A 71-year-old male patient has been treated with Procren Depot (leuprorelin) since August 1994. Two

Fråga: A 71-year-old male patient has been treated with Procren Depot (leuprorelin) since August 1994. Two-to-three months after the treatment was started, the patient developed a nummular skin eruption on the trunk and the extensor side of the arms. Could this particular skin rash be caused by the leuprorelin treatment?

Sammanfattning: Skin reactions caused by leuprorelin treatment have been reported. These seem to involve local hypersensitivity reactions at the injection sites, but may also involve type-I reactions with generalized urticaria, pruritus or Quincke´s oedema. Hypersensitivity to the copolymer vehicle, as well as to the drug itself may be causing these reactions. To a lesser degree some other type of skin reactions have been described during treatment with GnRH agonists, such as eczema. Cases of skin reactions similar to the ones shown by the patient in this question could not be found in the literature, but this does not exclude a causal relationship.

Svar: Leuprorelin is a synthetic form of gonadotrophin-releasing hormone, used for the suppression of testosterone in the treatment of malignant neoplasms of the prostate. It may be given as a depot preparation in a monthly dose of 3.75 or 7.5 mg intramuscularly; a monthly injection of 3.75 mg is also given subcutaneously.

According to FASS (1), rashes are a common side-effect with leuprorelin treatment, but the kind of rash is not further specified. Local reactions or pain may occur at the site of injection, with local or generalized rash, swelling or pruritus (2). An earlier Drugline document concerning skin diseases induced by GnRH agonists stated that several cases of apparent allergic reactions have been reported after treatment with gonadorelin, buserelin and goserelin (3). For example, a case of a man treated with gonadorelin who experienced generalized pruritus without urticaria or erythema. Another male patient, who had tolerated subcutaneous injections well, responded to an iv injection with malaise, localized pruritus and urticaria in the areas where the subcutaneous doses had been administered. A third case describes a woman treated with subcutaneous gonadorelin who had to discontinue the treatment after seven months because of urticarial reactions at multiple old injection sites (3).

One article could be found describing local reactions to depot leuprorelin therapy for central precocious puberty in children (4). In 365 children, treated with the depot preparation for several years in different centers, pain, induration, erythema, or abscess were reported in five per cent. According to the authors, the reactions seemed to be caused by the copolymer of lactic and glycolic acids used as a "vehicle" for the drug. However, hypersensitivity to leuprorelin itself may also be induced concomitantly with the initial response to the copolymer.

The Swedish Adverse Drug Reactions Advisory Committee (SADRAC) has received three reports of dermatological side-effects after treatment with gonadotrophin-releasing agents since 1989. One of the male patients developed an erythematous exanthema on both lower legs after treatment with goserelin Depot injections and Distalgesic. A 36-year-old female patient treated with Decapaptyl Depot (triptorelin) injections developed urticaria and Quinckes oedema after the second injection. The third case was that of a 69-year-old male patient treated with monthly injections of triptorelin who developed a dry itching eczema on distal arms and legs, a reaction that usually worsened, a few days after the injection was given. 1 FASS 1995, page 802-803 2 Martindale, The extra pharmacopoeia. 1993; 30th ed: 954 3 Drugline 07930 (year 1991) 4 Manasco PK, Pescovitz OH, Blozzard RM: Local reactions to depot leuprolide therapy for central precocious puberty. J pediatr 1993; 123: 334-335