Benzylthiouracil-induced ANCA-associated Vasculitis: A Case Report and Literature Review.

Iatrogenic antineutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) is not exceptional. Many cases of small vessel vasculitis induced by anti-thyroid drugs (ATD), mainly propylthiouracil (PTU), have been reported. We present a case of AAV related to another ATD: benzylthiouracil (BTU) and review the literature. An 84-year-old man with a 4-year history of multinodular goitre with hyperthyroidism was treated with BTU. He presented an acute syndrome with weakness, fever, epigastric pain and abdominal distension. Lactate and lipase tests were normal. An abdominal scan showed a thrombosis of the splenic artery with splenic infarction. We excluded a hypothesis of associated embolic aetiology: atrial fibrillation, atrial myxoma, intraventricular thrombus or artery aneurysm. Exploration of a possible prothrombotic state (complete blood count, haemostasis tests, activated protein C resistance, factor V Leiden, protein C, S, antithrombin III) gave normal results. Tests for antinuclear antibodies (ANA) and antiphospholipid antibodies (APL) were negative. However, testing for p-ANCA, with antimyeloperoxidase (MPO) specificity, was positive: 120.6 CU (N<20.0). We did not find other systemic manifestations, except a non-specific kidney failure. BTU was discontinued without steroids or immune-modulating drugs. Subsequently, symptoms disappeared progressively and titres of ANCA fell until normalization, 4 months later. Many patients treated with BTU present a high prevalence of ANCA, mainly, but not exclusively, directed against MPO. Vasculitis, however, remains an uncommon complication. The mechanism of this anomaly remains to be elucidated. Some studies suggest the possibility of an autoimmune reaction initiated by drug bioactivation mediated by neutrophil-derived MPO. The present observation is particular because the involved drug was BTU and clinical expression was unusual. LEARNING POINTS: ANCA-associated vasculitis related to anti-thyroid drugs is not exceptional, particularly in patients receiving long-term therapy with thioamides.Clinical manifestations are highly variable.Treatment consists firstly of stopping the anti-thyroid drug. Introduction of steroids and/or immunosuppressive therapy depends on the severity of organic impairments. Prognosis is less severe than primary ANCA vasculitis.

Impact of recommendations on crushing medications in geriatrics: from prescription to administration.

The practice of crushing drugs is very common in geriatric units. In 2009 a first study, performed in all geriatric units of a university hospital, showed that numerous errors were made during prescription, preparation and administration. The aim of this second prospective study was to assess the impact of regional and national recommendations in the same geriatric units. A survey of 719 patients (85.3 ± 6.7 years) was performed in 2013. For each patient who received crushed drugs, we recorded the reason the drugs were crushed, pharmacological classes, galenic presentations and the technique used for preparation and administration. Results were compared to the previous study. The number of patients receiving drugs after crushing was significantly lower than in the previous study (22.9% vs. 32.3%, P < 0.001). The number of crushed drugs was lower too (594 per 165 patients vs. 966 per 224 patients (P < 0.01). The main indication for crushing drugs remained swallowing disorders. The dosage form prevented crushing in 24.9% of drugs (vs. 42.0% in 2009, P < 0.001), but the drugs generally remained crushed all together. A mortar was used less often (38.6% vs. 92.6%, P < 0.001), with preference for individual-specific cups (56.1%). Mortars were more often cleaned between each patient (56.0% vs. 11.6%). The vehicle was more often neutral (water 88.5% vs. 5.7%, P < 0.001). This second study shows that regional and national recommendations have led to an overall improvement of practices for crushing drugs. Technical improvements are still possible, in association with appropriate pharmacological studies.

Antiplatelet drugs in the elderly: prescriptions often inappropriate and reduced tolerance by associated diseases and drugs.

To assess the conditions of prescriptions and tolerance of antiplatelet drugs (APD) in the elderly and to detail the parameters that influence the tolerance of these drugs. Prospective survey in a Department of Geriatric Medicine. Two hundred nineteen patients 70 years and older treated with one or two APD prior to admission were included during 7 months in 2008. We recorded the type of APD, associated diseases, main associated or co-prescribed drugs which could interact with APD and the bleeding adverse events including cutaneous bleeding. The mean age of the 219 patients was 84.5 ± 6.7 years (70-101 years), women 59.4%. Among patients 64.8% received aspirin (mainly 75 mg), 28.3% received clopidogrel and 6.8% received their combination; 16.9% of prescriptions were off-label; 51.6% of patients had an associated disease and/or an associated drug which could have increased risk of bleeding event. Among the patients who received a gastric-protective drug, the prescription followed the recommendations of the French Health Authority in 38.9%. We recorded bleeding events in 24.2% of patients at admission and in 18.3% of patients during the hospitalization. Bleeding events were significantly more frequent in patients treated with aspirin than clopidogrel (40.8 vs. 24.2%, P < 0.05) and/or with an associated drug (OR = 2.36, 95% CI 1.34-4.14, P < 0.01) and/or an associated disease (OR = 1.22, 95% CI 1.01-3.42, P < 0.05). APD treatment was stopped in 28.8% of patients, mainly because lack of indication or bleeding adverse events. Off-label prescriptions of APD were not rare in the elderly, and adverse events are frequent. The results of this preliminary study evoke that medical situations at increased risk of bleeding are perhaps insufficiently evaluated, either in case of prescription of associated drugs with increased bleeding risk or during the follow-up of patients with associated diseases. Cutaneous bleeding events should be more taken into account in prospective studies.