Pancytopenia, including macrocytic anemia, associated with leflunomide in a rheumatoid arthritis patient

Toyokawa, Yasuhiko; Kingetsu, Isamu; Yasuda, Chiho; Yasuda, Jun; Yoshida, Ken; Kurosaka, Daitaro; Yamada, Akio

doi:10.1007/s10165-007-0613-8

Cited by 7 publications

(2 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…There were no preexisting reports of definite causal association of TMA/TTP with leflunomide. Previous reports have noted pancytopenia with macrocytic anemia and schistocytes, thought to be secondary to drug-induced megaloblastic anemia [ 11 ]. A case of TMA with moderately reduced ADAMTS13 (35%) has been reported, but it was in the setting of hepatic and renal toxicity with long-term use of a combination of leflunomide and methotrexate [ 12 ].…”

Section: Discussionmentioning

confidence: 99%

A Novel Case of Leflunomide-Induced Thrombotic Thrombocytopenic Purpura

Shields¹,

Skelton²,

Laber³

et al. 2021

J Hematol

View full text Add to dashboard Cite

Leflunomide has not been previously associated with thrombotic thrombocytopenic purpura (TTP), a rare life-threatening clinical syndrome characterized by thrombotic microangiopathy (TMA) due to inability to cleave ADAMTS13. Here, we present the first case of leflunomide-induced TTP. Our patient developed encephalopathy, thrombocytopenia, anemia and hyperbilirubinemia 2 months after starting leflunomide. Schistocytes were noted on peripheral smear and ADAMTS13 activity was low (< 5%), consistent with acquired TTP. He received therapeutic plasma exchange, corticosteroids, rituximab and caplacizumab with normalization of hemolysis labs and ADAMTS13 activity. However, pancytopenia persisted, raising the suspicion for leflunomide toxicity. Oral cholestyramine treatment was empirically started before teriflunomide (a leflunomide metabolite) level was found to be elevated. Blood counts normalized after cholestyramine and have remained normal at last follow-up over a year later. This is the first reported case of TTP precipitated by leflunomide. Our case highlights the importance of recognizing drugs as an etiology of TMA and adds leflunomide to this list.

show abstract

Section: Discussionmentioning

confidence: 99%

A Novel Case of Leflunomide-Induced Thrombotic Thrombocytopenic Purpura

Shields¹,

Skelton²,

Laber³

et al. 2021

J Hematol

View full text Add to dashboard Cite

show abstract

“…Leflunomide fulfills the desired goals of disease modifying antirheumatic drugs (DMARDs): it reduces the diseases signs and symptoms; it inhibits structural damage and improves the physical function ( van Riel et al, 2004 ). The use of leflunomide is expanding during the last years but is accompanied by severe adverse reactions including hepatic, hematological, immune and respiratory systems ( Toyokawa et al, 2007 ). Further, the long half-life of this drug is approximately two weeks; this delays resolving of some of the adverse reactions.…”

Section: Introductionmentioning

confidence: 99%

Leflunomide Induces Dose-Dependent Lung Injury in Mice via Stimulating Vimentin and NLRP3 Inflammasome Production

et al. 2021

View full text Add to dashboard Cite

Recently, the therapeutic importance of the anti-rheumatic drug, leflunomide, has been increased after the involvement of leflunomide in treating other autoimmune diseases and its promising role in retarding human malignancies. Few studies have focused on the safety in human or animals without clear outlining of the pathologic features on target organs. One clinical study related leflunomide with significant pulmonary complications in predisposed individuals. The current study examined the dose-dependent lung injury produced by leflunomide in healthy mice. Albino mice were allocated into four different groups. Group (1): Vehicle control group, Group (2–4): mice received leflunomide (2.5, 5 or 10 mg/kg), respectively, for 8 weeks and then lungs were dissected from the mice for histopathological examination and fibrosis evaluation (Masson’s trichrome staining and α-smooth muscle actin immunohistochemistry). Enzyme linked immunosorbent assay was used to assess the vimentin and other inflammatory factors in the lung homogenate whereas Western blot analysis was employed to assess α-smooth muscle actin, vimentin and collagen 1. Results indicated that leflunomide induced dose-dependent pulmonary injury and the high dose and increased the vimentin, inflammatory markers (NLRP3 and interlukin-1β). Histologic examination showed distorted architecture, marked inflammatory cells infiltrate and increase collagen content. The findings were supported by Western blotting and the immunohistochemical study which showed greater pulmonary α-smooth muscle actin and vimentin content. In conclusion, the current results highlighted that leflunomide produced dose-dependent pulmonary toxicities that requires further investigation of the nature of injury.

show abstract