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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