E2 Answers

E2 G6PD Deficiency

The two vignettes below describe the same disease process. Read both of them and then answer the following questions.

Clinical Vignette 1
A 23-year-old man of Iranian origin consults his primary care provider about a skin rash. He has an intensely pruritic rash over his buttocks and back that has appeared spontaneously. He is referred to a dermatologist, who diagnoses dermatitis herpetiformis and prescribes dapsone. Two days later he develops severe nausea and exhaustion, and complains of passing dark urine. His wife notices he has become jaundiced. He goes to the  ER, where investigations reveal anemia (Hb 7.5 g/dL) and abnormal biochemistry (elevated blood urea, deranged liver function, and unconjugated hyperbilirubinemia). An urgent hematology consult is obtained and a diagnosis of drug-induced hemolytic anemia made.

Clinical Vignette 2
An 18-year-old Greek man presents to the ER with severe nausea, vomiting, and diarrhea. His mother explains that he had been at a lunch party with friends and none of the other guests were ill. The patient had ingested a meal of rice, meat, and freshly cooked beans. He has not had any significant illnesses in the past. Examination reveals a markedly dehydrated young man who is clinically anemic and jaundiced. Investigations show a hemoglobin of 5.1 g/dL, elevated WBC count with a predominant neutrophilia, elevated blood urea and creatinine, and deranged liver function. No urine can be obtained. Intravenous fluids are commenced, followed by a transfusion of packed red cells; the patient becomes acutely dyspneic, however, and chest x-ray shows features of pulmonary edema. A nephrologist is consulted. Intravenous diuretic therapy is prescribed, a urinary catheter inserted, and 30 mL of urine obtained that, on testing, shows a high urobilinogen and protein content.


A peripheral smear was done and is show below for both of these patients. What abnormalities do you see if any? Which of the two images was taken during active disease?

There are two images. The top left corner shows a supravital stain with Heinz bodies, which are inclusions representing denatured hemoglobin. The peripheral smear in the main box shows bite cells. Active hemolysis would be found during active intravascular hemolysis.


What do you think caused their visit to the ER? Name a reason for each patient. Was it an environmental or genetic cause? What is the their condition? Name other inciting factors.

Exposure to Dapsone. Ingestion of fava beans.

Genetic and Environmental. G6PD is an x-linked recessive(medit-greeks/italians and African americans) d/o that is activated when an oxidizing substance is encountered.

Oxidant stresses that induces hemolysis:
-infection (most common)
-Drugs (primaquine, chloroquine, dapsone, sulfonamides, nitrofurantoin)
-Fava beans (esp in Mediterranean variant)

What is a benefit of this condition? What anemia has the same benefit as this condition?

Plasmodium falciparum. Sickle cell anemia.

What is the main pathogenesis of this disease process in 3 sentences or less?

Decreased synthesis of reduced form of nicotinamide adenine dinucleotide phosphate(NADPH) and glutathoine (GSH) in the pentose phosphate pathway.

-GSH normally neutralizes hydrogen peroxide, an oxidant product in RBC metabolism
-in G6PD deficiency, peroxide oxidizes Hb, which precipitates in the form of Heinz bodies.

What is the treatment?

Avoid exposure to known oxidants. Usually hemolysis is self-limiting, with spontaneous resolution in a week or so.

(Clinical Vignette Adapted from EPOCRATES)