What's the Cause of Neck Swelling, Fever in Young Woman?

A 25-year-old Vietnamese woman presented to a hospital reporting several weeks of swelling in her neck along with a mild fever that developed every afternoon.

She told clinicians that she had no allergies or known medical conditions, had not traveled recently, and had not been scratched or bitten by a cat. In addition, she said, she had not been short of breath; had no cough, headache, chest pain, or change in weight; and had no known contact with anyone diagnosed with tuberculosis.

Clinical assessment revealed vital signs of respiratory rate of 17 breaths/min, temperature of 38°C (100.4°F), blood pressure of 130/70 mm Hg, and heart rate of 90 beats per minute.

On physical examination, clinicians noted that the patient had several tender soft lumps about 2 cm in diameter on the right side of her neck, although the skin there appeared normal.

Clinicians examined her mouth, ears, nose, throat, and thyroid gland based on suspicion of an infection, but found no evidence of a lesion.

Cardiovascular, neurologic, and respiratory tests identified nothing unusual; the patient's abdomen was soft on palpation, and bowel sounds were normal.

Laboratory tests returned normal findings for complete blood count, creatinine, electrolytes, C-reactive protein, and erythrocyte sedimentation. Clinicians ordered an ultrasound of her neck, which revealed several enlarged, hypoechoic lymph nodes on the right side; these were well-circumscribed, and there was no evidence of lesions in the thyroid or parotid glands.

Although the patient's Vietnamese ethnicity places her at risk for tuberculosis (TB), she reported having no known contact with any infected individuals. Given the ultrasound showing enlargement of the right supraclavicular lymph node, as well as the mild fever she noted having had in the afternoons for several weeks, clinicians arrived at a presumptive diagnosis of TB lymphadenitis.

They ordered a chest x-ray, which showed normal findings, and results of a QuantiFERON-TB Gold (QFT-G) test were negative, thus essentially ruling out TB lymphadenitis.

Clinicians then ordered antinuclear antibody and anti-double-stranded DNA tests to screen for systemic lupus erythematosus (SLE) -- both also showing negative results. Tests were also ordered to rule out Epstein-Barr virus (EBV) and cytomegalovirus (CMV), which are also known to cause cervical lymphadenopathy, but these tests were also negative for CMV immunoglobulin M (IgM) and EBV IgM.

To rule out the possibility that the patient might have cancer metastasized to the lymph nodes, clinicians ordered whole-body magnetic resonance imaging (MRI) and thoracic-abdominal computed tomography (CT) scans. Findings of the MRI included only abnormalities of the cervical lymph nodes; findings of the thoracic-abdominal scan were unremarkable.

Finally, clinicians performed a percutaneous ultrasound-guided biopsy of the patient's supraclavicular lymph node. Histopathology noted expansion of the lymph nodes into the paracortex and evidence of patchy, well-circumscribed areas of necrosis with nuclear debris and no neutrophils.

Based on these findings, clinicians diagnosed the patient with Kikuchi-Fujimoto disease (KFD) and initiated treatment with meloxicam 15 mg per day. Within 2 weeks, her symptoms had resolved, and the supraclavicular lymph nodes in her neck had returned to normal.

Discussion

Clinicians reporting this case of a young Asian woman with KFD noted that the diagnosis can be challenging due to its variable clinical presentation and nonspecific imaging findings, but that KFD should nonetheless be considered in young women who have cervical lymphadenopathy for a short time.

The case authors noted that this uncommon and benign cause of lymphadenopathy tends to affect young Asian women in Asia, and is rarely seen in the U.S., although there was one report of KFD in an 11-year-old boy in Michigan who was born in Vietnam and raised in the U.S.

Because KFD mimics other causes of lymphadenopathy, the incidence is not clear, the case authors observed, noting that while the cause and pathogenesis have not been delineated, KFD is generally thought to be related to infectious agents and an autoimmune response. Infectious causes suggested include EBV; varicella-zoster virus; human herpes viruses 6, 7, and 8; parvovirus B19; paramyxovirus; parainfluenza virus; rubella; and human T-lymphotropic virus type 1. KFD has also been linked with autoimmune conditions -- in particular, systemic lupus erythematosus (SLE).

The case authors noted that KFD may develop acutely or gradually, and symptoms typically resolve without treatment within several weeks. Lymphadenopathy is present in all cases, and is posterior cervical in up to 90% of cases, and generalized in less than 22% of cases. Over 80% of patients have tender swollen lymph nodes ranging from 0.5 to 4.0 cm in size, and up to 90% of KFD patients have a fever of 38.6°C to 40.5°C, which typically persists for about 1 week to 7 weeks.

Less common symptoms, the authors stated, include weight loss, nausea, vomiting, weakness, headache, night sweats, and upper respiratory symptoms, and other than the lymph system, skin manifestations such as papules, facial palmar erythema, plaques, and nodules are common.

Results of lab tests are typically nonspecific -- i.e., "findings of anemia, leukopenia, leukocytosis, thrombocytopenia, and elevations in liver enzymes, lactate-dehydrogenase levels, and erythrocyte sedimentation rate," the case authors wrote.

On imaging, the lymph nodes tend to have an irregular outer rim and "are less round than is seen with lymphoma," with a hypoechoic center and a hyperechoic rim on ultrasound, and homogeneous enhancement and little evidence of necrosis on CT scan, the authors explained.

Diagnosis of KFD remains a diagnosis of exclusion, confirmed by histopathologic examination of a sample from fine-needle aspiration or biopsy of the affected lymph node, characterized by "preserved nodal architecture, varying degrees of coagulative necrosis in the paracortical regions with abundant karyorrhectic debris, and an absence of eosinophils or neutrophils," the authors noted. The areas of necrosis are typically surrounded by crescent-shaped histiocytes -- which express CD68, myeloperoxidase, and CD4 -- and plasmacytoid monocytes.

Diagnosis of lymphadenopathy requires exclusion of numerous differentials, including "infectious agents, such as TB, toxoplasmosis, Bartonella henselae, HIV, and EBV; inflammation; SLE; lymphoma; and metastasis," the authors wrote.

Blood tests can help rule out other possible explanations for lymphadenopathy, such as toxoplasmosis due to cat-scratch disease, while histologic findings can help exclude cancer.

Since the disease is known to resolve on its own within a few months, patients are generally just observed for any symptomatic changes, although non-steroidal anti-inflammatory drugs and corticosteroids may be used to address troublesome symptoms or extranodal lymphoid organ involvement, the authors noted, adding that there are no guidelines for use of corticosteroids in KFD.

Long-term follow-up is crucial, since about 4% of patients have a recurrence up to 8 years after initial diagnosis, the authors emphasized.

Conclusion

The case authors concluded that KFD is a rare, benign disease with a variable clinical presentation and nonspecific imaging features that can mimic other diseases and that mainly occurs in young Asian women. Diagnosis should be considered in young Asian women who have cervical lymphadenopathy for a short time, and long-term follow-up is necessary to assess patients for development of autoimmune disease or recurrence of KFD.

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