Successful Treatment with Rituximab in a Patient with TTP Secondary to Severe ANCA-Associated Vasculitis

Asamiya, Yukari; Moriyama, Takahito; Takano, Mari; Iwasaki, Chihiro; Kimura, Kazuo; Ando, Yumiko; Aoki, Akiko; Kikuchi, Kan; Takei, Takashi; Uchida, Keiko; Nitta, Kosaku

doi:10.2169/internalmedicine.49.3135

Cited by 18 publications

(13 citation statements)

References 21 publications

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“…However, the prevalence in other countries is unclear, especially for renal TMA in ANCA-associated GN. As reported in previous case reports, patients with concomitant renal TMA in ANCA-associated GN presented with more severe renal injury (3)(4)(5)(6)(7)(8)(9). Patients with renal TMA in our cohort also had a higher level of initial serum creatinine, higher percentage of cellular crescents and fibrinoid necrosis, and more severe interstitial infiltration compared with patients without TMA, which, by a large cohort study, further extends previous findings.…”

Section: Discussionsupporting

confidence: 90%

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Clinicopathologic Characteristics and Outcomes of Renal Thrombotic Microangiopathy in Anti-Neutrophil Cytoplasmic Autoantibody-Associated Glomerulonephritis

Chen

Wang

Huang

et al. 2015

Clinical Journal of the American Society of Nephrology

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Background and objectives Thrombotic microangiopathy (TMA) in ANCA-associated vasculitis (AAV) has been mainly reported in isolated case reports. The aim of this study was to analyze clinical and pathologic characteristics and prognosis of patients with renal TMA in ANCA-associated GN in a large cohort of Chinese patients.Design, setting, participants, & measurements Clinical and renal histopathologic data of 220 patients with biopsy-proven ANCA-associated GN from 1996 to 2013 were retrospectively analyzed. Patients were followed up for a median period of 32 (interquartile range [IQR], 12-65) months, and outcomes of patients were analyzed.Results Among the 220 patients with ANCA-associated GN, 30 were identified having concomitant renal TMA by pathologic evaluation. Compared with the non-TMA group, patients with renal TMA presented with more severe renal injury, as evidenced clinically by a higher level of serum creatinine at diagnosis (5.0 [IQR, 3.5-9.0] versus 3.2 [IQR, 1.7-6.8] mg/dl; P=0.02) and pathologically by a higher percentage of cellular crescents (15.0% [IQR, 6.9%-34.9%] versus 6.9% [IQR, 0%-21.1%]; P=0.04) and more severe interstitial infiltration (2 [IQR, 2-2] versus 2 [IQR, 1-2]; P=0.03) in renal biopsies. Furthermore, multivariate analysis showed that renal TMA was independently associated with mortality of patients with AAV after adjusting for age, sex, initial serum creatinine, tubular atrophy, and interstitial fibrosis (hazard ratio, 1.92; 95% confidence interval, 1.08 to 3.41; P=0.03) or for age, sex, the histopathologic classification scheme proposed by Berden et al. (J Am Soc Nephrol 21: 1628-1636, tubular atrophy, and interstitial fibrosis (hazard ratio, 1.95; 95% confidence interval, 1.07 to 3.55; P=0.03).Conclusions Renal TMA in ANCA-associated GN is not rare and presents with more severe renal injury. Renal TMA is independently associated with all-cause mortality in patients with AAV.

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Section: Discussionsupporting

confidence: 90%

“…To our knowledge, TMA in ANCA-associated GN has only been reported in isolated case reports (3)(4)(5)(6)(7)(8)(9), with two patients showing pathologic features of renal TMA. The clinicopathologic characteristics, especially the prognostic value of pathologic findings of renal TMA, in ANCA-associated GN are far from clear.…”

Section: Introductionmentioning

confidence: 98%

Clinicopathologic Characteristics and Outcomes of Renal Thrombotic Microangiopathy in Anti-Neutrophil Cytoplasmic Autoantibody-Associated Glomerulonephritis

Chen

Wang

Huang

et al. 2015

Clinical Journal of the American Society of Nephrology

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“…Several reports in the literature have clearly shown that rituximab, an anti-CD20 chimeric monoclonal antibody, is highly efficient as an adjunctive therapy for TTP patients who do not respond adequately to a standard combination therapy of PE and steroids (29)(30)(31). Globally, the on-label therapeutic use of rituximab is for CD20-positive malignant B-cell lymphoma.…”

Section: Discussionmentioning

confidence: 99%

Therapeutic Modality of 11 Patients with TTP in a Single Institution in Miyazaki from 2000 to 2011

et al. 2013

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Objective Thrombotic thrombocytopenic purpura (TTP) is a life-threatening generalized disease with pathological features that are termed thrombotic microangiopathies. Since the discovery of the von Willebrand factor-cleaving protease [a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13)], it is widely known that approximately two-thirds of TTP patients have a severe deficiency of ADAMTS13 activity due to gene mutations or acquired autoantibodies to this enzyme. However, the remaining one-third of TTP patients have only moderately reduced or almost normal ADAMTS13 activity. To elucidate the clinical characteristics and outcomes of these two types of TTP, we have retrospectively analyzed the cases of acquired TTP patients treated in a single institution from 2000 to 2011. Methods Our case studies include 11 TTP patients, of which 5 were considered idiopathic and 6 had cases of TTP associated with underlying diseases such as non-Hodgkin lymphoma or connective tissue diseases. Results These patients were treated with a combination therapy of plasma exchange and steroids and with several adjunctive therapeutic regimens including the on-label use of cyclophosphamide and cyclosporine and the off-label use of high-dose steroid or immunoglobulin with rituximab. Splenectomies were not performed. As a result of these treatments, 6 out of the 7 patients with ADAMTS13 activity deficient TTP achieved a complete remission without relapse, but the remaining 4 patients with non-ADAMTS13 activity deficient TTP all died without complete remission. Conclusion We present herein the detailed clinical courses of 11 patients with TTP and address our experiences with the efficacy of various therapeutic regimens. This case-oriented study should be helpful to the physicians who directly care for TTP patients, and may provide a future direction for developing a more efficient treatment modality.

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“…TPE (16 sessions) and prednisolone slowly corrected her thrombocytopenia and the need for hemodialysis support in association with improvement in ADAMTS13 activity level (from 27% to 68%, ADAMTS13 antibodies not reported). The third case report described a 66-year-old woman with known MPO-antibody vasculitis on maintenance prednisolone therapy, who was hospitalized with acute vasculitic features, worsening renal function, and TTP [14]. Her ADAMTS13 levels were reported to be decreased (37.8%), but no inhibitory antibodies were detected.…”

Section: Discussionmentioning

confidence: 99%

Concomitant thrombotic thrombocytopenic purpura and ANCA-associated vasculitis in an adolescent

Agrawal

Vaidya

et al. 2011

Pediatr Nephrol

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Thrombotic thrombocytopenic purpura (TTP) rarely occurs with systemic vasculitis. A 17-year-old girl presented with non-bloody diarrhea, menorrhagia, and syncope. She had severe anemia (hemoglobin = 3.8 g/dl), thrombocytopenia (platelet = 7,000/mm(3)), and acute kidney injury (serum creatinine, Cr = 2.3 mg%). Peripheral smear examination confirmed the presence of microangiopathic hemolytic anemia. Additionally, she had a positive anti-nuclear antibody (1:1600) and normal complement levels. We considered the diagnosis of TTP, possibly associated with systemic lupus erythematosus, and promptly initiated pulse methylprednisolone and daily 3-4 l of plasma exchange therapy. Following resolution of her thrombocytopenia in 48 h, we performed a kidney biopsy that revealed diffuse proliferative, focal crescentic, and necrotizing glomerulonephritis with mild IgG immunofluorescence staining. Concomitantly, autoimmune work-up was significant for positive perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCA = 1:640) and decreased von Willebrand factor cleaving protease activity (<5%). A final diagnosis of TTP with microscopic polyangiitis (p-ANCA-mediated) was made and treatment with daily oral cyclophosphamide and prednisone resolved her renal injury over 2 months (follow-up Cr = 1.0 mg%). Our case highlights the importance of identifying systemic disorders such as ANCA-associated vasculitis with TTP.

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Successful Treatment with Rituximab in a Patient with TTP Secondary to Severe ANCA-Associated Vasculitis

Cited by 18 publications

References 21 publications

Clinicopathologic Characteristics and Outcomes of Renal Thrombotic Microangiopathy in Anti-Neutrophil Cytoplasmic Autoantibody-Associated Glomerulonephritis

Clinicopathologic Characteristics and Outcomes of Renal Thrombotic Microangiopathy in Anti-Neutrophil Cytoplasmic Autoantibody-Associated Glomerulonephritis

Therapeutic Modality of 11 Patients with TTP in a Single Institution in Miyazaki from 2000 to 2011

Concomitant thrombotic thrombocytopenic purpura and ANCA-associated vasculitis in an adolescent

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