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A 52-year-old woman presents to the hospital in Saudi Arabia, reporting that she has had a fever for the past week, along with painful swelling on the right side of her neck. She says she has no other symptoms, and tells clinicians that she has had these same symptoms twice before -- 7 and 13 years ago -- and they resolved without treatment.

Intake assessment confirms she has a fever of 38.5°C; other vital signs are within normal limits. Physical exam finds tender and firm right-sided cervical lymphadenopathy.

Clinicians order laboratory tests – complete blood count shows a white blood cell count of 7,200/cmm, hemoglobin of 12.6 g/dL, and platelets of 140,000/cmm. Other results:

• Blood urea nitrogen: 5.3 mmol/L

• Serum creatinine: 60 μmol/L

• Serum ferritin: 500 ng/mL

• C-reactive protein: 60 mg/L

• Nasopharyngeal SARS-CoV-2 polymerase chain reaction test is negative, as are results of other tests for Epstein-Barr viral antibodies, HIV, rheumatoid factor, and antinuclear antibodies

Clinicians consider possible infection, and after ordering a blood culture, start the patient on a course of broad-spectrum antibiotics. The patient undergoes ultrasound of her neck, which shows enlargement of several cervical lymph nodes, with the largest on the right side measuring 1.9×0.9 cm. Computed tomography of the neck and chest also reveals multiple right-sided cervical lymph nodes, the largest of which is 2.8×2.3 cm.

The patient remains feverish despite the antibiotics, and on her third day in the hospital, clinicians excise the right cervical lymph node. Biopsy indicates nuclear debris and necrosis with infiltration of many histiocytic cells, and no neutrophils. Lymph node cultures are negative for bacteria, fungus, and tuberculosis.

Based on the pathology results, the medical team makes a diagnosis of Kikuchi-Fujimoto disease (KFD).

Given the diagnosis, clinicians discontinue the patient's antibiotic treatment and start her on oral naproxen. Three days later, however, she is still not responding, so her treatment is switched to oral prednisone.

Over the next 3 days, the patient's fever subsides and her right cervical lymphadenopathy is responding to treatment.

She is discharged home with a short course of oral prednisone and instructions to return in a week for follow-up. At that outpatient appointment, assessment shows complete resolution of the cervical lymphadenopathy.

Discussion

Clinicians presenting of a woman who experienced undiagnosed cervical lymphadenopathy three times in 13 years before finally being diagnosed with KFD note that recurrence of this rare idiopathic cause of lymphadenopathy is also unusual, reported in only about 2%-3% of patients.

The disease, also known as histiocytic necrotizing lymphadenitis and first reported separately by and in Japan in 1972, tends to present with unilateral cervical lymphadenopathy, and more commonly affects young people, often females.

A study of in the incidence and clinical characteristics among patients with KFD found that while leukopenia and neutropenia were noted equally in about 55% of female and male patients, respectively, males with the disease were more likely to have abnormal liver function tests (15% vs 41%, P<0.001), elevated serum lactate dehydrogenase levels (61% vs 80%, P=0.021), elevated C-reactive protein (35% vs 78.4%, P<0.001), and thrombocytopenia (14% vs 29%, P=0.014), while female patients were significantly more likely to be positive for antinuclear antibody (32% vs 10%, P=0.006).

The case authors note that although most cases of KFD resolve within 1-3 months, early recognition is important to minimize potentially harmful and unnecessary evaluations and treatments.

Other research has referred to KFD as the , mimicking the clinical features of many dangerous conditions including tuberculosis, lymphoma, and adult-onset Still's disease.

The size of swollen lymph nodes in KFD is usually 1-4 cm (2.8 cm in this patient), although some reports have also noted sizes up to 6 cm.

Diagnosis requires biopsy and histology of lymph nodes, the case authors observe, adding that a lymph node may be only partially affected by the disease.

Typical histopathological features -- focal proliferation of histiocytic cells and abundant nuclear debris and absence of neutrophils -- are key to distinguishing KFD from other diseases, the authors explain, noting that the diagnosis of their patient was confirmed when histopathology of the cervical lymph node showed nuclear debris and necrosis with infiltration of many histiocytic cells.

KFD generally requires supportive treatment, and while most patients respond to non-steroidal anti-inflammatory drugs, those who do not usually have a good response to corticosteroids.

As noted, recurrence is rare; in this patient's case, the first two episodes of symptoms prior to her diagnosis spontaneously resolved, while the current episode required corticosteroid therapy to induce remission.

A study of 102 KFD patients with a mean age of 27 identified several characteristics associated with an increased : patients with recurrent episodes were more likely to have fever and fatigue with extranodal involvement, symptoms tended to persist longer, and patients were significantly more likely to have a positive fluorescence antinuclear antibody test result.

Conclusions

The case authors conclude that in recurrent febrile unilateral lymphadenopathy, excisional biopsy can lead to a definitive diagnosis and directed treatment, and that although recurrence is rare, long-term follow-up is needed.

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