scholarly journals Successful use of eculizumab to treat atypical hemolytic uremic syndrome in patients with inflammatory bowel disease

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Ramy M. Hanna ◽  
Noah Merin ◽  
Richard M. Burwick ◽  
Lama Abdelnour ◽  
Umut Selamet ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Hemolytic Uremic Syndrome ◽  
Lupus Erythematosus ◽  
Complement Activation ◽  
Bowel Disease ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Kidney Injury ◽  
Uremic Syndrome ◽  
Inflammatory Bowel ◽  
Case Presentations

Abstract Background Atypical hemolytic uremic syndrome is a rare group of disorders that have in common underlying complement amplifying conditions. These conditions can accelerate complement activation that results in a positive feedback cycle. The known triggers for complement activation can be diverse and include, infection, autoimmune disease, and malignancy. Recent reports suggest that certain autoimmune and rheumatological triggers of complement activation may result in atypical hemolytic uremic syndrome that does not resolve despite treating the underlying disorder. Specifically, patients with systemic lupus erythematosus and microangiopathic hemolysis may not respond to treatment of their underlying rheumatological trigger but responded to complement blockade. Case presentations We report two patients with inflammatory bowel disease complicated by development of atypical hemolytic uremic syndrome. In both cases, patients were on treatment for inflammatory bowel disease, that was not well controlled/flaring at the time. The first patient is a male who developed Crohn’s disease and microangiopathic hemolysis at age 5 and was treated with eculizumab successfully. Discontinuation of the medication led to multiple relapses, and the patient currently is being treated with eculizumab and has normal hematological and stable renal parameters. The second patient is a 49-year-old female with Ulcerative Colitis treated with 6-Mercaptopurine. She developed acute kidney injury and microangiopathic hemolysis. Prompt diagnosis and treatment with eculizumab resulted in the recovery of kidney injury along with a complete hematological response. Conclusions These two cases are the fifth and sixth patients to be published in the literature with atypical hemolytic uremic syndrome and inflammatory bowel disease treated with complement blockade. This confirms that C5 complement blockade is effective in treating complement mediated thrombotic microangiopathy/atypical hemolytic uremic syndrome when it is triggered in patients with inflammatory bowel disease.

Local complement activation in inflammatory bowel disease

1991 ◽  
Vol 10 (3-4) ◽  
pp. 485-492 ◽  
Author(s):  
Trond S. Halstensen ◽  
Per Brandtzaeg
Keyword(s):  
Inflammatory Bowel Disease ◽  
Complement Activation ◽  
Bowel Disease ◽  
Inflammatory Bowel

scholarly journals C4Bgene influences intestinal microbiota through complement activation in patients with paediatric-onset inflammatory bowel disease

2017 ◽  
Vol 190 (3) ◽  
pp. 394-405 ◽  
Author(s):  
E. Nissilä ◽  
K. Korpela ◽  
A. I. Lokki ◽  
R. Paakkanen ◽  
S. Jokiranta ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Intestinal Microbiota ◽  
Complement Activation ◽  
Bowel Disease ◽  
Inflammatory Bowel

scholarly journals Atypical hemolytic uremic syndrome secondary to lupus nephritis, responsive to eculizumab

2016 ◽  
Vol 8 (3) ◽  
Author(s):  
Alexander G. Raufi ◽  
Shruti Scott ◽  
Omar Darwish ◽  
Kevin Harley ◽  
Kanwarpal Kahlon ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Hemolytic Uremic Syndrome ◽  
Lupus Erythematosus ◽  
Multidisciplinary Approach ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Organ Damage ◽  
Atypical Hus ◽  
First Line Therapy ◽  
Autoimmune Attack ◽  
Uremic Syndrome

Among the spectrum of disease manifestations associated with systemic lupus erythematosus, lupus nephritis is particularly concerning due to the potential for renal failure. This autoimmune attack may not, however, be limited to the kidney and is increasingly being recognized as a trigger for atypical Hemolytic Uremic Syndrome (aHUS). Atypical HUS falls under the spectrum of the thrombotic microangiopathies (TMAs) – a group of disorders characterized by microangiopathic hemolytic anemia, thrombocytopenia, and end organ damage. Although plasma exchange is considered first-line therapy for thrombotic thrombocytopenic purpura – a TMA classically associated with autoimmune depletion of ADAMTS-13 – aHUS demonstrates less reliable responsiveness to this modality. Instead, use of the late complement inhibitor Eculizumab has emerged as an effective modality for the management of such patients. Diagnosis of aHUS, however, is largely clinically based, relying heavily upon a multidisciplinary approach. Herein we present the case of a patient with atypical HUS successfully treated with Eculizumab in the setting of Class IV-G (A) lupus nephritis and hypocomplementemia.

Systemic lupus erythematosus with inflammatory bowel disease-ulcerative colitis: case report

Lupus ◽  
2018 ◽  
Vol 27 (7) ◽  
pp. 1198-1201
Author(s):  
H Elsayed Mansour ◽  
S Gamal Arafa ◽  
W Abdelfatah Shehata
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Ulcerative Colitis ◽  
Inflammatory Bowel Disease ◽  
Lupus Erythematosus ◽  
Bowel Disease ◽  
University Hospital ◽  
Small Vessel Vasculitis ◽  
Antibody Testing ◽  
Systemic Lupus ◽  
Inflammatory Bowel

A 30-year-old female presented to the rheumatology outpatient clinic of the Internal Medicine Department, Ain Shams University Hospital, Cairo, Egypt, complaining of a large right leg ulcer consistent with pyoderma gangrenosum. There was history of recurrent attacks of bleeding per rectum of one-year duration. During hospitalization she noticed blurring of vision in the left eye with diffuse blackish discoloration of the feet and toes, consistent with small-vessel vasculitis. Colonoscopy with biopsy and histopathology confirmed the diagnosis of inflammatory bowel disease-ulcerative colitis (IBD-UC). Meanwhile, the patient fulfilled the SLICC classification criteria for systemic lupus erythematosus (SLE): recurrent oral ulcers, positive antinuclear antibody testing, proteinuria >0.5 gm/24-hour urine, positive test for lupus anticoagulant and consumed C3 complement component. Herein we report a rare case of coexistence of SLE and IBD-UC.

Eculizumab Modifies Outcomes in Adults with Atypical Hemolytic Uremic Syndrome with Acute Kidney Injury

2018 ◽  
Vol 48 (3) ◽  
pp. 225-233 ◽  
Author(s):  
Mercedes Cao ◽  
Bruna N. Leite ◽  
Tamara Ferreiro ◽  
María Calvo ◽  
Constantino Fernández ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Hemolytic Uremic Syndrome ◽  
Kidney Function ◽  
Case Reports ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Kidney Injury ◽  
Complete Recovery ◽  
Genetic Abnormalities ◽  
Uremic Syndrome ◽  
Meta Analyses

Background: Atypical hemolytic uremic syndrome (aHUS) is a rare disease associated with congenital or acquired genetic abnormalities that result in uncontrolled complement activation, leading to thrombotic microangiopathy and kidney failure. Until recently, the only treatment was plasma exchange or plasma infusion (PE/PI), but 60% of patients died or had permanent kidney damage despite treatment. Eculizumab, a complement inhibitor, has shown promising results in aHUS. However, data are mainly extracted from case reports or studies of heterogeneous cohorts, and no direct comparison with PE/PI is available. Methods: An observational retrospective study of adult, dialysis-dependent aHUS patients with acute kidney injury (AKI) who were treated with either PE/PI alone or with second-line eculizumab in our center. We compared the effect of PE/PI and eculizumab on kidney function, hypertension, proteinuria, hematologic values, relapse, and death. Results: Thirty-one patients were included (females, 18; sporadic aHUS, 29; mean age, 46 ± 20 years). Twenty-six patients were treated with PE/PI alone, and 5 were deemed to be plasma-resistant and received eculizumab after stopping PE/PI. Among patients receiving eculizumab, 80% attained complete recovery of kidney function, 100% stopped dialysis, 20% had decreased proteinuria, and no patient relapsed (vs. 38.5, 50, 15.4, and 11.5%, respectively, of patients receiving only PE/PI). At 1-year of follow-up, no deaths had occurred in either group. Conclusion: Eculizumab shows greater efficacy than PE/PI alone for the treatment of adult aHUS patients with AKI. Prospective studies and meta-analyses are warranted to confirm our findings and set guidelines for treatment, monitoring, and maintenance.

Cardiovascular Risk Assessment and Impact of Medications on Cardiovascular Disease in Inflammatory Bowel Disease

2020 ◽  
Author(s):  
Preetika Sinh ◽  
Raymond Cross
Keyword(s):  
Heart Failure ◽  
Cardiovascular Disease ◽  
Inflammatory Bowel Disease ◽  
Cardiovascular Risk ◽  
Lupus Erythematosus ◽  
Bowel Disease ◽  
Severe Heart Failure ◽  
Janus Kinase ◽  
Increased Risk ◽  
Inflammatory Bowel

Abstract There is increased risk of cardiovascular disease in patients with chronic inflammatory disorders such as rheumatoid arthritis, psoriatic arthritis, and systemic lupus erythematosus. Studies have shown association between cardiovascular disease (eg, myocardial infarction, heart failure, stroke) and inflammatory bowel disease. Medications such as infliximab and adalimumab (monoclonal antibodies to tumor necrosis factor α) may help decrease the inflammatory burden and cardiovascular risk; however, there have been reports of hypertriglyceridemia and worsening of moderate to severe heart failure with these medications. Janus kinase inhibitors, such as tofacitinib, have been associated with hyperlipidemia and thromboembolism. We aim to discuss clinical and imaging modalities to assess cardiovascular risk in inflammatory bowel disease patients and review the role of various medications with respect to cardiovascular disease in this population.

scholarly journals Complement Activation and Thrombotic Microangiopathies

2019 ◽  
Vol 14 (12) ◽  
pp. 1719-1732 ◽  
Author(s):  
Marta Palomo ◽  
Miquel Blasco ◽  
Patricia Molina ◽  
Miquel Lozano ◽  
Manuel Praga ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Hemolytic Uremic Syndrome ◽  
Acute Phase ◽  
Complement Activation ◽  
Hellp Syndrome ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Malignant Hypertension ◽  
Clinical Relapse ◽  
Thrombotic Microangiopathies ◽  
Uremic Syndrome

Background and objectivesAtypical hemolytic uremic syndrome is a form of thrombotic microangiopathy caused by dysregulation of the alternative complement pathway. There is evidence showing complement activation in other thrombotic microangiopathies. The aim of this study was to evaluate complement activation in different thrombotic microangiopathies and to monitor treatment response.Design, setting, participants, & measurementsComplement activation was assessed by exposing endothelial cells to sera or activated-patient plasma—citrated plasma mixed with a control sera pool (1:1)—to analyze C5b-9 deposits by immunofluorescence. Patients with atypical hemolytic uremic syndrome (n=34) at different stages of the disease, HELLP syndrome (a pregnancy complication characterized by hemolysis, elevated liver enzymes, and low platelet count) or severe preeclampsia (n=10), and malignant hypertension (n=5) were included.ResultsAcute phase atypical hemolytic uremic syndrome–activated plasma induced an increased C5b-9 deposition on endothelial cells. Standard and lower doses of eculizumab inhibited C5b-9 deposition in all patients with atypical hemolytic uremic syndrome, except in two who showed partial remission and clinical relapse. Significant fibrin formation was observed together with C5b-9 deposition. Results obtained using activated-plasma samples were more marked and reproducible than those obtained with sera. C5b-9 deposition was also increased with samples from patients with HELLP (all cases) and preeclampsia (90%) at disease onset. This increase was sustained in those with HELLP after 40 days, and levels normalized in patients with both HELLP and preeclampsia after 6–9 months. Complement activation in those with malignant hypertension was at control levels.ConclusionsThe proposed methodology identifies complement overactivation in patients with atypical hemolytic uremic syndrome at acute phase and in other diseases such as HELLP syndrome and preeclampsia. Moreover, it is sensitive enough to individually assess the efficiency of the C5 inhibition treatment.

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