To the Editor: Oral or injectable methadone is widely used in the treatment of opiate dependence. There are several side effects caused by methadone therapy, the most commonly reported being nausea, vomiting, dizziness, mental clouding, and pruritus. There have also been a variety of skin lesions associated with intravenous opiate treatment. The following report suggests that local urticarial reactions may be quite frequently caused by intravenous methadone use.

Five out of 20 patients participating in an injectable methadone research program, with a mean dose of 70 mg (SD=20) and a mean frequency of 5.1 injections/week (SD=0.7), developed red skin lesions and pain in the forearm and arm during and after intravenous methadone injection under clinical supervision. The patients showed slightly raised round red lesions with an annular border, some measuring up to 3 inches in diameter. The lesions were always proximal to the injection site but did not reappear after each injection. Occasionally, the lesions overlaid the veins along several dozen inches, sometimes with a lesion-free segment and other times continuously. Because most of the injections are administered to the arm or hand, most of the lesions were located on the arm. The lesions were associated with pain along the relevant vein and disappeared within 10 minutes to 2 hours after injection.

To our knowledge, this is the first report of localized urticaria associated with intravenous methadone use. Methadone can, as do other opiates, induce release of histamine by degranulation of mast cells by a nonspecific mechanism (1–3). It remains to be established whether prophylactic treatment with antihistimine type-1 receptor antagonists can alleviate pruritus or urticaria. As demonstrated by this report, local urticarial reactions to intravenous methadone can be frequent. These reactions can be considered a severe side effect, but in the context of severe opiate addiction, this manifestation, with transient localized pain, was not an exclusion criterion. In this study, in which written informed consent was obtained, subjects with allergic manifestation could be switched to an oral preparation. We observed, however, that this change in method lasted not more than 3 days before patients returned to intravenous administration. Nevertheless, this type of reaction may represent a risk factor for lower participation in intravenous methadone programs and higher illicit opiate use.