also obtained. The patient was found to be Mycoplasma positive, with slightly elevated antinuclear antibody and erythrocyte sedimentation rate levels. 

The echocardiogram showed a filamentous lesion on the mitral valve, described as an accessory chordae tendineae. A lymph node biopsy was obtained and sent for cytometry, cytogenetics, fungal/bacterial/viral/acid fast bacilli cultures, and Bartonella polymerase chain reaction. The biopsy showed patchy areas of cellular necrosis surrounded by fairly numerous histiocytes, activated T-lymphoid cells, and plasma cells. The findings were consistent with Kikuchi disease. 

Kikuchi disease, also known as histiocytic necrotizing lymphadenitis, is a rare, self-limiting lymphadenitis that is more commonly seen in Asian females. Kikuchi disease most frequently presents with cervical lymphadenopathy, persistent fevers, and leukopenia. Other symptoms include fatigue, generalized rash, rigors, and arthralgia. The exact pathogenesis is unknown, but presentation and histological changes suggests an autoimmune response to infection, most commonly viruses.1 Kikuchi disease may be confused with lymphoma and SLE, therefore a thorough evaluation must be obtained. Initial work-up includes labs, such as CBC with differential, inflammatory markers, LDH and autoimmune antibody studies.2

Imaging may initially include an ultrasound, but CT evaluation of the lymph nodes is crucial. A chest X-ray is also important to evaluate for tuberculosis and malignancy. Yet, the most definitive diagnosis is obtained through cytologic evaluation from a fine-needle biopsy. Histologic findings should include paracortical necrosis, histocytes, lymphocytes, macrophages, and karyorrhexis.3 In addition, an excisional biopsy may be required. 

Kikuchi disease is self-limiting and treatment is supportive. Corticosteroids or intravenous immunoglobulin may be used in cases with severe or persistent symptoms.4 The prognosis for affected patients is typically excellent. Symptoms usually resolve in 1 to 6 months, with reoccurrence seen in 3% to 4% of patients.1

References

 

  1. Lee KY, Yeon YH, Lee BC. Kikuchi-Fujimoto disease with prolonged fever in children. Pediatrics. 2004;114(6):e752-e756. 
  2. Chaitanya BN, Sindura CJ. Kikuchi’s disease. J Oral Maxillofac Pathol. 2010;14(1):6-9.
  3. Pilichowska ME, Pinkus JL, Pinkus GS. Histiocytic necrotizing lymphadenitis (Kikuchi-Fujimoto disease): lesional cells exhibit an immature dendritic cell phenotype. Am J Clin Pathol. 2009;131(2):174-182.
  4. Chen CK, Low Y, Akhilesh M, Jacobsen AS. Kikuchi disease in Asian children. J Paediatr Child Health. 2006;42(3):104-107.