Pathogenic role and diagnostic utility of interferon-α in histiocytic necrotizing lymphadenitis.

PURPOSE: Histiocytic necrotizing lymphadenitis (HNL) is an inflammatory disease of unknown etiology clinically characterized by painful lymphadenopathy. This study aimed to investigate the role of interferon (IFN)-α in the pathogenesis of HNL and the clinical significance of serum IFN-α levels for the diagnosis and monitoring of HNL disease activity. METHODS: This study enrolled 47 patients with HNL and 43 patients with other inflammatory diseases that require HNL differentiation including malignant lymphoma (ML), bacterial lymphadenitis, and Kawasaki disease. Expression of IFN-stimulated genes (ISGs) and MX1 in the lymph nodes was measured by real-time quantitative reverse transcription polymerase chain reaction and immunofluorescence staining, respectively. Enzyme-linked immunosorbent assay was used to quantify serum cytokine levels. The results were compared with the clinical features and disease course of HNL. RESULTS: Patients with HNL had a significantly elevated ISG expression in the lymph nodes compared with those with ML. MX1 and CD123, a specific marker of plasmacytoid dendritic cells (pDCs), were colocalized. In patients with HNL, serum IFN-α levels were significantly elevated and positively correlated with disease activity. The serum IFN-α level cutoff value for differentiating HNL from other diseases was 11.5 pg/mL. CONCLUSION: IFN-α overproduction from pDCs may play a critical role in HNL pathogenesis. The serum IFN-α level may be a valuable biomarker for the diagnosis and monitoring of disease activity in patients with HNL.

Kikuchi-Fujimoto Disease Preceding Overlap Syndrome of Sjögren's Syndrome and Systemic Lupus Erythematosus: Literature Review Based on a Case Report.

Kikuchi-Fujimoto disease (KFD) is a benign, self-limiting histiocytic necrotizing lymphadenitis systemic disorder with unknown etiology. KFD has been known for half a century, but difficulties in distinguishing it remain. Its diagnostic significance is related to the increasing prevalence of KFD with autoimmune diseases in various timeframes. Systemic lupus erythematosus (SLE) is the most prevalent autoimmune connective tissue disease (AICTD) appearing alongside KFD. An 18-year-old female presented with acute muscle weakness, shortness of breath, fever, and significant weight loss for 5 months before admission. Pain and morning joint stiffness had been felt for 9 months. One year ago, she lumped her right neck and was diagnosed with KFD from the excision biopsy and immunohistochemical staining (CD68). Creatine-kinase enzymes and C-Reactive protein were elevated with a high anti-Ku and anti-Jo-1 negative level. There was a low level of complements, high anti-nuclear antibody titer, with positive anti-SS-A. Sialometry and Schirmer test showed reduced salivary and lacrimal gland production. We diagnosed this patient as having an overlap syndrome preceded by KFD. The AICTD involved was Sjögren's syndrome and SLE. Although KFD is considered a self-limiting disease, its occurrence should be noticed regarding the possibility of other autoimmune conditions. KFD usually coincides with AICTD, although it could also precede or occur afterward. This case is reported to raise awareness of the overlap syndrome preceded by KFD.

Kikuchi disease complicated with aseptic meningitis following COVID-19 Vaccination: a case report.

BACKGROUND: Kikuchi Fujimoto disease is a rare self-limiting disorder mainly affecting young Asian females. The typical presentation is unexplained fever with associated cervical lymphadenopathy. It can mimic many sinister diseases such as lymphoma, tuberculosis, and systemic lupus erythematosus. Aseptic meningitis due to Kikuchi disease is extremely rare, and majority were reported from Japan. There have been no published cases of aseptic meningitis due to Kikuchi disease in Sri Lanka. CASE PRESENTATION: A 29 years old Sri Lankan female presented with a prolonged fever for three weeks with an associated headache for five days duration. She developed painful cervical lymphadenopathy during the hospital stay. She has been previously well and had been vaccinated against COVID-19 six weeks before. Her lumbar puncture showed lymphocytic pleocytosis with marginally elevated protein levels and reduced ratio of serum to CSF sugar. Lymph node biopsy was consistent with necrotizing lymphadenitis. She was subsequently diagnosed with Kikuchi disease complicated with aseptic meningitis. She responded to corticosteroids well and had an uneventful recovery. CONCLUSION: Kikuchi disease is a rare self-limiting disorder that can be complicated with aseptic meningitis on infrequent occasions. Other conditions such as tuberculosis, lymphoma, systemic lupus erythematosus, and adult-onset Still's disease should be considered as differential diagnoses. Knowledge of Kikuchi disease and its complications will prevent unnecessary investigations which delay the early diagnosis and treatment.

[Clinical characteristics and treatment in adults and children with histiocytic necroti-zing lymphadenitis].

OBJECTIVE: To analyze the clinical data of histiocytic necrotizing lymphadenitis(HNL), comparing the similarities and differences between children and adults, to deepen the understanding of the disease by clinical physicians, and to improve diagnostic rate and reduce misdiagnosis and mistreatment. METHODS: The clinical data of hospitalized patients with histiocytic necrotizing lymphadenitis diagnosed by biopsy from January 2010 to August 2023 in Peking University First Hospital were collec-ted, and the clinical features, laboratory examinations, pathological features, treatments with antibiotics and glucocorticoids, and prognosis of histiocytic necrotic lymphadenitis were analyzed. Grouped based on age, the differences of clinical characteristics, laboratory tests, treatment, and prognosis between the children group (< 16 years old) and the adult group (≥16 years old) were compared. RESULTS: Among the 81 enrolled patients, there were 42 males and 39 females. The median age was 21(14, 29) years, the median duration of disease was 20.0(13.0, 30.0) days, and the median length of hospital stay was 13.0 (10.0, 15.0) days. The first symptoms were fever, lymphadenopathy, and both. All the patients had enlarged lymph nodes with different parts and sizes, 96.3% (78 of 81) of the patients had cervical lymphadenopathy, 50.6% (41 of 81) had bilateral cervical lymphadenopathy, 55.6% (45 of 81) had supraclavicular, axillary or inguinal lymphadenopathy, and the median lymph node diameter was 20.0(20.0, 30.0) mm. Only one patient had no fever, the other 80 patients had fever, the median peak body temperature was 39.0(38.0, 39.8) ℃. Accompanying symptoms: rash (8.6%, 7/81), fatigue (34.6%, 28/81), night sweating (8.6%, 7/81), chills (25.3%, 25/81), muscle soreness (13.6%, 11/81), and joint pain (6.2%, 5/81). There were 17 cases (21.0%, 17/81) of hepatosplenomegaly, of which 12 cases (70.6%, 12/17) were splenomegaly. 68.8%(55/80) of patients had a decrease in white blood cell (WBC) count, with 47.5%(38/80)increased in lymphocyte(LY)proportion, 53.4%(39/73) increased in high-sensitivity C-reactive protein(CRP), 79.2%(57/72) increased in erythrocyte sedimentation rate(ESR), 22.2%(18/81) increased in alanine transaminase(ALT), 27.2%(22/81) elevated in aspartate transaminase(AST), and 81.6%(62/76) elevated in lactate dehydrogenase(LDH). All the 81 patients underwent lymph node biopsy, and 77.8%(63/81) of the patients showed that most of the structures in the lymph nodes were destroyed or disappeared, and 16.0%(13/81) of the lymph nodes were still in existence, hyperplasia and normal lymph node were 1.2%(1/81) respectively, and 3.7%(3/81) had normal lymph node structures. Immunohistochemical staining was performed in 67 cases. The percentages of CD3+ and CD68(KP1)+ were respectively 97.0%(65/67), and MPO+ were 94.0%(63/67). In the study, 51 patients (63.0%, 51/81) were treated with glucocorticoid therapy after diagnosis. The median time for temperature to return to normal was 1.0(1.0, 4.0) days after glucocorticoid therapy. when the glucocorticoid treatment worked best, the body temperature could drop to normal on the same day. There were significant differences in length of stay, predisposing factors, chills, the rate of increase in high-sensitivity CRP, antibiotic and glucocorticoid treatment between the adults and children groups (P < 0.05). CONCLUSION: In clinical practice, if there are cases with unexplained fever, superficial lymph node enlargement, and reduced white blood cells as clinical characteristics, and general antibiotics treatment is ineffective, histiocytic necrotic lymphadenitis should be considered. Lymph node biopsy should be performed as early as possible to clarify the diagnosis, reduce misdiagnosis and mistreatment, and symptomatic treatment should be the main treatment. Glucocorticoids therapy has a definite therapeutic effect.

Clinical features and recurrence predictors of histiocytic necrotizing lymphadenitis in Chinese children.

OBJECTIVES: To characterize the clinical features and to identify the predictors of recurrence of histiocytic necrotizing lymphadenitis (HNL) in Chinese children. STUDY DESIGN: This study retrospectively analyzed the clinical characteristics, laboratory and pathological findings, and recurrence status of children diagnosed with HNL at a single center in China from January 2018 to May 2023. Logistic regression analysis was employed to identify predictors of HNL recurrence. RESULTS: 181 Chinese children with histopathologically confirmed HNL were enrolled (121 males and 60 females). The mean age was 9.3 ± 2.9 years. The most prominent clinical features were fever (98.9%) and cervical lymphadenopathy (98.3%). Aseptic meningitis was the most frequent complication (38.5%), while hemophagocytic lymphohistiocytosis and autoimmune disease were rare (1.7% and 1.2%, respectively). Recurrence occurred in 12.7% of patients. Erythrocyte sedimentation rate (> 30 mm/h) was the significant predictors of HNL recurrence, with odds ratios of 6.107, respectively. CONCLUSION: Our study demonstrates that fever and cervical lymphadenopathy are the most frequent clinical manifestations of HNL in Chinese children, which often coexist with aseptic meningitis. HNL patients with risk factors require follow-up for recurrence.

Hypothermia, bradycardia, and hypotension during glucocorticoid or cyclosporine A therapy in a boy with Kikuchi-Fujimoto disease.

Kikuchi-Fujimoto disease (KFD) is an inflammatory disease of unknown aetiology characterised by fever and cervical lymphadenopathy. Although KFD is a self-limiting disease, patients with severe or long-lasting course require glucocorticoid therapy. We presently report a 17-year-old boy with KFD who had seven relapses since the onset at 4 years old. He suffered from hypothermia, bradycardia, and hypotension during the treatment with prednisolone or methylprednisolone. All of his vital signs recovered after cessation of the drug in addition to fluid replacement and warming. Thus, glucocorticoid was effective but could not be continued because of the adverse event. Although hypothermia developed during the treatment with 5 mg/kg/day of cyclosporine A (CsA) at his second relapse, he was successfully treated with lower-dose CsA (3 mg/kg/day). Thereafter, he had five relapses of KFD until the age of 12 years and was treated by 1.3-2.5 mg/kg/day of CsA. Hypothermia accompanied by bradycardia and hypotension developed soon after concomitant administration of ibuprofen at his fifth and sixth relapses even during low-dose CsA therapy. Conclusively, glucocorticoid, standard dose of CsA, or concomitant use of non-steroidal anti-inflammatory drugs may cause hypothermia, bradycardia, and hypotension and needs special attention. Low-dose CsA could be a choice for such cases with KFD.

Kikuchi-Fujimoto disease, simultaneously diagnosed with systemic lupus erythematosus in an Arabic female: an agonizing combination.

Kikuchi-Fujimoto disease (KFD), also known as histiocytic necrotizing lymphadenitis, is a rare, benign condition affecting young Oriental-Asian females. It is characterized by fever and tender cervical lymphadenopathy with an unclear aetiology, and in most longitudinal reviews, KFD occurs before systemic lupus erythematosus (SLE). Herein, the case of a 28-year-old Kuwaiti female without any relevant past medical history, who was simultaneously diagnosed with KFD and SLE following an Ebstein-Barr virus infection, is reported. The patient was treated with oral prednisolone, hydroxychloroquine, cyclosporin, and belimumab and her response was clinically and biochemically favourable. Although KFD is prevalent in Asian populations, it may affect all races. Early diagnosis of KFD is difficult, particularly when simultaneously diagnosed with SLE, but crucial to preventing inappropriate therapy. Clinicians need to know about this rare disease, especially when patients present with fever and swollen lymph nodes, due to a risk of misdiagnosis with tuberculosis or lymphoma, as these are more often thought to be the cause of such symptoms.

Kikuchi-Fujimoto disease evolves into lupus encephalopathy characterized by venous sinus thrombosis: a case report.

Kikuchi-Fujimoto disease (KFD) is a benign, self-limiting illness that can progress to systemic lupus erythematosus (SLE) in approximately 30% of cases. Neurological injuries can occur in both diseases, albeit with distinct presentations. Venous sinus thrombosis is a serious cerebrovascular complication in patients with neuropsychiatric SLE but is rarely observed in patients with KFD. The involvement of various antibodies, particularly antiphospholipid antibodies, can cause vascular endothelial cell injury, resulting in focal cerebral ischemia and intracranial vascular embolism in SLE. However, there are cases in which thrombotic pathology occurs without antiphospholipid antibody positivity, attributed to vascular lesions. In this report, we present a case of KFD and lupus encephalopathy featuring cerebral venous sinus thrombosis, despite the patient being negative for antiphospholipid antibody. We also conducted a comparative analysis of C3 and C4 levels in cerebrospinal fluid (CSF) and peripheral blood, along with the protein ratio in CSF and serum, to elucidate the pathological changes and characteristics of lupus encephalopathy.

Kikuchi-Fujimoto Disease: A Case Report of Prolonged Fever and Lymphadenopathy in a Young Girl.

Kikuchi-Fujimoto disease (KFD) is a benign and self-limited disorder that usually presents with regional cervical lymphadenopathy and fever. We report a case of a 12-year-old female who complained of fever, night sweating, significant weight loss, and tender right cervical lymph node enlargement for 2 months. A full workup including laboratory tests and imaging studies, an excisional biopsy, and histopathological analysis were done, and the diagnosis of KFD was confirmed. The patient was treated with analgesia and oral prednisolone, resulting in good improvement. A high degree of clinical suspicion is imperative for physicians, given the rarity of the disease and the associated diagnostic challenges.

A Rare Neurological Presentation of Kikuchi-Fujimoto Disease.

This case report describes a 17-year-old boy with reduced consciousness and T2-weighted hyperintensity, focal diffusion restriction, and microhemorrhages within the deep gray nuclei and surrounding white matter.

Kikuchi-Fujimoto disease associated with a flare-up of a leukocytoclastic vasculitis: A rare case report and review of literature.

RATIONALE: Kikuchi-Fujimoto disease (KFD) also known as histiocytic necrotizing lymphadenopathy is an exceedingly rare cause of cervical lymphadenopathy, commonly accompanied by systemic symptoms such as fever, fatigue, night sweats, myalgia, skin rash. PATIENT CONCERNS: In this paper, we report the case of a 22-year-old female patient who experienced a flare-up of leukocytoclastic vasculitis that was complicated by the appearance of a cervical lymph node with dysphagia, fever and nausea. DIAGNOSIS: Infectious and autoimmune workup came back negative. INTERVENTIONS: Excisional lymph node biopsy was done and the pathology results were consistent with histiocytic necrotizing lymphadenitis in keeping with Kikuchi-Fujimoto disease. OUTCOMES: Patient improved on intravenous corticosteroids and was discharged on per os prednisone. Six month follow-up shows complete resolution of her symptoms. LESSONS: KFD should be ruled out in patients with autoimmune or inflammatory diseases who develop lymphadenopathies.

Kikuchi-Fujimoto disease during early pregnancy.

Kikuchi-Fujimoto disease (KFD) is rare during pregnancy. It is characterized by necrotizing lymphadenitis and often occurs in young Asian women. We report a case of KFD during pregnancy, which was difficult to diagnose. A 37-year-old pregnant female (gestational week [GW] 7+5) was admitted to our hospital because of hyperemesis gravidarum. On the eighth day of hospitalization (GW 8+6), she suddenly developed a fever (38.0°C) with skin rash and posterior pharynx redness. Blood tests showed pancytopenia and abnormal liver function. The patient was misdiagnosed with severe Epstein-Barr virus infection and administered with prednisolone. Subsequently, cervical lymphadenopathy was observed, and biopsy results led to the diagnosis of KFD. Thereafter, her symptoms improved, and she was discharged at GW 13+4. KFD must be included as a differential diagnosis for patients with fever, abnormal liver function, and pancytopenia during pregnancy.

Occlusive Retinal Vasculitis in a Pediatric Patient With Kikuchi-Fujimoto Disease and Sickle Cell Trait.

A 13-year-old Black male patient with a history of Kikuchi-Fujimoto disease (KFD) and sickle cell trait presented with acute painless vision loss and no light perception vision (NLP) in his left eye. The examination was indicative of occlusive retinal vasculitis with near total central retinal artery occlusion (CRAO). He was started on oral steroids with dramatic reperfusion and improvement of the retinal hemorrhages. However, his vision remained at NLP. Oral steroids were tapered, and rituximab infusion was initiated. While ocular involvement is uncommon in KFD, vision-limiting complications, such as occlusive retinal vasculitis, ophthalmic artery occlusion, and CRAO can occur. Early systemic immunosuppression is key in achieving rapid remission. [Ophthalmic Surg Lasers Imaging Retina 2024;55:235-239.].

Histiocytic necrotizing lymphadenitis with hemophagocytic lymphohistiocytosis in adults: A single-center analysis of 5 cases.

BACKGROUND: Histiocytic necrotizing lymphadenitis (HNL) is a self-limited inflammatory disease of unknown pathogenesis. A very small fraction of patients with HNL could develop hemophagocytic lymphohistiocytosis (HLH), a hyperinflammatory disorder. These patients are diagnosed as HNL with HLH (HNL-HLH). HNL-HLH in the pediatric population has been systemically studied, however, the clinical, laboratory, and radiological features and outcomes of adult patients with HNL-HLH remain to be explored. We aimed to explore the clinical, laboratory, and radiological features and outcomes of adult patients with HNL-HLH. METHODS: We collected the clinical data of patients with HNL-HLH admitted to the First Affiliated Hospital of Nanjing Medical University from October 2010 to June 2015. All the patients underwent lymph node biopsy and have a pathological diagnosis of HNL. The age, gender, clinical presentation, lymph node signs, laboratory findings and imaging data, and pathological findings of the patients were collected. RESULTS: In this study, we reported five adult patients with HNL-HLH. All five patients showed enlarged lymph nodes and prolonged fever. Laboratory findings were consistent with the diagnosis of HLH. 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) showed enlarged lymph nodes with increased FDG uptake and splenic hypermetabolism could be present. All the patients responded well to corticosteroids and had a good prognosis. Two of the five patients were diagnosed with systemic lupus erythematosus during the follow-up. CONCLUSIONS: Our study demonstrated that adult patients with HNL-HLH showed distinct clinical, laboratory, and radiological features. And the prognosis is good and patients could be managed with steroids and supportive care.

[Recurrent lymphadenitis was Kikuchi-Fujimoto disease]. / Lymfadenit som mystiskt återkom var Kikuchi­Fujimotos sjukdom.

Kikuchi-Fujimoto disease, or histiocytic necrotizing lymphadenitis, is in most cases a benign disease which affects lymph nodes in the cervical region. Cervical adenopathy and fever are the most common symptoms, and young adults are mostly affected. Lymph node biopsy is the mode of diagnosis with demonstration of paracortical areas of apoptotic necrosis with abundant karyorrhectic debris and a proliferation of histiocytes, plasmacytoid dendritic cells, and CD8+ T cells in the absence of neutrophils. In most cases, the disease is self-limiting but it can be recurrent or evolve to SLE. Treatment varies from symptomatic to more systemic with cortisone and intravenous immunoglobulin.

A rare co-existence of histiocytic necrotizing lymphadenitis with metastatic papillary thyroid carcinoma and review of the literature.

Histiocytic necrotizing lymphadenitis (HNL) is a benign, self-limiting disease that is rare clinically. The coexistence of HNL and tumor is rarer. We report a male patient who was preoperatively diagnosed with papillary thyroid carcinoma with cervical lymph nodes metastasis, and the postoperative pathological examination showed histiocytic necrotizing lymphadenitis combined with metastatic papillary thyroid carcinoma in the same single lymph node. More interestingly, Epstein‒Barr virus was positive in these lymph nodes by in situ hybridization. This may suggest a trigger for the coexistence of the two diseases.

Immune-mediated necrotizing myopathy with concomitant development of Kikuchi-Fujimoto disease.

Immune-mediated necrotizing myopathy (IMNM) is a distinct type of idiopathic inflammatory myositis, pathologically characterized by myofiber necrosis and degeneration in the absence of lymphocyte infiltration. Herein, we present a case of IMNM with concomitant development of Kikuchi-Fujimoto disease (KFD), characterized by histiocytic necrotizing lymphadenitis, in a 36-year-old woman who had a treatment history for rheumatoid arthritis (RA). Treatment with oral prednisolone and tacrolimus as immunosuppressants resulted in the remission of the skeletomuscular involvement and lymphadenopathy. To the best of our knowledge, this is the first report of IMNM and KFD developing concomitantly during the clinical course of RA.