Journal of the association of physicians of india • vol 62 • november, 2014
57
Neurological Manifestations in a Patient of
Kikuchi’s Disease
Marina Vaz*, Carmen M Pereira**, Sindhoora Kotha***, Jamina Oliveira***
Abstract
Kikuchi’s disease is a rare condition that mainly presents in young females along with lymphadenitis.
Involvement of the nervous system is rare. We report a young female who presented with fever, headache,
vomiting, lymphadenopathy and neurological manifestations in the form of aseptic meningitis, ataxia
and paraparesis. Since the disease can be mistaken clinically and histologically for SLE, lymphoma
and tuberculosis it is important to differentiate it from these conditions. Also our case emphasizes the
importance of recognising this disorder in diagnosing patients with meningitis.
Introduction
K
ikuchi-Fujumoto disease was first described by Kikuchi in 1972 in Japan. Fujimoto
and colleagues independently described it in the same year. Also known as
histiocytic necrotising lymphadenitis, it is an uncommon, idiopathic, generally selflimiting cause of lymphadenitis. 1
No specific cause of Kikuchi’s disease has been found. Some kind of viral or post
viral aetiology has been proposed. It has also been linked to SLE. 1 The course is benign,
spontaneous resolution usually occurs within 2-3weeks. 2
Case Report
A 16 year old girl presented with one week history of fever, frontal headache,
instability while walking, weakness of both lower limbs, photophobia, abdominal pain,
loose motions, vomiting and rash over forearms. There was no history of weight loss,
past history or contact with tuberculosis.
On examination she had temperature of 102 o F, tachycardia, bilateral cervical
lymphadenopathy involving submandibular and posterior auricular lymph nodes,
measuring 2 x 3 cms which were firm, tender and mobile and left axillary lymph nodes
measuring 2 x 2 cms. There was a maculopapular rash over both forearms. Systemic
examination revealed a non tender liver palpable 1 cm below subcostal margin.
Neurological examination showed grade 3 power in both lower limbs with
exaggerated deep tendon reflexes and extensor plantars. Power in upper limbs was
normal. There was no sensory deficit or bladder involvement. Patient had bilateral
cerebellar signs in upper limbs with tremor and past pointing. There was also nystagmus
bilaterally and truncal ataxia. Nuchal rigidity was present.
Lecturer, **Associate Professor,
Jr. Resident, Dept of Medicine,
Goa Medical College, Goa
Received: 08.02.2013;
Revised: 09.04.2013;
Accepted: 25.05.2013
*
***
Laboratory investigations revealed haemoglobin of 11 g%, total WBC count of 4500
cells/cmm – stabs 16%, polymorphs 71%, lymphocytes 11%, monocytes 2% - and platelet
count of 1.5 lakh cells/cmm. ESR was 22 mm at end of 1 st hour, CRP was positive. CSF
examination revealed aseptic meningitis with absence of cells, protein 86 mg%, sugar
62 mg%. CSF culture was sterile, CSF ADA was negative, CSF PCR for TB was negative.
Plain and post contrast brain scan was normal. MRI of brain was normal. Abdominal
ultrasonography showed multiple para-aortic and mesenteric lymphadenopathy.
Sputum examination for AFB smear was negative. Liver function tests showed normal
bilirubin with elevated aspartate aminotransferase of 143 U/L. Renal function tests were
normal. Mantoux test was negative. Serological tests for leptospirosis and typhoid were
negative. HBsAg was negative, HIV ELISA was negative. Routine urine examination was
58
unremarkable and culture sterile. ANA and dsDNA
were negative. ECG showed sinus tachycardia, chest
X-ray was normal. FNAC cervical lymph node was
suggestive of reactive hyperplasia.
The patient was started on injection mannitol,
ceftriaxone 2 g iv 12 hourly and injection Acyclovir
10 mg/kg body weight 8 hourly with the possibility
of viral encephalomyelitis with cerebellitis in mind.
A submandibular lymph node biopsy showed effaced
architecture with large areas of coagulative necrosis
and histiocytes speckled with karyorrhectic debris
Journal of the association of physicians of india • vol 62 • november, 2014
and absence of granuloma suggestive of histiocytic
necrotising lymphadenitis consistent with Kikuchi’s
disease. Antibiotics and antivirals were witheld.
Patient was treated symptomatically for fever.
Headache and fever subsided in 10 days and cerebellar
signs and power in both lower limbs improved in
2 weeks. Rash subsided in 2 weeks. Lymph nodes
regressed by 4 weeks. Figures 1 and 2 show the
histologic picture of Kikuchi’s disease.
Discussion
Kikuchi’s disease has a higher prevalence among
the Japanese and other Asiatic individuals affecting
women more than men in a ratio of 3:1 although recent
reports suggest the ratio to be 1:1. It typically affects
young adults (mean age- 20-30 years). 3
Clinically it presents mainly as a relatively acute
onset of lymphadenopathy with fever and a flu-like
prodrome. 3 Cervical nodes are affected in about 80%
of cases and are usually painless or mildly tender,
firm and mobile, and tend to be 2-3 cms in diameter,
although masses of multiple nodes may reach 6 cms. 3
Fig. 1 : Low power magnification of lymph node biopsy
section showing effaced nodal architecture with
areas of focal necrosis
Less common symptoms include arthralgia, skin
rashes, weakness and night sweats, weight loss,
diarrhoea, anorexia, chills, nausea and vomiting.
Chest and abdominal pain seen in our patient have
Fig. 2 : High power magnification showing effaced nodal architecture, coagulative necrosis, histiocytes and karryorrhectic
debris (H and E)
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Journal of the association of physicians of india • vol 62 • november, 2014
also been noted. 1 Some patients may also have
hepatosplenomegaly. 1
Although involvement of the nervous system is
rare, aseptic meningitis, acute cerebellar ataxia, acute
brachial neuritis and brainstem encephalitis have been
reported to complicate the disease. 4 To our knowledge
paraparesis has not yet been reported. Acute cerebellar
symptoms are very rare. A case has been reported
wherein a patient presented with kinetic tremor and
gait ataxia preceeding clinical lymphadenopathy in
Kikuchi’s disease. 5 Brain and spinal MRI done in this
patient showed no structural abnormality. 5
Routine laboratory tests may be normal except for
an elevated ESR and C-reactive protein and a low
WBC count. 1 Fine needle aspiration cytology only has
a limited role in establishing the diagnosis with the
overall accuracy estimated at 56%. 1
Diagnosis is based on histopathological findings
of a lymph node biopsy, the pathologic hallmark of
which is paracortical necrotic foci, which are devoid
of neutrophils and surrounded by plasmacytoid
monocytes, immunoblasts and crescenteric histiocytes. 2
The coagulative necrosis and abundant karyorrhectic
debris can distort the nodal architechture. 1 The
immune phenotype of Kikuchi’s disease is primarily
composed of mature CD8 positive and CD4 positive
T-lymphocytes. The histiocytes express histiocyte
associated antigens such as lysosyme, myeloperoxidase
and CD68. 1
Kikuchi’s disease has to be included in the
differential diagnosis of lymph node enlargement such
as SLE associated lymphadenitis, malignant lymphoma,
tuberculosis, herpes simplex lymphadenitis,
plasmacytoid T cell leukaemia, Kawasaki’s disease,
nodal colonisation by acute myeloid leukaemia,
infectious mononucleosis, sarcoidosis and metastatic
adenocarcinoma. SLE associated lymphadenitis is
characterised by prominent foci of necrosis resembling
Kikuchi’s disease. However, serologic tests like ANA
and dsDNA are positive in SLE and histologically
it is characterised by the presence of haematoxylin
bodies, the Azzopardi phenomenon (i.e, encrustation
of blood vessel walls with nuclear material), paucity
of cytotoxic T cells and large number of plasma cells
in nodal tissue. 6
Kikuchi’s disease is differentiated from malignant
lymphoma by incomplete architectural effacement
with patent sinuses, presence of numerous reactive
histiocytes, relatively low mitotic rates and absence of
Reed-Sternberg cells. 1 Immunohistochemical staining
shows that the cells in Kikuchi’s disease are negative
for CD3 and CD20 and they are positive for CD68.
Positive immunostaining results by monoclonal
antibody Ki-M1P are seen in Kikuchi’s disease but
not in lymphoma. 3
Histologically it differs from tuberculosis by the
classic biopsy features and the absence of caseating
granulomas. Herpes simplex associated lymphadenitis
may also have the characteristic histiocytic infiltrates
and necrotic debris as in Kikuchi’s disease. However,
the infiltrate is less striking, neutrophils are often
present, the histiocytes are myeloperoxidase negative
and the diagnosis is confirmed by the presence of viral
inclusions.6 Plasmacytoid T cell leukaemia seen mainly
in elderly males presents with lymphadenopathy,
hepatosplenomegaly and weight loss. The lymph
nodes display T zone expansion by plasmacytoid–like
cells which do not express myeloperoxidase. 6 They
may later develop acute or chronic myelomonocytic
leukaemia. Infectious mononucleosis is diagnosed
on the basis of characteristic clinical, haematological
and serological findings. Kikuchi’s disease may
be mistaken for metastatic carcinoma since the
histiocytes seen may resemble signet-ring carcinoma
cells. However, the cells in metastatic carcinoma are
characterised by atypical nuclei and contain mucin
rather than cellular debris. 6
Table 1 summarises the clues to the differential
diagnosis of Kikuchi’s disease.
Treatment for Kikuchi’s disease is usually supportive
using NSAIDs to alleviate lymph node tenderness and
fever. Our patient was treated symptomatically and
improved. Corticosteroids have been recommended
for severe forms of the disease. 1
The disease runs a benign course and is usually
self-limiting, resolving in several weeks to months. It
has a recurrence rate of 3-4%. 1 In some patients, SLE
may occur few years later.
Conclusion
At h o u g h K i k u c h i s ’ s d i s e a s e i s s e l f - l i m i t i n g ,
the systemic symptoms such as fever can be very
distressing to the patient. Clinicians and pathologists
should be aware of this condition especially when
dealing with a young female patient with fever
and cervical lymphadenopathy. The possibility of
aseptic meningitis should be considered in patients
of Kikuchi’s disease who complain of severe systemic
symptoms such as fever and headache during the
course of the illness. Also Kikuchi’s disease should
be suspected in meningitis of unknown aetiology.
Early recognition of Kikuchi’s disease can minimise
potentially harmful and unnecessary evaluation
and thus prevent misdiagnosis and inappropriate
treatment.
Acknowledgements
We take this opportunity to thank Dr. Edwin Gomes,
Professor and Head of Department of Medicine, Goa
Medical College for his constant support and guidance
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Journal of the association of physicians of india • vol 62 • november, 2014
Table 1 : Differential diagnosis of Kikuchi’s disease6
Condition
Clinical Features
SLE-associated lymphadenopathy Elevation of ANA and dsDNA
titres; SLE features in the
follow-up
Herpes simplex–associated
Skin and mucous membranes
lymphadenopathy
have ulcerative lesions near sites
of lymphadenopathy
Non-Hodgkin lymphoma
Plasmacytoid T-cell leukaemia
Elderly men who have or will
develop MML
Kawasaki disease
Mostly children younger than 5
years; typical skin involvement
Nodal colonisation by AML
Metastatic adenocarcinoma
Infectious lymphadenitis
Histologic Features
Haematoxylin bodies; Azzopardi
phenomenon; sparse CD8 T cells;
abundance of plasma cells
Presence of neutrophils;
viral inclusions; no striking
polymorphous histiocytic infiltrate.
no striking polymorphous
histiocytic infiltrate; most T-cell
lymphomas CD4+
Proliferation of PC-like cells; no
striking polymorphous histiocytic
infiltrate
Geographic necrosis; fibrinoid
thrombosis; no striking
polymorphous histiocytic infiltrate;
presence of neutrophils; PC absent
or not prominent
No striking polymorphous
histiocytic infiltrate; lacking CD8
T cells
Signet-ring cells containing mucin
rather than nuclear debris
Occasional presence of
granulomas; usual presence of
polymorphonuclear leucocytes
Immunohistochemical and
Genetic Features
Histiocytes MPO–
Histiocytes MPO–; T-cell
arrangement gene–positive
PC-like cells MPO–
CD34+; neutrophilic elastase–
positive; HLA-DR+
Presence of cytokeratin absence of
histiocyte associated antigens
Histiocytes MPO
AML, acute myeloid leukaemia; ANA, antinuclear antibodies; MML, myelomonocytic leukaemia; MPO, myeloperoxidase; PC, plasmacytoid
cells; SLE, systemic lupus erythematosus.
in our work.
2.
Ali Mahmood, Rabia Mir, Salama R. Salama, Rameen M. Miarrostami,
Claudia Lapidus, Fernando Pujol. Kikuchi’s Disease: An Unusual
Presentation and a Therapeutic Challenge. Yale J Biol Med 2006;79:2733.
3.
Babu N Chaitanya, CS Sindura.Kikuchi’s disease. J Oral Maxillofac
Pathol 2010;14:6-9.
4.
We also thank our families and our colleagues for
all their encouragement.
Hyun-Duk Yang, Sung –Ik Lee, II-Hong Son, Seung-Han Suk. Aseptic
Meningitis in Kikuchi’s Disease. J Clin Neurol 2005;1:104-6.
5.
Finally we thank our patient and the relatives for
allowing us to study and publish this case.
Moon JS, II Kim G, Koo YH, Kim HS, Kim WC, Kim OJ, Oh SH. Kinetic
tremor and cerebellar ataxia as initial manifestations of KikuchiFujimoto’s disease. J Neurol Sci 2009;277:181-3.
6.
Xavier Bosch, Antonio Guilabert, Rosa Miquel, Elias Campo. Enigmatic
Kikuchi-Fujimoto Disease. A Comprehensive Review. Am J Clin Pathol
2004;122:141-52.
We thank the staff of the medicine ward for their
untiring help in treating our patients.
We are also grateful to the staff of department of
Biochemistry, Pathology and Radiology and Ranbaxy
laboratories.
References
1.
Sudhakar M K, Sathyamurthy P, Indhumathi E, Rajendran A, Vivek B.
Kikuchi’s disease: A case report from south India. International J Case
Reports and Images 2011;2:15-18.