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

Abstract

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.

Keywords: Multicentric Castleman’s disease; POEMS syndrome; Romiplostim; TAFRO syndrome; Tocilizumab.

Fig. 1

a Multiple raised erythematous lesions 5 mm in size on the trunk. b Edema of the bilateral lower extremities. c Computed tomography shows an enlarged mediastinal lymph node measuring 15 mm in size (arrow). d Computed tomography showed bilateral pleural effusions (large arrow) and slight accumulation of pericardial fluid (small arrow). e Computed tomography displays a small sclerotic lesion measuring 10 mm (arrow)

Fig. 2

Renal biopsy specimen. a There are diffuse lobular endocapillary proliferative changes with endothelial cell swelling, as well as infiltration of monocytes and neutrophils. b Immunofluorescence demonstrates positive staining of the glomerular capillaries and mesangium for IgM and κ light chain. c Immunohistochemical staining shows that podocytes are weakly positive for IL-6 (arrow head), but VEGF is negative. IL interleukin, VEGF vascular endothelial growth factor. d Electron microscopy reveals endothelial cell swelling and edematous expansion of the subendothelial space (arrow) in the GBM with no electron-dense deposits. GBM glomerular basement membrane

Fig. 2

Renal biopsy specimen. a There are diffuse lobular endocapillary proliferative changes with endothelial cell swelling, as well as infiltration of monocytes and neutrophils. b Immunofluorescence demonstrates positive staining of the glomerular capillaries and mesangium for IgM and κ light chain. c Immunohistochemical staining shows that podocytes are weakly positive for IL-6 (arrow head), but VEGF is negative. IL interleukin, VEGF vascular endothelial growth factor. d Electron microscopy reveals endothelial cell swelling and edematous expansion of the subendothelial space (arrow) in the GBM with no electron-dense deposits. GBM glomerular basement membrane