Kikuchi’s disease is a rare, benign
clinicopathological condition presenting with fever and lymphadenopathy.
Its association with Systemic Lupus Erythematosus (SLE) makes it
necessary to be aware of this condition and follow up these children. We
report this child with Kikuchi’s disease. Kikuchi’s disease should be
considered as differential diagnosis in young patients with cervical
lymphadenopathy and fever of unknown origin.
Case Report
An 11-year-old girl presented with history of fever
for 45 days. Fever was intermittent, high grade, accompanied by headache
and non- productive cough. She was anorexic with a weight loss of 3 kg.
Her parents had noticed swellings on the left side of her neck, which
were painful and had gradually increased in size over the last 2 weeks.
There was no history of vomiting, rash, arthralgia, breath-lessness,
mucosal bleed or contact with tuberculosis. On examination she was
conscious, febrile, not toxic. She had 5 to 7 tender, enlarged left
cervical lymphnodes of 2 × l cms size. There were no rashes or
generalized lymphadenopathy. The exami-nation of other systems was
normal.
Investigations revealed hemoglobin 11.2 g/dL, TLC
2,700 cells/mm3, with a normal differential count and peripheral smear,
platelet count 3.5 lacs/mm3 and ESR 29 mm/hr. Blood and urine cultures
were sterile. Mantoux, Widal, Leptospirosis-IgM, HbsAg and HIV by ELISA
were negative. Chest skiagram was normal and ultrasonography of the
abdomen showed mild splenomegaly. Paul Bunnel test, LE cell and ANA were
negative. Her complement levels (C3 and C4) were normal. Bone marrow
study was normal and culture was sterile. VCA (Viral Capsid Antigen) IgM
for EBV (Epstein Barr virus) was positive 18 U/mL (>12U/mL = positive).
Excision biopsy of the enlarged left cervical node was done and the
histopathology revealed lymphnode with essentially preserved
architecture with multiple areas of histiocytic aggregates showing
necrosis and karyorrhexis with few C-shaped monocytoid cells. No
granulomas were seen. There were no neutrophils in the area of
karyorrhexis. Sheets of foamy histiocytes amidst blood vessels were
seen. The findings were consistent with necrotising histiocytic
lymphadenitis i.e., Kikuchi’s disease.
Discussion
Kikuchi and Fujimoto independently first reported
Kikuchi-Fujimoto disease or histiocytic necrotising lymphadenitis
without granulocytic infiltration in Japan in 1972. It is considered as
a self-limiting benign systemic lymphadenitis, especially involving the
cervical nodes of unknown cause(1). Though it has been reported
worldwide, it still remains a poorly recognized clinicopathological
entity and is confused with malignant lymphoma and systemic lupus
erythematosus (SLE). There are only few case reports of this disease in
children(2).
The etiology of Kikuchi’s disease is not known.
Various etiological agents like human herpes virus (HHV6 and HHV8),
herpes simplex virus, adenovirus, parvovirus B19, cytomegalovirus,
varicella zoster, dengue virus(3), bacteria such as Mycobacterium
azulgai, yersinia and protozoa have been linked to the disease(1).
Kikuchi’s disease is included in the protean manifestations of chronic
EBV infection and could be a cause in this child. Neoplastic conditions,
autoimmune disorders and physiochemical agents have also been
postulated. These agents are thought to stimulate a particular immune
response resulting in this disease(1,4). Familial occurrence has been
reported and hence a genetic predisposition has been proposed(5). The
inter relationship between SLE and Kikuchi’s disease, though strong is
still complex. Some authors feel that Kikuchi’s disease is a forme
fruste of SLE. There are also reports that suggest that Kikuchi’s
disease may progress to SLE, hence it is mandatory to exclude SLE and
follow these children for several years to ensue early diagnosis of this
autoimmune disease, since the prognosis and management differ(5,6).
Pathologically malignant lymphoma resembles Kikuchi’s disease.
Hemophagocytic syndrome is also hypothesised as a part of this
diseas(7). It is postulated that the plasmacytoid monocytes play a role
in the pathogenesis of Kikuchi’s disease via a cell mediated cytotoxic
immune response(8).
The important clinical features of Kikuchi’s disease
are a female predominance (M:F 1:4) with a mean age of 30 years and
painless lymphadenopathy mostly in cervical region. The other reported
features are fever, myalgia, sore throat, localized pain with mild
leucopenia and increased LDH(1). Cutaneous lesions like facial rash,
exudative erythema, erythematous papules, vasculitis, plaques and
nodules are observed in 40% of cases. They manifest simultaneously or
after the illness(9). Arthralgia has also been reported. The symptoms
resolve spontaneously within two to three months. Biopsy of the
lymphnode is diagnostic. The pathological features of the affected
lymphnode are patchy or confluent area of necrosis, varying amount of
nuclear debris in affected area, aggregates of histiocytes, presence of
medium - large sized transformed lymphocytes (immunoblasts) and
plasmacytoid T cells, absence of neutrophils and eosinophils(8).
Cytoplasmic tubuloreti-cular structures resembling viral particles or
aberrant organelle structures have been identified by electron
microscopy(10). CT scan of the affected lymphnode shows hypodense
centers with peripheral ring enhancement corresponding to the central
necrosis. Kikuchi’s disease causes diagnostic difficulties because of
lack of specific signs, symptoms and serological markers. The diagnosis
is based on histopathological findings, overlapping of histological
features requires differentiating it from a number of infections,
autoimmune and lymphoproli-ferative disease. SLE is the most difficult
differential diagnosis, but the complete absence of neutrophils is a
good clue, though this does not exclude the possibility of evolution to
SLE. In the majority of cases it is a self-limiting disease, recurrence
has been reported in 3% cases. There are reports of rapid resolution
with steroids. The early recognition of this disease helps in avoiding
unnecessary investigations and treatment(4).
Contributors: MS and RV were involved in
conception and design of the article, acquisition of data, analysis and
interpretation of data; SoS was involved in drafting of the manuscript,
critical revision of the manuscript for important intellectual content
and final approval of the manuscript.
Funding: None.
Competing Interests: None stated.
