Kikuchi-Fujimoto Disease

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 , MD, PhD, Fréde MD, , MD, PhD, and Olivier Fain, MD, PhD (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. (Medicine 2014;93: 372–382) Abbreviations: ALAT = alanine aminotransferase, ANAs = antinuclear antibodies, ASAT = aspartate aminotransferase, CRP = C-reactive protein, CMV = cytomegalovirus, ENT = ear, nose, and throat surgery, EBV = Epstein-Barr virus, FDG-PET-CT = F18 fluorodeoxyglucose positron emission tomography/computed tomography, HLH = hemophagocytic lymphohistiocytosis, HIV = human immunodeficiency virus, IVIG = intravenous immunoglobulin, KFD = Kikuchi-Fujimoto disease, LDH = lactate dehydrogenase, NSAIDs = nonsteroidal antiinflammatory drugs, PCR = polymerase chain reaction, SLE = systemic lupus erythematosus, TDM = tomodensitometry. INTRODUCTION K ikuchi-Fujimoto disease (KFD) or histiocytic necrotizing lymphadenitis is a rare and benign cause of lymphadenopathy. Since the first description of the disease by the Japanese pathologists Kikuchi and Fujimoto, its etiology has remained unknown, although environmental factors, in particususpected. Links between KFD and ases, particularly systemic lupus erytheeen reported. olume 93, Number 24, November 2014 KFD classically affects young women. The distribution is ubiquitous, with an over-representation of Asian patients, possibly linked to some haplotypes. KFD is characterized by localized lymphadenopathy, fever, frequent upper respiratory symptoms, and odynophagia. The onset is typically subacute or acute, with a short course of symptoms. Nevertheless, KFD has been already described as a cause of fever of unknown origin. Other symptoms are less frequent, including chills, night sweats, arthralgia, and loss of weight. Involvement of the posterior cervical group is the most common feature. However, all areas can be involved. Usually, lymph nodes appeared painful, tender with a moderate size. Atypical presentations and extranodal involvement are possible, mainly cutaneous manifestations and aseptic meningitis. Generalized forms sometimes associated with splenic or hepatic enlargement have been already described. Laboratory findings are usually normal except for inflammatory syndrome or mild cytopenias, sometimes associated with hemophagocytosis. The clinical picture is not specific and may be consistent with several diagnoses as viral infection (as mononucleosis), bacterial adenitis (mainly tuberculosis or cat scratch disease), malignant lymphoma, or metastatic cancer, especially when constitutional symptoms are marked. Although KFD is not well recognized, it should be included in the differential diagnosis of ‘‘febrile lymphadenopathy.’’ Diagnosis is confirmed by analysis of an affected lymph node. Biopsy is generally preferred to fine-needle aspiration. Characteristic features include paracortical areas of necrosis, abundant karyorrhexis and mononuclear cells reaction (histiocytes, plasmacytoid monocytes, small lymphoid cells and immunoblast) around the necrosis foci. Granulocytes and plasma cells are typically rare or absent. Immunohistochemical analysis is helpful to rule out malignant lymphoma. It reveals a predominance of T cells, mostly CD8þ, and histiocytes, which express myeloperoxidase (MPO) and CD68 antigens. Distinguishing KFD lymphadenopathy and SLE-associated adenitis can be a challenge, because both share clinical and pathologic findings. Moreover, the diagnosis of SLE can precede, follow, or coincide with the diagnosis of KFD. However, some pathologic features could be helpful for the distinction. The outcome is usually favorable, although rare cases of fatal progression have been described. Most of the data in the literature regarding this disease have come from histopathologic studies, most often conducted in Asian populations. Thus, we conducted the present study to describe the characteristics of KFD in a Western country. Our secondary objectives were to compare severe forms of KFD with mild forms and to compare the forms of KFD associated with SLE with those that were not. PATIENTS AND METHODS