A 30 year old presented with a skin lesion in his right axilla. A presumptive diagnosis of staphylococcal skin carbuncle is made & patient is treated with empiric trimethoprim/ sulfamethoxazole. After 2 days, the patient came to emergency with excessive weakness, abdominal pain & dark coloured urine. O/E- vitals are normal & jaundice is present. Lab studies show a drop in Hb from 14 g/dl to 8 g/dl & rise in bilirubin levels. Urine dipstick is positive for bilirubin. Peripheral blood smear is shown below. What could be the possible diagnosis of the patient?

**Core Concept**
The patient's presentation suggests an adverse drug reaction, specifically hemolysis, following the administration of trimethoprim/sulfamethoxazole. This reaction is related to the mechanism of action of sulfonamides, which can induce hemolysis in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency.

**Why the Correct Answer is Right**
Trimethoprim/sulfamethoxazole is a sulfonamide antibiotic that can cause hemolysis in individuals with G6PD deficiency. The patient's presentation of jaundice, dark-colored urine, and a drop in hemoglobin levels suggests hemolysis. The peripheral blood smear would show evidence of hemolysis, such as schistocytes, spherocytes, or fragmented red blood cells. The mechanism of action of sulfonamides involves the inhibition of dihydropteroate synthase, which can lead to the accumulation of toxic metabolites that induce hemolysis in individuals with G6PD deficiency.

**Why Each Wrong Option is Incorrect**
**Option A:** This option is incorrect because it does not explain the patient's presentation of hemolysis following the administration of trimethoprim/sulfamethoxazole. While liver dysfunction can cause jaundice, it does not account for the patient's drop in hemoglobin levels or the presence of bilirubin in the urine.

**Option B:** This option is incorrect because it does not explain the patient's presentation of hemolysis following the administration of trimethoprim/sulfamethoxazole. While hemolytic uremic syndrome (HUS) can cause renal failure and hemolysis, it is typically associated with Shiga toxin-producing E. coli, not sulfonamide antibiotics.

**Option C:** This option is incorrect because it does not explain the patient's presentation of hemolysis following the administration of trimethoprim/sulfamethoxazole. While autoimmune hemolytic anemia can cause hemolysis, it is typically associated with autoimmune disorders, not sulfonamide antibiotics.

**Option D:** This option is incorrect because it does not explain the patient's presentation of hemolysis following the administration of trimethoprim/sulfamethoxazole. While G6PD deficiency can cause hemolysis following exposure to certain medications, including sulfonamides, this option does not mention the specific medication or the patient's presentation.

**Clinical Pearl / High-Yield Fact**
Sulfonamide antibiotics, including trimethoprim/sulfamethoxazole, can cause hemolysis in individuals with G6PD deficiency. This is an important consideration when prescribing these medications, especially in individuals with a history of hemolytic anemia or those from populations with a high prevalence of G6PD deficiency, such as individuals of African, Mediterranean, or Middle Eastern descent.

**Correct Answer:** D. G6PD deficiency

✓ Correct Answer: A. Glucose 6-phosphate dehydrogenase (G6PD) deficiency