Kikuchi–Fujimoto Disease: A Rare but Important Cause
of Fever and Lymphadenopathy in Pregnant Women
Fevzi Altuntas,1*Ismail Sari,1Ozlem Canoz,2Orhan Yildiz,3Bulent Eser,1
Mustafa Cetin,1and Ali Unal1
1Department of Hematology–Oncology, Erciyes University, Faculty of Medicine, Dedeman Oncology Hospital, Kayseri, Turkey
2Department of Pathology, Erciyes University, Faculty of Medicine, Dedeman Oncology Hospital, Kayseri, Turkey
3Department of Infectious Diseases, Erciyes University, Faculty of Medicine, Dedeman Oncology Hospital, Kayseri, Turkey
We report a case of Kikuchi–Fujimoto disease (KFD) in a 28-year-old pregnant woman
with prolonged fever and generalized lymphadenopathy. We evaluated the patient for
etiology of the fever and adenopathy, which were unresponsive to antibiotic therapy.
Cervical lymph node histology showed KFD. Currently, there is scant data available
regarding the course and treatment of KFD during pregnancy. We administered steroid
therapy (prednisone 1 mg/kg/day) to control severe systemic and constitutional symp-
toms. We observed a reduction in lymph node size as well as abatement of fever and
other constitutional symptoms. The patient carried the fetus to full term with no apparent
adverse effect. Our experience showed that steroid therapy may be used effectively to
control KFD-related symptoms after the first 16 weeks without terminating the preg-
nancy. Am. J. Hematol. 81:118–120, 2006.
ª 2006 Wiley-Liss, Inc.
Key words: Kikuchi–Fujimoto disease; treatment; steroid; pregnancy; fever; lymphadeno-
Kikuchi–Fujimoto disease (KFD) is a rare disorder
seen generally in women of childbearing age; it presents
nosis is based on histopathological findings, which are
characterized byhistiocytic proliferation and necrosisof
[1,2]. However, recurrent and even fatal cases have been
reported in the literature [3,4]. In addition, KFD has
been associated with lymphoma , systemic lupus
erythematosus (SLE) , rheumatic diseases , infec-
tious diseases [8,9], neurologic disorders , interstitial
lung disease , and hemophagocytic syndrome .
Anti-inflammatory treatment, steroids, and immuno-
suppressive therapy have all been used to control the
disease [1,13,14]. There is, however, very little data con-
cerning the management of pregnant patients with
KFD and its effect on mother and fetus. Our research
revealed only one self-limiting case during pregnancy
. In this report, we discuss the management of a
pregnant patient with severely symptomatic KFD.
ª 2006 Wiley-Liss, Inc.
A 28-year-old female, gravida 2, para 1, was
admitted to the hospital with complaints of fever,
painful and tender swelling in both sides of her neck,
rigors, fatigue, malaise, myalgias, arthralgias, and a 5-
kg weight loss over the previous 3 weeks. Upon exam-
ination, the patient appeared acutely ill; axillary tem-
perature was 38.5?C, which rose progressively as high
as 39?C, usually increasing at night. She had multiple,
discrete, and tender lymphadenopathies located in the
bilateral submandibular, cervical, and supraclavicular
areas; the largest was 2–3 cm in diameter. There was
no sign of splenomegaly or hepatomegaly. With the
*Correspondence to: Fevzi Altuntas, M.D., 1901 W. Springcreek,
Apt. #1113, Plano, TX, 75023.
Received for publication 11 February 2005; Accepted 7 June 2005
American Journal of Hematology 81:118–120 (2006)
exception of 3 months of oral iron therapy, history on
admission was normal. Laboratory studies revealed
the following abnormalities: erythrocyte sedimentation
rate, 54 mm/hr; CRP, 9.0 mg/dL (normal range, <3
mg/dL); Hb, 10.6 g/dL; Htc, 30%; WBC, 3.4 ? 109
(46% segmented neutrophils, 40% lymphocytes, 12%
band forms, 2% monocytes); AST, 216 U/L (normal
range, 10–40 U/L); ALT, 216 U/L (normal range, 7–40
U/L); GGT, 120 U/L (normal range, 0–40 U/L);
LDH, 1299 U/L (normal range, 0–450 U/L). Labora-
tory studies related to anemia showed that transferrin
saturation was 28% (normal range, 20–40%), ferritin
was 440 ng/L (normal range, 22–322 ng/L), vitamin
B12was 300 pg/mL (normal range, 211–911 ng/L),
folic acid was 16 ng/mL (normal range, 3.1–20 ng/
mL), and reticulocyte index was 1.42% (normal
range, 0.6–2.6%). Urinalysis revealed no abnormal-
ities. PPD test was negative. Bone marrow, blood,
urine, and throat cultures grew no organisms. Tests
for ANA, ANCA, anti-ds-DNA, and RF were all
negative. C3 and C4 complement levels were normal.
Serologic tests for hepatitis A, B, and C, HIV, EBV,
CMV, and parvovirus B19, brucellosis, syphilis, and
toxoplasmosis were negative. An X-ray of the chest
was clear. Ultrasonography of the abdomen revealed a
live, healthy, normal fetus of approximately 16 weeks.
A peripheral-blood smear was normal except for hypo-
chromia and microcytosis in the red blood cells. A
bone marrow biopsy revealed normocellular marrow
with no tumor cells or granuloma.
Although ampicillin (4?500 mg/PO/day) was given
over 10 days, there was no clinical improvement;
spiking fever and constitutional symptoms persisted.
Biopsy of a right cervical lymph node showed his-
tiocytic necrotizing lymphadenitis typical of KFD
(Figs. 1 and 2), and a hematopathogist subsequently
reported the diagnosis. Prednisone therapy was
started at 1 mg/kg/day ? 3 weeks. Tapered steroid
therapy was discontinued at 8 weeks. At 1-, 3-, and
5-month follow-up visits, the patient was symptom-
free with no clinical or laboratory evidence of KFD
or other concomitant diseases. However, gestational
diabetes mellitus was diagnosed; this was controlled
with dietary therapy. The patient carried the fetus to
full term with no apparent adverse effect. Growth and
development of child remain normal 6 months after
delivery and ongoing.
As previously discussed, the etiology of Kikuchi–
Fujimoto disease is unknown; it usually occurs in
young women [1,2]. It generally presents with
enlarged painful lymph nodes accompanied by a com-
bination of other associated nonspecific symptoms
and findings, which may include fever, cutaneous
manifestations, sweats, malaise, chills, nausea, vomit-
ing, weight loss, myalgias, arthralgias, fatigue, and
hepatosplenomegaly [1,2,16,17]. Diagnosis is con-
firmed via histopathological findings of lymph node
biopsy. Nevertheless, diagnosis of KFD should be
differentiated from other diseases such as lymphoma,
tuberculous, sarcoidosis, cat-scratch fever, still’s dis-
ease, toxoplasmosis, and angioimmunoblastic lym-
phadenopathy and SLE, all of which have different
treatments and prognoses [1,16–19].
While KFD symptoms generally resolve sponta-
neously over several months with a favorable outcome
in most patients [2,15], in some cases, the course of the
disorder appears to be unpredictable with respect to
severity, complications, response to therapy, and prob-
ability of development of other diseases . Also,
there have been a few, rare reports of fatalities regard-
ing patients with worsening, extensive disease, who
were also immune-compromised [3,4].
There are scarce data concerning therapeutic
requirements for this disease during pregnancy;
Dubois et al. report that there was no response to
antibiotic therapy, and that, without treatment,
KFD had no detectable impact on the course of
pregnancy, delivery, or infancy . Although there
is currently no consensus about therapy in patients
with KFD and corticosteroid therapy’s toxicities on
mother and fetus are well known, we used steroid
therapy to control the disease in a patient with a
prolonged course of severe systemic and constitu-
tional symptoms which showed no response to
ampicillin therapy. Steroid therapy is also recom-
mended in patients with SLE , hemophagocytic
syndrome , and rheumatic disorders  and in
those who are unresponsive to antibiotic therapy
or have severe symptoms [13,14]. After initiation
of steroid treatment, we observed a reduction in
lymph node size as well as abatement of fever and
other constitutional symptoms. However, we also
diagnosed gestational diabetes mellitus, which was
controlled with dietary therapy. The patient deliv-
ered a healthy baby and remains symptom-free at
follow-up and ongoing. It may be noted that an
alternative form of therapy, hydroxychloroquine,
has been used successfully in KFD  and may
be safely used in pregnancy.
Our experience leads us to conclude that the
workup for a differential diagnosis of prolonged
fever and lymphadenopathy resistant to antibiotic
treatment during pregnancy should include biopsy
for KFD. Because it usually has a self-limiting course,
KFD is not of itself an indication for termination of
pregnancy In the event of a positive finding, steroid
therapy may be used effectively to control KFD-
Case Report: Kikuchi–Fujimoto Disease in Pregnant Women119
related symptoms after the first 16 weeks, thus avoid- Download full-text
ing the need for termination of the pregnancy.
1. Lee KY, Yeon YH, Lee BC. Kikuchi–Fujimoto disease with pro-
longed fever in children. Pediatrics 2004;114(6);752–756.
2. Lin CW, Chang CL, Li CC, Chen YH, Lee WH, Hsu SM. Spon-
taneous regression of Kikuchi lymphadenopathy with oligoclonal
T-cell populations favors a benign immune reaction over a T-cell
lymphoma. Am J Clin Pathol 2002;117:627–635.
3. Tsai MK, Huang HF, Hu RH, et al. Fatal Kikuchi–Fujimoto
disease in transplant recipients: a case report. Transplant Proc
4. Lin SH, Ko WS, Lee HS, Hwang WS. Kikuchi’s disease associated
with lupus-like syndrome: a fatal case. J Rheumatol 1992;19:
5. Yoshino T, Mannami T, Ichimura K, et al. Two cases of histiocytic
necrotizing lymphadenitis (Kiku-chi–Fujimoto’s disease) following
diffuse large B-cell lymphoma. Hum Pathol 2000;31:1328–1331.
6. Chen YH, Lan JL. Kikuchi disease in systemic lupus erythemato-
sus: clinical features and literature review. J Microbiol Immunol
7. Cousin F, Grezard P, Roth B, Balme B, Gregoire-Bardel M,
Perrot H. Kikuchi disease associated with Still disease. Int J
8. Stephan JL, Jeannoel P, Chanoz J, Gentil-Perret A. Epstein-Barr
virus-associated Kikuchi disease in two children. J Pediatr Hema-
tol Oncol 2001;23:240–243.
9. Pasquinacci S, Donisi PM, Cavinato F, Belussi F. Kikuchi’s dis-
ease in a patient infected with AIDS. AIDS 1991;5:235.
10. Sato Y, Kuno H, Oizumi K. Histiocytic necrotizing lymphadenitis
(Kikuchi’s disease) with aseptic meningitis. J Neurol Sci 1999;163:
11. Sharma OP. Unusual systemic disorders associated with intersti-
tial lung disease. Curr Opin Pulm Med 2001;7:291–294.
12. Mahadeva U, Allport T, Bain B, Chan WK. Haemophagocytic
syndrome and histiocytic necrotising lymphadenitis (Kikuchi’s dis-
ease). J Clin Pathol 2000;53:636–638.
13. Famularo G, Giustiniani CM, Marasco A, Minisola G, Nicotra
CG, De Simone C. Kikuchi–Fujimoto lymphadenitis: case report
and literature review. Am J Hematol 2003;74:60–63.
14. Jang YJ, Park KH, Seok HJ. Management of Kikuchi’s disease
using glucocorticoid. J Laryngol Otol 2000;114:709–711.
15. Dubois RE, Bondell S, Krissman PH. Kikuchi–Fujimoto syn-
drome during pregnancy. South Med J 1991;84(8):1029–1030.
16. Mugnaini EN, Watson T, Guccion J, Benator D. Kikuchi disease
presenting as a flu-like illness with rash and lymphadenopathy.
Am J Med Sci 2003;325:3437.
17. Rezai K, Kuchipudi S, Chundi V, Ariga R, Loew J, Sha BE.
Kikuchi–Fujimoto disease: hydroxychloroquine as a treatment.
Clin Infect Dis 2004;39(12):124–126.
18. Chamulak GA, Brynes RK, Nathwani BN. Kikuchi–Fujimoto
disease mimicking malignant lymphoma. Am J Surg Pathol 1990;
19. Dorfman RF, Berry GJ. Kikuchi’s histiocytic necrotizing lympha-
denitis: an analysis of 108 cases with emphasis on differential
diagnosis. Semin Diagn Pathol 1988;5:329–345.
20. Santana A, Lessa B, Galrao L, Lima I, Santiago M. Kikuchi–Fu-
jimoto’s disease associated with systemic lupus erythematosus:
case report and review of the literature. Clin Rheumatol 2005;
21. Graham LE. Kikuchi–Fujimoto disease and peripheral arthritis: a
first! Ann Rheum Dis 2002;61:475.
120 Case Report: Altuntas et al.