Report
URTICARIA SECONDARY TO A COPPER INTRAUTERINE DEVICE lOEL R. BARKOFF, M.D.
From the Division of Dermatology, University of New Mexico School oi Medicine, Albuquerque, New Mexico
ABSTRACT: A 24-year-old woman developed an acute urticariai reaction secondary to a copper intrauterine contraceptive device. Allergy to copper was proven by scratch tests. The condition cleared with removal of the lUD. Tbis case report concerns a 24-year-old Caucasian woman wbo was seen in October 1974 for severe acute urticaria, joint pain and marked angioedema. Her past history was noncontributory except for aspirin taken one week before and considerable emotional upset. A copper intrauterine device bad been inserted one montb previously. Normal results were seen in CBC, erytbrocyte sedimentation rate, urinalysis, SMA12, ANA and Australian antigen. Over a period of 11 days, tbe patient's condition was finally brougbt under control witb bigb doses of adrenalin, systemic steroids and antibistamines. All treatment was stopped at tbe end of tbis time. Four montbs later, scrateb and patch tests were performed, using copper sulfate 1 % solution, copper wire, and the plastic material used in the lUD. Tbe patcb tests were negative. On 2 occasions, tbe patient sbowed a positive scrateb test reaction to 1 % copper sulfate (a large erytbematous flare, 3.5 cm in diameter) and a negative reaction to tbe copper wire, plastic and control. Her condition did not flare up. A nurse who was not wearing a coil sbowed a negative scratch test to tbese materials. Tbree weeks later, repeat scrateb tests were done, tbis time using glycerosaline 1:1 as a conPresented at tbe Noab Worcester Dermatology Society, Hollywood, FL, Feb. 28, 1976.
594
trol and bistamine 1 mg per ml for comparison (also as a control in case tbe patient was taking an antibistamine). After 15 minutes, tbe patient had a positive scratch test to bistamine and to copper sulfate 1% of tbe same size. The test to tbe glycerosaline was negative. Four other subjects gave a 3-|- to 4-\- reactions to histamine and negative reactions to copper sulfate 1 % . Tbe patient was advised to bave tbe lUD removed and subsequently, all signs and symptoms disappeared. Discussion The copper-containing intrauterine device was recently developed to overcome such undesirable side effects as, metrorrhagia, pain and expulsion, common to previous appliances. Metallic copper has anticonceptional properties. The CU-7 brand of intrauterine copper contraceptive (Searle) has a plastic component composed of polypropylene homopolymer with barium sulfate added to render it radiopaque. Its shape approximates the number " 7 " and is substantially smaller than previously available intrauterine devices. Coiled around the vertical limb is pure virginal electrolytic copper wire. This wire provides a surface area of 200 sq mm. The package insert mentions one case of an "urticariai allergic skin react i o n " developing in a woman wearing a copper lUD. Owing to the high affinity of copper for proteins and amino acids, it is probable all copper in the diet is bound in organic combination, except, of course, the metal present in drinking water.
No. 8
URTICARIA AND lUD'S
Copper is rapidly absorbed from the stomach or upper small gut and can be detected in the plasma and in red blood cells within 15 minutes of ingestion. In normal individuals, copper so absorbed is rapidly concentrated in the liver, from which it is later returned to the plasma as ceruloplasmin copper. Very few allergic reactions to copper have been reported in the literature. In 1969, Pande and Gupta of India reported a 17-year-old Moslem boy who developed thrombocytopenic purpura after ingesting 1 % copper sulfate solution (2 mg/day) given for vertiligo. This probably represented an allergic rather than a toxic reaction. In 1968, Reid reported that within 2 hours of having a premolar tooth temporarily filled with black copper cement, a woman became almost completely covered with an itching urticarial rash. In this instance, the patient had already suggested that she might be allergic to certain dental cements. The rash subsided after a few hours, although mild skin irritation persisted for 2 or 3 days. As early as 1972 an editorial warned against experimentation with pharmacologically active intrauterine devices, notably those wound with metallic copper wire. The rationale behind their develop-
Barkoff
595
ment is that copper ions have a directly contraceptive effect, so that devices can be kept small and other inconveniences minimized. For inactive devices, pregnancy rates appear to be roughly proportional to surface area and large devices carry compensating disadvantages. However, Wolfers' points out that pharmacologically active lUDs introduce a new dimension of unknown long-term hazards. We know little of use of the endometrium as a route for medication or of the efi^ects of continuous exposure to a weak solution oi copper salts on it, on myometrium or cervix. We have no experience of intermittent massage with such a solution on the vagina, the glans penis, and the urethral meatus. Allergic reactions, as with the topical use of copper salts elsewhere, are to be expected and are an added source of anxiety regarding carcinogenesis in both male and female genital tracts. This subject will have to be studied for 20 years or more. References 1.
Pande, R. S., and Cupta, Y. N., Thrombocytopenic purpura following copper sulfate therapy. ). Indian Med. Assn. .52:227, 1969. 2. Reid, D. ]., Allergic reaction to copper cement Br. Dent. J. 124:92, 1968. 3. Wolfeis, D., Pharmacologically active lUDs. Br. Med. 1. 1:112, 1972.
Scabies and Itch Animalcule A popular knowledge of the existence of the itch animalcLiie is probably coeval with the first development of scabies in the human race, since we find the earliest writers mention it as possessing a popular synonym. . . The earliest scientific information relative to the itch-animalcules that we find recorded dates as far back as the time of Aristotle, 350 years before the Christian era.—Erasmus Wilson: Diseases of tbe Skin, London, Churchill, 1842, p. 368.
URTICARIA SECONDARY TO A COPPER INTRAUTERINE DEVICE lOEL R. BARKOFF, M.D.
From the Division of Dermatology, University of New Mexico School oi Medicine, Albuquerque, New Mexico
ABSTRACT: A 24-year-old woman developed an acute urticariai reaction secondary to a copper intrauterine contraceptive device. Allergy to copper was proven by scratch tests. The condition cleared with removal of the lUD. Tbis case report concerns a 24-year-old Caucasian woman wbo was seen in October 1974 for severe acute urticaria, joint pain and marked angioedema. Her past history was noncontributory except for aspirin taken one week before and considerable emotional upset. A copper intrauterine device bad been inserted one montb previously. Normal results were seen in CBC, erytbrocyte sedimentation rate, urinalysis, SMA12, ANA and Australian antigen. Over a period of 11 days, tbe patient's condition was finally brougbt under control witb bigb doses of adrenalin, systemic steroids and antibistamines. All treatment was stopped at tbe end of tbis time. Four montbs later, scrateb and patch tests were performed, using copper sulfate 1 % solution, copper wire, and the plastic material used in the lUD. Tbe patcb tests were negative. On 2 occasions, tbe patient sbowed a positive scrateb test reaction to 1 % copper sulfate (a large erytbematous flare, 3.5 cm in diameter) and a negative reaction to tbe copper wire, plastic and control. Her condition did not flare up. A nurse who was not wearing a coil sbowed a negative scratch test to tbese materials. Tbree weeks later, repeat scrateb tests were done, tbis time using glycerosaline 1:1 as a conPresented at tbe Noab Worcester Dermatology Society, Hollywood, FL, Feb. 28, 1976.
594
trol and bistamine 1 mg per ml for comparison (also as a control in case tbe patient was taking an antibistamine). After 15 minutes, tbe patient had a positive scratch test to bistamine and to copper sulfate 1% of tbe same size. The test to tbe glycerosaline was negative. Four other subjects gave a 3-|- to 4-\- reactions to histamine and negative reactions to copper sulfate 1 % . Tbe patient was advised to bave tbe lUD removed and subsequently, all signs and symptoms disappeared. Discussion The copper-containing intrauterine device was recently developed to overcome such undesirable side effects as, metrorrhagia, pain and expulsion, common to previous appliances. Metallic copper has anticonceptional properties. The CU-7 brand of intrauterine copper contraceptive (Searle) has a plastic component composed of polypropylene homopolymer with barium sulfate added to render it radiopaque. Its shape approximates the number " 7 " and is substantially smaller than previously available intrauterine devices. Coiled around the vertical limb is pure virginal electrolytic copper wire. This wire provides a surface area of 200 sq mm. The package insert mentions one case of an "urticariai allergic skin react i o n " developing in a woman wearing a copper lUD. Owing to the high affinity of copper for proteins and amino acids, it is probable all copper in the diet is bound in organic combination, except, of course, the metal present in drinking water.
No. 8
URTICARIA AND lUD'S
Copper is rapidly absorbed from the stomach or upper small gut and can be detected in the plasma and in red blood cells within 15 minutes of ingestion. In normal individuals, copper so absorbed is rapidly concentrated in the liver, from which it is later returned to the plasma as ceruloplasmin copper. Very few allergic reactions to copper have been reported in the literature. In 1969, Pande and Gupta of India reported a 17-year-old Moslem boy who developed thrombocytopenic purpura after ingesting 1 % copper sulfate solution (2 mg/day) given for vertiligo. This probably represented an allergic rather than a toxic reaction. In 1968, Reid reported that within 2 hours of having a premolar tooth temporarily filled with black copper cement, a woman became almost completely covered with an itching urticarial rash. In this instance, the patient had already suggested that she might be allergic to certain dental cements. The rash subsided after a few hours, although mild skin irritation persisted for 2 or 3 days. As early as 1972 an editorial warned against experimentation with pharmacologically active intrauterine devices, notably those wound with metallic copper wire. The rationale behind their develop-
Barkoff
595
ment is that copper ions have a directly contraceptive effect, so that devices can be kept small and other inconveniences minimized. For inactive devices, pregnancy rates appear to be roughly proportional to surface area and large devices carry compensating disadvantages. However, Wolfers' points out that pharmacologically active lUDs introduce a new dimension of unknown long-term hazards. We know little of use of the endometrium as a route for medication or of the efi^ects of continuous exposure to a weak solution oi copper salts on it, on myometrium or cervix. We have no experience of intermittent massage with such a solution on the vagina, the glans penis, and the urethral meatus. Allergic reactions, as with the topical use of copper salts elsewhere, are to be expected and are an added source of anxiety regarding carcinogenesis in both male and female genital tracts. This subject will have to be studied for 20 years or more. References 1.
Pande, R. S., and Cupta, Y. N., Thrombocytopenic purpura following copper sulfate therapy. ). Indian Med. Assn. .52:227, 1969. 2. Reid, D. ]., Allergic reaction to copper cement Br. Dent. J. 124:92, 1968. 3. Wolfeis, D., Pharmacologically active lUDs. Br. Med. 1. 1:112, 1972.
Scabies and Itch Animalcule A popular knowledge of the existence of the itch animalcLiie is probably coeval with the first development of scabies in the human race, since we find the earliest writers mention it as possessing a popular synonym. . . The earliest scientific information relative to the itch-animalcules that we find recorded dates as far back as the time of Aristotle, 350 years before the Christian era.—Erasmus Wilson: Diseases of tbe Skin, London, Churchill, 1842, p. 368.
