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Managing Reactions

More than 25 percent of patients with Hansen's disease (leprosy) may have reactive episodes ("reactions") of varying degrees of severity during the course of their disease. Some of them occur before treatment is started or after therapy is completed, but most occur during therapy, particularly during the first year.

Reactive episodes appear to be less common in patients treated with clofazimine. Reaction should not be regarded as a side effect of any drug, rather it is apparently due to the destruction of bacilli and the immune response to released bacterial antigens. Chemotherapy should be continued in spite of reactive episodes but with the episodes themselves suppressed as needed by other therapy.

Reactions can be broadly divided into two main categories: erythema nodosum leprosum (ENL or type 2 reactions) occurring almost exclusively in borderline lepromatous and lepromatous patients, and reversal (type 1 reactions), occurring in borderline tuberculoid, mid-borderline and borderline lepromatous patients. A third type of reaction known as the Lucio's phenomenon is relatively rare. It occurs in patients with diffuse lepromatous leprosy who are from Mexico and some other areas. The patients develop multiple ulcers of varying size that are often difficult to heal. It is only occasionally seen and is managed with corticosteroids and treatment of the underlying infection.

Erythema Nodosum Leprosum

Erythema nodosum leprosum usually manifests with fever and painful erythematous nodules, but peripheral neuritis, orchitis, lymphadenitis, iridocyclitis, nephritis, periostitis and arthralgias may also occur. Mild episodes may require no therapy, or symptomatic measures such as aspirin administration may suffice. Several drugs are useful for the management of severe episodes.

Corticosteroids are effective in all patients and should always be used if an acute neuritis is present to prevent permanent nerve injury. Usually, 40-60 mg of prednisone daily (dosage of 1 mg/kg per day) is sufficient. When the initial episode has been completely controlled for several days, an attempt may be made to taper the drug dosage over a period of 2 - 4 weeks. Reaction often recur, however, and the dosage may be increased. If the process becomes chronic, prolonged therapy may be needed. In these patients it may be useful to try tapering the prednisone to alternate day therapy. The dosage is reduced still more slowly until either the drug is eliminated or the lowest possible maintenance level is reached. However, because steroid-associated side effects are often a problem, other forms of therapy should be considered in chronic cases. When prolonged use of corticosteroid is required, giving the rifampin only once monthly as in the World Health Organization regimens should be considered to avoid its adverse effect on corticosteroid levels.

Thalidomide (Thalomid) is extremely effective in treatment of ENL. The initial regimen is 100 mg four times daily, and reaction is usually controlled within 48 to 72 hours. The dosage is then tapered over 2 weeks to a maintenance level, usually 100 mg daily. Regular attempts should be made to taper or discontinue the drug, but patients may need to continue taking thalidomide for months to years before ENL reactions no longer recur. Side effects are few with drowsiness being the most common. Thalidomide absolutely cannot be given to fertile females because of its well known teratogenicity, except under strict conditions outlined by the manufacturer.

Clofazimine is also effective for the control of ENL. A dose of 100 mg two or three times daily usually is necessary, and the reaction should come under control during a period ranging from a few weeks to a few months, depending on its severity. Normally, reaction control is maintained with prednisone in these patients, and the dosage of prednisone is gradually diminished as the clofazimine begins to act. Because gastrointestinal symptoms may develop with high doses, clofazimine dosage should be reduced to 100 mg daily within a year, if possible. Pigmentation from clofazimine is usually quite marked in these patients. They should be fully cognizant of this complication before therapy is started, as well as educated about the potential benefits of this antibiotic.

Reversal Reactions

Clinically, reversal reactions are usually evidenced by edema and erythema of pre-existing lesions. Neuritis and occasionally new lesions or fever may also occur. If there is neuritis or ulceration, high doses of corticosteroids should always be used, e.g., prednisone at 1 mg/kg daily. This type of reaction usually is controlled within 24 to 48 hours, and only a short course of therapy may be necessary if the patient has minimally active disease and no neuritis. However, those with neuritis may require prolonged treatment (4 to 6 months) if neural damage is to be reversed. Patients with prolonged reactions may sometimes be managed with alternate day steroids as noted for ENL.

Other Complications

Neuritis or silent neuropathies (neuritis without nerve pain or tenderness) may occur independently of any reactive episode. Immediate treatment with high doses of corticosteroids is necessary to avoid permanent injury and recover lost function insofar as possible. Treatment should be continued for 4 - 6 months to recover as much function as possible using a gradually tapered course of corticosteroids.

Iridocyclitis (inflammation of the iris, ciliary body and choroid coat) is a medical emergency and best managed by an ophthalmologist. Atropine drops and corticosteroid drops must be started at once if permanent damage is to be avoided. Tear substitutes are used in patients with lagophthalmos and/or decreased lacrimation.

Orchitis (inflammation of a testis) may occur with or independently of a reactive episode. It usually responds quickly to corticosteroids but sterility may result.

Injuries are common in all patients with Hansen's Disease who have significant degrees of sensory and motor loss. The patient must be taught how to avoid them by frequent inspections of involved skin, and the use of protective measures such as wearing gloves or special footwear. When an injury does occur in an insensitive area, it must be protected from further damage during healing.