Rare disease

BMJ Case Reports: first published as 10.1136/bcr-2016-217500 on 4 January 2017. Downloaded from http://casereports.bmj.com/ on 4 November 2020 at Madagascar:BMJ-PG Sponsor.
CASE REPORT

TB or not to be? Kikuchi-Fujimoto disease: a rare

but important differential for TB
C McKenna,1 T Whitfield,1 N Patel,1 A Bonington1,2
1
North West Regional Centre SUMMARY had not returned to Pakistan or travelled abroad
for Infectious Diseases, North A 29-year-old British Pakistani woman presented with a for 5 years, and there was no history or suggestion
Manchester General Hospital,
Manchester, UK 2-month history of drenching fevers, night sweats, of TB in her family or close contacts. She had no
2
The University of Manchester, lethargy and tender cervical and axillary history of close contact with animals and employ-
Manchester Academic Health lymphadenopathy. Initial investigations, bloods and ment history was unremarkable.
Science Centre, North imaging were unremarkable. Fever persisted during her Clinical examination revealed: bilaterally
Manchester General Hospital,
admission, and treatment for tuberculosis (TB) enlarged, firm lymph nodes measuring 2×2 cm in
Manchester, UK
lymphadenitis was started postbiopsy until histology the cervical region, a palpable 2 cm right axillary
Correspondence to confirmed a diagnosis of Kikuchi-Fujimoto’s disease lymph node and 1 cm left axillary lymph node.
Dr C McKenna, (KFD). KFD has a non-specific presentation of fever,
christinemariemckenna@ night sweats and lymphadenopathy and commonly raises
doctors.org.uk
INVESTIGATIONS
a clinical suspicion of a number of other serious The predominance of systemic symptoms prompted
Accepted 18 December 2016 conditions such as TB, lymphoma, HIV, systemic lupus an extensive investigation. Chest X-ray was normal.
erythematous, toxoplasmosis and infectious A thoracic CT scan conducted on a previous admis-
mononucleosis. Although rare, KFD should be considered sion had reported non-specific findings: right axil-
to be a differential diagnosis for fever of unknown origin lary lymphadenopathy and a 1.3 cm left
and tender lymphadenopathy in otherwise well bronchopulmonary lymph node. Blood tests were
individuals. This case demonstrates the importance of a unremarkable apart from a rise in ALT (92 U/L)

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timely histological biopsy diagnosis to prevent an (normal range 10–35 U/L). White cell count, differ-
incorrect diagnosis and administration of unnecessary ential count and C reactive protein (CRP) were all
medications. within normal parameters. Blood cultures were
negative, malarial film was also normal and analysis
of a Ziehl-Neelsen stain of induced sputum found
BACKGROUND no acid-fast bacilli. Toxoplasmosis, rubella, cyto-
The triad of symptoms; tender lymphadenopathy, megalovirus (CMV), herpes simplex virus (HSV),
fever and night sweats can point a physician Epstein-Barr virus (EBV), HIV and syphilis screens
towards a number of different serious diagnoses were negative. A cervical biopsy was arranged as an
mimicking TB, lymphoma, HIV, systemic lupus ery- outpatient.
thematous, toxoplasmosis and infectious mono-
nucleosis. This case broadens the differential of DIFFERENTIAL DIAGNOSIS
such a presentation and highlights the importance The differential diagnosis in patients presenting
of a timely histological biopsy diagnosis to prevent with fever of unknown origin with lymphadenop-
the anxiety surrounding a misdiagnosis and the athy in this age group include TB, lymphoma,
administration of unnecessary medications. toxoplasmosis and infectious mononucleosis. It is
important to rule out HIV and syphilis.
CASE PRESENTATION
A 29-year-old Pakistani woman was admitted to the TREATMENT
infectious diseases unit with a 2-month history of Following cervical biopsy, this woman was treated
drenching sweats, lethargy, malaise and small for presumed tuberculosis with the standard antitu-
painful swellings on the right side of her neck and berculosis therapy of rifampicin, isoniazid, pyrazi-
axillae. She initially had intermittent low-grade namide, ethambutol and pyridoxine. After the first
fevers during the day which progressed to drench- day of therapy, a widespread erythematous rash
ing night sweats over the course of the 6 weeks. developed which resolved when the rifampicin was
Prior to this presentation, she had been investigated omitted.
for a painful left arm axillary swelling and lethargy
which was diagnosed initially as an axillary abscess OUTCOME AND FOLLOW-UP
and treated accordingly with a course of antibiotics At 4 days postbiopsy, the histology reported “A tan
without symptom resolution. Superficial thrombo- coloured nodule measuring 10×9×7 mm showing
phlebitis had also been considered and on another areas of early necrosis, apoptosis and collections of
To cite: McKenna C,
Whitfield T, Patel N, et al.
presentation to the emergency department she was histiocytes many of which have J shaped nuclei.
BMJ Case Rep Published diagnosed with lymphadenopathy secondary to a Apoptotic debris was identified and reactive blasts
online: [ please include Day viral illness. were present (see figures 1–3). The cell prolifer-
Month Year] doi:10.1136/ She had no significant medical history, and a ation noticed within the para cortex as well as in
bcr-2016-217500 recent blood borne virus screen was negative. She the subcapsular area is in keeping with Kikuchi
McKenna C, et al. BMJ Case Rep 2017. doi:10.1136/bcr-2016-217500 1
 Rare disease

BMJ Case Reports: first published as 10.1136/bcr-2016-217500 on 4 January 2017. Downloaded from http://casereports.bmj.com/ on 4 November 2020 at Madagascar:BMJ-PG Sponsor.
Figure 1 This low power view (×20) demonstrates the widespread
areas of necrosis within the lymph node.
Figure 3 Higher power (×400) showing histiocytes with J-shaped
nuclei. No neutrophils or eosinophils are present.
Fujimoto lymphadenitis/histiocytic necrotising lymphadenitis.
Immunohistochemistry revealed no CD30-positive
Reed-Sternberg type cells. The nodules of histiocytes stained The most common presentation of KFD is fever, night sweats
with CD68 in keeping with KFD.” and lymphadenopathy; less common symptoms include weight
This condition is self-resolving; therefore, all medications loss, rash, joint pain, diarrhoea and fatigue.4 These symptoms
were stopped barring antifever treatment. The patient was reas- mimic the presentation of a number of serious conditions such
sured and advised regarding the possibility of relapse. as TB, lymphoma, HIV, systemic lupus erythematous, toxoplas-
mosis and infectious mononucleosis.
Diagnosis is confirmed by biopsy of the affected lymph nodes
DISCUSSION which are usually firm, mobile and smooth in nature.
Kikuchi disease was first reported in the Japanese Journal of the Lymphadenopathy in KFD is normally isolated to a single loca-

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Haematological Society by Dr Masahiro Kikuchi in 1972 and tion in 83% of cases. Cervical nodes are most commonly
again, independently, by Fujimoto and his team in the same affected.5 Cases of generalised adenopathy involving axillary,
year.1 2 Dr Masahiro Kikuchi presented a case of lymphadenitis inguinal and mesenteric nodes are more unusual.5 Biochemical
characterised by follicular hyperplasia and paracortical expan- markers are non-specific. A raised CRP and erythrocyte sedi-
sion of histiocytes in the initial phase, T-cell and B-cell blasts mentation rate (ESR) is evident in 70% of patients and leuco-
and lymphocytes in the proliferative phase followed by necrotis- penia in 20–32% but otherwise blood tests are often
ing phase.1 Necrosis in the later stages is characterised by a pre- unremarkable.6 Anaemia of chronic disease, deranged liver func-
dominance of histiocytes without neutrophilic infiltrate.1 2 This tion tests and pancytopenia have also been reported.6 The aeti-
helps to differentiate it from other conditions and for this ology is unknown, theories postulated include an autoimmune
reason Kikuchi-Fujimoto disease (KFD) is also known as histio- aetiology with a possible infectious trigger with toxoplasmosis,
cytic necrotising lymphadenitis. CMV, human herpes virus, varicella zoster virus, para-influenza
The disease is predominantly prevalent in Asian countries, virus and Epstein-Barr virus all been implicated. Apoptotic cell
particularly within Japanese populations but it has been death mediated by cytotoxic CD8-positive T lymphocytes is the
reported in all ethnic groups. The disease has a female prepon- principal mechanism of cellular destruction. Histiocytes may act
derance in particular, those in the second and third decades of as enhancers.7 8 A possible autoimmune link with systemic
life.3 4 lupus erythematosus (SLE) has been considered to be some
patients have gone on to be diagnosed with SLE after
Kikuchi-Fujimoto diagnosis.9
Immunohistochemical stains are helpful in differentiating
KFD from lymphomas. The large cells are negative for CD3
and CD20, which excludes the possibility of lymphoma but
positive for CD68, which demonstrates their histiocytic
feature.10
Treatment is with supportive therapy, and symptoms normally
resolve within 4–6 months. In some cases, however prednisol-
one, antibiotics, intravenous immune globulins and hydroxycho-
lorquine have also been used to help aid recovery in those with
persistent symptoms.11–13 Relapse is also possible, and a positive
antinuclear antibody test is associated with a higher risk of
recurrence.8
Although rare, a substantial quantity of research has been con-
ducted on KFD. Only a small number of cases have been
reported in the UK.14 A literature search conducted in the BMJ
Case Notes reported 14 previous cases, and of those 14, 3 were
Figure 2 The abundant apoptotic debris admixed with histiocytes
(×200). in the UK and 1 in the Ireland.15 16

2 McKenna C, et al. BMJ Case Rep 2017. doi:10.1136/bcr-2016-217500

 Rare disease

BMJ Case Reports: first published as 10.1136/bcr-2016-217500 on 4 January 2017. Downloaded from http://casereports.bmj.com/ on 4 November 2020 at Madagascar:BMJ-PG Sponsor.
It is highly possible that cases are misdiagnosis by clinicians. regarding the accuracy or integrity of the article are investigated and resolved by all
Reporting such cases would increase awareness and consider- four authors, particularly CM, AB and TW.
ation of KFD as a differential diagnosis. KFD should be consid- Competing interests None declared.
ered in young patients presenting with fever, night sweats and Patient consent Obtained.
tender lymphadenopathy. A timely histological diagnosis could Provenance and peer review Not commissioned; externally peer reviewed.
prevent misdiagnosis and inappropriate use of antibiotics or
immunomodulatory drugs.10 REFERENCES
1 Kikuchi M. Lymphadenitis showing focal reticulum cell hyperplasia with nuclear
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Learning points A new clinicopathological entity. Naika 1972;20:920–7.
3 Aminiafshar S, Namazi N, Abbasi F. Kikuchi-Fujimoto disease in 21-year-old man.
Int J Prev Med 2013;4:964–6.
▸ Kikuchi-Fujimoto’s disease (KFD) should be considered to be 4 Kucukardali Y, Solmazgul E, Kunter E, et al. Kikuchi-Fujimoto disease: analysis of
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13 Srikantharajah M, Mahendra P, Vydianath B, et al. Kikuchi-Fujimoto disease: a rare
but important differential diagnosis for lymphadenopathy. BMJ Case Rep
Acknowledgements The authors thank Abdul Ganjifrock, Consultant
2014;2014:pii: bcr2014205470.
Histopathologist at Pennine Acute Hospital Trust, for approving and supplying them 14 Mannu G, Ahmed F, Cunnick G, et al. A rare cause of axillary lymphadenopathy:
with the figures for this publication. Finally, the author expresses gratitude to the Kikuchi’s disease. BMJ Case Rep 2014;2014:pii: bcr2013203100. .
patient for allowing them to use her case history as case study.
15 Mayooran N, O’Cathain E, Bresnihan MN, et al. Kikuchi-Fujimoto disease: an
Contributors CM and TW involved in the conception and design, acquisition of unusual cause of neck swelling in pregnancy. BMJ Case Rep 2015;2015:pii:
data or analysis and interpretation of data. NP came up with the concept. CM, TW, bcr2014206505.
NP and AB were involved in drafting the article or revising it critically for important 16 Ramanan A, Wynn R, Kelsey A, et al. Systemic juvenile idiopathic arthritis, Kikuchi’s
intellectual content, and all authors provided approval of the version published. All disease and haemophagocytic lymphohistiocytosis—is there a link? Case report and
authors agree to be accountable for the article and to ensure that all questions literature review. Rheumatology 2003;42:596–8.

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McKenna C, et al. BMJ Case Rep 2017. doi:10.1136/bcr-2016-217500 3