Approach

Treatment should be initiated promptly once the diagnosis has been made. The optimal duration of treatment is not known; controlled data are limited. As a general rule, a prolonged course of treatment should be expected. Folic acid should be given for at least 3 months and up to 1 year depending on clinical response. Antibiotic treatment has been given for periods between 2 weeks and 1 year, but most experience shows good outcomes with 3 to 6 months of treatment. Vitamin B12 supplementation is also recommended if symptoms last more than 4 months or in the presence of low vitamin B12 levels, regardless of symptom duration.

Folic acid supplementation

A large dose of folic acid should be given as the first-line treatment for all patients with TS.[31][32][33] This should be given when TS is suspected, even in patients without documented folate deficiency.[24] Although doses ranging from 1 to 10 mg daily have been studied, a dose of 5 mg/day is considered adequate. Clinical response should be prompt and dramatic. Improvements in megaloblastic anemia and pathologic villous blunting are seen within 2 days to 1 week of starting folic acid treatment.[36]

Antibiotic treatment

Observational data linking TS to bacterial infection of the small bowel laid the ground for considering antibiotics as a treatment. Antibiotics have proven effective and are now widely used as a first-line therapy.[36][37][38] The quality of evidence is limited by the era in which studies were performed. However, they are prescribed because of widespread availability, low cost, and proven efficacy. Tetracycline is the most commonly used. Other antibiotics (e.g., chloramphenicol) have been used in the past, but their use is not supported by as much empirical evidence. 

There are no studied antibiotic alternatives. Rifaximin would seem a reasonable choice, but there is no evidence to support it. Another alternative would be to refer tetracycline-allergic patients to an allergist to verify true allergy and perform desensitization.

Vitamin B12 supplementation

The benefits of treating with vitamin B12 are less clear. In most patients, folic acid alone is sufficient to improve symptoms and correct many laboratory abnormalities. Some favor an approach that only treats patients who have proven vitamin B12 deficiency, whereas others treat empirically with subcutaneous vitamin B12.

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