Thalidomide in gastrointestinal disorders

Thalidomide was originally marketed as a sedative, but was removed from the market in 1961 after it was associated with an epidemic of severe birth de fects. Subsequently, it has been shown to have therapeutic efficacy in a nu mber of the gastrointestinal tract conditions characterised by immune dysre gulation. The exact mechanism of the immunosuppressive effects of thalidomi de is unknown; proposed mechanisms include inhibition of tumour necrosis fa ctor alpha release and inhibition of angiogenesis. In chronic graft versus host disease, use of high dose thalidomide ( 1200 m g/day) may bring about a response in 20% of patients with refractory diseas e. Thalidomide 200 mg/day helps eradicate ulcers in 50% of patients with HI V-associated oral aphthous ulceration. In Behcet's disease, thalidomide 100 to 300 mg/day can decrease the number of mucocutaneous ulcers, although fu ll remission occurs in less than 20% of patients. In Crohn's disease, thali domide 50 to 300 mg/day may decrease the severity of mucosal disease and pr ompt closure of fistulae. Patients to be placed on thalidomide therapy must practice either abstinenc e or strict birth control: women must undergo regular pregnancy testing and utilise 2 forms of contraception. Other adverse effects include sedation ( present in nearly all patients), symptomatic neuropathy (present in approxi mately 20%), and skin rashes. Given the potential toxicity, thalidomide use should generally be limited to clinical protocols with institutional revie w board oversight.