Leprosy, thalidomide

In 1998, the FDA approved the use of thalidomide for the treatment of lesions associated with erythema nodosum leprosum. Because of thalidomide s potential for causing birth defects, the distribution of thalidomide was permitted only under tightly controlled conditions. Nevertheless, because of its use for patients with leprosy thalidomide has been identified again as a current teratogen, now in South America. 

R. L. Barnhill, A. C. Mcdougall, Thalidomide Use and Possible Mode of Action in Reactional Lepromateous Leprosy and in Various Other Conditions ,./. Am. Acad. Dermatol. 1982, 7, 317-323. 

Despite the bad reputation of thalidomide, it has since proved useful in alleviating a variety of disorders such as rheumatoid arthritis, leprosy,... 

Thalidomide (see also 1962) was placed back on sale to treat leprosy. It may also alleviate the symptoms of AIDS and some cancers. 

FDA information on their approval of thalidomide for treatment of leprosy. 

Thalidomide is approved for use in the United States for the treatment of cutaneous manifestations of erythema nodosum leprosum, a potentially life-threatening systemic vasculitis that occurs in some patients with leprosy. Although not approved for other indications, thalidomide has also been shown to be very effective in the management of Behget s disease, HIV-related mucosal ulceration (aphthosis), and select cases of lupus erythematosus. 

Recently, thalidomide (50-100 mg capsule form, approved by FDA), an immunomodulatory agent is used in erythema nodosum leprosum (ENL) which is a complication of leprosy occurring in approximately one half of borderline lepromatous and lepromatous leprosy patients. 

As a postscript, it should be mentioned that thalidomide now has been investigated for a number of therapeutic indications such as certain forms of cancer, leprosy, and severe ulcers. Unfortunately, more cases of malformations have appeared despite warnings and controls on its use. 

The following ball-and-stick molecular model is a representation of thalidomide, a drug that causes birth defects when taken by expectant mothers but is valuable for its use against leprosy. The lines indicate only the connections between atoms, not whether the bonds are single, double, or triple (red = O, gray = C, blue = N, ivory = H). 

Specifically, thalidomide produced a characteristic stunting of limb bud tissue, apparently due to interference with normal vascularization. The result was the development of a relatively unique syndrome known as phocomelia. At least 10,000 children, most of them German, were born with flippers instead of arms or legs. Unfortunately, some thalidomide babies are still being born in South America where the drug continues to be manufactured and many people are unaware of its proper uses (it is used fairly extensively for treating certain skin lesions in leprosy patients). 

Thalidomide was initially launched as a sedative/hypnotic drug (Fig. 1.13), but withdrawn because of its extreme teratogenicity. However, under restricted conditions (no administration during pregnancy, or to any woman of childbearing age), it found a new use as an immunomodulator. Thalidomide seems particularly effective in the treatment of erythema nodosum leprosum, a possible complication of the chemotherapy of leprosy [23]. 

Thalidomide has anti-inflammatory and immimo-suppressant actions and retains a limited specialist use in, for example, lepromatous leprosy, and oral ulceration in AIDS (some cases). 

Single or multiple lesions of erythema nodosum lepro-sum occurred in 60% of patients given intradermal interferon gamma for lepromatous leprosy, and severe systemic symptoms required thalidomide treatment in two patients (18). 

In patients with leprosy, HIV infection, and multiple myeloma, the incidences of somnolence, fatigue, and weakness were 36-43%, 48%, and 6-22% respectively (21). Administration of thalidomide at bedtime minimizes appreciation of the drowsiness that it produces, and daytime drowsiness usually abates over several weeks. 

Three of forty patients taking thalidomide for leprosy developed dermatitis herpetiformis, which was thought to have been caused by the treatment (79). 

Hastings RC, Morales MJ, Shannon EJ. Studies on the mechanism of action of thalidomide in leprosy. Pharmacologist 1976 18 218. 

In 1998, the FDA approved the marketing of thalidomide for erythema nodosum leprosy. Subsequently it has demonstrated activity against multiple myeloma, myelodysplastic syndrome, AIDS wasting syndrome, melanoma, and renal cell carcinoma. 

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