Open Journal of Pediatrics, 2011, 1, 67-71
doi:10.4236/ojped.2011.14016 Published Online December 2011 ( OJPed
Published Online December 2011 in SciRes.
An atypical presentation of Kikuchi-Fujimoto disease
mimicking systemic lupus erythematosus: case
report and literature review
Diane Belder-Preston1*, Catherine-Maude Pound1,2, Roman Jurencak1,3
1Department of Pediatrics, Children’s Hospital of Eastern Ontario, Ottawa, Canada;
2Division of Pediatric Medicine, Children’s Hospital of Eastern Ontario, Ottawa, Canada;
3Division of Rheumatology, Children’s Hospital of Eastern Ontario, Ottawa, Canada.
Email: *
Received 1 October 2011; revised 5 November 2011; accepted 18 November 2011.
Purpose: To report a case of atypical Kikuchi-Fuji-
moto disease (KFD) that illustrates several overlap-
ping features with systemic lupus erythematosus
(SLE). Methods: A case is reported followed by a re-
view of the current literature. Case Report: A 16- year-
old boy with an unusual manifestation of Kikuchi-
Fujimoto disease (KFD) is described. The patient
presented with fever, weight loss and severe abdomi-
nal pain, due to extensive necrotizing retroperitoneal
and mesenteric lymphadenopathy. During the course
of his illness, he developed several symptoms sugges-
tive of systemic lupus erythematosus (SLE): a peri-
cardial effusion, cotton wool spots on the retina and
antibodies against nuclear antigens (ANA), Smith
(Sm) and ribonucleoprotein (RNP) antigens. However,
no additional features of SLE were found. The pa-
tient subsequently fully recovered within two months,
without initiation of immunosuppressive therapy. His
autoantibodies became negative five months after
initial presentation and he remains well at his 23
month follow up visit. Discussion: We hypothesize
that the autoantibodies developed by our patient
were secondary to self-antigen induced autoimmunity
related to his extensive tissue necrosis. Despite ini-
tially having clinical features suggestive of SLE, our
patient’s full and spontaneous recovery strongly
supports the diagnosis of KFD. This illustrates the
need for careful diagnosis, in order to avoid unneces-
sary and potentially toxic treatment with immuno-
suppressive agents.
Keywords: Kikuchi-Fujimoto’s Disease; Retroperitoneal
Lymphadenitis; Systemic Lupus Erythematosus (SLE);
Antinuclear Antibodies (ANA)
Kikuchi disease, also called Kikuchi-Fujimoto Disease
(KFD) and Histiocytic Necrotizing Lymphadenopathy, is
a rare, benign, self-limited disease of unknown etiology.
KFD was first reported in 1972 by Kikuchi [1] as well as
independently, by Fujimoto et al. [2]. Typical features of
the disease include subacute regional lymphadenopathy
predominantly involv ing cerv ical lymph nodes as well as
fevers, often accompanied by leukopenia, high erythro-
cyte sedimentation rate (ESR), and anemia [3]. Exci-
sional biopsy of the affected lymph node shows non-
specific histopathologic features of cortical and paracor-
tical necrosis. No specific diagnostic imaging or labora-
tory tests are available and KFD remains a diagnosis of
exclusion. Clinicians must rule out other causes of ne-
crotizing lymphadenopathy, such as malignancy, sys-
temic connective tissue disorders, and infectious lym-
phadenitis, before diagnosing KFD. These other diagno-
ses have different therapeutic and prognostic implica-
tions. This can result in costly and invasive investiga-
tions, potentially causing significant distress to the pa-
tient and family.
We describe the case of a young man who presented
to a pediatric tertiary care centre with atypical features
of Kikuchi-Fujimoto Disease.
A 16-year-old, previously healthy, Caucasian boy pre-
sented to a pediatric tertiary care centre with a three-
week history of intermittent abdominal pain, vomiting,
anorexia and a seven-kilogram weight loss. He also had
a two-week history of intermittent fevers, up to 40 de-
grees Celsius, associated with a faint diffuse erythema-
tous rash involving the face and upper torso. Personal
and family histories were noncontributory.
Physical examination on admission revealed a pale,
D. Belder-Preston et al. / Open Journal of Pediatrics 1 (2011) 67-71
thin boy, weighing 59.7 kg. His vital signs were: heart
rate 120, blood pressure 121/81, respiratory rate 16 and
oxygen saturation 98% in room air. He was afebrile with
a faint malar flush. His abdomen was non-acute but dif-
fusely tender with no hepatosplenomegaly. The remain-
der of the examination was unremarkable. No peripheral
lymphadenopathy was appreciated.
Laboratory investigations showed elevated inflamma-
tory markers, mild non-hemolytic anemia, transaminitis
and markedly elevated lactate dehydrogenase (LDH)
(Table 1). Autoantibodies (anti-nuclear antibodies (ANA),
anti-neutrophil cytoplasmic antibodies, rheumatoid fac-
tor and antiphospholipid antibodies) were all negative.
Complement (C3, C4) and total immunoglobulin levels
(IgG, IgA and IgM) were within normal limits.
A Computerized Tomography scan of his abdomen
demonstrated significant lymphadenopathy in both the
retroperitoneum and the root of the mesentery. Explor-
ative laporotomy with lymph node biopsy showed ne-
crotizing lymphadenitis with extensive tissue necrosis,
without evidence of neutrophilic inflammation or pres-
ence of granulomas. In one section, a vessel with intra-
mural chronic inflammation suspicious for vasculitis was
observed. Special stains for infectious organisms and
immunophenotyping for neoplastic cells yielded nega-
tive results.
Given the absence of a definitive diagnosis, further
investigations were performed. These included bone
marrow studies to rule out malignancy, upper and lower
endoscopies with biopsies to rule out atypical inflam-
matory bowel disease and Whipple’s disease, as well as
an extensive infectious work up. Tuberculosis, Epstein-
Barr virus, toxoplasmosis, parvovirus, cytomegalovirus,
Streptococcus pneumonia, and fungal infections were
excluded. Ophthalmologic examination uncovered mul-
tiple retinal cotton wool spots. Cardiac echocardiogra-
phy demonstrated a moderate-sized pericardial effusion
with no hemodynamic compromise. Magnetic Reso-
nance Angiography of the abdomen, as well as a Mag-
netic Resonance Imaging of the hip and shoulder girdles
helped to exclude the diagnoses of vascu litis and myosi-
During his hospitalization, our patient received mainly
supportive care after a brief three-day course of a third
generation cephalosporin antibiotic pending negative
cultures. The severity of his abdominal pain was such
that he required morphine, gabapentin, ketorolac and
clonidine. Because of poor ap petite, food intoleran ce and
ongoing weight loss, total parenteral nutrition was initi-
Atypical Kikuchi-Fujimoto disease was suspected
based on the presence of necrotizing non-granulomatous
retroperitoneal lymphadenitis and the exclusion of other
disorders. Intravenous immunoglobulin therapy was
offered but declined by the patient’s family. Steroid
therapy was not offered as there was still a degree of
uncertainty in terms of the diagnosis of KFD at that
With supportive management only, the patient’s clini-
cal status improved. By day 30 of hospitalization, he was
ambulating, tolerating increasing naso-gastric feeds and
demonstrating consistent weight gain. At the family’s
request, the patient was transferred to another tertiary
care centre for a second opinion.
At the second hospital, approximately one month after
his initial biopsy, the patient underwent another laporo-
tomy with lymph node biopsy. Extensive bland necrosis
with numerous macrophages was reported. Histiocytes,
lymphocytes and minor plasma cell populations were
scattered throughout. Again, no neutrophilic infiltration
Table 1. Laboratory data.
Reference range During admission Eight weeks after admission Five months after admission
ESR (mm/Hr) 0 - 10 63 13 6
CRP (mg/L) <8.0 15 < 1 <1
Ferritin (ug/L) 24 - 336 1408 968
WBC (×109 L) 4.5 - 11 10.6 4.85 4.5
Hb (g/L) 120 - 160 90 129 153
Plt (×109 L) 150 - 450 382 393 229
AST (U/L ) 14 - 50 265 19 26
ALT (U/L) 10 - 55 143 17 20
LDH (U/L) 300 - 700 3016 399 468
ESR, erythrocyte sedimentation rate; CRP, C reactive protein; WBC, White blood cell; Hb, Hemoglobin; Plt, Platelet; AST, Aspartate aminotransferase; ALT,
lanine transaminase; LDH, lactate dehydrogenase. A
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D. Belder-Preston et al. / Open Journal of Pediatrics 1 (2011) 67-71 69
or granuloma was seen. Absence of hematoxylin bodies
was noted. No infectious etiology was identified. On
repeat testing, some of the patient’s autoantibodies and
immunoserologies became positive (Table 2). Labora-
tory methods used to detect these autoantibodies were
identical at both hospitals (ANA by indirect immuno-
fluorescence using Hep-2 cell line as substrate, ENA by
ELISA). Nonetheless, he continued to improve with
supportive treatment only, and no immunosuppressive
therapy was initiated. There was full resolution of his
pericardial effusion, and disappearance of the cotton
wool spots on his retina.
The patient was discharged home with a presumed
diagnosis of KFD. He now remains completely asymp-
tomatic 23 months after hospital discharge. His previ-
ously abnormal inflammatory markers and positive im-
munoserologies have completely normalized (Tables 1
and 2).
In this report, we present a case of atypical KFD with
retroperitoneal lymph node involvement and several
features initially suggestive of SLE.
Most of the literature on KFD comes from the adult
population, with the exception of several case series and
reports published in the pediatric literature [3-10]. Young
adults are predominantly affected, with a reported mean
age of 25 years, as shown by a meta-analysis of 181
worldwide publications looking at 244 patients [7].
Cases have however been reported in all age groups,
ranging from 19 months to 75 years [11]. Two recent
pediatric case series, one from Korea [6] and the other
from Taiwan [5], reported a mean age of 11 and 12.8
years respectively. Historically, there has been a higher
predilection for young women, although a recent com-
prehensive review reported a ratio closer to 1:1 [11]. In
the pediatric population, the ratio seems to be higher in
boys with reported ratios ranging from 1.4 to 2.8:1 [5,
KFD typically presents with cervical lymphadenopa-
thy. Low-grade fevers, fatigue, skin rashes affecting the
face and the upper body, nausea, vomiting, diarrhea and
weight loss are also reported [7,9,11]. Cases of non-cer-
vical lymphadenopathy have been described; generalized,
axillary, iliac and retroperitoneal lymphadenopathy (re-
ported in 0 to 3% of cases) [4,12,13]. Rimar et al. [14]
retrospectively reviewed 19 cases of possible KFD from
seven medical centers in Israel between 1980 and 2007.
In their study, a much higher rate of retroperitoneal and
generalized lymphadenopathy was reported as compared
to the rate reported in previous Far East studies. They
found that 21% and 26% of cases presented with retro p-
eritoneal and generalized lymphadenopathy, respec-
Our patient presented with severe necrotizing ab-
dominal lymphadenopathy without other lymph node
involvement. Moreover, during the course of his illness,
he developed several features suggestive of SLE (retinal
vasculitis with cotton wool spots, small pericardial effu-
sion and positive ANA, anti-Sm and anti-RNP antibod-
ies). There are several case reports discussing an asso-
ciation between KFD and SLE [7,15-18] and some pos-
tulating KFD as a self-limited SLE-like autoimmune
condition [19].
Our patient developed an autoantibody profile highly
suggestive of SLE. However, his autoantibodies were
positive only transiently and normalized within four
months, without the need for immunosuppressive ther-
apy. We hypothesize that the extensive necrotizing lym-
phadenopathy led to a release of self-antigens which, in
Table 2. Autoantibody t esting.
On admission Five weeks into the admission Four months after initial positive r e s u l t s
ANA Negative Positive Negative
ANA titer - 1:160 -
Anti-double stranded DNA - Negative Negative
ENA screen Negative Positive Negative
Anti Smith - Positive Negative
Anti RNP - Positive Negative
Anti Scl 70 - Negative Negative
Anti Ro - Negative Negative
Anti La - Negative Negative
NA, Anti-nuclear antibodies; RNP, Anti-ribonucleoprotein antibodies; ENA, Extractable Nuclear Antigens.
opyright © 2011 SciRes. OJPed
D. Belder-Preston et al. / Open Journal of Pediatrics 1 (2011) 67-71
the hyperinflammatory state, enabled mounting of a
pathologic immune response with production of autoan-
tibodies. Upon removal of the antigenic stimulation, the
pathologic production of autoantibodies ceased, leading
to their disappearance from the circulation. This hy-
pothesis is supported by the fact that, 23 months after
initial presentation, the patient remains off any therapy
and healthy.
Cotton wool spots, which were ob ser v ed in our patien t,
often indicate a serious systemic disease. They represent
acute, focal, inner retinal ischemia and may occur in any
disease that compromises arteriolar circulation to the
inner retinal layers which includes SLE and systemic
vasculitides where ischemia is caused by thrombogenic
effects from antigen-antibody complexes [20]. However,
similar to our patient, isolated, self-limited cotton wool
spots in patients with no identifiable systemic disease
have also been reported [21].
The presence of pericardial effusion in our patient
could indicate SLE as pericarditis is the most common
cardiac manifestation of this disease. However, transient
asymptomatic pericardial effusions are often seen in
instances of significant systemic inflammation, espe-
cially in the presence of accompanying hypoalbumine-
mia [22]. Our patient did have hypoalbuminemia (data
not shown). The pericardial effusion in our patient was
asymptomatic with spontaneous resolution. Pericarditis
accompanying KFD has not been previously described.
Histologically, SLE and KFD can be very challenging
to differentiate and at times impossible. In KFD, histo-
pathological findings include varying degrees of necrosis,
histiocytic proliferation with activated T lymphocytes,
small lymphocytes and plasma cells without granuloma-
tous inflammation with absent neutrophils and eosino-
phils. Adjacent vessels may be thrombosed. In contrast
to KFD, SLE lymphadenitis, demonstrates hematoxylin
bodies (aggregates of degenerated nuclear debris) and
Azzopardi phenomenon (degenerated nuclear material
aggregated in the walls of blood vessels). In SLE, abun-
dant plasma cells, prominent reactive follicular hyper-
plasia, sparse cytoxic T cells and capsular and pericap-
sular inflammation are seen [23,24]. In our patient’s bi-
opsy specimens, the presence of extensive necrosis
without neutrophilic inflammation or granulomas and
the absence of hematoxylin bodies support the diagnosis
of KFD rather than SLE or systemic vasculitis.
In conclusion, this report discusses a case of atypical
KFD and illustrates several overlapping features of KFD
and SLE. Our patient presented with retroperitoneal
lymphadenopathy, an unusual manifestation of KFD. He
demonstrated a transient elevation of autoantibodies
typically associated with SLE, as well as retinal vascu-
litis and pericardial effusion, not previously described in
patients with KFD. This illustrates the need for careful
differential diagnosis, as KFD is self-limited and, con-
trary to SLE, does not require long-term immunosup-
pressive therapy; ra ther, often only supportive ther apy is
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Kikuchi-Fujimoto disease (KFD),
Systemic lupus erythematosus (SLE),
Antinuclear antibodies (ANA),
lactate dehydrogenase (LDH),
erythrocyte sedimentation rate (ESR),
smith (Sm),
ribonucleoprotein (RNP),
C reactive protein (CRP),
White blood cell (WBC),
Hemoglobin (Hb),
Platelet (Plt),
Aspartate aminotransferase (AST),
Alanine transaminase (ALT).
opyright © 2011 SciRes. OJPed