Acenocoumarol is the most widely prescribed vitamin K antagonist (VKA) to prevent and treat thromboembolic disorders. It keeps a major place in many indications despite the introduction of new direct oral anticoagulants (DOACs). However, a narrow therapeutic range, an intra-individual variability and drug interactions may lead to serious adverse drug reactions.  Sometimes, a genetic or acquired resistance to this drug may lead to a risky situation. Hopefully, resistance to acenocoumarol is a very rare phenomen.Here in we present an unsusual case of a suspected resistance to acenocoumarol. This case was notified to the Tunisian National Center of Pharmacovigilance on October 2017 and registered under the number 2449/2017. A 67-year-old patient with hypertension, diabetes, and coronary disease was treated with captopril, atenolol, atorvastatin, and salicylic acid. In 2017, acenocoumarol treatment was introduced. At biological control, the prothrombin time (PT) was 100%. The doses of acenocoumarol were raised progressively with iterative controls of PT. PT was always 100% even when acenocoumarol reached the dose of 2 g/day. A resistance to acenocoumarol was suspected. The patient was referred to pharmacovigilance department for case analysis. During the patient interview, we discover that the patient was confusing acenocoumarol with atenolol. In fact, when his doctor was increasing the doses of acenocoumarol, the patient increased her intake of atenolol believing that it was acenocoumarol. A resistance to acenocoumarol was eliminated in this patient since she had never taken the drug. We highlight through this case the importance of patient’s interview. Explaining the indications and the potential adverse events of the drug to patients taking VKA is crucial to ensure a better efficiency of treatment without increasing the risk of bleeding complication.

Iopromide is one of the latest generations of non-ionic monomers (NIM) iodinated contrast media (CM). Its use is generally considered to be safe but can occasionally results in adverse events. The frequency of late adverse reactions to non-ionic monomers is between 0.52 and 23%. Delayed adverse reactions mainly manifest as skin reactions such as erythema, maculopapular exanthema and exceptionally as fixed drug eruption (FDE). To the best of our knowledge this is an exceptional case of bullous FDE diagnosed after administration of iopromide. This case was notified to the Tunisian Center of Pharmacovigilance on December 2020 and registered under the number 1925/2020. A 75-year-old woman, with a history of breast carcinoma underwent a chest CT scan with injection of contrast product (ultravist® iopromide) in November 2020. The same day, she developed four, 2 cm in diameter, well limited and oval shaped slightly erythematous itchy plaques on the trunk and right lower limb with a burning sensation. The next day, some of these lesions developed to bullae and erosions. There was not any pathological finding in the physical examination. Biopsy findings were in line with the clinical diagnosis of FDE. The skin lesions were treated with topical corticoids and showed complete resolution one month later with residual hyperpigmentation. Although very uncommon, bullous FDE induced by CM does exist and should be known by radiologists. In this case, we emphasize the importance of a thorough pharmacovigilance investigation with a detailed history and a careful examination of physical and histopathological findings, since patch tests expose the patient to the risk of reactivation and more severe reactions.

Drug-induced hypersensitivity syndrome also known as DRESS syndrome is considered as a severe and potentially life-threatening adverse drug reaction. The pathogenesis of DRESS syndrome is still partially understood. Prior research has implicated viral infection or reactivation, specifically, human herpes viruses 6 and 7, Epstein-Barr virus and cytomegalovirus.We report a case of DRESS syndrome induced by allopurinol occurring 22 months after starting the treatment and which might have been triggered by concomitant infections.A 72-year-old man was put on allopurinol in February 2021.  Twenty months later, he was hospitalized for Klebsiella urinary tract infection associated with erysipelas that had evolved well after two weeks of antibiotherapy. On November 20, he presented a second episode of Enterococcus faecalis urinary tract infection. On December 5, he developed a pruritic maculopapular rash with fever (39.5°C). Skin examination showed a generalized infiltrated erythematous maculopapular eruption and facial edema. Complete blood counts showed total leucocyte count at 10.6 × 103/µl with eosinophils at 1.58 × 103/µl (14.9%). Histological findings were compatible with DRESS syndrome. Allopurinol was stopped. Skin condition improved within a month.A prolonged delay between the start of treatment and the appearance of a febrile rash should never exclude the diagnosis of Dress syndrome or delay its management.

Background: Sofosbuvir, a very effective new direct-acting antiviral agent (DAA), has revolutionized the therapeutic management of people infected with hepatitis C virus. It has a low reported rate of side effects. Leukocytoclastic vasculitis can be associated with hepatitis C but can also be induced by many drugs. We describe a case of leucocytoclasic vasculitis induced by Sofosbuvir that resolved 3 days after drug withdrawal. We observed a temporal relationship between the treatment and the onset of vasculitis. We emphasize the multidisciplinary approach to patients with hepatitis C to make the difference between drug-induced skin damage and damage caused by the virus itself. Case presentation: A 61-year-old woman, with a history of hepatitis C virus infection started treatment with the combination ledipasvir sofosbuvir in June 2020, 400 mg per day. Five weeks later, she developed a slightly itchy erythematous and symmetrical rash on lower members. The patient initially suspected the treatment and she stopped it. Histological finding revealed a diffuse neutrophile infiltration of vessel walls confirming leukocytoclastic vasculitis. These lesions disappeared completely three days after drug withdrawal without any symptomatic treatment. Conclusions: Sofosbuvir is one of the several recent drugs that should be prone to further attention.