Two cases of carfilzomib‐induced thrombotic microangiopathy successfully treated with Eculizumab in multiple myeloma

Abstract Background Treatment with proteasome inhibitors like carfilzomib in patients with multiple myeloma (MM) can induce thrombotic microangiopathy (TMA) characterized by neurological symptoms, acute kidney injury, hemolysis and thrombocytopenia. Successful treatment with the monoclonal antibody eculizumab was described for these patients, but reports of ideal management and definitive treatment protocols are lacking. Case Presentation The first case describes a 43-years-old IgG-kappa-MM patient that developed TMA during the first course of carfilzomib-lenalidomide-dexamethasone (KRd) consolidation after autologous stem cell transplantation (ASCT). In the second case, a 59-years-old IgG-kappa-MM patient showed late-onset TMA during the fourth and last cycle of elotuzumab-KRd consolidation within the DSMM XVII study of the German study group MM (DSMM; clinicalTrials.gov Identifier: NCT03948035). Concurrently, he suffered from influenza A/B infection. Both patients had a high TMA-index for a poor prognosis of TMA. Therapeutically, in both patients plasma exchange (TPE) was initiated as soon as TMA was diagnosed. In patient #1, dialysis became necessary. For both patients, only when the complement inhibitor eculizumab was administered, kidney function and blood values impressively improved. Conclusion In this small case series, two patients with MM developed TMA due to carfilzomib treatment (CFZ-TMA), the second patient as a late-onset form. Even though TMA could have been elicited by influenza in the second patient and occurred after ASCT in both patients, with cases of TMA post-transplantation in MM being described, a relation of TMA and carfilzomib treatment was most likely. In both patients, treatment with eculizumab over two months efficiently treated TMA without recurrence and with both patients remaining responsive months after TMA onset. Taken together, we describe two cases of TMA in MM patients on carfilzomib-combination treatment, showing similar courses of this severe adverse reaction, with good responses to two months of eculizumab treatment.

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Adrenocortical carcinoma complicated by renal thrombotic microangiopathy, a case-series

BMC Nephrology ◽

10.1186/s12882-020-1703-5 ◽

2020 ◽

Vol 21 (1) ◽

Cited By ~ 1

Author(s):

Tristan de Nattes ◽

Lucile Moreau-Grangé ◽

Delphine Vezzosi ◽

Julien Hadoux ◽

Miguel Hie ◽

...

Keyword(s):

Hemolytic Anemia ◽

Thrombotic Microangiopathy ◽

Adrenocortical Carcinoma ◽

Renal Involvement ◽

Specific Treatment ◽

Case Series ◽

Kidney Injury ◽

Surgical Removal ◽

First Case ◽

Dismal Prognosis

Abstract Background Cancer-related thrombotic microangiopathy (CR-TMA) is a rare entity associated with a dismal prognosis. Usually, CR-TMA is associated with mucin-producing carcinomas among which stomach, breast, prostate, lung and pancreas tumours are the most frequent. Cases presentation We describe for the first time three cases of CR-TMA due to adrenocortical carcinoma (ACC). All of them had mechanical hemolytic anemia and thrombocytopenia without any other identifiable cause. Bicytopenia was diagnosed either simultaneously with ACC or at the time of metastatic evolution. Two patients had acute kidney injury (AKI) with severe pathological findings on kidney biopsy. Despite total adrenalectomy, chemotherapy, and specific treatment of TMA with plasma-exchanges, renal failure and hemolytic anemia remained. The only manifestation of CR-TMA in the third patient was hemolytic anemia, which resolved after surgical removal of ACC. The evolutions in these patients suggests ACC-related TMA may be related to a circulating factor. Conclusions CR-TMAs are rare. Here we describe the first case series of ACC-related TMA, among which two had renal involvement. This entity is associated with dismal renal prognosis despite specific treatment of TMA. According to patients’ evolution, the persistence of TMA may reflect an uncontrolled malignancy.

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Acute Kidney Injury Relevant to Tubulointerstitial Nephritis with Late-Onset Uveitis Superimposed by Thrombotic Microangiopathy: A Case Report and Review of the Literature

Kidney Diseases ◽

10.1159/000507668 ◽

2020 ◽

Vol 6 (6) ◽

pp. 414-421

Author(s):

Youlu Zhao ◽

Junwen Huang ◽

Tao Su ◽

Zhikai Yang ◽

Xizi Zheng ◽

...

Keyword(s):

Acute Kidney Injury ◽

Thrombotic Microangiopathy ◽

Tubulointerstitial Nephritis ◽

Late Onset ◽

Drug Hypersensitivity ◽

Oral Prednisone ◽

Kidney Injury ◽

Renin Angiotensin System ◽

Renal Recovery

Background: The syndrome of tubulointerstitial nephritis and uveitis (TINU) is an uncommon and multisystemic autoimmune disorder. This review reports a rare case of TINU being superimposed on thrombotic microangiopathy (TMA) and, by comparing with the available literature, also summarizes the clinical features, associated conditions, treatment, and outcome of patients with TINU. Summary: Herein, we report the case of a 37-year-old male patient with acute kidney injury (AKI) clinicopathologically identified as malignant hypertension-induced TMA superimposed by acute tubulointerstitial nephritis, which was suspected to be related to drug hypersensitivity. After treatment with oral prednisone combined with a renin-angiotensin system inhibitor, the patient achieved partial renal recovery and was withdrawn from hemodialysis. Recurrent AKI concomitant with new-onset asymptomatic uveitis was detected during routine clinical follow-up after cessation of prednisone. TINU was then diagnosed, and prednisone followed by cyclophosphamide was prescribed. The patient achieved better renal recovery than in the first round of treatment and maintained stable renal function afterward. By reviewing the literature, 36 cases were reported as TINU superimposed on other conditions, including thyroiditis, osteoarthropathy, and sarcoid-like noncaseating granulomas. Key messages: TINU could be complicated by many other conditions, among which TMA is very rare. When presented as AKI, kidney biopsy is important for differential diagnosis. The case also shows that recurrent AKI with concomitant uveitis after prednisone withdrawal strongly suggested the need for long-term follow-up and elongated prednisone therapy for TINU syndrome.

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Acquired Factor VII deficiency – a rare but important consideration

Scottish Medical Journal ◽

10.1177/0036933019853167 ◽

2019 ◽

Vol 64 (3) ◽

pp. 119-122

Author(s):

Mehmood Hussain Zaidi ◽

Arran Stanley ◽

Mohammed Khan

Keyword(s):

Case Series ◽

Kidney Injury ◽

Abdominal Sepsis ◽

Factor Vii ◽

Medical Setting ◽

Coagulation Disorder ◽

Factor Vii Deficiency ◽

First Case ◽

Clinical Scenarios ◽

Atypical Haemolytic Uraemic Syndrome

IntroductionIsolated acquired Factor VII deficiency is a rare coagulation disorder which is independent of vitamin K deficiency. The exact pathophysiological basis of this condition is unclear. We present a series of cases highlighting different clinical scenarios where this condition was encountered.Case seriesThe first case presented with intra-abdominal sepsis. The second was a patient admitted with acute kidney injury and subsequently diagnosed with myeloma. The final case presented with microangiopathic haemolytic anaemia and was suspected of having atypical Haemolytic Uraemic Syndrome. In each case, there was no family or personal history of a bleeding disorder. Follow-up Factor VII levels after recovery from illness was normal in all three cases.ConclusionAcquired Factor VII deficiency is an uncommon but important finding which should be considered in the general medical setting when an isolated prolonged prothrombin time is detected.

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Lymphangioma Circumscriptum of the Vulva- A Case Series

JOURNAL FOR CLINICAL AND DIAGNOSTIC RESEARCH ◽

10.7860/jcdr/2021/47435.14553 ◽

2021 ◽

Author(s):

Rashmi S Mahajan ◽

Yogesh S Marfatia ◽

Atmakalyani R Shah ◽

Kishan R Ninama

Keyword(s):

Late Onset ◽

Case Series ◽

Suspected Case ◽

Age Group ◽

The Third ◽

First Case ◽

History Of ◽

Subcutaneous Tissues ◽

Uncommon Condition ◽

Lymphangioma Circumscriptum

Vulval dermatoses pose a diagnostic and therapeutic challenge for the dermatologists. Lymphangioma Circumscriptum (LC) is a form of lymphangioma affecting the skin and subcutaneous tissues that is characterised by benign dilation of lymphatic channels. This uncommon condition is known to occur over the chest, mouth, axilla, tongue, and rarely in the vulva. In this series, authors present three cases of LC of vulva in women between the age group of 45 to 60 years with late-onset fluid-filled lesions over the vulva. The first case had history of hysterectomy prior to onset of lesions, the second case had a spontaneous onset of lesions while the third was a suspected case of pelvic tuberculosis with secondary lymphangioma.

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Multiple Myeloma as the Underlying Cause of Thrombotic Microangiopathy Leading to Acute Kidney Injury: Revisiting a Very Rare Entity

Journal of Investigative Medicine High Impact Case Reports ◽

10.1177/2324709617732797 ◽

2017 ◽

Vol 5 (3) ◽

pp. 232470961773279

Author(s):

Savneek Chugh ◽

Asim Kichloo ◽

Firas Jafri ◽

Liga Yusvirazi ◽

Robert Lerner

Keyword(s):

Multiple Myeloma ◽

Acute Kidney Injury ◽

Thrombotic Microangiopathy ◽

Kidney Injury ◽

Rare Entity

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Case Report of a Rare Incidence of IgH Amplification Leading to Acute Kidney Injury in a Multiple Myeloma Patient

Case Reports in Oncology ◽

10.1159/000510046 ◽

2021 ◽

pp. 274-278

Author(s):

Sowmya Thanikachalam ◽

Vijay Kumar Srinivasalu ◽

K.S. Nataraj ◽

Sharat Damodar ◽

Manjula Das

Keyword(s):

Multiple Myeloma ◽

Acute Kidney Injury ◽

Case Report ◽

Heavy Chain ◽

Kidney Injury ◽

Bone Marrow Aspiration ◽

Structural Abnormality ◽

Cell Transplant ◽

Multiple Myeloma Patient ◽

First Case

We present a case report of a 62-year-old male, treated for kappa light chain multiple myeloma with chemotherapy followed by autologous stem cell transplant (ASCT) in 2014. He has been in complete remission for 4 years. In 2018, he was evaluated for hypercreatinemia and acute kidney injury(AKI) with a suspicion of disease relapse; he underwent evaluation with bone marrow aspiration cytology which showed no evidence of relapse. However, careful cytogenetic analyses showed IgH amplification (14q32) which probably was the cause for AKI in the absence of any structural abnormality in the kidney. Heavy chain deposition leads to AKI in multiple myeloma, and its association with IgH amplification leading to AKI is reported here. Though heavy chain deposition leading to AKI is common, IgH amplification at chromosome level is the first case observed.

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Case series: coronavirus disease 2019 infection as a precipitant of atypical hemolytic uremic syndrome: two case reports

Journal of Medical Case Reports ◽

10.1186/s13256-021-03144-2 ◽

2021 ◽

Vol 15 (1) ◽

Author(s):

Christine J. Kurian ◽

Zachary French ◽

Patrick Kukulich ◽

Matthew Lankiewicz ◽

Sushil Ghimire ◽

...

Keyword(s):

Renal Failure ◽

Hemolytic Uremic Syndrome ◽

Thrombotic Microangiopathy ◽

Influenza A ◽

Case Reports ◽

Atypical Hemolytic Uremic Syndrome ◽

Case Series ◽

Oliguric Renal Failure ◽

History Of ◽

Uremic Syndrome

Abstract Background Atypical hemolytic uremic syndrome is an exceedingly rare thrombotic microangiopathy caused by accelerated activation of the alternative complement pathway. Case presentation Here, we report two cases of patients presenting with suspected atypical hemolytic uremic syndrome precipitated by coronavirus disease 2019 infection. The first patient, a 25-year-old Hispanic male, had one prior episode of thrombotic microangiopathy presumed to be atypical hemolytic uremic syndrome precipitated by influenza A, and re-presented with thrombocytopenia, microangiopathic hemolytic anemia, nonoliguric renal failure, and normal ADAMTS13 activity, with confirmed coronavirus disease 2019 positivity. The second patient, a 31-year-old Caucasian female, had no personal history of thrombotic microangiopathy, though reported a family history of suspected atypical hemolytic uremic syndrome. She presented with similar laboratory derangements, oliguric renal failure requiring hemodialysis, and confirmed coronavirus disease 2019 positivity. Both patients were treated with eculizumab with complete resolution of their hematologic and renal complications. Conclusion To our knowledge, this represents the largest case series of atypical hemolytic uremic syndrome precipitated by coronavirus disease 2019 in adults.

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