Discussion:
The assessment of causality was evaluated with the Naranjo adverse drug reaction probability scale(3). In this case the adverse event has a score of 5 and was classified as possible in front of the evocative delay, the favorable outcome after sofosbuvir withdrawal and the data of skin biopsy.
Leucocytoclasic vasculitis is a cutaneous small-vessel necrotizing vasculitis. The main symptom is a vascular purpura. It can be infiltrated, non-pruritic, petechial or papular and rarely necrotic. More rarely, the skin involvement may correspond to supra malleolar ulcers, Raynaud’s syndrome or urticarial vasculitis (4). Skin biopsy shows lesions of leucocytoclasic vasculitis involving small-calibre vessels with a mixed inflammatory infiltrate.
This condition can be idiopathic or associated with infections, neoplasms, autoimmune disorders, and drugs. Cutaneous manifestations generally resolve when the causal agent is eliminated.
Drug induced vasculitis was reported with penicillins, macrolides, nonsteroidal anti-inflammatory drugs, gabapentin and tumor necrosis factor inhibitors(5–8)
Sofosbuvir induced vasculitis was reported for the first time in 2015 in association with dalactasavir (9). A prospective cohort study of 3,000 patients taking sofosbuvir and ribavirin, showed that this drug association induced 85 cases of ANCA-associated vasculitis (10). In a French study of drug-associated ANCA vasculitis including 483 patients, sofosbuvir was the responsible drug in 46 cases (2).
One case of non-ANCA associated sofosbuvir-induced vasculitis was published in 2019. In this case, symptoms appeared one month after the beginning of the treatment. Skin lesions disappeared one month after the drug withdrawal (11). In our case, the patient recovered rapidly in only 2 days after stopping sofosbuvir without any symptomatic treatment. This was the main evidence that the condition was drug induced.
The responsibility of ledipasvir was evaluated as less likely in front of the lack of bibliographic data describing this side effect.
Although the efficacy and safety of sofosbuvir in patients with HCV has been amply proven in clinical trials, a specific prescriber attention to this drug is needed.
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