Disseminated Mycobacterium genavense infection mimicking TAFRO syndrome

Abstract

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.

Validated international definition of the thrombocytopenia, anasarca, fever, reticulin fibrosis, renal insufficiency, and organomegaly clinical subtype (TAFRO) of idiopathic multicentric Castleman disease

“…Bone marrow biopsy may also have diagnostic utility, considering the extent of thrombocytopenia observed in our study (the median pre‐treatment platelet: 37 × 10 3 /μl) and that approximately 90% of the cases had either reticulin fibrosis or increased megakaryocytes in the bone marrow specimen. Bone marrow biopsy is feasible without additional platelet transfusion in most cases and may provide useful information to exclude other differential diagnoses such as hidden hematologic malignancy and infectious diseases 41–43 . Given that prior definitions have defined the R in TAFRO as either renal dysfunction or reticulin fibrosis, we recommend defining R as either renal dysfunction or reticulin fibrosis (or other bone marrow features) and looking for one of these features as required of iMCD‐TAFRO.…”

“…Bone marrow biopsy is feasible without additional platelet transfusion in most cases and may provide useful information to exclude other differential diagnoses such as hidden hematologic malignancy and infectious diseases. [41][42][43] Given that prior definitions have defined the R in TAFRO as either renal dysfunction or reticulin fibrosis, we recommend defining R as either renal dysfunction or reticulin fibrosis (or other bone marrow features) and looking for one of these features as required of iMCD-TAFRO. A previous study reported that adrenomegaly or adrenal ischemia on CT scan could be early signs of TAFRO syndrome, 44 2 and 3, our present definition have been based on rigorous reviews of data from patients of different ethnicities and international discussions to establish a precise iMCD-TAFRO diagnostic definition.…”

Anti-interferon-γ Antibody-seropositive Disseminated Nontuberculous Mycobacterial Infection Mimicking POEMS and TAFRO Syndromes

“…Furthermore, we noted no pathological lymph node findings suggestive of TAFRO syndrome similar to the mixed type (mixture of vitreous vascular type and plasma cell type) of multicentric Castleman's disease in this case ( 3 , 19 , 20 ). One case report has described a DNTM case in which manifestations confusingly met the diagnostic criteria of TAFRO syndrome ( 21 ). In that case, the causative organism was M. genavence .…”

International definition of iMCD-TAFRO: future perspectives

“…In particular, atypical causes, such as disseminated cytomegalovirus or nontuberculous mycobacterial infections, uncommon types of lymphoma, autoimmune disorders, such as systemic lupus erythematosus, Sjögren's syndrome, or vasculitis, must always be considered. 27,[47][48][49]…”