 | | Hemolytic-Uremic Syndrome | | | Counselor, Hemolytic uremic syndrome (HUS) is a disease primarily of infancy and early childhood, although it has been seen in adulthood as well when associated with E.Coli diarrheal infections. It is characterized by the triad of hemolytic anemia, thrombocytopenia (low platelets), and acute renal failure. Diarrhea and upper respiratory infection are the most common precipitating factors. HUS is the most common cause of acute renal failure in children. We value all your comments, so, if you have a suggestion for a newsletter subject but haven't submitted it yet, or if you have already submitted one but think of another, please take a minute to let us know by clicking on your "Reply" button and dropping us a note. To learn more about AMFS, Inc., the organization run by Physicians and Attorneys that provides medical experts and case review services nationwide, and has produced the following informational newsletter to aid you in understanding complex medical issues, please click here - www.amfs.com.
| | |  | Pathophysiology: In children, HUS often follows an infectious disease, usually diarrhea (90%) and less often an upper respiratory infection (10%). Use of antimotility drugs such as Lomotil or Imodium may increase the risk of developing HUS. The most common cause of HUS is a toxin produced by Escherichia coli serotype O157:H7. Additional agents include Shigella, Salmonella, Yersinia, and Campylobacter species. The shiga and shigalike toxins, produced by some strains of Shigella dysenteriae and E coli O157:H7, respectively, have been associated with approximately 70% of cases of HUS in children. Transmission of E coli O157:H7 appears to be caused by contaminated food, such as ground beef and other cattle products that are undercooked, and unpasteurized dairy products. Food contaminated with E. coli does not look, smell, or taste bad. Person-to-person contact, as well as contamination of public water supplies, may also have a role in the transmission of this bacterium. E coli is normal flora in the gastrointestinal tracts of some healthy cattle, and children can contract it by petting a cow. HUS is also associated with viruses, including varicella, echovirus, and coxsackie A and B, as well as other infectious agents such as Streptococcus pneumoniae and Clostridium difficile. HUS has also been associated with AIDS, cancer, and the administration of chemotherapeutic agents. Mitomycin C is the most common chemotherapeutic agent associated with HUS. Malignancies found in conjunction with HUS include prostatic, gastric, and pancreatic malignancies. Some have suggested that HUS is mediated by immune complexes. Some cases of HUS are familial, which may reflect a genetic or human leukocyte antigen (HLA)–type predisposition. HUS and thrombotic thrombocytopenic purpura (TTP) represent different ends of what is probably the same disease continuum. Endothelial cell injury appears to be the primary event in the pathogenesis of these disorders. The endothelial damage triggers a cascade of events that result in microvascular lesions with platelet-fibrin hyaline microthrombi that occlude arterioles and capillaries. The platelet aggregation results in a consumptive thrombocytopenia. The epithelial damage may result from toxins released by bacteria or viruses. Many of the infectious agents and drugs implicated in HUS/TTP are toxic to the vascular endothelium. Although the vascular lesions are identical in HUS and TTP, involvement of the CNS (central nervous system) predominates in TTP, the renal system in HUS.
| | | | | | Frequency: HUS is characteristically a disease of young children. In individuals aged 5 years and younger, the average annual incidence is 2.65 cases per 100,000; in individuals aged 18 and younger, the average annual incidence is 0.97 cases per 100,000. Most adult patients are those with 0157:H7 E.coli and women who have been taking oral contraceptives, are postpartum, or are having obstetric complications (e.g.: preeclampsia, eclampsia). Incidence tends to parallel the seasonal fluctuation of E coli O157:H7 infections, which peaks between June and September. The mortality rate of HUS is 5-15%. Older children and adults have a poorer prognosis.
| | | | | | History: Children usually present following an acute diarrheal illness. The illness occurs a few days to a few weeks before the onset of HUS and may mimic ulcerative colitis, various enteric infections, and appendicitis. Risk factors for children include eating rare hamburgers, recent visits to a petting zoo, or even a nursing home visit to a relative with diarrhea. The clinical picture can suggest a GI bleed, as opposed to a toxic gastroenteritis, because the stool may be grossly bloody. The finding of grossly bloody stools in children is a strong indicator for E. coli disease. Fever is often absent in these cases. Urine output is reduced or absent. Neurologic symptoms may be observed in some patients and may result from uremia. Seizures may occur, in some cases secondary to the development of a hypertensive encephalopathy, but in general, if there are neurologic complications the underlying cause is most likely associated with TTP, not HUS.
| | | | | | Physical: Findings reflect those of the inciting prodromal illness. Petechiae, purpura, and fever are common. GI bleeding is often found. GI involvement may lead to symptoms of an acute abdomen, with occasional perforation. Cardiac involvement may lead to congestive heart failure (CHF) and arrhythmias. Microinfarcts in the pancreas may cause pancreatitis or, rarely, insulin-dependent diabetes mellitus. Ocular involvement may lead to retinal or vitreous hemorrhage. Hypertension and oliguria may be observed.
| | | | |  | Lab Studies: As in TTP, HUS is primarily a clinical diagnosis coupled with consistent laboratory findings. HUS produces a microangiopathic hemolytic anemia (hemoglobin typically less than 8 g/dL). This is the hallmark finding and is necessary to establish the diagnosis. The hallmark of HUS in the peripheral smear is the presence of schistocytes. These consist of fragmented, deformed, irregular, or helmet-shaped RBCs (red blood cells). They reflect the fragmentation of RBCs that occurs as the RBCs traverse vessels partially occluded by platelet and hyaline microthrombi. The peripheral smear may also contain giant platelets. This is a reflection of the reduced platelet survival time resulting from the peripheral consumption/destruction of platelets. Thrombocytopenia is present but is mild to moderate in severity, typically less than 60,000 per mL. In spite of this, there is usually no purpura or active bleeding. As with the anemia, the degree of thrombocytopenia is unrelated to the severity of the renal dysfunction. Prothrombin time (PT), activated partial thromboplastin time (aPTT), and fibrinogen are within the reference ranges, thus differentiating HUS/TTP from DIC (disseminated intravascular coagulation). Elevation of lactate dehydrogenase (LDH) and indirect bilirubin reflects intravascular hemolysis. The bilirubin rarely exceeds 2-3 mg/dL. Haptoglobin is very low. Blood urea nitrogen (BUN) and creatinine are markedly elevated. However, there is no correlation between the severity of anemia and the severity of the renal disease. Urine, if present, may contain protein and RBCs. The reticulocyte count is elevated. Coombs test results are negative, indicating that the hemolytic anemia is not immunologically mediated. A moderate leukocytosis may be present, but rarely more than 20,000 per mL. Normal stool culturing does not reveal E. coli O157:H7. The laboratory order must specifically request this analysis. Blood cultures are almost always negative for E.coli disease.
| | | | | | Treatment: Care should focus on supportive management, treatment of blood pressure elevation, blood transfusions, and admission with arrangement for prompt dialysis. Fluid overload should be avoided. Hyperkalemia should be promptly treated. Plasma exchange (plasmapheresis combined with fresh-frozen plasma replacement) is currently the treatment of choice. Plasma exchange is performed daily until remission is obtained. However, because 85% of children with HUS recover after supportive therapy alone, plasma exchange is generally reserved for the most severe cases, or for older children and adults. In HUS associated with diarrhea, maintain adequate fluid balance and bowel rest. Antibiotics are not effective except for certain forms caused by Shigella dysenteriae. In fact, antibiotic therapy may increase the risk of developing HUS in children with E. coli O157:H7 colitis. A hematologist and a nephrologist must be consulted.
| | | | | | Deterrence/Prevention: Prevention requires a reduction in fecal soilage of meat during slaughter and processing. New regulatory standards for food processing have been introduced in the United States and have reduced the contamination of meat sold commercially. It is also essential to ensure that foods are properly cooked. An internal meat temperature in excess of 155ºF (68.3ºC) is necessary. Development of institutional standards and public education concerning proper cooking of foods are important public health measures. Personal hygiene measures, especially hand washing, should also be followed. This is especially the case when children visit a petting zoo. It is also important to avoid routinely treating children with antibiotics for diarrhea. A study found that, in children younger than 10 years with E. coli O157:H7 infection, the relative risk was 17.3 for developing HUS following antibiotic therapy with trimethoprim-sulfamethoxazole or a beta-lactam antibiotic.
| | | | | | Medical/Legal Concerns: Medical/legal issues arise is the following situations: Failure to suspect HUS in a child with a recent diarrheal or upper respiratory illness who now presents with azotemia, fever, and hematologic abnormalities; restaurants that fail to maintain sanitary conditions or fail to properly cook meat; overtreatment of diarrheal illnesses with antibiotics; failure to diagnose and treat worsening hypertension, especially when administering fluids or blood transfusions; failure to consider HUS/TTP in pregnancy. It must be distinguished from the HELLP syndrome (hemolysis, elevated liver enzymes, and low platelet count). It usually resolves with delivery, although the fetal mortality rate is high.
| | | | | | Since 1990 and through 100,000+ nationwide cases, AMFS, Inc. (American Medical Forensic Specialists) has been providing plaintiff and defense attorneys in-house case evaluations as well as access to a carefully screened, nationwide panel of more than 7,500 board-certified medical experts practicing in all specialties and regions of the country. With just a single phone call, you reach an in-house staff physician who will assist you in clarifying the medical issues present in your case, identifying the medical specialties involved and interviewing prospective experts from our panel for your case. Whether you need a physician to review your case, testify as an expert, perform an IME, or perform any other task in the medical-legal field, in any region of the country, AMFS can help. As always, our mission is to provide counsel with the most efficient way to retain quality experts in a timely, cost effective manner. Call Today to Speak with an AMFS Staff Physician at NO Charge. Or use this handy form to submit a case for a Quick Review. Thank you for your time,
Attorney & Physician Advisory Board AMFS, Inc.
CALL TOLL FREE: 1-800-275-8903 | |
