Dysmorphic megakaryocytes in TAFRO syndrome: A case series from a single institute.

TAFRO syndrome is a rare systemic inflammatory disorder of unknown etiology characterized by thrombocytopenia, anasarca, fever, reticulin myelofibrosis, renal dysfunction, and organomegaly. The diagnosis of TAFRO syndrome can be challenging; however, prompt diagnosis is vital because TAFRO syndrome is a progressive and life-threatening disease. We have showcased five patients with TAFRO syndrome who had similar bone marrow (BM) findings that could be considered the findings that characterize TAFRO syndrome. All patients were treated with corticosteroids and tocilizumab; three of the five patients (60 %) responded positively to the treatment. The unique BM findings observed in this study were megakaryocytes with distinct multinuclei and three-dimensional and indistinct bizarre nuclei ("dysmorphic megakaryocyte"), similar to the megakaryocyte morphology observed in myeloproliferative neoplasms (MPNs). Notably, dysmorphic megakaryocytes were observed in all five cases, whereas only two of the five patients tested positive for reticulin myelofibrosis, and three of the five patients had megakaryocytic hyperplasia, which are considered typical findings of TAFRO syndrome. Thus, the BM findings of dysmorphic megakaryocytes could help in the correct and immediate diagnosis of TAFRO syndrome.

A case of TAFRO syndrome after vaccination, successfully treated with cyclosporine.

BACKGROUND: TAFRO syndrome is a rare disorder that causes thrombocytopenia, generalized oedema, fever, organ enlargement, and renal impairment. Few reports have suggested an association with vaccines, and few cases have undergone renal biopsy. TAFRO syndrome is often severe and fatal, and its cause is unknown. We report a case of TAFRO syndrome that occurred after vaccination with the coronavirus disease 2019 (COVID-19) vaccine. CASE PRESENTATION: An 82-year-old woman received two doses of the BNT162b2 mRNA vaccine 3 weeks apart. Two weeks later, she was admitted to the hospital with oedema, accompanied with renal failure and thrombocytopenia. After close examination, she was diagnosed with TAFRO syndrome. She was treated with steroids, cyclosporine, and thrombopoietin receptor agonists. The patient was discharged after several months in remission. CONCLUSIONS: Although an incident of TAFRO syndrome after COVID-19 vaccination has been previously reported, this is a rare case in which the patient went into remission and was discharged. A renal biopsy was also performed in this case, which was consistent with previous reports. The favorable treatment course for TAFRO syndrome provides valuable insights.

[Improvement of tissue fibrosis in TAFRO syndrome by prednisolone monotherapy].

We report the case of a 48-year-old man who presented with fatigue and weight loss. A local physician observed elevated alkaline phosphatase levels, anemia, thrombocytopenia, and renal dysfunction. Fever also appeared, and the patient was admitted to our hospital. Computed tomography revealed hepatosplenomegaly, pleural and ascitic fluid, and left axillary lymphadenopathy. Bone marrow biopsy indicated hyperplasia with increased megakaryocytes and reticulin fibrosis. Axillary lymph node biopsy showed Castleman's disease-like features. Liver biopsy revealed proliferation of reticulin fibrosis. Therefore, TAFRO syndrome was diagnosed and treatment with 1 mg/kg prednisolone was started. Anemia and thrombocytopenia improved, and after 24 weeks of treatment, serum hyaluronic acid and type IV collagen decreased to the normal range. Bone marrow biopsy after 18 weeks of treatment showed decreased reticular fibers. In TAFRO syndrome, improvement of liver and bone marrow fibrosis can be expected with adequate intervention, and serum hyaluronic acid and type IV collagen are useful for evaluating fibrosis.

TAFRO syndrome with fatigue and abdominal distension as the first symptom: A case report.

TAFRO syndrome is a peculiar and rare type of multi-centric Castleman's disease which contained a series of symptoms such as thrombocytopenia (T), anasarca (A), fever (F), reticulin fibrosis (R), and organomegaly (O). Here we provide a case of TAFRO syndrome with the manifestation of fatigue, abdominal distension, and low fever at primary diagnosis, characterized by multiple lymphadenopathy of superficial mediastinal and retroperitoneal lymph nodes, and it was finally confirmed by lymph node biopsy. The patient recovered speedy after receiving CHOP chemotherapy. In this case report, the patient has a history of dust-exposure and hepatitis B virus infection, which may be potentially related to the disease. In addition, this case suggests the importance of pathological biopsy of complete lymph nodes in diagnostic process.

TAFRO syndrome: A disease that known is half cured.

Thrombocytopenia, anasarca, fever, reticulin fibrosis/renal failure, and organomegaly (TAFRO) syndrome is rare in clinical practice. It is a systemic inflammatory disease caused by a cytokine storm. Its clinical manifestations include thrombocytopenia, systemic edema, fever, bone marrow fibrosis, renal insufficiency, and organ enlargement. The high mortality rate of TAFRO syndrome is due to the difficulty of acquiring biopsy samples for diagnosis and the rapid disease progression. This disease is poorly understood by clinicians. Early detection, accurate diagnosis, and timely treatment play key roles in prolonging the survival of the patients. This review summarizes the latest progress in the pathogenesis, diagnostic criteria, and treatment regimens of TAFRO syndrome, aiming to help clinicians better understand TAFRO syndrome and improve its diagnosis and treatment.

The experience of diagnosis and treatment for TAFRO syndrome.

Early identification, diagnosis and treatment of TAFRO syndrome are very importants. We retrospectively analysed 6 patients with TAFRO syndrome. Their clinical manifestations, treatment methods, survival and other aspects were summarized. All patients were pathologically diagnosed with Castleman's disease, with fever, an inflammatory storm state and varying degrees of anasarca. All patients received steroid therapy; four of them also received chemotherapy, and 1 received rituximab. Of the 3 patients with severe disease, only 1 patient who received the recommended dose of glucocorticoids survived. Early administration of glucocorticoids can improve the prognosis, especially in patients with severe disease, and adequate glucocorticoids are important.

Epstein-Barr Virus-Positive Cutaneous and Systemic Plasmacytosis with TAFRO Syndrome-like Symptoms Successfully Treated with Rituximab.

Histopathologic findings in the lymph nodes of patients with thrombocytopenia, anasarca, fever, reticulin fibrosis, renal dysfunction, and organomegaly (TAFRO) syndrome are similar to those of idiopathic multicentric Castleman's disease (iMCD), but TAFRO syndrome is different from iMCD in how it can progress rapidly and be fatal. These patients present scarce lymphadenopathy and low immunoglobulin levels. We present a case of cutaneous and systemic plasmacytosis (C/SP) that caused TAFRO syndrome-like symptoms which were successfully treated with rituximab. A 67-year-old woman presented with fever and a pruritic skin rash. Numerous plasma cells were observed in the peripheral blood and imaging revealed organomegaly, anasarca, and generalized lymphadenopathy. Subsequently, she rapidly developed thrombocytopenia as well as renal and heart failure. She tested positive for the Epstein-Barr virus (EBV), elevated immunoglobulins, and C/SP, which are also atypical for TAFRO syndrome, thereby complicating the diagnosis. However, after using the Japanese TAFRO Syndrome Research Group diagnostic criteria, we promptly administered rituximab to treat the C/SP with TAFRO-like symptoms and saved her life. Finally, histopathological observations of the lymph node biopsy helped confirm EBV-positive hypervascular-type iMCD. Therefore, diagnosing TAFRO-like syndromes based on the Japanese diagnostic criteria and following the associated treatment even without a confirmed diagnosis is crucial to improving the patient outcomes.

[Successful rituximab treatment of TAFRO syndrome refractory to glucocorticoids and tocilizumab].

A 53-year-old man was presented with fever, eyelid edema, and thrombocytopenia. Based on examination outcomes, he was diagnosed with immune thrombocytopenia. He was prescribed prednisolone (PSL) at 0.5 mg/kg/day; subsequently, his platelet count improved and fever improved. PSL dose was tapered and stopped without relapse. However, 1 month later, the patient presented to our hospital with fever, generalized edema, thrombocytopenia, and acute renal failure. Computed tomography revealed multiple lymphadenopathies, hepatomegaly, pleural effusion, and ascites. Bone marrow biopsy indicated reticulin fibrosis, and lymph node biopsy revealed mixed-type Castleman disease. Based on these findings, he was diagnosed with grade 5 TAFRO syndrome (very severe). Steroid pulse therapy and tocilizumab were ineffective in improving his condition. Therefore, rituximab was administered instead of tocilizumab, and his condition eventually improved. The optimal treatment for TAFRO syndrome is yet to be established. If tocilizumab is ineffective as the second-line treatment, then rituximab might be effective.

TAFRO syndrome with a fatal clinical course following BNT162b2 mRNA (Pfizer-BioNTech) COVID-19 vaccination: A case report.

TAFRO syndrome is a rare disorder that manifests as thrombocytopenia, anasarca, fever, reticulin myelofibrosis, renal dysfunction, and organomegaly. Although this disease often follows a severe clinical course, the cause remains unknown. The coronavirus disease 2019 (COVID-19) pandemic is a major global problem. Vaccination against COVID-19 has been successful; however, there are concerns about severe adverse events. Herein, we report a rare presentation of TAFRO syndrome triggered by the COVID-19 vaccine with a fatal clinical course. A 42-year-old Japanese man presented to our hospital complaining of fever lasting for 2 weeks that occurred a day after receiving the BNT162b2 mRNA (Pfizer-BioNTech) COVID-19 vaccine. The patient had a low platelet count, ascites, reticulin myelofibrosis, renal failure, and lymphadenopathy and was diagnosed with TAFRO syndrome. Despite administering several immunosuppressive drugs, the condition did not improve. The patient repetitively developed and eventually died of bacteremia caused by multidrug-resistant Klebsiella pneumoniae. We highlight the first reported case of TAFRO syndrome after COVID-19 vaccination.

TAFRO syndrome with renal biopsy successfully treated with steroids and cyclosporine: a case report.

BACKGROUND: TAFRO syndrome is an acute or subacute systemic inflammatory disease with no apparent cause, presenting with fever, generalized edema, thrombocytopenia, renal damage, anemia, and organ enlargement. Interleukin-6, vascular endothelial growth factor, and other cytokines are thought to be the etiologic agents that increase vascular permeability and cause the resulting organ damage. Only few reports of renal biopsy performed in patients with TAFRO syndrome exist. CASE PRESENTATION: A 61-year-old woman, with a history of Sjogren's syndrome, was admitted to our hospital with anasarca and abdominal distension. Based on the clinical course and various laboratory findings, we diagnosed TAFRO syndrome. Renal biopsy revealed thrombotic microangiopathy, including endothelial cell swelling, subendothelial space expansion, and mesangiolysis. She was treated with oral prednisolone and cyclosporine, with consequent resolution of anasarca, pleural effusion, and ascites, and improvement in renal function and urinary findings. The patient's platelet count also normalized after 2 months of treatment. CONCLUSIONS: Given that only few reports of improvement in the systemic symptoms of TAFRO syndrome using steroids and cyclosporine exist, our study investigating the relationship between the pathogenesis of TAFRO syndrome and renal disorders, as well as treatment methods, provides valuable insights.

TAFRO Syndrome with Renal Thrombotic Microangiopathy: Insights into the Molecular Mechanism and Treatment Opportunities.

TAFRO syndrome is an extremely rare form of idiopathic MCD, characterized by thrombocytopenia, anasarca, fever, reticulin fibrosis on bone marrow biopsy, and organomegaly. Like idiopathic MCD, renal involvement is also a common presentation in patients with TAFRO syndrome. Furthermore, membranoproliferative glomerulonephritis (MPGN)-like injury and thrombotic microangiopathy (TMA) are the most reported histopathologic findings of renal biopsy. Several molecular mechanisms have been previously postulated in order to explain the TAFRO syndrome symptoms, including abnormal production of interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), etc. The role of these cytokines in renal injury, however, is not well understood. The aim of this review article is to summarize the latest knowledge of molecular mechanisms behind the TAFRO syndrome and their potential role in renal damage.

[A case report of TAFRO syndrome].

The study is to improve clinicians' understanding of TAFRO syndrome, to explore the diagnosis and treatment of TAFRO syndrome and to identify TAFRO syndrome in the early stage. The clinical manifestations, laboratory examination results, imaging manifestations, diagnosis and treatment of TAFRO syndrome were reported, and the literature of TAFRO syndrome was reviewed. The main clinical manifestations of the female were intermittent vaginal bleeding, fever, depressive edema of both legs, red blood cell and thrombocytopenia, and renal function deterioration. The results showed that leukocytes increased, anemia, thrombocytopenia and severe renal dysfunction were found; With fever, C-reactive protein and procalcitonin increased significantly, bone penetration suggested that granulocyte proliferation was active, and megakaryocytes were seen. But anti-infection treatment was ineffective; CT suggested that there was a high uptake of multiple fluorodeoxyglucose (FDG) in many parts of the body; The lymph node biopsy was considered to be in accordance with the transparent vascular type of Castleman disease; Renal biopsy was used to return thrombotic microvascular disease with subacute renal tubulointerstitial nephropathy. In terms of treatment, the clinical condition of the patients was improved after methylprednisolone (60 mg, once a day), the temperature was normal, and the effusion in the serous cavity was better than before. The blood transfusion and platelet support therapy were intermittently given. Hemoglobin and platelets were increased in sex, and the urine volume increased to 1 000 mL/day. However, the platelet dropped at a later time, after 1 month of treatment with topizumab, the clinical condition of the patients was further improved. At present, the blood pigment and platelets returned to normal and had been separated from dialysis. TAFRO syndrome is a special subtype of idiopathic multicentric Castleman disease, and it is a group of systemic inflammatory diseases with its own characteristics. Its clinical manifestations and diagnosis and treatment are unique compared with other idiopathic multicentric Castleman diseases. For the enlargement of lymph nodes of unknown reasons, it is suggested to improve the lymph node biopsy actively. Renal insufficiency is an important part of TAFRO syndrome. Renal biopsy is of great significance to study the pathogenesis of TAFRO syndrome and to judge the prognosis of patients. The clinical diagnosis of the disease requires comprehensive clinical manifestations and the results of various examinations. Early diagnosis and early treatment of the disease can often achieve good clinical effect.

Intracranial Hemorrhage in a Patient with TAFRO Syndrome Treated with Cyclosporine A and Rituximab.

TAFRO syndrome, a rare subtype of idiopathic multicentric Castleman disease, manifests as thrombocytopenia, anasarca, fever, reticulin fibrosis, and organomegaly. Thrombotic microangiopathy, including renal dysfunction, is frequently associated with this syndrome. TAFRO syndrome can be life threatening and show rapid progression, and the diagnosis and management of this disorder remain challenging. A 48-year-old woman was diagnosed with TAFRO syndrome complicated by thrombotic microangiopathy based on the clinical and histopathological findings. After receiving high-dose steroids, her thrombocytopenia and anasarca did not improve. The patient subsequently received a combination of cyclosporine A and rituximab as second-line therapy, which resulted in a significant gradual improvement in the clinical symptoms. Meanwhile, her platelet count increased to more than 40 × 109/L; however, she developed intracranial hemorrhage. Following surgical evacuation, the patient recovered with an achievement of sustained remission. Based on these findings, attention should be paid to life-threatening bleeding associated with local thrombotic microangiopathy even when intensive treatment is administered for TAFRO syndrome.

Multicentric Castleman disease and the evolution of the concept.

The term multicentric Castleman disease (MCD) encompasses a spectrum of conditions that share some overlapping clinicopathological manifestations. The fundamental pathogenetic mechanism involves dysregulated cytokine activity, causing systemic inflammatory symptoms as well as lymphadenopathy. Some of the histological changes in lymph nodes resemble the histology of unicentric Castleman disease (UCD). However, based on current knowledge, the use of this shared nomenclature is unfortunate, since these disorders differ in pathogenesis and prognosis. In Kaposi sarcoma-associated herpesvirus (KSHV)-associated MCD, cytokine overactivity is caused by viral products, which can also lead to atypical lymphoproliferations and potential progression to lymphoma. In idiopathic MCD, the hypercytokinemia can result from various mechanisms, which ultimately lead to different constellations of clinical presentations and varied pathology in lymphoid tissues. The authors review the evolving concepts and definitions of the various conditions under the eponym of multicentric Castleman disease.

Tocilizumab for the treatment of TAFRO syndrome: a systematic literature review.

TAFRO syndrome is a newly recognized disease entity characterized by thrombocytopenia, anasarca, fever, reticulin myelofibrosis, renal dysfunction, and organomegaly. The objective of this study was to investigate the effectiveness of tocilizumab, an anti-interleukin-6 receptor antibody, in patients with TAFRO syndrome. We performed a systematic literature review from inception to July 5, 2020, for articles reporting tocilizumab administration for the treatment of TAFRO syndrome. We identified 31 patients with TAFRO syndrome treated with tocilizumab. The mean age was 49.8 years, and 61.3% of the patients were male. The mean observation period was 12.6 months. Tocilizumab was used at the standard intravenous dose (8 mg/kg) weekly or every 2 weeks in combination with other immunosuppressive drugs, such as glucocorticoids, rituximab, cyclosporine, or cyclophosphamide, in most of the patients. Eighteen patients (58.1%) received tocilizumab as a first-line treatment, while it was a second-line or a third-line treatment for 13 patients with insufficient responses to the prior treatments. Sixteen patients (51.6%) obtained complete response to tocilizumab treatment, whereas 15 patients showed only partial or no response. Detailed factors of ineffectiveness included persistent thrombocytopenia (n = 7), persistent anasarca (n = 5), persistent renal dysfunction (n = 2), and persistent fever (n = 2). A total of four patients (12.9%) succumbed to the disease, while the remaining twenty-seven patients survived. Two patients achieved drug-free remission at last visit, and disease remission was maintained with tocilizumab monotherapy in five patients. No new safety signal was reported. Tocilizumab was effective in ~ 50% of the patients, suggesting it could serve as a treatment choice for TAFRO syndrome. Poor clinical response to tocilizumab observed in other patients highlights the need for the additional therapeutic treatment options.

Acute Kidney Injury Caused by TAFRO Syndrome in a Chinese Patient: Efficacy of Long-Term Corticosteroids Combined with Bortezomib and Cyclophosphamide.

INTRODUCTION: Thrombocytopenia, ascites, myelofibrosis, renal dysfunction, and organomegaly (TAFRO) syndrome is a newly recognized and rare clinical subtype of Castleman disease. Renal involvement in TAFRO syndrome usually presents with mild proteinuria, microscopic hematuria, and acute renal injury requiring temporary renal replacement. There is no standard therapy available and treatment failures are common, leading to a poor prognosis. We report a case of acute renal failure caused by TAFRO syndrome, successfully managed by long-term corticosteroids combined with bortezomib and cyclophosphamide. CASE PRESENTATION: The patient was a 52-year-old female who presented with fever, anasarca, oliguria, and abdominal distension at first. She progressed rapidly to anuric renal failure requiring hemodialysis. She also demonstrated thrombocytopenia, anemia, coagulopathy, and a hyperinflammatory status. Her CT scan showed severe polyserositis, splenomegaly, and lymphadenopathy. Her serum vascular epithelial growth factor level was significantly elevated. Axillary lymph node biopsy showed hyaline-vascular type Castleman disease, supporting the diagnosis of TAFRO syndrome. Her renal function recovered after high-dose steroids and supportive treatment. A weekly dosing regimen of bortezomib, cyclophosphamide, and dexamethasone combined with medium dose prednisone in between were deployed. Her blood cell count and renal function remained stable after 6 months. The inflammation was suppressed and the polyserositis resolved completely. CONCLUSION: TAFRO syndrome is rare and has a poor prognosis due to the lack of standard treatment. Our patient might be the first TAFRO case successfully treated by bortezomib, cyclophosphamide, and corticosteroids.

Disseminated Mycobacterium genavense infection mimicking TAFRO syndrome.

TAFRO syndrome is a rare variant of idiopathic multicentric Castleman's disease, for which disseminated non-tuberculous mycobacteria (NTM) infection must be excluded. However, due to the slow and fastidious growth of the organisms, identification of the pathogen is often challenging. We herein describe a case of disseminated Mycobacterium genavence infection, in which manifestations of the patient were confusingly similar to those of TAFRO syndrome. A 69-year-old Japanese man presented with prolonged fever accompanying pain in his back and ribs on the right side. Systemic investigations revealed thrombocytopenia, marked elevation of alkaline phosphatase, anasarca (pleural effusion and ascites), megakaryocytosis in the bone marrow, and hepatomegaly. Magnetic resonance imaging (MRI) showed diffuse, T1-and T2-low-intensity spotted lesions on his vertebral bodies, but biopsy showed inconclusive results. The patient met the diagnostic criteria of TAFRO syndrome and was started on prednisolone, which improved his general condition shortly thereafter. Blood culture after 42 days of incubation revealed the presence of Mycobacterium; however, we considered it a contamination at that time because no organisms grew on conventional agars, and the patient was discharged. Ten weeks after the isolation of Mycobacterium, he developed persistent fever and was readmitted. This time, vertebral bone mallow biopsy demonstrated a large amount of mycobacterium, which was later successfully identified as M. genavense by sequencing analysis. Under a final diagnosis of disseminated M. genavense infection, we treated the patient with clarithromycin, rifampicin, and ethambutol. This case highlighted that disseminated NTM infection may follow a similar clinical course as that of TAFRO syndrome.

Comparison of the clinical characteristics of TAFRO syndrome and idiopathic multicentric Castleman disease in general internal medicine: a 6-year retrospective study.

BACKGROUND: Although thrombocytopenia, anasarca, fever, reticulin fibrosis and organomegaly (TAFRO) syndrome was first described as a variant of idiopathic multicentric Castleman disease (CD), patients with TAFRO syndrome demonstrate more aggressive clinical features. Because these patients may present with fever of unknown origin, general physicians need to recognise its characteristic laboratory data and clinical features during hospitalisation. AIMS: to describe the features, symptoms and characteristics of TAFRO syndrome and to compare them to those of idiopathic CD. METHODS: This was a retrospective study of patients with histopathologically confirmed TAFRO syndrome and idiopathic multicentric CD who were diagnosed and managed between April 2012 and June 2018 in a Japanese university hospital's General Medicine Department. RESULTS: We found that the hospitalisations were significantly longer among patients with TAFRO syndrome compared to those with idiopathic CD (median: 87 days; range: 34-236 days vs median: 30 days; range: 13-59 days; P < 0.01). Patients with TAFRO syndrome were more likely to present with fever, abdominal pain and elevated inflammatory markers and be misdiagnosed with an infectious disease during the first hospital visit. Approximately 40% of patients with TAFRO syndrome had no radiographically enlarged lymph nodes. CONCLUSIONS: TAFRO syndrome may present as an infectious disease with an aggressive clinical course. Our study highlights the importance of giving significance to chief complaints and laboratory data. Physicians need to recognise the clinical and laboratory features of this disease to avoid missing this potentially fatal disorder.

Kidney biopsy findings in two patients with TAFRO syndrome: case presentations and review of the literature.

BACKGROUND: TAFRO syndrome is a clinical subtype of idiopathic multicentric Castleman disease (iMCD) that is characterized by thrombocytopenia, anasarca, fever, reticulin myelofibrosis (or renal dysfunction), and organomegaly. TAFRO syndrome has only recently been described, and many clinicians are unaware of this disease, leading to delays in diagnosis and treatment. We present two patients with TAFRO syndrome in whom renal biopsies were performed. CASE PRESENTATION: Both patients had subacute onset and exhibited renal insufficiency, edema, anemia, thrombocytopenia, polyserositis and lymphadenopathy over the disease course. However, there were many differences in their clinical manifestations. Case 1 was a 30-year-old woman admitted due to intermittent vaginal bleeding for 3 weeks. Laboratory tests on admission showed severe renal insufficiency (creatinine: 624 µmol/L), severe anemia (Hb: 41 g/L), and moderate thrombocytopenia (61 × 109/L). Case 2 was a 42-year-old man. Acute epigastric pain was his initial complaint, and computed tomography (CT) revealed retroperitoneal exudation around the pancreas. He was diagnosed with acute pancreatitis, and after treatment with a proton pump inhibitor (PPI) and somatostatin, his abdominal pain still recurred. During treatment, renal failure gradually increased, with oliguria, fever, anemia, thrombocytopenia, edema and massive ascites. Lymph node histologies were consistent with the hyaline-vascular (HV) type and mixed type, respectively, and renal histopathologies were consistent with thrombotic microangiopathy (TMA)-like renal lesions and membranoproliferative glomerulonephritis (MPGN), respectively. Their general conditions improved after glucocorticoid therapy, but their renal functions did not recover completely. On the basis of glucocorticoids, second-line treatments with tocilizumab and rituximab, respectively, were applied. CONCLUSIONS: The diagnosis of TAFRO syndrome is based mainly on clinical manifestations and lymph node biopsies. A reliable early diagnosis and appropriate rapid treatment are essential to improve patient outcomes. Clinicians should deepen their understanding of this disease and similar conditions. Once the disease is suspected, lymph node biopsies should be performed as soon as possible. In addition, renal biopsies should be actively performed in patients with renal involvement.

[A report of six TAFRO syndrome: clinical characteristics, diagnosis and treatment analysis].

Objective: To explore the clinical characteristics, treatment and prognosis of TAFRO syndrome. Methods: All patients diagnosed as Castleman disease in Peking University People's Hospital between December 2011 and April 2019 were included.Among them,6 patients were diagnosed as TAFRO syndrome. Medical records were studied;the clinical manifestation, laboratory test, pathology, treatment and prognosis were analyzed. Recent related literatures were reviewed. Results: The average age of six TAFRO syndrome patients (5 males)was 41.5 years(range, 27-59 years). The patients presented as acute or subacute onset, manifested as fever, thrombocytopenia, polyserositis including pleural effusion and ascites, organomegaly, anasarca, and renal insuffciency. One patient was accompanied by hemophagocyticsyndrome, one patient was accompanied by hypothyroidism, six patients' serum IL-6 was elevated, four patients had received the test of serum VEGF and results were all elevated, six patients' HIV antibody were negative,four patients had received HHV-8 DNA test and results were all negative. For pathology, threewere plasma cell type, twowere mixed type andonewashyaline vascular type. Renal biopsies were performed in 2 patients, showing that renal thrombotic microangiopathyassociated with subacute tubulointerstitial nephritis and secondary capillary proliferative glomerulonephritis. CHOP chemotherapy wereused in 2 patients, glucocorticoid was used in 1 patient, and glucocorticoid combined with Rituximab or Tocilizumab were used in 3 patients. Among them, one patient died because of disease progression after 5 years, other five patientsare still stable. Conclusion: TAFRO syndrome is a rare disease, early recognition and appropriate treatment may improvethe prognosis.