Fatal Kikuchi-Fujimoto disease: the lupus connection

Kikuchi-Fujimoto disease (KFD) is a histiocytic necrotizing lymphadenitis found mainly in young women. Patients typically present with cervical lymphadenopathy and fever and follow almost always a benign course with excellent outcomes. The etiology of KFD remains unknown and controversial although several viruses have been associated with this disease. One theory proposes that KFD may be a self-limiting form of systemic lupus erythematosus (SLE). This theory is strongly supported by the fact that microscopic features of KFD can be very similar to those found in lupus lymphadenitis. Despite its usually benign course, several cases with fatal outcomes have been reported. We report here a case of clinically aggressive KFD, which featured several autoimmune-related events and resulted in a fatal outcome. Autopsy studies showed characteristic findings of SLE, which suggests a remarkable link between SLE and KFD. Early and intensive immunosuppressive treatment may be the only option for patients who develop very aggressive forms of KFD in order to avoid a fatal outcome.     

Autoimmune hepatitis associated with Kikuchi-Fujimoto's disease

We describe a 20-year-old woman with autoimmune hepatitis (AIH) with cirrhosis who developed Kikuchi-Fujimoto's disease (KFD) and de novo minor features of systemic lupus erythematosus (SLE). This is the first report of a patient with histologically confirmed AIH developing KFD (histiocytic necrotizing lymphadenitis). One previous case described KFD after AIH (diagnosed clinically but without biopsy). KFD is a rare condition of unknown aetiology, first described in 1972, characterized by fever and cervical adenopathy and has a self-limiting course. KFD is associated with SLE, and SLE in turn can be associated with abnormal liver function tests, which in a minority of cases may be due to AIH. The association of AIH, KFD, and SLE in our patient suggests an autoimmune pathogenesis of KFD.     

Systemic lupus erythematosus with simultaneous onset of Kikuchi-Fujimoto’s disease complicated with antiphospholipid antibody syndrome: a case report and review of the literature

Histiocytic necrotizing lymphadenitis, called Kikuchi-Fujimotos disease (KFD), is an idiopathic, self-limited condition rarely associated with systemic lupus erythematosus (SLE). The cause of concomitant KFD and SLE is still unknown. We describe a 19-year-old man simultaneously diagnosed with both KFD and SLE complicated with deep vein thrombosis (DVT). To the best of our knowledge, this is the first case report of KFD associated with SLE complicated with antiphospholipid antibody syndrome (APS). Our patient was successfully treated with intravenous pulse methylprednisolone, anticoagulation with heparin, oral hydroxychloroquine, azathioprine, and low-dose aspirin.     

Fatal Kikuchi–Fujimoto disease associated with SLE and hemophagocytic syndrome: a case report

Kikuchi-Fujimoto disease (KFD) or histiocytic necrotizing lymphadenitis is a rare, benign, autoimmune condition characterized by lymphadenopathy, fever, and neutropenia. KFD can frequently mimic various diseases including infection, malignancy, and autoimmune disease. KFD has also been infrequently reported in association with SLE, which can be diagnosed previously, simultaneously, or after the diagnosis of SLE. The author presents here the first case of fatal KFD simultaneously occurred with SLE complicated with hemophagocytic syndrome and severe infection. The recognition of this association is of significance for management of affected patients with early intensive immunosuppressive therapy for favorable outcome.     

Kikuchi-Fujimoto’s disease associated with systemic lupus erythematosus: case report and review of the literature

Kikuchi-Fujimotos disease (KFD) or histiocytic necrotising lymphadenitis is a benign and self-limited disease, of unknown aetiology, which affects mainly young women. It presents with localised lymphadenopathy, predominantly in the cervical region, accompanied by fever and leukopenia in up to 50% of the cases. KFD has been rarely described in association with systemic lupus erythematosus (SLE), and its diagnosis can precede, postdate or coincide with the diagnosis of SLE. We present a patient with the diagnosis of SLE characterised by arthritis, leukopenia, malar rash, photosensitivity and positive ANA, besides cervical lymphadenopathy whose biopsy was compatible with KFD, which improved after using prednisone. Although the presence of lymphadenopathy is not uncommon in SLE patients, particularly in the phases of disease activity, the concomitance with KFD has rarely been reported in the literature. Its recognition is necessary because one can avoid laborious investigation for infectious and lymphoproliferative diseases.     

Arthritis as an unusual manifestation of Kikuchi-Fujimoto disease

SIR, The cases are described of two young women presenting witharthritis, who were diagnosed with Kikuchi-Fujimoto disease(KFD; also called histiocytic necrotizing lymphadenitis). Arthritis has been described previously in patients in whomKFD is associated with other autoimmune disease, such as adultStill's disease and systemic lupus erythematosus (SLE). In ourpatients there was no evidence of coexistent autoimmune disease.To our knowledge, this is the first report of arthritis as apresentation of isolated KFD. We discuss the typical clinicalfeatures of KFD, its aetiology, associations and treatment. Case 1 (NM) was a 36-yr-old woman who recently immigrated toAustralia from Sri Lanka. She had undergone microdiscectomyfor left sciatic pain in Sri Lanka 6 months previously, andtook occasional paracetamol for residual pain. She was otherwisewell. NM was seen by her local doctor for worsening back pain.She displayed no     

Kikuchi-Fujimoto Disease: Retrospective Study of 91 Cases and Review of the Literature

Kikuchi-Fujimoto disease (KFD) is a rare cause of lymphadenopathy, most often cervical. It has been mainly described in Asia. There are few data available on this disease in Europe. We conducted this retrospective, observational, multicenter study to describe KFD in France and to determine the characteristics of severe forms of the disease and forms associated with systemic lupus erythematosus (SLE). We included 91 cases of KFD, diagnosed between January 1989 and January 2011 in 13 French hospital centers (median age, 30 ± 10.4 yr; 77% female). The ethnic origins of the patients were European (33%), Afro-Caribbean (32%), North African (15.4%), and Asian (13%). Eighteen patients had a history of systemic disease, including 11 with SLE. Lymph node involvement was cervical (90%), often in the context of polyadenopathy (52%), and it was associated with hepatomegaly and splenomegaly in 14.8% of cases. Deeper sites of involvement were noted in 18% of cases. Constitutional signs consisted mainly of fever (67%), asthenia (74.4%), and weight loss (51.2%). Other manifestations included skin rash (32.9%), arthromyalgia (34.1%), 2 cases of aseptic meningitis, and 3 cases of hemophagocytic lymphohistiocytosis. Biological signs included lymphocytopenia (63.8%) and increase of acute phase reactants (56.4%). Antinuclear antibodies (ANAs) and anti-DNA antibodies were present in 45.2% and 18% of the patients sampled, respectively. Concomitant viral infection was detected in 8 patients (8.8%). Systemic corticosteroids were prescribed in 32% of cases, hydroxychloroquine in 17.6%, and intravenous immunoglobulin in 3 patients. The disease course was always favorable. Recurrence was observed in 21% of cases. In the 33 patients with ANA at diagnosis, SLE was known in 11 patients, diagnosed concomitantly in 10 cases and in the year following diagnosis in 2 cases; 6 patients did not have SLE, and 4 patients were lost to follow-up (median follow-up, 19 mo; range, 3–39 mo). The presence of weight loss, arthralgia, skin lesions, and ANA was associated with the development of SLE (p < 0.05). Male sex and lymphopenia were associated with severe forms of KFD (p < 0.05). KFD can occur in all populations, irrespective of ethnic origin. Deep forms are common. An association with SLE should be investigated. A prospective study is required to determine the risk factors for the development of SLE.     

What is your diagnosis?: SLE and Kikuchi's disease: A rare association

Kikuchi–Fujimoto disease (KFD), or histiocytic necrotising lymphadenitis, is a rare benign, self-limiting cervical lymphadenitis of unknown aetiology. It predominantly affects young women and can closely mimic infective and immunological disorders. There is also a rare but documented association with systemic lupus erythematosus (SLE). We present the case of a young woman with biopsy-proven KD who was also diagnosed with SLE.     

Histiocytic necrotizing lymphadenitis (Kikuchi-Fujimoto's disease) mimicking systemic lupus erythematosus: a review of two cases

Kikuchi-Fujimoto's disease (KFD), or histiocytic necrotizing lymphadenitis, is a benign and self-limited lymphadenitis commonly found in young women. It often shares clinical features with systemic lupus erythematosus (SLE), such as arthralgias, fever and leukopenia. The etiology of KFD remains unknown and controversial. Clinical course is favorable, with spontaneous remission in less than four months in almost all cases. Herein, we present two cases. The former is a 53-year old woman presenting with cervical lymphadenopathy, arthralgia, pancytopenia and positive antinuclear antibody (ANA). Lymph node biopsy revealed histopathological features compatible with Kikuchi-Fujimoto histiocytic necrotizing lymphadenitis. The latter patient was a 20-year old woman presenting with left cervical lympadenopathy, a butterfly rash that was reminiscent of SLE, and a positive antinuclear antibody. Based upon clinical, histological and laboratory findings, the diagnosis of SLE was excluded. Careful attention should be paid to differentiating between KFD and SLE, because of their similar presentations, yet different clinical courses and therapeutic requirements.     

Necrotizing non-granulomatous lymphadenitis: a clinicopathologic study of 40 Thai patients

The purpose of this study was to describe the clinicopathological features of 40 cases of necrotizing non-granulomatous lymphadenitis in Thai patients. The clinical features, histomorphology and special stains were evaluated in 40 Thai patients from the pathology records of King Chulalongkorn Memorial Hospital from January 2001 to December 2003 in those diagnosed as having necrotizing non-granulomatous lymphadenitis. Of the 40 patients, 17 cases (42.5%) had Kikuchi-Fujimoto disease (KFD), 8 cases (20%) had tuberculosis (TB) lymphadenitis and 1 case (2.5%) had systemic lupus erythematosus (SLE) with associated lymphadenitis. Fourteen cases (35%) did not have a specific diagnosis due to a lack of follow-up data. KFD most commonly occurs in young women, and is characterized by the presence of coagulative necrosis and karyorrhexis often centered in the paracortex, an absence of neutrophils and plasma cells, proliferation of various cells composed of lymphocytes, histiocytes, immunoblasts and plasmacytoid monocytes and the absence of a granuloma. Tuberculous lymphadenitis usually occurs in women with a mean age of 34.25 years. The lymph nodes reveal extensive coagulative necrosis involving the cortex, paracortex and medulla, proliferation of mixed inflammatory cells, including neutrophils, lymphocytes and plasma cells in the necrotic area and the presence of proliferating histiocytes at the periphery of the necrotic area. The lymph nodes of SLE-associated lymphadenitis reveal large numbers of plasma cells and hematoxylin bodies. We suggest that necrotizing non-granulomatous lymphadenitis is not specific for any disease, but rather a common histologic change found in diseases, such as TB, SLE, and KFD. Further investigation to obtain a definite diagnosis should be done for appropriate treatment.     

Kikuchi disease]

Histiocytic necrotizing lymphadenitis or Kikuchi-Fujimoto disease (KFD) was described in 1972. Painful, palpable lymphadenitis is localized to one or two sites in the head and neck territories in young adults (third decade) and is associated with fever. Other clinical manifestations are infrequent: arthromyalgias, cutaneous rash, sweating, splenomegaly. Leukopenia is present in 50% of the cases with sometimes "atypical" lymphocytes. A spontaneously favorable outcome is noted after a mean 3 months. Histopathology of the lymph node is the key for the diagnosis of KFD showing lymph node necrosis of 25 to 75% of the surface, in the cortex and the medulla of the lymph nodes with histiocytic proliferation and plasma cells. Histochemistry shows positive straining for monocytic markers (CD68+, KiM1P+). Alpha-beta CD8+ T cells are abundant, NK and B cells are scarce. Pathological examination enables to differentiate KFD from other types of necrotizing lymphadenitis (SLE, malignant lymphoma, pyogenic infections). Kikuchi disease can be the result of local hyperimmune stimulation after viral, bacterial or parasitic infection. CD4+ cells would then become apoptotic cells. In some cases KJD is associated with systemic diseases such as systemic lupus erythematosus or adult Still's disease.     

Catastrophic antiphospholipid syndrome and Kikuchi-Fujimoto disease: the first case reported

The case of a man with diagnosis of Kikuchi-Fujimoto disease (KFD) and catastrophic antiphospholipid syndrome (CAPS) is reported. He presented prolonged fever, lymphadenopathies, arthralgia, weight loss, hepatosplenomegaly and positive IgM for cytomegalovirus. While he was empirically treated with tuberculostatic drugs, he suddenly developed systemic inflammatory response syndrome, multiple organ failure and distal necrosis. On suspicion of severe sepsis, antibiotics, corticoids and recombinant human activated protein C (XIGRIS) were administrated. Exhaustive laboratory searching was negative. Histopathologic examinations of lymph node first disclosed malignant lymphoma but later KFD was confirmed. One month later, laboratory tests showed the presence of antiphospholipid antibodies (aPL). The patient was discharged after two months of hospitalization. This case exhibits a KFD complicated by definite CAPS. Cytomegalovirus could be involved in the development of both CAPS and KFD. Because of the severity of the case, we believe that XIGRIS noticeable improved the altered coagulation profile associated with CAPS.     

Kikuchi-Fujimoto's disease: report of familial occurrence in two human leucocyte antigen-identical non-twin sisters

Kikuchi-Fujimoto's disease (KFD) is a self-limiting condition usually presenting as cervical lymphadenopathy, with fever and leukopenia, in young adult females. No specific aetiology has been identified yet, although some authors believe that KFD is a 'forme fruste' of systemic lupus erythematosus. Certain human leucocyte antigen (HLA) types have also been associated with KFD. We herein report KFD in two non-twin sisters with HLA-identical phenotype, who presented 10 years apart. Neither patient had evidence of recent infection or connective tissue disease. The familial occurrence emphasizes the possibility of genetic predisposition and calls for a more extensive search for a specific cause of KFD.     

Ankylosing spondylitis with Kikuchi–Fujimoto disease: A case report with literature review

We present the case of a patient diagnosed with ankylosing spondylitis (AS) along with Kikuchi–Fujimoto disease (KFD), possibly triggered by infection or autoimmunity. Both AS and KFD involved a similar immune pathway. Hence, clinicians should consider the possibility of KFD when lymphadenopathy is observed, especially in patients with infection or underlying autoimmune diseases.     

Kikuchi–Fujimoto Disease: analysis of 244 cases

Kikuchi–Fujimoto Disease (KFD) was first described in Japan in 1972. The disease frequently mimics tuberculous lymphadenitis, malign lymphoma, and many other benign and malignant conditions. To our knowledge, there is no previous study comparing the clinical and laboratory characteristics of patients from different geographical parts of the world. We searched literature records beginning from 1991 and analyzed epidemiological, clinical, and laboratory data of 244 patients (including cases diagnosed in our institution) reported in 181 publications. Of the 244 cases, 33% were male and 77% were female. Mean age was 25 (1–64) and 70% was younger than 30. Most of the cases were reported from Taiwan (36%), USA (6.6%), and Spain (6.3%). Fever (35%), fatigue (7%) and joint pain (7%) were the most frequent symptoms, while lymphadenomegaly (100%), erythematous rashes (10%), arthritis (5%), hepatosplenomegaly (3%), leucopenia (43%), high erythrocyte sedimentation rate (40%), and anemia (23%) being the most common findings. KFD was associated with SLE (32 cases), non-infectious inflammatory diseases (24 cases), and viral infections (17 cases). SLE was more frequent in cases from Asia than Europe (28 and 9%, respectively). The disease was self-limiting in 156 (64%) and corticosteroid treatment was necessary in 16 (16%) of the cases. The mortality rate was 2.1%. Early diagnosis is crucial as the clinical and laboratory presentation generally imitates situations needing lengthy and costly diagnostic and therapeutic interventions. Additionally, association with SLE needs further investigation.     

Histiocytic necrotizing lymphadenitis or Kikuchi's disease. CT radiologic features

Histiocytic necrotizing lymphadenitis, Kikuchi Fujimoto's disease (KFD) is characterised by fever and lymphadenopathy, usually large cervical, unilateral lymph nodes. Such clinical presentation demands a work-up to exclude serious medical conditions like malignancy and infections. Foci of necrosis with lymphocytic Histiocytic predominance in association with scarce polymorphonuclear cells on lymph node examination, confirm the diagnosis of KFD. Many different patterns of computed tomographic (CT) appearance of KFD have been reported. We describe the CT scan finding in two patients with this disease. All our cases showed, after two and three weeks of evolution respectively, enlarged lymph nodes with hypodense centres and peripheral ring enhancement. These radiological alterations correlated with the central lymph node necrosis found in the anatomopathological studies. In conclusion, KFD should be considered in patients with fever, cervical lymph node enlargement and CT scan showing hypointense centres and peripheral ring enhancement.     

Kikuchi-Fujimoto disease as a rare cause of fever of unknown origin in a septuagenarian

We report the case of a 72-year patient presented with fever of unknown origin. Initial clinical and radiological findings suggested a diagnosis of lymphoma. However, subsequent histology revealed Kikuchi-Fujimoto disease (KFD). KFD is predominantly a self-limiting disease of the young, but should be considered in the differential diagnosis of older patients presenting with fever of unknown origin or features suggestive of lymphoma.     

Bilateral anterior uveitis as an unusual manifestation of Kikuchi-Fujimoto disease

SIR, Kikuchi–Fujimoto disease (KFD) is a subacute necrotizinglymphadenitis of unknown origin and is usually a self-limitedcause of fever and lymph node enlargement [1]. KFD may be associatedwith a wide spectrum of immune diseases, such as polymyositis[2], systemic lupus erythematosus [3], arthritis [4] and uveitis[5]. However, as far as we are aware the simultaneous developmentof KFD and uveitis has not been reported. Here, we present thefirst case of KFD involving the     

Kikuchi Fujimoto disease associated with cryptogenic organizing pneumonia: case report and literature review

Background  

The association of Kikuchi Fujimoto disease (KFD) with cryptogenic organizing pneumonia (COP) is extremely rare. We report a case of simultaneous diagnosis of KFD and COP.     

Kikuchi Disease-Like Inflammatory Pattern in Cutaneous Inflammatory Infiltrates Without Lymph Node Involvement: A New Clue for the Diagnosis of Lupus?

Kikuchi–Fujimoto disease (KFD) is a rare and benign disorder that usually occurs in young adults with enlarged lymph nodes containing infiltrate of cytotoxic T cells and nuclear debris. It can be a manifestation of systemic lupus erythematosus (SLE) although the strength of this association has varied among studies. Although specific KFD cutaneous lesions are well described, pure cutaneous lesions have never been reported. We studied a series of patients prospectively entered into a database between 2007 and 2014 with skin biopsies showing diffuse or localized inflammatory infiltrates reminiscent of cutaneous KFD, without lymph-node-related KFD. We called these skin lesions “Kikuchi disease-like inflammatory pattern” (KLIP). Twenty-nine patients, whose median age was 49 years at the time of skin biopsy, were selected and retrospectively analyzed using standardized clinical and histology charts. In skin biopsies, KLIP was localized to restricted areas within the inflammatory infiltrate (17%) or diffuse (83%), and was the only histological finding (45%) or accompanied interface dermatitis with or without dermal mucinosis (55%). Clinical dermatological findings varied widely. A definite diagnosis could be established for 24 patients: 75% had connective tissue diseases or vasculitis, mainly cutaneous lupus erythematosus (CLE) (n = 16, 67%), including 5 SLE with satisfying American College of Rheumatology criteria; 3 of the remaining patients had malignant hemopathies. CLE patients were mostly young females with acute (n = 5), subacute (n = 4), or chronic CLE (n = 6) or lupus tumidus (n = 1). Two were classified as having anti-tumor necrosis factor-alpha–induced lupus. Because two-thirds of these patients were finally diagnosed with CLE, we think that KLIP may represent a new histopathological clue for the diagnosis of lupus based on skin biopsy, requiring clinical-immunological comparison to make the correct diagnosis. KLIP should not be considered a variant of classical KFD, but rather as an elementary pattern of cutaneous inflammation, that might be the expression of the same cytotoxic process within skin infiltrates as that involved in KFD. This lesion might reflect a particular T-cell-mediated autoimmune process directed against mononuclear cells within cutaneous lupus infiltrates.