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Tuesday, January 06, 2009

Drug of Choice for Type 2 Lepra reaction is Thalidomide Steroids

Question 62
Drug of Choice for Type 2 Lepra reaction is
a. Thalidomide
b. Steroids
c. Clofazamine
d. Rifampicin
Answer
Harrison 16th Edition Page 971
QTDF
Harrison
Quality
Spotter
Status
Repeat
Discussion
LL and BL patients may develop type 2 lepra reactions (ENL), while BL patients (but not LL patients) can have type 1 lepra reactions.
Explanation
  • In Type 2 lepra reactions, treatment must be individualized.
  • If ENL is mild (i.e., without fever or other organ involvement, with occasional crops of only a few skin papules), it may be treated with antipyretics alone.
  • However, in cases with many skin lesions, fever, malaise, and other tissue involvement, brief courses (1 to 2 weeks) of glucocorticoids (initially 40 to 60 mg/d) are often effective. With or without therapy, individual inflamed papules last for 1 week. Successful therapy is defined by the cessation of skin lesion development and the disappearance of other systemic signs and symptoms.
  • If, despite two courses of glucocorticoid therapy, ENL appears to be recurring and persisting, treatment with thalidomide (100 to 300 mg nightly) should be initiated, with the dose depending on the initial severity of the reaction.
  • Because even a single dose of thalidomide administered early in pregnancy may result in severe birth defects, including phocomelia, the use of this drug in the United States for the treatment of fertile females is tightly regulated and requires informed consent, prior pregnancy testing, and maintenance of birth control measures.
  • Although the mechanism of thalidomide's dramatic action against ENL is not entirely clear, the drug's efficacy is probably attributable to its reduction of TNF levels and IgM synthesis and its slowing of polymorphonuclear leukocyte migration. After the reaction is controlled, lower doses of thalidomide (50 to 200 mg nightly) are effective in preventing relapses of ENL.
  • Clofazimine in high doses (300 mg nightly) has some efficacy against ENL, but its use permits only a modest reduction of the glucocorticoid dose necessary for ENL control
Comments
  • Type 1 lepra reactions are best treated with glucocorticoids (e.g., prednisone, initially at doses of 40 to 60 mg/d).
  • As the inflammation subsides, the glucocorticoid dose can be tapered, but steroid therapy must be continued for at least 3 months lest recurrence supervene.
  • Because of the myriad toxicities of prolonged glucocorticoid therapy, the indications for its initiation are strictly limited to lesions whose intense inflammation poses a threat of ulceration; lesions at cosmetically important sites, such as the face; and the presence of neuritis.
  • Mild to moderate lepra reactions that do not meet these criteria should be tolerated and glucocorticoid treatment withheld.
  • Thalidomide is ineffective against type 1 lepra reactions; clofazimine (200 to 300 mg/d) is of questionable benefit but in any event is far less efficacious than glucocorticoids
Tips
Lucio's leprosy is an acute form occurring in pure diffuse lepromatous leprosy presenting irregularly shaped, intensely erythematous, tender plaques, especially of the legs, with tendency to ulceration and scarring.

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