Does iatrogenic scleroderma due to injection-site reaction to enfuvirtide impair absorption of the drug?

Background: 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. Methods: 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 (C-max) and the area under the enfuvirtide concentration-time curve (AUC) were assessed using blood sampling. Results: 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 C-max and AUC in patients with pattern 1. Conclusions: 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.