Kikuchi-Fujimoto Disease, the Masquerading Menace: A Rare Case Report.

Kikuchi-Fujimoto disease (KFD) or histiocytic necrotizing lymphadenitis is a rare, benign, self-limiting disease with unknown etiology characterized by regional lymphadenopathy. A 30-year-old female presented with fever, weakness, multiple joint pain, oral ulcers, erythematous facial rashes, hemorrhagic crusting on both lips, and cervical lymphadenopathy of 2-month duration. Clinically, the disease was mimicking systemic lupus erythematosus, but immunofluorescence was negative for it. Lymph node biopsy suggested a diagnosis of KFD.

What was known?

Kikuchi-Fujimoto disease is a rare lymphadenitis of unknown etiology associated with nonspecific skin manifestations.

Introduction

Kikuchi-Fujimoto disease (KFD) is a rare, benign, self-limiting cervical lymphadenitis.[12] Only a few cases of this disease with skin manifestations have been reported worldwide. The skin manifestations of our case mimicked systemic lupus erythematosus (SLE), but immunofluorescence and serology were negative for it.[3] A paucity of reports in literature with unusual skin manifestations has prompted us to report this case.

Case Report

A 30-year-old female presented with intermittent high-grade fever, weakness, pain in knee, wrist, and ankle joints, oral ulcers, erythematous rashes on face and upper chest, hemorrhagic crusting on lips and multiple, firm, tender enlarged bilateral cervical lymph nodes distributed mainly in the posterior cervical region of 2-month duration. Her initial clinical features were mimicking SLE [Figure 1].

Figure 1

Multiple, variable size maculopapular lesions on face with hemorrhagic crusting on lips

Routine hemogram showed anemia, thrombocytopenia, and mild leukocytosis. Antinuclear antibody and anti-double-stranded DNA (dsDNA) antibody were negative for SLE. Mantoux test, Widal, rapid dengue antibody test for IgM and IgG, rapid malaria test for Plasmodium vivax, hepatitis B surface antigen, hepatitis C virus, human immunodeficiency virus 1 (HIV-1), venereal disease research laboratory, rheumatoid factor, and chest X-ray were normal. Her blood and urine culture were negative.

Histopathological evaluation of left cervical lymph node revealed lymph nodal tissue with paracortical, well-circumscribed necrotic lesions, with karyorrhectic debris, and fibrin deposits. There was a proliferation of phagocytic foamy histiocytes and infiltration of plasmacytoid monocytes, histiocytes, and lymphocytes surrounding karyorrhectic debris [Figures 2 and 3]. Plasma cells and neutrophils were absent. No follicular hyperplasia and no atypia were noted. Staining for acid-fast bacilli was also negative. A diagnosis of KFD was made.

Figure 2

Proliferation of phagocytic foamy histiocytes and infiltration of plasmacytoid monocytes (H and E, ×10)

Figure 3

Plasmacytoid monocytes, histiocytes, and lymphocytes surrounding karyorrhectic debris (H and E, ×100)

The patient was treated with antibiotics, nonsteroidal anti-inflammatory drugs, and oral steroids for 10 days after which the lymph nodes regressed and other symptoms subsided.

Discussion

KFD, also known as histiocytic necrotizing lymphadenitis, was initially described by both Kikuchi and Fujimoto independently in 1972. Although it has been reported worldwide, it still remains a poorly recognized clinicopathological entity and is confused with lymphoma and SLE.

The exact etiology of KFD is not known. A lot of triggers have been incriminated which includes parvovirus B-19, Epstein–Barr virus, HIV, human herpes virus 6, human T-cell lymphotropic virus, dengue virus, and cytomegalovirus. Yersinia enterocolitica and other bacterial agents such as Bartonella and Brucella have also been implicated.[4]

KFD most often presents with cervical lymphadenopathy which may be tender and can be accompanied by fever, upper respiratory tract symptoms. Less common symptoms include arthralgia, skin rashes, weakness, weight loss, diarrhea, anorexia, chills, nausea, and vomiting. About 30% of patients with KFD are reported to have skin manifestation. These cutaneous manifestations can be nonspecific and can present as morbilliform and rubella-like eruptions, reddish plaques which resemble lymphoma, erythematous, and acneiform eruptions on face. Facial or malar “butterfly rash” may also be present.[5] Cutaneous involvement tends to occur in patients who have more severe and protracted course.[6]

Hematological examination of KFD shows leukopenia and raised ESR in some cases. Other nonspecific finding includes thrombocytopenia and pancytopenia, and 25% of patient may present with atypical blood lymphocytes.[7]

Diagnosis of KFD is based on histopathological findings of lymph node biopsy as no specific diagnostic laboratory tests are available. Biopsy of lymph node shows focal or complete loss of follicular architecture associated with necrosed cortical and paracortical areas. The extensive infiltrate consists of immunoblast cells, small lymphocytes, macrophages, and so-called plasmacytoid T-cells.[8]

Clinically, KFD may resemble SLE or lymphoma (especially T-cell non-Hodgkins lymphoma) as both these diseases can present with lymphadenopathy and fever. Furthermore, the skin lesions of KFD can mimic those seen in SLE.

According to some literature, KFD may be associated with SLE.[9]

A histological feature that helps in the differentiation of KFD from SLE is almost total absence of plasma cells in the involved nodal tissue in KFD.[10] Neutrophils are also rarely seen in KFD, which is also important differentiating feature from SLE. Moreover, diagnostic serologic and immunofluorescence tests can differentiate SLE as antinuclear and anti-dsDNA antibodies were done in our patient, and they were negative.

Histological feature that helps in the differentiation of KFD from lymphoma includes incomplete architectural effacement with patent sinuses, presence of numerous reactive histiocytes, relatively low mitotic rates, and absence of Reed–Sternberg cells [Table 1].

Table 1

Histopathological comparison of Kikuchi-Fujimoto disease, systemic lupus erythematosus, and lymphoma

No specific treatment is available for KFD. In supportive treatment, nonsteroidal anti-inflammatory drugs may be used to alleviate lymph node tenderness and fever. The course of prednisolone may speed resolution. The disease runs a benign course usually, and natural history is for spontaneous resolution in several weeks to months.[11] The disease showed a recurrence rate of 3.3% in a series.[5]

Conclusion

One should remain alert to the possibility of KFD when a young female patient presents with complaints of developing neck lymphadenopathy. Skin as well as clinical manifestation of KFD may mimic other systemic disease, specially lymphoma and SLE so careful histopathological examination has importance at clinching the diagnosis in such cases.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

What is new?

Certain skin features, such as the erythematous facial lesions, hemorrhagic crusting on lips, and oral ulcers, as evidenced in our patient, should be considered possible cutaneous manifestations of Kikuchi-Fujimoto disease.