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==Overview== | ==Overview== | ||
In [[medicine]], '''hemolytic-uremic syndrome''' (or '''haemolytic-uraemic syndrome''', abbreviated HUS) is a disease characterized by [[microangiopathic hemolytic anemia]], acute [[renal failure]] and a low [[platelet]] count ([[thrombocytopenia]]). It is due to the abnormal [[Blood-clot|blood clotting]] within the [[Capillary|capillaries]] leading to [[Red blood cell|RBC]] shearing and destruction while passing through clogged [[Capillary|capillaries]] and obstruction of [[kidney]] filtration system by damaged RBC's lead to [[acute kidney injury]] and is one of the leading causes of [[ | In [[medicine]], '''hemolytic-uremic syndrome''' (or '''haemolytic-uraemic syndrome''', abbreviated HUS) is a [[disease]] [[Character (biology)|characterized]] by [[microangiopathic hemolytic anemia]], [[Acute (medicine)|acute]] [[renal failure]] and a low [[platelet]] count ([[thrombocytopenia]]). It is due to the [[abnormal]] [[Blood-clot|blood clotting]] within the [[Capillary|capillaries]] leading to [[Red blood cell|RBC]] shearing and destruction while passing through clogged [[Capillary|capillaries]] and [[obstruction]] of [[kidney]] [[filtration]] [[system]] by damaged [[RBCs|RBC's]] lead to [[acute kidney injury]] and is one of the leading [[causes]] of [[acute renal failure]] in children. The two main types are typical and atypical Hemolytic uremic syndrome(HUS). Typical HUS is caused following a [[diarrheal]] [[infection]] by [[E.coli]] [[E.Coli OH157: H7|OH157: H7]] and is responsible for 90 percent of HUS cases in Children. Atypical HUS is not associated with [[gastrointestinal]] [[symptoms]] and also has a less favorable [[outcome]]. | ||
==Historical Perspective== | ==Historical Perspective== | ||
In 1955, Gasser et al first described hemolytic-uremic syndrome (HUS). There have been several outbreaks of HUS all over the world over past years. | In 1955, Gasser et al first described hemolytic-uremic syndrome (HUS). There have been several [[Outbreak|outbreaks]] of HUS all over the world over past years. | ||
==Classification== | ==Classification== | ||
HUS may be classified as | HUS may be classified as typical (Caused by [[Shiga toxin-producing E. coli|Shiga-toxin producing E.coli/]] [[Shigella]] [[Infection]]) or atypical (caused by [[complement]] factor abnormalities, other [[viral]] or [[bacterial]] [[Infection|infections]], [[HIV]], [[malignancy]], [[Organ transplant|organ transplantation]], and rarely [[SLE]] and [[pregnancy]] related). | ||
==Pathophysiology== | ==Pathophysiology== | ||
It is understood that | It is understood that hemolytic uremic [[syndrome]] is the result of microvascular [[endothelial]] cell damage [[Characterization (mathematics)|characterized]] by [[thrombotic microangiopathy]] ([[TMA]]) in [[renal]] [[glomeruli]], [[gastrointestinal tract]], [[brain]] and [[pancreas]] in all of which the main lesion is the thickening of [[vessel wall]] (mainly in [[Capillary|capillaries]] and [[Arteriole|arterioles]]), microthrombi in [[Platelet|platelets]] and [[obstruction]] of [[vessel]] [[lumen]]( partial or complete). Loss of [[physiological]] [[resistance]] to [[thrombus]] formation, [[complement]] consumption, [[leukocyte]] [[adhesion]] to damaged [[endothelium]], the abnormal release of Von Willibrand Factor ([[vWF]]) and [[Fragmentation (biology)|fragmentation]], and increased [[vascular]] shear stress lead to further [[amplification]] of [[microangiopathy]]. Typical/ [[Shiga toxin E. coli|Shiga-toxin-]]<nowiki/>associated hemolytic uremic syndrome (HUS) is usually caused by [[E.Coli]] and [[serotype]] O157: H7 is most common while [[congenital]] predisposing conditions like complement factor abnormalities may play a role in recurrent and [[familial]] forms<ref name="pmid11532079">{{cite journal| author=Ruggenenti P, Noris M, Remuzzi G| title=Thrombotic microangiopathy, hemolytic uremic syndrome, and thrombotic thrombocytopenic purpura. | journal=Kidney Int | year= 2001 | volume= 60 | issue= 3 | pages= 831-46 | pmid=11532079 | doi=10.1046/j.1523-1755.2001.060003831.x | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11532079 }}</ref>. | ||
==Causes== | ==Causes== | ||
| Line 50: | Line 50: | ||
| pmid = 28242109 | | pmid = 28242109 | ||
}}</ref><ref name="Lopes da Silva2011">{{cite journal|last1=Lopes da Silva|first1=Rodrigo|title=Viral-associated thrombotic microangiopathies|journal=Hematology/Oncology and Stem Cell Therapy|volume=4|issue=2|year=2011|pages=51–59|issn=16583876|doi=10.5144/1658-3876.2011.51}}</ref> | }}</ref><ref name="Lopes da Silva2011">{{cite journal|last1=Lopes da Silva|first1=Rodrigo|title=Viral-associated thrombotic microangiopathies|journal=Hematology/Oncology and Stem Cell Therapy|volume=4|issue=2|year=2011|pages=51–59|issn=16583876|doi=10.5144/1658-3876.2011.51}}</ref> | ||
*[[E. coli]] (70%)- Shiga-Toxin producing E.Coli (STEC) | *[[E. coli]] (70%)- [[Shiga toxin-producing E. coli|Shiga-Toxin producing E.Coli]] ([[STEC]]) | ||
**primary source of infection is usually undercooked or raw ground meat products, raw milk, or fecal contamination of vegetables | **primary source of [[infection]] is usually undercooked or raw ground meat products, raw milk, or fecal contamination of vegetables | ||
**other sources include swimming pools or lakes contaminated with feces | **other sources include swimming pools or lakes contaminated with feces | ||
**usually cause self-limiting infection but can lead to HUS in some, particularly in young children and elderly | **usually cause [[Self-limiting (biology)|self-limiting]] [[infection]] but can lead to HUS in some, particularly in young children and [[elderly]] | ||
**STEC is heat sensitive and destroyed by thorough cooking and WHO recommended guidelines for safer food should be used to prevent infections with foodborne organisms like STEC. | **[[STEC]] is heat sensitive and destroyed by thorough cooking and [[World Health Organization|WHO]] recommended guidelines for safer food should be used to [[Prevention|prevent]] [[infections]] with [[foodborne]] [[Organism|organisms]] like [[STEC]]. | ||
*Other Shiga-Toxin bacteria like Shigella Dysenteriae type-1. | *Other [[Shiga toxin|Shiga-Toxin]] [[bacteria]] like [[Shigella Dysentery|Shigella Dysenteriae]] type-1. | ||
Less common causes include: | Less common causes include: | ||
* Genetic [[Mutation|mutations]] of complement genes/ Complement Factor abnormalities | * [[Genetics|Genetic]] [[Mutation|mutations]] of [[complement]] [[Gene|genes]]/ [[Complement]] Factor abnormalities | ||
* Infection with Campylobacter Jejuni or Salmonella Typhi | * [[Infection]] with [[Campylobacter jejuni|Campylobacter Jejuni]] or [[Salmonella Typhi]] | ||
* Pneumococcal infection (commonly pneumonia, empyema, meningitis, and less commonly pericarditis, peritonitis, otitis media and bacteremia | * [[Pneumococcal]] [[infection]] (commonly [[pneumonia]], [[empyema]], [[meningitis]], and less commonly [[pericarditis]], [[peritonitis]], [[otitis media]] and [[bacteremia]] | ||
* Pregnancy | * [[Pregnancy]] | ||
* [[Autoimmune]] disease for example SLE, | * [[Autoimmune]] [[disease]] for example [[SLE]], [[antiphospholipid syndrome]] | ||
* Drug associated | * [[Drug]] associated | ||
** Antineoplastic, immunosuppressive and anti platelet | ** [[Antineoplastic]], [[immunosuppressive]] and [[Antiplatelet drug|anti platelet]] | ||
* Organ Transplantation | * [[Organ transplant|Organ Transplantation]] | ||
* Human [[immunodeficiency]] [[viral infection]] such as [[HIV AIDS|<abbr>HIV</abbr>/<abbr>AIDS</abbr>]] | * [[Human]] [[immunodeficiency]] [[viral infection]] such as [[HIV AIDS|<abbr>HIV</abbr>/<abbr>AIDS</abbr>]] | ||
==Differentiating [Disease] from Other Diseases== | ==Differentiating [Disease] from Other Diseases== | ||
==Epidemiology and Demographics== | ==Epidemiology and Demographics== | ||
The highest proportion of HUS cases (15.3%) occurred among children aged <5 years. HUS affects female more than male and white race more than other races. Mortality is more commonly seen in elderly patients in which disease is less common but more dangerous | The highest proportion of HUS cases (15.3%) occurred among children aged <5 years. HUS affects [[female]] more than [[male]] and white [[race]] more than other races. [[Mortality]] is more commonly seen in [[elderly]] [[Patient|patients]] in which [[disease]] is less common but more dangerous | ||
==Risk Factors== | ==Risk Factors== | ||
The most potent risk factor in the development of Hemolytic Uremic Syndrome in childhood is infection with Verocytotoxin (Shiga-like toxin)-producing bacteria, usually Enterohemorrhagic Escherichia coli (VTEC/STEC),and in some tropical regions Shigella dysenteriae type I<ref name="pmid24750096">{{cite journal| author=Majowicz SE, Scallan E, Jones-Bitton A, Sargeant JM, Stapleton J, Angulo FJ et al.| title=Global incidence of human Shiga toxin-producing Escherichia coli infections and deaths: a systematic review and knowledge synthesis. | journal=Foodborne Pathog Dis | year= 2014 | volume= 11 | issue= 6 | pages= 447-55 | pmid=24750096 | doi=10.1089/fpd.2013.1704 | pmc=4607253 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24750096 }}</ref> . Other risk factors include genetic mutations in Complement factors, Pneumococcal infections, | The most potent [[risk factor]] in the [[Development (biology)|development]] of Hemolytic Uremic Syndrome in childhood is [[infection]] with [[Verocytotoxin]] ([[Shiga-like toxin]])-producing [[bacteria]], usually [[Enterohemorrhagic escherichica coli|Enterohemorrhagic Escherichia coli]] (VTEC/[[STEC]]),and in some tropical regions [[Shigella dysenteriae|Shigella dysenteriae type]] I<ref name="pmid24750096">{{cite journal| author=Majowicz SE, Scallan E, Jones-Bitton A, Sargeant JM, Stapleton J, Angulo FJ et al.| title=Global incidence of human Shiga toxin-producing Escherichia coli infections and deaths: a systematic review and knowledge synthesis. | journal=Foodborne Pathog Dis | year= 2014 | volume= 11 | issue= 6 | pages= 447-55 | pmid=24750096 | doi=10.1089/fpd.2013.1704 | pmc=4607253 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24750096 }}</ref> . Other [[risk factors]] include [[Genetics|genetic]] [[Mutation|mutations]] in [[Complement]] factors, Pneumococcal [[Infection|infections]], [[autoimmune diseases]] like [[SLE]] and [[Antiphospholipid syndrome|antiphospholipid Syndrome]], [[pregnancy]], [[antineoplastic]] and [[Immunosuppression|immunosuppressive]] [[drugs]], [[Human Immunodeficiency Virus (HIV)|HIV]] [[infection]] and [[Organ transplant|organ transplantation]]. | ||
==Screening== | ==Screening== | ||
There is insufficient evidence to recommend screening for Hemolytic-Uremic Syndrome | There is insufficient [[evidence]] to recommend [[Screening (medicine)|screening]] for Hemolytic-Uremic Syndrome | ||
==Natural History, Complications, and Prognosis== | ==Natural History, Complications, and Prognosis== | ||
5 percent of patients with EHEC or Shiga toxin-producing E.coli infection will develop HUS presenting with bloody diarrhea, nausea, vomiting, and decreased urination. Common | 5 percent of patients with [[EHEC]] or [[Shiga toxin-producing E. coli|Shiga toxin-producing E.coli]] [[infection]] will develop HUS presenting with [[bloody diarrhea]], [[Nausea and Vomiting|nausea]], [[vomiting]], and [[decreased urination]]. Common [[complication]]<nowiki/>s of HUS include [[renal failure]] which can be [[acute]] ([[Acute kidney injury|AKI]]) or develop over time([[chronic renal failure]]), [[hypertension]], [[neurological]] problems like [[stroke]], [[seizure]], [[coma]] and eventually death. [[Prognosis]] depends on the associated [[Complication (medicine)|complications]] and about 12% of patients with [[diarrhea]]-associated HUS progress to [[end-stage renal failure]] within 4 years and about 25% have long-term [[renal]] impairment leading to 9% [[renal]] [[Kidney transplantation|transplant]]<nowiki/>s in children and [[Adolescent|adolescents]]. | ||
==Diagnosis== | ==Diagnosis== | ||
===History and Symptoms=== | ===History and Symptoms=== | ||
It usually starts with gastrointestinal prodrome including bloody diarrhea and fever that may occur 2-7 days before the onset of renal failure. Other symptoms include nausea, vomiting, abdominal pain and swelling, decreased urination, fatigue, irritability, and swelling of the body. | It usually starts with [[gastrointestinal]] prodrome including [[bloody diarrhea]] and [[fever]] that may occur 2-7 days before the onset of [[renal failure]]. Other [[Symptom|symptoms]] include [[nausea]], [[Nausea and vomiting|vomiting]], abdominal [[pain]] and [[swelling]], decreased [[urination]], fatigue, irritability, and swelling of the body. | ||
===Physical Examination=== | ===Physical Examination=== | ||
Common physical examination findings of Hemolytic Uremic Syndrome include edema and fluid overload, high blood pressure and often severe pallor. Gastrointestinal findings may include abdominal tenderness, distension and guarding. Bruising, purpura, petechiae or oozing from the site of venipuncture may b seen sometimes. | Common physical examination findings of Hemolytic Uremic Syndrome include edema and fluid overload, high blood pressure and often severe pallor. [[Gastrointestinal]] findings may include [[abdominal tenderness]], [[distension]] and [[guarding]]. [[Bruising]], [[purpura]], [[petechiae]] or oozing from the site of [[venipuncture]] may b seen sometimes. | ||
===Laboratory Findings=== | ===Laboratory Findings=== | ||
The classic laboratory findings in HUS include anemia, thrombocytopenia, and acute renal damage. Anemia is | The classic [[laboratory]] findings in HUS include [[anemia]], [[thrombocytopenia]], and [[Acute (medicine)|acute]] [[renal]] damage. [[Anemia]] is [[microangiopathic hemolytic anemia]] which low [[hemoglobin]] often < 8g/dl, high [[reticulocyte count]] and [[LDH]], low [[Haptoglobin]] level as well as fragmented [[RBCs|RBC's]] and Schistiocytes on the [[peripheral blood smear]]. [[Platelets]] are frequently less than 60,000 without active [[bleeding]] usually and [[renal]] damage is seen in form of high [[creatinine]], [[Blood urea nitrogen|BUN]], and [[electrolyte abnormalities]]. | ||
===Imaging Findings=== | ===Imaging Findings=== | ||
'''X-ray''': The classic laboratory findings in HUS include anemia, thrombocytopenia, and acute renal damage. Anemia is | '''X-ray''': The classic [[laboratory]] findings in HUS include [[anemia]], [[thrombocytopenia]], and [[Acute kidney injury|acute renal damage]]. [[Anemia]] is [[microangiopathic hemolytic anemia]] which low [[hemoglobin]] often < 8g/dl, high [[reticulocyte count]] and [[LDH]], low [[Haptoglobin]] level as well as fragmented [[RBC's]] and Schistiocytes on the [[peripheral blood smear]]. [[Platelet|Platelets]] are frequently less than 60,000 without active [[bleeding]] usually and [[renal]] damage is seen in form of high [[creatinine]], [[Blood urea nitrogen|BUN]], and [[electrolyte]] [[abnormalities]]. | ||
'''USG abdomen''': Abdominal | '''USG abdomen''': [[Abdominal]] [[ultrasound]] findings seen in HUS may include Increased [[parenchymal]] [[density]]/[[echogenicity]] in [[kidneys]], [[hepatomegaly]], [[splenomegaly]], [[ascites]], and [[Pleural effusion|pleural effusions]]. | ||
'''MRI Brain''': Brain MRI may be helpful in the diagnosis of pathological changes in patients with CNS manifestations/ | '''MRI Brain''': [[Brain]][[Magnetic resonance imaging|MRI]] may be helpful in the [[diagnosis]] of [[pathological]] changes in [[Patient|patients]] with CNS manifestations[[Complications|/ complications]] like [[Seizure|seizures]], [[AMS]], [[visual]] changes or others in patients of HUS. Findings on [[MRI]] may include [[basal ganglia]], brainstem, [[cerebellar]] or [[Thalamus|thalamic]] lesions. | ||
===Other Diagnostic Studies=== | ===Other Diagnostic Studies=== | ||
Other important diagnostic tests include | Other important [[Diagnosis|diagnostic]] tests include | ||
* Stool culture on Sorbitol MacConkey's agar or | * [[Stool culture]] on [[Sorbitol]] MacConkey's agar or detection of [[Shiga toxin]] with [[serological testing]] | ||
* Genetic testing if suspicion of genetic or complement-mediated HUS/ recurrent HUS | * [[Genetic]] testing if suspicion of [[genetic]] or [[complement]]-mediated HUS/ recurrent HUS | ||
* Blood, spinal, organ/tissue cultures may be needed in case of suspicion of other sources of HUS, for example, Pneumococcal infection | * [[Blood]], spinal, [[Organ (biology)|organ]][[Tissue culture|/tissue cultures]] may be needed in case of suspicion of other sources of HUS, for example, [[Pneumococcal infections|Pneumococcal infection]] | ||
==Treatment== | ==Treatment== | ||
===Medical Therapy=== | ===Medical Therapy=== | ||
* The main stray of therapy for HUS is supportive | * The main stray of therapy for HUS is supportive | ||
* RBC | * [[RBC]] [[transfusion]] indicated for low [[hemoglobin]] ( Hb < 6-7 g/dl) | ||
* Platelet infusion indicated only if massive hemorrhage or surgical procedure is needed, generally platelet infusion can worsen thrombotic microangiopathy | * [[Platelet]] [[infusion]] indicated only if massive [[hemorrhage]] or surgical [[procedure]] is needed, generally [[platelet]] [[infusion]] can worsen [[Thrombosis|thrombotic]] [[microangiopathy]] | ||
* Fluid and electrolyte replacement | * Fluid and [[electrolyte]] replacement | ||
* Dialysis may be recommended for patients with azotemia and fluid electrolyte imbalance not responding to general medical therapy | * [[Dialysis]] may be recommended for patients with [[azotemia]] and fluid [[electrolyte]] [[imbalance]] not responding to general medical therapy | ||
* Plasma exchange is used for the treatment of atypical HUS and for TTP. Not a first-line therapy in patients with typical/ Diarrheal HUS | * [[Plasma]] [[Exchange transfusion|exchange]] is used for the treatment of atypical HUS and for [[TTP]]. Not a first-line [[therapy]] in patients with typical/ [[Diarrhea|Diarrheal]] HUS | ||
* Eculizumab can also be used in the treatment of atypical HUS | * [[Eculizumab]] can also be used in the treatment of atypical HUS | ||
===Surgery=== | ===Surgery=== | ||
* Surgical intervention may be required in some patients who have gastrointestinal complications with severe colitis that progress to necrosis and in some cases lead to intestinal perforation | * Surgical [[Intervention (counseling)|intervention]] may be required in some patients who have [[gastrointestinal]] [[Complication (medicine)|complications]] with severe [[colitis]] that progress to [[necrosis]] and in some cases lead to [[intestinal]] [[perforation]] | ||
* Renal | * [[Renal]] [[transplantation]] is recommended for children with [[end stage renal disease]] (ESRD) following typical HUS or HUS with [[diarrhea]] and recurrence rate is extremely low. However [[transplantation]] is not recomended in atypical HUS induced [[renal]] [[disease]] as approximately 50 percent of [[patients]] can [[relapse]]<ref name="pmid17699195">{{cite journal| author=Bresin E, Daina E, Noris M, Castelletti F, Stefanov R, Hill P et al.| title=Outcome of renal transplantation in patients with non-Shiga toxin-associated hemolytic uremic syndrome: prognostic significance of genetic background. | journal=Clin J Am Soc Nephrol | year= 2006 | volume= 1 | issue= 1 | pages= 88-99 | pmid=17699195 | doi=10.2215/CJN.00050505 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17699195 }}</ref> | ||
===Prevention=== | ===Prevention=== | ||
==References== | ==References== | ||
{{reflist|2}} | {{reflist|2}} | ||
Latest revision as of 03:38, 20 September 2018
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sogand Goudarzi, MD [2] Anila Hussain, MD [3]
Overview
In medicine, hemolytic-uremic syndrome (or haemolytic-uraemic syndrome, abbreviated HUS) is a disease characterized by microangiopathic hemolytic anemia, acute renal failure and a low platelet count (thrombocytopenia). It is due to the abnormal blood clotting within the capillaries leading to RBC shearing and destruction while passing through clogged capillaries and obstruction of kidney filtration system by damaged RBC's lead to acute kidney injury and is one of the leading causes of acute renal failure in children. The two main types are typical and atypical Hemolytic uremic syndrome(HUS). Typical HUS is caused following a diarrheal infection by E.coli OH157: H7 and is responsible for 90 percent of HUS cases in Children. Atypical HUS is not associated with gastrointestinal symptoms and also has a less favorable outcome.
Historical Perspective
In 1955, Gasser et al first described hemolytic-uremic syndrome (HUS). There have been several outbreaks of HUS all over the world over past years.
Classification
HUS may be classified as typical (Caused by Shiga-toxin producing E.coli/ Shigella Infection) or atypical (caused by complement factor abnormalities, other viral or bacterial infections, HIV, malignancy, organ transplantation, and rarely SLE and pregnancy related).
Pathophysiology
It is understood that hemolytic uremic syndrome is the result of microvascular endothelial cell damage characterized by thrombotic microangiopathy (TMA) in renal glomeruli, gastrointestinal tract, brain and pancreas in all of which the main lesion is the thickening of vessel wall (mainly in capillaries and arterioles), microthrombi in platelets and obstruction of vessel lumen( partial or complete). Loss of physiological resistance to thrombus formation, complement consumption, leukocyte adhesion to damaged endothelium, the abnormal release of Von Willibrand Factor (vWF) and fragmentation, and increased vascular shear stress lead to further amplification of microangiopathy. Typical/ Shiga-toxin-associated hemolytic uremic syndrome (HUS) is usually caused by E.Coli and serotype O157: H7 is most common while congenital predisposing conditions like complement factor abnormalities may play a role in recurrent and familial forms[1].
Causes
Common causes of HUS may include:[2][3][4][5]
- E. coli (70%)- Shiga-Toxin producing E.Coli (STEC)
- primary source of infection is usually undercooked or raw ground meat products, raw milk, or fecal contamination of vegetables
- other sources include swimming pools or lakes contaminated with feces
- usually cause self-limiting infection but can lead to HUS in some, particularly in young children and elderly
- STEC is heat sensitive and destroyed by thorough cooking and WHO recommended guidelines for safer food should be used to prevent infections with foodborne organisms like STEC.
- Other Shiga-Toxin bacteria like Shigella Dysenteriae type-1.
Less common causes include:
- Genetic mutations of complement genes/ Complement Factor abnormalities
- Infection with Campylobacter Jejuni or Salmonella Typhi
- Pneumococcal infection (commonly pneumonia, empyema, meningitis, and less commonly pericarditis, peritonitis, otitis media and bacteremia
- Pregnancy
- Autoimmune disease for example SLE, antiphospholipid syndrome
- Drug associated
- Organ Transplantation
- Human immunodeficiency viral infection such as HIV/AIDS
Differentiating [Disease] from Other Diseases
Epidemiology and Demographics
The highest proportion of HUS cases (15.3%) occurred among children aged <5 years. HUS affects female more than male and white race more than other races. Mortality is more commonly seen in elderly patients in which disease is less common but more dangerous
Risk Factors
The most potent risk factor in the development of Hemolytic Uremic Syndrome in childhood is infection with Verocytotoxin (Shiga-like toxin)-producing bacteria, usually Enterohemorrhagic Escherichia coli (VTEC/STEC),and in some tropical regions Shigella dysenteriae type I[6] . Other risk factors include genetic mutations in Complement factors, Pneumococcal infections, autoimmune diseases like SLE and antiphospholipid Syndrome, pregnancy, antineoplastic and immunosuppressive drugs, HIV infection and organ transplantation.
Screening
There is insufficient evidence to recommend screening for Hemolytic-Uremic Syndrome
Natural History, Complications, and Prognosis
5 percent of patients with EHEC or Shiga toxin-producing E.coli infection will develop HUS presenting with bloody diarrhea, nausea, vomiting, and decreased urination. Common complications of HUS include renal failure which can be acute (AKI) or develop over time(chronic renal failure), hypertension, neurological problems like stroke, seizure, coma and eventually death. Prognosis depends on the associated complications and about 12% of patients with diarrhea-associated HUS progress to end-stage renal failure within 4 years and about 25% have long-term renal impairment leading to 9% renal transplants in children and adolescents.
Diagnosis
History and Symptoms
It usually starts with gastrointestinal prodrome including bloody diarrhea and fever that may occur 2-7 days before the onset of renal failure. Other symptoms include nausea, vomiting, abdominal pain and swelling, decreased urination, fatigue, irritability, and swelling of the body.
Physical Examination
Common physical examination findings of Hemolytic Uremic Syndrome include edema and fluid overload, high blood pressure and often severe pallor. Gastrointestinal findings may include abdominal tenderness, distension and guarding. Bruising, purpura, petechiae or oozing from the site of venipuncture may b seen sometimes.
Laboratory Findings
The classic laboratory findings in HUS include anemia, thrombocytopenia, and acute renal damage. Anemia is microangiopathic hemolytic anemia which low hemoglobin often < 8g/dl, high reticulocyte count and LDH, low Haptoglobin level as well as fragmented RBC's and Schistiocytes on the peripheral blood smear. Platelets are frequently less than 60,000 without active bleeding usually and renal damage is seen in form of high creatinine, BUN, and electrolyte abnormalities.
Imaging Findings
X-ray: The classic laboratory findings in HUS include anemia, thrombocytopenia, and acute renal damage. Anemia is microangiopathic hemolytic anemia which low hemoglobin often < 8g/dl, high reticulocyte count and LDH, low Haptoglobin level as well as fragmented RBC's and Schistiocytes on the peripheral blood smear. Platelets are frequently less than 60,000 without active bleeding usually and renal damage is seen in form of high creatinine, BUN, and electrolyte abnormalities.
USG abdomen: Abdominal ultrasound findings seen in HUS may include Increased parenchymal density/echogenicity in kidneys, hepatomegaly, splenomegaly, ascites, and pleural effusions.
MRI Brain: BrainMRI may be helpful in the diagnosis of pathological changes in patients with CNS manifestations/ complications like seizures, AMS, visual changes or others in patients of HUS. Findings on MRI may include basal ganglia, brainstem, cerebellar or thalamic lesions.
Other Diagnostic Studies
Other important diagnostic tests include
- Stool culture on Sorbitol MacConkey's agar or detection of Shiga toxin with serological testing
- Genetic testing if suspicion of genetic or complement-mediated HUS/ recurrent HUS
- Blood, spinal, organ/tissue cultures may be needed in case of suspicion of other sources of HUS, for example, Pneumococcal infection
Treatment
Medical Therapy
- The main stray of therapy for HUS is supportive
- RBC transfusion indicated for low hemoglobin ( Hb < 6-7 g/dl)
- Platelet infusion indicated only if massive hemorrhage or surgical procedure is needed, generally platelet infusion can worsen thrombotic microangiopathy
- Fluid and electrolyte replacement
- Dialysis may be recommended for patients with azotemia and fluid electrolyte imbalance not responding to general medical therapy
- Plasma exchange is used for the treatment of atypical HUS and for TTP. Not a first-line therapy in patients with typical/ Diarrheal HUS
- Eculizumab can also be used in the treatment of atypical HUS
Surgery
- Surgical intervention may be required in some patients who have gastrointestinal complications with severe colitis that progress to necrosis and in some cases lead to intestinal perforation
- Renal transplantation is recommended for children with end stage renal disease (ESRD) following typical HUS or HUS with diarrhea and recurrence rate is extremely low. However transplantation is not recomended in atypical HUS induced renal disease as approximately 50 percent of patients can relapse[7]
Prevention
References
- ↑ Ruggenenti P, Noris M, Remuzzi G (2001). "Thrombotic microangiopathy, hemolytic uremic syndrome, and thrombotic thrombocytopenic purpura". Kidney Int. 60 (3): 831–46. doi:10.1046/j.1523-1755.2001.060003831.x. PMID 11532079.
- ↑ Shannon E. Majowicz, Elaine Scallan, Andria Jones-Bitton, Jan M. Sargeant, Jackie Stapleton, Frederick J. Angulo, Derrick H. Yeung & Martyn D. Kirk (2014). "Global incidence of human Shiga toxin-producing Escherichia coli infections and deaths: a systematic review and knowledge synthesis". Foodborne pathogens and disease. 11 (6): 447–455. doi:10.1089/fpd.2013.1704. PMID 24750096. Unknown parameter
|month=ignored (help) - ↑ Chantal Loirat, Fadi Fakhouri, Gema Ariceta, Nesrin Besbas, Martin Bitzan, Anna Bjerre, Rosanna Coppo, Francesco Emma, Sally Johnson, Diana Karpman, Daniel Landau, Craig B. Langman, Anne-Laure Lapeyraque, Christoph Licht, Carla Nester, Carmine Pecoraro, Magdalena Riedl, Nicole C. A. J. van de Kar, Johan Van de Walle, Marina Vivarelli & Veronique Fremeaux-Bacchi (2016). "An international consensus approach to the management of atypical hemolytic uremic syndrome in children". Pediatric nephrology (Berlin, Germany). 31 (1): 15–39. doi:10.1007/s00467-015-3076-8. PMID 25859752. Unknown parameter
|month=ignored (help) - ↑ Fadi Fakhouri, Julien Zuber, Veronique Fremeaux-Bacchi & Chantal Loirat (2017). "Haemolytic uraemic syndrome". Lancet (London, England). 390 (10095): 681–696. doi:10.1016/S0140-6736(17)30062-4. PMID 28242109. Unknown parameter
|month=ignored (help) - ↑ Lopes da Silva, Rodrigo (2011). "Viral-associated thrombotic microangiopathies". Hematology/Oncology and Stem Cell Therapy. 4 (2): 51–59. doi:10.5144/1658-3876.2011.51. ISSN 1658-3876.
- ↑ Majowicz SE, Scallan E, Jones-Bitton A, Sargeant JM, Stapleton J, Angulo FJ; et al. (2014). "Global incidence of human Shiga toxin-producing Escherichia coli infections and deaths: a systematic review and knowledge synthesis". Foodborne Pathog Dis. 11 (6): 447–55. doi:10.1089/fpd.2013.1704. PMC 4607253. PMID 24750096.
- ↑ Bresin E, Daina E, Noris M, Castelletti F, Stefanov R, Hill P; et al. (2006). "Outcome of renal transplantation in patients with non-Shiga toxin-associated hemolytic uremic syndrome: prognostic significance of genetic background". Clin J Am Soc Nephrol. 1 (1): 88–99. doi:10.2215/CJN.00050505. PMID 17699195.