Successful Treatment with Cyclosporin A in Tocilizumab-resistant TAFRO Syndrome

Yamaga, Yusuke; Tokuyama, Kiyonobu; Kato, Takehiro; Yamada, Rie; Murayama, Masanori; Ikeda, Tsuneko; Yamakita, Noriyoshi; Kunieda, Takeshige

doi:10.2169/internalmedicine.55.4710

Cited by 39 publications

(39 citation statements)

References 11 publications

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“…The urine volume suddenly increased on day 30, and the platelet count returned to more than 10.0 × 10 4 /µL after 4 months [9]. In addition, Yamaga et al reported a 61-year-old man with TAFRO syndrome that was refractory to initial treatment with methylprednisolone pulse therapy [17]. Tocilizumab was initiated on day 42, but it was also ineffective.…”

Section: Discussionmentioning

confidence: 99%

TAFRO syndrome with refractory thrombocytopenia responding to tocilizumab and romiplostim: a case report

et al. 2018

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Thrombocytopenia, anasarca, fever, reticulin fibrosis, organomegaly (TAFRO) syndrome is a unique clinicopathologic subtype of multicentric Castleman's disease that has recently been identified in Japan. However, little is known about its renal histological changes and the optimal treatment for TAFRO syndrome. An 80-year-old Japanese woman was admitted to our hospital for evaluation of severe anasarca and weight gain (10 kg in a month). She had polyneuropathy, monoclonal plasma cell proliferative disorder with positive kappa M-protein, a sclerotic bone lesion, elevation of vascular endothelial growth factor (VEGF), skin changes, and extravascular volume overload, which fulfilled the diagnostic criteria for POEMS (polyneuropathy, organomegaly, endocrinopathy, and monoclonal protein, skin changes) syndrome. However, kappa-type M-protein and thrombocytopenia with positivity of platelet-associated immunoglobulin G antibody were unusual, and fitted the diagnostic criteria for TAFRO syndrome. Renal biopsy showed diffuse endocapillary proliferative glomerulonephritis with endothelial swelling and the infiltration of monocytes and neutrophils without specific immunoglobulin deposits. Her systemic symptoms were refractory to initial treatment with high-dose melphalan and glucocorticoids. Alternative therapy with an anti-interleukin-6 (IL-6) receptor antibody (tocilizumab) effectively controlled the symptoms, while a thrombopoietin receptor agonist (romiplostim) was effective for her thrombocytopenia. Results suggest that IL-6-VEGF axis and an autoimmune mechanism may be responsible for TAFRO syndrome with clinical features of POEMS and refractory thrombocytopenia, which can be successfully treated with combination of tocilizumab and romiplostim.

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Section: Discussionmentioning

confidence: 99%

TAFRO syndrome with refractory thrombocytopenia responding to tocilizumab and romiplostim: a case report

et al. 2018

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“…Fujiki et al reported a case of TAFRO syndrome complicated with severe infection during corticosteroid therapy, which was successfully treated with TCZ alone [17]. However, cases of TCZ-resistant TAFRO syndrome have been reported [15,18]. Clinical experiences of using rituximab, cyclophosphamide, and thalidomide have been reported from Japan [19][20][21] In the present case, as combination treatment with PSL and CsA appeared ineffective even after 5 weeks, and TCZ was considered an alternative immunosuppressant.…”

Section: Discussionmentioning

confidence: 62%

“…CsA is also a treatment choice if glucocorticoids alone are not effective [10]. Combination therapy with glucocorticoids and CsA was effective in previously reported cases [14,15]. Considering the mechanism of action of CsA, IL-2 may play a pivotal role in TAFRO syndrome in addition to IL-6 [14].…”

Section: Discussionmentioning

confidence: 99%

Severe refractory TAFRO syndrome requiring continuous renal replacement therapy complicated with Trichosporon asahii infection in the lungs and myocardial infarction: an autopsy case report and literature review

et al. 2018

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Background: TAFRO (thrombocytopenia, anasarca, fever, reticulin myelofibrosis/renal failure, and organomegaly) syndrome is a systemic inflammatory disorder and unique clinicopathological variant of idiopathic multicentric Castleman disease that was proposed in Japan. Prompt diagnosis is critical because TAFRO syndrome is a progressive and life threating disease. Some cases are refractory to immunosuppressive treatments. Renal impairment is frequently observed in patients with TAFRO syndrome, and some severe cases require hemodialysis. Histological evaluation is important to understand the pathophysiology of TAFRO syndrome. However, systemic histopathological evaluation through autopsy in TAFRO syndrome has been rarely reported previously. Case presentation: A 46-year-old Japanese man with chief complaints of fever and abdominal distension was diagnosed with TAFRO syndrome through imaging studies, laboratory findings, and pathological findings on cervical lymph node and bone marrow biopsies. Interleukin (IL)-6 and vascular endothelial growth factor (VEGF) levels were remarkably elevated in both blood and ascites. Methylprednisolone (mPSL) pulse therapy was initiated on day 10, followed by combination therapy with PSL and cyclosporine A. However, the amount of ascites did not respond to the treatment. The patient became anuric, and continuous renal replacement therapy was initiated from day 50. However, the patient suddenly experienced cardiac arrest associated with myocardial infarction (MI) on the same day. Although the emergent percutaneous coronary intervention was successfully performed, the patient died on day 52, despite intensive care. Autopsy was performed to ascertain the cause of MI and to identify the histopathological characteristics of TAFRO syndrome.(Continued on next page)

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“…These cytokines may be involved in the pathogenesis of TAFRO syndrome. On the other hand, some cases were resistant to TCZ, an anti-IL-6 receptor antibody [8].…”

Section: Discussionmentioning

confidence: 99%

Successful treatment by tocilizumab without steroid in a very severe case of TAFRO syndrome

et al. 2017

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A 59-year-old Japanese man was admitted to our hospital with leg edema, fatigue and fever. He had a past medical history of duodenal ulcer, fatty liver, hyperuricemia and positive rheumatoid factor, but was not receiving any medication. His son had died 2 years prior to this admission after following a clinical course that suggested TAFRO syndrome.The patient showed mild fever (about 37-38 °C), polypnea and severe leg edema on admission. Chest examination revealed decreased breath sounds in the right lung. No superficial lymph nodes were palpable. Laboratory tests on admission revealed mild thrombocytopenia, hypoproteinemia, elevation of C-reactive protein (CRP), alkaline phosphatase (ALP), creatinine (Cr), and urine N-acetyl-β-d-glucosaminidase (NAG) ( Table 1). Urine testing showed granular casts without proteinuria or hematuria. Concentrations of aspartate aminotransferase (AST) and alanine transaminase (ALT) were elevated, but unchanged compared with the results of a medical check 6 months before admission, and so were attributed to fatty liver. Chest X-ray and computed tomography (CT) showed mild lymphadenopathy in the mediastinum, bilateral pleural effusion and ascites (Fig. 1).Blood, sputum and urine culture tests were all negative and no other infectious diseases were present. Negative results were obtained for all autoantibodies. Among the tumor markers, only soluble interleukin-2 receptor (sIL-2R) was elevated. Bone marrow biopsy was performed to rule out malignant lymphoma, revealing normocellular Abstract Successful use of tocilizumab (TCZ) to treat TAFRO syndrome has recently been reported. In those cases, TCZ was used with steroid. We present herein the case of a 59-year-old man with very severe TAFRO syndrome who was successfully treated using TCZ without steroid. He showed rapidly progressive anasarca, acute renal failure and very severe thrombocytopenia. We initially used steroid, but its efficacy was limited. Moreover, steroid use had to be stopped as soon as possible, because hemorrhagic shock developed due to severe duodenal ulcer. After overcoming infections (about 40 days after stopping steroid), administration of TCZ was started and the patient was discharged in clinical remission.

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Successful Treatment with Cyclosporin A in Tocilizumab-resistant TAFRO Syndrome

Cited by 39 publications

References 11 publications

TAFRO syndrome with refractory thrombocytopenia responding to tocilizumab and romiplostim: a case report

TAFRO syndrome with refractory thrombocytopenia responding to tocilizumab and romiplostim: a case report

Severe refractory TAFRO syndrome requiring continuous renal replacement therapy complicated with Trichosporon asahii infection in the lungs and myocardial infarction: an autopsy case report and literature review

Successful treatment by tocilizumab without steroid in a very severe case of TAFRO syndrome

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