Hemolytic uremic syndrome

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Classification according to ICD-10
D59.3 Hemolytic uremic syndrome
ICD-10 online (WHO version 2019)

The hemolytic uremic syndrome (abbreviation HUS ), also Gasser syndrome , is a disease of the small blood vessels and thus one of two forms of thrombotic microangiopathy . As a result of various causes, mostly bacterial toxins , blood cells are destroyed and kidney function is damaged. This rare syndrome mainly affects young children and infants , where it is the leading cause of acute kidney failure . However, it can also occur in adults. It is one of the acquired hemolytic anemias.

Initial description

HUS was first described by the pediatrician Conrad Gasser and colleagues in 1955 in the Swiss Medical Weekly .

Characteristics and shapes

The HUS is indicated by

If all three symptoms are present, one speaks of complete enteropathic HUS , with only two of them an incomplete enteropathic HUS .

HUS is divided into a typical form, usually caused by infection, with accompanying diarrhea and an atypical form without accompanying diarrhea. Both forms occur in both children and adults. While the typical HUS (also HUS) is more common in children, the atypical HUS (also aHUS or HUS) is more common in adults .

causes

The typical HUS is mainly caused by Shiga toxin producing intestinal bacteria: Escherichia coli O157: H7 ( STEC / EHEC - Shiga Toxin - producing E. coli ) or other Vero toxin producing E. coli as well as by Shigella dysenteriae . Since the bacteria themselves remain restricted to the intestinal tract in this disease and neither cross the basement membrane of the intestinal epithelium nor enter the bloodstream, strictly speaking one does not speak of an infection , but of bacterial intoxication .

HUS has also been associated with viral infections, particularly influenza . Atypical HUS is caused by bone marrow transplants or immunosuppressive medication after transplants, in pregnancy, cancer, chemotherapy and HIV. Genetic factors also play a role.

Pathophysiology

In typical HUS, toxins bind to specific receptors on the glomerular endothelium , resulting in the death of these cells. As a result of the subsequent coagulation processes, blood clots are washed in, which lead to the closure of the glomerular microcapillary .

In the course forms caused by EHEC , the bacteria bind to surface molecules of intestinal epithelia. This binding is mediated by a protein encoded in the bacterial genome. This protein belonging to the adhesins is localized on the chromosomal gene eae . Since the number of these receptors on the cells is higher in children and infants than in adults, they are also more susceptible to this classic form of HUS. After attachment, the EHEC bacteria produce a cell-destroying toxin ( verotoxin or Shiga-like toxin STX2), which initially destroys the intestinal epithelial cells locally, thereby causing diarrheal disease. The STX2 then passes into the bloodstream, whereby it exerts a systemic effect on kidney epithelial cells as well as on cells of the central nervous system. This toxin is not encoded by gene segments of the bacterial chromosome, but the genetic information for the STX2 is transferred as phage DNA by prior infection of the bacterial strain with specific bacteriophages . In addition, EHEC encodes a hemolysin on a plasmid outside the chromosome , the bacterial product that destroys erythrocytes .

therapy

The therapy of enteropathic HUS (typical HUS triggered by EHEC) is primarily symptomatic in the phase of diarrhea, i.e. the loss of water and electrolytes is compensated by infusions if necessary . Suppression of diarrhea by drugs that paralyze bowel movements such as loperamide is not indicated, as this suppresses the desired flushing out of toxin-producing bacteria in classic HUS. In the case of an EHEC infection, the administration of antibiotics is absolutely contraindicated , since they do not work against the bacterial toxin, but there are indications that treatment with antibiotics promotes the development of HUS, probably due to increased toxin release.

ACE inhibitors may be indicated to control the high blood pressure, which is often caused by the systemic effects of the toxins . If necessary, dialysis or hemofiltration is used to remove the toxins from the bloodstream .

Since 2009 there have been a few case reports of the use of the monoclonal antibody eculizumab in children with HUS who did not respond to plasmapheresis , and in atypical HUS after kidney transplantation . On the basis of these reports, eculizumab has been used on a trial basis in some clinics in Germany since May 28, 2011 in severe cases that show no tendency to improve under plasmapheresis. According to Rolf Stahl, University Medical Center Hamburg-Eppendorf , whether and to what extent this measure leads to success can only be shown at a later point in time, around three to four weeks after the start of therapy. Nevertheless, according to information from the DGfN (German Society for Nephrology), therapy with eculizumab can be carried out in certain cases during the EHEC-HUS outbreak in Germany in 2011.

According to current information in the relevant literature (HEROLD / Innere Medizin 2015), the lethality of atypical HUS could be significantly reduced by the early administration of the monoclonal antibody eculizumab. According to this, a differentiation between a TTP , a Shiga toxin-associated HUS and an atypical HUS (aHUS) should be made at an early stage . Eculizumab binds to the complement protein C5 and thereby blocks its cleavage into the fragments C5a / b and thus the formation of the terminal complement complex C5b-9. A mutation-related increased activation of the complement system is considered to be the cause of the aHUS, which explains the aforementioned effectiveness.

Frequent occurrence

In May 2011 there was an increased incidence of HUS in Germany. By mid-June, over 800 HUS cases, including more than 20 deaths, had been reported to the Robert Koch Institute , and reports of new cases have been falling since then. It was possible to isolate an E. coli strain of the serotype O104: H4, which has so far rarely been detected and which has properties of an EHEC and an EAEC , among other things . In contrast to previous outbreaks of EHEC, it was noticeable that mainly adults (87% over 18 years), especially women (68%), were affected. The large number of severe disease courses, including central nervous symptoms, was also unusual.

Reporting requirement

In Germany, the clinical suspicion of illness and death from an " enteropathic haemolytic-uremic syndrome (HUS)" must be reported by name in accordance with Section 6 of the Infection Protection Act .

literature

  • Friedrich Carl Sitzmann: Pediatrics. 300 tables . 3rd revised and expanded edition. Thieme, Stuttgart 2007, ISBN 3-13-125333-9 , ( Duale series ), ( The dual textbook ).
  • Gerd Herold and colleagues: Internal medicine. A lecture-oriented presentation taking into account the subject catalog for the medical examination. With ICD 10 key in the text and index . Self-published, Cologne 2007.
  • W. Böcker, H. Denk , Ph. U. Heitz (Ed.): Pathology . 3rd completely revised edition. Urban & Fischer, Munich a. a. 2004, ISBN 3-437-42381-9 .
  • S. Razzaq: Hemolytic uremic syndrome. An emerging health risk. In: Am Fam Physician. 2006 Sep 15, 74 (6), pp. 991-996. Review. PMID 17002034
  • M. Noris, G. Remuzzi: Hemolytic uremic syndrome. In: J Am Soc Nephrol . 2005 Apr; 16 (4), pp. 1035-1050. Review. PMID 15728781
  • Lothar Bernd Zimmerhackl, Hege Verweyen, Angela Gerber u. a .: The hemolytic-uremic syndrome . In: Deutsches Ärzteblatt . tape 99 , no. 4 , 2002, p. 196–203 ( aerzteblatt.de [PDF; 181 kB ]).
  • AJ Waddell, LR Matz: Haemolytic-uraemic syndrome: a report of two cases in adults. In: The Medical journal of Australia Volume 2, Number 19, November 1966, pp. 893-897, PMC 238474 (free full text), PMID 5929390 .

Individual evidence

  1. ↑ Gasser C, Gautier E, Steck A, Siebenmann RE, Oechslin R: Haemolytic-uremic syndromes: bilateral renal cortical necrosis in acute acquired haemolytic anemia. Switzerland Med Wochenschr (1955), 85: 905–909 [1]
  2. ↑ a b S. Razzaq: Hemolytic uremic syndrome. An emerging health risk. In: Am Fam Physician. , 2006 Sep 15, 74 (6), pp. 991-996. Review. PMID 17002034
  3. ↑ C. Gasser, E. Gautier, A. Steck, RE Siebmann, R. Oechslin: Hemolytic-uremic syndromes: bilateral renal cortical necrosis in acute acquired hemolytic anemia. In: Switzerland. Med. Wochenschr. Vol. 85, 1955, pp. 905-909, PMID 13274004 .
  4. ↑ a b c Jingxuan Liu, Michael Hutzler, Cuizhen Li, Liberto Pechet: Thrombotic Thrombocytopenic Purpura (TTP) and Hemolytic Uremic Syndrome (HUS): The New Thinking . In: Journal of Thrombosis and Thrombolysis . tape 11 , no. 3 , 2001, p. 261-272 , doi : 10.1023 / A: 1011921122595 .
  5. ↑ Ana Farinha, Patrícia Carrilho, Joana Felgueiras u. a .: Haemolytic uraemic syndrome associated with H1N1 influenza . In: NDT Plus . tape 3 , no. 5 , 2010, p. 447-448 , doi : 10.1093 / ndtplus / sfq126 .
  6. ↑ Upton Allen, Christoph Licht: Pandemic H1N1 influenza A infection and (atypical) HUS — more than just another trigger? In: Pediatric Nephrology . tape 26 , no. 1 , 2010, p. 3-5 , doi : 10.1007 / s00467-010-1690-z .
  7. ↑ a b c Berthold Block: Internal Medicine - Guidelines 2007/2008: Compilation of evidence-based guidelines and recommendations . Georg Thieme, Stuttgart 2007, p. 42 ( limited preview in Google Book search).
  8. ↑ Franz Daschner, Uwe Frank: Antibiotika am Krankbett, p. 140 . Springer, Berlin / Heidelberg 2004, ISBN 978-3-540-40846-8 . Online: limited preview in Google Book search
  9. ↑ Dieter Adam: The Infectiology . Springer, Berlin / Heidelberg 2003, ISBN 978-3-540-00075-4 . , f. # v = onepage limited preview in Google Book search
  10. ↑ AL Lapeyraque, M. Malina u. a .: Eculizumab in severe Shiga-toxin-associated HUS. In: The New England journal of medicine . Volume 364, Number 26, June 2011, pp. 2561-2563, doi: 10.1056 / NEJMc1100859 , PMID 21612462 .
  11. ^ RA Gruppo, RP Rother: Eculizumab for congenital atypical hemolytic-uremic syndrome. In: The New England Journal of Medicine . Volume 360, Number 5, January 2009, pp. 544-546, doi: 10.1056 / NEJMc0809959 , PMID 19179329 .
  12. ↑ UKE currently cares for 64 patients who have developed the HU syndrome . ( Memento of the original from February 18, 2015 in the Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. Press release from May 28, 2011 @1@ 2Template: Webachiv / IABot / www.uke.de
  13. ↑ Notes on the use of eculizumab [in] patients with a severe course of EHEC-associated HUS ( Memento of the original from July 2, 2016 in the Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. . Retrieved June 4, 2011 @1@ 2Template: Webachiv / IABot / www.dgfn.eu
  14. ↑ C. Frank, MS Faber, M. Askar et al. a .: Large and ongoing outbreak of haemolytic uraemic syndrome, Germany, May 2011. In: Eurosurveillance , Volume 16, Issue 21, 26 May 2011