Histiocytic necrotizing lymphadenitis in the context of systemic lupus erythematosus (SLE): Is histiocytic necrotizing lymphadenitis in SLE associated with skin lesions?

Histiocytic necrotizing lymphadenitis (HNL), or Kikuchi's disease, is a benign and self-limiting lymphadenopathy that typically affects young Asian females. It presents with lymphadenopathy, usually cervical, accompanied by fever, chills and leukopenia. Although the association between systemic lupus erythematosus (SLE) and HNL is rare, the number of reports of HNL in SLE patients is increasing. We present nine cases of HNL in patients with SLE. Among the seven patients with diverse skin manifestations, three had skin manifestations that were histologically compatible with SLE. A review of previous reports in the literature showed that cutaneous involvement was commonly found in HNL in association with SLE. In the patients who had simultaneous onset of both diseases, lupus flare-ups were commonly observed. We suggest that HNL in SLE patients is associated with cutaneous manifestations. This report contributes to our understanding of the relationship between these diseases.     

Kikuchi's disease in systemic lupus erythematosus: an independent or dependent event?

Summary The authors describe necrotizing histiocytic lymphadenitis (Kikuchi's disease) in association with systemic lupus erythematosus (SLE). To our knowledge this is the first case report where SLE preceded Kikuchi's disease. Whether Kikuchi's disease is an independent event or directly connected with SLE is discussed.     

Parvovirus B19 infection can induce histiocytic necrotizing lymphadenitis (Kikuchi's disease) associated with systemic lupus erythematosus.

We report three cases of systemic lupus erythematosus (SLE) associated with necrotizing histiocytic lymphadenitis (Kikuchi's disease) and immunologically proven human parvovirus B19 infection. Simultaneous occurrence of SLE and Kikuchi's disease was a characteristic of the three cases. Kikuchi's disease is an uncommon disease that usually affects young women and is characterized by painless unilateral cervical lymph-node enlargement. T-cell regions of affected lymph nodes are exclusively involved with patchy paracortical necrosis surrounded by a polymorphous cell population of histiocytes and macrophages. However, lymphadenopathy in patients with SLE may be histologically indistinguishable from Kikuchi's necrotizing lymphadenitis. The cause of Kikuchi's disease remains uncertain, although infectious agents have been proposed. A positive IgM-specific anti-human parvovirus B19 antibody test in our three cases suggests that B19 can induce a necrotizing histiocytic lymphadenitis and possibly a clinical SLE flare. High-dose (1 mg/kg/day) and medium-dose (0.5 mg/kg/day) oral prednisone was an effective treatment for constitutional and visceral symptoms of Kikuchi's and SLE diseases.     

Treatment of histiocytic necrotizing lymphadenitis (Kikuchi's disease) with prolonged fever by a single course of methylprednisolone pulse therapy without maintenance therapy: experience with 13 cases

A 26-year-old man was hospitalized with a 1-month history of fever. Cervical lymph node biopsy showed necrosis in the paracortical area with abundant nuclear debris and proliferation of histiocytes. A diagnosis of histiocytic necrotizing lymphadenitis (HNL) (Kikuchi's disease) was made. He received methylprednisolone pulse therapy (MPT) (0.5 g/day for 3 days) without maintenance therapy and experienced dramatic improvement. We also used MPT for another 12 cases of HNL. All patients became afebrile within 1 day without adverse events. Four patients relapsed after the initial MPT, but only 1 patient relapsed during the following year. Our results suggest that MPT is warranted in HNL patients with prolonged fever.     

Parvovirus B19-associated haemophagocytic syndrome with lymphadenopathy resembling histiocytic necrotizing lymphadenitis (Kikuchi's disease)

A 15-year-old girl developed a haemophagocytic syndrome caused by human parvovirus B19 (PVB19). The cervical lymph node histology, resembling that of histiocytic necrotizing lymphadenitis (HNL, Kikuchi's disease), included several transformed lymphocytes, numerous histiocytes, and massive necrosis. We detected PVB19-positive cells in the lymph node by immunohistochemistry. Possible autoimmune mechanisms in HNL-like diseases triggered by PVB19 are discussed.     

Kikuchi's disease as a presenting feature of mixed connective tissue disease

Summary Necrotising histiocytic lymphadenitis (Kikuchi's disease) is a recognised cause of benign lymphadenopathy. It has been reported in association with both adult Still's disease, systemic lupus erythematosus (SLE), and mixed connective tissue disease (MCTD). We report a case of mixed connective tissue disease (MCTD), in which biopsy of enlarged lymph nodes occurring as a presenting feature showed the characteristic features of Kikuchi's disease. This finding supports the belief that Kikuchi's disease and the autoimmune rheumatic disorders may share a common aetiology.     

Kikuchi's disease accompanied by lupus-like butterfly rash

Kikuchi's disease (KD) is a benign and self-limiting lymphadenitis, particularly affecting young women. KD is often associated with fever, arthralgia, and leukopenia, features also found in systemic lupus erythematosus (SLE). Lymphadenitis associated with SLE is indistinguishable from that in KD, and the association of KD and SLE has been previously reported. We describe a case of KD who developed a typical butterfly rash, reminiscent of SLE. However, histological and laboratory findings excluded the diagnosis of SLE. This case emphasizes that careful differential diagnosis between KD and SLE is required.     

Kikuchi-Fujimoto's disease and the association with systemic lupus erythematosus

Kikuchi-Fujimoto's disease (KFD), Histiocytic Necrotizing lymphadenitis, is a rare self-limiting condition characterized by lymphadenopathy, fever and neutropenia. The aetiology of KFD is controversial, and its diagnosis is confirmed histologically. Although KFD has rarely been reported associated to Systemic lupus erythemotosus (SLE) should be ruled out given its different prognosis and management. We present the clinical, histological and evolution the two cases of patients with Kikuchi's disease; one case had evolution classic and the other case were associated with SLE.     

Histiocytic necrotising lymphadenitis in systemic lupus erythematosus.

Histiocytic necrotising lymphadenitis is the pathognomonic histological appearance of lymph nodes in Kikuchi's disease, a condition characterised by a brief systemic illness and lymphadenopathy. The case is described of a young man, originally diagnosed as having Kikuchi's disease by lymph node histology, who subsequently developed systemic lupus erythematosus with symmetrical polyarthritis, Coombs' positive haemolytic anaemia and haemorrhagic pneumonitis. The case emphasises that a range of diseases is associated with histiocytic necrotising lymphadenitis, belying the unitary impression given by the term Kikuchi's disease.     

Therapeutic response and long-term follow-up in a systemic lupus erythematosus patient presenting with Kikuchi's disease

Kikuchi's disease (KD) can occur in association with systemic lupus erythematosus (SLE). The treatment of concomitant diseases, however, is unclear. We describe a case of a 45-y-old man who presented with generalized histiocytic necrotizing lymphadenitis, fever, malaise and weight loss. Ten months later he also developed arthritis, serositis, anemia, leukopenia and lymphopenia. ANA, anti-Smith, anti-snRNP and anti-Ro antibodies were positive. He responded rapidly and favorably to mid-dose prednisone. Hydroxychloroquine, added 5 months later, allowed tapering down and discontinuation of prednisone treatment. He has remained in complete remission for 5 years.     

Expression of apoptosis-associated protein RCAS1 in macrophages of histiocytic necrotizing lymphadenitis

Receptor-binding cancer antigen expressed on SiSo cells (RCAS1), which is recognized by the 22-1-1 monoclonal antibody (MoAb) against human uterine adenocarcinoma cell line SiSo, has been identified on various kinds of cancer cells. RCAS1 appears to be an apoptosis-associated protein that induces apoptosis in activated T-cells and erythroid progenitor cells. We previously demonstrated that monocytes/macrophages express RCAS1. In the present study, we investigated RCAS1 expression by 22-1-1 MoAb in histiocytic necrotizing lymphadenitis (HNL), which is characterized by necrotic lesions consisting of T-cells undergoing apoptosis and macrophages in proliferation. Expression of RCAS1 was analyzed by immunohistochemical staining in 9 cases of HNL and in 9 cases of reactive lymphadenitis used as a control. The ratio of RCAS1+ cells to CD68+ cells (monocytes/macrophages) was significantly higher in the patients with HNL than in the patients with reactive lymphadenitis (P = .0002; paired t test). Our findings suggest that RCAS1 expressed on macrophages may play an important role in the induction of activated T-cell apoptosis in cases of HNL.     

Kikuchi's disease: an uncommon cause of fever of unknown origin

Kikuchi's disease or histiocytic necrotizing lymphadenitis is an uncommon clinical condition that causes diagnostic difficulties because of its lack of specific signs, symptoms and serological markers. Diagnosis is based on histopathological findings, but overlapping of the histological features requires a differential diagnosis among histiocytic necrotizing lymphadenitis and a number of infectious, autoimmune and lymphoproliferative lymphadenopathies. We report a case of Kikuchi's disease in a 19-year-old woman presenting with generalized lymphadenopathy and persistent fever.     

Kikuchi-Fujimoto's disease and connective tissue disease: a report of three cases

INTRODUCTION: Kikuchi-Fujimoto's disease or histiocytic necrotizing lymphadenitis, clinicopathological entity of unknown aetiology, is a rare and benign cause of cervical lymphadenopathies. It can be associated with various auto-immune diseases especially systemic lupus erythematous (SLE) or with some infectious agents. EXEGESIS: This report describes a survey of three patients who developed Kikuchi's lymphadenitis occurring concomitantly with connective tissue disease: LES in two cases and non determined connective tissue disease in the other case. Comparing the clinical, histopathological and evolutionary findings to the literature allows to identify the main features of this self-limiting disorder: occurrence in young women; clinical presentation with cervical lymphadenopathy in a context of fever and asthenia. The definite diagnosis is usually made through histopathological examination of a lymph node biopsy. Disease course is generally favourable with spontaneous resolution within few weeks. It may be improved with corticosteroid treatment in patients with systemic involvement. Prognosis is related to the associated disease. CONCLUSION: Kikuchi-Fujimoto's disease is a rare and benign cause of cervical lymphadenopathy that could resemble lymphoma, tuberculosis and may be associated with a characterized systemic disease.     

Kikuchi's lymphadenitis: report of a Yersinia enterocolitica-associated case and an overview of aetiology and clinical outcome.

Kikuchi's lymphadenitis (KL; histiocytic necrotizing lymphadenitis without granulocytic infiltration) is a generally benign, febrile disorder of unknown aetiology with distinct histological features. To date, a minority of cases reported have been associated with infectious agents. A typical pathological case of KL is described where involvement of Yersinia enterocolitica was shown by an indirect immunofluorescent assay applied to lymphatic tissue. The case is discussed with emphasis on recent insight into the course and aetiology of KL.     

Still's disease associated with necrotizing lymphadenitis (Kikuchi's disease): report of 3 cases

Necrotizing lymphadenitis (Kikuchi's disease) is recognized as one of the benign lymphadenopathies. Previously, this condition has not been described in Still's disease which is frequently associated with lymphadenopathy. We report 3 cases of Still's disease, 2 in adults and 1 in an older child, with the findings of necrotizing lymphadenitis on lymph node biopsy. Considering the common infectious and/or immunologic etiologies described in both disorders, coexistence of both conditions suggests the possibility that they share a common etiology.     

Pathogenic links between Kikuchi's disease and lupus: a report of three new cases

INTRODUCTION: Histiocytic necrotizing lymphadenitis or Kikuchi-Fujimoto's disease is a rare anatomoclinical entity whose etiology remains unknown. It is mainly reported in young adult female, presenting with cervical lymphadenopathies, fever and asthenia. The diagnosis is based on the histological examination of a lymph node biopsy. The disease course is usually uneventful, but sometimes Kikuchi-Fujimoto's disease can reveal or evolve into a cutaneous or a systemic lupus. EXEGESIS: We report three new cases of Kikuchi's disease: the first one mimicked a systemic lupus, the second one was associated with a lupus-like rash, and a the last one was a severe case with hemophagocytic syndrome and a primo-infection with Epstein-Barr virus revealing a systemic lupus erythematosus. CONCLUSION: Clinical and biological follow-up of patients presenting with Kikuchi's disease is necessary to look for an association with a lupus. We discuss the pathogenic links between Kikuchi's disease and lupus.     

Elevated serum-soluble fas ligand in Histiocytic necrotizing lymphadenitis

Recent studies have indicated that Fas and perforin-based mechanisms seem to induce apoptosis in histiocytic necrotizing lymphadenitis (HNL). In this study, we evaluated the serum levels of soluble Fas ligand (sFasL) in 30 HNL patients using paired sera. Elevations in sFasL levels were detected in 9 patients in the active stage. In the convalescent stage, the levels of sFasL decreased to an undetectable degree after 2 weeks. These findings indicate the possibility that sFasL plays an important role in the constitutional symptoms and pathogenesis of HNL and, furthermore, that it can act as a surrogate marker of the disease activity.     

Kikuchi's disease: a benign cause of fever and cervical lymphadenopathy

Histiocytic necrotizing lymphadenitis (Kikuchi's disease, KD) is a rare benign condition of unknown origin, usually characterized by lymphadenopathy and fever, affecting mainly young women. We describe three cases of patients, one man and two women, with biopsy-proven KD detected at our university hospital during the past 3 years and we review the literature.