Keywords
Kikuchi–Fujimoto disease - brachial plexopathy - histiocytic necrotizing lymphadenitis
- lymphadenopathy
Introduction
Persistent cervical and axillary lymphadenopathy is a common occurrence encountered
in clinics across Asian countries. The commonest presentation in young population
is secondary to infections of which extrapulmonary tuberculosis tops the list. Occasionally,
one encounters neoplastic lesions such as lymphomas.[1] In adults, these aberrant swelling warrant exclusion of metastatic malignant disease.
Kikuchi–Fujimoto disease (KFD) or subacute histiocytic necrotizing lymphadenitis is
a benign, rare, self-limiting disease, which usually presents itself with cervical
or axillary lymphadenopathy associated with fever.[2] Initially described in Japan, KFD was first reported in 1972 independently by Kikuchi
and Fujimoto et al. It has a higher prevalence among Asiatic individuals, often young
adults younger than 30 years with a female preponderance (female-to-male ratio, 4:1)[3]
We describe the case of a middle aged Indian woman who presented with cervical and
axillary lymphadenopathy due to KFD and its peculiar presentation as brachial plexus
neuritis.
Case Report
A 56-year-old woman presented with 2.5 months' history of fever, associated with swelling,
pain, and redness on the left side of neck and scapular region. She received several
courses of antibiotics without any benefit. Gradually, her pain started radiating
to left shoulder and was accompanied with paresthesia of left upper limb. Progressive
worsening of left hand grip was also noticed simultaneously. She denied sudden onset
of weight loss, dysuria, cough, and respiratory distress. There was no previous history
of tuberculosis or contact with a patient suffering from it, and she had no family
history of leukemia, lymphoma, systemic lupus erythematosus (SLE), rheumatoid arthritis,
or any other rheumatological disorders.
She had weakness in left elbow flexors, wrist flexors, finger abductors and adductors,
and thumb flexors and extensors. There was mild hypoesthesia over left C5 to C7 dermatome.
Regional examination revealed left tender supraclavicular and axillary lymphadenopathy.
The largest node was palpable in the left supraclavicular region and was ∼3 × 3 cm
in size. In addition, the nodes were also palpable in the anterior, central, and apical
group of the axillary lymph nodes. The cardiovascular, respiratory, and abdominal
systems were clinically normal.
Her blood investigations were unremarkable without any evidence of leucopenia. Additionally,
Mantoux test and polymerase chain reaction for mycoplasma were negative. The chest
X-ray showed no abnormality of bony thoracic cage with bilaterally normal lung fields.
An ultrasound of abdomen displayed an unremarkable study.
Magnetic resonance imaging (MRI) of cervical spine demonstrated a large lymph node
measuring ∼5 × 5 cm in the left supraclavicular region compressing over the upper
brachial plexus in the short T1 inversion recovery (STIR) sequences ([Fig. 1]). In addition, there were multiple lymph nodes along the cervical (level IV), superior
mediastinum, left subclavian, and axillary vessels. Incidentally, the patient also
had an annular disc bulge at C5–6 with right paracentral disc protrusion and right
oncovertebral osteophytes causing mild narrowing of the right neural foramina and
abutting the intraspinal nerve root.
Fig. 1 Magnetic resonance imaging (short T1 inversion recovery) of cervical spine showing
a large lymph node (arrow) in the left supraclavicular region compressing over the
brachial plexus.
Fine needle aspiration smears from the lesion exhibited mature lymphocytes, reactive
lymphoid cells, and macrophages without evidence of granuloma or atypical cells. An
excision biopsy of the largest supraclavicular lymph node was performed, upon which
the left upper limb symptoms of the patient resolved completely.
The excised specimen macroscopically had solid greyish surface with large area of
necrosis. The microscopic histopathology of sections showed features of necrotizing
lymphadenopathy with characteristic stellate necrosis rimmed with histiocytes and
immunoblasts and karyorrhectic debris without granulocytic infiltration. Multinucleate
giant cells or atypical cells were absent. Staining for acid-fast bacilli was also
negative ([Fig. 2]). Diagnosis of KFD was made on the basis of histological findings.
Fig. 2 Histopathology of lesion showing features of necrotizing lymphadenopathy with characteristic
stellate necrosis rimmed with histiocytes and immunoblasts and karyorrhectic debris
without granulocytic infiltration.
Following surgery, the patient was put on a regime of antibiotics, analgesics, and
steroids for 4 weeks to which patient effectively responded with resolution of neurological
deficits. A repeat scan after 4 months displayed significant resolution of lymphadenopathy
and patient remains asymptomatic till date ([Fig. 3]).
Fig. 3 Postoperative magnetic resonance imaging with reduction of lymphadenopathy.
Discussion
KFD is an extremely rare disease that shows sporadic worldwide distribution, but has
a higher prevalence amongst Japanese and other Asiatic individuals.[3] Its occurrence in the Indian subcontinent is rare. Mostly, sporadic case reports
find a mention from India and surrounding region. The largest series is from Pakistan
wherein Wahid et al documented 22 cases in the past decade.[4] The disease has a definite trend to manifest itself in young adults with an inclination
toward female preponderance. Mean age in various studies ranges from 25 to 30 years.
Although patients have also presented later in life as noted in studies by Dorfman
and Berry[2] (mean age, 30; range, 11–75) and Kucukardali et al[5] (mean age, 25; range, 1–64). Our patient presented with the disease at the age of
56 years.
Etiology of KFD is under speculation. Viral agent's role in pathogenesis of KFD remains
controversial and not convincingly demonstrated. Epstein–Barr viruses, human immunodeficiency
virus, human T-lymphotrophic virus 1, herpes simplex virus, and parvovirus B19 have
been suggested as causative agents. Bacterial agents such as Toxoplasma, Yersinia, Bartonella, and Brucella have also been implicated as causative agents.[6] Alternatively, an autoimmune mechanism has been proposed as electron microscopic
studies have identified tubular reticular structures in cytoplasm of stimulated lymphocytes
and histiocytes in KFD patients. These are also been identified in cells of patients
with SLE.[7] None of the causative agents or mechanisms could be identified in our case.
The onset of KFD is acute or subacute, evolving over period of 2 to 3 weeks. As in
our patient, cervical lymphadenopathy manifested as tender neck swellings and fever,
usually of low grade that are the hallmarks of the disease.[3]
[4] Patients, less commonly, may also have symptoms of arthralgia, skin rashes, weakness,
and night sweats. Few reports of weight loss, diarrhea, anorexia, nausea, vomiting,
chest, and abdominal pain are documented. Some patients may also have hepatosplenomegaly.[6]
Interestingly, KFD has been associated with various systemic complications, which
occasionally are completely unrelated to the disease itself. Panuveitis, cardiac tamponade,
isolated mediastinal lymphadenopathy, mesenteric lymphadenopathy, acute renal failure,
hepatitis, hemophagocytic syndrome, interstitial lung disease, and pleural effusion
have all been reported individually. In addition, rare central nervous system complications
like meningitis and aseptic encephalitis have also found mention. Peripheral neuropathy
has been reported as well.[8] To the best of our knowledge, there is only a single case report in the literature
wherein Sugiyama et al observed involvement of brachial plexus with right upper limb
paresis in a 22-year-old woman.[9] Brachial plexus neuritis was the unique feature of our case as well.
Differential diagnosis of KFD includes lymphoma, tubercular adenitis, lymphogranuloma
venereum and Kawasaki disease. Contrast-enhanced computed tomography and MRI (T2 and
STIR sequences) identify the enlarged lymph nodes distinctly and are good follow-up
tools to observe disease remission as well.
Owing to the acute onset and prolonged but benign, self-limiting course of the disease,
the treatment paradigm essentially encompasses achieving symptomatic relief for the
patient. Analgesics-antipyretics and nonsteroidal anti-inflammatory drugs are helpful
in alleviating the symptoms of fever and lymph node tenderness. Studies also mention
use of antibiotics and corticosteroids in severe, recurrent, and relapse cases and
have been found to be helpful.[5]
[10] Large lymph nodes that are symptomatic or lead to locoregional complications are
amenable to surgical excision. Otherwise the disease tends to resolve spontaneously
over several weeks to months.[2]
[5]
[11]
This case is unique for several reasons. First, the disease itself has a rare occurrence
and very few patients present this late in life. Second, the unusual involvement of
brachial plexus complicated the disease presentation, making it the second case ever
reported in literature. Finally, the extensive involvement of lymph nodes that is,
left supraclavicular, axillary, cervical, and superior mediastinal groups was also
a striking feature.
