A 26-year-old woman presents to the clinic with diarrhea, bloating, flatulence, and abdominal cramps. These symptoms have been going on for 2 months. She has lost 6 pounds (2.7 kg) over these 2 months. Her medical history is significant for mild intermittent asthma for which she uses an albuterol inhaler as needed. She is sexually active with 1 male partner. She recently returned from South India following a mission trip for 6 weeks. Her temperature is 98.6°F (37.0°C), blood pressure is 105/70 mmHg, pulse is 95/min, and respirations are 14/min. On examination, the patient’s skin is pale. Labs are obtained and show the following results:

Leukocyte count: 4,500/mm^3
Hemoglobin: 10.5 g/dL
Platelets: 110,000/mm^3
Mean corpuscular volume (MCV): 116 µm^3
Reticulocyte count: 0.5%

A biopsy of the small bowel reveals blunting of villi and a mixed infiltration of lymphocytes, plasma cells, and eosinophils. Which of the following is the most likely diagnosis?
Celiac disease
Crohn disease
Whipple disease
Tropical sprue
Tropical sprue
The patient is presenting with chronic diarrhea, weight loss, megaloblastic anemia (low hemoglobin and elevated MCV), and a biopsy showing blunted villi and mixed infiltrate following significant travel to South India. This is consistent with tropical sprue.

Tropical sprue is characterized by chronic diarrhea that occurs after travel to an endemic area. It is thought to be due to a bacterial overgrowth/infection that then damages the intestinal mucosa. Endemic areas include the Caribbean, Southeast Asia, and South India. Patients present with chronic diarrhea, abdominal discomfort/cramps, progressive weight loss, and clinical features of malabsorption. Patients with tropical sprue can develop megaloblastic anemia (low hemoglobin and elevated MCV) from a deficiency in folate and vitamin B12 absorption. A small bowel biopsy would show blunting of the villi and infiltration of lymphocytes, plasma cells, and eosinophils. Microorganisms may also be seen. Treatment is an oral tetracycline and folic acid for 3-6 months.

McCarroll et al. study the relationship between infectious gastroenteritis and tropical sprue. In a case-control study, the authors found that prior infectious gastroenteritis increased the risk of tropical sprue. The authors recommend treatment of suspected tropical sprue with oral folic acid replacement.

Incorrect Answers:
Answer A: Celiac disease can present similarly to tropical sprue with chronic diarrhea, abdominal pain, and weight loss. A small intestine biopsy can similarly show villous atrophy and a lymphocytic infiltrate, as well as crypt hyperplasia. Celiac disease is an immune response to gluten, while symptoms of tropical sprue are not diet-associated. The development of symptoms following significant travel (lasting at least several weeks) to an endemic country should raise suspicion for tropical sprue.

Answer B: Crohn disease presents with chronic diarrhea, abdominal pain, weight loss, skip lesions anywhere from mouth to anus, extraintestinal manifestations, and signs of malabsorption. A biopsy will show transmural inflammation with noncaseating granulomas, giant cells, and aggregates of lymphocytes in the lamina propria.

Answer C: Giardia is a parasite that is endemic in the tropics and North American mountain regions. Patients present with foul-smelling diarrhea, excessive gas, and nausea. Diagnosis can be confirmed with a stool analysis or immunoassay. Though a biopsy is normally not indicated, it would show mild lymphocytic infiltration and Giardia trophozoites on the intestinal surface.

Answer E: Whipple disease is caused by the bacteria Tropheryma whipplei. Patients present with diarrhea, abdominal pain, and signs of malabsorption. Extraintestinal symptoms such as arthritis are common. A biopsy of the small intestine would show Periodic acid-Schiff (PAS)-positive foamy macrophages in the lamina propria.

Bullet Summary:
Tropical sprue presents with diarrhea, abdominal cramping, weight loss, megaloblastic anemia due to malabsorption, and a small bowel biopsy showing villi blunting following travel to an endemic area such as South Asia or the Caribbean.