It has come to our attention that the TAFRO case we described in our paper in March was not the first case in Latin America. Our colleague from Argentina, professor di Fonzo, wrote to us informing that he and co-authors had already published, in 2015, another case. However, this was published in a non-indexed journal, the European Journal of Case Reports in Internal Medicine, and it went unnoticed by us.
In the previous report, the authors described the case of a 31-years old woman with TAFRO syndrome, treated with methylprednisolone and rituximab, one of a few cases in non-Japanese patients described in the world. Their patient presented with systemic inflammatory symptoms (fever, night sweats), lymphadenopathy, anasarca, renal failure, and hepatosplenomegaly. A right axillary lymph node biopsy revealed histopathological findings consistent with hyaline-variant Castleman's Disease (HV-CD). Bone marrow biopsy had mild fibrosis (grade 1). Blood work showed findings of a systemic inflammatory disorder, with elevated acute phase reactants, severe microcytic anemia (Hb 6.8 g/dL), elevated serum creatinine (1.9 mg/dL) and elevated serum levels of interleukin-6 (IL-6; 60 pg/ml). Pleural effusion and ascites were compatible with exudates. The patient was treated with transfusion of packed red blood cells, high-dose steroids (500 mg/day of methylprednisolone) and 4 weekly doses of rituximab. She had significant clinical improvement and was asymptomatic at the time of the report, 8 months post-diagnosis.
This case presents several similarities to the patient published from Brazil[1,2]. Both presented with the cardinal clinical findings of TAFRO syndrome, mainly thrombocytopenia, anasarca, myelofibrosis, renal failure and organomegaly, signs of a systemic inflammatory response, manifested by an increase in C-reactive protein and erythroid sedimentation rate. Interestingly, the patient from Argentina presented with more severe anemia than the Brazilian case, and also positivity for the Coombs test, but no signs of hemolysis were noted.
One important difference between both cases was that the patient from Brazil evolved with a severe clinical course during hospital admission, while the other patient had more protracted clinical development. This is probably related to the magnitude of increase in the level of IL-6, that was found to be much higher at the time of the admission of the Brazilian patient in the intensive care unit (722.6 pg/mL versus 60 pg/mL). Both patients received steroids and rituximab, while in Brazil the patient also received the anti-IL-6 monoclonal antibody tocilizumab. While it appears that the combination of steroids and rituximab may be sufficient for therapy of TAFRO syndrome[3,4], as seen in other cases of HHV-8 positive CD, we do believe that in more severe cases, anti-IL-6 therapy is indicated. One possible advantage of therapy with rituximab over tocilizumab is that it appears that maintenance is not needed with the former, and remissions seem to be durable with the anti-CD20 drug, even in other forms of CD[4-6].
In summary, Prof. Di Fonzo and co-authors reported the first case of TAFRO syndrome in Latin America in 2015. Comparison of both cases revealed a similar clinical presentation, but indicate that in some cases the patient may deteriorate quickly and treatment should be initiated promptly[1,6]. In the absence of clinical trials, it appears that steroids, rituximab, and anti-IL-6 antibodies remain the mainstay of therapy in this disease.
Fabio PS Santos1, Guilherme F Perini1, Ronaldo Piovesan2, Nelson Hamerschlak1
1Hematology, Hospital Israelita Albert Einstein, São Paulo, SP, Brazil
2Internal Medicine, Hospital Israelita Albert Einstein, São Paulo, SP, Brazil
Nelson Hamerschlak, MD, PhD
Hematology and Oncology Center "Família Dayan Daycoval"
Hospital Israelita Albert Einstein
Avenida Albert Einstein, 627/701, Bloco A, 3o Subsolo, 05651-901
São Paulo, SP, Brazil
1. José FF, Kerbauy LN, Perini GF, et al. A life-threatening case of TAFRO syndrome with dramatic response to tocilizumab, rituximab, and pulse steroids: The first case report in Latin America. Medicine (Baltimore) 2017;96(13):e6271.
2. Contardo D, Finocchietto P, Uehara T, et al. TAFRO Syndrome in a Patient of South-American Descent. European Journal of Case Reports in Internal Medicine. 2015;2:doi 10.12890/12015_000220. Available at: http://www.ejcrim.com/index.php/EJCRIM/article/view/220/321. Accessed 14 September, 2017.
3. Iwaki N, Fajgenbaum DC, Nabel CS, et al. Clinicopathologic analysis of TAFRO syndrome demonstrates a distinct subtype of HHV-8-negative multicentric Castleman disease. Am J Hematol 2016;91(2):220-226.
4. Jain P, Verstovsek S, Loghavi S, et al. Durable remission with rituximab in a patient with an unusual variant of Castleman's disease with myelofibrosis-TAFRO syndrome. Am J Hematol 2015;90(11):1091-1092.
5. Pria AD, Pinato D, Roe J, Naresh K, Nelson M, Bower M. Relapse of HHV8-positive multicentric Castleman disease following rituximab-based therapy in HIV-positive patients. Blood 2017;129(15):2143-2147.
6. Hiramatsu S, Ohmura K, Tsuji H, et al. Successful treatment by rituximab in a patient with TAFRO syndrome with cardiomyopathy. Nihon Rinsho Meneki Gakkai Kaishi 2016;39(1):64-71.