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 Table of Contents  
CASE REPORT
Year : 2021  |  Volume : 12  |  Issue : 4  |  Page : 210-212

Successful use of steroids in the management of two patients of diarrhea-associated adult hemolytic uremic syndrome


1 Department of Nephrology, Indira Gandhi Medical College, Shimla, India
2 Department of Medicine, Indira Gandhi Medical College, Shimla, India

Date of Submission05-Dec-2020
Date of Decision12-Apr-2021
Date of Acceptance17-Apr-2021
Date of Web Publication18-Jan-2022

Correspondence Address:
Dr. Ajay Jaryal
Department of Nephrology, Indira Gandhi Medical College, Shimla - 171 001, Himachal Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/joah.joah_230_20

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  Abstract 


Diarrhea-associated hemolytic uremic syndrome (HUS) occurs sporadically in the community. It is well known in the pediatric age group but also occurs in the adults, albeit with lower frequency. Prompt recognition of diarrhea-associated HUS is important, as it can be easily overlooked, as prerenal acute kidney injury. Besides this, management of diarrhea-associated HUS is different; varying from supportive care with meticulous observation for spontaneous recovery to occur, or to institute specific therapy such as plasmapheresis or immunosuppressant drugs, if it evolves into organ or life-threatening thrombotic microangiopathy (TMA). HUS is one type of TMA. Steroids have been used anecdotally either standalone or in combination with other therapies, in the management of TMA, especially if it is immune-mediated TMA. In our two cases of diarrhea associated TMA/HUS, we used steroids successfully as an empiric therapy for life threatening TMA.

Keywords: Acute kidney injury, hemolytic uremic syndrome, steroids, thrombocytopenia, thrombotic microangiopathy


How to cite this article:
Jaryal A, Vikrant S, Verma BS, Gautam S, Kumar D. Successful use of steroids in the management of two patients of diarrhea-associated adult hemolytic uremic syndrome. J Appl Hematol 2021;12:210-2

How to cite this URL:
Jaryal A, Vikrant S, Verma BS, Gautam S, Kumar D. Successful use of steroids in the management of two patients of diarrhea-associated adult hemolytic uremic syndrome. J Appl Hematol [serial online] 2021 [cited 2022 Sep 25];12:210-2. Available from: https://www.jahjournal.org/text.asp?2021/12/4/210/335940




  Introduction Top


The syndrome of thrombotic microangiopathy (TMA) has diverse aetiologies and presentations, with hallmark being microangiopathic hemolytic anemia, thrombocytopenia, and organ dysfunction such as acute kidney injury (AKI).[1] Hemolytic uremic syndrome (HUS) is one of the TMA syndromes which may or may not be associated with diarrhea. Many of the times it can be a self-limiting illness which improves with optimal supportive care. However, it may call for empiric therapy such as Plasmapheresis (PP) when it evolves into life-threatening illness.[1] Steroids have also been used anecdotally in the management of certain TMA syndromes, mainly for immune-mediated TMA syndromes. Herein, we report two adult patients with diarrhea associated HUS with life-threatening TMA who were treated with empirical steroids leading to clinical improvement and resolution of TMA.


  Case Reports Top


Case 1

A 61-year-old female with no other comorbidities presented with vomiting, diarrhea, and decreased urine output for the past 3 days. On investigation, she had HB 9 g/dl at admission which dropped to 5.7 g/dl over the next 2 days, total leucocyte count (TLC) 10,500/μl, platelet count 61,000/μl, potassium 7.4 mEq/L, prothrombin time (PT) 13.6 s, blood urea nitrogen (BUN) 120 mg/dl, lactate dehydrogenase (LDH) 512 U/L, creatinine 8.1 mg/dl, indirect hyperbilirubinemia, negative Coomb's test, antinuclear antibodies 2+ by immunofluorescence, and peripheral blood film showed schistocytes with reticulocytosis. Stool culture grew Escherichia coli. She was diagnosed as diarrhea-associated HUS. She was managed with hemodialysis. In view of TMA with severe AKI and worsening thrombocytopenia, she was given two sessions of PP on alternate days which led to normalization of platelet count, however, AKI and fall in HB continued to worsen. She refused further PP and due to non-improvement in AKI and falling HB, she was given intravenous methylprednisolone (MP) pulse 500 mg once a day for 3 days followed by oral steroids for 2 weeks which were tapered over course of the next 2 weeks. She improved symptomatically with the rise in urine output and fall in serum creatinine to 1.2 mg/dl and normalization of indices of intravascular hemolysis. She has normal blood pressure, estimated glomerular filtration rate (eGFR), hemogram, blood sugar, and urine sediment on follow-up at 1 year.

Case 2

A 32-year-old female with no other comorbidities presented with vomiting, watery diarrhea, oral mucosal bleeding, and pain abdomen for the past 5 days. Her investigations showed HB 7.4 g/dl, TLC 6100/μl, platelet 12000/μl, indirect hyperbilirubinemia, LDH 1205 U/L, BUN 55 mg/dl, creatinine 2.99 mg/dl, PT 16.1 s, corrected reticulocyte count 5.95%, negative Coomb's test, and peripheral blood film showed polychromatophilic red blood cell (RBC) with schistocytes. Stool culture was noncontributory. She was diagnosed as diarrhea-associated HUS. She was managed with optimal hydration. She was advised for PP in view of life-threatening thrombocytopenia but refused for the same. Hence, she was given injection of MP 500 mg once a day for three days followed by tapering course of oral steroids over a period of 4 weeks. Within 24 h of the first dose of MP, her platelet counts jumped upwards to a level where it was no more imminently dangerous to life. Over course of the next 5 days, her serum creatinine returned to normal range and all indices of intravascular hemolysis also normalized. She has normal eGFR, hemogram, and urine sediment on follow-up at 3 months.


  Discussion Top


HUS is a triad of thrombocytopenia, nonimmune hemolytic anemia, and AKI.[2],[3] AKI is a common occurrence because of the predisposition of glomerular capillary tuft for endothelial dysfunction. AKI is often a pointer to TMA when there is co-existing thrombocytopenia. Inciting event for TMA is endothelial cell injury which makes it more thrombogenic and activates complement and von Willebrand factor (vWF). It leads to the formation of microthrombi rich in platelets and fibrin and then these microthrombi lead to partial or total occlusion of microvasculature. Subsequently, thrombocytopenia occurs due to platelet aggregation in these microthrombi and hemolytic anemia occurs due to mechanical trauma to RBC during their passage through occluded microvasculature. TMA is a histopathological diagnosis but it can be established clinically by evidence of nonimmune mechanical intravascular hemolysis such as fragmented RBC (Schistocytes), raised indirect bilirubin, LDH, plasma and urine free HB, low haptoglobin and negative Coomb's test and normal PT, activated partial thromboplastin time (aPTT), fibrinogen, and D dimer.[1],[2] HUS can be associated with diarrhea (D + HUS/typical HUS) or not associated with diarrhea (D-HUS/atypical HUS).[3] Most cases of D + HUS in children are associated with Shiga-toxin-producing Enterohemorrhagic Coli (STEC), (the most common strain is O157:H7) and Shigella dysentriae type 1.[3] Most cases of diarrhea negative HUS are associated with underlying disorder of complement pathway. This distinction may not be relevant due to considerable overlap between typical and atypical HUS, as diarrhea is a trigger in 25%–30% of atypical HUS and even D + HUS may have underlying dysregulation of the complement pathway.[3],[4] The classification of TMA is continuously evolving. It can be either primary: HUS, TTP, or secondary to multiple causes such as drugs, infections, malignancies, accelerated hypertension, autoimmune diseases, organ transplant, and hematopoietic stem cell transplant .[1],[2],[3] TTP is pentad of HUS with fever and neurological dysfunction and is associated with either congenital or acquired ADAMTS 13 deficiency. ADAMTS 13 is metalloproteinase which breakdowns vWF multimers and prevents occlusion of microvasculature.[2],[4]

TMA/HUS can rapidly evolve into life or organ-threatening illness. Main differential diagnoses such as secondary causes of TMA need to be ruled in or out based on clinical and laboratory leads. Disseminated intravascular coagulation is suggested by elevated PT, aPTT, and low fibrinogen.[3] Being a syndrome itself the treatment of TMA can be started as the syndromic approach. First step is optimal supportive care and treatment of underlying cause. However, if there is life or organ threatening TMA, then PP becomes empiric therapy of choice. PP is the treatment of choice for TTP, and other therapies for TTP are plasma infusion or eculizumab (monoclonal antibody to complement factor C5).[5] The role of steroids in HUS is ambiguous. In one RCT the use of steroid versus placebo in childhood HUS was not associated with improved renal, hematological, or neurological parameters but was associated with more rapid decline in creatinine level.[6] Although, some authors have also successfully used steroids along with other immunomodulating therapies in aHUS with long-term remissions.[7],[8] It is well known that: (1) few patients of typical HUS may not have preceding diarrhea and may have transient activation of the alternative complement pathway, (2) Around 1/4th of patients with aHUS may have antecedence of diarrhea, and (3) STEC can precipitate HUS/TMA in patients with mutations in alternate complement pathway.[9] Diarrheal or nondiarrheal infections may be triggering 50% of adults and 80% of pediatric aHUS.[10] Both of our patients received optimal supportive care, but still, their TMA/HUS evolved into life and organ-threatening TMA. Steroids were only instituted after refusal for PP. The use of steroids led to amelioration of TMA without any immediate adverse effects and favorable outcomes on follow-up.


  Conclusion Top


D + HUS is a rare disease and a type of TMA. There is overlap in the pathogenesis of various HUS/TMA syndromes, and hence syndromic approach for the treatment is reasonable. Although PP is an empiric treatment of choice, steroids being immunomodulating drugs may be helpful in the patients unwilling for PP, either alone or as an adjunct to PP, as immune-mediated dysregulation of alternate complement pathway acts as a pivot in the pathogenesis of HUS/TMA syndromes.

Ethics

Written informed consent was obtained from the patients.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patients have given consent for their clinical information to be reported in the journal. Patients understand that their names and initials will not be published, and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Ruggenenti P, Cravedi P, Remuzzi G. Thrombotic microangiopathies, including hemolytic uremic syndrome. In: Floege J, Johnson RJ, Feehally J, editors. Comprehensive Clinical Nephrology. 4th ed.. St. Louis, Missouri: Elsevier Saunders; 2010. p. 344-55.  Back to cited text no. 1
    
2.
Arnold DM, Patriquin CJ, Nazy I. Thrombotic microangiopathies: A general approach to diagnosis and management. CMAJ 2017;189:E153-9.  Back to cited text no. 2
    
3.
Canpolat N. Hemolytic uremic syndrome. Turk Pediatri Ars 2015;50:73-82.  Back to cited text no. 3
    
4.
Pérez-Cruz FG, Villa-Díaz P, Pintado-Delgado MC, Fernández Rodríguez ML, Blasco-Martínez A, Pérez-Fernández M. Hemolytic uremic syndrome in adults: A case report. World J Crit Care Med 2017;6:135-9.  Back to cited text no. 4
    
5.
Brocklebank V, Wood KM, Kavanagh D. Thrombotic microangiopathy and the kidney. Clin J Am Soc Nephrol 2018;13:300-17.  Back to cited text no. 5
    
6.
Perez N, Spizzirri F, Rahman R, Suarez A, Larrubia C, Lasarte P. Steroids in the hemolytic uremic syndrome. Pediatr Nephrol 1998;12:101-4.  Back to cited text no. 6
    
7.
Patterson JM, Bolster L, Larratt L. Case series of 3 patients diagnosed with atypical hemolytic uremic syndrome successfully treated with steroids, plasmapheresis, and rituximab. Can J Kidney Health Dis 2018;5:2054358117747262.  Back to cited text no. 7
    
8.
Lionet A, Provôt F, Glowacki F, Frémeaux-Bacchi V, Hazzan M. A case of adult atypical haemolytic uraemic syndrome related to anti-factor H autoantibodies successfully treated by plasma exchange, corticosteroids and rituximab. NDT Plus 2009;2:458-60.  Back to cited text no. 8
    
9.
Fremeaux-Bacchi V, Fakhouri F, Garnier A, Bienaimé F, Dragon-Durey MA, Ngo S, et al. Genetics and outcome of atypical hemolytic uremic syndrome: A nationwide French series comparing children and adults. Clin J Am Soc Nephrol 2013;8:554-62.  Back to cited text no. 9
    
10.
Noris M, Caprioli J, Bresin E, Mossali C, Pianetti G, Gamba S, et al. Relative role of genetic complement abnormalities in sporadic and familial aHUS and their impact on clinical phenotype. Clin J Am Soc Nephrol 2010;5:1844-59.  Back to cited text no. 10
    




 

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