Cutaneous injection site reactions to long-term therapy with enfuvirtide.

OBJECTIVE Enfuvirtide is the first of a new class of antiretroviral agents. The drug is safe and well tolerated; injection site reactions are the most common adverse events. The aim of this study was the clinical and histopathological evaluation of injection site reactions in patients treated for 80 weeks. MATERIALS AND METHODS Six patients were evaluated. Five of them underwent cutaneous biopsies using a 4 mm punch. Sections were stained with haematoxylin-eosin, periodic acid-Schiff stain and Verhoeff's stain. Moreover, immunohistochemical studies were carried out using CD20, CD45Ro and CD34 antibodies. RESULTS Four different macroscopic patterns were presented: (a) no evidence of cutaneous lesions; (b) transient infiltrative lesions which auto-resolved within 24 h; (c) transient nodular lesions which auto-resolved within 7-15 days; and (d) stable lesions after more than 30 days with a scleroderma-like aspect. Histological examination showed three patterns: (1) an acute urticaria/vasculitis-like pattern with inflammation of the fat tissue; (2) a sub-acute pattern with an initial dermal sclerosis; (3) a chronic scleroderma-like pattern with connective tissue disposed around the adnexa, whose structure was intact. The immunohistochemical study evidenced a prevalence of T lymphocytes and a moderate neoangiogenesis. CONCLUSIONS In our experience, after a rather long period of treatment, cutaneous reactions comprised a variety of features largely independent of the virological and immunological outcome. The adnexa was unaltered in all patients, this indicating a tendency to a possible regression of the sclerotic lesions. Therefore, patients should be encouraged to rotate the sites of injection thus permitting the tissues to regenerate.