Kikuchi-Fujimoto Disease: A Case Report of Fever and Lymphadenopathy in a Young White Man

Discussion

KFD is a rare cause of cervical lymphadenitis that was first described in 1972. Although cases have been reported worldwide, it is seen with higher prevalence in Asian countries. KFD was previously thought to have a female predominance, but recent reviews suggest a female to male ratio close to 1:1.¹ The pathogenesis of KFD remains unknown, though some studies have suggested Epstein-Barr virus infection as a potential trigger.^4,5 Human herpesvirus (HHV) 6, HHV 7, HHV 8, HSV, HIV, and parvovirus B19 also have been implicated as potential triggers, though no causative relationship has been established.^2,5,6 Autoimmunity may also play a role in the pathogenesis of KFD given its histopathologic overlap with SLE lymphadenitis.^1,7

The most common presenting symptoms of KFD include fever and tender cervical lymphadenopathy. Many patients also experience constitutional symptoms such as weight loss, night sweats, and fatigue.² KFD is characterized by enlarged cervical lymph nodes, typically > 2 cm in diameter.³ Cutaneous manifestations of KFD are common and may manifest as nonspecific papules, plaques, nodules, or facial malar erythema.^1,2 Case reports also have described KFD manifesting with ataxia, arthritis, parotitis, or ocular pathologies such as conjunctivitis and uveitis.^1,2,8,9 Hepatosplenomegaly is a relatively rare manifestation of KFD seen in approximately 3% of cases.¹⁰ When present, hepatosplenomegaly may make the diagnosis of KFD especially difficult to distinguish from lymphoproliferative disorders such as lymphoma. Laboratory findings in KFD are nonspecific and include elevated levels of lactate dehydrogenase, erythrocyte sedimentation rate, C-reactive protein, and liver enzymes.³ Both lymphocytosis and lymphopenia have been described.³Definitive diagnosis of KFD is achieved through lymph node biopsy and histologic examination. Histopathologic findings of KFD include areas of coagulative necrosis and histiocytic proliferation within the cortical and paracortical regions of the lymph node. Scattered nuclear debris also may be seen, though this histologic finding also is seen with lymphoma. The absence of neutrophils is characteristic of KFD.² In our patient, a core needle biopsy was initially pursued but returned nondiagnostic. A PET-CT also was obtained, though KFD may mimic lymphoma on PET as was seen in this patient’s case as well as in prior case reports.¹¹ An excisional lymph node biopsy was ultimately performed and secured the diagnosis of KFD.

Although ultrasound-guided core needle biopsy was unable to yield the diagnosis for our patient, its diagnostic accuracy is still superior to that of fine needle aspiration and is therefore suggested as the primary diagnostic modality when KFD is suspected.¹² Core needle biopsy also is less invasive, less time consuming, and perhaps more cost-effective than an open excisional biopsy, which often requires the use of an operating room and monitored anesthesia care.¹² Understandably, our patient experienced significant stress while awaiting a final diagnosis. Whenever possible, lymph node biopsy should be prioritized over other diagnostic modalities to achieve a timely and definitive diagnosis.

KFD has no established treatment guidelines. Supportive care with antipyretics and analgesics is the most common initial approach, as KFD is typically a self-limited disease that resolves in 1 to 4 months.² Patients with severe, persistent symptoms have been successfully treated with corticosteroids and hydroxychloroquine, with monotherapy typically trialed before concomitant use.^2,13 After 2 courses of prednisone, our patient was prescribed single-agent hydroxychloroquine due to his recurrent symptoms and debilitating AEs from the steroids. Other case reports have described hydroxychloroquine as a treatment option when steroids fail to provide symptom relief or when there are recurrences of KFD.^14-19 Retinopathy can occur as a result of long-term hydroxychloroquine use. As such, patients anticipated to require long-term hydroxychloroquine therapy should receive a baseline eye examination within months of drug initiation and repeat examination after 5 years of therapy.²⁰

After symptom resolution, continued follow-up with a health care professional is recommended due to the potential for KFD recurrence or the development of a new autoimmune disease. The rate of KFD recurrence was previously described as 3%, but a more recent review found the rate of recurrence to be approximately 15% at > 6 months follow-up.^1,3 Recurrence is often described during or shortly after the tapering of steroids.^13,16,21,22 Recurrent KFD can be diagnosed with repeat lymph node biopsy, which also serves to exclude other disease processes.^13,16 However, recurrence also has been diagnosed clinically based on the patient’s symptoms and laboratory investigations.^21,22Continued surveillance of patients with KFD is also necessary to monitor for the development of new autoimmune diseases, especially SLE. SLE lymphadenitis shares many histopathologic characteristics with KFD. Case reports have described the development of SLE in patients with a history of KFD.^2,7 Other autoimmune conditions described in patients with prior KFD include Sjögren syndrome, Hashimoto thyroiditis, Graves disease, mixed connective tissue disease, and antiphospholipid syndrome.^3,23 Among patients with KFD, female sex, painful adenopathy, and cytopenias are significantly associated with the later development of autoimmune disease.²³