Case Presentation by Dr. Jeffrey Van Laere, MD
HPI: 5 year-old girl with who presents to the emergency department as a transfer from an outside hospital with abdominal pain and diarrhea for 2 days. The patient reports worsening abdominal pain, which she describes as 6/10, diffuse, but worse in the right lower quadrant. She also reports “nearly constant” diarrhea that is non-bloody and watery. Patient states that she feels nauseous, but has had no vomiting.
Negative for fever, vomiting, chest pain, shortness of breath, hematochezia.
Positive for diarrhea, abdominal pain, nausea.
PSH: Tonsillectomy and Adenoidectomy
Social History: Immunizations up to date. Grandmother with recent illness, lives in nursing home.
Vitals: P 126 BP 112/64 RR 18 T 37.4 O2 98%
General: Well developed, well nourished female, lying still, appears uncomfortable.
HEENT: Dry mucosal membranes, no mucosal lesions, EOMI, PEERL
CV: Tachycardic, RRR, no M/G/R
GI: Soft, Mild diffuse tenderness. Negative Murphy’s sign and pain at McBurny’s point. No hepatosplenomegaly.
MS: Full range of motion in extremities, no clubbing, cyanosis or edema.
Neuro: AAOx4, normal reflexes in biceps, triceps and Achilles tendons. Light touch sensation intact.
Question #1: After reviewing the patient’s laboratory values, you return to discuss the results with the family. What do you think is the most likely diagnosis?
A) Thrombotic Thrombocytopenic Purpura
B) Hemolytic Uremic Syndrome
C) Clostridium difficile Infection
Question #2: After discussing the diagnosis with the family, they are concerned and ask what the next step is in treating this?
A) Platelet transfusion
B) Start IV fluids and IV antibiotics
C) Supportive care
D) Consult General Surgery
Question #3: After discussion of the treatment plan with the family, they are comforted by knowledge of this disease. You discuss the concerns you have for this patient. What is the most serious complication of this disease?
A) Renal Failure
Answers & Discussion
1) Answer: B – Hemolytic Uremic Syndrome
Hemolytic Uremic Syndrome is a multi-system disorder resulting in acute renal failure, thrombocytopenia, and microangiopathic hemolytic anemia. The differential diagnosis for HUS includes TTP, DIC, appendicitis, gastroenteritis, and SLE. HUS and TTP share microangiopathic hemolysis, renal failure, and thrombocytopenia, however TTP will include a history of being febrile and neurologic changes in 40% of cases. While the patient may have symptoms of an infectious diarrhea, c difficile is an extremely rare cause of HUS. Appendicitis is a common cause of abdominal pain and leukocytosis, however this does not account for the patient’s thrombocytopenia, presence of schistocytes on peripheral smear, and elevated LDH.
2) Answer: C – Supportive care
While HUS is often associated with an infectious diarrhea, use of antibiotics for treatment is contraindicated, as it will increase the risk of development of HUS. Transfusion of platelets is contraindicated, as the thrombocytopenia is seen secondary to a consumptive process. Platelet transfusion will only exacerbate the underlying condition. As this is an infective process, there are no surgical indications, thus no need for a surgical consult.
3) Answer: A – Renal Failure
The pathogenesis of HUS includes the development of microthrombi that will migrate to the kidneys and deposit in the parenchema of the kidney. This will cause acute renal failure. These patients may develop hypertension, peripheral edema, oliguria or anuria. It is recommended to follow the patient’s renal function closely, as dialysis may be necessary. Dehydration is common in any diarrheal illness, but the majority of patients will survive the acute phase of the illness. Long term, up to one third of patients will have mild chronic kidney dysfunction. Many patients will develop purpura secondary to thrombocytopenia, however bleeding is not known to be a common cause of mortality in HUS. Arthritis is not associated with HUS.
Hemolytic-Uremic Syndrome is one of the most common causes of acute renal failure in children. It commonly presents early in life, with a mean age of presentation being 3 years old, but it may present later into childhood. The most common cause of HUS is E. coli O157:H7, however it may also be caused by Shigella, S. pneumonia, Pseudomonas, HIV, or as a result of medications.
Patients will often present early with watery diarrhea, abdominal pain, and possibly fever. As the disease develops, approximately day 2-5, the patients may develop bloody diarrhea. After the initial course of gastroenteritis, the patients will later develop the triad of thrombocytopenia, hemolytic anemia, and acute renal insufficiency.
The pathophysiology of HUS stems from injury to the renal vascular endothelium. There is an initial injury to the endothelium, followed by deposition of complement, platelets, and fibrin. This deposition will cause narrowed renal vessels that will cause injury to RBCs and the microangiopathic hemolytic anemia. The result of this hemolysis will be seen through elevated LDH, as well as schistocytes, tear drop cells, and burr cells on peripheral smear.
As previously discussed, the most important aspects of treatment are supportive therapy and early peritoneal dialysis. Given the patient’s acute renal insufficiency and diarrhea, you should rehydrate the patient, but be cautious to avoid fluid overloading. It is also important to follow the patient’s hyperkalemia and treat appropriately. Although these patients are often anemic, pRBCs are usually held until hemoglobin falls below 6 g/dL, and platelets are avoided unless life-threatening bleeding or procedures are necessary. Although there have been no studies, it is currently recommended that antibiotics be avoided due to concern for verotoxin release and worsening symptoms with administration. An important distinction in treatment between TTP and HUS is that plasmapheresis is used with TTP, and may be used with suspected HUS that exhibits neurologic involvement.
Rosen, P., Marx, J. A. (2014). Chapter 122. Disorders of Hemostasis. p. 1609-1612 Rosen’s emergency medicine: Concepts and clinical practice
Rosen, P., Marx, J. A. (2014). Chapter 174. Genitourinary and Renal Tract Disorders. p. 2222-2223 Rosen’s emergency medicine: Concepts and clinical practice.
Fauci, A. S., & Harrison, T. R. (2012). Harrison’s online: Featuring the complete contents of Harrison’s Principles of internal medicine, 18th edition. Chapter 115. Disorders of Platelets and Vessel Wall. New York: McGraw-Hill, Medical Pub. Division.