This methylxanthine's mechanism of action is unknown, but oral pentoxiphylline 400–800 mg 3 times/day appears to decrease levels of TNF-α. The major adverse effects are related to the gastrointestinal tract and central nervous system, but these effects are reduced by using a controlled-release formulation. Thalidomide outperformed pentoxiphylline in a randomized clinical trial in patients with type 2 reactions, in terms of limb edema and systemic symptoms, but 62.5% of patients in the pentoxiphylline group had symptom relief. Although this drug is not first line, it is a useful option when other therapies are ineffective or contraindicated.
Tumor Necrosis Factor Inhibitors
Since the mechanism of action of several drugs is proposed to inhibit TNF-α concentrations, biologic TNF inhibitors are a promising option for treatment of refractory type 2 reactions. Various case reports show successful treatment of difficult reactions with etanercept and infliximab.[65,66] However, these drugs are known to exacerbate infectious complications, and several case reports show development or worsening of disease with agents such as infliximab and adalimumab.[67,68] It is interesting to note that two patients who developed disease when starting infliximab also developed a type 1 reaction after its discontinuation. The true efficacy and safety of these drugs in type 2 reactions are still unknown, but these drugs may be useful in situations when all other therapies are ineffective and the patient desperately needs relief of symptoms.
T Cell Inhibitors
There is some evidence that drugs that disrupt T cell activation and function can provide relief during a reaction. Oral cyclosporine resulted in complete response in 3 of 4 patients, with the remaining patient achieving a partial response.[69,70] However, M. leprae grew more readily in BALB/c mice infected with M. leprae who were treated with extended courses of cyclosporine. Sixty-seven patients, with 20 experiencing chronic neuritis while receiving prednisone, were treated with cyclosporine 5 mg/kg reduced over 12 months. Therapy resulted in reductions of antibodies to nerve growth factor to normal levels and improvement of sensory impairment. One published case reported dramatic improvement of skin lesions after daily topical administration with tacrolimus 0.1%. Cyclosporine and other drugs that inhibit T cells are another option for patients not responding to standard treatment of a reaction.
There is little evidence that directly supports the use of nonsteroidal antiinflammatory drugs, but they are commonly used in very high doses to treat reactions, because of their antiinflammatory effects. Amitriptyline and gabapentin have also been used to mitigate neuropathy despite little evidence to demonstrate effect. Some evidence points to the utility of leukotriene inhibitors, such as zafirlukast, in the treatment of ENL. The Leprosy Mission in Bangladesh proposed a clinical study in 2006 to test montelukast. In Bangladesh, thalidomide is unavailable and clofazimine is difficult to obtain. However, no patients have been enrolled in this trial to date.
Pharmacotherapy. 2012;32(1):27-37. © 2012 Pharmacotherapy Publications