Atypical Hemolytic Uremic Syndrome and Chronic Ulcerative Colitis Treated with Eculizumab

Webb, Tennille N.; Griffiths, Heidi; Miyashita, Yosuke; Bhatt, Riha; Jaffe, Ronald; Moritz, Michael L.; Hofer, Johannes; Swiatecka‐Urban, Agnieszka

doi:10.9734/ijmpcr/2015/18771

Cited by 13 publications

(9 citation statements)

References 31 publications

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“…Such activation may be uncontrolled in patients with an underlying defect in complement regulatory proteins, leading to the clinical manifestations of aHUS. This may explain the sequence of events in which a diagnosis of IBD precedes the clinical onset of aHUS, such as patient 1 in our series and in other patients previously reported with the onset of unspecified HUS following a remote diagnosis of inflammatory bowel disease [8, 11, 12].…”

Section: Discussionsupporting

confidence: 53%

“…Less well described is an association between inflammatory bowel disease (IBD) and aHUS. There have been only six cases of HUS associated with IBD reported in the literature, nearly all of which were in adult patients [8, 9, 10, 11, 12]. We evaluated the genetic background of three cases of pediatric patients with co-existing aHUS and IBD to determine if there was a genetic predisposition of their aHUS and whether there were any correlations between aHUS and IBD.…”

Section: Introductionmentioning

confidence: 99%

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Comorbidity of inflammatory bowel disease with atypical hemolytic uremic syndrome in pediatric patients

Shin

Nester

Dixon

2019

CNCS

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Atypical hemolytic uremic syndrome (aHUS) is a form of thrombotic microangiopathy mediated by dysregulation of the alternative complement pathway. Complement-amplifying conditions such as respiratory and gastrointestinal infections, pregnancy, malignancy, and systemic autoimmune diseases such as systemic lupus erythematosus have been associated with the clinical manifestation of aHUS. Inflammation of the gastrointestinal tract is a potent stimulus for complement activation, and we describe a series of three pediatric patients with aHUS and comorbidity of inflammatory bowel disease (IBD). In two of the three cases, the diagnosis of aHUS preceded the diagnosis of IBD, perhaps suggesting a mechanistic link between complement dysregulation and thrombotic microangiopathy in the gastrointestinal tract and the ensuing inflammatory changes of IBD.

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Section: Discussionsupporting

confidence: 53%

Section: Introductionmentioning

confidence: 99%

Comorbidity of inflammatory bowel disease with atypical hemolytic uremic syndrome in pediatric patients

Shin

Nester

Dixon

2019

CNCS

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“…Only 2 cases of UC-associated aHUS have been reported in the literature (Table 1 ) [ 96 , 97 ]. In the case reported by Green et al [ 96 ], the patient was found to have complement factor H autoantibodies.…”

Section: Discussionmentioning

confidence: 99%

Atypical hemolytic uremic syndrome in the setting of complement-amplifying conditions: case reports and a review of the evidence for treatment with eculizumab

2016

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Atypical hemolytic uremic syndrome (aHUS) is a rare, genetic, progressive, life-threatening form of thrombotic microangiopathy (TMA) predominantly caused by dysregulation of the alternative pathway of the complement system. Complement-amplifying conditions (CACs), including pregnancy complications [preeclampsia, HELLP (hemolysis, elevated liver enzymes, low platelet count) syndrome], malignant hypertension, autoimmune diseases, transplantation, and others, are associated with the onset of TMA in up to 69 % of cases of aHUS. CACs activate the alternative pathway of complement and may be comorbid with aHUS or may unmask a previously undiagnosed case. In this review, three case reports are presented illustrating the onset and diagnosis of aHUS in the setting of different CACs (pregnancy complications, malignant hypertension, renal transplantation). The report also reviews the evidence for a variety of CACs, including those mentioned above as well as infections and drug-induced TMA, and the overlap with aHUS. Finally, we introduce an algorithm for diagnosis and treatment of aHUS in the setting of CACs. If TMA persists despite initial management for the specific CAC, aHUS should be considered. The terminal complement inhibitor eculizumab should be initiated for all patients with confirmed diagnosis of aHUS, with or without a comorbid CAC.

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“…***Heterozygous MTHFR mutations are not generally thought to cause aHUS, therefore a known causative mutation was not found in Webb et.al. [7]. ****Early on in Case 1 a borderline positive C3 nephritic factor antibody was found and complement testing revealed a high level of soluble membrane attack complex…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2019

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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.

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Atypical Hemolytic Uremic Syndrome and Chronic Ulcerative Colitis Treated with Eculizumab

Cited by 13 publications

References 31 publications

Comorbidity of inflammatory bowel disease with atypical hemolytic uremic syndrome in pediatric patients

Comorbidity of inflammatory bowel disease with atypical hemolytic uremic syndrome in pediatric patients

Atypical hemolytic uremic syndrome in the setting of complement-amplifying conditions: case reports and a review of the evidence for treatment with eculizumab

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

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