enfuvirtide and Urticaria

Chronic iatrogenic scleroderma is a possible obstacle to the absorption of subcutaneously administered drugs. This study correlated the clinical and histopathological pattern of injection-site reactions (ISRs) to the pharmacokinetics of enfuvirtide in patients with HIV.. Fourteen patients treated with an enfuvirtide-based antiretroviral regimen for a median of 45 weeks were enrolled and their ISRs were evaluated. Twelve patients with evidence of ISRs underwent cutaneous biopsies using a 4-mm punch. The maximum plasma enfuvirtide concentration (Cmax) and the area under the enfuvirtide concentration-time curve (AUC) were assessed using blood sampling.. Four different macroscopic patterns of ISR were identified: A--no evidence of cutaneous lesions; B--transient infiltrative lesions that auto-resolved within 24 hours; C--transient nodular lesions that auto-resolved within 7-15 days; and D--stable lesions after more than 30 days. Histological examination showed three morphological patterns: (1) acute urticaria/vasculitis-like pattern, (2) subacute pattern and (3) chronic scleroderma-like pattern. No differences among patients with the various patterns of ISRs were observed, except for a higher Cmax and AUC in patients with pattern 1.. These results confirm that although iatrogenic scleroderma is not related to impaired enfuvirtide absorption, higher Cmax and AUC values are observed in patients with urticaria/vasculitis-like patterns.

Topics: Adult; Anti-HIV Agents; Area Under Curve; Enfuvirtide; Female; HIV Envelope Protein gp41; Humans; Iatrogenic Disease; Injections, Intravenous; Male; Middle Aged; Peptide Fragments; Scleroderma, Localized; Skin; Urticaria; Vasculitis

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.. 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.. 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.. 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.

Topics: Administration, Cutaneous; Adult; Enfuvirtide; Female; HIV Envelope Protein gp41; Humans; Male; Middle Aged; Peptide Fragments; Skin; Time Factors; Urticaria